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Nothnagel’s Practice 





DISEASES OF ‘THE LIVER 
PANCREAS 


SUPRARENAL CAPSULES 


‘ BY 
LEOPOLD OSER, M.D. EDMUND NEUSSER, M.D. 
Professor of Internal Medicine, Professor of Internal Medicine, 
University of Vienna University of Vienna 
HEINRICH QUINCKE, M.D. G. HOPPE-SEYLER, M.D. 
Professor of the Practice of Medicine, Professor of Internal Medicine, 
University of Kiel University of Kiel 


EDITED, WITH ADDITIONS 


REGINALD H? FITZ, M.D. 


Hersey Professor of the Theory and Practice of Physic, Harvard University 


AND 


FREDERICK A. PACKARD, M.D. 


Late Physician to the Pennsylvania Hospital and to the Children’s Hospital, Philadelphia 





AUTHORIZED TRANSLATION FROM THE GERMAN, UNDER THE 
EDITORIAL SUPERVISION OF 


ALFRED STENGEL, M.D. 


Professor of Clinical Medicine in the University of Pennsylvania 


as 
aR 


| my Os 
PHILADELPHIA, NEW YORK, LONDON 
W. B. SAUNDERS & COMPANY 
| 1903 








Digitized by the Internet Archive 
in 2007 with funding from 
Microsoft Corporation 


http://www.archive.org/details/diseasesofliverpOOfitzuoft 


5). 


BULLOR Sohne rater 


TO" SECTIONS ON “DISEASES OP THE: PANCKEAS 
AND OF THE SUPRARENAL (ZAPSULES. 





SIncE the publication of the original edition of this volume, the 
surgical importance of the consideration of diseases of the pancreas has 
been made especially manifest by the comprehensive treatises of Korte 
and of Mayo Robson. 

It has been the privilege of the editor to avail himself of the writings 
of these authors, and especially to refer to the important contribution 
of Mayo Robson with regard to the etiology and treatment of chronic 
pancreatitis. His observations are a most significant addition to those 
of Opie concerning the influence of gall-stones in the etiology of acute 
pancreatitis. 

Reference to Opie’s work on this subject, and to the investigations 
by him, Flexner, and others on fat necrosis, will be found among the 
additions made by the editor. 

It will be noted that the possible significance of the islands of Lan- 
gerhans in the structure, function, and disease of the pancreas, made 
so prominent by Opie and others, did not appear till after the publication 
of the German edition. 

It is especially agreeable to observe the familiarity of Professor 
Oser with the writings of English and American investigators, and to 
acknowledge his courtesy in recognizing their influence in renewing 
interest in the diseases of the pancreas. 

The additions made to the section on Diseases of the Suprarenal 
Capsules which seem especially noteworthy are the investigations on 
the active principles of suprarenal extract by Abel and Crawford, v. 
Furth, Takamine, and others, and the discoveries concerning the thera- 
peutic properties of suprarenal extract. 

‘The editor wishes to acknowledge his obligation to Dr. Elliot P. 
Joslin for his assistance in revising the translation, and especially for 
his aid in collaborating the results of the chemical, physiologic, and 
therapeutic researches which have been made within the past few years. 


REGINALD H. Firz. 





EDITORS PREFACE 
TO SECTION ON DISEASES OF THE LIVER. 





Ir is my sad duty to write this preface to the section on Diseases of 
the Liver in place of the editor, Dr. Frederick A. Packard, whose un- 
timely death occurred while the volume was going through the press. 
Those who knew him mourn the loss of a man of singularly 
pure and lovable character, of intense earnestness of purpose, and 
yet of entire simplicity; and the profession has lost in him a dis- 
tinguished member, of great accomplishment and great promise. Dr. 
Packard’s careful clinical work and his interest in the diseases of the 
liver marked him as the most suitable person to edit the excellent mono- 
graph of Quincke and Hoppe-Seyler, and a survey of the pages of this 
work will show the numerous critical additions, some of which embody 
contributions that appeared after the German edition, and others ex- 
pressions of his own views regarding subjects under discussion. It is 
unnecessary to refer to the many topics which seemed to him to require 
amplification, but in general his practical and clinical interest will 
be seen to have led him to devote especial care to diagnosis and 
treatment, including the surgical procedures that have recently found 
their place in this field. With these additions the articles on diseases of 
the liver are brought fully up to date, and have no equal in our language. 


ALFRED STENGEL. 





CONTENTS. 





DISEASES ‘OF THE-PANGREAS. 
BY DR. L. OSER, OF VIENNA. 


PAGE 

Genemb Conciiemiions.s 19 cc ap ae a ye Re ss ae ee 17 

Anatomic Considerations (Dr. Emil Zuckerkandl)......... a Ui 

Remarks on Physiologic Chemistry of the Pancreatic Juice and on Phacreatie 

DiGESbION. fF as See e Waliaye ed, 80 aca Ne 29 

Physical Characteristics of the PAGE entic i UC Or ih Ghent mem Serco yw hes ees 29 

General Pathology and Symptomatology ........4.:s20-+-ecc cece 37 
FIRST GROUP. 

Diabetes and Glycosuria as Symptoms of Diseases of the Pancreas. . . . . 39 

Experimental Pancreatic Diabetes... . . 1. ss ss we ee ee ee 41 

Clinical and Pathologic-Anatomic Experience. ........... 56 

Fatty Stools as Symptom of Diseases of the Pancreas. . ......... 83 

Faulty Digestion of Albumin 02 fo eG aie wos eres Sr oe Rae aa Gre Sos 91 
SECOND GROUP. 

Changes, in the. Urine 9 5 sions Ae howe GO Sh oan Se 92 

BrOnZed ete ed Coteus aes Coie wat forgo Ga SA ey haw fe A le dee ae 96 

ET BOINUION oy bores Fe Ao Soe ee ee aah ON Ge SIR Ae Se acta Bas 99 

Salivation, or Sialorrhcea Bancrenticn: and Diarrhoea Panoreatios fe fbr ese 99 
THIRD GROUP. 

a ASIN OES TORBEN 60S eG mak ec dO BR! ee, Sk en ew ee WS 100 

RRRINORY £9 MRR ge ce es OR a ee aS eae ae eee ae 101 

Different Kinds and Degrees of Pain and Painful Bheaniois ig whee aside te 101 

Pressure on Adjacent Organs. ........ gy Ree ata wey ta te foe a atl ee 103 

Peso niaO Ot SPP NO TSS) he Tick ly 6 le ves Yo laren ¢ 2 0 06 0, #8 103 

cg a ee 104 

ete pe am OECGNET UREA SAT UNE 5 ly a iieise a Seok se 0 «je es 104 

FEVER Ma Tee eee Os Me whe ois Lath cet ei Aa le ce # oe 104 

General Statistics ae US ee) ea ee 105 

General “peters fs ee ek doa eee ere: ee 108 

Special: Commerationey oo. Sasi eee MEM he. A en 116 

Inflammations of the Pancreas. ......... A tas ee Se ae See ee 116 

Acute Hemorrhagic Pancreatitis. .. ..... Merson tag Sy eg 116 





6 CONTENTS. 

PAGE 
Suppurative Pancreatitis. Pancreatic ADOOCME 55 600 so 9 os Xe oe, J 
Primary Suppurative Pancreatitis. . .. +++ oe a! ate ee kl en 
Secondary Acute Suppurative Pancreatitis. ..... ae, ati ee 
Chronic Indurative Pancreatitis ....-+-. +s a Gettin let mars i Se ts ee 
Inflammation of the Entire Gland... ....+ +e ee ee roar 
Chronic Circumscribed Indurative Pancreatitis. . .......... 14 
Neoplasins: shat se ee ede Sie ree eae ee ee SS ty a Heo 5) te 
CANGUDOHND <0 4.260 ose Po es se ee ee Cone ee ae ee en ewe 4 ae 
SATOOIA, «sia ooo y adsl s ere See Ten wack: wy einen, Gay ueMate eho aeen es Rees ff | 
KGGNOMA- co tom Bane Gees a oO ca le ee oe ee cat ees 
Pi erCUlOmis. aie. cee eos eS ee ee see ain ee a a a a ae oo a 176 
kg 0100 | C1 a Ra ee en Re Ce oe oe a Re es Ca eT eR 179 
Py BtS 5.55 55 5 ewe ee, Rea eee 1G a ee Bee ee a ce 180 
Hemorrhage ....... Genes Meares Mar nee on eae or te teas 6 ae eR ee ae oe 207 
Pancreatic: Caewlis: ta aes oo oboe sie ac ee ener ae we ee ee oe oe os 223 
INGCIOSIS as ete noe ee eke we, Set eee po: Fa nies te Poh anwad e oe ale Vala wee-$ 233 
Necrosis from Tieeases of the: Pancreas... 0S. a. 5 a eae ee en ae tay ey eZ 233 
Necrosis due to Disease in the Vicinity of the Pancreas. .... eae ee 
Necrosis of the Pancreas from Indefinite Causes. . .......-s A gS alan a: eae 
Fat Necrosis, Necrosis of Fat Tissue... . . 6 ee ee ee ee ee . . 244 
ATOOWIY A. hy cic te Bea ele ee or ai oe el ace | artes @keree. On Ge. Oe $a ss BOR 
Fatty Degeneration. ...... +. ss seeee Fe es Sane Ss gg ap tae eas 
TAD GUA TORS eee ceo a os my Se ar fo ate ae ee ee Be es. ae elas ake Shia: Geom 
Amyloid “Degeneration: 3%... 6 is ask sw ee es oe ee is a ere ee 
Rupture of the Pancreas. . . .. .. 2.2 «+ REE NER GL Aaa a ee aN He 265 
Prolapse and Displacement of the Pancreas. . . . 2. 2 es s+ 2 2 ee ee eee 268 
Bullet: Womans eee icy Sar eat ee ew a ee edt cas co Ph ee igh BAL eOe 
Foreign Bodies in the Pancreas. ...... ow Pa Mee rors nae nae Py. cae eee 

DISEASES OF THE SUPRARENAL CAPSULES. 

BY DR. E. NEUSSER, OF VIENNA. ’ 

Anatomy and Histology of the Suprarenal Capsules .........24446-. 307 
MOOK TOMIGS os, a “Sa ease) ee eo} oan eee 
Pathologic Anatomy of the Suprarenal Carcales a oe a errr yee 
_ Abnormalities of Development. ........ peers 
Hypertrophy and Atrophy. ........ rare ee 
Oe ee A aT ae 2 err ey rr re 
Circulatory Disturbances Sere as 5 wih: epee 
BOMAFAMATIONS 6 eis ke ¢. oa aed asa eae soceciyl gk Saute etuaen 
Infectious Granulation Tumors oo, -f8' cian Oe se Lette Leukan igen aa 
PieoplasMs ... 6s 8 ee eee mre te NE 
ER er remit, ome ean ee ae ee re eS Herat 


Physiology of the Suprarenal Capsules. . . 1. we ee eee ee wee we Ol 


CONTENTS. 7 





PAGE 
Therapeutic Properties of Suprarenal Extract. ..... a oe, Be ile eave ca Qe GOR 
Symptomatology of Diseases of the Suprarenal Capsules. ...... er eta 
Milison’s Disease. 0 wc ee tt tee et tt Sie cyan ey sai Gaunt for Raia dal. Sane 
DISEASES-OF THE LIVER. 
BY DR. H. QUINCKE AND DR. G. HOPPE-SEYLER. 

Topographic Anatomy and Diagnosis ..........-. ee ne Se ete er ae 
POSIGION, SOIZ oak ale eal TW al Se Ming Se. Wee Bice te Wore, eee Be serena encene dems 383 
PPOPCUASIOE, 25 iaip Me Se ccy Goh chy fae cb St cave at Se ne Tat Gidea ogy ee Falhe! Ze 384 
PAIPATION oso. ae te Pa, Ws ee ee Ie: Sp Bras a ee yee, Seas oe 55. ce, ae (OOS 
Inspection, AuSCUITATION creo g0-8.na Ace SI aS gies ares ane ter 387 
Changes im S120 3s 625.6 ae hie ee ees Gis iid ok sah. Ca Ge eee or ee a. SY 388 
Changes in Form. (Corset Liver) ..... Ue i ae ae ar ee ae ee ee 390 
Changes:in Position; (Piosting Liver) 224. 6. 623 3 ge ee eS 395 
General Pathology and Physiology of the Liver ......... in ah ls Ge en os 400 
ADAM ANG IStOlORY Soin ee eke, a0 8 ee aye ar a ee ee 401 
PUNCHONSOU LHC LAVOE ys 55) erie: nse, SR Doe was Se a ae yee ets oi tyne > “ANS 
Excluding the Action of the Liver ........ ee re a ee 405 
INIGrOm@eia MIGTADG SIE - 55 ia - 4. aun a own Se ae etna ena iauane es ence 407 
Carbohydrate: Metabolism. .0-50)3)5. Gk. So ar cb Sie a AS aa aU 
Metabolism of Fat ......... a ge pan Fe Ga Se ae ee ee ee 410 
Detoxicating Function ......... See es, cca uss Sea ae 411 
The Formation of Bile. ... ....... OEE eee ee ee aa ee 414 
GATTO 1G oe, ice eA Soy ie eat Se ene ae ee ee ee 423 
General Etiology of Disoeses Ol Ge MVC he pce eon era ues Ac ea eee 451 
Diseases of the Bile-passages .............004-. 469 

Disturbances in the Canalization of the Bile; Narrowing and Occlusion of ine 
Biliary Passages .. . a ee a ee a et fe ae ee 473 
Chronic Obstructive J anndice phn ieintnigi eet et tee Rar A ee Ie 473 
Catarrh of the Bile-passages; Catarrhal Sholatipitis ss wera Aen ied vent Pete PON oe 476 
eabeaatimits PARAS. 965g ale ics, head en ihre can ce te owabon deren 477 
EAR OMUIE OUNMENOT Eo og. 6g SS 8 ae See a ee a ee 484. 
ERMC BOURNE oo he 4 8 ee ee ew we 485 
Menstrual Jaundice. .... ERE 8 6s AE eR eee a ers 486 
mle 0 e.g yn a 486 
Sramdiee tye 6h as ee a. gee ee 487 
Jaundice in New-born Infant .......... ‘eos para ae ae ae 489 
Jaundice due to Polycholia ..... Pater ciate eels hie ts ss 493 © 
Jaundice after Extravasation of Blood ..........-++.e.6-. 494 
Jaundice after Hemoglobinemia ............ Sd ne phat ie hd 495 
Teen SR Aa eG Ss ea Ss wl a es 496 
Jaundice in Infectious Tissasen hc RN te ‘a eae 500 
Epidemic Jaundi0e ie es PS Be SRE ete.) a's poo POR 
Infectious Jaundiee; Weil’s Disease. . . ....... ga 


Suppurative Cholangitis. .... DEE AUR DIC ou Wise Re EC arate CUT SO a SL 


8 CONTENTS. 


Inflammation of the Gall-bladder. . . ...... ee «© ew « ig; ca 


Dilatation of the Gall-bladder ....... pe eek te Ue a abet ey an eerie 
Hemorrhage into the Bile-passages . . . 2. 1. 2. 2 2 ee ee ee es ene od 
Solutions of Continuity of the Bile-passages . . . 1... 1 2 2 ee we ee 
PT GUTS oy Soe ng es a ne ca ne, et? aaa EP te er cae a eee ar ho 
PEPEGVAGIONS 5 3) hh as weg ge oi ee ie nes ob Utne Meath ale Dee test sth ek oaks 
Bistula:! <3. ccs (anise She Sed ui Sacree cn eh anes th are at einad teh ie pow os ae 
CHOLCUGII GSTS sl rao Fa eg a cise ae ee Ne Ng ae Ok sete 
DISEASES OF THE LIVER . . 3.4 + + 4 aA eae 4 Pan ene hares agen eR eee Sk 
ALY PECOMITA en GA SPA. eA! Ge sare aise ig Maerz Ee OC Ne MAS GE oe oar oie Ree ahs 
Passive Congestion: Vn. 4, ned Ae pak eae ak es See ae eee 
Active Hyperemia of the igor: Caneeniins Of tHesEnVeN crass) acters 
Hemorrhage intothe Liver. ....... Salary (ins Sh deen Bae tay alee aes pee 
PROP IUG AEDS to. oy ok GS! spt Jal ce, cis Sa WO? obs age Tah aah a Mae aE Tae aes Sat SEP oye ee ee 
A GUILE HT ep AtItIS <2 oo sei ds Re A ee a! as has ee a ee ee Ae edie ne eae 
Acute Parenchymatous Hepatitis. ...... rey Meet aise aie Pe eee 
Acute Aophy Of Che bIver: og): 24. aS a es Ae Ae ee eee a 
Aeute:- Interstitial Hepatitis: 554 c6- end a w (As Sere ce ane wee 
A DeCrSS OL TRE IIVOR > 22.05 S55, Gnd tee ace der nar ar ge gia ane pat Grad) ces 
Chronic Inflammation of the Liver. . ... .. 1... 2. eee eevee 
Cirrhosis of the Liver; Chronic Interstitial Hepaatia: sie eel nap irie-t - 
Hypertrophic Ghinhotis OL the Jainer, o> Soap saree alee arias OAS 
Carrhosis from: Stasis: of Bile >..%, < a..¢0405. 82 fos al Sek eee 
Cirrhosis from Stasis of Blood... 2... 2... 
Tubercular Interstitial Hepatitis and Tuberculosis "ét Tver in Ngan eral 
Cirrhosis Adiposa; Cirrhose Graisseuse ...........02e0. 
Hepatitis Interstitialis Flaccida . .. 0.06 6 se we See as 
War tA, TWEE ie og. 852 og es, at cae Si ge es Sak Ai oi ses atau 
Pigment Cirrhosis:-of Dinbeties:. 028 «Siar mele ck 4) Sid) a Petree ee 
Syphilitic Hepatitis. ... 2 2 sk ws a SR ae ae ee te ee ee OK 
DNCDP LARISA 5 Pe oo Gi on, eC Oe Une aa ae note ee eaten, Go) ae Sn Meee 
PL OMMAUR Seal ha. Sela Meet oe aria eae oes tole nea ate 
PMOAO Mie tles 23. cee hig ieee Mh Pn Gee ah ack Sea ee, ae og coe 
PSS! 00 sae Per es Babe Re eh et RIEU IE Si mS ae th, a PT Ee ees 
Carcinoma, Sarcoma, Adenoma. ..........-.008 802 ee 
Leukemic and Lymphomatous Tumors of the Liver ........ 
Parasites. Ols Ge DAVEY ce cng ghia se’ Se acraee a: Se ® ce me. ae te gs ee 
Cogeidia: ic) s.% ps ame i i eet Soest or oe. bets Behe 


Echinococcus Oasis 
Hoinoeseens: Alyeelaris-: 2 82: . ys 3> tae so) Ge arse a Ge es ae de as 
® Asearis LUMbTICOdes 73... 6° ed's) cess ow See cA Sng: sg os 
Distomata 


_ eo eo ee 0 @ @. 92° 1 oe” 2. 86 we ere Se 


Parenchymatous Changes and Beeeraniens a 4+ 4 \i« Sele ae ee 
Hypertrophy of the Liver, . . . . & «-« iseus!sacee oe 
Fatty Liver 
Chronic Atrophy ....... 
Amyloid Liver 


Pigmentation of the Liver. . 
Functional Disturbances of the Liver 
Neuralgia of the Liver ...... 


CONTENTS. 9 


PAGE 

Diseases of the Vessels of the Liver. ....... eee he dcbesh, ohana OO 
PRES OF THO: POVEAl VOUR. 2 er 2a ae ae Wee ws 18) Wed. Be Se 881 
Occlusion and NaIrOWInge. ojos ae ae ee oes SN eae es 882 
Inflammation of the Portal Vein ....... ee oa ee ee ae ee 889 
Other Pathologic Changes of the Portal Vein. ........... 892 
Diseases:ot the “Hepatic Artery “okie ao Lies os eee oe eas 895 
Anéurysny of Hepatic. Artery Gs. eas eA ee Se ee cee 896 
Diseases of the Hepatic Veins. ....... rere ee ae ae ee ae ee 898 
Narrowing and: OcOlaslOm 5 eo Sree a ee ee ee SS _. 899 
Inflammation of the Portal Veins ...........-. $id ees eocOU 





INDEX e e e e e e e 8 « 6 ee € ‘® © © “@ +e. @ 8 ee e e e e e e e e ° e e . 907 


Dre 4 








DISEASES OF THE PANCREAS. 


BY 


L.. -OSER,. M.D; . 








PREFAIORY NOTE. 





THE pancreas, perhaps, presents a greater contrast between its physi- 
ologic importance and the lack of clinical knowledge concerning its 
affections than any other organ of the human body. 

It is known that this is one of the most important glands concerned 
in metabolism, and, thanks to exact physiologic investigations, it is also 
known that its functions are manifold; the conclusion, therefore, is justi- 
fied that pathologic disturbances of its structure are followed by grave 
injury to the vital functions of the body; yet the positive knowledge of 
the pathology of the pancreas is very slight when compared with that 
of the pathology of the neighboring organs, the liver, the intestines, ete. 

Despite the energetic initiative of Friedreich, further investigation 
has progressed but slowly, although his classic treatise on diseases of 
the pancreas presented at the time, in the most suggestive form, the sum 
total of clinical knowledge on the subject, small as it was. A decided 
impulse, however, was given to investigators in this field by the persistent 
advance in surgery after Lister’s imperishable work. Surgery influenced 
the question from two sides. It now for the first time became possible 
to take into consideration the solution of certain questions by means 
of experiments upon animals. Only on the soil prepared by Lister could 
v. Mering and Minkowski establish the important fact of experimental 
pancreatic diabetes. On the other hand, the clinicians learned no less 
through therapeutic surgery. Certain processes, as cysts, abscesses, 
necroses, tumors, and chronic inflammations, which had generally been 
brought to view only by anatomists, were now placed within the realm 
of diagnostic knowledge. 

Within the past ten years interest in the pancreas has increased. A 
great impulse was given by American physicians, especially through the 
brilliant work of Fitz and Senn. The valuable and comprehensive 
treatises of Seitz and Nimier concerning several important subjects ap- 
peared in the same period. The surgeons Gussenbauer (1883), Senn, 
Ruggi, Krénlein, Biondi, Sendler, Riedel, and others, and in more recent 
timeS and in an especially prominent manner, Korte, published com- 
munications, and the noted operators of all lands made known the bril- 
liant results of the newly created pancreatic surgery. The pioneer ex- 
periments of v. Mering and Minkowski aroused eager investigation on all 
sides, and pathologic anatomy was greatly enriched by the valuable work 
of Orth, Balser, Langerhans, Ponfick, Chiari, Tilger, Olivier, E. Fraenkel, 
and others, and especially by the important treatises of Dieckhoff and 
Hansemann. A careful table of statistics and numerous monographs 
on different themes appeared during this same period. 

Notwithstanding this impulse, it must be admitted that we unfortu- 

13 


14 PREFATORY NOTE. 


nately stand at the very entrance of clinical knowledge. A correct 
diagnosis of a disease of the pancreas is an event almost worthy of pub- 
lication. This open acknowledgment should not alarm us, but should 
incite to renewed investigations. 

When I undertook to describe the present state of our knowledge of 
the disease of the pancreas, I was well aware of the great difficulties to 
be encountered. The reports of cases are entirely too few to enable us 
to use them as a basis of clinical classification. I could only combine 
these reports, and, therefore, was obliged to give more space to statis- 
tics than was their due as almost the only foundation of our present 
knowledge. 

I was aware from the first that, on account of the many-sided char- 
acter of the subject to be treated, nothing noteworthy could be accom- 
plished without efficient aid. The expression of this desire brought a 
rich response. Prof. Zuckerkandl has had the kindness to sketch the 
descriptive and topographic anatomy with especial reference to the 
clinical point of view. Some facts have thus been brought to light which 
should interest the clinician as well as the surgeon. 

Prof. Weichselbaum had the goodness to place at my disposal the re- 
sults of the postmortem investigations at the Vienna Pathologic Insti- 
tute for the last ten years. Dr. Zemann, the prosector, undertook to 
examine, with his usual thoroughness, the autopsies in my hospital which 
were appropriate for the purpose, and also contributed an interesting 
report on the results secured by him elsewhere. He examined also most 
of the microscopic preparations obtained from experiments on animals. 
To all these gentlemen I express my most heartfelt thanks. 

Pathologic material is only sparingly at the disposal of the clinician. 
A substitute, although not entirely satisfactory, can be gained from 
experiments upon animals. Thanks to the advances of surgery, it is pos- 
sible to produce different pathologic processes in the pancreas of animals, 
to study their course during life and the anatomic conditions after death, 
ang to examine these at a much earlier stage than is possible in the human 

ody. 

The accomplishment of this plan was rendered possible by the co- 
operation of my assistant, Dr. Katz, and the support of several younger 
colleagues. Several important morbid processes, as abscess, hemorrhage, 
induration, necrosis, and fat necrosis, were produced in animals. The 
course during life could be watched and immediately after death anatomic 
preparations could be secured. 

The experiments upon animals permitted the testing of the various 
alterations of the functions of the pancreas when partially or wholly 
destroyed. They were undertaken in a laboratory of the polyclinic. 
During 1893 and 1894 Dr. Theodore Zerner, Jr., conducted the opera- 
tions, and later, with the aid of my assistant physicians in the hospital . 
and in the polyclinic, the operations were performed by Dr. Katz, who 
has also carried on many laborious chemical investigations. To all 
these gentlemen I owe a debt of gratitude, but especially to my assistant, 
Dr. Katz, for his help in many different ways. 

The further I advanced in my work, the more was it impressed upon 
me that innumerable questions were to be solved, and that it would need 
many energetic workers from the most varied branches of theoretic and 
practical medicine to raise our knowledge of the diseased pancreas approx- 
imately to the level which would correspond to its physiologic importance. 


PREFATORY NOTE. 15 


I have made it especially my task to describe the present condition 
of our knowledge on the subject, to point out where it was deficient, and 
to stimulate to new work. 

Because of the variety and amount of the material to be mastered, 
and on account of the relatively short time which was at our command, 
the question could in most cases be only suggested; the answer was im- 
possible. The conviction is forced upon me that it needs only appropriate 
effort to bring many of these dark questions into the brightest light. 
The experiments upon animals in particular make it possible for the 
pathologist, the clinician, and the pathologic anatomist to gain an 
insight into the more deep-seated processes, to test the disturbances of 
function produced by morbid conditions induced at will, to study the 
minute histologic changes in their various stages, and to compare them 
with the observations made at the sick-bed and in the autopsy-room. 

The pessimistic view that clinical studies are and will remain without 
practical value is certainly not justified. Already surgeons have shown us 
that by correct knowledge of certain pathologic processes in the pancreas, 
and by interference at the right time, many cases can be cured. We 
have learned also from the surgeons to speak of the hopeful prevention 
of certain diseases. Is it not conceivable that the medical treatment of 
pancreatic disease may be broadened by rational methods, as already 
has happened for the neighboring organs, for instance, the intestines and 
biliary passages, with which the pancreas is so intimately associated? 

It is to be hoped that the time will come and is not far distant when 
it will be possible to present that clinical representation of the diseases 
of the pancreas which so vitally important an organ deserves. 


PROFESSOR OSER. 





DISEASES OF THE PANCREAS. 





GENERAL CONSIDERATIONS. 
I. ANATOMIC INTRODUCTION. 


BY PROF. EMIL ZUCKERKANDL. 


THE pancreas lies behind the stomach, crosses the spinal column at a 
point corresponding to the first lumbar vertebra, and extends from the 
concavity of the loop of the duodenum to the mesial surface of the spleen 
on the left. The length of the gland varies from 15-21 em. (6-8 inches), 

The form of the organ is not regular, but can for the greater part be 
compared with an elongated triangular prism. The right end represents 
the thickest part, and is called the head; the middle portion with the 
three surfaces clearly pronounced is the body, while the left pointed end 
is called the tail; these three portions of the pancreas show no distinct 
lines of demarcation. Such a line may be thought of only where the 
head and body are joined, as this is the thinnest portion of the gland. 

The head of the pancreas, distinguished by its breadth, lies attached 
to the concavity of the duodenum. When the head of the pancreas 
is especially thick, it may, by overlapping the sides of the intestinal loop, 
inclose nearly a third of the tube. From the middle of the head a pro- 
cess (lobe) extends upward as well as downward; the upper smaller lobe, 
if well developed, extends to the superior horizontal part of the duode- 
num. The lower larger lobe (pancreas parvum) follows the distal portion 
of the duodenum, and when well developed extends to the point at which 
the duodenum merges into the jejunum. | 

Between the head and body of the pancreas there is a groove for the 
superior mesenteric vessels. If the portion of the pancreas in front of 
this groove is cut through, the superior mesenteric artery is to be seen; 
also the union of the two mesenteric veins and the splenic vein, forming 
the portal vein. | . 

This groove may be imagined to have been developed in the following 
way: the narrow body of the gland failed to attach itself to the left end 
of the much broader head, but passed from the ventral surface of the 
head of the pancreas into the axis of the gland close to the duodenal 
wall. Thus only is to be explained the development of a broad groove 
between the ventral surface of the head and the dorsal surface of the 
body. Fi: body of the gland is thinnest in the region of this groove, a 

17 


18 DISEASES OF THE PANCREAS. 


- condition probably dependent upon the disposition of the large intestinal 
er ductus choledochus is embedded in a furrow which is, as a rule, 
soon transformed into a canal at the back of the head and at the side of 
the gland toward the duodenum. Hence a part of the common bile- 
duct varying in length from 0.5 to 3 em. is buried in the gland. The side 
of the glandular canal turned toward the duodenal wall is thin, as it 
usually consists of only a few lobes. This view is in direct opposition 
to that of O. Wyss,* according to whom the ductus choledochus traversed 
the pancreas only five times in 22 autopsies. F'rom the location of the 
duct it is easy to see how readily enlargement and .tumors of the pan- 
creas may lead to compression and obstruction of the ductus choledochus. 

The body of the gland has three surfaces: a ventral, in front, a dorsal, 
behind, and a caudal, below. One might also speak of a rectilinear 
surface, because the gland lies attached to the duodenal wall by a broad 
terminal surface. The ventral surface of the pancreas is free and has a 
delicate peritoneal covering. The dorsal surface lies upon the posterior 
wall of the trunk, while the caudal surface is attached closely to the 
transverse mesocolon. This last-mentioned surface is wide only at the 
left of the duodeno-jejunal flexure; at the right of this loop, however, 
and in the region of the superior mesenteric vessels, where the body of 
the pancreas is thinnest, it has a blunt edge. 

Opposite the caudal surface the gland is bordered by the so-called 
(anterior) edge. In this there are two long grooves for the splenic vessels. 
The anterior shorter groove contains the artery, the posterior longer one 
carries the vein; but it sometimes happens that there is only a single 
furrow present for both vessels. 

The tail of the gland, which really represents only the left end of 
the organ lying next to the spleen, is the least firmly attached portion 
of the pancreas. Occasionally a portion of the mesentery containing a 
lymph node lies between the tail and the mesial surface of the spleen, 
thus permitting a certain mobility to the tail of the pancreas. 

Regarded as a whole, the pancreas shows, in addition to the form 
already described, a distinct S-shaped bend (Fig. 1), which is plainly 
seen in preparations hardened in situ. The gland is thus bent by the 
neighboring organs, including the spinal column and the stomach. Since 
the posterior abdominal wall is uneven and the pancreas lies over the 
marked prominence of the spinal column, the corresponding portion of 
the body of the gland must be bent convexly forward. 

_ This convexity appears all the more sharply defined because on each 
side there are depressions ‘produced by the stomach. The depression 
on the left, extending from the prominence to the tail (umpressio gastrica), 
is large and is caused by the posterior wall of the stomach, which crosses 
the gland. The depression found at the right of the prominence (im- 
pressio gastroduodenalis) is considerably smaller and is determined by 
the position of the pylorus and the first part of the duodenum (Fig. 1). 

Consistency.—The pancreas has the firm texture which characterizes 
the other salivary glands. This organ, however, consists of large lobes, 
and the individual lobules are easily separated from each other in conse- 
quence of the loose texture of the interacinous connective tissue. 

Excretory Ducts.—Under normal conditions’ the pancreas has two 
excretory ducts: the pancreatic duct (ductus Wirsungianus) and the 

* “ Zur Aetiologie des Stauungsicterus,” Virchow’s Archiv, Bd. xxxv1, 1866. 

® 


“ANATOMIC INTRODUCTION. 19 


accessory pancreatic duct (ductus Santorini). The former (Fig. 2) 
traverses the entire length of the gland, closely following the axis. In 
its course from left to right, the duct increases in diameter through the 
reception of numerous side branches. When it reaches the head, the 





Fie. 1.—Relation of the pancreas to the duodenum and to the organs of the posterior abdominal 
wall: P, Pancreas; D, duodenum; R, kidney; N, suprarenal gland; M, spleen; Sp, esophagus; 
U, ureter ; A.a, aorta and celiac axis; C, vena cava inferior; V.p, vena porte; V.m.s, vena mesenterica. 

* superior; V.m.i, vena mesenterica inferior ; A.m.s, arteria mesenterica superior; V./, vena lienalis. : 


pancreatic duct turns backward and downward and unites at the end 
with the common bile-duct, both passing obliquely through the wall of 
the intestine and entering a little pouch lined with mucous membrane 
known as the diverticulum Vateri. The entrance to this pouch is indi- 
cated by a longitudinal fold of mucous-membrane (plica longitudinalis), 


20 _ DISEASES OF THE PANCREAS. 


which contains the mouth of the diverticulum, in which is a papilliform 
projection (papilla major, Fig. 2). This papilla lies in the projection of 
the pancreas parvum, near the place where the left wall of the duodenum 
becomes the dorsal wall; hence it is more posterior than anterior. When 
this portion of the duodenal diverticulum is incised, the upper part 
shows two openings, that of the ductus choledochus, and, further in, 
the opening of the pancreatic duct; the two are separated from each 
other by a narrow band. 

The caudal portion of the diverticulum is covered with delicate 
valve-like projections considered by Ch. Sappey to prevent the entrance 
of the intestinal contents into the two ducts. 

The ductus pancreaticus accessorius (Fig. 2) is limited to the head 
of the gland. It runs above the duct of Wirsung, with which its left 
end communicates by means of a wide opening. Near its entrance into 
the intestine the accessory duct is reduced in size. The opening of the 
ductus Santorini in the mucous membrane of the duodenum is marked 
by a small, wart-like prominence 2 to 3 cm. above and rather behind 
the diverticulum Vateri (papilla minor, Fig. 2). 

For a long time the accessory duct was regarded as inconstant, but 
Cl. Bernard,* Verneuil,t Sappey,t and very recently Hamburger,? have 
shown that it is constantly present. Hamburger found the duct always 
present in the 50 cases examined by him; Sappey, in 17 preparations, 
never found it wanting; in one case, however, he found the right part 
of it obliterated. There are no reports of the frequency of this oblitera- 
tion. 

As the pancreas lies immediately in contact with the wall of the in- 
testine, its excretory duct passes directly from the gland into the latter. 

The presence of two ducts in the pancreas is explained by the fact 
that the gland develops from prohypoblastic projections. <A single 
gland results from their fusion, and their excretory ducts thus com- 
municate with each other. It needs no detailed description to show the 
importance of the two ducts; it is sufficient to mention the fact that 
in the case of the obliteration of the main duct the accessory duct can 
carry off the secretion. 

Blood-vessels.—The pancreas is supplied with blood-vessels which 
communicate with the celiac artery, the superior mesenteric artery, and 
the portal vein. The arteries arise as follows: 

@) From the splenic, which sends a number of branches into the 
gland. 

_ (6) From the undivided trunk of the hepatic artery, which at times 
sends a large branch downward on the posterior side of the pancreas; 
this branch anastomoses with the arteria colica media and gives off 
smaller arteries for the head of the pancreas. 

(c) From the gastro-duodenal artery, which by means of the upper 
pancreatico-duodenal branch-nourishes the head of the pancreas. The 
arteria pancreatico-duodenalis superior, in its course toward the duo- 
denum, lies in a groove on the ventral surface of the head of the pancreas. ° 

_ (d) From the arteria pancreatico-duodenalis inferior, which also sup- 
plies the head of the gland, and likewise sends a lateral branch into the - 
body of the gland; on the concave border of the duodenum it forms an 


*Ph. C. Sappey, ‘‘Traité d’anatomie descriptive,” ‘i 4, Paris, 1873. 
tf Ibid., loc. cit. it tIbid., loc. cit. 
§ “Zur Entwicklung der Bauchspeicheldriise des Menschen,” Anat. Anz., 1892. 





ANATOMIC INTRODUCTION. 21 


arch with the arteria pancreatico-duodenalis superior. The arteria pan- 
creatico-duodenalis inferior rises from the trunk of the superior mesenteric 
artery or from the arteria colica media, which also sends some branches 
to the pancreas. 

The splenic artery provides chiefly for the body and tail of the pan- 
creas, while the other arteries supply more especially the head. 

The veins follow in general the course of the arteries. The vena 
pancreatico-duodenalis superior empties into the gastro-duodenal vein. 
The vena pancreatico-duodenalis inferior empties into the superior 


Dek 7 plein. 





Fie. 2,—Pancreas and duodenum. In the former the ducts are shown. The duodenum is so 
opened as to show the papille. D, Duodenum; P.maj., papilla major; P.min., papilla minor; P./., 
plica Pets tik upsets D.p., ductus pancreaticus; D.p.a., ductus pancreaticus accessorius ; D.ch., ductus 
choledochus, 


mesenteric vein and the superior mesenteric vein into a lateral branch 
of the vena colica media. The vena lienalis collects the blood from the 
veins which accompany the pancreatic branches of the splenic artery. 
The blood-vessels which are to be considered in operations on the 
pancreas are the glandular branches arising from the splenic, superior 
mesenteric, hepatic, and gastro-duodenal arteries, as well as the corre- 
sponding veins. But, in addition to these, sometimes one and sometimes 
another of the larger blood-vessels lying in the depressions on the gland 
may fall into the field of operation. In larger tumors of the gland even 
more distant vessels, as the cceliaca, hepatica, gastrica sinistra, and, 


22 DISEASES OF THE PANCREAS. 


according to Krénlein,* even the colica media, may be of importance. 
According to K. Franz,{ the origin of the arteria mesenterica superior 
and colica media may be found in a space the upper border of which lies. 
behind the pancreas, while the lower limit is 5 cm. below this gland. 

Of anomalous vessels which might be involved in operations on the 
pancreas, the following are to be mentioned: 

(a) The hepatic artery, when its branches (the right and left) arise 
separately, as not rarely happens; the left branch from the celiac artery 
and the right branch arising from the portion of the superior mesenteric 
artery covered by the gland. In the latter case the arteria gastroduo- 
denalis is usually given off from the right branch. 

(b) The two hepatic branches which arise separately from the celiac. 

(c) The hepatica communis, which arises, not from the celiac, but from 
the superior mesenteric. 

(d) The arteria suprarenalis sinistra, which is given off from the celiac 
and therefore passes through the bursa omentalis. 

Lymph-vessels are present in large numbers; these are divided, 
according to the situation of the lymph-nodes into which they enter, 
into the upper (accompanying the splenic artery), lower (with the supe- 
rior mesenteric artery), on the right (along the head of the pancreas), 
and on the left (in the mesentery of the tail of the pancreas). 

Nerves.—The nerves of the gland arise from the solar plexus. 

Structure of the Gland.—The pancreas is a branched alveolar gland 
with terminal alveoli as the essential constituents of the organ. The 
secretory cells of the alveoli present a different appearance according to 
the state of activity of the gland. The protoplasm at the bottom of the 
cell is homogeneous, while that next to the free surface is granular. 
This different condition of the two zones depends upon the physiologic 
condition of the gland. In hunger the lower zone of the cells is wide 
and well provided with granules; after an abundant secretion has taken 
place the cells, on the whole, are somewhat smaller and the granules are 
fewer. The protoplasmic upper zone increases in corresponding ratio. 
If the gland has secreted for some time, then there is a complete lack of 
granules and the whole cell consists of homogeneous protoplasm. 

It must be assumed, therefore, that during the resting period of the 
gland peculiar granules are formed at the expense of the protoplasm, 
and that they are the predecessors of the secretion (zymogen granules). 
During secretion these gradually disappear, while at the same time the 
fluid secretion appears in the lumen. The zymogen granules, however, 
have not as yet been seen in the secretion. 

After secretion the cells enlarge, attain their original volume, and 
again begin to form zymogen granules. The excretory ducts are lined 
by a cylindric, simple epithelium; goblet cells occur, but isolated, in the 
pancreatic duct (A. A. Bohm and M. v. Davidoff). 

[The islands of Langerhans were first described by Paul Langerhans, 


* “Klinische und top. Beitrige zur Chirurgie des Pankreas,” Beitrage zur klin. 
Chirurgie, Bd. xiv, Tiibingen, 1895. : 

+ It has happened that the arteria colica media had to be ligated, and gangrene 
of the transverse colon resulted. In such a case it would be advisable, in conjunction 
with the operation on the gland, to undertake resection of this part of the intestine. 

{ “ Ueber die Configuration der Arterien in der Umgebung des Pankreas,”’ Anat. 
Anz., Nr. 19, 20, 1896. 


_ §“Beitrage zur mikroskopischen Anatomie der Bauchspeicheldriise,” Inaug. 
Diss., Berlin, 1869. 


ANATOMIC INTRODUCTION. 23 


in 1869. He called attention to the presence in the lobules of the pan- 
creas of groups of small, spherical or polygonal cells differing in appear- 
ance from the ordinary cells of the gland. Laguesse * designated them 
“lots” of Langerhans, and they have been the subject of repeated 
investigation, especially of late years, as the possible source of the sup- 
posed internal secretion of the gland. They have been regarded as 
lymph-follicles or pseudo-lymph-follicles, as blood-glands, and as resem- 
bling the hypophysis and the carotid and coccygeal glands. It is generally 
admitted, however, that, in the adult at least, they are not, as a rule, 
in continuous relation with the efferent duct of the gland. It was found 
by Kihne and Lea} that they corresponded to groups of dilated and 
tortuous capillaries resembling renal glomeruli. Opie ¢{ has recently 
studied these structures, and finds them more numerous in the tail than 
elsewhere in the gland.—Eb.] 

Anomalies of the pancreas are relatively rare; they concern the 
gland itself, or the presence of pancreatic tissue in atypical places in the 
intestinal tract, or, still more rarely, the inclosure of atypical tissue in 
the stroma of the pancreas. The following may be mentioned among 
the peculiar anomalies of the pancreas: 

(a) Cases in which—as described, for instance, by J. Hyrtl 2—a 
portion of the head of the gland becomes separated and lies behind the 
mesenteric artery and superior vein, or an accessory pancreas as large asa 
dollar, with an excretory duct opening into the pancreatic duct, lies 
under the head of the gland at the inner side of the descending part 
of the duodenum (J. Engel||). 

(b) Separation of the head or tail of the pancreas, as described by J. 
Hyrtl.** In the one case the tail of the pancreas was detached and was 
connected with the gland only by a duct which communicated with the 
duct of Wirsung. Ina second preparation made from the body of a new- 
born child, Hyrtl saw the head of the gland separated from the body. 
In the space between the two parts were the superior mesenteric artery 
andvein. A pedicle 4 inch long, and formed simply of the pancreatic 
duct, united the two. 

(c) The case of A. Ecker,t+ in which the descending portion of the 
duodenum was surrounded by a ring of pancreatic tissue. Across the 
above-mentioned portion of the intestine was found a strip of gland 
which arose from the head of the pancreas and surrounded the duodenum 
by a continuous ring. The excretory duct of the abnormal piece of 
gland proceeded from the pancreatic duct, ran forward, and ended in 
the neighborhood of the main duct in fine branches. Finally: 

(d) A case observed by me, in which the groove for the superior 
mesenteric artery and vein formed a canal in consequence of the union 
of the descending lobe with the body of the gland. 

The second group of anomalies concerns, as already mentioned, the 
occurrence of pancreatic tissue in atypical places, and such accessory 


* Journ. de l’ Anat. et Phys., 1896, xxxtr, 208. 

+ “Untersuch. a. d. Phys. Inst. d. Univ. Heidelberg,” 1882, 11, 488. 

{Johns Hopkins Hosp. Bull., 1900, x1, 205. 

§ “ Topograph. Anatomie.” ~ 

|| ““ Ueber Krankheiten des Pankreas und seines Ausfiihrungsganges,”’ “‘ Medicin. 
Jahrb.,’’ Wien, 1840. 

** “Win Pancreas accessorium und Pancreas divisum,’”’ Sitzuwngsber. d. kazserl. 
Akademie, Bd. t11, Wien, 1866. 

tt “ Bildungsfehler des Pankreas,” etc., Zeitschr. f. rationelle Medicin, 1862. 


24 DISEASES OF THE PANCREAS. 


pancreatic glands have been observed (a) in the stomach, (b) in the 
duodenum, (c) in the jejunum, and (d) in the ileum. 

Accessory Pancreas in the Stomach.—J. Klob* found such a formation 
in the middle of the greater curvature, inclosed between the serous and 
muscular coats. According to Klob, the gland had no excretory duct, 
but, as Zenker justly remarks, Klob may have overlooked the duct. 

E. Wagner + observed an accessory pancreas in the anterior wall of 
the stomach near the lesser curvature, midway between the cardia and 
the pylorus. The gland, which was situated in the submucosa, was 
2 inches long, 24 inches thick, and 34 inches broad. 

C. Gegenbaur ¢ found in the lesser curvature, 2 cm. distant from the 
pylorus, in the submucosa, an accessory pancreas which was 14 mm. 
long and 6 mm. thick. 

Finally, Weichselbaum 2 describes a case in which, at the bottom of 
a diverticulum near the pylorus, there was a nodule of the size of a hemp- 
seed which showed the structure of the pancreas. He found also in the 
anterior duodenal wall an accessory pancreas as large as a bean and covered 
by the serous coat. 

Accessory Pancreas in the Wall of the Duodenum.—To this class belongs 
the above-cited case of Weichselbaum and also the observation of Zenker, 
of an accessory pancreas on the convex border of the duodenum opposite 
the head of the pancreas. 

Accessory Pancreas in the Wall of the .Jeyunum.—Klob || found an 
accessory pancreas in the dorsal wall of the first loop of the jejunum. 

I’, A. Zenker ** adds several similar cases. Twice he found the acces- 
sory pancreas quite near the duodenum; in a third preparation it lay 
16 cm., and in a fourth 48 em., below the duodenum. 

Accessory Pancreas in the Wall of the Ileum.—The first description 
of such an anomaly is that by Zenker.;+ Fifty-four centimeters above the 
cecal valve this investigator observed an intestinal diverticulum, with 
a mesentery containing a large amount of fat, and in which was the acces- 
sory pancreas. 

IX. Neumann {tt also saw an accessory pancreas in connection with an 
intestinal diverticulum in a child. The diverticulum was 2 feet above 
the cecal valve and its tip was connected by a pedicle with an accessory 
pancreas as large as a pea. The excretory duct of the gland entered 
the diverticulum. 

The last case in this category is described by C. Nauwerck.33 This 
author found hanging free in the abdominal cavity, 2.3 m. above the 
cecal valve, a pancreas 9 cm. long, provided with a serous covering. 
The excretory duct opened into a deeper portion of the intestine. As 
a Meckel’s diverticulum was present 80 cm. above the cecal valve, it is 
probable that in this case, as in those of Zenker and Neumann, the diver- 
ticulum, to which the accessory pancreas was related, was not a Meckel’s 


* “ Kleinere Mittheilungen,” Zeitschr. d. Gesellsch. d. Aerzte, Wien, 1859 
{ Archiv j. Heilkunde, 1862. eae 
t , Nebenpankreas in der Magenwand,”’ Reichert’s Archiv, 1863. 
_ § “Nebenpankreas in der Wand des Magens und Duodenums,” Bericht d. Rudolj- 
stiftung, 1884. 


|| Loc. cit. 

** “ Nebenpankreas in der Darmwand,” Virchow’s Archiv, Bd. xxi. 
tt Loc. cit. 

tt Archiv f. Heilkunde, Bd. xt, 1870. 

§§ “ Ein Nebenpankreas,” Ziegler’s Beitrage, Bd. x11, 1893. 


7 


ANATOMIC INTRODUCTION. 25 


diverticulum, but a malformation of some kind—a conclusion which 
seems well justified. 

[On the contrary, the observation of J. H. Wright * suggests that the 
development of an accessory pancreas may be connected with the per- 
sistent remains of the vitelline duct. He found a nodule of pancreatic 
tissue about 34 mm. in diameter in the vicinity of an umbilical fistula 
which had existed since birth in a child of twelve years. An efferent duct 
leading to the surface was not found. The peritoneal cavity was opened 
and explored, but the finger found no connection between the fistula 
and the intestine.—Eb.] 

Finally, it is to be noted that in all forms of accessory pancreas except 
that described by Klob [and Wright] an excretory duct of the gland 
could be found. 

The third kind of anomaly was described by Klob.t This anatomist 
dissected a body the pancreas of which showed a spherical enlargement 
of the tail. Further investigation disclosed that the enlargement was 
due to the inclusion of an accessory spleen. 

Abnormalities of Excretory Ducts —The following have been observed: 

(a) Lack of an accessory duct. 

(b) Three openings on the plica longitudinalis, of which two belonged 
to the pancreas and one to the bile-duct (Fr. Tiedemann f). 

(c) Four openings in papilliform prominences of the mucous mem- 
brane of the duodenum. Of these, the uppermost corresponds to the 
accessory pancreatic duct, the second, which is situated about 1.5 cm. 
lower and flanked by an obstructing valve, corresponds to the ductus 
choledochus. About 0.5 cm. below the latter opening was a third em- 
inence with the opening of the ductus Wirsungianus; finally, about 1 
cm. deeper is the opening of a duct also at the top of a fold of mucous 
membrane originating in the head of the pancreas (original observation). 

(d) A solitary duct; this passes through the whole length of the gland 
and opens on the papilla minor. The end of the duct accordingly corre- 
sponds to the ductus Santorini. The ductus choledochus alone opens 
into the diverticulum Vateri (original observation). 

(e) The typical two ducts are present; the ductus Santorini runs to 
the papilla minor, which is normally situated, while the ductus Wirsungi- 
anus, on the other hand, opens into the terminal portion of the ductus 
choledochus. The papilla major is lacking. In place of it is found a 
groove limited by wide folds of mucous membrane. The upper ends 
ofthe two folds are united, and at this point is found a larger opening, 
the mouth of the ductus choledochus. The other portion of the groove 
is crossed by transverse bands; it is clear, therefore, that in this case 
there is a cleft of the diverticulum Vateri (original observation). 

Topography.—In contradistinction to the liver and spleen, the pan- | 
creas does not lie in the greater peritoneal sac, but in the bursa omentalis, 
which represents an accessory space of the peritoneal cavity. In this 
bursa we distinguish an anterior and a posterior wall; the former is 
composed of the posterior wall of the stomach, the gastro-splenic liga- 
ment, and the anterior layer of the great omentum; the posterior wall is 
formed by the posterior layer of the great omentum. .A passage leads 
_from the right into this bursa, and is bounded anteriorly by the lesser 
* Jour. Boston Soc. Med. Sci., 1901, v, 497. + Loc. cit. 


{ “Ueber die Verschiedenheiten der ’ Ausfithrungsginge der Bauchspeichel- 
driise,”’ ete., Meckel’s Archiv, Bd. tv. 


26 DISEASES OF THE PANCREAS. 


omentum, posteriorly by the parietal peritoneum of the abdominal wall, 
and above and below by the fusion of the liver and duodenum with the 
parietal peritoneum. The entrance of the passage into the , bursa. is 
marked by a fold (plica gastro-pancreatica) running from the celiac end 
to the lesser curvature of the stomach and concealing the vasa gastrica 
sinistra, while toward the right the passage opens into the peritoneal sac 
through the foramen of Winslow. The lobus Spigelii is situated in the 
passage. | 

To expose the hidden position of the pancreas, even after the abdom- 
inal cavity is opened, the anterior layer of the greater omentum must be 
separated from the greater curvature of the stomach. The omental 
bursa can also be opened by cutting through the lesser omentum, but this 
method is advisable only in the case of small tumors of the head of the 
pancreas. 

The peculiar position of the pancreas is readily understood when the 
development of the mesogastrium is considered. The anlage of the 
gland is carried into the mesogastrium, which, stretched between the 
vertebral column and the greater curvature of the stomach, lies free, 
like the mesentery of the small intestine. This condition of the meso- 
gastrium persists in most mammals, and explains the great motility 
of the gland in these animals. In man, a mesogastrium free on both 
sides is found only as a temporary stage of development. Later the 
pancreas becomes fixed because the portion of the mesogastrium corre- 
sponding to this organ is fused with the parietal peritoneum of the poste- 
rior abdominal wall. 

When the fusion is complete, three lavers are to be recognized in the 
posterior fold of the great omentum; the upper is united to the pan- 
creas, the middle to the upper surface of the transverse mesocolon, and 
the lower portion hangs free over the coils of the intestine. It seems 
noteworthy that the caudal surface of the pancreas reaches the line of 
attachment of the transverse mesocolon, whence it results that the 
gland is visible when the transverse mesocolon is raised, especially 
when there is a lack of fat. 

The anterior layer of the great omentum is more simple; it extends 
from the greater curvature of the stomach to the free lower edge of the 
omentum, where it becomes the posterior layer of this structure. 

From the description given it may be assumed that the pancreas 
is neither retroperitoneal nor free in the bursa, but, as a formation of 
the mesogastrium, projects into the cavity named and is drawn over ‘to 
its ventral surface by the free dorsal plate of the mesogastrium. 

Of the topical relations of the gland to neighboring structures, that 
to the stomach is especially important. In a circumscribed spot just 
below the cardia a typical adhesion is found between the posterior wall 
of the stomach and the posterior abdominal wall. That large portion 
of the posterior wall of the stomach which lies adjacent to the impressio 
gastrica pancreatis, on the other hand, usually remains free. Not rarely, 
however, the above-mentioned fusion of the stomach extends further 
downward. The stomach and the pancreas may be united by bands, 
or the union may be formed by broad adhesions. 

Similar alterations occur also in the region of the pylorus. The 
upper horizontal part of the duodenum is fused with the head of the 
pancreas and the gastro-duodenal artery runs in the connective tissue 
forming the line of union. The stomach and the duodenum, therefore, 


ANATOMIC INTRODUCTION. 27 


cover the greater part of the pancreas, but one portion of it lies in the 
projection of the lesser omentum, especially in that of the upper hori- 
zontal part of the duodenum. 

The upper portion of the omental bursa lying behind the stomach 
is divided by adhesions into small recesses, and sometimes is wholly 
obliterated. 

The attachments described, leaving out of consideration the patho- 
logic cases, which may simulate them, belong to the category of physio- 
logic processes of fusion, which lower down establish connections between 
the two layers of the great omentum. 

That the fixation of the posterior wall of the stomach interferes with 
the mobility of the stomach can easily 
be understood. Under ordinary con- 
ditions the stomach, excepting at its 
attached portion, is freely movable. 
The ligaments and mesogastrium op- 
pose no obstacle to its distention, free 
motion being allowed by the consider- 
able length and purse-like structure of 
the great omentum, which has the sole 
purpose of securing extensive displace- 
ment and distention of the stomach. 

Extensive adhesions diminish, how- 
ever, the distensibility at least of the 
posterior wall of the stomach. They 
are of importance especially in con- \K 
nection with tumors of the pancreas 
and with adjoining ulcers of the stom- 
ach, since the latter give rise to adhe- 
sions resembling those produced by 
other pathologic processes. 

The length of the pancreas, as well 
as its sharply limited surfaces, will ex- 
plain the fact that small tumors of that 
organ show different topical relations 
according to the place or the surface 
from which they arise. A tumor of the 
head of the pancreas will show a differ- Fig, 3.—Sagittal section of the region 
ent position and different topical rela- Gf the duodenum (schematic) P Pancreas; 
tions to the neighboring organs from 4% liver; D.s, pars horizontalis duodent ; 
those exhibited by a tumor of the tail hepatoduodenalea 
of the gland. Of the neighboring organs, 
the stomach, the transverse colon, and the liver are of first importance. 
Tumors of the anterior surface of the gland will project into the bursa 
and approach the stomach, the ligamentum gastro-colicum, or both, but 
will not affect the transverse colon (see Figs. 4 and 5). If, moreover, 
the tumor is not.so large as to hinder the movement of the stomach 
downward, then the relationto the gastro-colic ligament will be depen- 
dent on the fulness of the stomach; for the empty and therefore con- 
tracted stomach approaches the diaphragm, causing a marked widening of 
the ligament, while the full stomach extends down to the transverse colon, 
producing a marked narrowing of this band. When the tumor develops 
at a place where the anterior surface of the gland is covered by the lesser 





power rn ttn rt tenn en 


we 


\ seh 
‘ 
* a el 








28 DISEASES OF THE PANCREAS. 


omentum, the growth, by pushing the omentum before it, may adhere 
to the abdominal wall between the lesser curvature of the stomach and 
the liver. If the tumor grows from that portion of the head of the pan- 
creas to the anterior side of which the upper horizontal portion of the 






































Fig. 4.—Sagittal section of the region of the Fic. 5.*—Sagittal section of the region of 
pancreas immediately to the right of the flexura the pancreas to the left of the flexura duodeno- 
duodenojejunalis (schematic): P, Pancreas; G, ar- _jejunalis (schematic): P, Pancreas; G, artery 
tery on its upper edge; M, stomach; D.i, pars hori- at the upper edge of the gland; M, stomach; 
zontalis inferior duodeni; C, colon transversum ; v, anterior, f, posterior layer of the great 
M.t, the two layers of the transverse mesocolon ; omentum; N, omental bursa; O.m, lesser omen- 
M.e, mesentery of the small intestine; v, anterior, tum; M.t, the two plates of the transverse 


h, posterior layer of the great omentum; N, omental mesocolon. 
bursa; O.m, lesser omentum, 


duodenum is attached, it may easily cause compression of this portion 
of the intestine, especially as in this region the lower surface and right 
end of the gland are flanked also by the duodenum ‘(see Fig.. 3 ). 


* The heavy line (Figs. 3-5) represents the layers of the great omentum; the 
dotted line represents the place where either the great omentum is united with the 
transverse mesocolon, or (as in h’) the pancreas is united with the parietal perito- 
neum. 
_{ This diagram was prepared from a sagittal section through the abdominal 
cavity of a human embryo. In the adult the part designated by a cross (+) is 


PHYSICAL CHARACTERISTICS OF THE PANCREATIC JUICE. 29 


Tumors on the left of the duodeno-jejunal flexure, where the lower 
surface of the gland lies directly on the transverse mesocolon, will have 
a tendency to crowd between the above-mentioned mesenteric plate 
and the posterior layer of the great omentum. If the enlargement of 
the growth is uniform on all sides, it will grow upward into the omental 
bursa and downward toward the central region of the abdominal cavity, 
arching the transverse mesocolon. The transverse colon lies in this 
case on a level with the tumor, while the stomach lies above it. If the 
growth of the tumor is more lateral, it will crowd either into the bursa 
or into the central region of the abdomen; in the former case the trans- 
verse colon lies at the lower border of the tumor, and in the latter case 
at the upper border. 

Relation to Blood-vessels and Organs of the Posterior Abdom- 
inal Wall.—It has been shown that the pancreas is very closely related 
to the large blood-vessels. These are the superior mesenteric vessels, the 
portal veins, the splenic and gastro-duodenal vessels, all of which lie in 
grooves of the gland. It may be remarked concerning the splenic vessels 
that they lie free and project considerably above the tail of the pancreas. 

A less intimate relation exists between the gland and the organs of 
the posterior abdominal wall, the crura of the diaphragm, the vena cava 
inferior, the aorta, the left adrenal gland, and the left kidney. There 
is direct contact between the pancreas, the vena cava inferior, the left 
adrenal gland, the left kidney, and the spleen. The lower lobe of the 
pancreas lies directly on the vena cava inferior, the body lies on the left 
adrenal, and the tail on the left kidney and on the mesial surface of the 
spleen. A space lies between the gland, the crura of the diaphragm, 
and the aorta because other structures intervene. Between the right 
crus of the diaphragm and the pancreas lie the vena cava inferior and 
some lymph-nodes; lymph-nodes are likewise found between the body 
of the pancreas, on the one hand, and the aorta and left crus of the dia- 
phragm on the other. The left adrenal also intervenes between the 
gland and the crus of the diaphragm on the corresponding side. 





II. REMARKS ON THE PHYSIOLOGIC CHEMISTRY 
OF THE PANCREATIC JUICE AND ON PAN- 
CREATIC DIGESTION.* 


Among all the glands of the digestive system, the pancreas has the 
most varied activity, since by means of its secretion all three groups of 
food-stuffs are changed into soluble, absorbable substances. 


PHYSICAL AAR ACTER TCE OF THE PAN CREATIC 


‘The knowledge of the physiologico-chemical activity of the pan- 
creatic secretion has been acquired by the study of the secretion secured 
from temporary and permanent fistulae. The appearance of the secre- 


lengthened. In consequence of which the space between the duodenum and trans- 
verse colon is enlarged. 


* From a cilledion of the most mecetath facts, made by Dr. A. Katz. 


30 DISEASES OF THE PANCREAS. 


tion varies according as it is obtained from a temporary or permanent 
ike secretion from a temporary fistula probably best corresponds 
with the condition in the organism. It represents a clear, colorless, 
tough, viscous fluid of strongly alkaline reaction. On cooling to O° NG 
(32° F.), a gelatinous substance separates, soluble in sodium chlorid and 
in weak acids, and consisting of a myosin-like body, which is never 
wholly free from ferment. Pre-formed peptone, leucin, or tyrosin 1s 
never present in the fresh secretion. By the action of alcohol a precipi- 
tate is formed, which is for the greater part soluble in water and con- 
tains a crude ferment, which, at 40° C. (104° F.), changes albuminous 
bodies into the well-known products of digestion. 

2. The secretion obtained from a permanent fistula is, as a rule, 
a thin fluid, which foams on shaking and has a low specific gravity. On 
cooling, no gelatinous substance separates. _ 

The pancreatic juice is a material which readily putrefies. On 
standing in the air, a fecaloid odor quickly arises, and on the addition 
of chlorin water a red coloring-matter is rapidly formed, and later indol 
also is produced. 

Relatively normal pancreatic secretion has been investigated by Herter 
and Zawadzki. The fluid examined by Herter came from an enlarged 
duct of Wirsung, which had been compressed at the place of exit by a 
carcinoma. It was clear yellow in color and strongly alkaline in reaction. 
Albumin, peptone, and sugar were not present. The ash was very rich 
in alkaline phosphates. The three ferment actions of the pancreas could 
be shown. Besides this, Herter investigated the contents of two pan- 
creatic cysts. In these three analyses the following results were found: 


i as. 1A III. 
Total COnas aie oa a howe ake ee 24.1% 24.1% 23.8% 
Organic constitutents......52.6..05: 17.9% 14.9% 18.5% 
BER Oo a ands homer Sate eR cee en ere 6.2% 9.2% 8.7% 


Zawadzki analyzed the secretion of a pancreatic fistula which remained 
in a young woman after extirpation of a cystic pancreatic tumor. The 
analysis of the juice, which was a very effective digestive, resulted as 
follows: 


Diry -COnBGICU ENS 5.5 6 2 divides 2 sssneeb shel hela’ aye 13.59%; of which 
PROGCHIS e265 ooo oe Raha ee ieee Sok eine .20% 
Mineral. constituents: 2.242656 oc4.9 6 6 Pee ea 0.34% 


The rest of the dry constituents were soluble in alcohol. 

3. Ferments.—The ferments are contained in the gland in the form 
of zymogens. They become effective only after long exposure to the air 
or through the influence of weak acids. The isolation of the pure ferments 
is attended with great difficulty, and, in spite of the many attempts 
which have been made, no one has yet wholly succeeded. 

(a) Trypsin.—The power of the pancreatic juice to digest albumin 
was first observed by Bernard, and more closely studied and demon- 
strated by Corvisart. This action is due to a ferment, which is called 
trypsin by Kiihne, who made a most careful study of it, and obtained it 
in the purest possible form. 

The secretion of trypsin in carnivora is not continuous, but is closely 
related to the taking of food. The secretion is most abundant from four 
to seven hours after eating. In the glands of animals which had not 


PHYSICAL CHARACTERISTICS OF THE PANCREATIC JUICE, 31 


eaten for some time, no ferment could be found by Lewaschew, Heiden- 
hain, and others, while the later investigations of Cavallo and Pachon, 
as well as Dastre, showed that the trypsin ferment could be obtained 
from the pancreas of dogs after five to twelve days of starvation. 

When precipitated with alcohol, trypsin forms an amorphous, color- 
less powder which easily dissolves in water, forming a clear straw-yellow 
fluid, which even when alkaline is relatively stable. It dissolves fibrin 
almost instantly at incubator temperature. Trypsin is much more 
energetic in its action than pepsin. The presence of water is quite 
sufficient for the beginning of the hydrolytic action; no definite re- 
action is required as with pepsin, although differences in reactions of the 
digestive fluids are not without influence on the intensity of the action 
of the ferment. This is entirely checked by the presence of free hydro- 
chloric acid. If there is sufficient albumin present so that the hydro- 
chloric acid exists only in the combined form, the deleterious influence 
is not noticeable. / 

Trypsin, moreover, is not destroyed by hydrochloric acid. According 
to Lindberger, if in a digestive mixture in which there is too much hydro- 
chloric acid the quantity is lessened by dialysis, or removed entirely, 
the trypsin becomes again effective. . 

The influence of the organic acids found in the intestinal canal was 
investigated by poe! with the following results: Acetic acid in a 
strength of 0.019%, especially if bile and sodium chlorid were also present 
at the same time, had a favorable influence, in many cases even hastening 
the action of the trypsin. In no instance were the small amounts used 
injurious. Lactic acid also had a favorable influence on the processes 
of digestion. In the presence of 0.02% of lactic acid and 1% to 2% of 
bile and of sodium chlorid, the solution of the fibrin took place more 
quickly than in an alkaline fluid. 

The acid reaction of the intestinal contents of the dog was estimated 
by Lindberger as equal to 0.005 to 0.01 to 0.02% of HCl. The last 
amount is very rarely observed. 

The organic acids formed in the intestine cannot, therefore, be con- 
sidered as having any injurious influence on trypsin digestion. 

The influence of bile on trypsin digestion was very carefully investi- 
gated by Chittenden and Cummings, with the following results: If bile 
be added to a neutral solution of trypsin, the influence of the ferment 
is not essentially altered; if the ferment solution is alkaline, its action is 
somewhat checked. Sodium taurocholate and glycocholate exert but 
slight influence on the proteolytic action. Taurocholic acid, however, 
added to a neutral solution, hinders the process decidedly. In a pan- 
creatic juice which contains 0.1% of combined salicylic acid, the ferment ~ 
action is greatly strengthened by the addition of 10% of bile. In the 
presence of combined hydrochloric acid, this addition has no influence. 

[Rachford * has called attention to the fact that the nearer an animal 
is to the carnivorous type, the more surely are the bile and pancreatic 
juice to be pressed into the intestine through one duct and the more 
closely to the pylorus is this-duct situated. He used freshly secreted 
pancreatic juice and bile for the study of the action of bile on proteolytic 
digestion. Thus he showed that the presence of bile increased the pro- 
teolytic action of the pancreas about one-fourth. 

Fibrin half saturated with hydrochloric acid was digested by pan- 

* Jour. of Physiol., xxv, 2, p. 165. | 


32 DISEASES OF THE PANCREAS. 


creatic juice more slowly than neutral fibrin, while fibrin niné-tenths 
saturated showed marked retardation of digestion. The proteolytic 
action of pancreatic juice was not wholly lost even if free hydrochloric 
acid was present. Similar results were obtained when bile was also 
present with the acid.—Eb.] ( 

The effect of temperature on fresh pancreatic secretion and on solutions 
of Kihne’s trypsin was investigated by Biernacki. Pure pancreatic 
secretion remains effective at 55° C. (133° F.). A trypsin solution 
in 0.2% sodium carbonate loses its efficiency after warming for five 
minutes at 50° C. (122° F.), while a temperature of 45° C. (113° F.) 
causes a marked weakening of the action, and at 40°C. (104° F.) its 
action is most effective. The addition of salts in concentration of 0.05 
to 4% protects the ferment from the influence of higher temperature. 
Each salt has a certain concentration in which its influence is most 
energetic. The addition of a mixture of two salts is especially favorable. 
Such mixtures may be heated to 60° C. (140° F.) without injuring the 
ferment. Amphopeptone which is free from salt and antipeptone in 
concentrations of 0.5 to 5% have a similar protective influence. Starch 
and sugar had no influence. In neutral and acid solutions, the bodies 
named have no effect whatever and the ferment is destroyed at 45° C. 
(113° F.). In a dry condition the ferment may be heated for hours 
to 100° C. (212° F.) without losing its power (Salkowski). 

Changes of the albuminous bodies by trypsin: The hydrolytic decom- 
position of albuminous bodies is carried further through the action of 
trypsin than by any other ferment. A number of amido-acids arise as 
ultimate products of the decomposition: leucin, asparagin, lysatin, lysin, 
and also tyrosin and ammonia. The whole albuminous molecule, how- 
ever, is not divided in this general manner. According to the careful 
investigations of Kiihne and his students, the albuminous molecule is 
made up of two groups of substances in about equal parts, which behave 
differently toward trypsin and are known as the hemi- and the anti- 
group. Antipeptone and hemipeptone are the result of the action of 
trypsin on the ampho-deutero-proteoses and the amphopeptones which 
are formed in the stomach. The antipeptone energetically opposes any 
further action of the digestive ferments. The hemipeptone is broken 
up into the above-mentioned products. According to the recent in- 
vestigations of Siegfried, antipeptone is’ identical with sarcolactic acid 
obtained by him from muscle. | 

The production of crystalline products of the decomposition of the 
albuminous bodies was formerly ascribed to the influence of bacterial 
action. JIiven very recently Duclaux attributes it to bacteria, which he 
asserts are never absent in the experiments with pancreatic juice. The 
majority of authors, among them Kiihne and Chittenden, regard these 
bodies as the direct products of trypsin digestion. 

Leucin and tyrosin may be regarded as the main representatives of 
these substances. Kiihne, and later Chittenden, also found them in 
the digestive fluids in no inconsiderable amounts. Thus the former, 
in one experiment, found 9.1% leucin and 3.8% tyrosin. 

_ Asparagic acid was found by Salkowski and Radziejewski in the 
digestion of blood-fibrin, and is to be regarded as amido-succinic acid. 

Glutamic acid, or amidopyrrhotartaric acid, has been shown by 
Knieriem in the digestion of wheat-gluten. 

Lysin and lysatinin were obtained by Hedin in the digestion of blood- 


PHYSICAL CHARACTERISTICS OF THE PANCREATIC JUICE, 33 


fibrin with trypsin. Drechsel was able to obtain urea directly from 
lysatinin, by boiling with baryta water. His experiments are therefore 
of great interest, because they show that urea could be produced directly 
from albumins by simple hydrolytic decomposition. Drechsel asserts that 
normally about one-ninth of the urea excreted originates in this way. In 
the breaking up of the albumin molecule, hypoxanthin (xanthin?) is pro- 
duced, and also a body, tryptophan, which gives a beautiful violet color 
by the action of chlorin and bromin water. The latter, in its elementary 
composition, shows a close relationship to the animal coloring-matters, 
bilirubin, melanin, etc. Nencki, to whom we owe this knowledge, ex- 

resses the view that tryptophan will eventually be brought into relation 
with the development of certain animal coloring-matters. 

Products resembling ptomains result from putrefaction of the pan- 
creas when mixed with albuminous bodies, but this is to be ascribed 
to bacterial influence and not to the action of the ferment. Werigo, 
however, asserts that in perfectly sterile pancreatic infusions penta- 
methylendiamin also is found, but in his experiment the quantity was 
very small: from 33 lbs. of pancreas he could secure only a few grams. 

One of Chittenden’s experiments shows that the decomposition of 
albumin into crystalline products takes place in the intestinal canal of 
an animal. He fed a dog with 400 gm. of meat and killed it six hours 
later; ? gm. of a mixture of leucin and tyrosin was obtained from the 
intestinal contents. 

The utilization of the albumins is much less when the pancreatic 
juice is lacking in the intestine than when it is present. According to 
Abelmann, the total is much more deleterious than the partial extirpa- 
tion of the gland. In the former case 44%, in the latter 54%, is absorbed. 
When pancreatic emulsion is given with meat, absorption reaches 74% 
to 78%. Renzi also has shown that the amount of nitrogen in the feces 
was greater after extirpation of the pancreas. The utilization of the albu- 
mins is still less if fat is fed at the same time. Abelmann was able to 
recognize macroscopically bits of muscle in the stools. 

Influence of the spleen on the formation of trypsin: The assertion 
was made by Schiff that the spleen during digestion secreted a juice 
which had the function of converting pancreatic zymogen into trypsin. 
This view is supported by later investigations of Herzen, which show 
that in the extract of the spleen at the time of digestion a ferment must 
be present having the property of changing zymogen into an active 
trypsin. This view could not be confirmed by the experiments of Ewald, 
Buffallini, Cavallo, and Pachon. Herzen, however, tries to support it 
in a later work. 

[Bellamy * confirms Herzen’s work. He believes that the ferment 
which is formed in the spleen and changes the zymogen into trypsin 
reaches the pancreas through the blood; that if the spleen is removed 
the pancreas is in a state of permanent atrypsia, though the zymogen will 
continue to be secreted; that the zymogen will then be converted into 
trypsin, as Pawlow has shown, through the agency of the mucous mem- 
brane of the small intestine.—Eb.] 

(6) Steapsin.—The fat-digesting ferment has not hitherto been isolated 
and preserved in a permanent form. The experiments in this direction 
were either performed with extract of pancreas, or the changes in its 
behavior to fats were ascertained after operation upon the gland of an 


* Jour. of Physiol., xxvit, p. 323. 
3 


34 DISEASES OF THE PANCREAS. 


animal. The emulsifying influence of the pancreatic juice does not need 
the assumption of a peculiar ferment; sufficient explanation is to be 
found in the viscosity of the secretion and in the presence of alkalis 
and soaps. The fat emulsion formed by the pancreatic secretion is far 
more permanent and complete than that obtained in any other way. 

The influence of the pancreatic secretion in decomposing fat into 
fatty acids and glycerin was known to Claude Bernard. If neutral 
butter was mixed with particles of the gland at an incubator tempera- 
ture, an acid reaction soon set in. Berthelot showed the action of the 
ferment by the use of monobutyrin, which is synthetically prepared 
and easily decomposed ; Nencki used tribenzoicin, the triglycerid of ben- 
zoic acid, combined in a manner analogous to that of the neutral fats. 
His investigations are the first which, by excluding the influence of the 
cleaving fungi, ascribed the decomposition of the esters to the unformed 
ferments of the pancreatic juice. 

The formation in the intestinal canal of the fatty acids from the 
neutral fats has probably the purpose of facilitating the absorption 
of the fats, since it was shown by Briicke and Gad that fats containing 
fatty acids are more easily absorbed than those having a neutral reaction. 
The favorable influence of bile on the decomposition of fat was shown by - 
Nencke, and later by Rachford, Hédon, and Ville. 

Their investigations permit the assumption that the conditions for 
_ the decomposition of the fats are best in the duodenum, while in the 
small intestine the conditions appear to be most favorable for its emulsi- 
fication. Bile and pancreatic secretion, working together, are necessary 
for the absorption of the fat into the circulation. Claude Bernard found 
in the rabbit, whose ductus choledochus and pancreaticus open sepa- 
rately into the intestine, that the chyle vessels contain milky chyle only 
below the place of opening of the bile-duct into the intestine. Dastre 
was able to establish the same facts experimentally in the dog. The 
most thorough investigations on the fate of the fat in the intestinal canal 
when the pancreatic juice is lacking have been made by Abelmann. 
After the total extirpation of the pancreas, unemulsified fat was not 
utilized, except when the animals were fed upon the minced pancreas 
of a hog. However, a cleavage took place in the intestine, probably 
through the action of bacteria. The results of the investigations will be 
referred to more in detail in a later section (p. 84). 

In a dog which had survived for twenty-five days the extirpation of 
the pancreas and the resulting diabetes, Baldi was able to show large 
amounts of fat in the stools after feeding with fatty meats. In the 
stools there was an oleaginous, fatty mass which was not solid at the - 
temperature of the room in spite of the fact that the fat at the time of 
its introduction had had a much greater consistency. If the small 
amount of fat in the stools of a dog having a biliary fistula is com- 
pared with the amount obtained from the -stools in this case, it must 
be concluded that the pancreas plays a much more important réle than 
the liver in the digestion of fat. 

The fat-cleaving ferment seems to pass over into the blood-serum. 
According to Hanriot’s experiments, this ferment, which he calls lipase, 
must have an important part in the circulation of the fat in the organism. 

(c) Pancreatic Diastase.—The influence of the pancreatic secretion and 
of the infusion of the gland on starch is, in its introductory stages, iden- 
tical with the diastatic influence of malt extract. The difference lies in 


PHYSICAL CHARACTERISTICS OF THE PANCREATIC JUICE. 35 


the fact that if the temperature is maintained for a longer time at 40° C. 
(104° F.), a part of the maltose changes into grape-sugar, which is not 
possible in the case of malt diastase. On the other hand, no ferment 
inverting cane-sugar is present in the pancreas. The transition prod- 
ucts are the same as in salivary digestion. The final product consists 
mostly of maltose with a small amount of dextrose. In salivary diges- 
tion the formation of grape-sugar does not usually take place. Glycogen 
as well as starch is changed by the pancreatic ferment; inulin and cane- 
sugar are not altered. 

According to the investigations of Martin and Williams, the presence 
of bile hastens the diastatic influence of the pancreas; the same is true of 
sodium glycocholate. Glycocholic acid hinders the action because of 
its acidity. The organic acids, if they are present in any considerable 
amounts, have an injurious influence. According to Hofmeister’s results, 
the presence of 0.01 to 0.03% of lactic acid, or of 0.008 to 0.04% of 
acetic acid, increases the diastatic fermentation; 0.04% or 0.05 to 0.06% 
decreases it; and it is suspended by 0.05% lactic acid or 0.08% acetic acid. 
It is a peculiar fact that in the presence of sodium chlorid the acetic 
acid shows its injurious influence much earlier than in the absence of that 
salt. The influence of the diastatic ferment is very quickly destroyed 
by mineral acids. 

After removal of the pancreas, 60 to 80% of amylaceous substances 
are utilized. Recently Hess has performed some experiments in which 
the absorption of starch was reduced to the minimum only after subse- 
quent removal of the salivary glands. Very recently, Rohmann found 
in the gland a second diastatic ferment forming isomaltose. 

In the newborn, the diastatic ferment does not occur, but is pro- 
duced in the first months of extra-uterine life. 

(d) The milk-coagulating ferment of the pancreas: If milk is mixed 
with weak pancreatic secretion, the casein, after a transformation into 
metacasein, becomes coagulated. Cooked pancreas loses this power, so 
that this peculiarity must be referred to a ferment existing in the gland. 
This is not identical with trypsin, as pure trypsin produced by Kiihne’s 
method does not show this peculiarity; the influence of trypsin and of 
the milk-coagulating fluids of the pancreatic juice may be shown by 
external agents to be markedly different. If on mixing milk and pan- 
creatic juice, no coagulation takes place, we can easily produce it by the 
addition of sodium chlorid or magnesium sulphate. Pure casein solu- 
tions also are coagulated by this ferment. 

[Weinland * has shown that the pancreas in dogs produces a ferment, 
lactase, which breaks up milk-sugar into dextrose and galactose, and that 
this ferment is increased after feeding with milk-sugar. In a further 
communication ¢ he shows that milk-sugar acts on the digestive tract 
in such a manner as to excite or increase the production of this ferment 
in the pancreas. The blood is not the medium through which the milk- 
sugar acts.—Eb. | 

4. Fate of the Pancreatic Ferments in the Organism.—The 
presence of trypsin in the urine was asserted by Griitzner and v. Sahli. 
As the influence of putrefactive organisms seems not to have been suffi- 
ciently excluded in their experiments, Leo has undertaken a new series 
of investigations, and has come to the conclusion that trypsin is never 
found in the urine. In the feces, also, it was sought in vain. In order 

* Zeitsch. f. Biol., 1899, Bd. xxxvut, p. 607. + Ibid., 1900, Bd. xu, p. 386. 


36 DISEASES OF THE PANCREAS. 


to ascertain more exactly its function in the intestine, Leo killed a dog 
in the process of digestion and by ligatures divided the intestine into 
five parts and investigated each part separately for the presence of 
trypsin. In the lower portions of the intestine no ferment was demon- 
strable. Tarulli, on the contrary, found in the normal urine a ferment 
having the same influence as trypsin. The amount varied according to 
the time of day. In cases of long inanition, an increase of the ferment 
was parallel with the decrease of the leucocytes of the blood. In order 
to ascertain the conditions of pancreatic secretion, the pancreatic duct of 
a dog was tied, when large amounts of enzymes appeared in the urine. 
In a second dog, after the extirpation of the pancreas, the ferment dis- 
appeared entirely from the urine. This also happened in a patient with 
diffuse malignant degeneration of the gland. 

5. Pancreatic Secretion.—(a) Innervation.—The dependence of 
the pancreatic secretion on nervous influence is shown by the fact that it 
has been possible to cause the production of an efficient secretion by 
reflex excitation. Gottlieb was able to stimulate the gland to secretion 
by the introduction into the stomach or intestine of certain substances, 
as oil of mustard, dilute sulphuric acid, or concentrated solutions of sodium 
carbonate. Likewise it was possible, by a pretense of feeding, to cause 
activity of the gland. Evidently the secretion of the acid gastric juice 
acts as a stimulator of the function of the gland. 

[Pawlow *: “The energetic action of acid upon the pancreatic gland 
is one of the most constant facts in all the physiology of the pancreas. 
Acid is so powerful an excitant of the pancreatic gland that it is the 
agent above all others which is capable of forcing the activity of the 
gland.’’ Red pepper and mustard inserted into the stomach instead of 
hydrochloric acid have not the slightest exciting action on the pancreas. 
Pawlow explains the contrary results of Gottlieb ¢ on the ground that 
the strength of the solutions of pepper and mustard which he employed 
destroyed the mucosa to such an extent that the centripetal nerves 
themselves were excited and not their peripheral extremities. The 
reader is referred to Pawlow’s lectures for the further discussion of this 
and other questions relating to the physiology of the pancreas.—Ep.] 

By direct stimulation of the nerve it has also been possible to establish 
the dependence of the secretion upon the vagus and splanchnic .nerves. 
The frequent failure of the earlier experimenters is explained by the 
fact that the vasoconstrictor fibers of the abdominal cavity are easily 
stimulated with the other nerves, and the anemia of the pancreas result- 
ing from this stimulation makes it impossible to cause the production 
of pancreatic juice. After excluding this source of error, Pawlow and his 
students, Mett and Kudrewetzky, were able to show that the main 
course of the stimulating nervous influence ran in the vagus; this could 
be shown with certainty by stimulation of the peripheral stump of the 
vagus in the abdomen, especially after a higher section of the cord. The 
splanchnic is to be regarded as the inhibitory nerve of the pancreas 
(Morat). The results of experiments in this line, however, are by 
no means so clear as those regarding vagus excitation. After consecu- 
tive stimulation of the sympathetic, the secretion caused by stimulation 
of the vagus is increased in amount and density, and the amount of 
ferment is also increased (Kudrewetzky). Section of the sympathetic 


* “ Le Travail des Glandes Digestives,” Paris, 1901, p. 185. 
t Arch. f. exp. Pathol. u. Pharmakol., Bd. xxxu11. 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 37 


plexus supplying the vessels of the gland leads to an abundant secretion 
(paralytic pancreatic juice—Bernstein). According to Popelski, a pupil 
of Pawlow, the nerves in the gland limiting its secretion run along the 
straight line parallel to the attachment of the pancreas to the duodenum. 

[K. Wertheimer and Lepage * severed the vagi and thoracic sympa- 
thetic, and having curarized the animal kept it alive by artificial respira- 
tion. In such an animal dilute solutions of hydrochloric acid (0.5% 
markedly increased the secretion of pancreatic juice if they were inserted 
not only into the duodenum, but also into the jejunum and ileum for 
one-fourth to one-third of its length. Below the appendix the acid 
was without effect, and the same held true of injections into the blood. 
In other experiments the dorsal and lumbar cords were cut in addition, 
and the duodenum and jejunum divided. The abdominal organs were 
thus completely severed from the central nervous system, but the acid 
acted in quite the same way as before. Wertheimer therefore concludes 
that the centers are in the celiac and mesenteric ganglia. 

Popielski + obtained similar results and by methods similar to those 
of Wertheimer, only he carried the investigation one step further by 
destroying the celiac ganglion in addition to the other structures above 
mentioned. He was therefore forced to the conclusion that the dilute 
hydrochloric acid acts on the gland itself or the nervous apparatus con- 
tained in it.—Eb.] 

(b) Effect of Different Foods on Pancreatic Secretion.—Wassilieff found 
that the amount of ferment was essentially different with various foods. 
Meat increased the amount of tryptic ferment and decreased its amylo- 
lytic power. A bread-and-milk diet had the opposite effect. After the 
formation of a permanent pancreatic fistula, only bread and milk should 
be given to the animals at first. Walter arrived at similar results. He 
asserted so marked an adaptability of the pancreas for the work of 
digestion that the existence of a very sensitive peripheral nerve appa- 
ratus in the mucosa of the digestive canal must be recognized. 

(c) Pancreatic Secretion in Fever.—Stolnikow investigated the secre- 
tion of the gland in the beginning of fever, and found it increased; later 
it was diminished, and finally ceased. The amount of ferment in the 
gland is likewise at first increased; in fever of longer duration, however, 
there is a decided diminution. But the gland is never entirely free 
from the ferment, even when the secretion is entirely stopped. The 
addition of an ichorous fluid hinders the influence of the ferment only 
when it is present in large amounts. 





II]. GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 


Tue physiologic significance of the pancreas is clear up to a certain 
point. It is known what function belongs to this gland in the collabora- 
tion and assimilation of food-stuffs, and what and how much it has to 
do; later another, the so-called internal function, which relates to the 
change of sugar, will be shown. One would think that in the event of 
a disturbance in the function of the pancreas from disease of this organ 


* Jour. de Physiol., 111, 5, pp. 689-708. 
t Pfliiger’s Archiv, Lxxxv1, 5, 6, p. 215. 


38 DISEASES OF THE PANCREAS. 


such distinct symptoms would result that the recognition of this dis- 
turbance both qualitatively and quantitatively would be very easy. 
The facts of the case, however, are quite different. Characteristic patho- 
logic symptoms are rarely found in diseases of the pancreas. The ex- 
planation is as follows: 

1. For each physiologic function of the pancreas which concerns 
digestion, a compensatory organ is present, which is qualified to do the 
work left by the failure of the pancreatic function. The stomach* 
takes care of the digestion of the proteids, the bile and to a certain extent 
the intestinal juice provide for the emulsification of the fats, while amyl- 
olysis is the work of the salivary glands and certain intestinal glands. 
Even the decomposition of fat is not the exclusive function of the 
pancreas. In the lower part of the intestine there are micro-organisms 
which participate in this work and even carry further the decomposi- 
tion of the free fatty acids into lower carbon compounds (Hédon and 
Ville). 

The anatomic structure is of importance. As a rule, in man the 
pancreas has two excretory ducts, and whenever one of these is obstructed 
or the portion of the gland corresponding to this duct is incapable of 
function, the other duct assumes its duties vicariously. The fact that 
the liver has only one duct explains the constancy of the pathologic 
symptoms in case of obstruction of this duct. 

3. A large portion of the gland may be destroyed or become incapable 
of function and the rest will be entirely sufficient for the work required. 
_ A considerable portion of the gland may be destroyed by acute or chronic 
inflammation, by hemorrhage, necrosis, new-formations, or cysts, and the 
remainder of the gland may perform the function sufficiently, especially 
with regard to the internal function. But this is also conceivable for the 
digestive action, if at least one excretory duct is available. These facts 
will be found illustrated in a great number of cases. 

4. Diseases of the pancreas are frequently combined with diseases 
of neighboring organs. They may occur as a part of the symptom- 
complex of diseases of the stomach, of the intestine, of the bile-passages, 
and of the liver. Ulcerations or tumors of the stomach may extend 
to the pancreas and there excite inflammation, ulceration, or tumor 
formation. An extension from the intestine is the most frequent occur- 
rence. Different processes, which are common in the small intestine, 
simple catarrhs, bacterial processes, deep-seated inflammations, and new- 
formations may be transferred from the intestine to the pancreas. They 
may lead to inflammations of the pancreatic duct or of the parenchyma 
of the gland, to obstruction of the pancreatic duct, or to cyst formation. 
From the neighboring lymph-glands, also, different pathologic processes 
may extend to the pancreas. : 

From the bile-passages inflammations or new-formations may extend 
to the pancreatic ducts and cause acute or chronic inflammations or new- 
formations in the parenchyma of the gland. Concretions in the bile- 


*[Volhard (Zeit. f. klin. Med., 1901, x11, p. 414) has again called attention to 
the digestion of fat in the stomach which was first suggested by Marcet (The Med. 
Times and Gazette, New Series, 1858, vol. xvir, p. 210) and confirmed by Cash, Ogata, 
and others, His conclusions are as follows: The gastric juice contains a fat-splitting 
ferment which is produced chiefly in the mucous membrane of the fundus. It can 
be extracted with glycerin and will pass through a Clay filter. Its action is hindered 
» and finally destroyed by pepsin-hydrochloric acid.—Eb.] . 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 39 


passages may lead to closure of the pancreatic duct, with the usual 
consequences. 

On the other hand, it happens in many cases of diseases of the pan- 
creas that the neighboring organs are likewise affected. Many patho- 
logic processes have their seat in the head of the pancreas and may in 
consequence lead to compression of the ductus choledochus, to icterus 
and its consequences. 

Inflammations, especially acute purulent processes, may extend to 
neighboring organs and new formations of the pancreas may be continued 
to the latter. Compression of the intestine with symptoms of obstruc- 
tion may result from ulceration, hemorrhage, abscesses, neoplasms, and 
cysts. Severe pain may be produced by pressure upon the neighboring 
ganglia of the inflamed, hemorrhagic, neoplastic, or cystic gland. 

Very confusing pictures may arise through these manifold combina- 
tions, because the symptoms which depend upon the diseases of the 
neighboring organs may be much sharper and more definite than the 
disturbances arising from the diseased pancreas itself. 

The facts mentioned explain sufficiently why the really character- 
istic symptoms, so far as they are known, are only rarely recognized, 
and why during life in most cases only such symptoms come to light as 
are common to diseases of the pancreas and a large number of diseases 
of the organs adjacent to the pancreas. 

The symptoms, according to their pathologic importance, form three 
groups: ? 

A. Characteristic symptoms. 

B. Symptoms which, according to the views of older or more recent 
authors, are to be referred to disease of the pancreas, although no very 
satisfactory proof has been brought forward. 

C. Symptoms which, although important and significant, show no 
features peculiar to a diseased pancreas. 


AD Hist GROUP. 


The characteristic symptoms which point to disturbances of the 
manifold functions of the pancreas are, naturally, in spite of their rela- 
tively rare occurrence, the important and determining ones; they accord- 
ingly demand a detailed and comprehensive representation in the general 
consideration, because they do not occur in any special diseases of the 
pancreas, but are symptoms of different processes, manifestations of a 
disturbance of function, which may be produced by various causes. 


1, DIABETES AND GLYCOSURIA AS SYMPTOMS OF 
DISEASES OF THE PANCREAS. 


The title indicates precisely the limits of my treatment of this sub- 
ject. It is not purposed to discuss here the whole question of diabetes, 
which is reserved in this handbook for the pen of a more distinguished 
writer. It is only suggested why and how glycosuria or diabetes may be 
a symptom of disease of the pancreas. The facts which relate to the 
occurrence of diabetes in diseases of the pancreas will be noted only, 


40 DISEASES OF THE PANCREAS. 


the prevalent views and hypotheses which are advanced to explain these 
facts will be mentioned, and the many loop-holes in our knowledge 
which must remain to be filled by later investigators will be indicated. 

In the search for an organ which should be responsible for the mysteri- 
ous pathogenesis of diabetes, the pancreas was long since thought of. 
The earliest noteworthy communication in this direction was published 
in 1788 by Cowley, who found diabetes in an alcoholic patient thirty- 
four vears old who was also very fleshy. At the autopsy the pancreas 
was found to be filled with small calculi, some as large as peas, firmly 
embedded in the substance of the gland; they were white and. raspberry 
shaped. In 1821 Chopart mentioned a case of diabetes with calculi in the 
pancreas. Bright reported in 1833 the case of a diabetic, nineteen years 
old, who had also jaundice and fatty stools and died of marasmus. At 
the autopsy he found the head of the pancreas changed into a hard, 
nodular tumor which was firmly united to the duodenum; the ductus 
choledochus was closed at its entrance into the duodenum and the gland 
was atrophied. Elliotson described the case of a diabetic, forty-five years 
old, who had fatty stools.. At the autopsy the pancreatic duct, including 
the large lateral branches, was found filled with concretions. Other 
similar communications were published by Fles, Hartsen, v. Reckling- 
hausen, Munk, and Silver. 

Since then the pathogenesis of diabetes has often been ascribed 
to the pancreas. Frerichs, Seegen, and Friedreich mention the not in- 
frequent concurrence of diabetes and pancreatic disease, without, however, 
expressing any decided views on the question. Friedreich says regarding 
it: “According to my opinion, the combination of pancreatic disease 
with diabetes has to be regarded in different ways. We must distinguish 
between preceding affections of the pancreas, as cancer, chronic indura- 
tive inflammation, stone formation, etc., in the course of which secondary 
mellituria occurs, and primary diabetes, in which a secondary disturbance 
of nutrition of the pancreas (simple atrophy, fatty degeneration) takes 
place.” Among 30 cases of diabetes mellitus in the postmortem records 
of the Vienna General Hospital atrophy of the pancreas, sometimes of high 
degree or combined with fatty change, was found by Seegen 13 times; 
once numerous calculi were found in the Wirsungian duct and once the 
pancreas was changed into a gray indurated band. 

According to Frerichs, atrophy, fatty degeneration, and induration 
of the pancreas are frequently found in diabetes. He laid especial 
weight on two cases in which diabetes was directly associated with an 
acute disease of the pancreas which ended in suppuration. 

A very pronounced stand on this question is taken by French authors. 
Bouchardat was the first, in 1875, to suggest the dependence of diabetes 
on disease of the pancreas, resting his conclusions on his own observa- 
tions and those of older writers. Soon afterward Lancereaux developed 
his theory of diabétes maigre, in which he claimed to have found always 
changes in the pancreas. His pupils, Lapierre and Baumel, brought 
forward new clinical facts to support the theory of pancreatic diabetes. 
In Germany an attitude of reserve was maintained toward the new 
doctrine. 

The pancreatic theory first received a firm support through the funda- 
mental experiments of v. Mering and Minkowski, and since their investi- 
gations this subject has remained not simply in the foreground of dis- 
cussion, but the diseased pancreas has been accepted as a cause of 


GENERAL PA THOLOGY AND SYMPTOMATOLOGY. 41 


diabetes by a large number of investigators, physiologists, clinicians, and 
pathologists; many of these even claiming that it is possible that the 
pancreas alone is responsible for the occurrence of diabetes. 

In order to explain with the greatest possible objectivity the present 
stand on this important question, it seems best to state the results of 
experimental and clinical investigations up to the present time and to 
examine into their value. 


(a) EXPERIMENTAL PANCREATIC DIABETES. 


For the purpose of ascertaining the function of the pancreas and the 
symptoms after elimination of the organ, attempts long ago were made 
to extirpate the pancreas in animals. The first of these experiments 
were made by L. Brunner, who removed a portion of the gland from 
young dogs. The animals lived and showed no changes. Later Bernard 
attempted the extirpation of the pancreas. He was unsuccessful with 
dogs, and declared it impracticable. In birds death occurred from maras- 
mus eight to ten days after extirpation. Berard and Colin found no 
disturbances of digestion after extirpation of the pancreas. After death 
only small bits of intact pancreas were found in the animals. Schiff 
also had negative results. He was able to keep alive only birds, ravens 
and pigeons, for some time after extirpation of the entire organ. In 1881 
Martinotti declared the extirpation of the pancreas in dogs to be possible. 
These animals were said to show no abnormality afterward. After the 
removal of the pancreas, nuclear division was found in the glands of 
Lieberkiihn as an indication that these glands were acting vicariously 
for the extirpated organ. In none of the communications above men- 
tioned was it stated whether sugar was found in the urine in these animals 
after extirpation of the gland. 

Of most decided importance in this connection were the experiments 
described in 1889 by v. Mering and Minkowski, who succeeded in a per- 
fectly unquestionable manner in producing genuine diabetes with all 
the manifestations of this well-studied disease of man. At about the 
same time de Dominicis reached nearly the same result, which, however, 
was published somewhat later. | 

Through the epoch-making discovery of v. Mering and Minkowski, 
a solid foundation for the first time was laid for further investigation 
in the hitherto rather barren discussion concerning pancreatic diabetes; 
further advance was next made by Minkowski alone. A large number 
of investigators of all countries then studied this subject: de Dominicis, 
Lépine, de Renzi and Reale, Hédon, Gley, Thiroloix, Gaglio, Capparelli, 
Harley, Schabad, Sandmeyer, Seelig, Rumbold, ete. 

With few exceptions all these investigators confirmed the views of v. 
Mering and Minkowski, but a number of very interesting and important 
details were also brought to light. Although at present a satisfactory 
solution of the diabetes mystery is still in doubt, yet a path has no doubt 
been opened which may lead to the desired end. 

The attempt to produce diabetes by extirpation of the pancreas has 
not succeeded in all animals. Minkowski was able to produce it in dogs, 
in a cat, and in a pig. Harley also had positive results in cats. In 
rabbits, Minkowski had no positive results, while Hédon produced dia- 
betes in several instances by the injection of olive oil into the ductus 
Wirsungianus of rabbits and by this means caused certain changes of 


42 DISEASES OF THE PANCREAS. 


tissue. The glycosuria, however, occurred first three to five weeks after 
the operation and lasted but a short time. The experiments on rabbits 
of Weintraud, who resected portions of the intestine in order to remove 
the pancreas as thoroughly as possible, and found sugar temporarily on 
the day after the operation in two cases, were not convincing, as glycosuria 
may easily occur after similar severe operations. ' 

In pigeons and ducks, Minkowski found no glycosuria after extirpation 
of the pancreas. After 15 out of 19 operations performed on ducks, 
Weintraud found no sugar in the urine, but in four of the series the 
excretion of the sugar was demonstrated. Kausch, who very recently 
again experimented on ducks, always removed at the same time the 
adjacent piece of the duodenum, as a complete separation of the pancreas 
was not possible in any other way. In nearly all cases (76 out of 83) 
the amount of sugar in the blood was increased. The same result oc- 
curred in 17 geese, but in these animals the amount of sugar in the blood 
increased much more slowly after the operation than in ducks. Occur- 
rence of sugar in the urine was noted in relatively few of the ducks oper- 
ated upon. Kausch concluded from his experiments that in ducks the 
extirpation of the,pancreas caused essentially the same changes as in mam- 
malia. The difference consists only in the fact that ducks use up the 
increased sugar in the blood, which w not the case in dogs. In birds of 
prey Langendorf and Weintraud found a glycosuria until the death of the 
animals, while in ravens the result was inconstant. In frogs and turtles, 
Aldehoff had positive results. In the former the glycosuria appeared 
slowly and developed only four to five days after the operation. In 
turtles it occurred in the first twenty-four to forty-eight hours. In 
every case the animals died after the operation. Minkowski was not 
able to show the presence of sugar in the urine of frogs. Marcus gener- 
ally had positive results in his experiments on frogs. Velich’s experi- 
ments showed that in nine out of fifteen frogs from which the pancreas 
was removed glycosuria developed after the operation. Capparelli 
operated on eels; glycosuria occurred twice in eleven cases. 

By far the most constant results are obtained in the operations on 
dogs, on which the most numerous experiments have been performed. 
The results of these experiments form the foundation for the following 
statements. 

An essential difference exists between the results of a total and a 
partial extirpation of the pancreas. 

According to Minkowski, the total removal of the gland regularly 
results in diabetes. This view is supported by Hédon, Gley, Gaglio, 
Capparelli, Harley, Schabad, Sandmeyer, Seelig, Rumbold, and Dutto. 
Lépine and Thiroloix noted the absence of diabetes only in those cases 
in which the animals had been starved for some time before the opera- 
tion. Other authors, as de Dominicis, de Renzi and Reale, Rémond, 
and Cavazzani deny the constancy of diabetes after the extirpation of 
the pancreas. 

De Dominicis is to be regarded as the main supporter of the theory 
of the inconstancy of the glycosuria. He assumes, however, that the 
removal of the gland or its elimination according to his method is always ~ 
followed by the other symptoms of diabetes, as emaciation, phospha- . 
turia, etc. 

Reale noted the occurrence of glycosuria in only 75% of the cases. 
In experiments undertaken by himself in company with de Renzi, dia- 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 43 


betes resulted in 18 out of the 22 dogs on which they operated. Rémond 
is likewise convinced that glycosuria does not always occur after total 
extirpation of the pancreas. Of three dogs which survived the operation 
for some time, only two were affected with diabetes. Also, in two dogs 
the gland which had become indurated by ligation of the excretory duct 
was removed without causing diabetes. In a third, fatal cachexia was 
observed, without glycosuria. The brothers Cavazzani also were not 
always able to show the occurrence of glycosuria after extirpation of the 
pancreas. In opposition to all these objections, Minkowski strongly 
maintains that the absence of the glycosuria can only be explained by 
the assumption that in the experiments mentioned the gland was not 
totally extirpated. 

After complete removal of the pancreas the excretion of sugar, accord- 
ing to Minkowski, is as follows: The time of the first appearance of sugar 
after the operation varies in different cases. Frequently it occurs after 
the first hour following the operation. Often it does not occur until later, 
and its first appearance has been observed on the third day. 

These differences are in part based on the condition of the gland at 
the time of the operation. In those cases in which diabetes did not 
appear until the third day, the gland at the time of its removal appeared 
very hyperemic and its function was evidently active. On the other 
hand, the kind and amount of nourishment given the animal before the 
operation are of great importance in determining the occurrence of 
glycosuria. 

As a rule, the excretion of sugar increases in intensity, and, even 
when no nourishment is given, it generally reaches its maximum of 8% 
to 10% on the third day. 

That the amount of carbohydrate present in the organism is related 
to the amount of the gradually increasing excretion of sugar is shown 
by the experiment of Minkowski, from which it appears that in the dog 
which had been abundantly fed beforehand on meat and bread the ratio 
between the sugar and the total nitrogen (D : N) increased most rapidly. 

The further course of the sugar elimination is essentially dependent 
on the nourishment. With abundant nourishment, an amount of 10% 
to 12% in the day’s excretion of 1 to 14 liters is not at all rare. Even 
after complete withdrawal of nourishment as long as seven days the 
sugar does not entirely disappear from the urine. With a pure meat 
diet or in starvation, a constant relation generally exists between the 
sugar and the total nitrogen (D:N). This ratio is usually about 2.8 : 1: 
All the grape-sugar introduced with the food may be found in the urine. 

When the affection has lasted for some time and the physical strength 
of the animal begins to diminish, the intensity of the excretion of sugar 
also diminishes, especially with the occurrence of complicating diseases. 

The views are widely different with regard to the cause of this 
diminution of intensity of the diabetes after the long continuance of the 
disease. Lépine, de Renzi and Reale, and Hédon assume that it is due 
to a vicarious assumption of the duties of the pancreas by other organs. 
Minkowski, on the other hand, believes that the cause is to be sought 
in a disturbance of sugar production, “perhaps also in a decomposition 
of the sugar under the influence of pathologic processes; for instance, 
under that of pathogenic bacteria.’’ He bases his view on an experiment 
which shows that even the dextrose introduced into the body leaves it 
without being utilized. If it were really a question of a better function 


44 DISEASES OF THE PANCREAS. 


of the powers regulating the digestion of sugar, then it would be im- 
possible to explain this continual impossibility of utilizing the sugar 
added to the organism. It perhaps may be a question of toxicogenic 
influences. Capparelli was able to show that injections of emulsified 
pancreas into the peritoneum of marasmic animals with diminished 
excretion of sugar caused the apparent weakness to disappear and at 
the same time produced an increase of the glycosuria, thus forming addi- 
tional proof that the lessening of the output of sugar did not indicate 
any improvement in the diabetes. 

Our own experiments correspond in the main with the results com- 
municated by other experimenters. 


EXPERIMENT oF NovEMBER 14, 1893.—The pancreas of a dog was entirely ex- 
tirpated. November 15th: Dog quite well. Bile pigment in the urine but no sugar. 
November 16th: No sugar in the urine. November 17th: The dog takes some milk. 
In the urine was found 4.8% of sugar. November 18th: Amount of sugar, 4.8%. 
November 20th: The dog ate some meat the day before; very much debilitated. 
No sugar. November 21st: Killed by bleeding. Amount of sugar in the blood 
0.16%. After the meat was eaten, the stools were rich in undigested meat; tuft-like 
arrangement of the fat-acid needles; few bacteria. After autopsy, adhesive 
peritonitis. . 


Result: (a) Appearance of the excretion of sugar on the third day 
after the operation; (b) disappearance of the excretion of sugar before 
death, normal amount of sugar in the blood; (c) in the stools, much un- 
digested meat. 


EXPERIMENT OF FreBruary 24, 1894.—Total extirpation of the pancreas under 
morphin narcosis. The operation lasted two and one-half hours. February 25th: 
Traces of sugar in the afternoon urine. February 26th: Amount of sugar, 1%. An 
intense diabetes developed without polyuria or azoturia. The maximum amount of 
sugar in the urine reached 13.6%. On the sixth of April the animal died of exhaus- 
tion, and 6.8% of sugar was observed in the urine two days before death. 


Result: (a) Excretion of sugar on the day after the operation (traces), 
1% on the second day, and 7.5% on the next day. (b) The maximum 
excretion of sugar reached 13.6%. Two days before death 6.8% was 
present in the urine. (c) The amount of indican in the urine was in- 
creased, but the excretion of sulphuric acid showed no marked variation 
from the normal. The animal lived forty-one days after the operation. 


EXPERIMENT OF JUNE 19, 1894.—Total extirpation of the pancreas. June 20th: 
The urine contained traces of sugar. Indican was present in moderate amount. 
June 21st: Urine icteric and contained 0.8% of sugar. June 22d: In the urine 3.1% 
of sugar and the indican increased. June 23d: In the urine 2.4% of sugar, no 
acetone. June 24th: Dog found dead. Hemorrhagic exudate in the abdominal 
cavity. 


Result: The glycosuria occurred on the day after the operation, but 
did not reach a high degree. 


After partial extirpation, v. Mering and Minkowski found no glyco- 
suria when the greater part (one-fourth to one-fifth) of the gland was left 
behind. On the basis of later experiments, Minkowski asserts that after 
partial extirpation of the pancreas the occurrence of glycosuria is deter- 
mined not so much by the size of the piece of the pancreas that is 
left as by the condition of the gland after the operation. In two 
cases diabetes of the severest form followed this operation, once after 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 45 


five days and the second time after three days; in both cases the autopsy 
showed that the portion of the gland remaining was entirely destroyed. 

At times the occurrence of the diabetes can be prevented by the 
presence of very small and morbid bits of gland. For instance, Thiro- 
loix reports an experiment on a dog weighing 33 lbs., in which no dia- 
betes occurred for twenty-seven days. At the autopsy a piece of sclerotic 
pancreas weighing 14 gm. was found. In other cases glycosuria occurred, 
even although pieces of pancreas weighing 3 or 4 gm. had been left 
behind. 

Minkowski was able to show the most varied degrees of diabetes 
after partial extirpation of the pancreas. In 15 of 32 cases transient 
glycosuria was found; in three cases, where one-eighth to one-twelfth of 
the gland was left, a diabetes of the lightest form developed as an ali- 
mentary glycosuria. In one case where the largest part of the gland 
was removed and only a small portion remained, after having been 
transplanted beneath the skin of the abdomen a diabetes of moderate 
severity developed. . . 

These observations therefore appear of the greatest importance, because 
they show that even mild cases of diabetes are referable to pancreatic dis- 
turbances. 

In order to show that the diabetes was not caused by some unavoid- 
able injury to nerves during the operation, Minkowski performed the 
following experiment: In one case he removed all attachments of the 
pancreas to the mesentery, so that it remained in connection only with the 
duodenum; in two other cases, after ligating the ductus Wirsungianus, 
he severed all connections with the duodenum. In none of these cases 
did diabetes occur. The same result was shown by other experiments 
of Minkowski. If the partial extirpation was so managed that the 
portions of the gland which were left behind in the one experiment were 
removed in the other, then the influence of accidental injuries or nerve 
lesions would be shown. As in all these cases no diabetes occurred, it 
proves that the cause of the diabetes is not to be sought in the accidental 
injuries. 

Sandmeyer, after partial extirpation of the pancreas with progressive 
atrophy of the portions of the gland remaining, observed a progressive 
diabetes, which, after some months, ended fatally. In a dog in which 
the vessels of the portion of the gland remaining had been ligated, dia- 
betes of a light form soon appeared, three months later increased in in- 
tensity, and lasted until death. In a second case, in which the blood- 
vessels had remained intact, the first traces of sugar appeared seven 
weeks after the operation; only after twelve months was there an in- . 
crease in the excretion of sugar, and only after thirteen and a half months 
did permanent diabetes develop, which eight months later caused the 
death of the animal experimented upon. At the autopsy the remains 
_ of the piece of gland which had been left behind were found adherent 
to the posterior wall of the stomach, midway between the pylorus and 
cardia. This remnant was 2.5 cm. long, 0.5 to 1.0 cm. wide, and 0.36 
gm. in weight, of firm consistency, and showed no trace of glandular 
tissue. Moreover, in the lowest portion of the duodenum a particle of 
about the size of a pea was found, which felt soft and had a distinctly 
lobular character. On microscopic examination the piece attached to 
the stomach showed no trace of gland structure. The piece found on 


46 DISEASES OF THE PANCREAS. 


the duodenum consisted for the most part of very slightly changed gland 


tissue. 
We may mention the following of our own experiments upon partial 


extirpation of the pancreas: | 


EXPERIMENT OF JANUARY 4, 1894.—A dog of mediumsize, weighing about 8 kilos, 
was operated upon under morphin narcosis. The large excretory duct of the pan- 
creas was tied. Isolation from the intestine of a portion of the middle. Extirpation 
of the two lateral portions. 

January 5th: Urine amber yellow. Specific gravity 1054, alkaline, 145 c.c. 
Total nitrogen 3.13%, 4.54 gm. in 145 c.c. Amount of sugar 3.0%, 4.35 gm. in 145 
e.c. N:D=1:1.04. Indican moderate in amount. 

January 6th: Urine brownish-yellow, clear, acid. Total nitrogen 5.42%. In- 
dican increased. Bile pigments present. Sugar not present. 

January 7th: The dog received in the forenoon 4 liter milk. No sugar in the 
urine. Traces of albumin and bile pigments are present. The total nitrogen reached 
2.2%. 

a the next days sugar was never demonstrable in the urine. With pure meat 
diet the dog excreted no sugar. The amount of the combined sulphuric acid was 
lessened. It reached: January 11th: Total SO;, 0.606; combined SOs, 0.032; ratio, 
1:19.2. January 12th: Total SO;, 0.662; combined SOs, 0.022; ratio, 1 : 22.3. 
January 13th: Total SO;, 0.394; combined SOs, 0.069; ratio, 1 : 20.2. 

On administration of grape-sugar, glycosuria occurred; after 10 gm. had been 
administered, traces of sugar appeared in the urine. _ For five days the animal re- 
ceived 220 gm. of horse meat and 50 gm. of sugar. During this time the amounts 
introduced and the amounts excreted were as follows: 


January 26th: N in the food, 13.32 gm.; in the urine, 9.69 gm.; sugar, 1.90 gm. 
zs (73 6c 73 6c iz bc 10 68 ia ‘c“ 3.04 


January 27th: 11.22 : ee 
dangary 2eche > 8. oS TET Et SE LO eae oa 21002 
January corn oo OO Ee ee ee Oo L300 
Janilary oot 8 Pe BS A te ee ie Se Eo ig 2.40 “ 


The total nitrogen in the stools during the time of the experiments reached 1.96 
gm. Imnall, the amount of nitrogen introduced was 67.17.gm.; sugar, 250 gm. The 
total amount of nitrogen excreted was 52.55 gm.; sugar, 11.24 gm. 

The estimation of fat in the stools yielded in 10 gm. of air-dried stool: 


Bithereal extract sc icccae bya Se aha oie aie 1.407 gm. 

Neiiral Tats on leu tn Lee ee ae oe ee 0.544 gm. 51.63% 
BreG AG ycA CIOS: 4 gc ta 3 eh os a a is ee 0.494 gm. 46.04% 
HORS Uke Mee aad st ee Nee ES cea oe 0.025 gm. - 2.33% 


After introduction of cane-sugar glycosuria occurred. The cane-sugar was in 
part excreted as such. 

On the 15th of May another operation was undertaken on the same dog, and the 
remaining piece of the pancreas, as far as possible, was removed. In this operation 
only a piece as large as a walnut remained behind. On May 16th the urine contained 
2.2% of sugar. On the next day no sugar was present. The same was true later. 
The dog was sick, feverish, and vomited several times. 

After the dog recovered he received on the 25th of May 50 gm. of grape-sugar. 
The urine secreted later was levorotatory. Subsequent additions of grape-sugar, 5 to 
10 gm., gave a negative result as concerned the production of glycosuria. 

June 27th: Subsequent laparotomy, from which the dog died. 


From this experiment the following conclusions may be drawn: 

1. Every operation on the pancreas was followed by transient glyco- 
suria. 

2. With exclusive meat diet, after 10 gm. of grape-sugar, a slight 
glycosuria occurred, and after 50 gm. it was more intense. Cane-sugar 
also caused alimentary glycosuria. 

3. i food was well assimilated and the glycogen content was in- 
creased. 


4. In the stools the free fatty acids and soaps appeared less than in 
the normal. 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 47 


EXPERIMENT OF OCTOBER 3, 1894.—In this operation, all of the pancreas was 
removed except the descending portion. The spleen appeared remarkably large. 
Tn the intestine occasional transparent areas. 

October 4th: Urine amber yellow; specific gravity 1024. Sugar not present. 
Phenylhydrazin test negative. Reduction test positive. Albumin not present. 
Acetone not present. Indican in small amounts. 

October 5th: Urine brownish-yellow; specific gravity 1037. No albumin, no 
sugar. Urobilin, small amount. No bile pigments. 

October 6th: Some vomiting after taking milk. Distinct urobilin reaction in 
the urine. Indican somewhat increased. 

October 7th: The dog was very ill. Urine as on the preceding day. Indican in 
large amounts. 

The stools were pultaceous and contained very numerous desquamated epi- 
thelial cells, mostly degenerated, but partly recognizable by their structure; they 
also contained a few bacteria, but no fat drops. 

October 8th: Dog found dead. On section, a peritonitis was found. 

EXPERIMENT OF JULY 10, 1894.—In a dog the lateral portions of the gland, with 
the exception of the duodenal piece, were extirpated. 

The first day after the operation the urine was contaminated by vomited matter. 
Sugar could not be shown init. The stools evacuated after the feeding of milk con- 
tained on microscopic examination numerous fat droplets. 

July 16th: The dog was found dead. Cause of death, peritonitis suppurativa. 


Results: In the experiments on partial extirpation of the pancreas 
we never succeeded in causing severe diabetes, but only transient glyco- 
suria. In some cases sugar was never found in the urine. 

If from the results hitherto communicated the conclusions are justi- 
fiable that the diabetes is not caused by nerve lesions or nerve injuries 
inflicted during the extirpation of the pancreas, the experiment per- 
formed by Minkowski of transplanting portions of the gland under the 
skin of the abdomen proves this conclusion even more conclusively and 
incontrovertibly. 

He was able in dogs to separate the extreme end of the descending 
portion of the gland and to implant it under the skin of the abdomen, 
without .injuring the arteries leading to that part. Under favorable 
conditions the implanted piece healed under the skin of the abdomen. 
Then the intra-abdominal portion of the gland was removed and no 
glycosuria occurred, not even the alimentary variety. The subsequent 
removal of the piece embedded under the skin produced the symptoms 
of a severe diabetes. The piece of pancreas embedded under the skin 
continued to secrete. Minkowski was able in five cases to form fistule, 
through which flowed a secretion which digested starch, and to a less 
degree fibrin. If the transplanted piece of gland is insufficiently nour- 
ished, then a slight degree of diabetes may develop. 

It is not necessary that the secretion should be entirely intact. In 
one case Minkowski ligated a vein which passed upward from the trans- 
planted piece, and yet no diabetes was observed. This experiment 
showed that a direct relation existed between the secretory function of 
the pancreas and that function which has to do with the production of 
sugar. Almost simultaneously with Minkowski, but independently of 
him, Hédon experimented, with like results. After extirpation of the 
intra-abdominal portion of the gland he observed emaciation of the 
animal experimented upon and increased secretion of nitrogen. At 
times Hédon also saw transient glycosuria after extirpation of the intra- 
abdominal portion of the gland. The removal of the implanted part of the 
gland was always followed by severe diabetes. The excretion of sugar 
was even greater than that following total extirpation of the pancreas, 


48 DISEASES OF THE PANCREAS. 


' perhaps because the operation was less severe and the nutrition of the 
animals was unaffected, since they continued to feed as usual. Accord- 
ing to Hédon, the extirpation of the transplanted portions of the gland 
must be undertaken while the strength of the animal is good. If the 
reverse is the case, the result is not direct. This operation was followed 
only by a slight elimination of sugar in a dog whose common duct was 
tied at the same time, since the animal was in a wretched condition. 

Thiroloix later obtained the same result. He concluded from his 
experiments that the pancreas possessed an internal and an external 
secretion, the former controlling the sugar transformation, and that both 
were wholly independent of each other. This view satisfactorily ex- 
plains the instance where severe diabetes results despite the unaffected 
secretion from the implanted portions of the pancreas. Evidently the 
internal secretion must have suffered. Thiroloix found in the implanted 
portions cystic degeneration as well as intact pancreatic tissue. 

Another view regarding the subject of implantation is held by de 
Dominicis. He implanted from one-third to one-fourth of the gland 
beneath the skin of three dogs and found that the extirpation of the 
intra-abdominal portion of the pancreas was immediately followed by 
glycosuria to the extent of 100, 90, 80% respectively. In two of the 
dogs, after the abdominal portion of the gland was extirpated, there was 
neither glycosuria nor any other evidence of the absence of pancreatic 
juice from the intestine. At the autopsy it appeared that the implanted 
portion of the gland was not wholly freed from the duodenum, but was 
attached at one point. In another case, after the removal of the intra- 
abdominal portion of the gland, all the disturbances arose which are 
due to the absence of pancreatic juice from the intestine. Even after 
the removal of the transplanted piece there was no glycosuria. 

These results have not been confirmed by other observers, but 
de Dominicis explains their experiments in the light of his theory by 
assuming, on the one hand, that the absence of pancreatic juice from the 
intestine is of essential importance in the production of glycosuria, while, 
on the other hand, after the extirpation of the intra-abdominal and 
transplanted portion of the pancreas the manifestations of diabetes with 
and without glycosuria develop. 

The experiments with transplantation show with great certainty , 
that the local extirpation of the pancreas is the cause of the diabetes 
and that the latter is the manifestation of the loss of a definite function 
of the pancreas. 

Whether this attribute belongs to the pancreas alone or exists in other _ 
organs is not at present determined. Minkowski considers it ‘“‘more 
probable” that it is a special function of the pancreas. De Renzi and 
Reale characterized the salivary glands as those organs the removal 
of which may result in diabetes. Minkowski showed that in this event 
the glycosuria never reached a high degree and never lasted long. This 
conclusion was reached also by Hédon, who tied the ductus Wirsungianus 
in a dog, extirpated the vertical branch of the pancreas, and in one 
operation removed all the eight salivary glands. As a result of this 
operation only a slight glycosuria, lasting one day, occurred. 

_ In like manner the glycosuria developing after resection of the intes- 
tine 1s not a true diabetes. Weintraud, under the direction of Minkowski, 
resected different portions of the intestine, the pieces being of different 
size. At times a glycosuria occurred, which, however, quickly passed 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 49 


away without further consequences. Lépine claims for the duodenal 
glands the characteristic of being able to take in part the place of the 
pancreas in its sugar-destroying (glycolytic) function. Talkenburg saw 
glycosuria develop after removal of the thyroid gland. All these experi- 
ments, as well as those especially of Hédon, Thiroloix, and Seelig, prove 
by no means conclusively that there are indeed other organs which may — 
act vicariously for the pancreas in its influence on sugar metabolism. 

Through the experiments which led to the production of pancreatic 
diabetes in animals a number of important and interesting results have 
been brought to light, which cannot here be referred to more in detail. 

The relation to pancreatic diabetes of phloridzin diabetes, piqtre, 
and many other forms of diabetes variously brought about have been 
studied, and it has been shown that there are indeed various ways which 
lead to the excretion of sugar in the urine. 

The loss of the digestive function of the pancreas which naturally 
results from the extirpation of this organ leads to severe disturbances of 
nutrition, to emaciation, and to rapid diminution of strength, and causes 
changes which become evident in the stools and in the urine. These 
important factors will again be referred to. 

A thorough investigation of sugar metabolism requires studies into 
the fate of the glycogen stored in the liver, in the muscles, and in the 
leucocytes after the extirpation of the pancreas. On the one hand, 
hyperglycemia, and, on the other, disappearance of the glycogen from the 
liver, the muscles, and the leucocytes, are facts which are stated by all 
authors to occur after removal of the pancreas. 

Nearly all authors who have made this theme a subject of experi- 
mental research have concerned themselves with the theory of the causa- 
tion of diabetes after extirpation of the pancreas. This is the more 
intelligible since if a satisfactory explanation of experimental pancreatic 
diabetes is found, an essential factor is certainly discovered which may 
lead to the clearing up of the mystery of diabetes. Unfortunately, in 
spite of much labor, experiment, and speculation, and although much 
enthusiasm has entered into the work, no hypothesis has yet been found 
which can be regarded as wholly satisfactory. 

Before the convincing experiments of Minkowski and v. Mering, there 
were certain clinical observations which indicated a relation between 
the pancreas and diabetes, and explanations were sought for such a 
relation. 

Bouchardat assumed that in the absence of pancreatic secretion the 
stomach undertook the task of digesting the starches. In consequence, 
a perverted function of the stomach resulted. The blood was over- 
filled with sugar and the liver was no longer in condition to store this 
excess. 

Popper believed that the liver formed the bile acids from the fatty 
acids resulting from the splitting-up of fat and from glycogen. If the 
cleavage of the fat was not accomplished by the pancreas, then the 

glycogen alone was changed into sugar, and when in excess was excreted 
' with the urine. A 

Zimmer ascribed to the pancreas the duty of changing glucose into 
lactic acid. If the function of the pancreas be lessened, then the sugar 
must pass over into the blood unchanged. 

All these hypotheses are pure speculations, and have been devised 

4 . 


50 DISEASES OF THE PANCREAS. 


to explain the connection of the pancreas with diabetes, a connection 
which had been only assumed, but not demonstrated. 

After the experimental proof of this connection presented by v. 
Mering and Minkowski, these experimenters, on the basis of their observa- 
tions, could suggest only the choice of two hypotheses: (1) Hither some- 
thing abnormal is accumulated in the organism after the extirpation of 
the pancreas,—that is, the pancreas has normally the power of destroying 
an injurious substance as it is formed,—or (2) a normal function is lacking 
—that is, the pancreas normally has the power of regulating the con- 
sumption of sugar. 

The former hypothesis was withdrawn by Minkowski on the basis 
of later experiments and only the second was considered plausible. Von 
Mering and Minkowski attempted to bring forward experimental proof 
of the existence of an injurious substance. They transfused a healthy 
animal with the blood of one at the acme of sugar excretion. <A positive 
result of this experiment would have had great significance. From the 
negative results which actually were obtained nothing could be decided, 
for the healthy dog has all the conditions in his normal pancreas necessary 
for destroying this injurious substance when it is present. Of just as 
little value was the experiment of Hédon, who injected the blood of a 
diabetic dog into an animal which, after extirpation of the pancreas and 
when fed on meat, excreted only traces of sugar in the urine. After the 
transfusion there was no increase of sugar excretion in the urine. 

Although the assumption of Minkowski that the diabetes after extir- 
pation of the pancreas is to be ascribed to the retention of some substance 
—that is, to a kind of auto-intoxication—cannet wholly be disregarded, 
still his deductions regarding glycogen metabolism, sugar consumption, 
and blood diastasis in diabetic dogs offer weighty reasons against it. 
Most authors incline to the view of Minkowski that the pancreas produces 
something which influences the consumption of sugar in the organism, 
and that the diabetes occurring after the extirpation of the pancreas is 
due to the cessation of this production. This function is characterized 
as the internal secretion or, as Hansemann asserts, the positive function. 
According to the experiments of Thiroloix and Minkowski, this internal 
secretion is independent of the secretion of the pancreatic juice. Trans- 
planted pieces of the pancreas may continue to secrete pancreatic juice 
and yet glycosuria occur, and, on the other hand, the secretion of the 
juice may cease in such transferred portions of the gland without the 
development of diabetes. 

Although authors so generally agree that the digestion of sugar is 
regulated by such an internal secretion, yet there is quite a difference in 
the views regarding the nature and kind of influence of the internal 
secretion. The hypotheses regarding this point advanced by French 
writers deserve a somewhat more extended mention. 

1. Lépine’s hypothesis: On the basis of numerous experiments and 
studies, Lépine reached the conclusion that glycolytic ferment was pro- 
duced in the pancreas, passed from the pancreas into the lymph, and 
thence into the blood, where it was contained in the white blood-corpus- 
cles. The consumption of the sugar in the tissues takes place through 
the influence of this ferment. If, through failure of the corresponding. 
function of the pancreas, this ferment is wanting, hyperglycemia and 
diabetes result. ‘ 

Claude Bernard knew that the quantity of sugar in the blood dimin- 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. ol 


ished after venesection. Lépine gave the term glycolysis to this process 
and attributed it to the presence of a ferment chiefly produced in the 
pancreas. The extirpation of the gland, therefore, would result in the 
disappearance of the ferment or its considerable diminution, in case 
small quantities of it are produced in other organs and there give rise to 
the accumulation of sugar in the blood, hyperglycemia, and glycosuria. 

The glycolytic power of the blood was ascertained by Lépine and 
Barral in the following way: They determined the amount of sugar in 
two portions of blood, one of which was examined immediately after it 
was drawn, the other after it had remained for one hour in the incubator 
at 37° C. (98.6° F.); in the second portion the experiment showed a 
diminution in the amount of sugar. In order to meet the objection that 
perhaps the glycogen which was present was transformed into sugar, a 
third portion was then heated to 54° C. (129.2° F.) in order to destroy 
the glycolytic ferment and then allowed to stand for one hour in the 
incubator. The amount of sugar was not changed. Thereby the absence 
of glycogen could be excluded. 

On the basis of these experiments, no doubt could be admitted as to 
the fact that glycolysis occurs in the blood. It was only necessary to 
prove that this destruction of sugar was brought about through the 
action of a ferment and was not a postmortem phenomenon. Lépine 
next advanced an indirect proof of the ferment character of the substance 
which caused the glycolysis. He had shown, on the one hand, that heating 
the blood to 54° C. (129.2° F.) was sufficient to hinder the glycolysis, 
and that, analogous to the conduct of other ferments, lower temperatures 
delayed its occurrence, while it was most intense at 50° to 52° C. (122° 
to 125.6° I°.). The production of fluids with powerful action by centri- 
fuging the blood with sodium chlorid solution presented a direct proof 
of the existence of a soluble body in the blood; Lépine undertook to prove 
that it was of the nature of a ferment by changing the diastase of the 
saliva and pancreatic juice into a glycolytic ferment. By treating these 
fluids with 1% sulphuric acid, he claims to have transformed the amylo- 
lytic into a glycolytic enzyme. 

That this ferment is not of postmortem origin is shown by the fact 
that the injection of a few drops of sterilized oil into the ductus Wirsungi- 
anus and section and stimulation of the nerves of the pancreas are suffi- 
cient to cause an increase of the glycolytic action of the blood. These 
experiments at the same time show the close relationship between the 
glycolytic ferment and the pancreas; they were confirmed by a further 
experiment of Lépine, in which he showed that electric stimulation of 
the peripheral stump of the vagus nerve increased the glycolytic power 
of the blood, while this influence was absent in animals in which the pan- 
creas had been extirpated. On the basis of all these experiments and 
observations it could be assumed that the glycolytic ferment was formed 
in the pancreas, taken up by the white blood-corpuscles, and carried into 
the circulation; but as the sugar is found only in the blood plasma, it 
will in reality appear first when the white blood-corpuscles are destroyed. 
The glycolytic action of the blood observed outside of the organism is 
accordingly dependent on two factors: the richness of the blood in ferment 
and the rapidity with which the leucocytes are destroyed. According 
to Lépine, this is influenced not only by the pancreas, but also by other 
organs, especially the duodenal glands, which appear to take part in the 
production of the ferment. 


52 DISEASES OF THE PANCREAS. 


The experiments on 150 dogs carried on by Lépine likewise showed 
that a diminution of the glycolysis in the blood went hand in hand with 
the extirpation of the pancreas. In man also he found a greater or less 
diminution, but did not venture to generalize on these facts. Very 
recently Lépine claims to have caused a diminution of the glvcosuria in 
some diabetics by the use of the glycolytic ferments produced from 
diastase. : 

Signorini also found that the pancreas had a marked glycolytic 
power. He believed that glycolytic characteristics could also be ascribed 
to the urine; this agrees very well with the assumption of a ferment, so 
much the more as, after heating, the power of destroying sugar is lost. 

Mansel Sympson also found that pancreatic extract had a glycolytic 
function, and that if sugar solutions were treated with it, the amount 
of sugar was much diminished after ten hours’ stay in the incubator. 
On boiling, this extract lost its power. 

Although this theory was apparently so well founded, yet a number 
of weighty objections removed its firm basis. The consideration of the 
process as a vital one, the ferment nature of the glycolytic agent, the 
constancy of its presence, and especially its diminution after extirpation 
of the pancreas as well as in human diabetes, were all questioned. 

Shortly after Lépine’s first publication, Arnaud took the ground 
that it was not a fermentative action, but a peculiarity inherent in the 
blood. Lépine and Barral could easily contradict this view by the proof 
that it was not easy to procure a fluid of glycolytic action by washing 
out the blood-corpuscles in the centrifuge with sodium chlorid solution. | 

In Lépine’s experiment of changing diastase into glycolytic ferment 
in order to establish the ferment character of the glycolytic agent, Nasse 
was not able to confirm Lépine’s results. Although Lépine has lately 
taken the opposite stand, yet it appears from more recent experiments 
that the transformation of the one ferment into the other is scarcely 
probable. | 

The most weighty objection against Lépine’s theory was, however, 
raised by Seegen, who showed that the process of glycolysis could hardly 
be regarded as vital. It can be shown that chloroform, which destroys 
the life of the cell, does not affect the glycolytic action; that the passage 
of air through contaminated blood at a high temperature causes con- 
siderable destruction of sugar; and especially that in the second and third 
hours after the removal of the blood the glycolysis is greater than in the 
first, increasing, therefore, at the time when the vital conditions in the 
_ blood are becoming poorer. 

Physiologic experiments also were made to show that glycolysis was 
not a vital process. Arthus examined the fluid blood drawn from the 
jugular vein of a horse and was unable to show any destruction of sugar, 
in spite of the fact that the blood was apparently alive. On the other 
hand, he added sodium fluorid to the blood taken from the vein, and in 
this way checked glycolysis, which was not stopped if a certain time 
intervened between the removal of the blood and the addition of the 
sodium fluorid. The value of this experiment was denied by Lépine; 
but it has recently been shown by the experiments of Colenbrander that 
glycolysis stands in close relation with the postmortem destruction of 
the white blood-cells, since the injection of leech extract, which preserves — 
the leucocytes, in contrast to other substances which restrict coagulation, 
hinders the destruction of sugar. 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 53 


By these facts, confirmed by other investigators, a specific glycolytic 
power of the blood is rendered very doubtful. It seems as if we are 
concerned in the consumption of sugar in the blood, with a property of 
one or more of the various tissues to act as oxygen-carriers (Spitzer). 

From this preliminary statement we can readily understand: the 
contradictions found by various authors (Sansoni, Kraus, Minkowski) 
in their investigations of the glycolytic ferment of normal and patho- 
logic, especially of diabetic blood. lLépine also, in his investigations on 
diabetics, found no constancy in the diminution of the glycolytic ferment, 
while his experiments on 150 dogs gave a constant diminution in the 
amount of ferment, although it varied in degree. Irom his standpoint, 
he reached the very justifiable conclusion that diabetes was not a noso- 
logic unit, and was not produced exclusively by changes in the pancreas. 

Experiments performed by A. Katz gave results corresponding per- 
fectly with the data mentioned, and showed that the doctrine of the gly- 
colytic ferment rested on a very insufficient foundation. 

(a) In spite of numerous attempts, he was unable by the action of 
1% sulphuric acid on the ordinary diastase of trade, as well as on the 
extremely active taka-diastase, to transform them into the glycolytic 
ferment. 

(b) An increase of the glycolysis could be caused by the addition 
of blood poisons, as sodium taurocholate. So, for instance, in one ex- 
periment, the percentage of the loss of sugar in the unchanged blood 
was 17.41%, and after the addition of the sodium taurocholate it reached 
30.84%; in a second experiment before the addition it reached 20.34%, 


and afterward 51.97%. 


(c) Glycolysis could also be increased by preventing the coagulation 
of the blood by the addition of leech extract immediately after the 
blood was removed from the vein. 

(d) A diminution of the glycolytic qcnen also takes place in blood 
prevented from coagulation by the injection of peptone. In one experi- 
ment the peptone did not have the desired effect and the blood taken after 
the injection was clotted. The loss of sugar before the injection was 
65%, and afterward 63%. In another experiment, in which the blood 
did not coagulate after the injection of peptone, the loss of sugar before 
the injection was 71.85%, and afterward 52.10%. From these experi- 
ments the conclusion is permissible that there is a parallelism between 
glycolysis and the postmortem process of coagulation of the blood, and 
that, accordingly, the glycolysis runs parallel with postmortem changes. 

(e) In order to diminish the percentage of loss of sugar it is sufficient 
to increase the amount of sugar in the blood by the injection of sugar. 
In one case the amount of sugar in the blood before the injection was 
0.226%, but fell to 0.146% after the blood had remained for two hours in. 
the incubator; after the injection of 30 gm. of grape-sugar the percentage 
was increased to 1.019, but after two hours in the incubator it was lowered 
to 1.017. Glycolysis therefore had not taken place. In another case 
the sugar-content was 0.221%, and after three hours’ stay in the warm 
oven it reached 0.191%; after the injection of the sugar the amount of 
sugar-content was increased to 1.706%, but after three hours ‘it had 


fallen to 1.604%. The percentage of loss was at first 14%, and later 


only 5.4%, although an absolutely larger amount of sugar had been 
decomposed. 
A diminution in the percentage of destruction of sugar can, therefore, 


54 DISEASES OF THE PANCREAS. 


be brought about by simply increasing the absolute amount of sugar, 
without causing any lesion of the pancreas. Even with the assumption 
of a glycolytic ferment, therefore, the diminution of the percentage of 
loss of sugar in a given time by no means warrants the conclusion that an 
injury of the pancreas is involved. ms 

Very recently Lépine transferred the stage of activity of the glyco- 
lvtic ferment from the blood to the tissues. By so doing, as Minkowski 
mentions in a critical review, he has eliminated a great portion of the 
above-mentioned objections, and the “assumption of such a ferment no 
longer appears impossible,” although the conclusive proof of it still is 
lacking. 

2. ee of Chauveau and Kaufmann: In opposition to those 
theories which explain the diabetes after extirpation of the pancreas 
as due to a diminution in the destruction of sugar, Chauveau and Kauf- 
mann assume an increase of the production of sugar in the liver. Re- 
garding the sugar-producing function, the liver and pancreas appear to 
them to be closely related and dependent upon each other. The pan- 
creas, through the mechanism of the nervous system, regulates the 
production of sugar in the liver. An inhibitory center for this function 
is situated in the medulla oblongata and a stimulating center in the 
upper part of the cervical cord. The former is in relationship with the 
sympathetic system through the rami communicantes of the upper 
cervical nerves, the latter through the rami communicantes of the upper 
portion of the dorsal cord. The pancreas exerts a reversed action on these 
two centers. 

If the spinal cord is cut below the fourth pair of cervical nerves and 
above the sixth dorsal nerves, then only the inhibitory center acts, as 
above the point of section fibers run from it to the sympathetic. The 
center for stimulation of glucose formation in the liver is, however, 
thrown out of service, and therefore extirpation of the pancreas can no 
longer lead to diabetes. 3 

If the medulla oblongata between the atlas and occiput is cut across, 
then the influence of the inhibitory center is lost and that of the stimula- 
tion center prevails, so that hyperglycemia and glycosuria occur. They 
are, however, not so severe as after extirpation of the pancreas, as in this 
case only the loss of one inhibition is concerned, while in the extirpation 
of the pancreas, which stimulates the inhibitory center and inhibits the 
stimulation center of the liver, there is a twofold restriction of sugar pro- 
duction, and therefore the hyperglycemia and glycosuria must be con- 
siderably increased. | 

This theory, which considered it necessary to appeal to nervous in- 
fluences in explaining the condition of pancreatic diabetes, was not, 
however, supported. Ina later work Kaufmann showed that, even when 
all nerves leading to the liver were divided, diabetes developed after 
extirpation of the pancreas. The influence of the pancreas on the liver, 
therefore, can be exerted directly without the intervention of the nerves. — 
Under this assumption, the transplantation experiments are explained 
in a perfectly natural way, since the products of internal secretion of 
the pancreas have a direct influence on the liver. 

The close relation found by Chauveau and Kaufmann between the 
pancreas, the liver, and the nervous system would teach, further, that 
disturbances of the internal secretion of the pancreas with all their con- 
sequences may be caused by changes outside of the gland, and so appear 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 55 


to justify those attempts to refer all cases of diabetes to one and the 
same type, which is represented by that form produced by extirpation 
of the pancreas. 

The soundness of the theory of Chauveau and Kaufmann was attacked 
especially by Minkowski, who contested its very foundation. Chauveau 
and Kaufmann hold that the consumption of sugar is not diminished in 
pancreatic diabetes, and support their opinion by an experiment which 
showed that the blood of the femoral vein in comparison to that of the 
femoral artery is poorer in sugar in the same ratio after extirpation of © 
the pancreas as in normal animals. Seegen had already raised well- 
founded objections regarding the exactness of this method. 

Minkowski, on the basis of his experiments, considers it absolutely 
certain that in experimental pancreatic diabetes there is no increase 
in the production of sugar, but that a disturbance takes place in the 
consumption of sugar. He has recently in a critical review called atten- 
tion to the following experiment: A diabetic dog, after géing without 
food for several days, received gradually 100 gm. of grape-sugar, after 
which it excreted in the urine 107.5 gm. of sugar besides 4.55 gm. of 
nitrogen. Before the sugar was given the animal excreted 115 c.c. of 
urine, in which were 7.8% sugar and 2.33% nitrogen. This excess in 
the elimination of sugar can be explained only by the fact that the sugar 
introduced passed off unconsumed. 

The same objections may be raised against— 

3. The hypothesis of the brothers Cavazzani: They declare that the 
occurrence of diabetes after extirpation of the pancreas is due to changes 
in the liver. It could be established experimentally that the amount 
of sugar in the blood of the liver is considerably increased by stimulation 
of the celiac plexus. An analogous irritation may be caused by extirpa- 
tion of the pancreas. In consequence of this there is an overproduction 
of sugar in the liver, an increased metabolism in the same, and a degenera- 
tion of the parenchyma of the organ. The exclusion of the pancreatic 
digestion leads to a diminished consumption of the albuminous bodies 
and to emaciation. The combination of the two results may explain fully 
the pathogenesis of diabetes. The results of transplantation of the 
pancreas also contradict this theory. 

None of the hypotheses mentioned can hold their ground as against 
the justified objections. The most persistent of all, that of Lépine, is 
not sufficiently established. It still remains for future investigators to 
advance the solution which shall perhaps satisfactorily settle the whole 
diabetes question. 

If the results of the experiments upon animals, so far as they 
interest us here, are collected, the following conclusions are reached: 

1. In a number of species of animals the total extirpation of the 
pancreas produces genuine diabetes. 

2. In partial extirpation, glycosuria and diabetes may be entirely 
absent. [requently there is a transient or alimentary glycosuria. In 
a number of cases diabetes of moderate or considerable severity developed. 
This occurred when the portion of the gland remaining gradually atrophies 
and becomes unfitted for its internal function. 

3. It is established that diabetes occurs through the failure of a special 
—the internal—function of the pancreas, and neither through a nerve 
lesion nor through the loss of the external—that is, the digestive— 
function of the pancreatic juice. 


56 DISEASES OF THE PANCREAS. 


’ 4. We are still entirely in the dark concerning the nature of this 
internal function. 


(6) CLINICAL AND PATHOLOGIC-ANATOMIC EXPERIENCE. 


Although for some time, as before mentioned, attempts have been 
made at the sick-bed and by postmortem examinations to discover the 
relation between the pancreas and diabetes, an evident advance of the 
investigations in these directions was made soon after the important 
and luminous discovery of v. Mering and Minkowski. Investigations 
have been made more frequently, and, therefore, more has been dis- 
covered. In the light of animal experimentation, the older results gained 
increased significance and an extensive material has gradually been 
collected, since not only clinicians, but especially pathologic anatomists, 
who for a long time were skeptical, gave important and well-founded, 
contributions. 

Notwithstanding, a final solution of the question is still remote. 
There are yet enough unsettled points and gaps in our knowledge, and 
there is still necessity for hard study, abundant statistics, and funda- 
mental investigation of individual cases, before a full understanding of 
the relation between diabetes and the diseased pancreas can be reached. 

In order to judge as objectively as possible, it is reeommended: 

1. To review, in brief, the existing clinical and anatomic material, 
and especially the clinical cases of diabetes in which changes of the 
pancreas have definitely been established. 

2. To investigate in these cases whether the disease of the pancreas 
is to be regarded as the cause or the effect of the diabetes, or whether 
both are co-ordinate, being accidentally associated. 

The older material collected before the positive experiments on animals 
succeeded has already been considered. ‘There are still some statistical 
communications to be mentioned, and these will be tabulated. Mention 
should be made also of the following evidence: 

Frerichs (1884), in diabetes, found the pancreas normal 28 times and 
atrophied 12 times. The weight varied from 1 to 5 ounces. Once almost 
the whole pancreas had undergone complete fatty degeneration and 
the ductus Wirsungianus was filled with a large concretion 3 cm. thick 
and 4 em. long, in addition to numerous mortar-like fragments. In 
another case in the head of the gland there was'a carcinoma with cyst- 
like dilatation of the duct and closure of the ductus choledochus. Once 
the pancreas was changed into an abscess as large as an apple, and in 
one case peripancreatitis and pancreatitis hemorrhagica purulenta were 
present. 

Windle (1881), among 139 cases, found the pancreas normal in 65, 
38 times there was simple atrophy, 11 times atrophy with fatty degenera- 
tion, 3 times atrophy with concretions in the Wirsungian duct, 5 times 
induration, and 3 times carcinoma; hyperemia, coffee-colored pigmenta- 
tion, and small hemorrhages were present each in one case. Among 
four of his own patients he found two with atrophy and cloudy swelling 
of the cells, one with atrophy and increase of connective tissue, and one 
with marked shrinkage. Since the first communications of v. Mering 
and Minkowski, the increased interest of authors in diabetes in its rela- 
tions to the pancreas has expressed itself in abundant and more detailed 
' statistics as well as by a number of concise pathologic works. 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 57 


Dieckhoff examined 19 cases of diseases of the pancreas. In 7 of 
them diabetes had been present, once in case of hemorrhage in the neigh- 
borhood of the pancreas with destruction of the gland, twice in chronic 
pancreatitis, once in subchronic pancreatitis, twice in simple atrophy, and 
once in chronic indurative pancreatitis with lipomatosis and fat necrosis. 
, Hansemann investigated the protocols of the Berlin Pathologic Insti- 

tute in the last ten years and found the following statistics: 


Diabetes without disease of the pancreas .................. 8 cases, 
Diabetes without any statement concerning the pancreas .... 6 “ 
Diabetes with disease of the pancreas .................... 40 =“ 
Diseases of the pancreas without diabetes ................. 19). 75 


Among the 40 cases of disease of the pancreas in which diabetes 
occurred there were 36 cases of simple atrophy, 3 cases of fibrous indu- 
ration, 1 complicated case. 

Hale White found among 6000 autopsies at Guy’s Hospital between 
1883 and 1894 the pancreas diseased in 99 cases, among which 16 were 
cases of atrophy; in 13 of these diabetes had occurred. 

One of my assistants, Dr. Sigmund Bloch, has, with the kind consent 
of Prof. Weichselbaum, examined the protocols of the General Hospital 
at Vienna for the years 1885 to 1895, and in 18,509 autopsies he found 
the following data: 


Diabetes with disease of the pancreas ................00. 12 cases. 
Diabetes without disease of the pancreas *................ 107, < 
Diabetes without any statement concerning the pancreas ...64 “ 
Disease of the pancreas without diabetes ................. 89 


In cases of diabetes atrophy was found 8 times, fat necrosis twice, 
pancreatitis suppurativa once, necrosis circumscripta once. In 86 cases 
of diabetes, therefore, diseases of the pancreas occurred 12 times. In 
89 cases of diseases of the pancreas there was no diabetes. If we take 
simply the years 1894 and 1895, in which the “normal” pancreas was 
also expressly noted, the following data are given: 


Diabetes with diseases of the pancreas .................26. 8 cases, 
Diahetes with normal pancreas .........2560.. cece sseees 10. == 
Diabetes without any statement concerning the pancreas .... 9  ‘“f 
Pancreatic disease without diabetes ................0.000: oh: OF 


Seegen has collected the results from the autopsy records at the 
General Hospital from 1838 to November, 1892. He found among 122 
cases of diabetes, changes in the pancreas 34 times. If we supplement 
these figures by the results of the estimate made by Dr. Bloch up to the 
end of 1895, it results that among 161 cases of diabetes examined in 
the General Hospital, changes of the pancreas were observed 42 times.t 


* These cases come from the years 1894 and 1895, in which it was expressly men- 
tioned in the protocols that the pancreas was normal. In the earlier protocols, if no 
disease of the pancreas in diabetes is mentioned no statement is made about the pan- 
creas, so that we cannot say with certainty that the pancreas was normal, although 
this can probably be assumed. " 

+ In the statistics given by Seegen diseases of the pancreas in diabetes seem 
more frequent than in the protocols examined by Dr. Bloch. These differences are 
due to'the subjective comprehension of the pathologist. At one time pigmentations, 
soft consistency, etc., are explained as postmortem phenomena and are not men- © 
tioned, while at another time they are stated as existing. 


- 


58 


DISEASES OF THE PANCREAS. 


The statistics, so far as they were accessible to me,* arranged accord- 
ing to the kind of disease,} give the following tables: 











T. ATROPHY. 
AUTHOR. AGE SEX. CONDITION OF THE PANCREAS. REMARKS. 
Bouchardat:,cited by| ? ? | Atrophy of the pancreas. 
Lapierre. ae 
Caplick: Diss. Kiel,| 12$ | M. Small, very pale. Died in coma. 
1882. 
Cruppi: Diss. Géttin- | 27 M. | Marked atrophy with indu- | Died with symp- 
gen, 1879. ration. toms of fever. 
Dieckhoff: “Beitr. z.| 57 M. | Pancreas very thin, smooth, | Diabetes for 
path. Anat. d. weighing 39 gm. years. 
Pankr.,’’ 1896. 27 F. | Pancreas weighs 30 gm. Ma- | Diabetes for 24 
croscopically and micro-| years. 
scopically, no essential 
change, only smaller than 
normal. 
Frerichs: “Ueber don| 37 F. | Small, flabby, tough, weighs | Diabetes for 2 
Diabetes,”’ 1884. 45 gm. Fibrillar connec-| years. 
tive tissue, with small re- 
mains of acini. 
25 F. | Very flabby and tough.| Thin, had dis- 
Fibrous connective tissue | easeof the lung 
with remains of acini.| and died in 
Gland cells small and| coma. 
transparent. 
Griesinger: “Arch. f.| ? ? | Atrophy of pancreas. 
Heilk.,” 1859, p. 44. ‘ 
Hartsen: “Donders’| ? 2? |High degree of atrophy. | Liver filled with 
Archiv,” 11. Gland not recognizable. small ab- 
scesses. 

? ? | Similar findings. Liver hyper- 
trophied and 
contains col- 
loid. 

Jaksch: “ Prager med. | 13 M. | Marked atrophy. Duct nar-| Acute course in 
Woch.,”’ 1883, p. rowed. Details of the| 22 days after 
193. gland indistinct. The| first § symp- 
| groove for vena lienalis| toms. Death 

is very wide. in coma. 

Klebs: “Handb. d. ? F. | Narrow and smooth. 
path. Anat.,’”’ 1868, ? F Weighs 25 gm. 

p. 536. 
Lancereaux: “Bull.| 61 But little of pancreas left. 


acad. méd.,’’ 1877. 











Connective-tissue bridge. 

_ Head and tail atrophied. 
Plexus normal. Duct. 
Wirsung. obliterated. 
Fatty degeneration of epi- 
thelium. 








* It is easily understood that in the following tables not all the published cases of 


diabetes with diseases of the pancreas are given. 


In the numerous reports of hospi- 


tals, of pathologic institutes, in collections of references, and in the clinical reports 
which have been published, of course numerous cases are found which belong to this 


list. 


} A strict division according to the kind of disease is impossible, because mani- 
fold combinations occur. There is a combination of new-formations, cysts, calculus 
inflammation with atrophy and calculi with cysts and fibrous degeneration carci- 
noma with chronic pancreatitis, lipomatosis with indurative pancreatitis, ete. 


In the table “ Atrophy” the corres 


nation are given so far as possible. 


ponding cases of atrophy without any combi- 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 


I. Arropuy.— (Continued.) 


59 








AUTHOR. AGE. | SEX. CONDITION OF THE PANCREAS, REMARKS. 

Lancereaux: ‘‘ Bull.} 29 M. |Small, weighs 10 gm., soft. | Diabéte maigre, 

acad. méd.,”’ 1877. Cells of acini, atrophied,| duration 14 
fatty, degenerated. years. Tuberc. 
pulmon. 

40 M. | Atrophied. | Duct obliter- | Diabéte maigre 
ated. Tuberculosis pul-| for two years. 
mon, 6% sugar. 

51 M. | Atrophy of pancreas. Head | Diabéte maigre 
and neck quite thin. for 14 years. 

Four hundred 
gm. of sugar 
per day. Sup- 
purative pleu- 
risy. 

Lecorché: “ Arch. gén. | 45 M. | Atrophy. 

Méd.,’’ 1861. 
Leroux: Cited by| 14 — |Atrophy of gland cells of |}6.1% to 7.1% 
Wegeli. pancreas with normal ar-| sugar in the 
rangement of connective| urine. 
tissue. . 

Leva: Cited by Wegeli.| 12 — | Atrophy. 3.3% to 6.5% of 

sugar in urine. 

Le Nobel: Maly J. B.| 61 M. | Atrophy of pancreas and | 2.27% sugar in 

1886, p. 449. disease of liver. urine after food 
rich in-carbo- 
hydrates, mal- 
tose. Neither 
indolnorskatol 
in feces. 

Noltenius: Diss., 1889.| 20 F. |Small, pale, brownish-red. | Died in coma. 

12 M. | Small, reddish-gray, weighs 
50 gm. 

50 F. | Highly atrophied. Small 
concretions in duct. 

Schabad: “ Zeitschr. f.| 22 M. | Size much diminished. Pig- 

klin. Med.,” 1894, mented atrophy of gland 

p. 108. cells. Spots of connective- 

tissue growth. 

Schaper: Diss., 1873. | 20 M. | Atrophied. Lobulesshrunk-| Diabetes after 
en. Fatty degeneration| injury to the 
of epithelium. _ skull. 

Scheube: “Arch. f.| 27 M. |; Pancreas atrophied. Marked emacia- 

Heilk.,” 18. Bd., p. tion. 

389. 

Seegen: “ Diab. mell.,”’| 35 M. | Flabby, small, dark-red, 

1893. acinous structure unrecog- 

nizable in many places. 
Epithelial cells fatty de- 
generated. 

Silver and Irving: 19 M. | Pancreas hard, atrophied, | Emaciation. 

“Trans. of the path. granulated. Phthisis. 

Soe.,”’ 1878. 

Thiroloix: ‘Diabéte| 45 M. | Pancreas changed into a| Acute begin- 

panc.,”’ 1892. fibrous band. Duct. Wir-| ning. Dura- 

sung. much  narrowed.| tion about 2 
Small cyst in head. Gland| years. Disap- 
tissue still. visible. pearance of 
the glycosuria 
about 24 days 
before death. 
Williamson: ‘“Med.| ? ? 


Chron.,” 1892, 3. 











Pancreas atrophied. : 








DISEASES OF THE PANCREAS. 


Hansemann’s table contains 36 cases of simple atrophy: 








SEx. | AGE. CONDITION OF PANCREAS. STATE OF NUTRITION. 
fo 24 | 50 gm., pale red, flabby. Marasmic. 
M. 22 | 50 gm., thin, atrophied. Marasmic. 
M. 62 | Small and thin. Emaciated. 
M. 30 | Atrophied. Fat. 
ee 66 | Very thin, 14 cm. long, head 3.5, tail 1.5, duct Emaciated. 
widened. Pars Wirsung. wholly lacking. . 
F; 55 | Body quite atrophied, toward the tail some- Well nourished. 
what more substance, but also marked atro- 
phy. Cicatricial retraction 
M. 60 | Very small and atrophied. Well nourished. 
M. 14 | Small and flabby. Poorly nourished. 
M. 42 | Atrophied. Marasmic. 
M. ? |Small and atrophied. Emaciated. 
F. 55 | Atrophied. Emaciated. 
F, 53 | Atrophied. Much emaciated. 
M. 40 | Atrophied. Emaciated. 
1 17 | Atrophied, 50 gm. Very well nourished. 
M. 26 | Atrophied, very flabby. Emaciated. 
M. 25 | Atrophied, 50 gm. Emaciated. 
M. 25 | Atrophied. Emaciated. 
M. 30 | Atrophy with induration. Emaciated. 
M. 48 | Small, atrophied. Emaciated. 
M. 29 | Small, atrophied. Emaciated. 
M. 33 | Atrophied. Marasmic. 
M. 39 | Atrophied. 
F. | 18 | Atrophied. Marasmic. 
F. | 25 | Half as large as normal. Marasmic. 
M. 50 | Atrophied. 
M. 32 | Much atrophied, 24 gm. Emaciated. 
F. | 15 | Small, flabby. Emaciated. 
M. | 4 Atrophied. Emaciated. 
F. 66 | Atrophied. Well nourished. 
M. | 31 | Flabby, pale, 65 gm. Emaciated. 
F. _67_‘| Much atrophied. | 
M. 22 | Atrophied. Marasmic. 
M. 32 | Fibrous degeneration with atrophy. Emaciated. 
rE. 36 | Atrophied, 35 gm. Moderate. 
M. 30 | Atrophied, 50 gm. Emaciated. 
M. 42 | Beginning atrophy and interstitial inflamma- 
tion, 97 gm. 

















To these hitherto published cases I wish to add three recent original 
Bo ons, in which microscopic investigations of the pancreas were 
made. | 


_ 1. A.R., clerk, twenty-one years, entered hospital March 31, 1896. Emacia- 
tion for several months, almost unquenchable thirst, great hunger. Body-weight 
45kg. Amount of urine 5000. 7.7% sugar. Specific gravity 1040. No albumin, 
no acetone. In spite of diabetic diet, 6.7% sugar increased to 8.1%. Goes to Carls- 
bad. On returning, 3%. Reentered hospital January 2, 1897. Evident phthisis, 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 61 


great weakness, much acetone, 45 kg. Sugar 3.3%. February Ist, coma, death. 
The anatomic diagnosis (prosector, Dr. Zemann) was marasmus eximius from dia- 
betes mellitus. Phthisis tuberc. lobi super. pulm. dextr. Infilt. lobular. tuberculosa 
pulmonis sinistri. The pancreas was quite firm, pale yellow, the lobules large. 
Microscopic examination showed atrophy of the pancreas. Weight 66 gm. 

2. S. B., merchant, thirty-seven years. Admitted December 31, 1896. For two 
years marked hunger and thirst. At the time of admittance passed 10 liters of urine 
perdiem. 6.4% sugar. Body-weight 44 kg.; before he was sick usually 80kg. In- 
creasing emaciation, 40 kg. 6% sugar. January 30, 1897, coma, death. Ana- 
tomic diagnosis (prosector, Dr. Zemann): Diabetes mellitus, tuberculosis pulmonum, 
catarrhus ventriculi chronicus, marasmus. Pancreas macroscopically flabby, red- 
dish-yellow on section, the acini quite small, soft, separated from each other by very 
loose connective tissue and some edematous fat tissue. Weight 70gm. Microscopic- 
ally: Size of gland lobules diminished and these are separated by quite abundant fat 
tissue, which, however, is undergoing serous degeneration. The gland cells small, 
markedly granular, and filled with fat drops. 

3. A. L., workman, thirty-five years. Admitted September 30, 1895. Since 
February, 1893, has had great hunger and thirst; has been in Carlsbad twice on 
account of diabetes. At the time of admission the amount of urine was 4 liters, spe- 
cific gravity 1026, 4.5% sugar, acetone 0.026. Body-weight47 kg. Sugar decreased 
to 3.1% and even to 2.3%. The patient left the hospital March 27, 1896, and re- 
entered April 20, 1896. At the time of admission he voided 5 liters of urine per day, 
specific gravity 1035, sugar 3.7%, much acetone, and great weakness. Could take 
but little nourishment. Coma, April 30th, death. Anatomic diagnosis (prosector, 
Dr. Zemann): Diabetes mellitus, tuberculosis circumscripta chronic. apic. pulmo- 
num, catarrhus ventriculi chronicus, marasmus eximius. Macroscopic examination: 
Pancreas quite narrow and very thin, flabby, poor in blood, the lobules small. Micro- 
scopic examination: The lobules of the pancreas somewhat small, the epithelium in 
a high degree of fatty degeneration and partly transformed into fat detritus. All the 
changes evidently related to the marasmus. 


From the results of the autopsies at the General Hospital, the follow- 
ing cases may be added: | 


1. 1892: Man aged fifty-five. Results of autopsy: Acetonemia, tuberculosis 
subacuta et chronica pulmon., atrophia pancreatis. 

2. 1894: Woman aged fifty-four. Encephalomalacia multipl. cerebr. ex end- 
arteriitide luetica, pneumonia hypostatica, atrophia pancreatis. 

3. 1894: Man aged sixty. Cirrhosis hepat. alcohol., tumor lienis chronicus, 
atrophia pancreatis pigmentosa. 

4, 1894: Man aged sixty. Cirrhosis hepat., ascites, atrophia pancreatis. 

5. 1895: Woman aged (?). Edem. acut. pulm. et cerebri, atrophia pancreatis. 

6. 1895: Woman aged twenty-two. Tuberculosis chronica glandul. bronch. ad 
hil. sin. subsequente tuberculosi hujus pulm., atrophia pancreatis, degenerat. ren., 
struma levis gradus, exophthalmos. 

7. 1895: Man aged sixty-one. Acetonemia c. degeneratione parenchym. 
hepat., ren. et cordis adipositate affect., encephalomalacia multipl. hemisph. sin. 
cerebri region. gyr. central. et in corpore striat. ex embolia, endarteriitis chronic. de- 
seemnane cum ulceribus ad arcum aortz, atrophia pancreatis eximia, hyperost. tibie 
ex lue. 

8. 1895: Man aged- forty. Atrophia pancreatis, induratio callosa caud. pan- 
creatis, tuberculosis pulm. The pancreas was surrounded by abundant fat tissue, 
the tail transformed into a callus, elsewhere indurated, considerably narrowed, in its 
calloused portion embedded in indurated fibrous tissue; was indurated; the lobules 
project from the cut surface as white granules. 


II. FATTY DEGENERATION. 





AUTHOR. AGE. SEX. CONDITION OF THE PANCREAS, REMARKS. 





Baumel: ‘“ Montpell.| 50 M. | Fatty degeneration of acini. | Abundant fat 


méd,” Slight increase of intersti-| tissue. Death 
tial tissue. from pneumo- 
nia. Large 


amount of su- 
gar. 

















62 


‘ DISEASES OF THE PANCREAS. 


II. Farry DeGeneration.—(Continued.) 








AUTHOR. AGE. | SEX. CONDITION OF THE PANCREAS. REMARKS, 
Caplick: Diss., 1882. 38 M. | Pancreas changed into mass | Duration of dia- 
of fat. Small, dense tu-| petes 6 years. 
mors in pancreas. Duct} Death ~ from 
ending blindly. Normal erysipelas. 
pancreas substance seen 
near the ductus choledo- 
chus. 
Chiari: “ Zeitschr. f.| 74 M. | Infiltrated with abundant | Death from men- 
Heilk.,’’ 1896. fat tissue. Microscopic- ingitis suppur. 
ally marked lpomatosis. 
Increase of interlobular 
and interacinous tissue. 
51 M. | Pancreasthin, soft. Micros.:} Death from gan- 
Fatty degeneration of] prena pulmon. 
cells. 
44 M. | Pancreas small. Fatty de-| Death from tu- 
generation of cells. berculosis. 
Dieckhoff: ‘Beitrag! 60 M. | Lipomatosis of pancreas. | Diabetes for 11 
z. path. Anat. d. Old chronic interstitial] years. Sugar 
Pank.,”’ 1895. pancreatitis. Areas offat-| between 6.4% 
necrosis. . and 1.5%. 
An _inebriate. 
Hemorrhage of 
stomach _be- 
fore death. 
Numerous ero- 
sions in stom- 
: ; ach. 
Friedreich: ‘“Krank-| ? ? |Pancreas dimin. in size.| Diabetes for 5 
heiten d. Pankr.,” Substitution of fat tissue.| years. Death 
1878. Here and there, remains of | in coma. 
acini undergoing fatty de- 
generation. 
Guelliot : “Gaz. | 67 M. | Pancreas enlarged, substi-| Disease lasted 
méd.,’”’ 1881. tution of fat, a cyst in] 1 year and 9 
head. A few remains of| months. Death 
glands surrounding the| in collapse. 
i a on ope e Zio pet, . 
oppe-Seyler: “Deut. : ancreas entirely changed to| Diabetes insipi- 
Arch. f. klin. Med.,” fat. No remains of fat} dus with fe 
1894. tissue. Calcification of| sient glyco- 
en blood-vessels. suria. 
Thiroloix: “Diabéte| 32 M. | Pancreas has undergone! Sudden onset. 


pancreat.,’’ 1892. 











fatty degeneration, small, 
of 50 gm. weight. Duct. 
Wirsung. permeable. 





Death from 
neumonia. | 
isease lasted 




















5 years. 
III. INDURATIVE PANCREATITIS. 
AUTHOR, AGE, SEx. CONDITION OF THE PANCREAS. REMARKS. 
Buss: Diss., 1894. ? ? | Induration of pancreas. Brown pigmen- 














tation of some 
organs, espe- 
cially of liver. 
Hemachroma- 
tosis (v. Reck- 
linghausen). 





GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 63 


III. InpuratiIvE PANcREATITIS.— (Continued.) 








AUTHOR. AGE. | SEX. CONDITION OF THE PANCREAS. REMARKS. 

Cantani u. Ferraro:| 38 M. | Pancreassmall, thin, fibrous | Marasmus, ace- 
“Tl Morgagni,’’1883, for the greater part, butin| tonemia. 
pet. some places penetrated by 

fat. Only in the tail are 
there areas of gland tissue. 

47 M. | Small, flabby, body fibrous, | Emaciation. 
remaining portions better| Death from 
preserved. pneumonia. 

50 M. |Small, granular connective | Emaciation. 
tissue between the lobules.| Death from 

: pneumonia. 

Dieckhoff: “Beitr. z.| 67 M. |; Chronic indurative pancrea- | Diabetes for 
path. Anat. d. titis. In head, a walnut-| about 1 year. 
Pankr.,’’ 1896. sized cavity with cream-| Between 5.0% 

like contents. Marked de-| and 1.3% 

velopment of fat tissue. sugar. Large, 
hard liver. 
Resistance in 
left hypochon- 
drium. 

4 M. | Pancreas small, flabby, and |} Eight months 
light, 60 gm. weight. Mi-| before death, 
croscop. exam.: subacute} sugar in the 
interstitial inflammation, | urine after 
with recent small-celled | taking cold; 
infiltration, partly diffuse | after trauma 
and partly in areas. 6 months later, 

repetition of 
the glycosuria. 
Death in coma. 

Fles: “ Donders’ ks ? | Pancreas entirely changed | Liver small. 

Arch.,”’ 111 fo connective tissue. No} Liver cells de- 
gland tissue recognizable | creased in size. 
even microscopically. 

Hadden: “Path. Soc. | 65 F. | Marked increase of connec- 
of London,” 1887, tive tissue in pancreas. 

1891. 

38 Marked _connective-tissue 
sclerosis. 

Hansemann: “ Zeit- 45 Pancreas large, very hard. | Death in coma. 
schr. f. klin. Med.,” On the cut surface and on} 4% sugar. 
1895. the free surface are acini] Corpulent man. 

separated from each other 

. by bands of connective 
tissue; some acini red, 
others white. Pancreati- 
tis interstitialis. 

58 M. | Fibrous induration of pan-| Syphilis. Bron- 
creas. Arterialienalistor-| chitis. Dilatio 
tuous. et hypertro- 

phia _ cordis. 
Endarteritis 
obliterans. 
Encephalo- 














malacia. 

















64 DISEASES OF THE PANCREAS. 
III. InpuRAtTIVE PANCREATITIS.—(Continued.) 
AUTHOR. AGE. | SEX. CONDITION OF THE PANCREAS. REMARKS, 

Hansemann: “ Zeit- 49 M. | Pancreas entirely degener- | Marasmus. 
sehr. f. klin. Med.,” ated. None of the sub-| Deathin coma. 
1895. stance present, except a 

thin layer of connective 
tissue, which surrounds 
the enlarged duct. A- 
round the head, more 
marked connective-tissue 
growth. Mouth of canal 
in duodenum obliterated. 
Artery not tortuous. Wall 
thickened. 

Noltenius: Diss., 1888.) 46 M. | Marked induration of ‘the 

pancreas. 

Obici: “Soc. di Bo-| ? ? | Interstitial pancreatitis in | Disappearance 
logna,” 1893. the neighborhood of the) of glycosuria 

blood-vessels and lymph-| for a short 
vessels. time under a 
pure meat diet. 

Rowland: “ Brit. Med. | 57 F. | Fibrous degeneration of the | Death in coma. 
Jour.,” 1893. pancreas. Lime concre- 

tions in the connective 
tissue. 

Roque, Devic and Hu-!| 39 M. | Pancreas small, connective | Duration of dia- 
gounenq: “ Rev. de tissue increased. Cells | betes, 2 years. 
med.;.” 1892, <p; small and do not stain} Deathin coma. 
995. (postmortem phenome- 

non). 
Rihle: Cited by 20 M. | Cirrhosis of the pancreas. | Diabetes melli- 
Dieckhoff. Enlargement of duct. In| tus for one 
the head, cysts the size of | year. Sugar at 
an apple with blood-clot. | last  alternat- 
ing. At the 
end ascites. 
Edema of 
lower extremi- 
ties and anuria 
at times. 

Seegen : “ Diabet. ? ? . | Pancreas changed to a gray 

Mellit.,’”’ 1893. calloused band. In the 
region of the head, re- 
mains of granular struc- 
ture. 

Williamson: “Brit.| 52 M. | Pancreas dense and heavy. | Diabetes and 
Med. Jour.,’”’ 1894. On micros¢opic examina-| paresis of 

tion, cirrhosis. Changes} right arm 
in spinal cord. muscles. 




















A case of connective-tissue growth in the pancreas of a diabetic, 
mentioned by Tylden and Miller, is also to be added. Indurative 
changes were found also in the cases recorded by Frerichs, Lancereaux, 
Dieckhoff, Goodmann, and Lépine, and listed in Tables I, I, VI, and X. 

The case of Baumel may also be added to this table, in which pan- 
creas, spleen, and stomach were found closely grown together. 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 65 


An interesting anatomic condition has kindly been communicated 
by Dr. Zemann: 


K. W., maid-servant, forty-five years of age, died December 20, 1896. Clinical 
diagnosis: Diabetes mellitus. . 

Result of postmortem examination: Extensive ichorous carcinoma of the left 
large and small labia of the vulva with phlegmonous inflammation in the region of the 
mons veneris and of the groins. Beginning gangrene of the skin on both sides, espe- 
cially on the right. Chronic tuberculosis of the apices of the lungs with induration. 
Acute, lobular, tuberculous infiltration of the lungs. Nearly complete cicatricial 
shrinkage of the pancreas, which is replaced by a small cavity, also a duodenal fistula 
just at the pylorus, the results of chronic ulcerative pancreatitis. Diabetes mellitus. 

On raising the liver, there appears in place of the lesser omentum a dense, white, 
radiating mass of cicatricial tissue, by which the lesser curvature of the stomach is 
much shortened and closely approximated to the liver; the contiguous portion of the 
capsule of the left lobe of the liver is white, thickened, and opaque, the fibrous tissue 
in the portal fissure is only slightly thickened. After cutting through the transverse 
mesocolon, there is seen in place of the pancreas a nodule about the size of a hazelnut, 
which is inclosed in very dense, white, fibrous tissue, radiating from the former, and 
by which the upper transverse piece of the duodenum and the pylorus are drawn and 
firmly attached to the nodule. On cutting the nodule open a transverse, egg-shaped 
cavity, about 12 mm. in the greatest diameter, is exposed; this occupies the right 
portion of the whole nodule, while the remaining left portion consists of connective 
tissue, which incloses a group, larger than a pea, of pale-yellow, soft lobules of pan- 
creatic structure. In the cavity is found a turbid, thick, slimy, dirty reddish-gray 
fluid, in which are fine sand-like particles and a hard concretion about 4 to 5 
mm. long, 1 mm. thick, and of irregular shape. The inner surface of the cavity is 
lined with smooth, delicate, grayish-red tissue. The wall, with the exception of the 
left portion, is formed of a layer of somewhat dense white tissue, 2 or 3 mm. thick, 
and calcified in places. On the right, the wall contains an opening, scarcely as large 
as a millet-seed, through which the closely approximated upper portion of the duo- 
denum is entered. The orifice of the duodenum, about 1 cm. from the pylorus, lies 
in a funnel-shaped pocket which is bounded by a thick projection of mucous mem- 
brane. The remains of the head of the pancreas, forming a mass 3 to 5 mm. thick, 
are found close to the duodenum. The lobules of this remnant of the pancreas are 
very small, and are separated by considerable intervening tissue. The pancreatic 
duct is not permeable. 


IV. CALCULI. 





AUTHOR. AGE. SEX. CONDITION OF THE PANCREAS. REMARKS. 





Baumel: “Montpell.| 50 M. | Pancreas incrusted with fine | Cause of death 
méd.,’”’ 1882. concretions. About the| tuberculosis. 
atrophic acini, abundant 
connective tissue. Stones 
weigh together 1.2 gm. 

and consist of CaCO . 


Capparelli: “Tl Mor-| ? F. | Pancreatic fistula for years. | After closure of 


gagni,”’ 1883. Discharge of calculi. No! the fistula, di- 
autopsy. abetes devel- 
oped. 

Chopart: cited by| ? M. | Fatty stools, calculi in pan- 

Klebs. : creatic duct. 

Cowley: “London | 35 M. | Calculi as large as a pea|Inebriate, very 
Med. Journal,” | wedged in gland sub-| corpulent. 
1788. | stance. Pancreas atro- 

phied. 

Elliotson: “ Med.-chir. | 35 M. | Duct as far as the lateral | Fat in stools. 
Transact.,” 1833. branches obstructed by 

calculi. 

















66 


DISEASES OF THE PANCREAS. 


IV. Caucuui.—(Continued.) 








AUTHOR. AGE. SEx. CONDITION OF THE PANCREAS. REMARKS, 

Fleiner: “Berl. klin. | 40 M. | Caleulus in duct. Gland | Inebriate. Much 
Wochenschr.,” almost wholly sclerotic,| emaciated. 
1894, p. 38. in the tail only was there 

some gland tissue. 

Frerichs: ‘“ Diabetes,” | ? ? |In the duct, together with 

1884. numerous fragments of 
calculi, were two spindle- 
shaped concretions. Gland, 
with the exception of a 
few acini, wholly degen- 
erated. 

Freyhan: “Berl. klin.| 35 M. | In the duct, calculi consist- | Insidious begin- 
W ochenschr.,” ing of calcium carbonate.| ning of dia- 
1893. Duct enlarged with lateral} betes. Up to 

pockets. Pancreas atro-| 3.1% sugar in 

phied, no gland structure. | urine. Pul- 

Fatty degeneration. monary _tu- 
berculosis. 

. F. | Duct dilated. In the tail,|/1.8% sugar in 
firmly fixed in the canal,| the urine. Pul- 
wasa hard caleculusaslarge | monary tuber- 
as a plum-stone, consisting| culosis. Disap- 
mostly of calcium carbon-| pearance of 
ate. Gland entirely | glycosuria be- 
changed into fat and con-| fore death. 
nective tissue. 

Gille: “Soc. d’anat.,”| ? M. |Calculus wedged in duct. 

1878. Gland atrophied. 

Holzmann: “Mun-| 68 M. |Concretions found in the | Traces of sugar 
chen. med. Woch- feces, after the at- 
enschr.,’”’ 1894. tacks of colic. 

Lancereaux: 1877,| 42 M. | Syphilis. Dilatation of 
“Bull. de l’acad. both ducts. Calculi of 
méd,” various size. 

? ? |Cited by Giudiceandrea 
without further details. 

Lancereaux: “Bull.| 45 F. | Mouth of ductus Wirsung. | Colic and fatty 
acad. méd.,’’ 1888. closed by calculi. Growth| stools before 

of connective and fatty| the beginning 

tissue. Gland tissue| of diabetes. 

atrophied. Diabéte mai- 
gre. Duration 
5 months, 

Lancereaux: 1888.| 25 F. | Body of gland atrophied. 

“Bull. de lacad de Hard calculi of the size of 

méd. de Paris,”’ peas. 

Seance 8°, mai, 

1888, cited by Giu- 

diceandrea, 

Lichtheim: “Berlin. | 36 M. | Calculi in duct. Fibrous 
klin. Wochenschr.,”’ degeneration with almost 
1894. total disappearance of 

gland tissue. . 

Lusk: Cited by Giu-| ? M. | Pancreas showed almost 


diceandrea 











complete calcification of 
the gland. 








GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 


IV. Caucuui.— (Continued.) 


67 








AUTHOR. AGE. | SEX. CONDITION OF THE PANCREAS. REMARKS. 

Moore: ‘Path. Soc.| 40 M. |In the pancreatic duct, 

London,” 1884. numerous irregularly con- 

toured calculi consisting of 
CaCO,. Marked enlarge- 
ment, especially in the 
head. No obstruction. 

Miiller: “Ueber Ic-} 21 M. | Dense, nodular. Duct much | Diabetes for two © 
terus,”’ ‘ Zeitschr. f. enlarged. Containing sev-| years. 3% to 
klin. Medicin,”’ Bd. eral yellowish-white con-| 6% sugar. 
xu, 8. 84. cretions of the size of a} Death from 

cherry-stone, with cylin-| phthisis  pul- 
dric_ dilatation behind | monalis. Caries 
them. Gland substance| of the petrous 
atrophied. Concretionsin| bone. Stools 
the lateral branches. always abun- 
dant, yellow, 
foamy, and 
of the consist- 
ency of thin 
porridge. 

Munk u. Klebs: “Na-| ? ? |Calculus formation. No 
turforscherver- remains of gland visible 
sammlung,’”’ 1869. macroscopically. Behind 

the omental bursa in the 
connective tissue  sur- 
rounding the blood-vessels 
single groups of cells were 
to be found with the mi- 
croscope. 

Nicolas u. Molliére:| 47 M. | Ductus Wirsung. obstructed | Occasional  at- 
“Bull. méd.,” 1897. by calculi, opens into a|_ tacks of colic. 

cavity filled with pus| Melena. Symp- 
which comprises thescen-| toms of dia- 
tral portion of the pan-/| betes 24 
creas. Sclerosis of the} months after 
gland. Fistula from the| the beginning 
pus-cavity into the duo-| of the disease: 
denum near the pylorus. sugar reached 
179 gm. a day. 
Caseous pneu- 
monia. Dura- 
tion of disease, 
six months. 
Stools normal. 

v. Recklinghausen? 26 M. | Large and small concretions | Gangrene of 
““Virch, Areh.,”’ in the much widened duct. |_ lungs. Dia- 
1864, Pancreas changed to a/|_ betes for some 

tumor consisting of fat.| time. 

Rorig: Cited by We-| 104 2? | In an accessory pancreatic | Diabetes. 
geli. * duct a calculus which en- 

tirely filled the lumen. 
Behind it, a cyst filled 
~with pancreatic juice. 

Seegen: “Diab. mell.,”| ? ? | Duct dilated by concretions 


1893. 











to the size of a raven’s 
quill. Concretions also in 
finest branches. 








DISEASES OF THE PANCREAS. 


V. CARCINOMA. 








AUTHOR. AGE. SEX. ConpITION OF THE PANCREAS, REMARKS. 

v. Ackeren: ‘Berl.| 49 M. | Carcinoma in head and tail | Maltose in urine. 
klin. Wochenschr.,”’ of pancreas. Carcinoma} Many muscle- 
1889. of pylorus. fibers in 

stools, 

Bouchard: ‘“Malad.| ? M. | Carcinoma in the head of 
par rallent. de la the pancreas. 
nutr.” 

Bouchardat: Cited by | ? ? | Carcinoma pancreat. 

Lapierre. 

Bright: “Med. Chir.| 49 | M. | Carcinoma of the pancreas, | Rapid cachexia. 
Trans.,” 1833. of cartilaginous density. Severe icterus. 

Courmont u. Bret:| 64 Carcinoma of the head of | Diabetes after 
Clinique, 1894. the pancreas, with sclerosis} trauma. Frac- 

of the whole gland. Par-| tyre of rib. Ic- 

enchyma of liver changed. | terus. Disap- 
pearance of 
sugar. 

Dieckhoff: ‘“ Beitr. z.| 75 F. | Cylindric-celled carcinoma|Jn the urine 
path, Anat. of head of pancreas.| taken after 
Pank.,” 1896, Chronic interstitial and} death there 

purulent pancreatitis. was a positive 
phenylhydra- 
zin test. 

Dreschfeld: ‘“ Med. ? ? | Pancreas firm, dense, and | Duration of 
Chron.,’’ Apr., 1895. infiltrated with cancer.| disease three 

Almost no normal tissue.| months. Stab- 

Portal vein compressed by bing pains in 

the new growth. epigastrium. 
Vomiting. As- 
cites. Hemat- 
emesis. Death 

: in collapse. 

Duffey: “ Dublin Jour-} 24 M. | Carcinoma pancreat. Gland | Duration of dis- 
nal,” 1884. substance entirely disap-| ease 2 months. 

peared. Dysenteric di- 
arrhea. Death 
in collapse. 

Fothergill: . “Brit. | 53 F, | Pancreas entirely destroyed. | Repeated 
Med. Jour.,’’ 1896. Carcinoma of peritoneum,!| cramps. Icter- 

mesentery, and omentum.} us, Tumor 
distinctly felt 
in abdomen. 
Operation. 
Hematemesis, 
Death. 
Frerichs: “Ueber d t ? | Head of pancreas changed 
: . ? ; ge 
Diabet.,”’ 1884. into medullary carcinoma 
and fused with the duode- 
num. Dilatation of duct 
of Wirsung. Atrophy of 
gland. 
63 M. | Diagnosis of cancer of the | Duration of dis- 


Galvagni: “ Rif. med.,” 
1896. 











pancreas, 





ease, 6 months. 
Marked glyco- 
suria. 





GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 69 


V. Carctnoma.—(Continued.) 








AUTHOR. AGE, SEX. CONDITION OF THE PANCREAS. REMARKS, 

Kesteren : “Path. | 60 M. | Primary carcinoma of pan-| Transient  gly- 
Trans.,’’ 1890. creas. cosuria, disap- 

pears after ap- 
propriate 
diet. Icterus. 
Pustule forma- 
tion on skin. 

Macaigni: Cited by| 69 F, | A large, very hard cancer of | Transient glyco- 
Thiroloix. the head of the pancreas,| suria for — 

replacing one-half of the| months, then 
gland, the rest of which; 11 months ca- 
was apparently normal.| chexia  with- 
Compression of bile-ducts. | out glyco- 
suria. Disease 
lasted 23 
months. 
Martsen: Thése, 1890.| ? ? |Scirrhus of head of pan-| Fatty diarrhea. 
creas. Complete oblitera-| Diabetes. 
tion of ductus Wirsung. 

Masing: “ Petersburg.| 46 M. |Scirrhus in head of pan-|Sick 7 months. 
med. Wochenschr.,”’ creas as large as child’s| Neuralgia co- 
1879. fist. Duct. choled. com-| liaca. Icterus. 

pressed, dilated. Nothing objec- 
tively demon- 
strable. 

Mirallié: “Gaz. des| ? ? | Carcinoma of pancreas. Fifty-eight gm. 
hopit.,”’ 1893. sugar a day. 

Servaes: “Berl. klin.| ? ? |Carcinoma of pancreas. Severe celiac 
Wochenschr.,”’ 1878. neuralgia for 

years. The 

last three 

years, bronzed 
skin. 

Suckling: ‘Lancet,’ | 33 M. | Carcinoma of pancreas. Rapid emacia- 
1889. tion. Jaundice. 

Stools ash- 
colored. 

Thiroloix u. Lance-| 60 F. | Epithelioma in head of pan-| Duration about: 


reaux: ‘ Didbete 
pancreat.,”’ 1892. 











creas. Obliteration of duct 
of Wirsung. Sclerosis and 
atrophy of the remaining 
portions of gland. 





7 months. No 
polyphagia. 
Azoturia. Sud- 
den death. 





Besides these are the cases of Collier, Marston, Santi, Musmeci, Choupin, and 
Moll, concerning which I have no further information. 








VI. CYSTS. 
AUTHOR. AGE. SEX. CONDITION OF THE PANCREAS. REMARKS, 
Bulls “New York| ? ? |No autopsy. Pancreatic} Tumor for 10 


Med. Jour.,” 1887. 











cyst containing 34 liters. 





months. Fatty 


stools, 5% 
sugar. Death 
34 months 
after opera- 


tion. 
































70 DISEASES OF THE PANCREAS. 
VI. Cysts.—(Continued.) 
AUTHOR. AGE, | SEX. CONDITION OF THE PANCREAS, REMARKS, 

Churton: “ Brit. Med. | 35 M. | Pancreas changed into fi- | Exploratory 
Jour.,” 1894. brous mass. Remainsofa]| puncture. Af- 

cyst in duodenal portion. | ter it, cireum- 

Duct partially obliterated..| scribed perito- 
nitis. Laparot- 
omy,  drain- 
age. After 5 
months, collec- 
tion of pus be- 
hind stomach. 
Second lapar- 
otomy. Death. 
Diabetes. 

Goodmann: “Phila-| 55 M. | Large cysts, in tail. Gland | Diabetes. Steat- 
del. Times,’ 1878. tissue atrophied. Fibrous}  orrhea. 

tissue in head. 

Horrocks and Morton:| 56 M. | Large cyst with thick fi-|In urine, some 
“Lancet,” 1897. brous wall. Inner surface} albumin and 

smooth, with small pro-| much _ sugar. 

jections. Nonormal pan-| Patient died 

creatic tissue. Duct of | on the next 

Wirsung impermeable. day after aspi- 
ration of the 
cyst. 

Malcolm Mackintosh:| ? M. | Large cyst under and be-| Marked _poly- 
“Lancet,” 1896. hind the spleen, withsome} uria. Death in 

pancreatic tissue on poste-| coma 11 days 

rior and lower part of| after discov- 

cyst-wall. ery of sugar 
in urine. Dis- 
ease lasted 4 
year. 

Mulert-Zweifel: Dis-| 64 F. | Pancreatic cyst removed by | Transient gly- 
sert., 1894. operation. cosuria. 

Nichols: ‘New York} 49 M. | Large serous cyst of pan- | Diabetes. 

Med. Jour.,’’ 1888. creas. No trace of gland 
tissue. 

v. Recklinghausen: 40 M. | Large cystic tumor, prob-| Diabetes for 4 
“Virchow’s Ar- ably caused by partial! years. 4% to 
chiv,”’ 1864. ectasia of the obliterated | 5% sugar. 

duct. 

Riegner : “ Berlin. klin.| 23 M. | Pancreatic cyst. Operated | Traces of sugar. 
Wochenschr. ,’’1890. upon. Many muscle- 

fibers in stools. 
VII. ABSCESS. 
AUTHOR. AGE. SEx. CONDITION OF THE PANCREAS, REMARKS, 

Atkinson: “Med.| 45 F. | Pancreatitis suppurativa, | Acute beginning 


News,” 1895. 











abscess breaking through 
into the intestine. 





of isease, 
vomiting,pain. 
Tumor in epi- 
gastrium. Pus 
in stools one 
day before 
death. Slight 
glycosuria. 





GENERAL PATHOLOGY AND SYMPTOMATOLOGY. (pi 


VII. Anscess.— (Continued.) 








AUTHOR. AGE. | SEX. CONDITION OF THE PANCREAS. REMARKS. 
Frerichs: ‘‘Ueber den | 27 F. | Head of pancreas normal, | Acute disease of 
Diabetes,”’ 1884. rest of the gland sur-| the pancreas, 
rounded by a cyst. On| ending in sup- 
posterior wall the atro-| puration. 6% 
phied pancreas. to 7% sugar. 
Tuberculosis. 
Frerichs: “ Diabetes,” | 31 F. | Pancreas, with the excep-| Cardialgia. Ic - 
1884. tion of the head, changed | terus. Sudden 
into an abscess the size of | onset of dia- 
an apple. The pus-sac}| betes. As high 
completely closed off, not | as 600 gm. of 
communicating with the} sugar daily; 
surrounding tissues. on animal food 
40 to 50 gm. 
Pulmonary tu- 
berculosis. Du- 
ration of dis- 
ease, 6 months. 
Frison: “Recueil | 28 M. | Pancreas enlarged to three | Afebrile uterus. 
méd. mil.,’’ 1876. times its natural size, in-| Anorexia, ady- 
filtrated with pus, a large| namia. Two 
abscess in the tail. Small | months later, 
abscess in liver, Gall-| edema, _poly- 
bladder dilated. phagia, poly- 
dipsia. Sugar 
in urine. 
Harley: “Trans, path.| 58 M. | Head of pancreas contains | Glycosuria de- 
Soc.,”’ 1862. a quantity of pus. En-| veloped three 
largement. Duct dilated.| weeks before 
Gall-stones present. death. 

















In the reports of the autopsies of the General Hospital the following 
case is found: Acetonemia. Pancreatitis suppurativa et necrosis tel. 
adipos pancreat. Tumor hypophyseos. Acromegalia. 


VIII. HEMORRHAGE. 


Sarfert, in 1895, reported a case of pancreatic apoplexy in a man aged thirty-nine 
on whom laparotomy was performed on account of symptoms of intestinal obstruc- 
tion. Death soon afterward. In the urine removed after death 1% sugar was 
found. At the autopsy, the pancreas, infiltrated with blood, was transformed into 
a mass resembling spleen tissue. Cutler’s communication is dated the same year. 
Diabetes developed in a woman of fifty-two years. At the autopsy the pancreas was 
found, enlarged to twice its size, firm, dry, dark. Disseminated fat necrosis in the 
surrounding tissue. 


Among the cases reported by Dieckhoff, there is one of hemorrhage 
into the pancreas, which, however, was certainly not the cause of the 
diabetes: 


A woman of middle age suffered for years from diabetes. During the last year, 
in repeated examinations, no sugar Was found in her urine. About four weeks before 
death she was attacked with severe pains in the abdomen, which lasted until death. 
At the autopsy a large effusion of blood was found surrounding the left kidney, the 
suprarenal capsule, and in part the pancreas; the blood formed a compact mass. A 
portion of the gland was quite well preserved, no alteration being recognizable. The 
fat tissue within and around the pancreas showed several isolated patches of necrosis. 


72 DISEASES OF THE PANCREAS. 


IX. NECROSIS AND FAT NECROSIS. 


Silver observed alterations of the pancreas, regarded by Hansemann 
as necrotic, in a diabetic aged twenty-three. Israel found gangrene of 
the pancreas with diabetes in a work-woman aged twenty-seven. 

In the reports of autopsies at the General Hospital, the following 


pertinent cases are found: 


1. Woman aged fifty-one. Glomerulonephritis, necrosis circumscripta in 


cauda pancreatis. 
2. Man aged forty-nine: Hyperemia cerebri, alcoholism. chron, (inebriate). 


Necrosis incip. tel. adipos. pancreatis. 
Woman aged nineteen. Necrosis text. adipos. in regione pancreatis. 


In the following table the cases are given in which no macroscopic 
alterations were found, but in which microscopic changes were seen: 


X. MICROSCOPIC CHANGES. 





AUTHOR. AGE. SEX. CONDITION OF THE PANCREAS, REMARKS. 





Bond and Windle:| 17 M. | Pancreas macroscopically | Death in coma 
“Brit. Med. Jour.,”’ normal. Microscopically,| after 4 days. 
1883. epithelium swollen and 

‘ granular. 

Caplick: Diss., 1882. 19 M. | Pancreas normal. Hyper- 

emic. 

Fleiner: “Berl. klin.| 57 F, | Tissue preserved only in the 
Wochenschr.,” head. Nuclei poorly 
1894. stained. (According to 


Hansemann, a postmor- 
tem change.) 


Harnack: “Arch: -f.-|' 33 M. | Pancreas macroscopically | Diabetes for 
klin. Med.,”’ 13, normal, microscopically | over one year; 
1874. shows fatty degeneration. | 600 to 800 gm. 


‘sugar. Intes- 
tinal catarrh. 
Slight glyco- 
suria at the 


end. 

Lépine: “ Rev. méd.,” | 40 M. | Pancreas’ macroscopically 

1892. normal, microscopically 

shows periacinous sclero- 

sis. 

ee - 54 M. | The same condition. Death in coma. 
N shed Union méd., 25 M. | Pancreas somewhat en-| Marked emaci- 
881. . larged, macroscopically | ation, fatty 
normal, microscopically | stools, death 
shows marked fatty de-| in extreme 


generation of the glandu-| marasmus. 
lar epithelium. 

















Changes in the pancfeas have been found, as appears from the above 
data, in 188 cases of diabetes; and of these, 78 cases showed atrophy, 
10 cases fatty degeneration, 22 induration, 24 calculi, 24 cancer, 9 cysts, 
6 abscess, 3 hemorrhage, 3 necrosis, 2 fat necrosis, and 7 showed only 
microscopic changes. 

Can the conclusion be drawn from these facts that disease of the 
pancreas is the cause of diabetes? Certainly not. Although doubtless 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 73 


these figures * could actually be multiplied many times, and from the 
frequency of diabetes the number of cases in which disease of the pan- 
creas could certainly be found at the autopsy would be very much greater, 
yet nothing would be proved. 

To solve the question with certainty in a statistical way would be a 
matter of great difficulty. It would be necessary to know in large num- 
bers of cases how often diabetes occurred in pancreatic diseases and 
how frequently pancreatic diseases occurred in diabetes, and only from 
constant or nearly constant relations could conclusions be drawn which 
would be available under certain conditions which will later be explained. 

The figures at hand for this purpose are too few and too dissimilar to 
admit comparisons and conclusions. 

A few data, as already mentioned, exist with regard to the ques- 
tion of the frequency of pancreatic diseases in diabetes. Windle found 
the pancreas changed 74 times in 139 cases of diabetes. Hansemann 
found in the protocols of the Berlin Pathologic Institute 54 autopsies 
of diabetics, among which changes were recorded in the pancreas 
40 times. 

The reports of autopsies at the General Hospital in Vienna give 
changes in the pancreas 42 times in 151 cases of diabetes. 

Concerning the frequency of pancreatic diseases in general there are | 
no available statistics, for the reason that in autopsies the pancreas is 
not always sufficiently studied, and where the diagnosis of the presence 
of some acute or chronic disease is evident, as tuberculosis, pneumonia, 
typhoid, etc., the pancreas is rarely examined in detail. 

With regard to the frequency of diabetes in diseases of the pancreas, 
some significant figures are given. 

Dieckhoff investigated 19 cases of diseases of the pancreas, in 7 of 
which there was diabetes; no other cases of diabetes at this time were 
examined after death. 

Hansemann found 59 cases of diseases of the pancreas, among which 
diabetes was present in 40. In 54 cases of diabetes postmortem examina- 
tions were made. 

Among 18,509 autopsies in the Vienna General Hospital between 1885 
and 1895, pancreatic diseases were noted 96 times, and in 12 of them 
there was diabetes. There were 86 autopsies of diabetics. 

These data are, of course, striking, but still not convincing, because 
it can be stated with certainty that the number of changes in the pancreas 
in general, aside from those in diabetes, is much ereater than the number 
given in the report of the autopsies. Atrophy especially, which is the 
condition so frequently found in diabetes, and which certainly is often 
found as marantic atrophy in old age and in cachexia, is regarded as 
irrelevant and is rarely noted. Tuberculosis of the pancreas, according 
to Kudrewetzky, is a frequent disease, and yet it is seldom mentioned 
in reports of autopsies. 

It will be shown in a special portion that diabetes occurs in diseases 
of the pancreas by no means so frequently as would be supposed from 
the reports of autopsies quoted. It will be seen that in acute and 
chronic inflammations, abscess, cysts, carcinoma, etc., diabetes is a rela- 
tively rare symptom. 

There is, then, a contradiction between the anatomic and clinical facts, 


* The numbers given in abstract, for instance, those from Seegen’s statistics 
from the Vienna General Hospital, are not included 


74 DISEASES OF THE PANCREAS. 


which can be decided only by frequent investigation on the part of clini- 
cians and anatomists. 

But even taking it for granted that the relations between pancreatic 
disease and diabetes, which, according to the autopsy reports given up to 
the present time, are shown in relatively few cases, were expressed con- 
stantly and in large numbers, it would still not always be proved that the 
disease of the pancreas found was the cause of the diabetes. If one should 
express in figures from the reports of autopsies the frequency of tuberculo- 
sis and diabetes and the frequency of the coincidence of the two diseases, 
he would find a large and probably constant number, and yet there is no 
doubt that tuberculosis is not the cause of the diabetes. 

A similar relation would be found also between diabetes and diseases 
of the kidney, and yet it is established for most cases that there is no renal 
diabetes. 

When clinical diabetes and anatomic affection of the pancreas are 
asserted, there are three possibilities: (1) That the diabetes is the result of 
the change of the pancreas; (2) that the diabetes is the cause of the change 
of the pancreas; (3) that the diabetes and the disease of the pancreas are 
co-ordinated but are independent of each other. Only when the two last 
possibilities can positively be excluded could even the existing few in- 
stances be regarded as of positive value. 

But this proof is not to be furnished without an exhaustive study of 
the individual cases. On the contrary, it is known definitely that there are 
cases of secondary diseases of the pancreas in diabetes. It is an undenia- 
ble fact that cachectic atrophy of the pancreas is found in diabetes. The 
only difference of opinion relates to the recognition as examples of 
cachectic atrophy of a greater or less number of the cases of pancreatic 
atrophy frequently found in diabetes, and not a few clinicians and path- 
ologists until most recently have inclined to the view that all the atrophies 
are secondary. 

The rare cases of necrosis also can be considered as secondary processes. 
The latter doubtless may exist side by side. When in the course of a diar 
betes which has existed for years, a cyst, carcinoma, an acute or chronic 
inflammation, a hemorrhage, or a fat necrosis develops, we certainly have 
ae the right to bring these lesions into etiologic relation with the dia- 

etes. 

The fact which has long been known, that diseases of the pancreas 
certainly occur as conditions resulting from diabetes, and also quite inde- 
pendently of it, has caused such distinguished investigators as Seegen and 
Frerichs to take so reserved a point of view. The frequent coincidence 
of affections of the pancreas with diabetes was known to them, and from 
it they came to the conclusion that in a number of cases the disease of the 
pancreas was possibly the cause of the diabetes. 

Only through animal experimentation did the familiar facts receive new 
light, and since in the mean time the number of reported cases was 
essentially increased, there was a greater certainty in the significance 
of the concurrence of diabetes and diseases of the pancreas. In order 
to use the results of animal experimentation in the solution of the ques- 
tions under consideration, it is necessary to investigate whether the data 
obtained from animals can be applied to man. It is evident that not 
all species of animals act alike, and that many are refractory. The most 
constant results are obtained in dogs. 

A positive proof that in man an experimental pancreatic diabetes 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 15 


may arise cannot, of course, be produced. There are, however, some 
suggestions which may be regarded in the light of such an experiment. 

Diabetes developed after a pancreatic cyst had been operated upon 
by Zweifel. In a woman sixty-four years old there was under the left 
ribs a tumor which finally grew rapidly. At the operation the tumor 
was found to be a pancreatic cyst. It was extirpated. A piece of the 
pancreas 3 cm. long remained. Before the operation the urine was free 
from sugar. On the ninth day after the operation sugar appeared at 
times in the urine. It was independent of the food taken. After four 
weeks there was still sugar in the urine, and three weeks later it was no 
longer present. In a case of suppuration and necrosis of the pancreas 
operated upon by Korte there was no sugar in the urine during the 
stay in the hospital, but later permanent diabetes developed. 

Although these cases cannot be regarded as absolute proof that the 
results in animals can without reservation be applied to man, and that 
the former are essentially an analogue of the partial extirpation of the 
pancreas with consequent diabetes in the dog, nevertheless such a con- 
clusion, I think, should be given careful consideration. 

This assumption would gain essential support if the facts hitherto 
known concerning diseases of the pancreas in diabetes could be so utilized 
that they would harmonize with the experiments on animals. 

There are two recent communications, each published by a repre- 
sentative pathologic anatomist, Hansemann and Dieckhoff, who have 
tried to establish this harmony. 

Hansemann propounds the following question: Is there any objection 
to transferring to man the results of the experiments on dogs? He 
divides the existing material into three groups. 

1. Diabetes without diseases of the pancreas. There is no doubt 
that there are cases in which, even with the most careful investigation, 
neither macroscopic nor microscopic changes can be recognized. Hanse- 
mann has distinctly found them. This fact obviously does not deny that 
there is a diabetes in man, attributable to alterations of the pancreas, 
analogous to the experimental diabetes in animals. 

2. Diseases of the pancreas without diabetes. ‘Those cases in which 
the pancreas is only partly diseased are separated from those in which 
a total destruction has taken place. In experiments on animals diabetes 
after partial extirpation is very inconstant, and generally is lacking. 
This observation corresponds with the fact that in man also diabetes 
is frequently lacking if the pancreas is only partially diseased. 

Hansemann examined 19 of his own cases of disease of the pancreas 
without diabetes, and found in most of them, even when the organ 
macroscopically seemed to be totally diseased, that there was enough 
normal gland tissue to explain the lack of diabetes. Among them, to be 
sure, were some cases of total destruction of the organ by diffuse car- 
cinoma, and Hansemann explained these by the hypothesis that even 
cancerous cells may be able to carry on the internal function of the pan- 
creas although they are of no value as regards the secretory function. 
In like manner, Lubarsch explains the absence of Addison’s disease in 
primary tumors of both adrenals. However ingenious this hypothesis, 
it cannot be regarded as proof. It takes for granted that which is to be 
proved. 

The cases of total destruction of the pancreas by hemorrhage, sup- 
puration, or necrosis without diabetes, Hansemann explains by reference 


76 DISEASES OF THE PANCREAS. 


to the animal experiment, in which the time between the extirpation 
and the appearance of the glycosuria varied, although the interval was 
usually short. When the above pathologic processes ran a rapid course, 
it, is clear that there was not time for the occurrence of diabetes. 
Since in man the glycosuria disappears not infrequently a short time 
before death, so in the rapidly fatal course of pancreatic necrosis ‘the 
disappearance of sugar from the urine may immediately follow the 
period of incubation.” Hansemann admits that this inference is not 
conclusive. 

3. Diseases of the pancreas with diabetes. The following varieties 
are distinguished: 

(a) Cases in which the disease of the pancreas is a result of the diabetes 
(cachectic atrophy). 

(b) Cases in which the diabetes is explained by the total or very wide- 
spread destruction of the pancreas. 

(c) Cases in which the disease of the pancreas assumes the character of 
an accidental affection with which the diabetes stands in no definite 
causal relation. 

(d) A typical variety of disease constantly accompanied by diabetes— 
namely, the genuine granular atrophy of the pancreas. This discovery 
of Hansemann in partial disease of the pancreas is of especial interest. 

The* most frequent lesion in diabetes is atrophy. Hansemann dis- 
tinguishes two forms: The cachectic, which is rare, and the diabetic, 
which is more frequent. According to Hansemann, the two varieties 
are distinguished macroscopically and microscopically. 

‘In cachectic atrophy the pancreas is sharply defined from the sur- 
rounding tissues; the adjacent fat tissue has disappeared corresponding 
to the general emaciation. The organ is cylindric; that is, its thickness 
and its height are about equal. It is also of firm or moderate consistency, 
according to the condition of digestion (even when it has not undergone 
self-digestion). On microscopic examination the lobules appear small, 
the individual cells are small, and the stroma is scanty. Gland cells 
and stroma are atrophied. There is no especial pigmentation of the cells. 

“In diabetic atrophy the pancreas is usually flabby and somewhat 
dark colored. The color is due to the condition of the connective tissue 
and to the small veins within it. The gland is especially diminished 
in its transverse diameter and is transformed into a flat structure. The 
gland lobules are small. The surrounding connective or fat tissue ex- 
tends into the organ, so that the latter often is removed with difficulty. 
At times large adhesions and new-formed bands unite the pancreas with 
the surrounding tissues. Under the microscope the secreting cells show 
no especial change aside from the atrophy; there are particularly no 
opacity, fatty degeneration, nor extensive pigmentation. The stroma, 
however, has not become scanty, as in the cachectic atrophy, but the 
gaps caused by the diminution in size of the gland lobules are more or 
less obliterated. It is largely fibrous, but here and there are recent 
patches of cellular infiltration. Thus an active process is added belong- 
ing to the group of interstitial inflammations, and presenting a decided 
similarity to certain forms of granular atrophy of the kidney.” 

Hansemann describes cases showing an early stage of this process 
with signs of an acute interstitial inflammation, and includes in this 
series the initial stage of the cases described by Lépine as sclérose péri- 


acineuse. 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 77 


According to Hansemann, the genuine granular atrophy of the pan- 
creas inevitably leads to diabetes, as the geniune atrophied kidney pre- 
sents from the beginning characteristic symptoms, while the other affec- 
tions cause diabetes only when they have continued long enough. 

This observation of Hansemann is especially noteworthy; it requires 
confirmation, however, in two ways: 

1. Does this condition actually occur only in diabetes? It may be 
possible that this process occurs also without diabetes, since at autop- 
sies the pancreas often is not carefully examined and is rarely examined 
microscopically, especially in certain groups of diseases of other organs. 
In such instances another explanation might be given. 

2. It might well be wished that the genuine, granular atrophy of the 
pancreas suggested and described anatomically by Hansemann, and 
maintained always to be associated with diabetes, should find general 
acceptance and be recognized with the same certainty as granular 
atrophy of the kidney. This question cannot be decided from reports 
of autopsies. The few cases investigated by us disclosed, as before 
mentioned, only cachectic atrophy. The material necessary to prove or 
disprove Hansemann’s view can be collected only very slowly. There 
is no doubt that a solid foundation for the existence of a pancreatic 
diabetes would be laid were Hansemann’s view correct, but the assump- 
tion urgently needs proof. 

The communications of Lépine on sclérose périacineuse of the pancreas 
in diabetes alone give evidence in its favor. Hansemann concludes that 
‘“‘there is no case in man which opposes the transference of the results 
of the experiments on dogs to men.” 

Dieckhoff proceeds from the certainly surprising fact that in 19 cases 
of pancreatic disease most carefully examined by him diabetes existed 
in 7, no examination was made for sugar during life in one, and diabetes 
was absent only in 11 of the patients. During the same period no other 
cases of diabetes were examined postmortem in the Pathologic Institute. 
Dieckhoff asks three questions: 

1. Is every case of diabetes referable to changes in the pancreas? 
Dieckhoff asserts that this question will hardly be answered in the 
affirmative in the light of the sugar-puncture and the presence of such 
changes in the fourth ventricle in diabetes as tumors, cysticerci, and 
sclerosis. 

2. What diseases of the pancreas cause diabetes? Experiments and 
anatomic observations have shown that diffuse diseases attacking the 
whole organ are more’liable to cause diabetes than diseases which attack 
certain areas. Slight changes in the pancreas, according to Dieckhoff, 
can be assumed to be related to the diabetes, only when changes in the 
fourth ventricle are excluded by the postmortem examination, and 
especially by the most careful microscopic investigation. 

The pathologic changes which are found in the pancreas are various, 
but they have this in common, that they affect to a greater or less extent 
the whole organ and cause its destruction. 

Dieckhoff collects from the literature and from his own: experience 
53 cases of severe diseases of the pancreas with diabetes, as follows: 


PUGIEDG ROTOMEIGME Lia ete kc eR ae wiel a \ paige ly ee cs 5 
CUO TIMATRGPODEIBIE OWEN Gog: Races bieiv oS on Uadletew stand vss 15 + (4?) 
BAER ME 8 i IRS A a a a ak 4 
Degenerative atrophy, lipomatosis .................005 21 


Bs Lt Seat Ba! Dart sie Sage ou. SRA AE a a CAS LAGE me MORAL Ot Re 4 


78 DISEASES OF THE PANCREAS. 


[The theory of Lépine that one of the functions of the normal pancreas 
was to produce a glycolytic ferment influencing the consumption of 
sugar in the organism, and the loss of which was regarded as the cause 
of diabetes, appears to have been materially strengthened by recent in- 
vestigations. It was suggested by Laguesse,* Schafer,t and Diamare t{ 
that the islands of Langerhans probably furnished this internal secretion, 
and Ssabolew 3 endeavored to solve this question experimentally. He 
found that the cells of these islands were more granular in fasting dogs 
than in those fed chiefly with carbohydrates and in whose blood sugar 
had been introduced. He found also that twenty days after ligation of 
the excretory duct the islands persisted, although the gland became 
atrophied. Furthermore, in two cases of diabetes he was unable to find 
islands of Langerhans in the pancreas. He therefore came to the con- 
clusion that the islands were blood-glands and bore some relation to the 
utilization of sugar in the organism. 

W. Schulze|| tied a ligature around portions of the pancreas and 
found the islands unchanged after eighty days, although the actual 
tissue of the gland was extensively replaced by fibrous tissue. He in- 
ferred that the portions of the gland which persist after ligation influence 
sugar metamorphosis, since diabetes results from total extirpation of 
the gland, but does not take place when the excretory ducts are tied 
and a successful transplantation has been made. 

E. L. Opie ** directed his attention especially to the conditions of the 
islands of Langerhans in diabetes. He recognized two varieties, an 
interlobular and an interacinar, of chronic pancreatitis. The islands of 
Langerhans are affected in the former only when the sclerosis is extreme, 
and in 11 cases of interlobular pancreatitis diabetes was present in but 
one, and was of a mild type. The pancreas, however, showed a very 
advanced degree of inflammation and the islands were altered. In two 
out of three cases of interacinar pancreatitis, on the other hand, the 
islands of Langerhans were invaded by the new-growth of fibrous tissue, 
were atrophied, and diabetes was present. In two other cases of dia- 
betes, in one of which the pancreas was soft and of a gray-yellow color, 
there was hyaline degeneration of the islands, and to such an extent in 
one case as to prevent their recognition. 

Opie showed that when diabetes is caused by a lesion of the pancreas 
the islands of Langerhans are injured or destroyed, and when the pancreas 
is diseased and there is no diabetes the islands are relatively unaffected. 
In chronic interacinar pancreatitis with diabetes the sclerosis may be so 
slight as to be definitely recognized only with the microscope, and where 
there is extreme sclerosis or atrophy without involvement of the islands 
of Langerhans there is no diabetes. 

Weichselbaum and Stangl +} examined the pancreas in 18 cases of 
diabetes, and found more or less striking alterations of the islands of 
Langerhans in all of them. They were diminished in number, absolutely 
and relatively, to a remarkable degree, and those which were seen were 

* Compt. Rendu Soc. de Biol., 1893. v, 819, Journal de l’Anat. et Phys., 1896, 
XxxiI, 208. 

t Lancet, 1895, 11, 321. 

t Intern. Monatsschr. fiir Anat. u. Phys., 1899, xv, 177 

§ Centralbl. f. allg. Path. u. path. Anat., 1900, x1, 207. 

| Arch. f. mikr. Anat. u. Entwickelungsgesche, 1900, iv, 491. 


** Jour. Boston Soc. Med. Sci., 1900, tv, 251; Jour. Exp. Med., 1901, v, 397, 528. 
Tt Wiener klin Woch., 1901, x1v, 968. 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 79 


more or less altered. In two cases they were hemorrhagic; many islands 
were atrophied and irregular in shape, as if compressed. Others were so 
homogeneous as to suggest obliterated renal glomeruli. Although in all 
cases the pancreas was atrophied, the atrophy differed from other varie- 
ties in the predominant affection of the islands of Langerhans. 

Further confirmation of Opie’s statements has been made by Wright 
and Joslin.* Portions of the pancreas from nine cases of diabetes were 
examined, and in two hyaline change in the islands of Langerhans were 
found. In the remaining seven cases there were no lesions of the pan- 
creas except in one in which there was a fibrinous cellular exudation in 
the fibrous septa of the gland. Herzog} examined the pancreas in five 
cases of diabetes with results well in accord with those above mentioned. 
As Opie justly remarks: ‘‘What has been learned concerning the relation 
of the pancreas to diabetes is the relation of the islands of Langerhans 
to the disease.’”’—Eb. ] 

3. How are the changes in the pancreas without diabetes to be ex- 
plained? In slight or circumscribed affections, as in the experiments on 
animals, sugar is not likely to occur in the urine. In extensive, diffused 
alterations a remnant of the gland sufficient for the function concerned 
always may be present. Even the microscopic examination does not 
positively settle this question. 

It is most difficult to explain these cases without diabetes in which 
the anatomic changes are often much more severe and extensive than in 
the cases with diabetes. Dieckhoff collects nine such cases, in which 
the pancreas was almost entirely destroyed and yet there was no diabetes. 
He explains this by the rapid course of the disease or by complications, 
as abscess or peritonitis, under which circumstances there was also no 
diabetes in the animals experimented upon. But this assumption does 
not explain all the cases. When disease of the pancreas exists a long 
time without diabetes, it is possible that the severe complicating disease 
is also to be regarded as a cause; “it is then necessary to conclude that 
the relation between the changes of the pancreas and the excretion of 
sugar 1n man are not so simple as in the dog.” 

If the results of animal experimentation, the tabulated collections 
of clinical and anatomic facts, the critical remarks concerning the pre- 
viously mentioned statistics, and the attempts of Hansemann and Dieck- 
hoff to reconcile the clinical and anatomic facts with the results of animal 
experimentation are borne in mind, it must be agreed that there is no 
difficulty in explaining the conditions found in man in the light of the 
experiments on animals: 

The cases of total or very extensive destruction of the pancreas 
with diabetes are analogous to the total extirpation of the pancreas 
and explain the occurrence of diabetes. 

The cases of atrophy not due to cachexia and affecting nearly the 
whole gland, of fatty degeneration, induration, calculus formation, with 
extensive atrophy or fatty change, of new formations or cysts replacing 
the whole organ, belong in the category of total extirpation. 

Limited diseases of the pancreas, abscess formation, and carcinoma, 
like partial extirpation, may cause a severe diabetes. The latter occurs 
in the experiments on animals when the rest of the gland gradually dies. 
All the instances of focal and partial diseases of the pancreas do not be- 


* Jour. of Med. Research, 1901, v1, 360. 
t Trans. Chicago Path. Soc., 1901, v, 15. 


80 


long in this series. 


DISEASES OF THE PANCREAS. 


In such cases the assumption is plausible that the 


pancreatic disease and diabetes occur simultaneously. This view is not 
in opposition to the experiments on animals. 
There are two objections to the transference to man of the results of 
the experiments on animals: 
1. There are cases of diabetes without any demonstrable changes in 


the pancreas. 


Neither the most careful macroscopic nor the most search- 


ing microscopic examination shows any noteworthy changes. A list of 
such cases is included in the following table: 


XI. NORMAL PANCREAS IN DIABETES. 








AUTHOR. AGE. SEX. CONDITION OF THE PANCREAS, REMARKS. 
De Bary: Wegeli, 1895 | 9 IF, | Pancreas smooth, flabby, 
pale, microscopically nor- 
mal, 
Cantani and Ferraro:) 53 F. | Pancreas normal.  Micro- 
oy Morgagni,”’ scopically no staining of 
1883. nuclei (a postmortem 
phenomenon). 
30 M. | The same condition. 
Heubner: Weegeli, v4 ? | Pancreas not atrophied. 
1895. Twelve cm. long. 
Hirschfeld: “ Zeitschr. | 61 F. | Pancreas narrow, 76 gm. 
f. klin. Med.,’’ 1896. No anomaly, either macro- 
scopic or microscopic. 
55 M. | Pancreas normal, 93 gm. 
56 F. | Pancreas normal, 93 gm. 
Lépine:“ Lyon med.,” | 40 M. | Normal microscopic appear- 
1301, ances in liver and pancreas. 
Obici: “ Boll. Scienze ? ? | No changes in pancreas, Severe diabetes 
med.,” 1893. of rapid 
course. 
Sandmeyer: ‘“Deut.| 9 F. | Pancreas normal. Death in coma. 
Arch f. klin. Med.,”’ 
1892. 
Thiroloix: ‘ Diabéte | 28 M. | Macroscopically and micro-| Sudden _ onset. 
pancreat.,”’ 1892. scopically normal. Very marked 
polyuria. 
69 F. | Pancreas and solar plexus | Emphysema. 
normal, Dilatation of 
heart. 

58 M. | Pancreas normal, Death with 
symptoms of 
uremia. 

60 F. | Pancreas normal, Death from 

pneumonia of 
. right side. 
Williamson: “Brit.| 21 F. | Pancreas small, weight light.| Rapid course of 
Med. Jour.,’”’ 1894. Microscopically no changes.| disease. 

















The pancreas in diabetes is elsewhere very frequently mentioned as 


normal; Hansemann mentions 8 such cases. Among the reports of 
autopsies at the General Hospital, the pancreas is characterized as normal 
in ten instances, but it is not stated that a microscopic examination 
was made. 

Closely allied are the conditions like cachectic atrophy, in which the 
alterations of the pancreas are distinctly to be regarded as results of the 
diabetes, or the cases in which the pancreatic disease followed the ‘dia- 
betes, or those in which the alterations probably were not present in 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 81 


life, but are to be regarded as evidence of an autodigestion. Table X 
doubtless contains such cases. Also to be included are those cases in 
which, as mentioned before, partial disease of the pancreas and the dia- 
betes are concurrent as accidental conditions without causal relations. 

There is no difficulty in explaining ‘this list, if it is assumed that 
diabetes is no isolated disease, but may result from various causes. 

This is not the place to further investigate this subject, but there is 
no doubt from the present state of our knowledge, that transient and per- 
manent glycosuria may occur from causes other than those which are 
referred to the pancreas. It is not denied that the time may come when 
it shall be discovered that the pancreas alone Dee the leading part in 
the pathogenesis of diabetes. 

At present it is not justifiable to decide that the pancreas is the sole 
cause of diabetes. By assuming that there are various causes of diabetes, 
all the cases may be explained; for example, those in which the pancreas 
is perfectly normal both macroscopically and microscopically, those in 
which there are secondary changes in the gland which with certainty are 
not to be regarded as the cause of the diabetes, those in which there 
are slight changes, to be considered as postmortem processes of diges- 
tion, and also the instances of localized affections in which the greater 
portion of the gland is normal. The cause of the diabetes which may 
accompany all of these conditions, according to our present knowledge, 
is to be sought elsewhere than in the pancreas. 

2. The real difficulty lies in the fact that extensive diseases of the 
pancreas, which have led to a destruction of the whole organ, are not 
infrequently without diabetes. In the following table a list of such cases 
is given: 


XII. TOTAL DESTRUCTION OF THE PANCREAS WITHOUT DIABETES. 





AUTHOR. AGE. SEX. CONDITION OF THE PANCREAS, REMARKS, 





Dieckhoff: ‘ Beitr. z. i M. | Tail of pancreas seques- 
path. Anat. d. trated, the rest partly de- 
Pankr.,”’ 1896. stroyed by suppuration 

and partly beset with 

areas of fat necrosis. Puru- 
lent peritonitis. 

60 M. | Pancreas contains numerous 

greenish-yellow masses of 

pus; in some places firm, 
indurated substance. Gel- 
atinous cancer of duo- 
denum. Hepatic abscess. 

Cireumscribed abscess be- 

tween stomach and omen- 


tum. 

Hansemann: “Zeit-| 52 F. | Pancreas cancerous through- 
schr. f. klin, Med.,”’ out. Numerous metas- 
1895. tases. 

41 M. | Diffuse carcinoma of pan- 
creas. 
56 M. .| Large primary carcinoma 
+ involving the whole 
gland. 


33 M. | Whole pancreas _trans- 
formed into a tumor of size 
of man’s head. Cancer of 
pylorus. 























82 DISEASES OF THE PANCREAS. 
XII. Toran DestrucTION OF THE PANCREAS WITHOUT D1ABETES.—(Continued.) 
AUTHOR. AGE. | SEX. CONDITION OF THE PANCREAS, REMARKS, 
Litten: “Charité- | 45 M. | Pancreas and solar plexus | Duration of dis- 
Annalen,”’ 1877. entirely concealed in a! ease one year. 
glandular mass infiltrated | Gradual, then 
with carcinoma. Medul-| very marked 
lary carcinoma of stom-| decline. Pain 
ach, omentum, left kidney,| in left lum- 
and left ureter. Both ad-| bar region. 
renals and abdominal} Urine:  albu- 
glands infiltrated. Can-| min, blood, no 
cerous metastasis in duo-| sugar. Stools 
denum. normal, 

28 M. | Pancreas changed intoacal-| Pains in right 
lus, without trace of gland} hypochondri- 
structure, embedded in| um. _ Ascites. 
degenerated lymph-glands.| Urine normal. 
Primary carcinoma ventr.| Appetite good. 
Carcinoma of diaphragm,} About three 
liver, and lymph-glands.| months in dur- 
Peritonitis carcin. ation. 

43 F, | Pressure atrophy of pan-| Always healthy. 
creas, replaced by edemat-| Duration of 
ous connective tissue.| disease 24 
Single small remnants of | months. High 
glands, with nuclei which |. degree of 
do not stain. General} dropsy, hydro- 
dropsy. Medullary swell-| thorax and 
ing of epigastric and] ascites. Other- 
mesenteric lymph-glands,/ wise no symp- 
fused with neighboring; toms. Urine 
organs (pancreas). normal, 

59 F. | Primary carcinoma of pan-| Ascites for 3 
creas with entire destruc-| months. Pains — 
tion of the organ. Can-| in right hypo- 
cerous embolism of portal| chondrium 
vein. Diffuse infiltration | during the last 
of liver. Gastric ulcer.| weeks. No 
Swelling of abdominal} disturbancesof 
lymph-glands. digestion. 

; Urine normal. 
Ziehl: “Deutsche | 34 F, | Primary carcinoma of pan-| Once intermit- 
med. Wochenschr..,’’ creas, growing around the| tent fever. 
1883. aorta and both adrenals. Acute  begin- 
ning with 

chill, —_ fever, 

and pains in 

: epigastrium. 
After one 
month, re- 














peated hema- 
temesis. Ema- 
ciation. After 
4 weeks, as- 


cites, icterus, 
attacks of 
pain in epi- 
gastrium 
daily; col- 
- lapse. Dura- 


tion of disease, 
94 weeks. 





GENERAL PATHOLOGY AND SYMPTOMATOLOGY. ° 83 


Hansemann describes also some cases in which, however, the micro- 
scopic examination showed that gland substance was present. 

The cases in which the pancreas is apparently entirely destroyed, 
while on microscopic examination normal gland substance can be shown, 
have their analogue in the experiments on animals. The whole gland 
apparently has been extirpated, permanent diabetes did not follow, 
and after death, a portion of the normal gland has been found. Those 
* eases, on the other hand, in which, in spite of entire destruction of the 
pancreas, diabetes has not developed, do not correspond to the results 
of experiments on animals. Hansemann, in speaking of a case in which 
the whole pancreas was transformed into a tumor (carcinoma) of the 
size of a man’s head, but which, on account of defective data, he did not 
consider sufficiently conclusive, says: “‘If a new similar observation were 
made with especial inquiry on this point, then I admit we should have 
to confess that there are exceptions, and with this admission, however 
rare the exceptions might be, the whole theory would lose much of its 

force.”’ | 

In spite of the attractive hypotheses which have been advanced, we 
have at present no satisfactory explanation of the lack of diabetes in 
many cases of total destruction of the pancreas. For instance, in the 
chronic cases of totally destroyed gland in which no carcinoma was 
found, even Hansemann’s hypothesis is not sufficient for explanation, 
and a gap exists which still is to be filled. 

Notwithstanding the important experiments on animals, there still 
remains much that is unexplained in the question of pancreatic diabetes 
in man, and further investigation is required to solve satisfactorily the 
whole question. 

The following conclusions only are to be drawn at present: 

1. The undoubted presence of diabetes when the pancreas is micro- 
scopically and macroscopically perfectly normal indicates, in connection 
with other experimental and clinical facts (sugar-puncture, disease of 
the fourth ventricle, etc.), that there are various causes of diabetes. 

2. Diseases of the pancreas may be regarded as one of these causes, 
as is shown by a number of clinical and anatomic facts, which fully 
correspond with the results of experiments on animals. 

3. The absence of diabetes in man in the not infrequent cases of 
total destruction of the pancreas cannot at present be definitely ex- 
plained. It is, however, possible that on further investigation a satis- 
factory explanation in harmony with the results of experiments on 
animals may be found. Facts, however, may be brought to light which 
in various directions will indicate that there is a difference in man and 
animals in the method of origin of pancreatic diabetes. 


2. FATTY STOOLS (STEATORRHEA) AS A SYMPTOM OF 
DISEASES OF THE PANCREAS. 


In the physiologic considerations the influence of the pancreatic 
juice on the digestion of fat has been stated, especially its emulsifying: 
property and its influence on the cleavage of fat, and the question now 
is whether in the diminution or total destruction of this pancreatic func- 
tion, through disease or entire destruction of the gland, symptoms of 
disturbed fat digestion would be demonstrable in the stools. 


84 DISEASES OF THE PANCREAS. 


As the emulsification and cleavage of the fat are functions not belong- 
ing exclusively to the pancreas, but are carried on also by the bile and — 
through the agency of intestinal bacteria, it can readily be under- 
stood that these symptoms will not occur regularly. 

In order to decide this question, it is desirable to examine the results 
of experiments on animals, and also to learn the clinical facts. 


(a) EXPERIMENTAL RESULTS. 

From experiments which caused the degeneration of the pancreas 
by means of the injection of fat, ether, and other substances into the 
main excretory duct, Claude Bernard came to the conclusion that the 
pancreatic juice had the following functions: (1) The cleavage of neutral 
fats; (2) the emulsification of these fats; (3) the promotion of the absorp- | 
tion of the fats through the presence of the pancreatic juice in the intes- | 
tine. 

Soon after Bernard’s communication appeared, the experiments were © 
repeated in France and Germany with various methods, and other results 
were obtained. . 

Frerichs tried to destroy the pancreas by numerous ligatures and fed 
the animals with fat; at the postmortem examination the lacteals were 
found more or less filled with white chyle. Herbst had the same result. 
Weinmann caused pancreatic fistula in dogs, fed the animals on food 
rich in fat, and found no fat in the feces. It must certainly be stated 
that these experiments show absolutely nothing, because, according to 
Weinmann’s statement, a portion of the pancreatic juice might have 
reached the intestine through a second pancreatic duct. 

Bernard’s teachings were opposed by Bidder and Schmidt in Germany, 
and by Bérard and Colin in France. The latter investigators extirpated 
the pancreas in five dogs and left only that portion lying next the portal 
fissure. The animals lived for eight months and showed absolutely no 
changes of the digestive functions and the feces contained no undigested 
fat. 

Schiff injected paraffin into the main excretory duct in dogs; he 
claims that the digestion of fats went on normally. 

Hartsen extirpated the pancreas in pigeons; the digestion of the fats 
is said to have been disturbed by this proceeding. The feces of the 
birds operated upon contained three times as much ether extract as the 
feces of healthy birds on the same food. Langendorff tied the pancreatic 
duct in pigeons, but was unable to confirm Hartsen’s results. 

Pawlow, by tying the Wirsungian duct of rabbits, caused atrophy 
of the gland. The absorption of fats was not disturbed, at least the 
feces appeared normal. The same result was obtained by Cash, Arnozan, 
and Vaillard. On the other hand, Senn, after extirpation of the pancreas 
in dogs and cats which lived several days after the operation, found in 
the feces much undigested fat. Martinotti (1888) extirpated the pan- 
creas in dogs, but not thoroughly, and probably not with the view of 
studying the influence of the pancreatic juice on the digestion of fat; 
he made no estimate of the amount of fat in the feces; but decided, 
because the animals did not diminish in weight, that the absorption of 
the fat had not suffered. 

The most thorough experiments were carried on by Abelmann, who, 
under the guidance of Minkowski, made metabolism experiments in the 
most careful manner on dogs from which the pancreas had been partially 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 85 


or wholly extirpated. He tried to ascertain the quantity of fat in the 
stools after the administration of certain definite amounts of fat, and 
also to estimate in the feces the amount of unchanged neutral fat, fatty 
acids, and soaps. From his experiments it appeared that when the 
pancreas was entirely lacking, non-emulsified fat was not at all absorbed, 
and emulsified fat only in small amount (18.5%). The absorption of 
fat in the form of milk resulted much more favorably: on the adminis- 
tration of large amounts, 30%, and with smaller amounts, 53%. In 
case of partial extirpation, small amounts of emulsified fat were about 
‘half used up; after the administration of larger amounts of 70 to 150 
gm. the consumption was not so good (lowest value 31.5%). Milk 
was very well used up to 80%. Administration of pig’s pancreas as 
food facilitated the absorption of fat after the extirpation of the pancreas. 
Abelmann concludes that all fat with the exception of milk needs un- 
questionably the influence of the pancreas for its absorption. 

Sandmeyer, in his experiments, found variable results: Non-emulsified 
fats were not utilized or slightly absorbed or from 30 to 78% was taken 
up; 42% of emulsified fat was absorbed. Like Abelmann, he was able 
to obtain a better utilization of the fat by the addition of pancreas to the 
food. 

The brothers Cavazzani, after extirpation of the pancreas, found 
that the fat was not used up. A dog the pancreas of which was extir- 
pated a few weeks before, rejected fat but ate soap with great eagerness. 
After a while there was a better absorption of the fat, since the bile 
assumed a portion of the function and acted energetically on the fats. 

Baldi, as previously mentioned, fed dogs from which the pancreas 
had been extirpated with meat from which the fat had not been removed, 
and was able to observe in the stools large amounts of oily fat, which 
was not solid at temperature of the room, in spite of the fact that the 
fat of the meat was solid. So high a degree of steatorrhea was never 
observed after tying the bile-duct. 

Rosenberg, by cutting the pancreatic duct and tying the arteries 
and veins, produced atrophy of the gland; the feces evacuated in large 
amounts were clayey and showed a large amount of fat. 

In one of our experiments on animals Katz found a surprising diminu- 
tion in the cleavage of fat after partial extirpation of the pancreas and 
tying of the main excretory duct. The analysis of the feces, the absolute 
amount of which was not abnormally large, gave the following result: 


UCU rg 6. 1 ea a a a 51.68% 
PRILY BOMAB io tai Sse nhck adele AS een OD We dea Hee es 46.04% 
BOBOR 66 Se bane pe iia 2 Rim beet i St Ree os Ae eee 2.338% 


(b) CLINICAL EXPERIENCES. 


There are three groups of clinical experiences with fatty stools: (1) 
Fatty stools in diseases of the pancreas; (2) diseases of the pancreas: 
without fatty stools; (3) fatty stools without diseases of the pancreas. 

1. The statistics of the concurrence of fatty stools and diseases 
of the pancreas are quite numerous. 

Kuntzmann (1820) was probably the first who associated fatty stools 
with diseases of the pancreas. He described the abundant evacuation 
of fat in the stools of a man who died from induration of the pancreas 
with obliteration of the Wirsungian duct, chronic jaundice, and dropsy. 


86 DISEASES OF THE PANCREAS. 


R. Bright, in 1833, reported 7 cases of pancreatic disease, in 3 of 
which fatty stools were found. As Lloyd states, ‘‘icterus was the only 
symptom common to all of Bright’s observations.”’ . 

Since then the interest of authors has been directed to the concurrence 
of fatty stools and diseases of the pancreas. At first Lleyd and Elliot- 
son published similar communications. Gould, in 1847, reported a case 
of calculus and cyst of the pancreas with a large amount of fat in the 
stools. 4 : | 

Reeves in 16 cases of fatty stools found diseases of the pancreas 11 . 
times: fatty degeneration, cancer, induration of the head with closure 
of the Wirsungian duct, cysts in the head of the pancreas with oblitera- 
tion of the pancreatic duct and ductus choledochus, concretions in the 
ductus pancreaticus, and 6 times there was simultaneous disease of the 
liver; in only 5 cases was the pancreas intact. Griscom reported 24 
cases (14 fatal) in which fatty stools occurred; 8 times an affection of 
the pancreas was shown at the autopsy; there was no postmortem ex- 
amination of four of the patients. Moyse gives a similar report. 

The communication of Fles, 1864, is of especial interest. A diabetic 
who had eaten much bacon and fat meat evacuated with the stools such 
a quantity of fat that it could be skimmed from the surface of the feces 
by the ounce. The fat disappeared from the stools when an emulsion 
prepared from the pancreas of a calf was given to the patient. As soon 
as the emulsion was omitted, the fatty stools again occurred. This 
experiment was repeated several times with like results. At the autopsy 
there was so complete a disappearance of the pancreas that only connec- 
tive tissue with scarcely any recognizable traces of gland substance 
remained. At the same time, however, there was also atrophy of the 
liver. 

Ancelet collected from the literature 16 cases of steatorrhea in dis- 
eases of the pancreas, in 5 of which the pancreatic duct, as well as the 
ductus choledochus, was closed. In three cases the former alone was 
closed and in one there was also a pancreatitis. 

Silver’s case was one of diabetes with fatty stools in a man thirty-two 
years old. The entire pancreas had undergone fatty degeneration; it 
was partly calcified and no gland substance was present. 

Friedreich reported 2 cases of steatorrhea. In both, jaundice was 
present. 

Bowditch (1852) reported diarrhea with a large amount of fat in the 
feces in a case of carcinoma of the pancreas. Carcinoma of the liver and 
jaundice also were present. . | 

Molander and Blix described a case of steatorrhea in carcinoma of 
the pancreas. Icterus was present. There was a similar condition in 
Ziehl’s case; a large amount of fat in the stools, about 50% of the dry — 
feces; there were also closure of the ductus choledochus and jaundice. 
Demme found an abnormal amount of fat (64% to 73.3%) in the asbestos- 
like feces of a case of congenital syphilis and atrophy of the pancreas. 
goer were also jaundice of the skin, perihepatitis, and gummata of the 
iver. 

There were fatty stools in the cases of pancreatic cyst reported by 
Goodmann, Bull, and Gould; also in the cases of cancer which were 
published by Clark, Besson, Marston, Martsen, Rocques, Luithlen, 
Labadie-Lagrave, Pott, Maragliano, and Mirallié. Jaundice was noted 
by Gould, Clark, Pott, Maragliano, and Mirallié. 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 87 


Harley reported a case of pancreatic abscess with fatty stools and 
jaundice. 

In a case of fibro-adenoma of the pancreas successfully operated upon 
and recently reported by Biondi, fatty stools were found, also traces of 
sugar and jaundice. 

Steatorrhea has been observed also in calculi of the pancreas; in 
addition to the cases already mentioned by Clark, Gould, Reeves, are 
those of Capparelli, Copart, Cowley, and Lancereaux. In the case de- 
scribed by Lichtheim, numerous fat crystals were found. 

A communication of Le Nobel is of interest. A diabetic sixty-one 
years old observed that his stools contained much fat. Although there 
was no jaundice, the stools were colorless and contained an abundance 
of fat. There was an entire absence of all biliary constituents, as well 
as of hydrogen sulphid, indol, skatol, leucin, and tyrosin. The feces 
had a sour odor like rancid butter, but no fecal smell. Microscopically 
no micro-organisms were present, but there was an abundance of fatty 
acid crystals without soaps. Bile pigments and bile acids were absent. 
No autopsy was held. 

Le Nobel thought that the lack of fat-acid salts, the absence of all 
products of putrefaction in the stools, and the occurrence of maltose in 
the urine were positive evidence of an affection of the pancreas. 

Clay-colored stools abounding in nitrogen and fat were found by 
Hirschfeld in 6 cases of diabetes. According to him, this sign, in con- 
nection with the colic frequently observed in this patient, might 
be used to place cases of this kind in a special category and to indicate 
that a disease of the pancreas was of pathogenic importance. 

The following observation is from my own experience, and further 
details will be given in the section on cancer: 

In a woman thirty-nine years old there had been diarrhea since the 
summer of 1892. The patient became emaciated, yet the appetite re- 
mained good. Fecal evacuations appeared regularly at night, were 
unusually copious, of the consistency of thick porridge and of cadaverous 
odor, chocolate-colored, and always abundantly covered with fat rings. | 
On the 11th of January, 1893, I saw the patient for the first time, and 
found steatorrhea. The investigation of the stools gave the following 
result: Large in amount and of the consistency of thick porridge; in 
the sediment were scattered white particles. Microscopic examination: 
(1) Very numerous fragments of striated muscle, in the main with well- 
preserved structure; (2) numerous fat-acid needles and fat-drops; 
(3) bacteria and detritus. : 

After drying the stools for several days on the water-bath in order to 
determine the amount of fat, there were obtained 4.6325 gm. of solid 
substance, in which 2.1265 was fat, representing 45.9% of the dried 
_residue. The ether extract consisted almost entirely of neutral fat. 
On the 18th of January I found in the epigastrium a distinct hard, round 
tumor, which was diagnosticated as carcinoma of the head of the pan- 
creas. In March, jaundice developed. At the, beginning of April an 
exploratory laparotomy was undertaken and the diagnosis was confirmed. 

2. The literature of diseases of the pancreas without fatty stools 
is abundant. In the special portion of this section but few statements 
are made regarding the presence of fatty stools in diseases of the pan- 
creas. In many cases nothing is said about the condition of the stools, 
and only in the rarest instances are exact chemical investigations under- 


- 


88 DISEASES OF THE PANCREAS. 


taken, so that the lack of a positive statement can in no case be regarded 
as evidence to the contrary. From the earlier collections of cases, it 
may be mentioned that Ancelet in 330 instances of disease of the pancreas 
found fatty stools 28 times. ; 

Statements also appear concerning the lack of fatty stools when 
the pancreas ‘is totally destroyed; thus, Litten reports four cases of 
total degeneration of the pancreas with normal stools and without dia- 
betes. 

Hartsen, in two diabetics, in whom the autopsy showed atrophy of 
the pancreas amounting almost to total disappearance of the gland, 
in spite of the daily administration of 8 to 10 teaspoonfuls of cod-liver 
oil, was unable to show the presence of any unusual amount of fat in the 
stools. 

The most important work in this connection is that of Friedrich 
Miller. In two cases investigated by him, one of total obliteration and 
the other of cystic degeneration of the pancreas, he was unable to find 
any increase over the normal amount of fat in the feces, although sufficient 
fat was given in the food. The feces, examined with the naked eye, 
microscopically, and chemically, were similar to the dejections of a 
normal individual. 

Miiller attributes the occurrence of fatty stools in diseases of the 
pancreas to disturbances in the secretion of bile, which in a very large 
number of observations take place at the same time; this conclusion is 
due to the fact that the withdrawal of bile always leads to the poor 
absorption of fat. From his investigations carried on with jaundiced — 
patients, Muller comes to the following conclusions: 

(a) If the bile is excluded from the intestine, the absorption of fat 
suffers very considerably. In his experiments, when there was a total 
lack of bile, 55.2% to 78.5% of the fat in the food was evacuated with 
the feces, while in the normal individual only 6.9% to 10.5% is found. 

(b) If the pancreatic juice is excluded from the intestine, there is no 
increase of fat in the stools, and it is doubtful whether steatorrhea is a 
symptom of purely pancreatic diseases. 

(c) The absence of pancreatic juice causes no quantitative change 
in the condition of the fat of the feces. The cleavage of the neutral fats 
is a function of the pancreatic juice. In three cases in which there was 
an obstruction of the Wirsungian duct and a degeneration of the gland, 
a much smaller cleavage of the fat than normal was demonstrable (39.8% 
as compared with 84.3%). Miller concludes that when there is a lack 
of pancreatic juice, the cleavage of the fats goes on less energetically 
than normally. i 

3. Fatty stools without alteration of the pancreas. 

(a) An abnormally large quantity of fat may occur in the stools of 
a healthy man when so large an amount of fat is taken with the food 
that all cannot be absorbed by the intestine. 

(6) Steatorrhea occurs when bile is absent from the intestine, as is 
ha especially by the investigations of Nothnagel, Gerhardt, and 

er. 

(c) The fat is increased in the stools, although the amount of fat in 
the food remains the same, when there is disease of the mucous mem- 
brane of the intestine and of its lymphatics, especially of the mesenteric 
glands, rendering the absorption of the fat difficult or impossible. The 
abundant fat in the stools is thus explained in extensive atrophy of the 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 89 


mucous membrane of the small intestine, in amyloid disease and tuber- 
culosis of the same, in caseation of the mesenteric glands, in chronic 
tuberculous peritonitis, and perhaps in some catarrhal processes (Noth- 
nagel). 

It is evident from the clinical facts reported that the presence of fatty 
stools alone is not of value in the recognition of diseases of, the pancreas, 
because steatorrhea may arise from different causes. The formerly well- 
accredited doctrine of the importance of steatorrhea in the recognition 
of diseases of the pancreas has recently been discredited especially on 
account of the thorough work of Friedrich Miller, whose results we have 
learned. 

Miiller’s proof is twofold. He shows the presence of fatty stools 
in the absence of any affection of the pancreas, especially when bile is 
excluded from the intestine, and he finds a normal amount of fat in the 
stools in undoubted disease of the pancreas. Miller says that it is 
difficult to believe that there are no fatty stools when the pancreatic 
juice alone is excluded from the intestine, especially as there have been 
no accurate metabolism experiments either on animals or man. 

At present, however, there are very suggestive and convincing experi- 
ments in this direction. Metabolism experiments on animals have been 
carried on by Minkowski, Abelmann, Sandmeyer, Cavazzani, Baldi, 
and Rosenberg, and on man by Hirschberg. The experiments on animals 
show with some variations that after extirpation, as well as after destruc- 
tion of the gland tissue, there is a poorer consumption of the fats, with 
the exception of that of milk. That the increased or diminished fat 
absorption is to be ascribed to the lack of-the pancreatic juice in the 
intestine is shown by the fact that in several experiments there was a 
better absorption of fats when the animals were at the same time fed 
with the minced pancreas of a pig. 

There is still much that is not clear in the experiments on animals; 
for instance, there is at present no answer to the question why in the 
absence of the pancreatic juice bile does not supply its place. 

Do the results of the experiments on animals harmonize with the 
clinical facts, especially with the somewhat diverging results of Miiller’s 
series of experiments? Miiller was certainly correct in assuming that 
it is not justified, in the relatively frequent cases of disease of the pan- 
creas and fat stools occurring at the same time with jaundice, to refer 
the steatorrhea with certainty to the disease of the pancreas, because 
the exclusion of bile from the intestine is alone sufficient to explain 
the poor fat absorption; but, on the other hand, the possibility must be 
admitted, because of the results of experiments on animals, that in 
these cases the consumption of the fat was poor even without jaundice. 

Miller says also that it is difficult to believe that there are no fat 
stools when the pancreatic secretion alone is excluded. 

Abelmann explains the two cases of pancreatic disease without fatty 
stools investigated by Miiller, as well as all similar negative cases, by 
the assumption that a portion of the pancreas, even if very small, 
still acts normally. For the case of pancreatic cyst which Miller 
investigated, this idea is plausible. For the other case, however, in 
which there was a closure of the Wirsungian duct by concretions, as a 
result of which the gland atrophied, this explanation is applicable only 
on the assumption that there was a second pancreatic duct through which 
some pancreatic juice reached the intestine. 


90 DISEASES OF THE PANCREAS. 


It must be admitted on the basis of experiments on animals that 
steatorrhea may occur in total or very severe disease of the pancreas. 
The relative infrequency of its occurrence undoubtedly depends on the 
fact that the bile assumes a vicarious function, and that the presence 
of a second excretory duct furnishes the pancreas a means of furthering 
the digestion of fat even in case only a small bit of the gland is 
connected with the open duct. 

The infrequency of the statements regarding the presence of fatty 
stools in diseases of the pancreas may also be explained by ‘the fact 
that examinations of the stools, and particularly metabolism experiments, 
are rarely made and especially are recognized only in striking instances. 
The most of the diagnoses of diseases of the pancreas are made either by 
an operation or by a postmortem examination, and careful examinations 
of the stools are rarely made before the operation or autopsy. One 
therefore can say nothing of most of the cases, and only a few data appear 
concerning Miiller’s important observation regarding the deficient 
cleavage of fat in diseases of the pancreas. 

It cannot, therefore, be positively stated at present what the condi- 
tions really are, as the literature gives no standard of judgment. In- 
vestigations are lacking on animals as well as on man. The knowledge 
regarding the absorption of fat has still many unsettled points. It is 
probably to be explained by the experiments on animals why, in total 
extirpation of the pancreas, the bile does not perform its function, and 
why the experiment with the simple ligation of the excretory duct, even 
where there was only one, caused no essential disturbance in the absorp- 
tion of the fat. There is a contradiction also between the experiments on 
animals and the observations in man in regard to the cleavage of fat. 
After total extirpation of the pancreas, Abelmann found normal fat- 
cleavage, while Miller showed a disturbed cleavage of the fats but no 
steatorrhea. It is mysterious and entirely unexplained why, after partial 
extirpation of the pancreas, although so conducted that no pancreatic 
juice could reach the intestine, up to one-half of small amounts of non- 
emulsified fat and up to 80% of milk were used up, while after total 
extirpation no emulsified fat was absorbed. In both cases there was an 
entire lack of pancreatic juice in the intestine, and yet there was this 
difference. Exact metabolism experiments in man are needed also, in 
order to ascertain whether, in case of simple obstruction of the ductus 
choledochus, the digestion of fat does not show essential qualitative and 
quantitative differences according to the open or closed condition of the 
pancreatic ducts and whether the disturbance in fat-cleavage observed 
by Miler really occurs only in affections of the pancreas, and how these 
facts are to be brought into harmony with the diametrically opposite 
results in the experiments on animals. 

In spite of the many gaps and obscurities, it must be asserted, on the 
basis of experiments on animals and of a small series of clinical and 
anatomic facts, that there are cases of fatty stools which under certain 
conditions indicate directly a disease of the pancreas. | 

What is known at the present time can be stated as follows: 

1. Steatorrhea alone gives no evidence which points to disease of 
the pancreas. 

2. It is possible that. disturbed fat digestion is caused by a disease of 
the pancreas when there are neither jaundice nor disease of the intestine. 

3. The probability that a disease of the pancreas exists increases and 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 91 


may become certain when, jaundice being absent, symptoms still occur 
which point to the pancreas, as, for instance, defective consumption of 
nitrogen (azotorrhea), diabetes, or a tumor in the region of the pancreas, 
as in the case observed by me. 

4. There may be diabetes and at the same time poor absorption of 
fat without disease of the pancreas. 

5. It cannot, at present, be stated positively to what extent the dis- 
turbed cleavage of fats, which is certainly an essential function of the 
pancreas, may be used as a pathognomonic symptom of an affection 
of the pancreas. Miiller’s cases give a positive indication. 


3, FAULTY DIGESTION OF ALBUMIN (AZOTORRHEA),. 


Experiments on animals give some evidence concerning the defective 
digestion of albumins. Abelmann found that when the pancreatic juice 
was lacking, the albuminous substances were partly absorbed, to the 
extent of about 44% in dogs which were without pancreas and 54% in 
dogs which still possessed a small piece of the gland. The variations in 
absorption were ascribed by Abelmann in part to the poorer consumption 
of the fat introduced at the same time, since steatorrhea certainly exerts 
an influence on the absorption of the other food-stuffs. When pig’s 
pancreas was given with the meat, in the one series 74% and in the 
other 78% of the nitrogen administered was absorbed. After the ad- 
ministration of pure pancreatin only 47% in the one case and 55% in the 
other was absorbed. The feces had a penetrating odor and visibly con- 
tained undigested muscle-fibers when meat was given. 

De Renzi also found increased nitrogen in the feces after total ex- 
tirpation of the pancreas in animals. A similar observation was made 
by the brothers Cavazzani. 

Sandmeyer found large amounts of well-preserved, striped muscle- 
fibers in the feces of animals fed with meat and bread after total extir- 
pation of the pancreas. After partial extirpation 62% to 70% of the 

albuminous bodies were used up. 

| Undigested bits of meat in the feces were found also by Rosenberg. 
The disturbed digestion of albumins was shown in a very marked way in 
one of our experiments after total extirpation, which was followed also 
by diabetes. Large pieces of undigested meat were found mingled with 
the stools after the first meat was taken. _On microscopic examination, 
numerous muscle-fibers with unchanged structure were distinctly recog- 
nized. On the other hand, no change in the appearance and composition 
of the stool could be shown in an animal which lived with severe diabetes 
for forty-one days after the operation. 

After partial extirpation no increase in excretion of nitrogen could be 
noted. The dog fed with meat was able to use no inconsiderable amounts 
of nitrogen from the food given. 

The oldest and most remarkable clinical statement is that of Fles, 
previously mentioned. He found in the stools of a diabetic very numer- 
ous unchanged and perfectly. well-marked bundles of striated muscle- 
fibers. The muscle-fibers disappeared from the stools when a calf’s 
pancreas was daily fed to the patient, and were found when the calf’s 
pancreas was omitted from the diet. 

Harley mentions the occurrence of large amounts of undigested 
muscle-fiber in the stools of a patient with pancreatic abscess. Le Nobel 


92 DISEASES OF THE PANCREAS. 


also observed large amounts of undigested muscle-fiber in a patient’s 
stools. A similar observation was made by v. Ackeren in a case of 
carcinoma of the pancreas. In a case of pancreatic cyst, Kister saw 
large amounts of undigested muscle-fiber in the feces even when the 
amount of meat in the food was very limited. In a case of calculus 
of the pancreas in a diabetic patient reported by Lichtheim the stools 
were found very rich in striated muscle-fibers. 

In the case of cancer of the head of the pancreas previously com- 
municated by me, very numerous bits of striated muscle-fibers were 
found, in the main with the structure distinctly preserved. 

The diminished consumption of nitrogen was found in several dia- 
betics by Hirschfeld. Upon an average, the feces contained, of the food 
introduced: 35.2% of the dry substance; 31.8% of the nitrogenous sub- 
stance; 34.8% of the fat. The normal quantity is from 6% to 7%. In 
these cases there was no postmortem proof of disease of the pancreas. 

The presence in the stools of numerous undigested muscle-fibers is 
certainly an important feature and deserves ‘especial attention. 

The azotorrhea alone does not permit the diagnosis of an affection of 
the pancreas, since the digestion of albuminous bodies is not exclusively 
the function of the pancreatic juice. When this sign is combined with 
the absence of jaundice and faulty digestion of fat or disturbance of the 
cleavage of the fat, and if neither gastric nor intestinal disease is demon- 
strable, the suspicion is wholly justified that a disease of the pancreas is 
present. The probability is materially increased when diabetes also 
exists, and becomes a certainty if a tumor in the region of the pancreas 
is demonstrable, as in the case observed by me. 


B. SECOND GROUP. 
J. CHANGES IN THE URINE. 


It would be of decided importance if evidence of a disease of the pan- 
creas could be found in the urine. 

The statements on this point already made unfortunately are not 
conclusive. 

Acting on my advice, and from the beginning of our investigations, 
A. Katz has paid special attention to this subject, but has been unable 
to obtain results in favor of the pathognomonic value of changes in the 
urine in disease of the pancreas. 

Especial weight was laid on the excretion of indican. Since this is 
derived from indol, which arises in pancreatic digestion under the in- 
fluence of bacteria, an important diagnostic value for the recognition 
of disease of the pancreas has been assigned to the quantitative estimation 
of indican in the urine. 

Gerhardi was the first who, in the year 1886, made the diagnosis of 
disease of the pancreas as the cause of the mechanical disturbance of the 
intestine on account of lack of increase of indican in a case of obstruction 
of the small intestine. Jaffe found, after ligating the small intestine, 
an enormous increase in the excretion of indican, although ligation of 
the large intestine had little or no effect on this excretion. In obstruction 
of the large intestine the indican is increased only when inflammatory 
changes occur and the small intestine participates in the disturbance. 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 93 


In Gerhardi’s patient there were several symptoms which indicated an 
obstruction in the uppermost portion of the intestine, but as there was no 
abnormal increase of the indican in the urine, and especially no _peri- 
tonitic symptoms, a loss of function of the pancreas or a disease of that 
gland was suspected. The autopsy confirmed this assumption of Ger- 
hardi. 

This view appeared to be supported by experiments on animals. 
Pisenti has estimated the amount of indican in the urine of dogs before 
and after tying of the pancreatic duct. He found in one case, before 
the operation, 11.70 to 19.90 mg. of indican pro die; after the operation, 
4.30 to 4.20 mg. pro die. In a second case, before the operation, 15.0 
to 21.0 mg. of indican pro die; after the operation, 6.0 to 9.0 mg. of indican 
prodie. The estimation of*the indican was made according to the method 
given by Salkowski. After the administration of pancreas peptone to 
dogs, the pancreatic duct of which had been tied, there was an increase 
of the indicanuria. | 

Some of the very few clinical observations which have been made 
support the assumption of Gerhardi, while others refute it. Stefanini, 
in a case of purulent pancreatitis, and Biondi, in a case of adenoma of 
the gland, observed lack of indicanuria. On the other hand, Schlagen- 
haufer asserts directly the increase of the indican in a case of syphilitic 
interstitial pancreatitis. 

The results obtained by Katz are in diametrical opposition to the 
statements of Pisenti. The former examined the amount of indican in 
the urine in the majority of our experiments on animals and showed 
very positively that there was absolutely no diminution in the amount 
of indican after lesions of the pancreas. In many cases a marked indican- 
uria could be proved. The amount of indican was greater and its in- 
crease could be shown distinctly in the days following the attack, espe- 
cially in those cases in which the animals took no nourishment after the 
operation, and even when they died quickly from duodenal necrosis. 
There was no diminution in the excretion of indican also in the animals 
which long survived the operation. On a pure meat and milk diet, 
abundant amounts of indican were found in the urine. De Renzi also 
-could show no change in the amount of indican in the urine in his experi- 
ments on animals, even after total extirpation of the pancreas. 

From these observations it is evident that the presence or absence 
of a disease of the pancreas is not to be concluded from the amount of 
indican in the urine. 

' The variations in the excretion of the indican may be founded on 
factors which have no direct relation to the activities of the pancreas. 
The conditions of absorption of the intestinal mucous membrane which 
are independent of the secretion of pancreatic juice, or processes in the 
organism which have their seat outside of the intestine, may have an 
influence on the excretion of indican. 

The latter assumption is favored by the fact that during inanition, 
in sulphuric-acid poisoning, in progressive anemia, in cholera nostras 
and Asiatica, in spite of the rapid passage of the intestinal contents, 
an increase of indican in the urine is to be shown. It is interesting that 
Hennige refers the increase of indican in cholera and lead-colic to an 
alteration in the pancreatic juice caused by nervous influences. 

The excretion in the urine of certain carbohydrates may be added 
to the symptoms which are regarded as characteristic of diseases of the 


94 DISEASES OF THE PANCREAS, 


pancreas. Maltose in rare instances, as well as glucose, has been found 
in the urine. Le Nobel observed, in a man sixty-one years old, who 
suffered from fatty stools and glycosuria, a reducing substance in the _ 
urine, corresponding, as he thought, to maltose. Von Ackeren, in a case 
of pancreatic carcinoma, found a like substance, and regarded its 
presence as pathognomonic of diseases of the pancreas. Later investi- 
gators were not able, however, to find maltose in the urine of diabetics. 
At any rate, the occurrence of maltose is very rare. 

The presence of pentose in the urine is of greater diagnostic impor- 
tance, according to Salkowski. Only a few cases heretofore have been 
known in which this pentatomic sugar has been found in the urine. It 
was shown first by Jastrowitz and Salkowski in the urine of a morphin- 
eater, who for a time suffered from glycosuria. 

Ferdinand Blumenthal reported the cases of two individuals in whose 
urine the presence of pentose was observed for some time, both inde- 
pendently of the diet and without further disturbance of the general 
condition. There was also a diminution in the amount of indican in 
the urine in both cases. Hammarsten found in the pancreas a nucleo- 
proteid containing mucin, which on cleavage gave rise to a pentose. 

Salkowski found that the pentosazon extracted from the urine was 
identical with the pentosazon obtained from the pancreas... The melting- 
point, the form of crystallization, the external appearance, the reaction 
to heat, and the solubility corresponded so perfectly in the two prepara- 
tions that the identity of the two substances was to be assumed ‘with 
a degree of probability bordering on certainty.”’ On the basis of this_ 
observation, Salkowski believes ‘“‘that the pentosuria depended on an 
abnormally increased formation and destruction of.the nucleo-proteid 
which forms the pentose, and as this nucleo-proteid predominates in the 
pancreas, the pentosuria is presumably to be regarded as an affection 
of this organ.” 

This conclusion was supported apparently by the statements of Kilz 
and Vogel, who found pentose in the urine of starving dogs which had 
become diabetic after extirpation of the pancreas. The presence of 
pentose was frequently shown also in diabetes in man. They examined 
the urine of 80 diabetics; in only 4 cases was there no pentose, in 12 cases 
the pentose test was weak or doubtful, in 64 cases it showed distinctly 
the red coloration from the use of the Tollen reagent (phloroglucin and 
fuming hydrochloric acid). As foods of plant origin very frequently 
contain pentose, the pentosuria may doubtless be of purely alimentary 
origin in many cases. 

The statements of Salkowski and Blumenthal are opposed to this 
positive evidence. The former never found pentose with the glucose 
in 9 diabetics. Blumenthal investigated 10 severe cases of diabetes, 
among which were the 9 cases examined by Salkowski, and was unable 
to find pentose with the grape-sugar. A diabetic who in seven weeks, 
under strict diet, showed a diminution in the amount of sugar from 
6.5% of glucose in 3500 ¢.c. of urine to none at all, never had pentosuria, 
although the morning and evening urines were daily examined for 
pentose. 

The cleavage of the nucleo-proteid of the pancreas, although the most 
prominent, is certainly not the sole source of pentosuria. In the cell- 
nucleus are found still other bodies belonging to the group of nucleo- 
albumins, the cleavage of which with dilute sulphuric acid also gives rise 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 95 


to pentose. In consequence, the pentose may arise from the nucleinic 
acid distributed throughout the animal body (Blumenthal). 

Pentosuria was constantly found by Capparelli after the injection 
of morphin. The assumption is probable that in this case the pancreas 
is not specially involved. 

The occurrence of fat in the urine, lipuria, is mentioned by the older 
authors as a result of disease of the pancreas. Tulpius describes a case 
in which fat was excreted with the feces and in the urine. Elliotson 
reports a like condition. In neither case was there an autopsy to con- 
firm the diagnosis of disease of the pancreas. 

Fat was found by Clark in the urine of a woman for a long time, 
and later fatty stools also occurred. At the autopsy carcinoma of the 
pancreas and nutmeg liver, with a very small amount of bile in the gall- 
bladder, were found. 

Bowditch reported the case of a man on the surface of whose urine 
numerous fat-drops were found. At the autopsy cancer of the liver 
and of a large portion of the pancreas were observed. 

Lipuria certainly cannot be utilized in the diagnosis of disease of the 
pancreas, since it results from most diverse causes. (See Lipuria, by 
Senator, ‘‘ Diseases of the Kidneys.’’) 

The changes hitherto described have been regarded by many as 
characteristic of diseases of the pancreas, but unfortunately their claim 
is not justified. In brief, the condition of the urine in diseases of the 
pancreas has no especial peculiarities. 

The appearance of the urine is, as a rule, not altered. The dark 
pigmentations noticed in bronzed diabetes are not to be ascribed directly 
to the disease of the pancreas, but probably originate in the disturbance 
of general metabolism and in the alteration of the liver. The jaundice 
often present in pancreatic diseases of course changes the color of the 
urine. Turbidity of the urine is found in cases of lipuria. The specific 
gravity of the urine is altered only when it is increased by the diabetes 
resulting from disease of the pancreas. 

The reaction of the urine is more strongly acid than normal, according 
to the observations of Jablonski on dogs with pancreatic fistule and ex- 
ternal discharge of pancreatic juice. Before the operation there was 
0.018% of oxalic acid, but after the establishment of the fistula the 
oxalic acid was 0.156%. Jablonski attributes this increase of acidity 
to diminished alkalinity of the blood, from the loss of alkalis contained 
in the pancreatic juice, and he succeeded in producing a normal acidity 
.of the urine by injecting a weak soda solution. There are no observa- 
tions upon man relating to this point. 

The amount of urine is affected by disease of the pancreas only when 
diabetes occurs. In bronzed diabetes, in spite of the excretion of sugar, 
the polyuria seems not so strongly marked as in the other forms of glyco- 
suria. De Dominicis, in his experiments, observed an increase of the 
amount of urine independently of the excretion of sugar. In our ex- 
periments, however, no abnormal increase of the amount of urine could 
be shown either as the result of pancreatic lesions or of extirpation of 
the pancreas. 

The amount of urea in ha urine was, as a rule, greatly increased. 
The azoturia generally was in proportion to the glycosuria. In some of 
the cases observed by de Dominicis, Hédon, and Thiroloix, azoturia 
without glycosuria occurred after extirpation of the pancreas. Azoturia, 


96 DISEASES OF THE PANCREAS. 


however, does not occur constantly in the experiments on animals. After 
partial extirpation, it could not be shown. 

There are no statements regarding the excretion of the urea-containing 
constituents of the urine—urea, uric acid, and ammonia. The excretion 
of the chlorids appears to be unaltered by disease of the gland. The 
excretion of the phosphates is increased. De Dominicis assumes that 
an increase of phosphoric acid is a characteristic of pancreatic lesion 
even in those cases in which there is no glycosuria. The excretion of 
sulphuric acid obviously is increased in cases of azoturia. 

Katz has devoted especial attention to the relation between the total 
sulphuric acid and the ether-sulphuric acids as a measure of the pro- 
cesses of decomposition going on in the intestine. According to his 
investigations, the amount of combined sulphuric acids showed no essen- 
tial variation from the normal after total as well as after partial extir- 
pation of the pancreas. Considerable variations were shown, as have 
been observed in dogs under other conditions, and were dependent 
upon the variation in the absorption of the food. When a dog was fed 
with easily and rapidly absorbed fish, Katz found small amounts of 
ether-sulphuric acid,—0.032, 0.022, 0.069 gm. daily,—the relation to 
the excretion of the total sulphuric acid being 19.2, 22.3, 20.2. 

When the dog made diabetic by extirpation of the pancreas was 
fed with pure meat, Katz found the amounts to vary very considerably ; 
relatively they were very high—0.076, 0.089; but also as low as those 
above mentioned—0.024, 0.025, 0.033, 0.039. The variations in the rela- 
tive amounts were, of course, correspondingly great according to the 
differences in the absolute amounts of ether-sulphuric acid and were 
between 21.0 and 4.5. These investigations of Katz do not permit the 
recognition of any constancy in the excretion of the ether-sulphuric acid 
after complete exclusion of the pancreatic juice from the intestine, as 
in the case mentioned, and the reason for the differences must be found 
in the varying conditions of intestinal resorption. | 

Acetone and acteo-acetic acid are not regularly found after extirpa- 
tion of the pancreas. Minkowski observed them especially when there 
was marked emaciation of the animals experimented upon. After ex- 
tirpation of the pancreas Baldi found a considerable increase of acetone. 
In the normal animal the daily amount varied between 0.0 and 0.105 
gm., while the amount of acetone excreted on the second day after the 
operation reached 1.043 gm., on the third day 0.652 gm., and fell later 
to 0.385 to 0.282 to 0.049 gm. 

According to Minkowski, oxybutyric acid did not occur constantly. 
in the urine and was excreted in small amounts. The diabetic organism 
is able to oxidize the oxybutyric acid introduced even after extirpation 
of the pancreas. The amount eliminated may, therefore, be smaller than 
the amount originating in the organism. Its occurrence might perhaps 
be regarded always as a complication of diabetes; it was present, espe- 
cially in the larger amounts, at a time when the amount of sugar was 
diminished (Minkowski). 


BRONZED DIABETES. 


This peculiar disease, which has been associated with affections of 
the pancreas, deserves mention at the close of the consideration of the 
changes in the urine occurring in disease of the pancreas. 

Trousseau was the first to report a case which may be regarded as 


GENERAL RATHOLOGY AND SYMPTOMATOLOGY. 97 


diabéete bronzé. Servaes described a patient with pancreatic carcinoma, 
bronzed skin, and diabetes. 

The clinical picture and the anatomic lesions were stated most care- 
fully and thoroughly by Hanot and Chauffard. They reported two cases. 
Letulle, in the same year (1882), published two new observations. In 
1886, Hanot and Schachmann reported another case. 

In 1888, Brault and Galliard published a new observation. Barth 

demonstrated a striking specimen in the Société d’anatomie. In 1892, 
Gonzales Hernandez mentioned another case in his thesis. In 1893, 
Palma reported two cases of diabetes with cirrhosis of the liver and 
bronze coloring of the skin. In 1895, Mossé and Daunie, in a man thirty- 
nine years old, who had suffered from diabetes for about a year, observed 
a dark brown color of the skin, moderate polyuria, 4 to 5 liters daily, 
marked glycosuria, and azoturia. At the autopsy the liver showed the 
picture of Hanot’s pigmentary cirrhosis. The pancreas was somewhat 
yellower than normal, firm, slightly sclerosed, and showed also on micro- 
scopic examination the picture of pigmentary sclerosis. The adrenals 
were normal. 

Buss described, in his dissertation in 1894, a case of diabetes mellitus 
with cirrhosis of the liver, atrophy of the pancreas, and general hemato- 
chromatosis. In 1895, de Massary and Potier reported another case 
at the Société d’anatomie. In the same year Marie published a striking 
case in a man fifty-one years old who, about four months before, had 
been attacked with the symptoms of diabetes mellitus and with edema 
of the lower extremities. The average daily amount of urine was 2.5 
to 3.5 liters, and that of the excretion of sugar 40 to 50 gm. The liver 
was distinctly enlarged. There was difficulty in breathing, sleeplessness, 
and distention of the abdomen. Six days before death there was no 
sugar in the urine. 

Aucher reported another observation in the Société d’anatomie. In 
their theses appearing in 1895, Achard and Dutournier took up the sub- 
ject of bronzed diabetes. Rendu and Massary reported at the Société 
des hépitaux the case of a strong man affected with diabetes and sub- 
sequent brown coloration of the surface of the body. The disease lasted 
about half a year. Jeanselme at the same meeting referred to two cases 
observed by him. One was the case of a man who had worked for ten 
days with litharge and red oxid of lead and then sickened with symptoms 
of a severe diabetes accompanied by discoloration of the skin, with a 
daily excretion of 5 to 7 liters of urine containing from 150 to 337 gm. 
of sugar. In the second case the disease developed as the result of an 
injury in the region of the umbilicus. The disease lasted five and a 
half months. Hitherto only 22 cases of the disease have been reported. 

Marie gave the following picture of the disease based on these observa- 
tions: Bronzed diabetes occurs especially in men between forty and 
sixty years of age. The youngest patient was thirty-seven, the oldest 
sixty-one years old. Among the etiologic factors are alcoholism, malaria 
in the case of Hernandez, and in one of Jeanselme’s lead-poisoning and 
in the other injury: The diabetes generally begins suddenly. Gastro- 
intestinal disturbances early occur, also diarrhea or affections.of the 
respiratory apparatus. The characteristic symptoms of diabetes, poly- 
dipsia and polyuria, are, as a rule, not so strongly marked as in the other 
varieties of this affection. The urine is generally dark, beer-colored, 
and free from bile pigments. The abdomen is swollen and its veins 

7 


98 DISEASES OF THE PANCREAS. 


distended, the liver is greatly enlarged, and the spleen is somewhat in- 
creased in size. At first there is little or no ascites; later, accumulations 
of 6 to 8 liters of fluid have been observed in the abdomen. 

Hanot and Chauffard, in one patient, noted a lymphangitis of the 
abdominal wall.- Digestion is frequently delayed. Toward the end of 
life diarrhea often is observed. The patients become rapidly and ex- 
tremely emaciated. In Brault’s case 55 pounds were lost in six months. — 
Finally, edema of the lower extremities and cachexia develop. 

The discoloration of the skin is general and uniform. Spotted pig- 
mentation is not seen. In contrast to Addison’s disease, there is no 
pigmentation of the mucous membranes. The color is not always bronze- 
like; in many cases the skin is blackish-gray, with a metallic luster, like 
the broken surface of cast-iron. Under certain circumstances, despite 
the characteristic change in the liver and internal organs, the pigmenta- 
tion of the skin is much less distinctly marked. The course of the 
disease is, as a rule, very rapid. The longest duration—two years— 
was in the case reported by Letulle; the shortest was five and a half 
months, in a patient of Jeanselme and five months in Marie’s case. In the 
last few days of life fever occurs, as a rule, and sugar disappears from 
the urine. 

The most striking of the anatomic changes takes place in the liver. 
This organ is large and hard; only very exceptionally, as in two question- 
able cases of Palma and Lucas-Champonniére, is there noted a diminution 
in the size of the liver. Its color is brownish-red, ‘‘like old red leather,”’ 
its surface is generally uneven, rarely smooth. The gall-bladder appears 
filled at times with colorless bile. Slate-gray coloring is seen also in the 
intestine, mesentery, omentum, and in the lymph-glands, especially 
in those of the abdomen. The spleen is rust-colored and sclerosed. 

The pancreas in most cases is sclerosed, rust-colored, and its excre- 
tory duct is patent. The heart, as a rule, is normal, flabby, reddish- 
yellow. In the lungs, tuberculosis is frequently demonstrable. On 
microscopic examination there are found in the liver granular degenera- 
tion of its cells, increase of the connective tissue, and deposition of pig- 
ment, especially in the interstitial tissue, less frequently in the liver- 
cells. 

In the pancreas the spaces in the connective tissue are much enlarged 
and much pigment is deposited both in them and in the cells. This 
pigment is of yellow-ochre color, rich in iron, and evidently to be regarded 
as a derivative of the blood coloring-matter. The development of the 
pigment is located in the liver by Hanot and Chauffard, and is regarded 
by them as an increase of its chromatogenic function. It is supposed 
that this pigment is transferred through the lymphatics from the liver 
to other organs. 

Letulle opposes this view by calling attention to the fact that the 
deeply pigmented cells are dead, and believes that the hemoglobin is 
locally reduced. Brault and Galliard consider the cirrhosis as the prim- 
ary, and the degeneration of the blood as the secondary, condition. 

Marie thinks that the hemoglobin is decomposed through some un- 
known cause and is transformed into the pigment. The latter is elimi- 
nated in part by the lymphatic system and thus causes degeneration, 
irritation, and connective-tissue growth in the various organs. 

Achard states that the changes in the liver have nothing to do with 
the diabetes, and that the latter is to be regarded solely as the result 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 99 


of the changes in the pancreas. This view regarding the chronologic 
course of events Buss considers improbable. 

Jeanselme explains the mechanism of the development of bronzed 
diabetes in the following way: First there is the degeneration of the red 
blood-cells in the capillaries of the gland parenchyma; the yellow ochre 
pigment originating in this way reaches the secretory epithelium and a 
sclerosis develops in all the organs overladen with pigment. If a sclerosis 
of the pancreas is added to the sclerosis of the liver, diabetes develops, 
and then is to be regarded as a purely secondary phenomenon. 

Rendu and Massary think the formation of the yellow ochre pigment 
takes place in the cells as a consequence of the normal metabolism. 
After the destruction of the cells the pigment reaches the connective-tissue 
spaces and is carried from them to the several organs by the lymph-cells. 

The diabetes cannot be made answerable for the disturbance of cell 
activity, as Hanot and Chauffard originally claimed, since a like change 
in the skin is repeatedly seen without diabetes; thus, it was observed in 
malaria in 1889 by Kelsch and Kiener, in 1895 by Brault in two cases 
without diabetes, and most recently by Letulle, Gilbert, and Grenet in 
hypertrophic cirrhosis of the liver. 

Reference may here be made to the cases in which affections of the 
pancreas occur without mellituria, but with bronzed coloration of the 
skin. Aran found the condition in a woman twenty-five years old in 
whose pancreas caseous foci were found containing cavities from softening. 
Jenni has mentioned an ashen-gray color of the face in a case of cancer 
of the pancreas. Kappeller and Moritz observed two cases of this affec- 
tion, in which there was a bronzed color of the skin. 


2. EMACIATION. 


The earlier authors regarded an especially marked degree of emacia- 


tion as a characteristic symptom of diseases of the pancreas. It is not 


surprising that this occurs in cases of diabetes or carcinoma, but it may 
be found also without these; for instance, when there are cysts. In Kis- 
ter’s case the patient lost 33 Ibs.in four months. Kister and Riegner 
ascribed the emaciation to the poor digestion of proteids. The weight 
not infrequently has increased rapidly after a successful operation. 

The cachexia in carcinoma of the pancreas at times presents certain 
peculiarities, which, however, are not to be regarded as pathognomonic, 
as has been claimed by many, especially French, authors. It indeed 
often develops much more quickly and intensely than in other carcino- 
mata of the upper abdomen. There is much weakness and prostration, 
which cannot be explained by the inanition alone. The subject will 
again be considered in the section on carcinoma. 

The occurrence of diseases of the pancreas in fat persons will repeatedly 
be noted in the special part of this article. Very acute processes, espe- 
cially, as hemorrhages, the so-called hemorrhagic pancreatitis, necrosis, 
and fat necrosis, are found quite often in corpulent people. 


3. SALIVATION OR SIALORRHOEA PANCREATICA, AND 
DIARRHOEA PANCREATICA. 


The spitting or vomiting of large quantities of fluid resembling 
saliva has been regarded as characteristic of diseases of the pancreas. 


100 DISEASES OF THE PANCREAS. 


The cause was assumed to be an increased secretion of saliva or of pan- 
creatic juice due to reflex excitation. In two cases of cysts, reported by 
Battersby and Ludolf, a flow of saliva is noted. Holzmann also reports 
salivation during the colic produced by pancreatic calculi. A similar 
observation was made by Capparelli and Giudiceandrea in lithiasis. 
From the rarity of its occurrence, it is evident that there is no causal 
relation between this symptom and diseases of the pancreas. 

It may be, as I'riedreich justly suggests, that the flow of saliva is 
referable to concurrent disease of the stomach. The thin viscid stools 
supposed to be composed of pancreatic juice and regarded as character- 
istic are of no greater importance. [Irom the older literature Friedreich 
mentions the following experience reported by Levier. In the cholera 
epidemic at Bern from 1861 to 1864, a large amount of leucin was found 
in the evacuations. ‘‘The idea can by no means be excluded,” writes 
Friedreich, ‘‘that there may have been an actual hypersecretion of the 
pancreas, an accompaniment of a peculiar form of acute epidemic intes- 
tinal catarrh.” 

Senn has recently suggested a causal relation between the profuse 
diarrheas occurring at times with cysts and a degeneration of the 
parenchyma of the gland. Lichtheim also, in a case of pancreatic cal- 
culus with diabetes, suggests the obstinate diarrhea as an important 
sign. 

Peculiar diarrheas may occur in consequence of the rupture of a 
pancreatic cyst into the intestine. Such was observed in Nothnagel’s 
clinic in Vienna. A tumor was demonstrable in the region of the pan- 
creas, but it disappeared after the evacuation of diarrheic stools and 
the vomiting of a bowl full of alkaline fluid containing grayish-red and 
reddish-brown shreds. ‘This result is obviously not identical with pancre- 
atic salivation. There is no further proof of this condition in recent 
communications. 


C. THIRD GLhOUCGP. 


This includes the symptoms which frequently occur in diseases of 
the pancreas. They present no peculiarities which point to the pancreas, 
with the exception of a distinctly palpable or visible tumor in the region 
of the pancreas. They are mostly morbid signs which may occur in the 
most diverse diseases of the digestive organs and are often the expression 
of a combination of diseases of various organs, as has already been stated 
in the introduction to the general part (p. 17). 

1. Tumor or resistance. A circumscribed or diffuse tumor, or an 
elevated, distinctly palpable, abnormal resistance, corresponding to the 
position of the pancreas, may be found in acute or chronic inflammation 
(abscess or induration), in cysts or new formations of the pancreas. 
A more or less sharply defined tumor or an indefinite resistance in the 
upper portion of the abdomen may be found in some cases of abscess, 
as in the cases reported by Kilgour and Percival. In Graeve’s case, also, 
an increased resistance was found. Thayer observed in the middle line 
above the umbilicus, a deep-seated resistance, which could not be sepa- 
rated from the liver. 

If a pancreatic abscess has ruptured, and a bursal abscess or a retro- 
peritoneal collection of pus has developed, then a fluctuating tumor may 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 101 


be found in the epigastrium (Korte, Rosenbach, Werth-Konig, Casper- 
sohn-Hansen). 

As will be stated in the special part, a palpable tumor may be recog- 
nized also in chronic induration. Riedel once felt beneath the abdominal 
wall a tumor of the size of a fist consisting of the head of the pancreas, 
which proved to be caused by chronic inflammation. The presence of a 
tumor in cases of cysts and neoplasms will be sufficiently treated in the 
special part. 

2. Jaundice is a frequent symptom of diseases of the pancreas. The 
anatomic position of the bile-duct, as has been shown in the preceding 
communication of Zuckerkandl, gives a satisfactory reason for this con- 
dition. According to his investigations, it is easily understood that 
when the ductus choledochus extends at least a half centimeter into 
the head of the pancreas, it may be compressed, even to entire closure, 
if the head is swollen or atrophied. Such swellings eventually may 
subside if the cause is temporary, as an inflammatory enlargement which 
may resolve. Many cases of so-called catarrhal jaundice may perhaps 
depend on such resolving swellings of the head of the pancreas. 

Jaundice may develop in like manner in chronic induration of the 
pancreas, as in Hjelt’s patient. Jaundice not infrequently develops from 
the pressure of cysts on the ductus choledochus. It may arise, however, 
in other ways. 

Ina case described by Gould, the jaundice was transient, and, prob- 
ably, was produced by duodenal catarrh. Cruveilhier refers to a scirrhus 
at the mouth of the ductus choledochus which caused both jaundice and, 
by closure of the pancreatic duct, also a pancreatic cyst. In a case 
described by Phulpin, a gall-stone in the ductus choledochus caused 
jaundice, and, by compression of the ductus Wirsungianus, also a pancre- 
atic cyst. In Friedreich’s case an annular cancer of the duodenum pro- 
duced jaundice and dilatation of the Wirsungian duct with numerous 
sac-like diverticula by compression of this duct. 

Jaundice is found most frequently in cancer of the pancreas. As a 
rule, it develops slowly and insidiously, but steadily. The jaundice 
may diminish toward the end of life. As the skin becomes pale and 
anemic, the yellowish color becomes less intense. 

Mirallié noted 82 instances of Jaundice in 113 cases of primary cancer 
of the pancreas. Among 36 additional cases collected by me, jaundice 
is noted 21 times; thus, in 149 cases jaundice is present in 103. The 
jaundice may be due also to disease of some neighboring organ which 
accompanies the affection of the pancreas. Diseases of the liver and 
of the biliary tract, especially gall-stones, extension of pancreatic 
diseases, particularly new-formations, to the liver and biliary tract, 
metastases in the liver, and, lastly, catarrhal processes may also cause 
the jaundice. 

3. Different kinds and degrees of pain and painful sensations 
play an important part in diseases of the pancreas. Without doubt, 
diseases even which extensively invade the pancreas may run their 
course without pain. In cancer,for example, pain may be absent through- 
out the whole course of the disease, as in the case described by Friedreich, 
_In which there was neither spontaneous pain nor tenderness. Also, in 
the case reported by Stiller no severe pain occurred. It may be absent 
even in abscess of the pancreas (Nathan). The pains may be occasional 
_ or continuous, and in the latter case temporary exacerbations may occur. 


102 : DISEASES OF THE PANCREAS. 


The occasional pains may have the character of colic or of cardialgia. 
They occur in acute as well as in chronic affections of the pancreas. 

The colicky pains are oftenest caused by stagnation of secretion 
due to closure of the excretory duct or of the ducts in the interior of the 
organ by concretions or by some other mechanical factor hindering the 
free evacuation of the secretion. The colic therefore occurs most fre- 
quently in calculus formation, compression of the excretory and secretory 
ducts by new-formations, scars, indurative inflammation, or hemor- 
hage. It is to be assumed also that catarrhal processes which lead to 
swelling of the mucous membrane at the outlet of the pancreatic duct 
may cause colicky pains. Not infrequently so-called nervous gastralgias 
may be referred to such stagnation of secretion. 

The pains in hemorrhage have mostly a colicky character; that is, 
they diminish or entirely disappear at times, and then return with in- 
creased violence. In tumor-formation, also, the pains may be only 
occasional. In pancreatic cysts the pains may occur in paroxysms and 
have the character of cardialgias or biliary colic, when the cyst develops 
in the head of the pancreas. The colic at times occurs with great 
violence, fainting, and symptoms of collapse. In cancer, also, pains 
may at times occur, and present the characteristics of colic and car- 
dialgia. They may represent the exacerbation of neuralgic pains pro- 
duced by pressure on neighboring ganglia, or be due to stagnation of 
secretion from compression of the excretory duct, or, lastly, there may 
be a real biliary colic, when the ductus choledochus is embedded in the 
carcinomatous mass. 

The continuous pains are of various kind and intensity, often remit- 
tent and occasionally with paroxysmal exacerbations, but frequently 
increasing gradually; they are present in acute and chronic processes in 
the pancreas, as pancreatic abscess, hemorrhage, gangrene, indurative 
pancreatitis, and tumor-formation. The pains may come on suddenly 
with great severity, as is usually the case in abscess of the pancreas, in 
hemorrhage, and in the so-called hemorrhagic pancreatitis and in gan- 
grene. In tumor-formation—cyst or carcinoma—the pains, as a rule, 
come on gradually and increase in severity with the growth of the tumor. 

The pains in cancer may be of especial violence and of peculiar char- 
acter. In the section on this subject their characteristics will be con- 
sidered in detail. To what extent the celiac ganglion or nerve-trunks 
arising from it are concerned in the production of these pains it is 
impossible to state at present. The designation “celiac neuralgia” was 
long since chosen for these pains. Although there is no proof that the 
pain is related to the celiac ganglion, it is very probable that pressure or 
traction on this ganglion actually causes severe pains. 

Pains of different kinds may of course be produced by the combina- 
tion of disease of the pancreas with diseases of neighboring organs. When 
the stomach or intestine overlaps it or becomes adherent to it, constant 
or remitting pains may be produced by the peristaltic movement de- 
pendent upon the function of these organs. Intense continuous pain 
may arise also from participation of the peritoneum. Concurrent affec- 
tion of other neighboring organs, as the liver, bile-passages, and lymph- 
glands, will give rise also to different kinds of pain. 

More or less extreme sensitiveness to pressure in the epigastrium, 
in the region corresponding to the pancreas, is found in connection with 
the’ most diverse processes in this gland: It must be mentioned, how- 


GENERAL PATHOLOGY AND SYMPTOMATOLOGY. 103° 


ever, that in many acute and chronic processes, even when diffused, it 
is especially noted that there is no sensitiveness to pressure. 

In a number of cases merely vague, troublesome sensations, not to be 
regarded exactly as pain, occur in the region of the pancreas. These 
are the discomfort, sense of distress, feeling of pressure, fulness, and 
tension, which are especially unpleasant in certain positions of the body. 

4, Pressure on adjacent organs may produce severe results in 
the course of the disease. Compression of the intestine first deserves 
consideration. The stomach, especially the pyloric portion, may also 
be compressed under certain conditions, and stenosis with dilatation 
of the stomach thus may be caused. This occurred in a case operated 
upon by Bardeleben; the diagnosis before the operation was closure of 
the pylorus by a compressing tumor. At the operation multiple carci- 
nosis of the liver and peritoneum were recognized and no relief could 
be afforded. After death cancer of the head of the pancreas, compressing 
the pylorus, was found. 

The compression of the intestine may give rise to stenoses, and symp- 
toms of obstruction may arise. Not infrequently symptoms of intes- 
tinal obstruction are the first marked evidence of disease of the pancreas, 
and in a number of cases laparotomy has been undertaken because intes- 
tinal occlusion was diagnosticated. At the operation the obstruction 
was sought in vain. 

Such instances of real or apparent obstruction of the intestine occur 
in various diseases of the pancreas. They are recorded in acute pro- 
cesses, as in the cases of Nathan, Fitz, Hirschberg, Sarfert, McPhedran, 
Parry Dunn and Pitt, Gerhardi, Balser, Rosenbach, Caspersohn, v. 
Bonsdorff, Hovenden, Simon and Stanley, Allina. 

The intestine may be narrowed or entirely closed by growing tumors. 
Intestinal occlusion may be due to cysts, as was found in the cases of 
Brown and Hagenbach, and transient obstruction was noted in the case 
of Lardy. 

Intestinal occlusion is reported in carcinoma by Kerckring, de Haen, 
Mondiére (2 cases), Holscher, Teissier, Tanner, Salomon, Wrany, Stans- 
field. 

Hindrance of intestinal function, meteorism, and constipation are 
frequent symptoms of disease of the pancreas. In pancreatic carcinoma 
Kellermann found constipation 60 times, diarrhea 12 times, and in 9 
cases alternate constipation and diarrhea. By pressure on the portal 
vein, ascites, enlargement of the spleen, and dilatation of the hemor- 
rhoidal veins may develop and edema of the lower extremities may 
result from pressure on the vena cava. One or the other ureter may be 
compressed by tumors, and thus hydronephrosis develop (Recamier, 
Reeve). 

5. Vomiting and nausea are remarkably frequent, and are nearly 
constant signs of disease. ‘They may appear at the beginning and persist 
throughout the disease. The various combined affections—the colic, 
the peritoneal disturbance, the intestinal obstruction, etc. —likewise 
lead to vomiting. 

Nausea and vomiting are usually present at the beginning of abscess- 
formation, and vomiting is likewise found frequently in chronic inter- 
stitial pancreatitis; there is vomiting also in hemorrhage, although in 
exceptional cases there is only nausea, or gastric disturbance may be 
entirely lacking. There may be vomiting of blood (Hooper) or vomiting 


"104 DISEASES OF THE PANCREAS. 


of a dark brown fluid (Fearnside). Vomiting is a very frequent symptom 
of cancer. Blood may be mingled with the vomitus, or pure blood may 
be vomited, especially when there has been perforation into the cavity 
of the stomach or into the duodenum. 

Vomiting frequently occurs in cysts also; at first only at intervals, 
during the attacks of colic, but later with greater frequency—perhaps 
after each administration of food. | 

6. Abnormalities of the stools have already been discussed in 
different places in this section. The frequency of constipation and the 
occasional occurrence of diarrhea have repeatedly been mentioned. 
Certain characteristic peculiarities of the stools, steatorrhea and azo- 
torrhea, have been reported in detail. 

Bloody stools occur at times in cancer. Such cases have been reported 
by Bohn, Friedreich, Kobler, Mariani, Molander and Blix, and Wesener. 
The hemorrhages were generally caused by ulceration of the intestine. 
Pancreatic cysts by rupture into the intestinal cavity also may cause 
bloody stools. In Pepper’s case a cyst of the head of the pancreas broke 
into the duodenum and caused hematemesis and bloody stools. A 
pancreatic abscess may break into the intestine, and blood and foul pus 
pass off with the stools (Percival, Atkinson). 

A sequestrated pancreas also may be evacuated with the stools 
(Rokitansky-Trafoyer, Chiari-Schossberger). Sometimes pancreatic cal- 
culi are found in the stools, as in the cases cited by Leichtenstern and 
Minnich. 

7. Dyspeptic disturbances are very frequently recorded: altered 
appetite and sense of hunger, especially anorexia, distaste for meat, 
discomfort after meals, sensations of pressure, fulness, epigastric tension, 
especially after meal-time, heart-burn, eructation, nausea, etc. 

It is clear that it cannot be considered that all these difficulties are 
to be ascribed to the pancreatic affection. They are mostly to be re- 
garded as resulting from a simultaneous disease of the stomach and 
intestine. 

8. Fever is found at times in acute as well as in chronic affections 
of the pancreas. In pancreatic abscess and in bursal abscess there is 
generally an irregular fever with intercurrent chill. Pancreatic abscess 
also may run its course without fever. The combination with peritonitis 
naturally becomes a source of fever. 

In cancer the fever generally depends upon complications, as cholan- 
gitis with abscess-formation in the liver, subsequent pancreatitis, and 
metastases in the lungs and pleura. The fever also may be related to 
the development of the tumor (Kobler). 

Fever may arise in cases of cysts also, in consequence of the occur- 
rence of pancreatitis or of the suppuration of the cyst. In gangrene 
and necrosis the fever may develop from the metastatic pleuritis, peri- 
carditis, leptomeningitis, etc. In cases of pancreatic calculi fever is at 
times noted. In the patients of Bonet and Galeati the type was tertian; 
but it could not be assumed with certainty that the fever had any relation 
to the lithiasis. ; 

In the case reported by Minnich and Holzmann fever (37.7° to 38.3° 
C.—99.9° to 101° F.) was shown during the colic. Subnormal tempera- 
ture has been found especially in the last stage of cancer (Bard and Pic). 
It is found not infrequently as a manifestation of collapse in various 
acute processes in the pancreas. 


GENERAL STATISTICS AND ETIOLOGY. 105 


IV. GENERAL STATISTICS AND BIOLOGY. 


TRUSTWORTHY statistics can be obtained under only two conditions: 
When the diagnosis can be made with certainty during life, and when 
there is a postmortem examination. These two conditions are not 
fulfilled in diseases of the pancreas. These affections are rarely to be 
recognized with certainty during life, and the anatomic statistics are 
not sufficiently complete, because the pancreas is not examined fre- 
quently enough at autopsies, certainly not with the same thoroughness 
as are the liver and kidney. 

In the diseases which are the most frequent causes of death, as tuber- 
culosis, cardiac and renal diseases, infections, cachexias of different kinds, 
and senile marasmus, it is probable that the pancreas is seldom examined 
thoroughly, and yet there is no doubt that tuberculosis causes frequent 
changes in this gland, and that in cachexias and marasmus atrophy of 
the pancreas is by no means rare. Statements about the pancreas are 
rarely found in postmortem records of the above-mentioned diseases. 

It is probable that another, even large series of diseased processes in 
the pancreas escapes observation, because not being recognized during 
life, healing takes place and no obvious trace is found at a subsequent 
postmortem examination. 

Catarrhal inflammations of the pancreatic duct, continued from the 
intestine or from the gall-bladder, circumscribed acute or chronic in- 
flammations, slight hemorrhages, disturbances of pancreatic secretion, 
formations of concretions, are certainly recovered from, as will later be 
shown. All of these processes are rarely recognized during life. After 
death, traces might exceptionally be found, but even if traces were 
present, search for them is rarely made. 

Pancreatic diseases, consequently, are by no means so rare as is 
repeatedly assumed. It is not at all clear why of the entire series of 
digestive organs—stomach, intestine, liver, pancreas—the latter alone 
should especially be protected from disease; why diseases of the blood- 
vessels, gland parenchyma, secretory canals of the blood, should spare 
only the pancreas whose vital functions are so important and manifold, 
while under quite similar conditions the neighboring organs are so fre- 
quently attacked. If the attention were given to the pancreas which 
it certainly deserves on account of its physiologic importance, the limited 
experience now at hand would certainly be enlarged. 

Although it is very probable, from the above statements, that diseases 
of the pancreas occur much more frequently than is known, yet it must 
be recognized that the number of fatal diseases of the pancreas is certainly 
much less than that of the neighboring organs. Tumors and general 
acute and chronic inflammatory processes occur without doubt more 
rarely in the pancreas than in the other organs of digestion. Statistics 
are continually being published, and even cases following a regular course 
are considered worthy of communication. This speaks decidedly for the 
relative rarity of severe diseases of the pancreas which, if marked, cer- 
tainly would not be overlooked at autopsies. 

The figures which hitherto have been given are insufficient as a 
basis for the determination of the absolute frequency of diseases of this 
organ. Claessen has collected all previous to 1842, and there are 322 
cases, 193 in men and 129 in women. It will be seen in the special 


106 DISEASES OF THE PANCREAS. 


part that the data which have become known in the last few years are 
relatively much more numerous. 

Recent statistics have been published by Hansemann. In ten years 
there were found in the postmortem records of the Berlin Pathological 
Institute (Charité and Augusta-hospital) 59 cases of disease of the pan- 
creas, 40 with diabetes and 19 without this condition. Among the 19 
cases, necrosis of the gland and fat necrosis were not included. 

In the postmortem records of the Vienna General Hospital from 1885 
to 1895 the following statistics were found: 


Diseases of the pancreas with diabetes .................... 12 cases. 
Diseases of the pancreas without diabetes ................ i 
96 cc 


The figures recorded in the years 1893 to 1895 show that there has 
been increased attention directed to this matter of late years. In these 
three years 49 cases have been reported, as against 47 in the seven pre- 
ceding years. Claessen states that more men than women suffer, 193 
of the former and 129 of the latter. In Hansemann’s statistics a similar 
relation was noted, there being 42 men and 17 women. In the post- 
mortem records of the Vienna General Hospital, among 94 cases, 42 
were men and 52 were women. 

Diseases of the pancreas may occur at any age. In late fetal life 
and in the newborn indurative pancreatitis, depending on inherited 
syphilis, is by no means rare. When there is a syphilitic affection of the 
liver in such children, syphilitic pancreatitis is frequently found. In 
early childhood and youth cancers have been noted. Bohn found cancer 
of the pancreas in a child seven months old, Kiihn in a girl two years old, 
and Dutil in a boy of fourteen. Cysts occur even in infancy. Railton 
found a cyst in a girl six months old, Lynn in a boy two years old, v. 
Petrykowski in a girl three and a half years old, and Fenger in a girl 
eight years old. The last three cases were operated upon successfully. 
MacPhedran describes a case of acute pancreatitis in a boy nine months 
old. In the special part the age is tabulated in a number of the diseases. 

Claessen gives the following statistics with regard to the relative 
frequency at different ages. Among 262 cases there were found: 


Ty the MEWDOMN. ncn cists ela tae eg ie ed eats 5 cases 
Ta Ghe first Vear fs... cts Gath nae Raa ct Woes eaten es a) 
From the first tothe tenth year ...........5..0.0ceeeees 7 | ed 
From the tenth to the twenty-fifth year ................. 41 ‘“ 
From the twenty-fifth to the sixtieth year ............... 156 “ 
Beyond the sixtieth years cco. cinch ewan ios ad eae 38S 


The postmortem records of the Berlin and Vienna Pathologic Insti- 
tutes for a term of ten years show the following relative frequency of 
these diseases at the different periods of life: 


BERLIN PATHOLOGIC INSTITUTE. 


AGE. NUMBER OF CASES. 
From 10 to 20 years ........600055 vse searhugk pelle Bee + 
* 21 to 30 “Loca cscs ets pele eee 12 
81 00 40 cca des ciccavea cal fe eee 12 
* 41 to BO kc ees tives ¥en bee 11 
Gh: | en erent meV one 9 
GL to 70 oe ad ae Sa 4a te es coat Oe ee 5 
6 TE 0 80. eee ee eee 4 


In two cases there is no statement regarding the age. 


GENERAL STATISTICS AND ETIOLOGY. 107 


VIENNA PATHOLOGIC INSTITUTE. 


AGE, NUMBER OF CASES. 

Pron 10 ti 20 OV ORts ae ia ulin eae eit ay aero 3 
Hie so Opes | 9 ROM > ean Aen belt ge aA TERI hee BRNO Sa S Or BURNS ETS Anne Car Ee Cy 5 
OO ees a CO Ne caine Sk is VintaR heer ah AR na One Rye eee a Ty 
SO, PASE PD COS Pe ele tat vod Garcia eee oe aed Cae a leer hd a as fad 21 
beding 51 tar tt, na ete a MONS SEP ne MAW Sikh nie et AE NOES eRe RORT ES TE 24 
BS Sth Oras ee np enter en eg re ete eh ee re eae ees ee Cate che eciaig 25 
BE ST EOL, Wo aire Wee ete epee eR MeL ecu atc react eiey 7 
Neer: Te ce te” | 6 On SRR etme OW ee oh MERE APA ce aT CT a ene 7 Rare eR ee 1 
.95 


In one case no statement was made concerning the age. 

The etiology of pancreatic diseases is usually obscure. The hereto- 
fore mentioned causes—as, prolonged use of mercury, misuse of tobacco 
and drastic cathartics, pregnancy (Mondiére), suppression of the menses 
(Schonlein)—are scarcely deserving of mention. The influence of 
syphilis and alcohol is undoubted. These certainly are a cause of chronic 
inflammations of the gland. 

Acute purulent processes are of bacterial origin and are to be 
attributed to the admission of organisms from the intestine or from the 
bile-passages. This subject will be treated more in detail in the special 
part. 

Chronic pancreatitis is, no doubt, due to a similar etiologic factor. 
Various processes which promote the entrance of micro-organisms, 
cholelithiasis, for instance, may give rise to chronic pancreatitis. 

Catarrhal processes in the pancreatic ducts resulting from the con- 
tinuation of catarrh from the intestine and biliary tract produce stagna- 
tion of secretion and its results. The secretion may become stagnant 
from other causes: for example, the formation of calculi in the pancreas, 
compression of the excretory duct by indurations, scars, tumors, calculi 
in the ductus choledochus, ete. Chronic pancreatitis and cyst forma- 
tion may result. 

The influence of injury in the production of cysts and hemorrhages 
is well established. Atrophy of the pancreas certainly may be a mani- 
festation of general cachexia and marasmus. Autodigestion of the pan- 
creas is also to be mentioned as a cause of pathologic changes. In the 
section on Necrosis and Fat Necrosis this question is more thoroughly 
treated. 

Venous hyperemia and stasis may result from disease of the heart, 
lungs, and liver. The continuance of processes which have their seat in 
the neighborhood (neoplasms of the stomach, duodenum, and liver, and 
ulcers of the stomach) may include the pancreas. Metastases of in- 
flammatory or neoplastic character may attack the pancreas. 

In acute and chronic infectious diseases there are various alterations 
of the pancreas: parenchymatous degeneration in acute infectious dis- 
eases, and gumma and tuberculosis as a part of general syphilitic and 
tuberculous infection. 


108 DISEASES OF THE PANCREAS. 


V. GENERAL THERAPY. 


From the rarity with which a correct diagnosis * of pancreatic disease 
can be made specialized treatment is not often possible. The patients 
with pancreatic disease recover or die generally without the disease being 
recognized ; therefore, apart from surgical treatment, a specific treatment 
affecting the diseased organ is usually not attempted. Therapeutic 
suggestions are sufficiently numerous, the older physicians having recom- 
mended a long list of medicaments and methods of treatment. 

Claessen enumerates the remedies suggested: Eyting saw a chronic 
pancreatitis wholly cured by chlorin and iron; Landsberg states that 
scirrhus was cured by ‘nitro-muriatic acid, foot-baths, tamarind whey, 
and laxative pills.’ Calomel has been recommended as a specific by 
various writers (Brera, de Haén, Harder, Berlioz, Claessen). Nasse 
claimed to have seen a very strikingly favorable effect from the use of 
corrosive sublimate in a severe case of chronic inflammation with indu- 
ration of the pancreas. In all these cases of so-called cure there is no 
proof of a correct diagnosis; therefore the value of these observations 
is very problematical. i 

When we can recognize the etiologic factors, a rational therapy is 
possible. Syphilis doubtless plays an important part in the production 
of pancreatic diseases, and the antiluetic treatment of chronic inflamma- 
tion or of gumma of the pancreas in a syphilitic patient might have 
favorable results. 

Diseases of the intestine may have a decided influence on the occur- 
rence of affections of the pancreas, and the rational treatment of catarrh 
and bacillary affections of the intestine may have a protective and 
healing influence on the pancreas. 

The connection between chronic inflammations of the pancreas and 
cholelithiasis has definitely been established by recent experience. There 
is no doubt that the timely removal of calculi from the gall-bladder or 
bile-ducts can save the pancreas from inflammation and is influential in 
promoting the resolution of existing inflammation. 

Other affections of the liver and biliary tract also are of influence 
in the production of diseases of the pancreas, and if the former can be 
directly treated, disease of the pancreas may be prevented and existing 
disturbances of the pancreas perhaps may be relieved. 

If alcoholism, arteriosclerosis, acute and chronic infectious diseases, 
affections of the heart, lungs, kidneys, and those causing disturbances 
of general nutrition, as diabetes (from extra-pancreatic causes), obesity, 
etc., which are of importance in the etiology of diseases of the pancreas, 
are checked, the dangers of impending diseases of the pancreas are 
lessened, or if actually existing, their course may indirectly be alleviated. 

For years much has been hoped from organotherapy in pancreatic 
diseases, but unfortunately no material advance has been made in this 
direction. Pepsin, and later pancreatin, were the first used, long before 
the present era of modern organotherapy. Some of the results obtained 
in patients gave much promise. Under this head belongs the case already 
mentioned of Fles, who gave to a diabetic, who passed in the stools much 


* The diagnosis of pancreatic diseases in general has been thoroughly considered 
in the section on General Pathology and Symptomatology, and the diagnostic value 
of the individual symptoms has been given at length. 


GENERAL THERAPY. -° 109 


fat and undigested meat, calf’s pancreas with the food, and in conse- 
quence caused -an improvement in the digestion of fat and meat. The 
pancreas was finely minced in a mortar, rubbed with 6 ounces of water, 
and strained. The resulting milk-like fluid was taken after meals. 
Hach day an entire calf’s pancreas was used. The case described by 
Langdon-Down also could here be mentioned: A man fifty-two years 
old, suffering from diabetes, fatty stools, and great emaciation, was 
greatly improved after the administration of pancreatin (Iriedreich). 

Organotherapy in the treatment of diseases of the pancreas has been 
strongly supported by the results of experiments on animals, as shown 
in a previous section. Abelmann, experimenting on animals from which 
the pancreas had been removed, found a marked improvement in the di- 
gestion of fats and proteids after pig’s pancreas was added to the food. 
Sandmeyer also saw an improvement of fat-digestion after adding pan- 
creas to the food. De Renzi, Cavazzani, and others had similar results. 

It is evident that when diabetes was supposed to be related to changes 
in the pancreas, the attempt was made to treat the diabetes by the 
administration of pancreas or pancreatic preparations, and numerous 
reports have been made. The question has not yet reached a satisfactory 
conclusion. Some authors report favorable results, while with others 
the reverse is the case. 

Since it is possible only in rare instances to make a diagnosis of pan- 
creatic diabetes with certainty during life, because other characteristic 
features are usually lacking, organotherapy was often used when the 
pancreas certainly was not the cause of the diabetes. The negative 
results in these cases are of course not convincing, either for or against 
the value of this treatment. But even in the cases with positive results, 
_ strict proof is generally lacking that a disease of the pancreas is the 
necessary cause of the diabetes, and the objection certainly is justified 
that any improvement is to be referred to other factors than the 
administration of pancreas or preparations of pancreas. 

Among the positive results, the following may be mentioned: 

Battistini obtained pancreatic juice from the fresh gland of a calf 
or sheep by maceration with physiologic salt solution or with glycerin. 
After filtration of the extract through sterilized paper and dilution of 
the glycerin extract with water, 5 c.c. at first, and afterward 15 to 20 c.c. 
were injected. In a man thirty-seven years old, the amount of urine 
before treatment was 4200 c.c., in which were 110 gm. of sugar; after 
three injections the amount of urine was 4110 ¢.c. containing 89 gm. of 
sugar. Later there were fever and a further diminution of the glycosuria. 
The amount of urea remained unchanged. 

In a woman thirty-nine years old the amount of urine fell from 3800 
c.c. to 2000 c.c., the amount of sugar from 111 gm. to 43.04 gm. After 
the injection of 15 c.c. the result was still more significant and continuous ; 
the amount of sugar reached only 3 to 5 gm. and the patient felt stronger, 
although her weight did not increase. 

In two diabetics, Hale White either gave internally 2 ounces of fresh 
pancreas or injected two drops of extract each morning and evening. 
The amount and specific gravity of the urine did not change, the urea 
in one case remained unaltered and in the other increased. The excre- 
tion of sugar was unaffected in one case but diminished in the other. 
The subjective condition of each patient was improved. 

In two cases Wood found improvement of the general condition, and 


110 DISEASES OF THE PANCREAS. 


in one there was a diminution in the amount of sugar. Rémond and 
Rispal saw decrease in the excretion of sugar in one case of diabéte maigre 
after injection of pancreatic extract. 

Sibley Knowsley used the freshly expressed juice or the slightly 
cooked gland. The result in one severe case of diabetes was very favor- 
able; the weight increased about 700 gm. and the subjective troubles 
and glycosuria diminished. 

Lisser used pancreatic enemata. The ox or sheep pancreas was 
minced finely, allowed to stand for twenty-four hours with an equal 
amount of physiologic salt solution, and 2 gm. of sodium bicarbonate 
were added to it after being slightly warmed. From 50 to 120 gm. were 
given daily in the form of an enema to a man seventeen years old who 
for three months had suffered from a severe diabetes with daily amounts 
of urine equal to 10 to 14 liters and an amount of sugar equal to 6.25%. 
After 34 enemata, the daily amount of sugar fell from 875 gm. to 425 
gm.; but when the remedy was omitted, the excreted sugar became 916 
gm. and then fell to 256 gm. The body-weight increased about 44 
pounds. In a second case also the result was very favorable. The 
weight increased 84 pounds. In the latter case diarrhea occurred 
after the enemata had been used two or three weeks. a0 

Bormann used the gland in a diabetic thirty years old. With a strict 
diet of meat the patient excreted 1500 to 2300 e.c. of urine with 30 to 
60 gm. of sugar, and with a diet of milk and meat 30 to 110 gm. After 
he had eaten on each of three days a slightly broiled pancreas, the amount 
of sugar was 17 gm., and four days later 40.5 gm. As the patient refused 
to take the gland, the juice was given in anenema. After four days the 
amount of sugar was 14.6 gm. and then increased to 30.3 gm. The 
sugar remained quite constant at this level, in spite of the fact that the 
patient received a daily subcutaneous injection of 14 ¢.c. of pancreatic 
extract. His subjective condition and his strength improved. The 
weight increased, the thirst and amount of urine had diminished. 

Ausset gave the pancreas of a calf internally to a man who daily 
excreted 38 gm. of sugar. After two days the excretion of sugar had 
fallen to 4.0 gm. On the ninth day the glycosuria had entirely dis- — 
appeared. The urine remained free from sugar for a month. 

Among the negative results, the following may be mentioned: 

Comby tried injections of the pancreatic juice of a guinea-pig, pre- 
pared after Brown-Séquard’s method, in a diabetic twenty-five years old. 
One-half ¢.c. was injected at first every second day, and later every day. 
The daily amount of urine reached 7 to 10 liters, the excretion of sugar 
varied between 800 gm. and 1000 gm., and the amount of urea had 
increased to 75 gm. The injections were well-borne, but were without 
influence on the course of the disease. 

In two severe cases of diabetes Mackenzie used the juice expressed 
from the fresh pancreas in daily doses of 15 gm. The amount of urine 
diminished during the treatment. The subjective symptoms, especially 
the thirst, became less. The glycosuria was not influenced. 

Firbringer, and also Renvers, used glycerin extract of pancreas in 
two diabetic patients without result. : 

Goldscheider used pancreatic extract in six cases of diabetes without 
any result. Senator had negative results with pancreatin. 

In a diabetic fifteen years old Williams tried the injection of extract 
of pancreas, and later undertook the implantation of the gland of a 


GENERAL THERAPY. suis 


sheep which had just been killed. The patient, however, died comatose. 
In two cases he gave the gland in part internally and in part subcu- 
taneously; in the first case no result. was to be noted, and in the second 
the result was probably to be ascribed to the diet and the administration 
of codein. 

The most recent communications concerning the treatment of pan- 
creatic diabetes with preparations of pancreas are those of Hugounenq 
and Doyon. They found that the excretion of sugar was not diminished. 

In conclusion, mention may be made of an observation by Mairet 
and Bosc, who found that in healthy men the injection of an emulsion 
of pancreas caused fever, acceleration of the pulse, weakness, increase 
of the amount of urine and of the excretion of urea. After injection of 
the glycerin extract of pancreas in 21 epileptics, an increase in the par- 
oxysms was observed. 

In a number of diabetic cases which were admitted to the Rothschild 
Hospital, I also have tried organotherapy. The preparations chiefly 
used were such as had earlier been tried with reference to their physio- 
logic activity. The ‘zymine” tabloids and pancreaticum siccum of 
Merck, introduced by Burroughs, Wellcome and Co., had the desired 
activity. In addition, pancreatic enemata prepared according to Lisser’s 
direction were tried. The pancreatic preparations recommended by 
Knoll were not used. 

The experiments were made with eight diabetic patients, and the 
following results are briefly sketched: 


1. H. R., man sixty-one years old, admitted on the 24th of December, 1895. 
Amount of urine 2 liters, specific gravity 1031, sugar 1.2%, no acetone. January 19, 
1896, sugar 2.7%. From the 20th of January daily administration of 2 zymine 
tabloids. February 5th, sugar 3.3%. ~< 

2. R. W., woman thirty-eight years old, admitted January 20, 1896. At the 
time of admission, amount of urine 44 liters, specific gravity 1030, sugar 6%, much 
acetone, body-weight 45.5 kg. March 27th, amount of urine 5 liters, 3.5% of sugar, 
much acetone, body-weight 44 kg. From the 7th of April, 0.5 gm. of pancreatin of 
Merck was given three timesaday. April 19th, 5 liters of urine, 5% of sugar. 

3. A. L., man thirty-five years old, admitted September 30, 1895. At the time of 
admission, 4.5% sugar, 0.026% acetone, acetic acid, specific gravity 1026, day’s 
amount 4 liters, body-weight 47 kg. December 5th, 2.3% sugar, 45.6 kg. body- 
weight. December 22d, 2 zymine tabloids, from January 3d 3 tabloids daily. Jan- 
uary 20th, 3.1% sugar, 46.5 kg. body-weight. March 16th, 43.5 kg. body-weight. 
March 27th, 1896, discharged. Admitted again April 20th, the patient very misera- 
ble, 3.7% sugar, 5 liters urine, large amount of acetone. Coma. Death. At the 
autopsy, marantic atrophy of the pancreas was found. 

4. J. R., man forty-five years old, admitted February 6, 1896. At entrance, 
34 liters of urine, specific gravity 1032, sugar 3.8%, 60 kg. body-weight. From the 
16th of February three zymine tabloids daily, sugar 1.4%, 3 liters. March 10th, 
4.2% sugar, 34 liters urine in one day, tabloids omitted. March 21st, 3 tabloids 
again. March 26th, 4 liters urine, 6.4% sugar. April 4th, 0.5 gm. daily ‘pancreatin. 
April 15th, 4.2% sugar, 3} liters urine. 

5. M. , man sixty-two years old, admitted March 27, 1896.. At entrance, 
body-weight 50 kg., 5 liters urine, 3. 2%, sugar, no acetone. After diabetic diet, 
5 liters urine and 1.4% sugar. From April 4th, 0.5 gm. ogo sane daily. April 
17th, 3 liters urine and 1.9% sugar. May 19th, 3 liters urine, 1.9% sugar, and 49.5 ~ 
kg. body-weight. 

6. A. R., man twenty-one years old, admitted March 31, 1896. At entrance, 
sugar 7.7%, specific gravity 1040, daily amount 5 liters, no acetone, body-weight 45 
kg. April 15th, after diabetic diet, sugar 6.7%, body-weight 46 kg., urine 5 liters. 
Three times a day, 0.5 gm. pancreatin. May 4th, body-weight 48 ke. ., 6.38% sugar. 
May 7th, pancreatin omitted on account of severe abdominal pains. The patient left 
the hospital May 31st, and reentered January 2, 1897, in a miserable condition. 
Phthisis, 8 liters urine, specific gravity 1032, sugar 3. 3%, much acetone, body- 


112 


DISEASES OF THE PANCREAS. 


weight 45 kg. Death February Ist, coma. 
pancreas was found. ; 
7. J. J., woman fifty-four years old, admitted March 2, 1897. Diabetes for ten 


years. 


specific gravity 1030, traces of albumin, 4.4% sugar, large amount of acetone. 
following table shows the data noted by Dr. Katz. : 
the patient received 15 pancreatic enemata made according to Lisser. 


At the autopsy, marantic atrophy of the 


In the year 1891, 8% sugar. At entrance, body-weight 56 kg., urine 3$ liters, 


The 


From March 7th to March 24th 
March 24th, 


the patient complained of severe colicky pains in the region of the stomach, -com- 
The patient had previously often suffered from anginoid 


bined with oppression. 























DATE. Sp.Gr. Nirrogey.| AmMmonra.) Sucar. | Acetone. | P.O; | y RE 
< 

March 4.) — | 1.030] 0.447% | 0.000% | 4.4% | 0.022% | — 

« 6) — | — | 0.746% | 0.054% | 4.5% = = 

Cee oe eee ee ms = “ereatie 

— | 1.032) 0.654% | 0.057% | 5.4% | 0.022% | — 

‘ sn coe nee nen 0.550 60 = 

“10, som nom 28% [008% | az | am | 

“srs | 8% | nowy | 0%, lowutes| 

“ 12) as no 2810 | 000 | 0 ome | 

eg esac ea eee: sr a. as = 

14) 8500 | 1.081 fon o4 gm. |1.833 go.llet? em} ~~ | — 

Badia are on ee 2331 gn once O877 wal = 

“  16,| 3250 | 1.030 Paee ee Sore = x 

*r) sso no 280% Lone | sae | | | 

* 19) soo) roo 20% awe | sae | | 

* sn tn) r| S67 00% | 480% lou, logs 

20.) 3500 |2.028 lor a4 gon lutea ga llso2 en} | 

© BE) 3750.11 022 Bay on 1665 oo. ae = = 

“mal com /1.0m 0a8e 00ne, | aise |_| 

“28, 8500 | 1.085 1808 gin 1410 gyo.|178.3 gn 0.770 gra 2718 a 

+ o4| mon sone cam agers am] — | Fee 

* aso so] 003% Lager | ate | naam pene 

“| aso] rons) — | S90 | a | non nga 

LOOT EH 27801 2:0814 | 2s me. 3.52% “is s¥. 


96.7 gm. 














GENERAL THERAPY. 113 


attacks. March 25th, vomiting after indigestion, repeated several times during the 
day. Tongue dry, pulse 120, temperature normal. March 27th, collapse, coma. 
March 28th, death. At the autopsy were found: Degeneratio myocardii adiposa ex 
endarteriitide chron. arter. coron. Cirrhosis hepatis in potatrice. Tumor lienis 
chronicus. Catarrhus ventric. et intest. chronicus. Diabetes mellit. The pan- 
creas large, dense, infiltrated with much fat tissue, which also lies between the lobules 
of the pancreas. The lobules, on section, appear sharply defined, separated from 
each other by loose connective tissue; reddish-gray. Weight 97 gm. Microscopic 
examination showed nothing pathologic. (Prosector, Dr. Zemann.) 

8. Ch. Sch., woman twenty-four years old, admitted March 9, 1897. The ex- 
aminations of the urine during the whole stay at the hospital were made by Dr. Katz 
in the same thorough manner as in the preceding case. At entrance, amount of 
urine 3000 c.c.; specific gravity 1038; sugar 5.9%, 177 gm. a day; acetone 0.015%, 
0.458 gm. a day. March 19th, 3500 c.c. urine, specific gravity 1033, sugar 4.73%, 
165.5 gm. in the day’s amount, 0.021% acetone, 0.752 gm. of acetorfe in the day’s 
amount of urine. Pancreatic enemata for nine days. March 28th, 2500 c.c. urine, 
specific gravity 1036, sugar 5.17%, 128.3 gm. in the day’s amount of urine. On 
leaving the hospital, April 8th, the amount of urine was 2000 c.c., specific gravity 
1035, sugar 5.6%, 112.2 gm. per day. 


The experiments showed, therefore, that the administration of pan- 
creatic preparations was without influence on the course of the diabetes. 
The variations observed, now an increase and now a diminution in the 
excretion of sugar, certainly had no connection with the treatment, 
and much more probably were due to the diet or other factors. In 
several of these cases, on account of the large amount of acetone or on 
account of advanced phthisis, a strict diabetic diet could not be ordered, 
and many patients avoided the diet prescribed despite the most careful 
watching. It is, therefore, not strange if figures appear which are to be 
explained only by the increased ingestion of sugar. 

Among all these cases there was not one which could be shown posi- 
tively to be one of pancreatic diabetes. Many of the patients presented 
during life the perfect picture of diabéte maigre. They were relatively 
young, thin, and the diabetes pursued a rapid course. It was certain 
that some adhered strictly to the prescribed diet, and yet a great deal of 
sugar always was excreted. The complication with tuberculosis, men- 
tioned by Lancereaux, was likewise present. Peculiar pancreatic symp- 
toms, as changes in the digestion of fat and proteids, etc., did not appear. 

In two fatal cases changes were found in the pancreas, but they were by 
no means such as could be claimed with certainty to be the cause of the 
diabetes. On the contrary, the assumption was justified that these 
were conditions of general marasmus produced by the diabetes. The 
experiments made by us, therefore, are not conclusive. It may still be 
possible that in cases of genuine pancreatic diabetes organotherapy would 
have a favorable influence. 


There is but little experience in the effect of pancreatic preparations 
on diseases of the pancreas. In one of my cases I believe I can justly 
assume a favorable influence of such preparations on the digestion of 
fats. Although the diagnosis of disease of the pancreas was not estab- 
lished by an autopsy, yet such marked symptoms were present that 
there seems to be scarcely any doubt. 

The case was as follows: J. N., forty-nine years old, many years before had an 
attack of pneumonia and malaria; for several years had frequent attacks of dis- 
turbance of digestion after errors of diet; seven months before our observations be- 
gan had noticed pains in the epigastrium gradually increasing in severity; the pa- 


tient felt these pains running across the upper portion of the abdomen. They were 
generally independent of eating, were sometimes slighter and sometimes more severe 


8 


114 DISEASES OF THE PANCREAS. 


after a meal. The patient lost flesh. As there was at the same time migraine, ring- 
ing in the ears, general weakness, and no abnormal objective signs, the diagnosis had 


been neuralgia or neurosis. ; 
When I saw him for the first time, there were circumscribed tenderness in the 


epigastrium and slight yellow color of the sclerotic in the urine; there was a faint reac- 
tion of bile-pigment, but no sugar. Under observation the jaundice became daily 
more intense, the stools were wholly free from bile, and the quantity was remarkably 
large in comparison to the relatively small amount of nourishment. 

The examination of the stools gave the following results: Stools formed, white, 
perfectly free from bile, of salve-like consistency. Microscopic examination: (1) A 
few remains of distinct muscle-fibers, with the structure well preserved *; (2) few 
vegetable cells; (3) fat-drops; (4) very numerous fat-acid needles; (5) bacteria, 
detritus. The examination of the urine resulted as follows: Specific gravity, 1018; 
acid; indican in large amounts; no abnormal constituents. 

The sensitiveness to pressure in the epigastrium increased and a resistance to the 
right of the median line and extending along the same could be recognized. The 
resistance became more and more marked and on certain days, especially when the 
stomach was empty, a hard mass very sensitive to pressure was very distinctly to be 
felt extending from the right across the median line of the abdomen; it moved some- 
what downward at each inspiration. The stomach was not dilated. The liver in- 
creased gradually in size, the gall-bladder could be more and more distinctly palpated 
as a pear-shaped tumor, and the poor digestion of fat and proteids became more and 
more pronounced. 


The coincidence of all these symptoms made the diagnosis of car- 
cinoma of the head and body of the pancreas seem very probable. The 
pains across the epigastrium for months, the emaciation, the gradually 
increasing jaundice, even to perfect closure of the ductus choledochus, 
the poor digestion of fats and proteids, the appearance of a tumor corre- 
sponding in position to that of the pancreas, the growth of this tumor, 
the lack of symptoms which would point to a pyloric or duodenal cancer 
or to cholelithiasis, all justified the diagnosis of cancer of the pancreas. 

Merck’s pancreatin, 1 gm. daily, was given to this patient, and the 
stools examined some days later showed a decided improvement in the 
digestion of fats. Repetition of the examination gave the same result. 
The patient also expressed himself as feeling better, and did not feel so 
weak as formerly. From news which I received some weeks later from 
the patient, I was able to decide that no essential change had occurred 
in his condition. This is the only case in which I could persuade myself 
that there was a real improvement in the digestion of fats and proteids 
from the administration of preparations of pancreas. 

[Salomon + increased the digestion of fat in a mild case of diabetes 
with fatty stools by the administration of fresh pancreas in capsules 
or spread on bread. In the periods before and after medication 51% 
-and 85% respectively of the fat ingested were unabsorbed, during the 
intervening period when the pancreas was given but 19% of the fat was 
unassimilated. In another experiment upon the same individual pankreon 
was used instead of the fresh pancreas. In the preliminary period 
38.4% of the ingested fat escaped absorption; in the next period 1 gm. 
_pankreon was given five times daily and the percentage of undigested 
fat fell to 21.3. 

Joslin { increased the digestion of fat 50% by the use of ox-bile given 
in pill-form.—Eb.] | 

The recommendation may well be made that further experiments in 

* The patient in the last few days had eaten only a very small amount of scraped 


eef, 
t Berl. klin. Wochen., 1902, p. 45. 
. } Jour. of Experimental Med., 1901, p. 513. 


GENERAL THERAPY. 115 


this direction should be undertaken. It is to be assumed that in disturb- 
ances of digestion which are caused by lack of the pancreatic juice a better 
utilization of the food would be brought about by the use of active pan- 
creatic preparations. For this purpose the pure gland, as in the earlier 
cases, or pancreatic preparations should be used. 

It is doubtful from experience thus far whether an efficient organo- 
therapy for the diseased pancreas can be found like that for diseases of 
the thyroid. 

Surgery, in the last few years, has been successful in the treatment 
of diseases of the pancreas. Cysts, abscesses, necroses, even tumors of 
the pancreas have been operated upon with brilliant results. To be 
sure, some operations were performed even before the time of Lister, as 
by A. Petit, Caldwell, Kleberg and Wagner, Wandesleben, but it was 
Gussenbauer who, by successfully operating on a cyst, opened the way 
for pancreatic surgery.. . 

Under Special Considerations the details of this important achieve- 
ment will be given, and it is to be expected that, with the advance of our 
knowledge of diseases of the pancreas, a rational surgical therapy will 
be placed on a firmer foundation. Symptomatic treatment alone is all 
that is left for the clinician, in the present state of our knowledge, when 
the etiologic treatment earlier described fails or is without hope. The 
narrow field of the physician’s activity is limited. Its object is to lessen 
pain, to provide sufficient nourishment, the eventual introduction of 
artificial feeding, the increasing of strength, in order to gain time, that 
a process capable of recovery may end favorably, and the alleviation of 
distressing symptoms caused by such complications as Jaundice. 


SPECIAL CONSIDERATIONS. 
I. INFLAMMATIONS OF THE PANCREAS. 


So far as present anatomic and clinical data show, the inflammations 
of the pancreas are, on the whole, rare diseases. Among the 18,509 
autopsies which were conducted in the Vienna General Hospital during 
the years 1885 to 1895, only 15 cases are found noted—1 of hemorrhagic 
pancreatitis, 9 abscesses (primary and secondary), and 5 cases of chronic 
indurative pancreatitis. 

Inflammations of the pancreas undoubtedly occur more frequently 
than is thought, because there are curable forms leaving no traces, as 
will appear later. 

In general we can distinguish the following varieties *: 

(1) Acute hemorrhagic pancreatitis; (2) suppurative pancreatitis; 
(3) necrotic pancreatitis; (4) chronic indurative pancreatitis. 

The variety of disease characterized by Friedreich and others as 
acute parenchymatous pancreatitis, and which is found especially in severe 
infectious diseases, ought not, as Dieckhoff states, to be included among 
the inflammations, but rather among the retrograde disturbances of nutri- 
tion. 

Mixed forms also may occur; thus, purulent inflammations with 
hemorrhages, purulent inflammations with indurative pancreatitis, puru- 
lent and chronic indurative inflammations with necroses. 


* 


1, ACUTE HEMORRHAGIC PANCREATITIS. 


There is no doubt that slight degrees of hemorrhage occur in the 
course of both acute and chronic varieties of inflammation. Hemor- 
rhages into the pancreatic tissue occur easily, as it appears, under certain 
conditions. This may be based on the anatomic structure (Fitz). .Hem- 
orrhages easily arose, in our experiments upon animals, in the attempt 
at extirpation of a portion of the gland or of the whole gland and in the 
artificial inflammations. . 

The term hemorrhagic pancreatitis is used by many authors to repre- 


* A catarrhal pancreatitis is also mentioned by many authors. The inflamma- 
tory processes in the parenchyma of the gland which take their origin from catarrhs 
of the excretory duct will be referred to in the following description. Doubtless 
there is a catarrhal inflammation of the excretory duct, which runs its course without 
inflammatory changes in the gland itself. A clinical presentation of this process 
appears impossible in the present condition of our knowledge, as neither the ana- 
tomic data nor the clinical symptoms are clear enough to enable a distinct picture of 
the disease to be formed. Further investigation. must be made in order to permit 
clinical recognition of these processes, probably of not infrequent occurrence and also 
curable. ; 

; 116 


Ld 


ACUTE HEMORRHAGIC PANCREATITIS. 117 


sent a process with characteristic symptoms in which more or less ex- 
tensive hemorrhage, affecting a large part of the entire gland, stands in 
the foreground. 

It is a mooted point whether in these cases the hemorrhage is only the 
consequence of the inflammation, or whether the hemorrhage is primary 
and the inflammation secondary, or whether there is simply a hemorrhage 
in which, because of the rapid course or for some other reason, no in- 
flammatory processes at all develop. 

Neither the pathologists nor the clinicians are agreed in their under- 
standing of the process. Orth says regarding it: ‘‘Parenchymatous 
pancreatitis is generally connected with hemorrhages, which were in 
many cases so considerable that the extravasated blood escaped through 
the pancreatic duct into the intestine. It is possible that some of the 
fatal hemorrhages are to be regarded as symptoms of a pancreatitis.” 
Birch-Hirschfeld mentions two cases which indicate the existence of a 
hemorrhagic pancreatitis leading quickly to death. According to Ziegler, 
hemorrhages may occur in the region of the pancreas as the consequence 
of inflammations, and may be so severe that the intrapancreatic con- 
nective tissue and the fat tissue are filled with blood, hematomata thus 
being formed. An opposite view is advanced by Dieckhoff. He states 
that in an exact investigation of the cases known it has been shown 
that a great part of the cases characterized as hemorrhagic pancreatitis 
had another cause for the hemorrhage, and the inflammatory phenomena 
were due to the hemorrhage. Dieckhoff considers it not improbable 
“that in an acute inflammation, through injuries of the vessel-wall, 
minute hemorrhages can occur in the pancreas as in other inflamed 
organs. This variety does not, however, receive the designation hemor- 
rhagic pancreatitis, which term is rather applied to those cases where 
hemorrhage predominates and where frequently the proof is absent.” 

The same divergency of views exists among the authors who consider 
the subject from the clinical point of view. Fitz takes the most decided 
position ; he describes hemorrhagic pancreatitis as an independent affec- 
tion from the clinical point of view, separates it from the hemorrhages, 
and collects from the literature 17 illustrative cases. 

Fitz assumes, to be sure, that the anatomic signs are not clear enough, 
but considers himself justified in assuming the presence of an inflammation 
if the symptoms indicate it. When the general symptoms of inflammation 
are present, says Fitz, and when the pancreas is described as infiltrated 
with blood, then such a combination of symptoms and lesions is to be 
reckoned rather among the inflammations than among the hemorrhages. 

Seitz, in a thorough and comprehensive study, investigated all the 
known cases pertaining to this subject, and came to the conclusion that 
inflammation as cause of considerable hemorrhage into the pancreas is, 
up to the present time, ‘‘not so clearly and positively shown as we might 
wish.”’ He does not deny the possibility of its occurrence, but inclines 
to the view that, so long as the opposite is not shown, the inflammatory 
symptoms are to be regarded as consequences of the hemorrhages. These 
inflammations, which may reach the highest degree, become much more 
probable through the communication of the pancreas with the intestine, 
through the great tendency of the gland to decomposition, and through 
the proximity of the peritoneum and through the chemical peculiarities 
of the pancreatic secretion. 

In spite of the observation of Seitz, so apt in many respects, the 


118 INFLAMMATIONS OF THE PANCREAS. 


idea of a hemorrhagic pancreatitis is maintained in recent publications, 
as those of Korte, Jung, Dettmer, Cutler, Parry, Dunn and Pitt, ete. 

The divergence of views just described is easily explained. In the 
clinical form of the process, which some term pancreatic apoplexy and 
others term hemorrhagic pancreatitis, there is absolutely no means by 
which it can be decided whether the hemorrhage is the result of an in- 
flammation or the inflammation is a result of the hemorrhage, or whether 
there is simply a severe hemorrhage without any inflammation at all. 

In all cases the pathologic picture is about as follows: Usually there 
is the sudden onset of the symptoms, violent pains in the region of the 
stomach and umbilicus, nausea, vomiting, frequently the appearance of 
intestinal obstruction, immediate occurrence of collapse with feeling of 
anxiety, great rapidity of pulse, dyspnea, rapid loss of strength, death 
from exhaustion in a few hours or at longest in a few days. 

This distinction between inflammation with hemorrhage and hemor- 
rhage with inflammation cannot in most cases be seen in the body after 
death, and so it happens that one author regards as a pure hemorrhage 
the same case which another considers as inflammation. Of the 17 
cases which Fitz regards as examples of hemorrhagic pancreatitis, Seitz 
recognizes no one of them as proved with certainty, and he considers it 
also more probable in all the cases that the inflammation is a secondary 
process. Even the cases which are generally regarded as hemorrhagic 
pancreatitis—those of Léschner, Oppolzer, Osler and Hughes, Hirsch- 
berg, Birch-Hirschfeld—do not, according to Seitz, present the proof 
that the inflammation was the cause of the hemorrhage. 


Léschner’s case: An inebriate, twenty-six years old, dyspeptic for five years, 
mostly in consequence of faults of diet. About three weeks before the last sickness 
there were repeated attacks of colic. Suddenly continuous torturing pain in the 
- upper abdominal region with great restlessness, vomiting of stomach-contents, con- 
stipation, slight fever, on the fourth day of the disease collapse, epigastrium dis- 
tended, very sensitive to pressure; burning, often stabbing pains, which extend to 
the right toward the duodenum and to the left toward the spleen and also radiate 
backward and toward the right shoulder; the constipation persistent, death from 
collapse. At the autopsy the pancreas was found dense, more than twice as thick as 
normally, of a violet color externally. On cutting into the gland, a large amount of 
dark blood gushed forth, the individual acini were greatly enlarged, dark-colored, and 
traversed with vessels distended with blood; the intervening cellular connective * 
tissue was infiltrated with blood, the mucous membrane of the excretory duct ap- 
peared dark red. In the head of the pancreas a finely granular, yellow exudation 
was seen here and there between the acini. 


Seitz rightly suggests that in this case it was.not thoroughly shown 
that a primary inflammation existed. Just as little is it shown in the 
case described by Oppolzer. 


A strong, previously healthy man had severe cardialgic attacks, which constantly 
increased. On entrance, there were great restlessness, vomiting of abundant bilious 
masses, very frequent pulse, cold extremities, drawn face, severe pain in the region of 
the stomach, increasing on pressure, constipation, high fever; death three days after 
admission into the hospital. At the autopsy the pancreas was found enlarged to 
three times its normal size, and on section a bloody exudation was seen between the 
dark-red acini; the surrounding tissues were infiltrated with blood. 


In this case, also, there is no proof that an inflammation was the 
primary process. In the case of Hirschberg there were symptoms of 
intestinal obstruction in a very fleshy woman fifty-six years old, on 
whom laparotomy was performed on the fourth day after the beginning 
of the disease. Death at the end of five hours. At the autopsy the pan- 


ACUTE HEMORRHAGIC PANCREATITIS. 119 


creas was found greatly enlarged, black from hemorrhages, there was 
fatty degeneration and general peritonitis. Signs of fat necrosis were 
seen at the operation as well as in the corpse. 

It is not shown positively in the cases of Birch-Hirschfeld also that 
the inflammation preceded the hemorrhage. 

Hawkins also came to the same conclusion as Seitz and Dieckhoff. 
It is questionable, says Hawkins, whether the cases of acute hemorrhagic 
pancreatitis in general are not to be regarded as primary hemorrhages 
with secondary inflammatory processes. ‘If the patient survives the 
first attack, it is certainly clear that secondary changes must occur, 
analogous to the conditions in renal infarction.” Although we must 
grant that Seitz, Dieckhoff, and Hawkins are right in the assumption that 
the hemorrhage is in most cases to be regarded as the primary factor, 
yet some facts are to be mentioned which do not easily dispose of the 
idea that inflammatory processes may be the cause of the disease which 
runs so rapid a course. These facts are as follows: 

1. Seitz has suggested the following question as one of the most 
important supports of his reasoning: Why are there no cases of im- 
mediately fatal inflammation reported without hemorrhage? The most 
recent literature reports two such observations. Cayley describes a — 
case of acute pancreatitis in a man thirty years old who had previously 
been healthy; probably alcoholic. Three days before admission to the 
hospital, without definite cause, pains began in the stomach, constipa- 
tion, but no severe feeling of sickness. Ol. ricini and laudanum were 
ordered. On the next day, continuous pain; in spite of this, the patient 
continued to work. Then there was vomiting. On the third day the 
condition became more threatening and the patient was brought to the 
hospital. 

Status presens: Deep collapse, extremities cold, skin moist, pulse about 150, 
scarcely perceptible, slight cyanosis, irregular respiration, temperature 37.0° C. 
(98.6° F.), falling to 35.2° C. (94.4° F.), violent vomiting of milk, no symptoms of 
regurgitation of intestinal contents, severe pain, sensitiveness to pressure in the epi- 
gastrium, abdomen not distended, everywhere tympanitic, liver dulness normal, 
anuria, small evacuation of stools after enema, collapse despite stimulants; a fluid 
stool before death, which occurred on the fourth day of the illness. 

Autopsy: Body very rich in fat, great omentum and retroperitoneal tissue over- 
laden with fat, liver shows marked fatty degeneration, heart enveloped with fat, 
about 4 liter of bloody serum in the peritoneal cavity, the peritoneum over the pan- 
creas and intestine dull, injected, and reddened, but showed no fibrinous exudation. 
Tissue about the pancreas infiltrated with bloody serum, the fat tissue here and in 
the adjacent mesentery shows distinct fat necrosis. On lying in the water, a milky 
fluid exuded, which was regarded by Vdélcker as saponified fat. The pancreas was 
enlarged, reddened, somewhat brittle, the lobules pale red, transparent, resembling 
salmon, doubtless in a condition of coagulation necrosis, organ edematous with 
bloody serum. Pancreatic duct normal, containing no calculi. Although there 
was a general infiltration of bloody colored serum in and around the pancreas, yet 


neither hemorrhage nor suppuration was to be shown in the gland. Other organs 
normal. 


On the basis of his observations, Cayley comes to the conclusion 
that hemorrhages are not an essential factor in the pathologic picture 
of acute pancreatitis. ate 

The absolute proof is not brought forward that there was really an 
inflammation, as an exact microscopic examination of the case was not 
made, although it is certain that the clinical picture of the preceding 
case corresponds to an acute hemorrhagic pancreatitis, on account of 
the epigastric pain for one or two days, the sensitiveness to pressure, 


120 INFLAMMATIONS OF THE PANCREAS. 


vomiting, the sudden occurrence of collapse, which lasted until death 
on the fourth or fifth day of the illness, and although there was certainly 
no hemorrhage in the gland. Certainly fat necrosis was present, and 
it may be that the same factor which led to this lesion caused the 
changes in the pancreas, either directly or in the way of the fat necrosis 
(see section on Fat Necrosis). Likewise an analogous case: reported by 
Kennan does not give absolute proof. 


A woman thirty-eight years old was attacked with vomiting and pains in the 
upper abdomen. The discomforts persisted, the abdomen became distended, on the 
day afterward some urine was evacuated, but after that the anuria was complete. 
On the day of admission to the hospital there was collapse, subnormal temperature, 
pulse scarcely to be felt, cold sweat, no vomiting, pain slight, sensorium perfectly 
free, no jaundice, obstipation. On the next morning, death. Duration of the dis- 
ease, forty-two hours. . 

At the autopsy the woman was very well nourished; the great omentum very 
rich in fat, adherent in places to the peritoneum of the pelvis; slight peritonitis; adhe-- 
sions between the intestinal coils; large intestine, especially the descending colon, 
injected in places, of a very dark color in the region of the splenic flexure, with numer- 
ous dark-colored extravasations of blood on its surface; the main mass of inflamma- 
tion in the neighborhood of the head of the pancreas. The pancreas itself was 
markedly infected and enlarged, ‘evidently by inflammatory changes.”” The duc- 
tus choledochus and gall-bladder contained numerous, whitish, faceted calculi. One 
of these was found in the duodenum; they were about the size of a pea and possessed 
a dark nucleus. 


The passage of a gall-stone into the duodenum, Kennan thinks, may 
have been sufficient to produce lesions which rendered possible the en- 
trance of infectious organisms through the duct into the pancreas. In 
this case also there was no careful microscopic examination, and it is 
not shown whether an inflammation really existed, although the possi- 
bility cannot be denied that in this, as well as in the case just described, 
primary inflammatory processes were present. : . 

2. Some cases are reported in the literature in which an inflammatory 
process certainly existed with the hemorrhage, and in which it must be 
granted that the inflammation was possibly the primary factor. 


1. Zahn’s case: Waiter twenty-one years old, previously always healthy; four- 
teen days before he suffered from a pain in the neck, which had disappeared com- 
pletely for eight days, when on the 19th of February he suddenly on awakening felt 
pain in the region of the umbilicus. The pains were so severe that he had to return 
to his bed, and they lasted until the following day. On entering the hospital, there 
was cyanosis of the hands and feet, small, scarcely perceptible radial pulse. The 
patient complained of fulness and weight at the pit of the stomach, the abdomen was 
distended and sensitive to pressure, especially in the region of the cecum, with occa- 
sional eructation and nausea. On the next day there was at first slight, but later 
constantly increasing delirium. There was diarrhea, urine normal. On the fourth 
day there was slight jaundice; the temperature varied between 36.0° C. (96.8° F.) 
and 37.6° C. (99.7° F.). Death February 27th. The clinical diagnosis was pyo- 
septicemia arising from the intestine. 

At the autopsy there was found, besides cloudy swelling of the kidney and liver, 
a fibrinopurulent inflammation of the peritoneum. The mesocolon in its whole ex- 
tent, even to the rectum, thickened by a large amount of blood, extravasated be- 
tween its layers. The root of the mesentery was also suffused with blood. On more 
careful investigation for the origin of the hemorrhage, the walls of the portal vein 
near its beginning were found thickened by inflammatory exudation and in the 
interior there was a firmly adherent white thrombus. The vein was also compressed 
by the enlarged pancreas in which inflammatory changes were to be distinctly recog- 
nized on cross-section. It was opaque where not discolored with blood. The pan- 
creatic duct contained a thick brown fluid; its wall, as well as the pancreatic tissue 
lying next to it, were colored brown. It opened by a very narrow mouth somewhat 
below the ampulla of Vater into the intestinal lumen. 


\ 


PEATE. 





~ 
~ 


AcuTE HemMorRHAGIC PANCREATITIS or Four Days’ DuRATION. 
(From the Warren Anatomical Museum of Harvard Medical School, Boston.) 





ACUTE HEMORRHAGIC PANCREATITIS. 121 


The great majority of the pancreatic cells showed cloudy swelling, part of them 
had undergone fatty degeneration and part hyaline degeneration. The pancreatic 
duct contained altered red blood-corpuscles, brown pigment, distinct round cells and 
epithelial debris, fat drops, and finely granular detritus. Epithelial cells were no 
longer found on the wall of the duct. This was abundantly filled with small round 
cells and red blood-corpuscles. The interacinous connective tissue had a similar 
appearance. It was everywhere filled with round cells, which were most abundant 
in the neighborhood of the veins, especially those obstructed by white thrombi. The 
arterial wall appeared normal, the lumen of the vessels empty. 

- The bacteriologic examination of very thin sections showed numerous and quite 
large colonies of very small bacteria in the pancreatic duct. Colonies were found in 
considerable numbers in the connective tissue surrounding the canal, also in the inter- 
acinous connective tissue and in the wall of the portal vein. 


Doubtless this was a case of parasitic (acute) pancreatitis, but it does 
not follow that this was the primary process. It might easily be imagined 
that the passage of microbes from the intestine was rendered possible 
by the occurrence of a preceding hemorrhage in the pancreas, and that, 
therefore, the inflammation was a secondary process. 

The conditions in a case described by Kraft were still less conclusive: 


The patient had sudden severe pain in the region of the stomach, vomiting, and 
obstinate obstruction of stools, so that laparotomy was undertaken on account of a 
supposed intestinal obstruction. At the operation, after the evacuation of a brown- 
ish, turbid fluid, there was no sign of a peritonitis nor of an intestinal obstruction. 
The death of the patient soon followed, and the pancreas was found embedded in 
clotted blood, double in size, and beset with yellow and dark red foci. The connec- 
tive tissue of the great omentum and ascending mesocolon and the retroperitoneal 
tissue appeared infiltrated. The microscopic examination of the pancreas showed 
bloody infiltration and numerous leucocytes between the acini. The latter appeared 
degenerated in spots, which were composed of granular detritus, with few poorly 
preserved nuclei. 


The fact that the liver was fatty, that evidences of inflammation 
previously not recognized were found at the autopsy, prevents the origin 
of the hemorrhage from being regarded as simply inflammatory. On 
the one hand, it may be assumed that the fatty degeneration might have 
been the cause of the hemorrhage, for yellowish foci were present in the 
pancreas; on the other, the evidence of a recent peritonitis shows that 
it might have been possible that the small-celled infiltration did not 
precede the hemorrhage, but rather developed in consequence of it. 

The conclusion is just as difficult whether the hemorrhage or the small- 
celled infiltration was the primary condition in the case observed by 
Haidlen of acute pancreatitis after delivery. 


The patient, a woman thirty-three years old, during the seventh, ninth, and 
tenth months of pregnancy had suffered from severe pains of such intensity that 
perforative peritonitis was suspected. In the sixth week after delivery attacks of 
violent pain in the region of the pylorus occurred quite suddenly. Vomiting, sensi- 
tiveness to pressure in the pit of the stomach, finally collapse. The skin was very 


_ pale, the pulse was from 110 to 120, and signs of intestinal obstruction appeared. 


On the second day of her sickness the pains diminished somewhat, the collapse, the 
coldness of the extremities increased more and more, meteorism became more marked, 
pulse was 130 to 140. Death after ninety-six hours. At the autopsy no marked 
pearenas; the pancreas was enlarged and changed into a brownish-red mass suf- 
used with blood. The peritoneum also was slightly hemorrhagic. Under the micro- 
scope a small-celled infiltration of the pancreatic tissue was seen in addition to the 
extravasation of blood. 


The case which Dittrich describes as genuine inflammation of the 
pancreas alsé suggests that the inflammation was secondary. 


122 INFLAMMATIONS OF THE PANCREAS. 


A prisoner twenty-one years old made an attempt to hang himself in his cell, 
was rescued, and became conscious. From that time he had severe colicky pains in 
the lower abdomen, which continued uninterruptedly until death the day after in 
collapse. Four weeks before death he was said to have had an attack of colic which 
lasted eight hours. 

At the autopsy, the pancreas was found 16 cm. long, and 3.5 cm. thick through 
the middle; its tissue was very loose, easily torn, and to a great extent infiltrated 
with extensive hemorrhages. In the head of the pancreas the normal structure and 
color of the organ could be distinctly recognized with the naked eye. But the tissue 
here also was loose. The middle portion and the tail were changed into a dark- 
brown mass, almost confluent from the slightest pressure. If the head of the pan- 
creas were compressed with a knife, large quantities of a reddish-gray, thick, puriform 
fluid could be scraped from the cut surface; on microscopic examination it appeared 
that the whole organ was invaded by an inflammatory process characterized anatom- 
ically by a dense small-celled infiltration, observable in many places.”’ 


Although it was shown in this case that there was a wide-spread in- 
flammation, yet there was no positive proof that the inflammation pre- 
ceded the hemorrhage. 

There can be no doubt, according to the above communications, that 
the hemorrhage and inflammation existed at the same time, but it is well 
enough apparent also how difficult it is even at the autopsy to decide 
whether an idiopathic hemorrhagic pancreatitis exists. This decision can 
be made much less easily at the bedside. 

Although, as mentioned earlier, the possibility cannot be denied that 
there is an acute idiopathic pancreatitis, which runs its course generally 
with severe hemorrhage, very rarely without hemorrhage and without 
suppuration, yet in the present condition of our knowledge a clinical 
separation of these processes from the severe hemorrhages with or without 
inflammation is impossible. It therefore will be most appropriate to 
postpone clinical presentation of this subject to the section on Hemor- 
rhages. 

It was impossible to decide these questions by experiments on animals. 
It will be shown later that hemorrhages, abscesses, chronic inflammations, 
necroses, and fat necroses could be successfully produced in animals in 
different ways, but it was not possible to produce a hemorrhagic pan- 
creatitis—that is, a primary pancreatitis without suppuration, which 
gives rise to hemorrhages—in order to prove the correctness of the view 
maintained by many authors that inflammation of pancreatic tissue is 
to be regarded as the primary feature in hemorrhagic pancreatitis. 

It was possible, as will be shown later, by means of parenchymatous 
injections of 5% chlorid of zine solution, or by injection of ~, normal 
sulphuric acid into the Wirsungian duct, to cause hemorrhages into the 
pancreas resulting in death within twenty-four hours. At the autopsy, 
however, only more or less extensive hemorrhages with destruction of the 
tissue of the pancreas were found, but no signs of inflammation. 


2. SUPPURATIVE PANCREATITIS, PANCREATIC ABSCESS. 


Historical.—Among the earlier writers are found solitary instances 
concerning the occurrence of suppuration in the pancreas. 

Lieutaud mentions that in the last century cases of pancreatic abscess 
were observed. The cases of Riolanus, Bonz, and Gaultier are referred 
to by Ancelet. Claessen calls attention to a preparation in the Anatom- 
ical ‘Museum at Strassburg which, according to Bécourt’s description, 


SUPPURATIVE PANCREATITIS, PANCREATIC ABSCESS. 123 


showed several foci of pus in inflamed tissue. He cites especially the 
communication of Blancard, 1688, in which a child who had died of 
smallpox showed small masses of pus on the surface of the pancreas; 
in addition, Tonnellé reports two cases of suppurative pancreatitis in 
puerperal fever. 

Doring found an abscess between the pancreas, transverse colon, 
and mesentery, containing about 4 ounces of a yellowish, offensive pus, 
originating apparently from the pancreas. 

Baillie saw a pancreas notably enlarged, in which a large quantity 
of thin pus was found. Tulpius (1652) gives a somewhat more detailed 
description of a patient from whom a caseous tumor of the testicles had 
been removed some years earlier. The disease developed with symp- 
toms of fever, pain in the abdomen, and very great dyspnea. At the 
autopsy the pancreas was found filled with smeary pus which oozed 
from the cut surface. The aorta and vena cava were compressed by the 
gland and made impermeable. Portal (1803) describes the case of a man 
who had earlier suffered from gout. After two or three spells of vomiting, 
collapse and rapid failure occurred. The whole pancreas was involved 
in the process of suppuration and embedded in pus. Claessen mentions 
also a case of suppuration of the pancreas with calculus formation, de- 
scribed by Fournier. 

In the literature accessible to me up to the end of 1896 there were 
46 cases. The number of cases which have been made known may be 
essentially larger, as only a part of those which have been examined 
after death have been published in detail, and many may have been 
overlooked. In reports from hospitals and autopsies pancreatic ab- 
scesses are not infrequently mentioned without further details, and pan- 
creatic abscesses occur still more frequently, which run their course during 
life under wrong diagnoses and are not examined after death. Primary 
and secondary suppurative pancreatitis may be distinguished according 
as the process originates in the pancreas, or proceeds from a neighboring 
organ, or occurs through metastases. 


A, PRIMARY SUPPURATIVE PANCREATITIS. 


Pathologic Anatomy.—Small, multiple foci are found distributed 
throughout the entire gland or are limited to individual portions of the 
same, or purulent foci varying in size from that of a walnut to that of an 
egg or even larger are to be found as the result of the confluence of small 
abscesses. 

Multiple abscesses are described by Drasche, Friedreich, Moore, 
Fraenkel, Musser, Dallemagne, Greve, Dieckhoff (8 cases), Leichten- 
stern. Extensive collections of pus in the pancreas were found in the 
cases of Salmade, Portal, Gendrin, Baillie, Perle, Fletcher, Kilgour, 
Riboli, Habershon, Frison (2 cases), Moore, Hansemann, Korte (2 cases), 
Macaigne, Dieckhoff. Isolated abscesses in the pancreatic tissue have 
been described by Fournier, Percival, Harley, Roddick, Nathan, Smith, 
Shea, Moore, Bamberger, Fitz, Thayer, and in the reports of St. George’s 
Hospital. No especial reference to other cases is possible. 

Necrosis of small or large parts of the gland may develop from the 
suppuration, or the whole gland may degenerate and lie as a sequestrum 
in the large pus-cavity. The pus assumes at times an ichorous character, 
and then gangrene of a part or the whole of the gland all the more easily 


124 INFLAMMATIONS OF THE PANCREAS. 


occurs. Such abscesses and putrid cavities, which contain gangrenous 
portions of the pancreas, may be cured by operative interference (Korte, 
Thayer). They may also be evacuated through the intestine during 
life (Chiari), and thus be cured. In such cases it can by no means always 
be decided whether the inflammation or the necrosis is primary. 

Peripancreatic abscesses (foci of pus in the omental bursa) may be 
brought about by various causes; thus, for instance, by suppurating 
lymph-glands, by peritonitis, or by continued inflammation (Orth), and 
necrosis and sequestration of a larger or smaller portion of the pancreas 
may thus result. | 

A reactive inflammation, a circumscribed peritonitis (Dieckhoff), at 
times is found in the neighborhood of the pancreas infiltrated with pus. 
The pancreatic abscess sometimes becomes encapsulated, as in the cases 
of Frison, Musser, Moore, Roddick, Smith, Dieckhoff. 

Abscesses of the pancreas may break into the omental bursa, and then 
the large pus-cavity above mentioned may develop as the result of the 
closure of the foramen of Winslow and appear encapsulated. The pus 
may burrow into the retroperitoneal tissue, extending in different direc- 
tions on the right as far as the right kidney, but far more frequently on 
the left to the spleen, following the course of the descending colon, even 
to the pelvis (Korte). This extension to the left is typical, as has been 
established by Korte with injections in the dead body. 

Pancreatic abscesses and peripancreatic foci of pus may perforate 
into the stomach and intestine. Hoggarth and also Atkinson mention 
a case of rupture into the intestine. In Fletcher’s case, the abscess of 
the head of the pancreas broke into the duodenum. In Drasche’s case 
two abscesses perforated into the stomach and into the duodenum. 
Abscesses of the omental bursa also may rupture into a portion of the 
intestine (Langerhans, Hansemann, Chiari, Rosenbach). In most of 
these cases gangrene of the pancreas was the cause of the inflammation. 

Rupture of a pancreatic abscess may lead to a general peritonitis 
(Friedreich, Moore, Perle, Dieckhoff). In one of Moore’s cases a pan- 
creatic abscess had ruptured into the abdominal cavity and had perforated 
the pancreatico-duodenal artery. Not infrequently in such cases there 
is thrombosis of the vena porte, vena lienalis, or the vena mesenterica 
superior or inferior (Drasche, Bamberger, Musser). Thrombosis of the 
femoral vein is also mentioned in the case described in the reports of 
St. George’s Hospital. Korte found a parietal thrombus in the splenic 
artery. Through the mediation of such thromboses, abscesses may easily 
develop in other organs. Drasche found an hepatic abscess as large as 
an egg; there were several abscesses in the liver in the second of Frison’s 
cases; Smith found an abscess in the diaphragm above the spleen and 
abscesses in several small lymph-glands in the neighborhood. Klob saw 
the posterior wall of the stomach, in which there was an abscess beneath 
the mucous membrane, firmly adherent to the pancreas. Korte found 
several splenic abscesses, the largest of which communicated with a sub- 
phrenic abscess. In one of Dieckhoff’s cases, and in a patient of Greve 
there was suppuration of alymph-gland. Whatever may be the changes 
observed in the body, it is noteworthy that the spleen is not, as a rule, 
enlarged ; not even when there is thrombosis of the splenic vein or portal 
vein (Dieckhoff). Kilgour, Stefanini, and Greve mention a slight enlarge- 
ment of the spleen. A mild degree of jaundice was found in the cases 
of Shea, Moore, Riboli, Roddick; Frison and Greve reported marked jaun- 


SUPPURATIVE PANCREATITIS, PANCREATIC ABSCESS. 125 


dice. In the first of the last-mentioned cases several abscesses were 
found in the liver; in the last there were swollen lymph-glands in the 
portal fissure and along the celiac artery. 

Etiology.—The following have been mentioned as causes of primary 
suppurative pancreatitis, although without any proof whatever: alco- 
holism, misuse of tobacco, pregnancy (Mondiére), suppression of men- 
struation (Schénlein), use of mercury. Whether suppurative pan- 
creatitis may arise from an injury, a push or blow on the epigastrium, 
is also doubtful. 

The entrance of pyogenic micro-organisms is necessary for the pro- 
duction of an acute suppurative pancreatitis. As Dieckhoff states, there 
are the three following possibilities: 

1. A hematogenous origin, in which the pyogenic irritant enters into 
the pancreas through the blood. Only metastatic processes are brought 
about in this way. | 

2. Suppuration penetrates from the neighborhood; for instance, from 
an ulcer of the stomach extended to the pancreas. 

3. The pyogenic irritant enters from the intestine through the excre- 
tory duct. 

The last form alone is to be considered in primary pancreatic abscess. 
Orth has already presented this as the cause of primary suppurative 
pancreatitis. ‘A catarrh of the duct—sialodochitis pancreatica—is 
caused by concretions in the excretory duct and becomes transformed 
into a suppurative inflammation by the entrance of inflammatory ex- 
citants from the intestine.”’ 

Virchow has already shown that in the salivary glands the inflam- 
mation proceeds from the gland-ducts and thence extends to the gland 
lobules. Hanau also showed that a like course was pursued in the 
infectious diseases in the so-called metastatic inflammations of the 
salivary glands. According to Hanau, the process originates from a 
suppurative inflammation of the larger salivary ducts, then attacks the 
smaller branches, and, continuing from the central intra-acinous ducts, 
it causes a purulent liquefaction of the gland lobules. 

According to Dieckhoff’s investigation, suppurative pancreatitis runs 
a similar course. He showed the advance of the process from the larger 
to the smaller excretory ducts. A purulent liquefaction of the tissue 
proceeded from the minutest excretory ducts of the gland and resulted 
in the formation of the actual abscess. In a case of gelatinous cancer 
of the duodenum described by him, he says; ‘‘The pyogenic organisms 
have certainly wandered from the intestine, perhaps from ulcerated 
portions of cancer, into the excretory duct of the pancreas and have 
produced there a desquamative catarrh. The liquefactive process has 
begun in the central intra-acinous ducts.” In a second case in which a 
gall-stone was found in the ductus Wirsungianus, the suppuration 
certainly originated from the excretory duct. The enlargement of this 
by the gall-stone gave opportunity for the entrance from the intestine 
of pyogenic agents. A similar condition was observed in two other 
cases reported by Dieckhoff. ~ 

Different investigations have been made into the nature of the micro- 
organisms. In a case of suppurative pancreatitis reported by Fitz, four 
different kinds of bacteria were isolated in the bacteriologic examination 
carried on by Jackson and Ernst: (1) A fluorescent bacillus which liquefied 
gelatin and was half as large as the bacillus of tuberculosis ; (2) a bacterium 


126 INFLAMMATIONS OF THE PANCREAS. 


similar to Staphylococcus pyogenes citreus; (3) short, thin, non-liquefying 
rods, which formed gray, wrinkled membranes on the surface of agar 
and gelatin cultures; (4) very large numbers of a small, plump bacillus, 
which did not liquefy gelatin and formed superficial colonies 2 or 3 mm. 
in size in the vicinity of the point of inoculation. 

Dallemagne in 1892 makes an additional bacteriologic report. He 
isolated from the contents of an abscess pure cultures of a bacterium 
which is easily stained with methylene-blue, does not take the Gram 
stain, and forms on gelatin round, grayish-yellow colonies with irregular 
borders and dark center. Good development in meat-broth at 37° C. 
(98.6° F.); coagulates milk and gives no indol reaction. After intra- 
peritoneal injection of 1 c.c. of the culture into a rabbit death followed 
in twenty-four hours with the symptoms of infectious peritonitis. The 
bacterium belongs probably to the proteus group (Hauser). Macaigne 
saw pneumococci in the abscesses. 

Korte twice saw rod-like bacteria resembling intestinal bacilli, and 
once streptococci. In the cases investigated bacteriologically by Dieck- 
hoff and Lubarsch, they were twice able to show with certainty micro- 
organisms from the group Diplococcus pneumonie of Fraenkel. Twice 
these were shown only microscopically. Once Bacterium coli com- 
mune occurred alone. ‘It appears, therefore,’ says Dieckhoff, ‘as if 
the primary suppurative inflammations of the pancreas were only ex- 
ceptionally caused by the invasion of organisms from the intestinal 
canal.” It is always difficult to explain why pancreatic inflammations. 
are relatively so rare in view of the frequency of the occurrence of micro- 
organisms in the intestine and in the vicinity of the opening of the Wir- 
sungian duct. The same factor which explains the relative infrequency 
of abscesses of the liver probably prevails here, although space and 
opportunity enough are given for entrance of pus organisms through the 
bile-ducts. Doubtless there must be also, as is suggested by Dieckhoff, a 
special disposition, a pathologic change or a lack of secretion, in order to 
produce the soil that is peculiarly fitted for the development of the pus 
organisms. 

In purulent parotitis Hanau assumes a suppression of the secretion 
as the condition of the entrance into the gland of the pus organisms. 
Dieckhoff proposes a similar postulate for the development of suppura- 
tive pancreatitis. As a rule, however, such pathologic changes are 
shown in but few instances. Among the pathologic processes which are 
seen in some cases, and possibly explain the disposition to suppuration, 
the following may be mentioned: | 

1. Fat necrosis: This was shown by Fitz, Korte, Thayer, etc. Also 
in a case of diabetes which was examined after death in the Vienna 
General Hospital in 1895, in addition to a suppurative pancreatitis, there 
was found a fat necrosis between the lobules of the pancreas. In 1887 
there were observed an abscess with necrosis of the pancreas and a necrosis 
of the subserous fat tissue. In Korte’s third case the fat necrosis was 
“very marked.” The patient was a man twenty-two years old, not, 
corpulent. Thayer saw a wide-spread disseminated fat necrosis in the 
omentum. 

It might be possible that the necrotic fat tissue facilitates the en- 
trance of pus organisms (Dieckhoff). But this is not proved, for fat. 
necrosis occurs quite frequently. On the other hand, it might be possi- 
ble that the fat necrosis is a consequence of the inflammation, as 


SUPPURATIVE PANCREATITIS, PANCREATIC ABSCESS. 127 


Dieckhoff considers very probable from the evidence furnished by two 
of his cases. 

2. Circumscribed chronic indurative pancreatitis occurs after long- 
continued suppuration (Klob, Perle, Shea, Musser). The induration is 
to be regarded as the consequence and not as the cause of the inflam- 
mation. 

3. The retention of secretion, the obstruction of the excretory duct 
by concretions, or compression of the duct by tumors or scars may be 
assumed with great probability as causes of the development of pan- 
creatic abscess. 

Alterations in the secretion or its stagnation and the development of 
catarrhal processes occur in this way (sialodochitis pancreatica, Orth), 
and the immigration of pus organisms from the intestine may arise as 
in analogous processes in the liver. In the case of Roddick several 
stones were found in the enlarged duct. Orth states that ‘the stones 
are generally present.”” In one of Dieckhoff’s cases there was a gall- 
stone in the ductus Wirsungianus. Shea found an ascaris 17 cm. long 
partly in the pancreatic duct and partly in the duodenum; Drasche also 
found one in a pancreatic abscess. It is possible, however, that in these 
cases the ascarides entered after the development of the abscess. 

Dilatation of the pancreatic duct in consequence of compression by 
tumors has been reported a number of times. Dieckhoff found an ulcerat- 
ing cancer at the mouth of the duct. At the Vienna General Hospital in 
1892 an autopsy was held of a case of lymphosarcoma of the duodenum 
with abscess in the head of the pancreas. 

Nevertheless the etiology of suppurative pancreatitis is not clear, 
and there is no satisfactory reason for the rarity of this affection when 
contrasted with the great frequency of micro-organisms in the intestine. 

Dieckhoff rightly suggests that the cause of suppuration is to be 
sought, not in the gross anatomic changes of the pancreas, but in other 
factors, among which are the following: 

1. The micro-organisms which have been found as the cause of sup- 
puration of the pancreas (Diplococcus Fraenkel, Streptococcus) are 
not constantly present in the intestine. 

2. It is possible for certain pathogenic organisms to become active 
in consequence of an alteration of the pancreatic and intestinal juices, 
such as occurs, for instance, in cholelithiasis with stagnation of the bile 
in the biliary tract. 

3. The variable virulence of the fission fungi may be of consequence. 

[The recognized importance of cholelithiasis in the etiology of acute 
pancreatitis has especially been emphasized by Opie.* He suggests that 
in certain cases the common bile-duct and the pancreatic duct may be 
converted into a continuous closed channel by an impacted gall-stone 
at the outlet of the two ducts in the duodenal papilla. The entrance of 
_ bile into the pancreatic duct thus may be permitted by retrojection. 
Halsted + and Opie showed that the injection of bile into the pancreatic 
duct of dogs caused an acute hemorrhagic pancreatitis accompanied by 
fat necrosis.—Ep.] 

Pancreatic abscesses may be produced experimentally in different 
ways. Claude Bernard found suppuration of the pancreas to occur after 
the injection of mercury. Kérte produced pancreatic suppuration in 


* Am. Jour. Med. Sci., 1901, cxx1, 27. Johns Hopkins Hosp. Bull., 1901, x11, 182. 
+t Johns Hopkins Hosp. Bull., 1901, xu, 179. 


128 INFLAMMATIONS OF THE PANCREAS. 


animals by the injection of fresh perityphlitic pus into the tissue of the 
pancreas, also by the injection of bacteria (taken from a pure culture » 
from fresh perityphlitic pus), and by cutting into the substance of the 
gland with the production of an extravasation of blood. 

The injection of fresh cultures of staphylococci into the excretory 
duct, with subsequent tying of the duct near the head, led to the forma- 
tion ‘of an extensive abscess in the part isolated by. the ligature, and 
caused death on the fifth day. Injection of oil of turpentine combined 
with the implantation of an excised piece of gland into the abdominal 
cavity likewise caused an abscess. In 16 experiments with the injection 
of pyogenic organisms or of substances irritating chemically there 
was the formation of an abscess in four. 

By the injection of oil of turpentine to which soot was added we 
produced an abscess, as the following record shows: 


October 26, 1896: The pancreas is drawn forward. From 0.1 to 0.2 ¢.c. Ol. 
terebinth. to which some soot was added were injected in three places in the body, in 
one place in the head, and in one in the tail of the gland. At the time of injection 
the black fluid was extensively diffused within the parenchyma of the gland. Sev- 
eral subperitoneal hemorrhages between the lobules. 

October 27th: The animal vomited somewhat in the night. The vomitus and 
a little feces were mixed with the urine. Fever. Urine and vomitus, 340 e.c., 
brownish-yellow. Specific gravity 1025. -Acidreaction. Tracesofsugar. Indican 
in small amounts. 

October 28th: No vomiting, fever, the animal drank some milk. Urine brown- 
ish-yellow, 220 c.c., albumin in small amounts. Nucleo-albumin is present. No 
sugar, no acetone. "Indican somewhat increased. Bile pigments present. 

October 29th: The dog was found dead in the morning. 

The autopsy showed: Abdominal wound closed. Spleen small. Liver jaun- 
diced. Kidneys not enlarged, capsule strips off easily. Pancreas swollen and mark- 
edly injected. The most striking changes at the point of injection on the posterior 
surface of the organ. In the decidedly s swollen head was an area about the size of a 
hazelnut sharply separated from the normal portion, black, and surrounded by 
suppurating tissue. The tissue around the suppurated part is strongly injected. At 
a greater distance from the place which is so changed there is normal tissue, appear- 
ing somewhat swollen, but showing a normal structure. 

The place of injection in the body of the gland shows analogous changes. On 
the anterior surface is an abscess about the size of a hazelnut, stained black in the 
middle by the injected soot. In its vicinity the pancreas is swollen, the peritoneal 
covering smooth and shining. A bridge of normal tissue’about 3 cm. long connects 
this portion of the gland to the tail. 

In the latter was a spot the size of a hazelnut, stained black and surrounded by 
purulent and hemorrhagic infiltration. 


Figure 6 * illustrates a cross-section through a part of the abscess. 

As can be seen in figure 6, the suppuration extends between the 
lobules, and can be seen in places between the acini. 

Statistics. —According to the data known at present, primary pan- 
creatic abscess occurs in men more frequently than in women. Among 
the 46 cases upon which these statistics are based, there are found, so 
far as is specified, 28 men and 11 women; in the autopsy reports of the 
Vienna General Hospital from 1885 to 1895 there were 3 men and 2 
women. 

The following statements regarding the age are noted in 30 cases: 


Lito, 20 ‘years: ids viewer 1 (10 days) .51 to 60 years ........ 3 
AE NS Oe a 11 61 10 70): AS Sek aoa 2 
DEO BO og Be gi 6 TL LOB tars 1 
A | Alaa ate 9 Oe ee 6 Ann 

30 


» * Figures 6, 7, 13-16 are drawn by Mr. Wenzl from sections by Dr. Katz. 


SUPPURATIVE PANCREATITIS, PANCREATIC ABSCESS. 129 


Most of the cases, therefore, are between the ages of twenty and thirty 
years. Fitz’s table gives a similar result. Among 21 cases which Fitz 
mentions, there are 17 men and 4 women. According to age, they are 
distributed as follows: 


ANA 22 CRI ih so Reo aie Ss HARE PONE NOLS DHE HC BER OIES 3 
PO ASSN ES A ences ao tar An wend, weenie ee eae aS ge aos a EOE 4 
OU Tay Baa Se is aya eng, Ug en a eee grind entry, ae aye 2 
BONO EUs So hired tone ta ont nevin ins dete pecan he walitcksgees 2 
AO By Eo Pe alee aot aver eee a oak erates Gates oN frart Paveued ee 3 
I EOS DOr or eur © haha Rit ae ean tae Care ae cen ae Me tie aria aly Site 1 
Pa COBO, Siow tht oe gine cs ese ek rue Sel Se Rr eee Bet art ) 
GOO Ga, eM aera deh Masonic he tem nies ens ON Mice She Weekes 1 
GOUT OP ae Bein Uh ate hae ah re MLD A aN Ali IN ee fas 1 


Symptoms.—The disease generally begins suddenly or after the 
occurrence of some disturbance of digestion or attacks of biliary colic 
(Korte) with severe pains in the epigastrium, which not infrequently radi- 
ate over the whole abdomen. Cases are described, however, in which 
there are no pains (Nathan). In some cases the pains are in the region 























of the spleen or gall-bladder, the latter being sensitive to pressure. There 
is almost constantly epigastric tenderness. Vomiting, or at least severe 
retching, nausea, and eructation are usually present even at the beginning. 
The vomitus is stained with bile or is described as a fibrillated brown 
fluid. These symptoms of course are not characteristic, and correspond 
to an acute gastro-enteritis, if the prostration, which is at times very 
pronounced at an early stage, does not point to a more severe disease. 

The process is generally accompanied by fever, which takes an irregular 
course with chills occurring at irregular intervals. At times there is no 
fever. As a rule there is constipation, although diarrhea has been ob- 
served either in the first twenty-four hours or as profuse, colliquative 
stools at a later stage of the disease. At times the constipation alternates 
with the diarrhea (Riboli). Blood and foul pus are often found in the 
stools in consequence of the rupture of an abscess into the intestine 
(Percival and Atkinson). In one case (Harley) the stools contained much 
fat and albumin. 

9 


130 INFLAMMATIONS OF THE PANCREAS. 


The liver is at times enlarged, the spleen slightly enlarged (Greve), 
but at times is surprisingly small, even in those cases in which, at the 
autopsy, the splenic or portal vein is found thrombosed. The intestines 
are distended and tympanitic. In some cases free fluid or other signs 
of peritonitis could be shown in the abdominal cavity. 

The epigastrium shows the most important changes. It appears dis- 
tended and tympanitic, and in some cases a more or less distinctly limited 
tumor or an indefinite resistance is found in the upper part of the abdomen. 
Such a swelling was present in the cases reported by Kilgour, Percival, 
Musser, and Fournier. In Greve’s case an increased resistance was found. 
Thayer found in the middle line above the umbilicus a deep-seated 
resistance, which could not be defined from the liver; percussion over 
this area gave a tympanitic sound and the tumor was quite sensitive on 
palpation. If the pancreatic abscess has ruptured and a bursal abscess 
has developed or a retroperitoneal collection of pus has formed, a fluctuat- 
ing tumor may be recognized, as a rule extending to the left, but more 
rarely to the right. Such a condition was reported by Korte in his cases, 
in two of which certainly there were pancreatic abscesses. 

In his other cases, as well as in those cited by him (Rosenbach, Werth 
and Konig, Caspersohn-Hansen), large quantities of pus were found in 
which either necrosis of the pancreas was the primary factor, or it was at 
least doubtful whether the suppuration was the result of the gangrene 
or the latter was the result of the suppuration. The place in which 
the tumor is felt, as Korte states, differs somewhat according to the 
point of exit of the pus and according to its development within the 
peritoneum, in the omental bursa, or behind the peritoneum in the 
posterior wall of the abdomen. 

Collections of pus originating in the head or body of the pancreas 
will cause a swelling in the middle line or to the right or the left of that 
line. If the suppuration begins in the tail of the pancreas, the swelling 
is to be felt in the upper left portion of the abdomen. The percussion 
note of the resistance or of the tumor is dull (Kilgour). Large bursal 
abscesses or retroperitoneal collections of pus likewise are dull on per- 
cussion (Korte, Rosenbach, Werth-Konig, Caspersohn-Hansen). In 
Thayer’s case there was a tympanitic sound on percussion over the 
resistance. The pus presents, as Korte found, certain peculiarities. 
He found twice in the omental bursa yellow contents like thick broth, 
mixed with many yellow, tallow-like fragments and brownish, discolored 
shreds. Microscopic examination showed fat-crystals, yellow pigment, 
_and either no pus cells or a few which were undergoing fatty degeneration. 
There was found in the pus a bright brownish fluid mixed with yellow 
necrotic fragments, which on microscopic examination were seen to 
consist of fat. 

Kérte leaves it undecided whether the clumps of fat contained in 
the pus and in the discharge from the wound are to be attributed to ex- 
isting, disseminated fat necrosis or to the influence of the pancreatic 
juice. 

The following statements relate to the condition of the urine: In 
one case normal urine was found, except that the specific gravity was 
1002; in Stefanini’s case 1005. Bamberger showed the presence of pep- 
tone; Musser and Korte, albumin. Harley, Frison, Atkinson, and Fre- 
richs found sugar, and Stefanini notes the absence of indican. . 

‘Jaundice is quite frequently found; according to Fitz, in nearly one- 


SUPPURATIVE PANCREATITIS, PANCREATIC ABSCESS. 131 


fourth of the cases. This may be caused by obstruction of the ductus 
choledochus by the swelling of the head of the pancreas, or by compression 
of the bile-duct by the abscess. In one case there was an abscess in the 
liver with dilatation of the bile-duct. 

Fitz mentions bronzed skin in one case. Korte found in four of his 
patients (abscesses and necrosis) a grayish-brown color of the skin with 
very dry, desquamating epidermis. The autopsy in one of the cases 
showed necrosis of the fat tissue in the left adrenal. In the more chronic 
cases there were marked emaciation, edema, and petechie; and death 
occurred in consequence of exhaustion or sudden collapse. 

Diagnosis.—The initial symptoms, the violent pain in the epigas- 
trium, generally extending over the whole abdomen, vomiting, nausea, 
eructation, atypical fever, constipation or diarrhea, sensitiveness to 
pressure in the epigastrium, feeling of severe sickness, and prostration 
are such universal symptoms, and may belong to so many processes, 
that it cannot even be suspected that a disease of the pancreas is in 
question. 

~ When, however, a more or less painful tumor appears in the epigas- 
trium, the pancreas may be thought of, and the diagnosis of the nature of 
the diseased process first becomes possible when with fever a large collec- 
tion of pus has formed in or behind the omental bursa and is associated 
with fever. It is impossible to diagnosticate small or multiple abscesses 
within the substance of the pancreas. It is probable that there is a col- 
lection of pus in or behind the omental bursa, when, associated with 
the above-mentioned symptoms so strongly characteristic of inflam- 
mation, there is an epigastric tumor disconnected with the liver, 
spleen, and stomach, dull or with a muffled tympany on _percus- 
sion and situated behind or between the stomach and colon, as can 
be shown by inflating these organs.* Distinct fluctuation is rarely 
to be felt. Korte found indistinct fluctuation in two cases of ab- 
scess in the omental bursa, and Thayer, though unable to demon- 
strate fluctuation in the case in which he made the diagnosis of 
acute pancreatitis, nevertheless had the impression that the tumor 
contained fluid. 

Examination under narcosis a the preliminary emptying of the 
stomach and intestine (Korte) are to be recommended for the purpose 
of deciding upon the location and nature of the tumor. Korte considers 
that exploratory puncture in the lumbar region should be performed 
without hesitation when there is retroperitoneal extension of the inflam- 
mation; it establishes the diagnosis more certainly, especially when 
turbid fluid mixed with fragments of fat escapes. Korte considers 
exploratory puncture not wholly advisable when the pus lies in or behind 
the bursa, and this procedure then should be employed only where it is 
to be followed immediately by the evacuation of the pus. 

Although the diagnosis of a collection of pus in or behind the omental 
bursa under favorable circumstances can now be made with some degree 
of probability, yet this condition does not always prove that there is a 
suppurative process in the pancreas as the cause of the abscess, for 
abscesses so situated may originate from various causes. Hemorrhage 
of the pancreas, necrosis, or the rupture or suppuration of a cyst may be 
the primary factor. The collection of pus in the bursa may also originate 

* For seat of pancreatic tumors see section on Cysts. 


132 INFLAMMATIONS OF THE PANCREAS. 


from an ulcer or cancer of the stomach or duodenum or from lymph- 
glands. The history may then give some indication. 

The view of the pancreatic source of the disturbance would be justified 
when there were no symptoms of ulcer or cancer of the stomach or of 
duodenal disease, When the process was of sudden onset without pre- 
cursory symptoms but with the rapid development of the maximum 
symptoms of inflammation, and when, as in the cases of Frison and Har- 
lev, and others, there was diabetes. The diagnosis of pancreatic abscess 
cannot be made beyond a certain degree of probability, and mistakes in 
diagnosis are unavoidable even with the most careful observation. 

It often happens that the disease is first correctly recognized during an 
operation. The condition of the pus, the large amount of fat, the pres- 
ence of necrotic fragments, give valuable evidence for diagnosis. 

The correct diagnosis at times is made only during the treatment of 
the wound, when a pancreatic fistula develops, from which characteristic 
pancreatic juice is evacuated. In the present condition of our knowledge 
it is absolutely impossible to make a correct diagnosis in the great majority 
of pancreatic abscesses, especially in those in which general peritonitis is 
combined with the local process. 

Prognosis and Course.—Suppuration -of the pancreas is certainly 
a fatal disease if the abscess does not rupture into the intestine (Chiari), 
which is very rare, or if the surgeon’s knife does not open it at the right. 
time. 

The course may be acute, subacute, or chronic. There have been 
cases which ended in death in a few days, and, on the other hand, patients 
with pancreatic abscess are known to have lived eleven months and more. 

Treatment.—Radical relief is not to be expected from medical treat- 
ment. The evacuation of the abscess by surgical methods offers the only 
means of permanent relief. 

Senn, in 1887, first proposed this method of treatment, and Fitz, 
Seitz, and Nimier, from the theoretic point of view, assigned the treat- 
ment of pancreatic abscess to the surgeon. The cases of Korte and Thayer 
were first successfully operated upon, with the exception of that of Wan- 
desleben, operated on before the days of antisepsis. 

Korte makes the following statement concerning the method of oper- 
ating: ‘If the presence of pus in the omental bursa is shown on investiga- 
tion, the operation should take place from the front, as in the treatment of 
pancreatic cysts. The incision is best made in the middle line. If the 
tumor lies distinctly on one side, the incision may be carried to that side. 
When the gastro-colic ligament is exposed, an exploratory puncture is 
made if this has not been done earlier, the abdominal cavity being pro- 
tected by gauze. A piece of the gastro-colic ligament large enough for 
incision and drainage is then sewed to the abdominal wall and the upper 
and lower parts of the abdominal incision are united by a row of sutures. 

‘“When the abdominal cavity is thus perfectly protected, the gastro- 
colic ligament is divided with a dull instrument,-as a hollow sound or 
blunt forceps, and the abscess is opened. The opening is enlarged with 
dressing forceps. After the purulent contents have escaped, a drainage- 
tube is.inserted and the cavity is washed out with sterile water or a very 
weak solution of lysol. Fragments of dead tissue are removed with the pus 
or drawn out with the dressing forceps. The subsequent treatment con- 
sists in washing out the cavity and in introducing gauze around the drain- 
age-tube. If the seat of the pus is largely retroperitoneal with burrowing 


SUPPURATIVE PANCREATITIS, PANCREATIC ABSCESS. 133 


toward the left lumbar region, it is desirable to make an oblique incision 
through the abdominal wall similar to that for extirpation of the kidney. 
The peritoneum should then be detached with a blunt instrument toward 
the tail of the pancreas and the abscess opened. The pus frequently has 
burrowed downward as far as the brim of the pelvis. 

“The skin surrounding the incision of either operation should be well 
anointed with zinc paste, in order to prevent corrosion.” 


B. SECONDARY ACUTE SUPPURATIVE PANCREATITIS. 


The secondary variety may arise in various ways: 

1. By extension of an inflammatory process from a neighboring organ, 
and especially from ulcer of the stomach. Observations on this point 
have been made by Thierfelder and Chiari. The former found, in a case 
of ulcer of the stomach at the base of which lay the pancreas, small ab- 
scesses in the connective tissue around the duct of Wirsung and penetrat- 
ing the gland. Chiari also reports a similar case. Dieckhoff describes 
secondary suppuration of the pancreas in a gelatinous cancer of the duo- 
denum. 

Several cases of secondary suppuration of the pancreas are found 
among the autopsies of the Vienna General Hospital in the last ten years. 
In 1887 a woman twenty-one years old was examined after death, and the 
anatomic diagnosis of abscess of the head of the pancreas from suppura- 
tion of the inferior vena cava was made. In 1888 an abscess of the liver 
and of the pancreas were found, the result of pylephlebitis, in a man twenty 
years old. In 1889, in the case of a man seventy-nine years old, the fol- 
lowing diagnosis was made: Carcinoma duodeni et diverticuli huius, 
dilatatio ductuum pancreaticorum, abscessus multiplex pancreatis cum 
perforatione in duodenum. The following anatomic diagnosis was made 
in 1892 in a man thirty years old: Lymphosarcoma duodeni valde exulcer- 
atum cum abscessibus capitis pancreatis et phlegmone textus cellulose 
retroperitonealis. 

2. Metastatic abscesses may occur in the pancreas in the course of 
pyemia and puerperal fever; such cases, however, are rare (Orth). In 
the reports of autopsies at the Vienna General Hospital for the last ten 
years no such case is found. 

3. The possibility of the occurrence of a metastatic pancreatitis in 
the course of a parotitis has repeatedly been considered. It is well known 
that in this affection metastases take place in the testes, ovaries, mam- 
mary glands, and labia majora. Mondiére has mentioned parotitis also 
among the causes of metastatic pancreatitis. 

Friedreich refers to the following cases which have been interpreted 
by many authors to signify that the pancreatic disease was the result of a 
metastasis from the parotitis. Canstatt, in the chapter on epidemic 
parotitis, mentions che occurrence of metastases to the pancreas. Bat- 
tersby relates that the symptoms of a pancreatic disease became more 
evident after the disappearance of saliva from the mouth. Andral and 
Mondiére state that either of the parotid glands may swell in the course 
of diseases of the pancreas. Roboica observed a case of severe parotitis 
in a man who suffered from a severe, deep-seated pain in the epigastrium 
after the parotitis suddenly disappeared. This pain also disappeared 
quickly, whereupon swelling of the testes occurred, after which parotitis 
returned. Schmackpfeffer relates the following case: In a syphilitic girl 


134 INFLAMMATIONS OF THE PANCREAS. 


who was pregnant, the sublimate cure was begun after delivery. After 
the disappearance of the syphilitic symptoms, severe salivation set in. 
When this diminished there was abundant diarrhea with marked thirst, 
fever, nausea, anxiety, and a deep-seated pain in the region of the stomach 
radiating toward the right hypochondrium. The diarrhea was profuse, 
the stools watery, resembling saliva, and yellow; suddenly the diarrhea 
ceased and there occurred a painful swelling of both parotids, but without 
salivation. The pulse became small and intermittent. The patient died 
in collapse the following night. At the autopsy the pancreas was found 
swollen, reddened, very rich in blood, and of considerable consistency. 
Both parotids were inflamed. 

“However little the symptoms just mentioned,” says Friedreich, 
‘seem sufficient to indicate the existence of a metastatic pancreatitis, yet 
the possibility of its presence ought not to be overlooked, in view of the 
last observation.” 

In the examination of the more recent literature there appears no 
report which could be interpreted to mean that pancreatitis occurs as a 
metastatic process after parotitis. Among reports of autopsies at the 
Vienna General Hospital in the last ten years there is one which suggests 
the occurrence of parotitis after a secondary pancreatic abscess. In a 
man seventy-nine years old the following conditions were present: Car- 
cinoma cap. pancreatis cum infiltr. partiali choledochi et stenosi ejus sub- 
sequente dilatatione viarum biliferarum. Icterus univers. Carcinoma 
secundarium hepatis. Suppuratio partis centralis tumoris capitis pan- 
creatis et cholangitis subsequente parotitide bilaterali et phlegmone colli 
cum pharyngitide et laryngitide phlegmonosa. 

It is impossible to produce at present a clinical picture of secondary 
suppurative pancreatitis. 


3. NECROTIC PANCREATITIS. 


The consideration of this variety is most appropriate in the section 
on Necrosis. 


4, CHRONIC INDURATIVE PANCREATITIS. 


PATHOLOGIC ANATOMY. 


The characteristic feature of this form of inflammation is the thicken- 
ing and fibrous transformation of the interstitial tissue, with destruction 
~of the substance of the gland. The changes in the gland may be primary, 
as in those varieties of inflammation which arise from the acute form, 
or from certain inflammatory processes to be further considered later, 
and which originate in the gland or in the ducts and lead secondarily to 
an increase of the connective tissue. It more frequently happens that 
the increase of interstitial connective tissue is primary and leads to de- 
generative changes and destruction of the gland. 

The inflammatory process may be diffused over the entire gland or 
may affect only certain portions. In the former instance even the altera- 
tion need not be spread uniformly throughout the entire gland, but ma 
be conspicuously limited to certain portions, especially the head. 


CHRONIC INDURATIVE PANCREATITIS. 135 


A. INFLAMMATIONS OF THE ENTIRE GLAND. 


Two groups can be distinguished, in general, according to the origin 
of the inflammatory process from the blood-vessels or from the excretory 
ducts and gland cells. 

The first group includes the indurative processes which occur in con- 
sequence of disease of the blood-vessels, arteriosclerosis, and endar- 
teritis obliterans, especially when resulting from syphilis and alcoholism. 
The second group includes the chronic indurative processes which de- 
velop in consequence of closure, narrowing, obturation, and inflammation 
of the excretory ducts. In many cases it is impossible to separate these 
two groups sharply from each other, because there are many transitional 
and mixed forms. 

1. Chronic Indurative Pancreatitis Originating from the Blood- 
vessels (Hematogenous Variety, Dieckhoff).—(a) Indurative Pan- 
creatitis, due to Endarteritis Obliterans.—The blood-vessels of the pan- 
creas are very frequently affected in the arteriosclerotic and endarteritic 
processes taking place throughout the body in general. They cause in 
this organ as in others a hyperplasia of connective tissue, and, in addition, 
produce throughout the entire gland or in individual portions of the same 
such secondary changes as fatty degeneration, atrophy, hemorrhage, 
and necrosis of the gland. 

The characteristic changes of a typical obliterating endarteritis are 
given in the case described by Hoppe-Seyler of a diabetic woman fifty- 
seven years old. 

The process was far advanced and the pancreas represented merely 
‘“‘a clump of fat tissue.” Yet the histologic investigation showed the close 
relation between a previous chronic interstitial inflammation and the 
existing fatty degeneration. The celiac, gastroduodenal, and splenic 
arteries, especially the last, were markedly calcified, and the smaller 
branches, which penetrated into the substance of the gland, were thick- 
ened. 

Hoppe-Seyler describes the development of the disease in the following 
manner: ‘The blood-vessels first become diseased, their walls thickened, 
their lumen narrowed or obstructed. In consequence there are disturb- 
ances of nutrition in the parts supplied by them, notably thickening of 
the connective tissue around the gland acini and degeneration and disap- 
pearance of the gland-cells. The interacinous fat tissue increases in pro- 
portion to the disappearance of gland tissue; indeed, it becomes so exces- 
sive that the pancreas is reduced almost to a mass of fat which may be 
larger than the normal pancreas.” The process is regarded by Hoppe- 
Seyler as analogous to that found in the atrophied kidney. 

Fleiner reports a similar case, also in a diabetic. This observer was 
able to distinguish the following pathologie processes in the pancreas: (1) 
Chronic obliterating endarteritis with hyaline degeneration of the vessel- 
wall, leading to a general narrowing of the arterial current and conse- 
quently to a greater or less degree of disturbance of nutrition, tending 
especially to hyperplasia of the connective tissue and atrophy of the 
parenchyma ; (2) acute arterial thrombosis and subsequent tissue nec- 
rosis; (3) septic infection of the necrotic parts of the tissue and beginning 
suppuration. 

Bacterium coli commune and another unidentified bacterium were 
isolated from the parenchymatous juice of the pancreas. It is worthy of 


136 INFLAMMATIONS OF THE PANCREAS. 


mention that Hansemann regarded the poor staining of the nuclei in both 
of the cases as the result of postmortem changes. 

The above processes are a transition to those which have of late been 
frequently recognized as chronic, indurative pancreatitis in diabetes, since 
the changes in the pancreas in this disease have oftener been sought for 
than formerly in consequence of the results of the experimental extirpation 
of the pancreas. Although atrophy of the pancreas and fatty degenera- 
tion of the gland are most frequently found, yet there are not a few cases 
in which a chronic interstitial pancreatitis, in consequence of changes in 
the blood-vessels of the gland or in their vicinity, is found at the autopsies 
of diabetics. 

Lépine assumes theoretically that the primary alterations of the 
pancreas, at first without change in the macroscopic appearance of the 
gland, must be found in the neighborhood of the veins. In the course 
of the last few years he has been able to make some observations in sup- 
port of his view, and similar contributions have since appeared, especially 
in French literature. 

Lépine, for instance, has observed “‘sclérose periacineuse”’ once in aman 
forty years old and again in one fifty-four years old. In both patients 
the macroscopic appearance of the gland was altered. Especially careful 
investigations were made by Lemoine and Lannois in three diabetic cases, 
in each of which the pancreas showed the like sclerotic induration of its 
connective tissue. ‘The microscopic examination of the apparently nor- 
mal organ showed that the hyperplasia of the connective tissue was 
especially connected with its veins and the lymph-vessels, and that there 
was both a considerable periacinous sclerosis, which separated the lobules 
by strong trabecule of connective tissue, and an intercellular sclerosis, 
which had given rise to a hyperproduction of the connective tissue lying 
between the individual cells. | 

It is to be especially mentioned that, in spite of these marked micro- 
scopic changes of the gland-substance, nothing abnormal was to be dis- 
covered on macroscopic examination, a point which strongly indicates 
the need of more exact microscopic observations, if chronic interstitial 
inflammation of quite marked degree is not to be overlooked. Similar 
conditions in diabetes visible to the naked eye, as induration and atrophy 
of the gland, had been mentioned by a number of authors. 

In the table headed “‘Indurative Pancreatitis” (page 62), and also in 
Tables I, II, and VI, pages 58, 61, and 69, similar cases are described, and 
among them that form of atrophy which Hansemann regards as the con- 
sequence of interstitial inflammations analogous to the granular atrophy 
of the kidney. It is, however, in most cases difficult to decide whether 
the process takes its origin from the blood-vessels or from the excretory 
ducts. Pancreatic sclerosis and excretion of sugar in the urine do not, 
however, by any means necessarily concur, as numerous cases show. 

Obici mentions two cases of interstitial pancreatitis, one of which 
showed the picture described by Lépine of ‘sclérose periacineuse”’ in its 
most perfect development, without any glycosuria. Hansemann also 
saw two cases of induration of the pancreas, in which there was no dia- 
betes during the life of the patient. In one of these cirrhosis of the liver 
was found, indicating that this case is to be regarded rather as one of 
pancreatic induration depending on chronic alcoholism. 

The following case described by Rosenthal (1892) is on the hondar: 
line of the forms of chronic interstitial pancreatitis due to syphilis: 


CHRONIC INDURATIVE PANCREATITIS. 137 


A girl sixteen and a half years old a year previously had chlorosis, in the course of 
which there were frequent attacks of fainting. Previously she had always been 
healthy; nothing was learned regarding any hereditary conditions (tuberculosis, 
syphilis). Her appearance became worse and worse, and finally rapid emaciation 
set in. For some weeks before her admission to the hospital she complained of 
backache, difficulty in urinating, and stabbing pain in the chest. Finally there was 
increased frequency of respiration and marked distention of the abdomen. 

On entrance, the physical examination resulted as follows: Skin pale, tempera- 
ture 37.8° C. (100.04° F.), pulse 120, respiration 60. In the lungs there was diffuse 
catarrh, the heart normal. The abdomen was markedly distended and contained 
free fluid. The liver projected somewhat beyond the edges of the ribs, was smooth 
and hard; the spleen was not enlarged. 

During the seven weeks’ stay at the hospital puncture of the abdomen had to be 
undertaken repeatedly; there was edema of the lower extremities with progressive 
failure of strength, and the patient died after the occurrence of symptoms of collapse. 
During the whole course of the disease there was no fever at any time, the urine was 
always normal, the stools now loose, now constipated, and again of normal consistency. 
The rapid failure of strength and the high degree of emaciation were especially note- 
worthy, the latter being such as is observed only in malignant neoplasms or in ad- 
vanced tuberculosis. 

The autopsy revealed as follows: Pylephlebitis chronica cum induratione pan- 
creatis, stenosis levis et thrombosis parietalis ven portz. Ascites. Bronchopneu- 
monia multiplex. Cdema leve glottidis. Degeneratio amyloides lienis. 

The pancreas was of normal size, the head appeared especially thick, but the 
structure could be distinctly recognized in places. Microscopically the alteration of 
the pancreas appeared as chronic interstitial pancreatitis and proliferating lymphan- 
gitis. The connective tissue appeared especially increased between the single acini. 
In the head and the extreme end of the tail, masses of round cells were found lying 
in the much dilated lymph-vessels. 


This result led Rosenthal, in spite of the previous history, to regard 
the case as one of latent congenital syphilis. 

(b) Chronic Indurative Pancreatitis from Syphilis —An increased growth 
of connective tissue occurs very frequently in syphilis. Chronic pan- 
creatitis is frequently observed, especially in the congenital variety. 
Rokitansky has suggested that induration of the pancreas, with similar 
but much more frequent alteration of the liver with or without gummata, 
occurs in syphilis. In 23 cases of hereditary syphilis more or less pro- 
nounced changes in the pancreas were found by Birch-Hirschfeld in 
10 children. In the severest cases the entire gland appeared swollen, 
doubled in size, very firm, white and shining, the structure entirely 
obliterated. On microscopic examination the interstitial tissue was 
found so greatly increased that the acini appeared to have entirely 
disappeared, and the organ seemed rather an actual fibroid than a gland. 
In some places the growth of connective tissue extended into the indi- 
vidual acini and caused the disappearance of the epithelium. Round, 
oval, and spindle-shaped cells were embedded in places in the connective 
tissue. Blood-vessels with thickened walls were only sparingly found. 
In cases in which the changes were not so extreme, there were found 
only a moderate growth and widening of the interacinous connective 
tissue, with slight compression of the lobules of the gland, but without 
disappearance of the epithelium, changes which previously were described 
by Oedmansson. The entire organ then appears enlarged and of a pale 
gray color. According to Birch-Hirschfeld, this change develops in the 
last months of fetal life. The most marked and most advanced altera- 
tions of the gland were found in a fetus which died in the fifth month 
but was delivered at the normal end of pregnancy. 

In the communication in Gerhardt’s ‘Handbook of Children’s Dis- 
eases,’ Birch-Hirschfeld states that he has found induration of the pan- 


138 INFLAMMATIONS OF THE PANCREAS. 


creas 27 times in 124 cases of congenital syphilis. Hecker, in 1869, showed 
similar changes in the pancreas in 22% of the cases. Wegner, in his 
article on hereditary bone-syphilis, mentions three cases of induration 
of the pancreas. In the body of a girl who died shortly after birth, 
Huber found a long and wide pancreas, which was not very hard and 
showed interacinous increase of connective tissue, in addition to pro- 
nounced syphilitic changes in the liver and in the bones. 

In 18 cases of hereditary syphilis Miller observed marked changes in 
the pancreas in two. In a fetus which was delivered dead at the fifth 
month there was found a considerable periacinous growth of granulation 
cells, which compressed the gland lobules and apparently led to the forma- 
tion of numerous miliary syphilomata. The second case described by 
him, of a child born dead at the normal end of pregnancy, belongs rather 
to the type of interstitial pancreatitis. The bands of connective tissue 
were widened and infiltrated with cells. Large accumulations of lymph- 
oid cells were found in place of the gland acini, the normal structure of 
the gland was retained onlv in single portions of the pancreas. Cases of 
syphilitic interstitial pancreatitis have been described by Friedreich, 
Demme, and Chiari. In the autopsy of an eight-months’ fetus, Beck 
found a pancreas which was much enlarged, very thick, and nearly 
as hard as cartilage. Huebner has recently reported the case of 
a boy three and a half years old in whom he found, in addition to a high 
degree of syphilis of the liver, an enormous syphilitic infiltration of the 
pancreas, causing an increase in the size of the organ from fourfold to six- 
fold. Analogous conditions have been mentioned by earlier authors, 
although they were not always attributed to syphilis. Thus, von Osterloh 
and Cruveilhier described such anatomic changes without expressing 
any opinion as to their actual etiology. In chronic pancreatitis developed 
in constitutional syphilis the increased connective tissue shows generally 
rather a succulent character, and its inflammatory origin is indicated 
by the abundant infiltration of round cells, while in the cases observed 
in adults the connective tissue is firmer, denser, and more like scar tissue. 


Thus, Drozda found a distinctly marked chronic pancreatitis in a man thirty- 
four years old who for years had suffered from syphilis. The patient four years before 
had jaundice; for three years there were periodical disturbances of digestion with 
vomiting and defined pain in the epigastrium, repeated distress, and attacks of 
fainting. The swelling of the cubital and inguinal glands showed the pres- 
ence of a syphilitic dyscrasia. There was at first scarcely anything demonstrable 
objectively except a constant sensitiveness in the region of the stomach. Ascites 
occurred subsequently, followed by general edema. Bilious, and later also bloody, 
vomiting were often observed. Nothing abnormal could be discovered in’the urine 
and stools. The temporary swelling of the parotid during the course of the disease 
was of interest; it was followed by purulent otorrhea of the right ear. Death oc- 
curred in collapse after about two and a half months of the above severe symptoms. 
At the autopsy the pancreas was found transformed into a hard callus. The original 
structure was still to be recognized in places only in the head of the gland. In some 
parts caseous masses were found embedded within the dense tissue. In the liver also 
were seen several indurated spots and an indurated scar was in the stomach. The 
spleen was increased to twice its size. In addition, there were chronic Bright’s dis- 
ease, general anemia, ascites, and dropsy. 


In a case of visceral syphilis in an officer forty-six years old, Chvostek 
found in the tail of the pancreas several cicatricial retractions, which gave 
a lobulated appearance to the affected portion. Of the three cases of 
induration in diabetesfound by Hansemann and mentioned in Table III 
{page 63), two had asyphilitic history. Dieckhoff reports the histologic 


CHRONIC INDURATIVE PANCREATITIS. 139 . 


findings in a case of interstitial pancreatitis also to be referred probably 
to a syphilitic condition. Cranial syphilis, pulmonary tuberculosis, and 
cancer of the stomach were found at the autopsy. Induration of the 
pancreas was quite distinct under a low power of the microscope. The 
connective tissue was largely arranged in circular bands surrounding the 
blood-vessels, excretory ducts, and gland- lobules; the intralobular tissue 
was increased i in many of the ‘last. 

(c) Chronic Indurative Pancreatitis jrom Alcoholism.—Chronie aleohol- 
ism may cause a hyperplasia of the stroma of the pancreas, as it may pro- 
duce serious changes in the connective tissue of the liver. Hence, such a 
pancreas may be spoken of as cirrhotic, although it does not appear 
yellow. Hansemann also protests against this use of the term, which 
may give rise to mistakes. [riedreich, in a most instructive case, already 
has described the occurrence of such changes in the pancreas associated 
with cirrhosis of the liver. 

Chvostek (1876), in an inebriate twenty-nine vears old, found the 
pancreas of cartilaginous density, tough, of the color of gray fat with a 
tinge of red, and with large lobes. Communicating cavities as large as 
beans, with smooth, firm, fibrous walls and soft, dark-gray contents, were 
found in the parenchyma. The liver appeared tenacious, tearing with 
difficulty, brownish-gray in color, finely granular, and brittle. Yellow- 
ish-brown, sharply circumscribed friable portions about the size of a 
walnut were found in different places in the parenchyma. There was 
also thrombosis of the portal vein. The case is to be regarded probably as 
one of interstitial pancreatitis dependent upon chronic alcoholism and 
complicated with pylephlebitis, to which latter lesion the further changes 
in the pancreas were attributable. 


The patient for about ten months had suffered from repeated cardialgic attacks 
lasting two or three hours; later there were stabbing pains in the upper abdomen, 
and, finally, tension in the lower portion, with increasing ascites, temporarily disap- 
pearing, but then reappearing, and not to be prevented despite puncture. There 
were sensitiveness to pressure in the hepatic region, and, in the left hypochondrium, 
dulness extending downward to the lower border of the tenth rib and in front to 
three finger-breadths below the level of the costal cartilages. The appetite at first 
was normal, but later there were anorexia, nausea, retching, and toward the end of 
life, vomiting. Diarrhea alternated with constipation. Nothing abnormal could be 
shown in the urine. The temperature of the body remained normal throughout the 
disease. At the end of about fourteen months there were sudden dyspnea, severe pain 
in the lower part of the abdomen, marked meteorism and vomiting, death finally 
coming in collapse. 


Hansemann (1894) also, as previously mentioned, found the pancreas 
very thick, markedly indurated, and the lobules not easily displaced in a 
man thirty-seven years old with cirrhosis of the liver. 

Dieckhoff describes a very instructive case. A man sixty years old, 
alcoholic, had diabetes for eleven years. The amount of sugar in the 
first ten years varied between 6.4% and 1.5%; in the last year, between 
2% and 4%. The patient, who in general felt well, after some physical 
exertion had a sudden hemorrhage from the stomach and died. The 
anatomic diagnosis was as follows: Cirrhosis of the liver, lipomatosis of 
the pancreas, and old, chronic interstitial pancreatitis. Dieckhoff dates 
the beginning of the pancreatic disease and the cirrhosis of the liver from 
the time when the diabetes first developed. 

Among the five cases of chronic interstitial pancreatitis which are 
recorded in the autopsy reports of the Vienna General Hospital in the last 


_ 140 INFLAMMATIONS OF THE PANCREAS. 


ten years, there is found also one case of hepatic cirrhosis in an ine- 
briate. | 

The cases of chronic interstitial pancreatitis associated with chronic 
interstitial nephritis should be considered after those due to alcoholism. 
Tylden and Miller (1891) showed that the simultaneous occurrence of these 
two processes must be very frequent, since among 15 patients with chronic 
nephritis a like alteration of the pancreas was found in eight. 

The previously described alterations of the pancreas designated simple 
diabetic atrophy by Hansemann bears a close resemblance to certain 
forms of granular kidney. The case observed by him proves that this is 
to be regarded as due to an interstitial pancreatitis. In a man forty-two 
years old who died with symptoms of acute phthisis after transient gly- 
eosuria and acetonuria had been shown, the lobules of the pancreas were 
found widely separated by connective and fat tissue. On section, abun- 
dant, somewhat reddened gland substance was seen. Microscopically the 
parenchymatous cells were not perceptibly changed. Wide capillaries 
and small vessels abounded in the stroma. There was no thickening of 
the vessel-walls. Inflammatory foci of small cells were numerous. The 
case is important because, according to Hansemann, it shows the early 
changes in the pancreas after disease of short duration: chronic fibrous 
and recent small-celled inflammation of the stroma. 7 

2. Chronic Indurative Pancreatitis Originating from the Excre- 
tory Ducts.—(a) From Inflammation of the Excretory Ducts (Sialangitis 
pancreatica).—This variety may perhaps be the more frequent and has the 
same etiology as the acute (suppurative) inflammation. It may develop 
in connection with any process which favors the immigration of micro- 
organisms, especially with cholelithiasis and cancer (Dieckhoff). 

Among the cases described by this author, there are two in which 
cholelithiasis is to be regarded as the starting-point of the pancreatitis. 
In one of these the ductus choledochus was found much enlarged as far as 
the entrance of the hepatic duct, and this as well as its larger branches 
also were enlarged. In the fundus of the gall-bladder was a concretion 
consisting of several stones closely packed together. The tissue of the 
pancreas apparently was densely fibrous, permeated by very large veins 
and widely dilated arteries. Occasional islands of parenchyma of a dirty 
gray color and of moderately firm consistency projected slightly above 
the cut surface. 

Chronic interstitial pancreatitis was found also in a second case of 
cholecystitis, hepatitis, and jaundice, and in one of cylindric-celled cancer 
of the pancreas. In two of the cases mentioned there was diabetes. 

According to Dieckhoff, the process develops as follows: ‘The con- 
nective tissue increases around the blood-vessels, excretory ducts, gland- 
lobules, and nerve-trunks. In the further course of the disease the intra- 
lobular tissue, which separates the acini from each other, is increased. The 
fat tissue also is increased; at the same time, fatty degeneration and disap- 
pearance of the parenchyma occur. The sclerosis may become so extreme 
that, finally, the entire organ is changed to a fibrous band and remains of 
gland-tissue can hardly be found even with the microscope.” ; 

The cases of indurative pancreatitis in cholelithiasis are of great prac- 
tical interest, and Riedel has made very interesting and important com- 
munications on this subject. ‘In connection with gall-stones,” says 
Riedel, ‘‘there is a severe inflammatory process in the head of the pan- 
ereas, which leads to the formation of a large tumor; an enlargement of 


CHRONIC INDURATIVE PANCREATITIS. 141 


iron-like density develops in a suspicious spot—namely, at the exit of the 
pancreatic and common bile-duct; starting originally from continued 
inflammation, it assumes a certain independent character, lasts for months 
and eventually years, until, after the removal of the cause of the disease, 
resolution takes place. This inflammation results not merely from a 
calculus in the common duct, but also may be caused by a concretion in 
the gall-bladder.”’ 

Riedel found induration of the head of the pancreas three times in 122 
cases of gall-stones. One of the cases will serve as an example: 

A man sixty-two years old was suddenly attacked in June, 1892, with biliary 
colic followed by jaundice. In the summer of 1893 there were repeated attacks of 
jaundice which became permanent and very severe. Cachexia. Liver enlarged. 
No ascites. Operation, August 8th, showed the liver without nodular tumors, gall- 
bladder large, filled with bile, containing a single large calculi. Cystic and common 
ducts extraordinarily wide, containing dark bile without calculi. In the head 
of the pancreas a tumor of iron-like density of the size of a small apple which was 
believed to be certainly cancerous. Cholecystenterostomy. The wound ran its 
course without reaction. Jaundice became gradually less, and after four weeks en- 
tirely disappeared. Stools colored. Patient recovered quickly, soon regained his 
former weight, and two and a half years after the operation was perfectly healthy. 
No tumor of the pancreas was perceptible either before or after the operation. 


An autopsy showed that a pancreatitis exists in such cases. The 
microscopic examination of the tumor revealed interstitial pancreatitis. A 
new-formation could be excluded with certainty. — 

[Robson * lays especial stress upon the production of chronic pancrea- 
titis by existing or probably pre-existing gall-stones, and publishes a num- 
ber of cases in support of this view.—Ed.] 

(b) From Closure of the Excretory Duct.—If the excretory duct is ob- 
structed,—by concretions, for instance,—or is impassable for any other 
reason, there gradually arises an enlargement of the ducts in the gland, 
combined with a destruction of the gland-cells and an induration of the 
interstitial tissue. Experiments on animals have shown this conclusion 
to be correct. Pawlow tied the ductus Wirsungianus in rabbits and found 
the following very striking histologic changes: The cells of the tubules are 
diminished in size, an interstitial increase of connective tissue occurs, 
beginning in the greatly dilated ducts and extending between the tubules, 
gradually assuming extreme proportions and causing the destruction of 
a portion of the secreting parenchyma. Langendorff obtained similar 
results in pigeons after tying the pancreatic duct. The interstitial 
growth of connective tissue and atrophy of the pancreas were greater in 
them than in rabbits. 

A similar process occurs in man after closure of the ductus Wirsungia- 
nus. Concretions in particular are the cause of such an interstitial in- 
flammation of the pancreas. The following cases are mentioned as 
typical: 

Fleiner had under observation a man forty years old who for some years had 
suffered from marked cardialgia. For several days he complained of great hunger 
and thirst. There was sugar in the urine. Four months after admission into the 
hospital he died of pneumonia, after severe diarrhea. Calculi were found in the 
excretory duct of the pancreas. The histologic changes were especially marked in 
the tail of this gland. In stained sections it could be seen with the unaided eye that 
only a few dark stained portions of gland tissue remained preserved. The main mass 
of the section of the gland was composed of thick connective tissue, poor in cells and 


rich in fibers, in which were scattered large and small masses of round cells, rather in 
connection with the excretory ducts than with the blood-vessels. Acini, alone or in 


* Lancet, 1900, 11, 235; Trans. Am. Surg. Assoc., 1901, xx, 144. 


142 INFLAMMATIONS OF THE PANCREAS. 


small groups or irregularly formed masses of epithelial cells scattered through the 
tissue, were separated by broad bands of fibrous tissue. The gland-cells were small, 
the protoplasm scanty, the nuclei well preserved and stained. The interacinous 
tissue was infiltrated in many places with small cells. The small excretory ducts 
of individual acini showed in many places a considerable, often quite irregular, bulg- 
ing and widening of the lumen. In many places the lining epithelium was well pre- 
served; in others it was desquamated and the lumen was filled with degenerated 
epithelium, round cells, and a finely granular, opaque mass. Small-celled infiltra- 
tion of the wall and of the surrounding connective tissue was often to be seen. 


Baumel describes the following case: 


In a negro fifty years old, addicted to alcohol and much emaciated, diabetes 
was found. Death was due to tuberculosis. The apparently normal pancreas was 
full of caleuli, which were found both in the head and in the tail of the pancreas, 
in the ductus Wirsungianus, and in the terminal pouches of the ducts. The shape 
of the stone was fitted to the space in which it was embedded and the concretions 
apparently interfered both with the removal of the-juice and the activity of the 
gland. Nevertheless the pancreas was normal in appearance and size. On micro- 
scopic examination the blood-vessels were found increased, their walls thickened, 
and the lumen widened. Thick fibrous trabecule proceeded from their walls and so 
divided as to enlace the gland-tubules. The lobules were separated from each other 
by the marked growth of connective tissue and many of them were destroyed. The 
walls of the excretory ducts were the seat of an active growth and transformation of 
connective tissue, which were perhaps more marked than in the blood-vessels. The 
ends of the excretory ducts were surrounded by fibrous trabecule and filled with 
small cells, which at times completely occluded the lumen (Nimier). 


Von Recklinghausen describes a case similar in many respects. There 
was a chronic inflammation of the ducts of the pancreas, probably caused 
by the formation of calculi, which led to fatty degeneration of the gland. 
In a case reported by Harley the closure of the Wirsungian duct was 
caused by a growth of connective tissue at the duodenal opening. In 
addition to an abscess in the gland, there was found hypertrophy of the 
pancreatic tissue caused by chronic inflammatory swelling. 


B. CHRONIC CIRCUMSCRIBED INDURATIVE PANCREATITIS. 


Localized affections of the pancreas, mostly secondary and due to the 
advance of inflammatory processes from the neighborhood, are much 
more frequent than general inflammation of the gland. As an illustra- 
tion may be mentioned the inflammation of the pancreas extending to 
the gland from an ulcer of the stomach or duodenum. When an ulcer has 
penetrated to the pancreas and has exposed this to a large extent, accord- 
ing to Orth’s description, the base is uneven and coarsely granular. The 
elevations are reddish-yellow or slightly brownish-yellow, and correspond 
to separate portions of the parenchyma. Dense, white, streaked bands 
of callous fibrous tissue are found between the divisions of the gland. 
On cross-section the bands, gradually narrowing, extend from the inter- 
stitial tissue in which they originated for some distance into the paren- 
chyma. The ulcerative process often attacks the pancreatic tissue itself, 
parts of which may even be destroyed, and thus small branches of the 
excretory ducts may be opened and their secretion be poured on the 
base of the ulcer, thus preventing its healing. This process is generally 
found in the head of the pancreas and in that portion lying adjacent to 
the lesser curvature of the stomach. 

Similar secondary processes of inflammation may be caused by aneu- 
rysm of the abdominal aorta or celiac artery, by ulcerating cancer, by 
preverterbal chronic inflammatory processes (Orth), and lastly by con- 


CHRONIC INDURATIVE PANCREATITIS. 143 


eretions which become fixed in the common duct, as it passes through the 
head of the pancreas. Riedel’s cases also belong to this series. 

Circumscribed inflammation also may be caused by such limited in- 
flammatory processes in the gland itself as may be due to a defined ob- 
literating endarteritis caused by syphilis or by the obstruction of a lateral 
duct by concretions. 

Senn has produced indurative pancreatitis in animals by injury of the 
gland tissue.and by ligation of the excretory duct. 

Indurative processes have frequently been seen after partial extirpa- 
tion in the study of experimental pancreatic diabetes, by Sandmeyer, for 
instance. The most extensive recent experiments have been made by 
Korte. After various injuries the gland was found denser in the injured 
portion. Here the interstitial connective tissue was markedly increased 
to such an extent that the gland-tissue became atrophied and in many 
places entirely disappeared. The portions beyond the ligature were 
atrophic and sclerosed. Injections of the pure culture of the colon bacil- 
lus led to a more or less extensive interstitial inflammation. Injections 
of oil of turpentine caused a very intense sclerotic inflammation. Where 
chronic inflammation was caused by oil of turpentine and the gland was 
injured four or five weeks later (by crushing, tearing, or cutting), a still 
more considerable growth of connective tissue occurred. 

In our experiments also a demonstrable indurative pancreatitis de- 
veloped, at times after the injection into the parenchyma of alcohol and 
zymine. 


EXPERIMENT OF FEBRUARY 2, 1895.—Small dog. Pancreas drawn forward. 
In each of four different places 0.3 ¢.c. of spirit. vini rectificati was injected. In the 
middle portion of the pancreas a circumscribed hematoma appeared immediately 
after the injection, while in the other places only a slight elevation of the peritoneum 
resulted. 

February 3d: Temperature 39.1° C. (102.4° F.). Animal takes very little milk. 
No urine passed. 

February 4th: Temperature 37.4° C. (99.3° F.).. Takes some milk. Urine red- 
dish-yellow, turbid. Amount 190 c¢.c. Specific gravity 1046. Sugar 0.6%. Indi- 
can in largeamount. Albumin not present. Turbidity on addition of acetic acid. 

February 5th: Animal received some milk. Cutaneous wound gaping, stitches 
cut through. No suppuration. JIodoform bandage. Dog quite lively. Tempera- 
ture 37.9° C. (100.2° F.). Urine reddish-yellow and turbid, 185c¢.c. Sugar not pres- 
ent. Indican in large amount. . 

February 6th: Urine mixed with stools. The latter contain numerous desqua- 
mated intestinal epithelium, detritus, bacteria, and fat-drops. 

February 7th: Urine 1050, brownish-yellow. No sugar. Indican in abundant 
amount. 

February 9th: Urine brownish-yellow. Indican in small amount (moderate 
reaction). Sugar, marked reaction with Fehling’s test, phenyl-hydrazin test 
doubtful. Stools formed. Large in amount, few flakes turning blue with iodin- 
potassium iodid (starch?). 

February 13th: Urine shows a very strong reaction with Fehling’s test. 

February 16th: Condition the same. Wound quite closed. 

March 15th: In addition to bread, the dog received 20 gm. of cane-sugar. Urine 
75 c.c. After inversion with sulphuric acid, reduction very marked, although pre- 
viously only slight. 

March 20th. The pancreas appears harder after total extirpation, the fibrous 
tissue thickened. ; 

March 21st: Dog found dead. 

EXPERIMENT OF FEBRUARY 12, 1896.—In each of five different places in the pan- 
creas injections were made of 0.2 c.c. of a5% zymine solution. In some of the places 
there were small hemorrhages, which were checked by compression. 

February 14th: No sugar in the urine. 

February 20th: Animal dead. 


144 INFLAMMATIONS OF THE PANCREAS. 


On section the pancreas appears somewhat thicker, in the two spots there were 
hemorrhages of the size of a pinhead, the interstitial tissue was somewhat denser, 
the lobules everywhere distinctly visible. On microscopic examination the fibrous 
trabecule between the lobules appeared enlarged. 

Similar macroscopic and microscopic appearances were seen by Katz 
and Winkler in their experiments, more complete reports of which will be 
given in the section on Fat Necrosis. | : 

EXPERIMENT OF JUNE 22, 1897.—Medium-sized, long-haired dog. After open- 
ing the abdominal cavity, the pancreas was drawn forward and ligatures were tied 
around the gland in nine different places. The pancreas became red during the 
operation; the lacteals were injected. 

June 23d: 0.25% of sugar was present in the urine. 

June 24th: Traces of sugar in the urine. 

June 26th: Urine free from sugar. The dog frequently vomited the milk taken. 

June 29th: Dog quite cheerful, appearance normal. On account of great rest- 
lessness could not be kept in the cage. The urine was examined at times and always 
found free from sugar. 

September 4th: Recent laparotomy. In this operation several peritoneal adhe- 
sions were found. The pancreas appears considerably smaller, very hard and firm. 
This is extirpated. Operation very difficult on account of numerous adhesions. 

September 6th: Dog found dead. 

The pancreas taken at the time of operation appeared distinctly smaller than 
normal, white, glistening, hard, and firm. On cutting into the organs, the normal 
gland structure is indistinct and white bands appear between the lobules. 


Examined with the microscope, as is shown in figure 7, these bands 
are composed of fibrillated tissue, which appears to penetrate also into 
the gland-lobules. | 

Symptoms.—Most of the cases of indurative pancreatitis have first 
been recognized at the autopsy, and only exceptionally was the diagnosis 
made during life, and even then only when the abdominal cavity was 
opened at an operation. This fact indicates clearly that there are no 
known pathognomonic symptoms which point with certainty to chronic 
inflammation of the pancreas. 

In the histories of the cases collected the symptoms mentioned are 
mostly general and indefinite—sensations of pressure in the region of the 
stomach and umbilicus, disturbances of digestion, vomiting, heartburn, | 
epigastric tenderness, cardialgia, colicky pains, constipation or diarfhea, 
jaundice, meteorism, hiccough, emaciation, general weakness, at times 
splenic tumor, wholly afebrile or slightly febrile condition. These symp- 
toms have such a varied significance that they may occur in every possible 
alteration of the digestive apparatus. This is the more easily understood, 
since in chronic pancreatitis other parts of this apparatus are likewise 
affected, for gastro-enteric processes and diseases of the biliary tract and of 
the liver are not infrequently the causes of the chronic pancreatitis, and 
in other cases the same factor which causes the pancreatitis produces 
also pathologic changes in other portions of the digestive system. 

Arteriosclerosis, endarteritis, syphilis, alcoholism, cholelithiasis, are 
recognized as causes of indurative pancreatitis, and it is easily understood 
that the anatomic changes produced by these processes in organs near 
the pancreas cause symptoms which often appear much more promi- 
nent in the clinical picture than the much rarer characteristic symptoms 
of pancreatic affection. Arteriosclerosis, syphilis, and alcoholism cer- 
tainly do not affect only the pancreas, but, in the stomach, intestine, and 
liver, cause changes which give rise to disturbances of function; these may 
be noticed earlier than the manifold signs of disturbed nutrition, which 
have so little that is characteristic. The general poor nutrition, increas- 


CHRONIC INDURATIVE PANCREATITIS. 145 


ing at times even to cachexia, the high degree of emaciation, and the pro- - 
gressive anemia are by no means factors diagnostic of affections of the 
pancreas, since they occur in the course of chronic and deep-seated dis- 
eases. When disease of the bile-passages or of the intestine gives rise to 
chronic inflammation of the pancreas, there are objective and subjective 
symptoms which generally obscure or, more accurately, do not allow to be 
recognized the symptoms produced by the disease of the pancreas. The 
jaundice observed at times may be caused by pressure of the enlarged 
head of the pancreas on the common duct. It may, however, be caused 
by gall-stones, which have given rise to the pancreatitis, or by a catarrh 





Fia. 7.—a, Increased fibrous tissue; b, fat necrosis of parenchyma. 


of the duodenum and of the bile-passages. If other symptoms, which 
will be mentioned later, do not point to the pancreas, the jaundice offers 
nothing especially characteristic, even when it develops gradually and is 
persistent. When chronic pancreatitis is due to closure of the excretory 
ducts, then the colic and disturbances of digestion which eventually occur 
may be regarded only as symptoms of retention or suppression of secre- 
tion, without indicating an indurative inflammation. 

Signs due to the inflamed pancreas may become prominent in a small 
number of cases of chronic pancreatitis. These are as follows: 


1. The occurrence of a tumor in the region of the pancreas: There is 
10 


146 INFLAMMATIONS OF THE PANCREAS. 


no positive evidence that the entire enlarged, calloused pancreas can be 
felt during life through the abdominal wall, as can the hard band at times 
found in the corpse after the abdomen has been opened. Some esteemed 
writers have stated that they have been able at times in especially thin 
individuals to palpate the normal pancreas. I have never succeeded in 
so doing, although for several years I have frequently tried. 

When the head of the pancreas is the seat of the induration, and is 
considerably thickened, enlarged, and hard, it may be felt through the 
anterior abdominal wall. There is certainly one such instance. Riedel, 
in his three cases of chronic pancreatitis in cholelithiasis, was twice able 
to feel a tumor of iron-like density in the head of the pancreas during the | 
operation, but only once did he feel through the abdominal walls a tumor 
as large as the fist in the head of the pancreas. He thought it the gall- 
bladder filled with calculi on account of its mobility, change of position 
with respiration, and superficial position. In another case a tumor of the 
head of the pancreas as large as a small apple could not be felt by Riedel 
either before or after the operation. 

It is easily understood from this experience of Riedel that such a pan- 
creatic tumor might compress neighboring organs and thus occasion 
severe symptoms, the cause of which might not be recognized during life. 
In Hjelt’s case, for instance, of indurative inflammation of the head of the 
pancreas, in addition to small cysts, there was severe jaundice from com- 
pression of the common bile-duct. Jaundice also was present in the cases 
of Dejerine, Demme, Dieckhoff, ete. Ascites may occur from pressure on 
the portal vein, and dropsy by pressure on the inferior vena cava (Rigal), 
according to Friedreich. There was ascites also in the cases reported by 
Chvostek, Drozda, and Rosenthal, although probably attributable to other 
causes. 

2. Diabetes: In the general part and in various places in this section 
a number of cases are given in which diabetes existed during life and 
chronic pancreatitis was demonstrated after death. Diabetes certainly 
may occur in the course of this lesion. It must be mentioned, however, 
that in none of the cases was the diagnosis of interstitial pancreatitis 
made, although the presence of the diabetes was recognized. In the cases 
reported by Riedel no sugar was present in the urine. 

3. Fatty stools: This sign is very rare. In a newborn child Demme 
observed a papularrash which almost disappeared after 10 sublimate baths. 
On the twelfth day of life slight jaundice occurred with painful distention 
of the abdomen and the stools became paler, grayish-white, ‘and fatty. 
_ Fat content 64.0% to 73.3%. In the urine were traces of bile-pigment, 
small amount of albumin, no formed elements. Death from scleroderma. 
At the autopsy the pancreas was found atrophied from chronic pancreati- 
tis. Fibrous degeneration of the head. Acini not recognizable. 

Friedreich mentions that fatty stools have been found at times, but 
does not describe the cases. In a patient whose diagnosis varied between 
chronic pancreatitis and catarrhal closure of the ductus Wirsungianus, 
he found “in the thin, grayish-yellow stools large and small clumps, 
greasy, tallow-like, and consisting of solid fat in considerable quantity.”’ 

Individual observers—Rosenthal, for instance—state expressly that: 
the stools were perfectly normal. It is certain, however, that the quality 
of the stool has been only rarely observed, and that in many cases at least, 
it would always be possible on more careful observation to discover char- 
acteristic changes. 


——=- ~~“ 


CHRONIC INDURATIVE PANCREATITIS. 147 


Diagnosis.—The obscurity of the symptoms indicates that the diag- 
nosis of chronic pancreatitis is very rarely possible, and even then is prob- 
able only to a certain degree. The distinction between cancer and indura- 
tion, especially in the early stage of the former, is difficult even when all 
the cardinal symptoms are present, as palpable tumor either of the 
entire pancreas or of the head, diabetes, fatty stools, and jaundice. 
Even if chronic inflammation of the pancreas were suggested from the 
existence of syphilis, alcoholism, or arteriosclerosis, the possibility of a 
new-formation in the pancreas could not be excluded. 

Riedel’s cases show that even large tumors are not felt through the 
intact abdominal walls, that even when the abdominal cavity is open 
inflammation cannot be distinguished from new-formation, and that one 
must wait a half-year or more before the true condition is known. If the 
tumor disappears, it was inflammation; if it grows and the patient dies, 
it was carcinoma. 

Chronic pancreatitis may be confounded not merely with cancer of the 
pancreas, but also with cancer of the duodenum, portal fissure, common 
bile-duct, and lvmph-glands, and with tumors of the vertebre. 

It is hardly possible to more than suspect indurative pancreatitis even 
when diabetes occurs in an alcoholic patient with cirrhosis of the liver or 
in a syphilitic patient, since enlargement of the pancreas is rarely observed 
and the thickened and indurated gland is seldom felt. Riedel’s observa- 
tions show that secondary pancreatitis is not so very rare in the course of 
cholelithiasis. If surgeons in operating for relief from gall-stones pay 
more attention to this matter, as is to be anticipated, indurative pancrea- 
titis will be more often diagnosticated, at least at operations, and data will 
be obtained for the recognition of the disease in its earlier stages. 

If such affections of the pancreas can resolve and heal perfectly after 
existing for years, it may positively be assumed that inflammations of the 
pancreas capable of undergoing resolution are much more frequent in 
disease of the bile-passages and duodenum than has been supposed, and 
have hitherto escaped recognition because they present no characteristic 
symptoms. It is a well-known fact that many patients suffering from 
gall-stones, even without permanent jaundice, become so very weak and 
rapidly emaciated that the development of a cancer is suspected, and vet, 
after a long time, the patients wholly recover. It is always possible that 
in such cases the pancreatitis may be recovered from without operation; 
that the stone in the gall-bladder, which kept up the inflammation of the 
pancreas, has passed out by the natural passages, and that the pancreas 
then has returned gradually to the normal condition, as happened in 
Riedel’s patient after a successful operation. At present the diagnosis 
of such a pancreatitis cannot be made, but it may be approximated if 
pancreatic symptoms are sought for in analogous cases. 

Since in Riedel’s cases a correct diagnosis was eventually established 
only a long time after successful surgical treatment, so medical treatment 
may succeed in many cases in healing processes whose nature first becomes 
clear after they are recovered from. . 

Prognosis, Duration, and Course.—Since it is almost impossible to 
make a diagnosis, it is almost as difficult to give a prognosis; that is, it 
will be a rare exception when it can be foretold what is to be the course of 
the disease. : 

Although most of the cases, especially those due to arteriosclerosis, 
are to be regarded as incurable, yet there is no doubt, according to the 


148 NEOPLASMS. 


most recent experience, that there are curable varieties, and it is impossi- 
ble at present to state whether these or the incurable kinds predominate. 
Recovery certainly is to be thought of. When the cause which leads to 
chronic pancreatitis can be eliminated, as gall-stones or calculi in the 
pancreatic ducts, or curable intestinal processes, or perhaps syphilis in 
many instances, recovery is possible, but only in the earlier stages when 
atrophic processes have not already led to destruction of the gland, ob- 
struction of the circulation, or cyst formation. Riedel’s observations 
show that a cure is possible even when there is a considerable tumor. 

The disease runs a slow course and the process may extend over years 
in favorable as well as in unfavorable cases. 

Treatment.—The rational treatment of chronic pancreatitis has been 
rendered possible by the information obtained from surgery of late years. 
Surgical experience has taught that if the cause which has led to the pan- 
creatitis can timely be removed, an integral restitution is possible up to a 
certain point. In this respect cholelithiasis holds the first rank. Inflam- 
mation of the pancreas is one of the many dangers which may arise in the 
course of cholelithiasis and may pursue an independent course, even after 
removal of the gall-stones, and prove dangerous to life if the process is not 
arrested at the right time. There is consequently a further indication for 
the operative treatment of cholelithiasis, which is demanded to prevent 
in time the further development of a secondary pancreatitis not amen- 
able to medical treatment. 

Preventive treatment should be considered for other processes also 
which may lead to pancreatitis, such as syphilis, alcoholism, and catarrhal 
inflammations of the intestine, which may be continued to the pancreatic 
ducts and cause them to be inflamed. . 

Surgical experience also offers a guide to the rational treatment of 
other varieties of chronic pancreatitis, although there are no facts in sup- 
port of this view. 





LL NEOGELASMS: 
J. CARCINOMA. 


CaRcINoma is the most important and frequent of the new-formations 
in the pancreas; in the light of our present knowledge it is perhaps to be 
considered the most common disease of the pancreas. The view is un- 
doubtedly correct, though at present not capable of proof, that certain 
affections of the pancreas—as diseases of the blood-vessels, circulatory 
disturbances, inflammations, catarrhal processes in the excretory ducts, | 
atrophy, fatty degeneration, tuberculosis, etc.—occur much more fre- 
quently than has been recognized on account of defective investigations. 
The relative frequency of cancer to other diseases of the pancreas is prob- 
ably about the same as in other organs, in which cancer certainly does not 
" assume the highest statistical importance. Carcinomata are much more 
rarely overlooked than other affections which perhaps are recognizable 
only on microscopic examination, which is generally omitted. 

The earlier literature and the contained statistics are of but little value 
in consequence of the frequency with which chronic inflammations of the 
pancreas were confused with scirrhus. There is some evidence with regard 








CARCINOMA. 149 


to the frequency of cancer of the pancreas, although the primary are not 
separated from the secondary varieties. Remo Segré collected the cases 
of pancreatic tumor observed in the Ospedale maggiore in Milan during 
nineteen years, and found 132 cases in 11,500 autospies—127 carcinomata, 
2 sarcomata, 1 syphiloma, and 2 cysts. . 

Biach found the following results among 18,069 autopsies in the 
Vienna General Hospital: 1270 carcinomata, 22 pancreatic carcinomata; 
5065 autopsies in Wiedener Hospital, 514 carcinomata, 6 pancreatic car- 
cinomata; 477 autopsies in Rudo!f’s Hospital, 221 carcinomata, 1 pan- 
creatic carcinomata. Therefore among 23,611 autopsies there were 2005 
cancers, of which 29 were in the pancreas. Thus he finds 8.5% of cancers, 
of which 1.5% were pancreatic cancers. 

From. Biach’s collection of the carcinomata observed in the Wiedener 
Hospital for the years 1860 to 1866, the following results show the relative 
frequency of the occurrence of this neoplasm in the stomach, liver, and 
pancreas: 


1860. 1863. 1864. 1865. 1866. 
Scomach «nisi. 29.54% 28.80% 21.15% 25.53% 34.42% 
TAMER aed tine 27.27% 23.07% 21.15% 21.28% 18.03% 
Pancteas: ~ioa02;-3 2.27% 3.85% 1.92% 2.13% 1.64% 


In this statement also the primary and secondary tumors are not dis- 
tinguished. 

Eppinger’s statistics are based upon 1314 autopsies. Among these 
there were 308 cancerous neoplasms in the different organs. The pan- 
creas was involved in 19 cases (5.5%). Only two cases (0.6%) were cer- 
tainly primary in the pancreas. 

Among 3950 autopsies, Soyka found 313 carcinomata, of which 3 (1%) 
were primary in the pancreas. Among 313 cases of cancer, Wrany found 
the pancreas involved 6 times. Among 639 autopsies in individuals 
dying of different diseases, Forster found pancreatic cancer 6 times, and 
it was always secondary. Among 467 autopsies of cancerous patients, 
Willigk found pancreatic cancer 29 times. 

The primary cancer of the pancreas is certainly much rarer than the 
secondary variety, but primary carcinoma of the pancreas is by no means 
a very rare disease. Friedreich collected only 15 cases. In statistics 
published in the year 1893 by Mirallié, 113 cases of primary carcinoma of 
the pancreas are reported. He eliminated all cases from consideration in 
which a cancer was found at the same time in any other organ, since it 
would render doubtful the primary origin of the tumor; he excluded also 
those cases in which he was unable to get any detailed account. It may 
certainly be assumed that among the cases excluded by Mirallié there 
were some which were primary, for metastases after primary carcinomata 
of the pancreas are by no means infrequent. 

To the above mentioned I have been able to add, up to 1896, 36 addi- 
tional cases of primary cancer. There are recorded in the reports of the 
Vienna General Hospital, from 1885 to 1895, 32 cases of primary cancer 
of the pancreas.* The number of actual cases is, of course, much greater. 
If the report of a large hospital or the autopsy reports of an anatomic insti- 
tute are examined, there will always be found individual cases of primary 


-eancer which are not published elsewhere. Since it is well known that 


* In the literature from the beginning of 1896 to July, 1897, the following cases 
are found: Abbe, Aigner (4 cases), Bandelier (5) cases, Fothergill, Gade, Gorbatow- 
ski, Hale White (2 cases), Liitkemiiller, Maxson (2 cases) Russel. 


150 NEOPLASMS. 


primary cancer of the pancreas is by no means rare, only such cases 
usually are published in which the diagnosis can be established or in which 
special features appeared during life or after death. 

It cannot be decided with certainty whether all cases described as 
primary pancreatic cancer really originate in the pancreas, since there 
are many cases, as Dieckhoff states, in which it is not possible, even at the 
autopsy, to answer exactly this question. ‘It not infrequently happens 
that a cancer which to the unaided eye gives at first the impression of a 
primary carcinoma of the pancreas shows on microscopic examination — 
that it originates from the glands of the duodenum, an occurrence which is 
especially emphasized in a careful study made by Olivier.”’ This writer 
concludes that it may happen that a neoplasm which, on macroscopic 
examination, appears as a primary tumor of the pancreas, originates in 
the duodenum and actually presents, after it has secondarily affected the 
pancreas, all the characteristics of an interstinal cancer. 

It may be at times, as Orth suggests, that even a microscopic examina- 
tion does not insure a positive conclusion, ‘‘since cylindric-celled cancers 
may proceed even from the pancreas,—that is, from its excretory ducts,— 
and the transition of the atypical growth of gland acini into cancerous 
alveoli, observed by some investigators, is by no means always so easily 
established in primary tumors.” 

Secondary carcinoma of the pancreas is far more frequent. This can 
be determined from the earliest statistics of Gussenbauer and Winiwarter. 
These observers examined the autopsy reports of the Vienna Pathologic 
Institute from 1817 to 1873 with reference to the relation of cancer of the 
stomach to its metastases. Among 61,287 autopsies there were 903 cases 
of cancer of the stomach. In these, there were 100 metastases in the 
pancreas, the liver was the seat of secondary cancer 259 times, the mesen- 
tery and intestine 173 times, the lymph-glands and pancreas 94 times. 
Among 542 cases of primary cancer of the stomach limited to the pylorus, 
there were metastases in the pancreas in 34. | 

The frequency of gastric cancer permits a conclusion to be drawn as to 
the frequency of secondary pancreatic cancer, since more than 10% of 
the metastases after cancer of the stomach affect the pancreas, which 
organ is not infrequently also the seat of metastases from cancers else- 
where. 


PATHOLOGIC ANATOMY. 


Seat of the Neoplasm.—The head of the gland is the most frequent 
seat of the neoplasm according to the earlier statistics of Ancelet, who 
collected 200 cases without discriminating between the primary and sec- 
ondary forms. . The tumor was found in the head 33 times, in the body 
5 times, twice in the tail, and 88 times it affected the entire pancreas. 
Among 73 cases of primary and secondary cancer of the pancreas col- 
lected by Biach the head was affected 19 times, the body 13 times, and 
the whole gland 31 times. The seat of the cancer was not stated in 19 | 
cases. In one case the upper edge of the gland alone was diseased. Remo 
Segré found the seat of the tumor 35 times in the head, 19 times in the entire 
gland, twice in the middle, and once in the tail. Mirallié writes: “In 
general, the head of the pancreas is the seat of the disease.”’ Among 
78 cases in which sufficient details were given for classification, the head 
was found the seat of the new-growth 39 times, the whole organ 19 times, 


CARCINOMA. 151 


the tail 4 times, head and body 3 times, middle portion and tail once, 
middle portion once, head and tail once; in 10 cases no exact statement 
was made. 

In the autopsy reports of the Vienna General Hospital from 1885 to 
1895, the following data were found: Among 32 cases of primary carci- 
noma it was found in the head in 20 cases, twice in the body, 3 times in 
the tail, and once throughout the entire gland. In 6 cases no exact state- 
ments were given regarding the location. Among 53 cases Boldt found 
the head diseased 25 times and the entire gland more rarely. 

Variety of Cancer.—The most frequent form is fibrous cancer with 
hard, dense nodules. Soft medullary cancer and cylindric-celled and 
gelatinous cancers are rare. Medullary cancers are reported by Allen, 
Harrison, O’Hara, v. Hauff, Kernig, Lubarsch, Mariani, Molander and 
Blix, and Wrany. Cylindric-celled cancers have been described by Wag- 
ner, Pott, Striimpell, Wesener, and Dieckhoff (two cases and a mixture 
of medullary and cylindric-celled cancer). Gelatinous cancer is reported 
by Liicke-Klebs and Mosler; alveolar cancer by Bruzelius and Key and 
by Seebohm (hard scar-like tissue with alveolar structure and epithelioid 
cells). Adenocarcinoma by Seebohm and by Ruggi. 

Segré found among his cases 29 of fibrous cancer, 19 of medullary, 2 of 
combined, and 1 of melanotic cancer. Of the 32 cases of cancer which 
were examined postmortem in the Vienna General Hospital from 1885 to 
1895, 19 are noted as scirrhus, 1 as medullary, 1 as adenocarcinoma, and 
3 as gelatinous (one of which was a gelatiniform fibrous cancer). In 8 
cases the exact characterization was not given. 

Cancer of the pancreas may proceed from the glandular epithelium or 
from the cells of the excretory ducts. ‘In general,” says Dieckhoff, ‘‘the 
conclusion may be justified that, in the pancreas, as in other organs, can- 
cer with ill-defined forms of epithelium originates from the glandular 
epithelium, while cancer with typical and conspicuously cylindric cells 
originates from the epithelium of the excretory ducts, and a number of 
small alveolar cancers even with less typical cylindrical epithelium also 
originate from the epithelium of the excretory ducts.” 

He coincides with the view of Olivier, who, on the basis of a careful 
investigation of three cases of cancer, comes to the following conclusion : 
‘‘Primary cancer of the pancreas may proceed from the epithelium of the 
small ducts even when ‘la faible proportion des formations neoplastiques 
canalicularies’—as Dieckhoff designates the small alveolar cancer—does 
not give the appearance of a cylindric-celled cancer.” Dieckhoff some- 
what modifies this view in a foot-note in which he refers to a case of med- 
ullary cancer observed by Lubarsch, where, ‘‘in spite of the large alveolar 
character of the new-growth, the origin from the excretory ducts was 
known by the fact that the cancerous strands penetrated as large bands 
into the normal pancreatic tissue, in which, however, there were no ex- 
cretory ducts; Thierfelder has described a similar condition in his case of 
pancreatic cancer.” 

Size of the Tumor.—The pancreas in the great majority of cases is 
enlarged. The nodes are described as being as large as a pigeon’s egg, a 
hen’s egg, a goose-egg, or as large as a child’s fist. Exceptionally, larger 
tumors are found. Terrier extirpated a neoplasm of the size of the head 
of an adult and weighing 54 pounds. In Sauter’s case the tumor was 
of the size of aman’s fist. Bard and Pic found a tumor of the size of the 
head of afetus. Isch-Wall found a tumor as large as a mandarin orange. 


152 NEOPLASMS. 


At times the pancreas appears smaller than normal, shrunken (Kuhn, 
Mosler), or of normal dimensions (Bard and Pic). 

The portion of the pancreas not affected by the cancer is either normal 
or hardened or atrophied by the new-formation of connective tissue. 

Extension to neighboring organs frequently takes place, and all tis- 
sues in the neighborhood of the cancerous pancreas may be involved in 
the neoplasm. In many cases it is certainly difficult to say positively 
what is the origin of the carcinoma. | 

Most frequently the liver, stomach, duodenum, gall-bladder, the 
larger bile-passages, and the neighboring lymph-glands are involved. 
The cancer may extend also to the omentum, the mesentery, the large 
intestine, the kidney, the spleen, to the aorta and the portal vein, the 
vertebral column, to the diaphragm and through this to the pleure and 
lungs. 

Metastatic nodules are found most frequently in the liver, but they 
are also observed in the skin, heart, lungs, and pleura, in the cardia, in 
the dura, in portions of the large intestine (cecum, rectum), in the plexus 
hepaticus and spermaticus, and in the ovary. Not infrequently a general 
carcinosis develops. The primary seat of the cancer, however, is doubtful 
in many cases. 

The growing tumor compresses the neighboring organs and obstructs 
the cavity of adjacent hollow organs and canals. The frequent seat of the 
neoplasm in the head of the pancreas and the relation of the latter to the 
ductus communis choledochus explain the frequent compression of this 
duct. 

It is easy to understand that when the head is degenerated, a mechani- 
cal hindrance to the flow of bile must frequently result from pressure on 
the common duct, since, according to the investigations of Zuckerkandl, 
this duct for about 4 to 3 cm. traverses the gland tissue in the head of the 
pancreas. 

Courvoisier found cancer as the cause of obliteration of the ductus 
choledochus from disease of the pancreas in 55 out of 66 cases. It is 
evident that the ductus Wirsungianus may be compressed or even in- 
volved in the neoplasm. Dilatation of the duct, and at times even a cyst- 
formation in the pancreas (according to Boldt, in about one-third of the 
cases), are necessarily present beyond the obstruction of the ductus 
choledochus and ductus Wirsungianus. The intimate relation between 
the head of the pancreas and the duodenum easily leads, when cancer 
develops in the head of the pancreas, to compression and obturation of 
the duodenum (de Haén, Mondiére 2 cases, Teissier, Holscher, Wrany, 
Stansfield, Tanner, Salomon). In the case reported by Wesener the can- 
cer was fused with the duodenum, and in Mariani’s case it had become 
attached to the concavity of the duodenum. 

Pyloric stenosis also may result from the compression, as in the cases 
of Bardeleben-Klemperer and Pilliet. Rahn reports compression of the 
cardia, and Petit states that the entire stomach was compressed and 
crowded toward the anterior wall of the abdomen. The colon was com- 
pressed, Battersby; the ureters, Recamier, Soyke, Bard and Pic; the vena 
porte, Faendrich, Molander and Blix, Wrany; the aorta, Teisser, Andral, 
Choupin and Molle, Battersby; the splenic artery and vein, Sandwith; 
superior mesenteric artery and vein, Williams. Compression of the 
inferior vena cava occurs not infrequently. According to Boldt, the 
aorta and vena cava inferior were compressed in about 10 cases, the aorta 


» 





CARCINOMA. 153 


alone in 5 cases. The compression of the thoracic duct also is noted. 
Thrombosis of the portal vein was found in the case of Wesener. 

Ulcers, which may perforate, result from degeneration of the cancer. 
Such cases are described by v. Hauff, perforation through the abdominal 
wall at the navel; Campbell, through the posterior wall of the stomach. 
Ulceration of the tumor after its growth into the stomach or into the duo- 
denum is reported by Muhry, Albers, and Kopp; perforation into the 
portal vein, noted by Bowditch, Molander and Blix, Litten; ulceration 
of the celiac artery by Cash. 


ETIOLOGY AND STATISTICS. 


The causes of the development of cancer of the pancreas are entirely 
unknown. The influence of heredity, predisposition, poor nourishment, 
and abuse of alcohol as etiologic factors is entirely hypothetic. Trau- 
matic factors are noted only in the rarest cases. In Clurg’s case the pa- 
tient attributed his disease to the pressure of a quantity of coal in the 
region of the stomach. Schupmann’s patient blamed the lifting of a 
heavy body. 

Cancer of the pancreas is found more frequently in men than in women; 
both earlier and later statistics are agreed on this point. Da Costa found 
among 37 cases, 24 men and 13 women; Ancelet among 161 cases, 102 
men and 59 women; Bigsby among 28 cases, 16 men and 12 women; Boldt 
among 56 cases, 35 men and 21 women; and Mirallié noted 69 men and 
37 women in his 106 cases. In addition to the above, I have found, up 
to the beginning of 1896, statements regarding 21 men and 20 women. 
Including Mirallié’s cases, there are 90 men and 57 women, hence 61.2% 
of the cases are men. This proportion is changed somewhat by the 
autopsy reports of the Vienna General Hospital from 1885 to 1895. 
Among 32 cases, 12 were men and 20 women. 

The age most frequently concerned is between forty and seventy years. 
According to Boldt, the greatest number of cases, 18, were found between 
fifty and sixty years; between forty and fifty there were 11 cases, and 
between sixty and seventy there were 10 cases. The following table is 
based upon 73 cases: 


YEARS. CASES. 


OBOE Sete tte Seige ern Mere Ga ees ees 1 (Bohn, 7 months) 
PAO210 isa nr eee ee eer eae Gee NS 1 (Kiihn, 2 years) 
BS 020) 60 5G Bea A eee ee eee 1 (Dutil, 14 years).* 
Be 60 SO) nuda ens bie peal eens ee Sees 3 
Oh BO A ie arg as fete ere oe ee 14 
AED UO DMRS Bae MRR Sst acs Bale on os re es oe 19 
PROG SO Ae Rea ott ale easy isd ae Tare a ered oe 20 
OMG pe Ri eta ll eR ee 10 
ED URES RB 2 a 4 

73 
SYMPTOMS. 


The symptoms of primary pancreatic cancer, according to the time of 
their occurrence, can be divided into three groups:  _ 
1. The disturbances of function of the pancreas and of its nerves and 


* Bandelier has recently reported the occurrence of cancer in a boy thirteen 
years of age. 


154 NEOPLASMS. 


canals resulting from alteration of the pancreatic tissue during the begin- 
ning and development of the neoplasm. 

2. The arrest of function of neighboring organs invaded by or involved 
in the extension of the growth from the pancreas. 

3. The result of metastases and of general carcinosis. 

This grouping cannot be strictly adhered to because many of the 
symptoms differing in intensity and quality are present in all three groups, 
and, therefore, should be considered in the description of each. Besides, 
our knowledge of the pathology of the pancreas is still so defective in many 
respects that the symptoms of the first group, which are caused by the 
partial failure of pancreatic function, generally disappear entirely and 
show nothing characteristic. Striking symptoms generally occur first 
when the cancer of the pancreas affects the function of neighboring organs, 
when, as one might say, it becomes cultivated. The following attempt 
to represent the frequency and importance of the symptoms is based upon 
published experiences, since a single observer has but little opportunity 
to discuss them from his own observation on account of the rarity of 
recognizable diseases of the pancreas. 

Disturbances of digestion are generally given as the first symptoms, 
diminished appetite and hunger, distress after eating, sense of pressure, 
fulness in the epigastrium, especially after meals, heartburn, eructation, 
nausea, retching. It cannot be decided that these symptoms are attrib- 
utable to the development of the cancer. 

It is possible that catarrhal processes of the stomach or of the small 
intestine precede or accompany the disease of the pancreas, and that the 
dyspeptic disturbances are due to them. In the course of the disease 
these symptoms appear much more pronounced. Complete anorexia 
frequently develops, also a loathing for food, especially for meat, and 
the aversion may become so extreme that all nourishment is refused. 
Numerous observations show that this distaste for food does not take 
place simply in case of the extension of the disease to the stomach. In 
certain cases the appetite suffers little or none. The patients eat well and 
with satisfaction, but become continually more and more emaciated, as 
was the fact in a case which I shall later describe. The disturbance of 
the appetite does not depend upon the carcinoma itself, as may be seen 
in a number of the cases, in which, on account of closure of the ductus 
choledochus by a pancreatic cancer, cholecystenterostomy was performed. 
After the anastomosis had been established and the jaundice had disap- 
peared, the appetite became good at times, although temporarily, and 
the patient’s weight increased (Reclus, Regnier, Terrier, Kappeller-Socin, 
Ruggi). 

Severe disturbances of digestion develop when there is a dilatation 
of the stomach with all the consequences of stagnation of the gastric con- 
tents from compression of the duodenum or pylorus. The frequent vom- 
iting of an earlier stage becomes the rule (Mirallié, Striimpell, Ziehl, 
Drozda). Blood may be mixed with the vomitus, or the latter may con- 
sist of pure blood, when the tumor has perforated into the cavity of the 
stomach or into the duodenum. 

The examination of the gastric contents, which only rarely has been 
made after a test-breakfast, repeatedly shows an entire lack of free hydro- 
chloric acid, although the stomach was entirely free from disease (Bottel- 
heim). In ‘the case of Klemperer-Bardeleben, in which the pylorus was 
compressed by a tumor of the pancreas and the contents of the stomach 


CARCINOMA. 155 


could not pass through the pylorus, the examination showed 2.6% hydro- 
chloric acid. On strong suction, there escaped from the stomach about 
50 to 80 c.c. of a greenish fluid, which distinctly contained mucin and 
bile pigment. 

The signs of disturbed digestion indicative of a loss of the function of 
the pancreas are rarely found in the stools. Fatty stools are noted several 
times. Mirallié mentions nine cases: Besson, Garnier, Marston, Musmeci, 
Roeques, Luithlen, Labadie-Lagrave, Pott, Mirallié.. In addition, fatty 
stools were noted by Bowditch, Clark, Friedreich, Maragliano, Marsten, 
‘Molander, and Blix and Ziehl. The last found silver-gray stools, three- 
fourths of which consisted of acicular fat-acid crystals. The chemical ex- 
amination showed that one-fourth of the weight was due to fat, half to 
water, and the remaining fourth to other substances. 

The case observed by me in which this symptom was especially striking 
was as follows *: 


M. M., born in 1854, manufacturer’s wife, family healthy. Father and mother 
still living. Has borne three children and had one abortion. After the abortion, in 
1889, she had a posterior parametritis. At this time there was also an intramural 
uterine fibromyoma as large as a fist in the posterior wall. In 1890 and 1891 she 
felt relatively well, but on account of anemia and the persistence of the parametritis 
exudation she took a course of treatment at Franzensbad. In the summer of 1892 
she was taken ill with diarrhea and became emaciated. Her appetite, however, was 
good. The stools were regularly evacuated at night, were uncommonly copious, of 
the consistency of thick broth, of offensive, extremely bad odor, chocolate in color, 
and always plentifully covered with fat-drops, in spite of the fact that she ate as little 
fat as possible. At the end of December, 1892, the rather large woman weighed only 
100 pounds. 

On physical examination, the lungs and heart were normal; abdomen flat, not 
painful on pressure. In the uterus was a myoma the size of a fist; in the urine no 
albumin and no sugar. 

January 11, 1893, I saw the patient for the first time and the stools were thor- 
oughly examined, with the following result: Stools moderate and like thick broth; 
white particles were scattered in the sediment. 

Microscopic examination: (1) Very numerous fragments of striated muscle- 
fibers, in the main with well-preserved structure; (2) numerous fat-acid needles and 
fat-drops; (8) bacteria, detritus. 

Chemical examination: After several days’ drying on the water-bath in order 
to estimate the amount of fat, 4.6325 gm. of dry residue were obtained, in which there 
were 2.1265 gm. of fat; that is, 45.9%. The ether extract consisted predominantly 
of neutral fat. 

At a subsequent examination, on January 28th, I found in the epigastrium a 
hard, round tumor, the size of a nut, the seat of which I located in the head of the 
pancreas. My diagnosis was carcinoma capitis pancreatis. In March the patient 
stayed for two weeks in Hungary, and there menstruated profusely and developed 
jaundice. es 

April 6, 1893, an exploratory laparotomy was undertaken in Eder’s Sanitarium 
by Professor Albert in the presence of Professors Schauta, Hochenegg, and Director 
Schopf. After cutting through the great omentum, especially the gastrocolic liga- 
ment, an attempt was made to isolate the tumor, which was found connected with 
the head of the pancreas. It appeared firmly attached to the surrounding structures, 
especially to the vena cava, so that it was necessary to give up the extirpation. The 
much reduced patient became steadily weaker after the operation and died on the 
13th of April. No autopsy was performed. 


A similar condition was reported by me (see page 113) in a case in 
which the diagnosis of cancer of the pancreas could be made only with 
great probability. , : 

The disturbance of the digestion of proteids deserves especial atten- 
tion. Besides the above observations in pancreatic cancer, there is only 


* The history was kindly supplied to me by Director Schopf. 


156 NEOPLASMS. 


one other on this subject—that of v. Ackeren. The latter quotes also a 
very similar case reported by Le Nobel.* 

In another case, to be mentioned later, and which may be regarded as 
cancer of the pancreas, there was a similar condition in the stools. It 
may probably often occur that many undigested muscle-fibers could be 
found in the feces on microscopic examination; Kiister, for instance, 
having found them in a case of probable pancreatic cyst. 

Bulky stools are a striking symptom, as has already been mentioned. 
They were present in one of the cases described by me, and were due to 
the fact that a large part of the food passed out undigested. It might be 
claimed that this disturbance of digestion was due tothe diseased pancreas, 
since there was no jaundice at first. The patient generally recognizes that 
he is evacuating a surprisingly large amount of feces in relation to the food 
he is taking. This symptom should certainly attract the attention of the 
physician. I have a number of cases in mind in which from this symptom 
I concluded that the pancreas was diseased. In a man over seventy years 
old there was diabetes. Later jaundice developed, which slowly increased 
and became very intense. There was found in the epigastrium to the 
right of the spinal column a resistance, which gradually increased in size. 
Aside from the rapid emaciation and persistently advancing cachexia, the 
most surprising symptom was the daily evacuation of very abundant, 
firm masses of fecal matter. On microscopic examination of the stools, 
many muscle-fibers and undigested vegetable cells were seen; fat in 
abnormal amounts was not present. Unfortunately no autopsy was 
allowed, but the assumption of a cancer of the pancreas seems fully justi- 
fied in this case. 

Such changes in the stools are certainly rare. Although in most of the 
publications no statement is made concerning the feces, yet in a number 
of cases it is expressly stated ‘stools normal.” 

Acholic stools and disturbances of digestion dependent on the want 
of bile often occur on account of the frequency with which the outflow of 
bile into the intestine is hindered by a growing cancer in the head of the 
pancreas. 

Bloody stools occur frequently, and have been reported by Bohn, 
Freidreich, Kobler, Mariani, Molander and Blix, Wesener. Hemorrhage 
occurs in ulceration of the duodenum or some other portion of the-intes- 
tine, after the cancer has spread to these parts. Constipation or diarrhea 
often occur as manifestations of disturbed intestinal function. Constipa- 
tion is the more frequent. Kellermann found it 60 times in the reports 
of cases investigated by him, while diarrhea was observed only 12 times; 
in 9 cases diarrhea alternated with constipation, and in the others the 
consistency of the stools was either noted as normal or no statement was 
made concerning them. In case of extension of the growth to the intes- 
tine or of compression of the latter by the tumor, there may be stenosis 
leading even to complete closure. Hagenbach mentions eight such cases 
(IXerckring, de Haén, Mondiére 2 cases, Holscher, Teissier, Tanner, Salo- 
mon), and describes Kerckring’ s case as follows: A man forty years old 
suffered for six days from irremediable obstipation, and died after having 
vomited fecal matter for three days. The pancreas, enlarged to three or 
four times its natural size, had completely compressed the ileum. 

Pain is one of the symptoms which generally accompany the process 


* In Maly’s “ Jahresbericht”’ regarded as atrophy (see General Considerations, 
pp. 59 and 92). 


CARCINOMA. 157 


from beginning to end. It is rarely wholly absent. In one of the cases 
reported by Friedreich the absence of pain, either spontaneous or on pres- 
sure, in the upper abdomen was very surprising; in Stiller’s patient also 
severe pains and cramps were lacking during the whole course of the dis- 
ease. Ina number of patients there were moderate pains, a feeling of 
pressure and tension in the epigastrium, a feeling of distress behind the 
stomach, sensitiveness to pressure, which increased during and from peris- 
talsis. As a rule, however, the pains are very severe, either continuous 
or paroxysmal, and assume the form of cardialgia and colic. The con- 
tinuous pains are seated in the epigastrium and radiate in all directions, 
especially into the right hypochondrium, when the cancer is in the head 
of the gland. They may radiate toward the chest, shoulder, abdomen, 
and back, and are of great intensity, being further increased by movement 
and by taking food. The patients may be unable to define exactly the 
kind of pain. They call it burning, boring, tearing, drawing, stabbing; 
but when it is most severe, they say only that they suffer beyond endur- 
ance. 

The nature and intensity of the pain, which is rarely so severe in other 
tumors of the upper abdomen, have led to the assumption that it was due 
to pressure upon or stretching of the celiac ganglion or the nerve-trunks 
proceeding from it, and, therefore, it has been designated celiac neuralgia. 
Similar suffering is seen only in the severe crises of tabes or other diseases 
of the central nervous system, but these disappear after a few days or one 
or two weeks, while the pains arising from pancreatic cancer, perhaps with 
ever-increasing intensity, last to the end of life. 

Constant or paroxysmal pains of another kind may arise, due to the 
adhesion of the pancreas to movable neighboring organs in consequence of 
the extension of the cancer to the adjacent peritoneum, every movement 
of which leads to stretching and pain. 7 

The paroxysmal pains come next, and are regarded as cardialgia, colic, 
perhaps biliary colic. They are of various duration and intensity and 
may originate from different causes. They are either paroxysms of the 
‘neuralgia previously mentioned as attributed to the participation of the 
celiac ganglion, or attacks of genuine pancreatic colic caused by stagnant 
secretion in the ductus Wirsungianus or in other secretory ducts of the 
pancreas, when they are compressed, stretched, or entirely closed by the 
cancerous growth within them. The pain may be actual biliary colic if 
the outflow of the bile is so disturbed by pressure on the ductus chole- 
dochus or by its involvement in the growth of the cancer, or by a bend of 
the common bile-duct, that concretions form, or if, as is not rarely the 
case, a cholelithiasis is actually present. True gastralgias also may be 
present, when the growth extends into the stomach and ulcerates or con- 
stricts the pyloric orifice. Intestinal colic arises when the action of the 
intestine is disturbed by the pressure on it of the cancer or cancerous 
glands, or when the coils become adherent in consequence of cancerous 
peritonitis. The continuous pains not infrequently are combined with 
the paroxysmal variety; the continuous, more or less intense pain is inten- 
sified at times, and, thus increased, may last for several days. Sensitive- 
ness to pressure occurs in,addition to spontaneous pains. This is present 
almost without exception, but there is, at times, pain produced by pressure 
so intense that the patients cannot bear the slightest touch. 

Jaundice is one of the most frequent symptoms of cancer of the pan- 
creas. In most cases it does not first occur when the cancer extends 


158 NEOPLASMS. 


beyond the pancreas, but arises from alterations in the pancreatic tissue 
and from pressure of the neoplasm on the common bile-duct in conse- 
quence of the usual passage of this duct through the head of the pancreas. 
Jaundice not infrequentlypis the first indication of the disease. It may 
occur suddenly after an attack of colic, and then is attributable to chole- 
lithiasis. As a rule, it develops gradually, insidiously, and when it has 
once appeared it increases, slowly but unceasingly advancing until it has 
all those peculiarities which are presented by jaundice from complete 
closure of the ductus choledochus. It always increases progressively 
although with differing rapidity. The skin, especially that of the face, 
becomes dark brown, and finally is almost black. The jaundice may 
apparently diminish toward the end of life, as sometimes happens in other 
varieties of permanent closure of the excretory bile-ducts. The color due 
to the bile-pigment seems to be less pronounced than before because the 
skin becomes anemic and pale. In many cases jaundice is slight at the 
onset, and first appears distinctly or increases in intensity toward the end. 
In a number of cases there is no jaundice. Mirallié found it 82 times in 
113 cases; in addition, it was noted 21 times in the 36 cases above referred 
to; hence, it has been reported 103 times in 149 cases. Jaundice was 
entirely lacking at first, and only appeared later in the patient reported 
by me as having marked fatty stools. In the cases of Ramey and Keller- 
mann, in which the head of the pancreas was considerably enlarged and 
hardened, no trace of yellow color was found in the skin. The retention 
of the bile is associated with all its consequences, as acholic, silver- 
colored stools, itching, slow pulse, weariness, bile pigment in the urine, 
and xanthopsia. 

In a later stage of the process the jaundice may be due to compression 
of the bile-ducts by the development of metastatic nodules in the liver, and 
thus jaundice may occur, even when the primary seat of the cancer is not 
in the head, but in the tail of the pancreas. 

The liver and gall-bladder are altered in connection with the stagna- 
tion of bile. These alterations, according to many writers, have especial 
peculiarities by which pancreatic carcinoma is said to be characterized. 

Bard and Pic state their experiences as follows: ‘‘The liver, as a rule, 
is hard, the edges are frequently sharp, but the organ is always small or at 
least but slightly enlarged. It is generally only slightly painful on pres- 
sure, except in the neighborhood of the tumor caused by the enlarged 
gall-bladder. The pain and tenderness associated with the condition are 
commonly most intense in the epigastrium. The liver has never been 
found hypertrophied, hard, and mammillated, as is so frequently the case 
in cancer of the digestive tract. These negative qualities form the most 
important characteristics of the disease, and do not depend on the absence 
of metastases in the liver; on the contrary, generalization of the cancer 
in the liver is almost an absolute rule. Although the liver is not enlarged 
in consequence, it is because metastatic cancer of the liver secondary to 
cancer of the pancreas is quite different from primary cancer of the liver 
secondary to cancer of the digestive tract. In the former case the 
secondary nodules are small, not elevated above the surface, and do not 
increase essentially the size of the liver.” 

These conclusions were reached by Bard and Pic on the basis of seven 
cases, but surely cannot be regarded as the general rule. It is first to be. 
mentioned that in the cases communicated by Bard and Pic there are 
some in which there is considerable enlargement of the liver. In Case 1 


CARCINOMA. 159 


the liver overlapped the false ribs about 8 cm. To be sure, two months © 
later, at the autopsy, it was not found enlarged. In Case 3 the liver over- 
lapped the false ribs about four finger-breadths. At the autopsy, per- 
formed one and a half months later, the liver was not enlarged. In Case 
5 the liver was enlarged even after death. Enlargement of the liver with 
and without metastases in it is not infrequent. Mirallié found enlarge- 
ment of the liver in 17 cases. Besides these, hepatic enlargement with 
metastases is mentioned in the cases of I'riedreich, Biach, Bohn, Marag- 
liano, Kellermann, Munkenbeck, Reinhardt, Aigner, and Bandelier; and 
without metastases in those of .Rankin and of Dieckhoff (two cases). 
Enlargement of the liver without any statement of the presence or ab- 
sence of metastases is mentioned by Miller, Rufus Hall, and Reclus. Be- 
fore the Société anatomique, 1887, Moutard-Martin demonstrated a liver 
the lower edge of which extended beyond the umbilicus; Chopin and Molle 
also refer to hypertrophic liver. In the two cases of Cochez the liver was 
enlarged and hypertrophic without secondary nodules. The liver was 
enlarged in two of my patients with jaundice. In a number of cases an 
enlargement first exists, but later the volume becomes diminished even 
below the normal size. In the case of Mirallié the liver was at first mark- 
edly hypertrophic, the lower border was smooth and sharp and extended 
to the level of the umbilicus; two and a half months later the lower border 
could be felt three finger-breadths below the false ribs, and two months 
afterward, hence five months after the first examination, the liver ex- 
tended scarcely below the false ribs and it was difficult to feel the lower 
edge. According to Mirallié and Cochez, therefore, there are two stages 
to be discriminated: the first that of enlargement of the liver, the second 
that of diminution in size, atrophy, analogous to the course of biliary 
cirrhosis. The size of the liver, therefore, will depend on the duration of 
the changes in it. If they have lasted but a short time, the liver will be 
enlarged; if hepatic cirrhosis has had time to develop, a more or less 
pronounced atrophy will be present. 

Even this wholly plausible explanation will not fit all cases. When 
metastases form, the liver may be enlarged even at the terminal stage, and 
even when the process has lasted a long time, especially since the small 
nodules regarded by Bard and Pic as characteristic are not always present. 
Nodules as large as those in metastatic cancer of the liver may occur when 
the primary tumor is not seated in the pancreas. 

Several medullary nodules of secondary cancer as large as a walnut 
were found within the liver in Friedreich’s second case. In the case re- 
ported by Kellermann the liver contained nodules of various size, one as 
large as an apple being found on the anterior surface of the right lobe. It 
certainly must be granted that small nodules only are found much more 
frequently. This may be due to the generally rapid course of pancreatic 
cancer. 

It is true that in a number of cases, in spite of the presence of jaundice, 
the liver was not only not enlarged, but was stated to have been normal 
or even diminished in size. Suckling and Wesener, for instance, found it 
small in spite of intense jaundice. In the cases of Drozda, Klemperer, 
and Stiller, the liver did not exceed the normal limits. Such statements 
are often made. ; 

It is therefore to be stated that there is no characteristic outline of the 
liver in all cases of cancer of the pancreas, but the liver frequently shows 
such changes as are caused by the gradually advancing closure of the bile- 


160 NEOPLASMS. 


duct and the resulting biliary cirrhosis, as well as those resulting from the 
development in it of secondary nodules. In a large number of cases a 
_ scanty secretion of bile and early atrophy are caused by the rapid occur- 
rence of cachexia and extreme anemia, and the liver assumes such a shape 
as rarely takes place in chronic jaundice produced by gradual closure of 
the common duct from other causes. The diagnostic importance of this 
factor will be considered later more in detail. 

The gall-bladder is almost always distended, and under favorable con- 
ditions is to be felt as a sensitive pear-shaped tumor, smooth, soft, or 
tense and at times fluctuating, usually displaceable with the respiratory 
movements, situated on the outer edge of the right rectus, either toward 
the middle or more toward the side, often reaching to or below the level 
of the navel. The gall-bladder may be grasped, at times drawn forward 
and pushed laterally, and its relation to the liver above can rarely be 
determined. The reason why no mention is made of an enlarged gall- 
bladder in many of the cases reported is probably due to the fact that 
the examination was not sufficiently exact or that the enlargement could 
not be determined during life. In the case of Reclus the gall-bladder 
could not be palpated; but at the time of the operation it was found to 
be twice the size of the fist. 

A special diagnostic value in distinguishing between pancreatic cancer 
and calculus in the common duct was ascribed by Courvoisier and later 
Terrier to this enlargement of the gall-bladder, to which Battersby, and 
especially Bard and Pic, had previously called attention. The calculus 
in the duct usually causes atrophy and shrinkage of the gall-bladder. 
Hanot explains this relation by the infection of the bile-passages so often 
present in the formation of calculi. The micro-organisms cause an in- 
flammation of the wall of the gall-bladder with formation of fibrous tissue, 
the retraction of which diminishes the size of the gall-bladder. In pan- 
creatic cancer, on the other hand, such an infection rarely occurs, and 
therefore the mechanical distention of the gall-bladder is not prevented. 

It should further be mentioned that the gall-bladder may also be nor- 
mal or contracted in pancreatic cancer, and that a distended gall-bladder 
may be found when there is an impacted calculus in the common duct in 
case of obturation of the ductus choledochus by stone. The gall-bladder 
was not enlarged in the cases of Choupin and Molle, Moncorge and Keller- 
mann. Cochez found a shrunken gall-bladder in two cases, and thinks 
that its condition depends upon the seat of the obstruction. The frequent 
atrophic condition resulting from obstruction by impacted calculi is due 
to the injuries, producing stenosis of the canal, following the passage of 
the calculus from the hepatic and cystic ducts into the common duct. On 
the other hand, the obstruction in pancreatic carcinoma is situated in the 
head of the pancreas, and the reservoir can distend at pleasure. If, on the 
contrary, the cystic or hepatic duct is compressed by the cancer or degen- 
erated glands, an atrophy of the gall-bladder will result. 

Distention of the gall-bladder is not infrequently found in cases with 
calculi in the common duct, even when there is not a combination with 
cancer of the pancreas. In the course of a year I had two such cases in 
the hospital. Cholecystotomy was performed on both; in one concre- 
tions were found in the distended gall-bladder; in the other there was 
empyema of the gall-bladder. The concretions in the ductus choledochus 
were found at the autopsy. 

It can be stated merely that when chronic jaundice is due to cancer of 


s 


CARCINOMA. 161 


the panereas, as a rule, the gall-bladder is distended, but it may also be 
shrunken. 

[R. C. Cabot * recently reports the data derived from 30 autopsies and 
56 operations. Of the 86 cases, 57 were of obstructing gall-stone in the 
common duct and 29 were of obstruction from other causes, almost in- 
variably from cancer of the pancreas. In but two of the 57 cases of 
calculus was the gall-bladder distended; while in the 29 cases, the gall- 
bladder was distended in all but two.—Eb.] 

A tumor may be felt when the alterations of the pancreas have reached 
a certain degree. This possibility is relatively rare because the pancreas 
lies concealed behind the left lobe of the liver and the stomach. In about 
one-fourth or one-fifth of the cases it is said to be possible to feel the tumor 
or at least a distinct resistance. It is then a question whether the dis- 
tended gall-bladder has not been confounded with the tumor. The 
difficulty is appreciable if the relations are recalled which at times are to be 
observed in operations for calculi. Even when the abdomen is opened, an 
impacted stone in the common duct is found with difficulty by the pal- 
pating finger, and sometimes is first discovered at the autopsy. 

The tumor must have reached a certain size to be surely felt, not only 
on account of its deep situation, but also on account of the frequent ex- 
treme tenderness. In a later stage, when ascites is present, the palpation 
is still more difficult or impossible. 

The tumor is smooth or rough, nodulated, spherical, rarely sharply 
limited, and is situated, when the head of the pancreas is involved, to the 
right of the spine at or somewhat below the region of the pylorus. In 
the case observed by me the tumor was the size of a nut, nearly round, 
and was prominent. As arule, there is no mobility, but there are cases in 
which the tumor can be displaced (Stein, v. Hauff, Klemperer). In the 
last case there was movement on respiration, while in mine the tumor was 
fixed and did not move with respiration. 

The tumor does not, as a rule, appear to the palpating finger as large 
as it actually is. Every surgeon knows how easily one is deceived in esti- 
mating the size of an abdominal tumor. An extensive tumor will often be 
felt only as an ill-defined resistance. The possible differences in size were 
earlier mentioned. The tumor may show pulsation, transmitted from the 
aorta (Andral, Battersby, Teissier, Labadie-Lagrave, Charlton-Bastian). 
This pulsation at times causes the growth to be confounded with aortic 
aneurysm. | 

In a number of cases it may be possible to feel two tumors, the dis- 
tended gall-bladder and the pancreatic cancer. Jrerichs describes a case 
with closure of the ductus choledochus and intense jaundice, in which 
during life he made the correct diagnosis of pancreatic cancer. He found 
_a hard, uneven, immovable, deep-seated tumor to the left of and some- 
what higher than the distended gall-bladder, which also was palpable. 

Symptoms may arise in consequence of the modification of function 
of the neighboring organs due to the pressure of the tumor on them. 
Pressure on the pylorus and on the common duct causes symptoms of 
gastric dilatation and jaundice. Through pressure on the intestine, mete- 
orism may develop in the portions-situated in the upper part of the abdo- 
men; obstruction and fecal vomiting may develop. 

Ascites may result from pressure on the portal vein, and progresses 
continuously and reappears quickly after puncture. It has nothing char- 


* Medical News, 1901. 
11 


162 NEOPLASMS. © 


acteristic and runs its course like the ascites of cirrhosis of the liver. The 
ascitic fluid is serous and only rarely contains chyle. Flavio Santi has 
reported two such cases. | 

The ascites may originate from the development of metastatic nodules 
in the peritoneum. The swelling of the spleen which sometimes occurs, 
and the hemorrhoids also, may be referred to compression of the portal 
vein. Pressure on the vena cava leads to edema of the lower extremities. 
Pressure on a ureter may lead to hydronephrosis (Recamier). Cachexia 
is one of the most essential and constant features, and is dependent upon 
the rapid and continuously diminishing nutrition, emaciation, and asso- 
ciated feeling of great fatigue and debility. 

In rare cases the nutrition remains good for a long time, as happened 
in the cases of Frerichs, Caron, Macaigne, and Mirallié, in which emacia- 
tion occurred late, but ‘then rapidly led to exhaustion. As a rule, the 
cachexia is prominent and occasionally appears more intense than would 
be expected from the other symptoms. Indeed, it may at times be the 
only abnormality pointing to severe disease of the pancreas, aside from 
ill-defined disturbances of digestion and more or less pronounced epi- 
gastric pain. Many authors consider the cachexia caused by pancreatic 
cancer as especially characteristic of that disease, particularly because of 
its rapid course and great intensity, which exceeds that caused by 
cancer elsewhere. They assume that the peculiarity of the severe 
cachexia is due, not simply to the cancer, but also to the absorption of 
pancreatic juice. 

Whatever one thinks of the cause of the cachexia in pancreatic cancer 
it may be regarded as fairly established by the testimony of many esteemed 
authors that the cachexia in this disease as a rule develops much more 
quickly and with greater intensity than in other cancerous affections 
in the upper abdomen. One peculiarity especially is frequently pro- 
nounced and manifest in the cachexia caused by pancreatic cancer— 
namely, the great weakness and prostration, which cannot be explained 
by the inanition alone. There are conditions of debility with attacks of 
fainting, or at least tendency to fainting. The sensation of weakness 
may be too great for words, and in consequence the patient avoids expres- 
sions of suffering, because it is worse to bear than the violent pains. The 
patients lie quiet and apathetic, and consequently present such a picture 
of disease as is much more rarely met in other degenerative processes in the 
abdomen. 

The above group of symptoms is absent in many cases and cachexia, 
emaciation, and debility are dependent upon faulty nutrition or dis- 
turbed digestion. 

The examination of the urine may give weighty and sanoataut evi- 
dence. The amount of urine may be decidedly increased, and some 
authors mention polyuria, without the presence of sugar (Kappeller, — 
Moutard-Martin). 

Albumin occurs very frequently. (Bard and Pic, 4 cases; Bruzelius, 
Choupin and Molle, Dreyfus, Drozda, Kellermann, Kihn, Krieger, Klem- 
perer, Musmeci, Rankin, etc.) Kobler mentions peptonuria. The pres- 
ence of sugar in the urine is very important. Mirallié showed that in 50 
cases sugar was found 13 times (v. Ackeren, Bouchard, Choupin and 
Molle, Collier, Frerichs, Lancereaux, Macaigne, Marston, Mirallié, Mus- 


~ meci, Santi, Servaes, Suckling). Besides these cases, sugar was dem- 


onstrated in the urine by Bright, Courmont and Bret, Dieckhoff, Dresch- 





CARCINOMA. 163 


feld, Duffey, Fothergill, Galvagni, Kesteren and Massing.* Alimentary 
glycosuria was found by Parisot and Dutil. 

Mirallié thinks that sugar would be more frequently found if the ex- 
amination were earlier made. He supports this view by the fact that in a 
number of cases (those of Marston, Frerichs, Collier, Macaigne, Mirallié) 
sugar was certainly found, but disappeared a longer or shorter time before 
death. In the case of Courmont and Bret also the sugar disappeared with 
the progress of jaundice. In Kesteren’s case it occurred only temporarily, 
and disappeared on a diabetic diet. Mirallié found that in the 35 cases in 
which there was no sugar, the examination was made just before death, 
and if the examination had been made earlier, sugar possibly might have 
been found, as in the above mentioned five cases. This assumption of 
Mirallié can be proved only by further observations. It is probable that 
mention would have been made by the patient of other symptoms of dia- 
betes, as polyuria or polydipsia, and would have led the physician to make 
earlier an examination of the urine or would have been referred to in the 
history of the case. 

Many cases of cancer of the pancreas doubtless run their course with- 
out sugar in the urine, and even when the pancreas is completely destroyed 
no sugar has been found, as in the cases of Ewald, Hansemann, Litten, 
Ziehl. 

The separation of the course of pancreatic cancer into two stages, 
one with and one without sugar in the urine, as attempted by Mirallié, is 
not justified by the facts known at present. 

Fat, in rare cases, has been found in the urine. To the best of my 
knowledge, the earlier observations of Clark and Bowditch are the only 
ones reported. As a rule, the urine presents no other deviation from the 
normal than that due to the small amount of food and the poor nutrition 
in general. The amount of urea is diminished. According to the state- 
ment of Mirallié, we have the following data: Arnozan found 12 gm. 
daily; Lancereaux, 12 to 20 gm.; Dreyfus, 13 gm.; Bard and Pic, 17 and 6 
gm.; Moutard and Martin, 7 to 15 gm.; Terrier, 14 to 18 gm.; Saguet- 
Lucron, 7, 15, and 14 gm.; Le Gendre, 6 to 8 gm.; Bret, 14 gm.; Mus- 
meci, 2 to 15 gm.; Klemperer, 9 to 10 gm.; Caron, 2 to 20 gm.; Mirallié, 

4 om. 

; According to Sahli, the urine in pancreatic cancer shows the loss of 
another function of the pancreas. As is well known, salol is broken up in 
the intestine into salicylic acid and phenol. This cleavage is said to be 
brought about by the pancreatic juice, and is therefore absent in cancer 
of the pancreas. According to Mirallié, two examinations have been 
made with reference to this point. Lucron found the cleavage of salol 
normal and De Hue found none. 

Fever is one of the rarest symptoms. The temperature usually is 
normal or subnormal, corresponding to the cachexia. If fever is present, 
it depends, in the first instance, on complications, as infectious cholangitis 
with pus in the liver as observed in a case in the Rothschild Hospital, or 
peritonitis or the development of metastases in the lungs, pleure, etc. It 
may also occur that fever is associated with the development of the 
tumor. In Kobler’s case the fever is directly attributed to the tumor. 

Bard and Pic lay especial stress upon subnormal temperature. The 
hypothermia at the end may, they say, be worse in certain cases on ac- 


* Two such observations are said to have been reported by Bouchardat and 
Martsen in the theses of Lapierre and Giorgi; these theses were not accessible. 


164 NEOPLASMS. 


count of abundant, numerous hemorrhages; but in the majority of cases 
it cannot be explained by any complication. The deep collapse with 
considerable fall of temperature below the normal is frequently found 
in the terminal stage of pancreatic cancer; it follows a long period of low 
temperature and seems to depend directly upon the lesion of the pancreas. 
In the cases observed by me the temperature was normal except in one in 
which there was elevation of temperature combined with chill in conse- 
quence of suppurative hepatitis. 

Certain alterations of the skin may occur rarely; bronzed color, as in 
Addison’s disease, is now and then mentioned (Jaccoud), also the hemor- 
rhages, as in purpura and metastatic nodules in the skin. Various symp- 
toms may occur as a result of metastatic processes in various organs, but 
their consideration is not now fitting. Mention should bé made of glan- 
dular swellings, especially of the occasional occurrence of such in the 
supraclavicular glands, because this has led to a diagnosis in many cases. 


DIAGNOSIS. 


The cardinal symptoms, which may lead to the correct diagnosis, are 
the following: jaundice with its consequences in the liver and gall-bladder, 
tumor, pain, cachexia, emaciation, and the chemical disturbances which 
are caused by the loss or alteration of the pancreatic function, and which 
are manifest in the urine or feces. 

Jaundice and tumor are the most prominent of the above symptoms. 
When both of these are absent, it is probably impossible to make a correct 
diagnosis. However pronounced are pain and cachexia, no inference can 
be drawn from them. Diabetes and fatty stools are such rare symptoms 
in cancer of the pancreas that when present, some other disease of the 
pancreas is first to be thought of, unless there is also jaundice or a pal- 
pable tumor in the region of the pancreas. 

Jaundice and tumor, therefore, are the most important signs in 
diagnosis, and it will be considered under what conditions these two fac- 
tors may become so characteristic that the diagnosis can be established 
with certainty or probability. Jaundice in pancreatic cancer usually has 
definite characteristics. It is chronic, as a rule develops gradually, 
rarely abruptly, commonly advances steadily, never diminishes or disap- 
pears, but may appear to fade shortly before death. 

It is clear that jaundice, with these characteristics, must always be 
present when the retention is one which develops gradually and when the 
stenosis increases gradually to complete closure. This type of jaundice, 
therefore, must always be found in all cases of gradually increasing com- 
pression of the common duct, as from tumors of the duodenum or pylorus, 
tumors or swollen lymph-glands in the portal fissure, or the head of the 
pancreas, either inflamed or containing a gumma. A similar form of 
jaundice may be caused by flexure of the common duct or by slowly con- 
tracting adhesions. Jaundice may slowly develop without appreciable 
remission in consequence of concretions which at first merely narrow 
the common bile-duct, but later, from further additions, completely ob- 
struct it. 

It may be very difficult or even impossible to distinguish between 
these different causes. The question most frequently arises whether the 
persistent jaundice is caused by a stone in the common duct or by a cancer 
in'the pancreas. As a rule, in cancer it develops gradually; suddenly in 


oe eee 


CARCINOMA. 165 


calculus. The exceptions already have been mentioned that a gradual 
development is possible with impacted calculi and a sudden development 
in cancer of the head of the pancreas. When a stone is in the common 
duct, the liver is more frequently large and the gall-bladder small; in 
pancreatic cancer the liver is more frequently of normal size or only 
slightly enlarged, while the gall-bladder is much distended. We have 
seen, however, a large liver in a considerable number of cases of cancer of 
the pancreas, and not simply from metastases; on the other hand, we 


_know that in closure of the common duct by concretions there may be a 


stage in which the liver is atrophied and small, and that often in an early 
period of cholelithiasis there is only a moderate enlargement of the liver. 
It is probably true that the gall-bladder is enlarged in most. cases of cancer 
of the pancreas, but there are frequent exceptions, and one finds at times 
a shriveled gall-bladder. It may happen also that on the most careful 
examination the enlarged gall-bladder cannot be felt. On the other hand, 
it is not so rare that the gall-bladder is enlarged from a calculus in the 
common duct. In such cases a decision is reached by the evidence of a 
preceding colic or pronounced cachexia. The diagnosis is frequently 
first established at the operation. The most difficult question, and often 
impossible to answer, is whether the cancer of the head of the pancreas or 
of a neighboring organ causes the jaundice. According to Bard and Pie, 
a large liver and a slowly developing cachexia indicate degeneration of 
the neighboring organs; a normal or only slightly enlarged liver and a 
rapid cachexia indicate cancer of the pancreas. It has been stated, how- 
ever, that a large liver and not infrequently a slowly developing cachexia . 
occur in cancer of the pancreas. On the other hand, it is to be assumed 
that even in an early stage of the degeneration of the organs near the pan- 
creas only small metastatic nodules are to be found in the liver. 

The second cardinal symptom, the tumor, is demonstrable in only a 
small number of cases, about one-fifth to one-fourth, and in most cases. . 
it will be doubtful whether the object felt is really the degenerated pan- 
creas. Surgical experience shows clearest what difficulties may be encount- 
ered. Inflammatory swellings of the pancreas, as Riedel has recently 
stated and illustrated by some very instructive cases, may appear to the 
palpating finger of “‘iron-like density,’’ even when the abdominal cavity is 
open, and only the subsequent course of the disease shows that there was 
no cancer. The differential diagnosis between inflammatory and cancer- 
ous tumors of the head of the pancreas, says Riedel, ‘‘is almost impossible 
at the operation, if there is no ascites.”’ The inflammatory pancreatic 
tumor is just as hard as cancer, and the jaundice in the two cases may be 
equally severe. In a long duration of the affection experience teaches 
that ‘the cancer will always lead to ascites, while the inflammatory affec- 
tion will not.” ' 

Cancer of the duodenum, common duct, or portal fissure, lymph-gland 
tumors, aneurysms of the hepatic artery, products of chronic inflamma- 
tion of a tuberculous nature, even cancers of the colon and pylorus, may 


here give rise to confusion. | 


By palpation alone, without reference to the other clinical symptoms, 
it is generally impossible to form a.correct opinion. In the case repeat- 
edly mentioned by me, in which there was a deep circumscribed resistance 
in the region of the head of the pancreas and the stomach was apparently 
normal, I should not have ventured to make a diagnosis of carcinoma of 
the pancreas if fatty stools had not been present. 


166 NEOPLASMS. 


The distinction between tumors of the pancreas and cancer of the pylo- 
rus or colon is usually based upon the fixation of the first and mobility of 
the last. In doubtful cases the diagnosis can be made positive by dis- 
tending the stomach and colon, by the chemical and microscopic examina- 
tion of the contents of the stomach and intestine, the demonstration of 
symptoms characteristic of stenosis attributable to constriction of the 
pylorus or colon, as well as by other clinical signs which indicate either a 
disease of the stomach or intestine or an affection of the pancreas. These 
methods of investigation also fail when, as is not rarely the case, the cancer 
of the pancreas extends to the neighboring organs or compresses them. 

It is much more difficult and often impossible to discriminate tumors 
of the pancreas from tumors arising in the duodenum or extra-hepatic 
biliary passages. The tumors which narrow the canal of the duodenum 
above the papilla of Vater, and which, as a rule, pursue the course of the 
cancer of the pylorus, as also those producing constriction below the 
papilla, may under favorable circumstances be distinguished from 
tumors of the pancreas, provided the latter do not narrow the duo- 
denal canal, by certain characteristic signs. These have clearly been 
presented by Nothnagel in the volumes on “ Diseases of the Intestines 
and Peritoneum”’ and ‘ Diseases of the Stomach.” 

The diagnosis of tumors of the duodenum which do not cause stenosis 
and cancers of the ampulla, on the contrary, frequently cannot be made. 
It has already been shown that the microscopic examination may leave it 
doubtful whether the cancer is of the pancreas or duodenum. How, then, 
. ean clinical methods make the diagnosis clear? 

The suggestions made by: Bard and Pic for differential diagnosis will 
again be mentioned. The cachexia may show peculiarities which are of 
diagnostic value. Its development is not infrequently as rapid as it is 
intense, a cachexia preecox, such as rarely occurs in other cancers. It is 
known how slowly the cachexia usually develops in mammary, uterine, 
and even in in| carcinomata. On the contrary, in cancer of the pan- 
creas it is early pronounced. The great weakness with tendency to 
fainting, the uncomfortable sensations, the extreme prostration, are essen- 
tial symptoms, often striking and of importance in diagnosis because they 
are rarely seen in such severity in cancers proceeding from other parts of 
the digestive apparatus. There are, however, cases in which the cachexia 
develops but slowly, and depends only on the poor absorption of food. 
This is best shown by the cases in which after cholecystenterostomy a 
prolonged improvement takes place with increased appetite, weight, and 
ability to work, as in the cases of Kappeler, Reclus, and others. 

It has already been mentioned that the pains in pancreatic cancer are, 
as a rule, more intense than in other tumors of the upper abdomen; that 
they may be peculiar not merely on account of their intensity, but also on 
account of their characteristics and the feeling of distress which accom- 
panies them, perhaps the result of a combination of intense pain and a 
high degree of prostration. These characteristics are less frequent in 
cancers of the duodenum, pylorus, liver, gall-bladder, and common duct 
than in cancers of the pancreas, and the cause may lie in pressure on the 
solar plexus or its involvement in the pathologic conditions. This celiac 
neuralgia differs in quality and quantity from the other varieties of pain 
in the upper abdomen, and although pain cannot be measured or weighed, 
and the individual sensitiveness of the patient of course plays the first 
part, yet the objective impression which this pain at times makes on the 


CARCINOMA. 167 


observer is so pregnant that it may, in connection with the other cardinal 
symptoms, establish the diagnosis. It is never safe to make a definite 
diagnosis from the character of the pain alone, because pancreatic pains, 
however caused, appear alike, and because, in spite of all that has been 
said, it is impossible to give a sharply defined, readily understood presen- 
tation of so-called ‘‘celiac neuralgia.” 

It has already been mentioned that cancer of the pancreas may run its 
course with little or no pain, and that the suffering described and attri- 
butable to the special involvement of the celiac ganglion not infrequently 
is entirely absent. 

The disturbances of digestion among the remaining symptoms are 
usually not characteristic. Even if a part of the pancreas is degenerated, 
and the whole or a large part of it is diseased, the loss of pancreatic func- 
tion is not striking, because other organs may vicariously assume its work. 
The results of the examination of the stools and urine are of diagnostic 
value, especially in connection with all, or at least a number of, the cardi- 
nal symptoms, only when fatty stools occur, particularly in the absence 
of jaundice, and when the digestion of proteids is notably poor or when 
diabetes is present. Unfortunately, the loss of function of the pancreas 
causes no symptoms in far the greater number of cases of pancreatic can- 
cer, and, therefore, is only exceptionally to be considered of value in con- 
nection with the diagnosis. 

In the absence of jaundice the diagnosis will rarely be correctly 
made. If there is no tumor to be demonstrated, and no definite indica- 
tions, as fatty stools or diabetes, call attention to the pancreas, no conclu- 
sions are to be drawn from the cachexia, however rapidly it may develop, 
‘even with such pancreatic characteristics” as the severe prostration and 
extreme degree of debility mentioned by French authors, or from the 
pains, although so peculiar as to lie within the obscure boundaries of 
celiac neuralgia. 

The concurrence of jaundice slowly proceeding but always advancing, 
generally associated with a large gall-bladder and frequently with a liver 
of normal size or only slightly enlarged, the distinct, slowly growing 
tumor in the region of the head of the pancreas, the rapidly developing 
cachexia, the peculiar severe pains, combined with marked feelings of 
weakness, and, in addition, such alterations of the feces and urine as the 
occurrence of fatty stools, of moderate passages of undigested muscle- 
fibers, or distinct diabetes, give so striking a picture that they justify a 
positive diagnosis of cancer of the pancreas. All these symptoms, how- 
ever, rarely occur together. The tumor is lacking in about one-fourth of 
the cases; fatty stools, disturbed proteid digestion, and diabetes are rela- 
tively rare; and, accordingly, the certainty of the diagnosis is essentially 
narrowed. 

The deep, chronic, progressive jaundice with extreme dilatation of the 
gall-bladder, the rapidly developing emaciation and cachexia with usually 
subnormal temperature, and the lack of any marked enlargement of the 
liver, form a group of symptoms which, according to Bard and Pic, if 
rightly understood and at the right time, make the diagnosis of cancer of 
the pancreas as easy and certain_as, for instance, the diagnosis of cancer 
of the stomach. These writers assert that cancer of the pancreas can only 
be confounded with certain manifestations of cholelithiasis or with cancer 
of the neighboring organs—namely, primary cancer of the liver and bile- 
passages, and of the stomach and duodenum with generalization in the 


168 NEOPLASMS. 


liver. In rare instances cholelithiasis presents the above-mentioned 
group of symptoms. If there is a stone in the common duct, the jaundice 
has not the gradually increasing and progressive character, the dilatation 
of the gall-bladder is neither so frequent nor so marked, and the general 
condition never shows that rapid change which is peculiar to ‘“ pancreatic 
cachexia.’ In addition, the temperature is low, as Bard and Pic found 
6 times in 7 cases, while in cholelithiasis there was usually fever. In can- 
cer of the liver the jaundice is frequently lacking or not so intense, the 
liver is always enlarged and painful, and ascites almost constantly de- 
velops. Cancer of the bile-passages is much rarer and the course not so 
rapid, and it is always combined with enlargement of the liver. When 
metastases occur in the liver in consequence of primary cancer of the 
digestive tract, jaundice does not develop until late, and secondary 
nodules form in the liver and rapidly increase in size. In cancer of the 
ampulla the course is much slower, the secondary nodules in the liver 
much larger, and therefore this organ is always enlarged. 

Although these statements contain much that is true, there are many 
objections that may be raised. In the first place, it is very questionable 
whether the group of symptoms is of such frequency as believed by Bard 
and Pic, and permit in the “immense majority” of cases the diagnosis of 
cancer of the pancreas to be easily and safely made. There is no jaundice 
in about a fourth of the cases, and it is difficult to show from the statistics 
at hand whether it is present in the majority of the remaining three- 
fourths. 

It is obvious that the liver is frequently enlarged, that the gall-bladder 
is at times not. distended, and that the cachexia may develop slowly even 
in pronounced cases of cancer of the pancreas. This group of symptoms 
occurred in none of the three absolutely demonstrated cases of caneer of 
the head of the pancreas under my observation. There was no jaundice 
in the first case, it appeared late in the second, and in the third the condi- 
tion seemed to be one of infectious cholangitis with abscess of the liver. 
The pathologic picture of the disease presented by Bard and Pic did not 
occur in the patient referred to by me (page 113), in whom the diagnosis 
of cancer of the pancreas was established only with great probability. In 
another case in which I suspected cancer of the pancreas on account of the 
marked jaundice, rapidly developing cachexia, and intense, peculiar pains, 
a cancer of the common duct extending to the duodenum was found at 
the autopsy. The liver scarcely reached beyond the border of the ribs 
and the gall-bladder was about the size of a goose-egg. A chronic, slowly 
developing Jaundice without being preceded by colic may certainly, even 
if only exceptionally, occur in the case of calculi which are incarcerated 
in the common duct and gradually increase in size; the gall-bladder may 
appear distended, the liver, on account of the cirrhosis, be not especially 
enlarged, and a certain degree of cachexia may develop, which is difficult 
to separate from the ‘‘ cachexie pancreatique.”’ 

On the other hand, a cancer of the pancreas doubtless may assume the 
characteristics of cholelithiasis : that is, after the sudden occurrence of 
jaundice it may pursue a slow course with gradually occurring cachexia 
and violent paroxysmal pains which resemble biliary cramps, especially 
when pancreatic colic arises from closure of the duct of Wirsung. Chole- 
cystenterostomy undertaken repeatedly with the idea that stones are pres- 
ent offers a proof. In such cases after a successful operation there has 
often taken place a more or less persistent improvement in the condition 


. 





CARCINOMA. | 169 


and in the nutrition, only to be explained by the assumption that the 
cachexia has become relieved for the time being, and to a certain extent 
by the removal of the harmful effects of the jaundice. 

The discrimination between cancer of the pancreas and that of the 
adjacent organs, especially of the duodenum and bile-passages, will always 
be difficult, since the size of the metastases in the liver and the nature of 
the progress, regarded by Bard and Pic as of diagnostic value, are very 
irregular. There is certainly a period in each process when there are no 
metastases, and, therefore, no means of differentiation. 

Relative frequency alone can be utilized in differential diagnosis. 
Cancer of the small intestine, on the whole, is rarer than cancer of the pan- 
creas, more frequently and earlier causes duodenal stenosis, but less often 
a rapidly advancing cachexia. The grouping of symptoms presented by 
Bard and Pic occurs without doubt in a number of cases of cancer of the 
pancreas, and it, therefore, will be possible, although by no means certain, 
to make the diagnosis of pancreatic cancer with some degree of probability 
because a similar grouping of symptoms rarely occurs in other diseases 
which might be confounded, and because many of them, as cancer of the 
duodenum and portal fissure, are, on the whole, more infrequent. 

If there is a tumor in the region of the pancreas and the stools and 
urine present the alterations previously mentioned, and if there is also 
some ascites, there can be no doubt about the diagnosis. 

Primary cancer of the pancreas gives a complicated picture of disease. 
Various combinations of the cardinal symptoms occur, some of which are 
attributable to severe diseases of the neighboring organs and depend upon 
the location, kind, size, stage of development, disturbances of function, 
whether local or produced in neighboring organs, the complications, and 
other circumstances, perhaps unknown, which cause either a rapid or a 
slowly progressing disturbance of nutrition. The possibility or impossi- 
bility of the diagnosis depends on the various combinations, some of which 
make the diagnosis easy and safe. Such cases, however, are rare, and a 
positive diagnosis is hardly possible without a demonstrable tumor and 
pancreatic symptoms. 

In a second series of cases the diagnosis is only more or less probable. 
Most of the diagnoses hitherto correctly made belong to this class, includ- 
ing those based on the “Bard-Pie group of symptoms.” Even in this 
series of cases the proof of a tumor will essentially raise the degree of prob- 
ability. The differentiation between cancer of the pancreas, duodenum, 
and bile-duct must always be made only with a certain degree of proba- 
bility. 

A tumor near the head of the pancreas, intense jaundice, slightly en- 
larged liver, large gall-bladder, a certain degree of cachexia, and even 
pancreatic symptoms may occur without cancer and be due to a stone in 
the common duct with induration of the head of the pancreas. Even 
laparotomy in such cases as observed by Riedel may not enable the de- 
cision to be made between cancer and induration. | 

In the majority of cases the diagnosis is impossible, unless suspecting 
and guessing are confounded with knowledge. It may be stated as prob- 
ably certain that a positive diagnosis, as a rule, is only made very late in 
the course of the disease. Even if the views of Bard and Pic are accepted, 
the small secondary nodules in the liver which form an essential feature 
do not appear until late. If cancer of the pancreas can be successfully 
operated upon,—and a few successful attempts have already been re- 


170 NEOPLASMS. 


ported,—the surgeons certainly will not be satisfied with a diagnosis 
made only after the occurrence of secondary nodules in the liver. 


DURATION, COURSE, AND PROGNOSIS. 


Since the nature of the early symptoms is wholly uncertain, the dura- 
tion of the disease is also indefinite. In some cases only two or three 
months elapsed from the appearance of the first symptoms to the time of 
death (Litten, Laborde). In other cases the disease is said to have lasted 
over two years (Molander and Blix, Crampton), and even, as Dieckhoff 
mentions, three or four years (Canfield, Bowditch, Battersby). Accord- 
ing to a collection of cases published by Da Costa, the duration of the dis- 
ease varied from two months to two years. A case under my observation 
(1880), in which purulent hepatitis caused death, lasted from the first 
symptoms to death, somewhat over fifty days; in two other cases rather 
more than a half year intervened. 

It is evident that the great variations in the duration of the disease 
depend on individual conditions, the quick or slow growth of the tumor, 
its histologic characteristics, the interference with the function of neigh- 
boring organs, complications, hemorrhages, etc. The average duration 
of the disease stated by many authors is given as six months, and coincides 
with the facts. 

In most cases death is at the end of a high degree of marasmus, but it 
may be sudden, as in the cases of Campbell, Huber, and Litten. The 
prognosis is unfavorable while surgery accomplishes so little. There have 
been but a few cases of neoplasm in the pancreas cured by operation. The 
hope of the physician unfortunately depends wholly upon a wrong diag- 
nosis. Recovery is possible only when the symptoms suggestive of a 
pancreatic cancer are due to a chronic interstitial pancreatitis, a gumma, 
or an impacted calculus in the common duct. 


TREATMENT. 


The medical treatment of cancer of the pancreas is merely symp- 
tomatic. The chief indications are the relief of pain by narcotics and 
the best possible nourishment, at first by the mouth, and, when this is. 
no longer possible, by means of nutrient enemata. The possible value 
of organotherapy has previously been stated. It will always be desirable 
to try some pancreatic preparation, which may improve the digestion 
of the food. The formula used by Boas is especially to be recommended 
for this purpose: 

kK. Pancreatin. 
IN REP NCAT DOWN oe arin tok eras geet aa 0.5 


M. f. pulv. comprim. 
S1a.—Two to four tablets to be used a quarter of an hour after meals. 


The jaundice and associated itching are to be treated merely as 
symptoms. If the obstruction is absolute, nothing, of course, can be 
accomplished by cholagogues. In an early stage it might, perhaps, be 
possible by increasing the pressure from behind or by diluting the bile 
to cause a temporary improvement. The most effective cholagogue— 
namely, the administration of mixed diet, largely of meat—is generally 
counterindicated by the marked anorexia, especially for meat. Sodium 
salicylate, 0.5 to 1.0 gm. several times a day, by the mouth or rectum, can 


CARCINOMA. eae a | 


be taken only for a short time, as the appetite lessens still more under 
its use. Of the other cholagogues which are recommended, the salts 
of the bile-acids in the form of the Fel tauri depuratum siceum (Naunyn) 
are to be mentioned. Little is to be expected of salol, euonymin, or 
podophyllin. Diuretics and the treatment of the skin are especially 
desirable to relieve the Jaundice and the annoying sequels connected 
with it. Some of the unpleasant features may be lessened by the use 
of mineral water, especially that containing an abundance of carbonic 
acid, and in large amounts, when there is no vomiting, for the flushing 
of the vascular system, or the administration of fluids by the rectum, 
when there is no diarrhea. 

Active sweating is contraindicated by the decided weakness. Diu- 
retics also, as diuretin or caffein, are probably of doubtful value. 

Itching of the skin, at times very troublesome, claims especial atten- 
tion, and must be treated as in other cases of chronic jaundice. The 
most effectual treatment consists in warm baths, especially when soda 
has been added in the proportion of + pound to the full bath, or in the 
form of bran baths. Unfortunately the application of the baths is often 
very difficult or impossible on account of the extreme weakness and 
severe pain, which cause the patient to shun anxiously every movement. 
Washing the skin with dilute vinegar, a teaspoonful, according to Leich- 
tenstern, to a liter of the decoction of bran of almonds, or weak carbolic 
acid solution 1% to 2% (to be avoided if there are excoriated spots), or 
rubbing with fresh lemon-peel, or spraying with 1% to 2% of salicyl- 
alcohol or 1% to 2% of menthol-alcohol is beneficial. 

Where the itching of the skin was very severe, Leichtenstern has 
used menthol (Menthol 5 to 10 gm., Spir. vini, A‘ther. 44 50.0 gm.) by 
means of the atomizer with temporary benefit. Spraying the skin with 
menthol gave decided relief. 


ec MODULO fay an Hae eo Ate eee a ance annals Tee 5.0 
Zinci oxydati 
Amyli 
DE ANCR Es Beatie et eae Aa arnt eave crane eR aa 
ad pully, quantitatemn... oc 3 fia voasok eos xe: 100.0 


Washing with hot water, often as hot as the patient can bear it, is 
frequently beneficial. The severe pain, when present, often requires the 
subcutaneous injection of morphin, and this remedy will give the most 
effectual relief to the itching. 

Radical treatment is to be hoped for only from an operation, and 
immediate prospect of such relief is very slight. Gussenbauer was the 
first to suggest this, at the time when he reported his operation upon a 
pancreatic cyst, in the following words: ‘‘I consider it possible that we 
shall be able in this way to operaté upon other tumors of the pancreas, 
when by larger experience and accurate study the suspected disease can 
be diagnosticated with certainty.” Senn, in 1888, expressed the opinion | 
that partial extirpation was possible under certain circumstances. The 
most favorable condition would be present when the tail of the gland 
is first affected, and the disease does not perforate the capsule. In such 
cases the excision of the splenic. end of the pancreas would present a 
prospect of permanent cure without endangering the digestive pro- 
cesses, “as still enough of the gland would remain in connection with the 
intestine to maintain pancreatic digestion.” 

Billroth in two cases partially resected the pancreas. In the one he 


172: NEOPLASMS. 


removed a portion of the head of the pancreas with cancer of the pylorus, 
in the other the tail was removed with a sarcoma of the spleen. Krén- 
lein, who recently has carefully studied this question, believes “that 
primary carcinoma of the head of the pancreas can be extirpated only ex- 
ceptionally and under the most favorable circumstances, especially when 
the tumor is a dense, circumscribed scirrhus, which is suspected by the 
demonstration of a palpable tumor in the region of the pancreas, but 
which causes the fewest possible symptoms referable to the bile-passages, 
the intestine, and the stomach. A positive diagnosis will, of course, be 
possible only after laparotomy has been performed and the tumor ex- 
posed. Primary cancer of the body and tail of the gland, especially of 
the latter, in general presents favorable conditions for extirpation, pro- 
vided the tumor is circumscribed and limited to the pancreas and is not 
adherent to the surrounding tissues.” 

The first successful operation on a pancreatic cancer was performed by 
Professor Ruggi in Bologna in 1889. The description of the case in 
brief is as follows: 


Woman fifty years old, frequent menstrual disturbances for the last fifteen years. 
Of late the distress more marked, tumor observed in the abdomen, use of baths of the 
salts of iodin ineffectual. 

Present condition: Abundant panniculus adiposus of the abdominal walls, some 
free fluid in the peritoneal cavity, two tumors in the abdomen, the lower a fibro- 
myoma uteri, and between them a distinct line of demarcation; the upper tumor is on 
the left side and extends from the left hypochondrium toward the umbilicus. The 
posterior limit corresponded to the extended mid-axillary line, the anterior to the 
extension of the parasternal line. The longer diameter was oblique and measured 
about 25cm. Surface smooth, hard, sensitive to pressure, tumor displaceable down- 
ward and forward, still more upward and backward, and disappears completely 
under the border of the ribs. In a half-sitting posture it reappears. Spleen, liver, 
kidney normal; in the urine nothing abnormal. Anorexia, nausea, poorly nourished. 
Profound melancholy. Retroperitoneal adenosarcoma arising from the kidney or 
pancreas suspected. 

Operation: Incision in the region of the left loin, across and somewhat obliquely 
downward and forward close under the border of the ribs; after the escape of the 
ascitic fluid the tumor drawn forward, small intestine clinging to it, great omentum 
adherent to the anterior surface. The tumor, which belongs to the pancreas, is quite 
diffuse and is as soft as brain. The intestine detached with blunt instruments, the 
omentum tied and separated, drainage, sutures in layers, healing in seven weeks. 
During convalescence good appetite, disappearance of melancholy. Patient wholly 
recovered. Tumor weighs 1 pound 7 ounces. The microscopic examination 
showed adenocarcinoma of the pancreas. 


Gade reports a second case of successful recovery. In a woman 
forty-nine years old a cancer as large as a child’s head in the tail of the 
pancreas was extirpated. There were no. metastases. The anatomic 
examination showed giant-celled cancer. According to Nimier, Terrier 
performed a still bolder operation, but with fatal result. 


Woman, fifty-one years old; for five years a gradual enlargement of the abdo- 
men, menopause one year ago, emaciation, loss of strength, disturbances of digestion. 

Present condition: Skin of abdomen traversed by subcutaneous network of 
veins, abdomen not symmetric, left side more prominent. In the umbilical region 
an irregular, three-lobed tumor, lying to the left; one lobe lost in the depths of the 
abdomen, the two upper tumors lie to the left and right. The tumor at the right is 
rounded below; that on the left is irregular below, shows a marked depression by 
which it can be grasped, and the consistency found to be greater than in other por- 
tions. The tumor on the right side fluctuates and is not movable from above down- 
ward, although slightly movable transversely. The whole tumor dull on percussion 
and is surrounded by a tympanitic zone. In the urine no albumin and no sugar; 
urea 26.50 gm. Specific gravity 1024. 

> 


CARCINOMA. 173 


December 3, 1892, operation: Incision in the median line. Tumor covered by 
omentum. This was cut through and a violet surface appeared, and fluctuation was 
apparent. Exploratory puncture negative. After enlargement of the incision the 
tumor was drawn forward, found to be three-lobed and without connection to the 
organs of the pelvis. Terrier believed the tumor to be mesenteric. Markedly dis- 
tended veins, especially in the right portion. After raising it from the peritoneal 
cavity, needles were inserted, elastic ligatures applied, the upper part cut off, thermo- 
cautery, marked hemorrhage, ligation of numerous veins. The separated mass 
weighed 53 pounds; pancreatic tissue on the surface of the pedicle, which was left 
outside; incision closed in two layers. Some hours after the operation, small pulse, 
rapid respiration, subnormal temperature, death in the evening. Autopsy: Pan- 
creas is represented by a thin layer of gland tissue in the loop of the duodenum, which 
surrounds the pedicle of the tumor. The tumor was as large as the head of a power- 
ful man. Histologic investigation resulted in the diagnosis: Epithelioma cysticum 
pancreatis. 


As palliative operations, cholecystotomy to carry off the bile or 
cholecystenterostomy to cause the bile to flow into the intestine are 
performed much more frequently than extirpation of pancreatic cancer. 
These operations certainly are performed much more frequently than is 
mentioned in the literature and here noted. 

According to the publications of Nimier (up to 1893), cholecystotomy 
in two operations was first performed by Socin in 1887 (the patient 
died of inanition); cholecystotomy at one operation was performed by 
Mackay, Chandelux, Jordan Lloyd, Krieger, Frey, Gersuny-Bettelheim, 
Reynier (2 cases), Herringham, Mayo Robson, Bennet, Duncan and 
Parry, Boeckel, Rufus B. Hall, and Terrier. An operation performed by 
Russel (1895) may be added. In all cases death occurred a short time 
after the operation, although in many there was temporary improvement. 
It is peculiar that in the case described by Gennett the feces regained their 
normal color after the laparotomy. Krdénlein also reports a cholecys- 
totomy performed by him in a case of pancreatic cancer. Death ten 
days after the operation. There is certainly no justification for chole- 
cystotomy, as the loss of the bile only hastens inanition. 

Cholecystenterostomy has been performed as follows: 

1. Monastyrski: Death three months after the operation; in the mean 
time stools of normal color. 

2. Kappeller: The patient, fifty-five years old, after the operation 
(June, 1887) at first regained normal-appetite, increased 14 Ibs. in body- 
weight, was able to resume work, and felt well up to the end of January, 
1888. Then pain returned, although the patient was able to continue 
his duties up to July; December 22d, death occurred in consequence of 
cachexia, one and a half years after the operation. 

3. Socin: Woman, fifty-one years old; the patient left the hospital after 
her weight had increased 11 pounds. 

4. Terrier performed cholecystenterostomy, July 13, 1889; improve- 
ment of appetite after the operation, general condition not bad until the 
end of 1889; died at the end of March, 1890, more than eight months after 
the operation. 

5. Reclus: Man, thirty-six years old; cholecystenterostomy per- 
formed August 13, 1892; three and a half months after the operation 
the color of the stools normal, appetite good, liver did not project beyond 
the false ribs, increase in weight 24 Ibs., and patient felt well. Death 
occurred the first of June, 1893, and cancer of the pancreas was found. 

6. Paul Reynier: Cholecystenterostomy, January, 1893; after the 
operation increase of strength and weight, but patient died in June, 1893. 


174 NEOPLASMS. 


7 and 8. Terrier: Two rapidly fatal cases after the performance of 
cholecystenterostomy. 

. Tillaux attempted cholecystenterostomy in two operations on a man 
thirty-eight years old; death fromi exhaustion some days after the opera- 
tion. A recent communication is from Abbe, who, in a case of cancer 
of the head of the pancreas, made an anastomosis between the gall- 
bladder and duodenum with the Murphy button; good result. 

The method of cholecystenterostomy introduced by Winiwarter is 
better justified than simple cholecystotomy. It may possibly prolong 
life, and for some time make the condition endurable. 


2. SARCOMA. 


Primary sarcoma of the pancreas is certainly very rare. Secondary 
sarcoma, especially the melanotic variety, has been observed a number 
of times in the pancreas. Chiari describes an extensive melanotic sar- 
coma of the pancreas. Isham found at an autopsy a spindle-celled 
sarcoma Weighing 25 pounds. The primary seat of the neoplasm could not 
be stated positively. As the pancreas was not found, Isham assumed 
that the tumor arose from this organ. Neve describes a secondary 
lymphosarcoma. In the autopsy reports of the Vienna General Hospital 
from 1885 to 1895, a metastatic lymphosarcoma of the head of the pan- 
creas and a lymphosarcoma of the duodenum with infiltration of the 
pancreas were noted. According to Orth’s conclusion, all tumors form- 
erly described as melanotic cancers probably belong under this head. 

The rarity of primary sarcoma of the pancreas is apparent from the 
fact that in most of the works on pathologic anatomy (for instance, 
Orth, Birch-Hirschfeld, Ziegler) it is stated only briefly that primary 
sarcoma of the pancreas occurs very rarely. Klebs does not speak at 
all of sarcoma. Triedreich knew only one positively proved case, which 
was found by Paulicki in the body of a young man who died of pulmonary 
and intestinal phthisis and presented no symptoms during life. On 
microscopic examination a small-celled sarcoma was found. Litten con- 
siders it difficult to decide whether this was really a case of sarcoma or 
of tuberculous disease. 

Two other cases are cited by Senn: 

1. Mayo: Man, thirty-five years old; duration of disease eight months, 
digestive disturbances, variable appetite, extreme anemia. The autopsy 
showed the pancreas much enlarged, of cartilaginous density, individual 
nodules were recognized as medullary sarcoma. 

2. Lépine and Cornil: Man, sixty-two years old; sick for eleven months, 
obstinate vomiting for seven months. Head of the pancreas much en- 
larged, pylorus thickened, its lumen narrowed, metastases in both kidneys. 
Microscopic examination showed sarcoma. There are recent observa- 
tions from Litten, Machado, Chvostek, Briggs, Schueler, Kronlein, Neve 
and Aldor. 


Litten’s case was that of a boy four years old, who was very well nourished until 
a few weeks before death; but had abdominal pain both spontaneous and on pres- 
sure. On palpating the abdomen, large tumors could be felt. Rapid emaciation 
and diarrhea occurred. Urine normal. The abdomen was greatly distended, the 
tumor very painful, both spontaneously and on movement, and of enormous size. 
At the autopsy the whole abdomen was found filled with the neoplasm. It was hard 
to determine the place of origin. The entire pancreas was transformed into an 

» 


SARCOMA. 175 


enormous tumor. There was not merely an involvement of the head of the pan- 
creas, but the tumor was formed by disease of the entire gland and its surroundings, 
and the fact that it was an abnormally large pancreas was distinctly to be recognized 
from the conformation of the tumor and its acinous structure. The microscopic 
examination made by Virchow showed a small-celled sarcoma, which bore a marked 
resemblance to a lymphosarcoma. 


Nimier’s report gives information regarding a successful operation by 
Briggs on sarcoma of the pancreas. A woman, forty-five years old, had 
in the upper abdomen a hard, smooth, globular, easily movable tumor. 
Puncture caused the escape of a coffee-colored fluid, which contained 
a large number of small bodies resembling degenerated hydatids. On 
opening the abdomen the tumor was found adherent to the omentum, 
transverse colon, and stomach. A ligature was applied above the ad- 
hesions and the tumor was removed with the tail of the pancreas. Re- 
covery without accident. The microscopic examination showed the 
tumor to be sarcomatous with old hydatids. Hooklets were found in 
the fluid obtained by puncture. It was, therefore, a case of an echino- 
coccus which had undergone sarcomatous degeneration. 


Schueler’s case concerned an alcoholic thirty-eight years old, who had a sudden 
attack of vomiting a year before; later ravenous appetite, then again vomiting after 
eating, constipation, stools yellowish-brown. Pains in the stomach and back. 

Present condition: Emaciated, pale, without fever, pain in the cardiac region 
and below the border of the ribs, radiating to the left to the vertebral column. Pain 
especially after eating, eructation, obstipation, abdomen below the xiphoid process 
very sensitive to pressure, abdominal wall very tense, palpation difficult, edge of liver 
somewhat higher than normal, spleen not enlarged, no free hydrochloric acid in the 
gastric contents. The liver was constantly smaller than normal. In the left hypo- 
chondrium in the region of the left lobe of the liver there was found a tense, elastic, 
somewhat fluctuating tumor, of the size of a hen’s egg and sensitive to pressure. 
The exploratory puncture gave brownish-red fluid; stools loose; otherwise nothing 
abnormal. The tumor increased in size, vomiting finally became fecaloid, death in 
collapse in three months. 

At the autopsy there was found below the stomach a large cystic tumor reaching 
down to the pelvis, distinctly fluctuating, cyst-wall very thin; cyst contained 2 
liters of a fluid colored like chocolate or coffee; pancreatic artery eroded in one 
place; there remained only a piece of the pancreas as large as a walnut, in which was 
a tumor as large as a hazelnut. There was beneath the spleen a tumor the size of a 
goose-egg; the rest of the pancreas was changed into a hemorrhagic cyst. 

Microscopic examination: Numerous large spindle cells; sarcomatous metasta- 
a in the right and left pleura, in the third and fifth thoracic vertebre, and in the 
ribs. 


Kroénlein extirpated a primary sarcoma: 


Woman sixty-three years old. Three years before admission there was at the 
level of the umbilicus a tumor of the size of a walnut, which gradually increased and 
became somewhat painful on pressure. In 1894 the tumor was as large as the fist, 
movable vertically and laterally, descending on inspiration. Liver dulness extended 
10.5 em. above the border of the ribs. On admission, in 1894, the skin and sclera’ 
were yellow; in the filtered gastric contents there was no free hydrochloric acid. 
At the operation it was seen, after the omental bursa had been sufficiently opened, 
that the tumor lay behind the pylorus, the pyloric part of the stomach, and the adja- 
cent duodenum, and without doubt belonged to the head of the pancreas. The 
posterior portion of the stomach, pylorus, and the upper part of the pars verticalis 
duodeni were fused with the tumor. After the ligation of many vessels (the pan- 
creatico-duodenal artery and the middle celiac artery and vein were tied in two 
places and cut through), the tumor could be set free. About 40 ligatures were neces- 
sary to tie the vessels exposed during the operation. Death seven days later. At 
the autopsy there was found a circumscribed gangrene of the transverse colon for 
about 16cm. Microscopic examination by Ribbert showed an angiosarcoma. 


176 TUBERCULOSIS. 


Neve found a sarcoma of the pancreas in a man forty-four years old, 
and Aldor in a man forty-five years old. That latter patient dated his 
first symptoms five months previous, complained of severe pain in the 
left hypochondrium, and had fever at times. At the autopsy the pan- 
creas was transformed into an irregular, uneven tumor of the size of a 
man’s fist, adherent to the spleen and transverse portion of the duo- 
denum, and still more strongly to the stomach. The middle of the 
fundus showed a perforation of the size of an apple, with ragged edge. 
The further macroscopic and microscopic examination resulted in the 
diagnosis of medullary sarcoma. 

In conclusion might be mentioned the typical angiosarcoma of the 
pancreas obsefved by Lubarsch and referred to by Dieckhoff. The same 
statements concerning diagnosis and treatment apply as in cancer. 


Adenoma also is mentioned in the recent literature, and one case 
was especially interesting because recovery followed successful operation. 
Biondi describes this case as fibroadenoma of the head of the pancreas. 
Two years after its extirpation the patient was well. 

A communication is made by Cesaris-Demel of a case of ‘‘ adenoma 
acinoso del pancreas.”’ The structure of the growth was similar to that 
of the pancreas. Its interstitial tissue, as well as that of the pancreas, 
was thickened. The author concludes that cirrhosis of the pancreas de- 
veloped upon a syphilitic basis incited the formation of the tumor. 

Neve described a case of adenoma in a woman fifty years old. There 
was a glandular tumor in the region of the pancreas, adherent to the 
duodenum; the latter was somewhat narrowed. Common duct narrowed 
and included in the tumor. 





tS BUBERECULOSIS. 


TuBERcuLosis of the pancreas was considered until very recently 
to be a very rare disease. Claessen wrote as follows in his monograph 
of 1842: ‘Recent observations have shown without doubt that tubercles 
occur in the pancreas. Clermont Lombard believes that he is able to 
determine their relative frequency in it as compared with other organs; 
according to his investigations, among 100 cases in children tubercles 
were found in the pancreas 5 times. Similar observations appear in the 
works of Varnier, Glatigny, Nasse, Bouillaud, Mitivié, A. Petit, Venables, 
Harless, and Schmidt, to which may be added the observation of Rey- 
naud, who found them in apes, and of Emmert, who noted their presence 
in cats. The tubercles were limited to the pancreas only in the rarest 
cases; in most of these they were present at the same time in several 
other organs, especially in the lungs and the liver.” 

This view of Claessen’s is not, however, accepted in the text-books 
of pathologic anatomy which have later appeared. On the contrary, 
pancreatic tuberculosis is everywhere regarded as an uncommonly rare 
disease; thus, by Rokitansky, Forster, and Klebs. Cruveilhier mentions 
only tuberculous disease of the lymph-glands on the surface of the pan- 
creas. Louis and Lebert doubt its occurrence. According to Fried- 
reich, “tubercles are found very rarely in the pancreas as a large or 


PATHOLOGY. 1A a f 


small collection of miliary granulations in the form of a more or less 
cheesy nodule, associated with chronic tuberculosis and phthisis of the 
lungs and intestine. What is usually regarded as tubercle of the pan- 
creas belongs rather to the group of chronic cheesy inflammations.” 

Tuberculosis of the pancreas is regarded in the recent text-books also 
as a rare disease. According to Birch-Hirschfeld, in addition to caseous 
processes in other organs large cheesy nodules are found in the pancreas, 
and miliary tubercles are present in the neighboring interstitial tissue. 
Orth states that a disseminated, general miliary tuberculosis may be 
seen exceptionally, whereas a partial miliary tuberculosis around large 
cheesy foci is somewhat more common. Such appearances are not so 
rare in the pancreas, especially near its surface; but, as a rule, they do not 
lie chiefly within the gland, but usually in the lymph-glands, which are 
embedded entirely or in part in interstitial tissue. Ziegler in his latest 
edition briefly states that tuberculosis, on the whole, rarely leads to pan- 
creatic disease. 

There are but few collections of cases besides those recorded by 
Claessen; in the earlier literature there are also the communications of 
Martland, Sandras, Berlyn. Aran found in 1846, in addition to tuber- 
culosis of the abdominal lvmph-glands and spleen, a tuberculous abscess 
in the tail of the pancreas of the size of a hen’s egg, the walls of which 
were about 2 cm. thick and contained numerous softened tubercles as 
large as hemp-seed. The patient had suffered from violent epigastric 
pains, was deeply bronzed, and had frequent vomiting. Roser and 
Barlow reported cases of miliary tuberculosis in children, in which miliary 
tubercles were found also in the pancreas. Chvostek describes a-case of 
chronic tuberculosis of the pancreas in which the gland was considerably 
enlarged and entirely changed into a firm, fibrous mass, inclosed in which 
were several foci as large as walnuts; there was no trace left of actual 
gland tissue. The pancreas, thus altered, produced marked obstruction 
of the descending part of the duodenum. 

Mayo describes a case of which Senn’s opinion of a primary disease 
of the pancreas may be accepted. 


The patient, thirty-eight years old, was sick for sixteen weeks, bedridden for 
seven weeks. The first symptoms consisted of pain in the abdomen, radiating from 
the right hypochondrium toward the spinal column. Twenty-eight days before 
death jaundice developed; later; dyspnea.. A large tumor was felt above the um- 
bilicus, a short time before death; the right arm and right side of the neck were 
edematous. At the autopsy an effusion into the right pleura was found and the gall- 
bladder was distended; the head of the pancreas was enlarged, forming an irregular 
spherical mass, 10 cm. in diameter, which compressed the bile-duct. The rest of the 
gland was enlarged. In places there was a normal gland tissue; elsewhere it was 
infiltrated with tubercular masses which at two or three points were softened and 
transformed into thick pus. There was a secondary affection of some lymph-glands, 
the thymus, and the kidneys. 


Bruen recently reported a case of tubercular disease of the pancreas 
the details of which I was unable to obtain. The most thorough in- 
vestigation on this subject was made by Kudrewetzky in Chiari’s Patho- 
logic-Anatomic Institute. He found that ‘the percentage of tuberculosis 
of the pancreas to tuberculosis elsewhere in the human body appears so 
high that this disease can by no means be regarded as so great a rarity 
as has previously been the case. Of 128 cases of tuberculosis examined 
successively, and in which tuberculosis of the pancreas was sought for, 
there were 12 positive cases—namely, 9.37%. Among 18 cases of general 

12 Pe 


178 TUBERCULOSIS. 


miliary tuberculosis, Kudrewetzky found pancreatic tuberculosis 6 
times; thus, 33.33%. Children furnished the greatest number. Kudrew- 
etzky found 44.44% of pancreatic tuberculosis in tuberculous children. 
He emphasizes the fact that tuberculosis of the pancreas occurs only in 
connection with tuberculosis of other organs; that is, as a secondary 
condition. 

‘Inthe majority of the cases the blood-vessels furnish the channel for 
the distribution of the bacilli of tuberculosis. Under favorable circum- 
stances an infection with the tubercular virus may arise from mere 
contact. It cannot be denied that some of the bacilli may enter the 
pancreas through the excretory duct, although there is no proof of this 
view. When the bacilli have entered the tissue of the pancreas, they 
cause either a miliary or a chronic tuberculosis. The former variety 
occurs as well in the chronic as in the miliary tuberculosis of other dis- 
eased organs. The chronic variety, on the contrary, is found only in 
chronic tuberculosis of other organs. The tubercles are situated usually 
in the actual gland tissue, in consequence of which whole groups of acini 
are destroyed by them and very soon suffer degenerative changes, hence 
such a tubercle always has a more or less cheesy center and only a narrow 
peripheral zone free from necrosis and frequently containing giant cells. 
The bacilli of tuberculosis are always present and are scattered through- 
out the entire tuberculous mass, often in enormous numbers. In the 
chronic form of tuberculosis of the pancreas large tuberculous masses 
may form, which, since they spread over the whole gland, may sometimes 
produce disease of the entire gland. In such cases there is, on the one 
hand, destruction of a large portion or ‘even of the entire gland and a 
corresponding loss of the function of the organ; on the other hand, cavities 
form which may open, for instance, into the stomach.” 

Paul Sendler has very recently made a very interesting communi- 
cation of practical importance on tuberculous disease of the lymph- 
glands of the pancreas as follows: A woman fifty-four years old, from a 
healthy family, was well until the beginning of the present illness, about 
nine months previously. Since then she has suffered from loss of ap- 
petite, feeling of pressure in the stomach, vomiting at times, discom- 
fort independent of food, and emaciation. | 

Present condition: Delicate, pale, thin woman; palpation shows above 
the umbilicus, almost exactly in the middle line, a slightly nodular 
movable tumor. When the stomach is inflated, the tumor is no longer 
to be felt distinctly. In the urine, neither albumin nor sugar. 

Laparotomy: Behind the stomach a nodular hard tumor is felt. In 
the head of the pancreas is a grayish-yellow tumor, nearly of the size of 
a walnut, which is sharply defined from the surrounding tissues. The 
tumor was extirpated, hemorrhage stopped by ligatures; convalescence 
only interrupted by an abscess in the abdominal wall and a periphlebitic 
abscess in the lower part of the thigh. The patient has since been per- 
fectly well (nine months after the operation). On microscopic examina- 
tion the tumor was found to be a tuberculous lymph-gland of the pancreas. 

The symptomatology of pancreatic tuberculosis is not at present 
perfectly clear. The cases of Mayo and Sendler show that a tumor in 
the region of the pancreas may be due also to tuberculosis. Other signs 
pointing to the pancreas have been absent in all the reported cases, unless 
the bronzed skin in Aran’s case is excepted. 

Under existing conditions it is impossible to make a correct diagnosis. 


» 


TREATMENT. 179 


In Sendler’s case the explanation was clear only on microscopic ex- 
amination after the operation. 

Senn has already suggested the surgical treatment of this affection, 
especially in consequence of the cases of Aran and Mayo. The only suc- 
cessful result, as above stated, was that obtained by Sendler. 





We SY HLS, 


SypHitis of the pancreas produces two lesions: chronic indurative 
pancreatitis and gumma. The two may occur together. Rokitansky 
has already mentioned two kinds of syphilitic disease of the pancreas. 

Indurative pancreatitis due to syphilis has already been described in 
the section on Chronic Indurative Pancreatitis, page 137. It occurs 
principally as a manifestation of congenital syphilis, and is quite frequent. 
The few known cases of indurative pancreatitis in acquired syphilis are 
mentioned in the same section. é 

The gumma is much rarer. Rokitansky mentions the occurrence of 
gummous inflammations, without entering into further details. Lance- 
reaux found, in many patients who died of visceral syphilis, that the 
pancreas was indurated either diffusely or in circumscribed areas, and 
in one case there was a circumscribed gumma. 

Rostan describes, in addition to multiple gummata, two tumors of 
the pancreas, whose gummous character was established by microscopic 
examination, in a man who, fourteen years before, had had a primary 
lesion. Klebs observed several gummous nodules in the pancreas of a 
fetus six months old. Among 124 cases of congenital syphilis Birch- 
Hirschfeld found gumma of the pancreas twice. In the case of indura- 
tive pancreatitis described: by Beck, miliary gummata were found. 

Schlagenhaufer has carefully studied the following case of indurative 
and gummous pancreatitis. 

A much emaciated married man, thirty-four years old, died after a 
short illness of bilateral lobular pneumonia. In the urine a reducing 
substance was found; acetone and indican were increased. The autopsy 
showed lobular pneumonia and purulent bronchitis in both lungs, sub- 
acute splenic tumor, fibrous pleuritis on both sides and chronic inter- 
stitial pneumonia with bronchiectasis, syphilitic scars in the liver, gumma 
in the pancreas, together with indurative syphilitic pancreatitis, syphi- 
litic induration of both testes and adrenals with gummata in those on 
the right side, syphilitic scars in the prepuce, chronic catarrh of the 
stomach and duodenum. 

The pancreas was 15 em. long, the head unusually dense and hard; 
on section the glandular lobules were to be seen, but appear small and 
atrophied (separated from each other by broad stripes of connective 
tissue). The portion adjoining the head of the pancreas was strongly 
curved for 4 cm.; on cutting into this portion a round, yellow, not sharply 
limited nodule was found, as large as a hazelnut, and softened in the center, 
surrounded by a broad zone of connective tissue; in which here and there, 
especially in the posterior portions of the pancreas, were solitary, well- 
preserved gland-lobules. The tail of the pancreas seemed macroscopl- 
cally to be normal. The ductus Wirsungianus was permeable. The 


180 CYSTS. 


larger blood-vessels, both in the pancreas and its vicinity and in the rest 
of the body, were normal. 

Microscopic examination resulted as follows: The head of the pan- 
creas, which, as above mentioned, was very dense and hard, showed a 
great increase of intra-acinous connective tissue; the lobules were sepa- 
rated from each other by a wavy fibrous tissue, poor in cells, which ex- 
tended into them as more or less broad bands, somewhat richer in cells, 
which so separated the acini that in places they formed small islands, 
in part necrotic, in part almost wholly destroyed. 

The larger blood-vessels, as well as the excretory ducts, were intact. 
Various appearances were found in the part evident to the naked eye as 
gummous. The nodule with central softening was a typical gumma: the 
cheesy necrotic center, containing isolated nuclei, was surrounded by a 
broad zone of round cells. Adjoining this was connective tissue, quite 
rich in cells, completely replacing the gland parenchyma—the excretory 
ducts alone remained—and in which were scattered numerous miliary 
-gummata in various stages of development; the smallest with cheesy 
center and radiating spindle cells, the larger with markedly cheesy center 
and spindle cells radiating about a circle of round cells, and large con- 
fluent gummata, with one or several giant cells. Toward the surface 
of the pancreas the connective tissue became poor in cells, surrounded 
the gland lobules, and caused them to atrophy to a greater or less 
extent. | 

The blood-vessels in this part were also abnormal from alterations 
indicative of syphilis. The adventitia, for instance, was studded with 
numerous small accumulations of round cells, the intima was hyperplastic, 
so that the lumen of the vessel appeared here and there much narrowed. 
There were no pathologic changes in the tail of the pancreas on micro- 
scopic examination. 

In conclusion, mention may be made of a case reported by Chvostek 
and Weichselbaum of probably syphilitic disease of the pancreatic vessels. 
In a soldier twenty-three years old they found patches of endarteritis 
with the consequent formation of aneurysm in numerous arteries, espe- 
cially in the pancreatico-duodenal artery, probably due to syphilis. A 
clinical description of syphilis of the pancreas is impossible in the pres- 
ent stage of our knowledge. 

What is to be said regarding the symptoms, course, diagnosis, and 
treatment of indurative pancreatitis has already been discussed. If 
diabetes, fatty stools, azotorrhea, and resistance in the region of the pan- 
creas appear in a syphilitic person, one would be justified in thinking of 
the pancreas. The diagnosis of syphilitic disease of the pancreas has 
never been made, so far as I am aware. 





V. CYSTS: 


Cysts without doubt belong to the fewdiseases of the pancreas which 
can rightly claim clinical and practicalimportance. Since surgery has 
taken, possession of this subject, and since recovery has been brought 


NATURE AND DEVELOPMENT. 181 


about in a relatively large number of cases by operative treatment, 
clinical interest in this question has been increased and some advance has 
been made in the knowledge of this condition with respect to the method 
of origin, diagnosis, and course. 

The domain of cysts is the most fruitful portion of the territory of 
pancreatic diseases, clinically so sterile; it is therefore justifiable to give 
considerable attention to this subject. Cysts of the pancreas are rare. 
The literature available to me contains but 1384. No doubt its occurrence 
is more frequent.* 

Since animal experimentation teaches very little with regard to the 
nature of this affection, our knowledge of cysts of the pancreas is based 
almost entirely upon reports of cases; and since our knowledge of the 
subject is only to be advanced by study of these cases, it is justified on 
account of the practical importance of cysts to enter more closely into 
details. 


NATURE AND DEVELOPMENT OF CYSTS OF THE 
| PANCREAS. 


There are many gaps in our knowledge of the nature and method of 
origin of pancreatic cysts. There are relatively few reports of autopsies 
and exact pathologic investigations, and insight into the more exact 
relations is rarely obtained at an operation. 

Three varieties of cysts are to be distinguished: 


A. RETENTION CYSTS. 


Dieckhoff, Tilger, and other authors agree with the earlier view, 
which was formerly generally accepted, that most of the pancreatic cysts 


* The cases considered were as follows: Agnew, Albert (2 cases), Anandale, 
Anger, Ashhurst, Bamberger, Barnett, Baudach, Bécourt, Bozemann, Brown, Bull, 
Challand-Rabow; Chew and Cathcart, Churton, Cibert, Clare, Clutton, Cornil, Cru- 
veilhier, Curnow, Dieckhoff, Dixon, Dreyzehner, Durante, Eve, Fenger, Filipow, 
Finotti (2 cases), Fisher (2 cases), Flaischlen, Giffen, Goiffey, Goodmann, Gould (4 
cases), Gross, Gussenbauer (3 cases), Hagenbach, Hartmann, Heinricius (2 cases), 
Herczel, Hersche, Hinrichs, Hjelt, Horrocks and Morton, Holmes, Hoppe, Hulke, 
Karewski (2 cases), Klob, Kootz, Kramer, Kiihnast, Kuster, Kulenkampf, Lardy, 
Ledentu, Lindner, Littlewood, Lloyd Jordan (2 cases), Lobstein, Ludolph (2 cases), 
Lynn, Malcolm Mackintosh, Martin, Martin and Morison, Mayo, Michailow (2 cases), 
Mumford, Newton-Pitt-Jacobson, Nichols, Ochsner, Osler, Parsons, Pepper, v. Petry- 
kowski, McPhedran, Phulpin, Railton, v. Recklinghausen, Reddingius, Reeve, 
Richardson (2 cases), Riedel (2 cases), Riegner, Rotgans, Salzer (2 cases), Savill, 
Schnitzler (2 cases), Schréder (2 cases), Schwarz (2 cases), Senn, Stapper, Steele, 
Stieda, Stiller, Stérk, Subotic, Swain, Thiersch, Thiroloix-Pasquier, Thorén, Tilger, 
Tobin, Tremaine, Treves, Tricomi, Trombetta, de Wildt, Witzel, Wélfler, Wyss, 
Zawadzki, Zukowski, Zweifel. 

It is certain that all cases have not been published, and that others exist in 
hospital reports, lectures, etc., and are found with difficulty. Certain cases could 
not be considered, because exact data were lacking; thus, for instance, Bas in his 
dissertation asserts that Heinricius has successfully made four incisions and two 
extirpations; Malthe also reports incision twice with recovery. Ko6rte, in_his 
“Beitrag zur chirurgischen Behandlung der Pancreas-Entziindungen,” mentions 
two operations conducted by him. A number of cases also may have been over- 
looked. In a large number the diagnosis is not made during life, and hence the cyst 
escapes recognition if no autopsy is made. Some, perhaps many, of the cases are not 
cysts of the pancreas. If there is no autopsy, it is often difficult, even after operation, 
to decide whether the cystic tumor really originated from the pancreas. 


182 CYSTS. 


were caused by retention of the gland secretion, the outflow of which is 
hindered in some way. Senn suggests a modification of the retention 
theory. He considers as the result of his experiments on animals “ that 
the closure of the pancreatic duct is not the only or the most important 
cause of the development of the pancreatic cyst.” Among all the cases 
of ligation of the pancreatic duct which he performed on different animals, 
he never saw the development of a pancreatic cyst, or any tendency to 
such formation, although without doubt the portion of the pancreas 
which was cut off continued to secrete, as was shown by the experiments 
in which external pancreatic fistule were established. The single visible 
result of the closure was always a moderate dilatation of the duct beyond 
the ligature. “The most important etiologic factor in the development of 
pancreatic cysts,” says Senn, “must be sought in the hindrance to the 
absorption of the pancreatic juice, which must depend either on a change 
of the pancreatic juice by the admixture of pathologic non-absorbable 
substances, or on a lessened activity of the absorbing vessels. The 
closure of the pancreatic duct probably may cause stagnation and accu- 
mulation of pathologic products, but can never be the sole cause of reten- 
tion of the pancreatic juice in an otherwise normal gland.” 

These remarks of Senn’s, which are chiefly based on experiments on 
animals, merely express the thought that retention is neither the only 
nor the most important factor in the pathogenesis of cysts, but they 
cannot be intended to mean also that the stagnation of secretion plays 
no part at all. 

The assumption is justified that the retention of secretion represents 
an essential, even if not the most important, factor in the occurrence of 
the cyst. The results of experiments on animals cannot straightway 
be transferred to the pathogenesis of pancreatic cysts in men. Senn 
caused a sudden closure of the excretory duct, while in far the greater 
number of cases of closure observed in men, the condition develops gradu- 
ally. In the cases of sudden closure, as by concretions, the formation 
of cysts rarely occurs. 

The development of cysts from retention is seen in other organs, 
especially in the salivary glands, physiologically so closely allied to the 
pancreas, and the occurrence of retention cysts in them is placed entirely 
beyond question. Senn’s remarks certainly deserve consideration in so 
far as they demonstrate that cyst formation does not follow all cases of 
retention, that simple dilatation frequently results, and that in the 
occurrence of true cysts other factors are of usually great influence, 
especially the activity of the retained secretion and the condition of, the 
absorbent vessels. In many cases of closure of the excretory duct there 
may not be cyst formation because the function of the accessory duct is 
still preserved. 

An experiment recently performed on an animal by Thiroloix suc- 
ceeded in producing a cyst. 


He tied the accessory duct in a dog and injected into the Wirsungian duct 7 c.c. 
of a mixture of soot and carbolized liquid vaselin. The vertical branch of the gland 
was resected. Two months later a second laparotomy. The pancreas was black 
and very hard. A piece 2 em. large of the sclerosed and a portion of the normal fis- 
sue apparently as large as a hazelnut were resected. Three weeks later the dog was 
killed. In the splenic portion of the pancreas a large cystic cavity was found, which 
contained a fluid as clear as water and a considerable number of hard, irregularly 
shaped calculi, of the size of a pinhead. The wall was several millimeters thick and 
was formed of very dense connective tissue; the Wirsungian canal was much dilated 


NATURE AND DEVELOPMENT. 183 


and filled with small calculi. The parenchyma of the gland was as hard as wood and 
difficult to cut. 


In this case the formation of the cyst was the result of indurative 
pancreatitis. The occurrence of a chronic pancreatitis has repeatedly 
been observed, as will be seen also in pancreatic cysts in men. 

Some authors object to the retention theory of the origin of large 
pancreatic cysts, because the hindrance to the outflow of the secretion 
often could not be shown, and therefore look for the etiologic factor in 
the inflammation of the gland itself. Doubtless such chronic inflamma- 
tions frequently exist ; but the explanation given by Tilger and Dieckhoff, 
for instance, for the pathogenesis of such cysts—namely, that the stag- 
nation of secretion is produced by the induration—certainly seems very 
plausible. 

The common factor in all such cases is the retention of secretion, and 
this justifies including them all under the term retention cysts. 

The outflow of the secretion may be hindered in different ways: By 
compression or obturation of the secretory duct or by a combination of 
both factors. 

(a) The most frequent cause is chronic indurative pancreatitis, in 
which compression and constriction of the ducts result from a new- 
formation of connective tissue, and consequently a stagnation of the 
secretion can take place. By such interstitial growths the duct may be 
bent, and by the contracting force of the newly formed connective tissue 
the excretory duct may become widened in places, and in the widened 
ducts the secretion can easily undergo such a chemical change that it 
assumes a firmer, more tenacious character, still further preventing its 
outflow. Dieckhoff thus explained the origin of the cyst in his case: 


In a merchant thirty-six years old, who rapidly became emaciated, there was 
found in the left mesogastrium an oblong tumor with the long diameter running from 
above downward. On puncture, a dark-red fluid was evacuated. At the laparotomy 
a cyst was found in connection with the pancreas. The cyst was sewed to the abdom- 
inal wound and drained. Recovery good. Patient was able later to resume his 
former occupation. Two years later jaundice developed. One year later, frequent 
attacks of colic, regarded as due to gall-stones. Then rapidly increasing ascites. 
Great loss of strength, death. At the autopsy the pancreas was found changed into 
a dense, firm mass which compressed the vena porte. In the head of the pancreas 
were the remains of a cyst-wall. The rest of the gland consisted of an extremely 
firm mass, with pancreatic structure in only a few places, in which were numerous 
large and small cavities, corresponding to the excretory ducts. From some of the 
spaces purulent fluid escaped, in others were yellowish and brownish concretions, 
some as large as beans. 


According to Dieckhoff, the development was as follows: First, from 
some unknown cause, a chronic indurative pancreatitis developed, be- 
ginning in the head of the pancreas and advancing insidiously; in con- 
sequence, enlargements of the excretory ducts, caused partly by the 
traction of the growing connective tissue and partly by the stagnation 
of secretion. The increasing dilatation of several cysts and disappearance 
of the intervening walls resulted in the formation of one large cyst, that 
operated upon. As the inflammation of the pancreas later advanced it 
led to the pathologic condition last described. : 

The like occurrence of a chronic interstitial pancreatitis has been 
regarded in many other cases as the cause of the cyst formation. 


In a man fifty-five years old who had steatorrhea and diabetes, Goodmann 
found, in addition to tuberculosis of the pancreas, a voluminous tumor in the tail, 


184 CYSTS. 


containing yellowish-green fluid. The cavity of the cyst was surrounded on all sides 
by thick, firm walls, and was nowhere connected with the ductus Wirsungianus, 
which ended near thetumor. At the place of transition from the head to the body of 
the gland, the duct showed a pocket-like enlargement, which contained masses 
resembling concretions. The gland tissue was atrophied. The head was changed 
into fibrous tissue, which sent out into the neighborhood fibrous bands compressing 
the excretory ducts and surrounding the blood-vessels. 


A similar condition is mentioned in the case of Hagenbach, Hjelt, 
Martin, Tilger, and others. 

(6) The ductus Wirsungianus may be closed from without. At the 
autopsy of a man who had suffered for months from jaundice, Cruveilhier 
found, in addition to marked dilatation of the gall-bladder, a tumor 
on the surface of the pancreas filled with watery fluid, following the long 
axis of the gland, and frequently showing transverse projecting folds 
from the interior. The tumor proved to be the much dilated ductus 
Wirsungianus, and as the cause of the dilatation was found a small 
scirrhous tumor closing the duodenal orifice of the duct and the ductus 
choledochus, which opened just at this point. 

In the cases reported by Virchow and Friedreich the compression was 
due also to duodenal tumors. Such a closure may be caused likewise 
by peripancreatic scars or swollen lymph-glands and adhesions, especially 
in the neighborhood of the head of the gland (Hoppe). In Phulpin’s 
case a gall-stone wedged in the ductus choledochus was the cause of 
compression of the lumen of the pancreatic duct from without. 


In a woman seventy-four years old, who for a year had suffered from jaundice 
and was greatly emaciated, several stones were found in the greatly dilated gall- 
bladder, and, in addition, there was a concretion impacted in the ductus choledochus, 
at a distance of about 2 cm. from the diverticulum Vateri. The ductus choledochus 
above this place was enormously dilated and showed a lumen almost equal to that of 
the small intestine. The pancreatic duct was compressed and enlarged at the place 
where it crossed the stone impacted in the excretory duct of the gall-bladder; on the 
distal side it was as large as the index-finger; on the other side it was normal. The 
pancreas appeared to have undergone cystic degeneration. About twenty cysts as 
large as hazelnuts were visible on the surface and collapsed on cutting into the gland, 
with the evacuation of contents resembling normal pancreatic juice. The develop- 
ment of the numerous cysts was probably due to the fact that the accessory duct of 
the gland was congenitally obliterated, and, therefore, there was no outlet for the 
pancreatic secretion. 


An impacted gall-stone in the ductus choledochus compressing the 
Wirsungian duct was present also in the earlier case reported by Engel, 
and more recently in those of Horrocks and Morton. 

(c) Obturation of the Wirsungian duct by concretions. The pressure 
of the enlarged sac filled with fluid on the surrounding tissue leads to 
the formation of large cysts, whose contents at times show similar con- 
cretions. In a case reported by v. Recklinghausen, a cyst was formed 
of the size of a child’s head. In Gould’s case the retention cyst was so 
large that it could be felt through the abdominal walls. 

The following communication with reference to this variety has re- 
cently been made by Tricomi: 


In a woman twenty-two years old a fluctuating tumor in the epigastric region 
developed with cramps. On exploratory puncture, a fluid was found containing 
albumin and diastase. Laparotomy was performed and 800 c.c. of a turbid yellow 
fluid were evacuated in which were necrotic pancreatic tissue, and small, very friable 
concretions. The ductus Wirsungianus was obstructed by a stone which lay some 
distance from its mouth. 

- 


NATURE AND DEVELOPMENT. 185 


The obturation of the ductus Wirsungianus may result from other 
factors. | 


Durante operated on a girl who came to the hospital suffering from a tumor of 
the right hypochondrium. In spite of the evacuation of the contents of the cyst, the 
patient died two days after the laparotomy. At the autopsy an Ascaris lumbri- 
coides was found wedged in the ductus Wirsungianus. The lumen of the duct was 
almost entirely closed in consequence, and the portion lying beyond appeared mark- 
edly dilated. A further result was softening of the gland, the remains of which were 
found as soft bodies in the interior of the fibrous wall of the cyst. 


(d) It is probable, but not certain, that a catarrhal affection may 
close the ductus Wirsungianus, as in the case of the ductus choledochus. 
In a case reported by Curnow, in which there was an enlargement of the 
duct and concretions, it appeared as if the duodenal orifice was closed 
by catarrhal inflammation and the pancreatic secretion was inspissated. 

(ec) Neoplasm in the pancreas, especially in the head, may compress 
or obliterate the excretory duct and thus dilate the secretory duct beyond 
the stenosis. There are no known cases of the occurrence of cysts in 
this manner. 


B. CYSTIC NEOPLASMS (PROLIFERATION CYSTS). 


Proliferation cysts (Dieckhoff) belong to a second, much more rare 
series of cases of cyst formations, and are to be regarded as the expres- 
sion of the formation of cysts in tumors or as a primary cystic degen- 
eration of the pancreas, analogous to that of the kidneys, testes, or 
mammary gland (Nimier), since there is no proof that there is a stagna- 
tion of the pancreatic secretion. 

The following are instances: 


The case of Baudach (cited from Dieckhoff): A man forty-one years old died of 
phthisis pulmonum. During life, with the exception of a slight sensitiveness to pres- 
sure in the epigastrium, there had been no symptom present which could have indi- 
cated any disease of the pancreas. At the autopsy a globular cyst as large as an 
orange was found in the middle of the pancreas. The contents were brownish-red, 
turbid, somewhat viscid, in which were numerous disintegrated white and red blood- 
corpuscles, granular detritus, granular corpuscles, and epithelial cells for the most 
part altered and disintegrated, but a few were well preserved, some with one very 
large, not excentric nucleus, and others with several nuclei. The cyst was distinctly 
multilocular; between the walls were projecting beams and villous excrescences. 
In some places the wall was 3 em. thick and showed also a lobulated sinuous structure 
with numerous depressions and pockets. In this part were the remains of the primary 
adenomatous neoplasms with increased blood-vessels and secondary myxomatous | 
degeneration. The neoplasm, according to Baudach, was an angioma myxoma- 
tosum intercanaliculare or an adenoma. 

The case of Hartmann (cited from Nimier): A woman fifty-three years old for 
some time had suffered from disturbances of digestion. For three months she felt 
ill. She complained of loss of appetite, great weakness, emaciation, vague pains in 
the left side at the level of the umbilicus, where was a rapidly growing tumor. 

For several months the patient could not endure fatty foods. In the morning 
there was frequent nausea, but never any vomiting. There was always constipation, 
but the stools were of normal appearance. On palpation a tumor was found to the 
left of the umbilicus, as large as two fists, dense, hard and smooth on the surface, 
extending on the right to the umbilical line, and on the left to the loin. It was 
easily distinguishable from the liver. The stomach appeared dilated. The urine 
was normal, Laparotomy was performed and the tumor proved to be a cyst, from 
which, on puncture, 7 ounces of chocolate-colored fluid were evacuated. Well for 
some weeks after the operation, then persistent vomiting set in and the patient died 
of general inanition. At the autopsy nodules of secondary cancer were found in the 
liver. The duodenum was compressed. Between the transverse colon and the 
greater curvature of the stomach there was a fistula which entered an empty cyst. 


186 . CYSTS. 


In addition, the pancreas was filled with cysts. . Their formation began where the 
arteria mesenterica crossed the pancreas. The cysts, from the size of a pea to that of 
the fist, surrounded the vena porte and were connected above with the left lobe of the 
liver, and one was connected with the wall of the stomach. They contained viscous 
or reddish fluid. The head of the gland only appeared normal. The intact ductus 
Wirsungianus passed through this agglomeration of cysts. The histologic examina- 
tion showed that it was a case of cystic epithelioma of the pancreas. 

In a case operated upon by Liicke, Klebs found, in addition to the large cyst, a 
section of macerated tissue, which showed all the characteristics of a colloid cancer. 

At the autopsy of one case, Menetrier saw a large cyst in the pancreas as large 
around as the head of a fetus at full term, also numerous smaller cysts. In the liver 
also similar changes were to be found. According to Gilbert’s microscopic examina- 
tion, this was a case of a cylindroma of the pancreas. 

Zukowski’s case: In a woman thirty-six years old a tumor had gradually been 
forming in the abdomen for two and three-fourths years. It was considered a cystic 
ovary. The abdomen was unequally distended. Tumor extended two hand’s- 
breadths above the umbilicus and showed distinct fluctuation. At the laparotomy 
a brownish-red fluid, containing much albumin and cholesterin, was evacuated. The 
inner wall of the cyst was quite smooth, only in places thickened by projections. A 
mass of papillary excrescences as large as a pigeon’s egg projected from the poste- 
rior surface. 

Thiroloix and Pasquier report a case which showed a great resemblance to 
congenital cystic degeneration of the kidneys. In a woman ninety-three years old, 
who died of bronchitis, the pancreas was found changed into a tumor consisting of 
5 or 6 cysts, of the size of hen’s eggs. The cysts did not communicate with each other. 
Between them was found fatty tissue in which were numerous small cystic spaces. 
The head of the pancreas was also beset with miliary cysts and infiltrated with fat. 
The parenchyma of the gland in all portions except a part of the tail resembled a 
sponge. The ductus Wirsungianus was normal and entirely permeable. The fluid 
filling the spaces was alkaline, light-colored, and clear and contained epithelial detri- 
tus and lymphoid cells in addition to much albumin. On microscopic examination 
the wall of the larger cyst appeared formed of fibrous, non-vascular connective tissue. 
The spongy portions of the gland were penetrated by walls formed of connective 
tissue and cellular trabecule. The cells were embryonal in character: small, round, 
crowded together, and having a nucleus which stained poorly. In places they 
appeared to have an alveolar arrangement. 


The case reported by Garrigues, in which small daughter cysts were 
found, might belong to this series (Orth). 


The case reported by v. Petrykowski is to be placed here; in this a cystic tumor 
of the Dancreze of an adenomatous character was removed from a boy three and a half 
years old. 

According to a communication from Cibert, Poncet removed from a woman 
twenty-six years old a tumor of the size of the head, which contained three liters of 
brown fluid and, according to the histologic examination conducted by Dor, was 
regarded as a teratoma or fetal adenoma. 


The cases of Riedel, Martin, and the second case of Salzer from the 
Rothschild Hospital (Zemann-Oser) probably belong in this series of 
cystic neoplasms. 

[The border-line between proliferating cysts and cystomatous cancer 
is not always to be sharply drawn, as is illustrated by the case of multi- 
locular cystoma of the pancreas reported by Fitz * and that of Ranso- 
hoff.t—Ep.] 


C, APOPLECTIC CYSTS. ° 


The question whether hemorrhages can give rise to the formation of 
cysts in the pancreatic tissue is still undecided, and most recent authors 
either dispute it or consider it uncertain. 

It is well known that cysts frequently have bloody contents, and 
* Trans. Assoc. Am. Phys., 1900, xv, 254. + Am. Med., 1901, 1, 138. 


» 


. 


NATURE AND DEVELOPMENT. 187 


it is almost the rule, as will appear subsequently, that the cystic contents 
are tinged with blood or contain more or less of this fluid. The presence 
of bloody or blood-stained contents is so frequent that, as Kiitser thinks, 
it is almost pathognomonic of pancreatic cysts. 

Most of the cysts containing blood are retention cysts, and there 
can be no doubt regarding their origin and that of the hemorrhage into 
the cyst. That the cyst is preformed and that the hemorrhage into it 
is secondary is shown without doubt by the situation of the cyst, its 
relation to the secretory ducts, the demonstrable hindrance to the outflow 
of the secretion through closure of the main excretory duct or of the 
secretory ducts by obturation or compression, mostly caused by chronic 
inflammation, leading to sclerosis of the gland and obstruction to the 
discharge. 

In many of the cases fresh hemorrhage could be shown. It occurred 
between the exploratory puncture and the evacuation of the cyst at the 
operation; hence the contents of the cyst removed at the operation con- 
tained much more blood that that evacuated by puncture. In one of 
Kiister’s cases there was a hemorrhage during the operation. 

Apart from these cysts, which have the same etiology, there are 
others mentioned in literature, of a different nature and which present 
at least the possible interpretation that hemorrhage was the primary 
and cyst formation the secondary factor. Such cysts are mostly large, 
solitary, develop in the tail of the pancreas, and the contents are 
markedly hemorrhagic; they show no relation to the excretory ducts and 
there are also no changes which point to a preceding chronic indurative 
inflammatory process. Ledentu was the first to suggest that cysts might 
develop from hemorrhages into the pancreatic tissue in two cases referred 
to by him. The first of these cases was reported by Anger. 

A man seventy-two years of age suffered in his youth from a severe injury with 
fracture of several of the left ribs. At the autopsy Anger found a tumor of the size of 
a child’s head at the level of the left kidney; the stomach lay in front of the tumor 
and below it the transverse colon. The tumor contained blood and fresh clot. The 
inner surface was irregular and resembled in structure the left ventricle or the “ Ves- 
sie 4 colonnes.”’ The wall was very thick in many places and was calcified. The 


microscopic examination showed the presence of glandular elements of the pancreas, 
and this aided in the diagnosis of a cyst of the tail. 


Anger was in doubt whether there was a hemorrhage into the pan- 
creatic tissue with a resulting cyst, or whether the hemorrhage was the 
result of the rupture of a vessel in a preformed cyst. Ledentu assumes 
the hemorrhage to be the primary factor, especially with reference to a 
second case, which he reported as follows: 


A man twenty-six years old received a blow on the abdomen two and a half 
months before death. A tumor of the size of a child’s head developed in the head of 
the pancreas. The Wirsungian duct was not involved. 


Ledentu refers to the literature up to that time, and cites the observa- 
tions reported by Bécourt, Gould, and Parsons concerning cysts with 
hemorrhagic contents. In Gould’s cases there was certainly a dilatation 
of the excretory duct, while in the two other cases there was no satisfactory 
interpretation. ‘ 

Following Ledentu, Friedreich has accepted this view, and distin- 
guishes between hemorrhagic cysts—that is, retention cysts with bloody 
contents—and apoplectic cysts. Under certain circumstances “large 
hemorrhagic foci develop in the pancreas, often, perhaps, in connection 


188 CYSTS. 


with pre-existing alterations of the blood-vessels. The so-called apo- 
plectic cysts, arising secondarily from such hemorrhages, are of course 
to be distinguished in their nature and genesis form those hemorrhagic 
cysts which are caused by hemorrhages into the contents of pre-existing 
cysts. Perhaps Stork’s case from the earlier literature belongs to the 
same category.” 

A woman twenty-eight years old, otherwise well, was attacked with severe vomit- 
ing during her menses, and the menstrual flow consequently ceased; there were 
fainting, palpitation of the heart, coldness of the extremities, and great feeling of 
anxiety. A pulsating tumor appeared in the epigastrium. After the latter symp- 
toms had lasted for three and a half months, bilious vomiting suddenly reappeared, 
accompanied with diarrhea, and death occurred after general emaciation and weak- 
ness. At the autopsy the pancreas was changed to a large sac, weighing 13 pounds, 
and was filled with bloody, in part lamellated contents. Its development could be 
referred to a laceration of the blood-vessels in the center of the pancreas. 


On examination of, the abundant literature of pancreatic cysts pub- 
lished since Friedreich’s treatise, it must be admitted that Tilger and 
Dieckhoff are correct in asserting that there are no cases of apoplectic 
cysts positively established. Among the more recent authors, however, 
many are found who support Friedreich’s point of view; Orth says: 
‘Large circumscribed hemorrhages into the pancreas may be absorbed, 
and, like the small ones, leave a pigmentation or cause the formation of 
cysts the inner surface of which appears rust-colored from pigment.” 
Senn, Schroeder, Kihnast, and Nimier also assume that cysts may 
develop in consequence of pancreatic hemorrhages. At the autopsy of 
an inebriate seventy-five years old, with marked cirrhosis of the liver, 
Kiuhnast found, in addition to a cyst in the body of the pancreas filled 
with blood and as large as an apple, that “the pancreatic duct, very 
much dilated, could be followed for 6 em., then continued into the cystic 
portion, in which, by careful search, it could be here and there discovered. 
It could not be determined that it communicated with the large cyst.” 
In the absence of an accurate microscopic examination, Tilger could not 
support Kihnast’s view. | 

Tilger, the most decided opponent of Friedreich’s theory, supports 
his view by the thorough study of his own case. There can be no doubt 
that in this case there was not an apoplectic cyst in Friedreich’s sense. 
There certainly was a high degree of chronic interstitial inflammation 
and increase of connective tissue in the tail of the pancreas, especially 
noticeable around the lobules, and the hemorrhage was of the secondary 
kind, largely due to erosion of the blood-vessels by the pancreatic secre- 
tion. 

Although there is some justification for Tilger’s view that in the 
' cases hitherto presented no convincing proof has been given of the ex- 
istence of apoplectic cysts, yet, on the other hand, the possibility cannot 
be put aside that cysts may develop from hemorrhages, as suggested by 
Nimier. Hemorrhages very easily occur in the soft, vascular pancreatic 
tissue, as can frequently be observed in experiments on animals, and it 
would not be impossible at the outset that such hemorrhagic cysts might 
occur. wre 
Some traumatic cases are mentioned in the literature, which allow 
the interpretation that hemorrhage was the primary factor. Littlewood’s 
case is in point: 

A man thirty years old fell from his horse and received a kick in the abdomen. 
Thirteen days later a tumor was found in the epigastrium and in the left upper por- 


PATHOLOGIC ANATOMY. 189 


tion of the umbilical region. On exploratory puncture dark blood was evacuated. 
For seven days the swelling increased slowly, but afterward it advanced rapidly with 
severe pain. At a second puncture, 10} oz. of an allsaline, sage-green fluid were 
evacuated. Laparotomy was then performed, the cyst was opened, and its walls 
were stitched to the abdominal wall. The cyst-fluid contained serum-albumin and 
trypsin, and possessed diastatic and fat-emulsifying properties and coagulated milk 
(Nimier). 


It must certainly be admitted that in this case it is possible that 
hemorrhage into the pancreatic tissue took place as a result of the in- 
jury (the first puncture brought pure blood); that in consequence of the 
hemorrhage and tearing of the pancreatic tissue the secretion from the 
latter became mixed with the blood; that the cavity became enlarged 
by the digestive power of this secretion, consequently when laparotomy 
was performed the cyst was found to contain fluid possessing the digestive 
properties of pancreatic Juice. At all events, it would be difficult to 
explain by any other assumption the appearance of pure blood at the 
first puncture, and the characteristic contents of a pancreatic cyst only 
at a later puncture. 

Paltauf supports Nimier’s assumption that pancreatic cysts may de- 
velop from hematomata with simultaneous laceration of the duct. Pal- 
tauf believes that the possibility of such a method of origin must be granted 
for various reasons (anatomic and histologic). In one preparation he 
was able to “convince himself positively that such a hematoma was a 
pancreatic cyst.” 

From what has been stated it is evident that it by no means has been 
positively shown that the so-called apoplectic cysts arise from hemorrhage 
into the pancreatic tissue; but, on the other hand, it is impossible to 
exclude the possibility that under certain circumstances after injury, 
cysts may arise in consequence of the hemorrhage. 

[In this connection especial attention should be called to the com- 
munication of Lloyd * concerning a method of origin of hemorrhagic 
cysts. This writer makes it very probable that many so-called pan- 
creatic cysts of traumatic origin are collections of fluid in the omental 
bursa, the result of a localized inflammation of this portion of the peri- 
toneum. It is readily apparent that blood and even pancreatic secretion 
might be present in the contents of the “cyst” from laceration of a 
portion of the pancreas at the time of the injury.—Ep.] 


PATHOLOGIC ANATOMY. 
SHAPE OF THE CYSTS. 


The shape of the cyst varies as it originates from the ductus Wir- 
sungianus or from the smaller canals within the gland. If the constric- 
tion of the duct is near the entrance into the intestine, either the main 
duct alone is distended or its branches also may be enlarged. In the 
former case there is a rosary-like dilatation of the whole excretory duct. 
Virchow reports such a case, and designates it ranula pancreatica from 
its analogy with the formation of cysts in the salivary glands. The 
dilatation was caused by a soft, villous duodenal tumor, which obstructed 
the common opening of the ductus choledochus and Wirsungianus. 

Many small cysts are formed. (acne pancreatica, Klebs) when numer- 


* Brit. Med. Jour., 1892, 11, 1051. 


190 CYSTS. 


ous small ducts are constricted by pathalogic processes, most frequently 
fibrous tissue formation in consequence of indurative pancreatitis, per- 
haps also by accumulation of catarrhal secretion. When there is partial 
cystic dilatation of the ductus Wirsungianus, very capacious sacs form, 
sometimes spherical, sometimes oblong (Klebs); the former being more 
frequently seen. 

The size may vary. It is worthy of note that pancreatic cysts are 
described as much smaller by the anatomist than by the surgeons. Vir- 
chow has seen sacs as large as a fist; v. Recklinghausen, likewise Birch- 
Hirschfeld, describe one as large as a child’s head; Klebs and Orth men- 
tion cysts of a size greater that that of a child’s head. The majority are 
from the size of an orange to that of a child’s head, but surgeons have 
reported much larger cysts; thus, Bozemann reports one containing 11 
liters; Salzer, Richardson, as large as a man’s head; Wolfler, twice the 
size of a man’s head; Stapper, containing 20 liters; Hersche, almost as 
large as a man’s head, etc. The wall of the cyst consists chiefly of dense, 
firm, fibrous connective tissue, poor in cells. Its thickness varies, but it 
is usually 2, 3, or4mm., and may even reach3 cm. _ Portions of unaltered 
pancreatic tissue are found not infrequently in the cyst-wall. Salzer 
found in the case operated upon by him that the posterior external sur- 
face of the cyst was formed of pancreatic tissue. The rest of the wall 
consisted of connective tissue poor in cells but calcified and containing 
pigment cells. 

In Dieckhoff’s case there were in the wall pancreatic lobules with dis- 
tinctly dilated excretory ducts. The interacinous connective tissue was 
increased in various degrees. Most of the gland cells were quite small, 
yet provided with nuclei which stained well, and lobules which merely 
diffusely stained were found only in places. 

The lining of the cyst is generally smooth, shining, and free from 
epithelium. In some cases, however, cylindric epithelium is found here 
and there, probably the remains of the epithelial lining of the former 
excretory ducts. A similar condition was found in the cases of Martin 
and Zukowski. In Salzer’s case the inner surface of the cyst was bare 
of epithelium and showed comb-like projections and septa, the remains 
of the original cysts, now transformed into a large single cavity. 

The clotted remains of previous hemorrhages are often seen in the 
form of a gray, sandy coating on the inner wall (Martin). Large or small 
deposits of fat are not infrequently seen in places. Under certain cir- 
cumstances there may be circumscribed necroses of the wall or of the 
remains of pancreatic tissue attached to it (Tricomi). 

The large blood-vessels run along the outer wall of the cyst and often 
form a most unpleasant complication at the operation. The large 
arteries and veins visible on the surface do not always belong to the 
vascular supply of the cyst itself. For instance, Salzer saw the splenic 
vessels on the surface of a cyst and their mistaken ligation led to serious 
consequences. 

ae cyst is more frequently seated in the tail than in the head of the 
gland. 

Among 134 cases examined with reference to this point, in 90 there 
was no statement regarding the location; in 14 the whole pancreas was 
involved; in 15 the tail was affected; in 11 the head and i in 4 the middle 
portion of the gland was involved. 

The amount of fluid contained in the cyst varies considerably and 


PATHOLOGIC ANATOMY. 19] 


corresponds to the size of the cyst, which is often enormous. In Stapper’s 

case, as already mentioned, there were 20 liters; in Osler’s 18 liters were 
evacuated and in Bozemann’s 11 liters; Riedel and Lardy each report 
10 liters; in the cases of Wolfler, Salzer, and Zukowski there were 5 liters. 
The contents in general vary from 1 liter to 3 liters. 

It is seldom that the contents of the cyst resemble water, light colored 
and transparent (Kramer, Schroeder, Cruveilhier, Thiroloix and Pas- 
quier, Kulenkampf). They are usually more or less turbid, slimy 
(Dixon, Gussenbauer, Salzer, Gross, v. Recklinghausen, Railton, Maleolm 
Mackintosh, Richardson, and others), syrup-like and gelatinous (Gould), 
colloid (Ludolph), purulent (Herezel, Ashhurst). 

The color is rarely bright yellow (Hjelt, Tricomi, Kiister), sometimes 
yellowish-green (Goodmann, Stapper), green (Flaischlen, Newton-Pitt- 
Jacobson, Littlewood). In most cases it is light brown, coffee-brown, 
or reddish-brown in color. When the quantity of blood in the contents 
is large, and if a long time has elapsed after the hemorrhage, the color is 
chocolate-brown, an appearance which has repeatedly been reported by 
different observers. In the majority of cases there is such an admixture 
of blood. Kuster, indeed, thinks, as already mentioned, that the presence 
of a small amount of blood in a cyst of the upper abdomen punctured 
for the sake of diagnosis is characteristic of a pancreatic cyst. 

The contents of the cyst at times are exclusively or chiefly liquid 
or partly clotted blood in consequence of the marked tendency for hemor- 
rhage to take place within the cavity, and Friedreich classifies such as 
hematoma of the pancreas, in contradistinction to the so-called apo- 
plectic cyst originating from hemorrhage into the tissue of the pancreas. 
Such cysts containing much blood are reported by Stork, Parsons, Pepper, 
Anger, Gussenbauer, Thiersch, Baudach, Challand and Rabow. 

The extravasated blood generally shows marked changes. Gussen- 
bauer found altered red and white blood-corpuscles and clumps of pig- 
ment. A deposit of blackish-brown masses is found at times in the wall 
(Parsons, Gussenbauer). Recent hemorrhages into cysts also were some- 
times noted (Parsons, Kiister). 

The reaction of the fluid, as a rule, is alkaline; only once is it noted 
as acid (Bozemann); in the cases of Kramer, Hersche, and Wolfler the 
reaction was neutral. 

The specific gravity was ascertained in but few cases: Tremaine, 1007; 
Richardson, 1008; Horrocks and Morton, 1009; Hinrichs, 1015; Tilger, 
1015; Stappe, 1019; Bozemann, 1020; Hersche, 1028. Complete analyses 
are given by Hinrichs, Kulenkampf, and Hoppe. 

In 100 parts of the fluid the following percentages were found: 


KULENKAMPF (SECRE- 
TION FROM THE 


HINRICHS,. FISTULA). 
DIPy BU PAOOG ole oo ee eyo aul 3.25% 1.222% 
OPP AIEC: TREE oes oe gs we es ee FO 2.55% 0.809% 
HTN: ok RA ed te Bcd sae Mdm Mal eae RIE dots 0.80% 
HOPPE. 
MNRIIONG OXUFACE 55 dec ee ese ee ese 0.87% 
Fr OOO 9 tg ee 0.49% 
Ee ee Oe, rr 0.57% 
MN RO ees athe 98d. il ard-3-9 isc ea 018 0.02% 
ese ne TE SERS = a: 0 ye 0.12% 
0 pe RNs ett rer ae 2.60% 


192 CYSTS. 


The organic substances in Kulenkampf’s case consisted of albumin 
precipitated by alcohol, 0.365%; other organic materials, 0.807%. 

There are some statements regarding the amount of albuminous sub- 
stances. In one of Kiister’s cases the amount of albumin reached 3%; 
in Wolfler’s case, 1.5%; in Tilger’s, 0.56%; in Stapper’s, 6.49%; and in 
Tremaine’s, 10%. 

Serum-albumin and serum-globulin of the proteid substances have 
been found. Littlewood noted in his case the presence of metacasein. 
In Tilger’s case peptone was said to have been present in the contents 
of the cyst. Obviously, blood pigment is found in a more or less changed 
form in the cases where 
hemorrhages had _ taken 
place. A large amount of 
mucus is exceptional. Gus- 
senbauer is authority for 
its occurrence in his case, 
which he designates a mu- 
cous cyst. 

Of other organic sub- 
stances, sugar has been 
found in rare cases: Bull, 
2.7% (diabetes) ; Tremaine, 
traces of sugar, and Gussen- 
bauer likewise. Cholesterin 
is more often found, and 
in well-formed crystals, by 
Zukowski, Wolfler, Lardy, 
Swain, v. Petrykowski, etc. 
The amount of urea is 
stated in Hoppe’s case to 
have been 0.12%. 

Leucin and_ tyrosin, 
which are rarely seen in 
the contents of cvsts, were 
found in the cases of Tilger, 
Newton Pitt, and Jacob- 
son. Jerments were not 
always present in the cystic 


Fie. 8.—Tumor of the ventral surface of the pancreas pro- contents. The cases of 


jecting into the bursa, The stomach lies in front of, the colon : : 
below, the tumor. ©, Stomach; C, transverse colon ; P, pan- Witzel, Swain, Salzer (2), 


erees} 2) colle of intestine; omental bares; 44 tet Brown, Stiller, Steeles Thy 
great omentum; 7, tumor. ersch, and Richardson were 

especially investigated with 
reference to the presence of ferments, but none were found. The three 
ferments, however, were found in the cases of Hinrichs, Subotic, 
Flaischlen, Tricomi, Richardson, Littlewood and Phulpin; they were 
present also in the secretion from the fistula in the cases of Kulenkampf 
and Richardson. 

Diastase was found in the cases of Lardy, Wolfler, Cathcart, Hersche, 
Fisher, de Wildt, Barnett, Schroeder, Martin and Morison, Schnitzler (2), 
Tilger, Kiister, Lindner, Stapper, Cibert. Trypsin was noted by Gussen- 
bauer and Stapper. Steapsin is reported in the cases of Kiister, Lindner, 
Schroeder, Tilger, Cibert. 





PATHOLOGIC ANATOMY. 193 


SITUATION OF THE CYST. 


Professor Zuckerkandl has shown in the anatomic introduction that 
tumors of the pancreas, according to their location or the surface from 
which they arise, the direction of their growth, and their size, present 
different topical relations to the neighboring organs, especially to the 
stomach, transverse colon, and liver. 








Fie. 9.—Tumor projecting into the omental 
bursa, pushing the lesser omentum forward. 
Stomach and colon lie below the tumor. J, 
Liver; M, stomach; C, transverse colon; P, 
pancreas; D, coils of intestine; N, omental 
bursa; L.h.g, ligamentum hepatico-gastricum 
(lesser omentum); ©.t, the two layers of the 
transverse mesocolon; /, posterior layer of the 


Fic. 10.— Tumor symmetrically developed 
in all directions, projecting between the pos- 
terior layer of the great omentum and trans- 
verse mesocoion. Stomach above, colon below 
the tumor. M, Stomach; C, transverse colon; 
P, pancreas; D, Coils of intestine; NV, omental 
bursa; Mt, the two layers of the transverse 
mesocolon ; h, posterior layer of the great omen- 





tum; 7, tumor. The anterior layer of the great 
omentum, which is pushed forward between the 
stomach and colon, corresponds to the gastro- 
cole ligament. 


great omentum; 7, tumor. 


To complete this consideration Professor Zuckerkand] has prepared the 
accompanying diagrams, which show the topographic relations of tumors 
of the pancreas to neighboring organs in five different ways. The 
situation of the cysts of the pancreas, which form the largest tumors de- 
veloping in the pancreas, corresponds to the accompanying diagrams. The 
third variety (Fig. 10) is found most frequently. The cyst pushes the 
gastrocolic ligament forward, the stomach lies above and the colon below 
the cyst. Smaller cysts may be found directly behind the stomach and 

13 . 


194 CYSTS. 


show no palpable projection. In figure 8 a larger tumor of this region is 
represented, as was found in Swain’s case. The cyst lay behind the stom- 
ach and contained a liter of dark brown fluid. Hersche’s case corre- 
sponded to the fifth variety (Fig. 12). ‘The colon embraced the upper 
border of the spherical tumor, which projected toward the front.” 
Ochsner also may have seen a similar relation. “The cyst-wall first 
became apparent when the omentum and intestinal coils which projected 
into the wound were pushed back.’’ The second variety (Fig. 9) was 
found in the cases of Riegner and Karewski. In the former the “gastro- 





im 
Hn 
Uh; 





Fie. 11.—Tumor of the same region, developed Fic. 12.—Tumor of the same region developed 
on one side, growth largely toward the omental on one side, growth largely downward toward 
bursa. Stomach lies above the tumor, and colon the mid-abdomen. Tumor lies below the colon 
in front of the lower portion. M, Stomach; C, and stomach. M,Stomach; C, transverse colon ; 
transverse colon; P, pancreas; D, coils of intes- P, pancreas; D, coils of intestine; N, omental 
tine; NV, Omental bursa; Mi, the two layers of bursa; L.h.g, gastrohepatic ligament; MM.t, the 
the transverse mesocolon; h, posterior layer of two layers of the transverse mesocolon ; h, pos- 
the great omentum; 7, tumor. terior layer of the great omentum; 7, tumor. 


hepatic ligament was tightly stretched by the tumor.” “After the cyst 
was evacuated, the sharp edge of the liver appeared in the upper and the 
stomach in the lower angle of the wound.”” After evacuation of the cyst, 
Karewski saw the stomach and colon ascend, and the left lobe of the liver 
appear in the wound. It is easily understood that there are many tran- 
sitions between the several varieties, and that the position of the neighbor- 
ing organs does not correspond to the diagrams in the case of very large 
tumors, which “almost fill the whole abdomen,” as in Riedel’s case. 
Salzer’s case also is atypical. The tumor began three finger-breadths 














COM PLICATIONS—ETIOLOGY. 195 


below the xiphoid process and reached nearly to the symphysis. The 
upper end of the tumor extended behind the upper portion of the stomach. 
The transverse colon surrounded the lower surface of the tumor and lay 
behind the symphysis. 

The place of origin and the direction of growth of the tumor explain the 
seat of cysts of the pancreas in the middle of the abdomen and again 
toward the side. 


COMPLICATIONS. 


Manifold complications are caused by the relation of cysts of the pan- 
creas to their surroundings. Among these are concerned the adhesions 
already mentioned. Large pancreatic cysts may cause not simply pres- 
sure upon and displacement of other organs, as the liver, stomach, colon, 
small intestine, and kidney, but may compress also the hollow structures. 
Jaundice may arise from compression of the common duct, as in the 
cases of Gross, Bécourt, Hoppe, Hjelt, Wyss, Friedreich, Dixon, Salzer, 
Gould, Stapper, Phulpin, Newton Pitt and Jacobson, Cruveilhier, Hor- 
rocks, and Morton. There was compression ,of the duodenum in the 
cases of Hagenbach and Hartmann. 

Compression of the right ureter was reported by Reeve. Dreyzehner 
observed an interesting case of axial twist of the right kidney. Ascites 
‘ from compression was observed in the cases of Battersby, Anger, Kiister, 
Tilger, and Dieckhoff. Cholelithiasis was reported by Phulpin and 
Curnow. Calculi in the pancreatic duct were seen by v. Recklinghausen, 
Goodmann, Tricomi, Dieckhoff, Clare, Gould, Michailow, and Curnow. 
An ascaris was found by Durante in the Wirsungian duct. Cirrhosis of 
the liver was seen by Hjelt, Klob, Phulpin, and Clark. | 

Rupture of a cyst of the pancreas is rare. In Pepper’s case a cyst 
of the head of the pancreas ruptured into the duodenum, and there were 
hematemesis and bloody stools. Reddingius also reports the rupture 
of a large cyst of the pancreas into the duodenum. Peabody mentions 
the rupture of a pancreatic cyst into the abdomen. 


ETIOLOGY. 


With the assumption that most pancreatic cysts are to be regarded 
as retention cysts, their etiology must be represented by the conditions 
which lead to the stagnation of secretion. It has already been stated 
that the most frequent cause of stagnation of secretion is chronic indu- 
rative pancreatitis, and mention should first be made of those causes 
which give rise to this inflammation. These are discussed in detail in 
the section on chronic. indurative pancreatitis. 

Cysts are much more rarely formed in consequence of calculi in the 
pancreas, catarrhal strictures, and compression or distortion of the excre- 
tory ducts by peripancreatic thickenings and adhesions, impacted gall- 
stones wedged in the common duct compressing the Wirsungian duct, 
and neoplasms in the pancreas or its vicinity. 

In the great majority of cases the cause of the formation of the cyst 
is obscure. Immoderate eating and drinking are frequently mentioned 
as a cause. It is possible in such cases that chronic pancreatitis leading 
to stagnation of secretion and to the formation of a cyst is caused by 
frequent attacks of gastritis and enteritis and by alcoholism. : 


196 CYSTS. 


Antecedent injury is quite often mentioned as a cause in the history 
of the cases reported. This is noted in 27 cases (Ledentu, Kulenkampf, 
Senn, Kister, Fenger, Steele, Lindner, Chew and Cathcart, Karewski 
(2 cases), Riegner, Richardson, Fisher (2 cases), Littlewood, Lloyd 
(2 cases), Barnett, Martin and Morison, Newton Pitt and Jacobson, 
Schnitzler, Brown, Lynn, Tilger, Michailow, Tobin, Eve). 


Walter Henry Brown reports a striking case. A man seventeen years old was 
well until March, 1893. After a fall from a locomotive there was a swelling of the 
abdomen. Splashing sounds were audible on shaking. On puncture, the evacua- 
tion of bloody fluid. After six weeks the puncture was repeated, with the same 
result. Well until the end of June. Then he fell from a beam, and immediately 
afterward there was severe illness with fecal vomiting. 

Present condition: Abdomen tense, markedly swollen, no passage of feces or 
gas. Urine: specific gravity 1039, small amount of albumin Laparotomyt evac- 
uation of large quantities of blood-stained fluid. Drainage. For a week quite well 
with escape of large amounts of fluid through the drain. Sudden exacerbation. 
Swelling, distention, great tenderness of the abdomen, swelling to the left of the 
median line near the navel. On the next day pains greater, vomiting, second lapa- 
rotomy. A dense cyst behind the stomach, which was pushed upward, and the great 
omentum. On puncture of the cyst, a peculiarly offensive dark fluid was evacuated. 
Its wall was stitched to the abdominal wound. Drainage. No ferment was found 
in the evacuated fluid. From that time the condition was good, the fluid flowed out 
through the drain. At times great pain, normal temperature. A week after the 
operation, pancreatic ferments were found in the fluid. Seven weeks later all the 
fluid was evacuated, condition excellent. In his remarks Brown observes that the 
case is important, because two organs, the pancreas and peritoneum, were injured. 
The fluid which was first evacuated evidently came from the peritoneum. The 
cyst of the pancreas developed slowly. 


Barnett reports a similar case: 


A man twenty-four years old after falling from a wagon suffered from dyspepsia 
and debility. After eight weeks, symptoms of a pleuritic exudation. Evacuation 
of 8 ounces of a turbid, dark fluid. This came from the peritoneum and entered 
the thoracic cavity after rupture of the diaphragm. At the end of a week an elastic, 
round tumor was found in the epigastrium. Percussion over it gave dulness. On 
aspiration 300 c.c. of an alkaline, turbid, albuminous fluid were evacuated. Re- 
newed swelling. The tumor was punctured a second time. 

The fluid last obtained contained a ferment, saccharifying starch. At the lapa- 
rotomy a cyst was found at the right of the stomach and near the stomach and liver 
and above the intestine. Cyst was sewed to the abdominal wall and drained. After 
five months the man was perfectly well and was able to resume heavy work. 


It is not easy to understand how injury can lead to cyst formation 
in the protected position of the pancreas. The great vulnerability of 
the organ, shown also in experiments on animals, and the.tendency to 
hemorrhages may here play important parts. 

_ The injury may cause the tearing of small excretory ducts and the 
escape of secretion, or cause hemorrhage, resulting in inflammation end- 
ing in the formation of scars and the contraction and constriction of small 
excretory ducts. The origin of apoplectic cysts could be easily under- 
stood if, as was earlier considered, their existence could be established. 
The occurrence of hemorrhages into the pancreas from injury are easily 
explained, and if a cyst could result from hemorrhage, the traumatic origin 
of the former is readily understood. 

It is possible that the trauma may act through the nervous system. 
Many authors advance this view. Thus, Fischer believes that, as in the 
‘Goltz experiment, a blow upon the abdomen may lead to severe nervous 
disturbances, and he explains the symmetric hemorrhages which some- 
times occur in the adrenals as the effect of injury to the sympathetic 


ia 


STATISTICS—SYMPTOMS. 197 


nervous system. He regards the fat necrosis resulting from trauma as 
a trophoneurotic disturbance. Compression of the excretory ‘ducts and 
stagnation of secretion and, therefore, cyst formation might always 
occur, according to Fischer, in consequence of such an occurrence of 
hemorrhage into the pancreatic tissue. 

It is stated that the formation of cysts takes place after infectious 
diseases, typhoid fever, influenza; and in such cases the cause has been 
sought in the action of bacillary toxins upon the gland either directly or 
through the mediation of the nervous system. 

It is obvious from the above that there is much which is hypothetic 
in the etiology of cysts, and much that is obscure still remains to be 
cleared up. 


STATISTICS. 


The following relation of age and sex is determined from the con- 
sideration of 134 cases: 


YEARS. MEN. WoMEN. 
qty TON oe eee NS Soe 8 or.5 SS ee 3+ 1 = = 4 (Railton } year) 
PWLOMEO. remade aoe pale latins sd ws 5 4= 9 
ADAG a en eine Sesh yeti A ha es Gate 10+ 21 = 31 
LEO AD, tages rag a aro ke ea a heats po) Me ame 6 ees 
ALLO OO Cees ai este wtaticn bo ees 8+ 7 = 15 
DO 10,00 Vet e ater aches 52 ayes 7+ 7= 14 
Ol OT ne ae woe ones eae aat eS ehh 0+ 3= 8 
TNA OD tas ree as nak NE Sohne cacciush nds 2+ 4= 6 
Ae NOt MV CM ee o ie Bete hia oa hes 4+ 4= 8 
60 + 61 = 121 
Neither age nor sex was given in 13 cases | 13 
134 


The number of women suffering from pancreatic cysts is, according 
to this table, scarcely larger than that of the men. Those most frequently 
diseased are between twenty and forty years of age. In men the greatest 
number is reached during the fourth and in women during the third 
decade. 


SYMPTOMS. 


Various obscure disturbances of digestion, pains, and loss of weight 
often precede for a long time the development of the pancreatic cyst. 
This may be explained by the fact that the original disease which gradu- 
ally leads to the formation of the cyst produces dyspeptic disturbances 
and pains, while the lowering of tne general nutrition is due to the 
actual disturbance of digestion. 

Chronic pancreatitis, as has already been shown, is the commonest 
cause of cyst formation, and the digestive function and the general 
nutrition must be variously influenced, according to the extent of the 
pancreatitis, the degree of the stagnation of secretion, and the resulting 
hindrance to the physiologic function of the gland. 

When the cyst has once begun, and is growing, disturbances of func- 
tion in other organs naturally arise, and the resulting symptoms are 
added to those dependent upon the affection of the pancreas. Pains 


198 CYSTS. 


are among the most frequent symptoms of cyst of the pancreas, but are 
inconstant. They may be paroxysmal or persistent, the latter especially 
when the cyst is large. They are felt either in the epigastrium, and 
then are designated cardialgias, or they may be referred to the right 
or left border of the ribs, according to the development of the cyst in the 
head or tail of the pancreas. When the pains are on the right, they are 
easily regarded as biliary colic. 

The pains may radiate in all directions into all regions of the abdomen, 
sometimes along the loins toward the sacrum, or they are sometimes 
referred to the navel. Doubtless these wide-spread pains are caused by 
the size of the tumor, and especially by the rapidity of its growth. The 
pains may occur at longer or shorter intervals as colic, and may then be 
of great severity, sufficient to produce fainting and symptoms of collapse. 
It may be questioned in such cases whether pressure on the solar ganglion 
is the cause of pain. 

It is not easily understood how such a constant, gradually increasing 
pressure should cause such severe pain only at times. As a matter of 
fact, attacks of colic very frequently occur in pancreatic cysts, and 
always represent a characteristic peculiarity of them (Leube), since a 
similar colic does not occur in other cystic tumors of the upper abdomen. 

Colic frequently precedes the dilatation of the duct of Wirsung, and 
the gradual formation of a cyst occasioned by the formation of calculi 
or other causes which temporarily or permanently obstruct the outflow 
of secretion. However, there certainly are pancreatic cysts in which the 
pains are not so violent, although they are periodic, and it is expressly 
stated in a series of cases that there is no pain at all. Violent continued 
pains may be present after the cyst has once formed. There is at times 
considerable sensitiveness to pressure over the tumor. It is to be noted, 
. however, that in many cases there is an actual lack of sensitiveness and 
of spontaneous pains especially in the region of the tumor. Conspicuous 
dyspeptic difficulties before and after the formation of thé tumor often 
occur. Not infrequently mention is made of a preceding gastric catarrh, 
nausea, morning vomiting, and anorexia. It is assumed that the process 
causing pancreatitis and the simultaneous or preceding catarrhal condi- 
tion of the stomach and intestine may be the cause of these symptoms. 
Large tumors must naturally interfere with function, especially with the 
mechanism of the stomach and intestine, and these disturbances may 
result in consequence of the size of the tumors. It is obvious that 
they are not characteristic, as similar symptoms occur in many diseases 
of the digestive tract. 

Vomiting is frequently noted in the histories of patients. At the out- 
set it occurs only at the time of the colic, as it is an accompaniment of 
biliary, intestinal, and renal colic; later it becomes more and more frequent, 
and under some circumstances may follow each meal, probably in con- 
sequence of the displacement of the stomach and intestine or by inter- 
ference with their mechanical function. The vomitus consists either of 
the food taken, or is an alkaline fluid at times bile-stained, at times 
bloody. 

Marked hematemesis also may occur, especially when a cyst filled with 
blood ruptures into the stomach or into the upper part of the intestine. 
Cysts so small as not to be palpable may perforate, as reported by 
Pepper. In a case observed in Nothnagel’s clinic, a cyst ruptured into the 
intestine some days after a liquid stool had "been evacuated, and a 


a 


SYMPTOMS. 199 


bowlful of a thin, grayish-red liquid, containing several reddish-brown 
shreds, was vomited. The reaction was alkaline. On microscopic ex- 
amination there were mucin and bacteria, but no blood-corpuscles. 

The action of the bowels is sometimes normal or there is constipation 
or diarrhea. The constipation is explicable when there are large tumors 
by the hindrance to intestinal peristalsis. The diarrhea was formerly 
regarded as characteristic. Authors have described as pancreatic diar- 
rhea, celiac flux, or pancreatic flux, the passage of thin viscous material 
supposed to consist of pancreatic juice, and have regarded it as a form 
of diarrhea especially characteristic of diseases of the pancreas (see 
General Considerations, page 99). In Nothnagel’s case above mentioned 
there were liquid stools after the disappearance of a tumor previously 
palpated, and which surely had ruptured into the intestine. 

In some cases of cysts of the pancreas there were peculiar changes in 
the stools, which certainly must have had some relation to the disease 
of the pancreas. In those of Bull, Goodmann, and Gould, fatty stools 
were mentioned as a symptom. In the case last named, there was at 
the same time jaundice. In by far the greater number of cases of pan- 
creatic cysts in which the stools have been examined—although this 
was relatively rare—it was expressly stated that there was no steatorrhea. 
It is noteworthy that there was an abnormal proteid digestion in some 
instances. Kuster found large numbers of undigested muscle-fibers in 
his case even when the amount of meat in the food was very limited. 
Riegner also found many undigested muscle-fibers in the stools. 

The displacement and compression of certain portions of the intestine 
by a large tumor may influence the condition of the stools. Slight de- 
grees of pressure may slightly diminish evacuation of the bowels (Martin), 
or, as in the case reported by Lardy, may flatten the colorless stool. There 
was complete intestinal obstruction in the cases of Brown and Hagen- 
bach and temporary obstruction in Lardy’s case. 

The jaundice appearing in cysts of the pancreas may be explained by 
the compression of the ductus choledochus by the tumor. In a case 
reported by Gould the jaundice was transitory, and may have been caused 
by a duodenal catarrh. Jaundice is not always caused by the pressure 
of the pancreatic cyst on the common duct. In the case described by 
Cruveilhier, a scirrhus situated at the exit of the common duct. caused 
both jaundice and, by closure of the Wirsungian duct, a cyst of the pan- 
creas. In the case reported by Phulpin, a gall-stone lay in the ductus 
choledochus and caused, on the one hand, jaundice, and, on the other, a 
cyst of the pancreas, by compression of the duct of Wirsung. In the 
case reported by Friedreich, also, an annular cancer of the descending 
portion of the duodenum closed the common duct, produced jaundice, 
and at the same time compressed the duct of Wirsung, which entered the 
duodenum separately from the common duct and caused its dilatation, 
with the production of numerous saccular diverticula. 

The ureter also may be compressed by a large tumor, and thus the 
outflow of urine from the kidney be prevented, as in Reeve’s case, 1n 
which the right ureter was obstructed. Ascites and edema of the lower 
extremities may result from the interference with the circulation in the 
abdomen, as in the case of all large abdominal tumors. 

Certain changes in the urine deserve especial mention, particularly 
the occurrence of sugar. Diabetes is mentioned in nine cases (Bull, 
Churton, Goodmann, Horrocks, and Morton, Malcolm Mackintosh, Nichols, 


200 CYSTS. 


v. Recklinghausen, Riegner [traces of sugar], Zweifel-Mulert). In the 
case operated upon by Zweifel there was no sugar previous to the opera- 
tion. Afterward the urine sometimes contained sugar and at times it 
was absent. There are reports from the autopsies of six of the cases. 
Nichols found that the pancreas was wholly destroyed by the formation of 
the cyst. Goodmann saw atrophy and Churton observed fibrous de- 
generation of the pancreas (see page 70). Kuster reports polyuria. 
Albuminuria is mentioned several times. 

Fever is often recorded, and may depend upon the accompanying 
diseases, peritonitis, hemorrhage into or suppuration of the cyst. Saliva- 
tion is to be mentioned among the symptoms which have been attributed 
to diseases of the pancreas. It is obviously not characteristic, because 
it has been observed only twice (Battersby, Ludolph). The interference 
with the action of the-stomach in these cases may have been of impor- 
tance in producing this condition. 

General emaciation is one of the most frequent symptoms. It occurs 
almost constantly, and is rarely noted as absent. It may be very great 
and rapidly occur. In Kister’s case the patient lost 15 kg. in four 
months. When the formation of the cyst is complicated with a malignant 
neoplasm, as in the case of Hartmann, the emaciation is not striking, and 
is sufficiently explained by the cachexia associated with the development 
of the neoplasm. The cause of the disturbance of nutrition and the 
feeling of weakness is equally obvious when there is diabetes. The 
emaciation, however, occurs in very many cases in which there is neither 
a neoplasm nor diabetes. In such cases the cause cannot be satisfactorily 
explained. It may be that in many cases, as in those of Kister and 
Riegner, a faulty proteid digestion contributes to the poor nutrition, 
but it also may be, especially in large tumors, that the interference with 
the function of other vital organs is responsible for the emaciation, or, 
as Kuster claims, the participation of the nervous system, especially 
of the celiac plexus, may exert an injurious influence on the general 
nutrition. All this, however, is at present mere hypothesis. It is certain 
that very frequently there is emaciation, and that after successful opera- 
tion there is often a rapid increase of weight and of strength. 

Among the objective symptoms, the physical conditions and the 
demonstrable tumor are especially important. The abdomen is flat 
or retracted (Hagenbach) but exceptionally, as in the case of small 
cysts. As a rule,it is more or less distended and swollen. The dis- 
tention is limited to one or another region, and eventually the entire 
abdomen is involved, according to the seat and size of the tumor. 
In far the greatest number of cases the distention takes place in the 
epigastrium. The left epigastrium, the mesogastrium, and the left hypo- 
chondrium are more frequently the seat of the tumor than the right half 
of the body, because the tail and the body of the pancreas are more 
frequently the seat of the development of the cyst than is the head. 

Large tumors may descend and occupy the meso- and hypogastrium, 
or may be found simply in the hypogastrium, as in Treves’s case, where the 
tumor lay between the umbilicus and pubes. Very large tumors fill the 
whole abdomen, as in the cases reported by Riedel, Ludolph, and Hulke. 
The distention of the abdomen from large tumors is at times uniform. 
Its circumference, under such conditions, may increase enormously, as in 
Martin’s case, in which it reached 61 inches, 

As a rule, the distention is rather localized, and the tumor projects 


a7 


DIAGNOSIS. 201 


distinctly on inspection of the abdomen. The surface of the tumor is 
generally smooth and is tensely stretched. Fluctuation is common when 
the cyst is hyperdistended, but the sense of fluctuation is indistinct and 
may even be wholly absent. On percussion over the tumor there is either 
flatness or a dull tympanitic resonance, the latter depending upon the 
situation of the tumor behind the stomach and colon. The modified 
tympanitic zone may be at the upper or lower border of the tumor or in 
both places, or over the entire tumor, according to the relations of the 
stomach and colon to the cyst. The character of the resonance may change 
according to the distention of the stomach and intestine with air and 
solid contents. The relation of the tumor to its surroundings as deter- 
mined by percussion will further be considered in the section on diagnosis. 
The tumor is sometimes movable with respiration, and in certain cases 
has been moved laterally. 


DIAGNOSIS. 


Cysts of the pancreas belong to the few diseases of that organ the 
recognition of which is possible during life. The knowledge and success- 
ful treatment of pancreatic cysts are due, above all, to surgery, which 
has reached the pancreas in its triumphal progress into the previously 
closed region of the viscera. 

“The diagnosis of the formation of a cyst in the pancreas,” says 
Friedreich, “will of course be possible only in those cases in which the 
tumor has reached a considerable size.” In 1878 he could state nothing 
of a diagnosis actually having been made during life. In 1883 Gussen- 
bauer came very near making the diagnosis of a pancreatic cyst, being 
in doubt only between a cyst of the pancreas and one of the adrenal 
gland. 

Following Gussenbauer, Senn in 1885, and in 1886 and 1887 Kister, 
Bull, and Subotic, made correct diagnoses. Wolfler was the first to 
make this in a woman. According to the published reports of cases 
at hand, the diagnosis was correctly made before an operation in 27 
instances. It must be stated, however, that it is by no means sure 
that pancreatic cysts were actually present in all these cases. In most 
of them the cyst was not extirpated, but merely drained after one or 
two incisions, and the diagnosis, as a rule, was based solely: on the fact 
that the cysts lay in the upper abdomen, did not communicate with the 
liver or kidney, and the contents were diastasic or emulsified fat. As is 
explained later, these are not positive proofs. Absolute proof is fur- 
nished only when pancreatic secretion, with all its qualities, including 
that of proteid digestion, is found; or when undoubted pancreatic Juice 
escapes from the fistula following the operation. 

An examination of the literature shows that these cysts are con- 
founded with the most diverse processes, oftenest with ovarian cysts and 
echinococci of the liver. Pancreatic cysts have been mistaken also for 
aortic aneurysms, for cysts of the peritoneum or of the retroperitoneal 
tissue, of the mesentery, of the adrenal, of the kidney, of the spleen, 
for abscesses of the abdominal wall, for echinococci of the omentum, for 
perinephritic abscess, for omental tumors, etc. The diagnosis of a pan- 
creatic cyst, then, is first to be considered when there is a palpable or 
visible tumor. Months or years may elapse between the beginning of 
the. disease and the development of the tumor, and during this time It 


202 CYSTS. 


is impossible to make the diagnosis. If in chronic pancreatitis dilata- 
tion of the gland ducts and consequent cyst formation has resulted 
from the gradual constriction of excretory ducts, then, as has been 
stated in the section on Pancreatitis, it will rarely be possible to more 
than suspect such a disease of the pancreas. An exact diagnosis beyond 
a certain degree of hypothesis, or at the most probability, will in such 
cases be wholly impossible. , 

The suspicion of a disease of the pancreas may certainly be aroused 
if there are occasional colic resembling celiac neuralgia, steatorrhea, many 
undigested muscle-fibers in the stools, or diabetes. The diagnosis of 
cyst first becomes possible when there is in the upper abdomen a visible 
or palpable tumor in which there is also fluctuation. 

The results of physical examination are important, and first of all 
palpation, which through resistance fixes the position and size of the 
tumor, and makes fluctuation evident. Percussion establishes the 
presence of dulness, tympany, or modified tympany over the tumor. 

It is important to establish the previously mentioned relation of the 
tumor to the stomach, colon, and small intestine. In order to determine 
this point, the distention of the stomach with carbonic acid is recom- 
mended, by means of the administration of tartaric acid and sodium 
bicarbonate, or with atmospheric air, and the filling of the colon with 
fluid or with air. 

The distention of the stomach with air is the most effective, as has 
previously been stated. When it is inflated with carbonic acid, the 
quantity of gas set free from the carbonated mixture cannot be accurately 
determined, while if air is used it may be introduced gradually and the 
stomach is distended slowly, thus rendering the condition much clearer. 
The intestine may easily be distended with a tube having two bulbs 
attached. 

The determination of the situation of the cyst with reference to the 
colon and stomach is one of the most important aids in diagnosis. The 
difficulty and not infrequent impossibility of a differential diagnosis is 
in many cases apparent from the numerous wrong diagnoses which have 
been made. 

The situation and size of the cyst cause it to be confounded with 
various tumors arising from other organs than the pancreas, but showing 
similar physical conditions. The following tumors situated in the upper 
abdomen are especially to be considered: echinococcus of the liver, 
spleen, mesentery, or peritoneum; hydronephrosis; dropsy of the gall- 
bladder; abscess of the abdominal wall; aneurysm of the aorta and its 
branches; soft apparently fluctuating sarcoma of the liver; cysts of the 
omentum or mesentery; cysts or collections of fluid in the omental 
bursa; cysts of the kidney or adrenal bodies. 

Many of these possibilities of error may be avoided by greater care 
in examinatron. Thus, aneurysm of the aorta or its branches, abscess 
of the abdominal wall, peritoneal tumor, or sarcoma of the liver may 
easily be excluded. The chief difficulty lies between echinococcus of 
the liver and cyst of the pancreas, since echinococci of the spleen, peri- 
toneum, and omental bursa are very rare. In this case percussion may 
decide, but it must be tried both in the recumbent and upright positions 
of the patient. When the stomach is inflated, it will lie in front of the 
pancreatic cyst, while in echinococcus of the liver, especially of the left 
lobe, the stomach, as a rule, lies behind the tumor. In many but not in 

. 


DIAGNOSIS. 203 


all cases it will be possible to find between the liver and the cyst a tym- 
panitic area which becomes diminished on deep inspiration. , 

The mobility of the tumor is of uncertain value in the differentiation, 
as pancreatic cysts also may be movable with respiration. If the patient 
is examined in the upright position, it may happen, as Kiister suggests, 
that the cyst will descend, and then it may be possible to recognize a 
distinct tympanitic area between the liver and the cyst, which could not 
be ascertained when the examination was made in the recumbent position. 

Puncture, which, however, is certainly not entirely free from danger, 
permits more exact differentiation between echinococcus of the liver 
and pancreatic cyst. Other cystic tumors of the liver do not attain so 
large a size, for cystic enlargements of the bile-ducts are small; hence 
puncture with the Pravaz syringe, recommended especially by Kiister, 
may clear up the diagnosis. Other surgeons also consider that puncture 
in these cases is not wholly free from danger, because echinococcus 
fluid or pus, even if there is suppuration of the echinococcus sac, may 
possibly flow into the peritoneal cavity. 

Karewski considers exploratory puncture dangerous, because other 
organs may be injured. In one of his patients he penetrated the 
stomach in spite of the fact that he was able to prove the presence of the 
stomach above the cyst. The stomach was pressed flat between the cyst 
and the abdominal wall, and only a small portion of it lay above the 
cyst. A possible puncture of the colon would not be wholly free from risk. 
Kuster, on the contrary, regards the danger of exploratory puncture 
as very slight, since the escape of echinococcus fluid and pancreatic 
secretion causes only temporary disturbances. 

According to my humble opinion, an operation should be undertaken 
whether there is an echinococcus cyst or one arising in the pancreas, 
because the operation will first definitely decide the nature of the cyst. 

The examination of the contents of the cyst in echinococcus of the 
liver shows clear watery fluid, free from albumin, in which on microscopic 
examination there are either hooklets or at least an absence of all morpho- 
logic elements, which likewise is to be regarded as characteristic. If, 
however, the echinococcus is sterile and the sac contains pus, the presence 
of hooklets indicates the existence of an echinococcus. Puncture may 
decide also between a cyst in the tail of the pancreas and echinococcus 
of the spleen. Other cystic tumors in the spleen are very rare, although 
Kiister found in it a cavity larger than the fist. 

The distinction between pancreatic cyst and hydronephrosis is diffi- 
cult, and in many cases is first made evident by the examination of the 
liquid contents. The history at times may give a clue. Hydronephrosis 
should first be thought of if there are renal colic, lumbar pain in the 
vicinity of the tumor, and urinary difficulties, or the previous escape of 
renal concretions or a characteristic condition of the urine. 

If the fluid at the operation is due to hydronephrosis, the sediment 
will contain epithelium from the calices or pelvis of the kidney. The fluid 
will also contain urea, which is rarely absent, and then only late in the 
disease; also uric acid and so-called mucin and metalbumin or par- 
albumin (Senator). Pancreatic-cysts may be confounded also with 
chylous cysts or cysts of the mesentery. Chylous cysts, according to 
Kiister, seldom, if ever, lie above the navel, since they correspond to the 
position of the receptaculum chyli just above or just below the umbilicus. 
~ Mesenteric-cysts are characterized by great mobility, which is lacking 


204 CYSTS. 


in cysts of the pancreas. As Hochenegg states, the mesenteric cyst which 
is seated somewhere in the vicinity of the navel may so be pushed upward 
as to disappear completely beneath the costal cartilages, and downward 
as far as the entrance to the pelvis. Pancreatic cysts never show such 
a degree of mobility. The large cysts which almost entirely fill the 
abdomen are echinococcus cysts of the liver and ovarian cysts. The 
means of differentiating the former have already been stated. The 
presence of a tympanitic area between the liver and tumor is in favor of 
a pancreatic cyst. 

The confusion between pancreatic and ovarian cysts is most frequent 
and most easily understood. An ovarian tumor is usually first thought 
of in consequence of its greater frequency and the relative rarity of cysts 
of the pancreas. The history in such cases aids in the distinction, and | 
women can often state where the tumor appeared first. The prominence 
of pancreatic cysts is above the navel, a position which contraindicates 
an ovarian tumor. Thorough, careful percussion in different positions 
of the body permits the recognition of even very large ovarian tumors, 
according to the experience of Kiister. ‘Large ovarian tumors fill at 
least one iliac fossa so completely that there is no tympanitic resonance 
below the tumor. On the other hand, they rarely reach so near the 
liver and diaphragm that it is impossible to recognize a tympanitic area 
above them. Nevertheless, it would scarcely happen that a pancreatic 
cyst descending from the upper abdomen would so completely fill only 
one side of the pelvis that no tympanitic zone could be distinguished 
between the upper border of the pubic bone and the tumor. But 
when it is suspected that there may be a pancreatic cyst, the inflation 
of the stomach with carbonic acid offers an excellent means of dis- 
crimination; for the stomach must lie in front of the pancreatic cyst, 
while the ovarian cyst must crowd it backward.” 

The examination of the fluid from the cyst permits the distinction 
in many but not in all cases. The objections to exploratory puncture 
with the Pravaz syringe have already been stated. Disagreeable results 
may follow the escape of pancreatic fluid, or the contents of a suppurating 
cystoma of the ovary, or the epithelial contents of a dermoid cyst. The 
last-mentioned tumors rarely become so large as to be confounded “ 
cysts of the pancreas. 

The value of the examination of the cyst fluid has been Sreteatiaiat 
by many. The contents of undoubted pancreatic cysts may, during 
their long continuance, undergo such changes after prolonged retention 
that they present none of the specific peculiarities of the pancreatic 
secretion. But even when certain characteristics are present, they prove 
nothing. Great weight has formerly been placed on the diastatic ferment, 
but this has proved erroneous. Von Jaksch found small quantities of a 
saccharifying ferment, at times transforming starch, in ascitic fluid and 
in the contents of abdominal cysts of other origin than the pancreas. 
It must be proved at least that the fluid after the addition of starch not 
only possesses reducing qualities, but maltose must be formed, for other 
diastatic fluids do not change starch to maltose (v. Jaksch). 

The diagnostic value of the frequently mentioned emulsifying quality 
is not much more satisfactory. It is undoubtedly absent in many pan- 
creatic cysts, but, as Frerichs has already stated, a slight emulsifying 
action on fats may be possessed by other cystic fluids of alkaline reaction 
and by transudates. 


DURATION AND COURSE. 205 


The presence of trypsin in the fluid is the real test and this is often 
absent in the contents of pancreatic cysts. 

If a fistula results, the secretion may represent pure pancreatic fluid, 
even if the fluid escaping at the time of the operation has none of the 
physiologic qualities of the pancreatic secretion. The presence of blood 
in the contents of the pancreatic cyst is, as Kiister states, an important 
diagnostic sign. Hemorrhagic contents occur only in an ovarian cystoma, 
with a twisted pedicle, but such tumors are relatively small, and do 
not extend to the upper abdomen (Kister). There are, however, enough 
pancreatic cysts in which there is no blood. 

Kuster regards the presence of fat granular corpuscles as charac- 
teristic of pancreatic cysts, but, as Karewski asserts, these may be 
absent. On the other hand, fat granular corpuscles may be found as 
the product of fatty degeneration of epithelium even in the contents of 
an ovarian cyst. | 

In spite of the above-mentioned numerous means of diagnosticating 
pancreatic cysts there is at times difficulty in making a diagnosis, which 
in many cases is first positively established after the operation or at a 
postmortem examination. 


DURATION AND COURSE. 


The statements widely differ regarding the time between the appear- 
ance of the first symptoms of a pancreatic cyst and the period when it is 
first seen, diagnosticated, and operated upon. Doubtless there are acute 
cases, while, on the other hand, the process very frequently extends 
over a period of vears. The onset can rarely be stated with certainty, and 
is possible only when it follows injury. In all other cases no positive clue 
to the beginning of the process can be drawn from the vague statements 
of the occurrence of colic, disturbances of digestion, pain, etc. If, as in 
most cases, chronic pancreatitis must be regarded as the cause, the 
beginning of the disease is naturally obscure and only approximately to 
be determined. 

Cysts may develop very rapidly after trauma. In Littlewood’s case 
an epigastric swelling occurred thirteen days after the kick of a horse. 
Three weeks after a trauma, Kulenkampf found a painful tumor in the 
epigastrium. In Fisher’s case fever, hematemesis, melena, and a small 
tumor developed a few days after a fall from a wagon; three weeks 
later an operation was performed. Ina boy two years old whose case was 
reported by Lynn, there was collapse and vomiting after the child was 
run over; three weeks later a swelling of the abdomen was noted. 

In contrast with this rapid development, there are certainly many 
cases in which the cysts have existed for years. In such, the growth 
is often periodical after being quiescent for a long period, or the enlarge- 
ment is very slow. Pregnancy causes no increase in size (Mayo). 

The assertions concerning the long duration are naturally to be 
accepted with considerable hesitation, because the physician can depend 
only on the statements of the patient, which cannot be further controlled. 
Thus, Hulke reports the existence of a tumor since childhood in a woman 
forty-seven years old. That a cyst may last sixteen years is definitely 
established by Martin. The first operation was performed in 1873 and 
an irremovable tumor was found behind the large intestine and meso- 


206 CYSTS. ; 

colon. In 1889 the abdomen increased rapidly in size and an operation 
was performed. In the case observed in my hospital and reported by 
Salzer, the cyst had certainly existed for twelve years.. A woman thirty- 
five years old, operated upon by Clutton, is said to have had a tumor in 
the left side of the abdomen for twenty years. In most cases one to 
three years elapse between the first symptoms of the disease and the time 
when the cyst was observed. 


PROGNOSIS. 


Pancreatic cysts may come to a standstill, and are then sometimes 
found unexpectedly at a postmortem examination. In very rare cases 
the cyst may rupture into one of the neighboring hollow organs, as the 
stomach, with consequent hematemesis, or into the intestine with subse- 
quent hemorrhagic stools or the evacuation of watery alkaline contents. 
If such a communication between the cyst and intestine exist for some 
time, there may be a thoroughly characteristic rise and fall in the size of 
the tumor, and the latter may wholly disappear at times, but at the next 
examination be again distinctly palpable. Operation exercises the most 
favorable influence upon the course. 


- TREATMENT. 


Nothing is to be expected from the internal treatment of pancreatic 
cysts. The formation of the cyst cannot be avoided even when its most 
frequent cause, chronic interstitial pancreatitis, can positively be diag- 
nosticated. The progress of the disease perhaps might be influenced by 
a timely treatment if there were positive indications that the condition 
was caused by gall-stones or syphilis. 

The great advance of surgery has included the pancreatic cyst in its 
field of successful treatment. Fifteen years ago Gussenbauer first intro- 
duced an effective means of operating and was successful, and now the 
number of cases of recovery increases from year to year. One hundred 
and one operations with 81 recoveries are to be found in 134 cases. 
Although it is by no means sure that in all of these pancreatic cysts 
were present, yet the facts mentioned must be accepted, and there is no 
doubt that the percentage of recoveries will become far more favorable 
as the method of operation is now quite well established and it is unneces- 
sary to make any new experiments in this direction. 

The following methods of operating have been employed: (1) Simple 
‘puncture; (2) Récamier’s procedure; (8) total extirpation; (4) partial 
extirpation with subsequent drainage; (5) incision in two operations. 

with drainage; (6) single incision with drainage. 7 

1. Puncture was undertaken 7 times with 5 fatal results. 


Dixon, simple puncture; Hagenbach, laparotomy, puncture, death from 
“jleus”; Horrocks and Morton, puncture and aspiration; Lloyd, puncture; Railton, 
puncture twice, the first time with aspiration and the second time with drainage; 
Lynn, puncture with aspiration, recovery; Stiller, exploratory puncture, recovery(?). 


_ 2. Récamier’s procedure was tried but once; then by Ledentu. At. 
- intervals of two to three days the cyst was cauterized five times with 
caustic potash; perforation then took place at the base of the eschar; 


TREATMENT. 207 


after two and a half days, death from peritonitis. The stomach was opened 
by the cauterization. 
3. Total extirpation was performed 11 times, two being fatal. 


Recovery in the cases of Bozemann, Cibert, Clutton, Eve, Heinricius (2 cases), 
Martin, Schroeder, Zweifel. Death in the cases of Riedel and Salzer. ; 


4. Partial extirpation 12 times with 4 fatal results. 


Recovery in the cases of Filipow, Emmet Giffin, Hersche, v. Petrykowski, 
Schroeder, Tobin, Trombetta, Zawadzki. Death in those of Hulke, Kootz, Ludolph, 
and Zukowski. 


5. The incision in two operations was performed 12 times, one proving 
fatal (diabetes). 
Recovery in the cases of Albert (2 cases), Annandale, Dreyzehner, Fenger, 


Finotti (2 cases), Kulenkampf, Steele, Subotic, Thiersch. Death from diabetes in 
Bull’s case three and a half months after the first incision. 


6. The single incision was performed 58 times with death in seven 
(but independent of the operation in four). 


_ Recovery in the cases of Agnew, Ashhurst, Barnett, Brown, Chew and Cathcart, 
Dieckhoff, Flaischlen, Fisher (2 cases), Goiffey, Gould (2 cases), Gussenbauer (3 
cases),* Herczel, Hinrichs, Holmes, Karewski (2 cases), Kramer, Kuster, Lardy, 
Lindner, Littlewood, Lloyd, Ludolph, Martin, Mayo, Mumford, Newton, Ochsner, 
Osler, McPhedran, Richardson (2 cases), Riedel, Riegner, Schnitzler (2 cases), Senn, 
Swain, Schwarz, Stapper, Thoren, Tremaine, Treves, Tricomi, de Wildt, Witzel, 
Wolfler. Death in the cases of Churton: second laparotomy on account of collection 
of pus behind the stomach, Durante; two days after the operation uncontrollable 
vomiting, Gould; peritonitis, Hartmann; death from cancerous cachexia seven 
weeks after the operation, Reeve; death from “fever” three months after the opera- 
tion, Savilli; spontaneous rupture of a pancreatic cyst, puriform infiltration behind 
the pancreas, laparotomy, suture of the sac, death in collapse; Schwarz, sepsis. 


The method which is now chiefly used and the details of which are 
given by Gussenbauer is the completion of the operation at once, the 
wall of the cyst being stitched to the abdominal wound and the cavity 
drained. 


Appendix.—There are but few observations regarding the occurrence 
of echinococcus in the pancreas. Claessen mentions several doubtful 
eases of Chambon de Montaux, Portal, and Engel. Heller states that 
echinococcus occurs rarely in the pancreas, and cites the case of Seidl. 
Tricomi asserts that seven cases are noted in the literature, but does not 
mention any of them. According to Nimier, Briggs extirpated an 
~ echinococcus sac which had undergone sarcomatous degeneration. Hook- 
lets had been found in the fluid obtained by puncture. 





VI. HEMORRHAGE. 


Hemorruace into the pancreatic tissue occurs relatively often. This 
statement, however, applies only to slight punctate hemorrhages, such as 
occur in diseases of the heart, lungs, and liver, as manifestations of stasis, 
in hemorrhagic diathesis (scorbutus, purpura, morbus maculosus Werlh.), | 


* A fourth case of successful operation by Gussenbauer was omitted by mistake. 


208 HEMORRHAGE. 


eclampsia (Schmorl, Lubarsch), phosphorus-poisoning, acute exanthemata 
or other infectious diseases, and in various inflammatory processes in 
the pancreas itself. 

In acute and chronic pancreatitis the hemorrhages are either fresh, 
often microscopically minute, or, if old, are evidenced by round or oblong, 
small, pigmented foci or spaces and gaps, which are filled with a more or 
less discolored serous fluid and are limited by dense, rust-colored walls 
which project toward the interior (Klob, Friedreich). The ready occur- 
rence of hemorrhage into the pancreatic tissue may be due to the anatomic 
structure of the organ and its vessels. Klebs seeks for the cause of the 
hemorrhages in the corroding action of the pancreatic secretion, and Fitz 
calls to mind the fact known to anatomists that when the arteries are 
injected, the fluid used easily escapes from the pancreas—a result which 
may, to be sure, as Dieckhoff suggests, be due to postmortem changes. 

Pancreatic hemorrhages easily occur, as already mentioned, in different 
experiments on animals, as total or partial extirpation, and artificially 
produced inflammations. 

Large hemorrhages into the pancreas may, at times, in spite of their 
extent, be only incidental and without essential influence on the course 
of the disease and the final outcome. They are then generally con- 
nected with extravasations of blood in other organs, and are results of 
severe circulatory disturbances. Doubtless such a condition would be 
much more frequently discovered and would be better known if the 
reports of autopsies relative to this matter were published. 

In the reports of postmortem examinations in 1894 at the General 
Hospital in Vienna, two cases of hemorrhage in the pancreas are noted 
—one from aortic insufficiency, the other in emphysema. To the cases 
of this kind mentioned in literature belongs that reported by Ger- 
hardt-Kollmann, relating to a woman forty-seven years old, who died 
with emphysema, diffuse bronchial catarrh, anasarca, ascites with evidence 
of a high degree of stasis, and marked cyanosis. 


At the autopsy the peritoneum over the convexity of the duodenum was 
found suffused with a considerable hemorrhage. Less extensive hemorrhages were 
found between the individual pancreatic lobules, while the retroperitoneal tissue 
behind the pancreas as far as the hilus of the spleen was infiltrated with blood. There 
was a group of smaller ecchymoses in the large intestine behind the cecum. 


The emphysema in this case is doubtless to be regarded as the cause 
of death, and the pancreatic hemorrhage as a secondary result of stasis. 
Kollmann reports a similar case in which a patient with mitral stenosis 
and left-sided pleuritic exudation died suddenly. 


At the autopsy the peritoneum was found suffused with blood in the region of the 
pylorus in consequence of a subperitoneal hemorrhage. The mucous membrane of 
the stomach, markedly injected, showed small. ecchymoses in two places, while the 
mucous membrane of the duodenum was suffused with blood along the convexity; 
the hemorrhagic infiltration extended from the curvature of the duodenum into the 
retroperitoneal tissue along the pancreas to the hilus of the spleen. The tail of the 
pancreas was hyperemic and showed a larger amount of hemorrhage than the head. 
The appearance of the pancreas gave no evidence of fatty degeneration. The 
semilunar ganglion was found entirely surrounded by the hemorrhagic infiltration: 


It is probably impossible to decide whether in this case the sudden 
death is to be ascribed to the diseased heart or to the pancreatic hemor- 
rhage so affecting the semilunar ganglion as to have caused an arrest of 
the function of the heart by reflex action. | 


ETIOLOGY. 209 


The communication of Rehm probably belongs under this head: A 
female mill operative thirty-seven years old was choked by a man and 
died a short time afterward. At the autopsy extravasations of blood 
from the size of a bean to that of a hazelnut were found in the connective 
tissue around the head of the pancreas, in the peritoneal covering of the 
diaphragm, and over the left kidney. Rehm attributed the death to 
suffocation from throttling, while Zenker, who made a report on the same 
case, regarded the hemorrhage into the pancreas as the cause of death, 
by its reflex influence on the nerve plexus there situated. Reubold sup- 
ported Rehm’s view, regarding the death as due to the throttling, and 
reports an analogous case: A man fifty years old hanged himself in prison. 
At the autopsy the middle third of the pancreas was dark red; the gland- 
lobules of the same portion contained numerous punctate hemorrhages, 
and from 6 to 10 separate spots could be distinguished in each lobule; there 
were larger hemorrhagic infiltrations between the lobules. 

Reubold also reports two cases in which there were hemorrhages 
into the pancreatic tissue, the one of morphin-poisoning and the other of 
bleeding to death. All the organs of the latter patient were found blood- 
less, but there was quite a large hemorrhagic infiltration of about one-third 
of the head of pancreas; there were a few ecchymoses also in the stomach. 
Large pancreatic hemorrhages have been observed also in other cases of 
extreme anemia; thus, in a puerpera observed by Lawrence, possibly a 
case of pernicious anemia, as held by Seitz, the pancreas was of a uniform, 
deep, dark red color, and from the outside felt dense. Large hemor- 
rhages affecting the pancreas alone are of much greater interest, and, 
at times, involve the whole organ and the surrounding tissue, and are 
the actual cause of death. They are not very rare, Dieckhoff having 
collected 62 such cases. 


ETIOLOGY. 


The causes of the hemorrhage can be established in but a few cases. 
The following factors are to be considered, most of which are based upon 
the able publication of Seitz. 

1: Disease of the blood-vessels (atheroma, fatty degeneration, 
alteration of the vessel-walls from alcoholism, syphilis, etc.) is to be 
regarded as the most frequent cause. The anatomic structure of the 
pancreas, already mentioned, favors the rupture of atheromatous vessels. 
Fitz includes among these anatomic factors the presence of numerous 
small vessels immediately influenced by the powerful aortic pressure, 
the great variation in their fulness in consequence of the action of the 
diaphragm and abdominal muscles, the stasis caused by the variations 
’ in the distention of the stomach and intestine, and, finally, the slight 
- counterpressure from the surrounding tissue, almost wholly composed of 
glandular cells. 

The following cases serve to illustrate the course: 


The second case of Prince: A woman sixty-five years old, much addicted to 
liquor; fell down-stairs while intoxicated, then went out and came home drunk. At 
daybreak she was found dead. The autopsy showed atheroma of the middle cerebral 
artery, also of the coronary arteries, and slight mitral stenosis. The subperitoneal 
tissue about the pancreas was moderately infiltrated with fresh blood. The tissue 
of the gland showed marked hemorrhagic infiltration throughout the whole organ, 
especially in the head. 

Draper: Sudden death from pancreatic hemorrhage. A woman forty-four 


14 


210 HEMORRHAGE. 


years old was found dead in her bed. She drank alcoholic liquors, but was rarely 
intoxicated, and the evening before was perfectly well. In the morning she com- 
plained of headache, returned to her bed, and later was found dead. At the autopsy 
the pancreas was seen infiltrated with blood throughout its whole extent, there was a 
moderate amount of blood in the retroperitoneal tissue, and eight ounces of reddish 
fluid in the peritoneal cavity. 

Draper: Duration of the illness three-quarters of an hour; death from pan- 
creatic hemorrhage. A type-setter thirty-one years old, intemperate, was attacked 
while in perfect health with sudden pains in the epigastrium, nausea, collapse, and 
died forty-five minutes later. The autopsy showed the pancreas and surrounding 
tissue infiltrated with blood; the heart was friable, the intima of the aorta showed a 
pre-existing endarteritis, the splenic artery was tortuous, its intima rough and of a 
finely granular appearance. On microscopic examination of the pancreas the gland 
cells appeared granular, and there was blood in the interlobular tissue. 


Seitz includes in this series the cases of Draper (three besides those 
mentioned), of Reynolds and Gannet (in a corpulent man sixty-six 
years old), of Williams (in a man seventy years old with peripheral 
arteriosclerosis), of Challand and Rabow, Whitney and Homans, Putnam 
and Whitney, Driver and Holt. 


Driver and Holt: Slender man, fifty-eight years old, awakened with severe 
abdominal pains, vomiting, great exhaustion. Pale, pulse very weak. Death in 
thirty minutes. The duodenal half of the pancreas was bluish-red, in strong contrast 
to the yellowish-gray splenic end. The darker part was infiltrated with blood, which 
lay in the interlobular tissue and could bé easily scraped from the cut section. 


Seitz regards the observation of Fearnside as a case of pancreatic hem- 
orrhage from uremic vascular sclerosis in atrophy of the kidney: 


A farmer forty-nine years old, not especially large, had for a year frequent deeply 
seated pains in the region of the stomach with emaciation, and for three months 
numerous and violent attacks of pain. Three days before death he had a sudden 
attack of fearful pain with fainting and vomiting of dark-brown fluid, and the next 
day jaundice developed. Hiccough, abatement of the pain. On the day of death 
Fearnside noted collapse, distention of the abdomen, and a deep-seated tumor be- 
tween the xiphoid process and the umbilicus. At the autopsy it was found that the 
tumor felt during life was formed by the pancreas. The: enlargement involved the 
entire organ, especially the right end of the gland, which was brownish-black and 
almost completely changed into a pap-like, pulpy mass. . 


The case shows also how many interpretations may be placed upon 
such observations. Seitz thought it possible that the case was one of 
pancreatic hemorrhage in consequence of uremic vascular sclerosis, be- 
cause the kidneys were small, indurated, and with an ill-defined cortex. 
Fearnside regarded chronic pancreatitis as the cause, and Fitz thought 
that a hemorrhage had taken place into a malignant tumor of the pan- 
creas. 

Seitz reports an original observation in which he attributed the sud- 
denly fatal pancreatic hemorrhage to syphilitic changes in the vessels. 


A muscular man twenty-eight years old was suddenly attacked with abdominal 
pain, and collapse soon followed. Vomiting, fainting; after six hours, death. At 
the autopsy a large collection—some 2 quarts—of blood was found in the peritoneum. 
Tissue between the stomach, duodenum, transverse colon, spleen, and pancreas was 
extensively infiltrated with blood. The bleeding point could not be located exactly, 
but probably one of the branches of the celiac axis had ruptured. The pancreas 
appeared perfectly normal, except for the hemorrhagic infiltration which had 
penetrated into the connective tissue between the lobules and only sparingly into the 
lobules. Seitz suspected that the case was one of syphilis, because the patient had 
undergone syphilitic treatment on account of chronic iritis and opacities of the 
vitreous body. On microscopic examination, Seitz found an endarteritis of the 
branches of the celiac, which extended into the surrounding glandular tissue and 
formed a small-celled tumor, Seitz regarded syphilis as the only explanation of this 
‘process. 

v 


ETIOLOGY. 211 


2. Fatty degeneration of the gland-cells and excessive fatty 
infiltration of the pancreas are to be considered as the cause of the 
hemorrhage in a number of cases. There may be also fatty degeneration 
of the vessel-walls and consequent ease of rupture. On account of the 
fatty degeneration of the gland parenchyma, the blood-vessels lose 
their support, can no longer sufficiently resist the blood-pressure, and 
rupture. The changes affect mostly the smaller vessels, but the larger 
ones also may be involved in the lesion. 

Alcoholism, general adiposity, and marasmus lie at the bottom of the 
process. It is doubtful whether there is not probably a primary disease 
of the pancreas as a cause for the obesity. It is certainly conceivable 
that at a certain stage in disease of the pancreas before there is diabetes 
an excessive development of fat may take place in accordance with the 
recognized relations between diabetes and obesity so clearly established 
by von Noorden. 

Bauer (Ziemssen’s clinic) reports an appropriate communication: 


Enormous fatty degeneration of the pancreas, old and recent hemorrhages. 
There was a spot resembling an ulcer in the head of the considerably enlarged pan- 
creas, and which seemed to have broken through the peritoneum and caused hemor- 
rhage in it. Peritonitis. 


Fatty degeneration of the gland and compact capillary hemorrhages 
occurred also in the case reported by La Fleur of a man fifty years old 
who had suffered from digestive disturbances for several years and was 
suddenly attacked by violent pains in the stomach, vomiting, and died 
in collapse. 


In the case of Hooper: Sudden violent pain, vomiting, and collapse after fre- 
quently recurring gastric disturbances—“ biliary attacks.”’ Sickness lasted two days. 
At the autopsy, small extravasations of blood were found in the gland-follicles 
throughout the pancreas. Fatty degeneration was regarded as the cause of the 
hemorrhage (Seitz). 


Zenker reported three cases of pancreatic hemorrhage with sudden 
‘death. In all three there were fatty degeneration and extreme hemor- 
rhagic infiltration of the pancreas. Zenker did not regard the loss of 
blood as the cause of death, but believed that the influence of nerves 
was to be thought of, as in Goltz’s experiment, in which repeated blows 
on the abdomen of frogs gives rise to diastolic cardiac paralysis. Zenker 
supported this view by the fact that he had found in two cases very 
striking venous hyperemia of the solar plexus with perfect integrity of 
the ganglion cells and nerve-fibers. Friedreich opposed this hypothesis 
by the statement that no mention was made in Zenker’s case of the 
hyperemia and dilatation of all the vessels in the abdomen constantly 
observed in Goltz’s experiment, and therefore must have been absent. 
He offers “as a cause of the fatal apoplexy an irritation of the semilunar 
ganglion and the solar plexus from pressure due to the rapid hemor- 
rhagic swelling of the pancreas,’ and “a consequent reflex disturbance 
_ of the heart (reflex paralvsis?).” 

Recent communications have been made by Sticker and Kotschau. 
The former observed in a woman seventy-eight years old the occurrence 
of sudden death with violent colic-like pains a short time after she had 
suffered from vomiting, diarrhea, and pain in the left hypochondrium. 
Although there was no autopsy Sticker explained the symptoms in 
accordance with a second case observed by him. 


212 HEMORRHAGE. 


A very fat woman, twenty-four years old, suffered from attacks of dyspnea, 
palpitation, and cramps in the stomach, in one of which death occurred. At the 
autopsy the liver was found much enlarged and fatty, and there were fresh hemor- 
rhages in the center of the pancreas and a large infarction in its vicinity. The pan- 
creas appeared transformed into a large mass of fresh blood which had forced the 
tissue apart and to a certain extent had disintegrated it. The ductus Wirsungianus 
was indicated only by a red thrombus of the size of the little finger, which extended 
to the papilla Vateri. 


Sticker did not regard the simple fatty condition of the pancreas and 
its surrounding tissues as the sole predisposing cause of the hemorrhage, 
since he had never seen anything similar in other organs. He thought 
rather that the pulling and tearing of the pancreas by the excessively 
fat mesentery, increased by the movements of the body, easily gave 
rise to interruptions of continuity in the pancreas and caused hemor- 
rhage. The hemorrhage spread more and more in consequence of the 
advancing fatty change. The occurrence of the colic indicated a renewal 
of the hemorrhage. 

Kotschau saw a woman twenty-four years old who was attacked by frequent 
cardialgic pains. On physical examination nothing abnormal wasfound. The pains 
ceased after an injection of morphin. The next night the patient complained of 
nausea, tension, and a feeling of fulness in the abdomen, collapsed quickly, and died 
the same night. The patient was accustomed to liquor. At the autopsy all the 
internal organs were extremely fatty, there were numerous fat necroses in the peri- 
toneum of the intestine, and abundant ecchymoses in the mucous membrane of the 
stomach. The liver and kidneys showed extreme fatty changes. There were several 
calculi in the gall-bladder. The heart was fatty to a marked degree. The pancreas 
lay behind the stomach as a black, structureless mass, tensely filled with blood and 
as large round asaman’sarm. Kotschau also regarded the traction on the pancreas 
of the root of the mesentery and the fatty intestines as the source of hemorrhage. 


3. Fat necrosis in the gland or in its vicinity is mentioned by many 
authors as the cause of pancreatic hemorrhage. Balser first attracted 
attention to the importance of this after an analogous condition in the 
bone-marrow had been shown by Ponfick. According to Balser, such a 
hyperplasia of young fat cells may occur in certain places in very fat 
individuals. Even in the marantic a surrounding inflammation may. 
occur through which the blood-vessels are affected. Various degrees 
of hemorrhage may be the consequence. 

Balser reports three similar cases. ; 

The first case was that of a very strong fat woman, thirty-two years old, who was 
attacked by violent vomiting and severe pain in the loins and back four weeks before 
her entrance into the hospital. Fever, pain in the head, extraordinary swelling of the 
body, dyspnea. Sudden death in five days. At the autopsy there were found areas 
of fat necrosis from the size of a pea to that of a bean. A cavity was formed similar 

to an abscess by the adhesion of the transverse mesocolon to the mesentery, and it 
contained a liter of fluid, in which were bits of necrotic fat tissue of different size. 
The dead portions of fat tissue were often surrounded by a hemorrhagic zone of rust- 
red to dark-brown color. The pancreas lay in the cavity. 


The appearances in the other two observations of Balser were similar, 
but the hemorrhage in the pancreas was much more intense. 

In a case reported by Gerhardi, the hemorrhage was so great that | 
an enormous swelling of the pancreas resulted, and in consequence 
compression and obstruction of the duodenum developed. In this case 
_ also the microscopic examination showed that there was necrosis of the 
fat tissue with hemorrhage into the surrounding tissue. Similar com- 
munications regarding cases of fat necrosis with hemarrhage have been 
presented by Konig, Marchand, Pinkham and Whitney, Guillery, Hirsch- 


ETIOLOGY. 213 


berg, and more recently by Simon and Stanley, Cutler (2 cases), Sarfert 
(3 cases), Parry, Dunn, and Pitt and Rachmaninow. It must be stated, 
however, that in these cases the causal relation between the fat necrosis 
and the hemorrhage is not established (see section on Fat Necrosis). 


A case observed by Simon and Stanley, and regarded as hemorrhage of the pan- 
creas, was that of a woman sixty-three years old. For five days there had been pain 
and distention of the abdomen, slight Jaundice, and later the vomiting was fecaloid 
and dark-brown. Two years before there had been, it was claimed, a similar attack. 
Laparotomy was performed on account of symptoms of intestinal obstruction. No 
occlusion was found. Death occurred a short time afterward. Autopsy: Body 
very fat, fat necrosis of the peritoneum. Pancreas much enlarged, infiltrated with 
blood, and showing fat necrosis. ‘There were hemorrhages also toward the pelvis. 
The adhesions found depended perhaps on the earlier attack. 

In a case reported by Cutler as “ hemorrhagic pancreatitis,” the patient was a 
woman fifty-two years old, and had 6.1% sugar. Disease lasted six days. 

Sarfert’s first case (“apoplexy of the pancreas’’) was that of a man thirty-nine 
years old, who, after carrying a heavy load, was suddenly attacked by pain in the left 
side of the abdomen. Nausea and retching. In the night, repeated vomiting, 
gradual swelling of the abdomen, constipation. On admission: Collapse, dyspnea, 
pulse scarcely perceptible; temperature 37.8° C. (100.04° F.), palpation painful, espe- 
cially in the region of the stomach, where was a dense resistance on deep pressure. 
Hiccough, vomiting. Diagnosis: Ileus, internal strangulation. Laparotomy: In- 
testine dark-blue, distended, no incarceration; death after the operation. Autopsy 
two hours after death. Pancreas double in size, infiltrated with blood, and trans- 
formed into a mass resembling the spleen. Numerous fat necroses in the mesentery, 
omentum, and peritoneal fat tissue. Urine obtained after death contained 1% 
sugar. 

In the case of pancreatic hemorrhage reported by Parry, Dunn, and Pitt, there 
were symptoms of intestinal obstruction in a man sixty years old. Laparotomy. 
Death four hours later. At the autopsy numerous small white or orange-colored 
areas of fat necrosis were found not far from the pancreas. ‘This organ large, indu- 
rated, and on section infiltrated with blood. . 


4, Hemorrhages in pancreatic cysts are not uncommon. In the 
section on Cysts this condition was thoroughly considered (pages 186 
and 190). 

5. Cases of hemorrhages from the disintegration of neoplasms 
have been reported by Cash and Huber. 


The first case was that of a woman sixty-one years old who had been sick for a 
long time, with constipation, attacks of pain in the umbilical region, nausea, and 
emaciation. Twice hematemesis occurred, the last time two hours before death. 
At the autopsy the stomach was distended with blood; pancreas enlarged, nodular, 
infiltrated with cancer; in the center was a large ulcerating cavity connected with 
the stomach by aragged opening. A branch of the celiac artery also was opened. 

Huber’s case was a muscular, corpulent brewer, thirty-five years old, who had 
several attacks of pain in the epigastrium, which were regarded as the result of chole- 
lithiasis; about eight months after the first attack of colic he suffered again from a 
violent pain in the region of the stomach. Soon afterward the pulse became ex- 
ceedingly small and death suddenly occurred. At the autopsy a tumor of the head of 
the pancreas was found which surrounded the common duct. The gross appearances 
of the tumor corresponded with those of Férster’s carcinoma simplex, and, in addi- 
tion, there were numerous pigmented and hemorrhagic spots. 


In Baudach’s case, previously mentioned, the hemorrhages occurred 
in consequence of erosion of the vessels in an angioma myxomatosum. 

6. Hemorrhage from embolism of a pancreatic artery is reported 
in a case observed by Molliére. 

7. Trauma may give rise to extensive hemorrhage in various organs 
of the abdomen, among which the pancreas and the surrounding sub- 
peritoneal connective tissue are included, or the pancreas and the sur- 
rounding connective tissue alone may be the seat of the hemorrhage. 


214 HEMORRHAGE. 


Nimier distinguishes three groups of traumatic pancreatic hemor- 
rhages: 

(a) The pancreatic hemorrhage is the direct and immediate conse- 
quence of the trauma. An extensive or pure hemorrhagic extravasation 
takes place suddenly in the spaces of the great omentum. 

(b) The trauma may cause hemorrhage and a rupture of the ductus 
Wirsungianus, and, in consequence, an admixture of pancreatic secretion. 
A eyst, therefore, forms in addition to the various symptoms of reactive 
inflammation. The contents are due to the activity of the escaped 
fluids modified by the inflammatory products of the neighboring tissue. 

(c) The trauma affects an already diseased pancreas, and in such cases 
even a slight injury may cause hemorrhage. 

The cases of Prince and of Foster and Fitz belong to the traumatic 
hemorrhages. 


Prince gives the history of a strong porter, twenty-two years old, who, being 
in prison for eight days before the beginning of the disease, complained of a severe 
pain in the lower part of the abdomen immediately after turning a handspring. 
Eight days later there was a sudden violent cramp in the stomach. Soon collapse 
occurred, and for about fourteen days a moderate fever, temperature varying be- 
tween 36.0° C. and 39.0° C. (96.8° F and 102.2° F.). Diarrhea. Vomiting. Meteor- 
ism. Increasing collapse. Death. At the autopsy, the region of the pancreas was 
black, consisting of dead, gangrenous shreds. 


It is probable that a pancreatic hemorrhage had occurred and gradu- 
ally ended in gangrene. It is certainly remarkable, as Seitz declares, 
that so slight an injury as turning a handspring should have produced 
such a hemorrhage, and it certainly is questionable whether there was 
not some other predisposing cause of the hemorrhage. [The trauma in 
this case was not from “das drehen eine Handmiihle,” as in the original 
German, but from turning a handspring, a much more violent procedure. 
—FEp.] 

It is at least doubtful, as Seitz maintains, whether in the case of Foster 
and [itz the hemorrhage was not the effect of the trauma upon pre- 
existing fatty degeneration of the vessels or from the production of fat 
necrosis. The man, fifty-nine years old and weighing 200 pounds, was 
thrown from a wagon, apparently without having suffered any injury, 
and four days later was attacked with pains in the abdomen and vomiting, 
and died on the tenth day. 

The second of the groups suggested by Nimier includes only the cases 

of hemorrhagic cysts due to trauma, and consequently has been suffi- 
ciently considered in the section on Cysts. 
_ §. Inflammations of the pancreas may give rise to more or less 
severe hemorrhages. The relation of extensive hemorrhage to inflam- 
mation has been thoroughly discussed in the section on Hemorrhagic 
Pancreatitis. 

Hemorrhagic pancreatitis belongs to the unsolved questions concern- 
ing the pancreas. The same case will be called by one author “hemor- 
rhagic pancreatitis,’ and by another “apoplexy.” 

It is certain that the hemorrhage often exists alone or with subsequent 
inflammation; it is possible that an idiopathic inflammation may give 
rise to an extensive hemorrhage. Further observations and investiga- 
tions will solve these important questions. Without doubt different 
factors act together in the production of hemorrhage, as is evident from 
the previously reported cases; for example, disease of the blood-vessels, 


PATHOLOGIC ANATOMY. 215 


obesity, alcoholism, trauma, etc. In the case of Prince, for instance, 
an old cardiac lesion, alcoholism, atheroma of the vessels, trauma. In 
the case reported by Seitz, great physical strain, obesity, alcoholism, and 
syphilis. 

In a number of cases the cause for the hemorrhage cannot be given, 
partly on account of defective data, as in the cases of Loschner, Oppolzer, 
Amidon, Osler and Hughes, Birch-Hirschfeld, Hudson Rugg, Maynard 
and Fitz, Harris, Paul, Dieckhoff, and McPhedran. 


Dieckhoff’s first case was that of a cachectic man, sixty-three years old, with 
hypertrophy of the prostate and paresis of the bladder, who died with symptoms of 
increasing collapse on the third day after being under observation. At the autopsy, 
the pancreas formed a dark, brownish-red tumor, smooth on section. The lobules of 
the gland and small portions of the fat tissue in the immediate vicinity of the hemor- 
rhage were necrotic. 

The second case was a middle-aged woman who had suffered for years from 
diabetes mellitus. In the last year no sugar was found in the urine on repeated ex- 
amination. At the autopsy there was an extensive extravasation of blood in the 
abdomen, which had destroyed also a portion of the pancreas. 


A case reported by McPhedran is of especial interest, as it concerned 
a boy nine months old, on whom laparotomy was performed. 


During the first three months of life there was frequent colic. Coagulated milk 
often was found in the stools. Intestines sluggish, stools soft and yellow. In the 
ninth month the stools became more fluid and contained numerous small, yellow, 
fatty particles. On-November 13, 1895, vomiting suddenly occurred. On Novem- 
ber 15th, temporary improvement, vomiting returned, followed by collapse. In 
the evening, colic for an hour, tenderness in the epigastrium, no dejection in spite of 
the use of purgatives. On November 16th, feeble and apathetic. Vomiting after 
taking food, no movement of the bowels in spite of laxatives. Abdomen slightly 
distended. An oblong mass as large round as the middle finger in the region of the 
ascending colon. It was hard, movable with respiration, dull on percussion. Intus- 
susception was thought of. Operation. ‘After the abdomen was opened, the re- 
sistance proved to be an accessory lobe of the liver. Intestine normal. Death the 
next morning. In making the diagnosis, the possibility of a hemorrhagic pancreati- 
tis also was thought of. Autopsy: The middle third of the pancreas and its imme- 
diate vicinity were deeply infiltrated with blood. 


PATHOLOGIC ANATOMY. 


Klebs presents the following picture in his work published in 1870: 
“ The pancreas is dark-red or violet, the meshes of the interstitial tissue 
are filled with fresh or altered blood, the acini dull gray, usually diffusely 
tinged with blood-pigment. The hemorrhagic masses extend also into 
the vicinity of the gland, and especially into the retroperitoneal connec- 
tive tissue. Moreover, the whole gland appears softened, friable, the 
serous covering of the anterior surface is partially destroyed, and the 
ichorous, hemorrhagic material escapes into the omental bursa.” 

The following statements are derived from reports in recent literature: 

The pancreas affected by hemorrhage appears, as a rule, enlarged, 
and only exceptionally of normal size (Draper). Fearnside states that 
in his case the gland was enlarged fourfold, while La Fleur, Putnam, and 
Whitney report that it was doubled in size. 

The hemorrhage may arise within the gland and affect the whole 
organ or certain parts of it, or it may have its main seat in the peripan- 
creatic tissue and from there penetrate into the gland. 

The consistency of the gland varies. It appears somewhat increased 


216 HEMORRHAGE. 


in those cases in which inflammatory processes have already been estab- 
lished, but, as a rule, the gland is softer than normal. The softening 
may affect either the whole or certain parts of the organ. In the most 
advanced cases the tissue is completely disintegrated and discontinuous. 
A gangrenous, dark-red, discolored pulp replaces the pancreas (Prince). 

Very frequently the gland is surrounded by a compact layer of tissue, 
infiltrated with blood, which must be cut through before the gland is 
exposed. 

The surface of the organ is generally smooth. In Rugg’s case a 

relatively large opening, resembling an ulcer, and containing a clot of 
blood as large as a walnut, was found on the anterior surface of the 
pancreas. 
The color varies according to the intensity of the hemorrhage. Often 
only circumscribed spots of blood are visible, while in other cases the 
entire organ is changed into a dark-red or dark-brown mass, in which 
no structure is recognizable when the hemorrhage is extreme. These 
variations in color are seen also on section of the gland. In consequence 
of the frequent combination of hemorrhage and fatty changes the section 
appears marbled, from the alternation of hemorrhagic and fatty portions. 
The fatty alterations are especially marked in the interlobular tissue, 
and it appears traversed by opaque, white, broad or narrow patches 
which surround the darker portions infiltrated with blood. At times, 
although rarely, the hemorrhage affects only a portion of the gland, the 
rest of the organ appearing entirely free and showing normal structure 
(Putnam and Whitney). 

Pigmented areas are found at times as the result of former hemor- 
rhages; for instance, in the vicinity of fat necrosis. 

When the hemorrhage occurs merely as the accompaniment of other 
conditions, or in death from suffocation, the extravasations, as a rule, 
are distributed through a part or the whole organ. 

The ductus Wirsungianus is either dilated or it is occluded in places; 
at times filled with blood, which escapes through it from the lacerated 
gland into the intestine. 

Hemorrhage is not, as a rule, limited to the pancreas, but generally 
extends into the surrounding tissue and infiltrates it more or less ex- 
tensively. Moderate hemorrhages may be found in the adjacent mesen- 
tery and in the subperitoneal and retroperitoneal tissue. The hemorrhage 
takes place at times also into the general peritoneal cavity. In other 
cases a peritonitis is present (Prince, Bauer, Fearnside, Hirschberg) or 
the peritoneum may be normal. Death may have occurred too early, 
perhaps, for inflammation to have taken place, since blood may remain 
for a long time in the abdominal cavity without producing signs of irri- 
tation, as is shown by the observations of Dieckhoff. 

The liver is stated in many cases to have been very fatty, a con- 
dition not to be surprised at when the usual etiologic factors are con- 
sidered. In K6tschau’s case the fatty liver appeared as one of the fea- 
tures of a general, excessive obesity. The serosa of the intestine showed 
numerous white deposits of calcium salts. Among the other changes of 
the abdominal organs, Kétschau mentions multiple ecchymoses in the 
mucous membrane of the stomach, Gerhardt-Kollmann ecchymoses in 
the mucosa of the cecum, Williams a small hemorrhage in the mesentery, 
Birch-Hirschfeld hemorrhagic contents in the duodenum. 

There are other anatomic conditions allied to the hemorrhage, as 


- 


PATHOLOGIC ANATOMY. 217 


fatty heart, atheroma of the coronary arteries, mitral stenosis (Prince), 
cardiac aneurysm (Zenker), aortic insufficiency, and emphysema (post- 
mortem records of the Vienna General Hospital). 

Fearnside found the kidneys abnormally small and indurated. The 
venous hyperemia of the solar plexus noted by Zenker in two cases should 
be mentioned, because he regarded it as intimately connected with the 
hemorrhage. 

The minute alterations of the gland structure can be investigated 
only in those cases in which there is no complete destruction of the 
tissue. The results of microscopic examination with regard to this 
point have been given by various authors. Lach of the two following 
examples represents a different type. In the first (Putnam and Whitney), 
death occurred three days after the beginning of the illness, while in the 
second (Dieckhoff), the disease certainly lasted more than three weeks. 


Putnam and Whitney found three sharply defined zones in the pancreas. In the 
middle zone was the interlobular fat tissue, continuous with the fat tissue sur- 
rounding the pancreas; it was extensively infiltrated with blood, and frequently 
made porous by the destruction of fat-cells. In other places it contained a fibrillated 
meshwork, finely granular material, bacteria, and numerous acicular fat crystals. 
In addition, foci of round-celled infiltration were found in this fat tissue between 
the relatively normal portions of the pancreas and the hemorrhagic and necrotic 
interlobular fat tissue. 

On one side of this middle zone the acini were sharply defined and the nuclei 
stained easily. Many lobules contained granular epithelium and indistinct nuclei. 
Intralobular and interlobular infiltration with blood-corpuscles and numerous col- 
lections of round cells were seen in places. On the other side of the hemorrhagic 
zone, although the lobules were distinct, the outlines of the acini were frequently 
confused. ‘The cells were granular, often not sharply defined, and the nuclei did not 
stain. In places the lobules were replaced by granular detritus and the cells were 
widely separated. Here and there between these necrotic acini, stained islands were 
found, evidently colonies of bacteria, thrombosed veins, and more rarely small col- 
lections of round cells (Fitz). 


The changes which occur at a later stage of the hemorrhage are de- 
scribed by Dieckhoff in both his cases: 


Dieckhoff found “the extravasated blood permeated in part by immature con- 
nective tissue proceeding from the living tissue in the neighborhood. The latter 
contained clusters of young connective-tissue cells, between which were polynuclear 
and single giant cells in addition to the wandering round cells; from this point the 
capillaries grew into the blood-clot, of which it inclosed large portions, and proceeded 
far into the tissue of the gland, and especially into the fat tissue. The gland-lobules 
and isolated small portions of the fat tissue in the immediate vicinity of the blood- 
clot were necrotic. The connective tissue also between the lobules and acini was 
dead.” 


The microscopic appearances of other inflammatory conditions and 
their relation’ to hemorrhage have already been mentioned in the cases 
of hemorrhagic pancreatitis (Zahn, Kraft, Haidlen, Dittrich). 

Osler and Hughes, in a case of hemorrhage in the pancreas, found an 
increase of round cells in the semilunar ganglion, cloudy swelling of 
this ganglion, and edema of the Pacinian bodies lying behind the duode- 
num and pancreas. In the two following éxperiments on animals the 
occurrence of hemorrhage into the pancreas was shown by us: 


‘EXPERIMENT oF JANUARY 17, 1895.—Injection of 5% chlorid of zine into the 
tissue of the pancreas; 0.2 ¢.c. of a 5% zinc chlorid solution was injected into four 
different places. A hematoma resulted in one place at the middle portion of the 
pancreas, elsewhere there was no alteration from the injection. Abdominal wound 
closed. On January 18th the animal was found dead in the morning. | 

Autopsy: The abdominal cavity contained a moderate hemorrhagic exudation. 


218 HEMORRHAGE. 


Pancreas appeared enlarged and infiltrated with blood except a place about as 
large as a kreuzer in the free descending portion. On section the structure in the 
duodenal portion was not recognizable. Elsewhere evidences of a lobular structure 
were seen in places. In the descending portion the structure of the normal pancreas 
appeared more distinct. Duodenum deeply injected; intestinal contents somewhat 
colored with blood. Liver of normal size and consistency, somewhat anemic in 
laces, 
. EXPERIMENT OF Fresruary 17, 1895.—Injection of 4; normal sulphuric acid 
into the ductus Wirsungianus. Dog of medium size; without food for thirty-six 
hours. The ductus Wirsungianus was opened at the point of entrance into the intes- 
tine and 4 c.c. of sulphuric acid were injected by means of a Pravaz syringe. The 
injection was easily made. As the fluid penetrated the tissue, the splenic portion of 
the pancreas became somewhat more succulent, the lobules stood out more dis- 
tinctly, and the venous injection of the previously pale organ, became more pro- 
nounced. Ligation of the duct and section between the ligatures. On February 





Fie. 13.—a, Blood-vessel distended with blood; b, extravasated blood in the parenchyma between the 
lobules ; c, normal pancreatic tissue. 


18th the animal was found dead in the morning. Life lasted about twenty hours 
after the operation. Urine and stools evacuated; vomiting of mucous fluid. Urine 
brownish-yellow, about 150 c.c. Sugar 2.2%. Acetone in small amount (shown in 
the distillate). Indican in small amount. 

Autopsy: Peritoneum pale, intestine contracted, empty, pale; the duodenum 
only somewhat more strongly injected. In the stomach about 20 c.c. of brownish, 
turbid, slimy fluid of neutral reaction. Pancreas of normal size, with a hemorrhage 
as large as a pea in the duodenal part corresponding to the ductus Wirsungianus. 
The tissue here is degenerated and the structure indistinct. In the splenic portion 
the tissue is more succulent, the lobules are indistinct and blurred. Tissue appears 
opaque. The remaining portion of the pancreas is of normal appearance and con- 
sistency. Spleen small and shows nothing abnormal. Liver appears normal. 


A microscopic preparation obtained from the experiment first de- 
scribed is shown in figure 13. 


v 


- SYMPTOMS. 219 


Résumé.—In the first experiment a hematoma occurred in one place 
as the immediate result of the injection. Both animals died within twenty- 
four hours. In the second experiment, glycosuria was present. At the 
autopsy on the first animal there was a hemorrhagic exudation in the 
abdominal cavity and an extensive destruction of the tissue of the whole 
pancreas in consequence of the hemorrhage, except of a portion of the 
size of a kreuzer in the free descending portion. On microscopic ex- 
amination distinctly enlarged blood-vessels are seen engorged with 
blood, and there is hemorrhage into the parenchyma of the gland, which 
is forced apart in different places. The parenchyma appeared normal 
without any signs of inflammatory changes. In the second case these 
changes could be seen only in circumscribed spots near the ductus Wir- 
sungianus. 


SYMPTOMS. 


Pancreatic hemorrhage is never wholly free from symptoms except in 
those cases in which small hemorrhages are found incidentally at the 
autopsy. 

A great variety of symptoms are mentioned in the cases of non- 
traumatic hemorrhages hitherto reported. It is scarcely to be assumed 
that years of constipation, disturbed appetite or digestion, have any 
thing to do with the later occurrences, but it may be that these are due 
to gradually developing changes in the pancreas, which afterward may 
become the cause of the hemorrhage. Likewise colic and attacks of 
cramps also which have occurred years before the hemorrhage can scarcely 
be considered as having any relation. It is different with the transient 
colicky pains in the region of the stomach, which occur without definite 
cause during the weeks or months preceding the hemorrhage. Although 
it is not easy to bring forward positive proof that they are perhaps related 
to the small hemorrhages in the gland, yet it is quite probable that the 
fatal hemorrhage is preceded by smaller hemorrhages which may be mani- 
fested by the appearance of such pains. It certainly is to be assumed 
that slight hemorrhages may be recovered from. In many cases, however, 
there are no prodromal symptoms. The attack occurs quite suddenly 
during the best of health and not infrequently causes sudden death. Vio- 
lent pain is the most frequent and constant symptom. Asa rule, it domi- 
nates the picture of the disease and lasts until death. 

The seat of the pain is not always the same. It is limited, as a rule, to 
the abdomen, although in a case reported by Hooper the disease began 
with severe pain below the left breast, and in that of Rugg there was pain 
in the left lumbar region. The point of most intense pain varies: at times 
it is in the region of the stomach, the left hypochondrium, the region of the 
right colon, and again the most intense pain is felt in the lower abdomen. 
The pain is generally colic-like in character and may abate at times or en- 
tirely disappear, and then return with increased severity. The degree of 
the pain also may vary. As a rule, it is very violent and almost unen- 
durable. Exceptionally there is only a dull, painful sensitiveness 
throughout the abdomen. Stojanovics divides this somewhat too 
categorically into two varieties: ; 

(a2) Epigastric pains with a sense of warmth; they occur especially 
when the stomach is empty, increase gradually, recur at shorter and 
shorter intervals, and are often accompanied by vomiting of a fluid 


220 HEMORRHAGE. 


resembling saliva, sometimes acid and sometimes tasteless, and which 
is evacuated with the sensation of burning pains along the esophagus. 

(b) Pains above the umbilicus. These are said to occur at a later 
stage. They radiate toward the spine, have a dull, intermittent char- 
acter, and occur with the greatest severity a few hours after eating. 
Opiates, as a rule, give no special relief. The development of these 
severe pains is explained by the close relationship between the pancreas 
and the sympathetic nerve apparatus. An enlargement of the gland 
must result in pressure on the semilunar ganglion, while, on the other 
hand, the mesenteric plexus is woven around the blood-vessels of the 
gland (Nimier). 

Vomiting naturally occurs very frequently in this as in every acute 
pathologic process in the abdomen. A mere inclination to vomit or the 
absence of vomiting is exceptional. The vomiting as a rule is cumulative. 
At times it intermits for a few hours or for a day or two; then it returns, 
perhaps with a fresh exacerbation of the hemorrhage or with a beginning 
peritonitis, and increases in severity toward the end of life. The vomited 
substance is often greenish, stained with bile. A dark brown fluid (Fearn- 
side) or actual blood (Hooper) are relatively rare. 

Hemoptysis was observed in a case reported by Draper. Fecaloid 
vomiting has been observed in several cases, for instance, those of Hoven- 
den, Simon, and Stanley. Hiccough has occurred under certain circum- 
stances, both with and before the vomiting. Jaundice was very rare. 

The abdomen is often distended and tympanitic. The meteorism is 
either extended uniformly over the whole abdomen and increases toward 
the end of life (Hooper), or it is limited to the upper part of the abdomen 
(Hilty). 

A tumor on palpation of the abdomen is extremely rare in pure hemor- 
rhage. Iearnside was able to feel a deep transverse tumor between the 
ensiform process and the umbilicus. Hirschberg was able to show on the 
right only a larger coil of intestine. McPhedran found in the region of the 
ascending colon an oblong mass as thick as the middle finger. This proved 
at the operation to be an accessory lobe of the liver. When there are 
hemorrhages in cysts or neoplasms or the formation of cysts from hemor- 
rhage, a tumor can be palpated. Fever rarely occurs in consequence of 
the rapid progress. Birch-Hirschfeld noted the presence of high fever in 
his two cases, and in some of the histories reported a moderate fever is 
noted. Morton Prince notes the occurrence of repeated chills. Sub- 
normal temperatures are easily understood in a disease in which collapse 
is so frequent. The pulse is usually small, weak, feeble, corresponding to 
the rapid diminution of strength, and collapse. 

The sensorium is, as a rule, well preserved. Loss of consciousness is 
noted among the on (Kotschau); also delirium (Birch-Hirschfeld, 
Hilty). 

Few changes in the urine are observed in the short course of the dis- 
ease. As a rule, the urine was not examined or there was complete an- 
uria. Whitney mentions the presence of albuminuria, and Gerhardi the 
lack of indican. In the case observed by Dieckhoff, diabetes had existed 
earlier, but the urine was free from sugar at the time of the hemorrhage. 
Cutler found 6.1% sugar in his patient. Sarfert found 1% of sugar in the 
urine removed after death. 

_The condition of the bowels varies; constipation is more frequent than 
diarrhea. The disease not infrequently develops with the symptoms of 


» 


COURSE. 221 


intestinal obstruction, as, for instance, in the cases of Gerhardi, Fitz, 
Hirschberg, Hovenden, McPhedran, Parry, Dunn and Pitt, Simon and 
Stanley, Sarfert, Allina. When cysts form, the intestine may be ob- 
structed by pressure. , 

Attacks of fainting were observed by Fearnside three days before 
death. Collapse is an extremely frequent occurrence, and forms one of 
the essential features of the disease. In the fulminating cases it develops 
quite suddenly after the patient has been perfectly well, or it appears a 
few hours after the first pain. In the cases progressing more slowly it 
occurs also somewhat independently two or three days after the existence 
of the symptoms. It is the forerunner of impending death, and it has 
never been overcome. 


COURSE. 


Hemorrhages may be divided into those with acute and those with 
chronic course, apart from the cases in which slight hemorrhages occur 
without disturbance, and which it is probable may be wholly recovered 
from. The former are the more frequent, and Nimier makes three sub- 
divisions: (a) the fulminating; (b) the very acute; (c) the acute. 

The cases are most numerous in which there is an interval of twenty- 
four to thirty-six hours between the first symptoms of the disease and 
death. The chronic cases include those in which the hemorrhage takes 
place at intervals and which, under certain circumstances, may recover, 
a part of the whole gland being sequestrated and discharged. Among the 
chronic cases also are those in which hemorrhagic cysts eventually form. 
These chronic cases may last for weeks or even months. 

In the fulminating cases, death occurs suddenly or in the course of an 
hour. What is the cause of this sudden death?* Undoubtedly in a 
number of cases it is not the quantity of blood lost and the resulting 
anemia. <A series of cases have already been referred to in which the 
quantity of extravasated blood was much too small to permit the death 
to be regarded as the result of hemorrhage. It is also improbable that 
the sudden disturbance of function of a part or of the whole gland should 
be regarded as the cause of death. This is contraindicated, in the first 
place, by the results of experiments on animals, which show that animals 
survive the sudden removal of the entire organ. 

Other factors must be presented in explanation. Mention has already 
been made of two hypotheses. Zenker believes death to be due to shock, 
analogous to Goltz’s experiment, and supports his view by his autopsies. 
In two cases he was able to show a very marked venous hyperemia of the 
celiac plexus; the heart was relaxed, the cavities distended, and contained 
no blood. The abdominal vessels also were hyperdistended, a condition 
analogous to that found in Goltz’s experiment. 

Sarfert found a similar condition in his second case: flabby, empty 
heart, abdominal vessels hyperdistended, venous hyperemia of the solar 
plexus. Friedreich considers it more justifiable to regard the death as 
due to the irritation of the semilunar ganglion by the pressure of the 
rapidly distended pancreas and a consequent disturbance of the move- 
ments of the heart. 

* The publication of Greiselius of 1672 is worthy of note: “ Observatio de repen- 


tina suavi morte ex pancreate sphacelato.” (Death of a man forty-two years old in 
an attack of colic, eighteen to nineteen hours after the beginning of the illness.) 


222 _ HEMORRHAGE. 


There are no new hypotheses advanced since the communications of 
Zenker and Friedreich, but Seitz remarked: ‘‘The future must decide 
whether the disturbed function of the pancreas lacerated by the hemor- 
rhage may not play a part.’”’ Doubtless there are cases in which death 
is wholly the result of hemorrhage, as in that reported by Seitz. 

The explanation of those cases in which the course is mild at first and 
becomes violent only in the last days or hours may be sought in the fact 
that the hemorrhage was periodic in its occurrence and only finally be- 
came intense enough to cause death. 

The chronic course may be brought about in different ways: by 
periodic occurrence of the hemorrhage, or by the subsequent develop- 
ment of a peritonitis, sepsis, necrosis, or suppuration of the pancreas, 
escape of the fluid into the peritoneal cavity or into the stomach and intes- 
tine. It has already been mentioned that in certain cases at such a 
stage recovery may take place by sequestration and discharge of the 
gland. 


DIAGNOSIS. 


It is perhaps impossible with our present means to diagnosticate posi- 
tively a pancreatic hemorrhage or a “‘ hemorrhagic pancreatitis.” Even 
under the most favorable circumstances it may be suspected that there 
is perhaps such a condition. To be sure, in the case observed by them, 
Fitz and Williams made the diagnosis of acute pancreatitis or pancreatic 
hemorrhage. ‘This was of course only a diagnosis based on probability. 

In the case of Williams, a man seventy years of age was suddenly 
seized with colicky pain in the region of the stomach which lasted five hours 
and radiated toward the left and toward the navel; the region of the stom- 
ach was not sensitive, there was vomiting, the pulse was regular and 
small, six hours later collapse occurred and sixteen hours afterward 
death took place. It must be admitted that in this case various diseases 
were to be thought of, and that it was not necessary to regard pancreatic 
hemorrhage or hemorrhagic inflammation as the only possibility. 

In fact, in most of the cases of pancreatic hemorrhage there was 
either no diagnosis or the affection was regarded as something quite 
different. Intestinal obstruction, peritonitis from perforation, perfor- 
ating ulcer of the stomach or intestine, pyosepticemia arising from the 
intestine, purulent peritonitis, etc., have been suspected. 

The diagnosis is made relatively most easily in traumatic hemorrhage. 
A pancreatic cyst from trauma may be thought of when after injury to 
the abdomen there are sudden violent pain and prostration and afterward 
a tumor appears more or less distinctly fluctuating behind the stomach 
between the navel and the costal cartilages. 

As a matter of fact, the diagnosis of a traumatic pancreatic cyst has 
been definitely established in certain cases by means of an exploratory 
puncture, and a successful operation has resulted. © 

In the present state of our knowledge, in certain cases the possibility 
of a pancreatic hemorrhage also, with or without inflammation, may be 
thought of with many other possibilities, when there are no further indi- 
cations for diagnosis, if an individual who in consequence of his constitu- 
tion, as in atheromatosis, syphilis, obesity, alcoholism, etc., is liable to 
diseases of the pancreas is suddenly seized in the midst of health by a vio- 


. 


TREATMENT. 223 


lent attack of pain in the epigastrium with vomiting and collapse, and 
speedy death occurs in a few hours or days. 

Even in the chronic cases in which there are manifestations of peritoni- 
tis or gangrene of the pancreas and rupture of ichorous cavities the nature 
of the disease is hardly more than to be suspected, and the condition must 
be made clear by an operation or the discharge in the feces of the seques- : 
trated pancreas. Even then, as in Chiari’s case, it will be doubtful 
whether the sequestration of the gland was the result of inflammation or 
of hemorrhage. 


TREATMENT. 


There can be no question of a rational treatment in an affection of so 
rapid a course, the correct diagnosis of which is so difficult. Nothing 
further need be said of the insufficiency of internal treatment. Simon 
and Stanley propose the prophylactic use of intestinal antiseptics, espe- 
cially salol; based on the assumption of the etiologic importance of a bacil- 
Jary infection from the duodenum, and because they regard the prolonged 
retention of chyme in the duodenum, especially in fat people, as increasing 
the danger of infecting the pancreas. 
Surgical treatment also is probably useless in the acute cases. A num- 
ber of successful results show. that an operation is indicated only in the 
cases in which cysts or abscesses develop. 





Vil PANCREATIC CALCUL, 


Tue formation of concretions in the pancreas has been recognized for 
along time. According to the thorough study of Giudiceandrea, the first 
communication dates from the middle of the seventeenth century. Graaf 
(1667) mentions two cases observed by Panarol and Gaeia. These were 
followed by the publications of Bonetus (1700), Galeati (1757), Morgagni 
(1765), Greding (1769), and Cowley (1788). 

In the beginning of the nineteenth century, Merklin and Baillie re- 
ported two cases of pancreatic calculi. After a long interval appeared the 
publications of Ellotson (1832), Gould (1847), and Fauconneau-Dufresne 
(1851). Soon afterward Virchow reported two cases (1852), and in 1864 
v. Recklinghausen published his important communication. Publica- 
tions have appeared more frequently since 1875, and especially in recent 
years a large number of very instructive observations have been commu- 
nicated by Freyhan (2 cases), Fleiner, Lichtheim, Minnich and Holzmann, 
and the comprehensive publications of Nimier and Giudiceandrea. The 
last-mentioned author collected 48 cases, to which two original cases were 
added.* 

There is no doubt that only a small percentage of calculi of the 


* Besides these the cases should be mentioned of Clayton, Crowden, Dieckhoff 
(2 cases), Fleiner, Frerichs, Gille, Gagliard, Leichtenstern (2 cases), Michailow, 
Moore (3 cases), Miiller, Munk and Klebs, Nicolas and Molliére, Rérig, Shattock. 
A case of pancreatic calculus is reported among the autopsies of the Vienna General 
Hospital in 1894, in a man sixty years old, with fatty degeneration of the substance 
of the gland and fibrous induration. Thus, in all there are 70 known cases. 


224 PANCREATIC CALCULI. 


pancreas found at autopsies is published. It is not very rare to find 
small concretions or sand in the pancreas or in the pancreatic ducts. 
Statements with reference to this condition are to be found in the text- 
books on pathologic anatomy by Ziegler, Birch-Hirschfeld, and Orth. 

Number of Calcult.—As a rule, several calculi are found. In the col- 
lection made by Ancelet (1860) in only three cases was there a solitary 
calculus; in individual patients 4, 7, or 8 and in two 12 calculi were found, 
while in eight other cases the occurrence of numerous concretions is noted. 

Not infrequently the main duct or the smaller excretory ducts are 
actually incrusted with sand. Sottas, for example, found numerous small 
calculi in the main duct and in the small adjoining ducts in addition to a 
calculus as large as a bean near the outlet of the duct in the duodenum. 
Numerous concretions were found in small, newly formed cavities in the 
sclerosed substance of the gland. Baumel also saw numerous calculi 
both in the excretory ducts and in the canals of the gland, in shape wholly 
adapted to the cavities in which they lay. In Curnow’s case, likewise, 
the smallest excretory ducts of the gland were entirely filled with calculi. 
Lancereaux found both excretory ducts occluded by large calculi, and, in 
addition, an extensive incrustation of the excretory ducts of the second 
order. 

Seat of the Calcult.—According to the cases thus far reported, the cal- 
culi are oftenest to be found in the excretory ducts near the duodenal 
opening, at times in the diverticule of the duct, as mentioned by Freyhan 
and Giudiceandrea. Concretions are rarely met in the caudal portion of 
the duct. The calculi are found also in the small and smallest excretory 
ducts in the parenchyma, even in sacculations of the ducts, and are either 
freely movable, enveloped in slimy fluid, or attached to the wall. 

Pancreatic calculi have been found at times in cysts (Giudiceandrea, 
Shattock) and in abscesses, as in the cases of Fauconneau-Dufresne, 
Fournier, Leichtenstern, Moore, Portal, and Salmade. 

Size.—As a rule, the size of the pancreatic calculi is not great; it is 
compared with that of a bean, pea, lentil, hemp-seed, hazelnut, or large 
cherry, in addition to the previously mentioned gravel-like concretions 
which incrust the pancratic canals like fine sand. The largest calculus 
on record was 24 inches long and } inch in diameter (Schupmann). 

Weight.—The weight corresponds with the size, and is usually small. 
Matani and Schupmann found the heaviest calculi; the weight reported 
by the former was 2 ounces, while that by the latter was 200 grains. 

The shapes of the calculi may vary exceedingly. They are spherical, 
ovoid, with smooth or rough surface, at times also are arborescent. The 
calculus described by Schupmann resembled the crystalline formations 
which are found on and around the frames at salt-refining works. Vari- 
ous pointed elevations—outgrowths, as it were—project like branches of 
a tree some lines above the surface; these are processes of the calculus 
which, proceeding from the body, have continued into the branches of the 
main excretory duct and have filled them. 

The color of the calculi is white, whitish-gray, or yellowish. Excep- 
tionally, dark and even black stones are described (Bonetus, Merklin). 

The consistency is either hard or soft, very friable. 

Chemical Composition.—Virchow found in the excretory ducts of the 
pancreas two small, microscopic, concentrically striated, somewhat firm 
concretions, with the microscope showing concentric lamellze, and com- 
posed of an insoluble coagulated proteid substance; statements of the 


% 


PATHOGENESIS. 225 


other authors agree that the pancreatic calculi most frequently consist of 
calcium carbonate and calcium phosphate. In addition to these, inor- 
ganic substances, as sodium phosphate, magnesium phosphate, and sodium 
chlorid, were found; and of organic constituents, cholesterin, leucin, 
tyrosin, xanthin, and the above-mentioned coagulated proteid substance 
found by Virchow. Henry analyzed a concretion which weighed 9 gm., 
was of the size of a nut, and was also interesting because of its external 


form. Projections from one surface extended into the tissue of the gland; 


the entire surface was surrounded by a hard, resistant membrane, the 
removal of which permitted the recognition of a system of hollow spaces 
which were filled with yellowish concretions and powdery sand. All these 
spaces were filled with a white, milky fluid, which held in suspension a cal- 
cium salt. Two-thirds of the concretion were composed of calcium phos- 
phate; the remainder was composed of equal parts of calcium carbonate 
and organic material. In addition, traces of sodium phosphate and 
sodium chlorid were demonstrable. The small bodies resembling grape- 
seeds consisted of calcium carbonate and organic matter. 

The occurrence of calcium phosphate in the eoncretions is mentioned 
also by more recent authors. Generally calcium carbonate also is found, 
and in rare cases the latter is present alone (Freyhan). In one of Frey- 
han’s cases the calculus, as large as a plum-stone, had a nucleus of pure 
calcium carbonate and a soft envelope of organic substance in which 
cholesterin especially was found. The calculi found by Minnich in the 
feces also consisted of calcium carbonate and calcium phosphate. The 
results of chemical analvsis show that in the formation of the calculi there 
is not a simple precipitation from the secretion of a normal gland, as the 
normal pancreatic juice contains only a small amount of calcium phos- 
phate and is entirely free from calcium carbonate. 

One of Shattock’s observations appears unique. Small calculi con- 
sisting of pure oxalate of lime were found in the contents of a pancreatic 
cyst. Shattock thought that the oxalic acid had been produced by micro- 
organisms. According to present knowledge, only Aspergillus niger in 
anaerobic growth can produce this acid. 


PATHOGENESIS. 


The causation of calculi in the pancreas is at present obscure. The 
material for investigation is rare, and therefore insufficiently studied to 


justify too positive assertions. In general, the assumption appears plaus- 


ible that there are the same determining factors as in the formation of gall- 
stones. The simple stagnation of the secretion is certainly one of the most 
important factors, but it is not the only decisive one. From anatomic 
reasons the secretion of the pancreas becomes much more rarely stagnant 
than is the case with the bile. If only one excretory duct is obstructed, 
the second duct can assume the function and permit the evacuation of 
the secretion into the intestine. In order to cause a complete retention, 
either both ducts must be obstructed, or, what is oftener the case, the 
second duct must be obliterated, either congenitally or from some 
acquired affection, or numerous itrapancreatic ducts must have become 
impermeable. 

That stagnant secretion alone does not cause the formation of concre- 
tions is supported by the clinical fact that in many cases of closure of the 

15 


226 PANCREATIC CALCULI. 


excretory ducts, whatever may be the cause, no calculi could be found. 
Calculi could not be produced, as a rule, in experiments on animals, either 
by tying the Wirsungian duct or by injection into it (Pawloff, Mouret). 
Thiroloix alone was successful in one instance. He injected sterilized soot 
into the ductus Wirsungianus. At the autopsy the gland was found atro- 
phied, and in the splenic portion surrounded by dense connective tissue, 
there was a cystic cavity, containing a fluid as clear as water, in which . 
were numerous very dense, irregularly shaped calculi of the size of a pin- 
head. The ductus Wirsungianus also was filled with small calculi. 

The fact already mentioned that there is no calcic carbonate in the 
normal pancreatic secretion, while pancreatic calculi very often are com- 
posed of this material, is in favor of the view that pathologic changes in 
the pancreatic juice precede the formation of the calculi; that is, that the 
stagnation first causes formation of calculi, when it is composed of a 
pathologic pancreatic secretion. 

Analogous to the pathogenesis of gall-stones, it may be assumed that 
a catarrh in the pancreatic ducts—a sialangitis catarrhalis—causes such 
changes in the pancreatic secretion that the resulting stagnation leads to 
the formation of calculi. An ascending duodenal catarrh in most cases 
is the probable origin of such a catarrh, and if both excretory ducts are 
simultaneously affected, a sufficient explanation is offered for the stagna- 
tion and also for the alteration of the pancreatic juice, which leads to the 
formation of the calculi. 

Changes in the pancreatic secretion and disturbances in the outflow of 
the secretion may be accomplished also by other causes. An abnormal 
secretion may be formed by morbid, especially indurative processes in the 
gland, and the resulting hindered outflow of secretion may give rise to 
the formation of concretions. In one of the cases of Lancereaux, syphilis 
and, in that of Baumel, chronic alcoholism, are mentioned as etiologic 
factors. It is conceivable that these processes leading toward the pro- 
duction of chronic indurative inflammation of the pancreas might cause 
stagnation of a pathologic secretion and thus give rise to the formation 
of calculi. . 

Pathologic processes in the vicinity of the pancreas which limit the 
outflow of the secretion from the gland may, together with stagnation, 
cause such changes of the secretion as to give the conditions necessary for 
the formation of calculi. Gall-stones which press on or are wedged in 
the ductus Wirsungianus, peripancreatic indurations, and neoplasms— 
although these are rare conditions—thus may cause lithiasis in the — 
pancreatic ducts. 

In the presence of a stagnant secretion sialangitis pancreatica must 
play the most important part in the formation of calculi in the pancreas, 
analogous to the condition of cholangitis in cholelithiasis. A lithogenic 
importance is ascribed by many authors to the immigration of bacteria 
from the intestine, a condition which is easily possible. Nimier sup- 
ports this view by the positive results of the examination by Galippe of 
salivary calculi which are chemically and nosologically analogous to pan- 
creatic calculi. In one of his cases Giudiceandrea found, in the midst of 
numerous calcium crystals and detritus, a large number of similar bacilli 
of the shape of Bacterium coli, and, in addition to these, a considerable 
number of long, delicate bacilli, which he was unable to identify. Ina 
second case investigated bacteriologically he saw numerous forms of cocci 
and bacilli of various kind and size, but, on the whole, in much smaller 


. 


——s =e 


PATHOLOGIC ANATOMY. 227 


numbers than in the first case. The normal pancreatic secretion was 
free from micro-organisms. 

Giudiceandrea considered it questionable what importance should be 
attached to the discovery of the colon bacillus in the nucleus of a pan- 
creatic calculus, but thinks it can hardly be denied that its presence may 
contribute to the progress of calculus formation. Farther investigations * 
are needed to decide whether this assumption can account for the devel- 
opment of pancreatic calculi or whether there is a direct bacterial influ- 
ence. 

It is well known that Naunyn has established the frequent occurrence 
of Bacterium coli commune in the biliary passages and inclines to the view 
that the invasion of this bacterium gives rise to a catarrh of the mucous 
membrane and thus to the formation of calculi. Further investigations 
must decide whether this view applies also to the origin of pancreatic 
calculi or whether there is a direct bacterial influence. The immigration 
of pathogenic bacteria from the intestine might have considerable im- 
portance in the causation of an infectious sialangitis, which would lead to 
the formation of an abscess if there were calculi in the pancreas. Un- 
fortunately there are no investigations at present tending to the solution 
of this question. 


PATHOLOGIC ANATOMY. 


The pathologic changes which have been found in the gland when 
calculi are present may be primary or secondary; that is, they may be the 
cause or the result of their formation. The presence of calculi in the gland 
gives rise to secondary changes of the parenchyma which may lead to 
the complete destruction of the secreting tissue. Fatty degeneration 
of the parenchyma may occur; this was true, for instance, in v. Reck- 
linghausen’s case, in which the pancreas was changed into a mass consist- 
ing of fat lobules, resembling the normal organ only in form and size, but 
showing no gland tissue. In Freyhan’s cases, also, only fat and con- 
nective tissue were present in place of the normal gland tissue. 

In other cases either induration or atrophy occurred. In one of 
Moore’s cases, in which the stone compressed the ductus Wirsungianus 
near its mouth and caused distinct dilatation, marked increase of connec- 
tive tissue was clearly visible to the naked eye. On microscopic examina- 
tion the interstitial growth of connective tissue was especially distinct and 
occasional bands of round cells showed that in certain parts of the gland 
the process was still advancing. The new-formation of connective tissue 
followed the marked dilatation of the pancreatic ducts and caused a pan- 
creatic cirrhosis, as disease of the bile-ducts in the liver causes a growth of 
connective tissue with the eventual result of cirrhosis. Similar condi- 
tions were shown by Lichtheim, Fleiner, Sottas (combined with fatty 
degeneration), and Lancereaux (associated with atrophy of the gland), 
and Baumel found the growth of connective tissue especially connected 
with the vessels and excretory ducts. Hansemann notes two cases of pan- 
ereatic calculi in which there was atrophy of the whole organ. Curnow 
also reports a case with marked atrophy of the pancreas. 

The occurrence of abscesses in consequence of calculus formation is 
relatively rare (Fournier, Salmade, Portal, Roddick, Moore, Fauconneau- 
Dufresne, Leichtenstern, Galeati). As a result of the obstruction from 
the calculus there is naturally a dilatation of the pancreatic ducts, which 


228 PANCREATIC CALCULI. 


may attain considerable dimensions, according to the size and number of 
the incarcerated calculi and the quantity of stagnant secretion. In v. 
Recklinghausen’s case a partial ectasia thus attained the size of a child’s 
head. ‘The dilatation is in many cases to be regarded as the result of the 
atrophy and shrinkage of the gland lobules. 

As has been previously described, the dilatation may extend to the 
smallest ducts. Diverticula may occur and incrustations may cover the 
entire wall of the small and smallest ducts as well as of the sacculi pro- 
ceeding from them. In rare cases cysts may form in consequence of this 
dilatation (Clark, Curnow, Dieckhoff, Goodmann, Gould, v. Reckling- 
hausen, Tricomi). The necrosis of fat tissue also at times is associated 
(Giudiceandrea). Cancer in rare cases also accompanies the calculus, 
and, according to Schupmann, may cause the latter by stenosis of the ex- 
cretory duct. 

Calculi in the biliary passages not infrequently accompany those: in 
the pancreas. Ancelet has collected eight such cases; this concurrence 
was found also in the cases of Curnow, Phulpin, and Dieckhoff. Renal 
calculi also may be found at the same time. In the earlier literature 
such a case is noted by Merklin. A woman thirty-six years old suffering 
for twelve years from renal colic, evacuated calculi with the urine, and 
a concretion as large as a nut was discharged in the feces. At the autopsy 
a calculus as large as a nut was found in the pancreas and there was a 
large abscess in the mesentery, which contained three calculi of the size 
of almonds and several smaller calculi. In the kidney there were none. 

In the small intestine there is at times a diffuse catarrh (Lichtheim), 
or hypertrophy of the duodenal glands (Lancereaux). 


STATISTICS. 


There are only a few statements concerning the frequency of pan- 
creatic calculi. Giudiceandrea states that in 122 bodies which were ex- 
amined after death within three months, calculi were found in the pan- 
creas twice. This may be regarded as a relatively high ratio. According 
to Naunyn, the proportion of gall-stones, judging from results of post- 
mortem examinations in the different pathologic institutes, is between 
5% and 12%. The ratio given by Giudiceandrea is 1.64%. Further 
observations are necessary in order to make more definite statements. 


AGE. 
In 32 cases the age is as follows: 
MEN. WOMEN. 
i 2 ROULO Venras oo See cae book hae ees ee banea 1 0 
DO LD See Geis Sie Ree a ee oe een 1 0 
PG 10 20) (6 ol doc a alah ne ae Lak Mee a eae 0 0 
A Be: a re ei errs Cee ee! PLA Taf. 2 1 
BO WO a ok aa bana 0 Slew ee Renee 2 0 
O00 BB oo aa 05444 aaa eee 2 2 
BO TO Ba oe bin a un bibs San ee ee 6 1 
A AS ec ten ss ob) eae eee eee 4 0 
AO Tee el ie Sa cline + 3 ly aR ee 2 0 
BE 10. GB) oP oo tyctsss isha wig & diets wl ee ee 2 0 
BB Le OO a ee pay ein. visa: 5k aide au Ree a a ee ee 1 2 
OU tO: Bee elite a canes ba carictileda cl 2 uae Rar en 1 0 
GE 00 TO ar Se AS to.» aad an eee ne 0 0 
V1: 76s O ANP AR ori es eee! Pek ae ee ee 2 Ox: 
ROCA ELSE rp el shld dn mle Sue pee ee eae 26 6 





SYMPTOMS. 229 


This table shows that calculi occur oftenest between the ages of thirty-six 
and forty-five years and are much more frequent in men than in women. 
& 


SYMPTOMS. 


Pancreatic calculi without doubt frequently cause no symptoms, espe- 
cially when they lie quietly in the place where they arise. Decided symp- 
toms first appear when the calculi begin to move or when the secondary 
changes in the gland give rise to especially prominent symptoms of dis- 
ease. The picture of the disease can be most clearly presented if a well- 
observed case is briefly reproduced, such as that described by Minnich: 


A man sixty-eight years old was attacked in his fortieth year by very severe 
biliary colic. Typical pigmented gall-stones were found in the stools by the physi- 
cian. After ten years there was a recurrence of the attacks with the discharge of 
pigmented cholesterin calculi during a period of six months. Quiescence followed. 
In the summer of 1893 the patient had several attacks of cramps which he regarded 
as biliary colic. In November, 1893, there were feelings of pressure and tension over 
the region of the stomach. The difficulty lasted for one month without the occur- 
rence of an attack of colic. Toward the end of the month there was diarrhea without 
pain for three days. On the third of December, Minnich saw the patient during an 
attack of colic. There were severe, cramp-like, writhing pains in the left hypochon- 
drium. The patient makes the following statement regarding the pains: There was 
first a dull sensation of pressure and constriction over the epigastrium and under the 
left border of the ribs, which caused him now to inspire deeply and again to press the 
painful places with his fist and to walk restlessly about the room. The pains soon 
became stronger and increased to actual paroxysms. They were localized especially 
in one spot, deep in the abdomen, close to the left border of the ribs within the mam- 
millary line. At the height of the attack the pains proceed in circles along the edge 
of the costal cartilages to the spine and dart violently beneath the left shoulder- 
blade. When the pains abate, they return to the above-mentioned spot beneath the 
left costal cartilage, and which the patient states that he could cover with a 5-franc 
piece. There is a slight tenderness to pressure in the place mentioned. The attack* 
stopped suddenly after two hours. Neither albumin, sugar, nor bile pigment were 
to be found in the urine. The attacks were of almost daily occurrence. The tem- 
perature was normal; pulse regular, 76. Liver not enlarged, gall-bladder not pal- 
pable, stomach not dilated. The examination of the feces showed round or flat 
concretions varying in size from a lentil to a cherry-stone; small crumbs and gravel 
also were found. The concretions consisted of a tough, semi-solid mass which could 
be crushed with the finger. The surface was smooth, the color light yellowish-gray. 
The cut surface was perfectly white and was similar to that of a fruit-seed. Lamina- 
tion and a central nucleus were not recognized. Microscopically the substance of the 
calculus appeared perfectly amorphous. The calculi were very readily soluble in 
chloroform which became opaque-white. On heating in a test-tube dense fumes of 
strongly aromatic odor arose; in the upper part there was some yellow water of 
condensation, and a perfectly white calculus which gave the reaction of calcium 
carbonate, and phosphate appeared in the residue. The attacks were repeated in the 
further course of the disease, but no more concretions were found. About three 
weeks after Minnich’s observation, Holzmann saw the patient in Eichhorst’s clinic. 
The attacks of colic occurred in the way above described, but some noteworthy 
symptoms had developed. During the attack the patient had a marked flow of 
saliva, over a liter of nearly clear viscid fluid, mixed with a few fragments of food, 
being discharged. The examination of the salivary fluid showed a weak potassium- 
sulphocyanid reaction, and it very actively changed starch into sugar. In the ex- 
amination of the urine sugar was found, all tests being positive: Amount, 1100 c.c.; 
specific gravity, 1022; no maltose was found. In the later attacks there was a 
moderate flow of saliva, but no sugar was found in the urine. Later there was a 
fever reaching 38.2° C. (100.8° F.). The feces contained here and there undigested 
muscle-fibers, no fat crystals; concretions were no longer found. 


Only a few of the cases which have been reported have had so typical 
a course as that just described. 


230 PANCREATIC CALCULI, 


The pains or unpleasant sensations may be of different kinds. There 
may be an almost continuous feeling of pressure or dull sensation of pain 
in the epigastrium, or there may be temporary attacks of more or less pro- 
nounced colic varying in intensity and duration. In the case of Minnich- 
Holzmann they were centered under the border of the left ribs. This 
may perhaps rarely be the case. They are generally concentrated in the 
epigastrium, radiate to both sides, and are in no way distinguishable 
from atypical biliary colic or gastralgia. These pains, as all violent ab- 
dominal colic, may be accompanied by nausea, retching, vomiting, and 
collapse. 

Salivation is not a frequent occurrence, in cases of pancreatic calculi. 
Capparelli, Holzmann, and Giudiceandrea alone have observed it. Diar- 
rheas are noted by Fleiner and Lichtheim. In the case described by the 
latter, the diarrhea lasted for a year and resisted all treatment. 

The occurrence of fatty stools 1s of great importance. They were 
present in the cases described by Clark, Gould, Reeves, Capparelli, Cho- 
part, and Lancereaux. Lichtheim found fat crystals very abundant in 
the stools. Faulty digestion of meat also was found at times. Holzmann 
occasionally saw a few undigested muscle-fibers. 

The presence in the stools of concretions originating from the pan- 
creas is the most important and most decisive symptom. There are two 
such observations up to the present time, those of Minnich and Leichten- 
stern. In Merklin’s case a calculus was found in the feces, but it was 
not proved that it came from the pancreas, although after death a cal- 
culus was found in the pancreas. 

The frequent occurrence of diabetes is of great importance, and was 
noted by Baumel, Capparelli, Chopart, Cowley, Elliotson, Fleiner, Fre- 
richs, Freyhan (2 cases), Gille, Lancereaux (in 4 cases), Lichtheim, Lusk, 
Moore, Miller, Munk and Klebs, Nicolas and Molliére, v. Recklinghausen, 
‘Rorig, and Seegen. Holzmann saw transient glycosuria. Diabetes, or 
at least transient glycosuria, was found 24 times in 70 cases examined 
with reference to this condition, giving the striking ratio of 34 per cent. 
The diabetes, if not regarded as an accidental associate of the calculus, is 
probably in most instances to be considered as the result of the changes 
developed in the gland in consequence of the lithiasis. Under such an 
assumption the diabetes can occur only late after the onset of the symp- 
toms of lithiasis. It may, however, be imagined that the same changes 
in the pancreatic tissue which lead to diabetes may also cause the forma- 
tion of calculi, since dilatation of the pancreatic ducts, alterations of the 
secretion, and its stagnation may develop in consequence of induration 
of the tissue. 

The various disturbances of digestion which are frequently found in 
patients with stone in the pancreas may be regarded as a consequence 
of the changes in the gland substance. The emaciation so often men- 
tioned may be considered as a result of these digestive disturbances or 
the diabetes. 

Jaundice belongs to the rare occurrences. In Galeati’s case it may, 
perhaps, have arisen from the simultaneous cholelithiasis. Minnich 
mentions only a slight discoloration of the conjunctiva. In a case de- 
scribed by Giudiceandrea there was marked jaundice resulting from the 
compression of the common duct. 

Fever is mentioned as a rare symptom. Holzmann regards it as 
analogous to the elevation of temperature so often observed in biliary 


% 


DIAGNOSIS. 231 


and renal colic. The observations hitherto made on this point are too 
few to determine the importance of this symptom. Bonetus and Galeati - 
speak of a tertian type of fever. In cases of infectious sialangitis with 
the formation of abscess an atypical fever with chills may develop (Rod- 
dick). 


DIAGNOSIS. 


The correct recognition of calculous disease of the pancreas is one of 
the most difficult tasks of the clinician, as may be illustrated by the fact 
that in the accessible literature of the subject the correct diagnosis was 
made only five times, and then by Lancereaux, Capparelli, Lichtheim, 
Minnich, and Leichtenstern. The last two found pancreatic calculi in 
the feces. Capparelli observed the passage of the stones from an ab- 
scess, and Lancereaux and Lichtheim based their diagnosis on the oc- 
currence of diabetes, preceded by attacks of colic. 

Among the cardinal symptoms, which may lead to the correct diag- 
nosis are pancreatic colic, the passage of characteristic concretions with 
the stools, diabetes, steatorrhea, and azotorrhea. The concurrence of 
the first two symptoms or the demonstration of characteristic con- 
cretions in the stools alone can render possible a correct diagnosis in the 
early stages of the disease. The occurrence of fatty stools, diabetes, 
and the disturbed digestion of proteids belong generally to a later stage 
of the disease, when there has been such deep-seated destruction of the 
gland, in consequence of the lithiasis, that the characteristic symp- 
toms of disturbed pancreatic function become manifest. The above 
symptoms only can become prominent before the symptoms due to the 
stone when a rare diffused disease of the pancreas gives rise to the for- 
mation of the calculus. The diagnosis of calculus in the pancreas can 
never be made from the pain alone. The pancreas cannot be regarded 
as the unquestioned place of origin of the pain even if it has a colicky 
character and shows also the paroxysmal type centering in the left hypo- 
chondrium, as described by Minnich and Holzmann. Such a localization 
may be found in biliary or renal colic, in beginning pericolitis in the 
region of the splenic flexure, even in colic originating in the appendix. 

Even if the attacks of colic are accompanied by salivation, the pan- 
creatic origin is not indicated, as paroxysmal pains from other sources 
may be accompanied by salivation. Generally, however, the latter have 
by no means the same localization as those in the case described by Min- 
nich. There are merely paroxysmal pains in the epigastrium radiating 
into both hypochondria and in no way to be distinguished from atypical 
biliary colic, gastralgia, and lead-colic. There are also certain negative 
signs, as absence of jaundice, tenderness and swelling in the hepatic 
region, which by no means justify the exclusion of biliary colic. 

The second of the cardinal symptoms mentioned is alone pathogno- 
monic.. If characteristic concretions are found in the stools, the diagnosis 
may be made with absolute certainty. But this happens very rarely; up 
to the present time, only in two cases. The soft, small, mortar-like con- 
cretions may easily be overlooked. 

The distinction between pancreatic and biliary calculi will, in most 
cases, present no difficulties. The demonstration of bile pigment indi- 
cates gall-stones; the pancreatic calculi are generally whitish or yellowish- 
white, and contain no bile pigment. They consist mostly of calcium 


232 PANCREATIC, CALCULI. 


carbonate and calcium phosphate, and only occasionally contain small 
amounts of cholesterin, while. the translucent gall-stones consist largely 
of cholesterin. Calcium carbonate occurs frequently in gall-stones, but 
biliary concretions consisting largely of calcium carbonate are very rare 
(Naunyn). As a rule, bile pigment also will be present in these concre- 
tions. | 

It is most frequently the case that the two cardinal symptoms, colic 
and diabetes, develop either in sequence or at a certain stage exist to- 
gether. Pancreatic calculi certainly are to be suspected, and perhaps 
regarded as somewhat probable, if attacks of colic which do not have the 
pronounced type of biliary colic with its associated symptoms precede for 
years the occurrence of diabetes. Such evidence, however, is not abso- 
lute proof, for the diabetes may have arisen from other causes than an 
affection of the pancreas, and the colic may depend on an atypical chole- 
lithiasis or be of other origin. Diabetes and cholelithiasis are so fre- 
quently associated that it may easily be assumed that the two conditions 
coexist without any causal relation. When attacks of colic precede dia- 
betes and are followed by other pancreatic symptoms, as fatty stools or 
faulty digestion of proteids, the probability that pancreatic concretions 
are present is materially greatér; even then the proof is not incontestable, 
because a severe pancreatic affection with its consequences and irregular 
cholelithiasis may accidentally occur at the same time. 

No diagnostic importance can be ascribed to the symptoms made 
prominent by many authors, as obstinate diarrhea, the occurrence of gly- 
cosuria rapidly disappearing after the attacks, emaciation, and fever. 
These aid in diagnosis only when they occur in connection with the cardi- 
nal symptoms. : 

The physician is oftenest concerned with the question whether gall- 
stones or pancreatic calculi are the cause of the colic. From the frequency 
of gall-stones and the rarity of pancreatic calculi in all doubtful cases 
cholelithiasis should first be thought of, and lithiasis of the pancreas should 
only be considered as at all probable when the above-mentioned symp- 
toms corresponding to the failure of pancreatic function are present. 
Absolute certainty can be reached only by finding characteristic pancrea- 
tic concretions in the stools. 

The diagnosis of infectious sialangitis which accompanies the lithiasis 
will be possible only when atypical high fever with chills, tenderness in 
the region of the pancreas, and eventually a demonstrable tumor in this 
situation, with the characteristic symptoms of abscess, are joined to the 
characteristic symptoms of lithiasis of the pancreas. 


TREATMENT. 


The difficulty of diagnosis renders the rational treatment of this affec- 
tion rarely possible. There is, however, a single instance. At Eich- 
horst’s clinic 4 to 1 ¢.c. of a 1% solution of pilocarpin was injected subcu- 
taneously into a patient suffering from an undoubted pancreatic lithiasis 
in consequence of the experimental observations of Kiihne and Lea, 
Heidenhain and Landau, and Gottleib, that pilocarpin increased the 
secretion of the pancreas. There was no result during the stay of the 
patient in the hospital, but after he had left it 1 c.c. of the 1% solution was 
injected three times a week. “The attacks of colic were said to have en- 


] 


CLASSIFICATION. 233 


tirely disappeared and the patient had not felt so well for a long time as 
after this treatment.” 

Abundant food is the best means of exciting pancreatic secretion, 
according to, the experiments on animals. The investigations of Dolinski 
show that hydrochloric acid and some other acids, also acid drinks and 
foods, when taken into the stomach promote an abundant secretion of the 
pancreatic juice. An investigation by Becker has shown that alkaline 
salts, given with or without food, check the secretion of the pancreatic 
Juice. Perhaps some therapeutic indications may be gained from the 
results of these experiments. 

As arule, the treatment is wholly symptomatic, the colic being treated 
by narcotics and any disturbances of digestion or diabetes by a dietetic 
treatment. In the present stage of our knowledge surgical treatment is 
indicated only when an abscess or a cyst has developed in consequence of 
the lithiasis. | 





VAL NECKOSIs. 


Tue death of a part or of the whole of the pancreas may occur in the 
course oz various processes which affect the pancreas or its surroundings. 
Necrosis begins when portions of the gland or the entire organ are deprived 
of nourishment by any diseased process. 


CLASSIFICATION. 


There are two groups, according to the etiologic factors: (1) Necrosis 
caused by diseases of the pancreas; (2) necrosis caused by diseases of 
the surrounding tissues. There is a third series of cases in which the 
cause cannot be ascertained, but it undoubtedly belongs in the two above- 
mentioned groups. 


(A) NECROSIS FROM DISEASES OF THE PANCREAS. 


The diseases are as follows: * 

(a) Necrotic Inflammations.—Various forms of inflammation, es- 
pecially the suppurative, may lead to necrosis. In the section on this 
subject reference has been made to the necrosis of large or small portions 
of the pancreas. 

In Gendrin’s case a large cavity communicating with the jejunum 
was found in the region of the pancreas. The pancreatic tissue was de- 
generated into a dense mass streaked with red, which formed the walls 
of the cavity. Habershon found a purulent, gangrenous inflammation 
of the head and middle of the pancreas and peripancreatic abscesses in 
the region of the duodenum and in the lesser omentum. Moore saw the 
pancreas destroyed to a great extent by suppuration and the tail infil- 
trated with pus and in shreds. 

In a case of traumatic suppuration reported by Hansemann the se- 

* The separation of these different factors is purely arbitrary, since there are 


numerous combinations between inflammation, hemorrhage, and fat necrosis, and 
each of these combinations may be connected with necrosis of the gland. 


234 NECROSIS. 


questrated pancreas lay in a cavity filled with pus. Dieckhoff reports. 
a similar case. The middle and tail of the pancreas were entirely de- 
stroyed and changed into a mass filled with greenish and yellow fragments 
and the tail was almost entirely detached. In the pancreatic abscess 
operated upon by KoOrte necrotic bits of tissue also were found in the 
evacuated pus, and on microscopic examination contained acinous struc- 
tures. In chronic inflammations also the necrosis of small portions may 
develop from the growth of the intima and the obliteration of the blood- 
vessels (Dieckhoff). In 1891 a case in point was examined after death in 
the Vienna General Hospital. Chronic pancreatitis with partial necrosis 
of the tail of the pancreas was found in a man forty-one years old with 
diabetes insipidus. . 

(b) Hemorrhages within and around the pancreas cause necrosis 
of small portions or of the entire organ. Such cases are reported by 
Haller and Klob, Prince and Gannett, Whitney and Harris, Homans and 
Gannett, Rosenbach, and Dieckhoff. The following case may briefly be 
mentioned as an example of the course of the disease: 


Homans and Gannett (quoted from Fitz): A woman forty years old had an 
umbilical hernia for two years after lifting a heavy weight; for the last two weeks 
it was irreducible and painful. On the day after entering the hospital there were 
vomiting, violent colic, small, fluttering pulse; the next day persistent vomiting, 
anxious expression, pulse 100, at times imperceptible; normal temperature. The 
day afterward the pulse was 140, temperature 38.2° C. (100.8° F.), vomiting ceased, 
coma, dyspnea, death on the fourth day. At the autopsy were found: Hemor- 
rhagic infiltration and gangrene of the pancreas, circumscribed peritonitis, gan- 
grene of the diaphragm, acute pleuritis and pericarditis. Thrombosis of the 
splenic vein. 


Circumscribed necrosis of the pancreas may likewise be caused by 
hemorrhages in consequence of arteriosclerotic changes in the blood- 
vessels. J had the opportunity of observing in the hospital such a case 
which also was clinically noteworthy. 


M. P., forty-four years old, admitted July 28, 1896: For two and a half months 
violent pains in the region of the stomach, loss of appetite, constipation, gradually 
increasing jaundice, and for four weeks considerable emaciation. At the time of 
admission there was a high degree of jaundice, cachectic appearance, great sensitive- 
ness to pressure, also pain under the edge of the right ribs, liver dulness reaches 
two finger-breadths below the border of the ribs, abdomen flat, no distinct tumor 
palpable, no ascites, edema of the lower part of the thigh, urine contained much 
bile pigment, but no sugar or albumin. Temperature 37.2° C. (98.96° F.). The 
patient complained of unusually violent, continuous pain in the epigastrium, radiat- 
ing over the abdomen, and was very weak. Later, the weakness gradually increased; 
there was dizziness on sitting up in bed, and the cachexia was marked. The patient 
almost refused to take any food on account of the pain. Nourishment by enemata. 
With marked exhaustion, death occurred November 7, 1896. 


The autopsy, conducted by Prosector Dr. Zemann, gave the following 
result: 


The body, much emaciated, showed a high degree of jaundice. Thorax much 
arched, abdominal walls slightly distended and of a dirty green color in the hypo- 
gastrium. Lungs of diminished substance and collapsed. Heart small, contracted. 
Valves showed yellowish spots and were opaque. The liver scarcely projected 
beyond the border of the ribs, small and flabby; its surface smooth, capsule easily 
torn. On section, the liver dark green, the acinous structure distinct, the acini 
very small. The bile-ducts slightly distended, a small amount of dark, greenish- 
yellow bile escaping. The gall-bladder flaccid, about as large as a goose-egg, 
contained a considerable quantity of uniformly colored, slimy bile. Spleen some- 
what enlarged, rich in blood, and soft. 


7 


CLASSIFICATION. 235 


The intestinal coils and the stomach were distended with gas. The great 
omentum was spread like an apron over the intestinal coils, to which it was agglu- 
tinated. The coils also were adherent by means of purulent fibrinous plates. Thin 
pus was to be found here and there inclosed in small spaces between the intestinal 
loops. The stomach contained gas and a little viscid, opaque, pale-gray, watery 
fluid. The mucous membrane was pale, covered with whitish mucus. Large 
amounts of dark-green bile in the duodenum, especially in the descending portion. 
The mucosa was stained of a bile-green color. 

Near the mouth of the common duct a slightly prominent portion of the intes- 
tinal wall for about 2 or 3 cm. formed a soft, disintegrated mass of tissue, stained 
dark yellow, within which the opening of the bile-duct at first was not to be found. 
The large bile-ducts were thin-walled, dilated, and collapsed, and contained a 
small quantity of bile. The wall of the common duct immediately beyond its 
mouth was replaced by a whitish, moderately soft, succulent neoplasm, which was 
continued into the above-mentioned disintegrated tissue of the duodenal wall. 
The common duct was rather narrow at this point, but easily penetrated. The 
adjacent head of the pancreas was formed of large lobes, and was easily separated 
from the duodenum. The pancreas, somewhat narrower and thinner than normal, 
was closely adherent to the posterior wall of the stomach. On the anterior surface 
oi the tail of the pancreas, bounded in front by the stomach and transverse colon 
and at the side by the spleen, was a spherical cavity about the size of a man’s fist, 
with a pocket as large as a plum on the upper edge of the tail of the pancreas. This 
cavity, filled with thin pus, was surrounded on all sides by a thin membrane, coated 
superficially with pus. Careful investigation showed that this membrane also 
separated the pancreas from the cavity. On the lower border of the body of the 
pancreas was a group of pancreatic lobules about the size of peas, softened almost 
to the consistency of pap, and of a dark reddish-black color. These were surrounded 
by lobules which appeared as usual. The pancreatic artery and its traceable 
branches were thick-walled and frequently calcified. The splenic, renal, and intes- 
tinal arteries were similarly altered. There were thin masses very darkly stained 
with bile in the small intestine and bile-stained fecal matter in the large intestine. 
The kidneys were somewhat smaller than normal, capsule stripped off easily, surface 
smooth. Bladder contracted. 

Diagnosis: Medullary carcinoma of the common duct extending to the duo- 
denum with stenosis of the bile-duct. Ulceration of the cancer with relief of the 
stenosis by means of the destruction of the neoplasm. Recent diffuse peritonitis 
with fibrinopurulent exudation and with cyst-like encapsulation in the region of 
the tail of the pancreas. Circumscribed necrosis of the pancreas with hemor- 
rhagic infiltration of the necrotic portion and chronic endarteritis and calcification 
of the pancreatic artery. Marasmus. General jaundice. 

The microscopic examination of the necrotic mass in the pancreas showed 
a transformation of the cells into a fatty detritus mixed with numerous red blood- 
corpuscles. The walls of the capillaries everywhere had undergone fatty degenera- 
tion. Outside of the necrotic area also there were spots of fatty degeneration of 
gland cells and of capillaries. 


The possibility of a cancer of the pancreas was thought of by me 
on account of the gradual development of a completely obstructing 
jaundice, the rapid progress of cachexia with extreme debility, the 
peculiar, violent pains, and the great sensitiveness to pressure under the 
right border of the ribs, as far as the middle line. 

At the autopsy it was shown that two processes were going on at the 
same time: (1) A cancer of the common duct extending to the duode- 
num and causing a stenosis of the bile-duct, which was somewhat relieved 
by the degeneration of the neoplasm. Recent peritonitis. (2) A cir- 
cumscribed necrosis of the pancreas with hemorrhagic infiltration of the 
necrotic portion in consequence of chronic endarteritis and calcification 
of the pancreatic artery. 

It is probable that the picture of disease resembling that of cancer 
of the pancreas was developed by the combination of cancer of the com- 
mon duct with the changes in the pancreas due to arteriosclerosis. 

(c) Fat necrosis is frequently stated to be the cause of the necrosis 


236 NECROSIS. 


of the gland. The hemorrhage caused by the fat necrosis or the extensive 
fat necrosis itself may lead to necrosis of the gland to a greater or less 
extent. It is not yet clear whether the same factor which has caused. 
the fat necrosis may not lead also to necrosis of the pancreas, or whether 
the fat necrosis is to be regarded as a result of the necrosis of the gland. 

Experiments on animals, as will be shown, permit the assumption 
that the fat necrosis may be caused by the action of the pancreatic secre- 
tion. Chiari’s observations also, which will be mentioned later, show 
that multiple, circumscribed necroses of the gland-parenchyma probably 
may be caused by the same factor—autodigestion. It is, therefore, 
quite conceivable that in man also fat necrosis and necrosis of the gland- 
parenchyma may be attributed to the same cause. The relation between 
fat necrosis and gangrene of the gland will be considered later in the 
section on Fat Necrosis. 

There are numerous communications on the subject of gangrene with 
or in consequence of fat necrosis: Balser, Mader-Weichselbaum, Farge, 
Whittier and Fitz, Gerhardi, Foster and Fitz, Langerhans, Hansemann, 
Konig, Caspersohn-Hansen, Korte, Simon and Stanley, Sarfert, Elliott, 
v. Bonsdorff. E. Fraenkel, Sievers, etc. Several of these cases will be 
mentioned in the section on Fat Necrosis. A brief sketch only of a few 
especially striking and clinically interesting examples follows: 


Mader-Weichselbaum: Coachman’s wife, forty-two years old, who four years 
before had suffered from jaundice due to gall-stones, was attacked with distention 
of the stomach, vomiting, and abdominal pain. On the next day jaundice developed. 
Two or three times a day there was a chill with subsequent fever and sweating. 

Present condition: Moderate jaundice, temperature 38° C. (100.4° F.). Pulse 
scarcely accelerated. Splenic tumor. Liver normal. In both lumbar regions 
there was circumscribed, pronounced edema of the skin. Vomiting. Two days 
later there was a chill, temperature 40.2° C. (104.4° F.), loss of consciousness, and 
on the next day symptoms of a beginning (metastatic) meningitis. Two days 
later, temperature 37.4° C. (99.3° F.), with almost constant unconsciousness. Ex- 
ploratory puncture in the region of the spleen produced a dirty, reddish fluid. Death 
on the next day. 

The autopsy showed purulent meningitis, enlargement of the spleen, throm- 
bosis of the splenic vein, marked softening of the tail and a portion of the body 
of the pancreas, which was grayish-black in color and infiltrated with a thin, ichorous 
fluid. The tissue around the pancreas presented the same appearances. The 
head was quite intact and contained several yellow patches, from the size of a pea 
to that of hemp-seed, consisting of a thick, greasy pulp. Microscopically the latter 
consisted of numerous fat granular corpuscles, very small fat-drops, and numerous »* 
fat-crystals. Similar foci also were found quite abundantly in the transverse meso- 
colon and in the upper portion of the great omentum, at times surrounded by a 
hemorrhagic zone. Occasional pancreatic veins opening into the splenic vein were 
obstructed by grayish-red thrombi. 

Weichselbaum concluded that gangrene of the pancreas resulting in pyemia 
had followed fat necrosis of the gland. 

Caspersohn-Hansen: A very fat woman, thirty-six years old, was attacked with 
vomiting and severe pain in the region of the stomach; improvement after fourteen 
days’ treatment. Then renewed vomiting, pain, slight distention of the abdomen. 

Diagnosis: Circumscribed peritonitis in consequence of ulcer of the stomach. 
Resistance in:the left upper half of the abdomen, small rapid pulse; exploratory 
ee: After section of the abdominal walls a tumor-like mass was seen 
which had become firmly united to the peritoneum and proved to be fat tissue which 
had undergone diffuse ‘tiraiie induration. The abdominal cavity was opened and 
an opaque ascitic fluid evacuated. There was no inflammatory focus. At the 
autopsy a large cyst was found behind the liver, filled with a clear, odorless, dark, 
coffee-brown fluid. The following conditions were apparent: (1) Total necrosis 
and partial separation of the pancreas; (2) remains of hemorrhage into the pancreas; 
(3) circumscribed chronic peritonitis of the omental bursa, the exudation containing 
hematin; (4) disseminated fat necrosis. 


v 


CLASSIFICATION. 237 


Caspersohn regarded the fat necrosis as the cause of the hemorrhage. 
Necrosis of the pancreatic tissue resulted from the effusion of blood. 
An active dissecting inflammation developed for the elimination of the 
degenerated portions and extended toward the peritoneum. The fora- 
men of Winslow became occluded and a cyst of the omental bursa was 
formed. ‘The increasing distention of the cyst caused pressure upon the 
nervous apparatus and consequent collapse followed by death. 


Korte *: Tinker twenty-two years old suffered for five years with attacks of 
pain in the stomach and vomiting. Was suddenly seized with violent abdominal 
ain, vomiting, and headache. Temperature 39.2° C. (102.6° F.). Pulse 140. 
Slight cyanosis, pain in the left lower abdomen and loin, serous pleurisy on the 
left side. Edema of the skin of the abdomen on the left side between the borders 
of the ribs and the pelvis. Puncture caused the escape of a brownish-red, turbid 
fluid, with crumbling fragments, in which were numerous long rod-like bacteria 
and fatty degenerated pus-corpuscles. Urine free from albumin and sugar. The 
skin was incised longitudinally along the anterior axillary line, from the border of 
the ribs to the brim of the pelvis. The retroperitoneal tissue was laid open and 
a large amount of the fluid described, containing numerous yellowish-brown crum- 
bling shreds, was evacuated from a considerable depth. Drainage. The fever con- 
tinued. Aspiration of the pleuritic exudation. An indistinct, fluctuating swelling 
was felt below the xiphoid cartilage. Laparotomy. Yellow, cheesy pus escaped 
on puncture. The gastrocolic ligament was divided, the wall of the abscess was torn 
in suturing, and a thick, brownish-yellow pus poured out, mingled with necrotic 
bits of tissue and fat-drops. Drainage; soon after the operation, collapse and death. 
Autopsy: Pancreas about one-half its normal size, infiltrated with blood, and 
the head changed into a greasy, light-gray mass of clayey consistency. Gall-bladder 
filled with small concretions; fat necrosis in the omentum; a section of the left 
adrenal shows bright yellow masses similar to those in the omentum. The yellow 
material evacuated from the abscess consists microscopically of fat, fat-crystals, 
and yellow pigment, but contains no pus-corpuscles. 

Sarfert: An extremely fat woman twenty-four years old was attacked fourteen 
days before death with sudden abdominal pain, abundant bilious but not fecal 
vomiting ; pronounced meteorism, great sensitiveness to pressure, fever and dyspnea. 
Stools were obtained by enemata of oil; there was temporary benefit, followed by a 
renewal of obstruction. The temperature became elevated, there were cyanosis, 
vomiting, rapid pulse, collapse. 

At the autopsy the abdominal cavity was filled with a yellow purulent mass 
in which floated numerous brittle, granular fragments of the color of yellow wax. 
The pancreas formed behind the stomach a dark-brown, shreddy mass surrounded 
by pus, the tail floating free. Foci of fat necrosis as large as beans were found in 
the mesentery, in the omentum, and in the preperitoneal fat. 


»  (d) Chiari recently has called attention to a peculiar form of pancreatic 
necrosis. In 1891 “an autopsy was performed, twelve hours after death, 
on a man twenty-five years old who had died three days after the extirpa- 
tion of a sarcoma of the left side of the neck, which had developed from 
the lymph-glands, from rupture of the left external carotid with conse- 
quent hemorrhage. In the left half of the body of the pancreas, which 
otherwise had the usual structure, although pale, there was a dark-green 
mass, about 1 cm. in size, irregularly formed and sharply limited from 
its surroundings, which immediately gave the impression of a circum- 
scribed necrosis of the gland.”” The microscopic examination confirmed 
the diagnosis. “The mass consisted of necrotic pancreatic tissue, in 
which the acini were still to be distinguished. Neither in the cells of 
the acini, nor in the interstitial tissue, which did not appear thickened, 
was a nuclear stain to be obtained. Everything had become necrotic.” 


* This case (No. IIT of his series) is regarded by Kérte as one of acute pancreati- 
tis, with consecutive necrosis of the gland and fat necrosis, previously mentioned on 


page 126. 


238 NECROSIS. 


The pancreatic tissue surrounding the necrotic portions showed quite a 
considerable increase of interstitial connective tissue, which generally 
appeared extensively infiltrated with small cells. It was, therefore, as 
Chiari suggests, a case of circumscribed necrosis of the pancreatic tissue, 
with resulting reactive inflammation around it. There was no doubt 
that the circumscribed necrosis came first and the reactive inflammation 
in the vicinity afterward. There was no evidence that the necrosis was 
caused by a disturbance of the circulation, interstitial inflammation, 
or injury. Chiari thought it most probable that a chemical agent had 
caused the necrosis of the acini and the interstitial tissue several days 
before death, in time for the development of a reactive inflammation. 
He regards the pancreatic juice as such an agent which had caused an 
autodigestion of the organ analogous to the method of origin of the 
peptic ulcer of the stomach. 

Two years later Chiari found a similar case. An autopsy was held 
on the body of a woman thirty-two years old who had suffered from diffuse 
bronchitis and erythema exsudativum multiforme. The pancreas was 
found somewhat larger than normal, of dense consistency and paler color. 
It contained numerous sharply defined, irregular foci, some as large as 
1 cm., but most of them much smaller, yellowish-white, homogeneous, 
quite firm, and surrounded by a red zone. On microscopic examina- 
tion, Chiari could distinguish three varieties: (1) Those in which the 
necrotic acini were not completely destroyed; (2) those in which the dead 
acini were destroyed in places; (8) those in which all the necrotic acini 
were more or less extensively destroyed. Elsewhere the pancreas showed 
throughout an increase of the connective tissue between the lobules and 
acini, in which there was a greater or less infiltration with small cells and 
moderate lipomatosis. There was, therefore, in this case also a reactive 
inflammation in the vicinity of the necrotic portion. There were also 
neither disturbance of the circulation, trauma, nor a precedent interstitial 
pancreatitis, hence Chiari considered it probable here likewise that the 
digestive action of the pancreatic juice had caused the necrosis. 


(B) NECROSIS DUE TO DISEASE IN THE VICINITY OF ‘THE 
PANCREAS, 


There are several observations of this sort. The gangrene is most: 
frequently produced by the passage of gall-stones, which cause inflam- 
matory and ichorous processes. 


Chiari and Schossberger: A man, thirty-eight years old, who had formerly 
suffered very little from sickness, had an attack of cholelithiasis; he was afterward 
well for one year. After an illness of twelve days occasional attacks of pain in the 
stomach appeared; then suddenly there were vomiting, severe colic, symptoms of 
intestinal obstruction, and collapse. On the next day there was no fever and the 
general condition was good. Two days later renewed symptoms of intestinal 
obstruction, pronounced meteorism, and vomiting which could not be relieved. 
After calomel and irrigation, there was a passage of very offensive stools, and the 
next day the condition was improved. Sixteen days later there was high fever, 
lasting three days, with renewed symptoms of intestinal obstruction; after passage 
of stools, the fever was again relieved, and for eighteen days free passage and ob- 
struction alternated. A piece of tissue was found in the stools which Chiari diag- 
nosticated as pancreatic tissue. For some time the patient noticed some sensitive- 
ee on the left side of the abdomen, but some years later he was still perfectly 
well. 

The piece of pancreas which escaped with the feces was about 13 cm. long 
quite uniformly cylindric, and of the thickness of the index-finger; on longitudin 

% 


CLASSIFICATION. 239 


section it showed a piece of a canal about 3 cm. long, which appeared exactly like 
the ductus Wirsungianus. On microscopic examination, remains of acini could be 
recognized. 


The following course of the affection could easily be imagined: 
A gall-stone perforated (probably from the common duct) and caused 
inflammation and suppuration of the tissue surrounding the pancreas, 
which opened into the duodenum or some other portion of the intestine, 
and the detached pancreas passed through this opening and was evacu- 
ated with the feces. 


Rokitansky-Trafoyer (museum preparation) : A wine-dealer fifty-two years old 
was suddenly attacked with severe colic two months after there had been disturb- 
ances of digestion. Diagnosis: Cholelithiasis. After a very severe attack, 18 gall- 
stones were found in the stools, and three days later there was another severe attack 
of colic. The next day a large discolored mass of tissue was passed, which Rokitan- 
sky recognized as the sequestrated pancreas. Complete recovery after three weeks. 
Seven years later the patient was still in perfect health. 


Chiari reports an interesting case of gangrene of the pancreas in 
consequence of perforation of the stomach by a round ulcer. 


An inebriate fifty-four years old suffered for seven years from pains in the 
stomach and vomiting; the stools were frequently black. In the latter part of this 
period, the pains in the stomach became much more severe. At the time of ad- 
mission the patient was fat and slightly jaundiced. Examination of the lungs showed 
dulness and bronchial breathing; the heart-sounds were clear but weak, the epi- 
gastrium painful, otherwise nothing abnormal. Temperature 37.7° C. (99.86° F.). 
In the third week of the stay at the hospital, bed-sores; in the fourth, parotitis on 
the left side, which disappeared after some days. Anorexia, progressive weakness, 
death after the patient had been in the hospital for six weeks. 

Autopsy: Extensive panniculus adiposus; cardiac muscle fatty degenerated; 
liver large, pale, infiltrated with fat; gall-bladder adherent to the duodenum and 
containing numerous concretions; in the stomach a fluid of offensive odor. In the 
posterior wall of the stomach, about half-way between the cardia and the pylorus, was 
a perforating ulcer, 1 cm. in diameter, through which a probe passed into the omental 
bursa; 3 cm. distant was a second round ulcer. Omental bursa transformed into a 
large ichorous cavity, entirely separated from the general peritoneal cavity by oc- 
clusion of the foramen of Winslow by adhesions; five perforations, some as large as 
the little finger, into the uppermost portion of the jejunum. Lying across the ichor- 
ous cavity was a cylindric shreddy mass of tissue, about 12 cm. long, of the thick- 
ness of the little finger at its left end and somewhat thicker at the right, entirely 
isolated and brownish-black in color. Near the descending portion of the duode- - 
num, the central end of the ductus Wirsungianus was found embedded in indurated 
tissue; it was about 3 cm. long and opened freely into the ichorous cavity. 


(C) NECROSIS OF THE PANCREAS FROM INDEFINITE CAUSES. 


Chiari: In a woman forty-six years old for some days there were severe pain in the 
abdomen, vomiting, diffuse peritonitis; seven hours before death, chill and vomiting 
of a black mass of offensive odor. At the autopsy the body was found very corpu- 
lent and there was a recent, diffuse, purulent peritonitis. Sequestration of the 
blackish-brown pancreas, which was attached merely by remains of connective tissue, 
easily torn. On longitudinal incision of the pancreas the duct was easily recognized. 
Putrefaction in the omental bursa. Perforation of the duodenum and transverse 
mesocolon, opening in the pancreatico-duodenal artery. The gall-bladder con- 
tained 60 polyhedral stones. 


In this case the sequestration of the pancreas might have been caused 
by a primary pancreatitis or peripancreatitis or by hemorrhage into the 
pancreas; on the other hand, “the possibility cannot be entirely excluded 
that the opening in the duodenum, which at the autopsy presented the 
characteristics of a perforation from without inward, in part, at least, 


240 NECROSIS. 


originated in the intestine, perhaps from injury of the intestinal wall 
by a small foreign body with perforation into the omental bursa, the 
opening later being enlarged by the ichorous process. It would not be 
difficult to understand the sequestration of the pancreas in consequence 
of a traumatic peripancreatitis and pancreatitis caused by such a foreign 
body, since, according to Bruckmiiller (‘Lehrbuch der pathologischen 
Zootomie’), this occurrence is said to take place frequently in dogs” 
(Chiari). 


Korte: Woman thirty years old; has borne three children; five days after the 
last confinement there was violent pain in the epigastrium with feeling of weakness; 
afterward fairly good condition. Six weeks later violent pains radiating from the 
upper abdomen over the body. She was admitted to the hospital on account of the 
severe pain. Slight jaundice, collapse, remittent fever up to 40° C. (104° F.). Sen- 
sitiveness of the abdomen, slight albuminuria, resistance in the left epigastric region 
extending to the kidney. Colon lies in front of the tumor; irregular variations of 
temperature for a month. The tumor remained at the left. Repeated puncture 
never. caused the appearance of pus, but gave a brownish-yellow fluid in which were 
cells showing extensive fatty degeneration, yellowish-brown pigment, and some 
bacteria. Renewed high fever, poor general condition. Operation: Horizontal 
incision in the lumbar region, exposure of the lower end of the kidney; a yellowish- 
gray mass as large as a walnut was exposed in which were fatty contents; drainage; 
the condition continued bad. Fourteen days later, the wound was enlarged down- 
ward and a retroperitoneal cavity was reached which contained a brownish fluid and 
yellow necrotic fragments. Curettage. A sequestrated piece of tissue 11 em. long 
and 2 to 2.5 em. wide was removed; the fever abated. A week later there was 
severe hemorrhage from the depths of the wound, which was repeated; death. Au- 
topsy: Large, ichorous, encapsulated abscess between stomach, spleen, diaphragm, 
and kidney. Only the head and a small piece of the tail of the pancreas were found, 
Parietal thrombosis of the splenic artery. Numerous calculi in the gall-bladder. 


It is not to be determined in this case that the gall-stones were in 
any causal relation with the process. It certainly would be possible that 
the inflammation caused by the cholelithiasis in the bile-passages might 
have been continued into the pancreatic duct. In the cases of gangrene 
of Middleton, Garzia, and Israel also, no definite cause of the necrosis 
could be assigned. 

Among reports of autopsies at the Vienna General Hospital for the 
last ten years there was likewise found a case of circumscribed necrosis 
in the tail of the pancreas of a diabetic, fifty-two years old, but no fur- 
ther information is given concerning the cause. 


PATHOLOGIC ANATOMY. 


The occurrence of partial or total necrosis as observed at operations 
and at autopsies is mentioned in the preceding statement. The ap- 
pearances vary according to the duration and cause of the development 
of the process. Fitz suggests the following scheme, based on the dura- 
tion of the process: 

After a period of four days, the pancreas is doubled in size, dark 
red, consistency diminished, the section red or mixed gray and red. The 
cut surface is shreddy or the whole gland is transformed into a dark- 
colored mass of offensive odor. After ten days the pancreas is dark- 
brown, hard, firm, surrounded by hemorrhagic masses or embedded in 
spongy, dark green masses. Toward the end of the second week the 
gland is changed into a soft, dark, ragged, gangrenous mass. After 
three weeks the pancreas, dark-brown, lies almost free in the cavity of 


> 


PATHOLOGIC ANATOMY. 241 


the omentum, connected with the wall only by a few bands that are 
easily broken or by fibrous tissue. During the fourth and fifth weeks the 
pancreas may become sequestrated and evacuated with the feces. To- 
ward the end of the seventh week it may appear changed into a ragged, 
cylindric, dark-brown mass. This mass lies in the cavity of the omentum, 
which is filled with dark fluid and communicates with the stomach and 
intestine. General peritonitis does not occur frequently, since adhesions 
form, which prevent the escape of the pus into the abdominal cavity. 
Adhesive peritonitis is not rare. Pleuritis, pericarditis, acute lepto- 
meningitis, and hypostatic pneumonia are found at times. 

In the case reported by Dieckhoff the necrotic portion was trans- 
formed into a mass containing numerous green and yellow fragments. 
The microscopic examination showed: 


“Scarcely any indication of pancreatic structure in the sequestrated portion of 
the gland, but there were merely large or small areas of necrotic tissue extensively 
infiltrated with pus-corpuscles, the nuclei of which were indented or fragmeritary, 
and, in addition, often stained with difficulty. There was an enormous accumulation 
of micro-organisms in this portion. On staining by Weigert’s method, there were 
found only lance-shaped diplococci and streptococci, which were sometimes within 
and sometimes between the cells. On staining with borax-methylene-blue, a few 
quite large, thick bacilli were found (probably Bacterium coli commune).”’ 


Chiari, as above mentioned, could recognize microscopically three 
different foci in his cases of multiple, circumscribed necrosis, probably 
due to autodigestion. 

(a) In the places where the necrotic acini were not entirely degener- 
ated he could readily observe individual acini, although the epithelial 
nuclei did not stain. The interstitial tissue was not thickened. Its 
nuclei were either stained or unstained. The focus was surrounded by 
a zone of thick, fibrous tissue, infiltrated with small cells. 

(b) In a second variety, as a rule, by far the larger portions of the 
necrotic acini were disintegrated into a finely granular mass. The in- 
terstitial tissue frequently showed slight nuclear increase and often con- 
tained clumps of brown granular pigment. The indurated tissue about 
these foci was generally more extensive than around those of the first 
variety. 

(c) Foci in which all the necrotic acini were destroyed. Usually the 
boundaries between the acini were no longer distinct, but were replaced 
by a granular detritus of which the septa between the individual acini 
at times formed a part. There was an extensive development of con- 
nective tissue forming thick capsules around these foci. The anatomic 
condition in gangrene of the pancreas as it occurs in fat necrosis is con- 
sidered in the section on Fat Necrosis. 

Experiments on Animals.—In one case necrosis of the pancreas was 
produced after the injection of olive oil into the parenchyma and liga- 
tion of the body of the gland. 


November 2, 1896: Small dog. Pancreas drawn forward. In the body and 
head of the gland 0.2 gm. Ol. olivarum were injected in three places. The mid- 
dle portion of the organ was ligated in three places, the blood-vessels being spared. 
During the operation digestion was at its height; the chyle-vessels were distended ; 
the pancreas was very large and ofa rose-red color. The operation lasted about 
three-quarters of an hour. . ; 

November 3, 1896: The dog was quite lively and drank water. Urine 65 c.c., 
golden-yellow. Amount of sugar 2.4%. No acetone. 

November 4, 1896: Dog very weak. 


16 


242 | NECROSIS. 


November 5, 1896: Refused food. No sugar in the urine. Bile pigment was 
resent. 
November 6, 1896: Dog found dead. 

Autopsy: Slight suppuration of the abdominal wall. The peritoneum smooth 
and somewhat redder than usual. No fluid in the peritoneal cavity. Pancreas as 
a whole somewhat enlarged. Upon the surface were pale red spots and yellowish- 
white patches, elsewhere the color was either bright or dark red. The structure of 
the gland is everywhere recognizable, and between the individual lobules the blood- 
vessels are hyperdistended with blood. On the border between the head and tail 
there is a part as large as a bean, its surface dark red, in which the glandular struc- 
ture is not to be recognized and which is surrounded by a yellowish-white zone. Im- 
mediately adjoining it, toward the tail, is a hemorrhage as large as a pea. Near the 
tail and separated by a ligature is a glistening chalk-like lobule in which no structure 
is to be recognized. The tissue everywhere feels denser and firmer than normal. 
The tail appears pale, dense, in places infiltrated with blood, but otherwise quite 
normal. The body shows the most marked changes and is dense. On section the 





Fic. 14.—a, Normal gland tissue; b, small-celled infiltration ; ¢, necrotic tissue. 


gland structure is in part indistinct. There are dense portions as large as peas, 
yellowish-white or green in color, sharply limited from the reddened tissue, in which 
the details are indistinct. There is a lobule as large as a pea infiltrated with blood 
at the point of transition from the body into the tail. On section of the head the 
structure of the gland is to be recognized, the lobules project as granules, and in 
places, especially toward the surface of the gland, there are glistening yellowish- 
white, dense portions of the size of the head of a pin or larger. Toward the body is 
a portion as large as a pea, infiltrated with blood and surrounded by glistening 
white points as large as pinheads. 


The microscopic examination gave the result shown in figure 14. 
There was an extensive small-celled infiltration around the necrotic 
focus, which extended also into the normal structure as far as the sur- 
face. 


SYMPTOMS. ; 243 


SYMPTOMS. 


Many processes which are active within or around the pancreas may 
result in necrosis. Such are acute and chronic inflammations of the 
pancreas, moderate or circumscribed hemorrhage, trauma resulting in 
hemorrhage or inflammation, fat necrosis causing necrosis either directly 
or through hemorrhage, if perhaps it is not due to the same cause as the 
gangrene of the gland, autodigestive processes due to unknown causes, 
during life suppurative and ichorous conditions due to perforating ulcers 
of the stomach or to perforating gall-stones and all other factors which 
lead to an abscess of the omental bursa. It is certainly to be considered 
in a number of cases, as has repeatedly been stated, that infectious organ- 
isms entering from the intestine under certain conditions may be the 
cause of suppuration, putrefaction, and necrosis. 

The numerous causes produce a varied course and a differing picture 
of disease. Moderate pancreatic hemorrhage, pancreatic abscess, ex- 
tensive fat necrosis, perforating gastric ulcer, resulting in a retroven- 
tricular gangrenous condition, inflammation due to the passage of gall- 
stones, must produce pictures of disease varying in their beginning, their 
development, and their course up to a certain point, at which the peculiar 
necrosis of the gland, with all the secondary changes due to it, is estab- 
lished. Sometimes the development of this condition is preceded by 
years of suffering, as in case of gastric ulcer or cholelithiasis, while at 
other times the severe disease, with the group of symptoms described 
in the sections on Pancreatic Abscess and Pancreatic Hemorrhage, ap- 
pears in the midst of perfect health, or at least when the condition is 
relatively good. It is obviously impossible that symptoms characteristic 
of the necrosis should become prominent when it is considered that the 
necrosis is the result of various processes, and when it occurs gives rise 
to new alterations in addition to the persistence and increase of those 
caused by the original disease. A pathologic condition thus arises not 
limited to the pancreas, but involving the neighboring structures, often 
for a considerable distance. Bursal abscess, retroperitoneal suppura- 
tion, the formation of a large gangrenous cavity which contains the 
necrotic pancreas, are then the prominent features. 

In all cases from the beginning there are violent pains, at first limited 
to the epigastrium, but later radiating in all directions over the abdomen, 
toward the back, and often only into the left hypochondrium. These 
are soon followed by vomiting, persistent nausea, meteorism, tenderness, 
prostration, progressive collapse, accelerated pulse, dry tongue, irregular 
fever sometimes with chills. An apparent, temporary improvement 
may occur in some cases, until another and much more violent attack in- 
dicates a new stage in the progress of the disease. Besides these symp- 
toms, intestinal obstruction is occasionally observed. In the cases of 
Gerhardi, Balser, Rosenbach, Hirschberg, Caspersohn, v. Bonsdorff, 
Allina, ete., the diagnosis of an internal constriction was made, and in 
several of the cases laparotomy was undertaken without any suceess 
in discovering the obstruction. 

When a bursal abscess or a retroperitoneal collection of pus forms, a 
tumor may be recognized or there is a diffused or circumscribed resistance. 
Thus, Rosenbach felt behind and below the stomach a tumor the size of a 
child’s head, K6nig found a resistance and dulness as large as the surface 


244 ‘ FAT NECROSIS. 


of the hand, Caspersohn showed a resistance in the left upper half of the 
abdomen, and Korte felt a resistance, perhaps a tumor, in the upper 
abdomen. The tumor corresponds to the collection of pus which has 
developed in the omental bursa or in a retroperitoneal cavity. The 
sequestrated pancreas is sometimes found at the bottom of the pus cavity, 
as in the cases reported by Langerhans, Hansemann, Caspersohn, Rosen- 
bach, Chiari, Israel, ete. 

The abscess may rupture into the intestine, as has already been 
mentioned, and the sequestrated pancreas also may pass off with the 
stools, as in the cases reported by Rokitansky and Chiari. 

Death occurs with the symptoms of rapid and continuous collapse 
or pyemia, peritonitis, fatal hemorrhage, embolism of the pulmonary 
artery, or metastatic pleurisy, pericarditis, or leptomeningitis—if the 
extremely rare event does not happen that the necrotic pancreas is dis- 
charged with the feces with resulting recovery, or if the latter event 
does not take place by the discharge of necrotic tissue and pus from a 
successful operation, as in Korte’s case. 


DIAGNOSIS. 


The diagnosis of gangrene of the pancreas can only be made when 
the sequestrated pancreas passes off with the stools or when necrotic 
portions of the pancreas are found at an operation upon a pancreatic or 
bursal abscess or a retroperitoneal collection of pus. In favorable cases 
the diagnosis can be made of a bursal abscess or suppuration proceeding 
from the pancreas. The section on Pancreatic Abscess contains what 
is to be said on this point. 

Successful treatment is possible only by means of an operation, and 
the section on Suppurative Pancreatitis states what is worthy~ of 
mention in regard to this subject. 





IX. FAT NECROSIS (Balser); NECROSIS OF FAT 
TISSUE (Langerhans, Chiari). 


Necrosis of fat tissue represents a peculiar disease of the pancreas, 
in many respects still mysterious, and of equal interest and importance. 
in its origin, course, and results. Balser, in 1882, first called attention 
to this condition, which is by no means a rare pathologic change. Ten 
years before, Ponfick had described the presence, in the fat-marrow of 
the cylindric bones of a cachectic girl twenty-one years old, of small 
white foci consisting of very large fat-granular corpuscles which resulted 
in complete necrosis of the marrow tissue. There is no doubt that Klob 
had earlier observed the condition described by Balser, but had not 
recognized the importance of the change. In cases of atrophied pancreas 
caused by passive congestion in valvular disease, Klob saw, within the 
interstitial tissue, small clear white spots of almost tendinous appearance, 
from which material resembling an emulsion could be expressed, consist- 
ing in part of chalk molecules and gland-cells and in part of clumps of 
radiating crystals, probably calcium margarate. 


» 


PATHOGENESIS. ‘ 245 


Balser gave a minute description of the process in his fundamental 
work. There were found not infrequently—5 times in 25 bodies of adults 
selected indiscriminately—between the lobules of the pancreas opaque, 
yellowish-white, punctate foci, at times larger than pinheads and as a rule 
oval on section. The larger of these were peculiar in that the cut surface 
was not uniformly smooth, but the center was more or less completely 
detached from the periphery. In other foci the center was filled with a 
tallow-like material. These peculiar foci were often found not only 
between the lobules of the pancreas, but also in the fat tissue around the 
pancreas. Balser also found similar changes in four other cases. Once 
in the fatty bone-marrow, again in the very abundant subpericardial fat 
tissue, on both occasions in elderly men. In the other two cases there 
were very extensive and very numerous areas of fat necrosis in the vicinity 
of the pancreas and in the mesenteric fat tissue. 

Balser regarded the fat necrosis as the probable cause of death in 
these cases. He summarizes the results of his observations as follows: 
“Opaque, yellowish-white foci may be found, in the interacinous tissue 
of the pancreas, and more rarely in the surrounding fat tissue in the 
bodies of many adults, whether fat or lean. In the rarer cases their ex- 
tent, number, and size, with an associated necrosis of the central portion, 
are increased to a serious extent. Occasionally similar foci are found in 
the fat tissue of the bone-marrow and of the heart. Infiltration of the 
tissue adjoining the necroses indicating old or fresh hemorrhages is found 
rarely where the changes are few, but extensively where the changes are 
abundant. The necrotic areas may become confluent and prove a cause 
of death by their extent and by the simultaneous sequestration of large 
portions of the fat tissue in which they lie.” 

Balser came to the conclusion that an increase of the fat-cells in the 
vicinity of the pancreas was at the foundation of the process, “that this 
increase exceptionally, especially in very corpulent people, may reach 
such an extent that the death of large portions of the abdominal fat 
occurs, and in consequence gives rise to death, either through its extent 
alone or from the associated hemorrhages. Chiari next investigated this 
peculiar pathologic change. He confirmed the observation of Balser 
in individuals who were very marantic, especially as a result of tubercu- 
losis, syphilis, progressive paralysis, cancer, alcoholism, etc., and also 
in five cases of severe disease of the pancreas. 

Chiari came to another conclusion regarding the development of the 
process on the basis of his histologic investigations. According to him, 
this fat necrosis is a degenerative process, parallel with the retrograde 
metamorphoses so often occurring in other tissues, and to be designated 
fatty degeneration and simple necrosis. 

The divergence of the views advanced by Balser and Chiari caused 
Langerhans to undertake an extensive histologic and experimental in- 
vestigation, the results of which rendered the anatomic conditions quite 
clear, but offered merely an hypothesis concerning the etiology the 
soundness of which is still to be shown. 

Fitz, in his frequently quoted article published in 1889, takes another 
view. He considers that there are necrobiotic and inflammatory forms 
of fat necrosis, the latter showing a tendency to gangrene; both varieties 
occur in the pancreas or in its vicinity. The inflammatory and the 
gangrenous forms are of especial importance, and in most cases are the 

result of an acute inflammation of the gland. 


246 FAT NECROSIS. 


A large number of authors have studied the question of the necrosis 
of fat tissue, and have added to the statistics or have contributed ana- 
tomic and experimental investigations. Without attempting to give a 
complete list, the following names may be mentioned: Benda, Bruck- 
meyer, Caspersohn, Curschmann, Dettmer, Dieckhoff, Farge, Fitz, E. 
Fraenkel, von Gieson, Hansemann, Hawkins, Hildebrand, Hlava, Jack- 
son and Ernst, Jung, v. Kahlden, Konig, Korte, Lubarsch, Mader and 
Weichselbaum, Marchand, Pinkham and Whitney, Ponfick, Rolleston, 
Sarfert, Sievers, Stadelmann, Lindsay Steven, Whittier and Fitz. 


PATHOLOGIC ANATOMY. 


The necrosis of fat tissue occurs in the form of small areas, the most 
of which are the size of a millet-seed or of a hemp-seed. Very large 
necroses may arise through the confluence of numerous neighboring foci. 
The color is usually pure white, intensely opaque, sometimes yellowish- 
or grayish-white. Many of the foci have a hemorrhagic or pigmented 
center, and most of them are found separated from the surrounding 
tissue. They are seated between the lobules of the pancreas and in its 
immediate vicinity. These alterations are found isolated in the pan- 
creas and are very frequent in its vicinity (according to Balser, in about 
20% of the bodies examined). Large numbers of fat necroses are found 
much more rarely at a greater distance from the pancreas, in the omen- 
tum and mesentery and in the paranephric fat. They are found at times 
also in the subpericardial fat, in the bone-marrow, and in the subcu- 
taneous fat (Chiari, Hansemann). In Balser’s first case there were 
numerous bright, sulphur-yellow, opaque depositions in the fat tissue, 
as a rule of the size of lentils, more rarely of the size of cherry-stones. 
They were disseminated in the subperitoneal fat tissue of the abdominal 
wall, omentum, and mesentery. In acase recently reported by E. Fraen- 
kel, “the fat tissue of the great omentum and the mesentery of the small 
intestine contained a number of foci, at times as large as beans, isolated 
and in groups sharply defined from the normal tissue, with the luster of 
stearin, at times somewhat depressed, and remarkable for their dense 
consistency.’’ The transverse mesocolon in the region of the splenic 
flexure, also the mesentery of the descending colon, were necrotic and 
perforated. in numerous places. The foci were most abundant in the 
region of the pancreas, although the necrosis of the fat tissue was dis- 
tributed extensively in the fat tissue of the abdomen. According to Balser, 
the small disseminated foci, either limited to the pancreas or its immediate 
neighborhood or distributed extensively throughout the fat of the entire 
abdomen, form the early stage of a process which is not at all uncommon 
in fat individuals. Similar necrotic conditions were found also by Balser 
in fat animals, especially in Hungarian and Algerian swine. He found 
almost constantly in them numerous foci of fat necrosis in the pancreas 
and its immediate vicinity, either punctate or at times as large as peas. 
Heller also has not infrequently seen fat necrosis in the fat of swine. 

In the further course of the process the small necrotic foci become 
confluent and then other anatomic changes develop. The fat necrosis 
may, as many authors believe, give rise to inflammation, suppuration, 
hemorrhage, and necrosis of tissue. Thus the changes which are at first 
of little importance often prove deleterious. Many combinations occur. 


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NS acide cellist 


PLATE: 2; 





DIsSEMINATED NECROSIS OF THE MESENTERIC Fat Tissue In AcUTE HEMORRHAGIC 
PANCREATITIS. 


(From the Warren Anatomical Museum of Harvard Medical School, Boston.) 


= 





PATHOLOGIC ANATOMY. 247 


Fat necrosis not infrequently occurs in acute and chronic inflammations, 
and it is an open question whether the fat necrosis has caused the in- 
flammation, or whether, according to Fitz, Korte, and others, the in- 
flammation has caused the fat necrosis, or whether both these conditions 
are attributable to the same cause. 

The characteristic anatomic conditions which have been thoroughly 
described in previous sections develop when the necrosis of the fat tissue 
has led to more or less extensive hemorrhage in the pancreas or its vicinity, 
and when, either in consequence of these hemorrhages or directly, necrosis 
of portions of the gland or of the entire organ have formed. 

The morbid process which is scarcely to be recognized at the outset, 
according to the view of those writers who maintain the idiopathic nature 
of fat necrosis, may lead to total destruction of the entire gland, which 
is to be found in a cavity filled with ichorous fluid and containing other 
shreds of necrotic tissue, either wholly sequestrated or loosely attached 
to its walls. In describing the microscopic appearances Balser, Chiari, 
and Langerhans, who first made extensive investigations of the subject, 
differ materially from each other. 


Balser observed in fresh sections from the vicinity of definite fat necroses that the 
fat-cells were pressed apart by more or less broad bands which contained the mi- 
nutest fat-granules, also large and small fat-drops, and wholly concealed all other 
structures—namely, cells of connective tissue, capillaries, and fibers. After extraction 
of the fat the oil drops were found to be contained in thin membrane. Balser regarded 
these small cells containing fat as young cells of fat tissue. In many sections he saw 
places which he regarded as the beginning of fat necrosis, and which were character- 
ized by the occurrence of an amorphous, nearly hyaline mass, generally in the form 
of rings or spherical shells. These hyaline shells wholly corresponded in size to nor- 
mal fat-cells; they were separated from each other by sharp lines and contained in 
the center a granular mass and a few formations resembling nuclei. According to 
Balser, in a later stage the spherical shells broke into smaller flakes, and thus a com- 
plete disintegration of the fatty portions occurs. In the change of fat-cells into 
granular balls Chiari observed small glistening bodies resembling chalk molecules, 
and, in addition, in the older foci peculiar flakes of the size and form of ordinary fat- 
cells. Neither Balser nor Chiari could establish the composition and significance of 
these flakes. Langerhans, however, succeeded in demonstrating by microchemic 
and chemical analyses that these masses consisted of a combination of fat acids and 
chalk. Sarfert showed combinations of sodium with fat acids in his investigation on 
fat necrosis. 

Langerhans, who introduced the term fat-tissue necrosis, obtained a clear picture 
of the process by study of the smallest foci, even those scarcely visible to the naked 
eye. He presented the following explanation of the microscopic appearances: The 
smallest foci are not as large as a fat-lobule, and are not bounded everywhere by 
connective tissue, but in places by intact fat-cells. Broad bands filled with fatty 
detritus (the bands of Balser) lie between the unchanged fat-cells. The fat-drops 
lie quite free, and are not surrounded by protoplasm, as Balser stated. Along the 
edge there is found at times cellular proliferation, but always corresponding to the 
position of the vessels and the accompanying connective tissue. The growth of 
young fat-cells, described by Balser, could not be shown. The old fat-cells contain 
fat and ovoid nuclei, and there were chalk molecules between the fat-cells and within 
the broad bands. More marked growths at the borders of the necrotic foci were to 
be seen only where the fat-lobules were bordered by connective tissue. Genuine 
granular corpuscles were formed in the latter in consequence of the fatty degenera- 
tion of spindle and stellate cells. A short distance within the necrotic area the bands 
between the fat-cells have almost entirely disappeared and the latter are more or less 
completely filled, not with a finely granular material, but with very fine needles, 
which have the faint luster and the-small curve of crystals of palmitic and stearic 
acids. These needles do not always’entirely fill the fat-cell, but often lie upon the 
periphery as clumps or rings or spherical shells. ‘The remaining space is then filled’ 
with fat-drops of various size. Nearer the center are yellowish-brown clumps with 
a faint luster, of very irregular shape and size. They are round, angular, jagged, 


248 FAT NECROSIS. 


star-shaped, or at times form distinct, broad rings (Balser’s bits of spherical shells), 
which, especially at the center of the focus, may occupy the entire space of the pre- 
existing fat-cell. All these round and angular clumps, rings, and large flakes con- 
sist of a combination of lime and fat acids. When the necrsis is so extensive that 
several adjoining fat-cells are involved, the fibrous septa between them die, but re- 
main as band-like strips projecting in a tongue-shaped fashion into the interior of the 
area of fat necrosis. If large blood-vessels lie within the necrotic foci, they con- 
stantly appear to have died; cells in the walls are frequently to be recognized, but 
the nuclei are no longer colored by any stain. If the blood-vessels are traced to the 
edge of the necrotic focus, a growth of the intima may be found at times, also throm- 
bosis with a proliferation of cells and diffuse blood pigment in the vicinity. At the 
border of many foci granular and diffuse blood pigment is found, of bright yellow or 
brownish-yellow color, which on the addition of concentrated sulphuric acid gives 
the changes of color mentioned by Virchow. 


Langerhans thus summarizes his observations: “The multiple necrosis 
of fat tissue begins with the decomposition of the neutral fat contained 
in the cells; the fluid constituents are eliminated and the solid fatty acids 
remain. The latter then unite with the calcium salts to form calcium 
salts of fatty acids. The entire lobule or several neighboring lobules then 
form a dead mass which is separated from the living tissue by a dissect- 
ing inflammation proceeding from the surrounding tissue. The multiple 
necrosis of fat tissue has nothing in common with ordinary fatty de- 
generation (Chiari’s view) or with a growth of fat-cells (Balser), which 
always leads to the formation of a lipoma, the occurrence of which in the 
mesentery is not so very common.” 


ETIOLOGY. 


The etiology of fat necrosis is not yet satisfactorily explained. A 
number of authors (Balser, Langerhans, Fitz, Jackson and Ernst, Hilde- 
brand, Dettmer, Jung, Ponfick, Lubarsch, Dieckhoff, Korte, E. Fraenkel) 
have sought an explanation by means of bacteriologic and experimental 
studies. We also have sought for information by means of experiments 
on animals. Hypotheses alone have been offered, the proof of which is 
lacking. Balser in his first communication looked for micro-organisms 
as the cause of the disease, but with entirely negative results. “With 
the means now at our disposal,” he says, “no formations foreign to the 
human organism can be demonstrated in fat necrosis.” 

In his address before the Eleventh Congress of Internal Medicine, 
in 1892, Balser reported positive results. He examined the necrotic 
foci from a “ Pagunerschweine”’ which macroscopically resembled ab- 
scesses, and succeeded, after careful fixation in a concentrated aqueous 
solution of picric acid, hardening in graded alcohol, and staining with 
the Ehrlich and the Ehrlich-Biondi tri-color mixture, in finding ‘‘ numer- 
ous gland-like formations of dark yellow or coffee-brown color, which 
bore a great similarity to the flower of a full aster These formations 
consist of oblong clubs, quite similar to those of actinomyces, but some- 
what smaller. They generally are arranged as rays around a point, 
but now and then are found isolated in the tissues.” 

The objection was raised that these bodies, on account of their partial 
staining, might be crystalloid formations. Balser believes that this ob- 
jection was invalid, because he also saw them in preparations which were 
carried through alcohol and water into concentrated acetic acid, and 
then, after boiling in alcohol and ether and preservation in alcohol and 


» 


ETIOLOGY. 249 


water, were stained with the same dyes. He also made bacteriologic 
experiments, but unfortunately his report was merely preliminary, and 
permits no definite conclusions. He found bacilli which caused no 
essential changes when implanted into the anterior chamber of the eye 
of two rabbits and one pig. “The injection of the cultures of these bacilli 
into the abdominal cavity of animals also had not caused at the time 
any especial sickness.’’? Lubarsch found numerous cocci and bacilli in 
the necrotic portions of a case of necrosis of fat tissue examined a few 
hours after death. Dieckhoff, who. reported the case, gives no further 
information. 

The results of the bacteriologic examination already mentioned 
(page 125) as made by Jackson and confirmed by Ernst also were ob- 
tained by the investigation of a focus of fat necrosis. 

Ponfick very recently has made a bacteriologic study, and is forced 
to the conclusion “that the fat necrosis as such can by no means be the 
nucleus and essence of so severe a general disease as is observed in such 
mysterious cases. On the contrary, the conviction is forced upon us 
that it offers merely the predisposition by furnishing certain points of 
attack in consequence of the peculiar instability of all necrotic tissue 
which is more receptive, and hence in greater danger of attack.”’ 

He cultivated a bacillus regarded by him as possibly allied to Bac- 
terium coli commune or at least belonging to this genus. It was obtained 
from the blood infiltrated beneath the peritoneum covering the posterior 
wall of the abdominal cavity, in front of the body of the second lumbar 
vertebra, of a man who had died soon after being attacked with the symp- 
toms of intestinal obstruction. Ponfick, however, considers it an open 
question whether this micro-organism in the retroperitoneal tissue can 
be regarded as a constant and essential accompaniment of fat necrosis. 

K. Fraenkel made thorough microscopic and cultural investigations, 
but with wholly negative results, and concluded “that the investigations 
hitherto made’are not calculated to give thorough support to the micro- 
parasitic etiology of the necrosis of fat tissue. 

Another method of obtaining light upon the pathogenetic factor was 
attempted. In his first work Langerhans had suggested “that during 
the metabolism within or around the cell some injurious substance ap- 
pears and causes the decomposition of the oil.”” He attempted to find 
by experiments this external injurious substance. With strict antiseptic 
precautions he crushed the pancreas of a freshly killed rabbit in a mortar 
containing distilled water and finely splintered glass, filtered the mixture, 
and injected it into the fat tissue of other rabbits. He succeeded in 
causing necrosis of the fat tissue in one only of the 12 experiments (9 in 
rabbits and 3 in dogs). At the autopsy there was seen at the place of 
injection, at the upper end of the left kidney, just under the peritoneum, 
an opaque, yellowish-white, very dense mass about 4 mm. in diameter, 
which was sharply limited from the surrounding fat tissue. “From 
the microscopic appearances,” says Langerhans, “there can scarcely 
be any doubt that the injection caused a circumscribed acute inflamma- 
tion and necrosis of small portions of the fat tissue.’”’ He was able to 
distinguish three zones: The central resembled in most respects an in- 
spissated abscess, the middle was composed of small, necrotic portions 
of fat tissue, and the outer zone corresponded to the fibrous septa between 
the individual fat-lobules and showed a decided cellular proliferation 
and the development of cells of higher order. 


250 FAT NECROSIS. 


Langerhans does not believe that the splinters of glass alone are 
responsible for the formation of the abscess, but considers it more prob- 
able that the fat-ferment in the fresh pancreatic tissue caused purulent 
inflammation by immediate contact with the various tissues and cleavage 
of the oil drops in the living fat-cells and consequent necrosis of the fat 
tissue by mediate and weakened action. 

When the above-mentioned communication was published, Langer- 
hans had not finished his experiments, and, therefore, was very careful 
in stating his conclusions. He believes it possible “to produce fat necrosis 
by the action of fresh pancreatic juice on living fat tissue,’”’ but considers 
that still other etiologic factors must be present. 

In his “Outlines of Pathologic Anatomy,” which appeared later, 
Langerhans states definitely that the causes of multiple necrosis of fat 
tissue are merely hypothetic. Jung and Dettmer almost simultaneously 
produced fat-tissue necrosis by experimental methods. The former 
placed in the opened abdominal cavity of a rabbit a gelatin capsule 
filled with trypsin, and in that of each of three other rabbits several 
pieces of a dog’s pancreas as large as the thumb. “ Fat-tissue necrosis 
was produced in each animal by the action of pancreatic ferment, espe- 
cially of fresh pancreatic tissue; at times it was superficial only, and 
again it was deeper seated. It seems fitting to ascribe this necrosis of 
fat tissue, partly to the fat-emulsifying and fat-decomposing ferments 
of the pancreatic Juice, but in greater part to the enzyme which causes 
the decomposition of proteids.”’ 

Dettmer began with the assumption that the agent causing the necro- 
sis of the fat tissue was either the normal pancreatic juice, the outflow 
of which was obstructed, and which, therefore, reached the surrounding 
tissue, causing necrosis, or that there escaped a product arising under 
pathologic conditions. He therefore tied the excretory ducts or the 
blood-vessels or both in cats‘and dogs. In a second series of experi- 
ments the pancreatic juice was conducted directly into the abdominal 
cavity. In order to find out which ferment in the pancreatic juice was 
active in the production of fat necrosis, he injected into the abdominal 
cavity in a third group of experiments pancreatic tissue, and in a fourth 
trypsin. Dettmer reached the following conclusions: 

1. When the outflow of the pancreatic secretion from the gland is 
disturbed by closure of the pancreatic duct, with or without simultaneous 
interference of circulation, changes occur in the interpancreatic and 
parapancreatic fat, which resemble those described by Balser and Lan- 
gerhans as multiple fat-tissue necrosis. 

2. The changes in the fat tissue described as fat-tissue necroses 
are caused by the fat-ferment of the pancreatic juice and not by the 
trypsin. 

The experiments were carried on under the direction of Hilde- 
brand, who reported them at the Congress of the Surgical Association. 
He referred to twelve experiments in which he had succeeded in pro- 
ducing typical fat necrosis in the pancreas, omentum, and mesentery. 
The arrangement of the experiments is that described by Dettmer, as 
above reported. 

The most careful and most instructive experiments were made by 
Kérte. He operated on 24 cats and 6 dogs, and succeeded in causing 
typical fat necrosis in 10 out of 29 successful experiments. In the first 
series the pancreas or its blood-vessels were injured mechanically; 


* 


ETIOLOGY. 251 


pieces of the gland were excised also and implanted in the abdominal 
cavity. In a second series he endeavored to cause inflammation of 
the gland by the injection of irritating or infectious substances at 
times associated with mechanical injury. In the third series he sought 
to determine the way in which the pancreas, previously inflamed by 
artificial means, bore its injuries. 

In the first series of experiments fat necrosis occurred only when, in 
‘addition to the injuries inflicted, pieces of the gland were cut out and 
implanted in the abdominal cavity. “The animals generally died be- 
tween the second and eleventh days after the operation; only one cat 
survived, and was killed a month later. At the postmortem examination 
necrosis of the fat tissue was found in four animals out of six; in two it 
was limited to the immediate vicinity of the pancreatic wound or of the 
implanted piece, while in the other two it was noticed in distant portions 
of the subperitoneal fat tissue; to be sure, the necrosis in these animals 
was not so extensive as usually is the case in the disseminated fat ne- 
crosis of man.”’ In the second series of experiments Korte found necrosis 
of fat tissue in 6 out of 16 experiments in which pyogenic or chemical 
irritants were injected. In the third series fat necrosis never occurred. 

Korte’s conclusions with regard to necrosis of fat tissue artificially 
produced is as follows: “ Necrosis of fat tissue may be produced by injuries 
and inflammations of the pancreas artificially produced, especially by 
solution of continuity and implantation of excised pieces of the glands. 
This result did not always occur, but only in a portion of the cases. The 
alterations obtained, however,—as Dettmer’s experiments also teach,— 
have but a faint resemblance to the changes observed in man. The 
tendency to hemorrhage so frequently noticed in the latter was entirely 
lacking in the experimental fat necrosis.”’ 

“From the experiments on animals, as well as from experience in man, 
it seems very probable in many cases that the fat necroses associated 
with diseases of the pancreas are to be regarded as the consequence of 
the latter.’ We observed repeatedly the occurrence of fat necrosis in 
the course of various operations on the pancreas, especially after partial 
resection with implantation, and after injection into the tissues. Some 
of the experiments are here described: 


Fat NECROSIS AFTER RESECTION AND IMPLANTATION OF PORTIONS OF THE 
PANCREAS. 


January 8, 1896: Laparotomy on a small dog. The two portions of the pan- 
creas which were not adherent to the intestine were removed and one part sewed 
into the subcutaneous fat tissue, the other into the great omentum. 

January 9th: Dog very weak. Nosugar in the urine. 

January 10th: Dog found dead. 

Autopsy: Peritoneum smooth and shining, spleen small. The dependent por- 
tions of the ileum and the omentum reddened, and in the latter are small hemor- 
rhages in places. No further change in the fat tissue. The cut surface of the tail of 
the panceas appears infiltrated with blood and contains bright red points in the dark 
red tissue. Analogous changes are to be seen on the cut surface of the body of the 
pancreas, which also is spotted with bright red points and is softened throughout. 
The bit of pancreas sewed into the subcutaneous tissue is softened, greenish-gray, 
but injected in places with red. In the neighboring fat tissue are yellowish-white, 
shining, round spots of the size of a pinhead (fat necroses). The portion of the 
gland implanted in the omentum appears dark red, brown, soft, the acini not recog- 
a epnet round, yellowish-red, sharply defined foci as large as beans are seen in 
places. 


252 FAT NECROSIS. 


Fat NECROSIS AFTER IMPLANTATION OF THE PANCREAS. 


January 23, 1896: A dog of medium size, pancreas drawn forward and a ligature 
applied between its head and body, the former cut off and implanted in a fatty fold 
of the great omentum. 

January 24th: Dog very weak. Bile-pigment and a small amount of sugar in the 
urine. 

January 24th: In the afternoon the dog was found dead. 

Autopsy: A large amount of bloody fluid in the abdominal cavity. The visceral 
peritoneum appears in places infiltrated with blood; there was a bright red extra- 
vasation of blood about a hand’s-breadth in size at the fundus of the stomach near 
the place where lay the portion of the omentum containing the implanted piece of 
pancreas; the blood-vessels of the intestinal mesentery were also markedly infil- 
trated with blood. The tail of the pancreas, which remained in position, appeared 
quite normal. In the portion of the body lying next to the duodenum were dull 
glistening round areas about the size of a pinhead, greenish-yellow in color, and 
surrounded by small, bright red extravasations of blood. Near the seat of the liga- 
ture was a hemorrhagic extravasation of the size of a hazelnut. The parenchyma 
of the pancreas was soft. The portion of the pancreas which was sewed into the 
omentum appeared very rotten and soft. Its structure was distinctly recognizable. 
On the surface lighter areas are found having a dull-white luster, and on cross-sec- 
tion forming distinct streaks. The great omentum is very full of blood. In places there 
were dense extravasations of blood as large as hazelnuts, generally dark brown, but 
in some parts smaller areas of a brighter red were seen. Certain portions of the 
fat were studded with bright red areas, and foci, some larger than pinheads, of a 
greenish-yellow color could be seen surrounded by a hemorrhagic zone. Spleen 
small, dense. Kidney bluish-red, with some lighter colored spots on the surface. 


PANCREATIC HEMORRHAGE AND Fat NECROSIS AFTER INJECTION OF CHLORID OF 
ZINC. 


November 8, 1896: A dog of medium size. Injection of 0.2 c.c. 5% solution of 
chlorid of zinc into each of three different places in the pancreas. A hematoma in 
the middle portion of the gland was formed at the operation. 

November 10th: The dog was found dead in the morning. 

Autopsy: The abdominal wound was infiltrated with blood. Hemorrhage into 
the abdominal cavity. Pancreas not essentially enlarged. The surface stained with 
blood in places, especially in the tail and the middle of the gland. These portions 
seemed somewhat swollen and enlarged. The head of the gland appeared quite 
normal. In the parts of the gland stained with blood are bright red areas about the 
size of the head of a pin (fat necrosis), and sharply and clearly distinguished from the 
surrounding dark, brownish-red tissue. A yellowish-white, glistening, dense area 
(fat necrosis), about the size of the head of a pin, projected above the surface of a por- 
tion of the body of the gland lying next to the intestine. Macroscopically, no signs 
of inflammation were visible. The microscopic examination of a portion which had 
undergone fat necrosis gave the appearances represented in figure 15, page 253. 


Fat NEcrROoSsIS AFTER LIGATION OF THE BLOOD-VESSELS. 


February 2, 1897: Very fat, old dog. Ligation of the afferent and efferent 
blood-vessels of the pancreas. The duodenal portion is isolated and the blood-ves- 
sels leading to the intestine are tied. At the operation a portion of the fat was re- 
sected. 

February 3, 1897: After an attack of hematemesis the dog was found dead. 

Autopsy: Several large and small yellowish-white areas, having a dull luster (fat 
necrosis), and surrounded by extravasations of blood of the size of a pea, are seen 
in the middle, and both lateral portions of the pancreas. Large and small whitish, 
necrotic areas, some as large as hazelnuts, having a faint luster, and often surrounded 
by large or small extravasations of blood, are found in the fat tissue of the great 
omentum. Ulcerations of the duodenum. The peritoneum over the greater curva- 
ture of the stomach was stained bright red. 


The following conclusions were drawn from these experiments: 

1. Resection of portions of the gland and their implantation caused 
fat necroses in the neighborhood of the cut surface and of the implanted 
part. 


ETIOLOGY. 253 


2. Ligation of the afferent and efferent blood-vessels of the pancreas, 
isolation of the duodenal portion, and ligation of the blood-vessels leading 
to the duodenum, were followed by fat necroses surrounded by large 
and small extravasations of blood in the pancreas and in the great omen- 
tum. 

3. The injection of ehlorid of zine into the tissue gave rise to fat 
necroses and also to marked hemorrhage into the gland. 

4. The transplantation into the subcutaneous connective tissue of 
a resected portion of the pancreas caused the development of foci of fat 
necrosis in the immediate neighborhood of the embedded piece. 

5. The fat necrosis was always most extreme in the neighborhood 
of the injured or implanted portion of the gland. 

In some cases the attempt was made to cause an outflow of the pan- 
creatic secretion by numerous slight injuries of the pancreas, or by cutting 
into the ductus Wirsungianus and opening its canal. In one case a 





Fic. 15.—a, Needles of fat acids; b, flakes; c, necrotic fat tissue. 


Pravaz needle was inserted into the gland in many places and the paren- 
chyma torn. There was no development of fat necrosis. Neither did 
this occur in the experiments of February 12, 1896, which already have 
been mentioned, in which a solution of zymin was injected into the 
tissues of the gland in five different places, with the hope that fat necrosis 
might be caused by means of the known peptic quality of zymin. An 
indurative pancreatitis only developed. 

It is evident on comparing the reported results of the many attempts 
to obtain a deeper insight into the etiology of fat necrosis that none 
of the hypotheses offered are entirely satisfactory. The view of Balser 
and Ponfick of the bacillary pathogenesis of the process is not established 
with sufficient certainty. 

The suggestion first made. by Langerhans, and later supported by 
Hildebrand, Dettmer, and Jung, is attractive and plausible; according to 


254 FAT NECROSIS. 


this, autodigestion, which perhaps plays a more important réle in the 
pathology of the pancreas than is yet known, demands attention as an 
etiologic factor. Although this view satisfactorily explains the altera- 
tion in the pancreas and its neighborhood by means of the contact with 
the escaped pancreatic secretion, yet it is scarcely sufficient to explain 
the extensive changes in quite distant portions of the abdominal fat, 
as often observed in man; the occurrence of fat necrosis in the subepi- 
cardial and subcutaneous fat and in the bone-marrow and the severe 
general disturbances, often of sudden occurrence and rapidly fatal, 
cannot thus be explained. Further, the possibility that microparasites 
play an important part in these experiments on animals, upon which 
this theory is based, cannot be denied. 

The question regarding the cause of the fat necrosis is obviously of 
far-reaching importance for the entire pathology of the pancreas. The 
relation of fat necrosis to the various processes, as “ pancreatitis hemor- 
rhagica,” abscess, hemorrhage, and necrosis, has been mentioned in divers 
places in this section, and the relation of these processes to each other 
are often wholly obscure. As a rule, nothing is known of the cause or 
method of action, and it is uncertain whether both are not concurrent 
effects of the same cause. There is no agreement on this question among 
the authors. Some (fitz, Korte) regard the fat necrosis (“in many cases 
very probably,” Korte) as the result of inflammation, necrosis, and 
hemorrhage, while others (Balser, Langerhans, Seitz, E. Fraenkel) re- 
gard it as the cause. Ponfick, Dieckhoff, Lindsay Steven, and Rolleston 
hold a different view. Ponfick believes that the fat necrosis merely creates 
the predisposition to the severe processes; Dieckhoff assumes that the 
fat necrosis may give rise to diseases of an inflammatory nature, but 
considers {t possible that the same cause (bacillary) which excites 
inflammation and suppuration also produces fat necrosis... Lindsay 
Steven regards the fat necrosis and the pancreatic necrosis as independent 
diseases, although he admits that extensive fat necrosis may lead to 
necrosis of the gland. Rolleston considers that the process is explained by 
changes in the sympathetic nervous system, especially in the solar plexus. 

There is no doubt that wide-spread, rapidly fatal fat necroses may 
occur without other affection of the pancreas, as is shown by the case 
reported by E. Fraenkel, which will later be mentioned. Many other 
obscure points in the pathology of the pancreas will be made clear with 
the perfect understanding of the multiform process of fat necrosis, which 
is now apparently a wholly inconspicuous and irrelevant observation 
at a postmortem examination and again a very complicated disease pro- 
ducing extensive and wide-spread ravages, often rapidly causing death 
like a stroke of lightning, but usually with severe affections of the pan- 
creas. 

After our experiments were ended, Katz and Winkler continued an 
independent study of fat necrosis. The following results have been 
derived from the 26 experiments on animals previous to January 24, 
1898: 

1. Fat necrosis may certainly be produced by the following methods: 
The abdominal cavity is opened, the pancreas drawn forward, the main 
excretory duct tied in two places and cut between them; ligatures are 
then tied around the entire gland in different places, the blood-vessels 
being spared as much as possible. The abdominal cavity is closed by 
layers of stitches, and the wound is sealed with collodion. In every one 


. 


ETIOLOGY. 255 


of the twenty dogs thus operated upon, fat necrosis to a greater or less 
extent occurred without exception. | 
The following experiment is reported as an illustration: 


EXPERIMENT OF JUNE 26, 1897.—Dog of medium size. At the operation the 
chyle-vessels of the intestine appeared injected. The pancreas was rose-red. Liga~- 
tion of the ductus Wirsungianus. Seven ligatures were tied about the entire gland, 
the blood-vessels being spared as much as possible. 

June 28th, dog found dead. 

Results of autopsy: Great omentum appears quite rich in fat. Numerous foci of 
fat necrosis as large as pinheads, confluent in places and surrounded by thickened 
fat tissue infiltrated with blood, are seen especially in the portion adjacent to the 


6 





Fie. 16.—a, Clumps of fat; 6, increased connective tissue. 


duodenum. Just under these are found marked alterations of the pancreas; dark 
red discolorations with brighter colored eechymoses as large as pinheads and obliter- 
ated gland-structure. The fat necrosis in the gland appears especially marked in 
those places cut into by the ligature, and is frequently continued into the neighbor- 
ing fat tissue. The pancreas appears less reddened toward the spleen. The sur- 
face is softened in places and studded with foci of fat necrosis, like splashes of 
plaster. The fat necrosis is most marked near the entrance of the ductus Wirsun- 
gianus into the intestine. The gland here appears as if eroded, and there are distinct 
gaps filled with mortar-like material. Suffused spots with beginning necrosis are 
found near the knot in the ligature. In the splenic portion and in the adjoining fat 
tissue are solitary necrotic foci as large as peas and numerous miliary fat necroses, in 
part distributed throughout the tissue, and in part forming long lines. On section of 
the gland the tissue in the duodenal portion is soft, infiltrated with much blood, and 
containing a yellowish center; near the mouth of the ductus Wirsungianus the necro- 


256 FAT NECROSIS. 


sis extends through the entire thickness of the pancreas, while near the surface in this 
region is a hemorrhagic nodule as large as a pea. There are numerous fat necroses, 
in part confluent, lying in the tissue infiltrated with blood, in a space about 4 cm., at 
the attachment of the great omentum to the greater curvature of the stomach. 

Reference has already been made to a second experiment performed in the 
same manner (page 144). In this case the animal survived the operation, and about 
ten weeks later laparotomy was performed and the pancreas was extirpated. On 
microscopic examination, besides the existing induration, the changes in the gland 
lobules produced by the fat necrosis and the associated induration are represented in 
figure 16. 


2. A very considerable leucocytosis in the animals experimented 
upon accompanied the fat necrosis. This was found in all cases (11) in 
which it was sought for and where there was extensive fat necrosis. 
The leucocytosis was present on the day after the operation. 

The following experiments serve as examples: 


EXPERIMENT OF NOVEMBER 17, 1897.—Dog of medium size. After the abdomi- 
nal cavity is opened, the pancreas is drawn forward, the main excretory duct tied, 
and ligatures placed around the middle, head, and tail of the gland, sparing the 
blood-vessels as much as possible. The number of white blood-corpuscles at the 
beginning of the operation was 12,500. 

November 19th: The dog was narcotized and blood withdrawn from the paw as 
at the operation. Number of the white blood-corpuscles, 310,000. 

November 26th: Dog found dead, after having refused food for a number of 
days, without any apparent reason. 

Autopsy: Cutaneous wound healed. No suppuration in the layers of the abdom- 
inal wall. Peritoneum smooth and shining. In the great omentum, especially 
along the blood-vessels, a hemorrhagic infiltration in which were numerous yellow- 
ish-white points as large as pinheads (fat necrosis). Pancreas palered. In the mid- 
dle, especially in the neighborhood of the mouth of the ductus Wirsungianus, the 
tissue 1s somewhat more red and dense and contains numerous small, yellowish- 
white spots (fat necroses). The gland-tissue appears as if forced apart by much en- 
larged bands of connective tissue. The two lateral portions of the pancreas show no 
additional changes. Spleen very small, of normal consistency. Liver normal. 

EXPERIMENT OF JANUARY 3, 1898.—Small dog. Pancreas is drawn forward, the 
main excretory duct is tied, cut across, and eight ligatures are placed around the 
gland. Number of white blood-corpuscles, 30,000. 

January 4th: In counting the white blood-corpuscles there is an unusually rapid 
coagulation of the blood. Number of the white blood-corpuscles, 135,000. The dog 
appears quite lively. Toward evening he becomes weaker, and dies at about ten 
o’clock in the evening. 

January 5th: Autopsy: Peritoneum smooth and shining. No exudation in the 
abdominal cavity; pancreas of normal size; areas of normal color alternate with 
those which are much infiltrated with blood, and in which the gland structure is 
partly obliterated. At the beginning of the body of the gland there is an area of nor- 
mal structure about the size of a hazelnut, adjoining which and between two ligatures 
is a dark violet portion of the gland containing several areas of a brighter red, with 
the structure obliterated. In the body of the gland the lobules are distinct, and 
toward the tail are some hemorrhages about as large as peas. Confluent foci of fat 
necrosis are found near the ligated duct, especially on the posterior surface. At the 
beginning of the tail the entire substance of the gland for about 4 cm. in length is in 
part dark violet and in part bright red, and the structure is wholly obliterated, espe- 
cially in the violet portion; on the posterior surface there are foci of fat necrosis of 
silvery luster and confluent in places. The tip of the tail is normal except for a hem- 
orrhage as large as a bean at the site of the last ligature. There are several foci of fat 
necrosis in the fat tissue and adjacent to the intestine, also on the surface of two 
neighboring lymph-glands. Spleen small, tissue firm, no evidence of sepsis. 

Microscopic examination: (1) The areas of fat necrosis show numerous fat-cells 
filled with acicular fat-acid crystals and others with hyaline flakes. (2) The lobules 
in the necrotic portion of the pancreas are beset with acicular fat-acid crystals and 
numerous very minute granules. After the addition of acetic acid, the nuclei of the 
cells are distinct and granular. (3) The areas which were infiltrated with blood but 
showed macroscopically no fat necrosis are largely filled with very minute granules 
and are traversed by numerous capillaries distended with blood. (4) The portion 


_% 


ETIOLOGY. 257 


of the pancreas which had not been tied and which is of normal appearance shows 
perniee very numerous minute granules, which, however, are found only within 
the lobules. 


The following control experiments were undertaken in order to make 
clear the relation between the fat necrosis and leucocytosis 

1. A blood count was taken before each operation, since a consider- 
able leucocytosis is at times found in dogs. It resulted that a very 
decided increase in. the number of white corpuscles took place after the 
operation even in those animals in which a definite leucocytosis was 
present before the operation: in one case an increase from 30,000 to 
135,000 in the cubic millimeter; an increase from 35,000 to 118,500 in 
the cubic millimeter in another. 

2. Narcosis (with morphin or chloroform) produced no essential 
influence, merely causing an increase from 5000 to 11,000 in a cubic 
millimeter. In a second case there was no modification. 

3. The laparotomy caused no essential increase, as has previously 
been stated by Tarchanow, Emelianow, and Jacoby: before the operation, 
7500; after the operation, 10,500 in the cubic millimeter; before the 
operation, 65,000; after the operation, 75,000 in the cubic milimeter. 

4. Laparotomy and extirpation of the omentum caused no hyper- 
leucocytosis. 

5. After the injection of turpentine into the tissues of the pancreas 
and the production of an abscess there was a slight increase (from 11,000 
to 15,000). 

6. In total extirpation, 31,200 in the cubic millimeter were found 
before the operation, on the day after the operation 90,000, and on the 
following day 27,500. 

It would be premature to draw any conclusions from this preliminary 
communication of facts requiring further confirmation. It must first 
be proved that the alteration of the blood stands in any relation to the 
fat necrosis. It is to be hoped that further investigation will advance 
the solution of the question concerning the true causes both of the local 
changes and the severe general symptoms. 

[Subsequent investigations have confirmed the observations of Lan- 
gerhans that fat necrosis can be produced by the contact of the con- 
stituents of the pancreas with fat tissue, and his hypothesis that the 
fat-splitting ferment of the pancreatic juice causes the necrosis by separat- 
ing the fat into fatty acids and glycerin. 

Abundant experimental evidence in support of the first statement 
has been furnished not only by the observers above mentioned, but also 
by H. U. Williams * and Flexner,} and the latter observer also has demon- 
strated by chemical methods the presence of the fat-splitting ferment 
in the areas of necrosis in a patient and in animals. 

Flexner t has shown also that hemorrhagic pancreatitis and fat 
necrosis may be produced by injections of hydrochloric acid, sodium 
hydroxid, and formalin into the pancreatic duct of dogs. Opie 3 was 
alike successful with bile, and Flexner and Pearce|| conclude from their 


* Boston Med. and Surg. Jour., 1897, cxxxvti, 345; Jour. Exp. Med., 1898, 111, 

585. ee Jour. Exp. Med., 1897, 11, 413. 
t “Contributions to the Science of Medicine,” dedicated to Wm. H. Welch, 

M.D., 1900, 743. | 

§ Trans. Assoc. Am. Physicians, 1901, xv1, 329. 

|| Trans. Assoc, Am. Physicians, 1901, xv1, 348. 


17 


258 FAT NECROSIS. 


experimental studies that the entrance into the pancreas of gastric juice 
and of bile are efficient causes of pancreatitis with hemorrhage and fat 
necrosis. 

The summary by Korte * with regard to the relation between fat 
necrosis and disease of the pancreas needs but little modification in 
consequence of recent investigations: 

“A slight degree of necrosis of fat tissue is not infrequently found 
in the pancreas and in the peritoneal fat in the absence of other al- 
terations of the gland and without the production of morbid symptoms. 

“Tt has been seen during life also without evident disease of the 
gland, and after a time has disappeared (personal observation). 

“Tt is usually associated with hemorrhagic affections of the pancreas 
and their consequences (necrosis), and more rarely accompanies sup- 
purative inflammation. 

“Experiments on animals have shown that fat necrosis can result 
from injuries to the gland and from the stagnation of blood and secretion 
and from inflammation artificially produced in it. In man also fat 
necrosis has so immediately followed injury to the organ as to be 
regarded with a high degree of probability as the result of the injury 
to the pancreas (Warren). 

“In accordance with such experiments and experience it is highly 
probable, in many instances at least, that the alterations of the peritoneal 
fat tissue associated with diseases of the pancreas are to be regarded as 
the result of the latter. 

“It is possible that, at times, disseminated necrosis of fat tissue 
may promote the origin of inflammation, hemorrhage, and gangrene of 
the gland, since thereby the tissues are made less capable of resistance. 

“The necrosis of fat tissue in rare instances is found without accom- 
panying hemorrhage or inflammatory changes in the pancreas. 

“Bacteria, especially intestinal bacteria, are not infrequently found 
in the foci of fat necrosis. Ponfick’s hypothesis that the microbes are 
the cause both of the fat necrosis and of the subsequent pancreatic hemor- 
rhage is not yet proved. It seems to me more probable that bacteria 
and irritants proceed from the inflamed, hemorrhagic or necrotic organ 
through the lymph-vessels into the surrounding fat tissue and produce 
in it the necrotic areas. It may be, as a third possibility, that bacilli 
advance from the diseased pancreas to the necrotic foci in the fat tissue 
and find in them a suitable soil for further development.’”—Eb.] 


STATISTICS. 


There are no satisfactory statistics regarding the frequency of fat 
necrosis. As already mentioned, it was found by Balser 5 times in 25 
bodies taken indifferently as small, punctate foci or as areas of the size 
of a pinhead between the lobules of the pancreas. The foci are found 
less frequently in the fat tissue surrounding the organ. In the reports 
of the autopsies at the Vienna General Hospital from 1885 to 1895, 11 
cases are recorded, of whom 6 were men and 4 women (in one case the 
sex was not stated); in 8 of these cases there was no diabetes. In 1891 
chronic pancreatitis following fat necrosis was noted in a man forty 
years old. In 1893 in a woman nineteen years old there was a partial 


* “Die Chirurg. Krankheiten u. d. Verletz des Pankreas,’’ 1898, 198. 


SYMPTOMS. 259 


fatty degeneration of the pancreas and disseminated fat necrosis with 
beginning suppuration, and in a woman twenty-seven years old fat necrosis 
of the pancreas and mesentery. In 1894 in an individual aged fifty-five 
years (sex not stated), fat necrosis of the pancreas and hemorrhages in 
the superficial portions were present. The pancreas is uniformly much 
increased in size, the lobes on the surface appearing large, the cut sur- 
face studded with bright yellow points; man, fifty-four years old, be- 
ginning fat necrosis; man, fifty-three years old, fat necrosis of the 
pancreas, deposits of calcium salts in the parenchyma; man, forty-six 
years old, fat necrosis of the pancreas and mesentery; in 1895, man, 
sixty-three years old (inebriate), fat necrosis of the pancreas. 

In three cases there was diabetes: 1889, in a woman, nineteen years 
old, fat necrosis in the region of the pancreas; 1890, an inebriate, forty- 
nine years old, beginning fat necrosis; 1895, fat necrosis in the pancreas 
with suppurative pancreatitis. 


SYMPTOMS. 


A clinical description of the morbid process just described, apart from 
the fact that it is Justified only when the fat necrosis is regarded as 
an idiopathic process, is difficult in so far as it affects the pancreas, be- 
cause the fat necrosis is usually not limited to the pancreas in all the 
cases productive of symptoms, but is diffused more or less over a large 
part of the abdominal fat. 

The earliest anatomic changes, which not infrequently can be found 
at the autopsy, cause no symptoms during life, and it is only the later 
stages which produce the extensive disturbances which, as a rule, do not 
concern the pancreas alone, but also other portions of the digestive 
tract. As concerns the pancreas, the fat necrosis is a cause or accom- 

animent or result of severe inflammation, hemorrhage, and gangrene. 

he symptoms are caused by these severe processes only and not by the 
causal, concurrent, or consequent factor, the fat necrosis. The symp- 
toms are the same whether the inflammation, hemorrhage, or pancreatic 
necrosis is caused by fat necrosis or by other conditions, and it is there- 
fore necessary only to refer to the descriptions given in the sections on 
Inflammation, Hemorrhage, and Necrosis. Cases are there reported in 
detail which allow the assumption that fat necrosis is the cause of these 
processes. The disease is manifold, complicated, and severe when the 
fat necrosis is situated not merely in the pancreas and the surrounding 
fat tissue, but is spread over a large portion of the abdominal fat and 
there is a destruction of larger portions, with or without hemorrhage. 

Types of the disease are furnished by some of the cases extracted 
from the literature and compared with the analogous reports given in 
previous sections. 


Von Kahlden: Woman sixty years old, very fat; a few days before death there 
were severe abdominal pains, vomiting, constipation, meteorism, no tenderness; the 
vomiting persisting, the stomach was washed out, after which the general condition 
was improved; asmall amount of fecal matter was passed, with some flatus. Death 
occurred in about eight days with symptoms of collapse. 

Autopsy: Intestinal peritoneum much injected, intestines adherent, in the omen- 
tum and mesentery whitish nodules as large as a ten-cent piece; the omentum 
contained so many that it appeared like a tumor. Similar nodules in the parietal 
peritoneum; pancreas enlarged and ‘contained large and small yellow and gray 
nodules projecting above the surface. 


260 FAT NECROSIS. 


E. Fraenkel: (a2) Woman forty-eight years old, brought to the hospital with the 
diagnosis of intestinal occlusion. Meteorism, jaundice, vomiting, pulse scarcely 
perceptible. On the next day, persistent collapse, passage of stools, death. Au- 
topsy: Abundant fat in the abdominal wall, numerous foci of fat necrosis in the large 
and small omenta and in each of the epiploic appendices of the large intestines, all of 
which contained abundant fat. The splenic flexure was firmly united to the fat tissue 
behind it, in which were numerous foci of fat necrosis, and to the anterior surface of 
the left kidney and to the tail of the pancreas. The gastrocolic ligament contained nu- 
merous foci of fat necrosis. This was cut through and the omental bursa opened and 
the fat tissue surrounding the pancreas was found transformed into a dark brown 
mass filled with fat necroses. The pancreas is of satisfactory consistency and only 
a few areas of fat necrosis were to be recognized in the interstitial tissue. 

(b) Woman fifty-two years old; about fourteen days before her admission to the 
hospital cholelithiasis was diagnosticated. Frequent nausea, vomiting, diarrhea, 
metorism, sensitiveness to pressure. When anesthetized and examined, a deep- 
seated, retroperitoneal tumor was felt. Laparotomy. Numerous small areas of fat 
necrosis were seen in the parietal and visceral layers of the peritoneum; therefore 
the operation was ended. ‘Two days later there was hematemesis and the passage 
of bloody stools. Death eleven days after admission. At the autopsy, besides the 
necrotic portions of the transverse and descending mesocolon, which were infiltrated 
with blood, multiple perforations were found in the jejunum and on the posterior 
wall of the stomach, and there was almost an entire absence of the pancreas. The 
fat tissue around the left kidney also showed many areas of fat necrosis. 


The manifestations of disease, whether consequences or complications 
of fat necrosis, are various. They sometimes resemble intestinal ob- 
struction, bursal abscess, retroperitoneal tumor, or perforative peri- 
tonitis, or, in consequence of the temporary violent colic, with collapse, 
they suggest gall-stones, poisoning, or a severe infection. 

Fraenkel communicates an interesting case: A patient was brought 
into the hospital with the suspicion of cholera and died. At the autopsy 
there was found an extensive necrosis of the greater portion of the ab- 
dominal fat, complicated with hemorrhage. 

At the session of the Society for Internal Medicine in Berlin, April 
27, 1896, Stadelmann reported the case of an individual twenty-three 
years old who formerly had been perfectly healthy, but was attacked 
within a few days by severe abdominal pains and quickly became coma- 
tose. On entrance the patient was in deep coma. The urine con- 
tained albumin, 3.4% of sugar, and there was a positive ferric chlorid 
reaction. Death occurred with increasing cyanosis. Benda demon- 
strated the specimen from this case. There was multiple fat necrosis 
of the peritoneum, associated with extensive disease of the pancreas. 
Nearly the entire gland was changed into hemorrhagic tumor, only a part 
of the head being preserved. 


DIAGNOSIS. 


The diagnosis of fat necrosis can be made with certainty only at an 
operation, as occurred in the cases reported by Korte and Fraenkel. 
The latter considers the diagnosis of fat necrosis possible when in obese 
persons there is a fluctuating tumor in the epigastrium, which disappears 
after preceding, very severe colic and with subsequent profuse diarrhea, 
to return after some time. The diagnosis is absolutely certain if necrotic 
fat tissue or pancreatic structure is found in the feces. The objection 
is to be raised that the eventual demonstration in the feces of such shreds 
of fat tissue or necrotic portions of the pancreas does not always prove 
that the necrosis of fat tissue is the cause of the process. The necrosis 


* 


TREATMENT. 261 


may just as well be the consequence of a gangrene which has developed 
in some other way. 


The only treatment is surgical. Langerhans states that he had been 
informed by Fitz and Welsh that recovery from multiple fat necrosis and 
sequestration of the pancreas had resulted from the removal of the gland 
at an operation. Langerhans gives no further information. [This case 
is that mentioned by Osler.* The patient was supposed to have acute 
intestinal obstruction; the abdomen was opened by Halsted, who found 
a thick, dense mass in the region of the pancreas and foci of fat necrosis 
in the omentum and mesentery. The exploratory incision was closed, 
and the patient recovered. Four years later he suffered from similar 
symptoms, but refused an operation.—Ep.] In Thayer’s patient with 
pancreatic abscess and disseminated fat necrosis recovery took place 
after the operation. 

Spontaneous recovery is to be thought of only when fat necrosis is 
associated with sequestration of the pancreas and the latter is discharged 
with the feces. 

[The surgical treatment of fat necrosis is so intimately connected 
with that of acute, non-suppurative pancreatitis that the treatment of 
the former condition is usually considered to include that of the latter. 
The exploratory incision reveals the foci of fat necrosis, and the dis- 
covery of an indurated, perhaps hemorrhagic mass in the region of the 
pancreas, in connection with the symptoms, is regarded as a sufficient 
justification for the diagnosis of acute pancreatitis. The latter diagnosis 
under these circumstances has repeatedly been confirmed by the post- 
mortem examination of the fatal cases, and seems warranted in those 
which recover. 

The following are to be added to the two cases above mentioned: 
That reported by Korte,t a combination of gangrenous pancreatitis and 
fat necrosis. This patient was in fairly good condition, although dia- 
betic, four and a half years later.t The case of omental fat necrosis 
and large nodular mass behind the stomach operated upon by Gerster 
and reported by Manges. Munro’s case of fat necrosis and mass in the 
region of the pancreas, reported by Lund|| and Munro.** The case of 
hemorrhagic pancreatitis mentioned by Fowler ++ and that of fat necrosis 
and greatly enlarged pancreas reported by Mayo.tt{—Eb.] 


* “ Principles and Practice of Medicine,” 4th Edition, 1901, 591. 
t Arch. f. klin. Chir., 1894, xuvim1, 721. 

t “ Die chir. Krankh. u. d. Verletz. d. Pankreas,’’ 1898, 187. 

§ Phila. Med. Jour., 1899, 111, 724. 

|| Boston City Hospital Report, 1900, 43. 

** Boston Med. and Surg. Jour., 1900, cxuii1, 543. 

tt Trans Am. Surg. Assoc., 1901, x1x, 180. 

{tt Jour. Am. Med. Assoc., 1902, xxxvit1, 107. 


262 ATROPHY. 


X. ATROPHY, FATTY DEGENERATION, LIPOMATOSIS, 
AND AMYLOID DEGENERATION. 


(a) A DROPHY:. 


Ir can readily be understood that atrophy is among the most common 
affections of the pancreas. Marantic or senile atrophy is found as a 
manifestation of old age, and is then usually the consequence of arterio- 
sclerotic processes or of general cachexia (cachectic atrophy). Lobstein 
has stated that the former is one of the frequent conditions in advanced 
years, and the following report of an autopsy performed by Dr. Zemann 
at the Rothschild Hospital is an example of the not infrequent senile 
atrophy: In a man eighty-four years old the aorta was found dilated, 
its walls flaccid, the intima of the arch markedly thickened ; the peripheral 
arteries were large, very tortuous, and the intima thickened in places; 
the pancreas was grayish-red, the lobules very small, the branches of 
the pancreatic artery were narrowed in many places by the thickened 
intima; there was gangrene of the left great toe and of the tips of the second 
and fourth toes. 

In simple atrophy the entire pancreas is diminished in size, the weight 
is often reduced to 1 to 14 ounces, while that of a normal pancreas, accord- 
ing to Vierordt, averages 3 to 34 ounces. In the section on Diabetes as a 
Symptom of Diseases of the Pancreas, Hansemann’s distinction between 
cachectic and diabetic atrophy is described (page 77). He states that 
the two varieties are to be distinguished macroscopically and micro- 
scopically. Diabetic atrophy belongs to the series of interstitial in- 
flammations, and there is a marked similarity between it and granular 
atrophy of the kidney. Granular atrophy of the pancreas, according to 
Hansemann, leads very rarely to complete destruction of the organ, 
and it is surprising how much gland-substance, as a rule, is still present 
in this variety of atrophy. If, however, the gland-substance is excep- 
tionally reduced to a minimum, the organ is transformed into a thin, 
flabby, fibrous body of less volume than the normal pancreas, at first 

sight giving the impression far more of atrophy than of inflammation. 
| It has already been stated that atrophy of the pancreas is no rare 
condition in diabetes. In 40 cases of diabetes in which there was disease 
of the pancreas Hansemann found simple atrophy in 36. Dieckhoff 
collected 53 cases of severe disease of the pancreas with diabetes, in 21 
of which were atrophy and lipomatosis. 

In the reports of autopsies at the General Hospital in Vienna from 
1885 to 1895, atrophy was recorded 8 times in 12 cases of diabetes. 
Atrophy was found 78 times in the 188 cases of diabetes with disease of 
the pancreas mentioned under General Considerations. 

I have seen several cases of atrophy of the pancreas in diabetes. 
Three of these, with the results of the autopsies by Dr. Zemann, are 
previously mentioned (page 60). Secondary atrophy of the pancreas 
may occur in consequence of pressure from without, by tumors (aneu- — 
rysms, neoplasms, degenerated lymph-gland), or in consequence of some 
internal cause, as calculus-formation in the duct with dilatation of the 
excretory duct, cyst-formation, hemorrhage, abscess, chronic inter- 


% 


FATTY DEGENERATION. 263 


stitial inflammation, lipomatosis, new-formations. Atrophy from pres- 
sure may reach such a high degree that the glandular substance may al- 
most wholly disappear and the organ be changed to a thin, flabby body. 
Its course may be run with or without diabetes. 


(b) FATTY DEGENERATION. 


Fatty degeneration of the parenchyma of the gland frequently occurs 
in the course of infections and intoxications. This process was earlier 
regarded as acute parenchymatous inflammation. It occurs as cloudy 
swelling in the parenchyma of the pancreas in various infectious diseases, 
as typhoid fever, variola, puerperal fever, yellow fever, plague, etc., 
analogous to the similar changes in the liver, kidney, and muscles which 
generally occur at the same time. Friedreich saw such a parenchy- 
matous degeneration in the course of a wandering, erysipelatous, double 
pneumonia in a strong young man. 

Macroscopically the gland appears enlarged, at first reddened on 
account of hyperemia, but later whitish or grayish-yellow on account of 
the advanced degeneration of the epithelium and the edema of the inter- 
stitial connective tissue. The microscope shows that the changes affect 
only or chiefly the parenchyma, the cells of which are in a condition 
of cloudy swelling, ending in fatty degeneration and destruction; they 
appear very granular, opaque, somewhat enlarged, the granules dissolving 
in acetic acid and caustic potash. Each cell contains two or three, 
even five, large round nuclei and nucleoli (Dieckhoff, Iriedreich). 

The diagnosis of cloudy swelling is at present impossible. According 
to Friedreich, its existence may be suspected when the clinical signs of 
acute parenchymatous degeneration of the liver (acute swelling) and 
of the kidney (albuminuria), in addition to a considerable splenic en- 
largement and high fever are present in a severe case of acute infec- 
tious disease. Friedreich thinks that many cases of Jaundice developing 
in the course of severe infectious diseases may be due to pressure of the 
swollen head of the pancreas on the ductus choledochus. 

Fatty degeneration of the gland-cells occurs also in inflammation 
whether caused by pressure from within (stagnant secretion) or from 
without, or by other causes (phosphorus-poisoning). The tissue of the 
gland assumes in consequence a brighter, more yellowish color, the ex- 
cretory ducts are filled with fat detritus and therefrom may be dilated. 
Such contents are to be found in the pancreatic duct even in complete 
fatty degeneration (Orth). 

Fatty degeneration is found also in general obesity, especially in 
_inebriates, analogous to fatty degeneration of the heart and blood-vessels. 
It. may lead to hemorrhage, as has already been mentioned in the section 
on this subject (Friedreich). 

Fatty degeneration of the gland is recorded twice in the reports of 
the autopsies at the Vienna General Hospital from 1885 to 1895. In 1893 
the case is mentioned of a woman nineteen years old who suffered from 
the excessive vomiting of pregnancy and died in collapse. At the autopsy 
the condition was as follows: Metamorphosis adiposa pancreatis partialis 
et necrosis textus adiposi disseminata cum suppuratione incipiente. 
Urocystitis chronica. Ruptura cervicis uteri. In 1894 the autopsy of 
a man sixty-six years old showed confluent lobular pneumonia, pancreatic 


264 ATROPHY. 


calculus, fatty degeneration of the gland parenchyma and fibrous indura- 
tion. 

The interstitial growth of fat which occurs in the course of simple, 
especially marantic atrophy, is the transition to genuine lipomatosis. 
The atrophy of the gland-cells is the primary affection and the resulting 
empty space is filled with the growth of fat tissue. The following case 
examined after death at the Rothschild Hospital by Dr. Zemann is an 
example: A man seventy years old was treated for emphysema, arterio- 
sclerosis, and general dropsy; at the autopsy the pancreas was found 
embedded in abundant fat tissue, very flabby, thin, speckled with red; 
on section, lobules (small, pale grayish-yellow) were forced apart by 
abundant flabby, edematous, dirty yellow fat tissue; the small branches 
of the pancreatic artery were very narrow on account of thickening 
of the intima, and at times almost completely closed by dense nodules. 

This condition is often combined with fatty degeneration and is 
represented by a new-formation of fat tissue, which gradually infiltrates 
the entire gland, the structure of which is replaced by fat. The pancreas 
becomes somewhat larger than normal, soft, and in extreme degrees the 
entire organ is transformed into a yellow or yellowish-white mass of 
fat. 


(c) LIPOMATOSIS. 


Lipomatosis is frequently combined with the formation of concretions. The 
instructive case reported by Dieckhoff is given as an example: A woman thirty-five 
years old two years before her admission into the Rostock Hospital suffered fron? a 
pneumonia of the left side, on account of which she was treated for eight weeks. 
Since then there have been persistent cough, expectoration, emaciation. At the time 
of admission the diagnosis was pyopneumothorax. An exploratory puncture made 
later showed a purulent exudation, in which were tubercle bacilli. Tubercle bacilli 
were found alsoin the sputum. There were irregular fever with evening exacerba- 
tions, fetid sputum, albumin in the urine at times, but no sugar. The ribs were 
resected and a large amount of very offensive pus was evacuated; there was at first 
improvement, but soon afterward the condition became worse, there were cardiac 
weakness, cyanosis, and death. 

At the autopsy Lubarsch found the pancreas large, very flabby, almost fluc- 
tuant. On section the substance was almost wholly transformed into a lobulated 
mass with the luster of fat, containing here and there whitish streaks, and large, di- 
lated ducts filled with calcium concretions. On chemical examination these concre- 
tions were found to consist predominantly of carbonate of lime and traces of phos- 
phate of lime. On microscopic examination the extraordinary increase of fat tissue 
was very noticeable. In many places there were also small necrotic foci, each of 
which contained but a few cells. 


In the section on Pancreas and Diabetes several cases of lipomatosis 
are mentioned (page 62). 

The formation of lipomata may be a feature of general obesity, 
especially in drunkards. It occurs, however, in emaciated individuals 
also, as is shown in the case mentioned before and by the following case, 
reported by Lépine and Cornil: 


A man fifty-seven years old, formerly a hard drinker, had lost flesh for about 
six months, suffered alternately from constipation and diarrhea, had neither fever 
nor vomiting. For two months slight edema of the legs. Marked emaciation, In- 
ternal organs showed no essential change. Autopsy: Pancreas of normal size and 
shape, fatty degenerated throughout resembling a Nivea: gland tissue wholly ab- 
sent. Between the lobules there is only fat tissue; the chief duct and accessory ducts 
contain a thick, white, slimy fluid and small concretions. 


» 


RUPTURE OF THE PANCREAS. 265 


(d) AMYLOID DEGENERATION. 


This occurs in connection with the same process in numerous other 
organs, and involves, as Friedreich has shown, only the small arteries 
and capillaries. This author could not confirm the statement of Rokitan- 
sky concerning the occurrence of localized amyloid disease exclusively 
limited to the pancreas, and also of the amyloid degeneration of the 
gland-cells. On the other hand, he was able to show in the body of a 
phthisical patient twenty years old both amyloid degeneration of the 
vessels of the pancreas and pronounced fatty degeneration of the gland- 
cells. The pancreas in this case was yellowish-white and of less than 
normal consistency; on section there was such extensive fatty degen- 
eration of the gland-cells that the organ appeared almost everywhere 
filled with fatty detritus; amyloid degeneration was found especially in 
the arteries of small and medium size, which ran in the interlobular 
tissue, and in the capillaries surrounding the gland lobules. 

Friedreich’s statement was confirmed by Kyber. He also found 
the pancreas degenerated in cases of general amyloid disease. As a 
rule, he saw single arteries entirely degenerated, giving the characteristic 
reaction. In two cases he found degeneration of the membrana propria 
of the acini in addition to that of the capillaries which surrounded the 
narrow lobules. The epithelial cells in these cases were to a great 
extent filled with fat granules and fat-drops, in part disintegrated, and 
of, a yellow color; there was an increased amount of interlobular 
connective tissue. The organ externally appeared merely dense and 
anemic. Increased density and abundant’ development of interlobular 
connective tissue were found in those cases also in which only indi- 
vidual arteries were degenerated. 

Among 155 cases of general amyloid disease, Hennings found amyloid 
disease of the pancreas in 3.9% of the cases. 





Al. RUPTURE; PROLAPSE: DISPLACEMENT,..AND 
BULLET WOUNDS OF THE PANCREAS. 


(a) RUPTURE OF THE PANCREAS.* 


InJuRIES of the pancreas are, on the whole, rather rare. The organ 
through its anatomic position is quite safely protected from injury. 
When the latter is applied to a limited part of the abdomen, it may, 
under certain conditions, affect the pancreas. The force of the blow, 
according to Leith, must be directed more or less toward the back, and 
not obliquely upward or downward, in order that the pancreas may be 
pressed against the resistant spinal column. The organ can be injured 
from the front only under especially favorable circumstances, because 


* The following statement is based on the comprehensive monograph of Leith. 


266 INJURIES OF THE PANCREAS. 


it is protected in front by the abdominal walls, the tension of the abdom- 
inal muscles, the stomach, the omental sac, the ascending portion of the 
transverse mesocolon; and from behind, but less easily, being protected by 
the vena porte, the vena cava inferior, the two crura of the diaphragm 
on both sides of the aorta, the trunk of the superior mesenteric artery, 
the left adrenal and kidney, and especially by the spine and the powerful 
muscles of the back. In order that rupture of the gland may follow even 
violence from the front, the force must be very considerable and the. 
stomach and intestineempty. Jor the occurrence of a more severe injury, 
the force must be directed not only toward the median line and from the 
front backward, but also must be very great. 

Leith divides ruptures into two groups: (1) Those ending fatally; 
(2) those pursuing a less severe course. 

He includes the following 9 cases in the first group: seven published 
previously, one of his own, and one reported by Goldmann.” In only 
two was the pancreas alone injured; in the remainder other organs also 
were affected: once the lungs were ruptured, once the spleen, once the 
duodenum, and four times the ribs were fractured in connection with 
other internal injuries, as rupture of the liver, kidney, or spleen. The 
cases reported by Leith are, in brief, as follows: 


1. Leith: Boy, four years old, kicked in the stomach by a horse, fell against 
the wheel of the wagon, but was able to get up. In the afternoon he felt ill and was 
unable to use his left arm. Annandale found, on examination, a transverse fracture 
of the lower third of the humerus, but no signs of any other injury. Later in the 
afternoon he appeared worse; there were shock, pain, indistinct symptoms of abdom- 
inal disturbance. In the evening he was in collapse, so that an exploratory lapa- 
rotomy was impossible and he died ten hours after the injury. The autopsy, fourteen 
hours after death, showed no evidence of injury except that of the leftarm. Inthe 
abdomen about 1 pint of clear, dark-brown, inoffensive fluid; peritoneum markedly 
injected, not so transparent as usual; no hemorrhage. Rupture of the duodenum 
near the end of the upper third, affecting about two-thirds of the circumference; 
escape of the duodenal contents, which appeared like coagulated milk. Deeper 
down in the mesentery of the jejunum was a small tear and a slight hemorrhage; 
transverse colon pushed down, pancreas lying free, the ascending part of the trans- 
verse mesocolon and the subjacent pancreas ruptured. The injury to the pancreas 
was less extensive than that of the mesentery, and was vertical, extending somewhat 
to the right and involving the entire width of the upper edge, but only a portion of 
the lower part. Main excretory duct and the splenic vessels were intact; a line 
drawn through the tear, if continued meets one drawn through the torn duodenum; 
the rupture was due probably to the direct influence of the kick and the pressure of 
the organ against the spine. The ruptured portions show a small gap and are 
slightly infiltrated with blood. There is some blood in the retroperitoneal connec- 
tive tissue toward the hilum of the spleen and near the suprarenal capsule. In com- 
parison with the severity of the injury there was surprisingly little hemorrhage. 
The foramen of Winslow was open. The fluid in the abdominal cavity was mixed 
with pancreatic juice; the aorta was uninjured; the liver, kidney, and lungs were 
very pale, as after a severe hemorrhage. 


According to Leith, the following points are noteworthy in this case: 
The nature of the injury, the absence of severe symptoms immediately 
after it, their subsequent rapid onset and severity, the lack of external 
injury to the abdomen, the absence of pain, the large quantity of exuda- 
tion in the peritoneum, the extent of the rupture of the pancreas, the 
slight hemorrhage. 

2. Goldmann: A young man suffered a severe injury from the fall of a heavy 
box on his abdomen. It was thought that a corner of this box had grazed the epi- 


gastrium. Symptoms of hemorrhage, intestinal occlusion, appearance of a tumor 
in the epigastrium, similar to a pancreatic cyst. Nothing abnormal in the skin of 


% 


RUPTURE OF THE PANCREAS. 267 


the abdomen; death occurred some hours after the injury. At the autopsy a 
transverse rupture of the pancreas was found, also marked hemorrhage into the 
eae Ot the lesser omentum and rupture of the spleen; the other organs were not 
injured. - 

3. Jaun: Man fifty years old. Results of an assault in which, after his knees 
and elbows were tied together, he was laid on his back, struck in the abdomen with a 
shoe, and pushed about; he then walked about a mile toward home, supported by 
two persons, and died about eighteen hours after his admission to the hospital. 
Autopsy: The pancreas ruptured on the right half-way through. At the place of 
rupture there were small clots of blood; the rest of the organ was injected and showed 
marked extravasation of blood in the gland-substance; hemorrhagic exudation in the 
peritoneal cavity; externally nothing abnormal. 

4, Wilks and Moxon: An adult man was run over. Pancreas ruptured in the 
middle, and divided into two halves, which lay near the spine. Some other slight 
signs of injury of the abdominal organs. 

5. Wandesleben: Pancreas and lungs were injured. A pancreatic abscess de- 
veloped which was opened by Wandesleben (K6rte). 


The four following cases were reported by Senn: 


6. Cooper: A man thirty-three years old was run over by a rapidly running 
light wagon. No external signs of injury, the left lower ribs were broken, the pan- 
creas was literally crushed and embedded in half-coagulated blood. He died some 
days afterward. 

7. Travers: A drunken woman was knocked down by the wheel of a post- 
wagon but was not run over. She lived only a few hours. Some ribs were broken, 
the pancreas was torn through transversely, likewise the liver, and much blood 
escaped. 

8. Stork mentions the case of a woman who was run over by a coach and who 
lived only a short time after the injury. Pancreas torn in two and embedded in a 
large quantity of semi-fluid blood. The liver torn, a number of ribs broken. 

9. Le Gros-Clark observed a case of rupture of the pancreas in a boy who had 
suffered other severe injuries and died soon afterward. 


The communications of Rose and Wagstaff are more recent: 


In Rose’s case a rupture of the posterior wall of the stomach, combined with 
laceration of the pancreas, occurred after a trauma. The meal last taken escaped 
into the omental bursa and became mixed with blood and pancreatic juice, in conse- 
quence of which inflammation of the bursa followed. There was probably closure 
of the foramen of Winslow. The case was operated upon (incision and drainage), 
after which a fistula formed, from which a fluid was evacuated which showed the 
characteristics of pancreatic Juice. 

Wagstaff: Fall from a wagon, contusion of the left side, fracture of the femur. 
On the third day symptoms of peritonitis developed and death occurred on the fifth 
day. Autopsy: No peritonitis, rupture of the pancreas, large retroperitoneal extra- 
vasation of blood. 


Symptoms.—Shock and collapse seem, as Leith states, to be the 
most prominent symptoms; they are usually caused by internal hemor- 
rhage. In some cases the collapse occurs only after a considerable 
interval, and is probably to be ascribed to the complications. In no 
patient have the symptoms pointed to the pancreas as the chief seat 
of the injury. According to Leith, the absence of all external signs of 
injury to the abdomen is surprising and noteworthy. From a medicolegal 
point of view this is especially to be borne in mind. 

Diagnosis.—It is impossible to make the diagnosis without laparot- 
omy. The nature of the force, its exact seat and direction, may at most 
lead to a suspicion of a pancreatic lesion. Leith has ascertained by 
examination of the cadaver that in the epigastrium, a little to the left, 
the anterior surface of the pancreas could be accurately outlined with 
the finger through a three-inch incision in the median line. The gland 


268 INJURIES OF THE PANCREAS. 


and its peritoneal covering can thoroughly be seen with an electric light 
introduced in a Ferguson’s speculum. _ 

Course.—In all the cases hitherto reported, with the exception of 
that of Rose, death occurred quickly. In six cases it was caused by 
internal hemorrhage, but it is probable that the hemorrhage from the 
neighboring organs simultaneously injured was the main cause. It is 
not to be assumed that the hemorrhage alone from a ruptured pancreas . 
is of importance, except when the splenic artery or vein is lacerated at 
the same time (Leith). 

Treatment.—It appears from the statements of Leith that “injuries 
of the pancreas rarely occur alone, and, further, as a rule present no 
marked symptoms. Hence the treatment should be expectant, except in 
those cases in which exploratory laparotomy has been decided upon. 
If a rupture of the pancreas then is found, it should be appropriately 
treated. The hemorrhage is to be checked by pressure and the lacerated 
ends are to be sewed together. The stitches should be relatively super- 
ficial and carried through the peritoneal covering and the superficial 
layers of the gland.”’ Senn had earlier stated the fundamental principles 
of surgical treatment on the basis of his experiments on animals. In 
Rose’s case the operation resulted in recovery. 

Leith’s second group comprises the much more frequent cases which 
run a milder course and are either entirely cured or suffer more or less 
severe after-effects. Large ruptures may lead to the passage of the 
pancreatic juice with blood and bits of destroyed pancreas through the 
foramen of Winslow and cause the production of a general peritonitis 
which usually runs a fatal course. In other cases the injury of the tissues 
may be followed by inflammation which may be healed with the forma- 
tion of cicatricial tissue. In a third group, as already repeatedly 
mentioned, the result is a cyst formation. 

In the section on Cysts cases are mentioned as “ traumatic,” being 
caused by an injury or a laceration of the pancreas. Leith mentions 
17 cases: Kulenkampf, Senn, Kiister, Fenger, Steele, Freiberg, Karewski 
(2 cases), Cathcart, Riegner, Pitt and Jacobson, Richardson, Littlewood, 
Lloyd (2 cases), Thomas Lynn, Brown; in the following 12 cases also 
there is the history of an injury: Ledentu, Fisher (2 cases), Michailow, 
Lindner, Barnett, Martin-Morison, Schnitzler, Tilger, Tobin, Eve, G. 
Hadra. ‘There is no doubt, as Tilger has previously suggested, that in 
a number of the cases mentioned pseudo-cysts only are found, caused by 
hemorrhage into the omental bursa. 

The clinical description of this variety corresponds to that of cysts, 
and is given in the section on the subject. 


(b) PROLAPSE AND DISPLACEMENT OF THE PANCREAS. 


Prolapse of the pancreas may arise in the course of penetrating 
wounds of the abdomen. Several communications have been made on 
this subject. Senn mentions first the case of Laborderie. The omen- 
tum, however, and not the pancreas, was concerned, as Laborderie stated 
some weeks after his first publication (Kérte). Hyrtl has suspected that 
in such cases the pancreas may be confounded with fat tissue hardened 
and soaked with blood. Senn further reports the observations of Dargau, 
Caldwell, Kleberg and Wagner, Thompson and Cheever. Odevaine 


» 


BULLET WOUND OF THE PANCREAS. | 269 


(1866) reports a case of a penetrating wound of the abdomen with pro- 
lapse of a large part of the pancreas; removal by ligature; recovery. The 
communication of Pareira-Guimaraes is most recent: 

A man thirty-three years old received a bayonet-stab in the left hypochondrium. 
The injury caused a hernia which the physician regarded as the prolapsed omentum. 
Antiseptic dressing was applied. Milk diet. Opium pills. The examination, made 
forty-eight hours later, a ta an oblique wound, about 4 cm. long, 10 cm. to the 
left of the linea alba and 8 cm. below the umbilical line. There was a bulging tumor 
5 cm. long, dark-red, conical, and somewhat flattened. Diagnosis: Hernia of the 
tail of the pancreas. The patient suffered also from beri-beri. Nevertheless, his 
condition was satisfactory. Wound enlarged and the organ replaced. A suture was 
applied. On the day of operation there was a slight fever, the temperature running 
up to 38.2° C. (100.8° F.). Otherwise the course was afebrile and recovery took 
place after twelve days. 


Displacement of the pancreas, especially of the tail, is possible on 
account of the anatomic relations. The tail is the least fixed portion, as 
Zuckerkandl emphasizes in his anatomic introduction to this article. He 
states that it is not infrequent for a piece of mesentery containing a 
lymph-gland to be pushed in between the tail and the mesial surface of 
the spleen, in consequence of which there is a certain mobility to this 
portion of the pancreas. Klebs states that the pancreas may be pushed 
downward by lacing, while it may be shoved upward and lifted away 
from the vertebral column by retroperitoneal tumors and aneurysms of 
the large blood-vessels. The pancreas, thus,—although in very rare 
cases,—may be ranked with those organs which are affected in enterop- 
tosis. 

Dobrzycki in 1878 reported a case of movable pancreas: 

A carpenter fifty-six years old fell from a height two years previously. Since 
then he suffered from symptoms resembling those due to movable kidney; vomiting 
of a fluid of the nature of pancreatic juice and having an alkaline reaction. There 
was a tumor in the region of the stomach, corresponding in shape and position to the 
pancreas. 

Cecchini (1886) reported a case of congenital ectopia of the head of 
the pancreas with subsequent gastrectasia. 

The pancreas may be situated in diaphragmatic and umbilical hernias. 
Several cases have been reported. The cases of Vecker, St. Andre, and 
Cavalier, in which the pancreas, colon, and omentum were dislocated 
into the thoracic cavity, through a rupture of the diaphragm due to a 
powerful emetic, as mentioned by Ancelet and Claessen. The displace- 
ment of the pancreas in diaphragmatic hernia has not infrequently been 
elsewhere noted. 

Claessen states that in the cases of Marrigues and Howel the pan- 
creas was contained in the sac of a congenital umbilical hernia. In- 
vagination of the pancreas into the intestinal canal also may take place. 
Claessen cites a case reported by Baud, in which a portion of the duo- 
denum, with the pancreas, the beginning of the jejunum, the transverse 
colon, and the right part of the great omentum, had been invaginated 
into the descending colon and the rectum. Claessen reports also the case 
observed by Guibert of invagination in a child three years old. 


(c) BULLET WOUNDS. 


Cases of this sort are reported by Otis and described in detail by Senn. 
The clinical description of these injuries belongs to surgical text-books. 


270 FOREIGN BODIES IN THE PANCREAS. 


XII. FOREIGN BODIES IN THE PANCREAS. 


ASCARIDES are the only foreign bodies except gall-stones which have 
been found in the pancreatic excretory ducts and their branches. 

Mauchard and Lieutaud, as stated by Claessen, mention the obstruc- 
tion of the ductus Wirsungianus by lumbrici. Engel reports a case in 
which several ascarides filled the pancreatic duct and its branches. Nu- 
merous lumbrici had invaded the bile-ducts even far in the liver. Da- 
vaine mentions four cases. The duct usually contains a single ascaris, 
but in one case (Hayner) seven were found. Klebs found in the slightly 
dilated duct of a corpse six specimens, three of which were males and 
three females. The first pair which entered went to the left end and 
turned half-way around; the other four turned their heads toward 
the left side of the pancreas. It is presumable in all these cases that the 
migration took place after the death of the patient. 

The following observation of Durante is recent: A pancreatic cyst 
was caused by closure of the ductus Wirsungianus by an ascaris. Shea 
found in a pancreatic abscess an ascaris 17 cm. long partly in the duct 
and partly in the duodenum. Drasche likewise saw an ascaris in a pan- 
creatic abscess. Nash also once found a lumbricus 6 inches long in the 
pancreas. In the three cases last named, the postmortem immigration 
cannot be excluded. 





BIBLIOGRAPHY.* 


Abbe: ‘ Acute Biliary Colic and Jaundice Due to Tumor of Pancr.,”’ “ Practit. Soc. 
of New York,”’ 5, 4, 1895. 

Abelmann: “ Ausnutzung der Nahrungsstoffe nach Pankreasexstirpation.”’ Disser- 
tation, 1890. 

Abelous: “ Action des antiseptiques sur les ferm. du pancréas,”’ ‘‘ Compt. rend.biol.,”’ 
1891, p. 215. 

Abercrombie: “ Pathol. of the Paner.,’”’ “ Edinburgh Med. and Surg. Jour.,”’ 1824, 
p. 243 et seq. 

— ‘“Pathologische und praktische Untersuchungen tiber die Krankheiten des Ma- 

gens.”’ Uebersetzt von Busch. Bremen, 1843, S. 501. 

Achard: “ Diabéte bronzé.”” Thése, Paris, 1895. 

v. Ackeren: ‘‘ Ueber Zuckerausscheidung durch den Harn bei Pankreaserkrankun- 
gen,” “ Berliner klin. Wochenschr.,’’ 1889, Nr. 14. 

Afanassiew u. Pawlow: “ Beitrag zur Physiologie des Pankreas,”’ ‘‘ Pfliiger’s Archiv,” 
1877, DO. RVI; So alo: 

Agnew, D. Hayes: “Cancer of the Pancr. and Stomach,” “ Proc. Pathol. Soc. Phila- 
delphia,”’ 1860, vol. 1, p. 84. 

— “Pancreatic Cyst,” “ Brit. Med. Jour.,”’ 1891, 1, 1284. Ref. in “Gaz. hebdom. de 
med.,”’ June, 1891. . 


* This list contains not merely the references of the authors mentioned in this 
book whose original articles have been examined, but refers also to such data as may 
be found in bibliographies, for example, the Index-Catalogue of the Surgeon-Gen- 
eral’s Office, United States Army, volume x, Washington, 1889, and in several vol- 
umes of the Index Medicus by John S. Billings. Only a part of the publicaticns in 
1897 are recorded in the following list. The earlier literature has thoroughly been 
reviewed in the works of Claessen and Friedreich. 


3 


BIBLIOGRAPHY. 271 


Agricolansky: ‘“ Einfluss des Strychnins auf die Pankreassecretion.”” Ref. in “ Méd. 
mod.,’’ 1893, S. 102. 

Aigner: “ Vier Falle von Carcinom des Pankreas.”” Dissertation, Miinchen, 1896. 

Aigre: (“ Pankreascarcinom’’) “ Bull. soc. anat.,”’ 1889, S. 253, cited by Mirallié. 

Albers: “ Einfacher Krebs des Pankreas,”’ “‘ Medic. Correspondenzbl. rhein. Aerzte,” 
1843, Nr. 8, S. 131, 144-244. : 

Albert: (‘Pancreatic Cysts, Two Cases”) “Arbeiten aus der chirurg. Kink,’ 
1892, Wien. 

Alberti: ‘“De morbis mesenterii et ejus quod pancreas appelatur.”’ Dissertation, 
Wurttemberg, 1578. 

Albertoni: (“ Behavior of Sugar in Organism’’) “ Annali di Chim.,”’ 1892, vol. xv1. 

— ‘‘ Ricerche sperimenteli,” 1877. 

— “Sui poteri digerenti del pancreas nella vita fetale,”’ “Sperimentale,” 1878, p. 16, 


Aldehoff: “Tritt auch bei Kaltbutlern nach Exstirpation des Pankreas Diabetes 
aul? “Zertsehr, f, Biol,” Ba. xxvii, S$: 293, 

Aldibert: (‘‘Pankreascarcinom’’) ‘ Bull. soc. anat.,’’ 1892, 8. 35; see Mirallié. 

Aldor: ‘“ Beitrage zur Casuistik der Pankreasgeschwilste,” “Gydégydszat,’’ 1895. 

Allen: “ Exsection of the Pancr.,’”’ “ Amer. Weekly,” 1876, p. 305. 

— “Pancreotomy,”’ ibid., 1877, p. 56. 

— (“Carcinoma of the Pancreas’’) “ Philada. Med. Times,”’ 1875. 

— Idem, “Trans. N. Y. Path. Soc.,’”’ 1879, 11, 8. 40. 

— “Fatty Stools Due to Disease of Pancr.,”’ “ Trans. N. Y. Med. Assoc.,’”’ 1884-1885, 
vol. I, p. 286. 

Allessandrini: “ Descriptio veri pancreat. glandularis et parenchymatosi in acci- 
pensere et in esoce reperti,”” Bonn, 1855. 

Allina: “ Ein Fall von Pankreasnekrose,”’ “‘ Wiener med. Wochenschr.,”’ 1896, Nr. 45. 

Amidon: (“Pancreatitis hemorrhag.’’) “Boston Med. and Surg. Jour.,’’ 1886, p. 
594. 

Ancelet: ‘ Etude sur les maladies du pancr.,”’ Paris, 1866. 

— “ssai analytique sur |’anat. pathol. du pancr.,’”’ Paris, 1856. 

— “De l’indigestion des graisses au point de vue des affect. du pancr.,’’ ‘Gaz. des 
hop.,”’ 1860, p. 463. 

— “Sur les malad. du pancr.,”’ ‘Gaz. méd. de Lyon,” 1864, p. 81. 

Anders: ‘Case of Cancer of the Pancreas,” “‘ Phila. Med. Times,’’ 1880, p. 803. 

Anderson: ‘‘ Case of Malignant Disease of the Pancr.,”’ “ Glasgow Med. Jour.,’’ 1884, 
p. 59. 

Andral: ‘Cancer du pancr. simulant un aneurysma de |’aorte abdom.,” “Gaz. des 
hoép.,” 1831, p. 61. 

— “Cancer du pancr.,’’ ‘‘ Arch des. sciences méd.,”’ vol. xxvu1, p. 117. 

Anger: ‘“ Kyste sanguin du pancreas,” “ Bull. soc. anat.,’’ Paris, 1865, p. 192. 

Annandale: (‘‘ Pancreatic Cysts’’) “ Brit. Med. Jour.,’’ 1889, 1, 1, vol. 1, p. 241. 

Annesley: ‘‘ Researches into the Causes and Treatment of the More Prevalent Dis- 
eases of India,” 1828, ‘2. Sammlg. auserlesener Abhandlungen,” Bd. x11, 1829. 

Antrum: (“Cancer of Pancreas”’) “ Assoc. Med. Jour.,’’ 1855, cited by Dieckhoff. 

Aphel: “Caso di cancro al pancr.,”’ “Gazz. di Torino,” 1885, p. 179. 

Apolionio: “Sopra un caso di pancr. e milza succenturiat,”’ ‘Gazz. di Milano,” 1887, 

. 196. 

Aran: “Observ. d’abcés tuberc. du pancr. et colorat. anormale de la peau,” “ Arch. 
gén. de méd.,”’ Paris, 1846, 111, p. 61. 

Armbruster: “ Ueber Aetiologie der Pankreas-Haimorrhagien.”’ Inaug.-Dissertation, 
Tubingen, 1896. 

Armstrong: “ Primary Cancer of Pancr.,”’ ‘Canad. Med. Assoc.,’’ 1885, p. 555. 

Arnozan: Vide Bonnamy, cited by Mirallié. : 

Arnozan et Vaillard: ‘“ Pancréas du lapin,.’’ “ Jour. de méd. de Bord.,”’ 1881, 3. April; 
“ Arch. de physiol. norm. et path.,’’ 1884, p. 287. 

— ‘Assoc. med. jour.,’’ 1855. 

— “Cirrhose total du pancr.,” “ Jour. méd. Bordeaux,” 1880, p. 584. 

Arthaud et Butte: ‘Recherches sur la déterminaison du diabéte pancr. expérimen- 

_ tale,” “ Compt. rend. soc. biol.,’’ 1890, p. 59. 

Arthus, Maurice: “Glykolyse dans le sang et ferment glycolytique,” “ Arch. phy- 
siol.,”’ 1891, p. 425; 1892, p. 337-. , 

— “Compt. rend. soe. biol.,’’ 1892. 

Ashhurst: ‘“Suppurating Cyst of the Paner.,” ‘Med. News,” 1894, p. 377. 

ar ae™ “Zur Kenntniss des Pankreas,” “Virchow’s Archiv,” 1888, Bd. cxt, 

. 269. 


272 BIBLIOGRAPHY. 


Atkinson: “Case of Suppurative Pancreatitis,” “ Med. News,” 1895, xv, 5. 

Aucher: “ Diab. bronzé,” ‘ Bull. soc. anat.,”’ in, 5, 1895. 

Aufrecht: “ Pathologische Mittheilungen, ”” 1881, 3. 126 (‘‘ Cancer of the Head of the 
Pancreas ’’). 

Ausset: (“The Administration of Pancreatic Substance in Pancreatic Diabetes’’) 
“Sem. méd.,” 1895, S. 377. 

Auvray: (“Carcinoma of the Pancreas’’) “Bull. soc. anat.,’’ 1893, xx111, 6; see 
Mirallié. 


Babington: “ Extensive Cancer. Degenerat. of the Pancr.,” “ Dubl. Quart. Med. 
Jour.,”’ 1855, p. 237. 
Baer: “ Pankreassteine bei einer Kuh,” “ Deutsche thierarztl. Wochenschr.,’”’ 1893, 


Baginsky : “Vorkommen von Guanin und Xanthin im Pankreas,”’ “ Zeitschr. f. phys. 
Chemie,” 1883, Bd. vir, S. 396. 
Bailey: “ Cancer of the Pancr., Liver, and Mesentery,”’ ‘‘ Phila. Med. Times,” 1873, 
667. 


Baillie: (“ Acute Pancreatitis”) ‘Morbid Anatomy,” 1833, p. 221. 
Baillie-S6mmering: “ Anatomie des krankhaften Baues von einigen der wichtigsten 
Theile im menschlichen Kérper,’’ 1820; see Claessen. 
Baines: “ Diseased Pancr.,’’ ‘‘ Med. Times and Gazette,” 1862, vol. 1, p. 281. 
Baldi: “ Rapporto fra glicosuria ed acetonuria nel diabet. speriment., BG Rif. med.,”’ 
1892, IV., Bd. tv, p. 15. 
— “To zucchero nel organismo animale,” “ Lo Sperimentale,” 1894, cv, p. 1. 
— (“Influence on the Digestion of Fats”) “ Arch. difarmacol. e terap., i 1394, Nr. 10. 
— ‘‘ Azione del Arsenico,” ‘‘ Arch. di farmacol.,’’ 1893, p. 449. 
Balser: “Fettnekrose des Pancreas,” “Verhandl. des XI. Internisten-Congresses,”’ 
1892. 
— “Ueber Fettnekrose, eine zuweilen tédtliche Krankheit des Menschen,” “ Vir- 
chow’s Archiv,” 1882, Bd. xc, 8. 520. 
Bamberger: (“ Acute Pancreatitis”) “Wiener klin. Wochenschr.,”’ 1888, Nr. 33. 
— “Krankheiten des chylopoetischen Systems,’ S. 626. P. Abscess. 
— “Krankheiten des chylopoetischen Systems,” S. 628. P. Cysts and Carcinoma. 
Barndelier: Bruno: ‘“ Beitrag zur Casuistik der Pankreastumoren.”’ Dissertation, 
Greifsw ald, 1895-96. 
Banham: “ Perihepatitis Causing Stricture of Bile and Pancreat. Ducts and Cystic 
Enlargement of Pancr.,” ‘ Med. Times and Gaz.,’’ 1885, 1, p. 314. 
Barbillon: (“ Carcinoma of the Pancreas 7)" eal soc. anat.,” 1884, p. 86; see Mirallié. 
Bard et Pic: “Contribution 4 |’étude clinique et anatomo-pathol. du cancer primitif 
du pancr.,”’ “ Revue de méd.,”’ 1888, vol. vim, p. 257. 
de Bary: ‘ Diabetes mellitus bei einem 9jahrigen Madchen,” ‘“ Archiv f. Kinderheil- 
kunde,”’ 1893. 
Bardeleben: (‘‘Carcinoma of the Pancreas’’) Vide Dissertation of Rosenthal, 1891. 
Bardenheuer: ‘“ De insania cum morbis pancreat. conjuncta,’”’ Bonn, 1829. 
Barfoth: “ De morbis pancreat. affect.,’’ Dissertation, Lund, 1779. 
Barlow: ‘Case of Tubercle of'the Pancr.,” “‘ Transact. Path. Soc.,’’ 1876, p. 173. 
Barnett: (“ Pancreatic Cysts”) ‘‘ New Zealand Jour.,’’ 1893; Ref. “ Brit. Med. Jour.,” 
Epit. 1894, No. 51. 
Barth: (“Carcinoma of the Pancreas’’) ‘Gaz. des hdép.,’”’ 1848, S. 600; ‘Bull. de 
soc. anat.,’”’ 1856, S. 110, 174. 
— “Diabéte bronzé, 7 Soe, anat.,”’ 1888, p. 50. 
Bartley: . Malignant Tumor of Pancr., ” «Ann, Anat. and Surg. Soc.,”’ Brooklyn, 
1880, p. 495. 
Barton: “Tumor of Pancr. and Pylor.,” “Trans. Path. Soc.,’”’ Phila., 1874, p. 71. 
Bartrum: “Case of Scirrhus of Pancr. and Stomach,” “‘ Assoc. Med. Jour.,’’ London, 
1855, p. 564, cited by Friedreich. 
Bas, Arséne: “‘ Des kystes volumineux du pancr.,”’ Thése, 1897. 
Bastian: “ Cancer of Pancreas,” ‘“‘ Med. Times, * 1883, 
Battersby: ‘Sur le diagnost. des malad. du pancr., ” “Gaz. méd. de Patis;’ ” 1844, 
p. 219, 617. 
— (“Cy st”) “ Arch. gén. de méd.,”’ 1844. 
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Battistini: Pi Zwei Fille von Diabetes mellitus mit Sotercusbnts behandelt,”’ “‘ Thera- 
peut. Monatshefte,” 1893, Nr. 10. 


. 


BIBLIOGRAPHY. 273 


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Bennet: (“ Pancreatic Cysts’’) “Clinical Lectures,” 1857. 

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Bigsby: “On Diseases of the Pancr.,’’ “ Edinburgh Med. Jour.,”’ 1835, p. 85. 

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Bimar: “Sur une disposit. anomale des conduits excreteurs du pancr.,” “ Gaz. hebd. 
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18 


274 BIBLIOGRAPHY. 


Blodgett: (“Cancer of Pancreas”’) ‘‘ Homeopath. Times,” New York, July, 1879; 
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Blumenthal: “ Klinische Beobachtungen tiber Pentosurie,”’ ‘ Berliner klin. Wochen- 
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Blumer: ‘‘ Adenocarcinoma of Pancr.,”’ “Johns Hopkins Hosp. Rep.,’” Sept., 1896. 

Boas: (Pancreatin) ‘‘ Magenkrankheiten,”’ Bd..1, 8. 295. 

Boccardi: ‘‘ Ricerche anat. pathol. sugli anim. privati del pancr.,” “ Rif. med.,” 1890, 
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Bodinier: ‘‘Terminaison du canal pancr dans le duoden., 4 4 cm. au-dessus du canal 
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Boé-Sylvius: ‘ Praxeos medicae idea nova,” “ Lugd. Batav.,”’ 1667, Bd. 111. 

Boeckel: ‘ Des kystes pancréat.’”? Thése, Paris, 1891. 

— (“Cancer of Pancreas’’) ‘Cong. franc. de chirurg.,’’ 1892; vide Nimier. 

Bogdan: ‘‘Carcinom primitif de la totalité du pancr.,” “ Bull. soc. méd. natural,” 
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Bohn: ‘“ Pankreascarcinom bei einem halbjahrigen Kinde,” “ Jahrbuch f. Kinder- 
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Boldt: “‘Statistische Uebersicht der Erkrankungen des Pankreas nach Beobach- 
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Bond and Windle: “ Diabetes Terminating in Coma,” “ Brit. Med. Jour.,’’ 1883. 

Bonet (‘‘Lithiasis pancreat.”) ‘Sepulchretum,”’ Bd. 1, S. 576, cited by Giudice- 
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Bonetus: ‘‘ Polyalthes s. Thesaurus medico practicus,” Bd. 11, Genf, 1691, S. 666, 
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Bonnamy: “ Etude clinique sur les tumeurs du pancr.,”’ Paris, 1879 

v. Bonsdorff: “ Pancreat. acuta gangraen. Finska handling.,’”’ ‘‘v. Boas’ Archiv,” 
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Bonz: ‘ Nova acta nat. curios.,’’ 1791, vii, cited by Claessen. 

Bormann: “Therapeutische Anwendung des Pankreas,’”’ “Wiener med. Blatter,”’ 
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Boucaud: (“Carcinoma”’) ‘Gaz. des hép.,”’ 1866, No. 10. 

Bouchard: “ Maladies par rallentissement de la nutrition,” p. 172, cited by Mirallié. 

Bouchardat et Sandras: “ Fonct. du pancr. et digestion des féculents,’’ ‘Compt. rend. 
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Bouillot: ‘ Arch. gén. de méd.,” 11, p. 198. Cited by Claessen, p. 345. 

Bourquelot et Gley: “ Propriétés d’un liquide provenant d’une fistule pancr.,”’ 
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Boutilier: ‘‘ Carcin. of the Pancr.,’’ ‘‘ New York Med. Rec.,’’ 1893, p. 221. 

Bowditch: (‘Carcinoma pancreat.’’) ‘Boston Med. and Surg. Jour.,’”’ 1852, xxv, 8. 

Bozeman: (‘‘Cyst of the Pancreas’’) ‘‘ New York Med. Rec.,” 1882, 8. 46 

Brault-Galliard: ‘“ Diab. bronzé,” “‘ Arch. de méd.,”’ 1888. 

Bréchemin, Gille: (‘Carcinoma pancreat.’’) ‘ Bull. soc. anat.,’’ 1879, p. 417; “ Progr. 
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Brera: Cited by Claessen, S. 155. 

Bressler: ‘‘ Krankheiten des Unterleibes,’”’ Bd. 11, Berlin, 1841, 8S. 251. 

Bret: (“Carcinoma pancreat.’’) “Province méd.,’’ 1891, p. 222; see Mirallié. 

Briggs: (“Sarcoma of the Pancreas.’’) ‘St. Louis Med. and Chir. Jour.,’”’ 1890, p. 
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Bright: “Cases and Observations Connected with Diseases of the Pancer.,’’ ‘Med. 
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Brockmann: ‘“ Pancreat. Cyst,”’ ‘‘Omaha Clinic,” 1893, v1, p. 260. 

Brown: (“Cyst of the Pancreas”’) “ Lancet,” vi, 1, 1894, p. 21. 

— “Some Diseases of the Paner.,”’ “Proc. Conn. Med. Soc.,” 1894, p. 135. 

Brown u. Heron: “ Ueber die hydrolytische Wirkung des Pankreas und Diinndarms,” 
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Brown-Séquard et d’Arsonval: “Injection dans le sang des extraits du paner.,” 
“ Arch. de physiol.,”” 1892, p. 148. 

Bruckmeyer: “ Ueber multiple Fettgewebsnekross.’”’ Dissertation, Freiburg. 

Bruen: “Case of Tuberculous Disease of the Pancr.,’’ ‘ Phila. Polyciinic,’”’ 1885, p. 7. 

“— Sst Pancreatis”’) “Boston Med. and Surg. Jour.,’’ 1883, p. 110, cited by 

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Brunet: (“Calculus’’) “Jour. de méd. de Bord.,” cited by Nimier: “ Lithiasis.” 

Brunner: ‘ Experimenta nova circa pancreas,’’ Amst., 1683. 

Bruschini: “Sul diabete mellito,” ‘ Gazz. degli osped.,’’ xx1v, 11, 1892. 

Bruzelius u. Key: (“Carcinoma of the Pancreas”) ‘Deutsche Zeitschr. f. prakt. 
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BIBLIOGRAPHY. 275 


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Manes “De damnis ex male affecto pancreate in sanitat. redundantibus,” Hal., 
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Buckingham: “Scirrhous Pancreas.,” ‘‘ Boston Med. and Surg. Jour.,”’ 1859, p. 89. 

Bufalini: ‘Sulla attivita digerente dal pancr. negli animali smilzati, ” “Univers. di 
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Burger: (“ Diagnosis of Diseases of the Pancreas’) “Jour. f. prakt. Heilkunde,” 
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Bulls“ Report of a Case of Pancreas Cyst,” “ New York Med. Jour.,’’ 1887, p. 376, 
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Caldwell: (“Injury of the Pancreas’’) “Transylvanian Journal of Medicine,’ 1828, 
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Call: “Case of Chronic Pancreatitis Resembling Malignant Disease,” ‘‘ Boston Med. 
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Cameron: “ Case of Scirrhus of the Pancr.,’’ ‘‘ Med. Times and Gaz.,’’ 1869, p. 491. 

Campbell: ‘Scirrhous Degen. of Pancr.,” “South. Med. and Surg. Jour.,”’ 1848, p. 
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Carbone, Tito: ‘‘ Adenomgewebe im Diinndarm,”’ “ Ziegler’s Beitrige,’’ Bd. v, 8. 225 
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Carmichael: “ Cancer. Degenerat. of the Head of Pancr.,”’ “ Dubl. Quart. Med. Jour.,’ 
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Carnot: (« Diabetes after the Injection of Cultures of Bacteria in the Pancreatic 
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Caron: (“ Pancreatic Carcinoma”) "These, Paris, 1889; see Mirallié. 

Carson: ‘‘Cancer of Pancr.,’’ “St. Louis Cour. Med.,”’ 1881, p. 342. 

Cash: ‘ Versuche tiber den Antheil des Magens und des Pankreas an der Verdauung 
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Casper: “‘ Einiges iber den Krebs der Bauchspeicheldriise,” “ Wochenschr. f. d. ges. 
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Caspersohn: “Pall von Blutung, Nekrose und Fettnekrose,”’ ‘‘Centralbl. f. Chirur- 
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Castelain: “ Hypertrophie du pancr.,”’ “ Bull. med. du nord,” Lille, 1863, p. 30. 

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Cavallo et Pachon: “ Activité digestif du pancr.,’’ “ Compt. rend. soc. biol., ”” 1893, 

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276 BIBLIOGRAPHY. 


de Cérenville: “ Effets de l’ingestion de substance pancr. dans le diabéte,” “ Rev. 
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Cesaris-Demel: ‘Adenoma acinose del pancr.,’”’ “Arch. per le scienze mediche,”’ 
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Challand u. Rabow: (“Pancreatic Hemorrhage”) “Bull. de la soc. méd. de la 
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Chambers: “ Post-mortem Specimen of Fatty Pancr.,” ‘Maryland Med. Jour.,” 
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Chambon de Montaux: “ Hydatiden im Pankreas,” “ Observat. cliniques,”’ 1789, p. 99. 

Chandelux: (“ Pancreatic Carcinoma’’) Vide Bard and Pie. 

Chantemesse et Griffon: “ Hemorrhagie peripancreat.,’”’ “Bull. soc. anat.,’”’ Paris, 
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Charmeil: ‘“Observat. anatomique,”’ “Jour. du méd. milit.,”’ 1783, p. 97. 

Charrin et Carnot: “ Infect. paner. ascendant par expér.,”’ “Soc. de biol.,’? xxv1, 5, 
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— u. Gley: (“Infectivity in Pancreatic Diabetes”) ‘Compt. rend. soc. biol.,”’ 1894, 

. 438. . 

Chatelain: “De inflammation du pancr.”’ Thése, Paris, 1841. 

Chauveau et Kaufmann: “Le pancr. et les centres nerveux,” “Compt. rend. acad. | 
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— — “Pathogenie du diabéte,” “ Compt. rend. acad, sciences,” 1898, p. 226. 

Cheever: (‘Injury’’) Cited by Senn, “‘ Surgery of the Pancreas,’ p. 34. 

Chew and Catheart: (“Cyst of the Pancreas”) “ Edinburgh Med. Jour.,”’ July, 1890. 

Chiari: ‘Sequestration des Pankreas,”’ “‘ Wiener med. Wochenschr.,’”’ 1876, Nr. 13; 
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— (“Melanotic Sarcoma of the Pancreas”) ‘Prager med. Wochenschr.,” 1883, 
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— ‘“Congenitale luetische Erkrankung der Gallenblase und grossen Gallenwege,”’ 
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— “Ueber sogenannte Fettnekrose,” “ Prager med. Wochenschr.,’”’ 1883, Nr. 30, 
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— ‘Ueber Selbstverdauung des menschlichen Pankreas,”’ “ Zeitschr. f. Heilkunde,”’ 
1896, 8. 69. 

Chicoli: “Calcoli pancreatici.”” Ingrassia, Palermo, 1885, 1, p. 321. 

Chittenden: ‘“ Proteolysis by Trypsin,” “ Med. Record,” v, 5, 1894. 

—and Cummins: (“Influence of the Bile on the Proteolytic and Amylolytic Ac- 
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— — (“Einfluss therapeutischer und toxischer Substanzen auf das Pankreassecret’’) 
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Chopart: ‘Mal. des voies urinaires.”” ‘‘ Diabetes with Calculus Formation,” cited 
by Klebs, 547. 

Choupin u. Molle: (‘Cancer of the Pancreas’’) “Loire méd.,” xv, 3, 1893, S. 62, 
141, Mirallié. . 

Churton: (“Cyst of Pancreas’) “Brit. Med. Jour.,” 1894, vol. 1, p. 1191; ‘‘Lan- 
cet,’’? 1894, vol. 1, p. 13874. 

Chvostek: ‘‘ Fall von Syphilis des Pankreas,”’ “Wiener med. Wochenschr.,” 1877, 
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— (“Diseases of the Panreas”’) “ Wiener med. Blatter,’”’ 1879, 8. 791. 

Chvostek-Weichselbaum: (‘“Syphilis’’) ‘ Allgem. Wiener med. Ztg.,’’ 1877. 

Cibert: ‘Gros kyste glandulaire de la queue du pancr.,”’ “Gaz. méd. des hép.,’’ 1896, 

47 


: p. 347. 
Cimbali: (“Primary Cancer of the Head of the Pancreas’’) “‘ Sperimentale,” 1889, 

Septembre, p. 282. . 

Claessen: ‘‘ Krankheiten der Bauchspeicheldriise,’’ Kéln, 1842. 

Clark: ‘“ Disease of the Pancr. and Liver Accompanied by’Fatty Discharge,” “ Lan- 
cet,”’ 1851, vol. 11, p. 152. 

_ Clarke: (“Calculus and Carcinoma”’) Cited by Friedreich. 

Clayton: ‘“ Calculi of the Pancreas,” “‘ Med. Times,’ 1849, xx, p. 37. 

Clutton: (“Pancreatic Cyst”’) ‘“ Lancet,” 1892, vol. 11, p. 1273. 

Cochez: “Les manifestations hepatique du cancer du paner.,” ‘“ Rev. de méd.,” 
1895, p. 545. 

— et Ramos: “ Deux cas de cirrhose biliaire par obstruction 4 la suite d’un cancer de 
pancr.,’’ “ Rev. de méd.,”’ 1887. 

Cohn: “Zur Kenntniss des der bei Pankreasverdauung entstehenden Leucins,”’ 
“ Zeitschr. f. phys. Chemie,”’ 1894, 8. 203. 


BIBLIOGRAPHY. 277 


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Colenbrander: “ Glykolytisches Ferment,” ‘ Maly’s Jahresb.,’’ 1892. 

Collard de Martigny: “ Pankreasconcrement,’’ cited by Klebs, 8. 55. 

Collier: (‘Cancer of Pancreas’’) ‘ Brit. Med. Jour.,” rv, 10, 1890; 11, p. 790. 
Comby: ‘ Pankreas,”’ “Sem. méd.,’’ 1893, No. 3. 

— “ Diabéte maigre chez un gargon de 14 ans.,” “ Méd. infant.,”’ 1895, 11, p. 29. 
Conradi: ‘‘ Handbuch der pathologischen Anatomie,” 1796, S. 219. 

Coolen: “ Action physiol. de la Phloridzine,” ‘“ Arch. de Pharmacodynamie,” 1894, 


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Cooper: (‘Rupture of Pancreas’’) ‘ Lancet,” 1839, Bd. 1, 8. 486, cited from Leith. 
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Corvisart: ‘‘Collection des mémoires sur une fonction peu connue du pancr.,” Paris, 
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Councilman: “ Primary Tumor of the Pancr.,” “Johns Hopkins Hosp. Rep.,’’ 1889, 
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Counnaille: “ Pancréatite suppurée,” “ Monit. scient.,’’ Paris, 1876, p. 375. 

Courmont u. Bret: (“Pancreatic Carcinoma and Glycosuria’’) ‘“ Clinique,” 1894, p. 
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Courvoisier: “Casuist. Statist.,” “‘ Beitrige z. Chir. der Gallenwege,’’ 1890. 

Cowley: “ London Med. Jour.,’”’ 1788, cited by Claessen. 

Crisp: “Scirrhous Enlargement of Pancr.,’” “Trans. Path. Soc. London,” 1861, p. 
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Crompton: “Scirrhus of the Pancr.,” “ Prov. Med. and Surg. Jour.,”’ 1842, p. 234. 

— (“Cysts of Pancreas’’) “ Birmingh. Pathol. Soc.,’’ December, 1842. 

Crowden: “Concretions in the Pancr.,” “ Brit. Med. Jour.,’”’ 1884, vol. 11, p. 966. 

Cruppi: “ Ueber Diabetes.”’ Dissertation, 1879. 

Cruveilhier: (‘Pancreatic Cyst’) ‘“Traité d’anat.,’’ 1856, vol. m1, p. 366; “Atlas 
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Cuffer: ‘Cancer of the Pancr. Modified by Transfusion of Blood,” ‘South. Med. 
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Curnow: “ Pancr. with Numerous Calculi in its Ducts,” “Trans. Path. Society Lon- 
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Curschmann: (“‘ Fat Necrosis’). Internistencongress, 1892. 

Cutler: (“ Hzemorrhag. Pancreat.’’) ‘Boston Med. Jour.,’’ x1, 4, 1895; Virchow- 
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Da Costa: (“Cancer of Pancreas”’) “North American Med. and Surg. Rev.,’’ 1858, 


Dahl: ‘‘ Pankreasfermente bei Rinder- und Schafsféten.”? Dissertation, 1890. 

Dallemagne: (“ Parenchymat. Infectious Pancreatitis”) ‘ Jour. méd. de Bruxelles,” 
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Dalton: “ Cancer of Pancr. and Duoden.,” “ Med. Chir. Rev.,’’ London, 1840, p. 590. 

Daraignez: “ Abscés du pancr.,” “‘ Jour. méd de Bordeaux,” 1887, p. 479. 

Dargau: (“Injury of Pancreas’’) ‘ Med. and Surg. Reporter,’’ Aug. 22, 1874, cited 
by Senn, 8. 33. 

Dastre: (‘Influence of the Bile on Fat Digestion”’) ‘Compt. rend. soe. biol.,’’ 1887, 
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— (“Absorption of Fats in the Intestine’’) ‘ Arch. de physiol.,’’ 1891, vol. 111, p. 
co! 


— (“Pancreatic Ferments”’) “Soc. de biol.,” xv11, 6, 1893; ‘Compt. rend. soc. biol.,”’ 
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278 BI. BLI OGRAPHY. 


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Dieckhoff: “ Beitriige zur pathologischen Anatomie des Pankreas,”’ Leipzig, 1896. 

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Drechsel: “ Abbau d. Eiweiss,”’ “ Du Bois’ Archiv,” 1891, 8. 254. 

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Dumegie “TInduration du pancr.,”’ ‘Compt. rend. soc. biol.,’”’ 1850, p. 65. 

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Iv, p. 359, 


» 


BIBLIOGRAPHY. 279 


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Finger: “Krebs der Driisen um das Pankreas,”’ etc., “Prager Viortalialiresehe, f; 
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280 BIBLIOGRAPHY. 


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8.9 
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Fossion: “Sur les fonct. du pancr.,’’ “‘ Bull. d’acad. belge,’”’ Bruxelles, 1877, p. 378. 

Foster and Fitz: (“Gangrene of Pancreas”) See Fitz: “ Med. Record, ”? 1889. 

Fothergill: ‘‘Case of Malignant Disease of the Pancr.,’”’ “ Brit. Med. Jour., ” 1896, 
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Fournier: “Jour. de méd. chir. et pharm.,” 1776, see Claessen. 

Frank, Josef: “‘ Praxeos medic univers preecepta, ” vol. 11, 1843. 

Frinkel, E.: ‘Fall subacuter Pankreasentziindung,”’ “ Zeitschr. f. klin. Medicin,” 
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Frerichs: “Leberkrankheiten, ”” 1858, 1, S. 146, 153 (Carcinom). 

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Fry: “ Dislocations and Malformations of the Pancr., ”” “Texas Med. and Surg. Rec.,” 
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Firbringer: es Behandlung mit Gewebsfliissigkeiten,’’ ‘‘Deutsche med. Wochen- 
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Fiirstenberg: Pankreasconcrement,” cited by Klebs, S. 544. 


Gabritschewsky: “ Glykogenreaction im Blute,” “ Archiv f. experiment. Pathologie,” 
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Gaglio: “Sul diabete, che segue all ’estirpazione del pancr. iY ’ “ Riforma med.,”’ 1891, 
I, p. 543 


> 


BIBLIOGRAPHY. 281 


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Galloupe: “ Cancer of the Pancr.,”’ “Boston Med. and Surg. Jour.,’’ 1881, p. 592. 

Galvagni: (“Pancreatic Carcinoma”) “Gazz. di Torino,” 1891, p. 181. 

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Gaultier: “ Dissert. de irritabilit. notione,’’ Halle, 1793; see Claessen. 

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Gavoy: “ Gastro-enteralg. symptom.,”’ “Jour. de méd. d’ Algérie, 0 1879, p. 144. 

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Giorgi: (“Diabetes”). Thése de Lyon, 1890. 

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Giudiceandrea: ‘Sulla calcolosi del pancr.,”’ “ Policlin.,’ ” 1896, pp. 33, 126. 

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Gonzales, Hernandez: “ Diab. bronzé.”” Thése, 1892. 

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03. 


282 BIBLIOGRAPHY. 


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Gould, Pearce: (“Cyst of the Pancreas”) Soc. for Med. Improvement, 1847, p. 217; 
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— (“Calculus”) Anat. Museum of Boston, 1847, p. 147. 

Graaf, Regnerus de: “‘ Opera omnia,”’ 1667; see Claessen. 

Graeve: “Pancreat. suppurat.,’’ Upsala Forhandl. Referat., “Centralbl. f. klin. 
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Grandmaison: “ Le diabéte maigre,” ‘ Méd. mod.,’’ 1892, p. 221. 

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Greding: ‘‘ Adversaria medic. practica,”’ 11, 135; 111, 86; 1769. 

Greene: “‘ Malignant Disease of the Pancr.,” “ Dubl. Jour. of Med. Scienc.,” 1846, 
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Greiselius: (“Gangrene of the Pancreas”) ‘“ Misc. Acad. curios.,’’ 1672, 1673, S. 74, 
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Griscom: “Transact. of the Med. Association,” vol. x1v, Phila., 1864. 

Griesinger: (“ Diabetes”’) “ Archiv f. Heilkunde,” 1859, 58. 44. 

Gross: “ Elements of Pathol. Anat.,’’ Philadelphia, 1857. 

— (“Pancreatic Cyst’’) ‘ Arch. gén. de Paris,” 1847, p. 215. 

— (“Carcinoma of the Pancreas’’) “ Phila. Med. Times,” 1872, p. 354. 

Gritzner: “ Ueber einige ungeformate Fermente,”’ “ Du Bois’ Arch.,’”’ 1876, S. 285. 

Guelliot: ‘ Glycosurie et inositurie,”’ ‘Gaz. méd. de Paris,’”’ 1881, Nos. 6 and 7. 

Guignard: “ Rapport sur le traité de l’affect. calculeuse du foie et du pancr.,’’ “ Bull. 
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Guillery: “ Entziindungen des Pankreas,”’ Berlin, 1879. 

Gussenbauer: “Zur operat. Behandlung der Pankreascysten,” ‘Langenbeck’s 
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— “Zur Casuistik der Pankreascysten,” ‘ Prager med. Wochenschr.,”’ 1891, Nr. 32. 

— “Zur Casuistik der Pankreascysten,” ‘‘ Prager med. Wochenschr.,”’ 1894, 8. 15. 

—u. Winiwarter: (‘Statistics Concerning Carcinoma”) Cited by Biach. 


Habershon: (“Gangrene of the Pancreas.’’) ‘On Diseases of Abdom.,” 1892, 


Case 114. 

Hadden: “Cirrhosis of Pancr. in Diabet.,” ‘“‘ Path. Soc. Lond.,” 1887, p. 163; 1890, 
p. 184. 

Hadra: (“Rupture of the Pancreas”) “Med. Record,” 1896, xv, 7; “Centralbl. f. 
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de Haén: Opuse. T.1, 8.217; see Claessen, S. 155. 

Hagenbach: “‘Complicirte Pankreaskrankheiten und deren chirurgische Behand- 
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Haggarth: “ Transact. of the College of Physicians of Ireland,” vol. 11, cited by Senn, 
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. 


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284 BIBLIOGRAPHY. 


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v 


BIBLIOGRAPHY. 285 


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286 BIBLIOGRAPHY. 


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BIBLIOGRAPHY. 287 


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Kiihn: “ Ueber primares Pankreascarcinom im Kindesalter,” “ Berliner klin. Woch- 
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Kihnast: ‘‘ Ueber Pankreascysten.’’ Dissertation, 1887. 

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—and Lea: (“Chronic Pancreatitis’) “Verhandlungen d. Heidelberger Arztl. 
Gesellsch.,’’ 1876. 

— — “Ueber die Absonderung d. Pankr.,’’ “ Unters. aus d. physiolog. Inst. in Heidel- 
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Kulenkampf: “Fall von Pankreasfistel,”’ ‘ Berliner klin. Wochenschr.,’’ 1882, Nr. 7. 

Kilz u. Vogel: “ Zur Kenntniss der Isomaltose,” ‘“Centralbl. f. med. Wissensch..,”’ 
1893, S. 817. 

— — “Pentosen bei Diabetes,” “ Zeitschr. f. Biologie,’’ Bd. xxx, 1895. 

Kuntzmann: (‘Fatty Stools’’) “ Hufeland’s Journal,” 1820, cited by Friedreich. 

Kiister: “Diagnose und Therapie der Pankreascysten,” “ Berliner klin. Wochen- 
schr.,’’ 1887, 8. 154. 

— “Zur Diagnose und Therapie der Pankreascysten,’”’ ‘Deutsche med. Wochen- 
schr.,’”’ 1887, S. 189, u. 215. 

Kyber: “ Untersuchungen tiber amyloide Degeneration,” ‘‘ Virchow’s Archiv,” 1880, 
Bd. txxx1, 8. 421. ~ 


beer iar jibe (“Cancer of Pancreas.’””) Thése de Dr. Salles, 1880, cited by 

Mirallié, - 

Labbé: (‘Cancer of Pancreas ’’) ‘ Bull. soc. anat.,’’ 1865, S. 267: 

Labes: ‘“ Malum pancreat. ex obstruct. alvi,’’ “Organ f. d. ges. Heilkunde,” 1861, S. 
17. ; 


288 BIBLIOGRAPHY. 


Laborde: ‘Cancer of pilticvbas: ” “ Gaz. méd. de Paris,’”’ 1860, Nr. 17. 
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84. 


Lachmann: (“Fall von primairem Pankreaskrebs.’’) Dissertation, 1889. 

Laennec: (“Cancer of Pancreas’’) ‘Gaz. méd. de Nantes,” 1892, S. 84, cited by 
Mirallié. 

Laguesse: ‘‘ Rech. sur l’histogénic du pancr. chez le mouton, 
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Lancereaux: “ Diabéte glycosurique,”’ “‘ Union méd., e 1890, p. 145. 

— et Thiroloix: “ Diab. pancr.,”’ ‘Compt. rend.,”’ 1892, p. 341. 

— (“Gumma of Pees as Bull. de la soe. d’anat. 1855. 

— “Traité de Syphilis,” Paris, 1874, p. 251. 

— (“Calculi of Pancreas, Diabetes’’) “ Bull. acad. de méd.,’”’ 1877, S. 1224; 1888, 


” “ Jour. de l’anat.,”’ 


vill, 5. 
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“Wiener med. Blatter,” 1888, 8. 716. 
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_ Landsberg: “ Krankheiten des Pankreas,”’ “Jour. f. prakt. Heilkunde, ” 1840, S. 15, 
4 


9. 
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252. 
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Lardy: “‘ Ueber Pankreascysten,”’ “ Corr. f. Schweizer Aerzte,’’ 1888, S. 279. 
Lauritzen: “On the Pancreas of Diabetes,’ ‘‘ Hosp. Tid.,”’ 1894, 
Lawrence: “Pancreas Found in a State of Inflammation, ”” “ Med.-chir. Transact.,”’ 
1831, p. 367. 
Lecorché: (“ Atrophy of Pancreas in Diabetes”) “ Arch, gén. de méd., ”” 1861, Bd. 
XVIE S70: 
Ledentu: (“Cyst of the Pancreas’’) “ Bull. de lasoc. d’anat.,’”’ 1865. 
Lediberder: ‘‘ Pemphigus foliacée, dégénérescence fibrokystique du pancr.,”’ “ Bull. 
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Lees: ‘‘Scirrhus of Pancreas,’’ “Dubl, Med. Jour.,’’ 1848, p. 188; 1854, p. 447. 
Legendre: (‘‘Cancer of Pancreas”) ‘Bull. soc. anat., si 1881, S. 136. 
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802. 
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Leo: “Schicksal des Pepsins und Trypsins im Organismus, ” “Pfliger’s Archiv,’ 
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Lépine et Cornil: “Cas de lymphéme du pancr.,” “Gaz. méd. Paris,” 1874, p. 624. 
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* 


BIBLIOGRAPHY. 289 


Lépine: “ Beziehungen des Diabetes zu Pankreaserkrankungen,” “Wiener med. 
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— “Sur laction du bain froid,” “ Lyon méd.,” 1892, p. 92. 

— (“Glycolytic Action of the Blood”’) “‘ Acad. des sciences,” 1893, xv1, 1. 

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— oe la glycosurie conséc. a l’ablat. du pancr.,” “Compt. rend.,” vol. CXXI, p 
457. 

— “Sur V’hyperglycémie conséc. 4 lablat. du pancr.,” ibid., p. 486. 

— “Etiologie et pathogénie du diabéte sucré,” “ Arch. méd. exp.,’’ 1891, p. 222; 1892, 
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— et Barral: “Sur le ferment glycolytique,” Soc. de biol., xxv, 4, 1891; “Compt. 
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— et Metzos: “Glycolyse dans le pancr.,” “Compt. rend. acad. sciences,” xv, 7, 


1893. 

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— “Pancreatite hemorrhagique,” “ Lyon méd.,’’ 1892, p. 303. 

— “ Etiologie et pathol. du diabéte,” “ Rev. de méd.,”’ 1894, p. 876. 

Lerche: “ De pancreatitide,”’ Hall, 1827. 

Leroux: “ Etude sur le diabéte chez les enfants,” ‘Gaz. des hépit.,”’ 1881. 

Letulle: (“ Bronzed Diabetes’’) “Semaine méd.,’’ 1885, p. 408. 

Leube: “ Bestimmungen des Fettgehaltes der Faces bei Diabetikern.” Dissertation, 
1891. 

— “Specielle Diagnose der inneren Krankheiten,’’ 1889. 

Leva: “Klinische Beitrage zur Lehre vom Diabetes mellitus,” “Deutsches Archiv 
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Levier: “Leucin im Darm,” “Schweiz. Zeitschr. f. Heilk.,” 1864, Bd. m1, S. 140, 
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Levére: “Studies in Phloridzin Glycosuria,” “Jour. of Physiol.,’’ 1894. 

Lewaschew: “ Bildung des Trypsins und Bedeutung der Bernard’schen Ko6rperchen,”’ 
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v. Lichtenfels: “Icterus e carcinomat. pancreat.,’”’ ‘‘ Bericht d. k. k. Krankenanstalt 
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Lichtheim: “Zur Diagnose der Pankreasatrophie durch Steinbildung,” “ Berliner 
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Lietaud: “ Hist. anat. méd. ed. Schlegel,’’ vol. 1, 1786, p. 296. 

de Lignerolles: ‘Cancer du pancr.,” ‘ Bull. soc. anat.,’”’ 1866, p. 38, 62. 

Lilienhain: “ Beitrige zu den Krankheiten des Pankreas,” “Jour. f. d. prakt. Heil- 
kunde,”’ 1825, Supplement, S. 78. 

Lilly: ‘‘ Case of Cancer of the Pancr.,”’ “ Med. and Surg. Rep.,’’ Phila., 1884, p. 422. 

Lindberger: ‘‘Trypsinwirkung bei Gegenwart freier Saiuren,’”’ ‘‘Maly’s Jahresb.,”’ 
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Lindner: ‘“ Fall von Pankreascyste,” “ Internat. klin. Rundschau,’’ 1889, Nr. 8. 

Lisser: ‘ Pankreasklysmen b. Diabetes,” “ Méd. gaz. (Russ.),’’ 1895; “Therap. Wo- 
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Litten: “ rae Faille totaler Degeneration des Pankreas,” ‘ Charité-Annalen,”’ 1877, 
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— “Primiéres Sarkom des Pankreas bei einem 4jaihrigen Knaben,”’ “‘ Deutsche med. 
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Littlewood: (“Traumatic Cyst of Pancreas”) “Clinic. Soc. of London,’ vit, 4, 
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Lloyd: ‘Case of Jaundice with Discharge of Fatty Matters from the Bowel,” “ Med.- 
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Lloyd-Jordan: (‘Cancer of Pancreas’’) “ Brit. Med. Jour.,” 1888. 

— “Injury of the Pancr.,” “ Lancet,’”’ November, 1892; “Brit. Med. Jour.,”’ 1892, 
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Lobstein: (“Cyst’’) “Lehrb. der pathol. Anat.,’”’ 1834, cited by Tilger. 

Lockridge: “ Disease of Pancreas,’’ “ Amer. Pract.,’’ 1876, p. 193. 

Léffler: “ Induratio pancreatis,” “ Zeitschr. f. Erfahrungsheilkunde,” 1848, S. 363. 

Loomis: “ Necrosis of Pancr.,’’ ““ New York Med. Rec.,’’ 1890, p. 105. 

Lésch: “ Primares Pankreascarcinom,” “ Petersburger med. Wochenschr.,”’ 1883, 8. 
205. 

Léschner: “ Pankreashimorrhagie,” “ Wiener med. Zeitung,” 1858, Nr. 45. 

— “Zur Pankreatitis,”’ “Weitenweber’s Beitrige zur Medicin,” 1842, Juli. 


19 


290 BIBLIOGRAPHY. 


Low: “Ueber die chemische Natur der ungeformten Fermente,” “ Pfliiger’s Archiv,” 
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Léwenhardt: “Fall von Degeneration des Mesenterium und des Pankreas,’’ ‘“ Wo- 
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Lubarsch, cited by Dieckhoff: “ Beitr. z. pathol. Anat. d. Pankreas.’’ 

Liicke u. Klebs: (“Carcinoma”’) “ Virchow’s Archiv,” Bd. x11, 1867, S. 9. 

Ludolph: ‘ Ueber operativ behandelte Pankreascysten.”” Dissertation, 1890. 

Ludwig, Christian: “ Adversaria med. practica,’”’ Leipzig, 1769, 111, S. 135 (Calculi). 

Luithlen: ‘Carcinoma pancreatis,”’ “Mem. aus d. arztl. Praxis,”’ 1872, Bd. xvu, S. 
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Lusk, cited by de Grazia: “ Rif. med.,” 1894, Bd. 11, S. 856 (Calculi) ; cited by Giu- 
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Lussana: “Il pancreas,” ‘Gazz. med. Ital. Lomb. Milano,” 1852, p. 297; ‘“ Annali 
univers. Milano,”’ 1868, p. 416. 

— “Pancreatitis,” “Gazz. med. Ital. Lomb.,”’ 1851, p. 237. 

Litkemiiller: “Care. medull. pancreat.,’’ “Jahrb. d. k. k. Krankenanstalten,” 3. 
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Lynah: “ Cancer of Liver, Absence of Pancr.,’’ ‘“ Charleston Med. Jour.,’’ 1852, p. 325. 

Lynn, Thomas: “Traumatic Pancreat. Effusion,” “ Lancet,” xxx1, 3, 1894, p. 799. 


Macaigne: “ Abcés du pancr.,’’ “ Bull. soc. anat.,”’ 1894. 

— “Carcinom du pancréas,”’ cited by Thiroloix. 

McBurney: “Cyst of the Pancr.,” “ Ann. Surg.,’”’ Phila., 1894, p. 492. 

McChupp: “Case of Scirrhus of Paner.,’’ “ Med. Examiner,” 1851, p. 640. 

McClurg: (‘‘Cancer’’) “Med. Examiner,” Phila., 1851. 

McCollom: ‘“ Cancer of Pancr.,” “ Boston Med. and Surg. Jour.,’’ 1872, p. 371. 

McCready: “ Concretions from the Pancr.,”’ “ New York Med. Jour.,”’ 1856, p. 78. 

McDowel: “Cancer of the Pancreas,” “ Dubl. Quarterly Med. Jour.,’’ 1850, p. 468. 

McPhail: ‘“Scirrhus of Pancr.,’’ “ New York Med. Jour.,” 1854, p. 227. 

McPhedran: ‘‘ Hemorrhagic Pancreatitis,” ‘Canad. Practit.,” September, 1896; 
“Lancet,” 1896, vol. 11, p 1324. 

Machado: (‘‘Sarcoma”’) “ Correio medico Lisb.,” 1883, p. 61. 

Mackenzie: “Treatment of Diabet. by Pancr. Juice,” “ Brit. Med. Jour.,” 14, 1; 1893, 
vol. 1, p 63. 

— “Cancer of Pancreas,’ “ Med. Examiner,” 1878, p. 126. 

Mackintosh, Malcolm: ‘Case of Pancreat. Glycosuria,”’ “ Lancet,” 24, 10; 1896, vol. 
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Madelung: (‘Surgery’’) In “ Penzoldt-Stintzing’s Handb.,” Bd. rv, 1896. 

Mader-Weichselbaum: ‘“Gangrin des Pankreas,’’ “ Bericht d. k. k. Krankenanstalt 
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Madre: ‘ Etude clinique cur le cancer primitif et second. du pancr.,’’ Paris, 1883. 

Maercker: “ De pancreate,’’ Berol, 1830. 

Maier: “ Fall von Verfettung des Pankreas,” ‘“ Archiv d. Heilkunde,” 1865, S. 168. 

Maigre: ‘Des phénoménes cliniques de la digestion & propos d’un tumeur du pan- 
créas,’’ Paris, 1866. 

Mairet and Bosc: (“ Experiments with Pancreatic Juice”) Soc. biol., xxv, 3, 
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Malassez: (‘Digestive Power of the Pancreas of Splenectomized Dogs’’) “ Gaz. 
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Maly: “ Pankreassaft” in “ Hermann’s Handbuch,” Bd. v, 2. Theil. 

Manley: ‘Case of the Pancr. Being a Solid Mass of Scirrhus,” “Trans. Wisconsin 
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Maragliano: (‘Cancer of Pancreas’”’) ‘ Rif. med.,’’ 1894, Bd. 1, S. 355. 

Marchand: ‘ Pankreasblutung,” ‘“ Berliner klin. Wochenschr.,’’ 1890, Nr. 23. 

Marchifaava: “ Necrosi del pancr.,’’ Soc. Lancisiania Roma, 11, 5, 1895; ‘‘ Gaz. degli 
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Marcuse: “ Bedeutung der Leber fiir das Zustandekommen des Diabetes,” “ Zeitschr. 
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Mariani: (“Cancer of Pancreas”’) “ Revue de méd.,’’ 1889, p. 7. 

Marie: “ Diab. bronzé,”’ “Sem. méd.,’’ 1895, p. 229. 

Marquet: “ Ginzliche Verknorpelung des Antrum pylori und des Pankreas,” “ Maga- 
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Marshall: “Treatment of Diabet. by Pancr. Extr.,” “ Brit. Med. Jour.,’’ 1893, p. 743. 

Marston: (“Cancer of Pancreas”) “Amer. Jour. of Med.,” 1854, p. 212, July 
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Martin: (“Cyst of Pancreas’’) “‘ Virchow’s Archiv,” Bd. cxx, 8. 230. 1890. 


BIBLIOGRAPHY, 291 


Martin and Morison: (‘‘Cyst of Pancreas”) “ Edinburgh Med. Jour.,’”’ July, 1893. 

— and Williams: (‘Influence of the Bile on the Pancreas”’) “Proc. of the Roy. 
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Matani: (‘“Calculus”’) “ Giorn. di med. Venezia,” vol. Iv, p. 174, Giudiceandrea. 

Mathieu: “ Malad. du pancr.”’ in “ Traité de médecine,”’ 1892, vol. 111, p. 399. 

Mauchart: “ De lumbrico terete in ductu pancreat. reperto.’”’ Dissertation, 1738, 
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Maxson: “Cancer of Pancr.,’’ ““ New York Med. Jour.,’’ xx1, 9, 1895. 

May: ‘‘ Casuistischer Beitrag zur Lehre vom Pankreasdiabetes,” ‘‘ Annalen d. stiidt. 
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Mayet: ‘Cancer primit. du pancr.,’’ “ Lyon méd.,”’ 1885, p. 31. 

Maynard and Fitz: (‘‘ Hemorrhage’’) See Fitz, 8. 189, 203, Fall 5. - 

Mayo: (“Tubercles of Pancreas’) ‘ Outlines of Human Pathology,” cited by Senn. 

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Mayo-Robson: (“Cancer of Pancreas’’) “ Brit. Med. Jour.,’”’ 1889. 

Mazzoni: (‘‘Cyst of Pancreas’’) “ Rif. med.,”’ 1894, Bd. 111, 8. 296. 

Medicus: ‘‘ Nonnulla de morb. pancreat.,”’ Berol, 1835. 

Meigs: ‘Cancer of Pancreas,”’ “The Med. and Surg. Rep.,’”’ 1862, p. 107, cited by 
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Melion: ‘ Beitraige zur Erkenntniss und Behandlung der Bauchspeicheldriisenkrank- 
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Mering and Minkowski: “ Diabetes mellitus nach Pankreasexstirpation,” ‘“ Klebs’ 
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Mett: “ Innervation der Bauchspeicheldriise,” ‘‘ Archiv f. Physiol.,’”’ 1894, 8. 58. 

Michailow: (“ Pancreatic Cyst’) from “ Wratsch,” “ Bull. med.,”’ No. 1, 1895, p. 1081. 

Michelsohn: “Fall von primirem Sarcocarcinom.”’ Dissertation, Wtrzburg, 1894. 

Middleton: ‘‘ Necrosis of the Pancreas with Cyst-formation and Fat Necrosis,”’ “ Glas- 
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Miller: ‘ Primary Carcin. of the Pancr.,’’ “ Med. Record,” xxx1, 8, 1895, p. 301. 

Milner: ‘‘ Krebs der Gekrésdriisen,”’ Tiibingen, 1856. 

Minkowski: ‘‘ Untersuchungen tber den Diabetes mellitus nach Exstirpation des 
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— “Diabetes nach Pankreasexstirpation,”’ ‘‘Centralbl. f. Pathologie,” 1892. 

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Minnich: “ Fall von Pankreaskolik,” “ Berliner klin. Wochenschr.,’’ 1894, 8. 187. 

Mirallié: “ Cancer primitif du pancr.,”’ “ Gaz. des hop.,”’ xtx, 8, 1893, p. 889. 

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Molander et Blix: “Cancer capitis pancr.,’’ “‘ Hygiea,”’ 1876. 

Mollard: “Sclérose du pancr.,’’ “ Lyon méd.,”’ 1891, p. 299. 

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Monari: “Carcin. del pancr.,’’ ‘Gazz. med. lomb.,’’ 1894, p. 443. 

Monastyrski: (“Cancer”). Thése, 1890, cited by Nimier. 

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Mondiére: “ Recherches pour servir & l’histoire pathol. du pancr.”? (Carcinoma, 
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/AXG 
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BIBLIOGRAPHY. 293 


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Paderi: (“Concerning the Reputed Glycolytic Action of the Blood, the Kidneys, 
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4 


294 BIBLIOGRAPHY. 


Pal: “Zur Kenntniss der Pankreasfunction,” “ Wiener klin. Wochenschr.,” 1891, 


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Paldamus: “De damnis ex male affecto pancreate in sanitat. redundantibus,”’ 
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Palma: (“ Diab. bronzé”’) “ Berliner klin. Wochenschr.,”’ 1893, xx1, 8. 

Paltauf: (“Cyst”’) “Ergebnisse der allgemeinen Pathologie und pathologischen 
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Panarolus: (“ Pankreas lapidosum”’) “J atrolo ismorum,”’ Rom, 1652, 8. 51. 

Panoff, Anna: “‘ Zerlegung der aromatischen Saureester im Organismus und durch 
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Parisot: (‘Cancer of Pancreas.’’) Thése, Paris, 1891, cited by Mirallié. 

_ Parry, Dunn, and Pitt: “ Case of Acute Hemorrhag. Pancreat.,” ‘ Lancet,” 1897, vol. 
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Pauli: “‘ Krebs der Bauchspeicheldrise,”’ ‘‘ Corr.-Bl. bayer. Aerzte,’’ 1849, 8. 553. 

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Pereira-Guimaraes: “ Hernie traumatique du pancr.,”’ “ Progrés méd.,”’ 1896, p. 236. 

Perle: “ eres pancreate ejusque morbis,” 1837. Dissertation. 

Petit, A.: (“Pancreatic Tuberc.’’) “Jour. de Leroux,” Boyer et Corvisart, XXII, 
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v. Petrykowski: “Cystom d. Pankreas.’”’ Dissertation, 1889. 

Phulpin: (“Cyst of Pancreas”’) “ Bull. soc. anat.,’’ 1892, p. 9. 

Pilliet: ‘Sclérose du pancr. et diabéte,”’ “ Progr. méd.,’’ 1889, No. 21. 

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Pinkham and Whitney: (‘‘ Pancreat. hemorrhag.’’) Vide Fitz, 

Pischinger, Oskar: “ Beitrage zur Kenntniss des Pankreas.” Inaugural-Disserta- 
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Polack: “ De pancreate ejusque inflammatione,”’ Prag, "1835. 

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— “Zur Pathologie des Pankreas, ae Verhandlungen d. med. Sect. schles. Gesellsch 
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a7; 


Pop: “Carcinoma pancreat.,’’ “ Geneesk. Tijdschr.,”’ 1866, p. 310. 
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Portal: (“ Pancreatic Calculi and Necrosis’’) ‘‘ Observations sur la nat. des malad. 
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& 


BIBLIOGRAPHY. 295 


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Prince: ‘“ Pancreatic Apoplexy,” “ Boston Med. and Surg. Jour.,” 1882, p. 28. 

Putnam and Whitney: (“ Pancreatic Hemorrhage”’) Vide Fitz, S. 202. 


Quénu: ‘ Pancreas ” in “ Traité de Chirurgie,” vol. v1, 1892. 
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Rabére: “Carcinoma.”’ Thése de Bonamy, 1879, cited by Mirallié. 

Rachford: “Influence of the Bile on the Fat-splitting Properties of Pancreatic 
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Radziejewski: ‘‘ Asparaginsiure bei Pankreasverdauung,” “ Ber. d. deutschen chem. 
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Railton: “ Pancreatic Cyst in an Infant,” “ Brit. Med. Jour.,”’ 1896, vol. 11, p. 1318. 

Ramey: “Carcin. du pancr.,’’ “ Jour. de Bord.,”’ 1883, S. 24, cited by Mirallié. 

Ramos et Cochez: ‘‘Cancer du pancr.,” “Rev. de méd.,’’ 1887, p. 770. 

Rankin: ‘“ Malignant Disease of the Pancr.,”’ “ Brit. Med. Jour.,’’ 1895, vol.1, p. 1033. 

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Reece: ‘Cancer of Pancr.,” ‘‘ Med. and Surg. Reporter,’ 1871, p. 6. 

Reeve: (‘‘ Degeneration of the Pancreas”’) “ Ann. of Surg.,’”’ August, 1893. 

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v. Recklinghausen: “Concretionen, Ektasie des Ductus, Diabetes,’ ‘ Virchow’s 
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Reichmann: “ Anwendung der Pankreaspriparate bei atrophischem Magenka- 
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—and Rispal: (‘Treatment of Diabetes with Pancreatic Juice’’) ‘Compt. rend.,” 
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Remy et Shaw: “ Expériences 4 propos des lésions du pancr. chez les diabet.,”’ 
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Reubold: “ Ueber Pankreasblutung vom gerichtsirztlichen Standpunkt.”’ Festschr. 
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Reynolds and Gannet: (“Pancreatic Hemorrhage”’) “‘ Boston Med. and Surg. Jour.,”’ 
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Rhode: “ be syphilide neonatorum,” 1825. 

— “Ueber Diabetes mellitus,’’ Wurzburg, 1880. 

Ria: “Carcinoma della testa del pancr.,” “ Alcune lez. di. clin. med.,” 1884, p. 359. 

Ribbert: ‘“ Folgezustinde der Unterbindung des Pankreasganges,” “Centralbl. f. 
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Riboli: “ Pancreat. acuta,” “Gazz. Sardin,”’ 1858. 


296 BIBLIOGRAPHY. 


Richardson: (“Pancreatic Cyst’) “ Boston Med. and Surg. Jour.,”’ xxrx, 1, 1891; 
v, 5, 1892; ‘ Bull. med.,”’ vir, 9, 1892. 

— ‘Case of Pancr. Cyst,” ‘‘ Boston Med. Jour.,” xx1, 3, 1895. 

Richmond: “ Carcin. of the Pancr.,’’ “ Buffalo Med. and Surg. Jour.,’’ 1889, p. 728. 

Riedel: (“‘ Pankreascyste’’) “ Langenbeck’s Archiv f. Chirurgie,” 1885, S. 994. 

— (“Pankreasstérungen bei Cholelithiasis’’) ‘‘Penzoldt u. Stintzing’s Handb. d. 
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Riegner: ‘“ Cyste des Pankreas,” “ Berliner klin. Wochenschr.,”’ 1890, Nr. 42. 

Rigal: ‘‘ Hypertrophie du pancr.,’’ Soc. méd. d’obst. Paris, 1866, 11, 310; ‘“‘ Wiener 
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Riolan: ‘“‘Commentar ad Fernel,’’ 1588, cited by Claessen. 

Riva-Rocci: (‘Cancer of Pancreas”’) “ Rivist. chir. e therap.,”’ Nov., 1891; “Gazz. 
di Torino,” 1892, No. 18. 

Roberts: ‘On the Existence of a Milk-curdling Ferment in Pancr.,”’ “ Proceed. 
Royal Soc.,”’ 1879, p. 157. 

— (“Cancer’’) “ Brit. Med. Jour.,”’ September, 1865. 

Robin: “Sur les propriétés émulsives du pancr.,” “ Jour. de l’anat.,”’ 1885, p. 455. 

Roboica: (“ Parotitis and Pancreatitis’’) Cited by Friedreich, 8S. 249. 

Rocque, Devic and Hugounenq: (“ Diabet. and Pancreatic Disease.’’) “Rev. de 
méd.,” 1892, 8. 995. 

Rocques: (“‘Cancer’’) Soc. d’anatom., 1857, 8. 247, cited by Mirallié. 

Roddick: ‘‘ Pancreatic Abscess,”’ ‘Canada Med. Jour.,”’ 1869, p. 385, cited by Fitz, 
Case 41. 

Rohde: “ Zur Pathol. d. Pankr.’”’ Dissertation, 1890. 

Rohrer: “Case of Scirrhosit. of the Pancr.,’”’ “Med. and Surg. Reporter,” 1862, p. 
201. 

Rokitansky: ‘‘ Lehrbuch der pathologischen Anatomie,” 1861, Bd. 111, S. 254. 

Rolleston: ‘“ Fatal Case of Pancreatit. with Hemorrhage,” “ Lancet,’ 1896, vol. 1, 


p. 705. 

— ‘Fat Necrosis with Disease of the Pancr.,” “Brit. Med. Jour.,’”’ 1892, vol. 11, 
p. 894. 

Rorig: ‘‘ Ein Beitrag zur Diabetesfrage,’’ “ Zeitschr. d. Vereins f. homodp. Aerzte,”’ 
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Rosborg: ‘ Pancreatit. suppurat. et indurat.,’’ ‘“‘ Hygiea,” 1885, p. 274. 

Rose: “ Beitrage zur inneren Chirurgie,”’ “ Deutsche Zeitschr. f. Chirurgie,” 1892, 
Bd. xxxtv, S. 12 (Rhexis). 

Rosenbach: “ EKinige bemerkenswerthe Laparotomien,” “Centralbl. f. Chirurgie,” 
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Rosenberg: ‘“‘Ausnutzung der Nahrunug,” “Sitzungsberichte d. physiolog. Ge- 
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Rosenthal: ‘ Fall von chronischer interstitieller Pankreasentziindung,” “ Zeitschr. 
f. klin. Medicin,”’ 1892, S. 401. 

— “Zur operativen Behandlung der Pankreasgeschwiilste,” Berlin, 1891. 

Roser: (Tuberc. of the Pancr.’’) “Schmidt’s Jahrb.,”’ Spplbd. rv, 184 (bei Kudre- 
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Rostan: (“ Lues’’) ‘ Bull. de la soc. anat.,’’ 1855, p. 26. 

Rotch: “Case of Cancer of the Head of Pancr.,’’ “ Boston Med. and Surg. Jour.,”’ 
1885, p. 175. 

Rotgans: (‘Cyst of Pancreas”) ‘ Nederl. Tijdschr.,’’ 1892; s. “Canstatt. Jahres- 
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Rotter: ‘‘ Pankreascyste,”’ “ Centralbl. f. Gynakologie,”’ 1893, S. 657. 

Roussel: “Cancer du pancr.,’’ “ Loire méd.,”’ 1888, p. 146. 

Routier: “Tumeur ganglion, de la region du pancr.,’”’ “Bull. mens. soc. chir.,” 
1891. . 

Roux: ‘Cancer et kystes du pancr.,” Paris, 1891. 

Rowland: “Cancer of Pancr.; Diabet.,’’ “ Brit. Med. Jour.,” 1893, vol. 1, p. 13. 

Rufus, Hall: (“Cancer of Pancreas’’) “New York Med. Record,’’ 1892. 

Ruge: “ Beitrage zur Chirurgie der Nieren und des Pankreas,” “Deutsche med. 
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Rugg-Hudson: (“ Pancreatic Hemorrhage’’) “ Lancet,’”’? May, 1850. 

Ruggi: 4 Intorno ad un cancro primitivo del pancr.,” ‘ Giorn. intern. delle scienz. 
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Rihle: (“ Pancreatitis’”’) Cited by Dieckhoff. 


BIBLIOGRAPHY. _ 297 


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Weir: ‘ Pancreat. Cyst from a Calculus,”’ “New York Med. Rec.,’’ 1893, p. 803. 
Weinmann: “ Absonderung des Bauchspeichels, ” « Zeitschr, f. rat. Madicin, ” 1853, 


S. 247. 

Weintraud: “ Pankreasdiabetes der Vogel, ” “ Archiv f. experiment. Pathologie,” 
1894, Bd. xxxiv, 8. 303. 

—u. Laves: “ Respiratorischer Stoffwechsel eines diabetischen Hundes nach Pan- 
kreasexstirpation,” “ Zeitschr. f. phys. Chemie,” 1895, Bd. x1x, 8. 629. 

Welch: “Cancer of the Pancr.,” “Transact. Med. Soc. New Jersey,” 1886, p. 231. 

Werigo: “Ueber das Vorkommen von Penthamethylendiamin in ’Pankreasinfusen,” 

Pfliiger’s Archiv,” 1892, Bd. x1, 8. 362. 
Wesener: “ Fall von Pankreascarcinom, ” “Virch, Arch.,” 1883, Bd. xcu1, 8. 386. 


302 BIBLIOGRAPHY. 


Westbroock: “Carcin. of the Pancr.,’’ “‘ Proc. Med. Soc. Kings County,”’ Brooklyn, 
1879, p. 16. 

Wethered: “Carcin. Pancr.,”’ “Path. Society of London,” 4, 2, 1890, cited by 
Mirallié. 

Weyer: “ Fall von Gallertkrebs des Pankreas,”’ Greifswald, 1881. 

White: “Treatment of Diabet. by Feed. on Raw Pancr.,”’ “ Brit. Med. Jour.,”’ 1893. 
vol. 1, p. 402. 

White, Hie. (“Cancer of Pancreas’’) “ Brit. Med. Jour.,”’ 4, 3, 1893. 

— “A Clinical Lecture on Carcin. of the Pancreas,”’ “‘ Lancet, »» December 26, 1896. 

Whitfield: “‘ Disease of Pancr.,’’ ‘‘ Lancet,’ 1841, vol. 1 aah 8 445, 

Whitney: “‘ Hemorrhage into ‘the Pancr.,” “Boston Med. and Surg. Jour.,” 1894, 
p. 379. 

— (Pancreat. hemorrh.’’) “ Boston Med. and Surg. Jour.,’”’ 1881, p. 592, cited by 
Fitz. * 

—and Harris: (‘“Gangrenous Pancreatitis”) ‘Boston Med. and Surg. Jour.,”’ 
1881, No. 25, cited by Fitz. 

— and Homans: (“ Hemorrhagic Pancreatitis’”’) Vide Fitz. 

Whittier and Fitz: (“ Necrosis’’) “ Mass. General Hosp. Rec.,”’ 1884, Bd. v, cited 
by Fitz, Case 67. 

Whitton: “Abscess of the Pancr.,” “ Austral. Med. Gaz.,’’ 1891, p. 276. 

Wilcox: (“Concretions of Pancreas’) “ Med.-chir. Transact., * Ba. xxv, cited by 
Klebs, 8. 545. 

de Wildt: (é Cyst of the Pancreas’’) ‘“ Nederl. Tydschr.,”’ 1892. 

Wilks: “Colloid Cancer of the Pancr.,”’ ‘Transact. Path. Soc. of London,” 1854, 
p. 224, 

—and Moxon: (“ Rupture of Pancreas”’) “‘ Patholog. Anatomy,’ 8. 491, cited by 
Leith. 

Wille, E.: “Ein Beitrag zur pathologischen Anatomie des Pankreas beim Diabetes 
mellitus,” ‘ Mittheil. aus den Hamburger Staatskrankenanstalten,” Bd. 1, 1897. 

Williams: “Cancer of pancr.,”’ “‘ Med. Times and Gaz.,”’ 1852, p. 131. 

—“ a ag Tumor of Stomach. and Pancr.,’’ “ Med. "and Surg. Rep.,”’ Phila., 1868, 

274. 

— “On Diabetes,” “Ther. Gaz.,’’ 15, 10, 1894; “ Brit. Med. Jour.,’’ 1894, vol. 11, p. 
1303. 

Williamson: (“Alterations of the Pancreas in Diabetes’’) “‘ Med. Chron.,”’ 1892, No. 
3; “ Brit. Med. Jour.,”’ 24, 2, 1894; “ Lancet,” 1894, vol. 1, p. 927. 

— “Diabetes Mellitus and Lesions of the Pancreas,’ ‘‘ Med. Chronicle,’’ May, 1897. 

Willigk: (‘‘Carcinom des Pankreas’’) “ Prager Vierteljahrsschr.,’’ 1856. 

Wilson: ‘‘ Extensive Disease of Pancr.,’’ “ Lancet,’’ 1841, vol. 1, p. 594; “ Med.-chir. 
Transact.,’’ London, 1842, p. 42. 

Windle: “The Morbid Anatomy of Diabetes,” “ Dubl. Jour. of Med. Sciences,’’ 1883. 

Witzel: (‘ Pankreascyste’’) ‘‘ Centralbl. f. Chirurgie, ” 1887, 58. 9. 

Wolff: “ Ossif. of the Arter. of Pancr.,’’ “‘ Lancet,’ 1836, vol. II, p. 825. 

Wolfler: ‘Zur Diagnose der Pankreascysten, ane Prager Zeitschr. d. Heilkunde,”’ 
1888, Bd. rx, S. 119. 

Wood: “Scirrhus of Duodenum and of the Head of Pancr.,”’ “ Med. and Surg. Rep.,” 

'  Phila., 1866, p. 228. 

— (“Treatment of Diabetes with Pancreas’’) “ Brit. Med. Jour.,’’ 1893, vol. 1, p. 64. 
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~Wrany: “Sectionsergebnisse der Prager pathologisch-anatomischen Anstalt,”’ 

“ Prager Vierteljahrsschr.,’’ 1867, S. 8 
Wyss: ee Aetiologie des eee “Virchow’s Archiv,” 1866, S. 454; 
1860, 8. 1. 


Yeo: “ Atrophy of the Pancr.,” “ Brit. Med. Jour.,” 1874, 8. 519. 


Zahn: “ Ueber drei Falle von Blutungen in die Bursa oment.,” ‘ Virch. Arch.,” Bd. 
CXXIV, 5. 238, 252. 

Zawadzki: “Chemische Analyse des Pankreassaftes beim Menschen,” “ Oesterr.- 
ungar. Centralbl. f. med. Wissensch.,”’ 1891, 9, S. 73. 

— (“Cyst of Pancreas’’) “ Lancet,” 1891, 25, 4, Bd. 1,8. 948. 

Zenker: “N ebenpankreas in der Darmwand, »»  Virchow’s Archiv,” 1861, Bd. xx1, 


— ‘“Hamorrhagien des Pankreas,” “Berliner klin. Wochenschr.,”’ 1874, Nr. 483. 
eee Naturforscherversamml., 1874; “Schmidt’s Jahrbuch, ” Bd. CLXXIII, 


BIBLIOGRAPHY. | 303 


Zeri: ‘Carcinoma primitivo del corpo del pancr.,’’ Congr. med. int., 1892, p. 447. 

— “Ueber tédtliche Pankreasblutung,” ‘ Deutsche Zeitschr. f. prakt. Medicin,”’ 
1874, Nr. 41. 

Ziegler: ‘‘ Lehrbuch der pathologischen Anatomie,” 1895, 8. Auflage. 

Zieh]: “ Fall von Carcinom des Pankreas,”’ ‘‘ Deutsche med. Wochenschr.,’’ 1883, Nr. 


37. 
Zielewicz: “ Zur Chirurgie der Bauchhéhle,” “ Berliner klin. Wochenschr.,” 1888, 
S. 294. ; 

Zielstorff: “‘ Fall von Unterleibscyste.”’ Dissertation, Greifswald, 1887. 

Zimmer: ‘‘ Zur Lehre vom Diabetes mellitus,’’ 1867. 

Zoja: “ Rare varieta dei condotti pancreat.,”’ “R. Ist. Lomb. discienz.’”’ Rendicont 
Milano, 1883, vol. xvi, p. 364. 

Zukowski: ‘‘ Grosse Cyste de. Pankr.,’’ “‘ Wiener med. Presse,’”’ 1881, Nr. 45. 

Zweifel: (“ Pankreascyste’’) ‘Centralbl. f. Gynakologie,” 1894, Nr. 27. 





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DISEASES OF THE SUPRA- 
RENAL CAPSULES. 


EDMUND NEUSSER, M.D. 


DISEASES OF THE SUPRARENAL 
CAPSULES. 





ANATOMY AND HISTOLOGY OF THE SUPRARENAL 
CAPSULES. 


THE suprarenal capsules are a pair of small organs, each of which is 
situated, like a helmet or cap, upon the upper extremity of the correspond- 
ing kidney. Although in such close proximity, the suprarenal capsules 
and kidneys are almost entirely independent of one another; thus in the 
majority of cases the suprarenal capsule does not accompany the kidney 
when dislocated. 

As a rule, these organs are not symmetrically situated. The right 
capsule (as also the right kidney) lies a little lower than the left and does 
not fit so accurately upon the upper extremity of the kidney, while the 
left capsule is displaced slightly to the inner side of the corresponding 
kidney. 

The suprarenal capsules are flattened bodies with two principal sur- 
faces, directed approximately anteriorly and posteriorly and frequently 
grooved in’ the adult. The two surfaces meet above in a broad and 
strongly convex border, while below they are bounded by a concave edge 
and separated from one another by a narrow concave surface. Thus their 
shape corresponds approximately to a triangle, rounded off at the top and 
with a somewhat concave base. There is a slight difference in the shape 
of the organs upon the two sides of the body, the right capsule heing 
‘noticeably narrower and higher than the left. This is caused by the vary- 
ing pressure of stfrrounding organs. 

The size of the suprarenal capsule presents marked individual differ- 
ences. In the negro these organs are conspicuous for their large size and 
abundant pigment. There are no distinct differences in size in the sexes, 
but it undoubtedly varies considerably with the age of the individual. 
In the first few months of fetal life these bodies considerably exceed the 
kidneys in size, by the sixth month they are only half as large, at birth 
the ratio is as 1 to 3 and in the adult as 1 to 28. In advanced age the 
suprarenal capsules undergo further atrophy and their consistence be- 
comes very firm. 

According to Orth, the dimensions of the normal adult suprarenal 
capsule are as follows: width 40 to 55 mm., length 20 to 35 mm., thick- 
ness 2 to 6 mm.; while their weight is 4. 8 to 7.3 grams. 

The suprarenal capsule is surrounded externally by a moderate layer 
of fat and possesses a tense fibrous capsule containing elastic fibers (tunica 
albuginea); radiating from this numerous fibrous septa penetrate the 
parenchyma of the organ. For this reason the capsule cannot be 
removed without injury to the parenchyma. 

307 


308 DISEASES OF THE SUPRARENAL CAPSULES. 


Near the base of the anterior surface of the organ there i is a deep groove 
through which the principal blood-vessels, lymphatics, and nerves enter 
and emerge, and which has therefore been termed the hilum. The color of 
the external surface is composed of various shades of yellowish-brown. 

On cross-section it is at once apparent, from differences in color, that 
the gland is composed of two distinct portions, the peripheral or cortical 
and the central or medullary portion. The cortex is of a yellow color, 
clearly shows radiating lines, and is of a firm consistence. The medulla is 
of a grayish-red color and of a soft spongy consistence, easily crushed. 
The junction of these two layers is marked by a narrow band of tissue, the 
intermediary zone of Virchow, which is really a part of the cortex and is of 
a deep brown color in advanced age. 

Entering now upon the consideration of the finer structure of the 
suprarenal capsules, two elements are to be differentiated: first, the 
fibrous stroma continuous with the capsule; and, secondly, the cellular 
parenchyma. 

The stroma consists of relatively thick septa which traverse the cortex 
in a radial direction toward the medulla, where they break up into a very 
fine network. Smaller septa are also given off in the cortex to form a 
coarse network inclosing large and small groups of parenchymatous cells. 
Immediately beneath the capsule the meshes and the inclosed groups of 
cells are small and circular; in the broad middle portion they form large 
long radii like the septa, while in the innermost division of the cortex they 
are once more small, round, and delicate, corresponding to the outer zone. 
With reference to these histologic appearances the cortex has been divided 
since the publication of Arnold into three zones, called from without in- 
ward the zona glomerulosa, the zona fasciculata, and the zona reticularis ; 
however, there is no sharp line of demarcation between them. 

Finally, an exceedingly delicate network arises from the coarser septa 
of the stroma and surrounds each cell of the parenchyma. 

In the medulla the stroma breaks up more uniformly into its compo- 
nent fibers and surrounds with an exceedingly fine network the individual 
parenchymatous cell. 

All the spaces of the stroma are filled with groups of parenchymal 
cells. In the cortex these groups assume various shapes, corresponding 
to the stromal spaces which contain them; thus, they are rounded in the 
zona glomerulosa, elongated columns in the zona fasciculata, which com- 
prises the greater part of the cortex, or'they may be irregular. 

A few observers have demonstrated also columns of cells with a delicate 
central fissure. Small, colorless, glistening granules have been found re- 
peatedly in the cells of these columns in both man and animals, and also 
in the blood of the suprarenal vein, in addition to brownish flakes. Their 
importance will be discussed later. 

The cells of the fasciculate zone are normally filled with fat-droplets 
of varying size (fatty infiltration), and the cells of the intermediary zone 
contain brown pigment-granules in abundance. 

The parenchymal cells of the medullary portion are irregular in shape, 
being polygonal or even stellate; they are stained dark brown by chromic 
acid or chromates. 

The rich blood-supply of the suprarenal capsules has been recognized 
and commented upon for a long period of time. The arteries are derived 
in part directly from the aorta (central suprarenal artery, the principal 
branch which enters:at the hilum); in part from the arteries of the dia- 


EMBRYOLOGY. 309 


phragm, descending branches (superior suprarenal arteries) ; in part from 
the vessels of the kidneys, ascending branches (inferior suprarenal arte- 
ries). These arteries, following the septa and finest ramifications of the 
stroma, subdivide into a dense capillary network which is best developed 
in the medullary portion. From this the blood is collected into venous 
branches, the largest of which (central suprarenal vein) empties on the 
right directly, on the left as a rule indirectly through the renal vein, into 
the inferior vena cava. 

It has been proved by the most careful histologic investigation that the 
relation between the capillaries and the cells of the parenchyma is a very 
intimate one, the endothelium of the capillaries immediately overlying the 
cell-masses of the parenchyma. Indeed, in the medullary substance, 
according to Manasse, large columns of cells project directly into the capil- 
laries and are immediately bathed in blood. 

The lymphatic vessels of the suprarenal capsules are very numerous; 
they originate between the cells of the cortex and form in the medullary 
portion a network surrounding the vein and emerge with it and empty into 
the lymphatic vessels of the kidney. 

The rich nerve-supply of the suprarenal capsules is equally striking. 
Some of these nerves are non-medullated sympathetic fibers from the solar 
plexus and other adjacent plexuses; others are medullated fibers from the 
splanchnic, vagus, and phrenic nerves. In the medullary portion, partic- 
ularly, whole clusters of ganglion cells lie embedded in the exceedingly 
delicate plexus of nerve-fibers. 





EMBRYOLOGY. 


GREAT differences of opinion exist among investigators as to the de- 
velopment of the suprarenal capsules. Not only do most authors admit 
that the cortical and medullary substances arise separately, but there are 
at least two opinions held as to the origin of each of these. 

According to the majority of authors, the medullary substance is de- 
rived from the anlages of the sympathetic ganglia. Rabl believes that 
the medullary cells represent detached ganglion cells which have remained 
at the embryonal stage of development. A small number of authors hold 
the opinion that.the medullary cells are derived from the cortical cells, and 
that only a few ganglion cells and nerve-fibers have entered from the 
sympathetic. ) 

It is thought by one group of authors that the cortical substance is de- 
rived from an accumulation of cells of connective tissue at the anterior 
extremity of the primitive kidney. Other observers derive the cortical 
cells from a growth of epithelial.cells in the body-cavity, which belong 
either to the genital ridge or to the primitive kidney. 

Michalkovic regards the suprarenal capsules as detached portions of 
the-genital glands which have remained at an early stage of development 
before sexual differentiation has occurred, and which, after the separation, 
have acquired other physiologic functions. According to Rabl, the corti- 
cal substance in birds is derived from the canals of the primitive kidney. 


310 DISEASES OF THE SUPRARENAL CAPSULES. 


The suprarenal capsules are developed at the same time as the sympa- 
thetic system, when the primitive kidney begins to disappear. 

The two separate anlages soon unite. That from the sympathetic 
(medullary substance) in the beginning at least forms a part of the outer 
layer. Later this relation is reversed, and the anlage of the cortical sub- 
stance gradually grows around that from the sympathetic. 

The discovery of the frequent occurrence of accessory suprarenal cap- 
sules is of the greatest importance for the whole pathology of these organs. 
Their presence has been demonstrated in animals as well as in man by a 
large number of observers. They consist of fragments of suprarenal 
structure, varying in size from a pin’s head to a pea or bean, scattered 
throughout the entire retroperitoneal space, but showing a special predi- 
lection for the region of the genital organs. 

They are said to occur very frequently at the hilum of the suprarenal 
body and in its immediate neighborhood, and when thus situated they 
probably represent lobes which have become separated from the main 
organ. They occur also in the solar plexus, in the celiac ganglion, beneath 
the capsule of the kidney, and in the cortex of this organ, opposite the 
sacro-iliac articulation, but particularly often along the course of the 
spermatic cord and internal spermatic vessels from the retroperitoneal 
space to the epididymis; in the female they may be found in the broad 
ligament close to the parovarium. They are said to occur more frequently 
upon the right than upon the left side. 

These accessory suprarenal glands occur frequently in man, being 
present, according to Schmorl, in 92% of all bodies examined. They 
occur also in animals, but, strange to say, they are very rarely found in 
certain species, notably never in guinea-pigs. Ordinarily these bodies 
consist of cortical substance only, though of late several cases have 
been observed where the medullary substance also was plainly de- 
veloped (Dagonnet, Pilliet). 

Their occurrence is important for two reasons: first, after destruction 
or impairment of function of the true suprarenal bodies, these accessory 
organs may hypertrophy and assume their function, so that, in spite of 
complete destruction of the suprarenal capsules, the symptoms character- 
istic of that condition may not appear; secondly, these rudimentary or- 
gans not infrequently degenerate and become the seat of malignant neo- 
plasms. 





PATHOLOGIC ANATOMY OF THE SUPRARENAL 
CAPSULES. 


{, ABNORMALITIES OF DEVELOPMENT. 


CoMPLETE absence of the suprarenal bodies in individuals otherwise 
healthy has been demonstrated by recent as well as early investigators. 
Some of these cases are not above the suspicion that a displaced hypo- 
plastic organ may have been overlooked, yet the most recent observers 
have proved that complete aplasia of the suprarenal capsules is not anny: : 
possible, but in rare instances has actually occurred. 


PATHOLOGIC ANATOMY OF SUPRARENAL CAPSULES. 3811 


Cases of arrested development (hypoplasia) have been observed more 
frequently, occurring, however, exclusively in certain monstrosities which 
are characterized by defects of the cerebrum; as, for example, hemiceph- 
alus, cyclops, encephalocele, microcephalus, and syncephalus. Other 
malformations, especially of the genital organs, were frequently associated. 
Hypoplasia of the suprarenal bodies was found to occur only when there - 
was absence of portions of the anterior cerebral lobes, which are known to 
originate at the very earliest period of fetal life. Hydrocephalus, which 
does not develop until a later period of fetal life, and defects of the poste- 
rior lobes, have no effect upon the development of the suprarenal bodies. 
[Ad. Czerny,* however, recently examined the suprarenal capsules of 
five cases of various degrees of hydrocephalus, and found them alike 
altered in all. The cortex was normally developed, but there was no 
medullary portion. This alteration of the capsules was regarded as repre- 
senting a much earlier period of development than was indicated by the 
excess of ventricular fluid.—Eb.] 

Zander, who has lately devoted considerable attention to this subject, | 
concludes from these facts that only the anlage and the differentiation of 
the suprarenal capsules depend upon the functional integrity of the ante- 
rior cerebral lobes. If the anlage has been completely differentiated, its 
further development is independent of the central nervous system, and is 
no longer influenced by injuries to the latter. The tracts which transmit 
this influence of the cerebrum upon the developing suprarenal anlage are 
wholly unknown. 

Displacements of one or both of the suprarenal bodies are of the rarest 
occurrence. It is also worthy of note that this organ practically never 
participates in dislocations of the corresponding kidney, but is always 
to be found in its normal situation. 

In a single case the two suprarenal glands were found fused, forming a 
horseshoe-shaped organ. 


2. HYPERTROPHY AND ATROPHY. 


In many cases it is quite difficult to decide whether the suprarenal is 
hypertrophied or not, for even under normal conditions these organs 
present wide variations in size. In well-developed, well-nourished indi- 
viduals they are larger and richer in fat than in the weakly and emaciated. 
Also, we must bear in mind their relatively greater size in children and in 
negroes. . 

However, we are justified in speaking of hypertrophy of these organs 
when we have to deal with a definite unilateral increase in size resulting 
from impairment of function of the opposite organ by disease or removal. 
This is termed compensatory hypertrophy, and both substances of the 
gland take part in the process. [Simmonds + reports such a case in which 
the left capsule was extremely atrophied while the right capsule was seven 
times as heavy and ten to fifteen times as thick as its fellow. All portions, 
especially the central, were enlarged. The atrophied capsule was regarded 
as tubercular.—Ep.] Similarly, any accessory suprarenal capsules which 
are present may hypertrophy and assume the function of the normal 
organ. 

* Centralbl. f. allg. Path. und path. Anat., 1899, x, 281. 
t Virch. Arch., 1898, cui, 138. 


812 DISEASES OF THE SUPRARENAL CAPSULES. 


Marchand reports a very peculiar case of hyperplasia of the suprarenal 
capsule. He found both organs enormously enlarged and an accessory 
organ situated in the broad ligament. The subject was a pseudohermaph- 
roditic female with atrophied ovaries. Marchand’s theory in explana- 
tion of this case is that an abnormally large part of the undifferentiated 
body epithelium (from which suprarenal capsules and reproductive organs 
are both developed) was utilized in the formation of the suprarenal bodies 
at the expense of the embryonic ovaries. 

Atrophy of the suprarenal capsules occurs normally in advanced age. 
The organs become smaller, thinner, and more flaccid. The fat disap- 
pears from the parenchymal cells and a considerable deposit of pigment 
usually occurs. Likewise in the various cachexias, the organ parts with 
more or less of its intracellular fat and becomes smaller. Thees atrophies 
possess no pathologic significance. 

In certain rare cases a true pathologic atrophy has been observed 
without any apparent cause. 


3. DEGENERATIONS. 


(a) Cloudy swelling of the suprarenal parenchyma occurs quite fre- 
quently in the acute infectious diseases, such as typhoid fever, pneumonia, 
septic infection, erysipelas, and scarlatina. This condition is identical 
with that occurring in the liver, heart, dnd kidneys. The cells appear 
crowded with granules; the outlines of the former and its nucleus are in- 
distinct. This form of degeneration is found particularly in the cortex. 

(b) Fatty degeneration is difficult to diagnosticate, because the cells 
of the cortex are normally infiltrated with fat, even in the new-born. It 
has been observed in hereditary syphilis, circulatory disturbances, phos- 
phorus-poisoning, and as an advanced stage of cloudy swelling. Fatty 
degeneration is differentiated microscopically from the normal fatty 
infiltration by the smaller size of the fat-drops and by simultaneous 
diminution of the cells and atrophy of their nuclei. 

(c) Hyaline and dropsical degeneration may be mentioned simply as 
curiosities. 

(d) Amyloid degeneration, on the contrary, is very common and pro- 
nounced, occurring in as marked a degree as in spleen, kidney, or intes- 
tine, and dependent upon the same causes as in amyloid degeneration of 
these organs. The capsules become large, dense, gray, and present a 
lardaceous appearance. The cortical and intermediary zones are affected 
chiefly, the medulla being involved to a lesser degree.. The degenerative 
process is confined primarily and principally to the walls of the blood- 
vessels; subsequently the connective-tissue septa are involved, but not 
the parenchymal cells. The latter are compressed rather by the swollén 
intervening tissue, lose their fat, and atrophy after long continuance of 
the disease. Large homogeneous flakes of amyloid connective tissue are 
observed, particularly in the medulla. 


4, CIRCULATORY. DISTURBANCES. 


@) Congestion of the suprarenal capsules is very common, but it is 
usually the passive variety. The general stagnation of the blood in all 


PATHOLOGIC ANATOMY OF SUPRARENAL CAPSULES. 313 


diseases of the kidneys, heart, and lungs is very pronounced in the supra- 
renal capsules by reason of their rich blood-supply. Venous hyperemia is 
of comparatively frequent occurrence in new-born infants with or without 
coincident syphilis. After this congestion has lasted for a considerable 
period of time the organ becomes indurated and the capillaries and veins 
distinctly dilated. 

Active hyperemia frequently occurs in acute infections, particularly 
profound septicemia. Capillary hemorrhages occur not infrequently 
during its course. In the guinea-pig these two conditions—active hyper- 
emia and punctiform hemorrhages—are invariably found postmortem 
after experimental inoculation with diphtheritic, typhoid, or pyocyaneus 
organisms. 

(b) Anemia and anemic necrosis practically do not occur, the vascular 
. network of the organ being too dense. 

(c) Hemorrhages are not unusual. In addition to the above-mentioned 
capillary hemorrhages, larger—indeed, often very extensive—hemorrhages 
occur as the result of trauma, especially in the new-born; or after venous 
hyperemia, hemorrhagic diathesis, leukemia, or malignant neoplasms. 
Such hemorrhages may be the immediate cause of death if rupture of 
the gland occurs. As a rule, however, they remain encapsulated, sur- 
rounded by suprarenal substance, forming the so-called hematomata, 
which may attain the size of a man’s head. When of long duration the 
blood undergoes the same changes here as in other situations. Coagula- 
tion occurs at the periphery, the blood-pigment is converted into methe- 
moglobin and hematin, giving a yellowish-brown color to the mass. 
Finally, most of the fluid is absorbed, the surrounding tissues contract, 
and lime salts may be deposited. Or this condition may terminate in the 
formation of a cyst, analogous to the apoplectic cysts of the brain. 

(d) Thrombosis of the smaller veins or even of the principal vein, some+ 
times continued from the vena cava, has repeatedly been observed. No 
considerable anatomic alterations are produced in the organ, as an ade- 
quate collateral circulation is established at once. Such thromboses have 
been found to contain lime salts; in other words, phleboliths were formed. 

Emboli occur in the form of capillary bacterial emboli complicating 
septic processes and giving rise to microscopic necroses and punctiform 
hemorrhages. 


5. INFLAMMATIONS. 


As acute inflammation Virchow described a form of “hemorrhagic 
inflammation” in which he found the suprarenal capsule swollen, ex- 
tremely hyperemic, and studded with hemorrhagic infiltrations. This 
condition was observed in profound general infections of a septic nature 
(septicemia, scarlatina, etc.), and is doubtless identical with the above- 
mentioned form of active hyperemia with bacterial emboli and hemor- 
rhages. 

Cellular infiltration and suppuration, whether metastatic or continued, 
are of relatively rare occurrence... Exceptionally abscesses have been ob- 
served to arise apparently spontaneously in one or both suprarenal cap- 
sules. Such abscesses may perforate into the surrounding connective 
tissue or into the intestine. 

Chronic productive inflammation characterized by new-formation of 
connective tissue and partial atrophy of the parenchyma has been ob- 


314 DISEASES OF THE SUPRARENAL CAPSULES. 


served as a manifestation of syphilis. A marked proliferation of connec- 
tive tissue is almost constantly present in chronic tuberculosis, and was, 
therefore, informer years frequently spoken of as an independent affection. 


6. INFECTIOUS GRANULATION ‘TUMORS. 


These comprise syphilis and tuberculosis. 

Syphilis occurs occasionally in the form of a typical gumma composed 
of granulation tissue terminating in central necrosis and peripheral cica- 
trization. As mentioned above, it may be manifested atypically in the 
form of a cirrhotic inflammation. Sometimes it is with difficulty differ- 
entiated from tuberculosis. Syphilitic thickening of the vessels is also 
observed. : 

Tuberculosis of the suprarenal capsules derives especial interest from 
its relation to Addison’s disease. 

Acute and subacute miliary tuberculosis are of rare occurrence. In 
the vast majority of cases we have to deal with a form of chronic tuber- 
culosis characterized by an unusually protracted course and by the abun- 
dant formation of granulation and scar tissue, together with a well-marked 
tendency to calcification or at least inspissation of the caseous mass. 

One or, more frequently, both organs may be affected; in the latter 
case the process is apt to be further advanced on one or the other side. In 
most cases it proceeds from the medullary portion, although the observa- 
tions are by no means rare in which it commences in the cortex or even in 
the capsule and pericapsular connective tissue. 

The typical form is the conglomerate tubercle, which is composed of a 
group of miliary nodules. Caseation begins at the center of the mass, 
while at the periphery there is abundant formation of granulation tissue 
containing fresh groups of miliary tubercles which in turn become con- 
fluent and cheesy. A large part of the granulation tissue is converted into 
a firm, fibrous callus. After several years’ duration the whole organ be- 
comes gradually involved, and it is not unusual to find absolutely no 
remains of normal suprarenal substance. Occasionally the new-forma- 
tion of connective tissue extends beyond the capsule (and a dense callus 
is formed around the suprarenal bodies which becomes united with the 
capsule of the kidney and the diaphragm) and in which a part of the solar 
plexus is embedded. As a result of this process, the suprarenal capsules 
become irregularly enlarged, nodular, and very dense. Amyloid degener- 
ation is frequently present at the periphery of the caseous mass. 

In the great majority of cases tuberculosis of the suprarenal capsules 
is secondary to tuberculosis of other organs, the primary growth occurring 
in the lymphatic glands, lungs, or genitals. Exceptionally a primary 
tuberculosis of the suprarenal capsule may oceur, and form the point of 
origin of a general miliary tuberculosis, in which case the rupture of the 
tuberculous focus into the suprarenal véin is demonstrable. , 


7. NEOPLASMS. 


Neoplasms may develop in the suprarenal capsules proper or in the 
accessory rudimentary bodies, the latter being especially prone to their 
formation. 

Excessive proliferation of circumscribed portions of suprarenal sub- 


PATHOLOGIC ANATOMY OF SUPRARENAL CAPSULES. 315 


stance gives rise in the first instance to small tumors resembling lipomata 
which have been termed suprarenal strumas or adenomata. These are 
situated in the cortex of the suprarenal capsule, or, more frequently, in 
accessory glands occurring in the kidney. In the latter situation the term 
of renal adenoma or “ heterologous renal struma”’ has been applied. They 
are small masses varying in size from a pin’s head to a pea, yellowish- 
white in color, sharply defined, and surrounded by a connective-tissue 
capsule. They are histologically identical with the suprarenal cortex, 
even the typical fatty infiltration of the parenchyma being present. 

As a rule, these tumors give rise to no symptoms during life and are 
only encountered accidentally at autopsies. Although they thus appear as 
wholly benignant, they are capable of undergoing metastasis like strumas 
of the thyroid. Such metastases often become much larger than the pri- 
mary tumor, and, since the latter present no symptoms, are suggestive of 
primary growths. They may readily be recognized by their structure 
and by the fatty infiltration of their cells. 

In addition to this formation of metastases, in itself a manifestation 
of malignancy, suprarenal strumas, after existing for a long period of 
time, tend to become malignant. They break through their capsule, re- 
place the surrounding tissue, and grow into the veins. 

Histologically these tumors are composed chiefly of polymorphous 
cells, the arrangement. of which may closely simulate adenocarcinoma; - 
although, according to the latest views, they are to be considered sarco- 
mata of the vascular perithelium (perithelioma). Formerly these tumors 
were described as carcinomata or sarcomata. They may develop appa- 
rently directly from displaced embryonic suprarenal bodies without the 
preceding formation of an adenoma. 

These malignant growths are further characterized by their extraor- 
dinarily rich, almost telangiectatic, vascular network, and by the fatty 
infiltration of their cells. The glistening, hyaline granules normally pre- 
sent in the suprarenal cortex are found both in the tumors and in the 
metastases. After attaining a moderate size these tumors may be recog- 
nized macroscopically by their numerous blood-vessels and resulting 
spongy structure, their fibers floating in water. 

The peritheliomata are characterized by a tendency to metastasis, 
especially in certain organs, as the osseous system (vertebre, bones of 
skull, head of femur, clavicle, etc.) and the brain. 

Moreover, they are subject to degenerative changes which are almost 
exclusively fatty ; the cells being predisposed to this variety by their normal 
condition of fatty infiltration. The center of the tumor becomes con- 
verted into fatty detritus into which hemorrhages frequently take place, 
causing a dissection of the spongy tissue in all directions and giving rise to 
a large or small hemorrhagic cyst. 

These cysts, like the original tumors, are frequently found in the kid- 
ney, and until recently their mode of origin was obscure. Grawitz was 
the first to throw any light upon the subject, and in his honor they have 
been called Grawitz’s tumors. ~ | 

Other primary tumors of the suprarenal capsules are rare. Angio- 
sarcoma and melanosarcoma have been observed in the cortex, also single 
instances of lymphosarcoma, angioma, and lymphangioma have been re- 
ported. Fraenkel has described a sarcoma, Virchow a glioma, and Weich- 
selbaum a ganglionic neuroma in the medullary portion. [Although 
malignant tumors of the suprarenal capsules are most commonly found in 


316 DISEASES OF THE SUPRARENAL CAPSULES. 


adult life, Orr * reports the occurrence of a sarcoma of the right adrenal 
with extensive metastases in the liver in a child of seven weeks. Brucha- 
now j states that a child fourteen months old had a cancer of the capsule 
twice the size of a man’s fist, with metastases in the lymph-glands and 
ovaries.—ED. ] 

Primary sarcoma and carcinoma in other organs, particularly the thy- 
roid gland, breast, and ovary, may give rise by metastasis to similar | 
growths in the suprarenal capsules. 

[Ramsay tf gives the following summary of the study of. sixty-seven 
cases of primary malignant tumors of the suprarenal gland: “(1) That 
while malignant tumors of the suprarenal glands are rare, they should be 
considered as one of the factors to be eliminated in the presence of an ab- 
dominal tumor; (2) that they are somewhat more common in the male 

sex; (3) that while in a certain proportion the symptoms are fairly well 

marked, there are many in which no symptom points to the suprarenal 
origin ; (4) that rapid loss of strength, debility, emaciation, digestive 
disturbances, and abdominal pain are the most prominent symptoms: (5) 
that skin changes are rather the exception than the rule; (6) that they 
run a rapid course, the duration being shorter than usual with a neoplasm 
in other organs; (7) that the diagnosis is impossible in many, and diffi- 
cult in all, cases; (8) that a differential diagnosis must be made from 
other suprarenal diseases, from renal tumors, from hepatic tumors, from 
diseased retroperitoneal glands, and from cysts and new-growths of 
the pancreas; (9) that the prognosis is always serious, even following a 
successful operation, from the great frequency with which both glands are 
found involved, and the tendency to early metastases; (10) that operation 
gives the only hope of relief, and that it has been successful in two cases; 
(11) that the principal difficulties in the operation are the friability of 
the tumor, the great tendency to estan and the frequency of the 
adhesions. »__Bp, ] 


8. PARASITES. 


Very exceptionally echinococcus cysts have been found in the supra- ° 
renal capsule, one case of multilocular cyst being reported. 





PHYSIOLOGY OF THE SUPRARENAL CAPSULES. 


THE suprarenal capsules were discovered by Eustachius in 1564, but 
no satisfactory theory as to their function was advanced until the investi- 
gations of Addison. He first called attention to the relation existing 
between disease of these organs and a peculiar group of symptoms, and 
expressed the opinion that their extensive destruction led to severe general 
disease and death. 

Experiments on animals were at once begun, and an Wart was made 


* Edinb, Med. Jour., 1900, 221. t Prager Zeitschr. f. Heilk., xx, 39. 
t Johns Hopkins Heap, Bull., 1889, x, 21. 


PHYSIOLOGY OF THE SUPRARENAL CAPSULES. 317 


to determine, first, whether the suprarenal capsules are or are not essential 
to life. 

The first investigator was Brown-Séquard, who, in 1856, sought to 
obtain some knowledge of the function of the suprarenal capsules by ex- 
tirpating these organs from different animals and by studying the symp- 
toms which followed. After removing both suprarenal bodies he found 
that all the animals died within one or two days with symptoms of general 
weakness, convulsions, delirium, and coma. By control experiments he 
excluded the possible cause of death by injury to adjacent organs (liver, 
sympathetic nerves) or by peritonitis or hemorrhage and determined that 
it was due solely to removal of the suprarenal bodies. Extirpation of one 
suprarenal capsule also resulted in death, but not until a much longer period 
of time had elapsed. Brown-Séquard reported as a cause of death the 
accumulation of pigment in the blood-vessels and numerous pigment- 
emboli. He concluded from these observations that the suprarenal cap- 
sules are absolutely essential to life. 

Very soon Brown-Séquard’s views were most positively contradicted 
by a whole group of observers as a result of their experiments. 

Gratiolet and Philipeaux succeeded in keeping several animals alive 
for weeks and months after removal of both suprarenal capsules. In 
their opinion this operation is not necessarily fatal, although the majority 
of animals subjected to it die from unavoidable injury to surrounding 
organs, especially the sympathetic plexuses and ganglia, the liver, and the 
peritoneum, or from purulent inflammation of this membrane. Brown- 
Séquard again brought forward several groups of experiments in support 
of his original theory, which he modified only in one particular—namely, 
that in animals with but little pigment (albinos) the suprarenal bodies 
were not absolutely essential to life, but maintained that the reverse was 
the case in pigmented animals. 

Practically all earlier observers joined the ranks of Gratiolet and Phili- 
peaux. Harley, especially, contradicted Brown-Séquard in every particu- 
lar, and mention should be made also of Berruti and Perusino, Chatelain, 
-and Schiff, who succeeded in keeping several animals alive for months 
after removal of both suprarenal capsules, while they attributed the death 
of the other animals to injuries accompanying the operation or to subse- 
quent accidents, for example, exposure to excessive cold. Nothnagel also 
‘soon agreed with them; he did not remove the suprarenal capsules, but 
exposed them and crushed them with forceps as completely as possible. 
He succeeded in keeping a number of animals alive for a year and a half 
without the occurrence of the symptoms mentioned by Brown-Séquard— 
namely, weakness, delirium, or convulsions. 

No further observations were made upon the importance and function 
of the suprarenal bodies until Tizzoni resumed the experiments in 1889. 
_ The results obtained by him with reference to the vital importance of 
this organ practically coincide with those of Brown-Séquard. Some of 
his animals survived the extirpation of both suprarenal capsules for almost 
three years, but eventually all*died. He maintains, therefore, that the 
earlier experimenters were led to oppose Brown-Séquard’s views because 
their animals were not kept under observation long enough, but were killed 
before the pathologic processes initiated by the operation had caused the 
animal’s death. 

Accordingly his conclusions are as follows: After the removal of both 
suprarenal capsules all animals die, without reference to age or color. 


318 DISEASES OF THE SUPRARENAL CAPSULES. 


Their death results from removal of the suprarenal capsules and not in con- 
sequence of injuries from the operation, because death may not occur for 
years afterward, therefore the suprarenal capsules are absolutely essential 
to life. At the postmortem examination of his animals, Tizzoni found 
extensive alterations in the brain, cerebellum, spinal cord, and peripheral 
nerves as the cause of death. 

From 1891 to 1893 Abelous and Langlois carried on a series of careful 
experiments upon frogs, guinea-pigs, and dogs. They found that removal 
of one suprarenal body gave rise to no special symptoms, but that death 
generally resulted if the greater part of the remaining capsule also was 
removed. When large portions of suprarenal substance were left behind, 
the death of the animal was long delayed or might not occur at all; in such 
cases the function of the suprarenal body was maintained, although very 
inadequately, by the remaining portions. After complete extirpation of 
both capsules, summer-frogs died within forty-eight hours; winter-frogs 
lived considerably longer, even a fortnight. All the guinea-pigs and dogs 
died within a few hours. If a portion of suprarenal body was grafted into 
these animals before the operation, their death was prevented. If these 
fragments were subsequently removed, the animals invariably died. It 1s 
also possible, after removal of both suprarenal capsules, to keep the ani- 
mals alive twice as long as usual by injections of suprarenal extract. 
From these experiments Abelous and Langlois conclude that their animals 
died because the function of their suprarenal capsules was lacking, having 
excluded, by control experiments, injury to the kidney as a cause of death. 

Thiroloix, Albanese, de Domenicis, and Marino Zucco also came to the 
conclusion that removal of both suprarenal capsules is fatal. The only 
opponent of this theory is Pal, who kept a dog alive four months and 
twelve days after complete extirpation of both suprarenal capsules, and 
demonstrated the absence of supernumerary suprarenal bodies at the 
autopsy. Finally, Szymonowicz, experimenting upon dogs, obtained the. 
same results as Abelous and Langlois. He believes the contradictory 
results of the earlier authors to be due to incomplete removal of the supra- 
renal bodies. Nothnagel even found remnants of normal tissue after sev- 
eral of his operations, and it seems very probable that some fragments 
were left behind in Tizzoni’s cases also. It is possible for such fragments 
to regenerate, assume the suprarenal function to some extent, and delay 
the fatal issue. Likewise any accessory suprarenal capsules which are 
present may vicariously assume the suprarenal function. 

Stilling’s experiments upon young rabbits furnish additional support 
for this view. He found after removal of one suprarenal body that the 
remaining organ almost doubled its original size, and that the accessory 
suprarenal bodies, previously invisible or at least very small, became 
enormously hypertrophied. This increase in size was due to the regenera- 
tion of both medullary and cortical substances. [The results obtained by 
Huttgren and Andersson * can similarly be explained. They removed one 
suprarenal from rabbits, allowed an interval to elapse, and then removed 
the other. Rabbits survived, but similar experiments on cats and dogs 
were lethal.—Ep.] Stilling decided that the suprarenal capsules possess 
without doubt an extrauterine function which is essential to life. Thiro- 
loix also found hypertrophy of the remaining organ several months after 
removal of one. 


% 


*Centralbl. }. Phys., 1899, x11, 503. 


PHYSIOLOGY OF THE SUPRARENAL CAPSULES. 319 


This completes the review of the experimental physiology of the supra- 
renal capsules. It is evident that Brown-Séquard’s view—that these 
organs are essential to life—is strongly upheld by the most recent ex- 
periments. A single dog experimented upon by Pal seems to contradict 
the universal opinion. This case is open to Tizzoni’s objection that the 
period of observation was too short, or accessory capsules may have been 
present; for, according to Pal’s report, search was made for these organs 
only at the site of operation on either side of the vena cava. Yet even if 
this case is admitted, a single exception is certainly not sufficient to over- 
throw the theory of the importance of these bodies. Goltz removed the 
entire brain from dogs and the animals subsequently lived without a 
brain, yet no one would believe that the brain was not important to life. 

The second question for the physiologists to solve relates to the func- 
tion of these organs. Three different ways have been proposed in order to 
answer this question. 

The first method consisted in the “clinical’’ observation of animals 
after removal of one or both suprarenal capsules. The results of these 
observations may be summed up as follows: 

1. Nutrition. Brown-Séquard—later Philipeaux, Foa, Nothnagel, 
Tizzoni, ete.—noticed extreme emaciation in animals dying sooner or later 
after removal of both suprarenal capsules. Tizzoni found in animals 
surviving the operation for a long period of time that the nutrition was 
maintained until shortly before death, when emaciation ensued. Tran- 
sient emaciation was noted by Abelous and Langlois after removal of one 
suprarenal body. In similar cases Szymonowicz sometimes failed to 
detect this, and even noted considerable increase in weight some time 
after the operation. Pal’s case above mentioned behaved similarly. 
When only very small portions of the suprarenal capsules were left behind, 
Thiroloix and Lancereaux observed extreme emaciation. 

2. Temperature. On this point the statements of different authors are 
very contradictory. Tizzoni, Abelous, and Langlois report a fall of tem- 
perature which is greater when both organs are removed. Szymonowicz 
was unable to demonstrate any considerable variation in temperature in 
either case. 

3. Disturbances of the nervous system. Brown-Séquard observed pro- 
found cerebral symptoms, such as epileptic convulsions, delirium, and 
vertigo; if only one organ was removed, the convulsions and contraction 
of the pupil were greater on the corresponding side. Tizzoni observed 
similar symptoms in rapidly fatal cases, and, in addition, diminished 
motor power and reflexes, opisthotonos with dilated and unresponsive 
pupils. In animals living a long time after removal of one suprarenal 
body he found weakness with contractures of the anterior extremities and 
impaired sensation upon the corresponding side. : 

Other authors, including Abelous and Langlois, noticed a preponder- 
ance of paralytic symptoms extending from the posterior extremities to 
the anterior, also the loss of faradic nervous irritability, while the direct. 
muscular irritability was’ unimpaired; death resulted from paralysis of 
the muscles of respiration. After removing both bodies Albanese ex- 
hausted his animals with faradic current and then observed clonic spasms, 
loss of reflexes, paralysis extending to the muscles of respiration, and 
arrest of the heart in diastole. Szymonowicz never observed convulsions 
after this operation, but, on the contrary, apathy, rigidity, weakness of 
the extremities, and difficult breathing. 


320 DISEASES OF THE SUPRARENAL CAPSULES. 


The anatomic alterations underlying these various nervous disturb- 
ances have carefully been investigated by Tizzoni, who finds them to be 
fundamentally different in animals dying soon after the operation and in 
those surviving for several months. In the former case these alterations 
consist of circulatory disturbances, stagnation of lymph, and irregularly 
scattered hemorrhages, together with exudation and secondary degenera- 
tion throughout the central nervous system (especially in the central 
canal), gray matter, and pia mater. In the brain and cerebellum these 
foci are irregularly distributed, while in the medulla oblongata they corre- 
spond closely to the nuclei of the eighth to the eleventh cranial nerves. 
The alterations are most intense in the medulla oblongata and in the cer- 
vical region of the cord, gradually diminishing toward the sacrum. In the 
second group of cases—animals surviving the operation for a considerable 
period of time—the alterations in the central and peripheral nervous sys- 
tems are primarily independent of circulatory disturbances. They com- 
prise degeneration of the posterior columns (especially the columns of 
Goll), extending even to the cerebellum, degeneration of the posterior 
roots, and atrophy of the posterior horns. The latter changes begin in the 
posterior horn of the side operated upon, extending thence to the ante- 
rior horn of the opposite side, and finally involving the whole gray 
substance. In the medulla oblongata the nuclei of the glosso-pharyngeal 
and vagus groups are atrophied, in the brain the changes are confined to 
the cortex. Finally, Tizzoni found degeneration of the celiac and mesen- 
teric plexuses of the sympathetic and of the peripheral nerves (sciatic). 
Tizzoni believes that these changes in the central nervous system are 
transmitted by the sympathetic, the degeneration extending from the 
abdominal plexuses of the latter, along the ganglionated cord to the spinal 
cord and brain. | 

4, Disturbances of the digestive organs. Loss of appetite was reported 
by most observers after removal of one or both suprarenal capsules, in the 
former case as a transient symptom. Nothnagel, Albanese, and Tizzoni 
observed increased peristalsis and diarrhea. Jacoby believes that the 
suprarenal capsules contain an inhibitory center for intestinal peristalsis; 
he bases this opinion upon the above-mentioned observations and upon 
original experiments, in which, after removal of the suprarenal capsules, 
an irritable condition of the intestine was produced by vagus stimulation. 
Pal only exceptionally obtained results corresponding with Jacoby’s 
view. 

5. Changes in the blood.. Brown-Séquard found a large excess of pig- 
ment in the blood and numerous pigment-emboli, and therefore concluded 
that the suprarenal capsules belong to the hemo-vascular glands and that 
there is a certain substance present in the body which is readily converted 
into pigment, and that the function of the suprarenal capsule probably is 
to so alter this substance that its peculiar property is lost. No subse- 
quent investigator has succeeded in confirming this observation of Brown- 
Séquard. There are conflicting reports as to the number of red and white 
corpuscles and percentage of hemoglobin, thesé being variously reported 
increased, diminished, or normal. The views of different authors concern- 
ing the chemical alterations in the blood are more in harmony, and are of 
the utmost importance for the physiology and pathology of the suprarenal 
capsules. 

Brown-Séquard had already discovered the following facts. After 
removal of both suprarenal capsules life may be prolonged by injecting the 


PHYSIOLOGY OF THE SUPRARENAL CAPSULES. 321 


blood of healthy animals. On the other hand, the blood of animals de- 
prived of both suprarenal capsules, when injected, hastens the death of 
animals from which only one organ has been removed. He therefore at- 
tributes poisonous properties to the blood of animals deprived of their 
suprarenal bodies. Abelous and Langlois obtained similar results in frogs. 
Later Langlois repeated these experiments with dogs and confirmed the 
poisonous action of the blood of animals subjected to this operation upon 
other animals similarly operated upon, but was unable to demonstrate any 
effect upon healthy animals. Marino Zucco and Raphael Suppino found 
that the blood of rabbits deprived of their suprarenal capsules acted like 
curare. These authors conclude that certain substances accumulate in 
the blood of these animals which, like curare, paralyze the motor nerve- 
endings and in part the muscles themselves; and that the function of the 
suprarenal capsules is to neutralize or destroy these substances. Ac- 
cording to this view, the suprarenal capsules are neutralizing organs. 

Abelous, Langlois, and Albanese investigated the origin of these pois- 
onous substances. In the course of their experiments they found that 
summer-frogs died much sooner than winter-frogs after removal of both 
suprarenal capsules; that frogs deprived of both suprarenal capsules die 
much sooner if their muscles are tetanized by the faradic current than if 
they are let alone; that the phenomena of exhaustion appear much earlier 
and last longer in animals subjected to this operation than in healthy 
animals; that the alcoholic muscle-extracts of exhausted but healthy 
animals when injected into frogs deprived of suprarenal bodies produce 
the same effect as the alcoholic muscle-extracts of animals similarly 
operated upon but not exhausted. They conclude, therefore, that the 
poisonous products of excessive muscular activity are identical with the 
poisons accumulating in the organism after removal of the suprarenal 
capsules. Normally these muscle-poisons are rendered harmless by the 
activity of the suprarenal bodies and only temporary exhaustion is noted, 
but as soon as the suprarenal capsules are extirpated these poisonous. 
substances accumulate. These authors believe the neutralizing action 
consists in oxidation of the muscle-poison. 

Albanese found that while ordinarily 4 mg. of neurin are required to 
kill a frog, 1 mg. suffices in animals deprived of their suprarenal capsules, 
and concludes that this is the substance which accumulates in the blood as 
the result of nervous and muscular activity and is neutralized by the 
suprarenal bodies. 

Thiroloix reached an entirely different conclusion as to the function of 
these organs. Although believing that animals deprived of their supra- 
renal bodies perish from the accumulation of toxins in their blood, he holds 
that the suprarenal bodies are not neutralizing (antitoxic) organs, but are 
rather regulators of cell nutrition. In the absence of these organs the 
nutrition of the cells is interfered with, and the metabolism of the poorly 
nourished cells becomes abnormal, resulting in the formation of toxic 
substances which cause the animals death. 

6. Szymonowicz investigated the pulse, respiration, and blood-pressure 
after extirpation of both suprarenal capsules, and found that the pulse and 
respiration were not constantly affected, but that a considerable fall of 
blood-pressure immediately followed the operation. [Strehl and Weiss * 
show that this same fall of blood-pressure follows section of the suprarenal 


_ * Pfliiger’s Archiv, 1901, Bd. txxxv1, 8. 107. 
21 


322 DISEASES OF THE SUPRARENAL CAPSULES. 


vein, providing the other adrenal has been removed. If the vein is simply 
clamped, the blood-pressure falls; when the clamp is released, the pres- 
sure rises even to a greater height than before. 

Moore and Purinton * studied the results obtained by the removal in 
cats and kittens of one suprarenal capsule and at a later period the re- 
moval of the remaining suprarenal body. ‘1n several instances the second 
operation was followed by death within a few hours. In three such cases 
large clots were observed in the right auricle with processes extending into 
the ventricle and venze cave. These clots bore all the appearances of 
antemortem clots. They therefore concluded that death was caused by 
cardiac thrombosis, which in turn was due to the lowering of blood-pres- 
sure following the total removal of the suprarenal capsules.—ED.] 

7. Changes in the skin and mucous membranes. A few observers report 
the development of abnormal pigmentation after extirpation of the supra- 
renal capsules. Nothnagel several times found spots of pigment in the 
buccal mucous membrane of young rabbits, but does not claim that they 
were the result of the operation. Tizzoni, however, found pigmentation 
in thirteen animals out of thirty which he had operated upon, independent 
of the mode of operation and color of the animal. He attributes this con- 
dition to alterations in the nervous system resulting from the operation. 
The pigment was situated around the snout, upon the nasal and buccal 
mucous membranes, and was especially characteristic on the under sur- 
face of the tongue. It never appeared earlier than two months after the 
- operation, increased in intensity the longer its duration, and never disap- 
peared. The pigment was situated in the deepest layers of the epithelium 
or epidermis and in the migratory cells of the subepithelial connective 
tissue. 

The second method for determining the function of the suprarenal 
bodies was the investigation of the action of suprarenal extracts. It is 
remarkable that these experiments were not undertaken sooner. Johannes 
Miller had already called attention to the method in his “Text-book 
of Physiology,” asking (p. 491, chap. Iv, vol. 11): ‘ Does the blood undergo 
a peculiar change in its passage through the vascular network of the cortex, 
escaping as altered blood through the suprarenal veins into the general 
venous system? The left suprarenal vein should be ligated in the living 
animal and the fluid in the vein and suprarenal body should be exam- 
ined.” | 

Foa and Pellacani, in 1879 and 1883, were the first to investigate the 
physiologic action of extracts of suprarenal bodies. They injected the 
extracts into frogs, guinea-pigs, rabbits, and dogs. Symptoms of poison- 
ing resulted, consisting of impairment of sensation and reflexes followed 
by general paralysis. 

Guarnieri and Marino Zucco confirmed (1888) the poisonous proper- 
ties of the aqueous extract of the suprarenal capsule. They attribute this 
action to neurin and organic phosphoric acids which they found abun- 
dantly present. Alzais and Arnaud experimented in the same direction, 
The most recent methodic and exhaustive investigations of the subject 
have been made by Schafer and Oliver, Szymonowicz and Cybulski, Glu- 
zinski, Velich and Biedl (1894-1896). 

[One of the most interesting and important facts regarding the material 
which is yielded by the suprarenals is the minuteness of the dose which is 
necessary to produce the results. As little as 0.0055 (54 mg.) of dried 

*Amer. Jour. of Phys., 1900-1901, 4, p. 51. 


PHYSIOLOGY OF THE SUPRARENAL CAPSULES. 323 


suprarenal is sufficient to obtain a maximal effect upon the heart and 
arteries in a dog weighing ten kilos. For each kilogram of body-weight 
the necessary quantity to produce a maximal effect is 0.00055 gm., or little 
more than half a milligram. The active principle is, however, contained 
only in the medulla of the gland, not in the cortex, and the medulla in all 
probability does not form more than one-fourth of the capsule by weight. 
Of the dried medulla certainly not less than nine-tenths are composed of 
proteid and other material which is not dialyzable and which otherwise 
does not conform to the chemical properties which are associated with 
the active substance of the gland.’”’*—Eb.] 

Oliver and Schafer injected both a glycerin extract and an aqueous 
extract into various animals and observed the following three principal 
effects: 

1. An enormous rise of blood-pressure, the result of excessive contrac- 
tion of the blood-vessels. This rise of blood-pressure was increased by 
section of the vagi or by paralyzing their peripheral terminations with 
atropin. Destruction of the medulla oblongata and the entire spinal cord 
and section of the peripheral nerves caused a similar increase of blood- 
pressure. Stimulation of the depressor nerve during the administration 
of suprarenal extract failed to produce a fall of blood-pressure. 

From these facts it follows that the rise of blood-pressure is the result 
of a direct action of the extract upon the muscular fibers of the heart 
and arteries. 

2. Slowing and ‘strengthening of the heart’s action and pulse. These 
result from stimulation of the vagus centers. After destruction of the 
medulla oblongata, section of the vagi, or paralysis of their peripheral 
terminations by atropin, the heart’s action was increased in frequency as 
well asin force. The increased frequency greatly exceeded that following 
section of the vagi alone, from which it is apparent that suprarenal extract 
increases the frequency of the heart’s action. The authors observed a 
like result also when the extract was applied to the excised frog’s heart. 

3. In frogs and mammals the duration of muscular contraction was 
lengthened. 

Its action upon respiration was inconstant. Large doses killed rab- 
bits within twenty-four hours. The enormous rise of blood-pressure pro- 
duced by this substance distinguishes it from digitalis and ergotin, which 
cause an inconsiderable rise. These authors deny that the active sub- 
stance is neurin, because the latter diminishes blood-pressure. Extracts 
of the medullary portion of the capsules alone were active. Suprarenal 
extract from healthy human beings was very powerful, while the extract 
from two cases of Addison’s disease was totally inert. Extirpation of the 
suprarenal capsules and ligation of the renal vessels apparently had no 
particular effect upon the result of the injection. 

These authors conclude that the suprarenal bodies elaborate an in- 
ternal secretion which maintains the physiologic tone of all the muscular 
tissues, especially of the heart and vessels. 

Szymonowicz in Cracow carried on experiments independently of these 
other observers. He employed aqueous and alcoholic extracts from dif- 
ferent animals with like results. Extracts from the medullary substance 
,alone were active, but the effect occurred sooner if an extract of the entire 
gland was administered. Szymonowicz therefore believes that the cortical 
substance may in some way further the action of the medullary portion. 

* “ Text-book of Physiology,” Schiifer, 898, vol. 1, p. 1957. 


324 DISEASES OF THE SUPRARENAL CAPSULES. 


The action of the extract was delayed in animals deprived of their supra- 
renal capsules, but lasted longer when once developed. The most striking 
action of suprarenal extract is a rise of blood-pressure greater than that 
produced by any other drug. The heart’s action is diminished in fre- 
quency but increased in force, and the respirations are shallow. The rise 
of blood-pressure sometimes exceeded 300 mm. of mercury; it was in- 
variably increased after section of the vagi, and the administration of 
atropin caused a rapid onset of the increased blood-pressure. On the 
other hand, section or partial destruction of the spinal cord very decidedly 
diminished this action of suprarenal extract, while complete destruction 
of the cervical and thoracic cord abolished it. Szymonowicz concludes 
that the vasomotor centers of the medulla oblongata principally, and to a 
lesser degree the centers in the spinal cord, are concerned with this rise of 
blood-pressure. The immediate cause is a contraction of the systemic 
blood-vessels which Szymonowicz demonstrated by direct measurements. 
After the slowing of the pulse had disappeared he repeatedly observed its 
increased frequency. When curare was administered very large doses of 
suprarenal extract were required to develop slowing of the pulse. After 
administration of atropin the rise of blood-pressure was invariably accom- 
panied by increased frequency of the heart’s action. Section of the vagi 
also accelerated the heart’s action, which after the injection was greater 
and was associated with increased blood-pressure. This effect of supra- 
renin upon the action of the heart is due to stimulation of the vagus in the 
medulla oblongata; electric stimulation of the peripheral end of the cut 
vagus may cause still further slowing of the heart’s action. Arrhythmia 
or allorhythmia was almost invariably noted after administering large 
doses of the extract, hence Szymonowicz concludes that the surparenal 
extract acts directly upon the nerve structures of the heart itself. Shal- 
low respiration was the only constant respiratory symptom noted, yet 
Szymonowicz is convinced that the substances contained in the suprarenal 
extracts are capable of stimulating the respiratory center and, in large 
doses, of paralyzing it. He observed no poisonous action, healthy ani- 
mals, indeed, bearing very large doses. None of the other organic ex- 
tracts—as, for example, from the brain, spinal ganglia, testes, or thyroid 
gland—possess similar properties, although a moderate fall of blood- 
pressure and acceleration of the heart’s action (7. e., the opposite action to 
suprarenal extract) were noted in two cases after injecting an extract of 
the pineal gland. 

The experiments of Szymonowicz were continued by Cybulski, who 
investigated the chemical properties of suprarenal extracts. 

He demonstrated*that strong solutions of the extracts proved fatal in 
rabbits. These animals are characterized by remarkably delicate blood- 
vessels, and in fatal cases he observed extravasations in the lungs, heart, 
brain, and medulla oblongata, and, in addition, infarctions and edema of 
the lungs. Weak solutions, on the contrary, were wholly harmless, even 
in considerable quantities. Large doses of suprarenal extract may com- 
pletely suspend the activity of the vagi and may paralyze the vasomotor 
centers. Very rarely Cybulski observed paralysis of the respiratory 
centers. The reflexes of frogs were slightly impaired by suprarenal ex- 
tract. In addition, he found that the active substance of suprarenal ex- 
tract is elaborated in the suprarenal capsules, entering the blood by dialy- 
sis. *Defibrinated blood of the suprarenal vein produces, when injected 
into animals, the same results as suprarenal extract but of less intensity. 


PHYSIOLOGY OF THE SUPRARENAL CAPSULES. 325 


The urine of animals after administration of suprarenin acted in like 
manner, though in less degree, proving, according to Cybulski, that supra- 
renin is in part excreted by the kidney. 

Cybulski especially emphasizes that suprarenal extract, or more par- 
ticularly its active principle, is very readily oxidizable, being rendered 
inert by a 1% solution of potassium permanganate. 

This explains, on the one hand, the transient action of the extract 
under normal circumstances, since it is speedily oxidized in the meta- 
bolism of the tissues; and, on the other hand, the accumulation of this sub- 
stance in the blood and the more decided production of its characteristic 
effects when the organism is poor in oxygen (for example, in asphyxia). 
With reference to the analogy existing betweeen the phenomena of as- 
phyxia (increased blood-pressure, slowing of the pulse, etc.) and the symp- 
toms produced by suprarenin, Cybulski believes that the toxicity of the 
blood in asphyxia results from the accumulation of suprarenin. This 
opinion is supported by certain experiments; thus, in the absence of supra- 
renin from the blood (after extirpation of the suprarenal capsules) the 
phenomena of asphyxia do not appear, but can be developed by injecting 
suprarenal extract; when the blood of asphyxiated animals is injected 
into healthy animals, its action is similar to though less powerful than that 
of suprarenal extract. Cybulski consequently believes that the supra- 
renal secretion is a physiologic tonic for the respiratory center, its function 
being to maintain the rhythmic activity of this center independently of all 
chemical or nervous stimuli. 

As the result of their combined observations, Szymonowicz and Cy- 
bulski conclude as follows: 

1. Extirpation of both suprarenal capsules causes a decided fall of 
blood-pressure; the pulse becomes small. 

2. Intravenous injection of suprarenal extract causes a marked rise of 
blood-pressure with slowing and strengthening of the heart’s action. 

3. The same symptoms, although less intense, are produced by the 
injection into the circulation of the blood of the suprarenal vein. 

4. The suprarenal body is an organ essential to life. 

5. The function of the suprarenal capsules is to elaborate and add to 
the blood a substance which stimulates the activity of the vasomotor 
centers, the centers of the vagus and accelerator nerves, and the respira- 
tory centers, and permanently preserves the tonic tension of these centers. 

6. The theory of the neutralizing action of the suprarenal capsules can 
be dispensed with, for the loss of the above-mentioned tonic influence is 
sufficient to explain all symptoms occurring after their removal. 

Gluzinski also confirms the rise of blood-pressure produced by supra- 
renal extract, but emphasizes, in contradistinction to Szymonowicz and 
Cybulski, the highly poisonous properties of the glycerin extract which he 
used; this is manifested, he states, by intense circulatory disturbances 
based upon the rise of blood-pressure which is brought about by injury to 
the medulla oblongata and spinal cord. Unless the death of the animals 
thus poisoned early followed the injection pulmonary edema and hemor- 
rhages into the lungs, pleura, and pericardium occurred. Gluzinski be- 
lieves these to be secondary results of the rise of blood-pressure and dis- 
turbance of the pulmonary circulation. Gourfein speaks similarly of the 
poisonous properties of suprarenal extracts. 

Thus all investigators agree that suprarenal extracts raise blood-pres- 
sure, but there are marked differencés o opinion as to whether the action 


326 DISEASES OF THE SUPRARENAL CAPSULES. 


is central or peripheral. While Szymonowicz and Cybulski attribute this 
effect to the action of the extracts upon the central apparatus in the 
medulla and cord, Oliver and Schafer explain it by direct action upon the 
heart and blood-vessels. Velich and Biedl recently instituted control — 
experiments in order to settle this point, and came independently to the 
same conclusion—that the suprarenal extracts act, as Oliver and Schafer 
maintained, upon the peripheral apparatus of the blood-vessels. They 
found that a considerable rise of blood-pressure was produced by injec- 
tions of suprarenal extract even after complete destruction of the spinal 
cord. This view was confirmed by Gottlieb, who injected suprarenal ex- 
tracts into animals narcotized by chloral. Even then the injection was 
followed by a considerable rise of blood-pressure, although the vasomotor 
centers were completely paralyzed by chloral. It has thus been proved 
beyond doubt that the rise of blood-pressure is caused by a peripheral 
action upon the heart and blood-vessels, but while Oliver and Schafer 
attribute this to a direct action upon the muscular fibers, Gottlieb be- 
lieves it to result from the specific action of the poison upon the intracar- 
dial motor ganglia and upon the peripheral vascular ganglia which control 
the dilatation of the vessels. 

The positive proof of the peripheral action of the extract was furnished 
by Biedl. He experimented with living, excised organs (kidneys, ex- 
tremities) by flushing them with blood charged with suprarenal extract. 
Such an excessive contraction of the vessels was caused that the outflow 
from the vein ceased, although the pressure applied to the entering blood 
was increased threefold. (Personal statement.) [Bardier and Fraenkel 
have shown that a similar change in the kidney also takes place when the 
suprarenal extract is injected intravenously.*—ED. ] 

Darier’s experiments furnish further proof of the peripheral action of 
suprarenal extract. When cocain fails to produce anesthesia of the con- 
junctiva because of excessive hyperemia, it may be combined with supra- 
renal extract. A single drop of this mixture produces a striking pallor 
and complete anesthesia of the conjunctiva. The suprarenal extract, 
therefore, produces a contraction of the conjunctival blood-vessels. 

[Mosse }¢ found that the direct application of the extract to the nasal 
corpora cavernosa diminished their injection. 

Blum t showed that the subcutaneous or intravenous injection of 
suprarenal extract may cause a considerable degree of glycosuria in ani- 
mals. This occurs not only when the diet is free from carbohydrates, but 
also in hunger even when all glycogen has disappeared from the liver. He 
ascribes the glycosuria to a toxic action upon one or more of the organs 
prominent in carbohydrate metabolism—the organ attacked most prob- 
ably being the pancreas. The presence of acetone, diacetic acid, and 
f-oxybutyric acid was not noted. 

Zuelzer 3 confirms Blum’s results. He obtained glycosuria in an ani- 
mal after fourteen days of starvation. Occasionally diacetic acid was 
detected, never acetone, but albumosuria frequently occurred. The gly- 
cosuria is the result of hyperglycemia and is not caused by a renal lesion. 
Levulose or lactose given at the same time as the suprarenal extract 
caused respectively levulosuria or lactosuria.—ED. ] 


*Soc de Biol., 1899, June 24, p. 544. t Therap. d. Gegenw., 1900. 
} Deut. Arch. f. klin. Med., 1901, txx1, Heft 2 u. 3. 
§ Berl. klin. W ochen., 1901, p. 1209. 


PHYSIOLOGY OF THE SUPRARENAL CAPSULES. 327 


The third method of physiologic investigation is the chemical. Addi- 
son first called the attention of chemists to the suprarenal capsules. Vul- 
pian, in 1856, was the first to investigate them. He found a substance in the 
juices of the suprarenal capsules which became dark colored, almost black, 
but with a tinge of blue or green, upon addition of chlorid of iron. Upon 
addition of oxidizing agents he obtained a beautiful rose color. Virchow 
and Vulpian showed that this substance was found only in the medullary 
juices, and believed it probably a sulphur compound. Virchow found, in 
addition, large quantities of leucin and myelin. Cloez and Vulpian suc- 
ceeded in demonstrating hippuric and taurocholic acids in the suprarenal 
capsules of sheep. These substances for a while played a rdéle in the 
pathology of Addison’s disease. Their presence has recently been denied 
(Stadelmann and Beier). 

A chromogenic substance was found in the suprarenal capsules by 
Seligsohn, Holm, and MacMunn. It was convertible by oxidation into a 

igment and was bclieved by the last-named author to be hemochromogen. 
Arnold finally succeeded in isolating a pigment in the form of dark red, 
oily drops which crystallized upon drying. The crystals were soluble in 
water and alcohol, insoluble in ether, chloroform, or carbon disulphid. 
Krukenberg continued the investigation of this pigment and its colorless 
progenitor; he proved that both substances were dialyzable and recog- 
nized that they were neither albuminous, resinous, nor fatty, but that their 
chemical behavior closely resembled that of pyrocatechin. He was in- 
clined to believe these substances identical. Brunner held the same view. 

Other authors called attention to various other substances. Alex- 
ander demonstrated an enormous amount of lecithin in the suprarenal 
capsules, much more than in any other organ outside of the central ner- 
vous system. He concludes that the suprarenal capsules elaborate this 
substance, so indispensable to the nervous system, and furnish it to the 
latter. Lubarsch found glycogen in the suprarenal capsules of the em- 
bryos of rabbits and guinea-pigs. Marino Zucco and Dutto, as already 
mentioned, proved neurin to be a constant constituent of the suprarenal 
capsules and ascribe the physiologic effect on the blood-pressure to a com- 
bination of this material with glycero-phosphoric acid. This was dis- 
proved by Oliver and Schafer. Manasse found a substance containing 
phosphorus and yielding sugar, closely related to jecorin. This probably 
was a combination of a carbohydrate with lecithin. In fresh blood from 
the suprarenal capsules of dogs he found small, hyaline, glistening, color- 
less granules which were stained by chromic acid and were soluble in alco- 
hol. These presumably correspond to the glistening granules found by 
Gottschau and Pfaundler in the blood of the suprarenal vein. All three 
authors believe these homogeneous masses are a secretion of the medullary 
substance which enters the circulation through the suprarenal vein. 
According to Lubarsch, they are closely related to Russell’s fuch- 
sin bodies, the latter consisting, in his opinion, of lecithin or glycogen or a 
combination of these substances with proteids. Nebarro found globulin 
and small quantities of albumin ;- Kiilz found inosit. 

Of late years considerable attention has been paid to the chemistry of 
the suprarenal capsules on account of the experiments with suprarenal 
extracts. Moore (the chemical collaborator of Oliver and Schafer) and 
Cybulski almost entirely agree that the active substance is soluble in water, 
glycerin, and alcohol; insoluble in ether, chloroform, and amyl-alcohol 
(carbon disulphid, ligroin—Moore). The substance was not destroyed by 


328 DISEASES OF THE SUPRARENAL CAPSULES. 


boiling or by dilute acids, but was decomposed by alkalies, especially upon 
heating. Its reducing property, already mentioned by Vulpian, was con- 
firmed. 

The substance is very susceptible to oxidizing agents, being decom- 
posed by a small quantity of a 1 % solution of potassium perman- 
ganate. It is dialyzable through animal membranes. According to 
Moore, it is neither a proteid, a glucosid, nor a sugar. 

Sigmund Fraenkel finally succeeded in isolating the active principle of 
suprarenal extract in the form of a syrupy, non-crystallizable substance, 
readily soluble in water and alcohol, soluble with difficulty in acetone. 
Even a trace of this substance produces the characteristic effect upon 
blood-pressure, and on account of this very conspicuous property it was 
termed sphygmogenin by Fraenkel. When this substance is treated with 
an aqueous solution of chlorid of iron, a deep green color is produced; no 
ammonia is set free upon boiling it with lye; no red color is produced with 
Millon’s reagent; it possesses strong reducing properties. 

It immediately reduces an ammoniacal silver solution, sets iodin free 
from iodic acid, but does not reduce Fehling’s solution. Solutions of the 
free substance are acid, but neither form salts nor can they be converted 
into ethers by ethyl alcohol and hydrochloric acid. This indicates, as 
Fraenkel says, that the acid reaction is due to hydroxyl. The substance 
is readily oxidizable; its physiologic action is suspended by hydrogen 
dioxid or potassium permanganate. It is not decomposed in the blood, 
but in the tissues the properties of this substance are impaired, since the 
rise of blood-pressure after subcutaneous or rectal injection is not so con- 
spicuous as after venous injection. Sphygmogenin is very susceptible to 
exposure to light, air, and prolonged boiling; by these means its solutions 
are rendered physiologically inert and no chlorid of iron reaction is pro- 
duced. According to Fraenkel, these two properties run a parallel course. 

According to its reactions, spohygmogenin belongs to the group of ortho- 
dihydro-oxybenzol derivatives. Krukenberg’s view—that the substance 
is identical with pyrocatechin—is contradicted by its wealth in nitrogen, 
slight solubility in ether, and by its reaction with lime-water, with which 
it yields a red instead of agreen color. It might, however, be a derivative 
of pyrocatechin containing nitrogen, and Fraenkel calls attention to the 
striking fact that pure pyrocatechin produces a similar rise of blood-pres- 
sure. The most recent chemical investigations of Miihlmann throw a 
new light upon this question. He treated with water and a little acetic 
acid the fresh, pulverized suprarenal capsules of cows or calves. The 
solution was filtered and evaporated, the brown syrupy residue was di- 
gested with alcohol, filtered, and the alcohol driven off. The residue was 
readily soluble in alcohol and water, soluble with difficulty in ether, and 
gave a red color upon addition of sublimate to its neutral or faintly. acid 
solution. The solubility of this residue and its further chemical reactions, 
particularly the reaction with sublimate, prove that pyrocatechin was not 
contained in it. 

Yet Mihlmann, upon boiling the residual substance with hydrochloric 
acid, succeeded in splitting it up and demonstrating pyrocatechin as a 
result. He thus proved that pyrocatechin exists in combination in supra- 
renal extract. Upon testing sections of fresh suprarenal capsules with 
chlorid of iron, the medullary substance alone yields the characteristic 
(ferric chlorid) pyrocatechin reaction, while the cortex remains unstained. 
From this fact, Miihlmann feels justified in concluding that pyrocatechin 


PHYSIOLOGY OF THE SUPRARENAL CAPSULES. 329 


is formed in the medullary substance of the suprarenal capsules, while the 
cortical substance furnishes the material. Mihlmann believes that the 
protocatechuic acid of vegetable food is the mother-substance of pyro- 
catechin. 

Although the chemical investigations have furnished much that is 
new, and have considerably extended our knowledge of the function of the 
suprarenal capsules, no definite results have been attained. The most 
striking constituents are sphygmogenin, pyrocatechin, neurin, and lecithin. 
Probably the next task will be to ascertain the nature of the residue con- 
taining nitrogen after the separation of the sphygmogenin. 

[Abel and Crawford, in 1897, showed that the constituent of the supra- 
renal capsule which raises the blood-pressure may be completely precipi- 
tated from an aqueous extract by benzoyl chlorid and sodium hydrate. 
On decomposing the resulting benzoyl products a residue is obtained which 
possesses great physiologic activity. This residue gives the color-reac- 
tions of Vulpian, reduces silver nitrate, and has the other specific qualities 
of suprarenal extracts. When contaminating substances are removed, 
the active principle is left as a highly active sulphate or hydrochlorate. 
It is therefore a basic substance. Abel, like v. Furth,? did not obtain 
pyrocatechin from it, nor was the former able to agree with Moore? that 
pyridin was the active principle isolated. 

In 1898 Abel* isolated the active principle in the form of a benzoate 
whose formula he expressed as C,,H,,NO,, and named it epinephrin. The 
free base could not be isolated without a loss of the physiologically 
active qualities. Its active salts, however, when applied locally markedly 
constringe the blood-vessels, have a faintly bitter taste, and cause a slight 
loss of sensation on the tongue. When introduced into the circulation 
these salts produce a marked increase of blood-pressure of long duration. 
They at first stimulate, then paralyze, the respiratory centers, and if the 
dose is further increased the heart is paralyzed. 

Von Firth,® working independently, isolated from suprarenal capsules 
an iron compound which he named suprarenin. He considers it the con- 
stituent of the gland which raises the blood-pressure and holds that its 
presence in epinephrin accounts for the physiologic activity of the latter. 
Abel,® however, has been able to show conclusively that epinephrin and 
suprarenin are in reality the same substance and that epinephrin can be 
prepared from v. Firth’s product. Epinephrin as first described by Abel 
is actually a mono-benzoyl-reduced epinephrin, which is expressed by the 
formula ©,,H,,NO,. Subtracting the benzoyl group C,H,CO, one gets 
C,,H,,NO,, which is the native or unreduced epinephrin. This is a very 
soluble, apparently very hygroscopic substance, which is quite unstable 
and does not reduce copper. It was at first isolated as a sulphate or bisul- 
phate by Abel,? but he recently gives a new and simpler process by which 
the active principle can be isolated as a basic, minutely crystalline com- 
pound, easily converted by mineral acids into a physiologically active sub- 
stance giving all the characteristic reactions of epinephrin. 

Takamine® has recently isolated from suprarenal capsules a substance 
—adrenalin—which he claims is the principle of the gland which raises the 
blood-pressure. Aldrich,® working independently, has confirmed Taka- 
mine’s work, but Abel? ° offers satisfactory proof to show that adrenalin is 
an impure product, closely related to epinephrin—being probably a mix- 
ture of native and reduced epinephrin with traces of foreign substances 
rich in nitrogen. 


330 DISEASES OF THE SUPRARENAL CAPSULES. 


Hunt * isolated from the aqueous extract of suprarenal capsules from 
which Abel had removed epinephrin a crystalline body which, injected 
into an animal, caused a marked fall of blood-pressure. The body was 
soluble in cold water, insoluble in alcohol, and gave the odor of trimethyl- 
amine on heating. The chemical and physiologic properties of the sub- 
stance agree with cholin. 

Jacoby ¢ has found a ferment in the medulla and cortex of the supra- 
renal capsule which oxidizes salicyl-aldehyde to salicylic acid. He did 
not determine its composition. 

Mention has already been made of Croftan’s diastatic ferment. 


LITERATURE ON EPINEPHRIN, SUPRARENIN, ADRENALIN. 


. Abel and Crawford: “Johns Hopkins Hospital Bulletin,” 1897, vim, p. 151. 
v. Furth: “Zeits. f. phys. Chemie,” 1898, 24, p. 142. 

Moore: “Jour. of Phys.,’’ 1897, xx1, p. 382. 

Moore and Purinton: “ Amer. Jour. of Phys.,”’? 1900-1901, m1, No. 8, p. xv. 
Abel: “ Johns Hopkins Hospital Bulletin,” 1898, rx, 214. 

v. Furth: “ Zeits. f. phys. Chemie,” 1898, 26, p. 15. 

Abel: “ Zeits. f. phys. Chemie,’”’ 1899, 28, p. 318. 

Abel: ‘“ Amer. Jour. of Phys.,’”’ 1899-1900, 111, No. 8, p. xvii. 

v. Firth: “ Zeits. f. phys. Chemie,’ 1900, 29, p. 105. 

Abel: “Johns Hopkins Hospital Bulletin,’ 1901, x11, p. 80. 

— “Johns Hopkins Hospital Bulletin,” 1901, x1, p. 337. 

8. Takamine: “Therapeutic Gazette,” 1901, xxv, p. 221. 

9. Aldrich: “ Amer. Jour. of Phys.,”’ 1901, v, p. 457. 

0. Abel: “Johns Hopkins Hospital Bulletin,” 1902, x1, p. 29. 


Soe Se 


THERAPEUTIC PROPERTIES OF SUPRARENAL EXTRACT. 


In consequence of the physiologic vasoconstrictor action of the supra- 
renal capsule, the attempt was made to make use of this property to 
diminish the blood-supply in diseased mucous membranes, especially of 
the eye and nose, and to arrest hemorrhage. The first to call attention to 
this action were Bates (eye), Hajek and Swain (nose and throat), Floer- 
sheim (heart and lungs), Griinbaum (alimentary tract), Churchill (uterus), 
Habgood and Heelas (prostate). Senator and others studied the influ- 
ence of the extract on metabolism and Stélzner employed it in rickets. 

At first the powdered capsules were employed, then aqueous solutions, 
but of late Takamine’s adrenalin has displaced all other preparations in 
local use. (For a description of adrenalin see p. 329.) 

Bates t applied a small quantity of a 10% aqueous solution to the eye 
in numerous cases of congestion and observed an immediate pallor which 
lasted for some time. He found the extract useful in prolonged opera- 
tions, for when repeatedly applied hemorrhage was prevented and cocain 
anesthesia indefinitely prolonged. 

Hajek is mentioned by Konigsten 3 as using suprarenal extract ex- 
perimentally in the nose, but Swain || was the first to publish a report on 
its extensive use in diseases of the nose and throat. It acted as a powerful 
local vasoconstrictor, contracted erectile tissue, and could be applied 


* Amer. Jour. of Phys., 1899-1900, vol. 111, No. 8, p. 18. 
+ Zeits. f. phys. Chemie, 1900, xxx, 135. 
tN. Y. Med. Jour., 1896, ux111, 647. 
gu 1% § Wien. med. Presse, 1897, Bd. xxvu, p. 857. 
|| Trans. of the Amer. Laryngological Assoc., 1898, p. 165. 


PHYSIOLOGY OF THE SUPRARENAL CAPSULES. 331 


without danger. Its widest application was in acute congestions, but it 
was also helpful in chronic conditions of the hay-fever type. 

Mandeville,* McKenzie, t and Reynolds { all have found the local use 
of suprarenal extract of great value in epistaxis. Reynolds maintains 
that a 1 : 1000 solution of adrenalin in sodium chlorid may be relied upon 
to relieve any case of epistaxis. He does not believe that it predisposes 
to secondary hemorrhage. McKenzie’s case was remarkable in that the 
patient had hemophilia. His experience is in contrast to that of Griin- 
baum,? who found it of no use in such states. Solis-Cohen|| used adre- 
nalin 1 : 5000 with great relief in hay-fever. 

The use of the extract in the eye and nose therapeutically and for pur- 
poses of diagnosis is now established, but elsewhere in the body and for 
other conditions its trial has not yet passed the experimental stage. 

Floersheim ** has studied the effect of suprarenal capsule administered 
internally in 82 cases of heart disease: He administered 3 grains at a dose 
and found that it exerted little influence on the normal heart. The action 
of a weak and irregular heart became stronger and more regular and the 
diffused apex-beat was more sharply localized. 

This observert7 also has employed suprarenal powder in a great variety 
of affections of the respiratory tract. He reports favorable results in 
acute and chronic bronchitis, bronchiectasis, asthma, congestion and 
edema of the lungs. In thirty-seven cases hemoptysis was checked by 
the internal administration. of suprarenal capsule in three-grain doses.ft 
Kenworthy 3% reports a similar experience in fourteen cases. Bates, in 
an excellent summary of the literature, |||| mentions six cases of edema of 
the glottis in which life appeared to be saved by the internal or local use of 
suprarenal extract. 

Griinbaum *** mentions benefit from the use of one or two five-grain 
suprarenal tablets in hemorrhage of the gastro-intestinal tract. 

Churchill is quoted by Bates ++} as having observed benefit from the 
internal use of suprarenal tablets in uterine hemorrhage. Floersheim ttf 
adds 23 similar cases. 

Habgood 33% gave five grains of suprarenal capsule twice daily for pros- 
tatic hemorrhage. This lessened and after some days disappeared, but 
the use of the medicament was attended with palpitation, and was there- 
fore stopped, but the hemorrhage returned. Heelas|||||| in a similar case 
injected locally a few drops of suprarenal extract (five grains to the dram) 
through an india-rubber catheter three times a day. The hemorrhage 
ceased and there were no deleterious general effects. 


* Cited by Bates, Med. Rec., Feb. 9, 1901, p. 207. 
t+ Brit. Med. Jour., April 27, 1901, p. 1009. 
t Am. Med., July 6, 1901, p. 32. § Brit. Med. Jour., Nov., 1900, p. 1307. 
|| Am. Med., Sept. 7, 1901, p. 376. 
**k N.Y. Med. Jour., Oct. 6, 1900; also tbid., May 4, 1901. 
+t Med. Rec., Nov. 17, 1900, p. 774. 
tt Loc. cit. and Med. News, Jan. 4,.1902, p. 17. 
§§ Med. Rec., Mar. 16, 1901, p. 415. 
|| || International Magazine, Dec., 1900, p. 885. 
*k* Brit, Med. Jour., Nov., 1900, p. 1307. 
ttt Med. Rec., Feb. 9, 1901. tit Med. News, Jan. 4, 1902, p. 17. 
§$§ Brit. Med. Jour., May 25, 1901, p. 1266. 
|| || || Brot. Med. Jour., June 8, 1901, p. 1402. 


332 DISEASES OF THE SUPRARENAL CAPSULES. 


Munro * claims benefit in acne rosacea from the combined use of the 
extract locally and internally. 

Reynolds,t} who has used adrenalin in 1222 cases, reports that in many 
instances prompt and sometimes lasting benefit follows the introduction 
of a drop of the adrenalin solution through the Eustachian catheter into 
the middle ear. 

Stolzner ¢ treated 76 children suffering from rickets with suprarenal 
extract and observed remarkable and rapid improvement. Neter @ failed 
to confirm these observations. Ko6nigsberger || tested Stdlzner’s state- 
ments in a large number of cases with chiefly negative results. There was 
no specific effect, but simply a slight improvement in the general condi- 
tion, which he attributed to the effect on the circulatory apparatus and 
the respiratory center. 

Theinfluence of suprarenal extract on metabolism is not striking. 
Senator ** sums up his conclusions, based on the study of the metabolism 
of a patient with Addison’s disease to whom he gave 34.8 gm. of tablets of 
fresh sheep’s suprarenals in eighteen days, in these words: there is nothing 
further to say than that they were well borne without any disagreeable 
effects, and on the whole stimulated the appetite. 

Pickardt tt studied a similar case and found a marked destruction of 
body albumin amounting in four days to 18.02 gm. nitrogen. Such a 
single unfavorable result naturally allows no conclusion to be drawn. 

Kaufmann ff investigated the question and came to the same conclu- 
sion as Senator.—ED.] 





SYMPTOMATOLOGY OF DISEASES OF THE SUPRA- 
RENAL CAPSULES. 


Ir is impossible to present any definite symptomatology of the supra- 
renal capsules until their function has been made wholly clear by physi- 
ology and experimental pathology. The specific and characteristic symp- 
toms afforded by impairment or loss of function are lacking. In fact, 
numerous cases are recorded presenting at autopsy extensive alterations 
of the suprarenal capsules without a single symptom during life having 
aroused the suspicion of disease of these organs. Apparently such cases 
have run their course without a single symptom, or at least no symptoms 
were produced which could not be explained by other coincident patho- 
logic processes. 

Another group of cases may produce local symptoms, such as a tumor, 
which eventually may cause effects of pressure upon adjacent organs, 
nerves, and blood-vessels, or may give rise to lumbar and sacral pain; 


* Cited in Gould’s “ Year-Book,” 1902, p. 566. 
+ Am. Med., July 6, 1901, p. 32. t Deut. med, Wochen., 1899, No. 37. 
§ “Jahr f. Kinderheilkinde,” 1900, 52, 600. 
|| Miinch. med. Wochen., 1901, No. 16. 
** Charité-Annalen, 1897, Bd. xxm1, 235. 
»tt Berl. klin. Wochen., 1898, xxxv, 727. 
ti Cited in Zeit. f. diatet. u. phys. Therapie, 1901, 5, 508. 


ADDISON’S DISEASE. 333 


however, in the majority of cases the symptoms are not characteristic and 
the diagnosis can be made only by exclusion, and then only with a certain 
degree of probability. 

In a third group of cases remote symptoms make their appearance, 
brought about by metastasis from a malignant suprarenal tumor. 

In spite of the absence of any apparent connection, these symptoms 
may arouse the suspicion, or at least suggest the possibility, of a primary 
suprarenal affection. 

Finally in a fourth group (by no means very small) local, remote, and 
general symptoms make their appearance in a combination which was first 
described as a type of disease by Addison, and has since been universally 
recognized as Addison’s group of symptoms. 

Although the occurrence of this group of symptoms permits the diag- 
nosis of suprarenal disease with a certain degree of probability, there is no 
doubt that this probability is by no means a certainty. In some cases of 
well-marked disease of these organs this group may be entirely absent or 
only a few of the symptoms capable of very numerous explanations be 
present; on the other hand, this group of symptoms may be particularly 
well developed without a trace of pathologic alteration in the suprarenal 
capsules. 

The conditions are still further extremely confused by the occurrence 
of numerous complications or by localization elsewhere of the lesion 
(tuberculosis, carcinoma) usually present in the suprarenal capsules in 
Addison’s disease. 

It is not only impossible to diagnosticate surely disease of the supra- 
renal capsules during life, but it is also exceedingly doubtful whether there 
are definite anatomic characteristics of such disease. 

Under such circumstances it can readily be appreciated that Leube, in 
his work on diagnosis, dismisses the subject with the statement that dis- 
eases of the suprarenal capsules as yet are incapable of diagnosis. 

It is therefore necessary, instead of discussing the clinical features of 
diseases of the suprarenal capsules, to describe in the first place Addison’s 
disease, and to supplement this by briefly mentioning those symptoms 
which in the absence of Addison’s group might possibly suggest disease of 
the suprarenal capsules as their origin. 





ADDISON’S DISEASE. 
PATHOLOGIC ANATOMY OF ADDISON’S DISEASE. 


In discussing the pathologic anatomy of Addison’s disease the changes 
in those organs which bear a causal relation to the disease will first be con- 
sidered. The structures concerned are the suprarenal capsules and the 
sympathetic nervous apparatus. 

The suprarenal capsules are the organs most regularly presenting 
anatomic alterations in Addison’s disease. Lewin’s extensive statistics 
show: Typical cases of Addison’s disease with healthy suprarenal cap- 
sules, 12%; typical cases of Addison’s disease with diseased suprarenal 


334 | ADDISON’S DISEASE. 


capsules, 88% ; diseases of the suprarenal capsules without bronzing of the 
a 28%; diseases of the suprarenal capsules with bronzing of the skin, 
2%. 

In most cases of Addison’s disease, tuberculosis of the suprarenal cap- 
sules is present in all its manifestations. As arule, both organs are simul- 
taneously affected, sometimes so completely that not a trace of normal 
tissue can be demonstrated. Both organs are not always alike affected 
by the disease. In some cases the two organs are only partially diseased ; 
in others only one organ is affected and may be more or less completely 
destroyed. In the majority of cases the tubercular process runs an ex- 
ceedingly chronic course, characterized by central caseation and periph- 
eral cicatrization. The latter condition is not confined to the organ itself, 
but involves the capsule and pericapsular connective tissue, thence ex- 
tending in all directions. Fibrous indurations thus form which may ex- 
tend to the celiac ganglion, penetrating it and enveloping the nerve-fibers 
passing from it to the suprarenal capsules and other nerve-bundles; they 
may extend also to the liver and duodenum. 

The bacilli of tuberculosis have been demonstrated repeatedly in the 
caseous suprarenal capsules. In but one case was the caseation caused 
by the bacillus of pseudo-tuberculosis of Hayem and Lesage. 

Malignant tumors of the suprarenal capsules, primary as well as sec- 
ondary, are next in frequency among the causes of Addison’s disease. 
Both medullary and scirrhous cancers occur, and angiosarcoma and 
melanosarcoma are found as well as the usual varieties of sarcoma. In 
isolated cases various other tumors of the suprarenal capsules are regarded 
as the cause of Addison’s disease—namely, adenoma (suprarenal struma), 
syphiloma, echinococcus cyst, and hematoma. 

Formerly chronic interstitial inflammation of the suprarenal capsules 
played an important role in the etiology of Addison’s disease, but in the 
majority of cases, if not in all, this condition should be considered as a form 
of tuberculosis. 

In a considerable group of cases simple or inflammatory atrophy of 
the suprarenal capsules, in a few cases hypoplasia of otherwise healthy 
organs or even the absence of one or both suprarenal capsules, have been 
advanced as causes of Addison’s disease. 

In contradistinction to all these processes, which are characterized by 
a more or less chronic course, Virchow observed an acute hemorrhagic 
inflammation of the suprarenal capsules in a few instances of rapidly pro- 
_gressing Addison’s disease. 

Exact microscopic investigations of the changes in the sympathetic 
system have only recently been made. Lesions have been observed both 
in connection with, and in the absence of, diseases of the suprarenal cap- 
sules. They may affect, first, the sympathetic ganglia in the substance of 
the suprarenal capsules and the pericapsular ganglia occasionally present, 
then the nerve-fibers running from the suprarenal bodies to the celiac 
ganglion, the ganglion itself and the solar plexus, in addition the sym- 
pathetic tracts, extending from this point even as far as the cervical 
ganglion of the ganglionated cord, and finally the splanchnic nerve. Very 
often the changes in the ganglia of the suprarenal body, in the pericap- 
sular ganglia, the fibers of the suprarenal and solar plexuses, and in the 
celiac ganglion itself are dependent upon tubercular disease of the supra- 
renal bodies and the resulting cicatrization; they may result also from a 
localization of the tubercular process in the abdominal lymphatic glands, 


PATHOLOGIC ANATOMY. 335 


Compression by other kinds of glandular tumors (carcinoma, sarcoma, 
pseudo-leukemia, leukemia) or by aneurysm of the abdominal aorta is 
rare. Even simple inflammatory processes in the retroperitoneal space 
have been observed as the cause of such degenerations. 

Minor alterations in various parts of the sympathetic system have 
repeatedly been considered by some authors as pathologic, while this is 
denied by others. Certain alterations, although admitted to be patho- 
logic, occur not only in Addison’s disease, but also in all other cachectic 
conditions, especially in pulmonary tuberculosis. For this reason, and 
also on account of their inconstant occurrence in typical Addison’s dis- 
ease, such lesions cannot be considered as the anatomic basis of this affec- 
tion. 

Extensive alterations of the sympathetic system are found in a com- 
paratively small number of cases. 

Kahlden, Fleiner, Ewald, and Brauer have made the most thorough 
histologic investigations of these conditions. The lesions of the ganglia 
comprise alterations in the ganglion cells, in the blood-vessels, and in the 
connective-tissue sheaths. The ganglion cells are more or less pigmented, 
the cells are often shrunken within their capsule, and the nuclei are 
disintegrated. Sometimes, indeed, the capsule contains only hyaline 
fragments. Hyaline degeneration of the walls of the blood-vessels and 
small-celled infiltration of the adventitia have been observed. Foci of 
small-celled infiltration, apparently originating in the blood-vessels, were 
repeatedly found in the connective-tissue sheaths of the ganglia. These 
alterations did not affect all or even a majority of the cells of the ganglia 
outside the suprarenal bodies, well-preserved cells being abundantly asso- 
ciated with degenerated ones. 

The changes in the nerve-fibers were manifested by irregularities of 
outline, globular or spindle-shaped swellings alternating with abnormal 
thinness of the fiber (beaded appearance), fragmentation or transforma- 
tion of the medullary sheath into flakes or minute granules, and in places 
almost complete destruction of the medullary fibers. Only occasional 
fibers as arule were involved. Jurgens found complete gray degeneration 
of a splanchnic nerve from compression by an aortic aneurysm. Extreme 
atrophy of these nerves was found by Fleiner; moderate atrophy was 
noted by Ewald. 

Feiner believes that the spinal ganglia also bear a causal relation to 
Addison’s disease. In two cases, in addition to changes in various por- 
tions of the sympathetic apparatus, he found degenerative changes in the 
spinal ganglia and the extramedullary portions of the posterior roots, in 
the vagus, and in a few peripheral spinal nerves. 

Several investigators also have found alterations in the spinal cord. 
Demange, as early as 1877, reported a case of Addison’s disease with 
tuberculosis of the suprarenal capsules in which he found also granular 
degeneration of the cells of the anterior horn and medullary destruction of 
the nerve-fibers in the lumbar cord. Burresi and Semmola also found 
alterations of the spinal cord which they considered of great importance; 
further, Abegg observed in one case small-celled infiltration of the pyra- 
midal tracts of the dorsal cord; and, finally, Kalindero and Babes demon- 
strated a striking increase of neuroglia and thickening of the blood-vessels 
in the antero-lateral tracts and posterior horns, and atrophy and medul- 
lary degeneration of the nerve-fibers of the posterior roots. Vucetic 
found degenerative changes in the posterior roots, particularly of the 


336 ADDISON’S DISEASE. 


lumbar cord. Kahlden found similar changes in several but not in all 
cases. He proved, however, that this was not a specific result of disease 
of the suprarenal capsules, because he found the same changes in the 
spinal cord of two phthisical patients without disease of the suprarenal 
bodies. 

Pathologic alterations in a number of other organs have been demon- 
strated in Addison’s disease; some of these are to be considered as sequels, 
others as complications. In the main, serous infiltration, anemia, hyper- 
emia, or atrophy, with edema or thickening of the meninges, were re- 
peatedly observed; in addition, though more rarely, cancerous nodules, 
tubercles, and multiple small areas of softening; several times tubercular 
meningitis, and in one case disease of the hypophysis. 

The thyroid gland was often strikingly small and bloodless; in other 
cases it was enlarged, or the seat of cancerous metastases. Occasionally, 
persistence of the thymus gland was noted. In more than half of all cases 
tuberculosis of the lungs and mediastinal glands was found; frequently 
pleural adhesions and in a few cases metastatic cancer in the lungs and 
pleura; other changes were unimportant or accidental. Brown atrophy 
of the heart, sometimes extreme, was very often present; fatty degenera- 
tion also was observed, and hypertrophy in rare instances and only in the 
presence of complications. Atheromatous degeneration of the valves and 
blood-vessels, even in young people, was frequently observed. 

In the digestive tract the following changes were found: injection, 
catarrhal swelling, and ecchymoses of the gastric mucosa; frequently a 
decided swelling of the solitary follicles and Peyer’s patches often com- 
bined with ulceration, and, in addition, very extensive slate-colored 
pigmentation of the mucous membrane and follicles, and in a large 
number of cases tubercular ulcers. Tuberculosis and carcinoma were 
of frequent occurrence in the mesenteric and retroperitoneal glands. 
The abdominal wall, mesentery, and omentum contained in many 
cases large accumulations of fat, although the rest of the body might 
be emaciated. The liver has variously been reported as small or 
large, containing much or little blood, amyloid or fatty, infiltrated 
with cancerous nodules or with tubercles. The spleen was often 
simply enlarged or in a condition of amyloid degeneration. As a rule, 
the pancreas was found to be large, hyperemic, dense or cancerous. Car- 
cinoma or tuberculosis of the genital tract was observed frequently; 
nephritis’ was an infrequent complication. In the osseous system, in ad- 
dition to metastases of malignant growths and caries (especially of the 
vertebral column), a wine-colored staining of the marrow was observed by 
Gabbi in two cases. The muscles in many cases were described as thin or 
lacking (“geschwunden’’). The histologic alterations in the skin will be 
more fully described elsewhere. | , 


SYMPTOMS AND COURSE. 


In the year 1855, Addison described the disease which has since been 
called by his name, and which he was the first to associate with alterations 
in the suprarenal capsules, as an idiopathic anemia, characterized by ex- 
treme loss of power and apathy, digestive and nervous disturbances, and 
bronzing of the skin. After running a chronic course with symptoms of 
progressive cachexia, it invariably ends in death, which may be attended 


SYMPTOMS AND COURSE. 837 


by violent symptoms, such as uncontrollable diarrhea, coma, or convul- 
sions. : 

After more than forty years, during which the disease has aroused the 
greatest interest, there is scarcely anything essential to be added to this 
description. 

Addison’s disease is, on the whole, rather rare. It occurs more fre- 
quently in men (60 to 67%). The majority of cases occur between the 
ages of fifteen and sixty; it rarely occurs in children and the aged, al- 
though it has been observed in them. The youngest case recorded was a 
child three years old, the oldest had already reached eighty years. 

The following have been mentioned as causes of Addison’s disease: 
malaria, alcoholism, exposure to cold, blows in the region of the kidney, 
malnutrition, mental worry, and pyschic disturbances—all of which 
have been regarded as important in the etiology of a great variety of dis- 
eases. A few of these may be of actual importance by weakening the 
organism and favoring the acquisition of tuberculosis, which is the most 
frequent anatomic lesion of Addison’s disease. 

[Interesting in this connection is the communication of Fleming 
and Miller,* who observed five cases—the mother and four children— 
of Addison’s disease in the same family.—Eb.] 

In the vast majority of cases the onset is so insidious that the 
patient is unable to tell when the disease began. As a rule, the first 
symptom noticed is early fatigue in the performance of accustomed 
duties. This is intermittent at the outset, but gradually increases and 
develops into a permanent sense of weakness and exhaustion accom- 
panied by a striking indisposition to work. In the beginning of uncom- 
plicated cases the lack of power and debility frequently present a striking 
contrast to the relatively good general appearance of the patient and 
the abundance of abdominal fat. Indeed, the patient for a long time 
may be free from all other symptoms of disease. 

Almost constantly the second cardinal group of symptoms—the 
disturbances of the digestive apparatus—gradually appear. The appe- 
tite little by little fails, the patient complains of a sense of pressure 
in the epigastrium, eructations, sometimes pyrosis, very often discomfort, 
nausea, and, as the disease progresses, more and more frequent vomit- 
ing, obstinate constipation, more rarely diarrhea, or an alternation of the 
last two conditions. There is very often intense epigastric pain radiating 
to the hypochondriac regions, and sometimes, by reason of its intensity, 
dominating all other features of the disease; or there may be similar 
fixed or radiating neuralgic pains in the lumbar and sacral regions. In 
other cases vague pains in the abdomen and extremities are complained 
of. Sometimes there are transient, severe pains in the various joints, 
apparently of a rheumatic nature, and occasionally accompanied by 
swelling. 

Sooner or later the third and most striking cardinal symptom of 
Addison’s disease is added—namely, a dark pigmentation of the skin. 

As a rule, this begins very gradually and inconspicuously, so that 
the patient himself knows nothing of it and has his attention first called to 
it by other persons. At the outset the color is a dirty yellow, yellowish- 
brown, or smoky gray; later, the shade deepens until it is a pronounced 
bronze or black, as in the negro, presenting sometimes a peculiar greenish 
or bluish shimmer. The pigmentation generally begins in parts of the 

| * Brit. Med. Jour., April 28, 1900, pp. 10-14. 
22 


338 ADDISON’S DISEASE. 


skin exposed to the sun’s rays, and in those naturally rich in pig- 
ment; the regions next affected are those which are considerably com- 
pressed by the clothing, and, finally (and very typically), the mucous 
membrane of the mouth, from the lips to the posterior pharyngeal wall, 
is involved, and more rarely other mucous membranes. The parts, 
therefore, which are first affected are the face, backs of the hands, genitals 
and nipples, axillary folds, and extensor surfaces of the joints, and these 
areas, as the pigmentation progresses, always present the deepest color. 
The pigment is never distributed uniformly over the whole surface of 
the body, but, as a rule, certain areas of the skin are very deeply colored, 
or the pigmentation may appear in the form of scattered, large, irregular, 
and faintly outlined spots interspersed with lighter areas of skin which 
are sometimes strikingly free from pigment (vitiligo). There may be 
quite often also, scattered over diffusely pigmented areas of skin, more 
sharply circumscribed, intensely dark spots varying in size from a poppy 
seed to a hemp-seed or lentil. Upon the mucous membranes the pig- 
mentation is very rarely diffuse, but generally regularly arranged in 
fairly well-defined spots or stripes: conjunctive, nail-beds, and hair 
present only rarely conspicuous alterations. 

Disturbances of other organs also are noted. In the nervous system 
there exist almost constantly very striking apathy, psychic depression, 
low spirits, and loss of energy. Very frequently, from the onset of the 
disease, the patient complains of insomnia, in rare cases somnolence; 
frequently there are headaches of varying inténsity and duration, and 
in some cases loss of memory or impairment of intellect. In a few cases 
temporary delirium and mild cerebral disturbances have been observed. 
Dizziness, ringing in the ears, spots before the eyes, and a tendency to. 
fainting are very frequent conditions. The symptoms of anemia, such 
as pallor of the skin and mucous membranes, murmurs in the veins of 
the neck and over the heart, may be absent for a while, but are, as a rule, 
always present in the later stages in addition to emaciation and cachexia. 
The intensity of these symptoms does not correspond to the extreme 
loss of strength or to the conditions observed in other cachexias (e. g., 
tuberculosis or cancer). The pulse is almost invariably very small and 
compressible, as a rule rapid, rarely slow or irregular. Upon ausculta- 
tion the heart-sounds are feeble. 

Palpitation and dyspnea may occur even in uncomplicated cases; 
the former particularly upon exertion or mental excitement, attended 
as a rule by a very rapid, small, and irregular pulse. In uncomplicated 
cases the temperature is usually normal or, as the disease progresses, 
it may become subnormal, the latter condition often being attended by 
a feeling of cold. In the absence of renal complications no important 
urinary symptoms are noted. Disturbances of menstruation have re- 
peatedly been observed. Dropsical swellings are of the rarest occurrence 
even with pronounced cachexia. 

The course of this disease is essentially chronic. The symptoms 
may remain stationary for a time or may even be considerably improved, 
but eventually they become more and more severe. The loss of power 
and debility may become extreme, but are practically never accom- 
panied by actual paralysis. Appetite is completely lost, but the thirst 
not infrequently is intense; vomiting becomes repeated, and hiccough 
often appears. With the continuance of these symptoms and increasing 
prostration, death may occur from cardiac weakness; more frequently 


SYMPTOMS AND COURSE. 339 


the fatal issue is preceded by an acutely occurring violent termination. 
The temperature rises and may become very high. Diarrhea takes the 
place of constipation. Vomiting and diarrhea may be uncontrollable. 
Alarming cerebral symptoms appear, such as delirium, more rarely 
psychoses with motor excitement, frequently choreiform spasms or even 
epileptiform convulsions, finally collapse and coma; in some cases the 
condition is not unlike the terminal stage of typhoid fever. After it 
has lasted for several days, death as a rule ensues. 

The duration of a typical case such as has just been described is at 
least a number of months, perhaps a few years. There are, however, 
many variations from the type both in symptoms, duration, and course. 

In the first place, the disease may set in acutely with symptoms 
of digestive disturbance, after which it may pursue a chronic course. 
Such cases are really quite rare, although Averbeck believed they formed 
the majority. Further, the sequence of the individual symptoms and 
their intensity may widely vary. Not infrequently digestive disturbances, 
more rarely pigmentation of the skin, form the first feature. One or the 
other of the cardinal symptoms (even melanoderma) may be absent or 
appear very late and be only imperfectly developed. 

The disease not only may begin suddenly with epigastric pain, diar- 
rhea, headache, and fever, but also may terminate fatally in a short time, 
even in less than a month, with symptoms resembling an acute toxemia, 
cholera, or typhoid fever. Such cases are exceedingly rare. [Sergent 
and Bernard * report an interesting series of cases of sudden death occur- 
ring in acute and subacute Addison’s disease. They consider it due to an 
acute or subacute functional insufficiency of the gland, superadded to 
the existing pathologic process and bearing the same relation to the 
latter that jaundice bears to acute or chronic hepatitis. Such adrenal 
insufficiency should be borne in mind in medicolegal cases as a possible 
explanation of sudden death.—Ep.] On the other hand, the duration 
of the disease may be unusually prolonged. In such cases the symptoms 
remain quiescent even for several years, or may show considerable im- 
provement, during which the patient feels almost entirely well and the 
physician even may hope that there is a permanent cure. As a rule, 
this improvement is suddenly interrupted by an acute exacerbation, 
speedily ending in death. The longest duration ever reported was ten 
to thirteen years. 

Amid all these variations nothing but the fatal termination can be 
predicted with absolute certainty. The few published cases of recovery 
from Addison’s disease are open to grave doubts as to the accuracy 
of the diagnosis. 

The most striking deviations from the type of this disease are brought 
about, as has already been mentioned, by the remarkably frequent 
complications. Tuberculosis heads the list of these both in frequency 
and variety of manifestation, since the localization of this affection in 
the suprarenal capsules is the most common cause of Addison’s disease. 

Tuberculosis is rarely actually confined to the suprarenal capsules. 
Minor manifestations in other organs do not obscure the symptoms of 
Addison’s disease. 

If in addition to tuberculosis of the suprarenal capsules there is 
extensive bacillary disease of the lungs alone or of other organs in addition, 
especially the intestinal canal; or if a general miliary tuberculosis has 

* Arch. gen. de méd., 1899, 11, 27. 


340 ADDISON’S DISEASE. 


been originated by the process in the suprarenal capsules, then the 
symptoms of Addison’s disease may not only be strikingly modified and 
obscured, but they may be forced entirely into the background and the 
diagnosis rendered impossible. Under these circumstances marked 
emaciation, intermittent fever, cough, night-sweats, diarrhea, and diges- 
tive disturbances are present from the outset. The localization of the 
tuberculosis elsewhere may dominate the disease; for instance, meningeal 
symptoms or paralyses (vertebral caries). 

Such symptoms as loss of power and vomiting, pain, and anemia, 
do not justify the diagnosis of a localization of the disease in the supra- 
renal capsules; nor does pigmentation even, for this may occur in ordinary 
tuberculosis. In like manner cancerous cachexia, and in rare cases 
syphilis, may influence the course of Addison’s disease and may render 
its diagnosis difficult or impossible. 

In addition to this general description of the disease, it will be neces- 
sary to consider in detail certain symptoms or groups of symptoms 
which are characterized by special variability or complexity. 


CHANGES IN THE SKIN AND MUCOUS MEMBRANE. 


Pathologic pigmentation is the only alteration with which we have 
to deal; it is the most striking sign of Addison’s disease, in consequence 
of which this affection has frequently been termed suprarenal melasma, 
bronzed skin. 

Pigmentation is only very rarely the initial symptom, but as a rule 
makes its appearance sooner or later after the occurrence of loss of power 
and disturbances of digestion. As the disease progresses the intensity 
of the pigmentation and the severity of the other symptoms run a fairly 
parallel course. There may be temporarily almost complete disap- 
pearance of the pigment during the occasional remissions of the disease. 
On the other hand, many cases have been observed where, in spite of 
remission of all other symptoms, the pigmentation of the skin remains 
unchanged. In one case reported by Labadie-Lagrave the melanoderma 
disappeared just before death. 

In a few cases in which melanoderma was absent until the end of 
the disease, the diagnosis of Addison’s disease was based upon the pro- 
gressive loss of power and digestive disturbances for which there was no 
other explanation. The principal lesion found at autopsy was disease of 
the suprarenal capsules (Fenwick). To be historically accurate, we 
should, as Lewin actually did, exclude cases without bronzed skin from 
the group of Addison’s disease. On the other hand, too strict adherence 
to the integrity of the three chief symptoms of Addison’s disease would 
lead to an imperfect understanding of the deviating types. Such a classi- 
fication is also justified by many analogies. 

For example, were those cases only to be regarded as Basedow’s 
disease which present all the characteristic symptoms, as tremor, exoph- 
thalmus, struma, and tachycardia in classic form, it would be necessary 
to exclude all those cases in which one or the other symptom was lacking. 
Yet such cases are sufficiently well known and recognized as “formes 
frustes” of the disease. In like manner scarlet fever may exist without 
arash, and pellagra without eruption. It is probable, therefore, that 
eases of Addison’s disease without melanoderma will maintain their 
place among the clinical types of the disease. 


SYMPTOMS AND COURSE. 341 


Nevertheless melanoderma is a very important lesion of Addison’s 
disease, particularly from the standpoint of diagnosis, and for this reason 
its clinical peculiarities, especially of location, must carefully be con- 
sidered. 

Beginning with the head, attention first may be called to the different 
ways in which this pigmentation may occur upon the scalp. Cases 
have been reported in which the pigmentation ceased more or less abruptly 
at the border of the hair and the scalp remained entirely free from pig- 
ment. In others a uniform and even very intense pigmentation of the 
scalp was noted. As a rule, the hair itself is not pigmented, although 
in a few cases a change of color from light brown to dark brown or even 
black has been observed. ‘The skin of the face is one of the most deeply 
pigmented regions, but otherwise presents little that is peculiar. Ger- 
hardt described the frequent and characteristic occurrence of a very 
dark band of pigment along the margins of the lids. 

The skin of the trunk as a whole is of a lighter shade, interspersed 
with relatively small areas of darker pigmentation. The distribution 
of the latter is dependent upon the normal excess of pigment in certain 
parts of the body and upon the constriction of clothing. The former 
manifests itself in an intense pigmentation of the areole of the nipples, 
especially in women who are or have been pregnant, of the anal folds, 
and of the genitals; the latter especially in men, in whom the penis and 
scrotum. are frequently described as almost black. In women who 
have been pregnant the linea alba also shows a very dark color. 

The effect of constricting clothing is most noticeable in thin people. 
In these there may be remarkably deep pigmentation, not only of the parts 
of the body affording support to the clothing, but also of all the bony 
ridges and prominences. Not only are the shoulders, axillary folds, and 
iliac crests very deeply pigmented, but also the skin over the clavicles, 
manubrium sterni, spines of the scapule, spinous processes of the verte- 
bree, and tuberosities of the ischia. In women and men who wear belts 
the waist is frequently encircled by avery intense brown ring corresponding 
to the position of the belt. The occurrence also of widely scattered, 
deeply pigmented spots over the whole surface of the trunk has already 


’ been mentioned. 


In the extremities the pigmentation usually is deepest on surfaces ex- 
posed to the sun and on the extensor surfaces and prominences near the 
joints. Onthe palms and soles the pigmentation is faintest ; in some cases 
there may be none at all, in others it may be faint or in spots or only on 
the crests of such folds as may be present. The absence of pigmentation 
from the bed of the nails is quite characteristic, although not without fre- 
quent exceptions. Yet even when the pigmentation of the matrix of the 
nails is present, it is rarely so intense as in the vicinity, and sometimes 
appears as distinct longitudinal stripes. 

The effect of accidental cutaneous lesions upon the pigmentation 
finally should be mentioned. Every abnormal irritant acting upon a cir- 
cumscribed area of skin produces.some effect upon its color. Local para- 
sitic diseases or eczema attended by itching and scratching cause a darker 
pigmentation; blisters and cupping usually produce a like effect. Cuta- 
neous scars may be deeply pigmented or may be entirely free from pig- 
ment; in the latter instance, however, they are surrounded by a dark 
brown areola. 

_Areas completely devoid of pigment may arise without any apparent 


342 ADDISON’S DISEASE. 


cause in the midst of this diffuse pigmentation. Such patches of vitiligo 
are inconstant, but when present in any number produce a very striking, 
often mottled appearance. One case is reported of the sudden appear- 
ance of vitiligo patches attaining a diameter of 5 cm. 

So much for the typical pigmentation. Not every case of Addison’s 
disease presents pigment in all these situations, or if present the intensity 
of the pigmentation may vary. Not infrequently the pigment is confined 
to certain parts of the body, as the upper extremities, or the face and neck; 
or a certain part of the body ordinarily pigmented may remain entirely 
free. It should again be stated that the occurrence of Addison’s disease 
without pigmentation is recognized. 

Pigmentation of the mucous membranes is of the greatest importance, 
particularly in differential diagnosis. In the majority of cases it appears 
here later than in the skin, and is only rarely diffuse. This pigmentation 
is of regular occurrence only in the mucous membrane of the mouth. 
Rarely the lips may present a diffuse, purplish or chccolate-brown colora- 
tion, much more frequently the pigment appears in the form of brown or 
black spots or lines, especially at the angles of the mouth. There is often 
a horizontal line of pigment on the mucous membrane of the cheeks, form- 
ing a continuation of the fissure of the lips. Upon the mucous membrane 
of the gums, hard and soft palate, and tongue, the pigment occurs almost 
exclusively in the form of spots. In very exceptional cases a smoky-gray 
coloration of the tongue and posterior pharyngeal wall has been observed. 
Pigment spots upon the larynx and small hemorrhages in the oral mucous 
membranes have been seen in rare instances. 

No constant changes are found in the other mucous membranes. It 
was stated for a long time that the ocular conjunctive, more particularly 
over the sclerz, never participated in the universal pigmentation, but, 
on the contrary, were conspicuous for their striking pearly-white color. 
Upon superficial examination this statement may still seem to hold good, 
but upon closer examination numerous deviations will be found. Although 
the whole conjunctiva is never pigmented to a noticeable degree, it is not 
unusual to find (as Leva particularly reports) small and not very dark 
spots of pigment upon both palpebral and ocular conjunctive. 

Pigmentation of the mucous membranes of the genitals is now and 
then noted. The nymphe and vaginal mucosa have been described as 
“black,’? and on the glans penis spots of brown pigment are quite fre- 
quently seen. 

Exceptional cases of genuine Addison’s disease may run their course 
and terminate fatally without any pigmentation of the mucous mem- 
branes. More rarely the mucous membranes are pigmented but the skin 
isnot. It is evident that both groups of cases present considerable diag- 
nostic difficulties. 

Apart from the occurrence of pigmentation, the skin and mucous 
membranes very seldom present any other alterations. As a rule, the 
skin is smooth and elastic; in rare cases the onset of pigmentation is 
attended by itching; dryness and desquamation have been observed, and, 
onthe other hand, excessive perspiration. 

In several cases a very disagreeable odor from the skin has been 
noticed, and in one case it was described as fish-like. In a few instances 
the breath has had a similar unpleasant odor. In one case a scanty 
roseolous eruption was seen combined with disease of the joints; in an- 
other case an eruption resembling purpura. Among complications, 


SYMPTOMS AND COURSE. » 348 


molluscum contagiosum, very rarely furunculosis, and psoriasis have been 
observed. 

The hair presents little that is abnormal beyond the occurrence of pig- 
mentation which may affect both the hair of the head and the beard. In 
several cases loss of hair was reported with or without subsequent restora- 
tion; more rarely the hair has turned gray during the course of the dis- 
ease; this took place in individuals of relatively advanced age. Alopecia 
areata is of rare occurrence. 


DISTURBANCES OF THE NERVOUS SYSTEM. 


The most frequent and, as a rule, the most constant symptom from 
the beginning to the end of Addison’s disease is the extreme physical and 
psychic loss of power, which is the result, at least in part, of injury to the 
nervoussystem. This condition is first manifested by the striking rapidly 
occurring fatigue in the pursuit of customary duties formerly carried on 
without difficulty. At first the exhaustion is intermittent, but soon in- 
creases in frequency and finally becomes permanent. As the disease 
progresses the patients not only become incapable of performing even a 
very simple task, but show an increasing distaste for activity and move- 
ment of any kind. Finally this may go so far that the patients lie passive, 
and even eating and drinking are distasteful. Psychic symptoms develop 
simultaneously—for example, increasing apathy, indifference, and ill 
temper; there is often complete loss of energy, the patients are low- 
spirited and apathetic, drooping, or actually melancholic; other patients 
may be angry or morose, obstinate and sullen. This loss of power is also 
manifested by diminished resistance to external injuries. A_ slight 
excess (alcoholic), a mild infection, such as a simple sore-throat, 
otherwise speedily overcome, may be attended by serious sequels and 
may produce an aggravation of the condition ending in death. 

Among the remaining nervous symptoms, cerebral symptoms must first 
be mentioned. Obstinate insomnia is one of the most frequent, and some- 
times is anearly symptom. Less often somnolence is observed, or the two 

conditions may alternate. In a few cases very frequent yawning has been 
- reported. | 

Headaches are frequent, but vary extremely in intensity, duration, 
character, and location. Sometimes their great intensity renders them 
tormenting. Vertigo, ringing in the ears, specks before the eyes, and a 
tendency to fainting are frequent symptoms. Fainting may occur in well- 
nourished, not visibly anemic individuals upon the slightest provocation; 
é.g., upon simply touching the epigastrium, sitting up in bed, or after pro- 
longed standing. Coincidently the face becomes pale, the pulse almost 
disappears, and a cold sweat often breaks out. 

The above-mentioned apathy may be accompanied by a progressive 
impairment of mental power, manifesting itself as loss of memory and in- 
telligence, thoughtlessness, but in isolated cases as stupidity, dementia, 
or idiocy. In other cases periods of stimulation or excitement are ob- 
served consisting of anxiety, restlessness, or jactitation, all characterized 
by a certain feebleness of action. Muscular tremors and choreiform 
twitchings have been noted in a number of instances; severe general con- 
vulsions and epileptiform attacks very rarely occur before the terminal 
stage. Raving, transient.delirium, <3 hee and religious insanity have 
all been observed a few times. 


344 » ADDISON’S DISEASE. 


The organs of special sense are very rarely affected, and then only to a 
slight degree. Impairment of smell and taste, partial loss of hearing and 
vision, and in one case night-blindness are reported. 

Although muscular weakness may be extreme, actual paralysis does 
not occur in Addison’s disease unless complicated by vertebral caries, cere- 
bral hemorrhage, etc. On the other hand, the sensory nerves are often 
affected, giving rise chiefly to pain, which not infrequently is an early 
symptom. The patient may complain of vague pains in all the extremi- 
ties, or there may be neuralgic pains confined to particular regions, such 
as the epigastrium, hypochondria, sacral and lumbar regions, the extremi- 
ties, and sometimes even the joints. The pain in the joints may be 
accompanied by transitory swelling, so that the condition has been 
correctly diagnosticated as articular rheumatism. Paresthesiz are of 
rare occurrence, consisting of a sense of numbness or local death, itching 
of the fingers, and formication; these are combined with pallor and cyan- 
osis, and are regarded as vasomotor neuroses. Diminished sensibility is 
still more rare. 

As yet, very little attention has been paid to the reflexes. In the pub- 
lications of the last few years numerous contradictory statements are 
found. Some of the reflexes are said to be normal or even increased, 
others are diminished or absent (especially the patellar reflex). 

The pupillary reflexes also are not uniform; they are present as a rule; 
in a few cases they were observed to be sluggish. 

In the last stage of the disease violent disturbances of the nervous sys- 
tem very often appear. They are manifested by delirium, hallucinations, 
periods of intense, even maniacal excitement; further, epileptiform con- 
vulsions followed by collapse, somnolence, and loss of consciousness, and 
finally complete coma. Irregular respiration, even Cheyne-Stokes’ breath- 
ing, has been reported in several instances. Ina few cases incoordination 
of the movements of the eye, rigidity of the neck, pinhead pupils or in- 
equality of the pupils, spasms of the muscles of the back, and involuntary 
micturition have been observed without any meningitic lesions being dis- 
coverable at autopsy. However, the last stages of the disease may be 
complicated by actual tubercular meningitis or by solitary tubercles in 
the brain which may produce similar symptoms. 


DISTURBANCES OF CIRCULATION. 


These may be central or peripheral. There is often progressively in- 
creasing weakness of the heart. The cardiac impulse is feeble; the sounds 
of the heart are faint; the pulse is small, weak, and generally somewhat 
accelerated. In rare cases slowing of the pulse has been observed. 

Even moderate physical exercise or excitement may cause extreme 
excitation of the heart’s action associated with palpitation and irregular- 
ity. Leva observed stenocardial pain in the region of the heart, associated 
with palpitation and dyspnea. Rarely anemic murmurs are heard over the 
heart and blood-vessels. The complication with atheromatous changes 
repeatedly observed even in young persons would be manifested by the 
well-known symptoms referable to the heart and vessels. Forcible pulsa- 
tion of the abdominal aorta is frequently seen, and is in striking contrast 
to the feebleness of the peripheral pulse. As the heart grows weaker in 
persons not anemic, more or less pronounced cyanosis also occurs. 


SYMPTOMS AND COURSE. 345 


CONDITION OF THE BLOOD. 


As yet, the examinations of the blood in Addison’s disease have yielded 
very contradictory results. 

Addison himself regarded the disease as the result of a specific anemia, 
and reported an increase of white blood-corpuscles in one case. Aver- 
beck also believes Addison’s disease to be a special type of anemia which 
is invariably fatal, and which depends less upon alterations in the elements 
of the blood than upon a diminution of its total mass and alteration of its 
composition. Buhl observed a considerable diminution of red corpuscles 
without leucocytosis, and a great reduction or complete absence of fibrin. 
Averbeck, on the contrary, reports a case in which the blood was very 
readily coagulable and there was a great tendency to the formation of 
rouleaux without any leucocytosis. The observations of other authors 
are just as contradictory. Some report normal conditions; others, oligo- 
cythemia, occurrence of microcytes and poikilocytes with diminution of 
hemoglobin; and, finally, the leucocytes are reported as increased, dimin- 
ished, or normal. 

According to Nothnagel, anemia is not a primary symptom of Addi- 
son’s.disease. He was unable to demonstrate either leucocytosis, a dimi- 
nution in number or disintegration of red corpuscles; or loss of hemo- 
globin or rouleaux formation; or, finally, the occurrence of free pigment 
in the blood. The recent examinations show no constant changes. 

The number of red corpuscles and percentage of hemoglobin have re- 
peatedly been proved to be normal or very slightly diminished. In afew 
cases they were increased, but this is readily explained by the concentra- 
tion of the blood in consequence of profuse diarrhea. The quality and 
quantity of the leucocytes presented no material differences. An increase 
of eosinophiles was not observed (Kolisch and Pichler). 

Tschirkoff carefully estimated the amount of hemoglobin. He found 
it but little changed even in late stages of the disease when the red cor- 
puscles were moderately reduced in number. In severe cases he found a 
relative increase of reduced hemoglobin, and apparently methemoglobin 
also was present in considerable quantity. 

These recent observations confirm Nothnagel’s view that pronounced 
anemia does not form a part of Addison’s disease. The abnormal blood- 
counts reported by several authors are explained by the occurrence of 
complicating tuberculosis or cancer of other organs or by the undue de- 
velopment of certain symptoms, as, for example, anorexia, obstinate 
vomiting, or severe diarrhea. 

Very recently F. H. Mueller found in the blood of a patient with Addi- 
son’s disease who was taking large quantities of milk, large numbers of 
actively motile and glistening granules in addition to poikilocytosis. These 
granules were not modified by several days’ exposure to osmic acid and 
were not soluble in acetic acid. He found the same elements constantly 
in normal blood, although in diminished numbers. 

In this connection the results of the examinations of the blood in two 
cases of Addison’s disease under my observation are reported. 

The first patient was a young girl who came from Mahren to my hos- 
pital in Vienna. In addition to pigmentation of the skin, particularly on 
the fingers, forehead, neck, and lower extremities, small spots of pigment 
were present also on the mucous membrane of the gums, tongue, and soft 


346 ADDISON’S DISEASE. 


palate. The girl was pale, and anemic murmurs were detected over the 
veins and heart. She had taken iron for chlorosis, but without avail. 
Her chief complaints were general. weakness, psychic and physical slug- 
gishness. I made the diagnosis of Addison’s disease and prescribed the 
internal administration of suprarenal extract. The patient continued 
this treatment at her home with temporary benefit. Several weeks later 
her relatives informed me that she had died, apparently of an-intercurrent 
pleurisy. There was no autopsy. 

On the day after the above examination was made, preparations of 
blood, stained by Ehrlich’s method, showed practically no changes in the 
red corpuscles, especially no polychromatophilia in Ehrlich’s sense, and 
no abnormal coloration of the plasma. The number of leucocytes was 
apparently normal. The differential count was as follows: 


Ol aticat Beep nies. SP siaMareac ware acuee eee hc aaa tee OG 
HOsMOPliiles si s4.ch oe Goan ae Rae are eee te meee ya Wee ye We ee MO 
PPrapsitionas forsee. 2s oo tht a reece ane aan aA s 
Large mononuclear . ee isua ya we a ayaa nah kecmecte 
Small mononuclear (lymphocytes) . Seeger eee ments A Gi 


The considerable increase of mononuclear forms, especially of lympho- 
cytes, in this case is striking. 

The second patient was a middle-aged woman who came to me after 
the diagnosis of Addison’s disease had already been made by Nothnagel. 
In addition to a faint, diffuse pigmentation of the face and hands this pa- 
tient presented a few scattered spots on the mucous membrane of the 
cheeks and gums and a slight pallor of all the mucous membranes, but 
otherwise no abnormal appearances. The blood-pressure was diminished, 
measuring, according to Basch, 125 mm. in the radial artery. I first saw 
the patient in the spring of 1896. At that time the examination of the 
blood was as follows: 


Redscorpuselese: icc cicnedana ae teneeeenee: eee 637 
White corpuscles — inion Gee enn ionigi a mu ae en co eRRAeRG 6,950 J ~ ° 

Hemoglobin ees Ls dhe cur aea denen en Bawa iia sien Gees sate SOD 
Color-index . TA NF vile tpi na lege Nets aden it Benny ee 


In the fresh preparation, blood-plates and fibrin present in normal 
quantity, rouleaux formation good; in the stained preparation, marked 
difference in the size of the red corpuscles, but no actual macrocytes or 
microcytes. No poikilocytosis, no nucleated red corpuscles. Differen- 
tial count as follows: 


Potynuclear neutrophilog r+ i600 s.0 05s oaaweais etiee 4 40d oe 
BOSNIODUUCA. 26/35 ua se ke enss we Oana Rt Sede Be Py AEA GaR ya aeeee 
Transitional forms: ¢ i eceae6- sc 520 <0 04 36 5+ 4) ome ne ein yes eh ee 
Large mononuclear . hu ithe se acpi onash ss aa 
Smail mononuclear (ymphoeytes) sede gm ncn lpek abe Buin ale ae 


At this time an excess of lymphocytes was lacking. The patient went 
to Franzensbad, took a four weeks’ cure, and again visited me. Her ap- 
pearance was somewhat improved. Another examination of the blood 
resulted as follows: 


Reed corpus hene od 5 cede vara sina igeley ain ety ds Mtbca di ok 8 ia ae 
_ White corpuscles . . oie kale tine aj etorm ete atta k naly gc g) gatas eata ahareabinae 5,600 
* Hemoglobin (Fleisch!) Eee ce ee re er ce ER on RED 80% 


Color-index ... os & Gib Diy bine MODS GR Ae ee reel Ott Goer 0.88 


SYMPTOMS AND COURSE. 347 


Examination of the fresh specimen: rouleaux formation good, blood- 
plates abundant, fibrin formation very slight. 

Examination of the stained preparation: no abnormalities of size or 
shape and no nucleation among the red corpuscles. 

Differential count of leucocytes: 


Polynuclear neutrophuilés-.40.05 640 Wee ot eee ne gece br 1a, 
Hosinophilési 3. 250.s oon acpebonass panties aa erase ee wes AOD, 
FPransitional for miecwar Aas oe hia ee et aha eee oh 2G 
Large mononuclear. . Leonia sale anes aiane were AOU. 
Small mononuclear (lymphocytes). . Oe gr et rene) BA 


In spite of the improvement of the anemia and the distinct increase of 
hemoglobin, there was found in the second examination of this patient’s 
blood a moderate increase of lymphocytes; at least, a relative increase as 
compared with the polynuclear forms. This condition has never been 
observed in recovery from other anemias, and has already been reported 
by Ehrlich, in connection with the account of a case of posthemorrhagic, 
pernicious anemia, as of unfavorable prognostic significance, since it indi- 
cates an abnormal, regenerative action of the spleen and lymph-glands as 
opposed to the bone-marrow. Although no positive conclusions can be 
based upon these few observations, I should consider it advisable to investi- 
gate this subject further in suitable cases, and to give a guarded prognosis 
if the relative number of lymphocytes is found to be progressively increas- 
ing, even though the patient may feel comparatively well. 


DISTURBANCES OF THE ABDOMINAL ORGANS, 


In Addison’s disease a large number of symptoms, both subjective and 
objective, are referable to the abdomen. 

On inspection of the abdomen there may be two abnormal conditions 
recognized: on the one hand, the abdomen may be swollen and tym- 
panitic; on the other, collapsed, or even hollowed. 

In many cases upon palpation nothing abnormal is found. In another 
considerable group the abdomen is the seat of spontaneous pain and ten- 
derness upon pressure. The former may be variously situated; some- 
times only a slight, indefinite pain “all through the stomach” is com- 
plained of, or the pain may be intense and increased by movement. In the 
latter case the whole abdomen, as a rule, is extremely painful on pressure, 
and this symptom has repeatedly led to an incorrect diagnosis of peri- 
tonitis. The interpretation of this symptom becomes still more difficult 
if, as has actually been observed, an indefinite resistance, diffuse or cir- 
cumscribed, is found upon palpation; for tubercular peritonitis has also 
been observed as a complication of Addison’s disease. 

Of more frequent occurrence are the sharply localized pains situated 
chiefly in the epigastrium and in the lumbar and sacral regions. 

The epigastric pain is the most frequent, and is apt to be very severe 
and persistent, often intensified by pressure, and frequently relieved only 
by bending the body forward. The neuralgic character of this pain some- 
times suggests lead colic or the gastric crises of tabes. The pain may 
radiate from the epigastrium in the form of a typical intercostal neuralgia, 
or may extend irregularly into the hypochondriac regions, toward the 
back, or into the shoulder and arm; so that hepatic colic may be simulated 
when on the right and gastric ulcer when on the left side. 

Next in frequency are the lumbar and sacral pains. These, as a rule, 


348 ADDISON’S DISEASE. 


are deep seated; although in some cases there may be well-marked cutane- 
ous hyperesthesia. A. Fraenkel explains this hyperesthesia as the result of 
radiation such as occurs in other neuralgias. In like manner he regards 
the attacks of dyspnea and subjective sensation of air-hunger seen in 
Addison’s disease as due to the abdominal neuralgia, analogous to the 
attacks of thoracic oppression and dyspnea occurring in ulcer of the stom- 
ach. According to Traube, these latter attacks are the equivalents of the 
neuralgic pains by transference of stimulation from the gastric to the pul- 
monary branches of the vagus nerve. 

Among all the organs of the abdominal cavity, the digestive apparatus 
most frequently presents severe symptoms, which may temporarily wholly 
dominate the clinical picture of the disease. It is true that cases have 
been reported in which all, or at least a majority, of the other symptoms of 
the disease were well developed, yet the digestive organs continued nor- 
mally to perform their function, and nutrition was maintained until the 
end and was extremely good, in contrast with the other severe symptoms. 
These cases are in the minority; in the great majority digestive disturb- 
ances are found, and these, together with the striking loss of power, are the 
most frequent early symptoms of the disease. They begin, as a rule, in- 
sidiously with impairment of appetite which the patient cannot account 
for. Often they immediately succeed some error in diet, and then become 
persistently worse. 

The anorexia is followed by a sense of weight and fulness in the epigas- 
trium, which is generally increased by eating. The tongue is moderately 
coated as a rule, rarely dry, and the breath is frequently fetid. As a re- 
sult, the patient frequently acquires a profound distaste for food, par- 
ticularly meats. To these symptoms are added eructations of gas, pyro- 
sis, in other cases typical and not infrequently very violent attacks of 
gastralgia, uneasiness, nausea and vomiting, and in a few cases also par- 
oxysms of obstinate hiccough. 

The chief gastric symptom is vomiting. At the beginning of the dis- 
ease it may be independent of the taking of food, occurring in the morning 
when the stomach is empty, the vomited matters being scanty and con- 
sisting of a colorless or bile-stained mucus, closely resembling the morning 
vomiting of alcoholics (Guermonprez). On the contrary, even from the 
very beginning, the vomiting may be associated with the taking of food, 
and this is always the case in the late stages of the disease. This symptom 
is subject to intermissions of weeks or months, which are followed by 
severe exacerbations, arising without any apparent cause, or as the result 
of a slight attack of indigestion. As a rule, however, the frequency, 
severity, and duration of vomiting are increased toward the end of the 
disease, nutrition is greatly interfered with, and the patient becomes very 
much reduced. In some cases there may be no gastric disturbances what- 
ever, while in others a hearty appetite may continue, although the loss of 
power is extreme and the patient suffers from severe cardialgia and fre- 
quent vomiting. Cases with ravenous appetite have been reported by 
Peacock, Kussmaul, and Laureck; these are very rare, and in the last case 
mentioned, anorexia occurred at intervals and was complete in the ter- 
minal stage. During the frequent periods of remission all digestive dis- 
turbances disappear ; the emaciated patient may again become well nour- 
ished and in every way improved. 

In contrast to the loss of appetite, thirst may be excessive, indepen- 
dently of any apparent cause, e. g., severe vomiting or diarrhea. 


SYMPTOMS AND COURSE. 349 


In the last stage of the disease the gastric symptoms are greatly in- 
tensified. Persistent, and in many cases uncontrollable, vomiting ap- 
pears, and the resulting exhaustion alone may be the immediate cause of 
death. When vomiting is particularly severe, traces of blood may be 
mixed with the vomited matters or ecchymoses or hemorrhagic erosions of 
the gastric mucous membrane may be found after death. Vomiting of 
large quantities of blood does not occur in genuine Addison’s disease, but 
is due to complications, as ulcer or cancer of the stomach. 

The physical examination of the stomach yields little of value, with the 
exception of more or less sensitiveness to pressure and occasional splashing 
sounds. The chemical examination of the gastric contents and of the 
vomited matters is also negative, asarule. Absence of free hydrochloric 
acid and of pepsin has been demonstrated in very few cases by Leichten- 
stern, Kahler, Minkel, and Brauer. 

Intestinal disturbances are often although not always present. Con- 
stipation and diarrhea occur with almost equal frequency. According 
to Lewin’s extensive statistics, diarrhea is the more common, but these 
statistics do not give a correct idea of these symptoms during the whole 
course of the disease. In my investigation of the literature of this subject 
constipation, sometimes indeed extremely obstinate, was found to be of 
more frequent occurrence at the beginning and during the further course 
of the disease with the exception of the terminal stage. In certain cases 
there was alternate constipation and diarrhea, and in a few instances after 
the administration of laxatives uncontrollable diarrhea supervened. In 
the terminal stage of the disease severe, profuse, and frequently uncon- 
trollable diarrhea occurs in the majority of cases, while the persistence of 
constipation until the end is very rare. The diarrhea is seldom accom- 
panied by colicky pains, and tenesmus is even more rare. Mucus is often 
present in the stools, blood very rarely and in mere traces. 

The gastro-intestinal disturbances vary if the disease pursues an ab- 
normal course or if intestinal complications are present. The disease 
rarely may be ushered in by an acute intestinal initial stage, which, after 
lasting one or two weeks, gradually subsides into the ordinary chronic 
course. The symptoms in these cases are usually rather violent, consist- 
ing of distress, anorexia, cardialgia, vomiting, and usually diarrhea. 
Further, those rare cases must not be forgotten in which the disease runs a 
rapid course with symptoms of an acute gastro-enteritis, terminating 
fatally with collapse and cramps in the legs, and strongly simulating acute 
arsenical poisoning or cholera. 

Even in chronic cases the gastro-intestinal symptoms are very often 
decidedly and considerably influenced and altered by the occurrence of 
complications which result chiefly from tuberculosis. Tubercular ulcers 
of the intestine and tuberculosis elsewhere are of frequent occurrence. 
Dysentery and typhlitis are much rarer complications. Hayem and 
Lesage report a case of Addison’s disease complicated by an enteritis 
due to the pseudo-tubercle bacillus. 7 

The other organs of the peritoneal cavity very rarely give rise to 
symptoms. Enlargement of the-liver and jaundice are caused by com- 
plications, and may be associated with enlargement of the spleen, or 
the latter condition may be present without the former. 

Concerning the retroperitoneal organs there is little to say. Disease 
of the suprarenal capsules rarely gives rise to other local symptoms than 
lumbar and sacral pain, except perhaps the presence of a tumor. 


350 ADDISON’S DISEASE. 


The reproductive organs rarely give rise to symptoms although 
amenorrhea at times occurs, but dysmenorrhea is very rare. In male 
patients impotence has occasionally been observed. Complicating tuber- 
culosis or cancer of the genitals is of more frequent occurrence. In 
women cancer of the uterus and ovaries is frequent, tuberculosis of the 
tubes and endometrium is rare. In men tuberculosis of the epididymis 
may occur. 


CONDITION OF ‘THE URINE. 


Hitherto the examinations of the urine in Addison’s disease have 
been incomplete and with but little method. The reaction was in most 
cases acid, the specific gravity somewhat diminished, the total quantity 
normal or diminished. The few cases of polyuria reported are of interest 
because Oliver and Schafer made use of suprarenal extract in the treat- 
ment of diabetes insipidus with apparently good results. Among patho- 
logic constituents, small quantities of albumin were found in the terminal 
stage; well-marked albuminuria occurred only in the presence of com- 
plicating renal disease. Small quantities of hippuric and taurocholic 
acids have been found. Marino Zucco, Dutto, and Albanese found 
neurin in the urine. Ewald found a hitherto unknown amin base with 
an elementary composition represented by the formula C,H,NO,. Uro- 
bilin was observed in a few cases; in the majority the urinary coloring- 
matters were reduced. Thudichum found uromelanin in one case. Ac- 
cording to previous analyses, the excretion of the normal constituents of 
the urine is not materially changed. The excretion of urea was dimin- 
ished in many, that of uric acid in a few cases. Leva reports in one 
patient the diminished excretion of creatin. Indican was frequently 
increased. Leva and Rosenstirn found all the constituents of the urine 
equally diminished, with the exception, according to the latter author, 
of sulphuric acid. Leva reports the striking marked increase, sometimes 
even twenty-fold, of the volatile fatty acids (acetic and formic). Noth- 
- nagel and v. Jaksch found acetonuria in a comatose patient with Addi- 
son’s disease. At a not very advanced stage of the disease, Kolisch 
and Pichler determined by careful quantitative analyses that the utiliza- 
tion of food and the destruction of albumin were normal. 

In my second case, mentioned above, Dr. Kolisch made a quantitative 
analysis of the twenty-four hours’ quantity of urine with the following 
results: Quantity 1000 c.c., specific gravity 1017, urine very cloudy from 
urates, dark yellow. No nucleo-albumin, no albumin, no sugar, no 
acetone, indican not increased. Total nitrogen 9.38 gm., ammonia 0.3, 
uric acid 0.42, uric acid nitrogen 0.14, xanthin basic nitrogen 0.12, total 
phosphoric acid 1.7, united to alkalies 1.3, united to earths 0.4. Acidity: 
100 ¢.c. urine correspond to 12 ¢.c. decinormal alkaline solution. 

Dr. Freund gave me the following analysis of the urine in another 
case of Addison’s disease: Quantity 1100 c.c., specific gravity 1023, 
reaction acid; acidity 2.1 gm. hydrochloric acid; alkalinity 1.3 gm. sodium 
hydrate. Urine almost clear, amber-yellow; sediment containing mucus, 
numerous spermatozoa, crystals of uric acid, leucocytes. Total nitrogen 
11.3; urea nitrogen 9.5; alloxuric bodies nitrogen 0.35, consisting of uric 
acid nitrogen 0.15 and xanthin basic nitrogen 0.20; ammoniacal nitrogen 
0.12. * Indoxyl and skatoxyl very abundant, oxalic acid increased. Oxy- 
acids, somewhat increased. Ether sulphuric acid 0.27, total sulphuric 
acid 2.5, sulphuric acid from sulphates 1.98. Total phosphoric acid 2.40, 


DIFFERENTIAL DIAGNOSIS. 351 


united to alkalies 2.1, united to earths 0.3. Chlorids 9.8. Albumin, 
sugar, acetone, diacetic acid, urobilin wanting. Albumoses present, 
traces of peptone. Melanin reaction negative, reducing power of the 
urine increased (uric acid solvent power 0.48). Glycuronic acids plainly 
demonstrable. : 


| DIFFERENTIAL DIAGNOSIS OF ADDISON’S DISEASE AND 
OF DISEASES OF THE SUPRARENAL CAP- 
SULES IN GENERAL. 


As the diagnosis of scarlet fever is usually determined by the presence 
of a typical rash, so in the absence of the latter the diagnosis of scarlet 
fever without rash is definitely established by other symptoms, therefore 
the differential diagnosis of Addison’s disease must be differently reached 
according as the case is one with pronounced pigmentation or one in 
which this most prominent diagnostic sign is lacking. 

It has already been stated that there are cases of Addison’s disease 
without melanoderma. In our opinion the bronzing of the skin is a 
symptom of as conspicuous diagnostic importance as the scarlatinal rash 
in the diagnosis of scarlet fever. Nevertheless it cannot be regarded as 
an essential constituent of the picture of the disease. In the first-men- 
tioned group of cases the pigment is obviously the starting-point in 
the differential diagnosis, and a large number of other affections must 
be considered which are characterized by a like pigmentation of the 
skin. . 

It is first to be borne in mind that there are different degrees of physio- 
logic pigmentation dependent upon race and climatic conditions. The 
attention is much more attracted by the dark coloration of a northener 
than by the like pigmentation in a southerner, or a mulatto. What is 
physiologic for the one may be pathologic for the other. So that in 
southerners or in races other than the Caucasian it may be necessary 
to differentiate physiologic pigmentation from that of Addison’s disease. 
For diseases of the suprarenal capsules may occur in any race, and Addi- 
son’s disease has actually been observed in a Hindoo, a mulatto, an 
Armenian, and in a girl from Lebanon (Lewin). In such cases, in addi- 
tion to the general symptoms of Addison’s disease, pigmentation of the 
matrix of the nails or of the buccal mucous membrane perhaps may be 
valuable. It is well known that in negroes and inulattoes the matrix 
of the nails is of the same color as the rest of the skin, while in Addison’s ° 
disease pigmentation in this situation is exceptional, or, if it does occur, . 
is generally less intense than in the surrounding skin. Pigmentation of 
the mucous membrane of the mouth would speak strongly for Addison’s 
disease, although not necessarily, especially if confined to the lips, for, 
according to Nothnagel, similar pigmentation of the lips may occur in 
perfectly healthy individuals. Pigmentation of the mucous membrane 
of the buccal cavity is more conclusive, although a few observers—e. g., 
Eichhorst—have found physiologic pigmentation even here. Nothnagel 
described a case of idiopathic cardiac hypertrophy which should be men- 
tioned in this connection. It presented, in addition to a moderate 
pigmentation of the skin, very conspicuous brownish-gray spots on the 
mucous membrane of the lips, cheeks, and tongue. There were no 


352 | ADDISON’S DISEASE. 


other symptoms of Addison’s disease, and at autopsy the suprarenal 
capsules were ‘found to be perfectly normal. 

The age of the patient must also be considered, for in very old people 
there is sometimes a diffuse pigmentation of the whole surface of the 
body, but it is never very intense, does not present the typical localiza- 
tion of the pigment of Addison’s disease, and never involves the mucous 
membranes. It is also important that Addison’s disease is of the rarest 
occurrence in the aged, and is characterized, in addition to other symp- 
toms, by apathy and depression of spirits, while old people are apt to be 
humorous and exceedingly talkative. Even in senile marasmus, the 
aged never present such intense asthenia as occurs in Addison’s disease. 

Among the pathologic pigmentations that occurring in malaria should 
first be considered. In this disease the differential diagnosis is based 
upon the history, the characteristic appearances in the blood (plasmodia 
and pigment), and upon the physical examination of the abdominal vis- 
cera. Malarial pigmentation does not occur in the form of circumscribed 
spots, but is rather diffuse, and of an ashen-gray or earthy hue. Pigmen- 
tation of the mucous membranes does not occur in malaria, and this sign 
is particularly valuable when Addison’s disease develops in an individual 
who has already had malaria. Several such cases have been recorded. 

In the last stages of pulmonary tuberculosis and in cancerous cachexia 
pigmentations are encountered similar to those in malaria. These may 
occur independently of any disease of the suprarenal capsules or of a lesion 
of the abdominal sympathetic. Such cases may present considerable 
difficulties, for all the characteristic symptoms of Addison’s disease, loss of 
power, vomiting, diarrhea, etc., may result from the underlying disease. 
The diagnosis of this condition is based upon a careful consideration of the 
relation and succession of the individual symptoms and upon the appear- 
ance of the pigmentation, which, on the whole, resembles that occurring 
in malaria. Furthermore, a moderate “cachectic dropsy” of the skin is of 
frequent occurrence in these affections, while in the cachexia of uncom- 
plicated Addison’s disease this condition is exceedingly rare. If the tuber- 
cular or cancerous process has involved the abdominal glands (exclusive 
of the suprarenal capsules), the differential diagnosis cannot be made. 

Pellagra is another disease in which there may be extensive pigmenta- 
tion of the skin. I refer here less to the circumscribed pigmentations on 
the neck, backs of the hands and feet, and face remaining behind after the 
specific torpid and indolent erythemas of pellagra, than to the diffuse or 
rarely spotted pigmentation of the remaining skin. In my studies of 
pellagra I have observed this not only in the dark complexioned Italians 
and Roumanians, but also in the blond Hungarians (Czangos) in Rou- 
mania. ‘The earlier students of pellagra (Strambio, Felix, Russel, Lan- 
douzy, and Billod) reported a similar pigmentation of the skin, often very 
intense, resembling the color of a Gipsy or of an Ethiopian. Their obser- 
vations were confined exclusively to pellagra occurring in the Latin races, 
as Italians, Spaniards, and Roumanians, whose skin is naturally rich in 
pigment. I wish to emphasize particularly the occurrence of pellagrous 
pigmentation in the skin of the blond Hungarian also, because these cases 
prove beyond doubt that the pellagrous poison bears a causal relation 
to the pigmentation, and fully justify an opinion which I have already 
mentioned—that there is a form of pellagra which runs its course with 
symptoms of Addison’s disease. If all the symptoms of the case are taken 
into consideration, these two diseases are not likely to be confounded. 


DIFFERENTIAL DIAGNOSIS. 3538 


In the first place, the erythemas already mentioned as occurring almost 
exclusively in the spring and fall are highly characteristic of pellagra. In 
cases uncomplicated by malaria, the mucous membranes are pale or livid 
and are unpigmented. There is frequently a very intense anemia, often 
suggesting pernicious anemia, but more frequently, to be sure, complicated 
with malaria or syphilis. Pellagra is very rarely associated with tuber- 
culosis. Out of 500 cases of pellagra I found in only one instance a condi- 
tion at the apex suggestive of tuberculosis. According to the report of 
the Mercy Hospital at Goerz, not a single case of tuberculosis occurred 
among their pellagrous insane patients during a period of several years, 
while almost all the other insane patients living in the same wards died of 
tuberculosis. It appears from this that pellagrous patients are, to a cer- 
tain extent, immune from tuberculosis. This is valuable from a diagnostic 
standpoint, because the relation between Addison’s disease and tubercu- 
losis is sufficiently well known. 

The contrast between pellagra and Addison’s disease is very well shown 
by the blood-count. In every case of pellagra in which I examined the 
blood I found, both during and after the erythema, a fairly constant in- 
crease in the number of the eosinophilic cells even in those cases where the 
blood gave no evidence of a qualitative anemia. | 

I was able to demonstrate a similar increase of eosinophilic cells in the 
mucous stools by treating the dried preparation with eosin-glycerin and 
subsequent staining with Lugol’s solution. This method also showed the 
abundant occurrence of clostridia, which were stained a deep violet by 
iodin. In the cases of Addison’s disease which Kolisch and I examined 
there was no increase of eosinophilic cells in the blood; this is a valuable 
distinction from pellagra. 

There are many analogies in the gastro-intestinal symptoms of the two 
diseases. Bulimia is more frequent in pellagra, anorexia is conspicuous 
in Addison’s disease. Diarrhea predominates in the initial stage of pella- 
gra, while in Addison’s disease obstinate constipation is the rule in the be- 
ginning, followed by diarrhea in the terminal stage. 

An important diagnostic sign of pellagra is the appearance of the 
tongue. In most cases there are deep indentations between the papille 
which may be regularly arranged like the squares on a chess-board or like 
alligator leather—the gercures of the French. Nothing of the kind is 
observed in Addison’s disease. 

The nervous symptoms of pellagra and Addison’s disease likewise . 
present many analogies. In pellagra the functional psychoses are of 
earlier and more frequent occurrence and comprise melancholia, mania, 
delirium, and tendency to suicide; while in Addison’s disease pronounced 
psychic disturbances are rarely found and only in the terminal stage. 
Pellagrous insanity terminates, as a rule, in paralytic dementia; the latter 
is never observed in Addison’s disease. Such symptoms as increased ten- 
don-reflexes, facial reflex, contractures, and muscular atrophies are fre- 
quently observed in pellagra, but do not form a part of the clinical picture 
of Addison’s disease. Pellagra occurs endemically, it is dependent upon a 
diet of maize, and pursues a regularly intermittent course with relapses in 
the spring and fall; while Addison’s disease pursues a gradually progres- 
sive course independently of these circumstances. 

Further, in many cases of pseudoleukemia a general pigmentation of 
the skin is observed. This may result from various causes. It may be 
caused by the pressure of enlarged retroperitoneal and mesenteric glands 

23 


304 ADDISON’S DISEASE. 


upon the abdominal sympathetic and its appendages, as has been de- 
scribed by Marvin, Wright, and F. Raymond; or it may be due even to 
lymphomatous infiltration of the suprarenal capsules themselves. All 
such cases actually belong to true Addison’s disease, and are mentioned 
in order to call attention to the fact that pseudoleukemia, and perhaps 
also leukemia, may present the clinical picture of Addison’s disease. On 
the other hand, this pigmentation may result from scratching in conse- 
quence of itching of the skin, especially when due to chronic irritation. 
The melanoderma in this case does not corespond to the type of Addison’s 
disease, being principally confined to the scratched areas, while the remain- 
ing symptoms of pseudoleukemia or leukemia will lead to the diagnosis of 
the underlying disease. A similar explanation answers for the pigmentation 
occurring in many other itching skin diseases; as, for example, prurigo, 
eczema, and the like. 

Vogt described as “ vagabond’s disease”’ another form of melanoderma 
occurring in destitute individuals infected with lice and exposed to all 
sorts of inclement weather. When such persons are also cachectic, Addi- 
son’s disease may be closely simulated, and just such cases led Hebra at 
one time to deny the existence of Addison’s disease as a distinct affection. 

The diagnosis is based upon the effect of baths and care of the skin; 
upon the fact that the skin is dry and scaly and presents numerous 
scratch-marks (of extremely rare occurrence in Addison’s disease); the 
pigmentation is confined to the covered parts of the body where the skin is 
immediately in contact with the clothing, while the hands and feet are but 
faintly pigmented, as a rule; finally, the mucous membranes are not 
affected, although there are exceptions. In many cases this differential 
diagnosis may be extremely difficult; patients with Addison’s disease 
through indolence and apathy may become destitute and infected with 
lice, and may present themselves in this condition for examination. 

In rare instances diffuse pigmentation may be caused by a primary 
melanosarcoma of the skin. A case of this kind was observed by 
Bamberger in the Rudolf Hospital at Vienna. A patient was ad- 
mitted to his wards who first gave the impression of Addison’s disease. 
Her skin presented a diffuse brownish-black pigmentation, but at the 
same time a firm glandular tumor was detected in the left groin. The 
tumor was firmly adherent to the subjacent tissues, while the overlying 
skin contained a large number of bluish-black spots varying in size from a 
pinhead to a lentil, scarcely elevated to the touch, and connected by dark 
lines. In the skin of the abdomen, on the back, and in the axilla, bluish 
tumors as large as a kreuzer were found, which, taken in connection with 
the above-mentioned glandular tumors, led to a diagnosis of melanotic 
sarcoma. ‘The dark urine gave a black color with chlorid of iron. 

The autopsy showed a melanotic sarcoma of the skin of the trunk and 
extremities, with metastases in the internal organs and intact suprarenal 
capsules. Upon microscopic examination numerous nodules of melanotic 
sarcoma were found, and, in addition, large numbers of wandering cells 
which had taken up pigment from these melanotic growths and were 
carrying it elsewhere. The diffuse pigmentation of the skin then arose. 

Pigmentation of the skin in Basedow’s disease has been reported. 
Personally, I have never seen diffuse pigmentation in this affection, but 
have observed a partial pigmentation of the skin of the face resembling 
chloasma uterinum. Chvostek reports a very interesting case of severe 
Basedow’s disease which presented, in addition to scattered dark brown 


DIFFERENTIAL DIAGNOSIS. 300 


spots, a diffuse bronzing of the skin which disappeared with subsidence of 
the symptoms of the Basedow’s disease, reappeared with their recurrence, 
and disappeared permanently upon cure of the disease. The nails were 
white and there were no deposits of pigment in the oral mucous mem- 
brane. The cases of recovery from Basedow’s disease with bronzed skin 
illustrate the diagnostic difficulties arising when cases of true Addison’s 
disease (resulting from disease of the suprarenal capsules confirmed at 
autopsy) are associated with the symptoms of Basedow’s disease, as have 
been reported by Fletcher and Greenhow. 

Slight diffuse and spotted pigmentation of the skin is frequently ob- 
served in scleroderma and sclerodactylia. The pigmentation is rarely so 
intense as to suggest Addison’s disease. Pigmentation of the mucous 
membranes is absent as a rule, although Nothnagel reports a patient who 
suffered from scleroderma but who did not have Addison’s disease, and in 
whom a deep grayish smoke-colored pigmentation of the buccal mucous 
membrane was present. The diagnosis is based upon the characteristic 
features of these diseases. Several cases of scleroderma with very intense 
and wide-spread pigmentation of the skin have been reported as compli- 
cated with Addison’s disease. At autopsy this statement was found to 
be incorrect, for no lesions of the suprarenal capsules or abdominal sym- 
pathetic were found. 

Diseases of the female reproductive organs form a special group which 
may eventually lead to pigmentation of the skin. Reference is not here 
made to the frequently occurring pigmentation of the face, areole, and 
linea alba, but especially to a diffuse coloration of the skin which, upon 
first sight, may suggest Addison’s disease. I recall a patient in whom 
there was a striking pigmentation of the extremities and trunk and ex- 
tensive ascites. The gynecologists found a resistance on both sides of the 
uterus in the vicinity of the adnexa, but were unable to state positively 
whether an ovarian tumor was present or absent. A prominent surgeon 
in Vienna declined to operate, suspecting disease of the suprarenal capsules 
on account of the bronzing of the skin. I found in the blood no evidence 
of cachexia, no diminution of red corpuscles, but an increase of eosino- 
philic cells. The patient finally decided to submit to an operation and 
Professor Albert performed bilateral oophorectomy for cystic degeneration. 
The most interesting feature of the case was that the bronzing of the skin 
disappeared quite rapidly after the operation. The case, therefore, was 
one of apparent Addison’s disease cured by removal of the ovaries. This 
case, in connection with a second observed by mein which a typical Base- 
dow’s disease appeared after extirpation of both ovaries, forms an inter- 
esting supplement to Chvostek’s case mentioned above. 

It may appear paradoxical to speak of the differential diagnosis be- 
tween jaundice and Addison’s disease. The ordinary forms of jaundice 
present scarcely any difficulty even when occurring in extremely cachectic 
individuals, as the cancerous and tubercular. Difficulty, on the contrary, 
may be afforded by those cases of Addison’s disease in which the bronzed 
skin is accompanied by jaundice due to an affection of the glands in the 
portal fissure (cancer, tuberculosis) or to metastases in the liver or to 
complications with diseases of the biliary passages. In such cases the 
correct diagnosis can be made only by an exceedingly careful separation 
of the symptoms of Addison’s disease from the clinical picture as a whole. 

In uncomplicated cases of the acute and chronic varieties of icterus 
gravis diagnostic errors are not only possible, but have actually been made. 


356 | ADDISON’S DISEASE. 


According to Cochran, in many cases of malignant yellow fever the skin is 
eventually of a bronze hue. Leva reports an unusually interesting case 
from Eichhorst’s clinic. The patient was a strong man and presented a 
“peculiar light bronze pigmentation of the skin, most marked on the face, 
in both axille, on the backs of the hands, on the mons veneris, in the hol- 
lows of the knee, on the back, genitals, and anal folds. Several spots of 
brown pigment were found on the mucous membrane of the lips, a series of 
brown spots of the size of peas were present on the mucous lining of the 
cheeks. The conjunctive were stained a faint yellow, not in spots.” 
The patient died in coma and the clinical diagnosis was morbus Addisonii 
comatosus. At autopsy atrophic cirrhosis of the liver was found, while 
the suprarenal capsules were intact. (Whether, as Leva believes, this was 
a case of simple melanotic jaundice must remain undecided in view of the 
existing cirrhotic degeneration of the liver.) 

Diabetes mellitus should first be mentioned among the other affections 
in the course of which melanoderma has been observed. French clini- 
cians, particularly Trousseau, Hanot and Chauffard, Letulle, Brault and 
Gaillard, and most recently Marie, have described cases of so-called diabéte 
bronzé. This type of the disease is characterized by rapid course, diarrhea, 
meteorism, and finally by a diffuse pigmentation of the skin in addition 
to the usual diabetic symptoms (dryness of the mouth, polydipsia, poly- 
phagia, polyuria, and glycosuria). The pigmentation is distributed over 
the whole surface of the body, is most intense on the face, extremities, and 
genitals, and is distinguished from the melanoderma of Addison’s disease 
only by the constant absence of circumscribed spots of pigment and of 
pigmentation of the mucous membranes. In particularly well-marked 
cases the pigmentation presents a metallic luster and a peculiar, grayish- 
black hue, resembling the broken surface of cast-iron. In these patients 
there is coincident enlargement and induration of the liver. It is worthy 
of note that several days before death the excretion of sugar may almost 
entirely disappear, and that, during the whole course of the disease, the 
striking diabetic symptoms of polydipsia, polyphagia, polyuria, and glyco- 
surla are not so conspicuous as in the ordinary forms of diabetes mellitus. | 
Upon postmortem examination the anatomic basis of this disease is found 
to be a hypertrophic, pigmentary cirrhosis of the liver (cirrhose hyper- 
trophique pgmentuire) with sclerosis of the pancreas and accumulation of 
pigment in various organs, particularly the heart and lymphatic glands. 
These observations are very suggestive of the “hemochromatosis” de- 
scribed by v. Recklinghausen. The pigment found in the organs con- 
tained iron, and therefore must be regarded as a direct derivative of the 
coloring-matter of the blood. Some authors consider this disease as 
diabetes mellitus complicated with hypertrophic pigmentary cirrhosis, — 
while Marie regards it as a peculiar form of disease, and places it at the side 
of pancreatic diabetes. This affection may easily be distinguished from 
genuine Addison’s disease by the symptoms already described; the diag- 
nosis could be difficult only in the terminal stage, after disappearance of 
sugar from the urine. 

There is still another group of cases in which glycosuria and melano- 
derma may be combined—namely, where glycosuria is due to disease of 
the pancreas and at the same time the latter has involved the large ab- 
dominal sympathetic nerve structures. 

In certain affections of the pancreas melanoderma may occur without 
glycosuria. Such a case was reported by Aran as occurring in a woman 


DIFFERENTIAL DIAGNOSIS. 307 


twenty-five years of age whose skin was the color of a mulatto and who 
died from progressive marasmus accompanied by vomiting and epigastric 
pain. At autopsy, caseous degeneration and cavity-formation were found 
in the pancreas and enlargement and calcification of the celiac and 
splenico-pancreatic glands.- The diagnosis of such conditions could be 
made only by determining the primary disease of the pancreas, either by 
the history (pancreatic colic), the discovery of a pancreatic tumor, the 
occurrence of maltose in the urine, under certain circumstances by a dimin- 
ished excretion of indigo, or, finally, by demonstrating the occurrence of | 
changes in the stools—steatorrhea, azotorrhea—brought about by an in- 
terference with the pancreatic secretion. 

A special variety of melanoderma results from the accidental or 
medicinal administration of inorganic poisons. First among these is the 
arsenical melanosis, a form of disease which has only recently been well 
understood. This is most often observed during the administration of 
arsenic for medicinal purposes, and may make its appearance relatively 
soon, disappearing, as a rule, entirely or almost entirely after discontinu- 
ance of the drug. In certain cases a permanent discoloration of the skin 
has been observed. The cutaneous distribution and localization of the 
arsenical melanosis is identical with the melanoderma of Addison’s dis- 
ease, but in the former condition the mucous membranes are not involved. 
In some cases melanosis is the only symptom; in others further symptoms 
of chronic arsenical poisoning may appear—e. g., disturbances of the diges- 
tive and respiratory organs and of the central and peripheral nervous 
system. 

In some cases the diagnosis of arsenical melanosis can readily be made; 
under other circumstances it may be exceedingly difficult, particularly 
when the arsenic has been introduced into the system w ithout the knowi- 
edge of the patient through the medium of wall-paper or furnishings. In 
such cases the diagnosis can be made only after a careful consideration of 
all the characteristic symptoms of arsenical poisoning, or by finding 
arsenic in the urine or feces. Even during the intentional medicinal 
administration of arsenic diagnostic difficulties may arise; for example, 
cutaneous pigmentation may appear in a tubercular patient for whom 
arsenic has been ordered. In such a case an incorrect diagnosis of Addi- 
son’s disease might very easily be made. . S 

The administration of silver also may produce a dark pigmentation of 
the skin. Reduced silver is deposited in the cutis and in the tunica 
propria of the sweat-glands. The pigmentation is deepest in parts ex- 
posed to the light. Silver is present in the form of minute granules of 
equal size, deposited outside of the cells. On the contrary, the pigment 
of Addison’s disease lies within the cells. * 

In January, 1892, during a course in diagnosis at the Rudolf Hospital 
I presented a patient whose appearance was of interest in this connection. 
The patient’s face was pigmented, the ocular conjunctiva was gray, like- 
wise the matrix of the nails and a few scars; the penis was not pigmented. 
It was learned that the patient had been treated with silver nitrate for an 
affection of the stomach thought to be gastric crises; so the diagnosis lay 
between Addison’s disease and argyria. In argyria ‘the color of the skin 
is at first pale gray, as if it had been marked with a lead-pencil, and the 
pigmentation is equally distributed over the whole surface of the body: 
If the administration of silver is continued, the color eventually becomes 
dark blue, and has even been mistaken for cyanosis. Gerhardt calls atten- 


358 ADDISON’S DISEASE. 


tion to such cases in his text-book on “ Auscultation and Percussion,”’ and 
offers as a method of differentiation the disappearance on pressure of the 
color of the lips in cyanosis, while in argyria the color remains unchanged. 
It is also to be borne in mind that pigmentation of the visible mucous 
membranes, especially of the mouth, occurs in addition to pigmentation of 
the skin in workers in silver. Small blue spots may be present on differ- 
ent parts of the body, especially on the hands and forearms, although the 
color of the remaining skin may remain unchanged. The pigmentation 
thus may correspond in every particular to that of Addison’s disease. In 
such cases there are still two aids in diagnosis: The first is excision and 
microscopic examination of a fragment of the pigmented skin; the other 
is examination of the urine for silver, although a positive result may not 
occur in actual argyria. In the above-mentioned patient the diagnosis 
was actually made by the discovery of silver in the urine. 

In the preceding paragraphs the diagnostic features of all possible 
forms of melanoderma have been presented and the feasibility of a correct 
diagnosis in the majority of the cases noted. That this cannot always be 
made is well shown by a case brought before my clinic. 

The patient was a man, thirty years of age, who presented a diffusely 
mottled pigmentation of the skin and pigmented spots upon the buccal 
mucous membrane. The conjunctiva and matrix of the nails were un- 
stained. His appearance corresponded in every particular with the 
melanoderma of Addison’s disease. The patient was an Italian, but did 
not eat polenta, and stated that his skin had been so brown since birth that 
he was frequently mistaken for a Gipsy. Some years before he had had 
intermittent fever which yielded to quinin. The physical examination 
showed splenic tumor and enlargement of the liver and of a gland in the 
left axilla. The patient had an attack of intermittent fever while at the 
hospital; no plasmodia were found, but leucocytosis was present. By 
occupation he was a gold-worker, and as such had a good deal to do with 
silver, but none was found in the urine. Finally, in addition to quinin, 
which now had no effect on his febrile attacks, the patient received arsenic 
. foraconsiderable period of time. Although loss of power and gastro-intes- 
tinal symptoms were absent, the case was thought to be one of Addison’s 
disease on account of the characteristic color and typical distribution of 
the pigment. In making the diagnosis I had to differentiate between no 
less than six forms of melanoderma; namely, congenital pigmentation, 
malarial cachexia, pseudoleukemia, argyria, arsenical melanosis, and 
Addison’s disease. The clinical picture did not correspond entirely to 
any one of these conditions, but it was finally decided that the case was 
most probably a protracted pseudoleukemia, localized perhaps in the ab- 
dominal glands. Whether this view was correct or not I do not know to 
this day, for the patient improved and left the hospital, and I have never 
seen him since. 

If the diagnosis of Addison’s disease is difficult in the presence of 
melanoderma, in the absence of this symptom it is often rendered quite 
impossible. Difficulties then can arise in all directions. Such a case of 
concealed Addison’s disease may possibly be suspected if the other cardinal 
symptoms, loss of power and gastro-intestinal disturbances with pain in 
the épigastrium and back, are typically developed without any apparent 
cause. It is impossible to formulate any general rules for the diagnosis 
of these cases; it is also impossible to discuss in detail the differential diag- 
nosis of every pathologic condition simulating this form of Addison’s 


DIFFERENTIAL DIAGNOSIS. 359 


disease. Such cases may be encountered in numerous disguises, for in- 
stance, in the beginning and subsequent course as neurasthenia, hysterias, 
hyperemesis gravidarum, aneurysm of the abdominal aorta, ulcer or 
cancer of the stomach, circumscribed peritonitis, etc.; in the terminal 
stage as meningitis, typhoid fever, acute general peritonitis, internal 
strangulation, uremia, acute arsenical poisoning, or even cholera. The 
endless reports of cases of Addison’s disease give numerous examples of the 
occurrence of such usually unrecognized cases. This polymorphism of 
the disease is largely based on the multiformity of the causes. 

It is, to say the least, strange that in the classic cases of Addison’s dis- 
ease with melanoderma very little attention is paid to the anatomic basis 
of the disease; while as soon as the bronzed skin is lacking we cling to the 
suprarenal capsules, not venturing to diagnosticate a given set of symp- 
toms as “ Addison’s disease without melanoderma”’ unless the suprarenal 
capsules are found to be diseased, either accidentally at operation or after 
death. In the latter event we are perfectly willing to admit that the 
essential diagnostic feature is afforded by the suprarenal capsules, while in 
the classic cases with melanoderma we are still inclined to attribute the 
chief rdle to the sympathetic system. One thus unconsciously proves 
how intimately connected melanoderma and the sympathetic system are, 
on the one hand, and the remaining symptoms of Addison’s disease and 
the suprarenal capsules, on the other; and thus also unconsciously admits 
that nevertheless the fundamental lesion of Addison’s disease is found in 
the suprarenal capsules. 

This being admitted, it remains to search for the diagnostic features 
by means of which pathologic changes in the suprarenal capsules may be 
recognized during life, particularly when the symptoms of Addison’s dis- 
ease are absent. The means at our disposal for the solution of this prob- 
lem are very insufficient, for there are only a few uncertain signs capable 
of calling our attention to the suprarenal capsules in the diagnosis of diffi- 
cult cases. 

In the first place, the local symptoms should be considered: severe 
lumbar pain causing difficulty in walking, sometimes relieved by bending 
the body forward, often radiating to the epigastrium. Further, the oc- 
currence of a tumor in the hepatic or splenic region which may extend 
downward almost to the iliac crest. In such cases all the means should 
be employed which are in use for the differential diagnosis of abdominal 
tumors. By thus excluding the connection of the tumor with the liver, 
spleen, kidney, pancreas, or retroperitoneal glands, its relation to the 
suprarenal capsules may be considered probable. A positive diagnosis 
can sometimes be made by exploratory puncture, particularly when the 
tumor is cystic or consists of soft, loose tissue. If scolices are found in the 
fluid obtained by puncture, the presence of an echinococcus cyst is proved. 
Fragments of the tumor perhaps may be obtained and the presence be 
demonstrated of the characteristic, large, flat, suprarenal cells containing 
numerous fat-drops and glycogen. If the cells are arranged in double 
rows about very numerous blood-vessels, the diagnosis of perithelioma 
may be possible. It must be borne in mind in such cases that accessory 
suprarenal capsules may be the origin of the tumors. 

A similar exact diagnosis may at times be made when portions of such 
a tumor escape in the urine. Then, of course, the perithelioma has either 
extended from the suprarenal capsules to the kidney or may have devel- 
oped primarily from an accessory suprarenal body in the kidney. 


360 ADDISON’S DISEASE. 


The possibility of such a diagnosis is demonstrated by a case observed 
in our clinic and diagnosticated by Professor Kolisko as suprarenal peri- 
thelioma by the microscopic examination of the clot containing fragments 
of the disintegrated neoplasm evacuated with the urine after preceding 
hematuria. The diagnosis was confirmed at autopsy. In the case of 
cystic tumors it might be possible to demonstrate the presence of supra- 
renal extract by injecting into animals the fluid obtained by exploratory 
puncture and observing its physiologic action in increasing blood-pressure. 

It is probable that tumors of the suprarenal capsules which contain 
the typical gland cells of the suprarenal bodies typically arranged even 
in their metastases possess the property of secreting, perhaps even in excess, 
the physiologically active substance of the suprarenal body; as adenocar- 
cinoma of the liver and its metastases may secrete bile, and as adenocar- 
cinoma of the thyroid gland and its metastases contain thyreoiodin. 

Two clinical observations recently made at the Vienna General Hos- 
pital support this theory. In the first case a moribund patient, twenty- 
five years of age, was admitted to the medical wards with symptoms of 
cerebral hemorrhage. The case was diagnosticated as Bright’s disease 
owing to the wiry pulse. At the autopsy multiple hemorrhages were 
found in the brain identical with those resulting from the increased blood- 
pressure of contracted kidneys. One suprarenal capsule was cancerous. 
There was no disease of the kidneys or blood-vessels as a cause for the in- 
creased blood-pressure. A similar case occurred in an elderly individual. 
These observations certainly prove that the occurrence of cerebral hemor- 
rhage with a pulse of high tension should suggest, particularly in young 
persons, the possibility of disease of the suprarenal capsules with patho- 
logically increased secretion. 

Fraenkel describes another case having an important bearing upon 
this subject, which, however, in the abstract at hand is not perfectly clear 
and free from criticism. A girl eighteen years old presented symptoms of 
weakness, headache, vomiting, pulse of high tension, hypertrophied left 
ventricle, albuminuric retinitis, large quantities of albumin, a few casts 
and epithelial cells in the urine, no edema, frequent epistaxis. Death oc- 
curred suddenly in collapse. At the autopsy a very vascular tumor, 
probably angiosarcoma, of the left suprarenal capsule was found. Both 
kidneys appeared normal, but there were hemorrhages in the renal pelves, 
the mucous membrane of the small intestine, the media and adventitia of 
the pulmonary artery, likewise into the endocardium and superficial 
muscular layers of the left ventricle. 

The clinical picture was identical with that of chronic nephritis (con- 
tracted kidney), while at the autopsy none of the corresponding altera- 
tions in the kidney were found. If this observation is correct, it is a ques- 
tion whether all these symptoms, including the albuminuric retinitis, 
were not caused by the primary disease of the suprarenal capsules, and 
whether the albuminuria noticed during life should not be considered as 
the expression of a toxic irritation from the circulating products of the 
suprarenal bodies. The occurrence of multiple hemorrhages in this and 
in the two cases previously mentioned is noteworthy in connection with 
the fact that some authors (Gluzinski) observed similar hemorrhages into 
-various organs (lungs, brain, pleura, pericardium, etc.) in animals after 
injections of suprarenal extract. 

To this may be added the following communication from Professor 
Kolisko. In young patients with diseased suprarenal capsules he re- 


DIFFERENTIAL DIAGNOSIS. 361 


peatedly observed endarteritic vascular disease for which no other cause 
was apparent. It is easily possible that this was not merely a coincidence, 
but that there was a close connection between the disease of the suprarenal 
capsules and that of the blood-vessels. Hereafter when thickened and 
tortuous blood-vessels are found in a young person and cardiac and renal 
disease, syphilis, and diabetes can be excluded as etiologic factors, the 
possibility of a disease of the suprarenal bodies should be borne in mind. 

A clue to the existence of primary malignant tumors of the suprarenal 
bodies is afforded by the occurrence of metastases in especial organs. The 
prostate, thyroid, mammary gland, and suprarenal capsule are charac- 
terized by the tendency of their malignant growths to form metastases 
apart from regional infections in the bones, particularly in the vertebre, 
long bones, and skull. If metastases are found in these places of predi- 
lection and the presence of a primary tumor in the breast, prostate, or 
thyroid gland can be excluded, the suprarenal capsule then should be 
thought of, especially if the metastases are soft and pulsating. Symptoms 
of cerebral tumor likewise should call to mind the fact that tumors of the 
suprarenal capsule are very prone to form metastases in the central ner- 
vous system, particularly in the brain (Kolisko). 

Finally, hypothermia should be mentioned as a very important symp- 
tom directing attention to disease of the suprarenal capsules. It has been 
stated repeatedly that affections of the suprarenal capsules are often char- 
acterized by abnormally low temperatures; this is true not only of tumors 
and uncomplicated tuberculosis of the suprarenal capsules, but also of 
acute purulent inflammation of these organs. Chvostek’s case is a classic 
instance in which a perinephritic abscess caused by calculus extended to 
the suprarenal capsules and was characterized in the final stage of the 
fever by temperatures of 36°, 34°, and even 32° C. (96.8°, 93.2°, and 89.6° 
F.). The occurrence of subnormal temperature in the course of acute 
suppuration instead of the expected fever is certainly very striking. There- 
fore, if hypothermia is observed in the course of an acute suppuration in 
the lumbar region, which has arisen either primarily or by extension from 
the renal pelvis, kidney, spleen, liver, or psoas, this fact should at once 
suggest the possibility of a primary or secondary participation of the 
suprarenal capsule in the suppurating process. 

Finally, attention may be called to two diagnostic procedures fur- 
nished by the most recent physiologic investigations. 

The experiments on animals by Brown-Séquard, Abelous, and Lang- 
lois showed that the blood of animals deprived of suprarenal capsules is 
poisonous, producing in healthy frogs symptoms similar to curare, while it 
hastens the death of animals whose suprarenal bodies have been removed. 
In cases of disease of the suprarenal capsule attended by suppression of 
function would not human blood possess similar poisonous properties, and 
would not frogs, both before and after removal of the suprarenal capsules, 
afford a sensitive diagnostic reaction for such blood? According to Cybul- 
ski, the urine of animals which have been injected with suprarenal extract 
increases the blood-pressure; might it not be possible that the urine of 
man with a disease of the suprarenal capsules associated with hypersecre- 
tion should contain the similar property of increasing the blood-pressure? 


In the foregoing pages a few suggestions only have been offered for the 
diagnosis of Addison’s disease in the absence of melanoderma; to apply 
these rightly at the bedside must be left to the judgment of the physician. 


362 ADDISON’S DISEASE. 


PROGNOSIS. 


In general, the statement holds good that Addison’s disease is fatal. 
The few cases reported as “cured” are either not above suspicion from the 
standpoint of diagnosis, or are to be explained by the fact that one of the 
well-known, lengthy periods of remission had been mistaken for recovery 
and reported as such. It is true that certain anatomic lesions do not abso- 
lutely preclude the possibility of cure. In the first place, this is true of 
syphilis; it also holds good for unilateral destructions of the suprarenal 
capsule which are accessible to operative treatment. This is conceivable 
in the case of an echinococcus cyst or in localized tuberculosis of one supra- 
renal capsule. A case of the latter kind was actually reported recently 
by Oestreich. There was Addison’s disease without melanoderma; the 
symptoms disappeared entirely after an operation (removal of the dis- 
eased suprarenal capsule) performed under a mistaken diagnosis. Whether 
the cure in this case will be permanent or not cannot yet be determined, 
although this possibility is by no means excluded. 

It is, as arule, impossible to decide whether or not a given case is suit- 
able for operation. In the majority of cases there is bilateral tubercu- 
losis of the suprarenal capsules, or coincident advanced tuberculosis of 
other organs, or an extension of the process to the adjacent nerve-plexuses, 
or malignant tumors—in all of which the prognosis is certain. 

The question as to the duration of life is based upon the diagnosis of 
the anatomic basis of the disease. Life lasts longest in uncomplicated 
tuberculosis of the suprarenal capsules; carcinoma here, as elsewhere, 
runs amore rapid course. The duration of the disease in most cases is 
one to three years. Exceptional instances are reported in which the 
disease terminated fatally within a few months, and others in which the 
duration was eight, ten, or even thirteen years. Even in these protracted 
and remittent cases the prognosis as to the duration of the disease must 
be very guarded, for even in the midst of relatively good health severe 
symptoms may suddenly appear to which the patient succumbs within a 
short time. 


TREATMENT. 


There is no causal treatment of Addison’s disease.. Perhaps in the 
future the fruits of physiology and chemistry will become available for 
therapeutic application in diseases of this organ, as is already the case with 
the thyroid gland. The first experiments in this direction have already 
been made. The internal administration of suprarenal substance or ex- 
tract in diseases of the suprarenal capsules has been followed by only 
transient improvement or by none at all. Likewise the subcutaneous 
injection of the extract, as undertaken by French investigators, in two 
cases beyond increasing the diuresis produced only negative results. . This 
should not deter from further trials, since it is known that the active prin- 
ciple of the suprarenal capsules is so very easily decomposed that when 
administered internally it probably produces no effect, and when 
administered subcutaneously only a partial effect. Perhaps intravenous 
injéction in appropriate cases would yield better results. 

The implantation of a dog’s suprarenal capsule into a patient with | 
Addison’s disease for therapeutic purposes has already been attempted by 
Augagneur, with the result that the patient, who, however, was also in an 


TREATMENT. 3638 


advanced stage of phthisis, died within three days. [According to Poll,* 
in the transplantation of the suprarenal the medullary portion, considered 
by the physiologists as the chief seat of the active substance, is completely 
destroyed. 

The effect of the treatment of Addison’s disease with preparations of 
suprarenal capsules cannot be determined, at present, with any degree of 
accuracy, owing to the inability to decide upon the exact nature of the 
questionable cases. The clinical characteristics of this affection are often 
not so sharply defined as to permit the diagnosis without a reasonable 
doubt. If the patient continues to improve, and eventually recovers, the 
condition of the capsules must always remain unknown unless a post- 
mortem examination eventually is made. A number of cases have been 
reported in which temporary improvement has fol’owed the use of 
suprarenal preparations and after death the capsules have been 
found diseased. Vollbracht + treated his patient for thirty-two days 
with suprarenal extract. Improvement occurred during this period, 
but the patient died a few weeks later with meninigitic symptoms, 
although evidences of meningeal infection were not found after death. 
The suprarenal bodies were almost completely destroyed, probably at a 
time when there were no clinical evidences of Addison’s disease. Edel f 
also used the extract and noticed improvement within a few days. The 
patient soon resumed his laborious occupation, and after five weeks the 
pigmentation had almost wholly disappeared. The remedy was discon- 
tinued with the onset of meningitic symptoms, and the discoloration of 
the skin soon became nearly as deep as before. Death took place after 
the meninigitis had continued for a week. There was a tubercular nodule 
of the size of a pea in the right suprarenal body, and the solar plexus and 
semilunar ganglion were embedded in dense fibrous tissue. Slight, transi- 
tory improvement from suprarenal extract was reported also by Foster. 
Trevithick, || on the contrary, obtained no benefit from its use. W. W. 
Johnston ** has tabulated from various sources fifty cases of asserted 
Addison’s disease treated with suprarenal preparations. Ten cases are 
stated to have recovered and sixteen to have improved. He adds one 
under his own observation who showed marked improvement with gain in 
flesh and strength during the five months’ use of suprarenal tablets. Box ++ 
states that of eight cases treated in St. Thomas’ Hospital four died during 
the first week of treatment. Two lived ninety-five and one hundred and 
twenty-one days respectively, during which time 3255 and 7200 grains, 
largely of the medullary portion of sheeps’ fresh capsules, were taken, 
chiefly by the mouth. No permanent improvement and no increased vas- 
cular tension were observed. Two other patients were treated with tablets 
by the mouth and with subcutaneous injections of the watery glycerin 
extract, which at first caused some discomfort. One patient did not im- 
prove; the other increased somewhat i in strength and the pigmentation 
diminished.—Eb. ] 

In a certain sense the possibility of treatment based on etiology is 
afforded by syphilis, but unfortunately cases of Addison’s disease thus 
caused are of rare occurrence. Finally, when symptoms of Addison’s 


* Cited in Centralbl. f. Phys., 1898, x11, 321. 

+ Wiener klin. Woch., 1899, x11, 736. 

t Miinch. med. Woch., 1900, XLVI, 1821. 

§ Lancet, 1899, 1, 1561. || Lancet, 1900, 11, 105. 

** Trans, Assoc. Am. Phys., 1900, xv, 65. = tt} Practitioner, 1901, Lxv1, 520. 


364 ADDISON’S DISEASE. 


disease arise from compression of certain portions of the abdominal sym- 
pathetic by tubercular or lymphomatous glands, intravenous injections of 
arsenic may cause a disappearance of these symptoms by reducing the size 
of the glands. 

The further treatment is entirely symptomatic. Considerable tem- 
porary improvement in a number of cases has followed the administration 
of glycerin, nitroglycerin, amyl-nitrite, and strychnin, or the use of fara- 
dic or particularly galvanic electricity. Apart from the employment of 
these agents, the usual indications are for strengthening diet and the use 
of tonics. 

Care must be observed in the treatment of the frequent constipation, 
for persistent and uncontrollable diarrhea may follow the administration 
of drastics. 


PATHOGENESIS OF ADDISON’S DISEASE. 


The difficulty in systematizing the various forms of Addison’s disease 
is due chiefly to our imperfect knowledge of the function of the suprarenal 
capsules, in part to the great variety of anatomic lesions occurring in 
these organs, in part to the unequal development of the pathologic 
process, and, finally, to the fact that disease of the suprarenal capsules by 
contiguity produces disease of adjacent organs (particularly the nervous 
apparatus). The greatest confusion has arisen because there are typical 
cases of this affection in which the suprarenal capsules are found to be 
perfectly normal at autopsy. 

Nevertheless the relation between Addison’s disease and the supra- 
renal capsules is so constant that the relatively few exceptions are not 
capable of casting a doubt upon it. Itis supported by the experience of 
the last forty years and Lewin’s extensive statistics, which prove the 
occurrence of disease of the suprarenal capsules in 88% of the typical cases 
of Addison’s disease. 

The suprarenal capsules, analogous to the thyroid, are sometimes 
classed as glandular organs with an internal secretion and sometimes as 
nervous organs. Numerous hypotheses have been advanced in explana- 
tion of the symptoms of Addison’s disease, among which two in particular 
deserve especial consideration. The first theory attributes the symptoms 
of Addison’s disease to changes in the abdominal sympathetic and its 
ganglia; the second or humoral theory explains Addison’s disease as an 
autointoxication resulting from disturbances of the function of the supra- 
renal capsules; this function is considered to render harmless or neutralize 
certain products of tissue change. 

The former theory was insufficient for those cases of Addison’s disease 
presenting no lesions in the sympathetic system and its tracts. The latter 
theory failed when cases were found presenting during life the symptoms 
of Addison’s disease, while at autopsy the suprarenal capsules were found 
to be intact, and yet changes were present in the abdominal sympathetic 
nerve and celiac ganglion; furthermore, because the symptoms of Addi- 
son’s disease were lacking when there were extensive lesions of the supra- 
renat capsules, even complete caseation of both organs or entire absence 
of them. 

Jiirgens reports a case of especial importance in which an aneurysm of 
the abdominal aorta St compression and consecutive atrophy of the 


PATHOGENESIS. 365 


splanchnic nerve ran its course under the typical clinical picture of Addi- 
son’s disease. 

Other cases presented during life the symptoms of Addison’s disease 
while at autopsy there was found a combination of diseases, involving, on 
the one hand, the suprarenal capsules; on the other hand, the sympa- 
thetic and splanchinc nerves and, further, the spinal cord. These cases 
are too obscure to permit any positive conclusions to be drawn, and the 
same is true of those cases in which the suprarenal capsules are said to 
have been lacking but no symptoms of Addison’s disease were present. 

The supporters of the sympathetic theory claim that unless the sym- 
pathetic nerves also are involved the symptoms of Addison’s disease do not 
make their appearance, although the destruction of the suprarenal cap- 
sules may be complete. It must also be borne in mind that accessory 
suprarenal capsules or other organs may exist which are capable of assum- 
ing vicariously the function of the suprarenal bodies. 

With reference to the second group of cases,—those presenting the 
symptoms of Addison’s disease, but with perfectly normal suprarenal 
bodies and sympathetic,—it must be observed that every case of “bronzed 
skin” does not justify the diagnosis of Addison’s disease, and that even in 
cases terminating fatally with symptoms of cachexia and bronzed skin 
diagnostic errors have frequently been made. 

It has been found necessary to classify as pseudo-Addison’s disease 
those affections incidentally complicated by loss of power and bronzing of 
the skin. 

On account of all these factors the greatest confusion has reigned with 
reference to Addison’s disease. It was known that it had something to do 
with the suprarenal capsules, but it was not possible to explain the cases 
occurring in the absence of disease of these bodies; and yet it seemed, 
in spite of the anatomic polymorphism, that the uniformity of the clinical 
symptoms was such that some explanation must be sought. 

The earlier physiologists regarded the suprarenal capsules as a part of 
the sympathetic nervous system. Briicke regarded this as probable 
“because, in proportion to the small size of the organ, a very large num- 
ber of nerves enter into it, and because these nerves do not form periph- 
eral end-organs, but rather such end-organs as are found in ganglia and 
in the central nervous system—namely, ganglionic bodies; these, as is 
already known from experience elsewhere, are to be considered not as the 
terminations but as the origin of nerves. There is no occasion for 
classifying these organs among the glands, because it is not known that 
they possess any secretory activity, and they do not even present a true 
adenoid structure, asis found in the spleen and thymus.” 

The more recent investigations of the physiologie action of suprarenal 
extracts have, as is already known, proved the suprarenal capsule to be an 
organ, analogous to the thyroid, which elaborates a physiologically active 
substance; in other words, this organ is really a gland with an internal 
secretion. It is perhaps remarkable that Funck and Griinhagen formerly 
expressed the opinion that the nerves of the suprarenal capsules were gland 
nerves bearing the same relation to gland cells as the nerves supplying 
the cells of the salivary glands (Pfliiger). At the Sixty-sixth Congress of 
German Naturalists and Physicians, held in Vienna, K6lliker emphatically 
stated that the nerve-endings in the medullary substance abounding in 
nerves bore a peculiar relation to the individual cells, each of which was 


366 ADDISON’S DISEASE. 


surrounded by a network or mesh of terminal fibrils; and that the cells of 
the medullary substance were not nerve-cells, but simple gland cells. 

He further states that the cells of the medullary substance, under the 
influence of nerves, elaborate certain substances which are furnished to 
the blood. He believes that the cells of the cortex also possess this func- 
tion, although to a lesser degree. 

Although the final solution of the problems of Addison’s disease must 
be left to the physiologists and experimental pathologists, I cannot but 
express at this point my personal view of the essential nature of Addison’s 
disease. 

This opinion conforms closely to an idea which I have already ex- 
pressed in my work on pellagra, published in 1887. The results of my 
observations at that time were summed up in the following words: “ Pella- 
gra is a chronic systemic disease consisting in delicate nutritive disturb- 
ances in the sympathetic nervous system and in the central nerves and 
blood-vessels pertaining to it. It is caused by a poisonous principle, the 
harmless antecedents (mother-substances) of which are contained in de- 
cayed corn. This substance is decomposed in the intestinal canal of a 
susceptible individual with the formation of a poisonous, apparently vola- 
tile radical which produces intestinal autointoxication.” 

Elsewhere, while enumerating the various diseases which pellagra may 
simulate, Addison’s disease was included, and the thought was added that 
in time, perhaps, a common theory might be forthcoming in explanation 
of the obscure etiology and nature of those diseases which are clinically so | 
similar to pellagra. | 

In view of the latest phyisologic investigations of the functions of the 
suprarenal capsules and of the changes occurring in the sympathetic sys- 
tem in Addison’s disease, I believe the theory which I have already ad- 
vanced in explanation of pellagra is equally applicable to Addison’s dis- 
ease; particularly in virtue of the following considerations.* 

In his lecture on the sympathetic Kolliker considers the sympathetic 
nervous system to be a many-linked chain composed of contiguous and 
interlacing motor and perhaps also of sensory units which originate in the 
cerebrospinal nerves, and regards them merely as an offshoot of the cere- 
brospinal system, for the latter is composed also of many psychic and 
somatic, centrifugally or centripetally conducting units or neurons. 

Waldeyer has shown that each neuron consists of three parts—the 
nerve-cell, the nerve-fiber, and the terminal filaments; and that impulses 
may be transmitted in either direction, from the cells to the filaments or 
in the reverse direction. 

If the suprarenal capsules are to be considered an organ provided with 
these terminal filaments of Waldeyer (and such were actually observed by 
Kolliker!) and inserted into the sympathetic nervous system, it is readily 
conceivable that the splanchnic nerve, with its radiation in the solar 
plexus, may act as the secretory and trophic nerve of the suprarenal 
capsule, just as the sympathetic nerve acts in relation to the submaxillary 
gland. The suprarenal capsules would then be connected by centripetal 
and centrifugal tracts with the gray matter of the spinal cord and the 
centers of the splanchnic nerve in it. 


* Unfortunately I did not receive Ewald’s paper upon this subject until after 
the following considerations and conclusions had been written; in this work he 
advances a theory similar to my own, assuming the disease to be of a system the 
centers of which lie in the suprarenal capsules and the celiac ganglion. 


PATHOGENESIS. 867 


This idea of the splanchnic nerve as a trophic nerve is supported in 
Jiirgens’ case of Addison’s disease above mentioned occurring in connec- 
tion with an aneurysm of the abdominal aorta. In this there was, in 
addition to pressure-atrophy of the splanchnic nerve, atrophy of the 
corresponding suprarenal capsule. 

It must be left for the experimental pathologists to furnish proof of the 
importance of the splanchnic nerve as a secretory nerve of the suprarenal 
capsules. Dr. Biedl has already undertaken experiments in this direction, 
from which it appears that upon stimulation of the splanchnic nerve the 
suprarenal capsule becomes hyperemic and the flow of blood from the 
suprarenal vein is increased; this shows at least that the splanchnic nerve 
exerts a positive vasodilating action upon the suprarenal capsules. The 
experimental pathologist can answer much more positively and more 
speedily than the clinician whether the hyperemia thus produced is 
attended by an increased secretion of the active suprarenal substance; or 
whether the same conditions prevail here as in the submaxillary gland 
upon stimulation of the chorda tympani and sympathetic, which, it is 
well known, possess an antagonistic action; whether the splanchnic nerve 
produces both vasodilation and increased secretion, as the chorda tym- 
pani does in the submaxillary gland; and, finally, whether the other nerves 
supplying the suprarenal capsules—e. g., the vagus—have any determin- 
ing action upon its function. 

It is known that the tonic centers of the splanchnic nerves are situated 
at the junction of the cervical and dorsal cord; that their central ganglion 
cells are most abundant between the eighth cervical and second dorsal 
nerves; but that these cells also are present in gradually diminishing 
numbers both above and below these points, so that the entire center ex- 
tends in the long axis of the spinal cord from the sixth cervical to the fifth 
dorsal nerve. The ganglion cells forming the center are situated in the 
motor areas of the gray matter of the cord. In the cervical cord they are 
situated in the lateral horns, in the dorsal cord in the lateral divisions of 
the anterior horns. These “sympathetic-motor” cells do not differ either 
in size or in structure from the voluntary motor cells of the anterior horns 
(Biedl). 

Therefore if the trophic centers of the splanchnic nerve bear the same 
relation to its peripheral distribution in the abdominal viscera as the 
centers of a motor nerve bear to its peripheral distribution, it is readily 
conceived that Addison’s disease may be the manifestation of such a sys- 
temic disease involving the central and peripheral tracts of the splanchnic 
nerve and also its intermediate and terminal organs (just as poliomyelitis, 
neuritis, and myositis all result in paralysis of the end-organ, the muscle). 

According to this view, the location of the degenerative process is 
immaterial, whether in the spinal center, in the course of the splanchnic 
nerve, in the celiac ganglion, which is in part an intermediate organ, or in 
the end-organ, the suprarenal capsule itself. 

In every case the result is a more or less complete suspension of the func- 
tion of the end-organ—and this is to be sought for in every case as the cause 
of Addison’s disease. 

Although the latest physiologic investigations have not positively 
determined the function of the suprarenal capsules, they have furnished 
important data. At any rate, it is known that this organ is a gland with 
an internal secretion and produces a physiologically active substance 
which is important to life. 


368 ADDISON’S DISEASE. 


One group of physiologists claim that the production of this substance 
is the sole function of the suprarenal capsules; others maintain that these 
organs exert a neutralizing action, by means of which the toxic products 
of nervous and muscular activity are rendered harmless. 

May not both views be correct? May not both functions be con- 
tained in the suprarenal capsules? From the standpoint of expediency 
this seems highly probable, and it is conceivable that the poisonous 
products of tissue changes in other organs may be carried to the suprarenal 
capsules and undergo various chemical processes (oxidation, reduction, 
decomposition, and reunion), and finally be synthetically elaborated into 
a secretion which is important to life. 

The theory of such a double function is compatible with the existence 
of two histologically different substances in the suprarenal capsules, and, 
to my mind, is not without analogy. The theory of the function of the 
thyroid is cast upon perfectly similar lines. 

It is assumed that out of the poisonous products (perhaps xanthin 
bases, Lindemann) of tissue change which are carried to the thyroid certain 
substances are synthetically produced which are essential to the nutrition 
and function of the brain. The function of the suprarenal capsules may 
similarly be explained, particularly since these organs are known to pre- 
sent many analogies. The suprarenal capsules may bear the same rela- 
tion to the solar plexus as the thyroid capsule bears to the brain, and, in- 
deed, the solar plexus has been called the abdominal brain. 

According to this theory, when the suprarenal capsules are the seat of 
organic or functional disease, the absence of their peculiar secretion results 
in impairment of the nutrition and function of this abdominal brain, 
while at the same time the poisonous products of metabolic activity are 
not destroyed, but accumulate in the system, causing an autointoxication. 
As the result of these two factors, the entire organism suffers as well as the 
nerves and blood-vessels of the sympathetic system which are primarily 
involved. 

Congenital imperfect development (tubercular) or acquired vulnera- 
bility of these nerves and blood-vessels predisposes to the early acquisition 
of these disturbances, which may be manifested merely by functional 
inefficiency or eventually also by anatomic alterations. No gross lesions 
of the sympathetic system will be found unless the underlying anatomic 
cause of the impairment of function of the suprarenal capsules is situated 
in the sympathetic tract primarily or has extended by contiguity from the 
suprarenal capsules to the adjacent sympathetic plexuses. 

Does this theory correspond to the anatomic lesions which are actually 
found in Addison’s disease? 

Statistics furnish incontestable proof that the suprarenal capsules are 
of the utmost importance in the production of Addison’s disease, patho- 
logic alterations being present in these organs in 88% of all cases. That, 
on the contrary, the changes in the sympathetic system are too insignifi- 
cant and inconstant to adequately explain all cases of Addison’s disease is 
supported by the statements of Brauer, who, after a careful consideration 
of all previous histologic conditions in the sympathetic system, came to 
the following conclusions: “It has not yet been proved that the under- 
lying cause of Addison’s disease is an anatomically demonstrable affection 
of the sympathetic nervous system. The inconstant occurrence of such 
lesions, the questionable significance of some of the alterations described, 
the occurrence of similar lesions in the sympathetic system without coin- 


PATHOGENESIS. 369 


cident Addison’s disease, and, finally, the entire absence of lesions occa- 
sionally reported render it highly probable that there is no constant rela- 
tion between Addison’s disease and changes in the sympathetic system. 
It seems more likely that the alterations in the sympathetic system are 
secondary to the as yet unknown cause of Addison’s disease or to the pro- 
found cachexia, and thus, perhaps, may produce or influence certain 
symptoms of the disease. 

If the fundamental cause of Addison’s disease is considered to be a’ 
progressive impairment and finally a complete suspension of the function 
_ of the suprarenal capsules, two sets of questions must be answered : 

1. What is the explanation of the symptoms of Addison’s disease when 
‘both suprarenal capsules are diseased? 

2. What is the explanation of those cases which present clinical or 
anatomic deviations from the type? 

With reference to the first question, the most prominent symptoms 
from the outset in the clinical course of Addison’s disease—asthenia and 
loss of power with its special manifestations in various organs—can be 
readily accounted for by this theory of the injury of the double function 
of the suprarenal capsules. The tone of the entire vascular system is 
impaired because of the deficient production of suprarenal secretion, 
which raises blood-pressure. This gives rise, in the first place, to atonic 
hyperemia of the abdominal viscera with anemia and impairment of func- 
tion of all other organs. Thus is explained the frequent contrast between 
the pulsation of the abdominal aorta and the small, soft, peripheral pulse 
which, together with its rapidity, is a manifestation of the loss of tone 
of the vagus roots from cerebral anemia. At the same time the toxic 
products of the metabolic activity which are only imperfectly neu- 
tralized in the suprarenal capsules produce their general systemic effect 
and increase the action of the first-mentioned element. The combin- — 
ation of these two factors accounts for a large group of nervous symptoms 
(vertigo, ringing in the ears, fainting, headache, etc.) and also for the 
violent symptoms of the acute terminal stage following sudden complete 
suspension of the suprarenal function. 

The gastro-intestinal symptoms are partly the result of these general 
' systemic disturbances, but in the majority of cases they are due to the 
local pathologic process in the suprarenal capsules, whether through ner- 
vous influence or by direct extension to the gastro-intestinal sympathetic 
tracts. 

The explanation of the third cardinal symptom, the melanoderma, 
requires a more detailed discussion, which I shall precede by a few remarks 
upon pigment formation in general. 

Histologic investigations seem to prove that the mode of production of 
pigment in health and in a great many pathologic conditions is identical. 
This view is based chiefly upon the results of Karg’s experiments. He 
grafted fragments of white skin upon a negro, excised portions of the graft 
at frequent intervals, and studied under the microscope the progressive 
formation of pigment in the grafts. These investigations led him to con- 
clude that the pigment is formed in the cutis vera by peculiar cells, the so- 
called chromatophores. These are very numerous in the immediate _ 
neighborhood of the papillary blood-vessels, show many branches, and 
gradually penetrate upward to the lowest layers of the epidermis, the rete 
Malpighii, finally sending their projections, stuffed with pigment-granules, 
between the separate rete cells. By a kind of phagocytosis the pigment 

24 


370 ADDISON’S DISEASE. 


contained in these projections is taken up by the cells of the rete. Karg 
succeeded in demonstrating the very same process in the pigmentation of 
Addison’s disease, and concludes that all varieties of pigmentation arise 
in the following way: “Pigmented cells from the cutis vera penetrate to 
the epidermis, send out processes in all directions, and yield their pigment 
to the epithelial cells.”’ 

This view is shared by most of the recent investigators of this ques- 
tion, the only difference of opinion being as to whether the chromatophore 
cells originate from connective tissue or epithelium. This question is of 
minor interest to the clinician. : 

Karg demonstrated in like manner the process of absorption of pig- 
ment in the reverse direction after grafting a negro’s skin upon a white © 
person. After six weeks the rete Malpighii was entirely free from pigment, 
but the cutis vera contained numerous leucocytes and wandering cells, all 
richly laden with pigment. In this case also stellate cells were found at 
the junction of the cutis vera and the rete Malpighii, sending processes 
into the latter. These processes were not so plainly visible, because they 
no longer contained pigment. According to other observers, at least a. 
part of the pigment is to be found in the lymphatic glands corresponding 
to the particular area of skin. 

It is necessary to establish a second fact underlying the theory of 
melanoderma—namely, that the formation of pigment in the lower ani- 
mals is directly controlled by the nervous system. 

Vulpian showed that in frogs the changes in the color of the skin are 
governed by special nerves, which, although following the distribution of 
the vasomotor nerves, possess an entirely different function. The frog’s 
skin contains large, branching pigment-cells, called chromoblasts, which 
are capable of contraction and expansion, producing alternately a light or 
dark coloration of the skin. The nerves which stimulate contraction of 
the chromatophores, thereby producing a lighter color of the skin, run in 
the tracts of the vasoconstrictor nerves, while those which cause expan- 
sion of the chromatophores and a darker color of the skin accompany the 
vasodilator nerves. 

As has just been stated, similar branching pigment cells, chroma- 

tophores, have been found by Karg and. many other observers in the 
pathologically pigmented and even in the normal human skin. 
_ There are many other arguments in support of the theory that in man 
both production and absence of pigment are dependent upon nervous 
influences. One fact is the occurrence of abnormal pigmentation, not 
only in organic diseases of the central and peripheral nervous system,— 
e.g., tabes, syringomyelia, and neuritis,—but also in functional neurosis 
and neuralgias. Doubtless the pigmentation developing during preg- 
nancy and in diseases of the female genitals (ovarian cysts) belongs to this 
category. 

The above-mentioned conditions observed in animals seem to justify 
the conclusion that the formation of pigment in man also is controlled by 
the vasomotor nerves, in other words, by the sympathetic nervous system, — 
acting through the medium of chromatophore cells. 

The origin of the pigment contained in the chromatophore cells is a 
question which cannot be answered so positively. The fact that the chro- 
matophores are most abundant around the blood-vessels, particularly 
around the capillaries of the cutis, suggested at once the thought that 
their pigment was derived from the blood, either directly from the hemo- 


lard 


PATHOGENESIS. 71 


globin or indirectly from the colorless albuminous bodies of the blood- 
plasma. This view holds good in spite of the fact that the pigment-gran- 
ules do not respond to the tests for iron, since it has repeatedly been shown 
that this reaction may be absent even from deposits of pigment positively 
derived from hemoglobin—e. g., extravasations of blood. The pigment 
formed by plasmodia is also free from iron, yet this is without doubt a 
product of the digestion of hemoglobin. 

It must frankly be admitted that no actual knowledge is possessed of 
the derivation of the pigment in Addison’s disease; in the first place, 
because the chemical composition of this pigment is unknown, and yet it 
is known that there are several different varieties of melanin. It may be 
taken for granted that the pigment is originally derived from the blood, 
but whether from the decomposition of red blood-corpuscles or from some 
colorless antecedent contained in the plasma it is impossible to decide. 
The analogy with the above-mentioned conditions observed in animals 
leads to the belief that the pigment formation in Addison’s disease also 
takes place under the control of the sympathetic system. 

The pigmentation of Addison’s disease may be compared with that 
observed in chronic arsenical poisoning, which may appear in some indi- 
viduals after the administration of Fowler’s solution of arsenic. Wyss 
investigated the microscopic appearances of the skin in this condition. 
He found an iron-free pigment situated primarily in the rete cells over- 
lying the papillary layer and the interpapillary areas, the intensity of the 
pigmentation corresponding approximately to that observed in the Mal- 
pighian layer of a moderately dark mammary areola. Another favorite 
site of this pigment was the papillary layer of the skin, especially in the 
neighborhood of the blood-vessels. Finally, the pigment may be de- 
posited in the perivascular lymph-spaces. In the latter situation the 
abundance of the pigmentary deposit depends upon the wealth of the 
corresponding cutaneous area in papille and upon the duration and inten- 
sity of the arsenical melanosis. 

Wyss bases his views as to the origin of this pigment upon Stirling’s 
examination of the blood in children during the internal administration 
of Fowler’s solution. Stirling found that the number of red corpuscles 
and the percentage of hemoglobin were reduced one-half, and for this reason 
Wyss feels justified in assuming that the pigment present in arsenical 
melanosis is derived from decomposed blood-pigment. 

The analogy between these conditions and those observed in Addison’s 
disease is striking. Even the abundant deposit of pigment in the lymph- 
atics of the papille is simulated by the occurrence of pigment in the 
peripheral lymph-glands in Addison’s disease as observed by Schmorl, 
who interprets this as an evidence of the transference of granular pig- 
ment from the skin into the peripheral lymphatic vessels. He also ex- 
plains the pigmentation of the cutaneous lymph-glands which he observed 
in two negroes and two mulattoés as a physiologic absorption of pigment 
from the skin into the corresponding lymphatic vessels. 

The idea is perhaps not foreed that the deposits of pigment observed in 
the cutaneous lymph-spaces in arsenical melanosis also is attributable to 
a reversed absorption of pigment. 

According to this view, the cutaneous melanosis of arsenical poisoning 
and of Addison’s disease would correspond in all important histologic 
details and in their manner of explanation. 

This striking similarity is of especial importance because it is known 


372 ADDISON’S DISEASE. 


that arsensic acts as a poison upon the sympathetic nervous system, par- 
alyzing the terminations of the splanchnic nerves. The theory that this 
pigmentation occurs through the agency of the sympathetic nervous 
system would gain in probability if in future cases of arsenical poisoning 
after relatively small doses of arsenic no destructive changes in the blood, 
particularly in the red corpuscles, were to be found. 

That an abnormal pigmentation of the skin also may arise during the 
course of other chronic poisonings characterized by delicate anatomic 
changes in the sympathetic nervous system is shown by those cases of 
pellagra which I and other authors have reported. | 

The following conclusions may be drawn: 

1. Since all cases of pigment formation, whether normal or pathologic, 
present the same histologic alterations; 

2. Since it must be taken for granted that the normal formation of pig- 
ment is controlled by the nervous system, particularly the sympathetic; 

3. Since abnormal pigmentation has been observed as the direct result 
of a number of diseases of the nervous system ; 

4, Since some sympathetic nerve-poisons are capable of developing an 
abnormal pigmentation in susceptible individuals ; | 

5. Finally, since a number of diseases having no connection with the 
suprarenal capsules (e. g., diabéte bronzé, ovarian cysts, Basedow’s disease, 
scleroderma, etc.) may be attended by extensive melanosis: 

The conclusion is justified that the pigmentation of Addison’s disease 
also is due to the same cause; that is, to a disturbance of innervation in 
the sympathetic tract. Neither experiments on animals, nor clinical ob- 
servation, nor postmortem examination, have furnished any evidence in 
support of the fact that the suprarenal capsules have anything directly to 
do with the formation or destruction of the antecedent of this pigment; 
on the contrary, these observations tend to prove that disease of the supra- 
renal capsules does not produce an abnormal pigmentation of the skin 
unless secondary involvement of the sympathetic system has occurred. 

Therefore melanoderma is not of equal rank in the pathology of Addi- 
son’s disease with, for example, loss of power. It is not a direct, but 
rather an indirect, suprarenal symptom; its frequent occurrence in disease 
of these organs being sufficiently explained by the intimate relation exist- 
ing between the suprarenal capsules and the sympathetic nervous system 
and by the regular extension of the pathologic process to the latter; in- 
deed, this symptom may be absent, even though the suprarenal capsules 
are entirely destroyed, as long as the sympathetic tracts controlling the 
formation of pigment remain intact. 

The facts that the melanoderma by no means always runs a parallel 
course with the severity and progress of the other symptoms of Addison’s 
disease; that in severe cases the melanoderma may be only partial or 
slight ; that this symptom often may not appear until the terminal stage, 
or, on the other hand, may be one of the first symptoms of the disease— 
these facts still further tend to prove that “melanoderma and disease of 
the suprarenal capsules do not stand in the simple relation of cause and 
effect.” 

seag does pigmentation of the mucous membranes, so important in 
the diagnosis of Addison’s disease, furnish any fundamental distinction 
between this and other melanodermata, for similar deposits of pigment 
have been observed in other diseases having absolutely no connection with 
the suprarenal capsules, and even in perfectly healthy individuals. 


PATHOGENESIS. 3738 


The cases presenting clinical or anatomic deviations from the type 
must be considered under different heads. 

1. How are those cases to be explained in which, in spite of complete 
destruction of both suprarenal capsules, the three cardinal symptoms of 
Addison’s disease are entirely or in part lacking? 

It is true that in some cases, in spite of extensive destruction of both 
suprarenal capsules, Addison’s disease was not diagnosticated, but it must 
not be imagined that these cases presented no symptoms attributable to 
the suprarenal bodies. Small pulse, loss of power, disturbances of the 
nervous and digestive systems, apparently were present, but were attrib- 
uted to the underlying disease (tuberculosis or cancer), simply because the 
conspicuous criterion for the diagnosis of Addison’s disease, melanoderma, 
was not present. It has Just been stated why this symptom may be ab- 
sent in such cases. 

2. How does it happen that tubercular disease of the suprarenal cap- 
sules is so generally accompanied by the typical symptoms of Addison’s 
disease, while in other forms of disease, particularly in cancer, this group 
of symptoms is very often lacking, although both glands may be exten- 
sively involved? ; 

The cause for this lies, in the first place, in the exquisitely destructive 
nature of the tubercular process, which completely destroys the specifi- 
cally active cells of the organ either by caseation or by the frequently added 
fibrous degeneration; and, in the second place, in the well-marked ten- 
dency to extension manifested by the tubercular disease. Other affec- 
tions which destroy the specific gland cells will be manifested by the same 
symptoms, as, for example, the simple sclerotic, chronic inflammations 
and the scirrhous forms of cancer. 

Primary adenocarcinoma and perithelioma behave in an entirely dif- 
ferent manner. In addition to the fact that these tumors are rarely 
bilateral, still another circumstance must be taken into consideration— 
namely, that the cells of these new-growths more or less completely main- 
tain the character of the original gland cells, and are capable of continuing, 
at least in part, the function of the latter. This has also been observed in 
cancers of other organs,—e. g., the liver,—for even the metastases from 
this organ are capable of secreting bile. That some forms of cancer lead 
rather to an increase than to a suspension of the glandular function seems 
to be shown by those cases which presented during life a wiry pulse and 
cerebral hemorrhages resulting from the rapid rise of blood-pressure. 
These cases were mentioned in the section on differential diagnosis; they 
form a supplement to those rare cases of carcinoma of the thyroid 
which run their course with symptoms of Basedow’s disease, and which 
are generally regarded as an expression of the increased functional 
activity of the gland. 

3. Why in severe cases of Addison’s disease is only unilateral or in- 
complete bilateral disease of the suprarenal capsules present at autopsy? 

When one suprarenal capsule is diseased, it must be borne in mind that 
the function of the other capsule may be suppressed through the agency of 
supposed trophic and secretory sympathetic nerve-fibers; this influence 
being transmitted to the abdominal ganglia of the sympathetic or to the 
centers of the splanchnic nerve in the spinal cord, which are connected by 
collaterals with those of the opposite side. The conditions may be similar 
to those observed in connection with the renal secretion, when the sudden 
arrest of the secretion of one kidney produces reflexly arrest of the func- 


374 ADDISON’S DISEASE. 

tional activity of the healthy kidney also; or it may have to deal with a 
process which Charcot makes use of in the explanation of muscular 
atrophy following chronic articular rheumatism, and which he terms “ tor- 
peur des cellules mortrices.”’ 

On the contrary, in some cases of unilateral suprarenal disease in which 
the symptoms of Addison’s disease are absent it must be assumed that a 
vicarious activity of the intact suprarenal capsule exists; just as disease of 
one kidney may give rise reflexly to hypersecretion from the opposite: 
kidney. Whether, in any given case, the function of the second organ will 
be suppressed or vicariously increased; and why at one time the one, at 
another time the opposite, occurs, it is entirely beyond our power to pre- 
dict. 

In explanation of those cases of fully developed Addison’s disease in 
which both suprarenal capsules are found intact, it must be assumed that 
the tropho-secretory system of the capsules is injured i in some place else- 
where, and that the function of the suprarenal capsules is consequently 
incomplete or arrested. As, for instance, a muscle, although anatomi- 
cally intact, loses its function when its motor nerve is diseased. 

Further, the theory that the splanchnic nerve is a trophic nerve for the 
suprarenal capsule would throw light upon those cases in which partial 
tubercular changes are found in the suprarenal capsules in the course of 
disease of some part of the splanchnic nerve. One could readily conceive 
how, in disease of the splanchnic nerves themselves or of their central 
tracts, secondary nutritive disturbances are set up in the suprarenal cap- 
sules, with the result that these organs furnish a locus minoris resistentie 
for the lodgment of the bacilli. There are plenty of analogies for this cir- 
cumstance. One needs only to refer to the frequent occurrence of de- 
cubitus or arthritic inflammation upon the paralyzed side in hemiplegia, 
or to the occurrence of trophic affections of the fingers and toes in syringo- 
myelia, ete. 

A similar influence to that exerted by a diseased suprarenal capsule 
upon its healthy fellow is manifested by a focus of disease upon its healthy 
surroundings within the same organ; in other words, the function of the 
healthy part of the organ may be suppressed because of circulatory 
disturbances or because of the local irritation—e. g., toxin (tuberculin)— 
proceeding from the focus of disease. This suppression of function may 
be permanent, in which case the Addison’s disease leads progressively to 
its fatal issue; or it may temporarily disappear in case the adjacent dis- 
eased process is arrested. The intermissions and remissions so frequently 
observed in the course of Addison’s disease are explained as soon as the 
action of the local poison is suspended by the recovery of those portions 
of the glands which still remain intact. The nature of the underlying 
tubercular process precludes the permanence of these remissions, for even 
after an arrest of several years this process may be lighted up anew, and 
may again exert its injurious influence upon its surroundings, leading 
either to temporary acute exacerbations or terenenne with violent 
symptoms, directly in death. 

4. How is Addison’s disease explained in the absence of disease of the 
suprarenal capsules? 

The explanation of these cases has already been given, when in the de- 
velopment of our theory it was stated that if the suprarenal capsules were 
not actually diseased, the cause of their functional inactivity must be sought 
for in an injury to the nerve-tracts controlling their function—~. e., in the 


PATHOGENESIS. 375 


spinal cord, in the splanchnic nerve, or in the celiac ganglion. An ex- 
ample of this type is the frequently cited case of Jiirgens, in which aneu- 
rysm of the abdominal aorta running its course under symptoms of Addi- 
son’s disease produced suppression of the function and secondary atrophy 
of the corresponding suprarenal capsule from compression of the splanch- 
nic nerve. . 

5. Finally, how are those cases of Addison’s disease to be explained 
without any pathologic changes in the entire apparatus? 

This question is a very difficult one to answer. In the first place, there 
are certain cases presenting during life the typical symptoms of Addison’s 
disease in which no alterations are found in the “apparatus” at autopsy, 
although extensive pathologic alterations in other organs are present. 
These cases cannot satisfactorily be explained by the existing methods of 
clinical diagnosis and pathologic technique. As the clinician is unable to 
decide, in a complicated case of this kind, whether the loss of power results 
from coincident disease of the suprarenal capsules or from the severe 
underlying disease,—e. g., cavernous phthisis, endocarditis, ete.,—so the 
pathologist is unable to predict from the appearance of the cell whether it 
was capable of performing its function during life or not. If cases should 
be found, although none are certainly known at present, terminating 
fatally with the typical symptoms of Addison’s disease although no lesion 
of the apparatus or any other severe disease is demonstrable postmortem, 
we could no more explain such cases than we now can explain the cases of 
chorea minor and hysteria which terminate fatally without any pathologic 
changes being found after death. 


Finally, our views as to the nature of Addison’s disease may be summed 
up briefly as follows: 

The suprarenal capsule is agland with an internal secretion. It pos- 
sesses a double function: first, the neutralization of the toxic products of 
the metabolic activity of other organs; second, the synthetic production 
of a substance which is essential to the sympathetic system maintaining 
its nutrition and a normal tone. 

In every case the symptoms of Addison’s disease result from impair- 
ment, or eventually complete suppression, of these functions of the supra- 
renal capsules, brought about by disease of the capsules themselves or of 
the nerve-tracts controlling their function. These nerve-tracts extend 
from the spinal cord through the splanchnic nerve and the celiac ganglion. 
This impairment and eventual suppression of the function of the supra- 
renal capsules account for the nutritive and functional disturbance of the 
sympathetic system, on the one hand, and for the general autointoxica- 
tion, on the other. In addition to these two principal factors, extension 
of the pathologic process in many cases to the abdominal sympathetic is 
responsible for the occurrence of some of the symptoms of Addison’s 
disease. 

Pigmentation of the skin and mucous membranes is not an integral 
part of Addison’s disease, and, though of decided diagnostic significance, 
is not an essential feature. It is rather an indirect than a direct supra- 
renal symptom, arising only through the agency of local or general disease 
of the sympathetic system. 


376 DISEASES OF THE SUPRARENAL CAPSULES. 


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378 DISEASES OF THE SUPRARENAL CAPSULES. 


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880 DISEASES OF THE SUPRARENAL CAPSULES. 


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wicz. . 


DISbeers Ol LA Lives. 


BY 
PROF. DR. H. QUINCKE 
AND 


PROF: (DRY G. HOPPE-SEYEER. 


Edited, with Additions, 


BY 


FREDERICK A. PACKARD, M.D. 





DISEASES OF THE LIVER. 





INTRODUCTION. 
(Quincke. ) 


1. TOPOGRAPHIC ANATOMY AND DIAGNOSIS. 
POSITION; SIZE. 


THE liver is situated in the lower part of the thorax closely wedged 
against the concavity of the diaphragm. The larger portion lies to the 
right of the median line, but a small portion extends beyond it to the left. 
Both anteriorly and posteriorly the greater part of its convex surface is 
directed toward the parietes and is covered by the ribs. It is in direct 
contact with the muscular walls of the abdomen only in the upper half of 
the epigastrium in the angle formed by the two costal arches. Above, 
it is bounded by the lower surface of the right lung, a small part of the left 
lung, and the heart. 

The lower surface of the liver, concave and irregular in outline, is in 
contact with the anterior and posterior surfaces of the stomach in the 
region of the lesser curvature, the upper part of the duodenum, the trans- 
verse colon, and the hepatic flexure of the colon, as well as with the right 
kidney and adrenal. Only when it is enlarged does the left lobe of the 
liver extend as far as the spleen. The right and left lobes are separated 
on the convex surface of the organ by the suspensory ligament, and on the 
lower surface by the ligamentum teres. The hepatic artery, the portal 
vein, and the bile-ducts enter the liver through a short, transverse fissure 
(the porta hepatis) situated in the middle of the lower surface. The gall- 
bladder is situated in a longitudinal fissure to the right of the porta, below 
and anteriorly, while the inferior vena cava occupies the posterior part 
of the fissure. The ligamentum teres (the obliterated umbilical vein) 
is seen in the longitudinal fissure to the left of the porta. This, together 
with the ductus venosus Arantii, is directed toward the inferior vena 
cava. 

The shape of the liver is considerably modified by the shape of adjacent 
organs, and varies in different individuals. The weight, too, is different. 
In a healthy adult the average weight of the liver is about 1500 gm. (3 
pounds). 


According to the investigations of Frerichs,* the weight of the liver fluctuates 
between one-seventeenth and one-fiftieth of the body-weight in people of different 
ages (in adults between one-twenty-fourth and one-fortieth of the body-weight), 
its absolute weight being from 0.82 to 2.1 kg. In children the liver is relatively 
larger, in the aged relatively smaller, than in middle-aged persons. In children, 
too, the left lobe is not so small in comparison with the right as it is in adults. 


* “Leberkrankheiten,” 2, Hefte 1, p. 18. 
: 383 


384 DISEASES OF THE LIVER. 


H. Vierordt * calculates that the average weight of the organ in an adult man 
is 1579 kg., in a woman 1526 kg. Assuming the average body-weight to be figured 
as 100 (in male subjects), then the liver weighs (according to Vierordt) : 


LENG DE WHOOP ne iid 3 Ge Ret ae eae eRe ee es ck’ 4.57 
Prom: one to nine Months ss ast ota Oia wee tae ee hoe VASES 2.9 
PLOW CON TO ClEVOO TAONUDS che. aceon Gao ed Stok cb aes RE we 4.9 
Mrony One CO Teen: VeREs n'y o 5 ats ale da i GA a ee 3.4 
From sixteen to twenty-five years... 05... ccc cee cee ven eses "2.7 


These figures, of course, refer to the liver after death and after the removal 
of all the blood. During life the organ is much larger, owing to the large quantity 
of blood that it contains. In the course of laparotomies this observation has fre- 
quently been made. According to an experiment by Sappey, a liver weighing 
1450 grams could contain 550 c.c. of fluid within its vessels. 

Monneret + found that:a liver weighing 1600 gm. when its vessels were ligated, 
lost 360 gm. of blood in twenty-four hours, and was able, on the other hand, to take 
up 1200 gm. of fluid if a forcible injection was used. 


PERCUSSION. 


The liver is examined during life by percussion, palpation, ausculta- 
tion, and inspection. The first method is the most frequently employed. 
The so-called absolute liver dulness—. e., the dulness over that part of 
the convex surface of the liver that is not covered by the lung—is first 
determined. It is not possible by percussion to determine the exact out- 
lines of the part of the liver in immediate contact with the dome of the 
diaphragm and the concave lower surface of the lung; for this reason this 
area of so-called relative liver dulness is, with few exceptions, of slight 
clinical value. ; 

The upper boundary of absolute liver dulness corresponds to the lower 
margin of the right lung. It intersects at the spinal column, the eleventh 
rib; in the scapular line, the lower margin of the ninth rib; in the 
axillary line, the lower margin of the seventh rib; in the mammillary line, 
the sixth intercostal space; in the parasternal line, the sixth rib. 

The extent of the absolute liver dulness, according to Bamberger, is as 
follows: 

In the axillary line, in men, 12 cm.; in women, 10.5 cm. 
In the mammillary line, in men, 11 cm.; in women, 9 cm. 


In the parasternal line, in men, 10 cm.; in women, 8 cm. 
Width of the left lobe, in men, 7 cm.; in women, 6.5 cm.t 


As a matter of fact, these measurements are only of limited utility, 
‘because they fluctuate greatly even in perfectly healthy persons of an 
average size, depending on the shape of the costal arch and of the lower 
thoracic aperture. In the case of the heart and the spleen it is possible to 
give normal measurements; but in the case of the liver the outlines of the 
organ itself and of the area of percussion dulness are determined by the 
relation of its margins to the margin of the thorax. Normally, the lower 
margin of the liver extends a little above the costal arch in the axillary 
line, crosses the costal arch in the mammillary line, cuts the median line 
half-way between the umbilicus and the ensiform cartilage, and extends 
from this point to the region of the apex-beat. Even these topographic 
relations fluctuate within wide limits, particularly in females. In them 
the lower margin of the liver may extend from 1 to 2 cm. further down- 


* ““Anatom.-physiolog. Tabellen,” Jena, 1893, pp. 20 to 23. 

t Archives générales de médecine, 1861, 1, p. 561. ‘ 

cae with many individual measurements are given by Frerichs, loc. cit., 
pp. 37-40. 


TOPOGRAPHIC ANATOMY AND DIAGNOSIS. 385 


ward. In children this is the rule, because the liver is larger and the ribs 
are less developed and run more horizontally. 

From a practical point of view it is of some value to measure the extent 
of the hepatic dulness in an individual case and to express it in figures, 
- because in this way it is often possible to determine changes in these 
dimensions that may occur in the course of disease. 

In order to determine the location of the lower margin of the liver it is 
best to percuss gently, beginning below and progressing upward. The 
first modification of the percussion sound should be noted. On account of 
the thinness of the margin this modification will be very slight. The 
tympanitic sound of the stomach and of the intestines, situated under- 
neath this sharp margin, frequently renders percussion of this part very 
uncertain. As we progress upward the tympanitic sound grows weaker. 
In some cases, however, it does not disappear entirely, but may persist 
even to the upper margin of absolute dulness. 

In order to percuss successfully, the abdominal muscles should be com- 
pletely relaxed. The absence of a large amount of subcutaneous fat ren- 
ders the proceeding more exact. If the stomach and intestines are dis- 
tended with gas, percussion is rendered difficult, as it 1s also if any air is 
present in these parts. 

In enlargement of the liver the lower margin usually moves down- 
ward, so that, in general, an extension of the absolute dulness downward 
occurs. If the liver is smaller and less thick than normal, the lower per- 
cussion boundary will move upward, the dull sound will be mixed with the 
tympanitic sound, or, in some cases, absolute dulness will disappear. 

At the same time, it must be remembered that, even if the liver is of 
normal size, the areas of percussion dulness may be changed owing to 
abnormalities in the shape of the thorax or of the abdominal cavity. An > 
increase of the antero-posterior diameter of the thorax produces a decrease 
in the hepatic dulness for the reason that the anterior part of the organ 
(in the erect position of the body) occupies a more horizontal position, 
and, consequently, is in contact with a smaller area of the anterior pari- 
etes below the lung. 

this change in the position of the liver has been called retroversion 
or “marginal position” of the liver, for reasons which, by the way, are not 
quite clear. The liver must be imagined as standing on its posterior dull 
margin when the body is in the horizontal position. 

This diminution in the area of percussion dulness, even when the liver 
is normal, is seen in the barrel-shaped emphysematous thorax, in the ky- 
phosis of old age, and in spondylitice kyphosis of the lower dorsal vertebre, 
as well as in slowly developing ascites in young persons whose thorax 
is still sufficiently pliable to permit of a barrel-shaped distention. 

On the other hand, the area of dulness may be enlarged, even when 
the liver is normal, if the antero-posterior diameter of the thorax is dimin- 
ished. This may occur in paralytic thorax or in cylindric corset-thorax, 
owing to the fact that the ribs are pressed downward, and are situated 
near to the spinal column, thus coming in contact with a larger portion of 
the anterior surface of the liver. In these cases the whole organ, particu- 
larly its anterior margin, occupies a more vertical position. This condi- 
tion has been called ‘* anteversion ”’ of the liver. 

If the enlarged gall-bladder extends below the hepatic margin, it can 
_ usually be detected by percussion, the area of dulness so produced being 
directly continuous with the hepatic dulness. 

25 


386 DISEASES OF THE LIVER, 


PALPATION. 


If the abdominal walls are normal, a normal liver cannot be palpated, 
since its thick right edge is hidden behind the costal margin, and the edge 
toward the left is so thin that it does not offer sufficient resistance tobe felt. 
The liver is only palpable if the abdominal walls are abnormally relaxed, 
or if the resistance of the organ is abnormally increased. The former is 
found in great emaciation, and in relaxation of the muscles following dis- 
tention, either as a result of pregnancy or of pathologic increase of the 
abdominal contents. Palpation is made particularly easy by separation 
of the abdominal muscles. The consistency of the substance of the liver 
is most frequently increased by fatty infiltration, passive congestion, and 
pressure from lacing. In the latter case the liver is, as a rule, enlarged 
and its lower margin forced downward. _Itis also possible to palpate large 
irregularities on the surface of the liver, such as carcinomatous nodules 
and gummata. If the abdominal walls are thin, even nodular irregularities 
of the surface, such as those present in cirrhosis of the liver, may be capa- 
ble of detection by palpation. In addition to the consistency and outline 
of the anterior surface, thickening and indentations on the lower margin 
may occasionally be distinguished by palpation. 

Exceptional thickness of the abdominal walls renders palpation impos- 
sible. Even when the abdominal walls are of medium thickness it is 
necessary that the muscles should be completely relaxed and that the pa- 
tient be placed in the horizontal position, and preferably be instructed to 
bend forward a little. The physician should place himself to the right of 
the patient, place the right hand flat upon the abdomen, and, following 
the respiratory rhythm, press downward with the tips of the fingers at the 
beginning of each respiration. .Palpation may be aided, particularly in 
thin females, by pressing the kidney and the liver forward from the lumbar 
region with the left hand. If the abdominal walls are stretched and re- 
laxed, as in many women, or immediately after aspiration of ascitic fluid, 
it is sometimes possible to palpate the lower surface of the liver. To ac- 
complish this, the four fingers of the left hand should be placed in the 
lumbar region and the thumb of the left hand in front below the costal . 
arch. In this way the liver is grasped from above, fixed, and, if possible, 
forced forward and downward. In some cases the right hand can now 
feel the sharp margin and grasp it between the fingers and the thumb.* 
Landau-Rheinstein + recommends in performing this method of examina- 
tion to have the patient in the erect position, as then the liver is forced 
forward and downward by its own weight. In some cases, according to 
Wijnhoff,t it is practicable to instruct the patient to sit on a chair and 
bend the body forward with his hands on his knees while the physician 
examines from behind and to the right of the patient. 3 

Normally, the gall-bladder can neither be felt nor percussed, because 
it never extends much below the margin of the liver. Even when it does 
protrude, it is impossible to palpate it, because its walls are not sufficiently 
tense as long as the bile-passages are permeable. It becomes palpable, 
however, as soon as the tension of its walls increases and it protrudes below 
the,margin of the liver. Thickening of its walls and concretions within 
the organ can frequently be felt. The gall-bladder is situated slightly 


* Glénard, Lyon méd., 1892, 11, p..191; 1890, 11, p. 345. 
t Berlin. klin. Woch., 1891. t Nederland. Tijdschrift, 1889, No. 2. 


TOPOGRAPHIC ANATOMY AND DIAGNOSIS. 387 


within the mammillary line, approximately where the margin of the liver 
crosses the costal arch. When the liver is enlarged or in an abnormal 
position, or when its outline is changed, the gall-bladder may be found in 
different locations. It is most frequently displaced downward, occa- 
sionally, however, laterally, particularly outward. In ascites and meteor- 
ism it is often useful to perform palpation by giving a sudden jog, by 
which the fluid or the coils of intestine are rapidly pushed away, mak- 
ing it easier to feel the liver. 

The liver is moved downward by the diaphragm with each inspiration, 
a circumstance that facilitates palpation of the organ. When the warmed 
hand is placed upon the abdominal wall and the patient instructed to in- 
spire deeply, the liver is alternately approximated to the finger-tips and 
removed. Owing to the fact that the liver is in contact with the dia- 
phragm over so large a surface, its respiratory motility is greater than 
that of other organs only indirectly in contact with it, as, for instance, the 
kidneys, the colon, and the mesentery. Sometimes it is possible to fix one 
~ of these latter organs in their inspiratory position with the left hand, the 
liver then alone moving upward with the ascending diaphragm. Only if 
the neighboring organs are adherent to the liver will they participate in its 
inspiratory and expiratory motility. This movement is not only palpa- 
ble, but can also be demonstrated by percussion—an important feature 
in the interpretation of dulness in the region of the liver, as it gives us the 
means of determining whether it is produced by that organ. 

Even on deep inspiration the lower margin of the liver rarely extends 
more than 1 or 2 cm. further downward. The upper margin of the abso- 
lute liver dulness may be moved downward from 1 to 5em., owing to the 
entrance of the sharp lower margin of the lung into the pleural sinus 
during inspiration. The area of the absolute liver dulness is therefore 
increased during each inspiration. 

If the liver is adherent to the anterior abdominal wall by peritoneal 
adhesions, the respiratory motility of the lower margin of the liver may 
be absent. If pleural adhesions fix the diaphragm or the lungs to the 
thoracic walls, the upper margin of the absolute liver dulness is only very 
slightly changed by respiration or does not move at all. 

Whenever we are in doubt whether we are dealing with a tumor of the 
liver or of some other abdominal organ, we may have recourse to alternate 
filling and emptying of the intestinal tract in addition to the determination 
of respiratory motility. This distention may occur physiologically, but 
it is better produced artificially by inflating the stomach with gas, or filling 
the intestine with water. In the former case the liver is pushed upward 
and to the right, in the latter only upward. In this manner the organ 
may be pressed upward against the abdominal wall, and thus the margin 
of the liver and the gall-bladder become more accessible to palpation. A 
tumor of the kidney, on the other hand, would be pressed backward by 
pee proceedings.* 


INSPECTION; AUSCULTATION. 


In rare cases inspection will give us information in regard to changes 
in the consistency and the form of the liver. If the volume of the liver is 
greatly increased, asymmetry of the thorax will be seen both anteriorly 
and posteriorly in the erect position of the body. If, on the other hand, 


*Q. Minkowski, ‘Die Diagnostik der Abdominaltumoren,” Berliner klin. 
W ochenschr., 1888, No. 31. 


388 DISEASES OF THE LIVER. 


the liver is normal in size, or only slightly increased in volume, and the 
abdominal walls are very thin and relaxed, the same will be observed. In 
these cases the outline of the liver or the gall-bladder may sometimes be 
more clearly perceptible to the eye than to the hand, particularly during. ’ 
forced respiration. [Inspection may also show a shadow ascending and 
descending with the movements of the diaphragm corresponding in its 
position with the margin of the liver and analogous to Litten’s dia- 
phragm phenomenon.—ED. ] 

Finally, we must consider a few special signs that are observed during 
examinations of the liver. 

A systolic pulsation combined with a systolic enlargement is found in 
tricuspid insufficiency when the liver is hyperemic from venous congestion. 
This pulsation is caused by a transmission of the blood-wave backward 
from the right heart, and is analogous to the venous pulse felt in the jugu- 
lar vein. It is differentiated from simple transmitted pulsations by the 
fact that it can be felt over the whole liver, and that the liver simultane- 
ously increases in size and consistency. Much more rarely a systolic 
pulsation is transmitted through the arteries in aortic insufficiency. 


Systolic blowing sounds over the vessels have been heard in aneurysm of the 
hepatic artery and in malignant neoplasms (Leopold, Martin, Rovighi) as well as 
in cholelithiasis (Gabbi, Martini). In a few cases these sounds were apparently 
caused by compression of the hepatic artery.* 


Friction sounds caused by fibrinous exudations from the peritoneum 
are occasionally heard over the liver as well as over other abdominal 
organs. These sounds can be perceived better by the sense of touch than 
by the ear. In the case of the liver they are caused by the respiratory 
movements of the organ, and can be differentiated from pleuritic friction 
sounds by their location. [In hydatid cyst of the liver the so-called “hy- 
datid fremitus’” may be felt; while “gall-stone crepitus’” has been 
claimed by some authors to be of diagnostic value in cholelithiasis.—Eb.] 


CHANGES IN SIZE, 


By one or the other of the above-mentioned methods it is possible in 
the majority of healthy and of sick subjects to outline approximately the 
part of the liver in contact with the parietes of the body. The interpreta- 
tion of the findings made by these methods must, of course, as we have 
already mentioned, frequently be modified, for the reason that in different 
individuals the formation of the body, and with it the formation of the 
liver, is different, and because changes in the position of neighboring or- 
gans can exercise an influence on the position of the liver relative to the 
parietes. As a rule, changes in the shape and size of the liver are deter- 
minable in that part of the organ that is accessible to palpation. The 
palpatory findings are more valuable and more positive than those of per- 
cussion; and wherever palpation can be performed, the results from it 
should be valued more highly than those obtained from percussion. 

An enlargement of the organ usually produces a dislocation of the lower 
margin downward: This is caused, on the one hand, by the effect of 
gravity; on the other, by the greater resistance offered by the diaphragm 


* Leopold, Archiv der Heilkunde, Bd. xvu, p. 395. Martini, Riv. clin. ttal., 


1891, No. 3. Gabbi, Riv. clin. ital., 1889, No. 1. Rovighi, Riv. clin. di Bologna, 
1886, No. 5. 


TOPOGRAPHIC ANATOMY AND DIAGNOSIS. 389 


as compared to the slight resistance offered by the gastro-intestinal tract. 
Tumors that develop on the convexity of the liver rarely produce a de- 
crease in the volume of the lung. Such a result is seen only in those cases 
where the lesion causes at the same time a reduced contractility of the 
right side of the diaphragm; and here we are usually dealing, not with a 
simple dislocation of the diaphragm, but with anatomic changes of its 
tissue following inflammation or the development of a neoplasm. Simple 
enlargement of the liver is found in hyperemia, hypertrophy, fatty and 
amyloid degeneration, leukemia, hypertrophic cirrhosis, and multilocular 
‘echinococcus. Enlargement of the liver with changes in its outline is 
found in carcinoma, echinococcus, and abscess. In corset liver, and in 
lobulation of the organ following syphilitic hepatitis, the change in the 
outline of the organ is more conspicuous than the increase in its volume; 
the latter change, in fact, may be completely absent. 

A decrease in the size of the liver is found in the atrophy of old age, in 
that form of chronic inflammation called atrophic cirrhosis, and, in the 
most conspicuous manner, in acute atrophy. As a rule, in these condi- 
tions the posterior dull margin of the liver remains unchanged, so that 
the decrease in the size of the organ usually produces a movement upward 
of the lower margin, and, in this manner, a decrease in the absolute liver 
dulness. In acute atrophy the organ collapses and seems to be folded 
upon itself.* The latter accident is prevented if the liver is adherent to 
the anterior abdominal wall, the liver in this case growing thinner while 
its surface area does not decrease. 


There can be no doubt that the size of the liver can be influenced by the rela- 
tive filling of its vessels with blood. We will discuss this at some length in the 
section on hyperemia of the liver. Normally such a change is not perceptible. 
Heitler = is the only one who makes the statement that the liver dulness may thus 
increase by 3 cm. within a few minutes. 


A change in the size of the liver may be simulated by changes that 
occur in neighboring organs, and by dislocations of the liver produced by 
such changes, particularly if the liver is by them approximated to or re- 
moved from the abdominal walls. Enlargement of the liver dulness may 
be simulated by the presence of inflammatory exudates or of tumors in 
the right pleural cavity, or by thickening of the lower margin of the lung. 
Large exudates on the right side force the diaphragm and the liver down- 
ward, the right lobe of the liver being dislocated more than the left. 
Left-sided exudates change the position of the left lobe, though to a lesser 
degree, the lower margin of the liver in this case running horizontally 
instead of diagonally across the abdomen. Pneumothorax, also, can pro- 
duce a dislocation of the liver downward. At first the area of dulness is 
reduced in size; later, when the distention with air assumes greater pro- 
portions it is increased. In emphysema the liver also occupies a lower 
position than normal, but, owing to the retroversion which frequently 
occurs at the same time, the area of dulness is smaller than normal. In 
shrinkage of the right lung the liver is drawn upward and the area of dul- 
ness is somewhat enlarged. 

Large pericardial exudates, and enlargement of the heart itself, may 
force the left lobe of the liver downward. As a rule, these lesions are 


* Gerhardt, Zeitschr. fir klin. Medicin, Bd. xxt, 1892, p. 374. 
T Heitler, “Die Schwankungen der normalen Leber- und Milzdimpfung,” 
Wiener med. Wochenschr., 1892, No. 14. 


390 DISEASES OF THE LIVER. 


accompanied by passive congestion of the liver, and in this manner pro- 
duce an enlargement of the whole organ. 

Inflammatory exudates occurring between the liver and the dia- 
phragm (subphrenic abscess) force the liver downward and the diaphragm 
upward, and in this way may simulate either enlargement of the liver or 
pleuritic exudates. 

The liver is more frequently dislocated downward than upward. The 
muscle of the diaphragm offers considerable resistance, and usually does 
not yield at all until increase of pressure within the abdominal cavity 
occurs, with distention of the whole abdomen as a result. The latter - 
occurrence is usually combined with dilatation and change in the form 
of the lower thoracic aperture, so that the liver is placed more horizontally, 
and the area of absolute dulness is diminished. As a rule, this area is 
rather difficult to determine. In the case of ascites this difficulty is due 
to the general dulness; in the case of meteorism, to the loud tympanitic 
sound. 

Finally, a decrease in the liver dulness can be produced by the (rather 
rare) entrance of air between the liver and the anterior abdominal wall, or 
by the intervention of the transverse colon or loops of small intestine 
between the liver and the abdominal wall. The latter accident occurs 
chiefly in enteroptosis and in general relaxation of the abdominal walls. 
As a rule, the true shape of the liver can still be determined by repeated 
examinations, particularly if the patient be placed on the right side or flat 
on his back, with depressed shoulders. 


CHANGES IN FORM. (CORSET LIVER.) 


The substance of the liver is ordinarily soft and plastic during life, 
although we usually see the organ after death, when postmortem changes 
have hardened it. The physiologic shape of the organ, therefore, is — 
largely determined by the mould of neighboring organs, particularly of the 
muscular and bony tissues. In the case of the liver more than in the case 
of any other organ the general outline is dependent in each individual on 
the shape of the thorax and the body generally. All pathologic changes in 
its surroundings produce considerable deviations from its normal form. 
For instance, scoliosis, tumors, or exudates that press upon the organ from 
above, from the side, or from below, may change its shape. As a rule, 
these deforming influences are permanent; where they are only transitory, 
—as, for instance, in large pleuritic exudates or in subphrenic ahscesses,— 
the plasticity of the liver tissue favors the establishment of the original 
shape. Tumors within the liver that do not change its substance but 
act mechanically—as, for instance, echinoccocus—may also produce dis- 
placement of liver-substance and a change in the normal form of the organ. 


In the opposite sense, the relaxation of pressure normally exercised on the 
surface of the liver may produce extensions of the liver-substance, so-called ectases 
of the liver. For instance, a hole in the diaphragm (Klebs *) or a hernial opening 
of the linea alba (Kusmin) may permit of such protrusions. 

For completeness’ sake the change of form that is seen in transposition of the 
viscera must be mentioned. In this anomaly the shape of the liver is the reverse 
of the normal. 


Furrows are occasionally found upon the convex surface of. the liver, 
which are produced by pressure of the ribs. Frequently the serous mem- 


* Virchow’s Archiv, Bd. xxxu, p. 446. _ 


TOPOGRAPHIC ANATOMY AND DIAGNOSIS. 391 


brane over these furrows is slightly thickened. On the convex surface 
of the right lobe of the liver deep, narrow furrows, called longitudinal or 
expiration furrows, are occasionally found running parallel to the suspen- 
sory ligament. They probably owe their origin to a lateral compression 
of the liver which occurs when the diaphragm is contracted and the ab- 
dominal muscles (particularly when the clothing is too tight) compress 
the organ. These changes in the form of the liver are not recognizable 
during life. 

Of the acquired changes of form, that variety which is called ‘‘ corset 
liver’’ is of considerable pathologic and clinical importance. This de- 
formity is not produced by lacing alone, but may be the result of wearing 
various kinds of tight-fitting clothing, particularly at a time of life when 
the body is not yet developed and the thorax is soft and pliable. In order 
to exercise their effect, these influences must, of course, act for a long time. 
Among the causes of the condition there may be mentioned here the use 
of corsets of various degrees of stiffness, softer bodies made of cloth, 
tight waists, either buttoned or laced, skirt-bands, belts, and straps. 
These articles of apparel influence the shape of the liver only in small 
part through the abdominal walls. In much greater part they act 
through pressure on the ribs and cartilages, by modifying the relative 
position of these parts and retarding their growth. In this way these 
irrational methods of dressing continue to exercise a pernicious effect for 
a long time after they have been discarded, and consequently produce 
permanent, irreparable, and sometimes progressive damage. 

Corset liver is naturally found chiefly in women, not only in those who 
wear corsets, but also in peasant women who wear waists and skirt-bands. 


According to the conventional custom, artificial deformation of the body begins 
with confirmation; that is, at about the fourteenth year, rarely sooner. 

According to the tabulations of Leue, based upon 3484 autopsies on subjects 
above sixteen years of age, corset liver was found in 1.9% of male bodies and 25.3% 
of female bodies. If changes of high degree are not considered alone, but also those 
changes that are barely recognizable, but can unquestionably be attributed to the 
effect of lacing upon the liver, it will be found that 5.7% occur in men, 56.3% in 
women. The percentage increases, with the increasing age of the subject, from 


2% to 73%. 


The deformities of the thorax and the liver that result from irrational 
clothing show wide variations. A great deal will depend on whether the 
pressure was exercised in a narrow or a wide zone, high up or low down. 
In the same individuals, in addition, the pressure may be exercised in 
different parts of the body in the course of many years, as the subjects 
change the style of their clothing with the changes of fashion. It is 
possible to distinguish four types, which, it is true, may merge into one 
another. : 

First, low waist, a very narrow ring underneath the costal arch; in 
still more marked cases a slight change of the costal angle and a slight 
inversion of the lower margin.of the thorax. Here the liver is contracted 
only near the lower margin of the right lobe, and its sharp edge is some- 
what atrophic and the serous covering thickened. 

Second, medium waist. The narrowest place is found below the 
xiphoid process; the costal arches are somewhat ectopic. 

Third, high waist. The narrowest point is at the level of the xiphoid 
process. Owing to the ectopic position of the costal arches the thorax 
assumes an hour-glass form. 


392 DISEASES OF THE LIVER. 


Fourth, cylindric-paralytic contracted thorax. This form is produced 
by tight waists or cylindric corsets without any waist-line. 

In the last form the lower part of the thoracic aperture is uniformly 
narrowed, the thoracic walls are thus pressed against the liver, and the 
organ is uniformly elongated so that the right lobe assumes a tongue- 
shaped form. On the other hand, in the narrow high waist (third type) 
only the upper part of the liver is compressed, so that the upper part of 
the growing organ is, so to speak, pressed into the substance of the lower 
part of the right lobe. In this manner the lower portion of the liver grows 
longer, wider, and thicker, really hypertrophic, assuming in some cases a 
cake-shaped or hemispheric outline. In the medium waist (second type) 
the greatest pressure is exercised lower down, so that the portion of the 
liver that is pressed downward is not so bulky. It is frequently sepa- 
rated from the upper part by a broad furrow running horizontally or diag- 
onally across the organ. 

The liver, elongated from narrowing of the thorax, usually protrudes 
considerably below the costal arch, so that, as a rule, the organ can be 
readily percussed and palpated, and its form determined. This is par- 
ticularly easy because the muscular walls and the adipose tissue become 
somewhat atrophic from the pressure. 

If pressure is continued for a long time the costal arch may be so forced 
into the liver-substance as to cause it to atrophy. In the same manner 
narrow and very tight skirt-bands act on the elongated lobe of the liver so 
that the bridge between the main mass of the liver and the lower part of 
the right lobe becomes thinner than the lobe. Ultimately this connecting 
band may become so attenuated that it forms merely a thin strip con- 
taining no liver-substance whatever, but only blood-vessels and bile-ducts. 
Frequently, before attenuation occurs to such a degree, pressure on the 
most contracted part of the liver has caused stasis of blood or of bile i in 
the separated lobe, and so causes the latter to increase in size. 

Those portions of the liver that are exposed to permanent pressure 
usually show changes of the serous covering ranging from a slight clouding 
to fibrous thickening. As a rule, the callosities run horizontally or 
approximately so, but they may bisect the anterior surface of the liver 
in different places from the lower margin of the right lobe up to the middle 
of the left. Rarely, a piece of the lower margin of the left lobe may be- 
come separated from lacing. 

We see, therefore, that the changes in the form of the liver that may 
be produced by the pressure of the clothing are of varying kind and of 
varying degree. Diffuse pressure produces an elongation of the liver and 
a folding inward of its convex surface; local pressure (frequently trans- 
mitted by the costal arch) produces local atrophy from pressure, and 
perihepatitis. 

Frequently inflammatory processes that originate in the serous part 
of the compressed surface may extend, and lead to adhesions with the 
abdominal wall or to thickening of the capsule. 

With elongation of the right lobe the biliary channels situated on the 
lower surface, particularly the gall-bladder, are also elongated, so that, fre- 
quently, by indirect compression of the cystic duct, the flow of bile is pre- 
vented, and dilatation or catarrh of the gall-bladder results, or, later, 
~ concretions may*form. 

Symptoms.—A corset liver may exist without causing any symptoms, | 
and usually the condition is discovered only when the abdomen is exam- 


TOPOGRAPHIC ANATOMY AND DIAGNOSIS. 393 


ined for some other reason. In rare cases the separated lobe causes 
symptoms through its volume, through pressure upon neighboring organs, 
or through its motility. Such symptoms may be transitory if the sepa- 
rated lobe becomes swollen or painful through stasis or inflammation. 
The rare cases of separation of a portion of the left lobe are said by Langen- 
buch to cause more marked symptoms. 

Elongation of the liver frequently simulates enlargement of the organ. 
The preponderating elongation of the right lobe in corset liver is of value 
in differentiating the two conditions. At the same time one should 
remember that it is more difficult to form a precise opinion in regard to the 
degree of enlargement of the liver in women than in men. 

In addition to being changed in form, the corset liver is of increased 
consistency. This is due in part to a local increase in the hepatic paren- 
chyma, in part also to the perihepatitis and passive hyperemia often 
observed in the separated lobe. If the separation is very marked, the lobe 
will appear like a tumor that has no connection with the liver, but seems 
to be connected with some other organ, such as the intestine, the kidney, 
the ovary, or the mesentery. If the separation is not so far advanced, 
and if there are no adhesions, the movements of the tumor with the phases 
of respiration will usually facilitate the recognition of its hepatic origin. 

The diagnosis is most difficult in those cases in which the separated 
lobe is joined to the liver by a narrow bridge of connective tissue. In such 
instances the lobe may be movable toward both sides as well as antero- 
posteriorly, or it may drop downward and become covered by the intestine. 
To arrive at a positive conclusion as to its nature, the growth must be 
examined several times and under different conditions (for instance, after 
distention of the stomach and intestine with gas). In a case of this kind 
the swelling may be confounded with floating kidney. It is well to re- 
member that, notwithstanding the motility of the lobe of the liver, this 
can be palpated better through the anterior abdominal wall, whereas the 
kidney can be reached much more readily through the lumbar region; 
and, further, that the distended ascending and the transverse colon are 
situated between these two organs. 

The diagnosis is particularly difficult if other pathologic conditions 
develop on the basis of a corset liver. This occurs quite frequently, for 
the reason that the primary cause,—~. e., lacing,—in addition to produc- 
ing deformities of the liver, causes a large number of disturbances in 
other organs, so that we are almost justified in speaking of a corset disease. 
Some of the lesions of this condition are the formation of gall-stones, with 
colic, inflammation and carcinoma of the gall-bladder, distention of the 
gall-bladder, and perihepatitis. The latter may originate partly from the 
gall-bladder, partly from the lacing furrow. The effect of lacing on the 
thoracic organs is to produce moderate degrees of passive congestion, 
and as a result enlargement of the whole organ. 

Other organs of the upper part-of the abdominal cavity may be affected 
by lacing as follows: Abnormal motility and dislocation of the right kid- 
ney, ptosis of the stomach and of the transverse colon, cardialgia, ulcer of 
the stomach, diffuse stasis in the portal system as a result of the compres- 
sion of the liver, and, following this portal stasis, intestinal catarrh, hemor- 
rhoids, attacks of colie, and constipation. The latter is particularly 
favored by the direct pressure that is exercised on the ascending and de- 
scending colon, particularly in the type of low waists. Compression of 
the upper part of the abdominal cavity causes a dislocation of its entire 


394 DISEASES OF THE LIVER. 


contents. This results in an abnormal distention of the abdominal walls 
below the umbilicus, and, if certain other conditions prevail, may lead to 
pendulous abdomen. 

It is true that of all these possible consequences of lacing only one may 
develop fully, so that it may happen that while pronounced changes are 
present in other organs, no lesion of the liver is discoverable during life. 
It is important, however, from a clinical and diagnostic point of view to 
remember the common cause of all these disturbances. An abnormal 
shape of the liver and deformity of the thorax, even though other symp- 
toms are not present, frequently give us valuable clues in diagnosticating 
and treating abdominal diseases. This obtains even when tight clothing 
has been discarded long before. 

A corset liver, no longer in an active stage of development, or secon- 
darily involved, may lead to confusion in the presence of other‘pathologic 
conditions and render the diagnosis more difficult. Among such condi- 
tions might be mentioned tumors of the kidney and of the suprarenals, 
psoas abscess, typhlitis, coprostasis, and inflammations in the region of 
the hepatic flexure of the colon. It is frequently impossible to arrive at a 
definite conclusion in regard to the presence or absence of one or the other 
of these diseases or in regard to the presence or absence of contracted liver, 
until the sensitiveness and inflammation in the region of the liver have so 
decreased that the different parts of the tumor may be palpated and 
differentiated. 


As mentioned above, the right lobe of the liver is usually considerably elongated 
downward. If acertain portion of the lower margin should be isolated by indenta- 
tion, this may become still more elongated, and extend downward in the shape of 
a tongue; such tongue-shaped processes are found with great frequency in the 
region of the gall-bladder, particularly toward the right. If the gall-bladder also 
enlarges, such a process becomes still more elongated, and, if it becomes inflamed, 
will become enlarged. A number of surgeons, particularly Riedel, have called 
attention to the difficulty that such a tongue-shaped process may cause in the 
diagnosis of gall-bladder diseases, and in operative procedures in diseases of this 
organ. [It is rather remarkable that such tongue-like processes are seldom felt 
in routine examinations of cases unless hepatic trouble calls particular attention 
to the liver.—Eb.] 


The milder degrees of the stationary corset liver do not call for any 
treatment.. The complications arising from this condition, however, 
must be attended to, particularly perihepatitis, passive congestion, and 
the various troubles due to gall-stones. In practice it is frequently im- 
possible to differentiate between these conditions and the other sequels of 
lacing, and the whole complex picture must therefore be treated together. 
The measures of treatment that are to be considered in this connection 
are a simple and non-irritating diet, a daily evacuation, courses of saline 
mineral water or of those containing chlorids, and the support of the re- 
laxed abdominal walls and the displaced intestine by a bandage or a band 
applied below the umbilicus. If the separated lobe of the liver extends 
very far downward and is very sensitive, it is impossible to apply any but 
a soft elastic bandage. In such cases a supporting pad (Landau) is 
more agreeable, and is very appropriate, for the reason that such an ap- 
pliance exercises pressure which is more firm and is limited to the lower 
half of the abdomen. 

In cases in which indirect support of a corset liver did not relieve the 
disturbances. Billroth and others have opened the abdominal cavity, and 
have attached the separated lobe to the anterior abdominal wall by su- 


TOPOGRAPHIC ANATOMY AND DIAGNOSIS. 395 


tures passed through the calloused part of the lobe. Langenbuch in one 
case ablated a separated lobe of the left side that was causing much dis- 
turbance. Sucha procedure will be found to be easy if much of the liver- 
substance has disappeared from the contracted furrow. 

The most important duty of the physician in regard to the condition 
under discussion is its prevention. However great the fear of tradition 
and of fashion, the chances of success in this direction are not bad. Form- 
erly physicians believed deformities of the liver alone were the result of 
lacing, but nowadays we know that numerous diseases involving other 
abdominal organs, in addition to the liver, may be the result of tight 
clothing. This knowledge has only been acquired within the last decade 
and will have to be gradually communicated to the laity by physicians. 
Even now many women follow the advice given, and the number will in- 
crease as the good effect of rational clothing becomes more apparent. 

It is necessary not only to combat the corset, but all forms of tight 
clothing, such as waist- and skirt-bands. Such articles of clothing are 
particularly detrimental while the body is in the stage of development, 
especially if the muscles are weak and the bones soft. The powers of 
resistance against the damages of lacing are not dependent on a definite 
age, but on the period of life in which development of the body is com- 
pleted, which, as we know, varies in different individuals. 

Particular attention should be paid, primarily, to the size of the 
waist that is worn. This should permit free respiratory movements. 
Further, a decrease in the weight of the clothing worn on the lower half 
of the body should be insisted upon (bloomers instead of skirts, and loose, 
adaptable materials), or the clothing should be attached to the shoulders 
by broad or conical straps.* 

The various articles of clothing that have been recommended by 
physicians and manufacturers, so-called “health corsets,” etc., only in 
part comply with the demands. The American corset seems the most 
practical, as it consists of a well-modeled underwaist made of some resist- 
ing material, with broad shoulder-pieces, to which the garments of the 
lower half of the body are attached by buttons. These corsets have a 
few flexible whalebones that are to be removed in laundering. 


CHANGES IN POSITION. 


We have already mentioned some of the moderate changes in the posi- 
tion of the liver that may occur: viz., rotation around the horizontal axis 
(retroversion and anteversion) and dislocation produced by diseases of 
neighboring organs. The latter usually occur downward, and may in 
some instances be remedied; it will depend on the primary cause of the 
trouble whether this is possible or not. 


FLOATING LIVER, 


Hepar mobilis s. migrans; Hepatoptosis; Descensus hepatis; Fove flottant; 
W anderleber. 
This consists of a marked displacement of the liver, together with 
abnormal mobility. The liver is anchored in its normal position in the 
concavity of the diaphragm by several peritoneal folds: viz., (1) The 


*Spener, “Die jetzige Frauenkleidung,” Berlin, Walther, 1897, und Deutsche 
med. W ochenschr., 1897, No. 1. 


396 DISEASES OF THE LIVER. 


coronary ligament, originating from two flat peritoneal folds on the pos- ° 
terior surface of the liver that are occasionally in contact with each other, 
forming a very short and tense mesentery, or, more frequently, leaving 
uncovered a portion of the liver surface, as broad as several fingers. 
To the right and left these ligaments separate and form the so-called tri- 
angular ligaments. (2) The suspensory ligament, a long reduplication 
of the peritoneum running from the diaphragm to the convex surface of 
the liver. It is attached at the porta hepatis and, together with the liga- 
mentum teres, extends to the umbilicus. . The liver is further attached 
to the spinal column and the diaphragm by the inferior vena cava, which 
is usually embedded in the posterior margin of the liver, but is often com- 
pletely surrounded by liver-substance. 

The connective-tissue strands that run through these ligaments would 
alone not be capable of supporting the large gland weighing 1500 gm. 
They in fact chiefly fulfil the purpose of preventing lateral displacement. 
The liver is really supported by the elasticity and tone of the abdominal 
walls, assisted by the stomach and intestine, which support it from below 
like air-cushions. In addition, the elastic traction of the lungs that main- 
tains the vault of the diaphragm, and the cohesion of the convexity of the 
liver with the diaphragm (preventing the separation of the two serous sur- 
faces and still permitting a gliding movement), are factors in supporting 
the liver. The ligaments simply circumscribe lateral movements. (At- 
mospheric pressure has as little to do with the support of the liver as it has 
with the fixation of the femur in the hip-joint.) . 

All these factors combine to prevent the separation of the liver and the | 
diaphragm, so that they nearly always remain in contact. If they are 
separated at all, it is only by asmall space. Slight degrees of descent of 
the liver occur in ascites, in which a layer of fluid, that may be several 
centimeters thick, may force its way between the liver, on the one hand, 
and the diaphragm and the abdominal wall, on the other. Greater degrees 
of descent are possible only if the above-mentioned suspensory ligaments 
become elongated. When this occurs, the liver may sink below the costal 
arch, even as far as the symphysis pubis, and fluid, tumors, or coils of intes- 
tine, particularly of the transverse colon, may occupy the place of the liver 
in the right vault of the diaphragm. Owing to the attachment of the 
ligamentum teres to the umbilicus, descent of the liver is usually combined 
with rotation of the organ, the right lobe thereby occupying the lowest 
position. Usually ptosis of the liver is combined with great motility of 
the organ, so that by pressure from without and changes in the position of 
the body it may be possible, in part or completely, to replace it in its 
- normal position. 

Frequency of Occurrence and Causes.—The highest degree of abnor- 
mal motility, floating liver proper, is not frequently seen. Cantani first 
described it in 1866, and since then it has been more frequently observed. 
It is found principally in women (approximately in the proportion of ten 
to one as compared with men). The chief cause is the relaxation and 
attenuation of the abdominal walls, so-called pendulous abdomen, usually 
following repeated pregnancies, particularly if the patient has gotten up 
too soon. The condition is usually combined with separation of the ab- 
dominal muscles. As a result of these causes the intestines drop forward 
and downward, and in this manner the liver is deprived of one of its 
normal supports. Large hernias may act similarly, even without stretch- 
ing of the abdominal walls, particularly if the hernial sac incloses many 


TOPOGRAPHIC ANATOMY AND DIAGNOSIS. 397 


coils of intestine. * Another mechanical factor must be considered in 
pendulous abdomen—+. e., the direct traction that the abdominal walls 
exercise on the liver through the umbilicus and the ligamentum teres 
(Landau, Langenbuch). 

Other favoring circumstances are the following: Violent exertion, 
persistent vomiting (Rosenkranz), coughing or sneezing (Landau), and 
acute mechanical influences, such as a fall or sudden violent’exertion. In 
a case described by Leube distention of the inferior vena cava following 
tricuspid insufficiency seems to have loosened the attachments of the liver. 
Stretching of the ligaments of the liver from a swelling of the organ that 
later recedes may also in some instances permit greater excursions of the 
liver. Lacing and rapid emaciation are only occasionally mentioned as 
causes; but they certainly have some influence, particularly when they are 
responsible for the relaxation of the abdominal walls. 

As the rare occurrence of floating liver is in contrast to the frequency 
with which the above-mentioned etiologic factors are present, we must 
conclude that in certain individuals some particular conditions must 
assist. Most probably a congenital tendency to relaxation and stretching 
of the ligaments of the liver must exist, of the same kind as that which 
makes thé formation of a true mesohepar possible. It has not been 
demonstrated so far whether the latter is congenital or preformed. 

Symptoms.—A floating liver forms a tumor in the right side of the 
abdomen, sometimes extending as far as the symphysis. Its convex sur- 
face is directed forward. It is usually possible to determine the hepatic 
outline by palpation, and this is facilitated further by the flaccid character 
of the abdominal walls. If lacing has been indulged in the form of the 
liver is frequently changed. In the erect and semi-recumbent positions 
the liver is low down in the abdomen, while in the dorsal position it is 
usually possible to replace the liver by manual pressure. In doing this 
the previously sunken epigastrium becomes filled out and the normal area 
of hepatic dulness is restored. When the liver is absent from its normal 
place, the percussion sound of the lung merges directly into that of the 
intestine. It is rare to find a dislocated liver attached in an abnormal 
position by adhesions (Richelot). If this is the case, it can, of course, 
only partly be replaced. 

Pressure exercised over the dislocated liver is usually not painful, but 
frequently produces sensations in remote parts. A floating liver may 
‘also cause spontaneous pain, particularly when its weight exercises 
a great degree of traction or when the traction that existed is 
suddenly increased, as, for instance, in jumping, walking, raising the 
arms (particularly the right one), sneezing, coughing, and yawning. 
Sometimes the pain. becomes paroxysmally exacerbated without any 
visible cause. Pain is usually relieved by manual or other fixation of the 
tumor, by sitting down, or by assuming the dorsal position or a position 
on the right side. The pain is felt in the right hypochondriac region 
and the epigastrium, and frequently radiates toward the right shoulder 
and the lumbar region. A feeling of bearing-down and of colicky pains 
may arise, while occasionally intestinal disturbances, or a feeling of fulness 
or of some living thing in the abdomen, may be complained of. Fainting 
spells may occur. 

In addition, numerous disturbances of the digestive tract are noticed, 
such as various gastric disturbances, belching, meteorism, and constipa- 
tion. These are explained by traction upon and temporary occlusion of 


398 DISEASES OF THE LIVER. 


the intestine. Respiratory disturbances and palpitation must be attri- 
buted to dragging upon the diaphragm. Occasionally symptoms of por- 
tal stasis are noticed, such as ascites, hemorrhoids, metrorrhagia, or, as a 
result of the twisting of the vena cava, edema of the lower extremities. 
[Albuminuria, increase in the quantity of the urine, and purpura are 
also seen at times.—Ep.] Icterus is rare, although this symptom 
might be expected as a result of the traction exercised on the biliary 
passages. A slight sub-icteric color is sometimes observed. [Mac- 
Naughton Jones has reported a case of recurring hemorrhage from the 
stomach apparently due to ptosis of the liver.—Eb.] 

Diagnosis.—The diagnosis of floating liver may be difficult at 
first, as the unusual size of the palpable tumor is startling. In gen- 
eral, however, the relaxation of the abdominal walls permits an accu- 
rate determination of the outline of the tumor by bimanual palpation, and 
the area of hepatic dulness is not found in the normal place. The most 
important diagnostic sign is the possibility of replacing the tumor into the 
region where the liver normally belongs; this is particularly easy if the 
patient is placed in the horizontal position. If the manceuver succeeds, 
the normal area of hepatic dulness will return. 

The descended liver will always appear larger than normal, even 
though no pathologic enlargement exists. This is due to the fact that it 
presents for palpation a larger surface than normal. 

The diagnosis of floating liver is particularly difficult if ascites exists. 
At the same time, the presence of fluid within the abdomen makes palpa- 
tion very difficult and, in addition, we are deprived of the knowledge 
derived from the area of hepatic dulness. In such cases puncture may be 
necessary in order to assist the diagnosis. 

In an oft-quoted case reported by P. Miiller, a peculiarly shaped and 
thickened mesentery was erroneously taken for a floating liver. In this 
case ascites existed and the liver was forced upward considerably, so that 
hepatic dulness was absent from the normal place. The fact that the 
apparently dislocated liver could not be replaced in its normal position 
had not been considered. It is also possible for the dislocated liver to 
become adherent, and in this way the diagnosis may be made very 
uncertain. [The misplaced liver has been mistaken for hydronephrosis 
(Peters), floating kidney (Terrier and Baudonin), renal tumor, and typh- 
litis (Richelot), the error being discovered at operation.—ED.] 

Treatment.—Replacement of the liver in its normal position can 
never be performed directly, but only indirectly through the agency of 
the abdominal organs. It may be brought about by applying an elastic 
abdominal bandage which replaces the tone of the abdominal wall, or by 
shortening the stretched abdominal wall by excising a wedge-shaped 
piece in the region of the linea alba and sewing the abdominal walls to- 
gether. Kispert proposed fixation of the liver by stitching, and tried it 
several times. Langenbuch has selected the lower costal cartilages as the 
line of fixation. All the other accompanying symptoms and sequels of 
floating liver must of course be treated. 

Prophylaxis can accomplish a great deal. The chief indication is to 
prevent the development of a pendulous abdomen and pathologic enlarge- 
ment of the abdominal cavity immediately after pregnancy by the em- 
ployment of faradization, massage, and douches. On the other hand, a 
re-establishment of normal abdominal dimensions and tone may be tem- 
porarily aided by the application of a suitable abdominal bandage [and 


TOPOGRAPHIC ANATOMY AND DIAGNOSIS. 399 


by abdominal exercises. The “straight-faced corset,’’ advocated for the 
relief of floating kidney, is usually more convenient and effectual than the 
elastic bandage. The production of adhesions between the convexity of 
the liver and the dome of the diaphragm by irritation of their surfaces, as 
in Talma’s operation for the relief of ascites, might be of value in conjunc- 
tion with the other methods mentioned. It has been suggested that the 
liver may be held in position by suturing the fundus of the gall-bladder to 
the parietal peritoneum.—ED. | 


LITERATURE. 


GENERAL WORKS ON DISEASES OF THE LIVER. 


- Budd, G.: “On Diseases of the Liver,’’ London, 1845. 

Charcot, F. M.: ‘“Legons sur les maladies des foie,’’ Paris, 1877. 

Chauffard, A.: in Charcot, Bouchard et Brissaud’s ‘ Traité de médecine,’ 1892, 
tome III, p. 663. 

Dupré, F., in “ Manuel de médecine” of Debove und Achard, 1895, tome v1. 

Frerichs: “ Klinik der Leberkrankheiten,” 2 Aufl., 1861. 

Harley, G.: “‘ Diseases of the Liver.” 

Langenbuch, C.:,“ Chirurgie der Leber und Gallenwege,” Stuttgart, 1894, 1897. 

Leichtenstern in Penzoldt und Stintzing’s “Handbuch der speciellen Therapie,’ 
Bd. tv, Abtheilung 6b, p. 138. 

Murchison: “Clinical Lectures on Diseases of the Liver,’’ London, 1877. 

Thierfelder, Ponfick, Leichtenstern und Schippel in v. Ziemssen’s ‘‘ Handbuch der 
speciellen Pathologie,” Bd. vii, 1880. 

Text-books on Pathologic Anatomy by Birch-Hirschfeld, Klebs, Orth, and Ziegler. 


CorsET LIVER. 


Bottcher: “Virchow’s Archiv,”? Bd. xxxiv, 1865, Taf. 1. 

Frerichs: loc. cit., 1, p. 47, with illustrations. 

Hackmann, K.: “Schnirwirkungen,”’ Dissertation, Kiel, 1894. 

Hayem: “ Maladie du Corset,” “‘ Archives générales de médecine,” 11, p. 169, 1895. 

Hertz: “ Abnormitaten in der Lage und Form der Bauchorgane, etc.,”’ Berlin, 1894. 

Langenbuch: loc. cit., 11, p. 107; “ Berliner klin. Wochenschr.,’’ No. 3, 1888. 

Leue, E.: ‘‘ Ueber die Haufigkeit der Schniirleber,”’ Dissertation, Kiel, 1891. 

Riedel: “Ueber den zungenférmigen Fortsatz des Leberlappens,” etc., “ Berliner 
klin. Wochenschrift,” 1888, pp. 577, 602. 

Spener: ‘Die jetzige Frauenkleidung,” Berlin, Walther, 1897. 

— “Deutsche med. Wochenschr.,” No. 1, 1897. 

Thierfelder, p. 37. Klebs, p. 361. 

“ Mittheilungen des Vereines fiir Verbesserung der Frauenkleidung,” Berlin, 1897. 


FLOATING LIVER. 


Cantani: “ Schmidt’s Jahrbiicher,” Bd. cxu1, p. 107, 1866. 

Curtius: ““Symptome und Aetiologie der Wanderleber,” Dissertation, Halle, 1889. 

Dolozynski: ‘‘ Virchow-Hirsch’s Jahresbericht,’’ 11, p. 218, 1894. 

Faure: “ L’appareil suspenseur du foie,” etc., Thése, Paris, 1892. 

Kispert: “ Berliner klin. Wochenschr.,”’ p. 372, 1884. 

Kranold: “ Wirttemberger med. Correspondenzblatt,’’ Nos. 21, 22, Bericht 1, p. 
200, 1884 (Section). 

Landau, L.: “Die Wanderleber und der Hangebauch der Frauen,” Berlin, 1885 
(45 Falle, Literatur), ‘‘ Deutsche med. Wochenschr.,”’ p. 754, 1885. 

Langenbuch: loc. cit., p. 119. 

— “Berliner klin. Wochenschr.,”’ No. 13, 1889. 

— ‘Deutsche med. Wochenschr.,’”’ No. 52, 1890. 

Leube: “ Wiirzburger Sitzungsberichte,” p. 100, 1893. 

— ‘Minchener med. Wochenschr.,’”’ No. 4, 1894 (Postmortem). 

nage b ghd ee Diagnose der Wanderleber,” “ Deutsches Archiv fiir klin. Medicin,” 

d. xiv, 1875. 

Richelot: “Fixation d’un foie déplacé,’”’ “Gazette des hdpitaux,’? No. 22, 1893, 
Bericht 11, 261. 

Rosenkranz: Ibid., p. 714. 1887. 

Thierfelder: loc. cit., p. 42. 

Wolff, G. : “ Enteroptose und Wanderleber,” Dissertation, Leipzig, 1896 (Literature). 


400 DISEASES OF THE LIVER. — 


2. GENERAL sbi ee AND PHYSIOLOGY OF THE | 


Our knowledge of the normal function of the liver has been increased 
by the study of a number of morbid conditions of this organ. The liver is 
larger than the other abdominal organs, and consequently any abnormal- 
ity in its consistency is the more readily detected. Considerable patho- 
logic significance has always been attached to such changes, and the exact 
interpretation of these various lesions was for a long time very inaccurate. 
In many instances an explanation was artificially constructed and based on 
preconceived ideas. Above all, the more apparent changes in the amount 
of blood and of fat that the organ contained were credited with an exag- 
gerated significance. The liver was looked upon as the organ in which 
blood was formed from the chyme, in which the veins originated, and in 
which the body-heat was generated. 

These various assumptions as to the significance of the liver in path- 
ology were disproved by closer criticism, and, following the example of 
Bartholinus, it was supposed that the only function of the liver was the 
manufacture of bile, disturbance of that function causing the conspicuous 
symptom of jaundice. The same confusion in regard to function that ex- 
isted in the case of the liver obtained in the case of the bile. All diseases 
that were complicated by jaundice were declared to be “ bilious” in char- 
acter and due to some deep-seated lesion. These “bilious”’ disturbances 
with participation of the liver are, even nowadays, a part of the pathologic 
teachings and views of many physicians, and in particular of the laity; 
more so in England and America than in Germany.* Such views, how- 
ever unfounded, fantastic, and entirely wrong they may have been, at the 
same time incorporated a correct idea. They signified that so important, 
so large, and so peculiarly constructed an organ as the liver, at all events 
had some other function besides the excretion of bile. Magendie and 
Tiedemann experimentally determined its function of assimilating certain 
constituents of the food. Claude Bernard and Hensen discovered gly- 
cogen in the liver and thereby established its relation to carbohydrate 
metabolism. Other observations, such as the occurrence of fatty liver 
after forced feeding, had previously made it probable that the liver had 
something to do with metabolism, but the discovery of the glycogenic 
function of the liver was the first exact demonstration of the fact that a 
gland, aside from forming an external secretion, could also manufacture 
a number of substances that returned into the general circulation and 
might play an important réle in the nutrition of the general organism. 
The researches of the last few years have demonstrated that a number of 
other glands have the function of producing both internal and external 
secretions. 


It must be remembered, at the same time, that the function we designate by 
these terms was not completely unknown and unrecognized up to that time. It 
was known of every organ that it not only absorbed substances from the tissue- 
juices, but also poured substances into them. As arule, it is true, these substances 
were regarded as excretions, and were not credited with any further significance 
in the economy. I will only mention the muscles, among other parenchymatous 


* This statement can hardly be considered entirely justified at the present 
time.—Eb. , 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 401 


organs, that secrete lactic acid, and carcinomata, that pour into the general circu- 
lation substances capable of influencing metabolism. 


It is probable that the internal secretion of no other organ is of such 
importance for the body as is that of the liver, and even to-day we are not 
able to estimate the true extent of its significance. There can be no 
doubt that its pathologic significance is far-reaching, more so than we can 
now appreciate. Particularly in the case of the liver is the close inter- 
dependence of internal and external secretion apparent, and we can readily 
observe in many lesions that an impediment in the outflow of the latter 
seriously interferes with the former. 


ANATOMY AND HISTOLOGY. 


We will limit ourselves to a brief review of the internal structure of the 
liver. The arrangement of. the parenchyma is, to a large extent, depen-. 
dent on the course of the numerous blood-vessels contained in the organ.* 
The large portal vein enters through the porta hepatis and ramifies into 
numerous branches and capillaries that are ultimately reunited to form the 
numerous hepatic veins which leave the organ at its posterior margin and 
empty directly into the inferior vena cava, while the branches of the hepa- 
tic vein of the liver are separated from the adjacent parenchyma by a very 
thin wall. The portal vein and its branches, on the other hand, are ac- 
companied along their whole course by a connective-tissue sheath called 
Glisson’s capsule. Within this capsule are also found the hepatic artery, 
the bile-ducts, the lymph-vessels, andsthe nerves corresponding to the 
course of the vessels. Certain areas are visibly outlined within the liver, ° 
forming the lobules. These measure from 1 to 1.5 mm. in diameter. 
Seen in sections, it will be found that each lobule has a small venous 
radicle in its center and that several branches of the portal vein and the 
hepatic artery enter it from the periphery. The capillary network within 
the lobule is arranged in such a manner that the different capillaries seem 
to radiate from the center and inclose the hepatic cells within its meshes, 
the latter thus also being arranged in radiating lines. These rows or 
columns of glandular tissue are unicellular in many animals (for example, 
the rabbit), but multicellular in man. From the interlobular biliary 
passages, with their gradually lessening wall of glandular tissue and cubi- 
cal epithelium, the biliary capillaries originate and penetrate the lobules, 
dividing in such a manner that each one is separated from the correspond- 
ing blood-capillary by at least one liver-cell. According to older views, 
these form an anastomosing network; but according to Retzius, they do 
not anastomose, but run a tortuous course and give off many branches. 
Each of these finest passages seems to terminate within a liver-cell in a 
knob-shaped opening (the “‘secretion-vacuole” of Kupffer). In this way 
each liver-cell is in contact on one side with a bile-capillary, on the other 
with a blood-capillary. 


According to Nauwerck + and others, the intracellular continuations of the bile- 
capillaries are in connection with an anastomosing network of capillaries surround- 
ing the nucleus. This is particularly apparent in biliary stasis and after staining 
with saffranin. According to Fraser and Nauwerck, an intracellular network can 
also be demonstrated by injection of the artery. I am inclined to consider the 


as ts good diagram of the portal tree after Rix is given by Langenbuch, pp. 
tT Nauwerck, “Leberzellen und Gelbsucht,’? Miinchener med. Wochenschr., 
1897, No. 2. 

26 


402 DISEASES OF THE LIVER. 


former network as more probably physiologic than the latter, and I think that it 
has not been clearly demonstrated that the two are not identical. 

[Schaefer * has recently found in the protoplasm of the cells varicose canaliculi 
filled with material injected into the portal vein. Housert} has found and more 
definitely described the intracellular capillary network.—Eb.] 

The nerve-fibers of the hepatic plexus are derived partly from the celiac plexus, 
partly from the vagus. They penetrate the liver together with the hepatic artery 
and ramify with it. Nothing definite is known in regard to their terminations. 

According to Disse,f lymphatic vessels lined with endothelium can be seen 
after injection. They are seen both in Glisson’s capsule, following the ramifications 
of the portal vein, and within the adventitia of the hepatic veins. They anastomose 
directly with one another, and are, furthermore, connected by lymph-channels 
that have no endothelial lining. The latter form sheaths around the blood-capillaries 
in the liver lobules, so that they are situated between the capillary walls and the 
liver-cells. They possess a membranous wall that is in direct contact with the 
liver-cells. These cells contain a relatively large, round nucleus, and, according 
to Disse, are identical with the stellate cells of Kupffer. Fibrillae extend from these 
membranes and enter the rows of liver-cells, in this manner connecting the sheaths 
of the capillaries. 


The liver-cells proper are constructed on the general type of epithelial 
cells. They have a long polygonal shape, varying during life. Their 
diameter is about 15 to 40 ». They have a round nucleus from 4 to 12 
in diameter. The appearance of the cells changes with the exercise of 
their physiologic function. During fasting each cell, like the whole liver, 
is smaller, the protoplasmic reticulum is narrower, and the granules em- 
bedded within itmuch finer. During digestion the appearance of the 
liver and of its individual cells changes in a different manner according to 
the kind of food that is ingested. After the ingestion of albuminous food 
- the liver becomes more vascular, but remains hard and resistant, while its 
cells are larger than during fasting and the fine granules within the proto- 
plasm are more numerous. After carbohydrate feeding the liver enlarges 
more than after proteid ingestion, while at the same time it grows softer, 
more friable, and grayish-yellow, and its capillaries become compressed 
owing to the enlargement of the liver-cells. The latter contain, inclosed 
in the meshes of their protoplasm, large masses of amorphous glycogen, 
staining withiodin. With both kinds of diet the changes in the liver-cells 
occur uniformly and in the same manner in the lobules of all portions. 

On a fatty diet the liver also enlarges and assumes a whitish-yellow 
color. The fat is primarily deposited in the periphery of the lobules, and 
as a result the outlines of the different lobules become more clearly visible. 
Kach cell contains the fat in the shape of minute droplets that later coal- 
esce to form larger drops. 

Sometimes the liver-cells, particularly those that are more centrally 
situated, contain a finely granular pigment of unknown constitution. A’ 
normal liver never contains bile-pigment. — - | 

According to Cavazzani,|| experimental irritation of the celiac plexus 
causes a diminution in the size of the liver-cells and reduction of their 
glycogen. His experiments were made on dogs and rabbits. After the 
operation a decrease of the glycogen and an increase of the sugar within 
the liver can be chemically determined. 


* Anatom. Anzeiger, 1902, Bd. xx1, pp. 18-20. 
~ tT Science, May 30, 1902, p. 874. 
‘t J. Disse, “Ueber die Lymphbahnen der Siugethierleber,’’ Archiv fiir mikro- 
skopische Anatomie, 1890, Bd. xxxv1, p. 208. (Gives the earlier literature.) 
§ Heidenhain, Hermann’s “ Handbats der Physiologie,” Bd. v, 1, p. 221. 
Affanassiew, Pfliiger’s Archiv, 1883, Bd. xxx, p. 385. 
|| Cavazzani, Pfltiger’s Archiv, 1894, Bd. tv, p. 181. 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 4038 


Changes in the liver-cells have also been observed after the adminis- 
tration of certain drugs. Thus Iwanow * found an enlargement, later a 
diminution, in the size of the nucleus in frogs after the administration of 
antipyrin, the enlargement being accompanied by a loss of chromatin and 
changed staining qualities of the protoplasm. Neumann + found in mice 
the cells very small after phloridzin, very large after administering 
cocain, cumarin, and in mouse septicemia. (For the influence of various 
poisons on the glycogen and fat in the liver see below.) 

The circulation of the blood within the liver is remarkable because of 
certain peculiarities in the arrangement of the blood-vessels and the 
enormous development of the capillary network. The blood-pressure in 
the main vessel that carries the blood to the liver, the portal vein, is less 
than in the arteries of the organ. Thus, v. Basch t found the blood- 
pressure in a dog whose splanchnic nerve had been severed to be from 
7 to 16mm. Hg; Heidenhain % found 5.2 to 7.2 mm. (4 to 4 of the bile- 
pressure) ; while J. Munk || found 26 to 30 mm. if he allowed a soap solu- 
tion to flow into the liver at the same time. The pressure will vary much 
according to the amount of blood present, the state of the portal capil- 
laries, and the resistance within the liver itself. 

[Sérégé,** by an interesting series of experimental, clinical, and path- 
o'ogic observations, as well as by certain facts derived from compara- 
tive anatomy, has shown that there are two distinct currents going to 
the right and to the left lobes of the liver through the portal vein, the 
one current being derived from the territory drained by the large mes- 
enteric vein and proceedihg to the right lobe of the liver; the other cur- 
rent representing the flow from the splenic and small mesenteric veins and 
going to the left lobe of the liver. Experimental investigation in ani- 
mals by the injection of India ink into the two mesenteric veins con- 
firmed the evidence of comparative and pathologic anatomy, while the 
freezing-point and specific gravity of the blood from the large mesen- 
teric vein and the small mesenteric vein with the splenic differed 
sufficiently to agree with the view that there is a more or less complete 
separation of the two currents after their entrance into the portal 
trunk.—EpD.] 

I have succeeded in finding only an isolated statement in regard to the 
rapidity of the blood-flow. Cybulski ++ found it to be from 2.4 to 2. ec. 
per second in a small dog. 

It is impossible to state, at present, what is the effect of the mixing 
of the arterial and portal blood upon the rapidity of the blood-flow in 
the capillaries. It is conceivable that the one might hinder or accelerate 
the other.tt 

The action of the heart and the respiration are of great significance in 


* Twanow, du Bois Reymond’s Archiv, 1887. 
+ A. Neumann, ‘ ‘Ueber den Einfluss von Giften auf die Grésse der Leberzellen,”’ 
Dissertation, Berlin, 1888. 
v. Basch, “ Arbeiten der physiologischen Anstalt in Leipzig,” 1875, x, p. 253. 
§ Heidenhain Hermann’s “ Handbuch der Physiologie,” v, p. 269. , 
|| J. Munk, Archiv fir Anatomie und Physiologie, physiologische Abtheilung, 
1890, Supplement, p..131. 
** Jour. de méd. de Bordeaux, April 12, 1901. 
tt Cybulski, quoted by Nencki, Archiv fir experimentelle Pathologie, 1895, Bd. 
XXXVII, p. 39. 
tt Compare Gad, “Studien iiber die Beziehungen des Blutstroms in der Pfor- 
tader zum Blutstrom in der Leberarterie,’’ Dissertation, Berlin, 1873. See also 
the section on Hyperemia of the Liver. 


404 DISEASES OF THE LIVER. 


regard to the blood-current in the liver. The hepatic veins are, by these 
functions, subjected to a continuous and rhythmic suction that is in- 
creased by the pressure exercised upon the convex surface of the liver by 
the diaphragm during each inspiration. 

It is probable (even if we cannot prove the assumption positively by 
measurement) that the blood flows more slowly through the capillaries of 
the liver than through the capillaries of any other region of the body. 
This is probably one of the reasons, though not the only one, why a large 
number of leucocytes are always found within the hepatic capillaries. It 
also explains why fine particles, like grains of cinnabar, malarial pigment, 
etc., are found either free or within the leucocytes in the hepatic capilla- 
ries. Thesame phenomenon is seen in the bone-marrow and in the spleen. 
Micro-organisms’ suspended in the blood are arrested in the liver in the 
same manner. From the capillaries, the fine granules enter Kupffer’s 
stellate cells and the connective-tissue corpuscles of the periportal tissues. 

The blood-current within the liver varies with the width of the afferent 
vessels and the nervous influences that govern this. 


Képpe * has demonstrated in dogs that a well-developed muscular layer, 
that is found not only in the arteries but also in the portal vein, is responsible for 
these changes. The main branch has no valves and is equipped with an internal 
circular musculature and an external longitudinal layer of muscle-fibers. The 
branches within the liver have more of the longitudinal fibers, while in the extra- 
hepatic branches coming from the intestine the circular fibers predominate. The 
latter are also found in the long and short intestinal veins that have no valves, 
while in the submucosa the veins have neither valves nor muscular fiber. 


The vasoconstrictor nerves of the liver are derived from the celiac 
plexus through the splanehnic nerve. From the cord they enter the 
sympathetic in the region of the sixth dorsal to the second lumbar verte- 
bree on both the right and the left sides. : 


Section of the nerves of the liver produces hyperemia and enlargement of the 
organ, as well as edematous swelling c of its interstitial tissue (Affanassiew ft). Faradic 
irritation of the splanchnic nerve { causes a diminution in the size of the organ 
from the influence upon the intrahepatic branches of both the portal vein and the 
hepatic artery as manifested by an increase of the blood-pressure within these 
vessels. Vasodilator fibers ‘reach the hepatic vessels from the vagus. 

That the smallest vessels of the liver are capable of independent contractions 
can be demonstrated by the fact that gently stroking the surface of the liver pro- 
duces a fine, pale line, as happens in the skin under similar irritation (Vulpian §). 

It is probable that the nerves derived from the splanchnic act not only on the 
vessels, but also on the liver-cells and the biliary secretion. (See Cavazzani above.) 

The effect of Bernard’s piqure is transmitted to the liver through nerves that 
pass through the cord and the sympathetic and reach the liver through the splanchnic 
nerves. The piqure produces hyperemia by an acceleration of the blood-current 
in ae liver. It is probable that the liver-cells are directly influenced by this opera- 
tion 

It may be well in this place to discuss the remarkable power of regeneration 
possessed by the liver after removal of portions of the organ by operation. Ponfick 
instituted experiments in this direction on rabbits and dogs, and found that after 


* K6éppe, “ Muskeln und Klappen in den Wurzeln der Pfortader,” Archiv fiir 
Anatomie und Physiologie, physiologische Abtheilung, 1890, Supplement, p. 168. 

+ Affanassiew, Pfliiger’s Archiv, Bd. xxx, 8. 419. 

t Frangois-Franck und Hallion, “ Recherches expér. sur Vinnervation vaso- 
constrictive du foie,” Archives de physiologie, 1896, p. 908. 
§ Cited by Frangois-Franck. 
| Langendorff, Archiv fiir Anatomie wnd Physiologie, physiologische Abtheilung, 
1886, S. 274. Morat and Dufour, “Les nerfs glycosécréteurs,” Archives de physi- 
ologié, 1894, p. 371 





GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 405 


removal of one-fourth to one-half of the total mass, the remaining portion began 
to increase in size at the expiration of only a few days, at the same time growing 
more fragile, softer, and more vascular, resembling in the latter respect the spleen. 
The parenchyma itself, if empty of blood, appears lighter than normal, shiny, moist, 
and the outline of the lobules is not very distinct. The liver remnant increases 
for several weeks, so that finally the original bulk of the liver is attained, while in 
some cases an overcompensation occurs. This compensatory growth and enlarge- 
ment occurs even after repeated ablation of pieces of the organ. The original shape 
of the liver, of course, does not return. The regenerated organ has a more plump 
shape which otherwise depends upon the location of the piece removed. The 
presence of other diseases does not seem to interfere with the regeneration of the 
liver. 

Microscopic examination reveals that the increase in size is due to a swelling 
of the liver-cells followed by cell-division. The new cells are distributed diffusely 
but irregularly throughout the whole of each lobule, and by the end of the second 
week may outnumber the normal liver-cells. They are distinguished from the 
latter by their rounder form, by a larger nucleus and stronger affinity for stains. 
Some of them contain two nuclei, so that the division of their protoplasm seems to 
occur later. A proliferation of blood-capillaries proceeds with the cellular prolifera- 
tion, the new capillaries varying in diameter and the lymph-channels surrounding 
them being in many places dilated. Owing to the proliferation of the hepatic cells 
and capillaries, the normal radiating type of vascularization within the individual 
lobules is converted into a cavernous one. Each individual lobule is increased, 
even to double its normal size, frequently altered in its structure, and furnishes 
small processes that, in their turn, possess their own central vein. Even the larger 
bile-vessels show proliferation in their epithelium and connective-tissue layer, but 
at no place lateral offshoots. The bile-capillaries no longer show the normal regular 
polygonal arrangement, but take an irregular, tortuous course corresponding to 
the new-formation of glandular cells. 

The whole process constitutes a process of regeneration of such unusual extent 

that Ponfick has proposed the name re-creation for it. It is probably brought about 
by the reaction of the body to the functional disturbances following removal of 
parts of the liver, and is a conservative process. 
. A similar process seems to occur in human disease, as in multilocular echino- 
coccus and in extensive localized syphilitic lesions.*. It is possible, too,, that the 
same obtains for the “ nodular hepatitis” described by Sabourin and others. Hoch- 
haus could not discover similar regenerative processes following local necroses of 
limited extent from ¢old. After a few hours, however, there occurred a determina- 
tion of leucocytes into the marginal zone with a mitosis of the nuclei of the connective 
tissue structures in that region. [Similar attempts at regeneration are seen in 
certain cases of atrophy of the liver (Meder and Ibrahim). See the section on 
Atrophy of the Liver.—Eb.] : 

[In spite of considerable discussion the significance and nature of the newly 
formed “‘ bile-capillaries ”’ seen in certain forms of hepatic cirrhosis are not as yet 
clearly determined.—Eb.] 


FUNCTIONS. OF THE LIVER. 


The most radical procedure advised for determining the hepatic func- 
tion is— 

Excluding the Action of the Liver.—The results of this procedure are 
complicated and not readily interpreted. Three experimental methods are 
possible: viz., extirpation, injury to the parenchyma by chemicals injected 
through the bile-passages, and interruption of the blood-supply. The last 
method is the oldest. In the earliest experiments the portal vein was 
ligated, and it was found that the animals-rapidly died with a great de- 
crease in the blood-pressure. Formerly it was thought that this was due to 
“bleeding to death into the portal vein” as a result of the excessive filling 
of the intestinal vessels with blood (Tappeiner). This view has never been 
proved, nor has the real cause of the phenomenon been discovered. 
Gradual occlusion of the portal vein did not lead to the desired goal, for the 


* Virchow, Virchow’s Archiv, Bd. xv, 8. 281. 


406 DISEASES OF THE LIVER. 


reason that the liver received blood from collateral paths (Oré). Von 
Schréder, later, combined ligation of the portal vein with conduction of 
its blood into the renal vein, and succeeded in keeping the animals alive 
in this manner for from one hour to an hour and a half. 

Ligation of the hepatic artery also led to necrosis of the whole organ 
and the rapid death of the animal (Cohnheim and Litten). Ligation of the 
aorta below the diaphragm and occlusion of the vena cava above the hepa- 
tic vein (Bock and Hoffmann) caused death within less than an hour. 
Ligation of the celiac and mesenteric arteries (Slosse) permitted the ani- 
mals to live for from five'to fourteen hours, but did not completely ex- 
clude the establishment of a collateral circulation to the liver (in this case 
from the colon), nor did it exclude the possibility that decomposition 
within the intestine and its walls was in part responsible for some of the 
symptoms. Kaufmann, in order to do away with the latter possibility and 
thus remove any objections to the whole procedure that might be made 
on that score, at the same time extirpated the intestines tributary to the 
portal system. 

All these procedures bring about the death of the animal within a few 
hours. Their life can be preserved for a longer period of time by making 
what is called an Eck fistula, by which the blood of the portal vein is 
carried through a permanent fistula into the inferior vena cava. Even 
after the establishment of such a fistula violent nervous manifestations, 
especially with a meat diet, endanger the life of the animal and may lead 
to its early death (Hahn, Massen, Nencki, Pawlow). 

The first method of disconnecting the liver (by extirpation) frequently 
fails, because this proceeding is followed by the same complications as 
simple ligation of the portal vein. In amphibious animals and in birds 
this difficulty is not so great, because a communication between the portal 
and renal veins permits the flow of blood from the former to the vena cava. 
Extirpation of the liver, for this reason, has been frequently performed in 
frogs (J. Miller and others), pigeons (Stern), and ducks and geese (Naunyn 
and Minkowski). The frogs could be kept alive for days, the birds as long 
as twenty hours. Nenckiand Pawlow finally performed extirpation of the 
liver in dogs after making an Eck’s fistula and kept the animals alive for 
six hours. 

The second method, chemical destruction of the hepatic parenchyma, 
‘consists in the injection of dilute acids into the bile-passages. E. Pick 
employed ; normal sulphuric acid solution with simultaneous ligation of 
the bile-duct; Denys and Stubbe used 2% to 5% acetic acid, which they 
injected into the bile-duct from the duodenum, thus allowing the bile-duct 
to remain patent afterward. Following these injections, wide-spread 
necrosis occurs, followed in from six to forty-eight hours by the death of 
the animal. 

The results of these different procedures appear in a different manner 
and after varying periods of time on account of the various secondary 
results that are produced, particularly in regard to disturbances of circu- 
lation. As a rule, the length of life varies inversely with the degree of 
the exclusion of the liver. Severe nervous disturbances appear, such as 
apathy, increasing somnolence, and, frequently, premortal spasms. In 
animals with an Eck’s fistula these symptoms are preceded by a period of 
excitation. Occasionally it is found that after the removal of the liver the 
formation of bile-pigment and of bile-acids stops, the blood loses its sugar, 
and less urea is formed and excreted than normally. Most investigators 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 407 


seem to be in doubt whether to attribute death to these perversions of 
metabolism or to poisons that are produced by other metabolic disturb- 
ances. 


The organism can well tolerate the loss of part of the liver, as is shown by 
a variety of diseases in which parts of the liver are destroyed. Ponfick, in his 
experiments on rabbits, has demonstrated how far this tolerance goes. He was 
enabled to remove even half of the liver without permanently injuring the animals, 
which recovered completely and seemed to prosper. In favorable cases even two- 
thirds of the liver could be removed with impunity, particularly if the whole amount 
removed was not taken away at one sitting. Ablation of four-fifths of the organ 
caused death in less than sixteen hours. In one animal partial extirpation was per- 
formed at three sittings, the second one month, the third four months, after the 
first. The animal survived the last operation by two days and a half, although 
only 15% of the normal liver was left. 

This tolerance is probably due to a compensatory increase of function in 
the remaining portion of the liver and is manifested by an enlargement of the 
remnant which occurs a few days after the operation. At the end of three weeks 
the enlargement is always quite pronounced, and in many cases progresses so far 
that the normal weight of the liver is reached or even exceeded (by as much as 
29%). In one case the remnant had increased to double its size within five days (the 
remnant amounted to about 25%). We have already described the anatomy of this 
wonderful compensatory growth. 

In those cases where the animals died and no direct results of the operation 
proper (embolus, inflammation, hemorrhage, etc.) caused death, the fatal issue 
must be attributed to a cessation of the hepatic function and the contraction of the 
vascular area. The latter effect also manifests itself in partial removals of hepatic 
tissue by the occurrence of hyperemia and hemorrhages within the intestine and 
stomach, particularly in their mucous membrane, and, further, by hemorrhagic 
exudation into the abdominal cavity. The colon never grows hyperemic, but the 
spleen, on the other hand, becomes very hyperemic and swells to twice its normal 
bulk. As a rule, these symptoms of stasis are most pronounced in larger extirpa- 
tions, varying in degree, however, in different cases. They are most pronounced 
on the first day after the operation, much less so on the days following, and finally 
disappear altogether. . 


Diseases of the liver characterized by a slow or rapid destruction of 
parenchyma (acute atrophy or atrophic cirrhosis) corroborate, as we shall 
see below, the results of these experimental studies. In fact, these dis- 
eases were the direct incitement to the performing of experiments along 
these lines. 

Extirpation of the liver gives us a general picture of the significance of 
the organ in general metabolism. Its true rédle can, however, be discov- 
ered only by analyzing the participation of the liver in the catabolism of 
the different groups of the constituents of the body. In the following a 
brief review of these processes is given. 

Nitrogen Metabolism.—We know in regard to the part that the liver 
plays in nitrogen metabolism that it converts ammonia and allied sub- 
stances into urea. This occurs on a large scale if ammonia in combination 
with carbon dioxid or oxidizable acids is artificially introduced (Haller- 
vorden, Coranda, v. Schréder). Physiologically a large quantity of am- 
monia is carried to the liver by the portal vein. This ammonia is gener- 
ated partly in the intestine, particularly after a meat diet, partly in the 
stomach and intestine from chemical processes that occur within the mu- 
cosa during the secretion of gastric and enteric juice (Nencki, Pawlow, and 
Zaleski). Disconnection of the liver increases the ammonia in the blood. 
and the urine and decreases the excretion of urea in the urine (Slosse, 
Nencki, and Pawlow). According to Nencki, the material for the forma- 
tion of urea is ammonium carbaminate, which is normally carried to the 


408 DISEASES OF THE LIVER. 


liver. In dogs with an Eck’s fistula it is said to exercise a toxic effect and 
to produce the spasms and other nervous phenomena (the latter is doubted 
by Lieblein). Nencki calls attention to the fact that the liver is probably 
not the only place in which urea is formed. : 

In birds uric acid, which is the end-product of their nitrogen metab- 
olism and corresponds to urea in mammals, is also formed in the liver. 
Following extirpation of the liver birds excrete only a small amount of 
uric acid, and in its place a considerable quantity of ammonium lactate 
(from 50% to 60% of the total nitrogen) (Minkowski). 


The same thing occurs after the administration of urea, which normally increases 
the formation of uric acid in birds. Horbaczewski’s synthetic production of uric | 
acid from ammonia and trichlorlactic acid makes it probable that uric acid is formed 
within the body from lactic acid and ammonia. 

The separation of ammonia from amido-acids that are administered can, at 
all events, occur elsewhere than in the liver. The excretion of urea is not markedly 
changed in birds by extirpation of the liver. Lieblein’s observation on dogs, that 
obliteration of liver-tissue is followed by an increased excretion of tric acid, can be 
attributed to an excessive catabolism of the nuclei of the liver-cells. 


In man a relative increase of the ammonia and a decrease of the urea (in 
proportion to the total nitrogen) is occasionally found in acute and chronic 
atrophy of the liver. It seems natural to attribute this to a disturbance 
of the urea-forming function of the liver. According to Weintraud, how- 
ever, this power seems to be preserved for a long time even in advanced 
cirrhosis, and it is probable that some of the ammonia remains untrans- 
formed only for the reason that it is needed to neutralize the abnormally 
formed acids. 

In a case of phosphorus-intoxication, Munzer could decrease the am- 
monia-nitrogen from 16.6% to 6.2% by administering bicarbonate of 
sodium. Engelmann and Minkowski also succeeded in decreasing the 
excretion of ammonia in geese whose livers had been extirpated, by giving 
bicarbonate of sodium. As, however, the quantity of uric acid was not 
increased, the disturbance of uric acid formation following the extirpation 
cannot be attributed to a binding of the necessary ammonia by lactic 
acid. 

Carbohydrate Metabolism.—When a quantity of carbohydrate in 
excess of the immediate needs of the body is ingested, the excess is stored 
in the liver and in the muscles in the form of glycogen. From these stor- 
age places the glycogen is gradually poured into the blood to be utilized - 
by the different organs. In long-continued starvation glycogen is, there- 
fore, absent from the liver or present only in traces: The dextrose and 
the levulose of the food are, according to C. Voit, the only direct sources 
of the hepatic glycogen. In the absence of these substances glycogen can 
be formed from fat and proteid, and be deposited in the organ, this‘forma- 
tion, according to Seegen, apparently taking place in the liver itself. 

The glycogen stored in the liver regulates the percentage of sugar in 
the blood. If the liver is disconnected by extirpation (Minkowski) or by 
interruption of its circulation (Bock and Hoffmann), the sugar rapidly 
disappears from the blood. : 

A decrease of the hepatic glycogen is found in starvation, in fever 
.(Manassein, Hergenhahn), in artificial elevation of the body-temperature 
(Paton, May, Schulte-Overberg), after injections of acid into the bile-ducts 
(F. Pick), in diabetes mellitus of man, and after extirpation of the pan- © 
creas in birds (Kausch). This decrease of glycogen is, in part, due to the 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 409 


decreased ability of the liver to retain the glycogen, so that more sugar 
enters the blood; in part, to an increased consumption of sugar. 

The interrelationship between hepatic activity and glycosuria is re- 
markable, and has been frequently studied. That the liver is the source 
of the blood-sugar is demonstrated by the following observations: (1) 
Glycosuria does not occur after piqure, strychnin-poisoning, or carbon 
monoxid intoxication, if the liver has been extirpated, or if it has been 
previously rendered free from glycogen by ligation of the bile-ducts (Wick- 
ham-Legg, Schiff, Gurtler, Langendorff). (2) In frogs pancreatic dia- 
betes does not occur if the liver has been previously extirpated (Marcuse). 
After extirpation of the pancreas the glycogen stored in the liver is more 
rapidly poured into the blood, as is demonstrated by the course of the 
excretion of sugar (Minkowski). 

Transitory glycosuria may, therefore, depend upon perversion of the 
function of the liver. Such perversion cannot, however, be made alone 
responsible for the persistent excretion of sugar that is seen in diabetes 
mellitus. The latter can only be caused by a diminution of the normal 
consumption of sugar in the organism. Clinical experience, moreover, 
reveals no relationship between diabetes and hepatic lesions.* If the two 
conditions are found at the same time, this must be considered as a 
coincidence, and no Significance can be attached to it. The only thing 
that has been positively determined is a reduction of the hepatic gly- 
cogen in human diabetes and in experimental pancreatic diabetes, and this 
is probably a secondary occurrence. 

Owing to the fact that the liveris recognized as a reservoir for glycogen, 
a number of French investigators have followed in the footsteps of Claude 
Bernard, who looked for alimentary glycosuria in diseases of the liver. 
Bernard found it in dogs after gradual obliteration of the portal vein, and 
explained the phenomenon by assuming that through the formation of a 
collateral circulation with parts surrounding the liver, the sugar ingested 
could circumvent the portal vein and enter directly into the systemic 
blood-vessels. In fact, Naunyn, Schopfer, and Seelig found that injection 
of sugar into the systemic veins produced glycosuria, whereas the same 
result did not follow the same injection into the mesenteric veins. Clinical 
observations on cases of disease of the liver have, however, led to very 
conflicting results. Even in the healthy the power of assimilating sugar 
varies considerably, ranging, according to Hoffmann, between 100 and 250 
grams. In atrophic cirrhosis this limit is occasionally somewhat reduced, 
but such a reduction is not observed in diseases of the liver in general.t 
According to v. Jaksch, it is reduced in phosphorus-poisoning, particu- 
larly in the stage of marked’swelling of the liver. [Strausst examined 38 
eases of various hepatic troubles and failed to find alimentary glycosuria 
except for a brief time in two cases of trauma in the hepatic region. 
Brault % has also studied the preservation of the glycogenic function in 
atrophic cirrhosis.—Ep.] Very little is known in regard to the quantity 
of glycogen stored in the liver_in disease (excepting in diabetes). This 
is due to the fact that postmortem changes can rarely be excluded. Still 
less is known about the process of glycogen formation in man. 


* Glénard, “Des resultats obj. de l’exploration du foie chez les diabetiques,”’ 
Lyon médical, 1890, No. 16-25. 

+ Minkowski, Ergebnisse der allgemeinen Pathologie von Lubarsch und Oster- 
tag, 1897, p. 720. 

t Berlin. klin. Woch., December 19, 1898. § Presse méd., May 29, 1901. 


410 DISEASES OF THE LIVER. 


Experimental investigation has taught us that the glycogen is reduced in 
poisoning by phosphorus, arsenic, and antimony,* and after thé administration of 
strychnin, morphin, chloroform,t and various other poisons. Kunkel believes 
that the most important in this respect are those forms of poisons that change 
the constitution of the blood entering the liver by the production of violent dis- 
turbances in the intestinal tract.{ According to E. Neisser’s || experiments on 
mice, glycogen cannot be found microchemically after administering phloridzin, 
papain, asparagin, coniferin, and cumarin, while after giving morphin, amygdalin, 
and mytilotoxin it is found, the latter substances exercising an inhibiting effect upon 
its conversion. , 


Metabolism of Fat.—The liver stores up fats as well as carbohydrates. 
The fat ingested is deposited here within a few hours after eating (more 
rapidly than in the connective tissue), and it is also readily given up again. 
This is the physiologic fatty liver which is particularly striking in suck- 
ling animals. The fat reaches the liver chiefly through the chyle vessels 
and the thoracic duct, so that it has to pass into the blood-current before it 
arrives at the liver. Within the chyle a little of the fat is in solution, either 
as fat or (as much as 2%) as soap, but the greater portion is seen in the 
form of neutyal fat in fine emulsion (according to J. Munk, even after 
feeding with fatty acids). Probably some fat also reaches the liver di- 
rectly by way of the portal vein in solution as soap, and is then changed by 

‘the liver (J. Munk). After feeding with fat the blood in the portal vein 
contains no more free fat than the blood in the carotid (Heidenhain). 

Feeding experiments show that fat can also be formed from carbo- 
,oydrates and can be deposited in the liver (as is seen in the purposeful 
fattening of livers of geese). It is not known where this conversion 
occurs. 

We’know still less in regard to the participation of the liver in the con- 
version of proteid into fat. It is certain, however, that under certain 
pathologic conditions such a conversion occurs within the liver itself. 

The liver is probably concerned not only with the storing of fat, but 
also with its further elaboration, as during starvation the deposit of fat in 
the liver decreases more rapidly than in other organs that store it. A cer- 
tain proportion of fat, however, always remains in the liver even after long 
periods of hunger. 


In dogs, according to Rosenfeld, the fat of the liver is reduced to about 10% 
of the dry residue by a total abstinence of five days. It is immaterial whether 
the animals are fat or lean. Rosenfeld could hardly ever reduce it to less than 10%, 
even after long periods of starvation. That fat plays a very important réle in the 
nutrition of the liver-cells is shown by Spee’s observation that in the embryos of 
rabbits and guinea-pigs the cells of the endoblast, and later only those cells that 
_ were to form the liver-cells, contained numerous droplets of fat, this being par- 
ticularly true for that half of the cells directed toward the mesoblast. This fat 
could not have come from the vitelline membrane. 


According to O. Nasse, the glycogen required for combustion is de- 
rived from the fat. This for the present is pure hypothesis. Under cer- 
tain conditions, however, there is a migration of fat from other places of 
deposit into the liver. This becomes particularly manifest after the exhi- » 
bition of phloridzin (Rosenfeld). If the percentage of fat in the liver of a 


* Salkowski, Virchow’s Archiv, Bd. xxxtv, p. 79. 

{| Béhm, Archiv fiir experimentelle Pathologie, Bd. xv, p. 450. 

{ Kunkel, “Einfluss von Giften auf den Glykogengehalt der Leber,” Wurzburger 
Sitzungsbericht, 1893, p. 135. 

|| E. Neisser, ‘‘Beitrage zur Kenntniss der Glykogens,” Dissertation, Berlin, 
1888. 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 411 


dog is reduced by a fast of five days, and if the animal receives a fairly 
large dose of phloridzin (2 to 3 grams for each kilo of weight) on the sixth 
and the seventh days, a large deposit of fat will, after forty to forty-eight 
hours, be found within the liver, and the organ will, moreover, be seen to 
be very much enlarged. The fat deposits are principally found in the 
center and in a narrow peripheral zone, later in the whole extent of the 
lobule. The quantity found amounts to about 25% to 75% of the dry 
residue. This fat has not been formed in the location where it was found, 
for the percentage of albumin in the liver is hardly changed. In addi- 
tion, this deposit of fat disappears within twenty-four hours if the animal 
is starved further. That the fat is carried to the liver through the 
blood is made manifest by the milky appearance of the serum and the 
percentage of fat found in the blood. The adipose tissue of the animal’s 
body furnishes this fat, as Rosenfeld proved by using dogs that had been 
fattened with mutton fat and showing that after five days of starvation 
the liver contained about 10% of dog fat, whereas after poisoning by 
phloridzin the liver of such animals contained from 50% to 60% of mutton 
fat in addition. 


It is a peculiar fact that phloridzin does not produce a fatty liver in animals that 
are fed on carbohydrate and meat, while feeding with fat increases the deposit of fat 
in the liver. It seems, therefore, that the storing of glycogen interferes with the 
storing of fat. The fat also disappears more rapidly after phloridzin-poisoning if 
meat alone, or meat and sugar, are given, than on starving; so the fat may even 
be reduced to from 3% to 4% below normal. 


Human pathology also teaches ‘Us that, particularly in phosphorus- 
poisoning, such a migration of fat to the liver can occur. 

According to F’. Hoffmann, the fat of the liver, even after feeding with 
neutral fat, contains more free fatty acids than the fat of any other organ 
(according to J. Munk, 5% to 10% of the neutral fat of the liver). This 
also demonstrates that the liver plays a peculiar réle in the metabolism 
of fat. 

In disease the fat of the liver varies in quantity owing to a number of 
causes. Sometimes the liver itself may be the seat of changes which are 
characterized by necrobiotic fatty degeneration of albumin or by a defi- 
cient elaboration of the fat entering the liver, sometimes general disturb- 
ances of metabolism may be present and occupy the foreground of the 
disease-picture. These may cause either a deficient or an excessive supply 
of fat to the liver. Sometimes the fat of the liver is so excessive that it 
determines the pathology of the disease. We will discuss fatty liver 
among the special diseases of the organ, and will recur to some of the 
details bearing on the question in that place. : 

Detoxicating Function.—Carbohydrates and fats are not the only 
substances that are stored in the liver. Some of the heavy metals; such 
as iron, copper, mercury, arsenic, and antimony, suffer the same fate. This 
property of the liver has a certain toxicologic significance. That the liver 
plays an important réle in intoxication by many other poisons has been . 
known for a long time; but it is only within the last decade that this sub- 
ject has received particular attention. The liver exercises a protective 
oe either by storing or by excreting poisons circulating through the 

body 


The protective action of the liver may be beted | in three ways: (1) The poison 
may be rapidly excreted with the bile; (2) the poison may be stored in the liver, 


412 DISEASES OF THE LIVER. 


in which manner the poison is removed from the general circulation, and thus, 
instead of producing acute poisoning, causes a more mild and protracted form; 
(3) the poison may be chemically transformed into a less harmful substance. 


The starting-point for all these investigations was the discovery made 
in Ludwig’s laboratory by Heger that nicotin added to the blood disap- 
peared if the blood was allowed to pass through the liver. After Heger, a 
number of investigators made experiments in different directions. Some 
compared the toxicologic action of different substances when they were 
introduced into the intestinal canal and into the subcutaneous connective 
tissues, or into a mesenteric and a systemic vein; while others attempted 
to identify the substance chemically or to test its toxicologic action after 
it had been allowed to flow with the blood through the liver or had been 
mixed with hepatic pulp. Thus, in addition to nicotin, hyoscyamin, 
strychnin, atropin, quinin, and morphin were tested in this manner. 
Heger states that one-fourth to one-fifth of the poisonous substance is 
retained by the liver, while Roger says that this amount varies from 50% 
to 100%. While Heger, Jaques, and others assume a simple storing, and 
explain the reduced toxic action from the more gradual entrance of the 
poison into the general circulation; others, again, as Lautenbach and 
Schiff, demonstrated a chemical transformation of the alkaloids. 


According to Buys and Heger, hyoscyamin is so changed by liver-pulp or 
filtered liver-juice that its presence can no longer be demonstrated physiologically 
or chemically.* The liver of a frog and of a rabbit acts more powerfully in this 
respect than does that of a dog. | 


In the case of curare the protective action of the liver, according to 
Lussana, consists in the excretion of the poison through the bile. Other 
authors (for example, Zuntz and Sauer in regard to curare, and René re- 
garding nicotin) claim not to have found this action. Roger concludes 
from his experiments that the protective action or the detoxicating 
power of the liver is proportionate to the amount of glycogen that it con- 
tains, and that the various poisons enter into combination with this 
substance. 


Kobert assumes that certain very insoluble compounds of the alkaloids with 
the bile-acids are formed. These were described by de l’Arbre.t He calls atten- 
tion to the fact that, according to Anthen,t the formation of the bile-acids is 
dependent on the glycogen contained in the liver. 


In the same manner as in the case of the alkaloidal poisons already 
mentioned, it has been shown that there exists a protective action of the 
liver against antipyrin, cocain, peptone,? the poisons produced by putre- 
faction, bacterial poisons, and the toxins of putrefaction that originate 
within the intestine. 


The blood from the portal vein of a dog is more poisonous to rabbits than is _ 
the blood from the hepatic and systemic vessels (Roger). Egg-albumen (Cl. Ber- 
nard), casein (Bouchard), and soap (J. Munk), if injected into the mesenteric veins, 
are changed in their passage through the liver. Sodium soaps injected into a systemic 


* Quoted from Hanot, p. 448, and Minkowski. 

t de l’Arbre, “Ueber die Verbindung einzelner Alkaloide mit Gallensiuren,” 
Dissertation, Dorpat, 1871. ‘ , 

t Anthen, “Ueber die Wirkung der Leberzelle auf das Himoglobin,” Disserta- 
tion, Dorpat, 1889. 
§ Questioned by J. Munk (loc. cit., p. 137). 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 413 


vein produce narcosis and death from paralysis of the heart (in doses of 0.29 gram 
per kilo of animal), whereas, when injected into a mesenteric vein, death occurs 
only after a dose from two and a half to five times as large. The liver has no de- 
toxicating power, in regard to digitalin, glycerin, acetone, or potassium and 
sodium salts, and a very slight action on alcohol. 


Bouchard has attempted to determine the toxicity of certain sub- 
stances found in the urine by injecting them into rabbits intravenously. 
He found certain differences in the urinary toxicity in healthy subjects and 
in persons afflicted with certain diseases. As the toxicity of the urine is 
increased in certain diseases of the liver, Bouchard’s pupil, Roger, con- 
cluded that the detoxicating power of the liver was reduced, a view 
borne out by the observation that in cases in which the toxicity of the urine 
was very high a mild glycosuria occurred, showing that the power of the 
liver to store glycogen had been reduced. Other authors, particularly 
in France, found the toxicity of the urine frequently, though not con- 
stantly, increased in diseases of the liver, and Bellati found the same in 
experiments on dogs. On the other hand, Queirolo found no excessive 
toxicity of the urine in cases of cirrhosis of the liver in dogs with an Eck 
fistula between the portal vein and the inferior cava. 


The conversion of carbaminate of ammonia and of other organic ammonia 
compounds into urea may be considered as a physiologic example of the protective 
action of the liver. We are, however, not justified in declaring this to be the main 
purpose of this conversion. 

The history of the bile-acids furnishes another example of physiologic pro- 
tective action. They are absorbed from the intestine by the intestinal mucosa, 
enter the liver, and are poured back into the intestine by the way of the bile-ducts. 
In this manner they circulate in the intestine and the portal system and are pre- 
vented from entering the systemic circulation in large quantities. 


The questions under discussion have only recently been subjected to 
careful examination, and are so complicated that we are for the present 
still far from having solved them. While suggestive, the teleologic point 
of view, which starts with the protective action of the liver, is perhaps 
unfavorable to a true solution of the problem. The conception of a 
“poison” is indefinite and one-sided. The specific character of the circu- 
lation and of the chemism of the liver, that causes the storing of important 
nutritive substances, probably has the same action in regard to other sub- 
stances. An elective power is, moreover, found in the case of other organs 
than the liver (for example, the kidneys, and the ganglion-cells), and we 
must agree with Queirolo, who attributes a greater protective power to the 
epithelium and the walls of the intestine than to the liver. Quite a number 
of examples can be quoted of the formation of double compounds or of 
synthesis in the liver by which the original substances are changed, as is 
true, for instance, of phenyl-sulphuric acid (Kochs), while the liver has no 
monopoly in regard to these chemical processes, and it is equally conceiv- 
able that it may increase as well as decrease the toxicity of different sub- 
stances. Our aim must be to examine each substance individually and to 
determine the changes that it undergoes. The mere determination of 
toxicity considers only the coarser properties in a very summary manner, 
and it is quite possible that the so-called “urinary poisons” found in cer- 
tain diseases of the liver may have been formed within the liver itself 
instead of being formed outside of the liver and passing through the de- 
ranged hepatic filter. 

Some authors attribute the detoxicating power of the liver to the 


414 DISEASES OF THE LIVER. 


fact that poisons are excreted in the bile. The quantity of poison ex- 
creted in the bile is, however, very small, and, in addition, it would be 
readily reabsorbed in the intestine; so that, both teleologically and in 
fact, the liver plays only a very insignificant réle in the elimination of 
poisons from the body. 

[In 1898* Adami described a minute diplococcus, resembling that 
present in Pictou’s cattle disease, which he had discovered in specimens 
of cirrhosis of the liver. Later the same organism was found by him in 
the normal liver, but in smaller number and staining with less intensity 
than in cases of cirrhosis. On injection of pure cultures of this diplo- 
coccoid or of the ordinary form of colon bacillus into the ear-vein 
of rabbits these organisms were found in large numbers in the hepatic 
cells, while the bile of the animal remained sterile. Within fifteen 
minutes after the injection some bacilli were found in the endothelial 
cells of the liver, and within two hours they were found in the hepatic 
cells themselves. It is probable, therefore, that the liver has a protec- 
tive and bactericidal function in addition to its detoxicating power.— 
Ep. ] 

The Formation of Bile.—The most important constituents of the 
bile are the bile-pigments, the salts of the bile-acids, and cholesterin. 

Bile-pigment is excreted by the liver in the form of bilirubin, “bile- 
yellow,” but is readily converted into substances of different color (bili- 
verdin, biliprassin, bilifuscin, and bilihumin). These conversions, that 
are in part surely oxidative, may in part be due to other chemical pro- 
cesses. They sometimes begin, if stasis of bile occurs, within the bile- 
passages, but they usually begin only where the bile has reached the 
gastro-intestinal tract or as a pathologic process in other tissues. In the 
intestine the greater part of the bilirubin is converted into hydrobilirubin 
by the action of bacteria. The significance and the genesis of this sub- 
stance will be discussed under icterus. 

We frequently see bilirubin formed from the hemoglobin of extra- 
vasated blood, partly in the form of crystals (hematoidin), partly in the 
form of diffuse imbibition of the connective tissue and of elastic fibers 
(Langhans, Quincke). We also know from experiments and from path- 
ologic findings that the hepatic cells possess particular powers of attraction 
for the bilirubin circulating in the blood, and seem to direct it toward the 
bile-passages. The bilirubin normally found in the bile is, however, not 
formed in other parts of the body to be later excreted by the liver, but is 
manufactured within this organ by a specific action of its cells. 

The material from which these pigments are formed is hemoglobin; 
for, as Tarchanoff, and later in a more exact manner Stadelmann, have 
shown, the injection into the blood of hemoglobin in solution is followed 
by an increased excretion of bilirubin. Of the hemoglobin so injected, 
however, no more than 1.9% is converted into bile-pigment. Numerous 
pathologic facts point in the same direction. The more bilirubin there is 
in the bile, the darker is the color and the greater the consistency of the 
latter (Stadelmann). 


With the exception of Baum, no one has so far ever been able to demonstrate 
directly the presence of bilirubin within the liver-cells under normal conditions. It 
is also very doubtful whether Anthen’s + observation that macerated liver-cells 


* Montreal Medical Journal, July, p. 485. 
+ E. Anthen, “Ueber die Wirkung der Leberzellen auf das Haimoglobin,” 
Dissertation, Dorpat, 1889. 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 415 


can destroy hemoglobin outside of the body will permit us to draw any conclusions 
in regard to their having this power as a vital process. For the present, therefore, 
the manner in which blood-pigment is elaborated within the liver-cells is altogether 
obscure, and the same obscurity surrounds the question as to how the hemoglobin 
reaches these cells. It can hardly be assumed that blood-corpuscles or debris 
of corpuscles are taken up by these cells. It is probable that hemoglobin (possibly 
in a changed form) enters the liver-cells by diffusion from its solution in the plasma, 
or, as is less probable, that it comes from leucocytes containing red blood-corpuscles 
and clinging to the walls of the hepatic capillaries. Although Naunyn and Min- 
kowski in birds poisoned with arseniuretted hydrogen saw bile-pigment formed 
in the cells containing blood-corpuscles within the hepatic capillaries, this discovery 
does not necessarily apply to mammals and to normal conditions. 


As bilirubin contains no iron, this element must be separated from 
hemoglobin in the formation of the bile-pigment. Iron is, in fact, found 
in larger quantities in the liver than in any other organ. It seems that the 
hemoglobin molecule in another way can be split and lose iron without 
forming bile-pigment. 


The bile always contains small quantities of iron. In man, according to 
Hoppe-Seyler and Young, bile from the gall-bladder contains about 6 mg. in 100 c.e. 
Kunkel * found the same quantity in the bile from a gall-bladder fistula in a dog. 
This, however, corresponded only to about one-seventh of the amount of hemo- 
globin used for the formation of the bile-pigment. In the gall-bladder, according 
to Tissier, D. Gerhardt, and Fr. Miiller, urobilin is also always present. Tissier, 
Hayem, and others regard the latter, as well as the indefinite substance “ bilirubidin,”’ 
as a product of the secretion of the liver formed in excess in diseased conditions 
of the organ. It could possibly be reabsorbed from the intestine and excreted 
by the liver (see page 421), or it might have originated as a product of the function 
of the walls of the gall-bladder. 

It is possible that hematoporphyrin (isomeric with bilirubin) is formed by the 
liver under certain pathologic conditions and is then excreted in the urine.7 


The bile-acids, glycocholic and taurocholic acids, are found in the bile 
in the form of their sodium salts, and are also formed by a specific action 
of the liver-cells. . 


Older statements in regard to their presence in the suprarenals (Vulpian f) 
must be considered doubtful. We know nothing definite in regard to the mother- 
substance or the method of formation of the bile-acids. It is stated that they 
are also formed more freely even outside of the body when the liver contains much 
glycogen.§ The formation of the bile-acids and that of bile-pigments, at all events, 
occur quite independently of one another (Stadelmann). 


When the salts of the bile-acid enter the blood, they are in great part 
excreted by the liver and the bile, in small part by the kidneys, || while a 
third portion is probably decomposed. They normally reach the blood 
through reabsorption from the intestine.** 


* Kunkel, Pfliiger’s Archiv, Bd. x, p. 359. 
t+ Schulte, “Ueber Himatoporphyrinurie,” Deutsches Archiv fiir klin. Medicin, 
1879, Bd. tv, p. 3138. 
t Vulpian, cited by Virchow, “ Zur Chemie der Nebennieren,”’ Virchow’s Archiv, 
Bd. x11, 1857, p. 481 . 
§ Kallmeyer, “Ueber die Entstehung der Gallensiuren,’”’ Dissertation, Dorpat, 
1889. Klein, “Ueber die Function der Leberzellen,”’ Dissertation, Dorpat, 1890. 
|| Naunyn, “Beitraige zur Lehre von Icterus,” Archiv fiir Anatomie und Physi- 
ologie, 1868. Vogel, “ Maly’s Jahresbericht,” 1872, S. 243. Hone, J. (and Dragen- 
dorff), “Ueber die Anwesenheit der Gallensiuren im normalen Harn” (about 0.07 
gm. in 1 liter), Dissertation, Dorpat, 1873. 
** The absorption does not take place in the duodenum; but glycocholic acid is 
absorbed from the jejunum and ileum, taurocholic acid and cholic acid exclusively 
fromtheileum. Tappeiner, “Sitzungsbericht der Wiener Akademie,” 1878, 111. Ab- 
theilung, April. 


416 DISEASES OF THE LIVER. 


If an excessive formation of bilirubin is experimentally produced, the 
excretion of the bile-acids in the bile decreases (Stadelmann). In the 
same manner a reduction is observed in fever (Paton and Balfour *) and 
in long-lasting stasis of bile (Yeo and Herroun *). Nothing is known in 
regard to the conditions that govern increased excretion. 


Cholesterin forms about 1% of the solid constituents of normal bile. It is of 
subordinate importance in general metabolism and in physiology, and only im- 
portant because it is a factor in the formation of biliary concretions. According to 
the researches of Naunyn and his pupils,+ it cannot be regarded as a product of the 
hepatic secretion for the reason that an increased introduction of cholesterin either 
from the intestine or by subcutaneous injections exerts no influence on the excretion 
of cholesterin in the bile (Jankau). The quantity of cholesterin found in the bile 
is independent of the diet (Thomas), and, except in cholelithiasis, not increased 
in disease (Kausch). Cholesterin, when found in the bile-ducts as well as in other 
locations, as in atheromatous cysts, must be considered as a disintegration product 
of the epithelium. It is quite probable that the presence of bile within the bile- 
ducts exercises a deleterious influence on the lining epithelial cells and causes an 
excessive disintegration of them beyond that of other mucous membranes. Pos- 
sibly disintegrating liver-cells also furnish a part of the cholesterin. Austin Flint’s 
and Miiller’s cholesteremia (an increase of the cholesterin in the blood) can no longer 
be considered a valid and justifiable clinical conception. 


The quantity of bile excreted has been carefully studied in animals, 
and has been found to be much greater in rabbits and guinea-pigs than in 
dogs and cats. In sheep the conditions are similar to those in the latter 
class of animals. The figures given for man are very indefinite, as they 
are chiefly obtained from cases with fistula, and usually after stasis had 
existed for some time. According to, v. Wittich, the quantity of bile 
excreted in twenty-four hours is said to be 530; according to West- 
phalen, 453 to 566 c.c.; according to Ranke, 14 gm. per diem per kilo.t 
Hammarsten found 600, Korte as much as 1200 c.c. excreted in the 
twenty-four hours. | 

The exact quantity of bilirubin and of the bile-acids excreted in 
twenty-four hours is not known. As regards bilirubin, Kunkle states 
that a dog of 4.7 kg. excretes 0.307 grams, Vossius that a dog of 25 kg. 
excretes only 0.108 grams. Noel-Paton || found in man an excretion of 0.2 
to 0.7 gm. of bilirubin in twenty-four hours. Bidder and Schmidt calcu- 
late 4 gm. of bile-acids for a dog, while in man Voit estimates it at 
11 gm., and Stadelmann at 8 to 10 gm. in the twenty-four hours. 

The conditions under which bile is secreted are manifold, and the quan- 
tity varies in different animals with biliary fistula, as well as in accordance 
with the rapidity of the blood-stream, nervous influences, and the phase of 
digestion. The taking of food, particularly, increases the excretion, the 
time at which an increase of the flow of bile occurs being stated differ- 
ently by different investigators. Heidenhain** assumes two maxima in 


* Quoted by Minkowski, in “ Ergebnisse der allgemeinen Pathologie,’ p. 697. 

{t Naunyn, “Klinik der Cholelithiasis,”? 1892, p. 12. Jankau, “Cholesterin- 
und Kalkausscheidung mit der Galle,” Archiv fiir experimentelle Pathologie, 1892, 
Bd. xxrx, p. 237. Kausch, “ Ueber den Gehalt der Leber und Galle an Cholesterin,”’ 
Dissertation, Strassburg, 1897. Thomas, “Ueber die Abhangigkeit der Absonderung 
ae Zusammensetzung der Galle von der Nahrung,” Dissertation, Strassburg, 

t Heidenhain, loc. cit., p. 252. 

§ Cited by Stadelmann, Berliner klin. Wochenschrijt, 1896, p. 184. 

|| According to Hammarsten. 

** Heidenhain, loc. cit., p. 269; see also Murchison, “Functional Derange- 
ments of the Liver,” p. 34. 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 417 


the excretion curve, the one in the third to the fifth hour, the other in the 
thirteenth to the fifteenth hour. It is probable that this varies according 
to the species of animal and the composition of the food. The increase is 
probably produced, on the one hand, by certain reflexes, particularly 
from the mucosa of the intestine; on the other, by the substances that are 
absorbed. ; 

If the flow of bile is profuse, there is an increase in the quantity both 
of water and of solid constituents. According to Heidenhain, even 
the ratio of the latter is greater. If abstinence from food is persisted 
in for a period longer than twenty-four hours, the bile is excreted less 
copiously and is more concentrated. A pure meat diet is most efficient 
in producing an increased flow of bile, a meat diet with carbohydrates 
acting to a lesser degree (Spiro). On a fat diet the excretion of bile, ac- 
cording to some authors, is small; according to Rosenberg and others, 
however, it is very copious. 

The specific gravity of the bile varies greatly (1005 to 1030). The 
solids amount to from 3% to 10%. The bile in the gall-bladder, owing 
to the absorption of water that occurs there, is always more concentrated 
than is the bile obtained from fistulas. I observed a specific gravity of 
1047 in man after a fast of several days. The bile from the gall-bladder, 
at the same time, is more viscid and frequently cloudy from the admixture 
of mucus and particles of pigment. It is not impossible that an absorp- 
tion of water, and possibly of matters in solution, occurs in the bile-pas- 
sages. The proportion ‘of the different constituents of the bile varies, and 
the conditions that govern their excretion are only in small part known 
to us. Certain relations between the secretion of the bile and the other 
processes that occur in the liver must exist, and it has been stated that 
this is true particularly of the flow of bile and the formation of glycogen, 
but nothing exact has been demonstrated. 

It is a remarkable fact that a part of the bile-acid salts are reabsorbed 
in the intestine, and that a part of them (according to Stadelmann, two- 
thirds or more) are again excreted with the bile. Possibly the same is 
true to a lesser degree in regard to the bile-pigments. These substances, 
therefore, in a way circulate between the liver and the intestine * (Schiff ) 
and enter the general circulation in small quantities only. It is possible 
that their chemical power is better utilized in this manner and that a sav- 
ing of useful material is secured. 


The bile-acids are undoubtedly broken up within the intestine into taurin 
and glycocoll, on the one hand, and cholalic acid, on the other, the latter alone 
appearing in the feces. In the dog 0.5 gm. or one-eighth (Hoppe-Seyler), in man 
3 gm. or one-fourth (Bischoff), of the secreted bile-acids are passed with the feces. 
Of the portion that is reabsorbed, a part is voided in the urine, a part is re-excreted in 
the bile, and a part is destroyed by combustion. It is possible that there are other 
substances that act in the same manner as do the salts of the bile-acids. Lussana 
claims that curare is such a body, and in this way attempts to explain its slight 
toxicity when taken by the mouth. 


If it is difficult to demonstrate increase and decrease of the excre- 
tion of bile in animal experiments; it is still more difficult to arrive at 
definite conclusions from the observation of pathologic conditions. The 
color of the feces has been utilized as a standard; but, while it is true that 
the chief coloring-matters of the feces are the bile-pigments, still a number 
of other factors are concerned in this coloration. As these must all be 


* Stadelmann, “Icterus,” p. 95. 
27 


418 DISEASES OF THE LIVER. 


considered, it is very difficult to reach definite conclusions.* In addition 
to the peculiar color of different articles of food, the transparency of each 
substance must be considered. If finely divided substances of different 
refractive power (fat-crystals, air-bubbles) are abundantly distributed 
through the feces, the latter will appear lighterin color. Besides urobilin, 
the feces always contain other derivatives of the biliary pigments whose 
constitution is unknown. They also contain a chromogen of urobilin, 
which is formed from it by further reduction, and which, in the presence 
of oxygen and on extraction with acid alcohol, is reconverted into uro 
bilin. The quantity of other pigments and of the chromogenic substance 
is very varying, and probably depends upon the bacterial flora of the in- 
testine. In individual cases, particularly if digestive disturbances exist, 
this may produce considerable change in the color of the feces. | 


Attempts to determine by extraction the quantity of bile-pigment derivatives 
present in the feces have been only partially successful so far, owing to the fact 
that these substances decompose so readily. G. Hoppe-Seyler ¢ found 0.7% to 
3.2% normally, and an average of 1.7% of impure urobilin per diem, while Boltz 
and Fr. Miller found 0.08% to 0.09%. 


In addition to urobilin, Fr. Muller frequently found cholecyanin in the 
feces (frequently in direct proportion to urobilin). In diarrhea the feces 
usually contained unchanged urobilin. . 

Notwithstanding the lack of exact data in regard to the excretion of 
bile and its fluctuations in pathologic conditions, the assumption of such 
clinical entities as acholia, hypocholia, oligocholia, on the one hand, and of 
polycholia, on the other, is fully justified. Here the proportion of bile- 
pigment to bile-acids may also be changed, so that the French have 
created an “acholie totale,’ an “acholie pigmentaire,”’ and an “acholie des 
acides biliaires.”’ 

The observations reported in regard to (completely or almost) colorless 
bile | are open to criticism. We can only say to-day that in fever 3 ex- 
perimentally produced, and after Brown-Séquard’s piqure, || the excretion 
of bile is deereased, and that frequently in chronic cachexias, in the fatty 
liver of tuberculosis, and sometimes in atrophic cirrhosis of the liver, the 
bile and the feces are very pale. 

Stadelmann ** found a decreased excretion of bile-acids in the ad- 
vanced stage of phosphorus-poisoning and in icterus from poisoning by 
toluylenediamin and arseniuretted hydrogen. It is probable that their 
formation is also decreased in chronic biliary stasis and in fever. _ 

Physicians have assumed theexistence of polycholia from the dark color 
of the feces and the occurrence of icterus (see below) in many forms of 


* Quincke, H., “Farbe der Fices,’’ Miinchener med. Wochenschr., 1896, No. 36. 
Hoppe-Seyler, G., “Ueber die Ausscheidung des Urobilins in Krankheiten,” Vir- 
chow’s Archiv, 1891, Bd. cxxtv, p. 47. ; f 

+ Hoppe-Seyler, G., “Ueber die Einwirkung des Tuberculin auf die Gallen- 
farbstoffbildung,” Virchow’s Archiv, 1892, Bd. cxxvitt, p. 43. 

t Ritter, M. E., “Quelques observations de bile incolore,”’ Journal d’Anatomie 
et de Physiolog. (de Robin), 1872, p. 181. Hanot, “Contribut. 4 l’état de l’acholie,” 
Archives générales de médecine, 1885, 1, p. 12. Létienne, “ De la bile 41’état patholog.,” 
Thése de Paris, 1891, p. 17. ; 

*§ Pisenti, Archiv fiir experimentelle Pathologie, 1886, Bd. xx1, p. 219. 

|| Naunyn, “Beitrage zur Lehre vom Diabetes,” Archiv fir experimentelle 
Pathologie, 1874, Bd. 111. 

a Stadelmann, Archiv fiir experimentelle Pathologie, Bd. xv, xv1; Bd. xxur . 
p. 433. 2 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 419 


dyspepsia as well as in the gastro-intestinal infections and intoxications. 
Affanassiew* experimentally produced this deeper color by section of the 
nerves of the liver. An increased formation of bile-pigment has been 
positively demonstrated only after poisoning with toluylenediamin and 
_ arseniuretted hydrogen (pleiochromia, polycholie pigmentaire). The same 
presumably occurs in those forms of intoxication coming under clinical 
observation in which a destruction of red blood-corpuscles takes place. 
In the beginning of phosphorus-poisoning, according to Stadelmann, an 
increase in the formation of bile-pigment is said to occur. 


Blumreich and Jacobi found the gall-bladder very much dilated by bile in 
rabbits some time after extirpation of the thyroid, and conclude that an increased 
formation of bile had occurred as a result of the procedure.t [Ligature of the 
bile- ye is, on the other hand, said to have caused an excess of secretion (Murray). 
—Ep 


As the assumption of disturbances in the flow of bile has occupied a 
large place in medical thought, attempts have been made to influence the 
flow of bile by therapeutic means. A large number of drugs were con- 
sidered cholagogues and were employed not only where a decreased secre- 
tion of bile was assumed, but also where obstacles to the outflow of the 
bile existed. A more careful analysis has shown that the conclusions 
reached were in many instances wrong, and that the error was caused both 
by the increased evacuation of the intestine that followed the administra- 
tion of many of these drugs and by the coloration of the feces by other 
substances. 


By employing dogs with biliary fistule, Prévost and Binet found on introducing 
different drugs, either subcutaneously or by the mouth, the following results: 


INCREASE OF SECRETION. INCREASE SLIGHT, INCONSTANT OR 

DOUBTFUL. 
Bile. Sodium bicarbonate. \ fi 
Salts of bile-acids. Sodium sulphate. 
Urea. Sodium chlorid, Carlsbad salts 
Oil of turpentine (? Stadelmann). Propylamin, Antipyrin. 
Potassium chlorate. Aloes, Cathartic acid. 
Sodium salicylate. Rhubarb. 
Salol. Hydrastis Canadensis. 
Sodium benzoate. Boldo. 
Euonymin. Antifebrin 
Muscarin. Diuretin (Stadelmann). 
Sodium oleinate (Blum, see below). Santonin 

DECREASE OF THE SECRETION. EXERCISING No INFLUENCE, 
Potassium iodid. Sodium phosphate. 
Calomel. Potassium bromid. 
Iron, Copper (subcutaneously). Lithium chlorid. 
’ Atropin (subcutaneously). Corrosive sublimate. 
Strychnin it in toxic doses, Sodium arseniate. 
Alcohol, Ether, Glycerin. 
Quinin. 


Caffein (? Stadelmann). 

Pilocarpin (according to Stadel- 
mann reducing, according to 
Affanassiew increasing). 

Kairin, Cytisin. 

Senna, Colombo. 


« Pfliiger’s Archiv, Bd. xxx, p. ard 
+ Pfliger’s Archiv, 1896, Bd. LXIV, 
t According to Lewaschew, quite ame according to Stadelmann, ineffective. 


420 | DISEASES OF THE LIVER. 


EXCRETED WITH THE BILE. 


Bilirubin. Arsenic. 
Urobilin. Iron, lead, mercury in traces. 
Salts of bile-acids. Caffein (2), 
Hemoglobin.* Fuchsin, Cochineal. 
Turpentine. Sodium ‘indigo-sulphate. 
Salicylic acid. Phyllocyanic acid from chlorophyl.t 
Potassium iodid and bromid. Grape-sugar, still more readily 
‘ Potassium chlorate. cane-sugar.{ 


Not DEMONSTRABLE. 
Antipyrin, Kairin. 
Benzoic acid. 

Quinin, Strychnin. 
Copper, Lithium, Urea. 


Stadelmann’s experiments show that water by mouth or by rectum 
does not increase the flow of bile in the least. Practical experience, on 
the other hand, particularly with Carlsbad waters, seems to contradict 
his experiments. 

The action of large quantities of oil as a cholagogue has been much 
discussed lately, since it appears to assist in the removal of gall-stones. 
While Rosenberg maintains that there is an increase in the excretion of 
bile in from thirty to forty minutes after the administration of the oil, 
Stadelmann and his pupils deny this effect. Blum % administered pure 
oleate of sodium (in doses of 2 to 5 grams) and noticed a marked increase 
in the flow of bile in dogs with biliary fistule, while in human beings he 
found his observation corroborated; a small quantity of the oleate seems 
to enter the bile. It is possible that the apparent contradiction in these 
experiments can be attributed to the varying quantities of fatty acids 
present in the oil. || 

Different factors are concerned in the movements of the bile through 
the bile-passages: namely, the pressure exercised by the secretion itself, 
gravity, respiratory movements, and contraction of the walls of the 
bile-ducts. 

The pressure of the biliary secretion is small in comparison to the 
pressure found in other glands (in the dog 110 to 220, an average of 
200 mm. of soda solution),** but always greater than the pressure in the 
portal vein. In man this pressure has so far not been measured. Gravity 
must necessarily, to some extent, assist the flow of the bile from the liver, 
owing to the topography of the organ. Respiration helps from the fact 
that each movement of the diaphragm exercises pressure and a slight 
degree of compression on the convex surface of the liver. 

Contractions of the walls of the bile-ducts, already described by 
Haller, Rudolph, and Johannes Miiller in pigeons,{t have recently been 


* When more than 0.02 per 1 kg. was injected into the rabbit, after the third 
hour. R. Stern, Virchow’s Archiv, 1891, Bd. cxxxmt, p. 33. 

tT Wertheimer, “Elimination de chlorophylle par le foie,” Archives de physiolog., 
1893, p. 122. 

t Mosler, according to Heidenhain, loc. cit., v, 1, p. 275. 

§ Blum, F., “Ueber eine neue Methode zur Anregung des Gallenflusses,’’ Der 
Grztliche Pratiker, 1897, x, No. 3. 

|| Prévost and. Binet, “Einfluss von Medicamenten auf die Galle,” Revue de 
médecine de la Suisse romande, 1888, No.5. Stadelmann, “ Ueber Cholagoga,”’ Ber- 
liner klin. W ochenschr., 1896, S. 180 und 212. Rosenberg, Discussion, Berliner klin. 
W oéhenschr., 1896, p. 216. "(Also references to earlier literature.) 

stag Heidenhain, loc. cit., v, 1, p. 269. 

tt For literature bearing on this question, see Daraignez,“ Ictére chai cdiciag 
Thése de Paris, 1890, 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 421 


observed in a number of mammals by Doyon and Oddi,* by whom 
careful studies were made on rabbits, dogs, and cats by direct and graphic 
methods. 


Peristaltic waves were observed running from the liver toward the ampulla and 
occurring about every fifteen to twenty seconds. In addition, there were slow fluctua- 
tions in the tension of the ductus choledochus and of the gall-bladder. These move- 
ments were still observed after the liver had been removed from the body, so that 
they are either purely muscular or due to the influence of peripheral ganglia. If 
the great splanchnic nerve is irritated, the bile-ducts contract along their whole length 
and the sphincter of the ductus choledochus at the duodenum may even close 
entirely (Oddi). If the central end of the cut splanchnic be irritated, a relaxation 
of the bile-ducts results (preceded, according to Oddi, by a brief but strong con- 
traction). The tonus of the sphincter of the ductus choledochus, according to 
Oddi, equals the pressure of 675 mm. of water. Reflexly, the innervation of the 
bile-ducts may be influenced with the result of inhibition or excitation, and the 
nerves of the ducts may also be influenced by irritation of the central ends of the 
vagus and of the sciatic. Irritation of the mucosa of the stomach and intestine 
usually produces spasm of the gall-bladder, sometimes also relaxation of the sphincter 
of the common duct. The center for these irritations is situated at the level of the 
first lumbar nerve in the dog, the anterior root of this nerve containing the motor 
branch for the musculature of the bile-ducts. 


Pathologically, this contraction of the bile-ducts is manifested par- 
ticularly in gall-stone colic, possibly also in other painful spasms and in 
spasmodic closures of the bile-ducts with icterus. 

If we briefly review the physiologic facts we have mentioned, we 
see that the function of the liver is manifold. Owing to its situ- 
ation, it is in intimate relation with the gastro-intestinal tract and 
helps to assimilate and stores nutrient material that it later pours into 
the blood-current. This applies to proteids, carbohydrates, and fats. 
In addition, the liver receives metabolic products from the systemic 
_ blood, in part converting them into other substances, in part returning 
them into the blood-current unchanged. In this manner the liver 
forms a central point of metabolism, and in comparison with this func- 
tion the secretion of the bile seems insignificant. The latter is, no doubt, 
intimately related to the other functions, but is not. by any means the 
chief function of the liver. 

In view of all this, we can understand that the function of the liver 
is important in numerous pathologic conditions, although we are able 
to appreciate only a small portion of these relations. In the clinical 
sense disturbances in the formation and the excretion of bile are of 
paramount importance, if for no other reason than that they lead to so 
conspicuous a symptom as the intense yellow discoloration of the skin 
called icterus. This symptom occurs so frequently and is so important 
that its origin and manifestations merit particular discussion. 


LITERATURE. 


GENERAL PATHOLOGY OF THE LIVER, 


Cohnheim: “ Allgemeine Pathologie,” 11, p, 57, 1880. 
Denys et Stubbe: (Loewen.) “Etude sur l’acholie. ou cholémie expérimentale,” 


*M. Doyon, “ Etude de la contractilité des voies biliaires,” Archives de physiolog., 
1893, pp, 678, 710; “ Action du syst. nerveux sur |’appareil excréteur de la bile,” 
ibid., 1894, p. 19. R. Oddi, Archives ital. de biologie, vol. vit, x. Sperimentale, 
1894, p. 180, Jahresbericht 11, p. 215; “Di una dispositione a sfinctere alla sboca 
del coledoco,’’ Lab. di Fisiol. di Perugia, 1887, cited by Dupré. Thése de Paris, 
. 1891, p. 27. jh Md 3 


422 DISEASES OF THE LIVER. 


“La Cellule,” 1893, p. 447. “Centralblatt fiir allgemeine Pathologie,’”’ Bd. rv, 
p. 102, 1893. 

Hahn, Massen, Nencki u. Pawlow: “ Die Eck’sche Fistel zwischen unterer Hohlvene 
und Pfortader,” etc., “ Archiv fiir experimentelle Pathologie,’”’ Bd. xxxm, p. 161. 

Hanot, V.: “Rapports de Vintestin et du foie en pathologie. Revue critique,” 
“Archives générales de médecine,” 1895, 11, pp. 427, 580; 1896, 1, pp. 65, 311. 

Heidenhain: “ Physiologie der Gallenabsonderung”’ in Hermann’s “ Handbuch der 
Physiologie,”’ Bd. v, 1. 

Hergenhahn: “ Arbeiten aus dem stddtischen Krankenhaus zu Frankfurt a. M.,” 
1896. 

v. Jaksch: “ Alimentaire Glykosurie bei Phosphorvergiftung,” “Prager med. Woch- 
enschr.,’”’ 1895. 

Kaufmann, M.: “ De l’influence du foie sur la glycémie,” “ Archives de physiolog.,”’ 
Vil,p; dol, 1896: 

Krehl: “ Pathologische Physiologie,” Leipzig, 1898. 

v. Lieblein: “Die Stickstoffausscheidung nach Leberverédung beim Saugethier,”’ 
“Archiv fiir experimentelle Pathologie,” Bd. xxx11, p. 318, 1894. 

_ Marcuse: “ Bedeutung der Leber fiir das Zustandekommen des‘ Pankreasdiabetes,”’ 

“Zeitschrift fiir klin. Medicin,’”’ Bd. xxvi, p. 225, 1894. 

Minkowski: “Ergebnisse der allgemeinen Pathologie. Lubarsch and Ostertag,” 
1897, p. 679 (Literaturbericht). 

—‘‘ Untersuchungen iiber den Einfluss der Leberexstirpation auf den Stoffwechsel,”’ 
“Archiv fiir experimentelle Pathologie,’ Bd. xx1, 1886. 

— ‘Ueber die Ursachen der Milchsiureausscheidung nach Leberexstirpation,” 
“Archiv fir experimentelle Pathologie,’ Bd. xxx1, 1893. 

Miunzer :“‘Der Stoffwechsel des Menschen bei acuter Phosphorvergiftung,”’ “‘ Deutsches 
Archiv fir klin’ Medicin,” Bd. tu, p. 199, 1892. 

— “Die Erkrankungen der Leber in ihrer Beziehung zum Gesammtorganismus des 
Menschen,” “ Prager med. Wochenschr.,” 1892, Nos. 34 and 35. 

— “Die harnstoffbildende Function der Leber,” “ Archiv fiir experimentelle Pathol- 
ogie,”” Bd. xxx1l1, p. 164, 1894. 

Naunyn und Minkowski: “Ueber den Icterus durch Polycholie,” ‘Archiv fir ex- 
perimentelle Pathologie,” Bd. xx1, 1888. 

Neisser, E.: “ Beitrag zur Kenntniss des Glykogen,”’ Dissertation, Berlin, 1888. 

Nencki, Pawlow and Zaleski: “Ueber den Ammoniakgehalt des Blutes und der 
Organe und die Harnstoffbildung bei Saugethieren,”’ “‘ Archiv fiir experimentelle 
Pathologie,” Bd. xxxvu, p. 26, 1895. 

Nencki and Pawlow: “ Zur Frage iiber die Art der Harnstoffbildung bei Saugethieren,”’ 
“ Archiv fiir experimentelle Pathologie,’ Bd. xxxvit, p. 215, 1897. 

Nencki and Zaleski: “ Archiv fiir experimentelle Pathologie,” Bd. xxxv1. 

Noorden, C. v.: “Pathologie des Stoffwechsels,”’ 1893. 

Ponfick, E.: “ Experimentelle Beitrage zur Pathologie der Leber (Exstirpation),’’ 
“Virchow’s Archiv,” Bd. cxvit, p. 209, 1889; Bd. cxrx, p. 193, 1890; Bd. 
cxxxvill, Supplement, p. 81, 1896. 

Pick, E.: “Versuche tiber functionelle Ausschaltung der Leber bei Saiugethieren,” 
“ Archiv fir experimentelle Pathologie,’ Bd. xxx11, p. 382, 1893. 

Pick, F. : “ Ueber die Beziehungen der Leber zum Kohlehydratstoffwechsel,’’ “ Archiv 
fir experimentelle Pathologie,’ Bd. xxx1m1, p. 305, 1894. 
Roger, F.: “Des Glycosuries d’origine hépatique,” “Revue de médecine,” p. 935, 

1886. 

Schiff, M.: “Ueber das Verhaltniss der Lebercirculation zur Gallenbildung ,”’ 
“Schweizer Zeitschrift fiir Heilkund.’”’ 1861. 

Schulte-Overberg: “Ueber Einwirkung hoher Aussentemperaturen auf den Gly- 
kogenbestand der Leber,” Dissertation, Wiirzburg, 1894. , 

Stern: “Ueber die normale Bildungsstitte des Gallenfarbstoffes,” Dissertation, 
Ké6nigsberg, 1885. 

Tappeiner, H.: “Ueber den Zustand deg Blutstromes nach Unterbindung der Pfort- 
ader,” “ Arbeiten aus der. physiologischen Anstalt zu Leipzig,” vu, p. 11, 1892. 

Weintraud: “Untersuchungen iiber den Stickstoffumsatz bei Lebercirrhose,”’ 
“Archiv fiir experimentelle Pathologie,” Bd. xxx1, p. 30, 1892. 


| 
Fat. 


Heidenhain: “ Pfliiger’s Archiv,” Bd. xx1, Supplement, p. 95, 1888. 2 
Hofmann, F.: “Ueber die Reaction der Fette,’”’ etc., “Beitrag zur Anatomie und 
Physiologie als Festgabe fir C. Ludwig,” p. 173, 1874. 


¢ 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 423 


Munk, J.: “Zur Lehre von der Resorption, Bildung und Ablagerung der Fette im 
Thierkérper, ” “Virchow’s Archiv,” Bd. xcv, p. 407. 

Nasse, O.: “ Fettzersetzung und Fettanhaufung im thierischen Kérper,’’ “ Biolog. 
Centralblatt,” VI, 235, 1886. 

Rosenfeld, G.: “‘ Ueber Fettwanderung,” ‘“ Verhandlungen des Congresses fiir innere 
Medicin, ” 1895, p. 414. 

— ‘Ueber Phlorizinwirkungen, ” “Verhandlungen des Congresses fiir innere Medicin,” 

1893, p. 359. 

Seegen: “ ene die Fahigkeit der Leber Zucker aus Fett zu bilden,” ‘ Pfliger’s 
Archiv,” Bd. xxxrx, p. 182, 1886. 


Fatry DEGENERATION IN PHOSPHORUS-POISONING. 


Lebedeff: “ Pfliiger’s Archiv,” Bd. xxx1, p. 15, 1883. 

Leo: “Zeitschr. fir physiolog. Chemie,” Bd. rx, p. 469, 1885. 

v. Starck: “Deutsches Archiv fiir klin. Medicin,” Bd. xxxv, p. 481, 1884. 

Rosenfeld, G. : “ Die Fettleber beim Phlorizindiabetes, ” “ Zeitschr. fir klin. Medicin,”’ 
Bd. xxvul, p. 256, 1895. 


DETOXICATING FUNCTION. 


Bellati, L.: “ Ueber die Giftigkeit des Harns bei Leberkrankheiten”’ (many references 
to Literature), Moleschott’s “Untersuchungen zur Naturlehre,” 1894, p. 299. 

Hanot, V.: “ Rapport de l’intestin et du foie en pathologie. Revue critique, a 8 AP 
chives générales de méd.,’’ 1895, 11, pp. 427, 580; 1896, 1, pp. 65, 311. 

Héger: “‘ Experiences sur la circulation du sang dans les organes isolés,” Bruxelles, 
Thése, 1873. 

— “Notice sur l’absorption des alcaloides dans le foie,” etc., “Journal de méd.,” 
Bruxelles, 1877. 

— “Sur le pouvoir fixateur de certains organes,”’ etc., “ Comptes-rendus de |’Acadé- 
mie des sciences,’ May, 1880, p. 1226. 

Kobert: ‘Lehrbuch der Intoxicationen,”’ p. 27, 1893. 

Minkowski: “‘ Ergebnisse der allgemeinen Pathologie,’ Bd. tv, p. 734, 1897. 

Munk, J.: “Ueber die Wirkung der Seifen im Thierk6rper,” “ Archiv fiir Anatomie 
und Physiologie,” physiologische Abtheilung, Supplement, 1890, p. 116. 

Queirolo, G. B.. “Ueber die Function der Leber als Schutz gegen Intoxication vom 
Darm,”’ Moleschott’s “Untersuchungen zur Naturlehre,” 1894, p. 228. 

Roger, G. H.: ‘‘ Action du foie sur les poisons,’’ Thése de Paris, Dp: 228, 1887 (copious 
bibliography), 


BACTERICIDAL FUNCTION. 


Adami: ‘‘ Montreal Med. Jour.,”’ July, 1898, p. 485; “Transactions of Association 
of American Physicians,”’ 1899, vol. XIV, Pp. 00. 


ICTERUS, JAUNDICE, 
Gelbsucht ; Morbus regius.* 


The term icterus is applied to that peculiar discoloration of the tissues 
by bile-pigments, so conspicuous as a clinical manifestation of various dis- 
eases in Caucasian races. In the clinical picture of certain diseases of the 
liver icterus plays an important réle. For this reason a detailed de- 
scription of its origin and of some of its individual symptoms is appro- 
priate in this place. The special pathology of icterus will be discussed 
in the section on diseases of the bile-ducts, and in the description of 
catarrhal icterus all other forms that are described as independent dis- 
eases will be discussed. 

In a healthy body bile-pigment is found only in the bile—the secre- 
tion of the liver. This pigment might be primarily formed in the blood 
and only excreted by the liver (like urea from the kidneys), or it might be 
formed within the liver. In the former instance icterus would be due 


* From color of gold, the rex metallorum. 


424 . DISEASES OF THE LIVER. 


to an interference of secretion (so-called “suppression icterus”’), in the 
latter to a reabsorption of the pigment that had been formed in the 
liver. From the experiments on extirpation of the liver in birds, per- 
formed by Naunyn and Minkowski, it may be stated as a positive fact 
that bile-pigment is normally not formed outside of the liver, so that 
there is no such thing as a “suppression icterus.”’ 


While ligation of the ductus choledochus in birds was followed by the appear- 
ance of biliverdin in the urine in one and one-half hours, and in the blood in five hours, 
this pigment was absent from the blood and present only in traces in the urine after 
removal of the liver. Though inhalation of arseniuretted hydrogen in normal 
geese produced polycholia and icterus (with biliverdin and bile-acids in the urine), 
the polycholia ceased upon removal of the liver, and both polycholia and icterus 
failed to occur in animals from whom the liver had been removed. 


It is possible that in certain pathologic conditions bile-pigment might 
be formed in other locations than the liver, and by entering the circula- 
tion produce a discoloration of the tissues. According to the different 
origin of the pigment, we might, therefore, speak of a “hepatogenous”’ 
and an “anhepatogenous” icterus. In fact, we know to-day (Langhans, 
Quincke) that bile-pigment can be formed from extravasated blood- 
pigment in the connective tissues, partly imbibed by these tissues, and 
in part appearing in the form of crystals (crystals of hematoidin and 
of bilirubin). Moreover, von Recklinghausen * found that bile-pigment 
developed in the leucocytes of a frog’s blood which had been kept in a 
moist chamber for from three to ten days. The quantity of bilirubin 
found in extravasations of blood is very small, and it seems to have 
little tendency to diffuse itself or to enter the circulation. We certainly 
know of no case in which general icterus arose from the formation of bili- 
rubin in such abnormal foci. In other words, we know of the formation 
of bilirubin outside of the liver, but we do not know of an anhepato- 
genous icterus. 


According to the formation of bilirubin in this or that organ or in this or that 
tissue (for example, the blood or the connective tissues), we would have to speak 
of an hematogenous or an inogenousf form of icterus. In accordance with cer- 
tain theoretic considerations, a number of investigators several years ago thought that 
* they were justified in assuming the occurrence of an “ hematogenous icterus.”” They 
placed this form in juxtaposition to the hepatogenous form without considering that 
there are still other locations outside of the liver besides the blood in which the for- 
mation of bile-pigment can occur. This method of designating the different forms of 
icterus led to additional confusion because these authors attempted to designate 
by their new names not only the location in which icterus was supposed to origin- 
ate, but also the material from which they thought the bile-pigment was formed. 
We know of no substance except hemoglobin from which bilirubin can be formed. 
The liver, therefore, can only form bile-pigment from the pigment of the blood. 
Therefore, the abnormal coloring-matter in every case of icterus, just as is the 
case with normal bile, must be of hematogenous origin as it is derived from hemo- 
globin. The term “hematogenous icterus”’ is therefore superficial. The same 
is true in regard to the term hemato-hepatogenous jaundice, by which Affanassiew 
would designate those forms of jaundice which are accompanied by increased 
disintegration of the red cells. For this condition the name of “cythemolytic,” 
proposed by Senator, would be more appropriate. [In this connection a case 
recently reported by Bettmann tf is of interest. He reports the case of a man aged 
twenty-nine years who for years had been deeply tinged with icterus, and also 
had hemoglobinuria.—Eb.] 

. 


* vy, Recklinghausen, “Allgemeine Pathologie,” 1883, p. 434. 
+ From ic (plural ivec), connective tissue. 
{ Minch. med. Woch., 1900, No. 28. 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 425 


We are, therefore, not justified in assuming that jaundice can occur 
without some participation of the liver in the process; but at the same 
time the details of the origin of hepatogenic icterus are still quite obscure. 

Icterus most frequently occurs as a result of the absorption of bile © 
from the biliary passages. This happens whenever its exit into the 
intestine is impeded (obstructive icterus, mechanical icterus, resorption 
icterus). The secretion-pressure of bile is very small, being in guinea- 
pigs and dogs equal to only about 200 mm. of water (Heidenhain).* 
Very slight obstruction, therefore, is sufficient to stop the flow of bile. 
Even when such an obstruction occludes only a few of the biliary pas- 
sages, or if only a partial obstruction exists in the main channel, at 
least a certain portion of the bile may be reabsorbed and cause icterus. 

Obstruction to the flow of bile may be produced in various ways. 
Their anatomic recognition is usually easy if the occlusion was com- 
plete, as the intestinal contents are then colorless and the usual post- 
mortem discoloration of the mucous membrane of the duct is absent 
below the point of obstruction. Where a stone or some object producing 
compression caused occlusion of one of the ducts, the decision is of course 
simple. Occasionally, however, all anatomic evidence of an obstruction 
is absent, even though during life the clinical symptoms pointed positively 
to stasis of bile. This may be due to the fact that before death the 
obstruction really was removed or that the occlusion was due to a spasm 
that relaxed after death, or, finally, because the cessation of all blood- 
pressure and turgescence after death may have changed the mechanical 
conditions that caused an obstruction during life. In addition, a com- 
plete examination of all the finer biliary passages to their finest sub- 
divisions is manifestly impossible. The causes of an obstruction of the 
biliary passages may be compression from without from tumors, kinking 
of the ducts themselves, occlusion of their lumen by concretions or other 
foreign bodies, neoplasms or inflammatory swelling of their walls. All 
these causes of obstruction may be present either in the main duct or in 
a number of its branches, even of its smallest ramifications. Particu- 
larly in the latter, swelling from hyperemia or inflammatory infiltration, 
shedding of degenerated epithelium, viscid mucus, and finely granular pre- 
cipitates play an important rdle. 

Even if the mucous membranes are intact, so that no viscid mucus 
is exuded, the viscid consistency of the bile itself, as it is sometimes seen 
in poisoning from toluylenediamin (Stadelmann, Affanassiew), may con- 
stitute an obstruction to the flow of bile. 

The smaller the bile-passage, the more occlusion is produced by even 
minute obstructions. We can readily understand the conditions pre- 
vailing in these cases by comparing them to similar conditions in the 
finer air-passages, where we can measure the degree of obstruction during 
life by auscultation. Catarrhal asthma and edema of the larynx should 
teach us how rapidly such obstructions can occur, and how rapidly 
again such swellings of the mucous surfaces can disappear, as well as 
how different the postmortem findings may be from the conditions that 
we knew existed during the life of the patient. 

Other factors that are concerned in the narrowing of biliary capillaries 
are compression by dilated blood-capillaries (venous stasis), by newly 
formed connective tissue, by swollen liver-cells (which probably occurs in 
phosphorus-poisoning), by distortion of the trabecule of liver-cells 

* Loc. cit., p. 268. 


426 ; DISEASES OF THE LIVER. 


(Hanot), and in various interstitial and parenchymatous diseases of the 
liver. As a rule, all these agencies will involve only single and dissemi- 
nated groups of capillaries. In view, however, of the diffuse nature 
of the primary lesions a great number of bile-passages may be affected. 

Besides mechanical obstructions to the outflow of the bile, certain 
other mechanical factors seem to be concerned in the reabsorption of 
the bile. In dogs we almost invariably find bile-pigment in the urine 
during fasting, while during digestion these pigments are not found. 
This is best explained by assuming that during the period of rest of the 
digestive organs the bile-ducts also are at rest, so that no peristaltic 
movement occurs. As a result, the bile contained within them may 
be absorbed, particularly since, under these circumstances, the bile stag- 
nates and undergoes thickening. Possibly the slight degree of icterus 
sometimes seen in the conjunctiva of human subjects during periods of 
inanition may be explained on the same grounds. 

The compression produced by the respiratory movements of the 
diaphragm exercises the same effect on the flow of the bile in the liver 
as it does on the flow of blood. It is quite possible that the cessation 
or reduction of these movements, that frequently occurs in diseases of the 
respiratory organs (pleuritis, pneumonia), may be instrumental.in pro- 
ducing a retardation in the outflow of bile. A portion of the bile-pig- 
ments that enter the intestine is reabsorbed, partly as urobilin, partly as 
bilirubin. The latter is, as a rule, again excreted by the liver. Only in 
the new-born does a part of the portal blood circumvent the liver and 
enter the systemic blood-vessels directly through the ductus venosus 
Arantii. In the new-born all the bile-pigments remain unchanged in 
the intestine, owing to the absence of a bacterial flora in that viscus, 
and they are abundant in the meconium formed during fetal life: The 
frequent occurrence of icterus neonatorum can be explained from a com- 
bination of these circumstances (Quincke). In adults, also, icterus may 
occasionally originate from reabsorption of bile-pigment from the intestine 
following polycholia (see page 498). 

Just as an increase of the pressure in the biliary capillaries may 
change the normal relation between the pressure of the bile and the 
pressure of the portal blood, so a decrease of the pressure in the portal 
and hepatic vessels may cause similar disturbances and lead to icterus. 
I'rerichs assumes that icterus originates in this manner in many. cases 
of stenosis of the portal vein and after psychic disturbances. 

While it is true that mechanical disturbances play a certain réle in 
the causation of icterus, careful consideration will show that these need 
not necessarily be present, but that the bile may readily enter the blood 
as the result of purely functional disturbance of the liver-cells. 

If these cells normally pour bile-pigment into the biliary capillaries 
and sugar and urea into the blood-capillaries, we can readily understand 
how a lesion of these cells may cause both quantitative changes in their 
function as well ‘as perversion in the direction in which they give off 
their products. This is seen in many other kinds of cells and glands. 
For instance, diseased renal cells pour albumin into the urinary passages, 
changes in the vessel-walls cause changes in the constitution of the 
lymph and have a share in the production of inflammatory exudates. 
Thus, as Minkowski says, it is not at all inconceivable, and we have 
analogies to strengthen our view, that under certain circumstances the 
liver-cells may pour the bile-pigments formed by them into the blood- 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 427 


capillaries instead of into the bile-capillaries. Minkowski ealls this 
process “parapedesis of bile.” Liebermeister and Pick also have at- 
tempted to explain certain forms of icterus by assuming functional dis- 
turbances in the liver-cells, either with or without demonstrable anatomic 
alterations. Liebermann has called this form of icterus “diffusion 
icterus” or “akathectic icterus” (from yaéeyev, “to hold fast’). E. 
Pick has called it “paracholia.” The latter author, we believe, goes 
too far in his belittling of the importance of the mechanical factor in the 
causation of icterus. 

The question arises as to where and how the bile enters the blood- 
current when its outflow is hindered. We must assume that absorption 
chiefly occurs at the center of the acini, because the greatest amount of 
staining by bile is found here. Heidenhain, it is true, was able to find 
indigo-sulphate of sodium, injected into the bile-ducts of living animals, 
only in the interlobular and not in the intra-acinous bile-passages. It is 
possible that his deduction, that absorption occurs only in the former, 
holds true for the particular stain he employed in his experiments; in 
the case of bile it is, however, certainly not true. Older investigators 
(for example, Frerichs, loc. cit., p. 98) have assumed that absorption 
occurs through the veins as well as through the lymphatics. In recent 
years the latter alone are considered as the channels through which 
absorption occurs, particularly since Fleischl and Kufferaht have shown 
that in a dog, after ligation of the main bile-duct, the lymph taken from 
a fistula in the thoracic duct contains bilirubin and bile-acids, whereas the 
blood does not. This finding corresponds with the statement that after 
ligation of the thoracic and the main bile-duct in dogs both the blood 
and the urine contain no trace of biliary constituents for several (as many 
as seventeen) days (v. Harley and v. Frey). The question as to what 
became of these remains unsolved. Moreover, bile still makes its appear- 
ance in the blood if the thoracic duct is ligated some days after the 
bile-duct. Microscopically, the livers of animals in whom such a stasis 
of both bile and lymph had been produced showed an enormous dilatation 
of the bile-capillaries and of the perivascular lymph-spaces. The liver- 
cells, owing to the pressure, were reduced to one-half their normal size 
and number, and were separated by fissures in which the two dilated 
systems of vessels communicated. 

D. Gerhardt, as was to be expected, saw icterus follow ligation of 
both the thoracic and the common bile-duct. It seemed to appear as 
rapidly and to be as intense as it was when the thoracic duct remained 
open.. We see,.therefore, that if there is occlusion of the lymph-channels, 
which ordinarily carry the bile away in case of an obstruction to its flow, 
the bile can be absorbed through other channels, and that these can only 
be the blood-vessels. [Queirolo and Benvenuti * have recently con- 
firmed Gerhardt’s results. They, however, believe that the lymph- 
vessels play a very slight part in absorption of bile, which they believe is 
accomplished through the intra-hepatic venous system.—Ep.] In 
recent obstructive icterus of man (and of the dog and cat) the liver- 
cells in the beginning contain no bile-pigment, the latter being seen only 
in the biliary passages and capillaries and in the connective-tissue cells. 
After the stasis of bile has persisted for some time the liver-cells also 
become impregnated with pigment (in Gerhardt’s experiments at the end 


* Tl Policlinico, 1900, No. 13 . abs. in Centralbl. 7. innere Med., 1901, No. 9, p. 224. 


428 DISEASES OF THE LIVER. 


of five to six days). The pigment, as we have already mentioned, is 
principally deposited in those cells that are situated near the center of 
the lobules, wherein yellowish lumps of different size and outline are seen. 
Nauwerck believes that he has demonstrated in these cells a fine capillary 
network surrounding their nuclei and anastomosing with the bile-capil- 
laries. In chronic stasis the latter are frequently filled with brownish 
and yellowish masses, as in an incomplete artificial injection. In the 
beginning, therefore, of stasis of bile the liver-cells are capable of getting 
rid of the bile-pigment which they form, but if the stasis continues for 
too long a time, they are no longer able to do so. D. Gerhardt also saw 
within the area of greatest stagnation endothelial cells filled with granular 
masses resembling bile. These cells were derived not only from the 
lymphatic sheaths, but also from the blood-vessels themselves, into the 
lumen of which they protruded. 

Other histologic changes frequently develop in the hepatic tissue, prob- 
ably because other factors besides biliary stasis play a réle. If the 
outflow of bile is impeded, the bile-passages are filled with secretion and 
distended, and the whole organ, as can be readily determined during 
life, is distended and enlarged in the same manner as after an artificial 
injection. Whether this distention is simply a concomitant feature of 
the stasis or is caused by it remains doubtful. This increase in size and 
tension, it is true, varies greatly, even though the degree of stasis at 
different times may be complete and equal. The color of the liver in 
recent stasis is very little changed ; only after a duration of weeks does 
discoloration of the center of the lobules become apparent to the naked 
eye. Gradually discoloration increases in intensity and extent until in 
the course of months there is a dark yellow or even greenish shade within 
the lobules. The gall-bladder and bile-ducts, and also the biliary pas- 
sages within the liver, may become greatly distended as a result of this 
long-continued stasis, so that their combined capacity may be equal to 
a liter. The substance of the liver in certain areas partly disappears 
under the influence of this pressure and the microscopic structure of the 
lobules may become changed. 


In long-continued stasis of this kind the contents of the finer microscopic 
bile-passages may consist of clear colorless mucus. D. Gerhardt found the intra- 
acinous passages in great part colorless, so that only a part of these and the liver- 
cells contained notable quantities of bile-pigment. 

As we can but rarely study in an early stage the anatomic changes produced 
in the liver by uncomplicated, complete stasis of bile in man, many investigators 
have attempted to study the subject experimentally. The results obtained vary, 
and are in many instances different from the conditions observed in human subjects. 
One of the principal reasons for this is the fact that the duration of the stasis 
and the time of observation differed in the different experimental series. As a 
rule, the latter was too short, as it rarely extended over three weeks and never 
reached more than five to six weeks. Another reason is the difference of the re- 
action in the different animals employed. Dogs and cats seem to be quite resistant, 
while guinea-pigs succumb in a few days, or at best after a week or two. Rabbits 
are not quite so susceptible, and occasionally survive the operation for five weeks. 
In all these animals death results, with loss of appetite and emaciation, and in acute 
cases coma and spasm may supervene. : 

The time at which icterus of the tissues is said to make its appearance varies 
greatly (from one to ten days). In casesof chronic stasis icterus is said to decrease 
gradually. Bile-pigment and bile-acids (not looked for by all authors) are 
present in the blood and urine (Lahousse), although, according to D. Gerhardt, 
Gmelin’s reaction may not be demonstrable in the urine for days at a time. 

The anatomic examination of the animals reveals that the liver is enlarged 
and vascular, and that necrotic areas are disseminated all through the organ. The 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 429 


latter may appear in the course of the first twelve hours, increase in size and number 
up to the third day, decrease from that time on, and disappear by the seventh to 
the tenth day. The smallest of these foci involve only a few of the liver-cells, the 
larger ones include several lobules. Lahousse states that the smallest foci are 
oval in outline; Steinhaus, that they are cone-shaped with their bases pointing 
toward the periphery of the lobule and their apices toward the center. These areas 
are distinguished from their reddish-brown surroundings by their grayish-yellow 
or bile-pigment color. In the beginning they are surrounded by a hyperemic ring. 

Under the microscope it will be seen that these necrotic liver-cells have an 
icteric color, are swollen, are undergoing hyaline degeneration, and show the forma- 
tion of vacuoles within them. The staining power of their nuclei is soon lost, and 
later also that of their protoplasm. In regard to the blood-capillaries in the necrotic 
areas, Beloussow states that they become occluded, Steinhaus that they are com- 
pressed by the swollen liver-cells, and D. Gerhardt that they remain patent. The 
lymph-channels are distended (Lahousse). 

Around these areas there then follows round-cell infiltration. Later absorp- 
tion of the necrotic foci is brought about through the formation of giant cells 
and the growth of connective tissue into and around the area. This connective 
tissue is at first rich in nuclei, but later becomes fibrous. Similar conditions were 
found in the case of pigeons examined by Stern up to the seventh day after liga- 
tion. While Steinhaus claims that the round-cell infiltration is limited to the 
immediate surroundings of the necrotic foci, and Foa and Salvioli state the same 
for the connective-tissue growth, nearly all other authors state that connective 
tissue, which in the beginning resembles embryonal tissue, and later shows oval nuclei 
and becomes fibrous, develops from the second to the third day in the interlobular 
spaces, and that this tissue is irregularly distributed, but altogether independent 
of the necrotic foci (D. Gerhardt, Pick). Soon this connective tissue begins to grow 
into the hepatic lobules from their periphery, advancing between the rows of liver- 
cells, but rarely reaching as far as the central vein. 

The bile-ducts, after ligation of the ductus choledochus, are dilated throughout 
and are filled with bile, not only in their main branches, but even in their finer 
ramifications (according to Popoff, even in their finest intercellular capillaries). 
In the finer interlobular bile-passages there are masses of detached epithelial cells 
filling the lumen, and also proliferation of the epithelium. After a period of three to 
six days diverticula form. These diverticula are lined by low, broad cells with old 
nuclei instead of cubical and cylindric epithelium. With this formation of new 
bile-ducts the canaliculi pursue a tortuous course and form anastomoses. The 
branches penetrate into the lymphatic lobules, where they are lost among the 
rows of liver-cells. According to some authors, an increase in the length of the 
bile-channels takes place through the flattening and the increase in the number of 
the cells at the periphery. 

The time at which the proliferation of the bile-capillaries begins is stated by 
Beloussow to be the fourth day, by Pick the third, by D. Gerhardt the second. 
Most authors agree in stating that the proliferation of the connective tissue and of 
the bile-capillaries occurs at the same time and in the same locations. D. Ger- 
hardt assumes that the two processes in general are independent of one another; 
Charcot and Gombault, on the other hand, regard the proliferation of the bile- 
passages as the primary event, the proliferation of connective tissue in the inter- 
(later intra-) lobular tissue as the secondary event. At all events, the two pro- 
cesses are not in any way related to the formation or resolution of the necrotic 
foci, as they persist for a long time (as long as ten days) after these have disappeared. 
During the fifth or sixth week the lobules of the liver may be seen to be surrounded 
by connective tissue, so that the cell-masses in their center become considerably 
reduced. As a result of all these processes, the whole organ seems smaller and 
harder than normal and its cut surface resembles the liver of a pig. 

In rabbits and guinea-pigs ligation of the bile-ducts leads in a comparatively 
short time to serious anatomic changes of the liver, and frequently causes death. 
The same experimenter may see different degrees and kinds of changes following 
this procedure. This is probably due to slight accidental variations in the oper- 
ation, such as duration of the operation, struggles of the animal, or to indi- 
vidual peculiarities of the animal. In this manner some of the contradictory 
statements of different investigators may be explained. The occurrence of necrosis 
in a large number of liver-cells following the sudden obstruction to the outflow of 
bile can hardly be attributed to mechanical factors alone (according to the control 
experiments of D. Gerhardt with injections of salt solution into the bile-duct), 
but must be regarded as the result of chemical injuries inflicted on the liver-cells 


430 | . DISEASES OF THE LIVER. 


by the bile. Similar changes can be produced outside of the organism by allowing 
bile to act on liver-cells, and can be readily recognized microscopically (Chambard, 
Steinhaus). If death occurs within the first few days, it must be attributed to the 
general damage that has been done to the parenchyma of the liver and to the serious . 
disturbances of metabolism resulting therefrom. In the later stages the bile no 
longer produces necrosis, possibly because it is carried off by the lymph-channels 
or because less is being secreted (according to Lahousse, icterus in these later stages 
decreases). At the same time the bile still stimulates the tissues to the formation 
of connective-tissue and to proliferation of the bile-passages; thus, it is possible 
that the animals can perish even after five weeks, convulsed from disturbances of 
the hepatic function. 

Dogs and cats react entirely differently to the operation. In these animals 
ligation of the common duct is followed by a dilatation of the larger bile-passages 
and of the gall-bladder with a thickening of their walls. While Leyden at one time 
observed fatty changes in these cells, later observers (ID. Gerhardt, Foa, and Salvioli 
in dogs) either found the hepatic cells unaltered or saw simple pressure atrophy 
in the peripheral parts of the lobules (Foa and Salvioli in cats, Popoff in dogs). 
Popoff alone reports an increase of the interlobular connective tissue in one case, 
and here only to a slight degree. Necrotic foci have never been observed. While 
it is true that the experiments performed on the latter class of animals are not so 
numerous by far as on the former, and while many of the experiments cannot be 
utilized for the reason that the bile-passages did not remain permanently imper- 
meable or that perforative peritonitis or abscesses occurred, still it may be said 
to be positively established that ligation of the bile-ducts produces much slighter 
anatomic changes in the liver and is less dangerous to life in dogs and cats than in 
rabbits and guinea-pigs. . 

Steinhaus attributes these differences to a greater secretion of bile and, as a 
result, to a greater increase in the pressure in the latter class of animals. Of the 
different animals, the following amount of bile per kilo of animal is secreted in 
twenty-four hours: . 


GUN E RR DIG 804 eens leet eke eee oa a Po ea bee ret 175.8 gm. of bile. 
TRADDIG 6S cette hy aie Ae OE el na eed 136.8.“ fy 
DOR 25 gists sooo teh eee oe Ue Ree UR gE ay Ec 20:0:. ss 
MC sg he Ri A as ers A IC ela We eB a eae aot 145° °° ne 


The difference might also be attributed to greater individual resistance of the 
liver-cells to the action of bile, or it might be due to the fact that in dogs and cats 
the bile can more readily escape into the lymph-channels. The experiments of 
V. Harley and of v. Frey, already mentioned, show that, if an obstruction is created 
both to the flow of bile and of lymph, distinctly visible communications are estab- 
lished between the two systems of vessels. 

The presence of bile-pigment in the blood and urine of cats and dogs during 
starvation might also be explained from the fact that in these animals the bile 
can more readily find an exit into the lymph-channels (Naunyn). 

As the slighter anatomic changes in dogs and cats as compared to guinea- 
pigs and rabbits coincide with the slighter vulnerability and greater resistance 
of the former animals to the operation, the conclusion seems justified that it is not 
the absorption of biliary constituents (that is equal in both classes of animals) 
into the general circulation that causes death after occlusion of the bile-ducts, 
but some other form of damage to which the liver is subjected. 

It appears that human beings resemble dogs in their reaction to stasis of bile. 
Man can survive for years with stasis of bile and the function of his liver may con- 
tinue unimpaired. Again, an occlusion lasting for months may be removed and be 
followed by no impairment of health or functional activity of the liver. Anatomic 
examination, it is true, has in many instances revealed more serious changes than 
the clinical picture during life would lead us to suspect. Janowski, for instance, 
examined ten cases of stasis of a duration of from two weeks to more than a 
year (eight being cases with gall-stones), and found necrotic areas with inflammation 
and a proliferation of the bile-passages and of the connective tissue. The necrotic 
areas were, as a rule, seen in the peripheral portions of the lobules, and were most 
numerous in recent cases. They are said to originate from extravasation of bile 
which damages the liver-cells and at the same time compresses the blood-capillaries 
and in this manner induces anemic necrosis. In the marginal portions of these foci 
cell-infiltration and dilatation of capillaries are seen, followed by the formation of 
connective tissue. The bile-ducts, too, show desquamation of epithelium, cellular 
infiltration of the walls, and new-formation of connective tissue. The bile-capillaries 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 481 


themselves proliferate, and here and there they seem to originate from rows of 
liver-cells. . 

Raynaud and Sabourin also report thickening of the walls of the large bile- 
passages from connective-tissue proliferation in chronic stasis of bile, and in many 
cases, in addition, hyperplasia of the glands of the bile-duct. Sauerhering found 
necrotic areas in the human liver less diffuse than those described by Janowski, 
and resembling more the experimental foci, and surrounded by connective tissue. 
Under certain conditions stasis of bile due to gall-stones may produce so intense 
a proliferation of connective-tissue that (aside from the intense icterus) the picture 
of atrophic cirrhosis may be simulated both clinically and anatomically (see atrophic 
cirrhosis). Brissaud and Sabourin observed the final result of chronic biliary 
stasis in two cases where the stone occluded only the left hepatic duct. In these 
cases the left lobe of the liver had almost completely disappeared, being merely 
represented by connective tissue and fibrous blood- and bile-vessels. Such a stage 
can be reached only if the stasis of bile is but partial, so that a part of the liver 
remains intact and can perform the functions necessary for the maintenance of life. 
In one case the cirrhotic process had extended to the right lobe, in which no stasis 
of bile existed. I made a similar observation recently in an autopsy. In this case 
the left lobe was converted into a structure that was only as large as two adrenals 
and resembled these organs in shape. The right lobe was vicariously hypertrophied 
(total weight of the liver 3 kg.). A biliary concretion was embedded close to the 

all-bladder and showed that at some time a gall-stone must have been impacted 
in the left hepatic duct and have caused the changes observed. 

To judge from these considerations it seems that some analogy exists after all 
between human beings and rabbits and guinea-pigs. 

What causes these differences in individual cases? In the first place, I attribute 
them to the differences in the rapidity with which the obstruction of the flow of bile 
occurs. With the exception of certain cases of gall-stone impaction, this never occurs 
so rapidly as in ligation of the ducts. The more gradual the increase in the pressure 
of the bile, the better the communication established between the bile- and the 
lymph-vessels. In the second place, certain complications usually coexist in the 
cases studied in human beings, particularly infection of the bile-ducts. For this 
reason the pathologic changes observed in man can only to a certain extent be 
compared with the findings in animals in which similar conditions have been pro- 
duced experimentally, bacterial infections in the latter instance being almost 
invariably excluded. When we consider, finally, that in animals in which the biliary 
stasis is apparently equal in intensity and duration different degrees of swelling 
of the liver and. of involvement of the general health are found, we will have to 
assume that, in the third place, possibly, individual differences in the rapidity 
of the outflow of the bile into the lymph-channels play a réle in human beings. 


If we summarize all these investigations, we see that in human beings 
in the beginning of the biliary stasis the liver-cells continue to secrete 
bile in a normal manner and to pour the excreted bile into the biliary 
capillaries. This bile is principally absorbed by the lymph-channels, 
but may in part and under certain conditions directly reach the blood- 
vessels. From anatomic investigation alone we are not able to state 
whether icterus is caused by stasis or by parapedesis of bile. 

As a result of long-continued stasis of bile the liver-cells become 
functionally impaired, so that the quantity of the bile-acids (possibly 
also of the bilirubin) decreases. As an evidence of other metabolic dis- 
turbances, we find a decreased power on the part of the liver to store 
glycogen. Soon bilirubin is seen within the cells, being either formed 
here and not excreted, or produced in other portions of the liver 
and pressed into the cells from the dilated capillaries that surround them. 
The liver-cells are damaged chemically by the bile and directly by 
the mechanical pressure and by the obstacles that are created to the 
outflow of bile through the blood- and lymph-channels. Anatomically, 
these conditions are manifested in the cells by reduction of their size, 
changes in their outline and structure, and, finally, by fatty degenera- 
tion, necrosis, and imbibition of bile. 


432 . DISEASES OF THE LIVER. 


This picture is, in addition, not rarely affected by the action of micro- 
organisms that reach the bile-passages from the intestine. The effect 
of such an invasion is not always manifested in the same manner, and 
may be different in extent and rapidity of development. The width of 
the bile-passages varies considerably in different individuals, and on 
this account individual tolerance against biliary stasis may vary in 
different subjects. In some cases we see simple pressure-atrophy of the 
hepatic tissue; in others, in addition, reactive growth of connective tissue. 
According to the presence or absence of the one or the other effect, we 
see elther simple intoxication from absorption of biliary substances or, 
in addition, a reduction and a perversion of other functions of the liver. 


Other substances that are injected into the bile-ducts under a degree of pres- 
sure in excess of that of the bile are absorbed ; for example, stains in solution (carmin, 
anilin-blue). Stains in suspension (India ink) penetrate the lymph-glands at the 
portal fissure by way of the lymph-channels and may even be carried beyond. If 
physiologic salt solution be allowed to flow into the ducts, the liver-cells are bleached 
out and sugar appears in the urine within a few minutes (Griitzner). 


Anatomico-histologic Changes in Other Organs.—The biliary con- 
stituents circulating in the blood soon penetrate the tissues. Very little 
is known in this respect in regard to the bile-acids, but bilirubin is, of 
course, readily recognized from the discoloration of the tissues that it 
produces. At first the latter enters the blood-stream and the plasma, 
where it can be recognized by the yellow color that it imparts to the 
plasma and by Gmelin’s reaction. It is also readily found in serous 
transudates and exudates, and in the fluid within the ventricles of the 
brain and in serum from blisters. [It has also been detected in cerebro- 
spinal fluid obtained during life by lumbar puncture.—Eb.] 

The discoloration observed in dead bodies is, according to Minkowski, 
much modified by a postmortem imbibition of the tissues with blood- 
serum andlymph. There can, however, be no doubt that certain tissues 
have a particular selective affinity for bile-pigment, especially connective 
tissue. The yellow color is, therefore, particularly conspicuous in the 
intima of the vessels, the fasciz, the connective-tissue layers of the skin 
and mucous membranes, and the subcutaneous tissues. Muscular and 
nervous tissue are only slightly colored by bile-pigment. The brain is 
slightly icteric only in the new-born; in adults it is colorless, and only 
_ the lymph in the perivascular spaces or the edematous fluid are colored 
slightly yellow. Gland-cells and epithelium, as a rule, absorb little bile- 
pigment, with the exception of the deepest layers of the rete Malpighii 
and the kidneys. In the former organs the pigment is seen diffusely all 
through the organ or in a granular form, as in all physiologic and patho- 
logic pigmentations. This massing of pigment, together with the im- 
ate of the cutis, causes the relatively deep coloration of the external 
skin. , 

Bile-pigment is excreted by the kidneys. In the beginning of icterus 
and in mild cases it stains the cortex diffusely; later it assumes the form 
of yellowish granules that are also seen in the lumen of the canals. The 
epithelial cells of the tubuli contorti are still more deeply stained than are 
those of the cortex. Here, too, if the icterus persists for a long time, 
the yellow masses appear in the lumen in greater number and more 
closely packed. They are most numerous in the afferent tubules, which 
also show the greatest defects of the epithelium. In these tubes are seen 
cylindric casts colored yellow, green, or brown, formed in part by necrotic 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 483 


epithelial cells.* In addition to pigmentary infiltration, the epithelial 
cells of the uriniferous tubules show swelling, cloudiness, a loss of cilia, 
and necrotic disintegration (Moebius, Lorenz), changes which, according 
to Werner, are due to the action of the salts of the bile-acids. Macro- 
scopically the cortex of the kidneys appears yellowish or even greenish 
in color, while the pyramids are streaked with dark green. More marked 
changes are seen only if complete stasis of bile has persisted for months. 
A few days after the stasis is relieved the cortex assumes its normal 
color, but the tubuli contorti and the parenchyma remain discolored 
for a longer period. Occlusion of the tubules and damage to the epi- 
thelial cells by constituents of the bile probably produce a diminution 
in the excretory power of the kidney, and may in this manner be detri- 
mental to the whole organism. 

The fetus of an icteric mother is also icteric, not, however, in propor- 
tion to the maternal icterus, the condition in the fetus being usually 
less marked. 

The pus from cellular tissues is icteric, but mucus or mucopurulent 
secretions of mucous membranes, on the other hand, are not. Intestinal 
mucus occasionally forms an exception to this latter statement. 

Symptoms of Icterus.—The presence of biliary materials in the 
general circulation produces a series of symptoms that are altogether 
independent of the primary cause of the trouble. These are of such 
significance that they merit separate discussion. They are most con- 
spicuous in obstructive icterus, and are the more apparent the more 
complete the obstruction to the flow of bile. The prototype of the acute 
forms of this condition is found in simple cases of catarrhal icterus; that 
of the chronic forms, in occlusion of the ductus choledochus by a gall- 
stone. 

The most conspicuous symptom is the yellow discoloration of the 
skin and visible mucous membranes. By almost imperceptible degrees 
the color merges from a light sulphur yellow to a lemon yellow, then into 
a greenish and olive color, and finally a dirty yellowish-gray (Melas- 
Icterus). The shades last described are only seen in cases where icterus 
has persisted for months. As a rule, the discoloration is more intense on 
the trunk and the upper half of the body than on the lower half. It is 
frequently masked by the normal pigment of the skin and by its vas- 
cularity, the milder degrees of icterus being, therefore, more readily 
overlooked in brunettes and in full-blooded subjects than in blond or 
pale subjects. The yellow color is sooner and more readily observed 
in the sclera of the eyeball than it is in the skin; but it must be remem- 
bered that many people, in addition to showing a yellowish tinge where 
the muscles are inserted, normally have yellowish sclera both of the 
eyeball and of the conjunctiva. Icteric discoloration is not readily 
perceptible in the mucous membranes of the mouth and throat, owing © 
to the blood-red color of these parts; but the paler lining of the gums 
occasionally shows it. 

Very frequently patients with icterus complain of a feeling of itching, 
often causing them to scratch themselyes severely. The scratched por- 
tions of the epidermis in these cases form dull whitish streaks that are 
clearly visible on the otherwise uniformly yellow skin. If the patients 
scratch themselves very vigorously, we see small papules and ulcers 
covered with scabs, or, if the skin be particularly delicate, the formations 


* See Frerichs’ “ Atlas,”’ Plate I, Figs. 8-11. 
28 


434 . DISEASES OF THE LIVER. 


of blebs and of eczematous rashes. This form of pruritus must be 
classified as a symptom of intoxication analogous to the drug exanthems. 
It is impossible to state whether the deposit of bile-pigment in the skin 
has anything to do with its occurrence. It appears in different cases at 
various stages of icterus, in some cases in the beginning, in others if the 
disease has persisted for some length of time. Although sometimes it 
persists during the whole course of the affection, in others, again, it 
disappears before the icterus. This pruritus occurs chiefly in obstructive 
jaundice of considerable severity, and, as a rule, disappears as soon as 
the bile-passages become patent again, even though the icterus of the 
skin may persist. [Herter is inclined to attribute the pruritus to dryness 
of the skin, in view of its occasional appearance before pigmentation.—ED. ] 


A peculiar skin lesion (not exclusively found in icterus) is seen in chronic 
icterus, called xanthelasma, or xanthoma. It consists in dirty, pale yellowish 
spots, that protrude very little beyond the level of the skin in the beginning, but 
later assume the tuberous form. They are chiefly found in the region of the eyelids. 
The pigmentation of these spots is not caused by bile-pigments, and, in fact, their 
connection with icterus is not definitely determined.* [In certain cases of long- 
standing jaundice peculiar areas of lighter yellow color are seen, looking as though 
the epidermis were raised by small quantities of serum. They are frequently 
linear in their arrangement.—Eb. ] 


The following secretions always contain bile-pigment in icterus: 
the urine, sweat, serous and inflammatory exudates, liquor amnii, pus 
from cellular tissues and from wound surfaces. Milk and pneumonic 
sputa are not constantly colored; while the tears, the saliva, and the 
mucus and mucopurulent secretions of the mucous membranes remain 
colorless. 

The coloration of the urine is the most important, and has the greatest 
practical significance, since through the medium of the urine the con- 
stituents of the bile (the bile-pigments and the bile-acids) retained in 
the body are to be removed from the organism. If any considerable 
degree of stasis exists, the urine always contains bilirubin, and is con- 
sequently colored yellow even in very thin layers, so that the foam on 
the top of the urine also is discolored. In the vessel the urine is of a 
brownish-yellow to brown color, occasionally being mixed with red or 
with a dirty opalescent green or brown tint. The former is caused by 
urobilin, the latter by higher oxidation products of bilirubin. These 
pigments are usually formed only after exposure to the air, but, espe- 
cially in chronic cases of icterus, may be seen immediately after the 
urine is voided. 

Under the microscope hyaline cylinders are, as a rule, found in the 
urine (Nothnagel). If the icterus is of long duration, these casts contain 
yellowish renal epithelial cells. In the new-born these epithelial cells 
are not stained, but inclose the pigment in the form of granules and 
needles. While it is true that Litten + finds hyaline cylinders in every 
normal urine by means of the centrifuge, still they are more numerous 
in icteric urine, and indicate that the passage of biliary substances through 
the kidneys has produced an irritation of these organs. 

Traces of albumin in solution may be found only after the icterus has 
persisted for a long time. 


* Michel in Grife-Saemisch’s “ Handbuch der Augenheilkunde,”’ Bd. tv, p. 425. 
Schwimmer und Babes, Ziemssen’s “Handbuch der speciellen Pathologie,” Bd. 
xiv, IT, p. 446. 

t Litten, Berliner klin. Wochenschr., 1896, p. 263. 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 480 


Bile-pigment is recognized chemically by methods which cause oxidation of 
bilirubin to green biliverdin. The most frequently employed method is to super- 
pose the urine upon impure nitric acid, whereby oxidation goes beyond the formation 
of the green tint, and higher products of blue, orange, and reddish-brown shades 
are formed in successive layers until finally complete decoloration occurs. As nitric 
acid gives a dark color to a number of other pigments that are found in the urine, 
it is essential that the green shade should be clearly perceptible. Instead of super- 
posing with nitric acid, the urine can be mixed with a few drops of a solution of 
nitrite of potassium and sulphuric acid be superposed. If the urine is mixed with 
only a few drops of impure nitric acid, a diffuse green color soon appears. This 
occurs more slowly if some other acid be added. Solutions of potassium 
iodid and chlorid of iron may also be employed as oxidizing agents by adding a 
few drops to the urine, when the green color appears gradually after one or several 
minutes. 

These reactions do not all succeed equally well in every instance, and it is 
frequently necessary to test the exact quantities of the reagents and the reaction- 
time. This is apparently due to other urinary constituents, possibly modifications 
of the pigments themselves. Among these might be mentioned a colorless chromo- 
gen that is formed by reduction and a brown substance formed by oxidation of 
bilirubin. Occasionally the reaction is more distinct if the pigment is distributed 
over filter-paper either by dipping strips of the paper into the urine to be examined 
or by filtering the urine through filter-paper. If paper so impregnated be touched 
with fuming nitric acid, rings of different colors will be found. Sometimes the green 
color will appear if the paper be allowed to dry in the air. In case the urine contains 
albumin and is boiled, a part of the pigment is apt to be precipitated with the 
coagulate. If the quantity of pigment is very small or if other pigments are present, 
the test of Schwerdtfeger-Huppert is of value and is very delicate. It is performed 
as follows: The urine is mixed with lime-water and a stream of carbonic acid gas 
is passed through the mixture. The biliary coloring-matter is carried down with 
the calcium hydrate in the precipitate. The residue left on filtration is then 
washed with slightly warmed alcohol to which has been added a few drops of sul- 
phuriec acid. If bile-pigment is present, the fluid assumes a greenish color. 

According to Gluzinski, icteric urine can be made green by boiling with a few 
drops of formalin solution, a test that is very delicate. On the addition of muriatic 
acid, the green color changes into violet. 

If only very small quantities of bile-pigment are circulating in the blood, as 
in the beginning or toward the termination of an attack of icterus of considerable 
severity, no bilirubin, but urobilin alone, will be found in the urine, and hence the 
color will be yellowish-red. Urobilin is also frequently found in the urine together 
with bilirubin during icterus, as a rule in abundant quantities, but usually dis- 
appearing as soon as the bile is completely absent from the intestine (for details 
see below). 

Urobilin can be detected directly with the spectroscope or after precipitation 
with ammonium sulphate. If bilirubin is present at the same time, it must first 
be precipitated with lime-water or baryta mixture, the urobilin being only in small 
part thrown down with these precipitates, the greater part remaining in solution. 
Hayem* recommends superposing the urine with water in a test-tube, urobilin 
diffusing upward more rapidly than bilirubin and being readily detected spectro- 
scopically in the watery layer. 


The liver itself produces no direct symptoms during life in the milder 
cases of icterus from stasis or from parapedesis. If the stasis of bile assumes 
more formidable proportions, the organ becomes distended and causes 
a feeling of fulness and discomfort, as well as tenderness on pressure 
by the fingers or by the overfull-.gastro-intestinal tract. Occasionally 
palpation seems to reveal an increased degree of resistance. Percussion 
shows an enlargement of the area of hepatic dulness. Sometimes the 
distended and full gall-bladder can be palpated and percussed. The 
degree of enlargement and resistance of the liver varies even where biliary 
obstruction is complete and occurs in a perfectly healthy organ. The 
anatomic findings in a liver affected in this manner may be perfectly 
negative. If the obstruction persists for many months, increase in the 


* Chauffard, loc. cit., p. 698. 


436 DISEASES OF THE LIVER. 


size and consistence of the liver will be found. If the obstruction per- 
sists still longer, the size of the liver recedes in part or returns to normal, 
because of pressure atrophy or interstitial hepatitis. 

No satisfactory explanation for this varying reaction of the liver 
can be given. It is probably due to differences in the width of the 
channels acting vicariously in carrying off the surplus of bile accumulated, 
these differences being founded on anatomic peculiarities. The presence 
or absence of infection of the bile-fassages or of parenchymatous or 
interstitial hepatitis would have an important bearing upon the secondary 
effects of obstruction. 


We might expect that increased pressure in the bile-capillaries would produce 
compression of blood-capillaries within the liver, particularly as the pressure in 
the portal vein is normally lower than it is in the bile-ducts. Betz has, in fact, 
noticed a lessening of the blood-stream in the portal system when the bile-ducts 
were filled. It is impossible to recognize such an occurrence clinically, as digestive 
disturbances and enlargement of the spleen may occur as the result of many con- 
ditions other than hyperemia from stasis. Even though increased transudation 
occurs from the serosa of the intestine as a result of the obstruction that exists 
to the outflow of this exudate, the parietal peritoneum may be stimulated to in- 
creased activity of its absorptive power, and in this manner the true condition may 
evade detection. 


The spleen is often found enlarged in the diseases that are accompanied 
by icterus. As a rule, this is a result of causes other than those dis- 
cussed above. It is usually due to infections or the excessive destruction 
of red blood-corpuscles producing a great accumulation of debris within 
the spleen. Even in simple acute obstructive jaundice (icterus catar- 
rhalis) the spleen is occasionally, but not always, enlarged. Perhaps 
infection from the bile-ducts, only recently appreciated, plays a rdle; 
perhaps, too, venous stasis may be responsible. It is less probable that 
the swelling of the spleen is due to an accumulation of debris from the 
great destruction of red blood-corpuscles by the reabsorbed biliary acids 
(spodogenous tumor of the spleen). 

The decrease in the normal quantity of bile poured into the intestine 
influences fat-absorption and putrefactive processes. In agreement with 
the findings of physiologic investigators, Fr. Miller found that the absorp- 
tion of amylaceous substances was not at all interfered with and that of 
proteids only to a slight degree, but that the absorption of fats is greatly 

decreased. Of a given quantity of fat administered with the food, 
from 55% to 78% were recovered in the feces, as against 7% to 10% 
in normal subjects. J. Munk found a slightly better utilization of the fat, 
even as high as 64%, if abundant fat was ingested. In this case the 
waxy fats were not assimilated as well as the oily ones. The assimilation 
of the fatty acids was not changed by the absence of bile. The splitting 
of the fat within the intestine, according to J. Munk, is less active and 
occurs to a lesser degree. Jr. Miller found that the splitting of the fat 
was only perverted if the pancreatic duct was at the same time occluded. 


Dastre’s experiment is a fine demonstration of the significance of the bile in 
the absorption of fat. He ligated the ductus choledochus in i and established 
a fistula between the gall-bladder and a coil of the intestine below. Only in the 
region below this fistula was the chyle found to be milky, pancreatic juice alone 
beihg unable to induce absorption of fat. 

It is not positively known what is the exact significance of the bile in the 
absorption of fat. It is possible that it acts purely physically by promoting the 
adhesion of the fat emulsion to the villi (Wisti Eien, or by exerting some in- 
fluence on the vital activity of the intestinal wall. 


+ 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 437 


The color of the feces, after exclusion of the bile from the intestine, 
is dependent only on the color of the ingesta. After a pure meat diet, 
for example, they are brownish-black. If the ingesta are colorless the 
feces are grayish-white or clay-colored. The pale color is increased by 
the mixture of large quantities of fat that is emulsified but not absorbed. 

In feces of this character the microscope frequently reveals long 
needles of fatty acids, and in particular a large quantity of needle-shaped, 
short crystals, arranged in sheaths. These consist of magnesium, potas- 
sium, and sodium soaps of the higher fatty acids. If they are very numer- 
ous, they may give the feces a shiny appearance. In partial stasis of 
bile the color of the feces may vary from a clay-colored, white, or brownish 
tint through all the different shades between this and the normal color. 
It is frequently possible by using acid-alcohol to extract urobilin from ap- 
parently colorless masses. In complete biliary obstruction traces of 
urobilin may be present, for intestinal mucus containing biliary coloring- 
matter may be mixed with the feces. Here, too, a reduction to chromo- 
gen’ may occur, so that the feces contain more pigment than would 
appear from inspection alone. 


According to Bidder and Schmidt, the bile has antiputrefactive properties, 
and the feces of icteric patients are credited with a particularly bad odor. I cannot 
indorse this. The scale of malodorousness is, of course, altogether subjective. 

Certain experiments show that the bile itself can readily putrefy, and that 
many bacterial species thrive exceedingly well in it (see page 472). The ethereal 
sulphates, that may be considered an index of intestinal putrefaction, were found 
increased in icterus by Brieger, Biernacki, and Eiger, not increased by Réhmann, 
Fr. Miller, Pott, and v. Noorden. [Lately Boehm* has found them greatly in- 
creased.— Ep. | 

In view of the complicated bacterial fauna of the intestine, this question is not 
a simple one and cannot be readily decided. The antiputrefactive action of the 
bile is by no means demonstrated. It is possible that the action of the bile may 
be favorable to the growth of certain bacterial species or, on the other hand, that it 
may be unfavorable to their growth. In either instance the composition of the 
bacterial mixture and of its products would be changed. 


Clinically the digestive disturbances following stasis of bile are very 
varying. As a rule, other disturbances of the stomach or intestine 
coexist, so that it is very difficult to decide how much is due to the absence 
of bile from the intestine. The frequent tendency to constipation may 
with some degree of. certainty be ascribed to this factor, as may possibly, 
also, the tendency to flatulency. Disturbances of the appetite and an un- 
unpleasant bitter taste in the mouth are frequently complained of in 
icterus, as is also a distaste for certain foods, sometimes for fats and 
usually for meat. 


It can hardly be assumed that the bile-acids circulating in the blood act directly 
on the nerves of taste and cause the bitter taste, since similar sensations are com- 
plained of in disturbances other than icterus (such as dyspepsia), and are, further, 
not proportionate-to the degree of biliary stasis. According to Hayem, hyper- 
chlorhydria of the stomach usually coéxists (?). 


In many cases of simple chronic biliary stasis digestive disturbances 
and loss of appetite are singularly absent or very slight. 

In addition to the yellow discoloration and the local disturbances 
produced by stasis, there are found in icterus a number of other symp- 
toms affecting the circulatory and the nervous systems and the special 
senses. | 
* Deutsches Arch. f. klin. Med., Bd. uxx1, Hft. 1. 


438 DISEASES OF THE LIVER. 


a 


The action of the heart is sometimes slower, the pulse usually smaller 
than normal. : 


Rohrig has shown that the salts of the bile-acids produce this effect from a 
paralysis of the intracardiac ganglia. Ranke, Traube, Feliz and Ritter, Léwit, 
and others ascribe it to their deleterious action on the heart-muscle. Léwit and 
Spalitta assume that, at the same time, the cardiac-inhibitory fibers of the vagus 
are irritated. That the latter certainly play an important réle is demonstrated by 
the experiments of Weintraud, who, in one case, was able to increase the pulse- 
rate from 40 to 120 by an injection of atropin (1.2 mg.). [Mendez * found this 
accelerator action of atropin in only one out of five cases.—ED.] 

According to the animal experiments of Rywosch, small doses of the salts 
of the bile-acids dilate the vessels, whereas large ones contract them. 

Herz + was enabled to determine a dilatation of the capillaries in icterus with 
the onychograph. It is also stated that a capillary pulse is seen (Drasche). 

Over the heart svstolic murmurs and a reduplication of the second pulmonary 
sound are occasionally heard. According to my observations, these signs are not 
more frequent in icterus than in many other conditions in which the general health 
isreduced. Potain, without sufficient proof, assumes that a spasm of the pulmonary 
capillaries occurs reflexly by stimulation from the bile-passages. ft 


The body-temperature, as well as the pulse, are occasionally below 
normal (the former usually only a few tenths of a degree). Janssen 4 
found such a reduction in 6 out of 18 cases of catarrhal jaundice. 

Disturbances of sight, such as xanthopsia, hemeralopia, and nyctal- 
opia, are quite frequent. 


It was formerly assumed that the phenomenon of yellow vision was due directly 
to the yellow discoloration of the vitreous. This purely physical explanation has 
of late been again advocated by Hirschberg. Against this theory we can argue that, 
if it were correct, we should find this symptom more frequently, and that the degree 
of yellow vision should be in proportion to the degree of icterus. It is much more 
frobable that a toxic nervous cause produces ‘this symptom. 

In five cases of chronic icterus Obermayer found changes in the bones—“ drum- 
stick”’ fingers and toes—and painful periosteal swellings in the epiphyses of the 
arm and leg. [Similar ‘“‘clubbing” of the extremities of the fingers and toes has 
recently been reported in a few cases of hepatic cirrhosis of different forms.—Eb.] 

As the addition of the salts of the bile-acids to the blood outside of the body 
produces a liberation of hemoglobin, disintegration of red blood-corpuscles from 
this cause has been looked for in icterus. It is possible that it occurs, but it has not 
been demonstrated. A quantity of these bile-acid salts large enough to dissolve 
hemoglobin in the test-tube is never found circulating in the blood. 

Hurthle has made the interesting observation that in dogs after ligation of the 
ductus choledochus or after poisoning with toluylenediamin, the cells of the thyroid 
show evidence of increased glandular activity, evidenced by a large quantity 
of colloid in the epithelial cells and in the lymph-spaces. Hutrthle assumes that 
some chemical irritant is carried off by the blood. Lindemann in four cases of 
grave icterus in human subjects found the lymph-channels of the gland filled to a 
greater degree than normal, and therefore assumes an increased formation of colloid. 
He ascribes to this colloid an antitoxic action destined to replace or compensate 
the disturbed detoxicating function of the liver. 


In addition to bile-pigment and urobilin mentioned above, the urine 
contains cholalic acid even in those forms of icterus that cannot positively 
be attributed to stasis of bile, as in pyemia. 


In order to demonstrate the presence of this substance it is necessary to isolate 
it (by extraction with alcohol, precipitation with baryta-water, etc.) and then to 
perform Pettenkofer’s reaction (the formation of a purple color on addition of a 
solution of cane-sugar and of concentrated sulphuric acid). The method of Strass- 


* Rivista de la Sociedad medica Argentina, 1895, No. 22. 

t “Verhandlungen des Congresses fiir innere Medicin,” 1896, p. 467. 
t Chauffard, loc. cit., p. 692. 

§ Deutsches Archiv fir klin. Medicin, 1894, Bd. tim, p. 262. 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 489 


burger is shorter, but, even if a positive result is obtained, unreliable. It consists 
in the addition of a solution of cane-sugar and impregnation of a piece of filter-paper 
with the mixture, the paper being allowed to dry and being then touched with 
a drop of concentrated sulphuric acid. If cholalic acid be present, a violet spot 
appears. 


The quantity of cholalic.acid found in the urine is always small. 
Bischoff in one instance found 0.34 per diem, but as a rule much less will 
be found. 


Cholalic acid is also responsible for the slight cloudiness that is occasionally 
seen on addition of acids to icteric urine. 


According to Lépine, the quantity of that fraction of sulphur that 
is oxidized with difficulty is increased in the beginning of biliary 
stasis, but may drop back to below normal at the expiration of several 
days. Normally the “neutral” sulphur amounts to from 14% to 25% of 
the total sulphur, but in icterus as much as 48% may be present. It is 
probable that all or the greater part of this sulphur is derived from the 
taurin of the bile.* 

In severe or long-continued icterus albumin is found in the urine in 
small quantities, but sugar is not found in icterus per se. Wyatt tT saw 
the sugar disappear from the urine in a case of diabetes in which severe 
icterus supervened, but after the disappearance of the jaundice the 
sugar reappeared. According to Bouchard and his pupils, the toxicity 
of the urine is increased in icterus (see above). 

Fr. Muller found that the urinary excretion of nitrogen was not in- 
creased in icterus. The finding of other authors (Wilischanin, R. Schmidt), 
who report an increase in the nitrogen excretion, must be explained by 
something other than the icterus. 

As already stated, the ethereal sulphates are in some instances in- 
creased, in other instances not increased. 

Icterus is usually followed by disturbances of the general health, 
with a diminution of the general physical and mental powers and a 
feeling of weakness, discomfort, and depression. These symptoms are 
particularly conspicuous in the acute forms, and may be due to the 
gastro-intestinal disturbances that usually coexist or to auto-intoxication. 

In chronic biliary stasis these symptoms persist for a longer or shorter 
period of time. When they diminish, we can assume that a tolerance 
to the action of the poison becomes established. In complete obstruction 
of bile the general health is always impaired. General nutrition suffers 
greatly even though the patients may live for months or even years. 
Quite frequently a tendency to hemorrhages in the skin, in the connec- 
tive-tissue structures, and from the free surfaces of the body develops. 
These hemorrhages are undoubtedly capillary, but may nevertheless 
lead to serious loss of blood from epistaxis, hematemesis, and hemor- 
rhages from the intestine. 

Finally, in chronic jaundice linfavorable symptoms may appear in a 
somewhat acute manner and lead to the death of the patient in the course 
of a few days. With increasing weakness and loss of appetite stupor 
may develop, and death may follow a slowly deepening coma, often 
preceded by a stage of excitation with loud delirium and spasms of — 
indefinite type. This syndrome, often appearing unexpectedly, resembles 
an acute intoxication, and has been considered as such and called “ cho- 


* Noorden, loc. cit., pp. 274, 282. + The Lancet, May, 1886. 


440 DISEASES OF THE LIVER. 


lemia.”’ The poison was thought to be the bile-constituents circulating 
in the blood, and they were believed to exercise their deleterious effect 
as soon as the kidneys refused to excrete them vicariously. 

In the light of our present knowledge such an explanation is inade- 
quate, as we frequently see such a termination in other diseases of the 
liver not accompanied by icterus (atrophic cirrhosis), and animal experi- 
ments have shown that partial destruction (Denis and Stubbe) of the 
liver or disconnection of the organ by an Eck fistula (Nencki and Pawlow) 
can also produce serious nervous symptoms with spasms and be followed 
by a fatal issue without the presence of any disturbance in the outflow 
of bile. As we know that in chronic biliary stasis the parenchyma 
of the liver is always damaged in one way or the other and is reduced in 
bulk, we are justified in concluding that in these cases disturbances of 
the non-secretory functions of the liver may lead to death. 

According to this view, we are dealing with an auto-intoxication of 
a very complicated character, for, besides the constituents of the bile, 
we have toxic effects from all those substances which the liver is no 
longer capable of elaborating and of converting. It is probable that 
carbaminate of ammonia, which Nencki particularly accuses of great 
toxicity, plays an important rdéle in this connection. In addition to. 
this, a number of other unknown substances are active, among these ~ 
being putrefactive products from the intestine and disintegration prod- 
ucts of the liver-cells themselves. . 

In favor of the mixed character of this self-intoxication is the varying 
picture of the symptoms, which here, as in other forms of auto-intoxica- 
tion, such as diabetic coma and uremia, is very striking. It might be 
useful to designate these individually different processes as hepatargia 
(from dpyta, “inactivity”) or as hepatic intoxication. The name 
cholemia is not appropriate for the reason that the bile plays only a 
secondary rdle, while still more misleading and even less appropriate is 
the “acholia” of Frerichs. 

Even though the symptoms of hepatic intoxication appear suddenly, 
it can hardly be assumed that they really begin when they first become 
perceptible. It is very probable that certain much earlier perversions 
of the internal secretion of the liver-cells exist and involve possibly only 
a portion of the cells, and consist not so much in qualitative disturbances 
of function, particularly in the beginning, as in quantitative ones. It 
is impossible to state at what period of the biliary stasis these disorders 
begin; but it is probable that, in those acute conditions in which the 
liver is distended and enlarged, they may appear very early, perhaps 
only a few days after the formation of the obstruction, and that often 
the early appearance of severe general disturbances may be attributed 
to these perversions. 

We are not always justified in making a bad prognosis if serious 
nervous disturbances appear in the course of icterus, for in infectious 
icterus, and even in acute yellow atrophy, patients have recovered 
despite the presence of such symptoms. It is worthy of mention that 
Damsch has on several occasions observed cataleptic rigidity in children 
afflicted with epidemic icterus, and considers this symptom to be of 
toxic origin. 

In order to explain the occurrence of symptoms appearing in parts other 


than the digestive organs in benign forms of icterus, earlier authors assumed that 
these were due to intoxication from constituents of the bile, and in fact they suc- 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 441 


ceeded in finding that the salts of the bile-acids did possess toxic properties. It is 
definitely established by experiment (see above) that these salts act on the heart, 
the nerves of the blood-vessels, the kidneys, the central nervous system, and the 
blood, but it has not been determined whether the itching and the xanthopsia are 
caused by them. Within late years the toxicity of bilirubin has been investigated. 
Bouchard felt called upon to assume a poisonous action for bilirubin from the fact 
that bile is not as toxic if it has been previously decolorized by animal charcoal. 
While de Bruin found that bilirubin was more toxic, Plasterer and Rywosch found 
that it was much less toxic than the salts of bile-acids. The effect postulated by 
the former investigator is due, according to the latter authors, to the disturbances 
poe by the intravenous injections as such, and to the effect of the sodium 

ydrate used as a solvent. Plisterer observed the death of frogs after an injec- 
tion of only 4 mg. of bilirubin, and attributes its action to the formation of insoluble 
compounds with the lime-salts of the tissue-fluids and the resulting formation of 
thrombi in the vessels. 

Flint has credited cholesterin with the primary réle in the production of the 
toxic symptoms in icterus, basing his view on the increase in cholesterin in 
the blood. Miller attempted to strengthen this view experimentally, but his ex- 
periments were not free from error (thrombosis of vessels, toxic action of glycerin). 
According to Jankau,* the organism has the power of destroying even considerable 
quantities of cholesterin. The hypothesis of a cholesteremia can, therefore, not 
be maintained.f 

Even though we can hold certain constituents of the bile responsible for certain 
symptoms of the intoxication, this by no means excludes the share of other sub- 
stances in their production. Itching of the skin occurs especially in icterus, but it is 
also occasionally observed in cirrhosis of the liver without icterus. The hemorrhagic 
diathesis is neither an exclusive result of icterus nor of hepatic diseases in general, but 
it is nevertheless possible that it is caused by the toxic actionof the bile. This is illus- 
trated by a case reported by Hayem, where no stasis of bile was present, but where 
the gall-bladder had ruptured and the bile was absorbed from the peritoneum. 


The results of partial stasis of bile are less characteristic than are 
those of the complete form. The former occurs either as the result of 
a partial obstruction of the large bile-ducts, whereby only a portion 
of the bile is allowed to flow into the intestine and the pressure back- 
ward is only slightly increased, or as the result of the complete obstruc- 
tion of the finer bile-passages while others are patent or are incompletely 
involved. It is of no significance for intestinal digestion which of these 
forms of partial obstruction is present, as the important point is the 
amount of bile poured into the intestine. To judge from clinical observa- 
tion, it appears that even a small quantity is of the greatest value in 
comparison to complete absence of all bile. 

The disturbances of the general health, too, are much less severe 
and characteristic in partial than in complete obstruction of the bile, 
and as a rule the degree of the disturbance is proportionate to the degree 
of stasis. This is true only in a general way and approximately, as the 
color of the feces, of the skin, and of the urine, as we have already stated, 
' gives us only an approximate estimate of the percentage of the bile escap- 
ing in unnatural directions. On the other hand, it is necessarily im- 
portant, in judging of general symptoms, to know whether only a relative 
obstruction exists in the large ducts causing the entrance of bile into the 
blood, or whether a part of the-smaller ducts is completely occluded. 
In the former instance, when the obstruction is situated in one of the 
large ducts, all of the liver-cells are exposed to abnormal conditions of 
a slight degree, while in the latter a certain part of the liver-cells is seri- 
ously damaged, and though, in this case, other healthy liver-cells may 
act vicariously and assume the functions of the diseased ones, thus 


* See Naunyn, “Cholelithiasis,”’ p. 10. 
+ For further details, see Thierfelder, loc. cit., p. 253. 


442 DISEASES OF THE LIVER. 


compensating the loss of function, at the same time the diseased cells 
produce abnormal metabolic products that are absorbed and act as 
poisons. It cannot be stated in a general way which of the forms of 
stasis is capable of doing the most damage, as this varies in different 
cases, and probably the disturbances differ qualitatively. 

During life it is much more difficult to determine which form of 
biliary stasis exists from the specific symptoms than it is from other 
clinical phenomena. 


Compared with other organs, the first form of partial biliary stasis would re- 
semble a stenosis of the larger air-passages, the second one a capillary bronchitis 
with atelectasis and lobular pneumonia; or, in the case of the kidneys, the first form 
would be like a stenosis of the ureters, the second would be analogous to a calcareous 
infarction of the straight uriniferous tubules. 


It is, further, impossible to differentiate the form of icterus from 
parapedesis from that due to partial stasis. 


The assumption pronounced at one time, that bile-acids are found in the urine 
only in icterus from stasis, has been shown to be erroneous. 


Course.—The degree and the course of icterus vary according to the 
primary cause of the disease. It may last one day only and may simply 
cause a faint yellow discoloration of the skin, or it may produce deep 
green shades of discoloration and persist for months and even years. 
The average duration of an attack of icterus is several weeks, for the 
reason that the formation and the removal of the obstruction require 
a certain time, while the same applies to the staining of the tissues with 
pigment and the subsequent decoloration. Those forms of icterus that 
are not certainly due to biliary stasis act in the same way. Complete 
obstruction with absence of all bile from the intestine is found only in 
a small number of cases, and here only for a limited time. Before and 
after the time of complete obstruction relative degrees of stasis exist, 
gradually shading into the normal conditions. We are able, neverthe- 
less, to distinguish acute forms of icterus, usually of only slight grade, 
developing in the course of a few days and disappearing in a few weeks, 
and chronic forms, persisting for a longer time and developing from acute 
forms or extending over a very long period of time and developing very 
slowly. 

The intensity of icterus is not proportionate to its duration, as we 
see acute icterus of a severe degree and chronic icterus of a slight degree, | 
and vice versa. 

At first the bile-pigment enters the blood-serum and the tissue- 
juices; later the skin and the conjunctiva turn yellow and the urine 
contains urobilin. No bilirubin is present in the urine at this stage, 
but later bilirubin is also excreted. In cases in which the stasis of bile 
develops very rapidly the reverse picture may be seen, the appearance 
of bile-pigment in the urine preceding any yellow coloration of the skin 
or conjunctiva. Such an occurrence, however, is rare. Since sudden 
stoppage of the flow of bile is usually due to the impaction of a stone, 
and as this accident is always signalized by the appearance of severe 
pain, we have a measure for the time that must elapse between the 
oceurrence of the obstruction and the appearance of icterus. Some- 
times a yellow tint of the skin and the conjunctiva may be noticed after 
twelve hours,* but several days must elapse before the icterus reaches 


* Schiippel, loc. cit., p. 240; also personal observations. 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 448 


its highest degree of intensity. Colorless feces are, of course, not passed 
until all the colored portions have been evacuated. 


In dogs icteric discoloration of the tissues is not noticed for two or three days * 
after ligation of the ductus choledochus. As will be shown below, we are not justified 
in drawing conclusions in regard to human subjects from experiments of this kind on 
animals. The urine in these animals contains considerable quantities of bilirubin in 
from sixteen to twenty-four hours after the operation, and at the time of profuse 
secretion of bile (soon after eating) the urine may contain pigment as early as eight 
to ten hours after the operation (D. Gerhardt). 


If bile is excluded from the intestine for long periods of time, urobilin 
may disappear from the urine and bilirubin alone be excreted. 

If the obstruction is suddenly removed, as by the passage of the 
stone, a slighter degree of biliary discoloration of the urine will be noticed 
and colored feces will be found after the evacuation of the remains of 
the clay-colored matter. In the first days after the passage of the stone 
the stools will contain excessive quantities of pigment, owing to the 
emptying of the dilated bile-passages that occurs as soon as the obstacle 
is removed, while solid feces may even contain unchanged bilirubin. I 
once saw this continue for four weeks in a patient taking little nourish- 
ment. If the obstruction to the outflow of bile is completely removed, 
bilirubin will disappear from the urine within two days, and after this 
time only urobilin will be excreted. At the expiration of from three to 
eight days this too disappears, although the icteric color of the skin 
persists for a much longer time. 





SKIN. SERUM. URINE. FECES. 





Bile-pigment ©. 
1. Very light yellow. | Bile-pigment ©. | Urobilin © or a | Normal color. 
little only. 


Bile-pigment ©. 











2. Slightly yellow. Bile-pigment ++. Urobilin +. Colored. 
Bile-pigment +. | Usually somewhat 
3. Yellow. Bile-pigment ++. Urobilin +. dos than nor- 
mal. 
Bile-pigment +-. 
4. Deep yellow. Bile-pigment +. Urobilin + or ©. | Very little color or 
colorless. 





+ means presence, © absence, of the substance indicated. Hayem and Tissier 
arrange a scheme similar to this, with the exception that they find urobilin in the 
serum wherever it is present in the urine. 


In the majority of cases, however, icterus does not appear so sud- 
denly nor are the effects of the stasis of bile removed so speedily as in 
the examples quoted above. As a rule, several obstructions will be 
found in different divisions of he bile-duct system. The degree of 
obstruction, too, will vary, as is manifested by the varying coloration 
of the feces at different stages of the disease. The color of the stools, 
on the one hand, the quantity of urobilin and bilirubin excreted, on the 
other, are an index of the degree of stasis. In moderate degrees of biliary 
stasis considerable degrees of cutaneous icterus may be present and the 
urine at the same time contain no bile-pigment, but only a quantity 


* Frerichs, loc, cit., 1, p. 99. 


444 . DISEASES OF THE LIVER. 


of urobilin larger than normal; yet in these cases bile-pigment may be 
present in the tissues and be readily found in serous exudates if 
any are present, or in a blister raised for the purpose of making such 
examinations. The tissue-juices may contain a small quantity of bile- 
pigment, sufficient to stain the tissues, and at the same time not enough 
to be excreted unaltered in the urine. In the mildest degrees of cutaneous 
icterus bilirubin is absent even from the serum. It is possible to dis- 
tinguish four degrees of icterus, as shown in the table on page 443. 

This scheme is purely diagrammatic, and presupposes a certain 
uniformity in the different degrees of icterus. If the stasis increases or 
decreases, however, variations in the above may occur; thus, if the degree 
of obstruction increases, the urine may contain bile-pigment while the 
skin is only slightly colored or not colored at all;* on the other hand, if 
the degree of obstruction decreases, the skin may still be quite yellow 
and the bile-pigment and even the urobilin be completely absent from 
_ the urine. 

Even though the degree of stasis remains the same, the color of ~ 
patients with icterus changes daily, probably because of the varying 
degrees of turgescence of the skin and amount of blood in the cutaneous 
capillaries at different times. 

In long-continued obstruction it is probable that the formation of 
bilirubin decreases, and possibly the dirty yellowish color of such patients 
can be explained in that way. 


In addition to those cases that have been designated as instances of icterus from 
diffusion, and in which biliary stasis cannot be demonstrated, there are a number of 
cases that do not correspond to the picture of icteric discoloration of tissues and ex- 
cretions just described. Thus Andral,} for example, reports the case of a patient in 
whom the sweat and urine contained bile-pigment, but whose skin and conjunctiva 
were not colored yellow. I have observed a case of catarrhal icterus ¢ in which the 
stools were completely decolorized and in which the skin was colored intensely yellow, 
while the urine, which was darker than normal and of a brownish hue, at no time 
contained urobilin or bilirubin. Hayem reports the complete absence of bile-pig- 
ment or of urobilin in the urine of a case of icterus persisting with varying intensity 
for many months, and this in spite of the fact that both bile-pigment and urobilin 
were found in the blood-serum.§ Hanot and Gombault, || in a case of carcinoma of 
the pylorus and cirrhosis of the liver, found no icterus, although the ductus chole- 
dochus was occluded by cicatricial tissue. As in this case the hepatic artery 
was occluded (?) and the portal vein narrowed, it is possible that there was a de- 
creased secretion of bile. 

The symptoms of icterus from stasis are very different in animals and in man, 
This fact has not always been considered in drawing conclusions from animal experi- 
ments in regard to the phenomena observed in human subjects. In human beings 
occlusion of the bile-ducts leads to icterus of the urine and of the skin in from twelve 
to twenty-four hours, while ligation of the common bile-duct is not followed by 
icterus in dogs for two or three days (Tiedmann and Gmelin, Frerichs), in guinea-pigs 
for six days (Steinhaus) , and in rabbits Stadelmann and Gerhardt saw it occur in two 
or three days, and occasionally slight icterus on the first day. Gmelin’s reaction is not 
given by the urine for several days. 

In one experiment by Kiihne general tissue-icterus, and on certain days urinary 
icterus, were absent in a dog even after the bile-duct had been ligated for twenty-two 
days. The ramifications of the bile-passages were filled with crystalline and amor- 


* Compare, for example, Courvoisier, Correspondensblatt fir Schweizer Aerate, 
1896, p. 691. 

f Clinique médicale, 111, p. 373, cited by Frerichs, 1, p. 109. 

‘*t Quincke, V: irchow’s Archiv, Bd. xcv, p. 139. 

§ Soc. méd. des hdpitaux, May 14, 1897, cited in Berliner klin. Wochenschr., 
1897, p. 511. 

| Gazette méd. de Paris, 1881, p. 270, cited by Mangelsdorff, Deutsches Archiv fiir 
klin. Medicin, Bd. xxx1, p. 603. 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 445 


phous pigment, but none was seen in the liver-cells. V. Harley and v. Frey ligated 
both the bile-duct and the thoracic duct in a dog and found that even after many 
days (seventeen) the blood and the urine contained no bile-pigment. From these 
experiments we must conclude that icterus does not occur so readily in these animals 
as in human beings, either because they form less pigment or because their tissues are 
not so readily impregnated with bile-pigment. 

In contradistinction to this, it is known that bile-pigment very readily and 
easily enters the urine of dogs, so that these animals frequently show a slight degree 
of choluria when in a perfectly normal state, or at all events when starving. Naunyn* 
observed this in the majority of dogs, particularly older animals, and in cats. The 
presence of a biliary fistula does not alter this occurrence. As bile-acids also were 
found in the urine in larger quantities, the phenomenon was not due to concentration 
of the urine. In these animals diminution of the peristaltic action of the bile-pas- 
sages and a decrease in the portal pressure seem to cause an absorption of bile-acids 
and of bilirubin within the liver, and these small quantities are then excreted in the 
urine. Steiner makes a similar statement in regard to the urine of rabbits. Accord- 
ing to Stadelmann, choluria in the latter animals occurs only during starvation, and 
not constantly then. 

New-born children in this respect behave entirely differently from dogs. Here the 
most severe degree of tissue-icterus may exist and still the urine be clear and com- 
pletely free from bile-pigment in solution. On the other hand, the renal epithelium 
found in the sediment contains crystals and needles of bilirubin. The latter are also 
found as bilirubin infarcts in the collecting tubules of the kidneys (Virchow), and the 
pigment is seen in a crystalline form in the blood of the heart, both in icterus (Neu- 
mann) and occasionally without icterus (v. Recklinghausen). In new-born children, 
therefore, the tissues and the urine possess very slight solvent properties for bilirubin. 
Adults seem to occupy an intermediate position between the new-born and dogs in 
regard to the relative facility with which bilirubin can enter the tissues and the urine. 
Possible individual differences exist, so that different subjects incline more in the one 
or in the other direction. 

In man there is occasionally observed a condition analogous to the excretion of 
bile-pigment in the urine of dogs during starvation. 


The relation of urobilin to icterus merits special discussion. We 
have already mentioned that in slight degrees of icterus, as well as after 
or preceding severe degrees of obstructive jaundice, urobilin is excreted 
in the urine and colors it reddish-brown. This clinical observation 
induced Gubler to differentiate “ctére biliphéique,” or ordinary bile 
icterus, and an “ictére hémaphéique,” in which the coloration of the 
tissues and the urine was due to a pigment other than the ordinary 
bile-pigments. This new pigment, hémaphéin, was said to color filter- 
paper reddish-brown or salmon-colored instead of bile-yellow, and to 
be characterized by the appearance of a brown-red ring when super- 
imposed with nitric acid. He thought that it was formed in the liver 
in cases of an “insuffisance hépatique” in place of the ordinary bile- 
pigment. 

When C. Gerhardt discovered urobilin in the reddish urine of icteric 
subjects, he substituted so-called “urobilin icterus” in the place of the 
indefinite “ictére hémaphéique,” for the nitric acid reaction may be due 
to a variety of different pigments. 

Both forms are. said to be different from ordinary icterus, not only 
in regard to the pigment excreted in the urine, but also in the shade 
of the discoloration of the skin. Other authors have not confirmed | 
these observations and have not been able to discover urobilin in the skin 
by spectroscopic methods (Quincke). On the other hand, bilirubin is 
found in the blood-serum (Quincke) and in the sweat (Leube) of these 
patients, so that many of these cases are clearly aggravated instances 
of icterus from stasis of bile. 


* Loc. cit., p. 581. 


446 DISEASES OF THE LIVER. 


Genuine urobilin icterus, in which bile-pigment is replaced by uro- 
bilin, therefore, does not seem to exist; at least its existence has so far 
never been demonstrated (Quincke, Kelsch and Kiener, Tissier, D. 
Gerhardt, Fr. Miller). The cases that have been designated by this 
name are nothing more than mild cases of bilirubin icterus. It appears 
to me, therefore, that the name “urobilin icterus” is not happily chosen, 
for the reason that it is misleading. 

On the other hand, the cases designated with this name are of great: 
importance in the understanding of the pathogenesis of icterus, for the 
reason that they give us a clear insight into the subsequent fate of the 
bile-pigment in the body. We know that urobilin (“hydrobilirubin”’ 
of Maly) is normally found in the urine (Jaffé) and in the feces (“sterco- 
bilin” of Vanlair and Masius). In the same manner as it can be formed 
in the test-tube by the action of nascent hydrogen on bilirubin (Maly), 
so is it formed within the intestine by the reducing action of certain 
bacteria in the colon. In the meconium, therefore, bilirubin is found 
alone, and it is only after the expiration of several days that urobilin is 
found in the feces of the new-born. In the urine, in pathologic states, 
urobilin is readily recognized by its reddish color. That a relationship 
exists between this reddish color of the urine and certain digestive dis- 
turbances was known a long time before the discovery of urobilin. The 
discoloration of the urine by urobilin is increased in febrile diseases, 
particularly the infectious diseases, in heart lesions, in pneumonia, in 
certain diseases of the liver with and without icterus, and, finally, after 
parenchymatous hemorrhages or hemorrhages into the body-cavities. 
It is particularly among these cases that the defenders of “hemato- 
genous icterus’”’ formerly sought their chief evidence in support of their 
views. 

G. Hoppe-Seyler, D. Gerhardt, and Fr. Miiller have attempted to 
estimate urobilin quantitatively by weighing and by spectroscopic 
methods. The task is complicated by the presence of other pigments, 
the frequent occurrence of a chromogen, and, finally, by the fact that 
urobilin is so readily decomposed. The figures obtained, therefore, are 
only approximately correct. 


G. Hoppe-Seyler found (by weighing) normally in the total daily urine from 0.08 
to 0.14 grams, an average of 0.123 grams. 

It was increased in icterus with complete stasis (0.17 to 0.22 grams), in icterus 
immediately after the removal of complete obstruction (0.2 to 0.4 grams), in extrava- 
sation of blood (as much as 0.57 grams), as well as in pneumonia with icterus, in 
Basedow’s disease, and in retention of feces. 

It was decreased in complete exclusion of bile from the intestine (0.05 to 0.09 
grams), sometimes after the disappearance of an attack of icterus (0.06 to 0.09 grams), 
and in inanition, anemia, and cachexia. In these latter cases a diminution in the 
formation of bilirubin had probably occurred. 

Fr. Miller and D. Gerhardt estimated the urobilin by spectrophotometric 
methods. During fasting they found it much decreased (9 mg. instead of the normal 
13 to 20 mg. in twenty-four hours). It was increased in pneumonia whether accom- 
panied by icterus or not, in plumbism, heart lesions, hemorrhagic infarction, sepsis, 
scarlatina, erysipelas, phthisis, hemorrhage, hepatic disease with or without jaun- — 
dice, and in jaundice without reference to its intensity. 

The determination of urobilin in the feces is still more inaccurate and uncertain. 
(compare page 418). 

. a 


Some authors do not consider urobilin a uniform substance. Mac- 
Munn differentiated several kinds, particularly those of the urine and 
those of the feces. Jolles differentiates certain forms of urobilin that. 


GENERAL PATHOLOGY AND PHYSIOLOGY OF THE LIVER. 447 


are physiologic and are formed from the oxidation of bilirubin, and 
pathologic forms that are the product of the reduction of bilirubin, the 
former showing a diffuse absorption-band, the latter one that is sharply 
defined. For the present it is hardly possible to utilize these views in 
this place. 

There can hardly be any doubt that a large part of the urobilin that 
appears in the urine is absorbed from the intestine. In favor of this 
view we have the fact that urobilin is increased in digestive disorders 
and in constipation, and that it is decreased or disappears altogether 
(not only from the urine, but also from the bile and transudates, accord- 
ing to Fr. Miller, as is seen below) in complete exclusion of bile from the 
intestine, and is subsequently increased if the obstruction be suddenly 
removed so that large quantities of bile reach the intestine. 


Fr. Miller has also shown that in cases in which no bile can enter the intestine, 
and where consequently no urobilin is found in the urine, the latter can be made to 
appear if bile is given by the mouth. The administration of hemoglobin, on the 
other hand, does not cause it to appear. Traces of urobilin that are found in the 
feces and the urine even in complete obstruction of the bile-ducts may be derived 
from icteric mucus secreted by the mucous membrane of the intestine. 


A number of other observations, however, do not coincide with the 
purely enterogenous origin of urobilin. Above all, the typical cases of 
so-called “urobilin icterus,’’ in which less bile than normal enters the 
intestine, seem to contradict such an assumption. Moreover, this is 
still further proved by those cases in which hemorrhage with or without 
icterus is followed by urobilinuria (as, for example, the cases of Dick), 
where the only possible explanation would be to assume that the hemor- 
rhage produced polycholia and that this was followed by icterus. Several 
authors have, therefore, claimed that urobilin can be formed in the 
tissues by reduction of bilirubin, and that icterus disappears in this 
manner, the bilirubin being first reduced to urobilin in the tissues and 
then this pigment, which is more readily diffusible, being excreted by 
the kidneys (Kunkel, Quincke). Leube assumes that the bilirubin, 
circulating in the blood, is reduced in the kidneys. Fr. Miller, on the 
other hand, was not able to demonstrate that such a reduction occurred 
when he caused blood containing bilirubin to flow artificially through 
the kidneys. 

Bile-pigment is not necessarily the only source of urobilin. Hoppe- 
Seyler succeeded in making it from hematin by the action of nascent 
hydrogen, which makes it appear possible that urobilin can be formed 
directly from hemoglobin either in the liver or outside of that organ. 
_ In support of this view the occurrence of urobilinuria after blood-extrava- 
sation might be adduced. Here the explanation that it is formed after 
the occurrence of polycholia will not apply, particularly when the hemor- 
rhage occurs in patients with icterus in whom there is present an obstruc- 
tion to the outflow of bile (D. Gerhardt). This author found hemato- 
porphyrin in addition to urobilin in the urine after extravasations of blood, 
and, as this is another derivative of hemoglobin, its presence under 
these circumstances speaks directly against the above theory and lends 
support to the theory that urobilin is formed directly from hemoglobin 
and not through polycholia. Finally, it is possible that the liver under 
pathologic conditions may form urobilin. This assumption forms the 
basis of Gubler and Dreyfuss-Brissac’s “insufficiency of the liver.” 
Hayem and Tissier have recently defended this view, but they undoubt- 


448 DISEASES OF THE LIVER. 


edly go too far, as they-claim that urobilin can be formed only in the 
liver, and that its appearance in the urine is an index of the degree of 
disturbance of the liver and of the destruction of the red blood-corpuscles. 

As a matter of fact urobilin is usually found in the gall-bladder (Fr. 
Miller, Tissier) under conditions that make it improbable that it is a 
postmortem change (Tissier). D. Gerhardt and Beck claim that this 
urobilin is absorbed from the intestine and excreted by the liver, and 
base their statement on the observation that in dogs this urobilin was 
absent from the bile flowing from a fistula after ligation of the ductus 
choledochus and reappeared after the administration of bilirubin by the 
mouth. | 

TD. Gerhardt and Fr. Miller found urobilin in the blood-serum with 
and without icterus, and in serous exudates. | 

Giarré adduces as evidence of the formation of urobilin outside of 
the intestinal tract the observation that in infants with fever this sub- 
stance may be found in the urine although not in the intestine. 

The facts quoted contain many contradictions and make it impossible 
to make definite statements in regard to the genesis of urobilin and its 
significance in icterus. We cannot expect much from animal experi- 
ments for the reason that urobilin, when found at all in the urine of 
animals, is present only in very small and varying amounts. The greater 
part of the urobilin found in the urine is derived from the intestine, but 
it must be remembered that the quantity of urobilin absorbed in this 
manner is dependent not only on the quantity of pigment present in 
the intestine, but also on the degree of absorption, which is subject to 
many fluctuations. 

I consider it very probable that under certain circumstances urobilin 
can also be formed outside of the intestines, either from bilirubin or from 
hemoglobin directly. In case it is ever formed in the liver under patho- 
logic conditions, it may travel along a path different from that traversed 
by bilirubin. For instance, it may enter the lymph- or blood-channels 
directly from the liver-cells, or it may first enter the bile-passages and 
later be reabsorbed. 

Diagnosis.—The diagnosis of icterus is made from the yellow dis- 
coloration of visible parts of the body. The yellow color of the sclera 
is usually noticed first, but it is necessary to remember that in health 
these tissues are occasionally tinged with yellow. The yellow color of 
the hands and of the face is not so readily recognized as is the discolora- 
tion of the trunk. It is important to differentiate the strictly yellow 
shade from other possible tints, and it is of practical importance to re- 
member that the yellow color of the skin can only be properly observed . 
by daylight. By candle, lamp, or gaslight it cannot be seen, or is barely 
perceptible; while in electric light or Welsbach light it is more readily 
visible. It is sometimes useful to compare the color of the skin with that 
of white linen. 

The dark color of the urine is of diagnostic importance, but it should 
never be forgotten that it may be due to pigments other than bilirubin. 
Many cases of icterus are accompanied, during a part or all of their 
course, by the presence of urobilin alone in the urine. Bilirubin is 
présent only where more severe degrees of biliary absorption are present, 
and the demonstration of its presence by Gmelin’s reaction is an index 
more of the degree and the stage of the absorption of bile than of its 
existence. 


LITERATURE ON ICTERUS. 449 


The color of the feces must always be observed. With the reserva- 
tions made above, their color gives valuable information in regard to 
the existence of biliary stasis and of its intensity. 

Of the other concomitant symptoms of icterus, itching of the skin 
is very frequent, slowing of the pulse is present only in a small number 
of cases, and visual disturbances are observed very rarely. 


Whereas all other forms of pigmentation of the skin (sunburn, cachexia, morbus 
Addisonii) can be readily distinguished from icterus by their brownish shade, the 
administration of picric acid and of its salts produces a discoloration of the skin and 
sclera hardly distinguishable from icterus following biliary stasis. This form of 
discoloration follows, for instance, the administration of potassium picronitrate 
(0 5 to 1.0 per diem) in the treatment of tapeworm, and malingerers have occasion- 
ally used the drug for this purpose. The urine here is colored yellow in the begin- 
ning, later reddish-brown, but naturally does not give Gmelin’s reaction for bilirubin. 
Large doses of picric acid cause hemolysis, albuminuria, and hematuria.* 


LITERATURE ON ICTERUS. ‘ 


Affanassiew: “Ueber anatomische Verinderungen der Leber wihrend verschie- 
dener Thatigkeitstzustande,”’ ‘‘ Pfliger’s Archiv,” Bd. xxx, p. 424, 1883. 

Biernacki: “ Darmfaulniss bei Nierentziitundung und Icterus,”’ “ Deutsches Archiv fiir 
klin. Medicin,”’ Bd. xurx, p. 87, 1891. 

Brieger: ‘ Einige Beziehungen der Faulnissproducte zu Krankheiten,’’ “ Zeitschr. 
fir klin. Medicin,”’ Bd. 111, p. 465, 1881. 

Brissaud, E., et Ch. Sabourin: “‘ Deux cas d’atrophie du lobe gauche d. f. d’origine 
biliarie,”’ ‘ Archives de physiolog.,’’ 1884, 1, p. 345, 444. 

Damsch und Cramer: “ Ueber Katalepsie und Psychose bei Icterus,”’ “ Berliner klin. 
Wochenschr.,’’ 1898, p. 277, 300. 

Dastre: ‘‘ Recherches sur la bile,’ ‘‘ Archives de Physiolog.,’’ 1890, p. 315. 

Dick, R.: “ Ueber den diagnostischen Werth der Urobilinurie fur den Gynikologen,”’ 
“ Archiv fir Gynakologie,’”’ Bd. xxur. _ 

Dreyfuss-Brissac: ‘“ De l’ictére hémaphéique.’”’ Thése de Paris, 1878. 

Gerhardt, C.: “Ueber Urobilinicterus,” “Correspondenzblatt des allgemeinen irzt- 
lichen Vereins in Thiringen,” 1878, No. 11. 

Gerhardt, D.: “Zur Pathogenese des Icterus,” “ Verhandlungen des Congresses fiir 
innere Medicin,”’ 1898, p. 460. 

— “ daa Hydrobilirubin und seine Beziehungen zum Icterus.”? Dissertation, Ber- 
in, 1889. 

— “Ueber Urobilin,” “ Zeitschr. fiir klin. Medicin,” Bd. xxx, p. 305, 1897. 

Gluzinski: ‘‘ Formalinprobe des Harnes,” “ Wiener klin. Wochenschr.,’’ 1897, No. 52. 

Gorodecki, H.: “Ueber den Einfluss des Hamoglobins auf die Zusammensetzung 
der Galle.”” Dissertation, Dorpat, 1889. 

Grimm, F.: ‘ Ueber Urobilin im Harn,” “ Virchow’s Archiv,”’ Bd. cxxxu, p. 246, 
1893. 

Harley, V.: “ Leber und Galle wihrend dauernden Verschlusses von Gallen- und 
Brustgang,” “ Archiv fiir Anatomie und Physiologie,’’ Physiologische Abthei- 
lung, 1893, p. 290. 

Hayem: “ Ictére biliphéique; hémophilie,” “ Gazette des hépitaux,’’ 1889. 

Hiirthle: “Ueber den Secretionsvorgang in der Schilddriise,” ‘Deutsche med. 
Wochensch.,”’ 1894, No. 12, p. 267. 

Janowski: “‘ Beitrige zur patholog. Anatomie der biliiren Lebercirrhose,” “ Ziegler’s 
Beitrige zur patholog. Anatomie,” 1893, p. 79. 

Jolles, A.: “Ueber das Auftreten und den Nachweis des Urobilins im normalen und 
pathologischen Harn,” “ Wiener klin. Rundschau,” 1895, No. 46-48. 

Kiener und Engel: “Sur les conditions pathogéniques de l’ictére et ses rapports avec 
Vurobilinurie,”’ “ Archives de Physiolog.,”’ 1887, p. 198. 

Kihne, W.: “ Beitrag zur Lehre vom Icterus,” “ Virchow’s Archiv,” Bd. x1v, p. 310, 


1858. 

Kunkel: “Ueber das Auftreten verschiedner Farbstoffe im Harn,” “Virchow’s Ar- 
chiv,” Bd, Lxxrx, p. 435, 1880. 

Langhans: “Virchow’s Archiv,’’ Bd. xrx, p. 66. 


* Kobert, “ Lehrbuch der Intoxicationen,” p. 496. 
29 


450 DISEASES OF THE LIVER. 


Lépine: “Sur un nouveau symptome de trouble de la fonction biliare,”’ “ Revue de 
Médecine,”’ 1881, p. 27, 911. 

Létienne, A.: “ De la bile 4 l’état pathologique.”’ Thése de Paris, 1891. 

Leyden, E.: ‘ Beitrage zur Pathologie des Icterus,’’ Berlin, 1886. 

Liebermeister: “Zur Pathogenese des Icterus,’” ‘ Deutsche med. Wochenschr.,’”’ 
1893, No. 16. 

Lindemann, W.: “Ueber das Verhalten der Schilddriise beim Icterus,” “ Virchow’s 
Archiv,’’ Bd. cxu1x, p. 202, 1897. 

Lorenz, H.: “ Ueber den Burstenbesatz an pathologischen und normalen Nieren,”’ 
“ Zeitschr. fur klin. Medicin,’”’ Bd. cuit, p. 436, 1898. 

Léwit: ‘‘Ueber den Einfluss der gallensauren Salze,” ‘Prager Zeitschr. fiir Heil- 
kunde,” 1881, p. 459. 

Minkowski: “ Verhandlungen des XI. Congresses fiir innere Medicin,” p. 127, 1892. 

Mobius, P. L.: “Ueber die Nieren beim Icterus,’” “ Archiv der Heilkunde,” Bd. 
Xvi, p. 83, 187. 

Miller, Fr.: ‘‘ Untersuchungen uber Icterus,”’ “ Zeitschr. fiir klin. Medicin,”’ Bd. x1, 
p. 45, 1887. 

— “Ueber Icterus.’”’ Discussion in the Medical Section of the Silesian Gesselschaft 
fir vaterlandische Cultur, January, 1892; Sitzungsbericht des XI. Congresses 
fiir innere Medicin, 1892, p. 118 

Miller, K.:“‘ Ueber Cholesterimie,”’ ‘‘ Archiv fiir experimentelle Pathologie,” Bd. 1, 
p. 213, 1873. 

Munk, J.: “ Ueber die Resorption von Fetten, etc., nach Ausschluss der Galle vom 
Darmcanal,” “ Virchow’s Archiv,”’ Bd. cxxt, p. 302, 1890. 

Nauwerck, C.: “Leberzellen und Gelbsucht,’ ‘‘Miinchener med. Wochenschr.,” 
1897, No. 2. 

Naunyn and Minkowski: ‘‘ Ueber den Icterus durch Polycholie,” “ Archiv fur ex- 
perimentelle Pathologie,’’ Bd. xx1, 1886. 

Naunyn, B.: “ Beitrige zur Lehre vom Icterus,’’ ‘Reichert und du Bois’ Archiv,” 
1868, p. 401; 1869, p. 579. 

v. Noorden: “ Pathologie des Stoffwechsels,”’ 1893, p. 264. 

Obermayer, F.: ‘ Knochenverinderungen bei chronischem Icterus,”’ “ Wiener klin. 
Rundschau,” 1897, Nos. 38, 39. 

Pick, E.: ‘‘ Ueber die Entstehung des Icterus,” “ Wiener klin. Wochenschr.,”’ 1894, 
Nos. 26-29. 

Plaesterer, R.: ‘ Ueber die giftigen Wirkungen des Bilirubins.”” Dissertation, Wurz- 
burg, 1890. 

Poncet: “ De l’ictére hématique traumatique.’”’ Thése de Paris, 1874. 

Poth: “Stoffwechselanomalien in einem Falle von Stauungsicterus,” “ Pfliiger’s 
Archiv,” Bd. xtv1, p. 509, 1890. 

Quincke, H.: “ Beitrage zur Lehre vom Icterus,”’ “ Virchow’s Archiv,” Bd. xcv, 1884. 

Raynaud et Sabourin: ‘‘ Note sur un cas d’ énorme dilatation des voies biliaires,”’ 
etc., “ Archives de physiolog.,’’ 1879, 11, p. 37. 

v. Recklinghausen: ‘‘ Allgemeine Pathologie,” p. 434, 1883. 

Rohrig: “Ueber den Einfluss der Galle auf die Herzthitigkeit.” Dissertation, 
Wurzburg, 1863. 

Rywosch: “Ueber die giftigen Wirkungen der Gallensduren,” “ Kobert’s Arbeiten 
des pharmakologischen Institutes zu Dorpat,” 11, p. 102, 1888. 

— “Ueber die Giftigkeit der Gallenfarbstoffe,” ibid., vi, p. 157, 1891. 

Sauerhering: ‘ Ueber multiple Nekrosen der Leber bei Stauungsicterus,” ‘‘ Virchow’s 
Archiv,” Bd. cxxxvil, p. 155, 1894. 

Schmidt, R. (Neusser): “Zur Stoffwechselpathologie des Icterus catarrhalis,” 
“Centralblatt fiir innere Medicin,” 1898, No. 5. 

Schrader: “Der himatogene Icterus,’”’ “Schmidt’s Jahrbiicher,” Bd. ccxvi, p. 73, 
1887. 

Senator: “‘ Ueber Icterus,” “ Berliner Klinik,” No. 1, 1888. — 

Spalitta: “Die Wirkung der Galle auf die Herzbewegung,” “ Moleschott’s Unter- 
suchungen zur Naturlehre,’”’ Bd. x1v, p. 44, 1889. 

Stadelmann: “Ueber die Natur der Fettkrystalle in den Faces,’’ “‘ Deutsches Archiv 
fiir klin. Medicin,” Bd. xu, p. 372, 1887. 

— “Der Icterus,” Stuttgart, 1891, “ Archiv fiir experimentelle Pathologie,” Bd. x1v, 

» p. 231; Bd. xv, p. 422; Bd. xvi, p. 118; Bd. xxrv. 

— “Ueber den Kreislauf der Galle im Organismus,’’ “ Zeitschr. fiir Biologie,’ Bd. 
xxxiv, 1897. 

Stern: “Ueber die normale Bildungsstite des Gallenfarbstoffs.” Dissertation, 
K6nigsberg, 1885. — 


~ 


GENERAL ETIOLOGY. 451 


Tissier, P.: “ Essai sur la pathologie de la sécrétion biliaire.”” Thése de Paris. 1889, 

Weintraud: “Ueber die Ursackien der Pulsverlangsamung im Icterus,” “ Archiv fiir 
experimentelle Pathologie,’”’ Bd. xxx1v, p. 37, 1894. 

Werner: “ Einwirkung der Galle und gallensauren Salze auf die Ni ieren,” “ Archiv fir 
experimentelle Pathologie,’ Bd. xxiv, p. 31, 1888. 

Wyss, O.: “ Beitrage zur Histologie Sad ikter. "Leber, ”” “Virchow’s Archiv,” Bd. 
CCCLI, p. 553, 1866. 


EXPERIMENTAL BILIARY OBSTRUCTION. 
(D., Dog; C., Cat; R., Rabbit ; G., Guinea-pig. ) 


Beloussow : ‘‘ Ueber die Folgen der Unterbindung des Ductus choledochus” (G,. R.), 
“Archiv fiir experimentelle Pathologie und Pharmakologie,”’ Bd. xiv, p. 200, 
1881. 

Chambard: “Contribution 4 l’étude des lésions histologiques du foie consécutives 4 
la ligature du canal choledoque” (G.), “‘ Archives de Physiologie,”’ ete., 1877. 

Charcot et Gombault: “ Note sur les altérations du foie consécutives aA la ligature 
du canal choledoque”’ (G.), ‘ Archives de Physiologie normale et pathologique,”’ 
1876, p. 271-299. 

Foa e Salvioli: “ Ricerche anatomiche experimentali sulla pattologia del Fegato 
(G., C., D., R.), “ Archivio per le science mediche,” vol. 11, 1878, and ‘“ Central- 
blatt fur die medicinischen Wissenschaften,” 1878, No. 33. 

v. Frey: “ Ueber Unterbindung des Gallenganges und des Milchbrustganges bei Hun- 
den,” “ Verhandlungen des Congresses fiir innere Medicin,”’ 1892, p. 115. 

Gerhardt, D.:‘ Ueber Leberverainderungen nach Gallengangsunterbindung” (R.., 

D.), “ Archiv fiir experimentelle Pathologie,” Bd. xxx, p . 1, 1892. 

Lahousse: ‘‘ Recherches expérimentales sur |’influence exercée sur la structure du foie 
par la ligature du canal choledoque” (G., R.), “ Archives de Biologie,” vol. vu, 
1, Fasc., 1887. 

Legg, Wickham: “On the Changes in the Liver which follow Ligature of the Bile- 
ducts” (C.), “St. Bartholomew’s Hospital Reports,” vol. rx, London, 18738. 

Leyden: “ Beitrage zur Pathologie des Icterus” (D.), p. 83, Berlin, 1866. 

Litten: Klinische Beobachtungen, 1, ‘‘ Ueber die biliare Form der Lebercirrhose und 
den diagnostischen Werth des Icterus” (G.), ‘ Charité-Annalen,”’ 1880. 

Mayer, H.: “Ueber Veranderung des Leberparenchyms bei dauerndem Verschluss 
des Ductus choledochus” (C., R.), “ Medicinische Jahrbiicher,’’ Wien, 1872. 
Pick: “Zur Kenntniss der Leberveriinderungen nach Unterbindung des Ductus 

choledochus”’ (R.), “ Zeitschrift fir Heilkunde,” Bd. x1, 1890. 

Popoff, L.: “ Ueber die natiirliche pathologische Injection der Gallenginge und einige 
andere, bei der Unterbindung | des Ductus choledochus bei Thieren beobachtete 
pathologische Erscheinungen”’ (D.), ‘ Virchow’s Archiv,’ Bd. Lxxx1, 1880. 

Simmonds: “ Ueber chronische interstitielle Erkrankungen der Leber” CR. ) , “ Archiv 
fiir klin. Medicin,”’ Bd. xxvn, p. 85, 1880. 

Steinhaus: “Ueber die Folgen des dauernden Verschlusses des Ductus choledochus” 
(G.), “ Archiv fiir experimentelle Pathologie und Pharmakologie,”’ Bd. xxvin, 
p. 432, ff., 1891. 

Stern, H.: “Ueber die normale Bildungsstatte des Gallenfarbstoffes” (in pigeons). 
Dissertation, Kénigsberg, 1885. 


3. GENERAL ETIOLOGY. 


Diseases of the liver may be caused by mechanical, chemical, and 
nervous influences. 

Among the mechanical causes. traumata are rarely responsible for 
lesions. A more frequent cause is long-continued and slowly acting 
pressure from without, producing the corset liver. The pressure exerted 
upon the parenchyma. of the liver by prolonged distention of the blood- 
capillaries (as in cardiac lesions) or of the bile-capillaries (as in biliary 
stasis) causes both disturbances in nutrition and atrophy. 

Chemically, the liver can be-damaged by substances that enter it 
either in solution or undissolved. They act primarily on the different 
systems _ channels within the organ, either through the afferent blood- 


452 DISEASES OF THE LIVER. 


vessels (portal vein and hepatic artery, especially the former), through 
the bile-passages (as in stasis of bile and invasion by micro-organisms), 
or, more rarely, in a direction contrary to the blood-current, through 
the hepatic veins and the lymphatics. 

The substances noxious to the liver are, as a rule, introduced from 
without with the nourishment, but may also be formed within the organ- 
ism. Such substances are alcohol or phosphorus or arsenic, antimony, 
chloroform, etc., introduced experimentally. Probably included in this 
group are a whole series of substances which are partly introduced as such 
with the food and partly formed within the intestine by the action of bac- 
teria. These latter bodies, in particular food-products and toxins, are 
very difficult to detect owing to their small quantity, yet they are very 
harmful. All these substances acting chemically enter the liver by the 
portal vein, so that they first affect the cells in the peripheral parts of 
the hepatic lobules. This may explain why so many diseases of the 
liver originate in this particular region. 

It is further probable that many products of internal metabolism 
possessing toxic properties enter the liver. 

Micro-organisms play a very important réle in the pathology of the 
liver. The bacteria circulating in the blood-current accumulate within 
the hepatic capillaries from mechanical causes, or perhaps for other 
reasons, and may there be seen either free or within leucocytes. Among 
these must be mentioned the bacillus of typhoid, of tuberculosis, and of 
anthrax, actinomycosis fungus, and streptococci and staphylococci. 
The parasite of malaria belongs to the same group. [Adami’s discovery 
of colon bacilli, especially in cirrhosis, is of great importance in this 
connection.—ED.] 

We know comparatively little of the exact effect of these germs on 
the liver in acute diseases, but it can hardly be doubted that they act 
both mechanically and by the action of their specific toxins, producing 

the alterations in the parenchyma frequently seen in these diseases. 
- Occasionally miliary abscesses (as in pyemia) or changes in the liver-cells 
(as in typhoid fever) with conglomerations of leucocytes are seen around ~ 
these bacterial colonies. These little colonies are occasionally seen in 
enormous numbers, and may develop into larger foci in long-lasting 
diseases, as in tuberculosis and actinomycosis. Corresponding to the 
peculiar arrangement seen in the deposits of grains of cinnabar, these 
foci seem to show a certain predilection for the periphery of the lobules. 

Micro-organisms may enter the liver by another channel: viz., the 
bile-passages. They do not follow the course of the bile, but enter 
the liver from the intestine. They probably begin to multiply within the 
larger bile-passages; in time, however, they penetrate and damage the 
smaller bile-passages and the parenchyma of the liver. The most im- 
portant of these bacteria are Bacterium coli, staphylococci, and strepto- 
cocci. Here the separation cannot be made between a local infection 
alone and a general infection with local manifestations. 

Larger forms of parasites (echinococcus, distoma, and ameba) enter 
the liver from the intestine, entering the blood-vessels and being carried 
along in the blood of the portal vein. In the same manner large and 
srhall abscesses are formed in the liver when ulcerative processes or foci 
of suppuration are present in the intestine (as in dysentery); while 
carcinomatous infection of the liver may occur in the same way from 
cancer of the gastro-intestinal tract. 


GENERAL ETIOLOGY. | 453 


Abscesses and neoplasms rarely originate within the liver as a result 
of infection through the general circulation (by way of the hepatic arteries 
or veins). Still more rare is infection through the lymphatics from the 
stomach by way of the portal glands. From the peritoneum inflamma- 
tion and formation of neoplasms extend only into the most superficial 
portions of the organ. In some diseases, such as typhoid fever, involve- 
ment of the liver may occur through several of these channels. 

We see, therefore, that nearly all the infections of the liver occur 
from the intestine by way of the portal blood, or by way of the bile- 
passages, and that micro-organisms play an important rdle, partly 
mechanically, partly by the toxins which they produce. 

It is difficult to form a correct estimate of the significance of nervous 
influences in the production of diseases of the liver. While we cannot 
always definitely state that they are the cause in a given instance, and 
while we frequently wrongly attribute certain lesions to their action, 
we are not justified in altogether ignoring their significance, since there 
can be no doubt that they can exercise an important predisposing influence, 
and we know positively that the blood- and bile-currents are influenced 
by the nervous system. Moreover, we have reason to believe that in all 
probability the functional activity of the liver-cells is affected by nervous 
influences. In addition, certain psychic and other nervous influences 
exercise an indirect effect on the liver through diminished cardiac activity 
and disturbance of digestion. 

The frequency with which diseases of the liver occur varies in different 
countries and at different times. According to medical tradition, dis- 
eases of the liver are more frequent in tropic countries and during the 
warm seasons of the year. Exact proofs of these statements are lacking, 
and would be difficult to obtain. We can, of course, readily understand 
the localized occurrence of lesions caused by certain parasites, such as 
echinococcus, of the relative frequency of dysentery and amebic abscesses 
in tropic countries, and of malaria in southern Italy. These differences, 
particularly in regard to the geographic peculiarities, are also explainable 
by differences in the mode of life of different peoples, such as the quan- 
tity of alcohol consumed, perhaps the general character of the food, 
and the amount of exercise taken. These are all important determining 
factors. The statements made in regard to the influence of hot climates 
are based principally on observations made on Europeans that had im- 
migrated into those countries. The appearance of “bilious” diarrheas 
accompanied by fever, so frequently noted, has led to the conclusion 
that the functional activity of the liver was increased. Even did these 
attacks signify an increase in the formation of bile, it would not neces- 
sarily indicate an increase in the metabolic functions of the liver. We 
are, it is true, justified in drawing such a conclusion indirectly from the 
fact that, owing to a smaller demand for the production of body-heat, 
less oxygen is absorbed and oxidation is reduced. As a result of this, 
we might expect that some of the intermediary products of metabolism — 
would not be completely oxidized and would accumulate in the liver. 
In this manner both an excessive functional strain is imposed and quali- 
tative changes in the function of the liver are produced. This condition 
will occur the more readily, the more food is ingested beyond that re- 
quired for the needs of the body. Thus, the first few years of a sojourn 
in the tropics are particularly deleterious to Europeans for the reason 
that the adjustment of general metabolism to the new conditions is — 


454 DISEASES OF THE LIVER. 


only slowly accomplished, and because the necessary reduction in the 
amount of food taken is not made at once. Among the natives, and among 
the women and children of the European residents, diseases of the liver 
(aside from the parasitic forms) are not more frequent than in other regions. 
In men the greater disposition to these diseases becomes less noticeable 
in proportion to the care they exercise in changing their accustomed 
mode of life by adopting a more moderate and less nitrogenous diet. 
According to the general consensus of opinion, the use of alcohol in even 
moderate doses is especially pernicious, just as in other countries similar 
quantities of alcohol act more unfavorably if less bodily exercise is taken 
or if the stomach is empty. 


According to Cayley, the following proportion of diseases of the liver is seen 
among the British troops in India for each 1000 per annum: 


EUROPEAN SOLDIERS. NATIVE SOLDIERS. 
Cases of sickness............. 24.5 per mille 1.6 per mille. 
NMOrtanty tse kore On ae 1.43 per mille 0,11 per mille. 


The predisposition to dysentery and malaria, on the other hand, is the same for 


In India Europeans seem to suffer more from diseases of the liver than they do in 
Ceylon and in the West Indies. This is particularly the case in Madras, where the 
temperature is uniformly high during the whole year. In India residence in the 
mountainous districts is not favorable for patients with diseases of the liver because 
of the diarrheas and chillings to which they are subject in such localities. 

The following table shows the influence of alcohol on diseases in general: 


IN THE WHOLE ARMY. AMONG THE TEMPERATE. 


DiSGAROA > bboy he ee anew eae 75 per mille ' 41 per mille. 
MOrtalieyes soe cc yuo es ees 15 per mille 3 per mille. 


Whenever the liver, for any of the reasons detailed above, is in a 
state of unbalanced equilibrium, it is readily seen that even slight ex- 
ternal influences may produce actual diseases. Such a rdéle is played 
by dyspepsia. Other agencies, also, that would not be considered 
important predisposing factors at home, such as the heat of the sun, 
fatigue, sudden chilling, particularly during sleep, are capable of doing 
much harm under these conditions. 

The forms of hepatic lesions peculiar to warm climates are acute, 
_ parenchymatous, and suppurating hepatitis, chronic enlargement of the 
liver, and the complication of jaundice in all acute diseases. 

The seasonal differences in the appearance of certain diseases of the 
liver, as shown by the frequent occurrence of icterus even in temperate 
climates, perhaps depend upon differences in the bacterial flora of the 
articles of diet and the consequent changes in the bacterial contents of 
the intestinal tract. 

The relation between the action of the liver and disturbances of 
metabolism is probably very intimate, and at the same time is very 
little understood. ‘ French and English authors particularly, more in- 
stinctively than from any exact reasoning, attribute a great significance 
to the liver in the causation of gout (a term by them widely applied). 
There. can be no doubt that the function of the liver is perverted in 
diabetes mellitus, and in many cases of obesity it is probable that some 
one of its many functions is overactive. 

Such qualitative changes and perversions of its function may be 
followed by anatomic changes and permanent impairment of function. 


GENERAL SYMPTOMATOLOGY. 455 


A primary functional disturbance of the liver may often produce these 
metabolic perversions. 

As in the majority of diseases, a combination of a variety of condi- 
tions and defects is almost always necessary to produce lesions of the 
liver; any one of the different factors alone would probably not have 
been able to cause the lesion. 


LITERATURE. 


Cayley, H.: “Tropical Diseases of the Liver,” in A. Davidson, ‘“‘ Hygiene and Diseases 
of Warm Climates,’”’ Edinburgh and London, p. 612, 1893. 

— “Tropical Affections of the Liver,” Transactions of the Eighth International 
Congress for Hygiene in Budapest, p. 695, 1894. 

Hirsch: “ Histor.-geographische Pathologie,” 111, p. 267, 1886. 

Scheube: “ Krankheiten der warmen Lander,” p. 374, Jena, 1896. 


4, GENERAL SYMPTOMATOLOGY. 


In the clinical picture of diseases of the liver local symptoms, both 
subjective and objective, are inconspicuous. The same, as we have 
seen, applies to the study of the physiology of the liver, in which the local 
manifestations of functional activity are less apparent than, for ex- 
ample, in the case of the thoracic organs or even of the stomach and 
intestine. The shape and size of the liver are changed only in severe 
and in long-continued diseases. We have already discussed the method 
of determining these changes and the degree of accuracy of the results. 

Pain is of subordinate importance as a symptom, as the parenchyma 
of the liver is non-sensitive, and consequently a great many diseases 
of the liver run their course without producing any pain. Among these 
we can mention fatty infiltration, amyloid degeneration, the various 
forms of cirrhosis, and echinococcus disease. Even great enlargement 
of the liver, if it progresses and develops slowly, may be painless and 
may only cause disagreeable subjective symptoms by impeding some 
of the movements of the body, by interfering with respiration, and by 
interfering with the function of neighboring organs, such as the heart, 
stomach, and intestine. 

Pain proper in the hepatic region is caused by lesions of the serous 
covering of the organ and of the bile-passages. 

Pain in the serous covering is most frequently caused by direct 
inflammation of this tissue or, less frequently, by distention of the capsule 
of the liver in very rapid enlargement of the organ. Consequently, a 
great many diseases of the liver are occasionally, though not constantly, 
painful. Examples of these are rapidly developing hyperemia, phos- 
phorus-liver, abscess, and syphilitic hepatitis. Carcinoma and acute 
atrophy are also occasionally very painful. Sometimes the pain is 
distributed over the whole organ; in other cases, particularly in localized 
lesions, it is found only in the diseased area. 

Pressure usually aggravates all forms of hepatic pain, as.do move- 
ments and all forms of succussion, such as riding on horseback. If the 
patient lies on the left side or bends the body toward the left, pain origi- 
nating from the serous covering of the liver is usually ameliorated, while, 
on the other hand, if the liver is very much enlarged, the position on the 
right side seems to afford more relief and to remove some of the pressure 
exercised on neighboring organs. 


456 DISEASES OF THE LIVER. 


Pain in the right shoulder is a peculiar symptom that is found in 
many diseases of the liver, either in connection with or independent 
of localized pain. The pain may radiate from the shoulder to the side 
of the neck, to the scapula, or into the right arm. It may be either 
indefinite in character, or drawing, tugging, or burning, and is often 
aggravated by pressure over the liver or by movements of the arm. It 
is found chiefly in abscess and in hyperemia, but also in echinococcus 
disease and in carcinoma, and occasionally in syphilis and cholelithiasis. 
This pain seems to be present only in diseases that involve the convex 
surface of the liver. In abscess of the left lobe it may be occasionally 
felt in the left shoulder. It is a referred pain, and is explained by the 
anatomic distribution of the sensory nerves supplying the shoulder and 
the serous covering of the convex surface of the liver. The phrenic 
nerve sends sensory branches to the liver through the suspensory liga- 
ment. This nerve arises from the fourth cervical nerve, and from the 
same place come the sensory branches to the region of the right shoulder. 
Irritation traveling along the branches of the phrenic is transmitted 
along these fibers to the fourth spinal segment, and is there transmitted 
from ganglion cell to ganglion cell. 

This shoulder pain is of clinical importance, inasmuch as it may, in 
certain stages of different diseases of the liver, be the only symptom 
pointing to an involvement of this organ. 

The pain starting from the bile-passages does not originate in the 
mucous lining, but in the muscular wall of these ducts, and is caused 
directly by the stretching of their walls and by spasmodic contraction. - 
The character of the pain is altogether different from that of the other 
just described, in that it is called a colicky pain, like all similar forms 
of pain emanating from hollow organs. It is usually observed in impac- 
tion of gall-stones, and will be described in a following section. It is 
distinguished from other forms of hepatic pain by its intensity, its periodic 
exacerbations, and the fact that it is comparatively independent of 
external pressure. This colicky pain usually radiates into remote parts 
of the body, into the epigastrium, and toward the back. It is frequently 
accompanied by reflex symptoms, such as vomiting, general pallor, 
collapse, and chills with elevation of temperature. 


. Some interesting information in regard to the origin of the pain was obtained 
from the study of a patient whose gall-bladder was opened under local anesthesia by 
Professor Bier, and a large number of gall-stones removed. Tugging at the gall- 
bladder produced violent pains similar to those that the patient had experienced 
during her attacks of gall-stone colic. Pain in the shoulder was absent during this 
manipulation, although the patient had complained of it six months previously to 
the time when she was admitted to the clinic with the diagnosis of perityphlitis, 
the pain in the shoulder then first directing attention to the liver as the seat of trouble. 


Of all the disturbances of the hepatic functions, those concerned in 
the formation of bile-pigment would be the most readily recognizable 
were it not for the fact that the proportion of bile normally evacuated 
with the feces is so varying and changeable. ‘We are altogether unable 
to control this, and, consequently, cannot determine fluctuations in the 
amount of pigment'contained therein. It has been already shown above 
why the color of the feces is no index for the amount of bile-pigment 
secreted. i 

From a symptomatic point of view the reabsorption of bile is more 
important, as it is this which leads to icterus. As this condition is 


GENERAL SYMPTOMATOLOGY. 457 


readily recognized, it acquires a great clinical significance, but it has a 
very different significance in different cases. 

Disturbances of the appetite and of the bowels are important, although 
in only a certain proportion of cases are these the direct result of the 
disturbed secretion of the liver, being more frequently manifestations 
of concomitant disturbances in the function of the stomach, the intestine, 
or the pancreas. 

Changes in general metabolism as a result of diseases of the liver are 
clinically manifested by changesin the urine. This is frequently diminished 
in quantity, forms a sediment, and is darker in color, these changes being 
due partly to a greater concentration, partly to the presence of bilirubin, 
and partly to an increase in the quantity of urobilin and indoxyl. It is 
true that these changes in color may be due to still other causes, and that 
they cannot, as was formerly thought, be interpreted to signify in all 
cases that the liver is involved. Decrease in the excretion of urea, in 
the excretion of ammonia, alimentary glycosuria, and increased toxicity 
of the urine are all found in diseases of the liver, but the methods of 
determining these changes are too complicated and tedious for practical 
use, particularly as their significance is not positively determined. The 
French school of investigators especially emphasize and somewhat over- 
rate the significance of these urinary abnormalities. For the present 
they have a theoretic interest only. 

The hemorrhagic diathesis may be considered an indication of per- 
verted nutrition and of changes in metabolism. It is found after icterus 
has existed for some time, and occasionally before the appearance of 
other grave symptoms of hepatic disease. Hemorrhages into the retina 
make their appearance especially early (Litten). 

The disturbances of the general health vary greatly in diseases of 
the liver. In localized lesions they may be slight or absent, but in 
diffuse diseases of the whole organ they are always present. This applies 
even to diffuse but transient forms, such as catarrhal icterus. These 
general disturbances consist in a change of disposition, the aspect of 
illness, loss of strength, and emaciation. According to various external 
conditions and the temperament of the patient, these different symp- 
toms appear with varying prominence, and the physician should take 
them into consideration for both diagnosis and prognosis. As a rule, 
the disturbances are slowly developed, but they often suddenly and 
unexpectedly arise. They are found not only in pronounced icterus, 
but also when it is absent or when the skin is only slightly discolored. 
It appears that such patients are in a state of unstable equilibrium, so 
that small external causes may produce serious aggravations of their 
condition. One of the causes of these sudden exacerbations is a diminu- 
tion in the excretory function of the kidneys, which, it would appear, can 
for a long time act vicariously. 

Disturbances of circulation in.the area of the radicles of the portal 
vein are frequently found, as a result either of primary disturbances of 
the circulation in the hepatic capillaries or intrahepatic branches of the 
portal vein (cirrhosis, syphilis), or of compression of the portal vein itself 
(more rarely, of the hepatic veins), or of diseases of its walls. If these 
circulatory disturbances reach a high grade, ascites and swelling of the 
spleen occur, the former being often so pronounced that it obscures all 
other evidences of disease. 

The action of the heart and the respiration are impaired only as a 


458 DISEASES OF THE LIVER. 


result of the disturbance of the general health, mechanically by the 
ascites, or occasionally by contiguity. As symptoms of these conditions 
Labadie- Legrave names palpitation, intermittent cardiac action, a feeling 
of oppression, and attacks of angina pectoris. In icterus the action of 
the heart is usually slowed. 

Disturbances of the nervous system are quite frequently observed, 
especially when jaundice is present. Pruritus, slowing of the heart, 
and disturbances of vision are those most frequently presented. If 
the icterus persists for a long time, but occasionally even without the 
existence of icterus, severe nervous symptoms are seen where chronic 
disease of the parenchyma of the liver has produced marked organic 
changes, especially if atrophy is pronounced. As in uremia, these may 
appear suddenly or develop gradually. In the more chronic cases they 
are usually preceded by loss of strength and disturbances of nutrition. 
The chief nervous disturbances observed are pruritus and changes in 
disposition and the amount of psychic energy. The mental disturbances 
may progress to drowsiness, unconsciousness, and coma. The more 
severe degrees of disturbances of the nervous system may be accom- 
panied or interrupted by delirium and convulsions. 

Those states that have been called delirium or coma hepaticum re- 
’ semble, as previously explained, both the symptoms seen in animals 
after experimental removal of the liver and certain forms of intoxication. 
It is, in fact, probable that they are produced by an auto-intoxication 
with substances that are formed within the body; in other words, it is an 
hepatotoxemia. 

The poisons may be of various origin. They may be either products 
of the diseased liver-cells themselves or substances which should normally 
be retained and excreted by the liver, but which, when the organ is 
diseased, enter the circulation. Among these toxic substances must be 
mentioned carbaminate of ammonia, which has been especially incrim- 
inated by Nencki. Other factors may consist of toxins produced by 
putrefactive processes within the intestine and intermediary products 
of general metabolism (among the latter, possibly certain acids). At 
times some of the constituents of the bile participate in this hepato- 
toxemia or hepatic auto-intoxication. (Compare page 440.) 

It is possible that the sudden development of severe nervous symp- 
toms occurs at a time when the vicarious excretory function usually 
assumed by the kidneys or other organs suddenly becomes insufficient, 
so that the body is suddenly exposed to the bad effects of an uncom- 
pensated insufficiency of the hepatic function. When the latter, which 
may be called hepatargia, is developing slowly, it is manifested clinically 
by less violent symptoms, such as slight changes in the general nutrition, 
slight loss of strength, and slight changes in the disposition of the patient. 

The same is seen in uremic and diabetic forms of intoxication. Here, 
also, those cases that occur suddenly are the most striking, yet a great 
many cases develop less significant symptoms whose dependence upon 
the systemic poisoning can only be discovered on very careful examina- 
tion. There are, also, all grades of transition between these two. All 
three forms of intoxication (hepatic, uremic, and diabetic) have specific 
symptoms, but they all resemble each other in that the nervous symp- 
toms are rather vague and indefinite (appearing either as irritability or 
depression) and differ in almost every case. This variability in the 
intensity of the manifestations of toxemia is in all probability due to 


GENERAL SYMPTOMATOLOGY. 459 


differences in the constitution of the toxic material and the rapidity 
of its accumulation. . 

As a rule, acute attacks of hepatic auto-intoxication appear within 
a few days before death, and are, therefore, premortal or terminal symp- 
toms. This form of auto-intoxication terminates favorably much more 
rarely than does that. of uremic and. diabetic poisoning, and a patient 
hardly ever recovers after it is well developed. In the milder and more 
gradually developing forms of hepatargia a restitution to normal is 
possible, particularly in cases in which the disturbance of the hepatic 
function is due to removable biliary obstruction. These are the cases 
that formerly were wrongly called bile-intoxication or cholemia. 

It is not possible in some cases to state definitely that a certain 
syndrome of nervous symptoms is due to hepatic toxemia, because a 
number of other diseases can produce similar states. Among those 
capable of producing coma should be mentioned chronic alcoholism, 
nephritis, meningitis, tuberculosis, and certain febrile complications. 
Chronic alcoholism and lead intoxication, also, may cause delirium and 
convulsions. Frequently there is a mixture of causes of nervous symp- 
toms, such as the combination of alcoholism and chronic nephritis. 
The form that these nervous disturbances assume is manifold and but 
slightly characteristic, at times even simulating insanity. The diag- 
nosis must be made from other symptoms pointing to an involvement 
of the liver. LL. Levy, who has collected a number of these cases, is of 
the opinion that in hepatic coma mydriasis is more frequently seen, 
while in uremia myosis is usually present. 

Ocular manifestations are seen only in severe cases of hepatic disease. 
They are xanthopsia, hemeralopia, retinal hemorrhages (particularly if 
a severe degree of icterus is present), retinitis pigmentosa, and, in cir- 
_rhosis, choroiditis atrophicans. 

The temperature of the body is rarely changed in diseases of the 
liver, but in advanced stages of general disturbances of health as a result 
of disease of the liver and in icterus the temperature is sometimes sub- 
normal. 

In suppurative processes, involving either the parenchyma of the 
liver or the mucous membrane of the bile-passages, the temperature is 
usually raised. As the bile-passages are very narrow, suppurative pro- 
cesses within them, as a rule, lead to swelling of the mucous membrane, 
with retention of pus and fever from absorption. These forms of re- 
sorption fever are found in diseases of the liver, even when the suppura- 
tion is of very slight degree and extent, and even in those infections 
of the bile-passages in which only very small quantities of pus are formed. 
The fever sometimes assumes so irregular a type that it may be con- 
founded with malaria, particularly as the attacks of fever occasionally 
run a course that resembles that of the tertian or the quartan type. 

Those forms of febrile attacks: ushered in by a chill and following 
the impaetion of a gall-stone are especially peculiar.. They may be only 
in part due to absorption. 

Concretions of bile are frequently seen in combination with an infectious or sup- 
purative form of cholangitis, so that the fever due to impaction may very well be 
combined with a fever from absorption. Following Charcot, French authors distin- 
guish a definite type of fever, “ febris intermittens hepatica.’”’ This is hardly justified, 
since in many other situations a purulent focus can exist whose source and nature may, 


as in this situation, remain often for a long time hidden from recognition and cause 
a similar “intermittent fever.” | 


460 DISEASES OF THE LIVER. 


The fever under discussion may be distinguished from malaria (aside from the 
blood examination) by an evening exacerbation that is typical of all forms of fever 
from pus absorption, and that is particularly marked in hepatic suppuration owing 
to hyperemia of the liver during digestion. The taking of the temperature at short 
intervals will, in addition, show a very irregular type of fever. 


LITERATURE. 


Baas, K. L.: ‘“Beziehungen zwischen Augenleiden und Leberkrankungen,” 
“Munchner med. Wochenschr.,”’ No. 32, 1894. 

Charcot: ‘“ Maladies du foie,” p. 95, 178 (Fever), 1877. 

Chauffard: ‘De la guérison apparente et de la guérison réelle dans les affection 
hépatiques,”’ “ Archives générales de médecine,” 1890, 11, p. 399. 

Labadie-Legrave: (“As to Symptoms in Connection with the Vascular System’’) 
“T’Union méd., 1891, No. 131. 

Leopold, Levi: ‘Troubles nerveux hépatiques,” “ Archives générales de médecine,’ 
1896, 1, 58, 219, 535; 11, 19, 157. 

Litten: “ Verinderungen des Augenhintergrundes,” etc., “ Zeitschr, fiir klin. Medi- 
cin,”’ Bd. v, Heft 1. 

Renvers: “ Zur Pathologie des intermittirenden Gallenfiebers”’ (with Charts), ‘“Char- 
ité-Annalen,” vol. xvu1, p. 174, 1892. 

Wagner, E.: “ Febris hepatica intermittens,’’ ‘‘ Deutsches Archiv fiir klin. Medicin,’” 
Bd. xxxIv, p. 529, 1884. 


5. DIAGNOSIS IN GENERAL. 


In view of the great number and the variety of the functions of the 
liver, it will usually be found that when the liver is diseased other organs 
also are involved. Sometimes the liver is primarily involved, sometimes 
secondarily, and occasionally the lesions of the liver and of the other 
organs are caused by the same agency. It is not always possible to. 
decide, even at autopsy, into which category the lesions fall, and from 
the clinical picture the participation of the liver in a given syndrome 
is not always clearly indicated. We can distinguish four types, as. 
follows: 

I. The changes in the liver (anatomic or functional) are accompani- 
ments of other diseases and are not recognizable in the symptom-complex, 
although they have a share in its production. To this,class belong the 
changes in the hepatic parenchyma seen in the course of many infectious 
diseases, miliary pyemic abscesses, many cases of miliary tuberculosis 

and of secondary carcinoma of the liver, and probably, also, certain of 
the secretory anomalies observed in gastro-intestinal catarrhs. 

II. The changes that occur in the liver are recognizable by certain 
symptoms and signs, but are insignificant in comparison to the symp- 
toms of the primary disease. Such conditions are congestion of the 
liver in the course of certain cardiac lesions, fatty degeneration of the 
liver in general obesity, and those mild degrees of chronic hepatitis that 
occur in the course of those cases of alcoholism chiefly presenting mani- 
festations of involvement of the heart or brain. 

III. Diseases of the liver proper in the narrower sense, where the — 
hepatic lesions dominate the picture. Examples of this class are catar- 
rhal icterus, cholelithiasis, and many cases of abscess and echinococcus 
of the liver and of pronounced atrophic cirrhosis. 

IV. Diseases in which the symptoms produced by the liver are con- 
spicuous, but in which the liver is not really the organ primarily involved 
and is only affected as the result of a general intoxication or infection. 
To this group belong cases of acute phosphorus-poisoning, many cases. 


PROGNOSIS IN GENERAL. 461 


of icterus gravis, many cases of “alcohol liver”’ and of syphilis of the 
liver. In all of these diseases other organs are damaged too, but not 
to such a marked degree as the liver. This relative preponderance of 
the symptoms attributable to the liver has to be kept in mind in forming 
a clinical judgment and arriving at a conclusion in many instances of 
disease. 

From a practical point of view it is well, finally, to remember here, 
as in the case of other organs (as, for example, the lungs), that different 
diseases of the liver that have been discussed separately may occur in 
the organ at the same time and may exercise an influence on each other. 
As an illustration of this, we may see at the same time fatty infiltration, 
cirrhosis, hyperemia from stasis, catarrhal icterus, and, in addition, 
possibly in the same individual, gummata or concretions. 


6. PROGNOSIS IN GENERAL. 


In those cases in which a disease of the liver is only apparently the 
cause of illness (in the sense of the preceding section), but in which in 
reality some general disease is causing certain manifestations of hepatic 
involvement, the prognosis is naturally unfavorable. When jaundice 
is present, the course of the disease may be our only guide in deter- 
mining whether the hepatic or the general disease is primary. 

In case the liver alone is involved, it is important to determine whether 
the organ as a whole is affected, or whether the lesion or lesions are 
localized and the organ is only partially changed. Localized dis- 
eases (abscesses, echinococcus, gumma) are of themselves important 
because a certain portion of the organ remains capable of forming the 
internal and external secretions and can act vicariously for the diseased 
areas. Ceteris paribus all diffuse diseases of the liver offer a less favorable 
prognosis. — 

Diseases involving one or more of the large systems of vessels and 
ducts are especially important because they show a tendency to become 
diffuse. This applies most markedly to the bile-passages, and to a 
lesser degree to the blood-vessels. Purely mechanical lesions of these 
vessels and ducts are, as a rule, more favorable prognostically than are 
infectious lesions. 

Toxic diseases are usually diffuse, and the prognosis depends on the 
removal of the primary toxic agent early in the disease. This is par- 
ticularly the case in alcohol poisoning, perhaps in the lesions produced 
by digestive toxins, and, finally, in malarial infection. 

In all diseases of the liver it is of paramount importance, from a 
prognostic point of view, to determine whether the liver-cells themselves 
are involved. It must be remembered, at the same time, that the degree 
of functional impairment is not necessarily proportionate to the degree 
of anatomic alteration. 

Even when true degeneration of liver-cells occurs and when many 
cells perish, these changes, as a rule, progress gradually and in an irregular 
manner, so that the relatively intact portions can vicariously assume 
the réle of those parts that are undergoing degeneration. In this manner 
the interruption of the hepatic functions is very gradual and the picture 
of hepatargia, or the hepatic insufficiency of the French authors, de- 
velops very slowly and imperceptibly. However, in these cases the 


462 DISEASES OF THE LIVER. 


picture of hepatic auto-intoxication may suddenly appear. We must 
consider the prognosis uncertain, therefore, in every case of icterus of long 
duration or obscure origin, as well as in those accompanied by pronounced 
general symptoms. The same applies to those cases in which, even 
without jaundice, there is reason to expect a high degree of parenchy- 
matous change. As a rule, the clinical symptoms of these conditions 
are not very significant for prognostic purposes. The condition of the 
urine is important in the sense that a decreased excretion and a dark 
color are prognostically unfavorable, whereas a copious excretion and a 
light color (sometimes presenting the clinical picture of a urinary crisis) 
are prognostically favorable. 

In many cases of icterus apparently running a mild course a sudden 
aggravation of the general condition, that may even terminate fatally, 
is sometimes seen. Both during the treatment of the disease in its 
active stages and in the after-treatment it is well to remember how 
uncertain the prognosis may be in such cases. 

As in the case of many other diseases involving important organs, 
a cure in the clinical sense does not really constitute a cure. Asa matter 
of fact, a certain degree of functional weakness of the affected organ 
usually remains, or a slow, latent progression of the disease continues. 


7. GENERAL TREATMENT. 


In view of the intimate relation of the liver to the processes of nutri- 
tion dietetic measures form an important portion of treatment. The 
liver may be rested, so to speak, by withdrawing all food for a time. 
This measure is not practical, however, for the reason that it can be 
carried out for so short a time, and because of all organs the liver, 
particularly, suffers from deficient nutrition. On account of the great 
significance of the liver in general metabolism, it is dangerous to allow 
its functional activity to sink below a certain point, and a certain amount 
of nourishment must be ingested to maintain its proper action. 

Acute catarrhal icterus and acute parenchymatous hepatitis, in par- 
ticular, call for the smallest possible amount of food, partly in order to 
spare the liver, partly also for other reasons. In all other cases it is 
only necessary to limit the amount and the kind of food. In the latter 
respect the general constitution of the patient must be considered as 
much as the general state of the liver; for example, the amount of fats 
and carbohydrates may have to be limited. In hot climates, it is said 
that a vegetarian diet best protects the liver. In febrile diseases, accord- 
ing to French authors, a meat diet is particularly bad, because the 
detoxicating function of the liver is said to be reduced. They recom- 
mend milk, starches, and sugars for the formation of glycogen. Such 
a diet corresponds essentially to the long-employed fever diet. There 
can be no doubt that it is indicated for many other reasons more im- 
portant than the saving and protection of the hepatic function. 

In general, it may be said that any limitation of the diet to any one 
class of food will be followed by an excessive strain on the liver in diges- 
tion of that one class. In the absence of special indications the following 
rules may be formulated for the regulation of the diet in diseases of the 
liver: viz., Restriction as to the quantity of the food, with a mixed diet 
of simple composition and preparation, and avoidance of all irritating 


EEE 


GENERAL TREATMENT. 463 


articles of food. The three types of food, proteids, carbohydrates, and 
fats, should be represented in the food. The diet should be as free as 
possible from all indigestible residue and the composition of each meal 
should be as simple as possible, thus avoiding overloading of the gastro- 
intestinal tract, retardation of digestion, and the occurrence of putre- 
factive changes. The last point is particularly important because it 
seems that the bacteria of the intestine can produce toxic products 
capable of irritating the liver in the same manner as does alcohol. The 
latter article is to be particularly avoided, as it seems to be very harmful 
to the liver, especially when taken in concentrated form or on an empty 
stomach. Naturally, in the case of alcohol, as of other articles of food, 
the liver alone cannot be considered, and in patients that have been 
used to the taking of alcohol the stomach, heart, and nervous system 
must be considered, and it may be necessary to administer carefully 
graduated doses of certain alcoholic beverages. As a general rule, both 
the laity and physicians are in the habit of prescribing too large doses 
in cases of this kind. The same remark applies to spices, which, in 
addition to acting harmfully on the liver, are dangerous because they 
stimulate the patient’s appetite and cause him to take too much food. 
Among this class of foods we would mention in particular mustard, 
the different kinds of pepper, radishes and horseradish, onions, celery, 
ginger, cinnamon, cloves, etc., also coffee, strong meat-broths, large 
quantities of salt, and the empyreumatic substances that are formed 
in baking and roasting. Because of the latter, white meat and boiled 
meat are preferable to red and roasted meat. 

It is also well to remember that during digestion the demand upon 
all of the functions of the liver is increased, so that the quantity of food 
given at each meal should be small. It is well, therefore, to prescribe 
both the number of meals and the hours at which they should be taken, 
thus both regulating the amount of work that the liver has to do and 
obtaining certain periods of rest for the organ. Larger and less frequent 
meals are indicated only when one desires to produce a more copious 
outflow of bile for the purpose of flushing the bile-passages, as in certain 
diseases of the bile-ducts. 

A milk diet is frequently prescribed for certain diseases of the liver, 
particularly cirrhosis. Milk, in fact, fulfils nearly all the indications 
in regard to dosage, simplicity, and absence of all irritating qualities. 
The ingestion of large quantities of fluid which is incidental to a milk diet 
is desirable. Besides milk, buttermilk and kefir should be mentioned as 
desirable articles. Glutinous articles of food are useful, as they are so 
readily assimilated. Sometimes a vegetable diet, so especially advocated 
by French authors, is indicated, particularly when torpidity of the 
intestine exists with a tendency to a putrefaction of proteids. 

It is well to rest after meals, both for the sake-.of the liver and for 
other reasons, because by this precaution the functional hyperemia of 
the organ, so useful for digestion; is not disturbed. 

As many chronic diseases of the liver (hyperemia, fatty degeneration, 
chronic hepatitis) are accompanied by a condition of general plethora 
and a general retardation of metabolic processes, it is necessary to pre- 
scribe a certain amount of physical exercise. By this circulation is 
increased and combustion is advanced, and the flow of blood through 
the liver, in particular, is accelerated, because with increased respiratory 
efforts the liver is rhythmically compressed and the venous blood is 


464 . DISEASES OF THE LIVER. 


made to flow more rapidly into the heart. The kind of exercises pre- 
scribed must be adapted to the general health of the patient and to 
external circumstances. 

It is well to avoid all compression by the clothing, in view of the 
great influence that such compression exercises on the flow of blood and 
of bile within the liver. 

Different kinds of baths, particularly mud-baths, are useful in the 
hyperemias and in hypertrophy from overingestion, chiefly because 
they exercise a beneficial effect on the general circulation and on meta- 
bolism. 

The regulation of the intestinal evacuation is very important in all 
diseases of the liver, if for no other reason than that retention of feces 
produces pressure on the organ, and a mild degree of catharsis is always 
indicated in these cases. It is useful here, too, because it promotes a 
more rapid elimination of the toxins that may have been formed. Salines 
are particularly suitable, notably the sulphates of sodium and of mag- 
nesium, the tartrates, as well as rhubarb, aloes, and cascara. 

It has been attempted to prevent the formation of intestinal toxins 
by the administration of intestinal antiseptics. However seductive this 
plan may appear on theoretic grounds, it is uncertain in practice, as a 
disinfection of the intestine proper can hardly be produced. Just as 
the bacterial flora of the intestine in health changes as regards its com- 
position and products in accordance with the ingesta, so certain medica- 
ments and foods may produce similar -alterations in disease; yet this 
subject is not at all understood, and what investigations are recorded 
are tentative, incomplete, and chiefly based on an unconnected mass of 
empiric observations. We can mention the following substances that 
might be employed for the disinfection of the intestine: calomel (0.1 to 
0.2 per diem) in small divided doses (Hanot recommends 0.01 to 0.02 
in the morning on an empty stomach for a week, to be repeated after 
a week, possibly several times); the subnitrate or salicylate of bismuth 
(2.0 to 6.0 per diem); salol (2.0 to 6.0 per diem); naphthalin (2.0 to 4.0 
per diem); resorcin (1.0 to 3.0 per diem) ; #-naphthol (1.0 to 3.0 per diem). 
Hydrochloric acid, by its influence on gastric digestion, acts indirectly. 
I have employed pure cultures of brewers’ yeast with great advantage 
(dose 30 to 60 c.c. per diem).* 

The excretion of the urine has to be considered in the treatment of 
diseases of the liver as well as in the diagnosis. The indication is to 
produce the excretion of a considerable quantity of moderately con- 
centrated urine. In the first place, this is evidence that plenty of fluid 
is circulating through the liver; in the second place, that the kidneys 
are acting as a safety-valve for the removal of abnormal quantities of 
biliary constituents and other noxious substances that may have 
entered the circulation. 


In icterus the regulation of the diet must be governed chiefly by the 
condition of the gastric and intestinal mucosa, and, secondly, by the 
diminution or the absence of the bile from the intestine. The latter 
contingency demands a restriction in the amount of fat because this. 
would not be absorbed so well; for which reason the carbohydrates must 
be given as a substitute for the fat, even though they are apt to produce 
fermentation and meteorism. Meat, even in the absence of bile, is well 

* “ Verhandlungen des Congresses fiir innere Medicin,” 1898. 


——" (SSS. 


Ee eee 


GENERAL TREATMENT. 465 


digested. When there is much putrefaction in the intestine, the meat 
must be replaced by eggs or by vegetable albumin. In icterus with 
simple obstruction of bile it is necessary to individualize in regard to the 
diet. This is made apparent by the great differences observed in different 
patients in regard to the assimilation of fat, and the diet will have to be 
modified according to the degree of fermentation or putrefaction that 
happens to be going on in the intestine. 

In every form of icterus it is well to give plenty of water in order to 
promote a copious secretion of urine. When sufficient water is not 
taken by the mouth, it is well to administer enemata or even to give 
hypodermic injections of normal salt solution. Frequent bathing also 
exercises a favorable influence on the urinary secretions. 


Mosler and Krull have recommended the methodical use of enemata of water in 
icterus and in a number of other diseases of the liver. The former prescribes half a 
liter of lukewarm water three times daily, the latter orders from half to one liter of 
water, of a temperature of from fifteen to twenty-two degrees, given slowly and re- 
tained as long as possible. These enemata act by the water absorbed, by the flushing 
of the intestine, and by stimulating peristalsis, possibly even in the bile-ducts. The 
latter effect (increased peristalsis) 1s produced by the cool enemata, while absorption 
is greater after those that are warm. Their primary effect is on the blood and the 
blood-current in the portal vein, and in this way perhaps they improve the nutrition 
of the liver-cells and the secretion of the bile. Certain animal experiments by 
Stadelmann and others disprove such an action and do not show that the absorp- 
tion of water is followed by such beneficial effect. Occasionally certain intestinal 
antiseptics, as salicylate of sodium and naphthol, are added to the enemata. 


Among the drugs that are employed in the treatment of diseases of 
the liver, the so-called cholagogues have heretofore occupied a high place. 
Careful tests have, however, shown that a number of these remedies (such 
as calomel, rhubarb, and others) are not really cholagogues, although this 
does not diminish their therapeutic value, empirically discovered, but 
merely necessitates some other explanation of their action. 

The following may be mentioned among the cholagogues that possess 
some clinical value: 

The bile-acids (cholate of sodium in doses of 0.3 to 1.5 per diem), 
which act better than bile itself, are excreted by the liver and have a 
tendency to increase the quantity of bile-salts normally circulating 
through the liver. 

Salicylate of sodium in doses of 2.0 to 4.0 per diem and salol in doses 
of 1.0 to 3.0 per diem (according to Lewascheff and others) were found 
by Lépine and Dufour to produce hyperemia of the liver. Benzoate 
of sodium belongs to the same class. 

Oleate of sodium (advised by Blum in dose of 0.25, four to eight 
doses per diem) is a more rational prescription and seems to produce 
less injury than large doses of olive oil or of lipanin used as recom- 
mended by Kennedy. 

In addition, oleum terebinthine, terpene hydrate, euonymin (0.1 
once or twice daily or oftener), and podophyllin (0.02 from two to four 
times daily) have been with reason recommended as cholagogues. The 
cholagogic action of sodium bicarbonate, sodium sulphate, and sodium 
chlorate is not positively established. The most reliable physiologic 
cholagogue is a full meal consisting of meat, fat, and amylaceous ma- 
terial. All purgatives act as cholagogues in the sense of stimulating the 
peristaltic action of the bile-ducts. 


A decrease in the excretion of bile always follows an increase as a 
30 


466 DISEASES OF THE LIVER. 


natural reaction. The flow of bile is also lessened directly by iodid of 
potassium and atropin. 

In addition to producing quantitative changes in the secretion of the 
bile by dilution, the attempt has been made to modify it qualitatively 
by introducing certain substances that are excreted by the liver. These 
were expected to act partly upon the diseased mucous lining of the bile- 
ducts, and partly upon the bacteria present in these passages. As 
“biliary antiseptics” sodium salicylate and salol in particular have been 
employed. Oil of turpentine and chloric acid enter the bile in the same 
manner as does salicylate of sodium. This does not apply to the alkaline 
carbonates, according to Stadelmann and his pupils, although these salts 
have, for a long time, been administered for this purpose in the form 
of mineral waters. 

With regard to the action of drugs upon the other functions of the 
liver-cells we know much less than we do in the matter of the secretion 
of bile. Among the drugs from which some such action is expected the 
following need mention: iodid of potassium and mercury (particularly 
in the form of calomel) in chronic inflammations, especially when inter- 
stitial proliferation is present; alkaline carbonates and sulphates, and 
sodium chlorid, particularly in fatty infiltration and in hyperemia from 
overeating. | 


It is said that oil of turpentine increases oxidative processes within the liver—a 
very doubtful point. We know that, in addition to mercury, other metals, such as 
iron and lead, are arrested in the liver and are therefore capable of exercising an in- 
fluence on its function. So far no use has been made of this property in the therapy 
of diseases of the liver. The same applies to certain substances that are especially 
toxic for the liver, namely, phosphorus, antimony, and arsenic. 

It was formerly believed that sulphuretted hydrogen and the alkaline sulphids 
in certain mineral waters could act as solvents (Roth), but it is probable that the 
action of these substances can be explained in a different manner. 


It may be stated generally that the medicamentous treatment of 
diseases of the liver is based more on empiricism than on an exact ex- 
perimental basis. When the attempt has been made to found a rational 
therapeusis on an experimental basis, the results obtained in many 
instances have not agreed with clinical observation. At the same time, 
it must be remembered that the functions of the liver are exceedingly 
- complicated, so that the effects of medicaments influencing them must 
necessarily also be complicated and difficult to understand. In addition, 
the sphere of action of a certain drug may frequently be in a totally differ- 
ent region than is expected, while the funetions of the liver are unques- 
tionably in many instances modified indirectly either by the effect of a 
given drug on the heart, on the digestive tract, on respiration, or on the 
excretory function of the kidneys. In view of all this, the treatment of 
diseases of the liver must still rest upon clinical observation and ex- 
perience, which can be controlled only by experiment. 

Besides dietary regulations, the group of purgatives seem to play the 
most important réle in the treatment of hepatic diseases; but it is not 
definitely determined that their beneficial effect can be attributed to 
their evacuating action alone. 

» The administration of mineral waters is very important in the treat- 
ment particularly of chronic diseases of the liver. The most important 
of the alkaline waters are Vichy, Neuenahr, Ems, Bilin, and Salzbrunn; 
of the alkaline-saline are Carlsbad, Bertrich, Marienbad, Franzensbad, 


——s eC — 


GENERAL TREATMENT. 467 


Elster, Rippoldsau, and Tarrasp; of the hot salt springs are Wiesbaden, 
Aix-la-Chapelle, Baden-Baden, Bourbonne, Kissingen, and Homburg. 

It may be said that the hot waters mentioned act chiefly upon the 
parenchyma of the liver directly and on the secretion and composition 
of the bile, whereas the cold springs principally affect intestinal digestion 
and promote the peristalsis both of the intestine and of the bile-ducts. 
Of the latter less is probably absorbed. For the purpose of promoting 
peristalsis we can also employ the bitter waters. 


The attempt has been made to influence the functions of the liver 
by certain local measures, such as local abstraction of blood, massage, 
and electricity. 

Local bleeding by leeches applied to the region of the liver is of value 
in all forms of painful perihepatitis of whatever origin. As it is not 
possible to influence the blood-current within the liver by these means, 
from three to ten leeches have been applied to the region of the anus, 
for the purpose of relieving congestion in the portal system, just as 
occurs in spontaneous hemorrhoidal hemorrhages. This procedure was 
formerly very popular, but has lately fallen into disuse, probably without 
justification. Sacharjin recommends the application of leeches to the 
coccyx. 


G. Harley attempted to withdraw blood from the liver directly (so-called ‘‘ phle- 
botomy of the liver’). He anesthetized the patient and introduced a trocar having 
a diameter of 24 mm. from right to left to a distance of about twenty centimeters, and 
withdrew about six hundred cubic centimeters of blood. We can only warn against 
the employment of this measure. It is recommended particularly in “enlargement 
and inflammation” of the liver. In one case it produced a copious hemorrhage into 
the bile-passages. 


The application of the ice-bag, of Priessnitz compresses, and of 
cataplasms has been proved to be useful in inflammatory and other 
pains originating from the serous covering of the liver and from the 
gall-bladder. It is very doubtful whether these measures can exercise 
any influence on diseases of the hepatic parenchyma itself. 

Mechanical treatment of diseases of the liver can be carried out by 
breathing exercises and general gymnastics, particularly by such exer- 
cises as bring the abdominal muscles into play. Unless it is enlarged 
the liver is not accessible to manual massage, and these manipulations 
are, moreover, hardly indicated. It is, at the same time, not impossible 
that the lower surface of the liver, and possibly the bile-passages, may 
be influenced by general abdominal massage if the abdominal walls are 
considerably relaxed. C. Gerhardt has recommended direct massage 
of the gall-bladder, if possible combined with manual compression, in 
icterus simplex, in order to thus remove the obstructing plug of mucus. 
In case the gall-bladder cannot be reached, he recommends the ap- 
plication of a strong induced current with slow interruptions over the 
region of the gall-bladder. There is no doubt but that the good results 
claimed for this method of treatment must be attributed in large part. 
to the increased peristaltic action of the intestine and of the bile-ducts 
that it produces reflexly. 

The puncture of the abdomen for the removal of ascitic fluid also 
acts beneficially in a mechanical way by the removal of the excessive 
pressure and permitting normal circulation of the blood and of the bile 
to be re-established. 


468 DISEASES OF THE LIVER. 


Surgical procedures are often crowned with success, and within late 
years are being employed more and more. They are usually directed 
toward the removal of biliary concretions and a correction of the lesion 
resulting from their impaction. In addition, abscesses of the liver, and 
echinococcus cysts are amenable to surgical treatment, and tumors 
can sometimes be removed. [In regard to the operative treatment of 
ascites see page 714.] 

The injection of certain medicaments into the parenchyma of the liver 
has been attempted tentatively here and there; but the procedure 
promises very little. The injection of corrosive sublimate solution (1 : 
1000) into echinococcus cysts has been successfully employed. 


In conclusion, a few points in regard to the special treatment of 
icterus may be mentioned. 

It is frequently necessary to relieve patients suffering from cutaneous 
pruritus, and measures directed toward an amelioration of this symptom 
are indicated in addition to the general measures that are being em- 
ployed. Of greatest importance is the care of the skin by warm sponging 
and bathing. Washes containing dilute acetic acid, lemon juice, slippery- 
elm, or ammonia are beneficial, and baths containing bran, potash, or 
soda are recommended. The itching may be relieved also by powdering 
the skin with starch or lycopodium, to which salicylic acid or menthol 
may be added, or by washing with tar soap or solutions of carbolic acid 
(2%) or chloral hydrate (3%) in water or alcohol, or with chloroform, 
ichthyol, or menthol, or salicylic acid dissolved in alcohol, oil, or ether. 

These different measures have to be tried to determine the most 
useful in the individual case, and if the icterus is of long duration it is 
frequently necessary to alternate them (see Leichtenstern, loc. cit., p. 
27). The best internal narcotic is amylene-hydrate in the dose of from 
one to two grams. 

Stimulation of the secretion of bile is frequently advocated in icterus. 
This is indicated only in those cases in which an obstacle to the outflow of 
bile is situated in the larger bile-passages and where the obstacle does not 
produce a complete occlusion of the duct and is presumably removable. 
This may be the condition in certain catarrhal states and in small concre- 
tions. In one respect an increase in the secretion of bile must act harm- 
fully in every case of icterus, for the reason that, as an increased amount 
of biliary constituents enters the blood-current, it produces certain. toxic 
symptoms and perhaps acts deleteriously on the structure of the liver 
itself. This bad effect will increase with the degree of obstruction 
presented to the outflow of bile, a factor impossible to estimate during 
life. 

Stimulation of the peristaltic action of the bile-ducts will cause an 
Increased absorption during the time of the contraction of the ducts in 
case an obstruction exists in the common duct and the pressure is trans- 
mitted backward throughout the whole system of biliary canals. On 
the other hand, an increase in the peristaltic movements could act by 
shutting off the pressure-wave in the direction of the liver so that the 
increase of pressure would occur only in the direction of the bile-stream. 

e do not know in which direction the peristaltic wave is propagated. 
Mechanical compression of the gall-bladder is a more dangerous pro- 
ceeding. If the external orifice of the bile-duct is occluded, this manipula- 
tion must necessarily produce a considerable increase of the bile-pressure 


LITERATURE. 469 


even as far as the bile-capillaries, and in this manner might cause minute 
extravasations of bile and necrotic degeneration of portions of the hepatic 
parenchyma. 

[In the original German edition the possibility of forming an external 
fistula of the gall-bladder in cases of chronic jaundice was discussed, and 
the possible advantages of such a procedure were considered. Since the 
appearance of the work this has earned a place among the well-recognized 
means of surgical relief of the condition. A consideration of this and 
the many other surgical measures employed at the present time in cases 
of more or less permanent biliary obstruction, would be out of place 
here and may be found in many of the more recent text-books on surgery 
and in numerous monographs and journals.—ED.] 

The making of such an external ‘gall-bladder fistula seems to me to 
possess certain advantages over a gall-bladder-duodenal fistula (chole-_ 
cystenterostomy) for the reason that the latter is much more readily 
infected, both during the operation and subsequently, and in this way 
it may cause a general infection of the bile-passages. 

In hepatic auto-intoxication the intestine should be emptied, diuresis 
should be stimulated, and the activity of the skin should be promoted 
by baths. In cases of severe coma, blood-letting may be of use (L. 
Levi). 


LITERATURE. 


Gerhardt, C.: “ Volkmann’s klin. Vortrige,’’ No. 17, 1871. 

Glass: “Ueber den Einfluss einiger Natronsalze auf Secretion und Alkaliengehalt der 
Galle,” “ Archiv fiir experimentelle Pathologie,’ Bd. xxx, p. 241. 

Harley, G.: “Phlebotomie der Leber,” “ Miinchner med. Wochenschr. »” 1893, p. 887. 

Hoffmann, F. A.: “ Vorlesungen tiber allgemeine Therapie,” p. 163, Leipzig, 1865. 

Krull, J.: “ Behandlung des Icterus catarrhalis,” “Berliner klin. Wochenschr.,’’ 
1877, No. 12. 

Leichtenstern in Penzoldt und Stintzing’s “Handbuch der Therapie,” Bd. 1v, Ab- 
theil. vi, p. 139. 

Moritz, F.: “ Grundziige der Krankenernahrung,” pp. 187, 379, Stuttgart, 1898. 


’ Mosler: “ Zur localen Therapie der Leberkrankheiten,” ‘‘ Deutsches med. Wochen- 


schr.,’’ 1882, No. 16. 
Sacharjin: % Klinische Abhandlungen,” Berlin, 1890. (Calomel, bleeding.) 
Stadelmann, E.: “ Ueber alesone? (with bibliography), “Berliner klin. Woch- 
enschr., » 1896, No. 9. 





DISEASES OF THE BILE-PASSAGES. 
(Quincke. ) 


DisEasss of the bile-passages only rarely occur as the result of noxious 
influences affecting them through their external walls by continuity, 
although inflammation and neoplasms may so involve them. Diseases 
of their mucous lining are far more frequent, for the mucosa may suffer 
injury by substances coming from the liver-cells or the bile-capillaries 
and descending with the stream of bile, and also by substances from the 
intestine, which ascend in a direction contrary to the bile-current. 

The first kind of i injury may be inflicted by the bile itself as a result 
of a change in its normal composition or owing to an admixture of toxic 


470 DISEASES OF THE BILE-PASSAGES. 


substances. Instances of this kind are, for example, catarrh of the 
smaller bile-passages in acute phosphorus-poisoning, the experimental 
form of poisoning seen after the administration of toluylenediamin, the 
latter converting the bile into a viscid slimy substance and making 
it more difficult for the bile-ducts to excrete 1t. 

Such descending forms of disease may play an important réle in many 
acute and chronic forms of hepatitis, but these lesions cannot be sepa- 
rated clinically from the primary disease. The inner surfaces of the 
bile-passages may here be damaged either by the same noxious substances 
as are the liver-cells themselves or by the morbid excretions of the prim- 
arily diseased liver-cells. 

It is further conceivable, although so far not demonstrated, that 
bacteria may gain an entrance into the bile-passages from the blood 
and may produce lesions of these tissues. 


Experimentally various micro-organisms have been found to gain access to the 
bile. Thus, Bernabie found the bacillus of rinderpest, the bacillus of anthrax, 
Friedlander’s and Fraenkel’s pneumococcus; and Pernice and Scagliosi found staphy- 
lococci, anthrax bacilli, and Bacillus subtilis in the bile. Gilbert Dominici failed 
to find streptococci in the bile after injecting them into the blood. These authors, 
with Thomas and Sherrington, believed that microbes enter the bile only if foci of 
disease are present within the liver (Dominici, loc. cit., p. 101). [For statements 
regarding contamination of bile within the gall-bladder see below.— ED. ] 


The bile-passages are much more frequently involved in the second 
manner above mentioned, namely, by ascending from the intestine. 

In order to understand the mechanism of this occurrence, it is neces- 
sary to recall the peculiar manner in which the main bile-duct enters 
the intestine. It passes obliquely through the wall of the intestine 
and terminates in a papilla or a fold of the mucous membrane of the 
duodenum, a strong muscular sphincter surrounding the orifice. 


The pars intestinalis of the ductus chloedochus is 2.4 em. long and about 0.5 cm. 
in diameter, being narrower than the rest of the duct. About 3 to 12 mm. before its 
entrance into the intestine it is joined by the pancreatic duct. The common funnel- 
shaped duct formed in this manner is called the diverticulum of Vater. Both the ~ 
pancreatic and the bile-duct have at their orifice papillary excrescences which act 
like valves. The orifice of this common duct measures about 2.5 mm. in diameter 
but is capable of a great deal of stretching.* 


The narrow orifice of this canal can very easily be occluded by a 
plug of mucus forming within it, as occurs, for example, in catarrhal 
swelling of the duodenal mucosa. The orifice may be either closed 
from pressure exercised from without or from an extension of inflam- 
matory processes in its vicinity by direct continuity of tissue. Such 
an inflammation may extend for some distance into the main duct. 

In view of the fact that the papilla of the ductus choledochus is 
continually dipping into the intestinal contents, it might be expected 
that some of this could readily penetrate the duct. As a matter of 
fact, however, intestinal contents very rarely enter the bile-duct. This 
is due to the small mucous fold at the orifice and to the oblique direction 
of the last portion of the duct, which form a sort of valvular protection. 
In addition to this, the periodic, automatic action of the sphincter closes 
the,orifice and the periodic outflow of bile flushes the passage, these two 
factors together keeping it free from foreign material. 


* Luschka, “Die Pars intestinalis des gemeinsamen Gallenganges,” Prager 
Vierteljahrsschr., 1869, Bd. c1u1, p. 86 (with illustrations). 


ETIOLOGY. 471 


The normal bile and the bile-passages are sterile, and bacteria are 
only found in abnormal states. [For a further discussion of this point see 
the section upon cholelithiasis.—Ep.] The species most frequently found 
are Bacterium coli, staphylococci and streptococci, the pneumococcus, the 
bacillus of typhoid, diplococci, and liquefying, putrefactive species. 
One or the other species may be seen sometimes alone, sometimes com- 
bined. This finding refutes the old theory that the bile always is an- 
tagonistic to all putrefactive processes and to bacteria. It is even 
possible to cultivate the above-named bacteria in the bile outside of 
the body. They enter the bile-passages in a direction contrary to that 
of the bile-current and probably adhere to the superficial layer of the 
mucous membrane (in exceptional cases being introduced by intestinal 
worms). The same conditions obtain in the case of the bile-ducts as in 
the case of the salivary glands and the urinary passages. Occasionally, in 
all these passages the protection afforded by the outflow of the secretion 
and by the muscular closure of the external orifice grows insufficient (as 
at the orifice of the urethra and the ureters), and the different bacterial 
species succeed in penetrating them either by the growth of the microbes 
or by their motility (Bacillus typhi, cholere, coli). They may also succeed 
in gaining an entrance into the duct in case peristalsis or pressure from 
neighboring organs produces abnormal relative differences in pressure 
within the duodenum and the ductus choledochus. It is quite probable 
that here, as in other organs of the body, isolated bacteria may occa- 
sionally gain an entrance and do no harm because of their being speedily 
washed out again or of not finding conditions favorable to their develop- 
ment. In order that they may develop, there must be a number of 
favorable circumstances. Among these must be mentioned, as in the 
case of the urinary passages, the existence of mechanical obstructions 
to the outflow of the secretion (such as swelling of the mucosa in the 
region of the papilla, or impaction of concretions), partial or complete 
failure of the flushing process, or diminution in the nutrition and resisting 
powers of the mucous lining. These causes are all favored by an existing 
catarrh of the passages. 

Other factors may be active in addition to those mentioned, such as 
a diminution in the quantity of the bile or changes in its constitution, 
perversions in the nutrition of the mucosa, disturbances of the innerva- 
tion of the musculature of the bile-passages, etc. These different condi- 
tions may be the result of acute febrile and other diseases, or of acute 
digestive troubles and even of certain nervous disorders. 

The consequences of the invasion of the biliary passages by bacteria 
differ according to the species and virulence of the invading microbe. 
Particularly in the case of Bacterium coli do we find these differences 
marked. Owing to these different conditions, we see all grades of in- 
flammation of the mucous membranes. Beginning with an increased 
desquamation of epithelial cells and an increased secretion, the process 
may progress to suppuration and ulceration. Slight degrees of infection, 
particularly if they involve only the larger bile-passages or the main 
trunk, can presumably be overcome by the protective powers of the organ- 
ism, so that the tissues again become sterile. On the other hand, we may 
occasionally find bacteria in the bile-passages without any symptoms 
that can be attributed to their presence and without any anatomic 
changes of the mucous membranes. This may be due to the fact that 
such a latent infection is very mild from the beginning or that it con- 


472 DISEASES OF THE BILE-PASSAGES. 


stitutes the remnant of a severe infection that is in process of cure. 
Such a condition is clinically important for the reason that the bacteria 
present may without evident cause suddenly increase in virulence and 
thus cause a renewed infection of the bile-passages. 

The process of self-purification of the bile-passages is most difficult 
in the gall-bladder (which is practically a diverticulum of the ducts), 
chiefly on account of the narrowness of the cystic duct which constitutes 
a mechanical obstacle to the outflow of bile. 

Our knowledge of the anatomy and of the genesis of the diseases of 
the mucous lining of the bile-passages is very incomplete because milder 
cases and cases in their incipiency rarely come to autopsy. In addition, 
it is impossible to examine the diseased secretion of the mucosa, as can 
be done in the case of similar inflammations of the urinary or the respira- 
tory passages. The part that microbes play has been studied for a few 
years only. However important these “dnjections biliaires”’ may be, 
we must not overestimate their significance. I do not think, above all, 
that we are justified in following the example of many French authors, 
who teach that such infections alone can explain the pathology of all 
diseases of the bile-passages. 


There is no justification in assuming that the bile has antiputrefactive proper- 
ties, a view to which many investigators are inclined from the fact that feces contain- 
ing no bile were particularly offensive. Bile itself readily undergoes putrefactive 
changes, and, according to Kossel and Limberg, it can exercise an inhibiting effect 
on putrefaction of the intestinal contents only when it is in great concentration. 
Staphylococcus aureus and Bacillus coli can be cultivated in bile as well as in 
bouillon (Létienne). Gilbert and Dominici injected microbes into the bile-passages 
of living animals and found Bacillus coli and typhi and the streptococcus and 
staphylococcus after from two to four weeks, the cholera bacillus and pneumococcus 
after from two to five days; all in an active and virulent state. [The length of time 
during which the typhoid bacillus may remain in the gall-bladder is further con- 
sidered in the section on cholelithiasis —ED.] 

Normal bile removed from the gall-bladder during life or a few hours after death 
has in from fifty to seventy per cent. of the cases been found to be sterile. It cannot 
be determined positively whether the bacteria found in the remaining cases contami- 
nated the bile as a result of defective technique in removing and examining the bile 
or as a result of postmortem immigration. It is not impossible that in some in- 
stances bacteria may have gained an entrance into the gall-bladder during the agonal 
stage. Duclaux and Netter found Bacterium coli and Staphylococcus aureus in the 
terminal portion of the ductus choledochus in normal animals. Girode found the 
cholera bacillus in the bile-passages fourteen times in twenty-eight cases of cholera. 
and among these cases he observed suppurative inflammation in only one instance, 
In case Bacillus typhi has gained an entrance into the bile-passages, inflammatory 
reaction is less rarely absent. ‘This germ may remain in the bile-channels for from 
five to eight months after convalescence. The bacillus of typhoid, in particular, 
may gain an entrance into the bile-ducts by way of the liver, 2. e., by the descend- 
ing path. Létienne, in one case, determined the same for Bacillus tuberculosis. 
Bacillus coli is the parasite most frequently found in these tissues. It is always pres- 
ent in the duodenum, and as it is favored by its motility, it may gain an entrance 
into the bile-passages in almost any primary disease of these parts, as, for example, 
in typhoid fever either alone (Dupré) or together with the typhoid bacillus (Gilbert 
and Dominici). As arule, Bacillus coli produces an inflammation, but occasionally 
if the virulence of the germ is slight, no inflammation may result. It appears that 
this microbe may even participate in the formation of gall-stones. (For the literature 
on infection of the bile-ducts see the section on cholangitis suppurativa.) 


The symptoms of disease of the bile-passages are, on the one hand, 
icterus; on the other, disturbances of the general health. : 

Icterus, in case it was not present before, is caused by the swelling 
of the mucous lining of the bile-passages. In this manner an obstruction 
is created to the outflow of the bile. In view of the narrowness of the 





CHRONIC OBSTRUCTIVE JAUNDICE. 473 


bile-ducts such an obstruction is readily formed either by the swelling 
of the mucosa or by an increased desquamation of epithelial cells and 
an increased secretion of mucus. This is particularly the case in the 
finer passages. It is important to remember that the morbid products 
of a diseased mucous membrane may cause the precipitation of certain 
substances from the bile which gradually form masses and may form 
the nuclei of concretions. These, in their turn, keep up the catarrh 
and constitute an obstruction to the flow of bile, thus completing a 
vicious circle. 

The general symptoms are either a result of the stasis of bile as such, 
or of the infection of the bile-passages, or of the absorption of the in- 
flammatory products formed. We therefore have fever, and, in case 
the liver is secondarily involved, various perversions of the hepatic 
function. 

As a rule, icterus and disturbances of the general health are seen 
together ; yet it is possible for one or the other to be absent. 


DISTURBANCES IN THE CANALIZATION OF THE BILE; 
NARROWING AND OCCLUSION OF THE 
BILIARY PASSAGES. 


(Quincke. ) 


Whenever the lumen of the bile-passages is narrowed an obstruction 
to the outflow of bile is created, and dilatation of the passages above the 
narrowing is produced by the dammed-up bile. If the ductus chole- 
dochus is occluded, all the bile-passages are affected in this manner. 
If the ductus hepaticus or some of the smaller bile-ducts are occluded, 
their tributary branches alone become dilated. Occlusion of the cystic 
duct does not interfere with the circulation of the bile, but only stops 
the storing function of the gall-bladder. In this section we will discuss 
only those cases where the outflow of bile is impeded altogether, or at 
least in great part and for a long period of time. 


CHRONIC OBSTRUCTIVE JAUNDICE. 


Etiology.—Occlusion of the main duct may be produced either by 
the entrance of some foreign body that acts as an obturator, by some 
change in the walls of the duct, or by compression of the duct from 
without. 

I. Gall-stones are the most frequent cause of obstruction. As a rule, 
they become impacted behind the narrow orifice into the duodenum 
and act as a plug or a ball-valve. In case inflammatory processes super- 
vene as a result of the pressure of the stone on the walls of the duct, the 
narrowing may be still more increased. . 

Parasites are more rarely the cause of the obstruction. Of these, 
the echinococcus is the most frequent. In case the mother-cyst ruptures, 
daughter-cysts, whole or in fragments, may enter the bile-ducts. The 
much smaller cysts of the Echinococcus alveolaris can only occlude 
smaller bile-ducts, but, as a rule, they occlude many at a time. Echino- 
coccus vulgaris rarely produces obstructive icterus by the pressure it 
exercises from without; in the case of Echinococcus alveolaris, on the 
other hand, both compression and inflammatory processes in the walls 


474 DISEASES OF THE BILE-PASSAGES. 


of the ducts may cause stasis and occlusion. Distomata and ascarides 
may penetrate the bile-ducts from the intestine, develop within these 
passages, and by growing produce occlusion and (chiefly owing to bac- 
teria that they carry with them) inflammation of the walls of the ducts. 

Blood-clots and plugs of mucus may also produce obstruction. The 
former are very rarely seen, the latter very frequently. Although they 
do not properly deserve to be classified among foreign bodies, they are 
capable of causing occlusion of the intestinal end of the common duct 
in the same manner as do the latter. 

II. Inflammatory processes of the wall of the main bile-duct, in case 
the mucous membrane alone is involved, rarely produce complete occlu- 
sion for more than a few days, or at most a few weeks. A more per- 
sistent occlusion results if the connective-tissue structures of the wall or 
of the surrounding tissues are involved; for in such cases new-formation 
of connective tissue occurs, followed, as a rule, by the development of 
cicatricial tissue. Chronic phlegmonous inflammations of this kind can 
be caused by gall-stones impacted in the common duct, or, more rarely, 
by simple catarrhal inflammations (as a rule, bacterial in origin). In 
either instance cicatricial strictures of the passages are produced analo- 
gous to those seen in the urinary passages, notably the urethra. In 
exceptional cases the walls of the duct may grow together and a true 
atresia be the result. 

Fibrous inflammations may also involve the duct from without by 
direct continuity of tissue, as from an ulcer of the stomach or duodenum, 
from cholecystitis, or from a perihepatic inflammation in the region of the 
porta hepatis developing as a result of cirrhosis, gzummatous hepatitis, etc. 
The occlusion is produced either by the direct pressure of the cicatricial 
tissue or by traction or kinking following cicatricial contraction. 

Occasionally the closure of the orifice of the bile-duct is congenital or 
develops shortly after birth, probably not as a congenital anomaly, 
but as the result of intra-uterine disease. 

III. New-formations and tumors. Carcinoma of the ductus chole- 
dochus rapidly causes occlusion of its lumen. Obstruction is more 
frequently caused by carcinoma in the vicinity of the duct (stomach, 
duodenum, pancreas, gall-bladder), which may either compress the duct 
from without or grow into its walls and so occlude it. Even though 
such carcinomata are of small size, they may produce occlusion of the 
bile-ducts if they develop in their vicinity, particularly in the case of 
cancer of the stomach with metastases to the lymph-glands in the porta 
hepatis. The same mechanism may act in enlargement of the lymph- 
glands in the region of the porta due to tuberculosis, lymphoma, or 
secondary syphilis. Occasionally the enlargement of these glands causes 
compression of the portal vein with a resulting ascites from stasis. 

Other agencies that can produce occlusion of the common duct by 
transmitted pressure, traction, or displacement are tumors of the right 
kidney or suprarenal, carcinomatous and tuberculous swellings of the 
mesenteric and retroperitoneal glands, aneurysms of the abdominal and 
of the superior mesenteric artery, the accumulation of masses of fecal 
matter in the hepatic flexure of the colon following prolonged constipa- 
tion, the uterus when it is enlarged from pregnancy, and, finally, tumors 
of the ovary. Often many coexisting lesions occur to cause occlusion 
of the bile-duct, especially through the presence of slight peritoneal 
adhesions in the neighborhood of the porta. 


CHRONIC OBSTRUCTIVE JAUNDICE. 475 


Anatomy.—tThe bile-ducts are dilated above the obstruction. As a 
rule, the longer the duration of the stasis, the greater this dilatation. 
The main bile-ducts run a tortuous course and may become as large as a 
finger. On the surface of the liver there are areas in which even the 
smaller channels are dilated, forming net-like strands and resembling 
lymph-vessels. In certain portions of the liver great numbers of these 
dilated bile-channels are seen. The contents of the bile-passages may 
measure as much as a liter and the contents of the gall-bladder may be 
as much again. In the beginning the fluid contained in these vessels con- 
sists exclusively of bile; later the color disappears and the fluid grows 
colorless, mucous, or serous, and contains nothing but products of the 
mucous membrane and of its glands altered in character by the long-con- 
tinued stretching and tension. It seems that under these conditions the 
production of bile decreases, and that what little bile is formed is not 
poured into the bile-passages and mixed with their secretions, but is 
directly absorbed into the general circulation. In the bile-capillaries 
numerous yellow plugs are seen under the microscope. We have already 
described the changes in the liver itself and have shown that they may 
either be atrophic or inflammatory in character. 

In case the bile-ducts are infected with bacteria, we see, in addition to 
the changes just described, certain inflammatory lesions of the bile-pas- 
sages and of the liver itself. 

Symptoms; Diagnosis.—The symptoms of icterus that we have de- 
scribed above (see p. 433) are seen in a pure and uncomplicated form in the 
types of uncomplicated obstructive icterus that we are discussing. They 
occupy so prominent a part in the general morbid picture and make it so 
uniform that both the etiology and the prognosis are often for a long time 
difficult to determine. In order to solve the problem it is necessary to con- 
sider carefully the symptoms of lesions in other organs, the age and constitu- 
tion of the patient, and the appearance and the course of the icterus itself. 
Sudden appearance of icterus, great fluctuations in its intensity, its sudden 
disappearance, and a repetition of the attack at long intervals, sometimes 
years apart, speak for gall-stones or the impaction of some other foreign 
body. This suspicion will be strengthened if, in addition, the attack of 
icterus begins with pain and an accession of fever. Compression and in- 
flammation, as a rule, set in gradually and do not show such violent fluc- 
tuations in the intensity of the icterus. In addition, examination of 
the urine and the feces usually enables us to arrive at a diagnosis. At 
the same time, it must be remembered that compression may occasionally 
cause a sudden occlusion, and that, on the other hand, concretions may 
produce a gradual occlusion of the duct without other striking symptoms. 

The condition of the gall-bladder sometimes gives valuable diagnostic 
clues. In compression and inflammatory occlusion of the bile-duct the 
bladder is frequently distended, in gall-stones it is usually contracted 
(Courvoisier). [Recent investigations would seem to permit an even 
stronger statement as to the value of this diagnostic point. Courvoisier’s 
dictum is that in obstruction from causes other than gall-stones distention 
of the gall-bladder is the rule (Gewéhnliche). Cabot * has found only four 
exceptions to the “law” in 86 cases.—Eb.] 

Frequently the special diagnosis can be made only when the icterus is 
fully developed, or from its course, or even after it has subsided. 

Prognosis ; Duration.—The prognosis is dependent on the character 

* Med. News, Nov. 30, 1901. | 


476 DISEASES OF THE BILE-PASSAGES. 


of the occluding agency. In many instances death occurs altogether in- 
dependently of the existence of icterus, from cancer, suppurative inflam- 
mation, or gastric insufficiency. On the other hand, in certain cases of 
obstruction by stricture, concretions, or plugs of mucus death may occur 
from obstructive Jaundice alone. : 

The prognosis is in general more unfavorable if icterus has persisted 
for more than two months, and grows worse as stasis continues beyond that - 
time, not only because it becomes less probable that the obstacle will 
ever be removed, but also because the intoxication with bile becomes 
cumulative in its effect and the appearance of hepatargia with hepatic 
autointoxication may be expected at any time (see p. 440). Even in 
those cases where the stasis of bile is well borne for the first three or four 
months the strength and general nutrition will begin to suffer, and at the 
end of from eight to ten months, if icterus persists, serious nervous symp- 
toms may suddenly develop, and in the course of a few days lead to death. 

It is true that there are exceptional cases on record in which the condi- 
tion of chronic biliary stasis was borne for a much longer time. Budd 
reports a case in which it persisted for four years, and Murchison, Barth, 
and Besnier speak of cases in which recovery occurred after six years.* 


Hertz t+ describes a case of occlusion of the ductus choledochus by a gall-stone, 
in which the stools were of a light gray color for two years and a half and the skin 
was only slightly discolored to a dirty grayish-yellow. Eight times during this 
period attacks of icterus occurred that lasted, on an average, for six days and were 
accompanied by intermittent fever. The urine during the attacks was dark brown 
in color, but gave only a very slight Gmelin reaction, Hertz assumes that in this 
case the bile was completely absent from the intestine owing to the occlusion of 
the ductus choledochus, so that the only explanation for the non-appearance of 
icterus was the assumption that no bile was being formed. I believe that the 
obstruction (except during the attacks) was very slight, and that the greater part 
of the bile succeeded in entering the intestine through the bile-duct and a fistula 
that existed between the gall-bladder and the colon, and that the bile-pigment was 
here converted to the chromogen of urobilin by reduction.{ [In many respects 
the case resembles some of the reported instances of “ ball-valve stone.” —Ep.] 

Legendre, Gailard, and Debove § describe cases in which icterus, resulting 
from complete occlusion, existed for twenty-five years without seriously interfering 
with the general health of the patient. 


The treatment of biliary stasis is dependent on its cause; and at best is 
symptomatic. If the stasis persists for a long time, the establishment of 
a biliary fistula, even for a short time, seems indicated. 


CATARRH OF THE BILE-DUCTS; CHOLANGITIS 
CATARRHALIS 


(Quincke.) 


In the clinical sense, icterus catarrhalis and catarrh of the bile-duct are 
identical. From the anatomic point of view they are slightly different, 
since, on the one hand, we see catarrh of the bile-duct without icterus, and, 
on the other, we see attacks of so-called icterus catarrhalis that are not 

* Cited by Schiippel, p. 127. 

*+ Hertz: “ Wie lange kann ein Mensch leben bei vélligem Abschluss der Gallen- 


wege nach dem Darme?” Berliner klin. Wochenschr., 1877, pp. 76 and 91. 
* t Quincke, “Ueber die Farbe der Faces,” ““Mzanchner med. Wochenschr., 1896, 


o. 36. . 
§ Berliner klin. Wochenschr., 1897, p. 371. . 


CATARRH OF THE BILE-DUCTS. 477 


caused by catarrh of the bile-ducts. For the present we are unable, in 
individual cases, positively to localize the trouble in the large or the small 
bile-ducts, nor can we determine the exact pathogenesis in each case. 
For this reason we will first describe the clinical picture of catarrhal icterus 
and discuss the disease on this basis. After discussing this form in all 
its varieties, and after describing its mode of origin, we will proceed to a 
discussion of the other clinical forms of essential icterus. Some of the 
latter are certainly identical with catarrhal icterus, and should be classified 
with it; others probably originate in a particular manner and merit sepa- 
rate discussion. 


ICTERUS CATARRHALIS, 


Catarrhal Jaundice; Icterus gastro-duodenalis; Icterus simplex; 
Icterus benignus. 


Etiology.—The most frequent cause of catarrhal icterus being a gastro- 
intestinal catarrh, we frequently see it after overloading of the stomach, 
after eating very fatty, spoiled, or indigestible food, after taking much ice 
or drinking very cold beverages, and after the abuse of spirituous liquors. 
In many instances a slightly chronic condition, such as chronic alcoholism, 
exists and paves the way for the occurrence of an acute attack. Some- 
times the attack of icterus is preceded by a chilling or a wetting. In some 
instances several of these predisposing factors coexist, and a number of 
persons are exposed to the same harmful influences, so that it appears as 
though icterus occurred epidemically. 

The predisposition is increased by previous attacks of catarrhal jaun- 
dice, and by hyperemia or conditions of chronic enlargement of the liver. 

In some instances no etiologic factor of any kind can be discovered, 
so that we are forced to assume a particular, individual predisposition to 
icterus. 

Catarrh of the bile-passages is seen in the course of a variety of infec- 
tious diseases—among others, malaria, typhoid fever, and cholera; and in 
them icterus is at times seen. The jaundice seen in phosphorus-poison- 
ing is also probably due to a catarrh of the smaller bile-ducts. 

Concretions, by the mechanical pressure they exercise, sometimes pro- 
duce a swelling of the mucous lining of the bile-passages. These concre- 
tions, however, are themselves usually the effect of a catarrh of the bile- 
passages, and are capable only of i increasing the severity of the catarrh 
already existing. 

Catarrhal icterus is a common disease and is seen more frequently in 
young subjects than in the old and the middle-aged. In view of its causes, 
it is more often seen in men than in women. 

In children the disease is seen most frequently from the second to the 
seventh year, seldom during the first and second years of life. 

Symptoms.—As arule, following the different etiologic factors above 
enumerated, the symptoms of a gastric catarrh appear, with a feeling of 
pressure in the region of the stomach, loss of appetite, a coated tongue, 
nausea, and vomiting. In addition, headache, vertigo, depression, and, 
occasionally, fever are present. The bowels are, as a rule, constipated, 
rarely the opposite. The urine is scanty, reddish in color, and deposits a 
sediment. After the expiration of a few days icterus of the skin and a 
biliary discoloration of the urine are seen, and the feces grow light in color 
but are rarely altogether free from bile-pigment. After this condition has 


478 DISEASES OF THE BILE-PASSAGES. 


persisted for from one to two weeks the symptoms of the gastric catarrh 
diminish, the tongue becomes clean, and the appetite improves. Soon the 
signs of biliary stasis disappear, at first from the urine, later from the skin. 
As soon as the digestive organs begin to functionate normally, the general 
health seems to improve, not as rapidly, however, as might be expected 
from the reestablishment of normal digestion and the proper assimilation 
of food. 

The duration of the whole disease until the complete disappearance of 
the jaundice usually is from three to four weeks. It takes several weeks 
more, however, before health is completely reestablished. 

There are many exceptions to this usual course of an average case. 
The individual symptoms of an attack may vary and the duration of the 
disease may be longer or shorter. . 

The initial symptoms of a gastric catarrh are, as a rule, very pro- 
nounced, and precede the attack of icterus proper by three to four days, 
more rarely in a milder form by several weeks. In exceptional cases, 
icterus may develop before the appearance of gastric disturbances. Even 
in the cases where there is a complete obstruction to the entrance of bile 
into the intestine, this state exists for a few days only, so that varying 
quantities of bile are poured into the intestine at different times during 
the course of the disease, as is manifested by the varying color of the feces. 

The symptoms of biliary stasis, as such, have been described above. 
In catarrhal icterus they are seen in their most typical form, varying, of 
course, in intensity and duration. Of the nervous symptoms, the itching 
of the skin is the most frequent, the slowing of the pulse less so. The 
milder and the shorter cases of catarrhal icterus, as well as the stage of 
convalescence from well-marked attacks, correspond to the picture of 
urobilin icterus described above. 

The symptoms observed in the liver are varying and not character- 
istic. Sometimes a feeling of pressure is experienced in the region of 
the liver in addition to the feeling of oppression often complained of in 
the region of the stomach at the beginning of the attack. Increase in 
the size of the organ and in its consistency are found only in the very 
severe cases, probably in those only that are the result of infection. 

In a certain proportion of cases (one-third to one-half) the spleen is 
enlarged. 

The urine contains biliary constituents, or urobilin, hyaline casts 
(Nothnagel), rarely albumin. 

Fever may be observed in the first few days of an attack of simple 
catarrhal icterus, but is not a frequent or conspicuous symptom. In the 
later course of the disease the temperature is sometimes subnormal. 

Course.—The above description of catarrhal icterus applies to cases 
of medium severity. There are, however, other forms, as follows: 

I. Abortive forms of slight degree, which are shorter in duration and 
in which the stasis of bile does not persist for so long atime. The mildest 
forms of this kind differ from a simple gastric or intestinal catarrh only 
in that the skin may be colored slightly yellow for afew days. Asa 
rule, the severity of the disease corresponds to the duration and the 
severity of the biliary stasis. 

II. Occasionally catarrhal icterus runs a protracted course and may 
persist for from two to five months. During this time it may be uniform 
or may fluctuate in intensity, the exacerbations being usually due to a 
repetition of the indiscretions that primarily led to the attack, the 


CATARRH OF THE BILE-DUCTS. 479 


catarrh in process of cure being aggravated by a new acute attack. In 
those cases where febrile disturbances are seen with the recurrence of 
such an attack it is to be assumed that an infection of the bile-passages 
has occurred. 

III. In the cases where the attack of catarrhal icterus persists for 
several weeks with the same intensity, the symptoms of gastric and intes- 
tinal catarrh as a rule recede and the symptoms of pure uncomplicated 
biliary stasis become more apparent (disturbances in the general health, 
depression, emaciation, a feeling of weakness, and, in a word, those symp- 
toms described under the caption of Hepatic Autointoxication, page 440). 
It is, as a rule, impossible to decide whether the obstruction to the out- 
flow of bile is situated in the main duct or in some of its branches. 

The general clinical picture often so closely resembles the syndrome 
of biliary obstruction from some other cause, such as impacted gall- 
stones or some compressing neoplasm, that no definite decision can be 
arrived at until later in the course of the disease or until the permeabil- 
ity of the bile-ducts has been re-established. Recovery from these in- 
tense and long-lasting forms is slow, but generally complete. 

IV. Occasionally it will be found that the symptoms of the initial 
gastric catarrh are very severe, resembling the initial stages of an attack 
of typhoid fever. Violent pain in the limbs with headache, great depres- 
sion, Insomnia, high fever with chills, swelling of the spleen, and gastric 
symptoms without any objective findings in any of the other organs, 
all point to a general infection. If icterus appears at the end of the first 
week, it is frequently mistaken for a secondary symptom or some com- 
plication. Occasionally, at this stage, tenderness over the liver and 
a slight degree of enlargement of the organ are found. The fever usually 
runs an intermittent course and fluctuates between 39° and 40° C. (102.2° 
and 104° F.). Itmay persist for several weeks and then disappear slowly, 
as do all the other symptoms. The whole course of this form resembles 
an attack of typhoid fever. This form is rare, but has been described 
for along time. The attacks are usually, and probably correctly, attri- 
buted to a infection of the bile-ducts, and have been called infectious 
icterus (see below). Here, too, we encounter cases of different severity 
and duration resembling, on the one hand, simple catarrhal icterus, and, 
on the other, approaching in severity the fatal cases of icterus gravis. 
According to Chauffard, the toxic action of certain ptomains plays an 
important réle in this form. 

Sequels.—Catarrhal icterus is not infrequently followed by other dis- 
turbances, either following immediately in its train or not developing for 
several weeks after the attack. Among these must be mentioned the 
recurrence of attacks of icterus, which are analogous to the repeated 
occurrence of attacks of catarrh in other mucous membranes. It is 
probable that in these cases the swelling of the mucosa has not fully 
subsided, so that the latter reacts to some slight damaging agent, or, 
possibly, the orifice of the bile-duct was particularly narrow. In many 
instances the formation of concretions starts from catarrhal icterus, 
especially from the recurring form. Suppurative cholangitis may develop 
from a simple catarrh with or without concretions. 

The catarrhal condition may subside in the main bile-ducts, but 
persist in the cystic duct and in the gall-bladder, so that we may see the 
development of hydrops of the gall-bladder or persistent inflammation 
follow such repeated attacks of catarrhal icterus. 


480 : DISEASES OF THE BILE-PASSAGES. 


Occasionally catarrhal icterus, and here again particularly the recur- 
ring form, is the starting-point for chronic inflammations of the hepatic 
parenchyma, such as Hanot’s hypertrophic form and, possibly, of other 
forms of cirrhosis of the liver. In rare instances acute yellow atrophy of 
the liver has been known to develop after catarrhal icterus. 

Anatomy.—The anatomic changes ordinarily seen in other catarrhs 
are occasionally seen in catarrhal icterus—namely, a loosening of the 
mucous membrane, desquamation of epithelial cells, and the secretion of 
mucus containing a varying number of leucocytes. All these changes may 
be seen at autopsy, even though the presence of a catarrh of the bile- 
passages was not suspected during life. On the other hand, the anatomic 
findings in a case of catarrhal icterus may be such that they do not at all 
explain the occurrence of icterus and of biliary stasis. As a rule, the 
presence of a plug of mucus in the intestinal portion of the bile-duct, ab- 
sence of bile-staining of the ducts, and difficulty in emptying the gall- 
bladder by pressure, are considered evidence of its occlusion and imper- 
meability during life. Both positive and negative findings in regard to 
these points are of only relative value, and must always be considered in 
connection with the color of the contents of the duodenum and the amount 
of material contained within the bile-passages. It can be seen that acute 
degrees of stenosis from swelling of the mucous membranes can be greatly 
changed after death if we study the conditions existing in such places as 
the larynx, which is much wider than the bile-ducts and consequently 
more easily examined. Opportunities for examining cases of recent ca- 
tarrhal icterus postmortem rarely occur. It is probable that there are 
cases where we might expect to see the intestinal end of the ductus chole- 
dochus compressed by the swollen mucosa of the duodenum without its 
being itself diseased, others with catarrh of the bile-passages ascenting for 
varying distances into the duct, and others again that, as in phosphorus- 
poisoning and in hyperemia of the liver from stasis, involve the finer bile- 
passages alone. The latter cases would correspond to the so-called 
“capillary bronchitis,” but would not in reality have anything to do 
with the bile-capillaries. Such a catarrh of the finer passages is developed 
in an irregular manner and does not involve all portions of the liver 
uniformly. Partial catarrh is seen in the intrahepatic bile-passages 
associated with concretions. 


Whenever the terminal portion of the ductus choledochus is occluded b 
swelling or by a plug of mucus, the pancreatic duct also is usually occluded. 
This does not occur if the joint orifice of these two passages is abnormally con- 
structed or if an auxiliary passage is present. Nothing definite is so far known in 
regard to the clinical significance of stasis of pancreatic juice occurring at the same 
time as stasis of bile.* (Salol is decomposed within the intestine, and, therefore,— 
whether the pancreatic juice be present or not,—cannot be employed for diagnostic 
purposes. ) 


Pathogenesis.—From the differences seen in the various clinical pic- 
tures of catarrhal icterus, and from the uncertainty of the anatomic find- 
ings, we are forced to the conclusion that this disease is not a clinical — 
entity, but is composed of a group of different conditions varying with 
the anatomic seat of the trouble and the mode of origin. | 

‘For the present it is impossible to decide what réle bacterial infection 
plays in this disease of the bile-passages.' This point can be settled only | 


*Fr, Miiller, “Untersuchungen iiber Icterus,’’ Zeitschr. fir klin. Medicin, 
1887, vol. x11, p. 80. 


CATARRH OF THE BILE-DUCTS. 481 


by continued investigation of many cases. Exact conclusions are ren- 
dered particularly difficult by the possibility of secondary infection and of 
postmortem changes and microbic invasion. It is probable that bacterial 
infection forms the basis of many more cases than we suspect, and it is 
even possible that the majority of all cases are due to this factor. I think, 
however, that we are not justified in assuming such an origin for all cases 
of catarrhal icterus. [Fever and disturbances of the general health in 
combination with icterus cannot be considered as diagnostic of bacterial 
infection of the bile-passages, for such an infection (as by Bacterium coli) 
may exist without producing any fever or even icterus. On the other 
hand, various serious disturbances of the general health may be caused by 
the absorption of toxins from the intestine or from simple stasis or bile or 
hepatargia. 

Diagnosis.—The diagnosis of catarrhal icterus in those cases where it 
begins in a typical manner with the symptoms of a gastric catarrh is 
plain. In the cases, on the other hand, in which it begins less acutely, or 
in which the onset deviates from the typical course, the diagnosis is not so 
simple. In cases of the latter kind there is always danger of making 
the diagnosis of catarrhal icterus because of its greater frequency, the sub- 
sequent course making a revision of the diagnosis necessary. This is par- 
ticularly the case in impaction of gall-stones, which may occur without 
causing any pain, and in cases of compression of the common duct by 
tumors—two cofiditions which may lead to the rapid development of 
icterus. For these reasons the only method of arriving at a diagnosis is 
by exclusion and-by observing whether the disease runs a favorable course 
or not. In many instances, however, the youth of the patient, a knowl- 
edge of the primary cause of the trouble, such as a gastric catarrh, will 
assure the diagnosis. On the other hand, it must not be forgotten that, 
even though the icterus persists for many months, this does not exclude 
the catarrhal nature of the trouble. 

Prognosis.—While the prognosis of this: disease is favorable, as arule, 
it can never be positively made, particularly in regard to the probable 
duration of the case and the length of convalescence. If the case begins 
acutely with fever, we can usually prognosticate that the disease will last 
for several weeks and will produce a considerable loss of strength and a 
reduction in the general nutrition of the patient. At the same time, a 
mild onset and incomplete stasis may be followed by a protracted attack. 
Those cases are particularly uncertain, especially as to the length of con- 
valescence, in which a tendency to recurrence exists and in which errors 
of diet and hygiene have already been, or in all probability will be, com- 
- mitted by the patient. In old people an attack of simple catarrhal itcerus 
may end fatally from long-continued stasis of bile.* Toelg and Neusser 
have described the case of a strong well-nourished man who died within 
eight weeks with numerous puibeensaHey into the cellular tissues and into 
the peritoneal cavity. 

Treatment.—The treatment of hanie catarrhal icterus is identical 
with that of acute gastric or intestinal catarrh. The only difference is 
that, owing to the complication with icterus, these cases need more time 
and greater care before a cure can be effected. 

Only in those comparatively rare cases in which a chilling has preceded 
the attack is a course of sweating indicated. Wherever, with the appear- 

* Leichtenstern, loc. cit., p.9. Fr. Miller, Zeitschr. fiir klin. Medicin, 1887, 
vol. x11, p. 80. 

31 


482 DISEASES OF THE BILE-PASSAGES. 


ance of icterus, a free evacuation of the bowels has not occurred, it is 
necessary to empty the bowels. Abstinence from all solid food, and limi- 
tation of the nourishment to tea, water, mineral waters, and thin soups 
will usually meet the patient’s wants, and are indicated as long as the 
tongue is coated or fever exists and a feeling of pressure in the gastric 
region is present. The remedy indicated at this period is a solution 
of sodium bicarbonate (5:100). Hydrochloric acid is very popular, 
but not so appropriate. Large drafts of water, drunk as hot as the 
patient can tolerate, with dram doses of sodium phosphate three times 
daily have a beneficial effect upon the gastroduodenal catarrh.—Eb.] 

It is well to obtain a free evacuation of the bowels by drugs. For 
this purpose one or several doses of calomel (0.3 to 0.5) are indicated; 
later laxatives, such as Glauber’s salts, Epsom salts, the tartrates, and 
rhubarb. The administration of castor oil is not so suitable, particularly 
for repeated use, and should not be used if much gastric disturbance 
exists. It is useful chiefly in the beginning of an attack where intesti- 
nal symptoms and colic predominate. [Sodium phosphate probably acts 
as well as any other laxative, and is unirritating.—Eb.] 

It is not necessary to combat existing diarrhea, especially at the 
outset. As arule, it will disappear spontaneously if the patient observes 
the proper rules. In case it seems necessary to control it, hydrochloric 
acid, astringents, bismuth subnitrate, or tannigen (four doses of 1.0), 
may be used; but opium should only exceptionally be administered, and 
then only for the relief of violent colic. 

The rules in regard to the general mode of life are important and 
should be carefully observed. Even in the absence of fever the patient 
should remain in bed as long, at least, as symptoms of acute dyspepsia 
are present. As soon as these symptoms disappear, and the patient 
begins to take a little nourishment, he may be permitted to leave the 
bed for a few hours at a time, and, where it is possible, stay in the open 
air, and may even be permitted to walk afew steps. All sustained bodily 
exertion and all exposure to chilling should be avoided as long as the 
flow of bile is not completely re-established. Particularly in protracted 
cases and during convalescence from dyspeptic disturbances careful 
regulations in these particulars should be made by the physician. The 
stage of the disease should, of course, not be Judged from the color of the 
skin, but from the color of the feces and urine. With the return of appe- 
tite a little food can be administered, but all chemically and mechanically 
irritating articles of diet should be carefully avoided. Thickened soups, 
_ lean meat, white bread, and zwieback should be given first. Although 
theoretically milk is not a good article of diet because of its contained fat, 
practically it seems to be well borne; while meat, for no physiologic rea- 
son, is repugnant to patients, possibly because of the closure of the pan- 
creatic duct. In regard to general principles of treatment, see page 462. 
The increase of the dietary should be governed by individual conditions 
in the same manner as in any other form of gastric catarrh. It is par- 
ticularly important that each meal should be simple, that alcohol and 
narcotics should be avoided, and that little food should be given at each 
meal. The latter rule should also be observed during convalescence, 
when the appetite is frequently inordinately increased and its gratifica- 
tion may become dangerous to the patient. 

In those cases that persist for several months the gastro-intestinal 
catarrh has usually ceased, and the general nutrition of the patient must 


a 


CATARRH OF THE BILE-DUCTS. 483 


be maintained and a more generous diet allowed, even though the stasis 
of bile persists. In such cases it is well to imit the amount of fat and 
to replace it by a corresponding amount of starchy food. 

The administration of the remedies that are given during the time of 
the acute catarrhal attack should be stopped as soon as the dyspeptic dis- 
turbances are better or have disappeared. When the tongue is no longer 
coated, hydrochloric acid may be given with meals, and the administra- 
tion of rhubarb may be continued, either alone or in combination with 
such bitters as gentian, calamus, or cascarilla in small doses. 

As long as the stasis of bile persists wholly or in part, alkaline or alka- 
line-saline watérs or the waters of different hot springs can be administered 
to advantage, especially the warm or hot waters, like Vichy, Neuenahr, 
or Carlsbad. The cold waters, such as Eger, Marienbad, Tarasp, and Rip- 
poldsau, are indicated only in case there is a tendency to constipation. 

The administration of enemata once or several times daily at the height 
of biliary stasis has been recommended in quantities of from one to one and 
a half liters (Mosler, Krull). The rationale of this method of treatment is 
based on the unsupported experimental finding of Stadelmann that the 
secretion of bile is increased by such injections. Possibly these injections, 
if they are retained for a long time, stimulate peristalsis, and in this man- 
ner promote the outflow of bile. I have occasionally employed injections 
with some success and other clinicians report the same. In view of the 
variable course of the disease it is a difficult matter to determine the true 
effect of the various remedies. 

It has been the desire of physicians of all times to find remedies that 
would produce an increased flow of bile in biliary stasis. As a result, the 
action of certain drugs, such as calomel and rhubarb, whose beneficial 
effects in this disease were known, was explained on the idea that they 
were cholagogues. We know, however, particularly in the case of the two 
drugs named, that they do not possess this property. Where a large 
amount of mucus is present in the bile-passages and hinders the flow of 
bile, we would expect that a remedy that could dilute the bile or could 
exercise a solvent action on the mucus would aid in removing the obstacle 
to the outflow of bile. In this sense it is possible that the administration 
of much water by the intestine or by the stomach will act beneficially. 
The same applies to common salt, alkalies, and certain mineral waters, 
and to laxative remedies, and even food acts reflexly. As we have 
seen above, many theoretic objections could be formulated against the 
possibility of an increase of the secretion of bile by the administration of 
cholagogues. 


Gerhardt: “‘ Ueber Icterus gastroduodenalis,” “ Volkmann’s Sammlung klin. Vor- 
traige,’”’ No. 17, 1871. 

Heitler: “Zur Klinik des Icterus catarrhalis,” ‘“Wiener med, Wochenschr.,’’ Nos, 
29 to 31, 1887. 

Herzenstein, Helene (Dieulafoy) : “ Contrib. a étude de Victére catarrhal. prolongé.”? 
These de Paris, 1890. 

Senator: ‘‘ Ueber Ieterus; seine Entstehung und Behandlung,” “ Berliner Klinik,” 
part 1, 1888. 

Sommer, P.: “Ueber Icterus catarrhalis im Kindesalter.” Dissertation, Kiel, 1896. 

Toelg and Neusser: “Ein Fall von Icterus catarrhalis mit tédlichem Ausgang,” 
“ Zeitschr. fiir klin, Medicin,” vol. vit, p. 321, 1884. 


(See also Literature on Cholangitis, p. 514; on Icterus, p. 449; and on Icterus 
infectiosus, p. 507.) 


cd 


484 DISEASES OF THE BILE-PASSAGES. 


ICTERUS EX EMOTIONE. 
Icterus psychicus; Icterus spasticus. 


In the eyes of the laity the secretion of bile and the hepatic functions 
in general are intimately connected with a disagreeable mood or a gloomy 
temperament. Such expressions as a “bilious temperament” and “his 
bile overflows” are illustrative of this idea. Jaundice, too, is usually 
attributed to an attack of anger, and in certain classes this idea is so 
deeply rooted that such an attack is postulated in every case of jaundice 
and the patient will try to remember when it occurred. It is not surpris- 
ing that, as arule, the patient will remember that he was angry a short or 
a long time before the occurrence of Jaundice. 

* As examples of the dependence of jaundice upon psychic disturbances 
cases are adduced in which Jaundice suddenly appeared a few hours or 
even afew moments after an attack of anger with a complete absence of all 
other predisposing factors or other symptoms of disease. Such examples, 
it is true, are rare and are transmitted by hearsay (see the summary by 
Daraignez). The causes given, besides anger, are sudden fright, mortal 
terror, and a gross insult. Besides jaundice, there may be seen, as a 
result of psychic injury, a feeling of great anxiety, pressure in the epigas- 
tric region, or violent diarrhea. | 

It is stated that emotional icterus does not persist for a long time, at 
most for a week, and that complete recovery rapidly ensues. In a few 
cases acute atrophy of the liver has been reported. 

Different explanations of emotional icterus have been attempted, as 
follows: 

I. Polycholia. The basis of this assumption is the theory that 
psychic disturbances are capable of causing an increased excretion of bile. 
This has not been proved, and even if it had it would not suffice for an 
explanation (see page 493). 

IJ. A paralysis of the bile-passages (Laborde). 

III. Disturbances in the circulation and particularly a sudden reduc- 
tion in the tone of the abdominal vessels. In this way a diminution in the 
blood-pressure in the portal vein would be produced, and thereby bile 
from the bile-capillaries would be diffused into the blood-capillaries. In 
addition, fright might produce a sudden reduction in the strength of the 
heart-beat and of the respiratory movements, all factors that would tend 
to facilitate the above diffusion (Frerichs). 

IV. Spasm of the bile-passages. It is said that a spasmodic closure 
of the ductus choledochus occurs and that stasis of bile is caused in this 
manner. It might even be that a general spasmodic contraction of other 
bile-passages supervened, and that in this manner still greater biliary 
pressure would be caused. [Débove* has supposed it possible that relaxa- 
tion of the sphincter of the choledochus might occur from emotion and 
thus favor infection of the bile-passages.—ED.] 

Of all these explanations, the last one seems to have the best founda- 
tion, because we know that the bile-passages are, in fact, capable of con- 
traction, and that it is quite possible, to judge from analogous conditions 
obServed in other organs, that disturbances in their normal movements 
can occur, and that these may be either spasmodic or paralytic in char- 
acter. 


* Gaz. hebdom. de Méd. et de Chir., 1901, No. 33. 


CATARRH OF THE BILE-DUCTS. 485 


The older view, that biliary stasis must persist for several days in order to 
produce icterus, although based on animal experiments, has not been borne out 
by the facts observed. To judge from observations made in cases with impacted 
gall-stones, it seems that from six to twelve hours are sufficient (see page 444). 
An animal experiment (by Lépine and Douillet *) is worthy of mention, inasmuch 
as it shows that the constituents of the bile, which ordinarily enter the blood by 
way of the lymph-channels and the thoracic duct, can enter the hepatic veins 
directly in case the pressure within the bile-passages is suddenly increased. 

It is true we do not know whether a spasm of the bile-passages lasting for 
several hours really occurs. We can concede, however, that such a thing is physio- 
logically conceivable; so that we must agree that, hypothetically at least, icterus 
spasticus is possible. In many cases, in addition, the blood-pressure in the portal 
vein may be reduced, and in this manner a second factor be adduced that favors 
the entrance of bile into the blood. 


A certain time, at all events, must elapse before a sufficient quantity 
of biliary constituents can enter the blood-serum, and after that a certain 
time must again elapse before the skin can become discolored. I am 
inclined to think that from three to four hours is the minimum time in 
which this can occur. We must seek another explanation for the cases 
of instantaneous jaundice that have been known to occur when persons 
were suddenly brought face to face with death, etc. In these cases either 
a slight degree of icterus existed at the time but was not noticeable until a 
_ sudden pallor of the skin occurred; or the skin of the patient was naturally 
yellow and the color did not appear until a sudden anemia supervened. 

Those cases, too, in which from one to two days elapsed between the 
psychic disturbance and the appearance of jaundice can be explained in 
still a different manner. As a result of the fright a sudden stoppage of 
the functions of the stomach may occur with subsequent swelling of the 
mucous membrane. This would produce a simple catarrhal icterus. It 
is also conceivable that the psychic disturbance may lead to serious dis- 
turbances in the innervation and the peristalsis of the duodenum and the 
bile-passages, so that a paralysis of the sphincter of the ductus choledo- 
chus occurs, and in this manner some of the intestinal contents gains an 
entrance into the ducts and causes a bacterial infection of the bile- 
passages. 


Chauffard: “ Archives générales de médecine,” 1890, 11, p. 410 (case 3, 1 hour). 
Daraignez, J.: “ Pathogénie de l’ictére emotif,’’ Thése de Paris, 1890. 
Hardy: “ De l’ictére émotionel,”’ “Gazette des hépitaux,” 1882, No. 2. 
‘Nagel: “Un cas d’ictére émotif, accompagné d’une éruption généralisée de lichen,” 
“ Progres méd.,”’ 1886, No. 34, 14. Aodt. 
Patoin: ‘“Icterus from Emotions,” “The Med. and Surg. Reporter,’”’ 1891, No. 114 ; 
“T’Union méd.,” No. 70. 
— “Tetére spasmodique immédiat,”’ “Gazette des hépitaux,”’ No. 31, 1884. 
Rendu: “ Bulletin de la société clinique,” p. 134, 1884 (# of an hour). 


ICTERUS GRAVIDARUM. 


Just as is the case with other individuals, pregnant women may become 
afflicted with simple, so-called catarrhal icterus. Toward the end of preg- 
nancy an attack is favored by the pressure exercised on the lower surface 
of the liver by the enlarged uterus. In those cases where corset liver is 
present or where constipation with accumulation of fecal matter in the 
lower bowel exists the predisposition is still greater. As arule, this simple 
form of icterus runs a benign course, in some instances not receding until 
after the child is born and the dislocation of the abdominal organs and 


* “Thése de Lyon,’ 1884. 


486 DISEASES OF THE BILE-PASSAGES. 


the traction on the liver are corrected. In rare cases the occurrence of 
icterus during pregnancy causes the death of the fetus or a miscarriage. 
[Benedict * has recently reported the cases of two sisters who had repeated 
attacks of jaundice with enlargement of the liver synchronously with preg- 
nancy and disappearing after abortion or premature delivery.—Eb.]| 

In rare instances acute yellow atrophy of the liver may develop from 
an apparently simple icterus. A knowledge of this possibility should 
induce us to be very guarded in our prognosis of icterus occurring during 
pregnancy, and to treat such an attack with great care. 


Frerichs: Loe. cit., 1, p. 200. 
Miller, P.:“ Die Krankheiten des weiblichen Kérpers,” etc., Stuttgart, 1888, p. 119. 
Spiegelberg: ‘Lehrbuch der Geburtshilfe,” p. 246. 


ICTERUS MENSTRUALIS. 


Senator has described four cases of recurring icterus appearing imme- 
diately before or during menstruation. As soon as the menstrual flow 
became profuse the icterus disappeared. In several of these attacks the 
liver was found to be swollen, the feces to be decolorized, and the gastric 
functions disturbed. In the interim the general health was unimpaired. 
Senator assumes that in these cases a hyperemic condition of the liver, 
quite frequently observed during menstruation, was complicated by a_ 
swelling of the mucous lining of the bile-passages. According to Senator, 
mild degrees of icterus are often seen during menstruation. 

Frerichs + describes under the caption of “neuralgia of the liver” 
a case in which for several years attacks of icterus accompanied by violent 
pain and swelling of the liver immediately preceded menstruation. 


Miller, P.: Loc. cit., p. 118. 
Senator: ‘“ Berliner klin. Wochenschr.,”’ 1872, No. 57. 


ICTERUS EX INANITIONE (STARVATION JAUNDICE). 


In cases of starvation lasting for a few days or for a longer period of 
time (such as occurs in occlusion of the esophagus, or on refusal to take 
food, etc.) a slight degree of icteric discoloration of the conjunctiva or of 
the skin is occasionally observed. Trendelenburg (quoted by Naunyn) 
mentions one case of this kind in which he observed a slight reaction for 
bile-pigment in the urine. , 

These cases are analogous to those that occur in dogs when they are 
starved for experimental purposes; here also some bile-pigment is 
usually found in the urine (see p. 445). In both instances the peristaltic 
action of the bile-passages is increased, and at the same time the blood- 
pressure within the portal vein falls, so that absorption of bile is the 
natural result. In the case of human beings bilirubin, after absorption in 
the liver, seems more easily to enter the tissues, whereas in the dog it is 
more easily excreted in the urine. 

Grimm ¢ reports the constant occurrence of urobilinuria in an opium-eater 
who was on a restricted diet (milk and eggs). Occasionally he would exhibit 
a mild degree of icterus of the urine and of the skin. ; 

{t must be mentioned here that a great many persons, otherwise per- 
fectly healthy, occasionally show a yellowish discoloration of the con- 


* Deutsche med. Woch., April 19, 1902. + Loc. cit., u, p. 528. 
t Virchow’s Archiv, 1893, vol. cxxxt1, p. 265, 


CATARRH OF THE BILE-DUCTS. 487 


junctiva that can hardly be distinguished from a true icteric discoloration. 
These attacks may occur without causing any symptoms or they may be 
accompanied by a slight feeling of malaise. No definite statements in 
regard to the mode of origin and the significance of these attacks can be 
made. 


ICTERUS SYPHILITICUS. 


Aside from its occurrence as an accidental concomitant of syphilis, 
jaundice may be due to this infection and may originate in different ways. 
In the tertiary stage of the disease gummatous or diffuse hepatitis may 
lead to icterus (for examples of this form see Otto, loc. cit.). We are only 
interested in this place in that form of icterus seen in the earlier stages 
of syphilis which is called icterus syphiliticus and to which the prefix 
‘“‘precox”’ is occasionally added. This is a form of icterus from stasis 
and resembles simple catarrhal icterus as regards its duration, course, and 
degree. As arule, too, it recedes in the same manner as does catarrhal 
icterus. Gubler (1854) was the first to call attention to the connection 
of this form of icterus with syphilis. 

This form is not frequent in the secondary stage. Engel-Reimers 
states that it occurs in 1.4 % of all cases; later (according to Wer- 
ner) in 0.3 % as studied in fifteen thousand cases of early syphilis. 
It seems that it occurs with varying frequency, as I observed six cases in 
four years, while in all the years before and after this period I saw only one 
other (see Otto, loc. cit.).  Lasch has collected forty-six cases from the 
general literature and three of Neisser’s. According to Fournier, syphil- 
itic icterus is more frequent in women than in men. [Werner also found 
this preponderance in women.—Ep.] 

_Jaundice appears usually with the first secondary symptoms on the 
skin and mucous membranes, sometimes not until a secondary exacerba- 
tion occurs. At the height of the disease the stools are, as a rule, but not 
in all instances, decolorized. Those cases of syphilis that are complicated 
by icterus usually run a severe course and develop serious secondary 
symptoms, usually with an initial rise of temperature and profuse 
eruptions in the skin and mucous membranes. In 80 % of the cases the 
lymph-glands are much swollen (Werner). Its duration varies, usually 
lasting, according to Werner, from three to four weeks. With appro- 
priate and anti-syphilitic treatment the icterus usually disappears together 
with the other symptoms. 

As catarrhal icterus is so frequently met with, it might be assumed that 
the combination ‘of icterus and syphilis was a coincidence. The fact, 
however, that icterus is seen particularly during the stage of eruption 
speaks against the assumption that the simultaneous occurrence of the 
two conditions is a matter of chance. Further, the absence of the usual 
initial symptoms of simple catarrhal icterus (gastro-intestinal disturb- 
ances) and of the usual causative factors (errors in diet or taking cold) 
speaks distinctly against the identity of the form of icterus under discus- 
sion and catarrhalicterus. It is not surprising that the eruption of syphilis 
can bring about disturbances in the general health, and we know that 
stasis of bile produces similar disturbances. A leading argument in favor 
of the syphilitic origin of this icterus is the fact that it disappears under 
anti-syphilitic treatment, just as do all the other specific symptoms. In 
one case reported by Engel-Reimers icterus reappeared together with other 
symptoms of syphilis during a recurrent attack of the disease. In another 


488 DISEASES OF THE BILE-PASSAGES. 


ease that I observed (Case 5 in Otto’s series) ascites and swelling of the 
spleen developed simultaneously with icterus, all the symptoms disap- 
pearing again after a course of mercurial treatment had been instituted. 

Sometimes acute yellow atrophy is seen to develop following the attack 
of icterus (Ingel-Reimers, Senator, Neisser in Lasch’s work). Engel- 
Reimers, in his three cases, observed a very considerable swelling of the 
lymph-glands in the region of the porta hepatis that is not, as a rule, seen 
in acute yellow atrophy. 

Pathogenesis.—There can be no doubt that icterus syphiliticus is 
a form of obstructive jaundice. 

A number of different explanations have been given for the occurrence 
of this stasis. The first theory, advanced by Rampold, was that it was 
due to the action of mercury. His position, however, is untenable, as this 
form of icterus is frequently seen before any treatment is instituted. 
Gubler assumed that the mucous membrane of the duodenum and of the 
bile-passages was swollen as a result of a specific involvement of these tis- 
sues, as is the case with the mucosa of the mouth, pharynx, and larynx; 
but such mucous lesions are never seen in the intestinal mucosa. Lance- 
raux’s theory is much more probable. He assumes that the glands of 
the porta hepatis are swollen in the same manner as are so many other 
glands of the body, and that they occlude or compress the bile-duct from 
without. This idea is supported by the finding of Engel-Reimers reported 
above, and by my observation of the occurrence of ascites and enlarge- 
ment of the spleen in one case, appearing and disappearing with the 
icterus. [In 41 out of Werner’s 50 cases there was marked general 
glandular enlargement.—Ep.] It is probable that in this condition the 
enlarged glands compress both the bile-duct and the portal vein, as 
they so often do in carcinomatous enlargement. , 

It can be readily understood why icterus syphiliticus is not seen more 
frequently when we consider that the same variation in regard to syphilitic 
enlargement probably exists in the case of the internal lymph-glands as of 
the external ones, and that, further, the anatomic relation of the portal 
lymph-glands to the bile-duct is different in different individuals. 


Mauriac’s theory must be regarded as altogether hypothetic. He states that 
an interstitial hepatitis, occurring at an exceptionally early stage of the disease, 
causes compression of the finer bile-ducts. Against the validity of this theory we 
can adduce the complete absence of anatomic foundation and the fact that the 
disease runs a short course in many instances, and, finally, that the stools are often 
completely colorless. 


In addition to cases in which the syphilitic origin of the attack of jaun- 
dice is established beyond a doubt, there are many cases that are atypical 
and in which the mutual relations of the two diseases are not so distinct 
and definite. In cases where icterus appears alone and the symptoms of 
syphilis do not develop for some time, or, again, in cases in which icterus 
does not appear until after the disappearance of the secondary symptoms 
of syphilis, it is difficult to state whether they are independent or not. In 
the latter instance the icteric attack, in a way, takes the place of or is 
equivalent to arecurrence. Cases of this kind can be explained as well by 
the theory of mucous membrane involvement as by that of glandular 
swelling, because we often see glands and mucous membranes swollen as a 
result of constitutional lues some time before other localized manifesta- 
tions of the disease appear. In all such doubtful cases it will be necessary 
carefully to consider the possibility of a non-syphilitic origin of the attack 


CATARRH OF THE BILE-DUCTS. 489 


of icterus; and occasionally it will be impossible to arrive at a positive 
conclusion. 


Baumler; “ Ziemssen’s Handbuch der speciellen Pathologie,” ur, 1, p. 192. 

Eng el-Reimers: “ Ueber acute gelbe Leberatrophie in der Frihperiode der Syphilis,” 
“ Jahrbuch der Hamburger Staatskrankenhauser,” 1, 1889. 

— “Ueber die visceralen Erkrankungen i in der Friihperiode der Syphilis,” “ Monats- 
hefte fir praktische Dermatologie,” xv, p. 478, 1892. 

Gubler: ‘‘ Mémoire sur lictére, qui accompagne quelques fois les éruptions syphili- 
tiques précoces,”’ “Mémoires de la société de Biologie,” vol. v, p. 235, 1853. 

Josef : “ Ueber Icterus im Frihstadium der Syphilis,” “ Archiv fiir Dermatologie und 
Syphilis,” vol. xxrx, 1894. 

Lanceraux: “Traité historique et pratique de la Syphilis,” 1. édition, p. 146, 1866. 

Lasch, O. (Neisser): “ Icterus syphiliticus praecox,”’ “Berliner klin. Wochenschr., . 
No. 40, p. 906, 1894 (3 cases). Mentions 49 cases from literature. 

Otto, M.: “ Ueber Icterus syphiliticus.” Dissertation, Kiel, 1894 (7 cases, Quincke), 
Ref. in “Berliner klin. Wochenschr.,” p. 1116, 1894. 

Quincke: XII. Congress fiir innere Medicin, p. 180, 1893. 

Senator: “ Ueber Icterus und acute gelbe Leberatrophie bei Syphilis,” ibid., p. 185. 

Thimmel, K. : “ Ueber Icterus in der Friihperiode der Syphilis.” Dissertation, Berlin, 
1894 a case, Senator). 

Werner, S.: “ Beitrag zur Pathologie des syphilitischen Icterus” (material of Engel- 
Reimers), ‘“‘ Munchener med. Wochenschr.,’”’ No. 27, 1897. 


ICTERUS NEONATORUM. 


The name icterus neonatorum is applied to a form of icterus that is 
very frequently seen in the new-born and that occurs independently of any 
other lesions and runs a favorable course. 

This disease must not be confused (as it has been occasionally) with 
icterus occurring in the new-born and due to a variety of possible causes, 
such as septicemia or syphilis. 

Jaundice is seen in about two-thirds of all new-born infants. Different 
investigators furnish various statistics (Cruse, 85%; Porak, 80%; 
Kehrer, 69%; Elsasser, 50%; Epstein, 42%; Seux, 16%). The disease 
is seen more frequently in boys than in girls, and occurs more often in 
small than in large children. It is frequently seen in the prematurely 
born, and also if the delivery was performed under chloroform (Hofmeier). 
It is more intense and more frequent in children whose skin is congested. 
The character of the food given has nothing to do with its occurrence. 

It is probable that external conditions are in some way concerned in 
the appearance of the disease. Epstein states that it is rare in private 
families, whereas the statistics of different public institutions reveal vary- 
ing degrees of frequency. 

The icterus begins on the second or third day of life and, as is usual in 
adults, appears first on the face and the chest. The sclera becomes dis- 
colored later than in adults and becomes icteric only in the more severe 
cases. The yellow discoloration sometimes persists for a few days only, 
but as a rule remains visible until the middle of the second week, occa- 
sionally as long as the third and fourth weeks. Recurrence is rare. 
The general health and the functions of the infant seem to be undisturbed, 
although in very pronounced cases a little languor or sleepiness may be 
noticed. The urine is of a normal, light yellow color, but if it is very 
concentrated it may be a little darker and may contain a trace of albumin. 
This is more frequently seen in icteric than in other new-born children. 
Bile-pigment in solution is never seen;* but in th@ sediment bilirubin is 


* Zweifel, Hofmeier; in exceptional cases, according to Cruse, loc. cit. 


490 DISEASES OF THE BILE-PASSAGES. 


found within the desquamated renal cells either as a diffuse staining or 
in the form of yellowish granules or needle-shaped crystals. The stools 
have their ordinary golden yellow color. The pulse is not retarded. Hof- 
meier showed that in icteric children the initial decrease in weight is 
greater and the subsequent increase in weight is less than in normal 
infants. The excretion of urea and of uric acid is increased. These 
abnormalities are about in proportion to the intensity of the icterus. The 
prognosis as to life in infants with this form of icterus is the same as it is 
in normal babies. 

The icterus gradually disappears spontaneously and requires no treat- 
ment other than a specially careful supervision of general hygiene. 

Anatomic investigation reveals no typical changes that would explain 
the occurrence of this form of icterus. The liver, as in all new-born 
children, is very vascular, but not icteric. The bile within the gall- 
bladder is frequently thickened and contains much bile-pigment, but no 
obstruction is found in the bile-passages. Birch-Hirschfeld claims to 
have found an edematous swelling of the periportal connective tissue at 
the time of the development of the icterus. Orth states that there is 
constantly present an infarct of uric acid or of bilirubin in the medulla of 
the kidneys, most marked in the neighborhood of the apex of the papille. 
In addition, the latter author describes the finding at autopsy of numerous 
crystals of hematoidin and of bilirubin in the blood-clots of the heart 
and in all of the organs. 


In the new-born obstructive icterus can of course also occur. Cases of this 
kind must, however, be distinguished from true cases of icterus neonatorum. Thus 
Virchow, and also Raudnitz, report cases of simple catarrhal icterus;* Kehrer 
describes a congenital narrowing of the common duct, and Birch-Hirschfeld reports 
the occurrence of congestive edema of the connective tissues surrounding the porta 
hepatis in cases of asphyxia following retarded labor. Pyemic icterus, too, is 
occasionally though rarely seen, but has nothing to do with icterus neonatorum 
[The occurrence of congenital narrowing or obliteration of the bile-ducts,especially 
described by Thomson, of Edinburgh, should here be mentioned as an additional 
and necessarily fatal cause of icterus in the new-born which should be held in 
mind as a cause of icterus not coming properly under the heading of icterus neo- 
natorum.—ED. ] 


Pathogenesis.—The frequency and the benign character of icterus 
neonatorum show that this condition is due to the great changes occurring 
in the child and its surroundings at birth, and that it may be almost re- 
garded as a physiologic occurrence. As nearly all the functions of the 
body participate in this change, a great number of explanations of its 
occurrence have been offered. 

The assumption that a stasis of bile produces this form of icterus is the 
least well founded of these, as the feces are never void of color. The oc- 
currence of edema in the periportal connective tissue, as described by 
Birch-Hirschfeld, is not proved to be constant, although it is possible that 
now and then this condition may assist in the production of the icterus. 

In view of this complete absence of all anatomic alterations in the bile- 
passages, icterus neonatorum was at one time looked upon as an example 
of jaundice of hematogenous origin. The yellow discoloration of the skin 
was genetically combined with the hyperemia of the skin present in the 
first days of life; but no proof could be adduced for the formation of the 
bile-pigment in the skin from extravasated blood (Zweifel) or imbibed 
blood-pigment (Porak). Hofmeier showed that soon after birth a great 


* Prager med. Wochenschr., 1884, No. 11. 





CATARRH OF THE BILE-DUCTS. 491 


many red blood-corpuscles were destroyed, and this discovery seemed to 
be a strong argument in favor of the hematogenous origin of this icterus, 
as was also the view that artificial plethora of the infant, produced by 
pressure on the placenta and a late ligation of the umbilical cord, intensi- 
fied the icterus (Porak, Violet).* It is true that by these procedures the 
material for the formation of bile-pigment is increased, yet, here as in 
other forms of jaundice, we can assume that the conversion of blood into 
bile-pigment occurs in the liver alone, while the participation of this organ 
in the process is further demonstrated by the presence of bile-acids in the 
urine and in the pericardial fluid (Hofmeister, Halberstam and others). 

Frerichs attempted to explain the origin of this icterus by circulatory 
disturbances in the liver, since the blood-pressure falls in the portal vein 
as soon as the blood no longer flows through the umbilical vein, and diffu- 
sion of the bile-constituents from the bile-capillaries into the capillaries of 
the portal vein could take place. It is true that this decrease in the portal 
pressure occurs, but it seems very probable that the differences in pressure 
would soon be equalized in the same manner as in ligation of vessels, where 
sudden changes in the blood-current are produced, but where the differ- 
ences in the blood-pressure within the affected vessels are equalized within 
a few hours. 

The theory, first pronounced by P. Franck, and later elaborated by the 
author, that icterus neonatorum is due to absorption of bile from the 
intestine has a surer foundation. Meconium contains much bile-pigment 
(according to Hoppe-Seyler, about 1 % in the meconium of a calf). As 
as soon as food is taken, both the secretion of bile and the absorptive 
_ powers of the intestinal mucosa are stimulated. In an adult the biliary 
constituents absorbed from the intestine are excreted in the bile after 
reaching the liver through the portal vein (intestinal hepatic circulation, 
see page 417); in the new-born, on the other hand, a part of the portal 
blood rich in biliary constituents flows directly into the vena cava by way 
of the ductus venosus Arantii, which remains patent for several days 
after birth. In this manner biliary constituents reach the general circu- 
lation and can produce icterus of the tissues. 

The following additional factors must be considered: (1) The destruc- 
tion of numerous red blood-corpuscles is followed in all probability by an 
increased formation of bile-pigment in the liver; (2) the formation of 
urobilin in the intestine as a result of bacterial action occurs in adults but 
is absent in the new-born; and is slight until after the end of the first 
week. We see, therefore, that a number of factors combine to increase 
the amount of bilirubin in the intestine and its absorption into the general 
circulation. 7 , 

Another important factor is the difficulty with which the urine of a 
new-born child dissolves bile-pigments. As a result of this, the vicarious 
excertion by way of the kidneys is decreased. The observation of Orth, 
mentioned above, that crystals of bilirubin are found in the blood and tis- 
tues of the new-born shows, further, that the power of the tissue-fluids in 
general to dissolve bilirubin is less than it is in the adult. This factor, 
too, must therefore be considered favorable to the origin and the continua- 
tion of icterus neonatorum. 


Orth and Neumann found that bilirubin also crystallizes from the blood in 
non-icteric new-born infants. Neumann, in particular, saw such crystals in the 


* A. Schmidt, on the contrary, found the icterus more frequent and obstinate 
in children after immediate ligation of the cord. 


492 DISEASES OF THE BILE-PASSAGES. 


fat-cells of the mesentery. This finding of Orth and Neumann must be interpreted 
‘to signify that probably in all new-born infants a certain amount of bile-pigment 
is found in all the tissues and in the general circulation, but that in only a few 
cases are sufficient quantities present to cause icterus. 

Many authors conclude from the microscopic examination of the blood that 
red blood-corpuscles are simultaneously both destroyed and formed (Hayem, 
Hofmeier, Silbermann). Knépfelmacher, it is true, could not verify these state- 
ments, nor did he discover any changes in the isotonia of the red blood-corpuscles. 
It is said that the red blood-corpuscles, when they are destroyed, furnish the material 
for the formation of abnormal bile-pigments. Silbermann assumes that, in addition, 
as aresult of the destruction of red corpuscles, ‘‘fermentemia”’ with stasis and throm- 
bosis supervenes in the portal capillaries, and that in this manner some of the intra- 
and inter-lobular bile-passages are occluded and obstructive jaundice results. 

Rosenberg found droplets of fat on the epithelial cells of the gall-bladder in 
cats, dogs, mice, and rabbits, after feeding these animals with fat or after subjecting 
them to a long fast. He assumes that these droplets prevent the absorption of the 
bile from the gall-bladder. As in the new-born no fat is found on the gall-bladder 
epithelium before the first food is ingested, he assumes that this leads to absorption 
of bile and icterus. (Why not then also in the fetus?—Q.) 


In the new-born two other diseases are seen that are accompanied by 
icterus—acute fatty degeneration and the epidemic form of hemoglobin- 
uria described by Winckel.* It is possible that these diseases are in some 
way related to simple icterus neonatorum in the sense that the processes 
that lead to the “physiologic” form of icterus (icterus neonatorum) in a 
measure predispose to certain noxious agencies and prepare the ground for 
the other diseases and determine the characteristic features of these dis- 
eases. 


v. Birch-Hirschfeld: ‘ Virchow’s Archiv,” vol. Lxxxvu, p. 1, 1882. 
Cnopf: “ Miinchener med. Wochenschr.,”’ p. 283. 
Cruse, P.: “ Archiv fiir Kinderheilkunde,” 1880, 1, p. 353. 
Epstein. A.: ‘Ueber die Gelbsucht der Neugeborenen,” “ Volkmann’s Sammlung 
klin. Vortrage,’’ No. 180, 1880. 
Frank, P.: ‘‘ De curandis hominum morbis epitome,” Tubingen, 1811, vol. v1, part 3, 
333 


Pp: : 

Halberstam: Dissertation, Dorpat, 1885. 

Hofmeier, M.: “ Virchow’s Archiv,” vol. Lxxxrx, p. 493, 1882. 

— “Zeitschrift fiir Geburtshilfe und Gynidkologie,” vol. vim, 1882. 

Kehrer: “ Oesterreichisches Jahrbuch fiir Pidiatrik,’’ 1861. 

Knopfelmacher, W.: ‘“‘ Das Verhalten der Blutkérper beim Neugeborenen,”’ ‘‘ Wiener 
klin. Wochenschr.,”’ 1896, p. 976. . 

Neumann, E.: ‘“ Virchow’s Archiv,” vol. cxiv, p. 394, 1888. 

Orth, J.: ‘ Ueber das Vorkommen von Bilirubinkrystallen bei Neugeborenen,”’ “ Vir- 
chow’s Archiv,” vol. Lx, p. 447, 1875. 

Porak: “Revue mensuelle de médecine,” 1878. 

Quincke, H.: “ Virchow’s Archiv,” vol. xcv, 1884. 

— “Archiv fiir experimentelle Pathologie,” vol. xrx, 1885. 

- Quisling, A.: “ Archiv fiir Kinderheilkunde,” vol. xvi1, 1893. 

Rosenberg, S.: “ Ueber den intermediiren Kreislauf des Fettes durch die Leber und 
seine Beziehungen zum Icterus neonatorum,” “ Virchow’s Archiv,’ vol. cxxuI, 
p. 17, 1891. | 

Runge, M.: “Krankheiten der ersten Lebenstage,” p. 216, 1893. 

Schiff, E.: “ Archiv fir Kinderheilkunde,” vol. xv, p. 191, 1893. 

Schmidt, A.: “ Archiv fiir Gynikologie,” vol. xiv, p. 283, 1894. 

Schreiber, E.: “ Berliner klin. Wochenschr.,’”’ No. xxv, 1895. 

sc O.: “ Archiv fiir Kinderheilkunde,” vol. vu1 (copious bibliography), 

Stadelmann: Loe. cit., p. 220. 

Violet: “ Virchow’s Archiv,” vol. Lxxx, p. 353, 1880. 

Zweifel, P.: “ Archiv fiir Gynikologie,” vol. x11. 


* See also Baginski, ‘‘ Lehrbuch der Kinderkrankheiten,”’ 1892, pp. 59 and 61. 


rf 





CATARRH OF THE BILE-DUCTS. 493 — 


ICTERUS POLYCHOLICUS. 


The assumption that icterus can be produced by an excessive forma- 
tion of bile is based on those cases of icterus in which, in addition to the 
yellow discoloration of the skin, the feces are not only not colorless, but, on 
the contrary, are more intensely stained with bile-pigments (urobilin), or 
in which profuse bile-colored diarrheas are seen. The absorption of bile- 
pigment formed in excessive quantities could occur either in the intestine 
or directly inthe liver. Certain experiments by Naunyn speak in favor 
of an absorption from the intestine. This investigator, after injecting 
20 c.c. of pig’s bile (or 0.1 of bilirubin) into the small intestine of a 
rabbit, found bile-pigment in the urine; but no icteric discoloration of 
the tissues was seen, probably owing to the short time during which an 
excess of bile-pigment was present. 

An exeess of bile might possibly be absorbed directly in the liver, be- 
cause it might not be able to flow through the bile-ducts as rapidly as neces- 
sary. In fact, Stadelmann and others have demonstrated that bile con- 
taining a great deal of bile-pigment is viscous, as is seen after the injection 
of hemoglobin or of hemolytic poisons (toluylenediamin, arseniuretted hy- 
drogen), whereby pleiochromia (an increase of pigment) is produced. As 
this bile is viscid and cannot be poured out as readily as normal bile, a rela- 
tive degree of stasis is produced within the bile-passages, and, as a result, 
a jaundice from reabsorption of bile occurs. In this manner it is demon- 
strated experimentally that icterus polycholicus exists, caused by pleio- 
chromia and the resulting viscidity of the bile. Grawitz* assumes that 
the icterus seen in certain cardiac lesions is due to polycholia, because, in 
this condition he found free hemoglobin in the blood-serum. 

The only manner in which this question could be settled clinically 
would be by determining the quantity of bile-pigment or of urobilin ex- 
creted in the feces and the urine. G. Hoppe-Seyler attempted to do this 
in that form of icterus that occurs after the injection of tuberculin. This 
icterus is accompanied by an enlargement of the liver and of the gall- 
bladder. Normally 0.123 of urobilin is excreted in the urine, 1.7 in 
the feces. In the cases examined these figures rose to 0.89 and 4.7. 
G. Hoppe-Seyler further examined cases of icterus in exophthalmic goiter 
and in pneumonia (loc. cit., p. 42) and found an increased excretion of 
urobilin, from which he concludes that the icterus seen in these cases is due 
to polycholia. 

Weare not justified in assuming from the dark color of the feces alone 
that we are dealing with a case of icterus from polycholia, as has been done 
by a number of authors—for example, Chauffard and Banti. At best, 
this is an assumption that is not based on solid grounds. Chauffard and 
others after him (for example, Girode) assumed that, particularly in ic- 
terus due to infections, the liver-cells are stimulated to increased activity 
by certain intestinal ptomains and_other toxins, and that the bile-passages 
are unable to eliminate the excessive amount of bile. As opposing this 


idea we can only emphasize the fact that a considerable degree of partial 


stasis of bile can exist without causing a lighter color of the feces, and that 
normally the intensity of the color of the feces may vary within wide 
boundaries. 
In many of those cases of icterus that are said to be due to polycholia 
we can venture an explanation on the basis of the hypothesis that diapede- 
* Deutsches Archiv fiir klin. Medicin, vol. tv, p. 611. 


494 DISEASES OF THE BILE-PASSAGES. 


sis of bile occurs directly into the blood as a result of the disturbed func- 
tion of the liver-cells (Minkowski, Liebermeister). 

We shall have to recur to this icterus polycholicus, or, better, pleio- 
chromicus, in subsequent sections. 


Hoppe-Seyler, G.: “Ueber die Einwirkung des Tuberkulins auf die Gailenfarbstoff- 
bildung,” “ Virchow’s Archiv,” 1892, vol. cxxvin, p. 43. 

— ‘Ueber die Ausscheidung des Urobilins in Krankheiten,” “ Virchow’s Archiv,” 
1891, vol. cxxiv, p. 42. 

Naunyn: “ Beitrige zur Lehre vom Icterus,’’ Reichert and du Bois-Reymond’s 
“Archiv,” 1868, p. 432; 1869, p. 579. 

Stadelmann: “ Der Icterus,’”’ 1891, p. 242. 


ICTERUS AFTER EXTRAVASATION OF BLOOD. 


Icterus is frequently observed after large extravasations of blood. 
Although authors are sometimes guilty of careless interpretations of the 
causal connection between icterus and blood-extravasations, and have 
in some instances (Poncet, for example) failed to exclude the possibility of 
icterus neonatorum or of lesions of the liver, still we can hardly doubt that 
icterus may occur as a result of hemorrhage. Of course, the yellow color 
seen in the skin over hemorrhagic foci is not included under this caption. 

Icterus following extravasation of blood has so far only been observed 
in man. It has been seen to occur after large traumatic or scorbutic 
hemorrhages occurring in the cellular tissues or into the body-cavities, as 
well as after spontaneous hemorrhages into the peritoneal cavity in 
lesions of the female sexual apparatus. 

Icterus of the skin and of the conjunctive appears several days (three 
to eight, according to Dick, eight according to Poncet) after the hemor- 
rhage and is very rarely intense. As arule, it disappears after a few days 
or weeks. Urobilinuria is present at the same time, usually beginning a 
short time before the icterus becomes visible. The discoloration of the 
urine is frequently perceptible to the naked eye from the very beginning. 
Hoppe-Seyler made a quantitative determination of the urobilin in a case 
of hemorrhage into the uterine cavity and found it increased. Un- 
changed bile-pigment is rarely found in this form of icterus. 

As both crystals of hematoidin (Langhans, Quincke) and a biliary 
imbibition of the connective tissues are seen after extravasation of blood, 
it might be assumed that all the bile-pigment that is found in different 
parts of the body might have been formed at the place where the extrava- 
sation of blood occurred. This, however, is not the case, for the bile- 
pigment formed here is generated much too slowly, and is not absorbed 
with sufficient rapidity to account for the general discoloration. What- 
ever bile-pigment is formed within the blood extravasation seems to 
have a tendency to adhere to the tissues in its immediate vicinity. The 
explanation of the process is that within the extravasation hemoglobin 
is liberated from the red blood-corpuscles and enters the circulation, 
and that_on reaching the liver this blood-pigment is converted into bile- 
pigment, so that we are here dealing with an icterus pleiochromicus, 

In hemorrhages of small extent no icterus of the skin is seen, but only 
urobilinuria. It is not decided whether all the urobilin is formed by the 
liver or whether a part is formed at the place of extravasation. An ob- 
servation by D. Gerhardt seems to speak in favor of the latter supposition, 
inasmuch as he found that in icterus with occlusion of the bile-ducts 
extravasations of blood may lead to urobilinuria. 


CATARRH OF THE BILE-DUCTS. 495 


Different authors have at times emphasized the significance of uro- 
bilinuria in the diagnosis of blood extravasations not discoverable by 
other means. In view of the many interpretations that are possible for 
the appearance of urobilin in the urine such a connection must be carefully 
criticized before it is accepted (compare also Mandry). 


In animals no one has so far positively demonstrated the occurrence of icterus 
or of urobilinuria following extravasation or injections of blood (Angerer, Quincke, 
and others). We are, therefore, not se fortunate as to possess an adequate and 
satisfactory explanation or experimental evidence of the conditions under which 
the formation of the substances under discussion occurs (compare pages 445 ef seq.). 


Angerer, O.: “ Klinische und experimentelle Untersuchungen tber die Resorption von 
Blutextravasaten,’”? Wurzburg, 1879. 

Dick, R.: ‘Ueber den diagnostischen Werth der Urobilinurie fiir die Gnyakologie,”’ 
“ Archiv fiir Gynakologie,” Bd. xxim. Also Mandry, ibid., 1894, vol. xxv, 


p. 446. 

v. Teneo “ Zeitschr. fir Heilkunde,” p. 49 (icterus in scurvy), 1895 

Kunkel, A.: ‘“ Ueber das Auftreten verschiedener Farbstoffe im Harn, ” “Wirchow’s 
Archiv, ”” 1880, vol. Lxxrx, p. 455. 

Poncet, A.: “De Victére hématique traumatique.”’ Thése de Paris, 1874. 

Quincke, H.: “ Beitrage zur Lehre von Icterus,” ‘“‘ Virchow’s Archiv,” vol. xcv, 1884. 
“ Zur Physiologie und Pathologie des Blutes,” ‘ Deutsches Archiv fur klin. Medi- 
cin,’ 18838, vol. xxx, p. 31. 

Stadelmann: “ Der Icterus,’”’ 1891, p. 242. 


ICTERUS AFTER HEMOGLOBINEMIA. 


The destruction of red blood-corpuscles within the blood-current is 
followed by the same results as the extravasation of blood. This is due 
either to a disintegration of red corpuscles or to the formation of 
‘‘shadows”’ whereby the hemoglobin is dissolved and enters the blood- 
current. The most striking effects are seen in paroxysmal hemoglo- 
binuria, in which, as a result of malaria, syphilis, or some other un- 
known predisposing factor, cold or excessive physical exertion brings on 
an attack. The attack begins with fever and usually produces hemo- 
globinuria, swelling of the spleen, and icterus of the skin. The urine, too, 
may contain bile-pigment but is always free from bile-acids.* In cases of 
this kind we must consider, in addition to the hemoglobin that produces 
the polycholia, the mechanical effect exercised by the stromata of the red 
blood-corpuscles, and possibly the toxic action of these and of other sub- 
stances. In the kidneys this effect is particularly manifested by acute 
inflammation, a decrease in the quantity of urine voided, and the appear- 
ance of albumin and of casts. 


The experiments of Schurig and v. Starck demonstrate that the aoe quantity 
of hemoglobin circulating in the blood is not alone responsible for the appearance 
of icterus. These investigators repeatedly injected large doses of hemoglobin into 
dogs and rabbits, and yet never witnessed the occurrence of icterus. 


It appears that that form of icterus first described by Winckel in the 
new-born, and representing an epidemic form of hemoglobinuria with 
icterus, is due to some infectious agency of unknown origin. This disease 
is seen in children that are otherwise healthy. It appears at about the 
fourth day of life, beginning with cyanosis and followed by icterus and an 
acceleration of the pulse and of the respiration. The skin is cool and a 
very scanty amount of thick dark blood can be made to ooze from an inci- 


*Leube, “ Sitzanaanericht der physiologisch-medicinischen Gesellschaft zu 
Wirzburg,” 1886. 


> 


496 DISEASES OF THE BILE-PASSAGES. 


sion. Occasionally vomiting and diarrhea are seen. Theurine contains 
hemoglobin, albumin, granular casts, and blood-corpuscles. The disease 
usually terminates fatally, in convulsions, at the expiration of from nine 
hours to two days. On autopsy, punctiform hemorrhages are seen 
throughout the internal organs. In addition, swelling of the spleen and 
fatty degeneration of the liver, heart, and kidneys are found. In the lat- 
ter respect the disease corresponds to the picture of acute fatty degenera- 
tion described by Buhl. Icterus in this case is due in part, as in paroxys- 
mal hemoglobinuria, to pleiochromia of the bile, in part to acute lesions 
of the parenchyma of the liver. 


v. Birch-Hirschfeld: Loc. cit., p. 702. 

Runge, M.: “ Krankheiten der ersten Lebenstage,’”’ 1893, p. 172. 

Hoffmann, F. A.: “Constitutionskrankheiten,’”’ 1893, p. 165. 

Ponfick: “ Ueber Hamoglobinamie und ihre Folgen,” “ Berliner klin. Wochenschr.,”’ 
1883, p. 389. 

Schurig: “Ueber die Schicksale des Himoglobins im Thierkérper,” “ Archiv fiir 
experimentelle Pathologie,” vol. xxxrx, 1898. 

v. Starck: “Ueber Hamoglobininjectionen,’’ ‘ Minchner med. Wochenschr.,”’ 
1898, Nos. 3 and 4. 

Winckel: ‘‘ Deutsche med. Wochenschr.,”’ 1879, Nos. 24-36. 


ICTERUS TOXICUS. 


Icterus is found in a number of intoxications. In the case of those 
poisons that produce a dissolution of red blood-corpuscles and hemo- 
globinemia the occurrence of icterus is readily understood. These forms 
of toxic icterus are closely related to the forms discussed above. 

Among the poisons that can produce hemolysis are arseniuretted hy- 
drogen and two mushroom poisons—helvellic acid from the truffle, and 
phallin, a toxic proteid substance from Agaricus phalloides. Occasionally 
cases of poisoning with the two latter substances have been studied in 
human beings. Experimental investigations have been made with toluy]- 
enediamin, glycerin, the bile-acids, and saponin substances. In addition 
to causing the separation of hemoglobin, some of these bodies, particularly 
toluylenediamin and phallin, cause destruction of red blood-corpuscles 
(rhestocytemia). 

Another class of poisons, in addition to exercising the above effect 
on the red blood-corpuscles, act directly on hemoglobin and convert it 


_ within the corpuscles into methemoglobin. Among these poisons are the 


chlorates, pyrogallol, anilin and its derivatives (antifebrin, lactophenin, 
etc.), nitrobenzol, nitroglycerin, and the nitrites. In addition to these 
substances, which occasionally produce poisoning in man, there are a 
number of other substances that have only been investigated experiment- 
ally but are known to exercise a similar effect. 

The results of the changes in the blood are the same in the case of pois- 
oning with these drugs asin paroxysmal hemoglobinuria. The liberation 
of large quantities of hemoglobin causes pleiochromia and thickening of 
the bile (polycholia), which in its turn leads to obstructive icterus. These 
results have been made the object of careful experimental investigation in 
the case of arseniuretted hydrogen and of toluylenediamin (Stadelmann 
and Affanassiew). It is probable that each of these substances acts 
somewhat differently in regard to the injury they do to the red blood-cor- 
puscles; while also it is very probable that they exercise individually differ- 
ent effects on certain organs, such as the liver and the kidneys. Whereas, 





CATARRH OF THE BILE-DUCTS. 497 


therefore, the primary intoxication is the same in the case of all these 
substances, the general clinical picture presented varies considerably. 
Especially has it been observed that the frequency and the intensity of 
the icterus are not proportionate to the hemoglobinuria. The principal 
effect of all is not to be sought in their action on the blood. The toxic 
action of the different poisons varies qualitatively and in regard to its 
significance. 

After the administration of toluylenediamin, fatty degeneration and 
interstitial proliferation are found in the liver. These pathologic changes, 
in addition to the polycholia, probably lead to icterus. The urine is 
diminished in quantity and contains casts of brown granular masses and 
epithelial debris, hemoglobin, methemoglobin, and bile-pigment. The 
spleen is enlarged owing to the destruction of red blood-corpuscles taking 
place within this organ, the leucocytes gathering up the fragments of the 
erythrocytes and accumulating in the spleen. If the blood in such a case 
is examined at the right time, it will be found to contain the shadows and 
' fragments of red blood-corpuscles described above, and, on centrifuging, 
it will be seen that the serum is tinged red by the hemoglobin in solution. 

The icteric discoloration of the skin and the conjunctive in these 
intoxications does not appear until the second day or later, and is fre- 
quently modified by cyanosis and by congestion of the face and the per- 
ipheral parts of the body. After poisoning with the second group the 
brown color imparted to the tissues by methemoglobin (from the red 
blood-corpuscles and the serum) still further obscures the icteric color. 
We see, therefore, that the shade, the intensity, and the duration of 
icterus may vary greatly in these cases according to the severity of the 
case and the character of the poison. 


The entrance of dissolved hemoglobin into the liver-cells and its subsequent 
elaboration into bile-pigment is readily understood, but it is not entirely clear 
whether, and if so how, the fragments of red blood-corpuscles can be transformed 
by the liver-cells. According to the view of Affanassiew, which can hardly be 
accepted, icterus occurs more particularly in fragmentation of red blood-corpuscles 
(rhestocytemia) and not at all in true hemoglobinemia. 

Affanassiew was enabled, further, to produce similar symptoms of intoxication 
by injecting into an animal its own blood changed by heat, so that bluod heated 
to 53° C. (127.4° F.) chiefly destroyed the red blood-corpuscles, while after using blood 
heated to 56° or 57° C. (130.8° or 135.6° F.) a solution of the hemoglopin in the 
serum was produced. In extensive burns methemoglobinuria without icterus has 
been observed in human subjects. 

It is possible that the form of icterus occasionally seen in pernicious anemia 
is toxic in character and is caused by a poison having hemolytic properties. 

Lactophenin is ranked among the hemolytic substances. Strauss, however, 
who observed icterus with colorless stools in three patients who had taken 4.0 gm. 
daily for from nine to twenty-one days, states that this icterus is the result of a 
gastro-intestinal catarrh. 


In the case of some of the poisons to be spoken of below, and which 
are accompanied by jaundice, the cause of this symptom is attributed 
with more or less reason to a destruction of the red blood-corpuscles. 

In many of the older reports the administration of ether, chloroform 
and chloral hydrate was said to be followed by icterus. I fail to find 
recent statements in regard to this in the literature. No very definite 
reports seem to have been made of late, and I personally have made no 
observations in this direction. 


As ether, in the same manner as the bile-acid salts, is capable of dissolving hemo- 
globin from red blood-corpuscles, it would not surprise us if this substance had 
32 


498 DISEASES OF THE BILE-PASSAGES. 


the power ascribed to it of producing icterus. Naunyn injected ether subcu- 
taneously into rabbits (1.0 and more) and found bile-pigment in the urine in one- 
fourth of the cases. If the ether was injected into the small intestine, bile-pigment 
was constantly found in the urine, for the reason, probably, that the hemoglobin 
ee ee within the portal vein and in this manner was carried directly into 
the liver. 

Geill reports a patient of fifty-eight years who took 2.0 grams of chloral 
hydrate on twenty-five successive days. At the expiration of this time an 
exanthem due to chloral appeared, on the third day thereafter icterus developed, 
and on the fourth day death occurred. The liver was enlarged owing to passive 
congestion and was strewn with a large number of stained areas varying in size 
from that of a lentil to that of a pea. The cells of the liver in the center of the 
lobules were comparatively well preserved, but elsewhere the cells were in a state 
of granular degeneration, contained pigment, and had no nucleus. 

The administration of carbolic acid by the mouth does not seem to be followed 
by icterus. The latter has only been observed in three cases where carbolic acid 
was injected into the umbilical region of new-born infants or was applied to an 
abscess in the pelvic region. It is possible that in these instances a direct action 
on the liver was produced by way of the portal vein. 


Icterus has occasionally been seen after a course of treatment for the 
expulsion of a tapeworm with extract of filix mas. It seems to have been 
particularly frequent when oil was administered at the same time, because 
this promoted the absorption of the poisonous filicic acid. Grawitz as- 
sumes that in these cases a solution of the hemoglobin occurs within the 
liver with resulting polycholia, and possibly there is also a direct toxic 
effect exercised on the liver-cells themselves. 

In poisoning with santonin icterus has frequently been seen. Here, 
too, the chief effect may be exercised on the blood, as Jaffe saw hematuria 
in dogs following the use of the drug and Cramer observed in one human 
case fever and swelling of the spleen. 

We will discuss phosphorus-poisoning, which leads to icterus and a con- 
siderable swelling of the liver, in another section. In this place we will 
only mention that Stadelmann in his experiments observed an increased 
excretion of bile-pigment occurring in the same way but more slowly than 
after toluylenediamin-poisoning; 2. e., after about ten hours. In the be- 
ginning a simple irritation of the liver-cells occurs, leading to pleio- 
chromia. Later the increase in size of the liver-cells, interstitial prolifera- 
tion, and catarrh of the bile-passages constitute additional obstacles to 
the flow of bile. It is possible that in these cases parapedesis of bile 
(Minkowski, Liebermeister) plays a certain réle. 

Icterus of a very mild degree is often seen in lead colic. Usually it is 
attributed to catarrhal conditions of the bile-passages, but it is not im- 
possible that in this form of intoxication tonic spasms of the bile-ducts 
occur or that a direct toxic effect is exercised on the hepatic parenchyma. 


Freyhan mentions a form of icterus observed in workmen engaged in the 
manufacture of storage batteries. He considers it toxic, but in his report does 
not distinctly state whether he attributes it to lead intoxication or not. 


Icterus frequently appears with great rapidity after snake-bite, and it 
is said that it occurs in cases of this intoxication having a chronic course. 
Its mode of origin in this condition is altogether unknown. 

The icterus seen after injections of tuberculin must be included among 
the toxic varieties. Hoppe-Seyler has shown that this icterus is accom- 
panied by an increase of urobilin in the feces and urine, so that we may 
assume that it is caused by a polycholia resulting from destruction of red 
blood-corpuscles (see page 493). 





CATARRH OF THE BILE-DUCTS. 499 


LITERATURE. 


ARSENIURETTED HYDROGEN. 


Kobert: “ Intoxicationen,” p. 471. 
Stadelmann: “ Archiv fiir experimentelle Pathologie,” vol. xv1, p. 220, 1882. 
— “Der Icterus,” p. 193, 1891. 


PHALLIN. HELVELLIC ACID. 
Kobert: Loc. cit., pp. 60, 457. 


TOLUYLENEDIAMIN. 


Affanassiew: “ Zeitschr. fiir klin. Medicin,” vol. v1, p. 318, 1883. 

Hunter, W.: ‘The Action of Toluylenediamin: A Contribution to the Pathology of 
Jaundice,” “Journal of Pathology and Bacteriology,” m1, 1895. 

Auld, A. G.: “The Experimental Evidence of Hamatogenous Jaundice,” “ Brit. 
Med. Jour.,”’ January, 1896. 

Pick: ‘“ Zur Kenntniss des Toluylenediamin-Icterus,”’ ‘‘ Wiener klin. Wochenschr.,’’ 
1892. 

Stadelmann: “Der Icterus,” p. 117, “ Archiv fiir experimentelle Pathologie,” vol. 
XIV, p. 231, 1881; vol. xv1, p. 118, 1883; vol. xx111, p. 427, 1887. 


CHLORAL HYDRATE. 


Arndt: “ Archiv fiir Psychiatrie und Nervenkrankheiten,” vol. 111, p. 673, 1872. 
Geill: “ Vierteljahrsschr. fiir gerichtliche Medicin,” vol. x1v, p. 274, 1897. 
Pelmann: “Trrenfreund,” 1871, No. 2. 

Wernich: ‘‘ Deutsches Archiv fur klin. Medicin,” xm, 1874, p. 32. 


CaRBOLIC ACID. 
Geill, Chr.: “ Vierteljahrsschr. fiir gerichtliche Medicin,” vol. x1v, 1897, p. 282. 


ETHER. 


Naunyn: “ Reichert und Bois-Reymond’s Archiv,” 1868, p. 438. 
Kappeler: ‘‘ Anaesthetica” in Billroth-Liicke “ Deutsche Chirurgie,” part 20, pp. 57 
and 60, 1880. 


PHOSPHORUS. 
Stadelmann: “ Archiv fiir experimentelle Pathologie,” vol. xxiv, p. 270, 1888. 
— “Der Icterus,” p. 176, 1891. 

LACTOPHENIN. 


Strauss, H.: ‘“Therapeutische Monatshefte,” 1895, p. 469. 
Wenzel: “ Icterus nach Lactophenin,” “ Centralblatt fiir innere Medicin,” xv11, 1896. 
Witthauer: ‘Therapeutische Monatshefte,”’ 1898, No. 2. 


ANILIN. 
Dehio: “Berliner klin. Wochenschr.,” 1888, p. 11. 


SNAKE-BITE. 
Frerichs: Loc. cit., p. 167. ; 
Kobert: Loc. cit., p. 335. 

SANTONIN. 


Kobert: Loc. cit., p. 633. 
Cramer, H.: “ Deustche med. Wochenschr.,’”’ vol. xv, 1889. 


Extract or Finrx Mas. 


Freyhan: “Berliner klin. Wochenschr.,” 1896, p. 263. 
Grawitz: “ Berliner klin. Wochenschr.,’’ 1894. 


500 DISEASES OF THE BILE-PASSAGES. 


ICTERUS IN INFECTIOUS DISEASES. 


Acute infectious diseases may be accompanied by other lesions causing 
icterus which may either have existed, possibly latent, before the infec- 
tion (cirrhosis, cholelithiasis) or which may complicate the disease after 
it has begun to run its course (catarrhal icterus, acute yellow atrophy). 
Aside from these instances, we see icterus so frequently in some of the 
infectious diseases that we cannot consider its occurrence as an accidental 
complication. It is seen, moreover, more frequently in some infectious 
diseases than in others, so that we are forced to assume some close connec- 
tion between icterus and the specific disease that it complicates. Among 
the diseases that are most often accompanied by icterus we may mention 
yellow fever, recurrent fever, Griesinger’s type of bilious typhoid, pyemia, 
and pneumonia. In all these diseases the stools remain colored, so that 
the obstacle to the outflow of the bile is only a relative one, and can, as a 
rule, not be demonstrated at all. The appearance of icterus in these cases 
has been attributed to an occlusion of the smaller bile-passages by 
catarrhal inflammation of the ducts or catarrhal swelling of the hepatic 
cells. It is possible that here, too, we are dealing with pleiochromia or 
parapedesis of bile as a result of functional disturbances of the liver-cells. 


This effect can either be exercised by the bacteria themselves or by the toxins 
leaborated either in the intestine or in other organs situated in parts of the body 
remote from the liver. Tuberculin is such a bacterial toxin, as it produces icterus 
even when injected in remote parts of the body. It is true, however, that in the 
clinical course of tuberculosis such an effect is never observed. 


Recurrent fever is frequently accompanied by icterus, in some epidem- 
ics one-fourth of all the cases developing it. Griesinger observed bilious 
typhoid or typhus biliosus in Cairo, and characterized it as an atypical 
form of recurrent fever. According to the observations of Kartulis in 
Alexandria and of Diamantopulos in Smyrna, however, this disease is 
different from recurrent fever both in regard to its general course and in 
regard to the absence of the typical and specific spirilla. Some authors, 
among them Fiedler, are inclined to classify this bilious typhoid with the 
form of infectious icterus described by Weil. 


Icterus is quite frequently seen in typhoid fever. In the first weeks of the 
disease it has usually been attributed to a catarrhal swelling of the bile-passages 
and is of subordinate importance. It is possible, at the same time, that even this 
initial icterus may be due to bacterial infection. In that form of icterus seen 
in the second half of the disease it is still more probable that the specific microbe 
plays a rdéle, as this icterus is very much more severe and may even lead to the 
death of the patient. 


In acute croupous pneumonia slight degrees of icterus are not infre- 
quently seen, and in some epidemics this complication is quite common. 
These cases of pneumonia, designated as “bilious,’”’ seem to run a more 
severe course at certain times than at others, although at the same time 
the fact that they are complicated with icterus does not make the progno- 
sis less favorable. On account of the gastric symptoms so pronounced in 
pneumonia, this icterus has been attributed to catarrhal conditions; 
while other authors (Gerhardt) have attempted to connect this icterus 
with the hemorrhagic character of the pneumonic exudate and to draw an | 
analogy with the appearance of icterus in other forms of hemorrhagic 
extravasation. 





CATARRH OF THE BILE-DUCTS. 501 


In septicemia icterus is quite frequently seen. As a rule, it appears 
as a faint yellowish tinge, and rarely as a more intense discoloration. It is 
seen after septicemia following external wounds, after puerperal sepsis, 
after sepsis following lesions of mucous membranes, in that form arising 
from the endocardium, which is designated as endogenous and which, 
in case no distinct origin can be found during life, is called cryptogenetic 
septicemia. While it is true that icterus may be absent in many cases of 
septicemia, at the same time its appearance is a diagnostic sign of consid- 
erable value, particularly if a differential diagnosis has to be made be- 
tween septicemia and certain infectious diseases. 


The form of icterus occasionally seen in revaccination and called icterus epi- 
demicus (see below) is in no way related to vaccinia itself. It must be regarded 
as a complication that occurs from unknown causes. 


LITERATURE. 


TYPHUS. 


Griesinger : ‘‘ Virchow’s Specielle Pathologie,” vol. 11, 22d Ed., p. 203, 1864. 

ee ee “ Ziemssen’s Handbuch der speciellen Pathologie, ” vol. 11, lst and 
2d Ed., p. 168, 1876. 

Pal: “Wiener kin.’ Wochenschr.,’”’ 1894. 


Briuious TypHorp. 


Diamantopulos: “Ueber den Typhus icterodes in Smyrna” (cited by Kartulis). 

Kartulis: “ Deutsche med. Wochenschr.,”’ 1888, Nos. 4 and 5. 

Karlinski: ‘ Icterus bei Recurrens,”’ “ Fortschritte der Medicin,”’ 1891, p. 456. 

Becker: (Case following general diphtheritic infection.) ‘Berliner klin. Woch- 
enschr.,’’ 1880, p. 447. 


ICTERUS EPIDEMICUS. 


The appearance of icterus in many persons at the same time is well 
known to the laity. As such an occurrence is so striking that it could 
hardly be overlooked, we have descriptions of this epidemic form dating 
from the beginning of the eighteenth century. Hennig has collated over 86 
large and small epidemics from the literature. Among these only 8 
extended over large areas, and these were found particularly near the 
seashore. The majority of these epidemics are circumscribed in extent 
and attack only single families or certain communities, such as one house, 
barracks, prison, or boarding-house. Only 5 epidemics lasted for a 
considerable period of time—seven to thirteen months. In three epi- 
demics the disease attacked children alone or at least to a great extent. 

Of the epidemics recorded, 26 occurred among soldiers, 6 among sol- 
diers and civilians, the rest among civilians alone. The epidemics that 
occurred among the soldiers are more reliable in regard to statistical in- 
vestigations, and consequently merit particular attention. In some 
instances such epidemics assumed remarkable dimensions. For example, 
during the first year of the Civil War in the United States 10,929 cases of 
jaundice were observed with 40 deaths; in the Franco-Prussian war 2.4% 
of the men of the First Bavarian Division were afflicted from February 
to May. As a general rule, recently enlisted soldiers were more liable to 
attack than were the more seasoned men. 

The course of the disease is, in general, benign. It resembles the sim- 
ple, afebrile, catarrhal form of icterus, and the symptoms, aside from the 


502 DISEASES OF THE BILE-PASSAGES. 


yellow discoloration, are frequently very slight. In other epidemics, 
again, the course is similar to that form of infectious icterus known as 
Weil’s disease. Damsch claims to have seen cataleptic rigidity, particu- 
larly in the epidemic form of icterus that occurs in children, and states 
that it is more frequent in this than in the sporadic form. 

In only 7 of the epidemics mentioned was the disease severe and ac- 
companied by many deaths. It appears that in pregnant women and 
women in the lying-in period the prognosis is grave. 

The causes of epidemic icterus are manifold. Among them may be 
mentioned damp weather, particularly if, as in the case of soldiers, indi- 
viduals are forced to wear wet clothes for a long time. The great major- 
ity of the 86 epidemics mentioned occurred in the winter and fall. Froéh- 
lich found that in the epidemics among soldiers the spring months seemed 
to be the most dangerous. 


The following factors may be named as further predisposing causes: 


errors in diet, poor or inappropriate food, a monotonous diet, bad drink- 
ing-water or the swallowing of impure river-water during bathing, and the 
breathing of polluted air (as in trenches containing stagnant water, from 
bad drains or defective foundations). In camping on moist, dirty soil 
several of these noxious influences may be combined. 

The appearance of icterus after revaccination is very peculiar. This 
was observed in an epidemic that occurred in Bremen (Lurmann, Pletzer), 
in which over 200 workmen of a manufacturing establishment out of a 
total of 1500 men became afflicted with icterus in the course of four 
months. The limits of the incubation period were from a few days to 
several months. A transmission by contagion was never seen. 

It is possible, therefore, to divide the predisposing factors into three 
groups: (1) Atmospheric, telluric, or climatic causes; (2) dietetic influ- 
ences; (38) infectious causes. 

It is probable that a combination of all these factors often is present, 
and that, for example, the first two may predispose the patient to the 
influence of the third. We can hardly say that infection always plays a 
role, for many of the cases present the picture of a simple catarrhal icterus 
that is altogether benign in character. Thus, a single company among the 
soldiery of a large barracks were afflicted with this simple form of icterus 
upon receiving a very monotonous diet, while in another company icterus 
appeared after these men had been ordered to take a daily bath in the 
river immediately after eating. In these two instances the disease dis- 
appeared as soon as the conditions mentioned were changed. 

In those cases, of course, where the external conditions are such that it 
seems possible for bacteria to develop, it is quite probable that microbic 
influences play an important part in the production of icterus. Such 
favoring conditions are, for example, the breathing of bad air or the drink- 
ing of polluted water. The bacteria, if they enter the intestine, probably 
in many cases penetrate the bile-ducts and cause an inflammatory reac- 
tion leading toicterus. There is the possibility, further, that all the symp- 
toms are produced by intoxication with the ptomains elaborated by the 
bacteria in the intestine and absorbed. In fact, the benign course of this 
icterus make the latter assumption very probable. In those cases where 
‘the breathing of polluted air seems to be the chief causative factor the 
intoxication theory is still more probable. | 

The only plausible explanation of the occurrence of icterus after 
revaccination is the occurrence of wound infection. It is true that the 





" 


a ee ee Ye 


et 


CATARRH OF THE BILE-DUCTS. 503 


infective agency must be of a special kind, otherwise we would not see 
an incubation period enduring for eight months. 


Damsch: “ Berliner klin. Wochenschr.,’”’ 1898, p. 277. 
Frélich, C.: “Ueber Icterusepidemien,” “Deutsches Archiv fiir klin. Medicin,”’ 
‘vol. xxiv, p. 394, 1879. 
Hennig, A.: “Ueber epidem. Icterus’” (literature), “Volkmann’s Hefte,’’ 1890, 
new series, No. 8. 
Hirsch: “ Historisch-geographische Pathologie,” 111, p. 287, 1886. 
Kelsch: “ De la nature de l’ictére catarrhal,” “ Revue de médecine,” 1886, p. 657. 
Kirchner: ‘ Deutsche militar-arztliche Zeitschr.,” p. 193, 1888. 
Kramer: “Eine Epidemie von Icterus catarrhalis bei Kindern,” Ugeskrift f. Lager, 
1894. 
Lirmann: “ Eine Icterusepidemie,” “ Berliner klin. Wochenschr.,”’ 1885, p. 24. 
Meinert, E.: “ Icterusepidemie,”’ ‘‘ Jahresbericht der Gesellschaft fiir Natur- und 
Heilkunde zu Dresden,” 1890; “‘Schmidt’s Jahrb.,” vol. ccxxx1, p. 27, 1891. 
Pfuhl: “ Berliner klin. Wochenschr.,’’ 1891, p. 178. 
Pick, A.: “ Prager med. Wochenschr.,’”’ No. 24. 
Pletzer: “ VII. Jahresbericht iber den 6ffentlichen Gesundheitszustand in Bremen,” 
1889, p. 35. 
Rankin, W.: “ Brit. Med. Jour.,”” May 26, 1894. 
Schiuppel: Loc. cit., p. 16. 


ICTERUS INFECTIOSUS; WEIL’S DISEASE. 
(Icterus gravis.) 


It has been customary to distinguish, on the one hand, favorable cases 
of icterus as icterus simplex and icterus catarrhalis, and, on the other 
hand, cases designated as icterus gravis which begin acutely, and run a 
severe and often fatal course lasting from several days to several weeks. 
Chronic icterus, even if it finally leads to death, does not properly belong 
under the head of icterus gravis. It is clear that a group of diseases char- 
acterized by one predominant symptom and a severe course must be a 
mixture of a great variety of diseases of different origin. Just as formerly 
fever received undue notice as the characteristic symptom of a vast num- 
ber of different diseases, so now the extreme discoloration of the skin by 
bile may receive too exclusive attention and so lead to error. 

At times pronounced changes in the hepatic parenchyma are found in 
some of the diseases included under icterus gravis, as in acute atrophy of 
the liver, in the acute terminal lesions of chronic hepatitis, in phosphorus- 
poisoning, in mushroom-poisoning, and in acute fatty degeneration and 
Winckel’s disease produced by still unknown substances. At other times, 
again, autopsy reveals very little of note in cases of icterus gravis, and 
pathologic alterations in the liver might have been absent or could not be 
found with the incomplete methods of older investigators. We can read- 
ily, therefore, understand why older clinicians, in cases of the latter kind 
particularly, attempted a classification by designating all such cases as 
icterus gravis. Among cases of this description we can mention, for ex- 
ample, icterus following septicemia. Here, even in the most severe cases, 
no gross pathologic changes are found; and it is frequently difficult, even 
nowadays, to discover the place of primary infection. Bacteriologic ex- 
aminations first threw some light on this subject, and we are enabled to- 
day to state that a great many cases of icterus gravis are of infectious 
origin, and that, as a rule, the bile-passages are infected. For these rea- 
sons there is a tendency to identify icterus gravis with icterus infectiosus. 
This is not correct, however, for the latter includes only a part of the 


504 DISEASES OF THE BILE-PASSAGES. 


cases of icterus gravis. Again, icterus infectiosus and infection of the bile- 
passages are not identical, for we see, on the one hand, cases of bacterial 
lesions of the bile-passages and of the liver without icterus, and, on the 
other hand, septicemia or infectious gastro-intestinal diseases that simu- 
late icterus gravis without any infection of the bile-passages. We see, 
therefore, that for infectious icterus no definite disease-picture can be de- 
lineated and no satisfactory definition can be formulated from the fact 
that we are only beginning to gain an insight into the true pathogenesis of 
this group. The more we learn of it, the less uniform the different forms 
seem to be. 

Clinically, icterus infectiosus is characterized by the appearance of all 
the symptoms of a severe infection and by icterus. In one case the one, 
in another case the other, of these two classes of symptoms may predomi- 
nate, both in regard to intensity and in regard to the time of their appear- 
ance and their duration. In this section we will limit our discussion to 
those cases in which no serious lesions of the hepatic parenchyma can be 
found; while the latter will be described in the sections on hepatitis and 
acute yellow atrophy. 

In our discussion of catarrhal icterus we called attention to the fact 
that a number of cases are seen that run their course with high fever and 
serious disturbances of the general health. We also mentioned the fact 
that it is very improbable that these grave symptoms could be due to 
biliary obstruction or to gastro-intestinal catarrhs alone. Cases of this 
character are the connecting-link between catarrhal icterus and that dis- 
ease-picture that was first described by Weil in 1886 as a special form of 
icterus. This disease, since Weil’s description, has held the attention of 
clinicians and has been designated as one (but not the only) type of 
icterus infectiosus. 

Symptoms.—Weil’s disease begins suddenly, without any prodro- 
mata, with fever, chills, and a rapid rise of temperature. At the same 
time the patient complains of vertigo, lassitude, and headache, as a result 
of which the sufferer soon takes to bed. Stupor early develops, and this is 
followed by delirium, so that the patient falls into a typhoid state much 
sooner than in typhoid fever. The picture resembles the latter disease 
more than any other infection, the tongue being coated, the spleen en- 
larged, and occasionally diarrhea supervening. Between the third and 
fifth day, rarely sooner, jaundice appears and rapidly grows intense, and 
at the same time the liver enlarges and becomes tender. The urine con- 
tains a moderate quantity of albumin, a few hyaline and epithelial casts, 
and, sometimes, a few blood-corpuscles. According to Fiedler, the swell- 
ing of the spleen and the liver are not observed in all cases, and albumin- 
uria may be very slight and transitory. 

The stools at this period are, as a rule, thin, contain bile in the begin- 
ning, and later, if the icterus be very intense, become clay-colored. 

The temperature remains around 40° C. (104° F.) with fluctuations for 
several days. On the fourth to the eighth day of the disease the tempera- 
ture drops, with remissions, and reaches normal at the end of from four to 
six days. At the same time the severe general symptoms disappear and 
the liver and spleen resume their normal size. The urine, too, becomes 
normal. Icterus persists for from ten to fourteen days, and then, too, 
gradually disappears. 

In a minority of the cases (40%) a recurrence occurs some three to 
eight days after the final drop of the temperature to normal, manifesting 








= ae 








mt, ga aN = 


CATARRH OF THE BILE-DUCTS. 505 


itself by a rise of temperature and, as arule, by a repetition of all the 
other symptoms. This recurrence is not so severe as was the primary 
attack. 

_ The loss of weight that the patient suffers during the febrile period 
amounts to from 5 to 10 kilos (12 to 25 pounds). 

In most of the cases the subject complains of violent muscular pains 
from the beginning of the trouble. These are chiefly localized in the mus- 
cles of the calf. During the period of stupor they are less apparent, but 
they persist through the febrile stage and into the stage of convalescence ; 
in fact, they may be the last symptom to disappear. Occasionally, in the 
beginning of the disease, a spotted erythema is seen on the trunk, also 
at times there are found herpes facialis and an angina. As aresult of the 
icterus there may be itching of the skin and a relative slowing of the pulse 
as compared with the temperature. Sometimes the hemorrhagic diathesis 
appears with hemorrhages into the skin, the conjunctive, and the retina, 
epistaxis, and blood in the urine, stools, and sputa. Parotitis, paresis of 
the vocal cords (Gerhardt), neuritis (Kausch), and iridocyclitis are amqng 
the rarer complications. 

The duration of the febrile period, as already mentioned, is about 
eight to ten days; that of the apyrexia, one to eight; and that of the re- 
lapse, from five to eight days. The total duration of the disease up to 
complete recovery is from three to four weeks, while a feeling of weakness 
may persist for a much longer time. 

As the termination of this disease is, as a rule, favorable, very few op- 
portunities for postmortem study have been presented. As a result, we 
know very little of the anatomic changes present. Several reports of au- 
topsies are on record, but they probably refer to cases that did not properly 
belong in this category. According to the reports of Wassilieff, Sumbera, 
and Neelsen, recent enlargement of the liver and spleen are seen, the 
spleen being soft and vascular. The cells of the liver are cloudy, their 
nuclei are increased and show mitoses. The kidneys, too, are enlarged, 
and in one case were seen to be filled with punctiform hemorrhages, and 
the renal epithelium was degenerated. In Neelsen’s case there was a 
small-celled infiltration of the cortex of the kidneys, particularly in the 
region of the Malpighian bodies, the heart-muscle was in a state of 
fatty degeneration, and there were hemorrhages into the meninges and 
into the gastric and the intestinal mucosa. 

Occurrence.—Weil’s disease is not frequently seen. As a rule, it 
appears sporadically; but occasionally it affects groups of people living 
within circumscribed districts, and during a brief period of time, usually 
in hot weather. As arule, persons in the third decade of life are afflicted. 
[Kissel* has recorded 96 cases in children between the ages of one and 
thirteen years.—Ep.] Over 90% of the cases are seen in men, while in 
children and in persons over fifty itis rare. It seems that butchers (Fied- 
ler 50%, Wassilieff 20%), tanners, and laborers in sewers are particularly 
predisposed to the disease. In a few cases it could be shown that the use 
of impure drinking-water or the swallowing of contaminated river-water 
during bathing caused the disease. The latter was particularly apparent 
in different large and small epidemics that occurred quite frequently 
among soldiers and that had been observed and recorded long before 
Weil’s publications appeared (Pfuhl). [Kissel states that the disease is 


more common in the autumn and winter than at other seasons.—ED.] 


* Jahrb. f. Kinderheilk., 1898, Bd. xuvii, p. 235. 


506 DISEASES OF THE BILE-PASSAGES. 


A form of the disease has been described that is caused by drinking or uninten- 
tionally. swallowing polluted water, appears in epidemics, and resembles Weil’s 
disease in every particular with the exception of the absence of icterus. It is 
well to remember these cases, as they are of value in the understanding of the patho- 
genesis of this group of diseases.* 


Nature of the Disease.—In the light of our present knowledge it is 
quite impossible to state whether Weil’s disease is a clinical entity or not. 
At all events, the clinical picture presented resembles, on the one hand, 
severe cases of catarrhal icterus, and, on the other, febrile forms of gastro- 
intestinal diseases that run their course without icterus and resemble an 
abortive form of typhoid fever. The latter are probably caused by the 
invasion of microbes other than the specific germ of typhoid fever. 


That Weil’s disease is a special form of typhoid fever produced by the entrance 
of the bacillus of typhoid into the bile-passages can hardly be granted. Both the 
occurrence of the disease and its course speak against such a theory. The French 
employ the name “typhus hépatique” for this disease (Landouzy, Mathieu), but 
this designation must be considered inappropriate and misleading. It is purely 
symptomatic. 

Weil’s disease resembles more the disease called bilious typhoid, or typhus 
biliosus, described by Griesinger in Cairo and by Kartulis in Alexandria. Fiedler 
is very positive in his statement that these diseases are identical. 


Many investigators have attempted to find a specific bacterium in 
Weil’s disease. Proteus flavescens, a bacillus cultivated by Jager from 
the urine of living cases and from the organs of a case dead of the disease, 
appears to be a likely cause. 


Jager (Ulm) found the same organism in a disease of fowls, observed in a village 
near Ulm and characterized by icterus with enteritis. The same germ was also 
found in the water of the Danube in that vicinity. It is probable that the microbes 
had been poured into the river with the waters of a brook that flowed through the 
village. Some of his patients subsequently bathed in the river and probably swal- 
lowed some of the germs. 

Banti succeeded in cultivating a proteus from the splenic blood of a man who 
was afflicted with a mild febrile icterus. This author attempts to establish certain 
distinctions between this germ, called by him Bacillus icterogenes capsulatus, and 
that of Jager, in which the capsule is not regularly found. Banti claims a hemolytic 
action for his bacillus, and considers the icterus to be pleiochromic, but gives no valid 
arguments in support of his assumption. 


Even if we should find that this parasite of Jager really was the cause 
of the disease in a number of cases, we can still assume that other cases 
of infectious icterus are caused by other forms of parasites; in fact, I 
personally am very much inclined to this belief. 

The micro-organisms could infect the bile-passages and could reach 
the liver directly from these or they could be brought to the liver from the 
intestine through the portal vein. In still other cases a simple intoxica- 
tion with intestinal ptomains may be the cause of the trouble. All these 
factors must be weighed and carefully considered in every case, as general 
conclusions cannot be drawn from the results obtained in any one case. 


In the French literature the question of the existence of an infectious icterus 
has been widely discussed. Landouzy, Kelch, and others assume that a bacterial 
infection occurs. Chauffard lays particular stress on autointoxication with in- 
testinal putrefactive products, and even creates the word “ Toxi-infection” to desig- 
nate those cases where both microbian and ptomain activities are possible. 


* Miller, Fr., “Die Schlammfieberepidemie in Schlesien,” 1891, Mudinchner 
med. Wochenschr., 1894, Nos. 40 and 41. Globig, Deutsche militdérdratliche Zettschr., 
1891. Possibly also Schulte, part 4 of “ Veréffentlichungen aus dem Gebiete des 
Militar-Sanitatswesens,” 1893. 





CATARRH OF THE BILE-DUCTS. 507 


As a matter of fact, many authors have included under the heading 
of Weil’s disease several affections that do not properly belong there, such 
as santonin-poisoning (Cramer *), septicemia (A. Frankel t), and acute 
parenchymatosis (Aufrecht {). Leiblinger’s view,? that Weil’s disease is a 
form of polyarthritis rheumatica complicated by an icterus from absorp- 
tion, has met with very little favor. 

Chauffard is not at all justified in his statement that the recurrence 
of icterus and the other symptoms is characteristic of Weil’s disease, 
although the frequency with which a relapse of the fever occurs is, it is 
true, quite remarkable. 

It is astonishing that at the time when icterus appears, the fever and 
the general disturbances begin to recede. Some investigators have ex- 
pressed a suspicion that the appearance of the former is responsible for the 
disappearance of the latter. At the same time, it is difficult to see why 
this should be; and it is quite probable that icterus and the other symp- 
toms are produced at the same time, but that the former appears later 
than the other symptoms. 

Treatment.—The treatment of Weil’s disease is that of simple ca- 
tarrhal icterus, on the one hand, and that of all infectious febrile diseases, 
on the other. The general rules and regulations that apply to the treat- 
ment of typhoid fever are proper in the treatment of this disease. Careful 
dietary regulations directed toward protecting and sparing the gastro- 
intestinal tract, evacuation and disinfection of the intestine (at least as far 
as this is possible), cool bathing, sponging, and the cold wet pack are 
symptomatically indicated. In view of the short duration of the fever, 
these measures are necessary for a short time only. 

The administration of large quantities of water injected as enemata or 
even hypodermically is indicated, and has been demonstrated to be of 
practical value (Leick, Damsch). 


LITERATURE. 


Banti: ‘Ein Fall von infectiésem Icterus levis,’ ‘“‘Deutsche med. Wochenschr.,”’ 
1895, Nos. 31 and 44. 
Chauffard: “ Revue de médecine,” 1885, p. 9; Septembre, 1887. 
“Deutsche militir-airztliche Zeitschr.”: Alfermann, 1892, p. 521; Hueber, 1888, 
p. 165; Kirchner, 1888, p. 195; Pfuhl, 1888, p. 385; Schaper, 1888, p. 202. 
Fiedler, A.: ‘‘ Deutsches Archiv fiir klin. Medicin,” vol. xu, p. 261, 1888; vol. L, p. 
320, 1892 (Literature): 

Freyhan, Th.: “ Berliner Klinik,” part 68, 1894 (Literature). 

Girode: ‘‘ Archives générales de médecine,” 1891, 1, pp. 26 and 169; 1892, 1. 

Goldenhorn: “ Berliner klin. Wochenschr.,’”’ 1889, p 734. 

Goldschmidt, F.: “ Deutsches Archiv fiir klin. Medicin,” vol. xu, p. 238, 1887. 

Haas: “ Prager med. Wochenschr.,”’ 1887, Nos. 39 and 40. 

Jager: “ Die Aetiologie des infectiédsen fieberhaften Icterus (Weil’sche Krankheit),”’ 
“ Zeitschr. fiir Hygiene,” vol. x11, p. 525. 

— “Der fieberhafte Icterus, eine Proteusinfection,”’ ‘‘ Deutsche med. Wochenschr.,’’ 
1895, Nos. 40 and 50. : 

Kausch, W.: “Ueber Icterus mit Neuritis,” “ Zeitschr. fiir klin. Medicin,’”’ vol. 

- xxx, p. 310, 1897. 

Kelsch: ‘ De la nature de l’ictére catarrhal,’”’ “‘ Revue de médecine,” 1885, p. 657. 

Leick, ge “Drei Falle,’”’ etc., “Deutsche med. Wochenschr.,’’ 1897, Nos. 44, 45, 
an A 


* Deutsche med. Wochenschr., 1889, p. 1067. 

+ Deutsche med. Wochenschr., 1889, p. 165. 

t Deutsches Archiv fiir klin. Medicin, 1887, vol. xu, p. 619. 

§ “Ueber Resorptionsicterus im Verlauf der Polyarthritis rheumatica,’’ Wiener 
med. Wochenschr., 1891, No. 20. 


508 DISEASES OF THE BILE-PASSAGES. 


Levi, L.: “Contribution 4 l’étude du foie infectieux d’une hépatite subaigue in- 
fectieuse primitive,” “ Archives générales de médecine,” 1894, 1, pp. 257 and 
444 (resembling old cirrhosis with secondary bacillary infection). 

Mathieu, A.: ‘“ Typhus hépatique bénin.,” “Revue de médecine,” 1888. 

Neelsen: ‘‘ Deutsches Archiv fir klin. Medicin,” vol. L, p. 285. 

Minzer, E.: “ Zeitschr. fir Heilkunde,” 1892. 

Pfuhl, A.: “ Berliner klin. Wochenschr.,’”’ 1891, p. 178. . 

Roth: “Deutsches Archiv fur klin. Medicin,” vol. x1, p. 314, 1887. 

Stirl, O. (Rosenbach): “ Deutsche med. Wochenschr.,” 1889, p. 738. 

Wagner, E.: “ Deutsches Archiv fiir klin. Medicin,”’ vol. xi, 1887, p. 621. 

Wassilieff, N. P.: “Ueber infectiésen Icterus” (17 cases), ‘ Wiener Klinik,” 1889, 
parts 8 and 9. 

Weil, A. : “ Ueber eine eigenthiimliche mit Milztumor, Icterus und Nephritis einherge- 
hende acute Infectionskrankheit,”’ ‘‘ Deutsches Archiv fiir klin. Medicin,” vol. 
XXXIX, p. 209, 1886. 

Werther: “ Deutsche med. Wochenschr.,’”’ 1889. 

Windscheid: “ Deutsches Archiv fiir klin. Medicin,” vol. xiv, p. 132, 1889. 


CHOLANGITIS SUPPURATIVA (EXSUDATIVA, 
INNFECTIOSA). 


(Quincke. ) 


- Purulent inflammation of the bile-passages is less frequently met 
with than the simple catarrhal form of inflammation. In the former the 
secretion contains more cells and more or less resembles pus, and the con- 
nective tissues of the walls of the bile-passages and of their surroundings 
show a small-celled infiltration; in the latter there is simply an increased 
secretion of mucus and a greater desquamation of the superficial epithe- 
lium. If the disease is of long duration, connective-tissue thickening of 
the walls, particularly of the larger bile-passages, is seen. As arule, there 
is, in addition, obstruction to the outflow of bile, so that dilatation of the 
passages occurs. In this manner there is created a condition analogous 
to cylindric bronchiectasis. Occasionally the mucous membrane will be 
seen to be ulcerated in certain places, from the action of concretions or 
from diphtheritic or croupous inflammation. Whenever the suppurative 
inflammation involves the finer bile-passages, miliary accumulations of 
pus are formed, which are first found in the peripheral portions of the 
lobules. Only occasionally do these small purulent foci appear as 
globular collections of pus bounded by the walls of the dilated bile-pas- 
sages; as a rule, they are true abscesses formed by circumscribed disin- 
tegration of the hepatic tissue. In the former case, cylindric epithelial 
cells from the bile-passages are seen in the pus; in the latter, we find 
hepatic cells in different stages of disintegration. Sometimes these small 
alveolar abscesses enlarge and become confluent, so that larger abscesses of 
irregular shape and distribution are formed. The contents of these cavi- 
ties frequently shows an admixture of bile. Inaddition to the purulent 
disintegration, there is also seen at the periphery the development of 
connective tissue and degeneration of the hepatic cells. 

Occurrence.—Purulent inflammation of the bile-passages is not very 
frequently met with. As a rule, it is not recognized until after the death 
of the patient. This form of inflammation is usually seen in subjects of ad- . 
vanced years and in cases where some obstacle to the normal flow of bile 
exists in the bile-passages. This obstacle may be either a concretion or 
an intestinal parasite. It is also seen as a complication and a sequel of 
typhoid fever, cholera, pyemia, and dysentery. Sometimes it appears 
without any demonstrable cause. | 


CHOLANGITIS SUPPURATIVA. 509 


Etiology.—As a rule, though not necessarily always, it will be found 
that some microbic infection is the cause of this suppurative form of 
cholangitis. This fact was not recognized until recently, and we are 
indebted chiefly to French authors for its elucidation. Its recognition has 
led to an understanding in general of the importance of infections of the 
bile-passages. As we have seen above (page 471) microbes, as arule, enter 
these passages from the intestine and travel in a direction opposed to that 
of the current of bile; less frequently they enter the bile-passages from 
the liver—1. e., directly or indirectly from the systemic blood-stream. 
In the latter instance they produce a descending infection. In excep- 
tional cases, finally, they may enter from the gall-bladder by penetrat- 
ing the walls of this viscus from the intestine or from some neighboring 
focus of disease. 

Microbic infection, so important in the diseases of the bile-passages, 
does not necessarily always produce a suppurative form of infection, but 
may lead to a simple catarrhal inflammation. 

It is possible that occasionally the contents of the bile-passages does not re- 
semble pus in appearance, but that at the same time (e. g.,in the case of Bacillus 


coli, according to Trantenroth) it may have a distinct feculent odor and very toxic 
properties, being capable of causing fever. 


Sometimes the action of microbes remains altogether latent during the 
life of the patient, and even no anatomic changes are seen after death. 
As the bile-passages may present a normal appearance, cultural experi- 
ments and a microscopic examination are necessary to determine the réle 
played by the bacterial invaders. By the latter procedure an increased 
desquamation of the epithelial lining of the bile-passages may be dis- 
covered. From the etiologic point of view, therefore, no sharp distinction 
can be drawn between the suppurative form of inflammation and the 
simplest catarrh of the biliary passages. 

Bacillus coli is the most frequent cause of suppurative cholangitis, 
acting singly or in combination with streptococci or with Staphylococcus 
aureus or albus. In case the bile-passages are temporarily or incompletely 
occluded these microbes may penetrate beyond the obstruction and may 
find a suitable nidus for their development in the stagnating contents 
of the ducts above, from which they may even penetrate the mucous 
membrane, making their removal a very difficult matter. 

Similar conditions favorable to a penetration of the mucous ceonrane 
by bacteria are seen in cases where the flow of bile is sluggish or where the 
peristaltic action of the bile-passages is reduced or the sphincters are weak. 
This occurs, for example, in febrile diseases of long duration in which the 
muscular tone of the whole body is reduced. Aside from the pathogenic 
germs already mentioned, a number of other bacterial species that are 
essentially harmless may gain an entrance and do damage only in the 
sense that they produce a liquefaction of tissues. 

A number of cases of icterus that are in the beginning simply catarrhal 
or of a mild infectious type may form the starting-point for severe forms of 
suppurative cholangitis. This occurs if other bacteria invade the in- 
flamed ducts or if some of the species that are already there acquire toxic 
properties. 

- When intestinal parasites, particularly ascarides, enter the biliary 
passages from the intestine, a suppurative cholangitis may result. This, 
as a rule, is probably not due to the action of these parasites themselves, 
but to bacteria that they carry with them. 


510 DISEASES OF THE BILE-PASSAGES. 


Of all the infectious diseases, typhoid fever is most frequently compli- 
cated by a suppurative inflammation of the bile-passages. Hdlscher, 
among 2000 autopsies on cases of typhoid fever found evidence of this 
condition in 5 cases, nearly all of which were in the stage at which the in- 
testinal ulcers were beginning to heal, although sometimes suppuration 
does not develop until the stage of convalescence. [Or even long after the 
termination of the systemic infection. A sufficient number of carefully 
recorded cases have been published within recent years to prove that in a 
very large number of cases of typhoid fever (50%, according to Cushing) 
the bile contains Bacillus typhosus, Chiari * having even found the 
micro-organism in 19 out of 22 cases.—Ep.] Gilbert and Girode found 
typhoid bacilli in the purulent contents of the gall-bladder and its walls 
five months after convalescence from typhoid. Dupré found the bacteria 
after eight months under similar conditions. [Miller + has recorded a case 
of cholelithiasis in which typhoid bacilli were found in pure culture in the 
gall-bladder seven years after the attack of typhoid fever, Droba ¢ has 
found typhoid bacilli in the center of gall-stones seventeen years after the 
primary infection, and Hunner 2 isolated typhoid bacilli from the bile at 
operation for suppurative cholecystitis eighteen years after the attack of 
typhoid fever. (For further particulars as to the réle of the typhoid 
bacillus in affections of the bile-passages see page 471.)—Ep.] Gilbert 
and Dominici found the bacillus: of typhoid fever and Bacillus coli 
together. The bacillus of typhoid is occasionally found in the wall of the 
gall-bladder without inflammation of the parts. It is not improbable 
that this form of inflammation may occur by the descending route from 
colonies of the typhoid bacillus that are present in the liver. 

In cholera, suppurative cholangitis and cholecystitis are found still 
more frequently than in typhoid fever. It seems, however, that the bacillus 
of cholera is present in many cases without causing any inflammatory re- 
action. Girode found the bacillus in the bile fourteen times in twenty- 
eight cases of cholera, but saw an inflammation of the bile-passages 
extending into the finest canals in only one case. 

Pneumonia, among other infectious diseases, is occasionally compli-. 
cated by suppurative cholangitis. In the cases reported the pneumo- 
coccus was found within the bile-passages in combination either with pyo- 
genic microbes or with Bacillus coli; while in some instances the latter was 
found alone (Gilbert and Girode, Klemperer, Létienne). It is possible 
that in pneumonia the mild form of icterus so often seen in this 
disease is caused by local infection. 

We may expect that the new point of view given by recent bacterio- 
logic research in regard to the origin of these forms of suppurative cho- 
langitis and their significance will throw light on a number of other ob- 
servations. We may state now that the presence of certain infectious 
germs alone is not sufficient to produce suppurative cholangitis; we must 
have, in addition, either a certain virulence of the bacteria or a reduction 
of the natural resisting power of the exposed tissues. The greatest 
differences in this respect seem to exist in the case of the cholera bacillus, 
next to this in the case of the bacillus of typhoid fever and of Bacillus coli, 
while in the case of staphylococci and streptoccoci such differences are not 


* Zeitschr. f. Heilkunde, Bd. xv, p. 199. 

t Johns Hopkins Hospital Bull., May, 1898. 

t Wien. klin. Woch., Nov. 16, 1899. 

§ Johns Hopkins Hospital Bull., August-September, 1899, p. 163. 


CHOLANGITIS SUPPURATIVA. oll 


so marked. It is important to remember that the gall-bladder in particu- 
lar seems to be so frequently involved for the reason chiefly that here there 
are present the favoring condition of stagnation of fluids, whereas in 
the other portions of the bile-passages the constant stream of bile seems 
to effectually prevent a localization and development of bacteria. 

Symptoms.—The symptoms of suppurative cholangitis are not char- 
acteristic and frequently are so indefinite that the disease is not recog- 
nized; or they may be so mild that the condition is not even suspected. 

Icterus as asymptom is not so marked as are disturbances of the general 
health. Whenever icterus is marked, it is, as a rule, not due to cholan- 
gitis, but to some occlusion of the bile-passages that may have existed 
before the occurrence of the inflammation of the ducts; or it may be due 
to the occlusion of the bile-passages as a result of the formation of concre- 
tions. 

Fever and the occurrence of enlargement of the spleen are important 
symptoms. Asin other suppurative processes, the fever is of a remitting 
type with evening exacerbations, and frequently complete intermissions 
in the morning. Again, as in other forms of fever from absorption of 
purulent material, this type of fever is not necessarily maintained, but 
may vary in different directions. Both the number of daily maxima and 
minima and the time of day at which they occur may vary. ‘The rise of 
temperature may be accompanied by a chill and the time of a decline by a 
sweat; or, again, periods of subnormal temperatures or even long afebrile 
periods may occur. Occasionally, the type of fever caused by the suppu- 
rative process is modified by variations in temperature induced by the 
impaction of gall-stones. The fever described has been called febris 
intermittens hepatica or febris bilioseptica, the latter designation being 
particularly in favor with French authors. This fever, like any other 
fever due to the absorption of constituents of pus, may run a similar course 
and cause the same subjective symptoms as the intermittent type of ma- 
larial fever; and it is even stated that a tertian and a quartan type are 
occasionally observed. It is not, in my opinion, demonstrated that this 
fever, provided careful records of temperature are made every two or three 
hours, resembles these malarial types of fever more than any fever from 
absorption of products from other suppurative foci. In both cases the 
fever is caused by the absorption of toxins capable of producing a febrile 
rise of temperature, but this does not explain the remitting type that the 
fever assumes. In the most serious cases microbes may even enter the 
blood-current. 

In case other poisons capable of acting on the heart or the kidneys or 
of depressing the temperature are absorbed, other more or less severe 
general symptoms may appear. The causes of such an occurrence and 
the conditions under which such an absorption may take place are as un- 
known to us as in the case of suppurative pyelitis or of putrid bronchiecta- 
sis. The latter conditions in more ways than one resemble suppurative 
cholangitis and present many analogies to it. In the disease under dis- 
eussion, however, the effect of biliary stasis and of the interference with 
the hepatic function add a specific and distinguishing factor. 

In addition to icterus, which, as we have seen, is not constantly pres- 
ent, pain or a feeling of tension in the hepatic region often call attention 
to the liver as the diseased organ. In case the gall-bladder is involved, 
the pain as a rule is more severe. In addition to these symptoms, dis- 
turbances of the digestion, diarrhea, and vomiting are often present. 


512 DISEASES OF THE BILE-PASSAGES. 


[Pick * has called attention to the absence of leucocytosis during the 
afebrile periods and to the diminution in the nitrogen in the urine during 
the days of fever. Boas + has recently called attention to a tender area 
in the region of the twelfth dorsal vertebra from 2 to 3 cm. from the middle 
line in cases of even latent inflammation of the bile-ducts.—Eb. ] 

Some of the possible complications of suppurative cholangitis are pyle- 
phlebitis, true septicemia, endocarditis (Netter and Martha), purulent 
meningitis (Jossias), and, usually starting from the gall-bladder, peri- 
tonitis (Chiari). 

Course.—The onset of suppurative cholangitis is, as arule, insidious 
and not determinable. In case cholelithiasis exists, the symptoms of 
cholangitis are superadded to those of biliary stasis and of the impaction 
of the stone. They frequently run parallel to these symptoms, inasmuch 
as an increased obstruction to the flow of bile will be accompanied by 
an increased absorption of toxins from the pus. In cases of this kind 
the symptoms may vary in intensity for months, until finally the im- 
pacted stone is forced into the intestine. When this occurs, the pus 
that has formed finds an exit and the cholangitis may subside. The 
fever in these instances does not recede at once, but gradually (own 
observation). In the majority of cases the outflow of pus is not com- 
plete, but.only partial, or occurs only at intervals. The body becomes 
accustomed to the absorption of toxins, so that the temperature may 
remain normal for a time; yet at the same time the fact that recovery 
is slow and incomplete soon directs attention to a focus of disease existing 
somewhere. If not relieved, the liver will gradually be destroyed by a 
process of slow purulent destruction of tissue and the patient succumb in 
the course of a few weeks or months. Hectic fever is always present 
in these cases. 

In the case of infectious diseases where no obstruction of the bile- 
passages exists the symptoms are still more obscure. Icterus is, as a 
rule, absent; or if present at all, is usually slight. The fever and 
sometimes pain in the hepatic region are the only symptoms, and they 
are not characteristic. In typhoid fever these symptoms do not develop 
until the stage of convalescence and after the disease proper has run its 
course. Where the gall-bladder is particularly affected, symptoms 
directed to this viscus will appear (see below). 

Prognosis.—The prognosis in the majority of cases is unfaypantibal 
Where concretions exist, all the dangers of biliary stasis are present, 
with, in addition, the danger of multiple abscess formation. At the 
same time, if operative or spontaneous removal of the stone can be 
brought about, complete restitution to normal is possible. It seems 
that even ascarides can wander back into the intestine (Kartulis). [Ogil- 
vie { has reported a case in which jaundice ceased after the expulsion 
per anum of around worm one-third of the length of which was stained by 
bile as though it had been for a time impacted in the common duct.—Eb.] 
The typhoid form of infection seems to be the most dangerous of all, 
for the reason that ulceration of the gall-bladder may occur and lead to 
perforation and peritonitis. 

Diagnosis.—In those instances where other signs point to the existence 
of some disease of the biliary passages, notably gall-stones, the appear- 

* Deutsches Arch. f. klin. Med., Bd. uxtx, Hft. 1 and 2. 


+ Minch. med. Woch., 1902, No. 15. 
t British Medical Journal, Jan. 12, 1901. 


—seT = 


CHOLANGITIS SUPPURATIVA. 5138 


ance of a remitting type of fever and a general loss of strength will lead 
us to suspect cholangitis. When icterus is absent, or is so slight that 
it is diagnostically valueless (it might, for example, be secondary and 
due to pyemia), and when other local symptoms are absent, malaria 
might be suspected. The decision will in such a case have to be rendered 
from a careful study of the temperature curve. If the maximum occurs 
during the first half of the day, or if regular intervals, a continuous type 
of rise and fall, and longer periods of complete apyrexia are seen, the 
probability is great that the case is one of malaria; whereas the fever 
due to the absorption of toxins from pus usually reaches its maximum 
toward evening, there are more frequent rises to the highest point, and 
a greater irregularity in their occurrence, subnormal temperatures occur 
at times and the periods of apyrexia are short and not distinct. A 
skilled observer, in addition, will know how to interpret the absence of 
the plasmodium and of pigment from the blood. [The presence or 
absence of leucocytosis would also have great weight in differentiating 
the two conditions.—EbD.] 

If the diagnosis of fever from absorption has been made, local symp- 
toms will have to direct attention to the bile-passages as the place of 
suppuration. These are, in addition to icterus, pain in the region of 
the liver and the gall-bladder. [And possibly the tender area described 
by Boas.—Ep.] Certain points in the past history of the case have an 
important bearing on the diagnosis, such as a history of previous attacks 
of gall-stone colic, a recent attack of typhoid fever or of cholera. 

In many respects the symptoms of suppurative cholangitis resemble 
those of abscess of the liver so much that it is impossible to make a 
differential diagnosis. In the case of the latter lesion, however, the 
symptoms due to involvement of the bile-ducts are not so apparent, nor 
is icterus or the pain in the region of the gall-bladder so marked. In 
the case of cholangitis fever is more apt to be absent than in the case of 
abscess of the liver. [Too much stress should not be placed upon the 
temperature in excluding a possible abscess of the liver, as in this con- 
dition the rise of temperature may be slight or even absent, while leuco- 
cytosis is frequently absent at any rate after the abscess has existed 
for some time.—ED. ] 

It is possible that later, when we shall have more experience, the 
determination of the species of bacteria that have infected the bile- 
passages may be of some diagnostic value. For the present the history 
of an attack of typhoid fever or of cholera alone may give us aclue. The 
character of the fever cannot be utilized in the determination of this 
point. 


Netter’s statement, based on some animal experiments, that Bacillus coli, 
in contradistinction to pyogenic microbes, causes subnormal temperatures, is cer- 
tainly not universally applicable. Future investigations will have to decide whether 
it is at least applicable to some of the cases observed in human beings. 


In the presence of symptoms pointing to cholangitis, the discovery 
of ascarides in the stools may reveal a possible cause. 

Treatment.—One of the chief indications in the treatment of chole- 
lithiasis is the prevention of suppurative cholangitis. The careful treat- 
ment of simple catarrhal icterus, too, has a certain prophylactic value. 
The importance of so-called disinfection of the intestine by drugs and 
milk diet, favored by French authors, is doubtful. 

33 


514 DISEASES OF THE BILE-PASSAGES. 


Cholangitis should be treated in the same manner as catarrhal icterus. 
As a general rule, the possible presence of concretions should be con- 
sidered. ‘The administration of cholagogues and the disinfection of the 
biliary passages is indicated on theoretic grounds, and both measures 
are recommended and employed. ‘The drugs in use for this purpose are 
salicylic acid, salol, oleum terebinthine, benzonaphthol, and oleate of 
sodium. In cases of cholangitis due to ascarides the repeated adminis- . 
tration of calomel and of santonin is indicated. 

Kehr, of late years, has attempted to fulfil the apparently most urgent 
indication—that is to say, drainage of the pus that has accumulated 
within the bile-passages—by opening the main bile-duct and establishing 
permanent drainage through the skin. Sometimes opening and draining 
the gall-bladder is beneficial and exercises a favorable effect on the other 
bile-passages, particularly in those instances where the cystic duct itself 
is exceptionally wide and can be drained. [Terrier * has also strongly 
urged drainage of the biliary passages by cholecystotomy in this condition. 
Wilms + has reported a cure by drainage of the gall-bladder in a case 
of multiple abscesses due to cholangitis and cholecystitis.—ED. ] 


Aubert, Pierre: ‘De l’endocardite ulcéreuse végétante dans les infections biliaires,’’ 
Thése de Paris, 1891. . 

Chauffard: Loc. cit., p. 704. 

— ‘Etude sur les absces aréolaires du foie,” “ Archives de physiolog.,’’ 1883, 1, p. 
263. 

Dmochowski and Janowski: “Cholangitis suppurativa durch Bacterium coli,’ 
“Centralblatt fir allgemeine Pathologie,’”’ 1894, No. 4. 

Dominici: “Des angiocholites et cholécystites suppurées,’’ Thése de Paris, 1894 
(fully treated, quoting largely from literature). 

Dupré, E.: “ Les infections biliaires,’”’ Thése de Paris, 1891, “ Archives générales de 
médecine,” 1891, 11, p. 246. 

Frerichs: Loe. cit., 0, p. 426. 

Gilbert et Dominici: “Société-de biologie,’ 1893; January and February, 1894. 

Gilbert et Girode: ‘‘Société de biologie,” 1890; 1891, Nos. 11 and 16; 1892. 

Holscher: “Ueber die Complicationen bei 2000 Fallen von letalem Abdominal- 
typhus,” “ Miinchener med. Wochenschr.,” 1891. 

Jossias: “ Progrés médical,” 1881. 

Kartulis : “ Ascariden-Cholangitis,” ‘‘Centralblatt fir Bakteriologie,” vol. 1; “ Bericht 
iiber den VIII. internationalen Congress fiir Hygiene in Budapest,” 1894, vol. 
11, p. 646. 

Kehr: “ Miinchener med. Wochenschr.,’”’ 1897, No. 41. 

Létienne: “ De la bile dans l’état pathologique,’”’ Thése de Paris, 1891. 

— “Recherches bacteriol. sur la bile humaine,” “ Archives de méd. expér.,’”’ 1891, 
p. 761. 

Naunyn: ‘Cholelithiasis,” p. 103. 

Netter et Martha: “ Archives de physiolog.,’’ 1886, p. 7. ; 

Pick, Fr.: “ Zur Kenntniss der Febris hepatica intermittens,” ‘Congress fiir innere 
Medicin,”’ 1897, p. 468. : 

Rothmund: “ Endocarditis ulcerosa”’ (does case 10 also belong here?), Dissertation, 
Zurich, 1889. 

Schiippel: Loc. cit., p. 36. 

Sittmann: “ Bakterioskopische Blutuntersuchungen” (14 cases of diseases of the 
liver), ‘‘ Deutsches Archiv fiir klin. Medicin,” vol. Lu, p. 336, 1894. 


* Rev. de Chirurgie, 1895, p. 966. + Manch. med. Woch., 1902, No. 13. 








ad 


INFLAMMATION OF THE GALL-BLADDER. 515 


INFLAMMATION OF THE GALL-BLADDER. 
Cholecystitis; Cystitis fellez. 
(Quincke.) 


Inflammation of the gall-bladder is intimately related to inflamma- 
tion of the bile-passages; as the former is probably always a complication 
of inflammation of the latter parts. For this reason the same etiologic 
factors that play a rdle in the causation of inflammations of the bile- 
passages can be made responsible for the same condition in the gall- 
bladder. Clinically, on the other hand, cholecystitis is distinguished 
by certain typical features, as the parts involved in this instance form 
a closed sac whose only exit is a narrow passage. This anatomic arrange- 
ment causes peculiarities in the development of inflammations in these 
parts, and also makes a cure of the affection difficult. It is for these rea- 
song that diseases of the gall-bladder must be discussed independently. 
A very important element is the fact that gall-stones develop chiefly in 
the gall-bladder. These concretions are the most prolific cause of in- 
flammations, since they act not so much mechanically, as was formerly 
assumed, but through the agency of bacteria that surround them. Many 
cases of gall-stone colic are not purely spastic in character, but are usually 
complicated by inflammatory processes in the wall of the gall-bladder 
and the tissues surrounding it. [For a discussion of this point see page 
556.—Epb.] The inflammation affects the mucous membrane, at first 
causing a thickening of this tissue and the secretion of an abnormal 
quantity of mucus in the cavity of the bladder (cholecystitis catar- 
rhalis). This excessive secretion is soon thickened by the admixture of 
numerous desquamated epithelial cells, and as the walls of the cystic 
duct are at the same time swollen, both the viscidity of the fluid in the 
gall-bladder and the narrowness of the duct prevent an outflow of its 
contents. As a result the bladder becomes dilated. In the mean time 
the inflammatory process extends to the muscular wall of the bladder 
and to the serous membrane covering it. As it also involves the con- 
nective-tissue structures in the wall, a connective-tissue thickening of 
these parts results, often with peritoneal adhesions. When, later, the 
contents of the gall-bladder are absorbed or succeed in gaining an exit, 
the changes in the wall of the gall-bladder will cause a contraction of the 
organ, leading to a permanent reduction in its size. In addition, the 
gall-bladder may be distorted in shape or attached in an abnormal posi- 
tion, while its walls may undergo calcification. 

This form of fibrinous inflammation of the gall-bladder is quite 
frequently seen in corset liver, where it originates from stasis of bile 
within the bladder caused by traction and pressure upon the cystic duct. 
In addition to this, gall-stones may be present and aggravate the condi- 
tion. In other instances this form of inflammation extends by con- 
tinuity from the serous covering of the gall-bladder in such a manner 
that the peritoneal investment, as a result of traumatic influences, be- 
comes inflamed and the process extends to the internal coats of the viscus. 

Purulent inflammations of the gall-bladder are less frequently met 
with than fibrous inflammations. The pus that is formed from the 
mucous lining of the gall-bladder as a rule distends the viscus, provided 
it was normal in size before the process began. Distention of and ulcera- 


516 DISEASES OF THE BILE-PASSAGES. 


tive processes in the gall-bladder, particularly in typhoid fever, may 
lead to perforation. In case suppuration follows chronic cholelithiasis, 
the gall-bladder is usually so thickened by previous attacks of inflam- 
mation that it is not distended by the pus, and, moreover, is less liable 
to perforation. At the same time a circumscribed peritonitis may result 
under these circumstances, or, if adhesions exist, a fistula may be formed 
that opens into the intestine or externally through the skin. In this 
manner drainage may be established, the pus evacuated, and the em- 
pyema be cured. Conditions of this kind are not infrequently found at 
autopsy. 

The microscopic changes seen in the wall of the gall-bladder are 
analogous to those seen in the bile-ducts. If repeated attacks of in- 
flammation occur and the wall becomes very much thickened, the glands 
of the mucous membrane disappear. In acute suppurative forms of in- 
flammation the mucous membrane, and sometimes the whole wall, is 
seen to be in a state of small-celled infiltration. Occasionally, as in the 
case of typhoid fever, small mural abscesses may form that perforate 
either into the lumen of the gall-bladder or through its wall. 

Symptoms.—The chief signs of inflammation of the gall-bladder are 
pain and enlargement. The pain may be truly inflammatory in char- 
acter. In these cases it is particularly severe in acute inflammations and 
in involvement of the serous coat. In other instances it is caused by 
the distention of the wall of the gall-bladder following occlusion of the 
cystic duct and the filling of the bladder. The pain is increased by 
pressure, respiratory and general movements, and by distention and 
violent peristaltic movements of neighboring portions of the intestine, 
particularly of the duodenum and the hepatic flexure of the colon. 

In cholecystitis a swelling in the region of the gall-bladder can usually 
be discovered by palpation and percussion. In case the gall-bladder 
is intact and the inflammation is recent, this swelling may be caused 
by an increase in the contents of the bladder and by distention. In 
other cases it is due to inflammatory and edematous thickening of the wall 
of the gall-bladder and of the neighboring peritoneal covering of the 
liver, abdominal parietes, and colon, or to serofibrinous masses inclosed © 
by these inflamed parts of the peritoneum. In the first case the tumor 
has the same shape as the gall-bladder; in the latter, its outline is irregular 
~ and not so readily palpable, owing to the pain in and the resulting ten- 
sion of the abdominal muscles. The swelling may move with the liver 
on respiration; but frequently this respiratory motility is impaired 
on account of the pain, and in other instances adhesions exist and 
prevent it. Sometimes fecal matter accumulates in the hepatic flex- 
ure of the colon, particularly if the wall of the bowel is inflamed, and 
these accumulations form a mass that lies so close to the gall-bladder 
that it changes its outline and modifies the area of greatest pain. Owing 
to these possible complications, it is frequently impossible, when the 
disease is at its height, to diagnose more than a swelling in the right side 
of the abdomen, and the further course of the disease will have to reveal 
whether the gall-bladder, the vermiform appendix, or the colon is the 
seat of the trouble. 


In cases of corset liver the tumor can assume a very peculiar shape from the 
thickening and elongation of the tongue-shaped piece of liver that is separated 
from the main mass of the organ by the indentation, while this piece or the thin | 
margin of the liver situated in front of the gall-bladder may become thickened by 


INFLAMMATION OF THE GALL-BLADDER. 517 


a direct extension of the inflammatory process. As soon asthe inflammation sub- 
sides this local change in the shape of the hepatic margin is corrected and normal con- 
ditions are reestablished (Riedel, compare page 394). 


The intensity of this simple inflammation of the gall-bladder may 
vary greatly, its duration covering from one day to several weeks. Very 
often cystitis and pericystitis follow an attack of gall-stone colic. This 
is particularly true in long-drawn-out attacks; while in recent cases 
running an acute course the colicky seizure may be purely spastic in 
character. 

In cases where the inflamed mucous membrane of the gall-bladder 
secretes pus in the place of mucus and epithelial debris, pain and swelling 
are particularly severe; while at the same time the fever, which may 
have been of a continuous type in the beginning, assumes the remitting 
type of an absorption fever. However, as is the case in cholangitis, 
this does not always occur. Pain and swelling, too, may be slight, so 
that, in those cases especially where purulent cholecystitis complicates 
some other disease, no marked change inthe symptoms occurs. It may 
happen in this way that the condition we are discussing may not be 
discovered. This occurred, for example, in 11 out of 14 cases of typhoidal 
cholecystitis that Hagenmiiller collected. In typhoid cases, in par- 
ticular, it frequently happens that the small abscesses in the wall of the 
gall-bladder lead to perforation and fatal peritonitis (Chiari and others). 

The diagnosis, therefore, of cholecystitis is in many instances as diffi- 
cult or as impossible to make as is that of cholangitis. All in all, it is 
more easy than that of cholangitis without involvement of the gall- 
bladder. This is due to the more superficial position of the bladder 
and the typical and strictly localized symptoms that are produced by 
inflammations of the peritoneal covering of the organ. According to 
the general conditions observed and the history of the case, it is fre- 
quently an easy matter to decide what the character of the cholecystitis 
is and whether the bladder alone is involved or whether cholangitis 
coexists. 

Adhesions with the abdominal parietes may be accompanied by cir- 
cumscribed areas of edema of the skin. In the case of Trantenroth 
there was an edematous area as large as an adult hand in the hepatic 
region, although no peritoneal adhesions were found. 

In regard to the advisability of exploratory puncture, the same argu- 
ments as in the case of simple dilatation of the gall-bladder exist, but are 
even more applicable than in the latter condition. [Exploratory punc- 
ture has no place in either condition at the present time. The facts 
learned are fewer and the danger much greater than is the case with ex- 
ploratory laparotomy, while a cure is not to be expected from the former 
method.—EbD.] 

Treatment.—Both the acute and the chronic relapsing forms of cho- 
lecystitis call for rest of the inflamed parts. For this reason the patient 
should be instructed to remain in bed, the diet should be restricted, and 
opium should be administered in small doses in order to quiet the peri- 
staltic action of the bowels. In cases where great sensitiveness to pres- 
sure exists it is advisable to apply from four to six leeches to the sore spot, 
applying them over as small an area as possible. An ice-bag, provided 
it is not too heavy, also relieves. Whenever the pain is distributed 
over a wider area, and where it is not so acute in character nor so violent, 
it is better to apply heat, either by Priessnitz bandages, or, in the more 


518 DISEASES OF THE BILE-PASSAGES. 


violent forms, by poultices that are kept at a constant temperature by 
a thermophore (Quincke). We can usually get along without hypodermic 
injections of morphin at the height of the disease. When the acute 
symptoms subside, it is well to remember that accumulations of fecal 
matter may occur in the hepatic flexure, and that such masses should be 
removed in good time either by careful enemata or by the internal ad- 
ministration of castor oil, a measure that may greatly ameliorate the 
local symptoms and favor resolution of the exudate. [The adminis- 
tration of an opiate is objectionable in the case of cholecystitis for 
the same reasons as prevail in appendicitis and it is important to bear 
in mind in both conditions that the relief of pain is accompanied by 
the danger involved in obscuring the symptoms and furnishing a false 
sense of security.—Eb.] 

If, from the local or the general symptoms, a purulent or a bacterial 
form of cholecystitis has been diagnosed, operative procedures must be 
considered. In fact, the appearance of symptoms of purulent inflam- 
mation of the gall-bladder is, as a rule, the chief indication for the surgical 
removal of gall-stones. If a history of previous inflammation leads us 
to suspect a thickening of the wall of the gall-bladder, operative inter- 
ference is not so urgent. In cases, however, where the contents of the 
gall-bladder are very infectious, and where the bladder becomes rapidly 
distended, or where, as in typhoid fever, there is danger of ulceration 
and perforation into the peritoneal cavity, the operation should be per- 
formed as soon as possible. 


Cadéac, A.: ‘De la mioicorsues suppurée,’’ Thése de Paris, 1891. 

Chiari: “ Ueber cholecystitis typhosa,” “ Prager med. Wochenschr., ”” 1893. 

Dungern: “ Ueber Cholecystitis typhosa, eas Neen hance med. Wochenschr., ” No. 26, 
1897. 

Kcklin, Th. (Courvoisier): ‘Ueber das Verhalten der Gallenblase bei dauerndem 
Verschluss des Ductus choledochus,”’ Dissertation, Basel, 1896. 

Fuchs: “ Berliner klin. Wochenschr.,’’ 1897, p. 647. 

Gilbert et Girode: Société de biologie, 1893. 

Hawkins, Fr.: “On Jaundice and on Perforation of the Gall-bladder in Typhoid 
Fever, ” “ Med.-chir. Transactions,” vol. Lxxx, 1897. 

Kleefeld (Naunyn): “Ueber die Punction der Gallenblase, ” ete. (diagnostic), 
Dissertation, Strassburg, 1894. 

Mason, A. Lawrence: “ Gall-bladder Infection in Typhoid Fever, ” “Boston Med. and 
Surg. Journal,” vol. txxxvi, No. 19, 1897. 

Naunyn: “Deutsche med. Wochenschr. , ”” 1891, 

Quincke: ‘‘ Thermophor,” “ Berl. klin. Wochenschr., ”” 1896, No. 16. 

Souville, R.: “Cholécyst. scléreuse d’origine calculeuse et ‘pericholécystite, ” Thése 
de Paris, 1895. 

Trantenroth: ‘“Mittheilungen aus den Grenzgebieten der Medicin und Chirurgie,” 
I, p. 703, 1896. 


DILATATION OF THE GALL-BLADDER. 
(Quincke.) 


Dilatation of the whole system of biliary passages, either partial or 
throughout all its ramifications, occurs as soon as the outflow of bile 
from one area or the other is impeded. The longer the stasis of bile 
persists, the more extended the dilatation. As soon as the obstacle is 
removed, the dilated condition in a measure recedes; but it may persist 
to a varying degree. Occasionally, small ectatic protuberances are 
formed that are situated laterally from the main axis of eg vessel, 





DILATATION OF THE GALL-BLADDER. O19 


The occurrence of dilatation of the bile-passages accompanying stasis 
of bile has been discussed under that heading. In case, however, the 
dilatation persists, the condition becomes important, for the reason that 
it favors infection from the intestine. During life this chronic and per- 
sisting dilatation is not recognizable, and dilatation of the gall-bladder 
is clinically more important. The viscus in this condition may contain 
(1) bile, (2) a colorless fluid, (3) pus; and in all three cases gall-stones 
may at the same time be present. 

The gall-bladder is distended with bile in general biliary stasis or in 
cases where the opening of the cystic duct is occluded by a gall-stone. 
The obstruction may be so situated as to permit the entrance of bile 
into the bladder and at the same time prevent its exit. In addition to 
stones in the cystic duct, concretions may also be present in the bladder 
itself. In cases of this kind two factors are at work—viz., first, the direct 
obstruction to the outflow of the bile; second, a number of inflammatory 
processes in the bladder-wall and possibly paresis of its musculature. 
It is not decided to what extent such paretic conditions can lead to an 
enlargement of the gall-bladder without the presence of some mechanical 
obstruction to the flow of bile. [Kehr believes that dropsy of the gall- 
bladder may result from an acute infectious cholecystitis of mild grade, 
and that it is exceptionally due to obstruction of the cystic duct by a 
stone alone.—ED. | ' 

In cases where the cystic duct is permanently occluded by a stone, 
cicatricial tissue, twisting, or swelling of the mucosa, the contents of the 
gall-bladder are absorbed and nothing remains but a colorless liquid 
free from all bile constituents (hydrops cystidis fellee). This fluid is 
usually clear, resembles mucus, is viscid or may be very thin and watery. 
It contains mucin, squamous epithelium, and occasionally albumin from 
inflammatory exudation (Kleefeld). In cases of this kind the gall-blad- 
der is usually very tense, like a cyst, and, as a rule, a little or occasion- 
ally very much larger than normal. The larger the gall-bladder, the 
thinner its wall; and, asa result, the glands of the mucosa are destroyed 
and the cylindric epithelium is replaced by squamous cells. 

If the contents of the gall-bladder consist of pus (empyema), the 
fluid contents may be really pus or a mixture of pus and serous fluid 
that may be colored by bile. This fluid, as.a rule, contains some albumin, 
occasionally mucin, cylindric and squamous epithelium and cells in a 
state of fatty degeneration, and also bacteria. 

Symptoms.—Both the transverse and longitudinal diameters of the 
gall-bladder increase when the viscus becomes dilated and a swelling is 
formed that can often be felt during life. In slight degrees of dilatation the 
gall-bladder extends below the lower margin of the liver. Its outline is 
that of a segment of a sphere some two or three centimeters in diameter. 
Only when the abdominal walls are thin can the enlarged bladder be 
palpated. The larger the gall-bladder, the more it extends below the 
hepatic margin, assuming a pear-shaped outline. At the same time its 
motility, as compared to that of the margin of the liver, increases, par- 
ticularly in a lateral direction and backward and forward. This motility 
is particularly apparent when the patient is lying on his side and on 
bimanual palpation; but the organ always quickly returns to its original 
position underneath the margin of the liver. With each respiratory 
excursion the bladder rises and falls synchronously with the margin of 
the liver. If the bladder becomes very much elongated, its longitudinal 


520 DISEASES OF THE BILE-PASSAGES. 


axis may become twisted so that the outline of the organ resembles a 
cucumber (Courvoisier). The fundus is turned forward and may appear 
to be separated from the margin of the liver by a coil of intestine that has 
entered between the bladder and the liver. The fundus, of course, follows 
all the movements of the liver. In cases of corset liver the gall-bladder 
may become dislocated downward and toward the median line to a con- 
siderable degree. If the gall-bladder is very much dilated,—and cases 
are on record where the contents of the organ amounted to over one 
liter,—the swelling may be confounded with echinococcus cysts, hydro- 
nephrosis, or ovarian cyst. The connection of the tumor with the liver 
will have to be determined in order to arrive at adecision. If the growth 
is the gall-bladder, it will be attached to the liver above and be situated 
in close contact with the abdominal wall. Ovarian cysts, on the other 
hand, are attached by a pedicle in the pelvis, and hydronephrosis starts 
from behind. Sometimes distention of the stomach with gas may be of 
some assistance, as this manceuver will push the gall-bladder forward and 
bring it in closer contact with the anterior abdominal wall. 

If the abdominal walls are very thin and very much relaxed, the 
gall-bladder, if it is enlarged, is sometimes even visible. Palpation is 
less satisfactory than might be expected from the close proximity of the 
organ to the anterior abdominal wall. This is due to the fact that no 
resistance is offered behind the bladder, so that it escapes from the hand 
pressing on the abdomen. It is a comparatively easy matter, however, 
to determine whether the consistency is elastic and cystic or not, whether 
the walls are thickened, and whether concretions are situated within the 
bladder. On the other hand, it is rarely possible, even if the bladder is 
very much enlarged, to elicit fluctuation by bimanual palpation. 


Dulness on percussion, that might be expected when the bladder is very much 
enlarged and distended with fluid, can only be elicited on light percussion for the 
reason that the fluid contents allow the impulse to be transmitted to neighboring 
coils of intestine so that a tympanitic sound is produced. 


Dilatation of the gall-bladder rarely causes subjective symptoms. 
Symptoms of this character, it is true, are caused by the disease that has 
produced the dilatation or by inflammation that may be present at the 
same time. In the majority of cases the diagnosis of dilatation of the 
gall-bladder is difficult, and it is necessary to utilize all the symptoms 
— of complicating conditions together with the anamnestic data of the case. 
These, in combination with the scanty objective symptoms presented, 
may lead to a satisfactory diagnosis. The same applies to the deter- 
mination of the nature of the fluid contents of the bladder. Exploratory 
puncture has occasionally been performed for the latter purpose; but as 
this procedure may easily lead to peritonitis from extravasation of some 
of the inflammatory contents (Naunyn), many authors condemn it abso- 
lutely. If performed at all, it should be done with a thin and very long 
needle. [In this, as in other exploratory punctures, it would seem that 
aspiration of even a small quantity of fluid might tend to diminish the 
danger always present in intra-abdominal exploratory punctures. The 
simple hollow needle does not relieve tension sufficiently to render un- 
likely leakage into the peritoneal cavity. The removal of a larger quan- 
tity of fluid relieves tension to a greater degree and lessens this imminent 
_tisk.—Ep.] Nowadays, when we have all the improved technique of 
modern surgery at our disposal, exploratory laparotomy must certainly 


oh 


HEMORRHAGE INTO THE BILE-PASSAGES. 521 


be preferred. This operation is more complicated but far less dangerous; 
while, in addition, the opening of the gall-bladder for therapeutic purposes 
can follow the exploratory opening of the abdomen whenever indicated. 

The prognosis and the treatment of dilatation of the gall-bladder 
must depend altogether on the origin of the trouble and on other cir- 
cumstanees. Dilatation alone would call for extirpation of the organ 
only in those cases where harm is being done from pressure on surround- 
ing organs or where a rupture of the bladder is to be feared from too rapid 
distention. [Even in these cases drainage without extirpation is now 
found to be sufficient, and is a much simpler procedure.—Eb.] 


HEMORRHAGE INTO THE BILE-PASSAGES. 
(Quincke. ) 


Small extravasations of blood into the mucous membrane are occa- 
sionally seen in hyperemia and inflammation, and have no significance. 
Larger hemorrhages into the lumen of the bile-passages and the gall- 
bladder, causing the bladder and the ducts to contain a bloody fluid, are 
rare, but may become clinically important. They are occasionally seen 
in passive congestion of the liver. In the cases reported no source of the 
hemorrhage could be found, so that it is probable that the blood oozed 
from the capillaries. 

Quinquaud described a case of hemorrhagic cholangitis in which so 
large a quantity of blood was poured into the bile-ducts and into the 
intestine that death followed from hemorrhage. In this case the walls 
of the bile-passages were thickened and showed connective-tissue hyper- 
plasia, were hyperemic and covered with ecchymotic spots, and the 
blood within the passages was coagulated. The patient had at different 
times been a sufferer from attacks of colic, although no gall-stones were 
found on autopsy. Cases of this character have also been reported 
among patients with yellow fever, in sufferers from the hemorrhagic di- 
athesis, in carcinoma and ulceration of the gall-bladder, in contusions 
and abscesses of the liver, and in aneurysms of the hepatic artery that 
have burst into the bile-passages (see the section on this subject). 

If the flow of blood into the bile-passages is very copious, the signs 
of acute anemia may become apparent during life. At the same time 
the stools will contain blood, and occasionally hematemesis will be ob- 
served. If the hemorrhage occurs very suddenly, the bile is washed out 
of the bile-passages, so that the blood following is pure ‘and can coagulate. 
These coagulates may in their turn act as obturators and cause obstruc- 
tive icterus and spasmodic contraction of the bile-ducts. It is possible, 
therefore, to determine that the bile-ducts are the source of blood appear- 
ing in the intestinal contents. 

Treatment can only be directed against the disease that is the primary 
cause of the bleeding. In only one class of cases could treatment of the 
hemorrhage itself be successful—namely, when it would be possible to 
diagnose an ulcer of the gall-bladder (possibly after typhoid fever) and 
to remove it by surgical procedures. 


Schiippel: Loe. cit., p. 62. 
Quinquaud: “Les affections du foie,” Paris, 1879, cited by Schiippel. 


522 DISEASES OF THE BILE-PASSAGES. 


SOLUTIONS OF CONTINUITY OF THE BILE-PASSAGES. 


Rupture; Perforation; Fistula. 
(Quincke.) 


The different possible forms of solution of continuity of the bile- 
passages are: 

1. Rupture of the distended or of the normal wall of the bile-passages 
from pressure exercised by the contents or from without. This is seen 
more frequently in the gall-bladder than in the bile-passages. 

2. Perforations from ulcerative processes. These occur more fre- 
quently from within outward than vice versé. They, too, are more often 
seen in the gall-bladder than in the ducts. Perforation occurs either 
into the abdominal cavity directly or into some neighboring cavity after 
adhesions have formed between it and the gall-bladder (fistula). Dis- 
eases of the bile-passages complicated with stones or those that are in- 
flammatory in character, owing to the presence of stones, are most 
frequently complicated by perforations. The direct pressure of the 
gall-stones may also lead to ulceration. Ulcers of a typhoidal or a 
carcinomatous origin are comparatively rare. 


There are also so-called “primary” ulcers of uncertain origin. They have 
sharp margins, are circular in shape, and resemble gastric ulcers. Budd draws 
an analogy between the two, and infers that the ulcers seen in the bile-passages are 
caused by the action of the bile on the mucous membrane of the gall-bladder. 
Glaser has reported a case of this kind in which perforation occurred. 


The diseases that may cause perforation from without into the bile- 
passages are usually lesions of the liver-substance itself, as abscess, 
echinococcus cysts, and, less frequently, purulent inflammations of the 
surrounding tissues, such as circumscribed accumulations of pus within 
the peritoneum. 

Whenever perforation into some other body-cavity occurs, the bile 
flows into it. In case the bile flows into the intercellular tissues, these 
become infiltrated with bile. 

Symptoms.—If the solution of continuity does not allow the bile 
to flow into the intestine, or if the bile cannot leave the body through 
some other channel, it must necessarily come in contact with deep-seated 
tissues. As a rule, inflammation results. Until recently this inflam- 
mation was attributed to the chemical action of the biliary constituents. 
Recent experiments, however, have shown that, although the bile is — 
normally sterile, and can produce but slight inflammation, in almost 
all cases where marked inflammation is produced the bile is contaminated 
by irritating products. In these cases, therefore, the bile itself does not 
produce the inflammation, but certain inflammatory products of the 
mucous membranes, pus, or bacteria play the chief rdle. As a matter 
of fact, pure bile is hardly ever poured into the peritoneal cavity or into 
the tissues even if the trauma that causes the abnormal exit of the bile 
in human beings is indirect. In those cases in which the bile-passages 
were diseased before the perforation occurred, the bile, of course, is never 
sterile, so that peritonitis, either circumscribed or diffuse, is the natural 
result. 

The symptoms of such a perforation are altogether similar to those 
seen in any other form of perforation, as of the stomach or the intestine, 








SOLUTIONS OF CONTINUITY OF THE BILE-PASSAGES. 523 


and vary, like these, in degree, intensity, and virulence according to the 
nature of the fluid that is poured out. That a perforation of the bile- 
passages has occurred can be determined only from the history of the 
case and from the exact location of the pain. In those cases where normal 
or only mildly infectious bile is poured into the peritoneal cavity (as in 
trauma) the symptoms of inflammation, pain, and fever are very slight. 


-The bile that enters the peritoneal cavity forms a strictly circumscribed 


sac of fluid that, to judge from the large quantity of albumin that it 
contains, consists in large part of peritoneal exudate. In some instances 
this fluid may contain flakes of fibrin or may be separated from the 
abdominal cavity by a capsule of fibrin. Langenbuch quotes a number 
of cases of this kind. Many liters of exudate tinged with bile may gradu- 
ally be poured into the abdominal cavity, and yet, as I have myself seen, 
recovery may ultimately occur. Occasionally, a mild degree of icterus 
of the skin and the urine is noticed, although the flow of bile from the 
bile-passages seems to be unimpeded. This is probably caused by the 
absorption of large quantities of bile from the peritoneum. 

Perforations of bile into the cellular tissue always cause inflammation, 
which with very few exceptions leads to suppuration. 

The treatment is the same as in any other form of perforation followed 
by peritonitis. In those cases where it is possible to determine at an 
early stage of the disease that the perforation occurred from the gall- 
bladder it may be possible to open the abdomen and to drain the peri- 
toneal focus of inflammation through an indirect biliary fistula through 
the skin. 

3. Fistulea.—Whenever ulceration of the bile-passages leads to adhe- 
sions with one of the neighboring organs, and when ultimately, as the 
disease progresses, the wall of this organ is perforated, we have a direct 
biliary fistula. Whenever a long tortuous passage of an ulcerative char- 
acter passes through connective tissue or adhesions or through a portion 
of the peritoneal cavity that is walled off by adhesions, we have what is 
called an indirect biliary fistula. 

Fistulee usually start from the gall-bladder; next in frequency fom 
the intrahepatic bile-passages. The following varieties of fistula are 
described in their order of frequency: 

(a) Gastro-intestinal Biliary Fistule.—As a rule, perforation occurs 
from the gall-bladder into the duodenum, less frequently into the trans- 
verse colon, and still less frequently into the stomach. It is usually pro- 
duced by stones, not so often by carcinoma of the gall-bladder. Direct 
perforation into the duodenum from the ductus choledochus as the result 
of impaction of gall-stones may also occur. The presence of such a 
fistula can be suspected in all those cases in which large concretions are 
passed with the stools. If icterus has existed for a time and suddenly 
disappears, a fistula of the ductus choledochus is more probable than a 
fistula of the gall-bladder. In cases of this kind the chances of subse- 
quent infection are greater. Anatomic findings have taught us that 
fistulee of the gall-bladder may occasionally heal. 

(b) External Fistule.—Fistule leading outward through the skin 
rarely originate from abscesses of the liver containing bile. Asa rule, 
they start from the gall-bladder. They are frequently indirect with a 
long channel. The external orifice may correspond to the position of 
the gall-bladder, which in these cases is, as a rule, dislocated; or, on the 
other hand, the fistulous passage may lead along the ligamentum teres 


524 DISEASES OF THE BILE-PASSAGES. 


to the umbilicus or to some other even more remote portion of the abdom- 


inal wall. [Porges * has reported a case of fistula in the thigh from 
which gall-stones were discharged.—Ep.] Formerly fistule of this kind. 


occurred only as the result of spontaneous rupture of an ulcerated gall- 


bladder ; nowadays they are often made on purpose by surgical procedures 
or result against the wish of the operator as the result of defective surgical 


methods in operations on the bile-passages. Usually bile mixed with . 
mucus and pus or with concretions is poured from these fistulous open- 
ings. Only in rare instances do we see one of these four possible | 


constituents poured out alone. 
If bile escapes through the fistula, and if, at the same time, some 
obstruction to the flow of bile within the liver exists, such an exit may 


be very desirable. We must refer to the surgical treatment of chole- 


lithiasis for a discussion of the various points of view that have a bearing 
on this question. 

(c) Perjoration into the Air-passages.—This may occur in cases of 
perforating hepatic abscess or in echinococcus cysts. ' Occasionally 
cholangitis may produce it. The color and the taste of the bile in the 
sputa are usually perceived by the patient himself. In favorable cases 
such a perforation may establish drainage, the pus-sac may empty itself 
completely, and a restitution to normal occur. [Graham + has reported 
3 cases of broncho-biliary fistula, and has collected 10 recent cases in 
addition to the 24 collected by Courvoisier.—ED. ] 


(d) The establishment of a fistulous connection between the bile-passages © 


and the urinary bladder is a very rare occurrence. In cases of this kind 
gall-stones may be voided with the urine. In one case the establish- 
ment of the fistula was favored by the anomalous persistence of a patent 
urachus. 

(e) The occasional occurrence of a fistulous communication between 
the bile-passages and the blood-vessels will be discussed in the section 
on the diseases of the latter. 


Budd: Loe. cit., p. 163. 

Langenbuch: Loe. cit., pp. 362 and 346 (literature). 

Schiippel: Loc. cit., pp. 147 and 64 (literature). 

Riedel: “ Chirurgische Behandlung der Gallensteinkrankheiten,” Penzoldt u. Stintz- 
- ing’s “Handbuch der speciellen Therapie,” vol. Iv, part 6b, p. 68. 

Glaser: ‘‘ Jahrbuch der Hamburgischen Staatskrankenanstalten,” 11, 1890. 


Other diseases of the bile-passages that merit discussion are neo- 
plasms, parasites, and foreign bodies in the bile-passages. The neo- 
plasms and the parasites are clinically so closely related to those seen 
in the liver that it appears to be more practical to discuss them together. 
Among the foreign bodies that are found in the bile-passages, or rather 
among the abnormalities of the contents of the bile-passages, concretions 
are by far the most important. These will be discussed in a separate 
section and their réle in the production of a variety of diseases explained. 
We will only mention in this place that other substances that occlude 
the lumen of the bile-passages may produce symptoms similar to those 
of gall-stones, such as icterus and attacks of pain. Among these are 
echinococcus, distomata, ascarides, and blood-clots. All these are found 
much less frequently than gall-stones; but their presence must always 

* Wien. klin. Woch., 1900, No. 26. 

+ Brit. Med. Jour., June 5, 1899, p. 1397, and Trans. Assoc. of American 
Physicians, vol. x11, p. 247. 


ee en — Se ¥ 


a ed Ee 


CHOLELITHIASIS. 525 


be considered, and if possible excluded. [Membranous casts apparently 
formed within the gall-bladder have been found in the feces following 
an attack of obstructive jaundice.—ED.] 


CHOLELITHIASIS. 
(Hoppe-Seyler.) 


HISTORICAL. 


Gall-stones are seen so frequently nowadays that it is astonishing to find so little 
‘mention of this condition among the medical authors of antiquity, who are otherwise 
renowned for the accuracy of their observations. No data are given in the writings 
of antiquity that allow us to infer with certainty that the physicians of that day 
knew of this disease or any description that would lead us to believe that cases 
described were sufferers from gall-stones. In Hippocrates and in Galen, it is true, 
we find a few brief communications on pain in the hepatic region, on icterus as a 
result of constipation without fever, but these descriptions, as compared to the pre- 
cise and exact communications on renal colic, convey only a very inadequate idea 
of hepatic colic. Nowhere, further, do we find mention of concretions in the bile- 
passages and in the gall-bladder. The discovery of stones in the stools is mentioned, 
and we are possibly justified in seeing a connection between the two. In view of the 
fact that the old Greek physicians were good clinical observers, and at the same time 
thorough students of anatomy, we are forced to the conclusion that gall-stones were 
less frequent in those days than they are in modern times. An explanation for this 
difference might be sought in the mode of life. The people of Greece ate other food 
than we do, and their whole régime was different. The food, moreover, was prepared 
in an altogether different manner than nowadays; the meals were simpler; physical 
exercise was an important factor during the years of adolescence, forming a large 
part of the curriculum of every youth, and in later years the men continued to 
indulge in much and varied physical exertion; the clothing, too, did not cause any- 
thing that is analogous to our corset liver. 

In the middle ages medicine made very little progress. It therefore does not 
astonish us to find little mention of gall-stones. According to Donatus, it is true, 
Gentilis of Foligno in the fourteenth century is said to have found stones for the first 


time in the gall-bladder and the cystic duct of a corpse that he was embalming. No 


definite statement in regard to this discovery is made in his works. In the four- 
teenth and the fifteenth centuries concretions were discovered in other organs. Gall- 


‘stones were first mentioned by Antonius Benivenius, who died in 1592. He describes 


gall-stones that were seen in the case of a woman who had been a sufferer from pain 


‘in the abdomen. They were found both in the gall-bladder and in a sacculated cav- 


ity on the surface of the liver. He assumes that the death of this patient was caused 
by these stones. Ccelius Rodiginus and Lange subsequently reported similar cases. 


-Vesalius and Fallopius, in spite of their exhaustive anatomic knowledge, say very 
little on concretions in the liver and the gall-bladder. Fernelius, in 1554, gives 


a very good description of gall-stones and of the symptoms which they pro- 
duce (by some error Frerichs has dated Fernel’s work 1643). The author named 


‘seems to be familiar with the fact that occlusion of the ductus choledochus leads to a 


swelling of the gall-bladder, a white discoloration of the feces, and the passage of 
dark urine, and that, in occlusion of the hepatic duct, the gall-bladder isempty. He 


‘states, further, that the concretions seen in the gall-bladder are usually black and of a 


low specific gravity, so that they always-float on water. According to this author, 
they are formed from bile when this fluid cannot be evacuated, remains too long in 
the gall-bladder, or is not renewed. He also states that they are seen especially 
where an occlusion of the cystic duct exists. The symptoms of this condition are fre- 
quently so indistinct that the disease cannot be diagnosed. Colombus (who died in 
1557) reports that in the liver, portal vein, kidneys, and lungs of the Jesuit General 
Ignatius de Loyola numerous concretions were found, and Camenicenus reports to his 
teacher Mattiolius, 1651, on a case in which the ductus choledochus was occluded by 
astone. In this case icterus was seen, and, in addition, numerous stones were found 
in the dilated ramifications of the portal vein. It is probable that in this case, as well 
as in the case of Loyola, as Morgagni says, the intrahepatic bile-passages were con- 
founded with the branches of the portal vein. Matteoli believed that the formation 


526 DISEASES OF THE BILE-PASSAGES. 


of stones occurs from the thickening of the bile and mucus as a result of an elevated 
bodily temperature, following in this respect the old theory of Galen, who assumes 
that all concretions of the body are formed in this manner. The same author makes 
the statement that stones in the gall-bladder are probably more common than is 
usually assumed, and that they frequently pass unnoticed or are confounded with 
intestinal concretions. 

All the authors mentioned so far were under the influence of Galen’s teachings. 
Paracelsus freed himself from all these venerable beliefs and proceeded to introduce 
clinical observation and chemical investigations into the study of medical phenom- 
ena. Thanks to him, a complete revolution in the views in regard to the nature of 
gall-stones was brought about. His doctrine of “tartarus” is based on the belief 
in chemical changes within the organism. In his discussion on the “tartarus dis- 
ease’”’ (1563) he mentions stones in the liver as precipitates of impure material 
brought about in the same way as are wine-stones from wine. ‘ Tartarus”’ could 
also be formed from the nourishment or through destruction of the constituents of the 
body. He believes that the bile coagulates tartarus. In order to avoid this, gas- 
tric digestion must be regulated by the administration of amara, acids, and carbon- 
ated waters, and the diet must be regulated in such a manner that tartarus is burned 
and metabolism is stimulated. Paracelsus was familiar with jaundice and the 
attacks of colic that accompany gall-stones. As in the case of gout, also attributed 
to the presence of tartarus, heredity is supposed to play a certain réle and to 
predispose to gall-stones. 

Johann Kentmann, in 1565, in an epistle reprinted in Gessner’s work (“De om- 
nium rerum fossilium genere”’) describes gall-stones of different sizes and shapes, and 
illustrates them. He states that the more numerous they are, the more they assume 
an angular shape, and that on the broken surface they seem to be composed of cir- 
cular structures due to their formation from bile that gradually becomes thickened. 
Ferrandus (1570) publishes a case of rupture of the gall-bladder caused by a large 
gall-stone, followed by a pouring out of tne bile into the peritoneal cavity. W. 
Coiter (1573) describes a case in which a great accumulation of gall-stones occurred 
in the gall-bladder and the ductus choledochus in a woman with icterus. In this 
patient violent vomiting of a bilious fluid was seen. In another instance he saw a 
severe form of icterus get well after the passage of a gall-stone by way of the intestine. 
Forestus is of the opinion that gall-stones are formed in those cases where the 
gall-bladder is not properly emptied and the cystic duct is occluded. He attributes 
icterus to occlusion of this duct, and states that it runs from the gall-bladder to the 
intestine. He also mentions that the feces are colored white on account of the ab- 
sence of bile. Healso states that Arculanus of Verona (1457) was the first physician 
to attribute icterus to an occlusion of the bile-duct following inflammation of the 
intestine, and that this investigator recognized that in these conditions the orifice of 
the bile-duct is occluded. According to Plater (1536-1614), concretions are formed 
in the liver and the kidneys as a result of an earthy consistency of the serum and a 
separation of the mineral constituents of the latter fluid, for which reason concretions 
may be seen at the same time in these two organs. He reports a case in support of 
his view. He was in part cognizant of branched stones in the hepatic duct that are 
difficult to remove so that they remain in the body until the death of the animal or 
human being. Cardanus also knew of stones of this kind, and says that they cause 
incurable pain. Fabricius Hildanus (1612) describes the lamellated structure of gall- 
stones. He found his specimens in a count who was a sufferer from icterus, his de- 
scription tallying with that of Kentmann. Van Helmont expresses the belief that 
concretions are formed by the action of a peculiar ferment that has the power of 
causing the petrifaction of all substances that come in contact with it, basing his 
theory on the study of renal concretions. Scultetus makes the statement that 
icterus is not always found in occlusion of the bile-passages. He also mentions that 
carcinomata of the colon, of the uterus, etc., can cause retention of bile. Hulden- 
reich expresses similar opinions and reports a case in which stones were found in the 
gall-bladder and in the cystic duct in addition to calcareous masses in the mesentery. 
Bonet, too, is a believer in this action of retained bile, and attributes a corroding 
action to this excretion and believes that a case of “ peri-pneumonia”’ that he ob- 
served was caused by its presence. 

The anatomic examinations of Glisson (1654) were of fundamental importance 
in the further development of our knowledge of gall-stones. He described stones 
that had the shape of coral branches in the bile-passages of cattle, and noticed that 
they were formed more frequently in winter, when the animals are fed on stable for- 
age, than in summer, when they can eat fresh herbs and are driven to pasture. He 
even states that old concretions can disappear when the animals begin the new 


ee eae 





| 


CHOLELITHIASIS. 527 


régime. He also describes (chapter xxx, page 265) his own case, and delineates a 
good picture of an attack of hepatic colic combined with icterus, and the peculiar 
pain of this condition radiating into the region of the clavicle. As he was unable to 
demonstrate the presence of nerves in any other parts than in the hepatic capsule 
and in the walls of the bile-passages, he states that the pain, in the absence of nerves 
within the parenchyma of the liver, must originate in the bile-ducts. Wepfer (1658) 
utilized Gillsson’s researches to draw the conclusion that the bile is formed in the 
liver and is poured through the bile-passages and the common duct into the intestine. 
He deduces from this that icterus can never occur as the result of occlusion of the 
cystic duct unless the ductus choledochus be occluded at the same time. In one 
case of hepatic colic without icterus he attributes the disease to the presence of a 
stone in the gall-bladder. According to this author, the pain in the precordial region, 
and in that of the processus ensiformis, is due to the pressure exercised by the stone 
on the neck of the bladder. Bartholinus (1657), quoting from Tinctorius, describes 
the passages of three large three-cornered stones with the stool. The latter author 
saw a case in which violent pain in the right side was present and a considerable 
quantity of blood and pus was passed. He assumed that an erosion of the ductus 
choledochus had occurred and that the stone had passed into the intestine in this 
manner. Bartholinus, on the other hand, expresses the belief that all these symp- 
toms could have been produced by a simple dilatation of the ductus choledochus, 
and describes cases of this kind that he had seen. Bobrzenski (“Sepulchr. Ana- 
tomic,”’ Lib. 111, Sect. xv1, page 281) describes the appearance of numerous gall- 
stones in the ducts of the liver where the gall-bladder contained no bile but was filled 
with gall-stones. One of these was wedged into the cystic duct. From these find- 
ings he draws the conclusion that the bile is formed in the liver and is only stored in 
the gall-bladder, and that icterus appears as soon as bile accumulates in the bile- 
passages. 

At the same period we encounter the first descriptions of the formation of ab- 
scesses as the result of gall-stones. Blasius (“Sepulchr.,’’ Lib. 11, Sect. xvi, Ob- 
serv. 13) describes in a cirrhotic liver an abscess containing a black stone. Stalpart 
van der Wiell and Thilesius describe the evacuation of gall-stones on opening an 
abscess. It is unfortunate that at this time the wrong idea of Sylvius, viz., that the 
bile is formed in the gall-bladder and is poured into the liver by way of the cystic and 
hepatic ducts and later mingles with the portal blood, influenced many of the investi- 
gators that followed him, even van Swieten declaring himself a disciple. Sylvius ex- 
plains the formation of gall-stones by assuming that certain acrid and acid substances 
enter the body and mingle with the bile and blood within the gall-bladder and cause 
the coagulation of the latter fluid and of the bile. He seems to have been familiar 
with the symptoms of biliary colic, but states that these attacks originate in the 
colon. He also knew the symptoms of icterus, and describes the urine in this disease 
and states that it is dark in color and has the power of staining paper and linen 
yellow. Ettmiiller gives a much more lucid description of all these conditions. In his 
dissertation entitled ‘“ De ictero flavo, nigro et albo’’ (“ Oper. med.,’”’ Tom. 11, page 1, 
Colleg. pract., Sect. 17, Cap. 4, Art. 4, page 442) he speaks of pain (dolor compres- 
stvus) in the precordial region, that appears in icterus and is accompanied by nausea, 
difficult respiration, and a reddish color of the urine. Fever is described as fre- 
quently present and in many cases pain in the right hypochondrium, which may 
either be readily removed or be very difficult to cure, or, lastly, may be removable, 
but shows a tendency to recur. In cases of the latter kind stones are said often to 
be found in the gall-bladder. He states that colic and icterus are also sometimes 
seen after child-birth, and that icterus frequently follows the attack of colic, that 
icterus is frequently the result of an obstruction to the flow of bile into the intestine 
or of insufficient secretion of bile by the liver, as is seen from the fact that icterus 
may occur without any obstruction in the bile-passages, following fever, the bite of 
wild animals, abuse of blood-letting, ete. He further says that icterus does not 
necessarily always follow gall-stones, and that gall-stones may be present in the 
bladder without causing icterus. Ettmiiller bases these statements on his knowl- 
edge of the fact that the gall-bladder can be extirpated without endangering the life 
of the animal, and he quotes the important experiment of one of the students in 
Leyden, who extirpated the gall-bladder in a dog without observing any bad results. 
He affirms that, if the ductus choledochus is occluded, no bile is poured into the 
intestine, the feces turn white, the bile regurgitates into the blood, and in this manner - 
icterus is produced. This investigator also assumes that an acid or acrid consistency 
of the blood leads to a thickening of the bile as it is formed in the liver or after it has 
reached the gall-bladder, and speaks of a “sal volatile oleosum” that, he thinks, 
degenerates and coagulates in the form of gall-stones. He also speaks of spasm of 


528 DISEASES OF THE BILE-PASSAGES. 


the bile-passages transmitted from the intestine and causing a constriction of the 
ductus choledochus and icterus, and intermitting, so that the color of the feces is seen 
to vary at different times. He claims that the chief diagnostic clue for the presence 
of gall-stones must be their passage per alvum. Finally, according to this author, 
there is no remedy for. gall-stones. 

Borrichius reports a case of ulceration in the region of the liver following a severe 
attack of pain. A number of gall-stones were passed, their derivation being correctly 
attributed to the gall-bladder. This investigator, and before him Plater, Schneider, 
and Wepfer, report the occurrence of gall-stones and concretions in the kidneys in the 
same individual. An interesting case is described of a woman who was a sufferer 
from bilateral pain and urinary difficulties. She passed a few stones with the urine, 
but the pain in the right side did not cease, but, on the contrary, grew worse. Sud- 
denly this pain, too, stopped, but no stones were passed with the urine. The author 
here made a correct diagnosis by assuming that at the time of the pain a gall-stone 
attempted to leave the gall-bladder, and finally did get out, as manifested by the 
sudden cessation of the pain in the right side. Later, he found the gall-stone in the 
feces, and was, in this way, enabled to verify his diagnosis. 

The discovery of glands in the walls of the gall-bladder and the bile-passages was 
important for the understanding of gall-stone pathology. We are indebted to Mor- 
gagni for this discovery. He draws a parallel between the occurrence of gall-stones 
in i nee and the appearance of concretions in the parotid gland and other glands 
of the body. 

Sydenham (“ Prax. med.,” Sect. 1v, Chap. vu, Par. 16) has frequently been cred- 
ited with discoveries that have thrown light on the pathology of gall-stones. In 
reality, however, he considered gall-stone colic as an hysterical symptom, and de- 
scribed its occurrence in female subjects who were sufferers from other forms of hys- 
terical seizures. He describes the symptoms of cholelithiasis at great length, men- 
tions icterus, but says nothing whatever of gall-stones. At the same period Tyson, 
in the “ Philosophical Transactions,” for the first time mentioned a fever of ‘a septic 
type with transitory icterus. According to him, it is caused by the presence of pus 
in the liver and of gall-stones in the gall-bladder and the bile-passages. Morton 
attributed pain in the gastric region to gall-stones and the dilatation of the bile- 
passages by obstruction to the flow of bile. Baglivi, who directed particular atten- 
tion to the chemical and clinical aspects of the question, mentions that the gummy 
portions of the bile are combustible, and that the bile is colored green by nitric acid. 
He also attempted to explain the occurrence, in the same subject, of gall-stones and 
renal concretions. Where obstinate icterus with a tendency to recurrence existed he 
positively assumed the presence of gall-stones and attributed the pain of gall-stone 
colic to spasmodic contraction (crispatura) of the bile-passages. Bianchi attributed 
the pain in the hepatic region to the hepatic plexus and to the sensitiveness of the sur- 
face of the liver and of the ligamentum teres; and believed that the painful irritation 
of these nerve-fibers causes the contraction of the bile-ducts followed by icterus. Gall- 
stones, according to this investigator, are never seen within the parenchyma of the 
liver, but only in the bile-passages. His pupil Guidetti reported cases in which gall- 
stones and renal concretions were seen at the same time. He also mentions (according 
- to Lentilius) abscesses caused by gall-stones, and subdivides gall-stones into two di- 
visions—viz., black, hard, non-combustible, and yellowish, soft, easily combustible, 
and having a low melting-point. He indulges in a number of exaggerated statements, 
attributing a great variety of ailments to the presence of gall-stones, and expresses 
the belief that, whenever present, gall-stones must necessarily cause grave symp- 
toms. His treatment of gall-stones is quite correct. He advises the employment of 
rhubarb, herb extracts, and alkalies. Vater (1722) attributed the fever often seen 
when gall-stones pass to an irritation of the nervous system following the impaction 
and the passage of the stone through the narrow lumen of the bile-passages, just 
as Hippocrates had explained the same occurrence in the case of renal concretions. 
Vallisnieri, at about the same time, made the discovery that gall-stones are soluble 
in alcohol and turpentine, and draws the deduction from this finding that turpentine 
is a preventive of gall-stones. Heexpresses himself more cautiously, however, than 
Durande and many others after him even to this day, for he does not state that tur- 
pentine has the power of dissolving gall-stones after they are formed, but limits him- 
self to saying that possibly it may prevent their formation and development. He 
explains the occurrence of icterus by spasm of the walls of the bile-ducts, and the 
pain by assuming that the walls are stretched and dilated and that the rough surfaces 
of the stone scratch their lining membrane. ‘He also makes the statement that the 
passage of a stone through the cystic duct is more painful than through the ductus 
choledochus, and explains this from the relative narrowness of the former channel. 


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CHOLELITHIASIS. 529 


The passage, finally, of a stone from the common duct into the intestine is said to 
be particularly painful, owing to the narrowness of the external orifice of the duct. 

Friedrich Hoffmann, in his “ Medicina Rationalis Systematica,”’ carries us a step 
further. He attributes the formation of gall-stones to stagnation of bile, and ex- 
presses the belief that eating little and at long intervals favors their formation. 
This is due, he thought, to the fact that normally the stomach should be sufficiently 
distended to exercise a certain pressure on the liver and in this manner favor the ex- 
pression of the bile from the gall-bladder. According to this author, the chief predis- 
posing factors are age, the abuse of alcohol, especially of beer, and the female sex, par- 
ticularly at the time of the menopause and immediately thereafter. He attributes 
the radiating pain, particularly the shoulder pain, to irritation of the phrenic nerve. 
Colic, he says, is particularly liable to occur at night. A violent pain in the right 
hypochondriac region, followed by severe icterus and the passage of gall-stones in the 
stools, are given as important diagnostic signs. He also stated that if the gall-stones 
lie quietly in the gall-bladder no pain is experienced, but as soon as the highly sensi- 
tive bile-passages are dilated pain is felt; and also that gall-stones may grow in bulk 
by gathering bile within the ducts. His treatment consisted in the use of almond 
oil, milk, warm compresses, laxatives, ferruginous and alkaline waters. Tacconi 
described the occurrence of an abscess of the gall-bladder followed by the evacua- 
tion of a gall-stone from the fistula that formed. In this case icterus was 
absent, and the author explains this phenomena by the patency of the ductus 
choledochus. The same writer also describes an autopsy on a case in which hydrops 
of the gall-bladder was found following the impaction of gall-stones in the cystic duct. 
In 1742 Gottfried Miller observed a perforating abscess of the gall-bladder that 
burrowed through the stomach and the abdominal walls. The external opening was 
enlarged and the stone within the gall-bladder fragmented, notwithstanding which a 
fistula remained that continued to excrete bile and chyme. One year later J. Petit 
called attention to this form of suppuration of the gall-bladder after gall-stones, and 
emphasized the necessity of draining the pus. He only operated, however, in cases 
where adhesions were present between the gall-bladder and the peritoneum (as 
shown by immobility of the gall-bladder and inflammation of the skin). He advised 
puncture, the finding of the stone with a probe, enlargement of the fistula, and ex- 
traction of the stone. He points to the analogy with concretions in the urinary 
bladder, and makes the statement that the formation of stones in either case is due 
to some obstacle to the normal outflow of the contents or to weakness of the bladder- 
walls. These views of Petit were generally regarded as too bold, but van Swieten 
defends them. The latter writer has given us a splendid description of cholelithiasis 
and an explanation of the progression of the stone. He states that it is caused by the 
gathering of bile behind the stone combined with the pressure of the diaphragm and 
the abdominal muscles. He also remarks that large concretions can usually effect a 
passage through the narrow bile-ducts owing to the elasticity of the latter. He 
recommended the administration of opium for colic, and advised walking and driving 
for the expulsion of the stone. He claims that this facilitates the progression of the 
stone and prevents its enlargement. Schurig, in his work entitled ‘“ Lithologia,”’ 
mentions many cases of gall-stones, the abscess formation, colic, icterus, etc., without, 
however, describing anything new (1744). 

In the second half of the eighteenth century more light is thrown on the pathol- 
ogy of gall-stones. The etiology and the general symptoms of the disease are eluci- 
dated by the following researches and writings: The pathologico-anatomic studies 
of Haller and Morgagni, the summary of all that was known on the subject up to the 
time of Morgagni by the latter author, the chemical examinations of Pouillettier, 
Fourcroy, Vicq d’Azyr,Soemmering, and others. A great deal, too, was learned by all 
these investigations in regard to the composition of the bile. Haller saw a great many 


of the possible sequels and complications of gall-stones in his numerous autopsies 


(peritonitis, adhesions and perforation of the gall-bladder, contraction of the gall- 
bladder as a result of occlusion of the cystic duct, etc.). He found that the bile is 
not secreted in the gall-bladder but in the liver, and that certain substances can 
exercise a direct chemical irritation on the gall-bladder and the ductus choledochus, 
causing contractions of these parts. On these grounds he assumed the presence of 
muscular fibers in the walls of these organs, but was unable to demonstrate their 
presence. Sabatier (1758) gives some very good clinical descriptions of gall-stone 
colic, hydrops vesicz fellee, and empyema of the gall-bladder as a result of occlusion 
of the common duct. He also mentions the occurrence of ileus following the pas- 
sages of large gall-stones, of which Boucher also reported an instance. Sauvage 
(1760), in his “ Nosologia methodica,’”’ furnishes some very clear clinical reports. 
Morgagni delineated a very lucid picture of the state of knowledge of that day in his 


34 ' 


530 _ DISEASES OF THE BILE-PASSAGES. 


celebrated work, “De sedibus et causibus morborum.” After carefully sifting and 
collating all the literature on the subject of cholelithiasis, he reports a number of 
original observations, and finally arrives at important conclusions in regard to the 
etiology, pathology, and therapy of this class of diseases. Occlusion of the bile- 
passages, according to this writer, is the result of a simple contraction of the ducts, 
a thickening of their mucous lining, compression of the passages by swollen glands, 
etc. This occlusion is always followed by icterus; if the cystic duct alone is occluded, 
icterus is not observed. The age of the subject, sedentary habits, and other factors 
are mentioned as predisposing causes. He gives a detailed description of the ap- 
pearance, color, form, and structure of gall-stones, and opposes the erroneous view 
prevalent at that time that dark stones are seen in old people and light ones in 
young subjects. He further gives irritation of the glands of Malpighi in the wall of 
the gall-bladder as another predisposing cause for gall-stone formation. Gall-stones 
that remain quietly within the gall-bladder are said to cause no symptoms, and 
the same applies to concretions within the cystic duct. He gives as the most positive 
diagnostic sign of gall-stones the passage of concretions in the feces, and assumes 
that all concretions found in the feces must have passed through the ductus 
cholehochus. 

Pouilletier de la Salle, Galleatti (1748), J. F. Meckel (1754-1759), and Vicq 
d’Azyr worked out the chemical aspects of the question. The first-named investi- 
gator succeeded in isolating cholesterin for the first time; the last-named drew 
a distinction between gall-stones that consisted of this substance alone, others that 
constituted a mixture of cholesterin and the yellow bile-pigment, and others that 
contained the pigment alone. Fourcroy found phosphoric acid in gall-stones. 

Durande, in 1782, discovered that gall-stones were soluble in turpentine, and 
founded a method of treatment on this fact. He used both turpentine and ether 
internally. Soemmering, however, in 1793, expresses doubts in regard to the 
efficacy of these remedies, and does not believe that they ever really reach the gall- 
stones. According to the latter author, gall-stones are not formed from the thick- 
ening or the decomposition of the bile, but as a result of certain excretory anoma- 
lies of the bladder-wall and the formation of acids, as tartaric and acetic acids, 
within the gall-bladder, these acids being said to coagulate the bile. 

The surgical treatment of gall-stones was inaugurated by Sharp and Monaud 
(according to Gottfried Miller and Petit). Bloch, in 1774, proposed the artificial 
formation of adhesions in the region of the gall-bladder. Chopart and Désault, 
F. A. Walter, and Richter improved these methods. Herlin, L’Anglas, and Duchai- 
nois studied the ligation of the cystic duct, and the incision and extirpation of the 
gall-bladder as early as 1767. 

In his work entitled “ Anatomischen Museum,” published in 1796, Walter gives 
a good description of gall-stones of various forms and furnishes very good illustra- 
tions. G. Prochaska (“ Opp. min.,’’ Pt. 2, p. 219) succeeded in differentiating the gran- 
ular periphery of gall-stones from their crystalline center. Coe gives a fair picture 
of the etiology and the symptomatology of cholelithiasis. Pujol, in particular, in 
his ‘Mémoires sur les coliques hépatiques,’”’ describes the diseases caused by gall- 
stones, based to a large extent on his own experience. He attributes the pain and 
the thickening of the gall-bladder to this condition. Contractions of the gall-bladder 
are said by him to drive the stone out of the bladder into the cystic duct, where the 
colicky pains are produced, the pain stopping either as a result of the cessation of 
contractile efforts, or because the tissues adjust themselves to the dilatation, or, 
finally, because the stone may drop back into the gall-bladder. He also states that 
almond oil may form peculiar concretions in the gastro-intestinal tract that may be 
mistaken for gall-stones. He gives a good description of the different steps in the 
diagnosis, and mentions as one of the most important clinical symptoms, that 


the patient complains of pain in the gastric region assuming the character of» 


very painful tension as soon as pressure is exercised in the region of the gall- 
bladder. Portal, in 1813, described the dilatation of the bile-ducts if the larger 
passages are occluded, also the possibility of perforation of a stone into the intestine, 
the soft character of some of the stones, their nucleus and their chalky consistency. 
Bramson, Hein, Buisson during the following decades occupied themselves in trying 
to find the origin and constitution of gall-stones. Meckel von Hemsbach was the 
first to emphasize in a clear manner the significance of catarrh in the formation of 
concretions. Andral, Trousseau, Frerichs, and others furnished valuable contri- 
butions to the clinical knowledge of cholelithiasis. Fauconneau-Dufresne, in par- 
ticular, gave very detailed clinical descriptions. Charcot attempted to explain the 
intermittent type of fever that is seen in diseases of the bile-passages and in gall- 


stones. His example has stimulated French investigators, in particular, to continue . 


— 
ify 





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CHOLELITHIASIS. 531 


investigations on this question and on cholelithiasis. As a result, we possess a clear 
picture of cholelithiasis, thanks chiefly to the discoveries of bacteriology. Ana- 
tomic and experimental physiologic research have thrown a brilliant light on many 
of the symptoms of this disease. The formation of gall-stones, too, is fairly well 
understood, particularly since physiologic chemistry has taught us much in regard 
to the nature and origin of the different biliary constituents. Naunyn especially has 
contributed much that is valuable to this subject. 

In regard to the treatment of cholelithiasis, the greatest advance has of late 
years been made in the operative treatment. This is due to the discovery and intro- 
duction of aseptic methods and the application of improved methods of operating. 
The first attempts at surgical treatment that we have described above made a very 
slight impression. Kocher and Sims are really the fathers of modern gall-stone sur- 
gery, they having first attempted cholecystotomy. Langenbuch later performed 
cholecystectomy, Kiister and Courvoisier the operation of cholecystendysis. These 
were followed by methods for re-establishing the flow of bile into the intestine in 
cases where the common duct was occluded, cholecystenterostomy, choledochotomy, 
etc., first taught by Winiwarter and others. The experience that these surgeons 
gleaned has thrown a great deal of light on the general picture of gall-stone disease 
and its complications. In addition to the surgeons mentioned, Riedel, Kehr, Thiriar, 
Lawson Tait, and others have contributed much to our knowledge on the subject. 

eIf we look backward over the long history of cholelithiasis, we see that even in 
the days of remote antiquity many physicians of genius possessed correct ideas in 
regard to this disease. As a rule, however, these correct ideas were buried under a 
mass of purely speculative deductions that were enunciated by authors of renowned 
authority in those days. Asaresult of this, the kernel of truth was lost. It was not 
until modern chemical, anatomic, and physiologic research constructed a solid and 
immovable basis of facts that these old theories were established on a stable founda- 
tion. 


PROPERTIES AND CLASSIFICATION OF GALL-STONES. 


Guidetti, the pupil of Bianchi, distinguished two kinds of gall-stones 
—blackish ones, that were hard and non-combustible, and lighter ones, 
that melted in the flame and burned. The former, according to modern 
investigations, consist of bilirubin-caleium and carbonate of calcium; 
the latter consist of cholesterin. Gall-stones are composed of these three 
substances chiefly. As a rule, cholesterin and the calcium compound of 
bile-pigment are mixed in about equal proportions. The stones gener- 
ally show a concentric arrangement similar to urinary calculi, a pecu- 
liarity to which Kentmann called attention long ago. The different 
layers vary in color owing to the different proportion of contained bile- 
pigment. Generally the nucleus is soft and the external covering hard. 
In addition, a radiating structure can be discerned. This was first de- 


seribed by Morgagni, and was attributed by Meckel to the peculiar 


manner in which the cholesterin that the stones contain crystallizes. 

As we have stated, the chief constituents are cholesterin, bile-pigment 
(particularly bilirubin) in combination with calcium, and carbonate of 
calcium. The following substances are occasionally present in small 
quantities: Phosphoric acid combined with calcium and magnesium, sul- 
phate of calcium, bile-acids, sodium, potassium, free bilirubin, silicic 
acid, copper, manganese, and, in some animals, occasionally zinc. A 
little mucus is alwaysfound. There is also a peculiar nitrogenous com- 
pound that remains undissolved if the gall-stones are treated with certain 
solvents. This is probably a product of the epithelial cells that are 
destroyed while the stone is in process of formation. 

On analysis of gall-stones it will be found that the different con- 


stituents occur in varying quantities. There may be over 90% of choles- 


terin (v. Planta and Kekulé). In the small, dark stones, consisting 
chiefly of pigment and calcareous salts, and found principally in the 


532 DISEASES OF THE BILE-PASSAGES. 


ducts, pigment-calcium and the carbonate of lime are the principal con- 
stituents. In this variety of stone copper, manganese, and iron in com- 
bination with bilirubin are usually found. Free bile-pigment is found 
only in traces in concretions and probably enters into their composition 
from imbibition. The same applies to the small quantities of bile-acids 
that are sometimes found. In the bile-passages, however, Virchow found 
a pultaceous mixture of bilirubin crystals and cholesterin. It is stated 
that uric acid is occasionally found in gall-stones (Stéckhardt and Mar- 
chand). It is possible, however, that in many of these cases gall-stones 
were confounded with urinary calculi. In addition to the ordinary bile- 
pigments, bilirubin and biliverdin, a number of other pigments have 
been seen that were probably formed from them—viz., bilihumin, bili- 
fuscin, biliprasin (the latter, according to Maly, being identical with 
biliverdin). In gall-stones examined after they have been kept for a 
time, it is possible that many of these substances are simply decomposi- 
tion or transformation products formed by contact with the air or from 
putrefaction. 

The color of the stones is essentially dependent on the quantity and 
the character of the pigment they contain. The stones that consist of 
cholesterin alone are the only ones that are almost pure white. If they 
contain a small amount of pigment, their color may be golden yellow or 
greenish. If they contain much pigment, it will be reddish-brown to 
black. The stones are never uniformly tinted throughout. The cortex, 
the shell, and the nucleus are always colored differently. In the shell 
the peculiar concentric arrangement and the striated radiating structure 
are seen. The surface of gall-stones is sometimes scintillating like 
mother-of-pearl], particularly if the shell is formed by thin layers of choles- 
terin that has crystallized in horizontal layers. | 

The consistency will also depend on the composition of the stone. 
The more calcium-compounds the stones contain, the harder will they 
be. The lighter forms of cholesterin stones can, as a rule, be easily 
scratched with the finger-nail, or can even be crushed between the fingers. 
Young concretions are generally soft. The shell, if it consists of cal- 
careous compounds, is usually the hardest part of the stone. Occa- 
sionally it is seen to be as thin as the shell of a sparrow’s egg, the contents 
of the stone in these cases consisting of a gruelly mass of cholesterin. 

The shape of gall-stones differs according to their number and their 
place of origin. If several stones of medium size are present in the gall- 
bladder at the same time, they become faceted when still soft; from the 
fact that they are squeezed together when the gall-bladder contracts. 
It is also possible that new layers, as they form, adapt themselves to the 
outline of their surroundings. Octahedral, tetrahedral forms, etc., are 
seen if several large stones are present in the gall-bladder. The surface 
of the stones turned toward the mucous lining of the gall-bladder is 
usually rounded and rough, while the surface that is directed toward the 
other stones is flat and smooth. This is rarely due to grinding and 
polishing of one surface against the other, as it is seen that on cross- 
sections the individual layers are distinctly developed at the different 
places where compression has occurred, although of course they appear 
a little narrower here than at the edges. If they are colored, the stain 
is more intense at the narrowest point—/. e., at the points of contact. 
This may probably be considered as proof of the assumption that the 
change of form is produced by compression. Large isolated stones are 











CHOLELITHIASIS. 533 


round or oval, and usually correspond more or less in shape to the cavity 
in which they have developed—~. e., the gall-bladder. Nodular, rasp- 
berry-shaped concretions are occasionally met with, these being formed 
from the coalition of several smaller stones glued together and subse- 
quently covered by a common layer of new deposit. If numerous small 
stones are present, they are usually rolled about by the contractions of 
the gall-bladder, so that the mass assumes a spherical shape. Leaf- 
shaped stones and others that are twisted and distorted in many ways 
may be produced by the pressure of the gall-bladder. These, however, 
are comparatively rare. Within the bile-passages cylindric structures 
may be formed, and in some instances coral-shaped stones have been 
found similar to those found in cattle (Glisson). Sometimes portions of 
the stones are dissolved in the gall-bladder, or the cholesterin may crystal- 
lize; so that the stones are broken or nicked and fragments of different 
size and shape are found. 

The Weight of the Stones.—In former days it was considered a char- 
acteristic feature of gall-stones, and one that distinguished them from 
other forms of concretions, that they would float in water. As a matter 
of fact, only dry stones do this occasionally. Haller has called attention 
to the fact that this is done to air-bubbles that they contain and that 
become incarcerated within the cavities and cracks that are formed when 
the stones become desiccated. Their specific gravity varies according 
to their composition. If a large central cavity is present, it is lower; 
if they contain a large amount of calcium and are very dense and com- 
pact, it is greater. Thus, Batillat found the specific weight as high as 
1.966, and Bley 1.580. 

[In regard to size the concretions vary greatly. From barely per- 
ceptible grains they may attain a size which, when they reach the intes- 
tinal canal, may be sufficient to seriously interfere with peristalsis or 
indirectly produce complete obstruction. Among the larger stones the 
following are noteworthy: Richter records one weighing three ounces and 
five drams removed from the common duct at autopsy. Schiippel states 
that he has seen one measuring 7.5 cm. in length, 4 cm. in width, and 12 
cm. in circumference, and refers to one (reported by Meckel) which 
measured 15cm. by 6em. Russell reports one measuring 53 by 44 inches. 
Thornton removed from the common duct during life a stone 2 inches 
long and 34 inches in circumference. Frerichs says that he has seen a 
number of stones measuring from 2 to 24 inches by 1 inch. It may be 
roughly stated that the size of the stones as a rule varies inversely with 
their number.—Eb.] 

If all these different properties and modes of origin are taken into 
consideration, the following classification of gall-stones may be attempted. 

To begin with, we can subdivide them into small stones that are not 
larger than a hazelnut, and large stones that are as large as a hazelnut 
and larger. Haller subdivided them into round, white, solitary, and 
small angular, multiple stones. Walter differentiated between concre- 
menta striata, lamellata, and corticata. Hein, according to their com- 
position, divided them into homogeneous and mixed stones. 

Meckel von Hemsbach arranged eight classes, some of which, how- 
ever, represent different stages in the development of the same class of 
stones: (1) Multiple jagged stones; (2) multiple warty stones (usually 
formed from the former by impregnation with cholesterin) ; (3) brown, 
solitary stones of round or oval shape and with layers of different color; 


534 DISEASES OF THE BILE-PASSAGES. 


(4) solitary, cholesterin stones formed from the foregoing and oval in out- 
line, produced when the process of crystallization advances as far as the 
periphery; (5) granular stones without any defined structure, with a 
nodular surface and containing much calcareous matter and pigment; 
(6) black, jagged stones, small and fairly hard; (7) stones with a metallic 
luster, loosely constructed; (8) stones consisting chiefly of carbonate 
of calcium, fragile, nodular, brown on the outside and white inside. The 
latter class is very rare, Hein having found only five concretions of this 
kind among 632 specimens. 

Naunyn, on the ground of his careful and thorough investigations, 
arrived at the following more consistent classification. He distinguishes: 

1. Stones consisting of cholesterin alone. These are usually perfectly 
spherical, pure white or yellowish, rarely colored more intensely on their 
surface, and smooth. On transverse section no arrangement in layers 
is seen, but a clearly marked, radiating, crystalline structure is found. 
There are only very small quantities of brown deposit, particularly near 
the central portions of the stone. 

2. Stones consisting of cholesterin and arranged in layers. These 
are usually quite solid and become fissured and cracked on desiccation. 
The color of their surface varies, and they are faceted. On transverse 
section several layers are seen, of different thickness and color. Of 
these layers the external ones are frequently amorphous; the inner ones, 
particularly near the center, crystalline. Starting from this crystalline 
center, long streaks of crystallized material radiate toward the periphery. 
In addition to cholesterin, which constitutes some 90% of their bulk, 
they contain small quantities of bilirubin- and biliverdin-calcium, with, 
in addition, a considerable quantity of carbonate of calcium. 

3. Ordinary gall-stones of different size, shape, and color. To this 
class belong the greatest number of gall-stones. They rarely grow 
larger than a cherry and are usually smaller. They are faceted and of a 
brown or white, less frequently greenish, color. When they are fresh, 
they are often soft and can be easily crushed; on desiccation, they grow 
harder and contract without forming fissures. Their shell is hard and 
arranged in layers; their kernel is soft and mushy and frequently contains 
an irregular cavity filled with a yellowish, alkaline fluid. Macroscopic- 
ally no crystalline structure can be distinguished. 

4. Mixed bilirubin, stones. These are usually about as large as a 
cherry or larger. They occur singly or in numbers of two or three, and 
are found either in the gall-bladder or in the bile-ducts. They are ar- 
ranged in concentric layers of dark or reddish-brown masses that are 
rarely altogether solid. The nucleus is not laminated. On drying, the 
outer layers contract and form cracks and fissures. The different layers 
readily peel off, so that sometimes different spherical layers are shed, 
the middle layers often being lighter in color and consisting of large 
crystallized masses of cholesterin. Cholesterin is also found in the ex- 
ternal layers (even though these may appear very dark in color, they 
may contain as much as 25% of cholesterin). The rest of the stone con- 
sists almost exclusively of bilirubin-ealcium. 

5. Small stones consisting almost exclusively of bilirubin-calcium. 
They are not larger than a grain of sand or at most a pea, and are seen 
in two different forms: | 

(a) Solid, black-brown concretions with an irregular nodular surface, 
usually soft, sometimes partly compressed and conglomerated. It is 








tle — aan 


ee 


CHOLELITHIASIS. 5385 


probable that the larger stones originated from these smaller ones. On 
drying they contract considerably and disintegrate very easily. 

(b) Harder stones of different forms, frequently spindle-shaped, with 
a smooth or a slightly nodular surface, either steel-gray or black in color, 
with a metallic luster that is particularly apparent when they are pow- 
dered, hard, solid, and brittle. The larger varieties show a spongy 
structure. These small stones of both kinds consist in great part of 
calcium compounds of bilirubin and its derivatives. In addition to 
bilirubin-calcium, which constitutes the bulk of the stones, small quanti- 
ties of biliverdin-calcium and some bilihumin (up to 60%), and rarely 
biliprasin, are seen. Free bilirubin and cholesterin are present in small 
quantities only. 

Naunyn mentions the following varieties as rarities: 

(a) Amorphous and incompletely crystallized stones of cholesterin. 
They look like pearls and contain a nucleus consisting of small masses of 
black bilirubin-caleium or mixtures of bilirubin and cholesterin. 

(b) Chalk-stones that are very hard and consist chiefly of carbonate 
of calcium. These are either prickled or smooth, and inclose cavities 
containing cholesterin, pigment-calcium, etc. In ordinary gall-stones 
calcium carbonate is also seen either in the shape of spheres or in columnar 
arrangement. As a rule, this chalky material radiates from the center 
of the stone toward the periphery. 

(c) Concretions with inclosures, and conglomerate stones. In some 
stones whose shell consists of bilirubin-calcium a cholesterin stone will 
be found in the place of a nucleus, or, vice versd, a stone with a choles- 
terin shell will contain a bilirubin stone of dark color in the place of the 
nucleus. Different kinds of stones are also occasionally seen conglomer- 
ated and covered with a common shell. Foreign bodies proper are rarely 
found within gall-stones. The following substances have been found in 
them: A worm of the species Anguilla (Lobstein), a piece of a Distoma 
hepaticum (Bouisson), a needle (Nauche), the kernel of a plum (Fre- 
richs). Small particles of mercury have also been found in the inside 
of gall-stones by Frerichs, Lacarterie, and Beigel, the patients being all 
subjects who had been taking mercury. Recently Homans has reported 
gall-stones in persons who had undergone the operation of cholecystotomy 
for the removal of old gall-stones; here new stones had formed around 
the sutures of the first operation. [Kehr mentions three cases of a similar 
kind.—Eb.] 

(d) Casts of the bile-passages. These are rarely seen in human beings. 
They consist chiefly of bilirubin-calcium, rarely of cholesterin (Naunyn) ; 
they are more frequently found in cattle (Glisson). 

Of the different varieties of stones enumerated, the large cholesterin 
stones (1 and 2) and the ordinary mixed stones are principally found in 
the gall-bladder and in its recesses; but they are also seen in the cystic 
and the common ducts, usually wedged in tightly and conglomerated in 
masses of several stones. They are frequently adherent to the mucous 
membrane, or the latter may send processes into and around them. 
Their surface is, as a rule, rough or warty. Occasionally they are sus- 
pended in the bile and are covered with crystals. The pure form of 
bilirubin stones are found in the gall-bladder, and also quite frequently 
in the ducts of the liver. : 


536 DISEASES OF THE BILE-PASSAGES. 


ORIGIN OF GALL-STONES. 


Following Galen’s original idea, the belief was prevalent for a long time that 
gall-stones were formed from the coagulation of the bile. It was imagined that this 
occurred as a result of an increase in the temperature of the liver. Paracelsus, by 
teaching, his doctrine of ‘‘tartarus’”’ and of the precipitation of concretions in the 
body owing to certain chemical processes, is the father of the conception that 
disturbances of the digestion produce an acidulation of the blood, the acids formed 
acting on the bile and causing the formation and precipitation of concretions (Ettmiil- 
ler et al.). Even in recent years the view has been brought forward that during fasting 
and on an exclusive meat diet an acidulation of the bile occurs, and that, as a result, 
decomposition of the alkaline carbonates takes place, followed by a precipitation of 
the cholesterin and bilirubin-calcium that these substances held in solution. In this 
manner, it was believed, gall-stone formation could occur. In the eighteenth century 
amore exact knowledge of the different constituents of the bile was acquired and the 
theory was formulated that under certain conditions the bile might contain too much 
of one or the other of its normal constituents, and that in this case a precipitation 
would occur. This view has some adherents to this day. Meckel von Hemsbach, 
following an idea of Morgagni, called attention to the réle of chronic catarrhs of the 
mucous membranes of the gall-bladder and bile-passages, and expressed the belief 
that such chronic catarrhs could be made responsible for the formation of stones 
(stone-forming catarrh). Bramson believed that when the bile contained much 
calcareous matter and little alkali, pigment-calcium was precipitated and led to the 
deposit of cholesterin. Austin Flint’s and Dujardin-Beaumetz’s theory of choles- 
teremia following excessive nervous work and cerebral activity (?) led to the theory 
that gall-stones were formed as soon as abnormal quantities of cholesterin were 


poured into the blood. Thénard assumed that a precipitation of bile-pigment 


occurred as soon as the percentage of sodium salts in the bile was reduced. __Frerichs, 
too, was inclined to see a connection between the frequent occurrence of gall-stones 
in old people and the increased quantity of cholesterin that the blood of the aged 
contains. At the same time he assumed that an excessive formation of carbonate of 
calcium takes place as a result of catarrhal conditions of the mucous membranes of 
the bile-passages. Hein assumed that gall-stones are formed around plugs of mucus 
that, in their turn, are the morbid product of diseased mucous membranes; and, 
further, that changes in the composition of the bile within the bile-passages are fol- 
lowed by the precipitation of bile-pigment stones, and that these reach the gall- 
bladder and form the nucleus for larger concretions. Finally, he believed that an 
excessive quantity of cholesterin is formed later as a result of alterations in the tissues 
of the liver itself or from a tendency to fatty deposits. Seifert believed that the 
epithelial cells play a certain réle in the formation of gall-stones, for the reason that 
they are frequently found in the insoluble residue of dissolved gall-stones. A number 
of other authors attribute some importance to desiccation of bile (Fernelius, Boer- 
have; van Swieten, and others). Itis known, however, that the bile may remain for a 
long time in the gall-bladder,—as, for instance, in occlusion of the cystic duct,—and 
that this is followed by hydrops of the gall-bladder, but not by inspissation of bile. 
If bile is concentrated outside of the body by evaporation, no concretions resem- 
bling gall-stones are precipitated. 


The investigations of Naunyn and his pupils have, of recent years, 
thrown a great deal of light on the question of gall-stones. A summary 
of all the results obtained speaks in favor of the old view enunciated 
by Meckel von Hemsbach. According to this investigator, all that is 
needed for the formation of gall-stones is a center of crystallization. 
Mucus, small particles of pigment-calcium, etc., are not sufficient to cause 
the formation of concretions. It is found that if small particles of 
cholesterin, bilirubin-calcium, etc., are placed in the gall-bladder of a 
dog after ligation of the cystic duct, all these foreign bodies are absorbed 
in the course of a few months (Naunyn and Labes). 

According to Naunyn, stones in the gall-bladder originate in the 
following manner: The bile contained in the gall-bladder always contains 
some desquamated epithelial cells from the mucous lining. These, as a 
rule, show no degenerative changes. In old people, however, and in 








= 


CHOLELITHIASIS. 537 


sufferers from tuberculosis, febrile diseases, or cardiac lesions, it will be 
found, on autopsy, that they are in a state of fatty degeneration. _ This 
is particularly the case if gall-stones are present in the gall-bladder. 
Within the desquamated cells are seen large and small droplets of fat 
or myelin. These collections of myelin leave the cell and conglomerate 
to form little balls of myelin. They consist chiefly of cholesterin. In 
addition to soft masses, hard ones are sometimes seen, which may be 
crystalline. In addition, we may see a number of swollen epithelial cells 
which are in part disintegrated and form heaps of granular brownish 
debris. Other structures are seen that are apparently formed from 
myelin, and in which a shell of cholesterin may be seen inclosing a kernel 
of brown, granular material. Around these bodies new layers are formed, 
and in this manner the little stones continue to grow. 

Another mode of origin is the following: In human bile we usually 
find a sediment consisting of flaky, granular, brown lumps that are com- 
posed of brownish granules and yellowish pultaceous masses. These 
contain cholesterin (almost 25%), and still larger quantities of bilirubin- 
calcium (39% in one case), fat (as much as 20%), and alkaline salts of 
the bile acids (as much as from 15 to 20%), albumin, and mucus. From 
these masses the bile-acid salts are soon eliminated and concretions form 
in one of the following two ways: (1) They may become covered by a 
hard, thin shell of bilirubin-calcium while the center remains soft. In 
this case a crystallization of the cholesterin occurs, the bilirubin-calcium 
forms granular masses; and the two constituents, in their changed form, 
are then deposited on the inner surface of the shell, in such a manner 
that in the center nothing is left but some fluid, so that when the stone 
dries out a cavity is found in the middle. (2) The solid parts of the 
eruelly mass described above may form a soft shell of crystalline choles- 
terin and amorphous bilirubin-calcium, again leaving nothing in the 
center but some fluid. 

These first predecessors of future gall-stones may in some cases be 
poured out with the bile. In case, however, stasis of bile occurs, they 
undergo further changes. The contractions of the gall-bladder force out 
all the fluid, so that the concretions are consolidated or are pressed to- 
gether into conglomerate masses forming the above-mentioned raspberry- 
or mulberry-shaped stones. : 

Within the bile-passages small stones, consisting of bilirubin-calcium, 
are formed and remain embedded in thickened bile. These concretions 
are not simply formed from inspissated bile, but they contain a number 
of pigments, as biliverdin, bilicyanin, etc., that can only have been formed 
from bilirubin by oxidation. Naunyn assumes that bacteria are the 
primary cause of this oxidation. As a rule, stasis of bile occurs in all 
these cases. ) 

Subsequently cholesterin is deposited in layers over these minute 
concretions, and the same substance penetrates into and through the 
little stones, so that they are infiltrated with cholesterin, which later 
becomes crystalline. 

The different layers formed in this manner may either consist of pure 
white cholesterin or of cholesterin mixed with bilirubin- or biliverdin- 
calcium. The latter mixture, of course, is colored. The layers of pure 
cholesterin are, as a rule, thinner than those that contain the pigments. 
The central cavity for a long time remains filled with fluid. Further 
deposits of pigment can occur only if the bile comes in contact with the 


538 DISEASES OF THE BILE-PASSAGES. 


stones, while cholesterin can be deposited even though no bile reaches 
the stones. 

The most interesting feature of the further transformation of gall- 
stones is the recrystallization of cholesterin and the infiltration of the 
concretion with this substance, a phenomenon to which Meckel called 
attention. He was aided in his attempts to explain it by his knowl- 
edge of geologic phenomena of a similar character. In the interior 
of the stone the cholesterin crystallizes in a direction vertical to the 
layers of the shell. Only in exceptional cases do we see a crystalliza- 
tion in a horizontal plane. The crystals are formed from cholesterin 
already present in the stone, which recrystallizes, and from cholesterin 
that filters into the stone at a comparatively late period of its develop- 
ment. At first, the cholesterin crystallizes in pockets within the kernel 
of the stone. In many of the stones no distinct nucleus can be seen, 
the different layers being indistinct and the general structure crystalline. 
Stones are also seen in which marked differences exist between the shell 
and the kernel, and in which the latter may have a geodic or stalactite 
structure. The recrystallization of cholesterin starts from the nucleus, 
and the crystals shoot out toward the periphery. Cholesterin that is 
present in the stone at this period undergoes recrystallization, and, in 
addition, more cholesterin filters into the stone and, in its turn, assumes 
a crystalline structure. The latter occupies chiefly the fissures, cracks, 
and canals within the concretion. <A transverse section of the stone will, 
as a rule, reveal these processes with great distinctness. The calcium 
compounds of the bile-pigments are dissolved in the mean time or are 
mechanically removed, so that, under certain conditions, a pure choles- 
terin stone may be formed from a mixed, laminated stone. A stone 
of this kind will have a radiating structure and will show very little of its 
former laminated arrangement. As the result of contraction of the 
peripheral parts of the stone or of expansion of the masses of cholesterin 
that are being deposited in the interior of the stone, cracks and fissures 
occur, so that the layers of the stone are pushed apart. Those parts of 
the different layers that contained more of the pigments naturally 
assume a darker color. Sometimes this tearing apart of the stones, com- 
bined with the dissolving properties of the bile, may lead to a complete 
destruction and solution of the gall-stone (Meckel), and in this manner 
a spontaneous cure of cholelithiasis may be brought about. The 
metamorphosis of gall-stones, in general, may be said to depend on the 
proportion of concretion-forming or concretion-dissolving substances that 
are present in the bile. We can readily appreciate that this proportion 
must vary considerably when we remember that all gall-stones are dis- 
tinguished by layers of different substances that are imposed one upon 
the other without any semblance of uniformity. In hydrops of the 
gall-bladder we may also see a destruction of gall-stones following the 
change in the nature of the fluid contents of the gall-bladder. In the 
same manner indentations and disintegration of gall-stones may occur 
in the intestine. In view of all these circumstances, we must concede 
that Meckel was at least partly correct when he stated that the cavities so 
often seen in the center of gall-stones owe their origin to the solution 
of ‘the central nucleus. | 

The most important factor in the development of gall-stones is the 
formation of a large amount of cholesterin in the gall-bladder. The 
old view that cholesterin is formed after the ingestion of large quantities 


CHOLELITHIASIS. 539 


of fat is untenable, Naunyn and his pupils having definitely refuted it. 
The theory of Bristowe, according to which cholesterin is formed from 
the disintegration of the epithelial cells lining the gall-bladder and the 
bile-ducts, seems more probable (compare page 416). The amount of 
calcareous matter found in the bile does not depend upon the 
amount of calcareous matter circulating in the tissue-fluids or ingested 
with the food, as it is also a product of the mucosa of the bladder and 
ducts. Informer times it was believed that an abnormally large per- 
centage of calcium in the serum or the drinking of large quantities of 
calcareous water could produce cholelithiasis. 

According to Naunyn, the diseased mucous membrane excretes a large 
amount of calcareous matter, and this causes the formation of sediments 
that contain bilirubin and that play a certain rdéle in the formation of 
gall-stones. Steinmann has demonstrated experimentally that the albu- 
minous products of the degeneration of the bladder cells mixed with egg- 
albumen and calcium solutions are capable of causing the precipitation 
of bilirubin-calcium, a substance which in a measure favors the conglomer- 
ation of cholesterin masses. That this is its mode of action may be 
deduced from observations on atheromatous cysts, where we have large 
quantities of cholesterin but no bilirubin-calcium, and as a result we 
do not see the formation of concretions. 

In gall-stone cases a number of glands are also seen in the wall of 
the gall-bladder that are not normally present. It is probable that 
these abnormal glands are in part responsible for the increased formation 
of cholesterin and of the calcium-containing mucus. They have the 
same type of epithelium as does the rest of the mucous membrane of 
the gall-bladder (Adolf Miller). 

Large stones that enter the bile-ducts from the gall-bladder continue 
to increase within the ducts. This is due to the fact that the epithelial 
lining of these passages is similar to that of the gall-bladder (according 
+o Ranvier) and also secretes cholesterin and calcium. We are forced to 
this conclusion, if for no other reason, because gall-stones are often 
found in the common duct which are so large that they could not possibly 
have passed the cystic duct (Friedr. Hoffmann). The occurrence of 
gall-stones within the bile-ducts of animals that have no gall-bladder 
(for example, elephants) is another argument in favor of this supposition. 
In the smaller bile-passages no epithelial lining is seen, and for this 
réason, of course, no degenefative changes and new-formation of cells 
like that seen in the gall-bladder and the larger bile-ducts occurs. As 
a result of this, then, no increased formation of cholesterin occurs in 
this location. 

From all that has been said, we learn that a diseased condition of 
the mucous membrane of the gall-bladder and the bile-ducts, leading to 
an increased formation of cholesterin and of calcium, is the primary cause 
of gall-stone formation. ~ 

The question arises as to how catarrhs of this character originate. 
There are two possibilities: The catarrh may either be caused by certain 
noxious agencies that reach the mucosa by way of the .blood-current, 
or certain poisonous principles may be present in the bile and act harm- 
fully on the mucous lining of the bladder by direct contact. On the 
former assumption, many authors have postulated a connection between 
cholelithiasis and a great variety of diseases. Among these are: certain 
diseases of metabolism, such as gout, rheumatism; excessive mental 


540 DISEASES OF THE BILE-PASSAGES. 


exertion, arteriosclerosis, etc.; certain infectious diseases, such as tuber- 
culosis, typhoid fever, cholera, etc.; and, finally, disturbances of nutrition, 
~ such as the taking of too much food or too little food, eating at too great 
intervals, ete. (Frerichs). 

With regard to the second possibility—.e., the direct effect of 
poisonous principles contained in the bile on the mucous membrane of 
the gall-bladder—different theories have been formulated. Some authors 
believe that stasis of bile can produce the catarrh for the reason that bile 
is a strong protoplasmic poison. This injurious effect of the bile on the 
epithelium would be exaggerated if the bile should decompose, and it 
was assumed that this occurred regularly in stasis. 

In later years the action of bacteria has been adduced. as the most. 
important factor in the causation of the catarrh under discussion. It 
was formerly believed that the bile possessed distinctly antiseptic proper- 
ties, the idea being chiefly based upon the supposed increase of intestinal 
putrefaction in cases of occlusion of the biliary passages and the ap- 
parently slight tendency of the bile and its contents to cause inflamma- 
tion upon contact with the peritoneum. Several authors agree in the 
statement that the bile is a culture-medium in which bacteria could 
develop abundantly but not so energetically as in bouillon (Létienne, 
Mieczkowski, Miyake, and others). Talma has found great variability 
in the supposed inhibiting action of bile on bacterial growth in different. 
species of animals and in the same species under varying conditions. 
Netter, Naunyn, and others claimed that the bile of animals is normally 
sterile. Miyake has recently in part confirmed their results, having found 
micro-organisms (except in | out of 76 animals) only in the lower portion of 
the common duct. Ehret and Stolz, on the other hand, have found the 
bile in lower animals by no means free from micro-organisms. Gilbert, 
Girode, and Naunyn found the bile obtained from human cadavers 
sterile. Ehret and Stolz and E. Fraenkel and Krause, on the contrary, 
find that the bile obtained at autopsy contains micro-organisms in a 
large proportion of cases. 

Of more significance are the bacteriologic findings in human bile 
obtained during life. Mieczkowski found the bile sterile in all of 15 
cases from whom it had been obtained at operation for some affection 
other than cholelithiasis; on the other hand, in 18 out of 23 cases of chole- 
lithiasis coming to operation the bile was found infected. The same 
conclusions regarding the presence of micro-organisms in the bile in 
cholelithiasis have been reached by other observers. Gilbert and Do- 
menici found, by both direct and cultural examination, micro-organisms 
in two recently formed calculi; in two old calculi no micro-organisms 
were found; in one old calculus bacteria were found by staining but not 
on culture; and on examination of an old and a recent stone derived 
from one patient the former showed no micro-organisms, while the latter 
contained colon bacilli. Gilbert and Fournier examined 36 gall-stones, 
including 3 from cattle. Of these, 22 (one of which was bovine) showed 
no bacilli; while 9 (one of which was bovine) contained colon bacilli. 
In two of their cases dead bacilli were found in the calculi, the bile being 
sterile. Since these observations were made they have received ample 
confirmation. It is, therefore, definitely proved that the bile is sterile 
in at least a large majority of cases without calculi, that in cases of chole- 
lithiasis the bile contains micro-organisms in those coming to operation, 
that in recently formed calculi micro-organisms are usually found, that 


CHOLELITHIASIS. 541 


in old calculi micro-organisms incapable of growth may be found while 
the bile shows no evidence of infection, and that in an old calculus there 
may be no bacteria while a more recently formed stone in the same case 
may contain the colon bacillus. 

In order to determine the significance of the presence of bacilli in 
concretions Gilbert and Fournier tested the permeability of gall-stones 
for bacteria; gall-stones were placed in tubes of bouillon, fractionally 
sterilized. and then the tubes were inoculated with colon bacilli. In 
five days bacilli were found in the center of the calculi. The importance 
of- this finding is offset by the discovery of bacilli in the center of calculi, 
the surrounding bile being sterile. It has, however, a distinct bearing 
upon recurring cholecystitis in cholelithiasis. 

The question as to whether the infection of the bile is to be looked 
upon as the cause or the effect of the formation of calculi has given rise 
to much discussion. The micro-organisms most frequently found are 
the members of the colon group and Bacillus typhosus. So constantly 
is one of these forms present that Gilbert and Fournier divided chole- 
lithiasis into two groups, those due to the colon bacillus and those due 
to Bacillus typhosus. There is sufficient clinical evidence to prove 
that there is a distinct connection between typhoid fever and cholelithiasis. 
Chauffard found that symptoms of gall-stones were present in only 10% 
of a series of cases that had had typhoid fever, while 20% of cases of 
cholelithiasis gave a history of a previous attack of typhoid fever. Ehret 
and Stolz have collected from the literature 32 cases in which either at 
operation or at autopsy typhoidal cholecystitis was found. In 20 of 
these gall-stones were present. Hanot and Milan found Bacillus ty- 
phosus in the center of recently formed gall-stones and in the walls of 
the gall-bladder and bile-ducts. Since these observations abundant 
confirmation of the frequency of infection of the bile in typhoid fever 
has been obtained (50% of fatal cases, according to Cushing). There 
is evidently, therefore, apparently some connection between infection 
of the bile by typhoid bacilli and the formation of gall-stones, although 
this infection does not necessarily lead to the latter. The determining 
factor may receive its explanation in an interesting observation made by 
Richardson. In a case of cholecystitis he found typhoid bacilli clumped 
“as if a gigantic serum-reaction had taken place in the gall-bladder.” 
Similar large clumps of typhoid bacilli in the bile were found in five out 
of six cases of typhoid fever. In the sixth case the blood-serum had no 
agelutinating power. Richardson injected 0.5 c.c. of typhoid bourllon 
culture clumped by the addition of typhoid serum into the gall-bladder of 
one rabbit, two drops of ordinary bouillon culture of typhoid bacilli into the 
gall-bladder of another rabbit, and used a third animal as a control. 
Four months later all three animals died. In the gall-bladder of the 
“control”? animal he found a small number of rounded bodies arranged 
in concentric rings; in the animal-injected with ordinary typhoid culture 
nothing was found, while in the animal injected with the clumped culture 
the gall-bladder was contracted about a rounded concretion. 

It has been proved by many experiments that the gall-bladder can 
readily rid itself of micro-organisms, and in purulent cholecystitis it is 
known that bile and biliary pigment (Ehret and Stolz) are absent—two 
facts which, in addition to the absence of constant infection of the bile, 
may account for the escape of some cases from calculus formation after 
typhoid fever. 


542 DISEASES OF THE BILE-PASSAGES. 


The effect of stasis of bile upon infection of that fluid is decided. 
After ligation of the common duct micro-organisms were found in the 
bile by Charcot and Gombault, by Naunyn, and by Netter. Recent: 
observations by Ehret and Stolz and by Miyake even more definitely 
prove this influence. 

Attempts to cause the formation of gall-stones in animals throw 
considerable light upon human cholelithiasis. The injection into the 
gall-bladder of virulent cultures produces severe cholecystitis; the injec- 
tion of attenuated cultures may be followed by the formation of con- 
cretions, particularly if the flow of bile be hindered. Gilbert and Do- 
minici injected into the gall-bladders of three dogs cultures of typhoid 
bacilli, and in that of one dog the bacillus of Escherich. In none of these 
did concretions develop. Gilbert and Fournier injected into the gall- 
bladder of a rabbit a culture of Bacillus typhosus attenuated by heating 
a bouillon culture for ten minutes at a temperature of 50° C. (122° F.). 
Six weeks after the injection of three drops of such an attenuated culture 
into the gall-bladder the rabbit was found dead. The thickened gall- 
bladder contained bile of a slightly yellow color and two concretions 
adherent to the mucous membrane. Section of these showed a central, 
whitish portion, from which typhoid bacilli were obtained in pure culture, 
and a pigmented shell. According to Miyake and others, the injection 
of pure or mixed cultures into the gall-bladder may be followed by chole- 
cystitis, but is not followed by the formation of calculi if no other factors 
are present. Ehret and Stolz found that diminution of motility of the 
gall-bladder, or anything promoting the accumulation of residual bile, 
aids the growth of micro-organisms within the gall-bladder, while 
Mieczkowski found that stasis of bile increased the virulence of the 
bacteria present. Cushing produced true biliary concretions by injecting 
typhoid bacilli into the gall-bladder of rabbits when there was simul- 
taneous restriction of motility of the gall-bladder or its ducts. 

The effect of foreign bodies in the production of concretions was well 
illustrated by a case reported by Homans. Twenty months after a 
cholecystotomy for cholelithiasis pain returned, and a second operation 
revealed that five out of seven calculi present had developed about the 
remnants of two of the silk sutures remaining from the first operation. 
Kehr states that he has on three occasions seen a similar formation about 
fragments of sutures. Jacques Meyer introduced small hollow balls of 
ivory and of clay into the gall-bladder of dogs and failed to see any 
evidence of stone-formation after one year. A small amount of sediment 
was noticed, but no concretion even in the cavity of the balls. Small 
pieces of agar disappeared completely. Mignot combined the introduc- 
tion of attenuated micro-organisms and sterile foreign bodies. Attenu- 
ation was obtained by diluting cultures of the micro-organisms in bile 
through the addition of progressively smaller quantities of bouillon or 
of ascitic fluid. The attenuated organisms were injected into the gall- 
bladder, and, after allowing a time to elapse sufficient to permit of their 
becoming implanted in the mucous membrane, sterile porous tampons 
were placed in the gall-bladder for ten or twelve days. The tampons 
were then withdrawn and at the same time a small sterile foreign body 
was introduced and fixed to the wall of the gall-bladder. After the 
lapse of one or two months this foreign body was found covered by a 
deposit of cholesterin. Foreign bodies of a size sufficient to prevent 
their entrance into the cystic duct, impregnated with attenuated cultures, 


CHOLELITHIASIS. 543 


and placed in the gall-bladder soon became covered with cholesterin. 
A similar proceeding with the later extraction of the foreign bodies was 
followed at the expiration of six months by the formation of true stratified 
cholesterin stones in 7 out of 19 animals. Mignot, therefore, concludes 
that two causes are necessary for the production of gall-stones—a weak- 
ened micro-organism and stagnation of bile. 

Miyake found that the injection of pure cultures of colon bacilli ob- 
tained from a case of cholelithiasis was followed by the formation of con- 
cretions only when the caliber of the cystic duct was diminished. When 
there was no obstruction to the outflow of bile, simple cholecystitis resulted 
from either the injection of bacteria, injury to the mucous membrane, 
or the insertion of foreign bodies. Similar conclusions were reached by 
Ehret and Stolz. These authors have demonstrated the fact that the 
presence of foreign bodies within the gall-bladder has the same effect 
as does mechanical hindrance to the outflow of bile because of the layer 
of bile between and around these bodies, so insuring the presence of 
residual bile and resulting bacterial growth. 

The following conclusions seem at present justified: 

1. Infection of the gall-bladder by virulent micro-organisms causes 
acute cholecystitis without the formation of concretions, the elements 
necessary to their production being absent in such cases. 

2. So long as complete exit of bile from the gall-bladder is possible, 
a cure without the formation of concretions may occur. 

3. Micro-organisms of attenuated virulence only produce concretions 
if the complete evacuation of bile cannot occur. 

4, Foreign bodies have the same effect as obstruction to the outflow 
of bile because of the layer of bile around, between, and within them. 

5. The presence of inflammatory products or of foreign bodies pur- 
posely placed or accidentally present in the gall-bladder may cause the 
formation of concretions by virtue of the residual bile about them. 

6. It is possible that the “clumping” of typhoid bacilli within the 
gall-bladder may furnish an explanation of the frequency of post-typhoidal 
cholelithiasis. 

According to all these experiments and the anatomic findings re- 
ported, it seems probable that the stone-forming catarrh of the gall- 
bladder and the ducts can be attributed to microbian infection. It is, 
further, probable that these germs penetrate the gall-bladder during 
certain diseases, and that their power is increased as soon as stasis of 
- bile occurs. As a result of catarrhal inflammation, degeneration of epi- 
thelium and desquamation of dead and dying cells occurs. At the same 
time the mucous membrane continues to regenerate, new glands are 
formed, and these in their turn furnish a mass of degenerated cellular 
material. This process is followed by the accumulation in the gall- 
bladder or the ducts of cholesterin and pigment calcium in about equal 
quantities. The concretions that-are formed later, therefore, are com- 
posed of equal amounts of the two ingredients, and are more or less uni- 
form in structure. Naunyn calls attention to the fact that wherever 
numerous gall-stones are found they seem to be exactly alike. He draws 
the conclusion from this fact that cholelithiasis is, as a rule, caused by 
one single infection and one lesion of the walls of the gall-bladder, and 
that recurrences of this condition are rare. In addition to the factors 
enumerated, all those agencies must be considered which, by obstructing 
the flow of bile, prevent the evacuation of micro-organisms, concretions, 


544 DISEASES OF THE BILE-PASSAGES. 


etc., from the gall-bladder. These agencies will be discussed below. They 
may consist in certain anatomic changes in the parts or may be rendered 
active by an irrational mode of life, ete. As a final result of all these 
factors, the gall-stones continue to enlarge and to consolidate until finally 
the picture of a fully developed cholelithiasis is presented. 

The question arises as to how the bacteria penetrate the gall-bladder. 
There are two possibilities: They may either gain an entrance by way 
of the blood-current or they may be derived from the intestine. Both 
experimental and anatomic evidence is overwhelmingly in favor of the 
latter supposition, which is made particularly apparent by the fact that 
Bacillus coli, the micro-organism that is most frequently seen in the 
gall-bladder, has its natural habitat in the intestine. It is probable 
that catarrhal conditions of the duodenum and ducts have something 
to do with this invasion, and an analogy must be sought between this 
condition and the invasion of the ducts in catarrhal icterus, in both in- 
stances the germs that cause the catarrh having penetrated the bile- 
ducts. In those cases where a partial obstruction to the flow of bile 
exists in the ductus choledochus, and where stasis of bile obtains, such 
an invasion is favored. Foreign bodies and parasites (thread-worms, 
flukes, etc.) may act as carriers of bacteria, and may in this manner, in 
addition to causing irritation and impeding the flow of bile, be the direct 
cause of catarrh. 

Concretions form in the intrahepatic bile-passages, particularly in 
the course of cirrhosis of the liver. This is due to the contraction of the 
hepatic tissues, which causes constriction of bile-channels and impedes 
the flow of bile. In those cases where the flow of bile is impeded by 
compression of the ductus choledochus or hepaticus, or where tumors, 
parasites, or gall-stones occlude the bile-ducts, not only does cholangitis 
exist, but concretions of bilirubin-caleium are formed. These enter the 
gall-bladder and there form the nucleus of larger gall-stones. The dif- 
ferent stages of this development can be clearly seen in cross-sections 
of the bladder and ducts. 

Fernelius and Forestus were the first to point out the significance 
of biliary stasis in the formation of gall-stones. All modern authors 
concede that this is the most important predisposing factor. The flow 
of bile may be impeded by adhesions in the region of the porta hepatis, 
occlusion of the bile-ducts by parasites, etc., compression of the bile- 
passages by tumors of the portal lymphatic glands, the head of the pan- 
creas, and the duodenum. Diminished contractile power of the gall- 
bladder may also lead: to stasis, as pointed out by Petit. Charcot claims 
to have found in the aged atrophy of the musculature of the gall-bladder, 
and as a result poor evacuation of the viscus. 

Constriction of the body by tight clothing may also constitute an 
obstruction to the flow of bile. Cruveilhier found that corset liver and 
gall-stones are often seen together, an association to which Heller and 
Marchand have especially drawn attention. Rother found evidence of 
corset liver in 40% of all women with gall-stones, Peters saw the same 
in 23%, while Schloth, in 95 cases of corset liver, found gall-stones in 
15.3%. Bollinger and Riedel advocate the same view. Lacing seems 
to cause stasis of bile, because, in the first place, the excursions of the 
diaphragm during respiration are impeded so that the bile is not forced 
out of the bladder as well as normally; secondly, the liver becomes elon- 
gated downward, the gall-bladder becoming dislocated to the same ex- 


CHOLELITHIASIS. 545 


tent, and the cystic duct, as a result, becoming twisted or bent; thirdly, 
the cystic duct may be compressed, especially if floating kidney of the 
right side exists at the same time; finally, the catarrhal conditions of the 
stomach and the duodenum that are engendered by lacing, as well as the 
compression of these parts, may readily lead to catarrh of the bile-ducts 
and bladder. 

In women the influence of pregnancy must be considered. The uterus, 
when it becomes enlarged, may exercise pressure on the bile-ducts and 
interferes with the excursions of the diaphragm and the action of the 
abdominal muscles on the gall-bladder. As soon as the child is de- 
livered this abnormal pressure may suddenly cease, and we not infre- 
quently see symptoms of the passage of gall-stones following the im- 
proved evacuation of the gall-bladder. The general ptosis of the viscera, 
the stomach, intestine, kidneys, and uterus, that occurs after preg- 
nancy, also exercises an unfavorable effect, producing traction on the 
large bile-passages or torsion of the ducts (Weisker, Litten, and 
others). The frequent relaxation of the abdominal walls is not un- 
important, as it impedes the normal evacuation of the bile as the result 
of the action of these muscles. Schréder examined 115 bodies of women 
who had died during the sexual period and who had been sufferers from 
gall-stones. Among these, 99 had positively been pregnant at some 
time; in 11 only could pregnancy be definitely excluded. 

All the facts enumerated, particularly the influence of pregnancy 
and of lacing, account for the fact that the female sex is more liable to 
gall-stones than the male. Attention has been called to this by nearly 
all authors since the day of Friedr. Hoffmann. Craz states that in 
nearly all the women examined postmortem in Bonn gall-stones were 
found. Hein found that the relative frequency of gall-stones in men 
as compared with women is as 2 to 3." Fiedler found gall-stones in 15% 
of females and in only 4% of males, Roth (Basel) in 11.7% and 4.7% (a 
ratio of 5 to 2), Rother (Munich) in 9.9% and 3.9%, Schréder (Stras- 
burg) in 20.6% and 4.4%, Peters (Kiel) in 9% and 3%. [Mosher * 
found that in America gall-stones were present in about 10%.—Eb.] 

It is not impossible that the sedentary habits of most women and lack 
of exercise play a rdle. Such a mode of life has been considered a pre- 
disposing factor in cholelithiasis since the days of antiquity. Thus, 
Friedr. Hoffmann, Haller, Coe, S6mmering, Morgagni, J. P. Frank, and 
others state that scholars and prisoners are frequently afflicted with gall- 
stones. A long period of convalescence with enforced rest in bed is 
said to predispose to gall-stones. It is possible that in the latter case 
stasis of bile may occur as the result of the slight movements of the dia- 
phragm and of the abdominal muscles and from the pressure exercised on 
the cystic duct by the intestines. Frerichs has explained the occurrence 
of gall-stones in the bile-passages of cattle in winter (Glisson) by the long 
period of rest in the stable; while. Glisson is inclined to attribute it to 
the change in diet. According to Bollinger, liver-flukes are the true 
cause. Another factor must be considered in judging of the significance 
of sedentary habits, and that is the possibility of catarrhal conditions of 
the intestine and other digestive disturbances that readily follow such 
a mode of life. We have no reliable statistics in regard to all these ques- 
ae and, in the very nature of the inquiry, can hardly expect to procure 
them. 

35 * Bull. Johns Hopkins Hosp., August, 1902. 


546 DISEASES OF THE BILE-PASSAGES. 


[Brockbank * has drawn attention to the relative frequency of gall- 
stones in cases of heart disease, and especially those with mitral stenosis. 
Among 1347 autopsies gall-stones were found in 5.4% of cases without 
and in 10.9% of those with cardiac disease. Mitral stenosis was accom- 
panied by gall-stones in a larger proportion than was any other heart 
lesion. He found that, on standing, bile from cases of cardiac disease 
showed a larger deposit of cholesterin crystals than was the case with 
bile obtained from cases where disease of the heart was not present. 
Probably the more or less sedentary life led by these patients accounts 
in part for the presence of gall-stones among them. Passive congestion 
and repeated catarrhal inflammation of the gastro-intestinal tract and its 
related glands may play a réle.—ED.] 

Certain anomalies of metabolism have been credited with an important 
role in the causation of gall-stones, among them being gout, rheumatism, 
diabetes, obesity, arteriosclerosis, etc. French authors claim that gout, 
in particular, predisposes to the formation of calculi. In men, however, 
gout is more frequent than in women, whereas the latter are more often 
sufferers from cholelithiasis. The rdles of obesity and of diabetes are 
altogether uncertain. Beneke found arteriosclerosis and _ gall-stones 
together, and has attempted to formulate some connection between the 
two. As both diseases are frequently seen in old people, this connection 
is probably a mere coincidence. Peterssen-Borstel, moreover, failed to . 
find any relationship between the two conditions in all the postmortem 
examinations he made in Kiel. | 

It has been claimed, further, that the taking of too much food could 
favor the development of cholelithiasis. This statement can be proved 
as little as the inverse one that poor food or deficient nourishment plays 
such a role. 

The abuse of spirituous liquors (beer, etc.), too much meat, and too 
much fat have al! been accused of causing gall-stones; but no proof for 
these assertions has been forthcoming. The only possible connection 
would be a predisposition to intestinal catarrhs that might be created 
by an inappropriate diet. According to Friedr. Hoffmann and Frerichs, 
irregular meal hours, long periods of starvation, or eating at long intervals 
could act unfavorably, for the reason that under these circumstances the 
gall-bladder is not emptied as frequently as it should be, it being known 
that the bile flows from the gall-bladder chiefly during the time of di- 

gestion. 

The réle of heredity, chiefly advocated by Fauconneau-Dufresne 
from the experience of the spa physicians in Vichy, is exceedingly doubt- 
ful. [Ehret + has reported cholelithiasis occurring in four generations. 
—EDp.] 

The increasing frequency of gall-stones with advancing years is very 
striking. Friedr. Hoffmann, Morgagni, Haller, Coe, J. P. Frank, and 
others have emphasized this fact, and it is established by all autopsy 
reports. As the latter alone furnish conclusive evidence, we are justi- 
fied in believing that such a connection exists. According to Peters 
(Kiel), only 0.62% of gall-stones were found in subjects under thirty, 
between thirty and forty there were 3.24%, between forty and fifty were 
4.44%, between fifty and sixty were 6.98%, between sixty and seventy 
were 9.53%, between seventy and eighty were 13.02%, and over eighty 


* Edin. Med. Jour., July, 1898, p. 51. 
+ Nereins-Beilage der Deutsche med. Woch., May, 1902, p. 143 


CHOLELITHIASIS. 547 


years there were 16.36%, etc. Rother (Munich) states that the following 
relations between the age of the subject and the prevalence of gall-stones 
exist: One to thirty years, 3%; thirty-one to sixty years, 6.9%; sixty-one 
and over, 19.2%. Schroder (Strasburg) gives the frequency as from birth 
to twenty years, 2.4%; twenty-one to thirty years, 3.2%; thirty-one to 
forty years, 11.5%; forty-one to fifty years, 11.1%; fifty-one to sixty 
years, 9.9%; sixty years and over, 25.2%. We see, therefore, that a 
gradual increase seems to occur with the progression of years. It is true, 
on the other hand, that in earliest youth gall-stones are occasionally 
met with. Bouisson found three gall-stones in a new-born infant with 
narrowing of the common duct; Portal saw stones in children both in the 
ductus choledochus and in the bile-passages of the liver; Frerichs saw 
gall-stones in a girl of seven years. [John Thomson * has reported a 
ease of gall-stones in a new-born infant. Still ¢— has reported cases at 
the ages of eight and nine months and has collected twenty published 
cases.—Ep.] The greater tendency to cell degeneration, with a resulting 
increase in the formation of cholesterin, in old people may be considered 
a valid reason for the greater frequency of gall-stones in the aged; and 
the same applies to arteriosclerosis, where, as we know, the percentage 
of cholesterin found in the blood is markedly increased. According 
to Kausch, the bile of old people contains more cholesterin than does 
that of young subjects. Another factor, according to Charcot, is the 
weakness of the musculature of the gall-bladder and the bile-ducts in 
old people as a result of degeneration of the muscle-fibers of these parts. 
The action of the diaphragm and the pressure exercised by the abdominal 
walls are also weaker (Heidenhain). Disturbances of digestion and 
catarrhs of the intestine are more frequent, food is taken at longer in- 
tervals, and the production of bile is smaller—all factors that favor chole- 
lithiasis. Finally, it must be remembered that the longer a person has 
lived, the more frequently has he been exposed to conditions that favor 
the development of the various diseases of the bile-passages that may 
lead to gall-stones. 

In reviewing the different statistical reports, and in considering, of 
course, only those that are based on autopsy findings, it will be seen that 
gall-stones are seen more in certain localities than in others. This may 
in part be attributed to differences in the pathologic material, as in one 
location (Kiel) the majority of the autopsies were performed on children, 
whereas in another (Strasburg) the subjects were nearly all older people. 
In Kiel, according to Peterssen-Borstel, gall-stones were found in 3.95%; 
according to Peters, in 5%; in Munich, according to Rother, in 6%; in 
Dresden, according to Fiedler, in 7%;.in Erlangen, according to Schloth, 
in 7.2%; in Basel, according to Roth, in 9 to 10%; in Vienna, according 
to Frank, in 10%; in Strasburg, according to Schréder, in 12%. [Mosher 
(loc. cit.) found gall-stones in 6.94% -of 1655 autopsies in Baltimore. 
—Ep.] Naunyn is inclined to credit the differences in these statistics 
to the fact that the observers examined for gall-stones with more or less 
thoroughness. The observation that differences seem to exist in various 
locations in regard to the frequency with which gall-stones are seen in 
people of different ages speaks strongly in favor of a special tendency 
to the disease in these locations. The finding of gall-stones by Schroder 
in Strasburg in 25% of people over sixty, by Rother in Munich in only 


* “ Wdinburgh Hospital Reports,” 1898, vol. v. 
¢ “Trans. Pathological Soc. of London,” 1899. 


548 DISEASES OF THE BILE-PASSAGES. 


19.2%, and by Peters in Kiel in 11.3%, for example, shows an apparent 
local variation in frequency. 

It is, & priort, probable that the disease would be found with greater 
frequency in certain places, as has been claimed for a long time. Even 
in the different provinces of Germany it may be said that the mode of life 
is different. In addition, the influence of certain endemic diseases must 
be taken into consideration, causing variations in the frequency of catar- 
rhal conditions of the gastro-intestinal tract and of the bile-passages, 
and in this manner indirectly leading to cholelithiasis. 


PATHOLOGIC ANATOMY. 


Gall-stones are often found at autopsy. In Munich (Bollinger- 
Rother) they were seen 66 times in 1034 autopsies (that is, in 6.3%); 
in Copenhagen (Poulsen) 347 times in 91,722 autopsies (that is, in 3.7%); 
while Conradi excluded autopsies in children and found gall-stones 87 
times in 4000 autopsies (that is, in 2.4%). Halk, in 4140 autopsies in 
subjects over fifty, found them in 29%; Hiinerhoff (G6éttingen) in 4.4%; 
Fiedler (Dresden) in 7%, Frank (Vienna) in 10%, Schroder (Strasburg) 
in 12%, Roth (Basel) 9 to 10%, Schloth (Erlangen) in 4%, Peters (Kiel) 
in6%. [Brockbank (loc. cit.) in 1347 autopsies at Edinburgh found gall- 
stones in 4% of males and 15% of females dying from all causes, and 
Mosher in this country in 6.94%.—Ep.] As a rule, the subjects during 
life had complained of no symptoms of gall-stones. According to Poul- 
sen, symptoms were present in only 8% of the cases. Other authors state 
that in many instances the disease runs its course without producing 
any symptoms, and that, notwithstanding the presence of large accumu- 
lations in the gall-bladder, no disturbances in the flow of bile, no pain, 
and no inflammatory phenomena become manifest. [Kehr states that 
only about 5% of peoplé with gall-stones are troubled by their presence. 
—EDb. 

Sometimes only one large stone is found in the gall-bladder; in other 
cases the viscus is filled with a mass of small concretions. The bile- 
passages within the liver may be completely filled with these small stones. 
In one case Friedr. Hoffmann counted 3642, in another Otto found 7802, 
and Naunyn has reported 5000. As a rule, in these cases, the stones are 
more or less uniform; but occasionally different varieties are seen. Walter 
was the first to report such a finding, and Hein states that in 632 cases 
he found multiform stones in 28. In the great majority of cases the 
stones are seen in the gall-bladder alone; they are less frequently found 
in the large bile-ducts and the bile-passages within the liver. Conradi, 
for example, in 97 cases that he examined, found stones in the bladder 
alone in 92 cases, in the bladder and the ducts in 10 cases, and in the bile- 
passages alone in 5 cases. Hiinerhoff in 85 cases found stones in the 
intrahepatic bile-passages once, in the hepatic duct twice, in the cystic 
duct 8 times, and in 84% in the gall-bladder. Charcot is inclined to the 
belief that the stones that are found in the bile-passages may be derived 
from the gall-bladder in cases where the ductus choledochus is occluded. 
In general, however, the stones found in the bile-passages consist of biliru- 
bin-calcium, and were formed where they are found. 

Within the gall-bladder the concretions are usually free and suspended 
in fluid, but in some instances they are adherent to the walls of the bladder 
or connected with it by thread-like processes. In rare cases all the 








CHOLELITHIASIS, 549 


stones are found within a capsule of connective tissue that is subdivided 
into several compartments. A conglomeration of gall-stones of this 
kind may perforate into the intestine as a whole and be passed in the 
stools. These masses must be explained by the outpouring of a fibrinous 
exudate between the stones, the material thus poured out later being 
converted into fibrous tissue. In many cases the stones are seen em- 
bedded in the walls of the gall-bladder, either inclosed in little erypts 
(Hedenius) or in glandular excrescences (as reported by Malpighi). Mor- 
gagni saw the formation of stones within these structures of the gall- 
bladder wall. In these cases trabecular hypertrophy of the connective 
tissue and of the musculature plays a réle. Sometimes it appears as 
though the stones had exercised pressure on the walls of the gall-bladder, 
causing ulceration of its surface, and had succeeded in penetrating in 
this manner. This process would be analogous to the method in which 
the stones perforate the wall and succeed in entering neighboring organs. 
The action of the stones within the gall-bladder may produce indenta- 
tions and separation of certain portions of the gall-bladder. Pro- 
tuberances are frequently seen in the region of the exit of the cystic 
duct, the “bassinet” of French authors, which may cause a change 
in the channel of the cystic duct so that it starts laterally from such a 
diverticulum. Within the cystic duct gall-stones may form cyst-like 
protuberances, as is also seen in the ductus choledochus, where they may 
be very marked (Morgagni, Cruveilhier, Frerichs and others). Within 
the intrahepatic bile-passages cylindric and sacculated dilatations are 
occasionally seen in cholelithiasis, which in rare cases may form peculiar 
cyst-like structures altogether separated from the duct from which they 
arose. 

Distinct changes can usually be seen in the gall-bladder, due, as a 
rule, to the mechanical action of the gall-stones, to the action of bacteria 
that have entered the bladder, and to stasis of bile. The gall-bladder, 
as a rule, is distinctly enlarged, and consequently protrudes below the 
lower margin of the liver. [In long-standing cholelithiasis the gall- 
bladder is apt to be small and tightly contracted about the concretions, 
a condition produced by inflammatory thickening of the walls.—Eb.] 
In corset liver the gall-bladder is usually dislocated in this manner to- 
gether with a tongue-shaped piece of the liver (Riedel), from the fact 
that a portion of the liver in close contact and connection with the gall- 
bladder is pulled down with it. The mucous lining of the bladder shows 
distinct evidence of catarrh, such as degeneration, desquamation and 
regeneration of epithelium, round-celled infiltration in certain locations, 
and here and there deeper destruction of tissue consisting in ulcerations 
of its surface. The inflammation may in some cases extend to the serous 
- covering of the gall-bladder and in this manner produce adhesive peri- 
tonitis and adhesions with neighboring parts, as the abdominal walls, 
the duodenum, the colon, the ileum, etc. As a result of the chronic 
irritation the wall of the gall-bladder becomes thickened; the connective- 
tissue part of the wall increases, glands are formed, and in rare instances 
cysts containing cholesterin and devoid of an epithelial lining are present 
(Adler). The muscularis of the bladder, too, may hypertrophy, and in 
this manner the inner surface assumes a trabeculated structure analogous 
to the conditions seen in the urinary bladder (vessie & colonnes) in chronic 
catarrh of this organ and in lithiasis of the urinary passages. Within 
these indentations and spaces stones may become lodged and may enlarge 


550 DISEASES OF THE BILE-PASSAGES. 


there (Barth and Besnier, Charcot, Bouchard, Souville, and others). 
Particularly in the case of rough angular stones do we see this sclerosis of 
the walls of the gall-bladder, as well as in impaction of stones in the 
neck of the bladder and whenever very many stones are present (Durand- 
Fardel). Hitinerhoff in 57% of his cases found changes in the walls of 
the gall-bladder, in 20% the fibrous form being observed. In the begin- 
ning the musculature, as a rule, is hypertrophied, but later perishes 
altogether in the overgrowth of connective tissue. The latter, under 
these circumstances, assumes the character of scar-tissue and imparts a 
erating feeling to the hand when cut with a knife. Sometimes it calcifies, 
so that a calcareous mass is found in place of the gall-bladder. In other 
cases the gall-bladder contracts around the stones. Here, as a rule, 
it is surrounded by dense adhesions in which stones or fragments of con- 
cretions may be found. Under these circumstances it may be a very 
difficult matter to discover the remnant of the gall-bladder. What is 
left of the organ generally contains a few stones and a little mucus but no 
bile. The inner surface of the viscus is cicatrized and is no longer covered 
by epithelium. When a stone occludes the lumen of the cystic duct, 
or when ulcerative processes produced by stones occlude the canal and 
the neck of the gall-bladder, thus causing an obliteration of the viscus, 
hydrops vesicee may occur. The inflammation of the gall-bladder may 
extend to the side nearest to the liver or may even involve the latter 
organ by direct continuity. As a result the gall-bladder may become 
anchored to the liver by solid bands of adhesions or the hepatic tissues 
may undergo sclerosis. If pus-forming organisms penetrate the gall- 
bladder when it is filled with gall-stones, violent inflammation of its 
mucous membrane with reddening, swelling, eechymosis, desquamation 
of epithelial cells, diphtheritic changes, or even necrosis of the mucosa 
(Jacobs, Tadéac), may be seen. The necrotic parts in these cases are 
colored greenish by bile-pigment. In this empyema of the gall-bladder 
we find that the walls of the organ are infiltrated with round cells and 
are brittle, so that they easily rupture, and that the serosa is often ad- 
herent to other organs by fibrinous material. 

Similar changes may be produced in the larger bile-passages (the 
cystic, hepatic, and common ducts) whenever gall-stones are present. 
Diverticula are frequently seen in the cystic duct containing gall-stones, 
the stones seeming to be arrested here whenever the duct is twisted. 
The ductus choledochus, too, may be very much distended by gall-stones, 
and particularly near its exit do we see concretions, for the reason that 
this portion of the canal where it penetrates the wall of the intestine is 
very narrow. Gall-stones lodge less frequently in the hepatic duct, for 
the reason that this passage grows wider as it approaches the common 
duct; only in cases where the latter is filled with gall-stones do we see 
them in the hepatic duct. In cases of this kind the wall of the bile-ducts 
is inflamed or even ulcerated. In some instances, owing to ulcerative 
processes, the walls become very thin and perforation occurs, or, as in 
the walls of the gall-bladder, fibrous thickening and hypertrophy of the 
musculature are seen. These various inflammatory processes may ex- — 
tend to the serosa and cause peritoneal irritation, fibrinous exudation, 
aiid later connective-tissue adhesions with neighboring organs. As a 
result, particularly in the case of the cystic and the common duct, the 
walls of the passages may ultimately become embedded in a mass of 
solid cicatricial tissue, and as this contracts a considerable obstruction to 





= —- ~~ 


——— 





CHOLELITHIASIS. 551 


the flow of bile is produced. These changes are readily transmitted to the 
finer biliary passages within the liver, in which case cholangitis is pro- 
duced; the bile-passages become dilated, especially if stasis of bile super- 
venes; and as a result we see proliferation of the interstitial tissues in the 
liver with new-formation of bile-passages—in other words, biliary cirrhosis. 
These processes develop particularly in those cases where stones are pres- 
ent in the intrahepatic channels. These passages, if the common duct 
is completely occluded, may become dilated to such a degree that atrophy 
of the true hepatic tissue occurs. In the midst of this atrophic tissue 
are seen the bile-passages that sometimes attain the size of a finger (Ray- 
naud and Sabourin), a process analogous to the changes seen in the kid- 
neys in hydronephrosis. If the pressure that the stones exercise on 
the walls of the bile-passages becomes so great that perforation occurs, 
the stones may wander into the tissue of the liver itself. In other in- 
stances, ulcers will develop and lead to the formation of cicatrices, and 
ultimately to obliteration of the passages or to stenosis. In this manner 
a cystic cavity may be formed within the liver. If pus-forming organisms 
penetrate the bile-passages during the course of cholelithiasis, suppura- 
tive cholangitis is the result, with all its serious consequences; such as 
necrosis of the mucosa, ulceration, perforation, and the passage of gall- 
stones into the surrounding tissues. -If perforation of the large bile- 
passages occurs, general or circumscribed peritonitis will be the result; 
if perforation occurs in the intrahepatic bile-passages, abscess cavities 
will be formed within the liver, the latter sometimes containing one or 
many gall-stones. 

In this manner mile abscesses may be formed that contain staphy- 
lococci, streptococci, Bacillus coli, less frequently Bacillus typhosus, 
the comma bacillus, and the pneumococcus. At the same time suppu- 
rative cholangitis may be observed. As the venous blood from the gall- 
bladder and the bile-passages is poured into the portal vein, micro- 
organisms may be transported into this vessel, causing pylephlebitis, 
inflammatory thrombosis of branches of the portal vein, and multiple 
abscesses. In this manner large and small abscesses consisting of numer- 
ous minute purulent foci, varying in size from that of a millet-seed to 
that of a hazelnut (abscés aréolaires), are formed and involve the branches 
of the hepatic veins. In addition to suppurative processes, the presence 


_ of pus-forming organisms may cause other changes, as follows: if gall- 


stones are present and stasis of bile occurs, the microbes may penetrate 

the hepatic tissues proper and cause localized areas of necrosis (hepatitis 

sequestrans, Schiippel), the same form of hepatitis being produced ex- 

perimentally by the injection of pyogenic organisms and other infectious 

germs into the bile-passages (Dominici). These gall-stone abscesses may 
perforate through the liver into passages that lead out of the body, thus 

breaking into the abdominal walls, the intestine, through the diaphragm, 

into the lungs, ete., and produce purulent inflammations of surrounding 

tissues and organs, such as pleuritis, peritonitis, etc., in the same manner 

as is described in the section on abscess of the liver. 

Another complication of gall-stones that is quite frequently seen is 
carcinomatous degeneration of the bile-passages or of the gall-bladder. 
This is seen particularly in old people in those locations where the irrita- 
tion and the pressure exercised by the concretions have caused cicatricial 
constrictions and thickening. Carcinoma is caused by gall-stones and 
not gall-stones by carcinoma. It has been stated that the stasis of bile 


552 DISEASES OF THE BILE-PASSAGES. 


caused by gall-stones can be made responsible for the formation of car- 
cinomatous growths; that this is not the case will be shown at length in 
the section on the tumors of the liver and the bile-passages. Here, too, 
the typical changes in the mucous lining of these parts will be described. 

Ulcerative processes occurring in the gall-bladder are particularly 
important for the reason that they predispose to perforation of the walls 
of the viscus and the migration of gall-stones into other organs. Acci- 
dents of this character produce fistule and inflammations in the surs 
rounding tissues, and complications of this kind may altogether dominate 
the disease-picture. 

The ulcerative processes described above may lead to phlegmonous 
inflammation in the wall of the gall-bladder. As a rule, however, they 
are seen in the wall of the bladder without undermining its structure, 
so that a simple perforation occurs that causes no symptoms while in 
process of formation. All around the ulcer inflammatory processes 
naturally develop and adhesions form between the different layers of the 
peritoneum. In this manner it is brought about that the stones or jagged 
fragments of the concretions, when they bore through the wall of the 
gall-bladder, do not enter the free peritoneal cavity but are received in 
sacculated diverticula of the peritoneum or in connective-tissue structures. 
Processes of this kind are apt to develop particularly in the region of the 
fundus of the gall-bladder. If the fundus is situated in the usual place, 
it is in contact with the duodenum and the transverse colon. The fundus, 
therefore, can readily become adherent to these parts and the stone per- 
forate into these divisions of the intestine. If the gall-bladder is situated 
more toward the median line, adhesions will form with the second part 
of the duodenum and the pylorus. If it is situated more externally, 
adhesions will form with the second part of the duodenum, the right 
kidney, and the first part of the transverse colon. In cases where the 
fundus is dislocated downward to a considerable degree, as a result ‘of 
elongation of the liver (corset liver) or dilatation of the gall-bladder, 
adhesions may form with the jejunum. In this manner stones may 
perforate into the duodenum (the most frequent occurrence), the colon, 
the stomach, the jejunum, or the pelvis of the right kidney, without, at 
the same time, producing any local inflammation of the peritoneum. 
Adhesions with the abdominal walls may also occur in those cases where 
the gall-bladder is in contact with it, so that the concretions are ultimately 
expelled through the skin. On autopsy remnants of such fistulous pas- 
sages are frequently seen, represented by connective-tissue bands and 
adhesions, and by protrusions and diverticula from traction in different 
parts of the intestine. Occasionally an open fistula is seen; but, as a 
rule, the lumen is occluded by cicatricial tissue. In other cases, again, 
a round peptic ulcer of the duodenum may be formed at the point of 
adhesion corresponding to the opening of the fistula (Ottiker). 

Gall-stones may, further, gain an entrance into masses of connec- 
tive tissue formed on the serous surface of the gall-bladder and may . 
remain there. In this position they may constitute an irritant and pro- 
duce peritonitis, the inflammation sometimes extending and ultimately 
leading to the formation of much cicatricial connective tissue in the 
region of the porta hepatis. The stones may also migrate within the 
peritoneal cavity and may, as a result, be encountered on autopsy in 
almost any part of the abdomen (Thiriar), as in the iliac fossa (Lecreux), 
in the female genitals, etc. In the same manner they may occasionally 








" 

: 
, 

4 
. 
, 

. 

i 





CHOLELITHIASIS. 553 


wander to the convex surface of the liver, to the lower surface of the 
diaphragm, producing inflammation and ulceration on this location, fol- 
lowed by pleuritis with adhesions with the lower surface of the lung, 
or they may penetrate the lung and be expectorated from the bronchi 
(Leyden, Aufrecht, Courvoisier, Graham, and others). In rare instances 
they may enter the urinary passages or may wander through the remnant 
of the urachus, and enter the urinary bladder. This occurs if by some 
chance they reached the region of the umbilicus. 

Perforation into the free abdominal cavity is comparatively rare. 
As a rule, such an accident is followed by purulent peritonitis caused 
by the micro-organisms that usually cling to the gall-stones; whereas, 
if the bile were sterile, such a complication would not occur. Perforation 
of this kind usually follows trauma, parturition, or violent attacks of 
gall-stone colic. In cases where only a partial infection of localized 
areas of the peritoneum occurs and the pocket of pus is sacculated, the 
pus may burrow along the descending colon into the pelvis, perforate 
the rectum or the vault of the vagina, and thus be evacuated (Schabad). 

Fistule may start from the bile-passages in the same manner as 
from the gall-bladder and cause ulceration of their walls. In this manner 
the ductus choledochus may become adherent to the duodenum, the 
pylorus, etc., and later become perforated, so that gall-stones that were 
unable to pass the opening of the duct enter the intestine or the stomach 
by this route. The occurrence of double common ducts or of a common 
duct with two orifices must be explained in this manner. Occasionally 
multiple fistule are formed, such as between the gall-bladder and the 
duodenum, on the one hand, and the common duct and the duodenum 
on the other (Ottiker). 

Large concretions principally pass from the bile-passages into the 
intestine in this way. In old persons who have died of ileus large gall- 
stones are often found that constitute an obstruction within the lumen 
of the intestine. As a rule, the duodenum is the seat of the obstruction, 
less frequently the ileocecal valve or the lower portions of the intestine; 
in rare cases the stone has been found in the vicinity of the sphincter 
ani. These concretions may be the direct cause of ulceration, gangrene, 
and perforation of the intestine. The intestine is irritated by the presence 
of the stone and contracts around it; at the same time the muscles of 
its walls contract spasmodically, so that great pressure is exercised in 
the region of the stone producing the accidents»named. In rare cases 
the stones enter the vermiform appendix and produce inflammations of 
this organ and of the adjacent tissues. 

Gall-stones may also perforate from the bile-passages into the portal 
vein. They may gain an entrance into this vessel either directly from 
the large bile-ducts after adhesions have formed between these passages 
and the wall of the vein, or by a gall-stone abscess of the liver caus- 
ing circumscribed suppuration atthe porta hepatis, eroding the vein 
and allowing the perforation of a stone into it. Many cases of this 


. kind, that have been reported particularly in the older literature, are 


doubtful, as it is not impossible that the different authors confounded 
this condition with perforation into intrahepatic bile-passages. 

In cases where cholelithiasis is complicated with much inflammation 
of the bile-passages (cholangitis and cholecystitis) due to virulent bac- 
teria, the latter seem to penetrate the blood-stream, even though no 
suppuration occurs in these parts, and infect the heart. In this way 


504 DISEASES OF THE BILE-PASSAGES. 


endocarditic deposits may be formed on the leaflets of the tricuspid and 
mitral valves (Murchison, Luys, Mathieu and Malibran, P. Aubert, Netter 
and Martha, and others). [Oddo * has reported a case of pericarditis 
complicating hepatic colic.—Eb.] 


SYMPTOMS AND COURSE, 


In many, in fact in the majority, of the cases of concretions within 
the gall-bladder or the bile-passages, all symptoms are absent and the 
condition is only discovered at autopsy (compare page 548). In some 
instances, while examining a patient for some other trouble an enlarge- 
ment of the gall-bladder will be discovered that rouses our suspicion 
in regard to the presence of cholelithiasis. In some cases large gall- 
stones may be passed per rectum, and this may be the first symptom 
to reveal their existence. As a rule, however, symptoms make their 
appearance as soon as the stone begins to move and attempts to enter 
the intestine by way of the bile-ducts. Symptoms also appear when the 
stones are causing inflammation and ulceration of the walls of the bile- 
passages, or when stasis of bile occurs, and, as a result, pus-forming 
microbes gain an entrance into the bile-passages and develop there, 
causing violent inflammatory reaction. Complicated cases of this kind 
may be appropriately designated as irregular cholelithiasis. Whenever 
the stones, on the other hand, remain in the location where they were 
formed,—. e., in the gall-bladder,—they usually produce no symptoms. 

A number of prodromal symptoms have been described that are said 
to indicate the impending formation of gall-stones. These consist chiefly 
in certain gastric and intestinal disturbances that are probably catarrhal 
in character and may extend to the bile-passages and there produce the 
stone-forming catarrh. It is, however, a difficult matter to determine 
to what extent catarrhs of the stomach, the duodenum, and the bile- 
passages precede the actual formation of gall-stones, and what is their 
true significance in this respect. In many instances a careful anamnesis 
fails to reveal that they were ever present. The same applies to catarrhal 
jaundice, which is said to predispose particularly to gall-stone formation 
owing to the stagnation of bile and the inflammation of the mucosa of the 
gall-bladder and the bile-ducts that accompany it. A review of the 
literature on this subject fails to yield satisfactory information. 

The first symptoms as a rule, therefore, do not appear until the stones 
are formed and fully developed. 

In cases where the stones remain quiescent and do not move, the 
patients frequently complain of a sensation of heaviness in the hypochon- 
driac region. This sensation changes its location with changes in the posi- 
tion of the body, and is particularly annoying if the patient sits or stands 
for a long time, especially several hours after eating—that is, toward the 
end of gastric digestion. In cases of this character the patients may 
also complain of a dull pain in the right portion of the epigastric region, 
radiating toward the hypogastrium, the thoracic organs, the right shoul- 
der, or the lumbar region. At the same time the appetite may be very 
capricious, periods of anorexia alternating with bulimia. Slight errors 
of diet may be followed by nausea and vomiting of bile-colored masses. 
Patients of this class are apt to complain of a “weak stomach.” At 
the same time certain nervous disturbances may be present, such as 


* Rev. de Méd., Sept. 10, 1893, p. 829. 








ee a ee ee 


CHOLELITHIASIS. 555 


great irritability, depression, and a feeling of oppression in the epigastric 
and precordial regions. All these symptoms may lead us to diagnose or 
to suspect some trouble with the stomach or heart. A number of cu- 
taneous sensations, as itching, burning, etc., may be experienced, due 
to nervous irritation. Among other symptoms must be mentioned 
disturbances of sight, of hearing (Alison), coryza, headache (cephale 
lithiasique), migraine, neuralgias, etc. All these symptoms may be 
explained by assuming that the gall-stones irritate the gall-bladder, 
and that certain nervous areas are reflexly irritated, that certain neu- 
rasthenic and hysteric conditions of the central nervous system are caused 
in this manner, and that in this way the innervation of the affected parts 
is disturbed. The same effect is manifested in alterations that are 
brought about in the composition and the secretion of the gastric juice, 
chiefly in regard to an increase or a decrease of the hydrochloric acid, etc. 
Possibly the well-known aversion to laxatives (Cyr) displayed by these 
patients is based on similar perversions. Such substances as rhubarb, 
senna, etc., are said to produce dyspeptic disturbances. 

Examination of the abdomen frequently reveals that the gall-bladder 
is enlarged so that it can be palpated; its surface will appear nodular; 
in exceptional cases, when the gall-bladder contains many stones, it is 
possible to feel the concretions within the bladder, particularly if the 
viscus protrudes beyond the margin of the liver. In cases of this kind 
the gall-bladder will feel like a sac filled with nuts in which the different 
stones can be moved about. Some authors state that a peculiar rattling 
sound can be elicited on auscultation. This, probably, is heard in very 
exceptional cases only. In many instances the gall-bladder extends very 
far downward to the region of the crest of the ilium, and at the same 
time is freely movable, so that the impression is created that the 
swelling is a tumor of the intestine or the mesentery, or that it is a 
floating kidney. This will be the case particularly when the gall-bladder 
is covered by the colon, a contingency which is, however, rare. As a 
rule, it is an easy matter to determine that the tumor felt extends up to 
and beneath the margin of the liver, and that it is freely movable 
with respiration and follows the excursion of the diaphragm, provided, 
of course, that it is not adherent to the abdominal wall. The liver in 
these cases is, as a rule, distinctly enlarged, due perhaps to stasis of bile, 
or, in the case of women, to the effects of lacing. That portion of the 
liver to which the gall-bladder is attached is often elongated downward, 
forming a tongue-shaped extension, as described by Riedel. If the 
cystic duct be patent, so that the bile can enter the gall-bladder freely, 
it will often be found that the size of the bladder increases and decreases, 
following the increased or decreased secretion of bile or the closure or 
opening of the sphincter of the choledochus. In exceptional cases it 
may even be possible to evacuate the gall-bladder by pressure exercised 
from without, so that the organ collapses into an empty, flaccid sac 
(Gerhardt). 

If the gall-stones are situated in the intrahepatic bile-passages they 
remain latent. Only in exceptional cases is it found that they cause 
symptoms, either by exercising direct pressure that may be painful and 
cause enlargement of the liver, or by producing icterus. As a rule, in 
oe cases, the symptoms are so indefinite that their diagnostic value is 
slight. . 

If the concretions are situated in the large bile-ducts, they rarely 


556 DISEASES OF THE BILE-PASSAGES. 


remain quiescent, but, as a rule, begin to move, and in this way produce 
symptoms of violent inflammatory irritation and of icterus. 

As soon as the stones begin to move severe disturbances of the general 
health are noticed. Such disturbances need not necessarily appear in 
every case; we know that occasionally gall-stones are passed with the 
stools without having revealed their presence to the patient by any 
symptom that could be interpreted to indicate the passage of concre- 
tions through the bile-ducts. In some of the cases of this kind ulcera- 
tive processes in the wall of the gall-bladder or the bile-ducts in all 
probability favored perforation into the intestine through fistule (Fied- 
ler), a supposition made particularly probable from the large size of the 
stones passed in many instances. Another factor that favors the passage 
of large gall-stones without symptoms may be gradual dilatation of the 
bile-ducts following the frequent passage of concretions, so that subse- 
quent stones can pass through without any difficulty. This would be 
analogous to the dilatation of the ureters after the passage of many con- 
cretions from the kidneys. In general, however, the passage of gall- 
stones is accompanied by violent symptoms that have been grouped 
under the name of hepatic or gall-stone colic. The question arises, What 
causes the gall-stones to enter the cystic duct from the gall-bladder and 
to move along the bile-ducts? 

The following are some of the causes of characteristic attacks of gall- 
stone colic: Violent movements of the body; all kinds of succussion, 
such as horseback-riding, driving, dancing, jumping, etc. ; stretching of the 
body for the purpose of reaching some object above the head; gastric and 
intestinal disturbances following the excessive ingestion of food or drink; 
and, finally, attacks of colic are often seen to follow the removal of tumors 
from the abdomen, the delivery of a child, the appearance of menstrua- 
tion. Psychic excitement, anger, fright, and excitement of various kinds 
have for a long time been regarded as factors that predispose to attacks 
of gall-stone colic. 

Of late years the action of the musculature of the gall-bladder and 
the bile-ducts has been made accountable for the peculiar mechanical 
features of the progression of gall-stones during an attack of gall-stone 
colic. Formerly a great deal of significance was attached to the effect 
of the stream of bile itSelf. As the pressure of the bile, however, is very 
slight (according to Friedlander and Barisch, Heidenhain, and others, 
equal to only about 200 mm. of water), this factor can hardly be credited 
with such a réle. On the other hand, contraction of the wall of the 
gall-bladder, capable of being produced experimentally in animals by 
irritation of the gall-bladder, and observed in human subjects, could 
very readily force a gall-stone into the cystic duct. As soon as the stone 
reaches the duct, it is grasped by the muscular fibers, which contract 
around the impediment, and in this manner hold it tightly in its position. 
Strong peristaltic action of the musculature of the bile-passages is often 
caused by active peristaltic action of the duodenum communicated to 
the bile-ducts (compare page 421). In this manner can be explained 
the coincidence of attacks of gall-stone colic with certain digestive dis- 
turbances, indigestion, catarrh, etc., accompanied by an increased activity 
of the intestine. The same is true of many cases in which a migration 


of gall-stones is observed during an attack of typhoid fever or in the 


course of arsenical poisoning. In these latter cases the intestine is irri- 
tated, as shown by the appearance of diarrheic stools, and, as a result, 


q 











CHOLELITHIASIS. . 557 


there is increased peristalsis of the intestine that, as we have seen, can 
be communicated to the bile-ducts. If, in emergencies of this kind, the 
pile-passages are filled with bile (and this will usually be the case in 
digestive disturbances following the ingestion of too abundant or un- 
suitable food), the latter will have a tendency to force the stones forward 
in the bile-ducts, for the reason that it is itself being propelled forward 
by the pressure of the muscles of the gall-bladder and the duct that con- 
tract behind it. In cases where the body is violently shaken, a displace- 
ment of the stones may occur, and at the same time the stones moving ~ 
to and fro within the narrow passage will exercise an irritation on the 
mucous lining of the ducts, and indirectly on the musculature, that will 
be followed by expulsive efforts. Patients under these circumstances 
frequently complain of a feeling of distress or of pain in the region of 
the gall-bladder or of the bile-ducts without at the same time develop- 
ing any of the symptoms of impaction of gall-stones. The symptoms 
enumerated are, of course, due to the irritation exercised by the stones 
on the mucous lining of the bile-ducts and the gall-bladder. An irritation 
of this character may lead to muscular contractions of the walls of the 
parts, and in this way produce the same result as the other factors already 
mentioned. 

Contraction of the abdominal muscles also has a certain significance 
in the expulsion of gall-stones. Such contractions followed by colic 
may occur after stretching movements of the body, after coughing, def- 
ecation, etc. This will be particularly the case if the gall-bladder and 
the bile-ducts are filled with bile, as is the case after a full meal, dinner 
or supper, at the time of digestion. 

It is not quite easy to understand the effect that certain psychic 
alterations, such as emotional disturbances, sorrow, fright, etc., seem 
to exercise on the propulsion of gall-stones. The supposition that they 
influence the peristaltic action of the bile-passages in the same manner 
as they affect the musculature of the stomach and the intestine must 
be considered, especially as fibers of the vagus and the splanchnics in- 
nervate the musculature of the bile-passages and the duodenal sphincter 
of the common duct. Attacks of hepatic colic following nervous excite- 
ment without the presence of concretions can be best explained on the 
same basis. The possibility that the various emotions may exercise a 
cholagogue action is not probable, but cannot, at the same time, be com- 
pletely ignored. Another factor that must be considered is the con- 


traction of the abdominal muscles that occurs during laughing, crying, 


sobbing, ete. 7 

It is probable that a certain nervous factor is responsible for the 
occurrence of gall-stone colic following menstruation. There can be 
no doubt that in many cases the peristaltic action of the intestine is 
stimulated during menstruation. It is possible that this peristalsis 
may occasionally be so excessive that it is transferred to the bile-ducts 
and the gall-bladder. . 

Pregnancy and abdominal tumors have a twofold effect on gall- 
‘stones, for, on the one hand, the increased abdominal pressure present 
in these conditions favors the formation of gall-stones, and, on the 
other, the pressure exercised on the gall-bladder favors the expulsion 
of gall-stones that are already formed. As soon as the great abdominal 
pressure is relieved by the delivery of the child or the removal of the 
tumor, the gall-stones will enter the narrower portions of the ducts, 


558 DISEASES OF THE BILE-PASSAGES. 


whereas previously they were located in the wider portions filled with 
bile. In this manner they produce symptoms of impaction by irritating 
the mucous lining of the ducts, producing spasmodic contractions of the 
walls, ete. During parturition it is not impossible that the action of 
the abdominal muscles favors the propulsion of gall-stones along the 
bile-ducts. 

Riedel makes an inflammatory exudation of fluid into the gall-bladder 
and the bile-passages responsible for gall-stone colic. According to 
this investigator, the mucous membrane of these parts swells as a result 
of the irritation exercised by the concretions, the lumen of the passages 
becomes occluded, and in the parts behind the obstruction, following 
an extension of the inflammation, exudation is seen. All this causes 
the pressure within the bile-ducts to rise. It is possible that inflam- 
matory irritation of this kind may occasionally be observed, but it can 
hardly be considered the exclusive cause of colic. [He distinguishes two 
kinds of jaundice from gall-stones—“inflammatory” and “true litho- 
genous icterus.”’—Ep.] Riedel bases his views on his experience during 
operations. In the majority of his cases, however, old foci of inflam- 
mation of the bile-ducts and of the surrounding tissues were present. 
In uncomplicated gall-stone colic no inflammatory symptoms are demon- 
strable after the passage of the stone, as is the case after attacks of 
nephrolithiasis. As arule, normal conditions are re-established almost. 
at once after the stone has passed, so that we are hardly justified in 
assuming that a very strong inflammatory irritation occurs. [It is 
possible that the difference in the views of Riedel and, for example, Nau- 
nyn arise from the fact that Riedel has reached his conclusions from 
cases requiring surgical interference—in other words, cases of gall-stone 
colic plus inflammatory conditions.—ED.] 

Numerous obstacles exist to the free propulsion of gall-stones. As 
soon as they leave the gall-bladder they enter the narrow cystic duct, 
where they can progress only with difficulty. This duct forms an angle 
very soon after leaving the gall-bladder, runs a tortuous course through- 
out, and, being attached to the neck of the gall-bladder by a mesentery, 
is prevented from becoming very much distended. In addition, a fold 
of the mucous lining runs along the whole inner surface of the duct; in 
a longitudinal direction, it is true, but twisted in a corkscrew manner. 
For all these reasons even small stones pass the duct with difficulty, 
and in passing cause much pain. As soon as they enter the wider channel 
of the common duct they can progress more rapidly toward the intes- 
tine. As soon, however, as they reach the last part of the ductus chole- 
dochus,—namely, that portion that runs through the wall of the duo- 
denum,—they are again arrested by the sphincter-like contraction of 
the muscular coat of the intestine that surrounds the orifice of the duct. 
At times this contraction may constitute an almost insurmountable 
obstacle. For this reason it will often be found that the stones remain 
in the common duct for a long time or even permanently. For a time 
they may cause some disturbances, but ultimately show a tendency to 
become quiescent. In the latter case they produce no symptoms. If 
the stones are able to pass through the orifice of the common duct into 
the intestine, they cause most violent, spasmodic pain until they succeed 
in passing, when the pain stops suddenly. 


Another serious obstacle to the passage of the stones is the spastic | 


contraction of the musculature of all the bile-passages caused by the 


i ee 





CHOLELITHIASIS. 559 


irritation of their mucous lining. Simanowski was enabled to demon- 
strate experimentally that the introduction of a foreign body into the 
ductus choledochus caused a contraction of its muscular fibers. This 
factor is probably less active in old people, for the reason that their 
musculature is atrophic. Riedel claims that another impeding cause 
may be the swelling of the mucous membrane around the concretion. 

Very much depends on the elasticity of the walls of the ducts and 
the degree to which they are able to yield. This elasticity is probably 
considerable during life; much greater, at all events, than would appear 
from postmortem examination of the parts. After death it is frequently 
quite difficult to force even a very small concretion through the bile- 
passages. At the same time the natural elasticity of the bile-passage 
may be much hampered by adhesions with neighboring parts, the forma- 
tion of cicatrices, tumors, etc., in the vicinity of the bile-ducts. 

The size and the shape of the stone are, of course, very important. 
Very large stones—that is, stones as large as a hazelnut—probably pass 
the bile-ducts in exceptional cases only. In many instances stones of 
this character are expelled through fistule that develop in a latent 
manner (Fiedler). Rough and angular stones have a tendency to cause 
spasmodic contractions of the musculature, and become impacted very 
readily, more so than those which are round or oval. Faceted stones 
do not completely fill the gall-bladder, but allow some of the bile to pass. 
As a result they do not lead to such degrees of stasis of bile, and in con- 
sequence the vis a tergo is smaller. If long stones occupy a position 
transverse to the direction of the duct, they cannot pass. As a rule, 
however, a change of position is brought about, so that their longitudinal 
axis is pointed in the same direction as that of the cystic duct. Stones 
of this kind, if they are oval or cone-shaped, are particularly liable to 
cause gradual dilatation of the duct, by acting like a bougie. I once 
saw a gall-stone as large as an almond impacted within the common 
duct. It had almost passed into the duodenum, and was situated so 
that its narrowest, cone-shaped end protruded into the duodenum, while 
the bulk of the stone was still in the duct. The duodenal end of the 
duct was greatly dilated by the action of the stone. Stones that are 
very soft or have brittle walls may sometimes be broken by the contrac- 
tion of the muscles of the walls of the duct, and in this way succeed in 
passing without any difficulty and much more readily than old, hard 
stones. 

The forces that impel the concretions forward are approximately 
the same as those that cause the original migration of the stone and 
precipitate the attack of colic. The pressure of the biliary secretion 
is of subordinate importance in this respect, and has probably been over- 
estimated. The pressure within the gall-bladder and the bile-ducts, 
however, is increased as soon as stasis of bile occurs. At the same time 
stasis exercises pressure on the dilated portions of the bile-ducts, ulti- 
mately acting on the constricting portion of the channel, and in this manner 
aiding the propulsion of the stone. As the portions of the bile-passages 
that are situated immediately behind the stone are congested with bile, 
pressure that is exercised in remote parts of the system of biliary pas- 
sages is transferred as far as the stone. In this manner such agencies 
as contractions of the musculature of the gall-bladder and the bile- 
ducts, compression from tumors situated in the vicinity of the gall- 
bladder or of the liver in general, the action of the abdominal muscles 


560 DISEASES OF THE BILE-PASSAGES. 


or of respiratory movements, etc., may all help to increase the pressure 
behind the stone. As the fibers of the musculature of the bile-passages 
run in a longitudinal direction in man, a contraction of these strands 
must primarily cause a shortening of the bile-passages. As a rule, it 
will be found that the portion of the bile-duct situated behind the 
stone is filled with bile, while that situated in front of the stone is 
empty. Naunyn has determined, by a series of animal experiments, 
that the contraction is most violent in the portion of the duct 
a short distance above the obstruction. As a result, the con- 
traction will, in a way, pull the walls of the duct backward over the 
stone, and at the same time the stone will move onward in the direction 
of least resistance, that is, away from the portion of the duct that is 
filled with bile; in other words, the stone will progress toward the intes- : 
tine. The assumption that the pressure exercised by voluntary con- 
traction of the abdominal muscles is often brought to bear in order 
to aid the expulsion of the stone is seemingly justified, especially as we 
know that an increase in the intra-abdominal pressure can produce a 
dislocation of the abdominal contents in many different directions. In 
the majority of instances, however, the patients do not employ this 
adjuvant, owing to the consequent increase of pain. In other cases, 
again, it can be clearly demonstrated that the patients perform violent 
contractile efforts during an attack of colic. The same effect is exercised 
by the gagging and vomiting that occur during many of the attacks, since 
these acts cause violent contractions of the abdominal walls which 
certainly aid in the propulsion of the gall-stone. At the same time the 
evacuation of the stomach that follows vomiting is a valuable adjuvant. 

In many instances the attack of gall-stone colic proper is preceded 
by certain prodromal symptoms, such as pain in the region of the liver 
or the gall-bladder, and a distressing feeling of pressure in the same 
region due to swelling of the liver, to the filling of the gall-bladder, or 
to the incipient irritation of the mucous lining of the bile-ducts by the 
concretion. 

The attack usually begins with violent pain. Suddenly, as a rule 
after midnight or during the late afternoon hours, a boring, stabbing, or 
tearing pain is felt, this being usually so violent that the patients become 
very much excited, scream, or shriek, or moan. Women describe the 
pain as much more violent than the pains of child-birth. The pain 
is frequently localized in the right hypochondriac region, in the site of 
the gall-bladder. In many cases it appears to be rather in the epigas- 
trium, or it may even be felt in the left hypochondriae region, in the 
mamma, etc. It radiates in all directions, toward the abdomen, the 
chest, the back, occasionally toward the right shoulder, the extremities, 
less frequently toward the genitalia. If the pain is most pronounced in 
the back and in the right side, the suspicion may be aroused that the case 
is one of renalcolic. If the painis feltin the epigastrium, the possibility 
of gastric pain—for instance, from gastric ulcer—must be excluded. 
The latter may be the case where the formation of gall-stones occurs 
within the intrahepatic bile-passages, as in this case the pain is located 
in the epigastrium. If the pain appears suddenly after a meal, the sus- 
picion of some intoxication may be aroused. Respiration, in particular 
inspiration, is painful, for the reason that respiratory movements, by 
causing movements of the diaphragm, exercise traction or pressure on 
the sensitive parts. As a result, respiration is, as a rule, accelerated and 








CHOLELITHIASIS. 561 


shallow and of a purely costal type. The patients in their efforts to 
avoid all pressure on the part frequently twist the body toward the 
right side in order to relax the abdominal muscles of the right side 
as much as possible, and at the same time they draw up their legs or 
rest the chin on the knee. On the other hand, we not infrequently see 
tonic rigidity of the abdominal muscles and spastic contractures, par- 
ticularly on the right side, notwithstanding the great pain that these 
spasms produce. The pain may remit temporarily, only to be renewed 
with greater violence. At times a long pause may occur, particularly 
in case the stone has succeeded in entering the common duct. As soon, 
however, as the stone attempts to pass the orifice of this duct the pain 
reappears with great intensity. The latter pain usually ceases suddenly. 
The pain may also stop in case the stone drops back into the gall-bladder, 
or if the spastic contraction of the cystic duct ceases, or, finally, if the 
stone comes to rest in the common duct. In case a feeling of soreness 
persists after the cessation of the violent pain, and the region of the 
gall-bladder is still sensitive, this indicates that the stone is still within 
the gall-bladder or the bile-ducts, but that the contractions of the walls 
of these parts have ceased. During motion or during digestion, how 
ever, the pain is very liable to recur. 

The pain caused by the migration of the gall-stones (compare page 
456) is chiefly due to the spasmodic contraction of the musculature of 
the bile-passages, as was first emphasized by Baglivi. It is also in part 
caused by the pressure exercised on the sensitive mucous membrane; 
in other words, it is a true colicky pain. Simanowski was enabled to 
determine that in animals violent pain was experienced and a contrac- 
tion of the bile-duct was observed when foreign bodies were introduced 
into the ductus choledochus. Riedel, as has been said, attributes the 
pain to inflammatory processes going on in the wall of the bile-passages, 
and, consequently, does not make a clear distinction between this pain 
and that felt in ulcerative processes and in circumscribed forms of peri- 
tonitis. 

The distribution of the pain follows, in general, the distribution of 
the phrenic and the sympathetic nerves. The irregularity of the pulse 
sometimes observed may be due to an involvement of the vagus 
system by which an influence is exerted, by reflex action, on the heart. 
In some instances the pain may be due to a swelling of the liver and an 
irritation of the nerves in Glisson’s capsule. These nerves can easily 
transmit the irritation to the phrenic nerve and the nerves that anasto- 
mose with it. 

As a result of the violent nervous irritation the central nervous system 
becomes excited, as is manifested by a variety of nervous disturbances 
of a general character, such as spasms, hysterical seizures, etc. (the 
“hystero-traumatisme” of Bychofski). 

In many people the passage of the stone is accompanied by no symp- 
toms whatever or is characterized by very slight disturbances only. 
This may be due to the slight irritability of their mucous membranes 
or to weakness of the musculature of the bile-passages, as is particularly 
the case in old subjects. It may also be seen in those who have been 
sufferers from repeated attacks of gall-stone colic, for the reason that 
here a gradual dilatation of the bile-passages has occurred as a result 
of the frequent passage of stones. 

oa with pain, vomiting may be present, and, as a rule, vomiting 


562 DISEASES OF THE BILE-PASSAGES. 


in this condition is very violent. At first remnants of food are vomited, 
later masses of material that are tinged deeply with bile. During vomit- 
ing of this character it is even possible for gall-stones that are in the 
duodenum to be vomited (Petit, Fauconneau-Dufresne, and others). 
The vomiting of bile is an indication that the common duct is at, least 
not altogether occluded. In rare instances stones have been known 
to enter the stomach through some abnormal communicating passage 
between the gall-bladder and that viscus, and to have been evacuated 
per os in the act of vomiting. Occurrences of the latter character, how- 
ever, are certainly very rare. Notwithstanding the violent and the 
persistent character of the vomiting feculent masses are rarely raised; 
this occurs only when a large gall-stone occludes the lumen of the intes- 
tine in some place; and in the course of regular cholelithiasis a compli- 
cation of this kind can never occur. 

A feeling of chilliness, or even a real chill, may be complained of in 
the course of an attack of gall-stone colic. At the same time a rise of 
temperature may be observed, the thermometer indicating tempera- 
tures as high as 40° C. (104° F.). In some cases a rise of temperature 
may occur without any feeling of chilliness, so that there is complaint 
only of the sensation of heat that usually should follow chilliness. Sweat- 
ing is less frequently seen. The fever, as a rule, persists for a few hours 
only; rarely, for several days. It may, however, reappear later during 
subsequent attacks. In general, it may be said that the rise of tem- 
perature follows the attacks of colic pretty closely. In case the attacks 
are frequently repeated a rapid rise and fall of the temperature may 
at times be noticed; in other words, an intermittent type of fever. This 
fever is strictly differentiated from that type that Charcot has called 
fievre hépatique intermittente. The latter is an expression of the septico- 
pyemic action of infectious agencies that have penetrated the bile- 
passages, the former is characterized by the close connection that is 
seen to exist between it and the attacks of gall-stone colic. The type 
of fever described by Charcot, it is true, is quite often seen in chole- 
lithiasis, but it is also observed in carcinoma, compression, etc., of the 
bile-passages. This is due to the fact that micro-organisms can readily 
penetrate the bile-passages in all these conditions owing to the stasis 
of bile accompanying them. Under conditions of this kind bacteria 
can readily exercise their deleterious influence. 

[Special mention should be made of the not infrequent “ ball-valve ” 
action of astone in the ampulla of Vater. Suspicion of the existence 
of such a condition should be aroused by recurring attacks of pain 
followed by chilliness, rise of temperature, and renewed or increased 
jaundice. Between the periods of occlusion the health may be but 
little impaired, although usually infection of the bile-passages causes 
a mild toxemia.—ED. ] 

It is for the present undetermined whether micro-organisms parti- 
cipate at all in the production of the fever that accompanies attacks of 
gall-stone colic. Numerous investigators have compared this type of 
fever to the fever following catheterization of the urethra, so-called 
urethral fever. It is quite conceivable that the severe irritation of the 
mucous membranes may be transmitted to the central nervous system 


and may cause a rise of temperature. In support of this view the ob- Y 


servation might be adduced that the temperature returns to normal 
immediately on the cessation of the attack. Riedel attributes the fever 








CHOLELITHIASIS. 563 


to a transitory inflammation of the mucous lining of the bile-passages, 
even in the absence of bacteria. This view seems quite tenable. An 
argument against it is the fact that other symptoms of inflammation 
are frequently absent. As bacteria have occasionally been found on 
puncture of the gall-bladder during an attack of gall-stone colic (Osler), 
and as bacteria are, in general, frequently found in the bile-passages in 
cholelithiasis, the possibility that they play an important part in the 
causation of the fever under discussion cannot be denied, even though 
in many instances the bacteria found were not very virulent. 

For a long time icterus has been regarded as one of the most important 
symptoms of gall-stone colic. It is true that icterus is not always present. 
If it is present, however, it constitutes one of the most important diag- 
nostic clues. As long as the origin of the bile was misunderstood and 
investigators believed, for instance, that it was formed in the gall-bladder, 
the significance of icterus as a symptom in cholelithiasis was not thor- 
oughly appreciated nor understood. Wepfer was familiar with the 
fact that icterus is absent in those cases where occlusion of the neck of 
the bladder alone existed; and Ettmiller mentions the fundamental 
experiment of a medical student in Leyden who extirpated the gall- 
bladder of a dog without causing any disturbances in the general health 
of the animal. It was not until the end of the eighteenth century that 
the researches of Haller, Morgagni, and others definitely cleared this 
question. Icterus can only arise in the course of cholelithiasis if the 
ductus choledochus or hepaticus or large branches of these passages are 
occluded. If, on the other hand, the cystic duct alone is occluded in 
the course of uncomplicated cholelithiasis, icterus does not occur, even 
though the gall-bladder be filled with bile and the occlusion be com- 
plete. Wolff stated that he had seen icterus in only one-half of the 
cases he observed in which the existence of cholelithiasis was demon- 
strated by the discovery of gall-stones in the stools. Firbringer saw 
icterus in only one-fourth of his cases. In cases where the stone enters 
the cystic duct and remains there after the irritation of the mucous lining 
and the spasmodic contraction of the muscularis have ceased, icterus 
does not occur—a statement which applies also to cases in which the 
stone drops back into the gall-bladder or in which it enters the ductus 
choledochus but does not completely occlude the passages owing to its 
angular form or its small size. Again, a gall-stone may succeed in 
migrating into the intestine without having caused occlusion of the 


~ common duct that was sufficiently complete or lasted for a sufficient 


period of time to produce icterus from stasis of bile. In view of these 
different possibilities, it cannot surprise us to encounter cases that present 
all the clinical features of an attack of gall-stone colic, but in which icterus 
is absent. In the same subject a second attack may be complicated 
by short and mild attacks of icterus, or, again, the subject may become 
afflicted with severe and protracted. forms of icterus. In other instances 
icterus may be absent for the reason that the gall-stones succeed in 


_ entering the intestine through a fistulous opening. We are not justified, 


however, in assuming that the formation of a fistula has occurred when- 
ever we find gall-stones in the intestine without the occurrence of icterus, 
for we know that, particularly in old chronic cases of cholelithiasis in 
which a great many stones have passed through the ductus choledochus 
at one time or another, this passage may be so dilated that gall-stones 
can traverse it without causing any stasis of bile; or, on the other hand, 


564 DISEASES OF THE BILE-PASSAGES. 


the gall-stones may be faceted, and as a result, allow a certain propor- 
tion of the bile to pass through the duct. Gall-stones that occlude 
smaller channels within the liver may not cause icterus because of the 
small size of the district in which stasis occurs. Icterus will only 
be seen if one of the large biliary passages or a number of the smaller 
ducts are occluded. Attacks of gall-stone colic of this kind, that run 
their course without producing icterus, particularly those that occur 
in the region of the smaller intrahepatic channels, present the greatest 
diagnostic difficulties. They are frequently confounded with cardialgia, 
symptoms of gastric or cardiac lesions, hysterical or other nervous 
seizures, intestinal colic, ete. 

Icterus does not appear at the beginning of the attack of gall-stone 
colic. As a rule, several hours, often twenty-four, elapse before it is 
noticed. This’can readily be explained. The gall-stone, as a rule, must 
pass through the cystic duct before it enters the common duct, where 
alone it can produce stasis of bile within the liver. Besides, it is essential 
that the stone become impacted in the common duct, and this does not 
always occur at once. The same applies to gall-stones that come from 
the intrahepatic bile-passages. They, too, as a rule must enter the 
common duct before they can produce icterus. But even in those cases 
in which the gall-stone enters the common duct at once or was already 
present within this channel icterus cannot occur until a certain amount 
of bile has been secreted, an amount sufficient to constitute a stasis of 
bile. The bile-passages behind the impacted gall-stone must be filled 
with bile before biliary constituents can enter the blood and cause icterus. 
Further, some time must elapse before the bile-pigments that enter 
the blood can color the skin, sclera, etc., sufficiently to make the colora- 
tion visible to the eye. Icterus, moreover, is difficult to detect in arti- 
ficial light; for which reason, if icterus appears at night or in the even- 
ing, it may not be recognized until the morning. 

In this manner it may happen that the true nature of the disease is 
not recognized for a day. Sometimes we must be content to make the 
diagnosis post festum, because the irritation of the mucous membranes 
and the spasmodic contractions of the musculature may have subsided 
before icterus appears and suddenly throws light on the diagnosis. In 
some instances icterus is of a transitory character, in others it may persist 
for weeks or months. It may persist long after the attack itself has 
subsided, as occurs in those cases where a gall-stone becomes impacted 
in and occludes the common duct. In cases of this character we see 
the development of hepatic intoxication (cholemia) which will be de- 
scribed below. In addition, we see intense coloration of the skin and 
mucous membranes, while in the icterus that accompanies ordinary 
attacks of gall-stone colic the coloration of the skin and mucous mem- 
branes is only slight. 

At the same time bile-pigment is found in the urine. As a rule, the 
quantities excreted are very small, so that the urine is colored only 
slightly reddish-yellow. Bilirubin appears in the urine before it is depos- 
ited in the tissues, and, on the other hand, disappears more rapidly 
from the urine than from the skin, mucous membranes, etc. Con- 
sequently the absorption of urobilin can in many instances be demon- 


strated from an analysis of the urine before icterus appears, and, on. 


the other hand, no bile-pigment may be discovered in the urine even 
though it is noticed that the skin and mucous membranes are stained. 


y, fire /2, 
f At) nw é 
a i ee if —_ 








L 


CHOLELITHIASIS. 565 


Corresponding to the rernoval of the obturator, the urine becomes very 
dark-red owing to the excretion of large quantities of urobilin. This is 
due to the fact that as soon as the obstacle to the flow of bile is removed 
there occurs a sudden outpouring of a large quantity of bile that was 
arrested behind the gall-stone. In the intestine the bile-pigment is con- 
verted into urobilin and is voided as such in part by the urine. Urobilin 
can be recognized in the urine by spectroscopic methods and by the 
fluorescence seen on the addition of ammonia and a little chlorid of zine. 
At the same time, it is not impossible that a part of the urobilin may 
be formed within the bile-passages, as sometimes bacteria enter them 
and inaugurate different processes of reduction, in this manner causing 
the reduction of bilirubin to urobilin. The consensus of opinion nowa- 
days condemns the theory that the exclusive excretion of urobilin with- 
out the presence of any bilirubin in the urine is due to so-called hepatic 
insufficiency (insujfisance hépatique, Gubler); that is, a deficient forma- 
tion of bilirubin in the liver; nor is it believed that the yellow color of the 
various icteric tissues is due to the presence of urobilin (compare page 
445). : 

The obstruction to the flow of bile into the intestine and the con- 
sequent absence of bile from the intestine is manifested, further, by the 
passage of whitish or grayish stools containing very little converted bile- 
pigment or none at all. In this manner it is often possible to determine 
that occlusion of bile has occurred even after several days have elapsed. 
Even in the complete absence of icterus, the periodic passage of stools 
without bile-staining may lead us to suspect cholelithiasis, even though 
no attacks of gall-stone colic were at any time complained of. On the 
other hand, icterus of the skin and the mucous membranes may exist 
and attacks of gall-stone colic may occur, yet the stools retain their 
color. This may happen, in the first place, if the obstruction to the 


‘flow of bile through the ducts is almost but not quite complete, a small 


quantity of bile being able to pass, but the greater part being retained 
within the ducts; in other words, the quantity entering the intestine 
not corresponding to the quantity that is secreted. In cases of this 
kind the contents of the intestine may still be decidedly colored by bile- 
pigment. In the second place, complete decoloration of the stools may 
not be seen in cholelithiasis when even large parts of the system of bile- 
passages within the liver are obstructed with stasis of bile in these areas, 


causing some bile-pigment to enter the blood, provided that, at the same 


time, a small quantity of bile can flow into the intestine through those 
channels that are not occluded. The stools appear very dark and con- 
tain a great deal of urobilin whenever the obstruction of the cystic, 
hepatic, or common ducts is suddenly removed, so that large quantities 
of retained bile are poured into the intestine at once. 

Enlargement of the liver and of the gall-bladder are also related to the 
stasis of bile. The older authors were familiar with this phenomenon, 
and Charcot has called attention to the fact that a swelling of these parts 
can be determined in almost every case of gall-stone colic if the patients 
are only examined with sufficient care. Particularly in cases of com- 
plete occlusion of the common duct do we find the bile-passages greatly 
dilated ; the gall-bladder, too, enlarges considerably, provided, of course, 
that it is not contracted as a result of previous inflammations or that 
the duct that leads from it is not. occluded. [More emphasis must be 
placed upon the absence of enlargement of the gall-bladder in long- 


566 DISEASES OF THE BILE-PASSAGES. 


standing cholelithiasis (Courvoisier’s law).. In primary attacks with . 


but little thickening from previous catarrhal processes the gall-bladder 
may be distensible, but absence of gall-bladder tumor points strongly 
to cholelithiasis as compared to other causes of biliary obstruction in 
chronic jaundice.—Ep.] As a result of the rapid enlargement of the 
liver its capsule is distended and severe pain results. At the same time, 
a distinct contraction of the abdominal muscles will be noticed, par- 
ticularly of the right rectus. Owing to this muscular rigidity and con- 
traction, it is often a difficult matter to satisfactorily perform percussion 
and palpation of the liver, and to determine whether the organ is en- 
larged or not. In many instances, however, the enlargement of the liver 
is so great that it can be readily detected and the gall-bladder may be felt 
at the margin of the rectus muscle as a round, tense, elastic, tender swell- 
ing. In very rare cases it may even be possible to determine a swelling or a 
shrinkage of this tumor following the retention or the liberation of bile 
when the cystic duct is alternately occluded and patent. Different factors 
may lead to this: new stones may cause occlusion of the cystic duct after 
the first one has passed, or the original stone may change its location so 
that in one position it occludes the duct and in another permits the bile 
to pass. Again, an increase or a decrease in the degree of spasmodic 
contracture of the musculature of the duct or the secretion of inflamma- 
tory exudates into the duct may all lead to alternate occlusion and 
patency of the channel. In cases in which the cystic duct alone is 
occluded, the gall-bladder alone may be enlarged; in cases, on the other 
hand, in which the common duct is occluded both the liver and the gall- 
bladder are liable to swell. As soon as the gall-stones have passed, the 
swelling is reduced very rapidly and the tenderness ceases. In cases, of 
course, that are complicated—where, for instance, a severe degree of 
cholangitis or of cholecystitis exists—the swelling of the organ and the 


pain will persist for a longer time. In complications of this kind a’ 


tumor of the spleen may also be observed, although this complication is 
rare and is invariably absent in ordinary cholelithiasis. 

The effect of the attack of gall-stone colic on the digestive tract is 
manifested by a loss of appetite, that may persist after the attack itself 
has subsided, and by constipation. In some cases, particularly if the 
patient vomits a great deal, severe thirst may be complained of. 

The demonstration of the presence of gall-stones in the stools is, of 
course, of paramount importance in determining the cause of an attack of 
colic. It is true that many cases occur in which no stone can be found 
in the feces even though cholelithiasis has existed for a long time. Many 
authors (for instance, Wolff) claim to have found gall-stones in every case 
that they examined; others claim that they have not found them in the 
majority of cases. A great deal will depend, in the first place, on the 
method of examination that is employed. If the stools are not examined 
with the greatest care, and if the examinations are not performed for 
several consecutive days, they may be readily overlooked. At a time 
when the belief was prevalent that gall-stones always float on water it 
was customary to stir up the feces with water and then to examine only 
those portions that rose to the surface. By this method, of course, it is 
a very easy matter not to find the gall-stones. The method described 
was originated by Prout. It is necessary to dilute the feces with much 
water and then to filter the mixture through a hair-sieve, the insoluble 
solid particles remaining on the sieve, where they can be examined. 


; 
; 





- CHOLELITHIASIS. 567 


One should persist in these examinations for days, as the concretions 
may remain in the intestine for a varying length of time. Even if all 
these precautions are taken, the stones are not always discovered. There 
are several possible explanations for the absence of gall-stones in the 
stools after the termination of an attack of gall-stone colic. Among 
these are: 

1. Dropping back of the stone into the gall-bladder (Charcot), prob- 
ably not a frequent occurrence. 

2. Cessation of the contractions of the musculature of the bile-duct 
or cessation of the irritability of its mucous lining. If this occurs, the 
stone will remain quietly in one place. 

3. Entrance of the gall-stone into the wide, common duct. 

4, Disintegration and dissolution of the stone in the intestine. 

Naunyn in particular has emphasized the latter possibility. He ad- 
ministered several gall-stones of the size of peas by the mouth, but despite 
the most diligent search did not succeed in recovering all of them from 
the feces. Only those that had a solid shell of cholesterin retained their 
original shape and size, those that consisted of bilirubin-chalk and the ordi- 
nary laminated forms of gall-stones seeming to be readily disintegrated. 
It has also been known for a long time that gall-stones leaving the body 
per rectum show a variety of indentations and fissures. For all these 
reasons, the occasional absence of gall-stones in the feces following an 
attack of gall-stone colic is not surprising after all, and we are not justified 
in drawing the conclusion from their absence that a large proportion of 
gall-stone attacks, so called, are not due to the passage of gall-stones. 
The theory advanced by Riedel that such attacks are simply the mani-. 
festation of inflammations of the gall-bladder and of the bile-passages, 
that appear and disappear suddenly, seems hardly tenable. 

It is true that a great variety of different things that are found in the 
stools are occasionally taken for gall-stones. Thus, the hard masses 
found in pears and all those hard particles that are found around the 
kernel of different kinds of fruit may be mistaken for concretions. All 
these substances are insoluble in acids and alkalies, in ether, alcohol, 
etc. If oilis administered by mouth, soft masses of various kinds are often 
seen in the stools. They consist of soaps (the salts of oleic acid). In 
case it is doubtful what kind of concretions are present, it is well to ex- 
amine for cholesterin. For this purpose the concretions are powdered 
and treated either with a mixture of ether and alcohol or with chloro- 
- form, the solution being then evaporated. If cholesterin be present, 
it will crystallize in characteristic needles that give the typical reaction 
with iodin and sulphuric acid. The solution in chloroform also gives 
a characteristic color-reaction with concentrated sulphuric acid, etc. 
If the concretions seem to consist of the calcium compound of bilirubin, 
the latter substance may be detected by Gmelin’s reaction. 

We have already mentioned that gall-stones that can pass through 
the common duct are rarely larger than a hazelnut. Quite frequently 
very large numbers, possibly hundreds, of smaller stones are passed in 
the feces. As a rule, they are faceted and are all approximately of the 
same size. They are either passed in several small batches or pass all at 
once. In this manner it may occur that conglomerates of many stones, 
held together by ordinary intestinal contents, are discovered in the feces. 
It may also occur that a large quantity of material resembling sand, 
consisting principally of bilirubin-calcium, is passed with the stools. 


568 DISEASES OF THE BILE-PASSAGES. 


If all the stones are passed after an attack, a recurrence is rarely seen, 
_ from the fact that the formation of gall-stones rarely occurs again— 
in other words, the passage of all the stones frequently constitutes a 
cure of the disease. 

The principal sequels of an attack of gall-stone colic aside from the 
complications that may arise as the result of violent inflammatory pro- 
cesses, etc., consist in a feeling of weakness, loss of appetite, defective 
nutrition, disturbed sleep, etc. In general, however, sufferers from 
cholelithiasis feel fairly well after the attack is over. Only in those 
cases where the stones do not succeed in entering the intestine, or where 
a more violent irritation of the mucous lining of the bile-passages exists, 
or where, finally, infectious agencies gain an entrance into the ducts 
or the bladder, a swelling of the gall-bladder or of the liver and a general 
feeling of distress and of pain may be present. Death rarely occurs 
at the height of the attack; when it does occur, it follows after 
the patient has shown alarming symptoms of increasing weakness, an 
irregular and weak heart-beat, etc. Itis often impossible on postmortem 
examination to find a definite cause for the fatal issue. [Chauffard* 
has reported a case of sudden death after the disappearance of the pain, 
and attributed by him to toxemia.—ED.] 

_ Finally, a peculiar accident that has been reported several times 
may be mentioned in this place.. It has happened that the mucous 
membrane of the bile-ducts ruptured, that the stone, as a result, per- 
forated the wall of the duct, and, together with a certain quantity. of 
bile, entered the peritoneal cavity. In cases where the mucous lining 
of the bile-ducts is intact, an accident of this character can probably 
never happen. It might be possible, however, that long-continued 
pressure exercised by the gall-stone might weaken the wall to such 
an extent that it finally yields. If the bile—as, for instance, 
in long-standing uncomplicated cholelithiasis—contains no virulent 
bacteria, the peritonitis that results from an accident of this kind 
need not necessarily be fatal. A serous fluid tinged with bile will accu- 
mulate in the peritoneal cavity in these cases. If the fluid be evacuated, 
or if the opening made by the perforation be closed by operation, com- 
plete recovery may ensue. If, on the other hand, virulent colon bacilli, 
pyogenic cocci, etc., gain an entrance into the abdominal cavity, the 
course of the disease is naturally quite different (see below). 

If we summarize the symptoms of the general disease-picture and 
the course of an attack of gall-stone colic, the following can be stated: 

In the beginning certain vague symptoms described above may exist 
pointing to the existence of gall-stones; or, on the other hand, there 
may be no premonitory symptoms whatever and the attack set in sud- 
denly and unexpectedly. As a rule, the first symptom is a violent pain 
in the right hypochondriac region and the epigastrium. The patients, 
as a rule, go to bed at once. They bend the body toward the right side 
in order to relieve their distress. The region of the gall-bladder is usually 
painful to pressure, while the liver may be enlarged and its margin may 
be palpable. Vomiting now sets in; there is a complete loss of appetite; 
in many cases a chill and a rise of temperature; occasionally, irregular 
action of the heart. Frequently, icterus appears after the lapse of a 
certain time. The pain usually stops after a few hours, but may recur 
again as violently as before. A condition of this kind may persist for 

* Gaz. des Hép., 1899. 





CHOLELITHIASIS. 569 


days. Then, suddenly, all pain stops and the patient, aside from a slight 
feeling of lassitude as a result of the suffering undergone, may otherwise 
be none the worse for the attack. In general, the stools are not colorless 
until after the attack is over. The concretions, too, are naturally found 
after the attack. 

Abortive attacks of gall-stone colic may precede the ty pical seizure. 
They consist in attacks of mild headache, pain in the epigastric and 
hypochondriac regions, loss of appetite, a tendency to vomiting, certain 
nervous symptoms, as excitement and peculiar undefined sensations in 
various parts of the body; occasionally, too, slight degrees of icterus are 
seen with temporary decoloration of the feces, a slight degree of swelling 
of the liver, and tenderness over the region of the gall-bladder and the 
liver. Attacks of this kind are apt to occur if the gall-stones are small 
or if the mucous lining of the bile-ducts or of the gall-bladder is only 
slightly irritated or possibly is normally less irritable. Finally, they may 
occur in subjects whose bile-passages are dilated and relaxed. 


COMPLICA TIONS. 


Irregular Cholelithiasis.—Uncomplicated regular cholelithiasis pre- 
sents many varying symptoms, the difficulties of diagnosis are considerable, 
and the disease may assume a very grave character. If this is the case 
in the regular form of the disease, so called, how much more must all 
these difficulties be emphasized in those cases that are irregular in their 
course owing to the occurrence of various complications! Complica- 
tions may consist in infection of the bile-passages by virulent pathogenic 
bacteria followed by cholecystitis and cholangitis or by the formation 
of abscesses of the liver. In the regular form of cholelithiasis, we fre- 
quently encounter bacteria in the bile-ducts and the gall-bladder, but, 
as a rule, they are harmless or not very virulent forms and only pro- 
duce slight symptoms of irritation and of inflammation wherever they 
happen to be located. Other serious and dangerous complications may 
occur if the stones become impacted. Among these are, for instance, 
ulcerations, cicatricial constrictions or strictures, formation of pockets, 
and separation of parts of the ducts. Permanent occlusion of the bile- 
passages may be brought about, leading to renewed stasis of bile and 
the formation of more concretions. This is seen particularly in cases 
where the ductus choledochus is occluded; and is then often followed by 


‘the formation of new concretions in the hepatic duct and its main branches 


by stasis of bile, changes in the smaller intrahepatic ducts, and, finally, 
of the interstitial tissues of the liver itself (cirrhosis). The retention of 
bile within the liver following occlusion of the common duct is, further, 
particularly dangerous in view of the grave form of icterus that it may 
cause. Finally, very serious complications may arise in cases where gall- 
stones attempt to penetrate the walls of the gall-bladder or of the bile- 
ducts and cause inflammation of surrounding parts. This inflamma- 
tion of the neighboring tissues may be purulent in character, but, as a 
rule, leads to the formation of solid masses of connective tissue. "After 
this, fistule are easily formed, so that the gall-stones can wander into 
other organs and there cause serious disturbances. 

Occlusion of the cystic duct by a gall-stone or cicatricial contraction 
of the walls of this duct and obliteration of its lumen is not generally 
followed by any very serious CORARIIEDES The gall-bladder in cases 


570 DISEASES OF THE BILE-PASSAGES. 


of this kind is reduced in size. At first its contents are reabsorbed; 
then the bladder contracts around any gall-stones that it may still 
contain, forming a mass resembling cicatricial tissue. This is often 
seen during laparotomies for gall-stones. It may happen that the gall- 
bladder cannot be felt, or that it may be difficult to find even 
after opening the abdomen during a laparotomy. It is often par- 
ticularly difficult to find the gall-bladder under these circumstances, 
for the reason that inflammatory processes occasionally develop around 
the organ, so that it becomes embedded in a mass of connective tissue. 
In other cases, again, in which occlusion of the cystic duct occurs, the 
gall-bladder may be felt as a tumor protruding beyond the margin of 
the liver. In such an event it is generally filled, tense and elastic at the 
same time; and in some instances fluctuation can be elicited. In the 
latter case we can assume that hydrops of the gall-bladder (hydrops 
vesice fellee) has occurred. Hydrops as well as contraction of the gall- 
bladder may develop without causing any symptoms, the patients ex- 
periencing no abnormal sensations. In the case of hydrops of the gall- 
bladder, they occasionally complain of a sensation of weight in the right 
hypochondriac region. In cases where the gall-bladder is contracted 
and small, stones or fragments of concretions may attempt to perforate 
the walls of the bladder, causing circumscribed peritonitis to develop. 
Attacks of this complication resemble in general outlines any attack of 
gall-stone colic; but they do not run so typical a course, not beginning 
and ending so suddenly. Icterus is always absent in this localized form of 
peritonitis except in those instances where adhesions form in the region 
of the hepatic or the common duct and later contract and occlude these 
ducts. Vomiting, loss of appetite, and pain may all be present, as in an 
attack of gall-stone colic. In case pyogenic germs enter the gall- 
bladder, hydrops of the organ may be followed by symptoms of inflam- 
mation, peritonitic irritation, ete. 

Whenever the ductus choledochus is occluded, a variety of serious 
complications may occur. Permanent icterus with all its dangerous 
consequences may often be seen as a sequel of this condition. Icterus, 
as a rule, appears after several attacks of gall-stones have occurred and 
have passed off; and it is rare to see it immediately after the first attack 
or without the appearance of any symptoms of colic. After it has once 
appeared icterus may persist for many months. In case the bile cannot 
escape, the disease-picture of hepatic intoxication (cholemia) appears, 
which is characterized by a tendency to hemorrhages, digestive disturb- 
ances, a weak heart action, finally coma, etc. The bile usually, however, 
succeeds in forcing an exit into the intestine or some other organ. This 
may result from expulsion of the stone from the duct or from the forma- 
tion of a fistulous communication between the bile-passages and the 
intestine or with the exterior through the skin. The latter exit is created 
by ulcerative processes followed by adhesions and perforation. Finally, 
the accumulated bile may be liberated by one of the many possible 
operative measures that we have at our disposal. 

In cases where the bile is completely prevented from entering the 
intestine, we see the skin and mucous membranes turn an intense yellow 
of greenish-yellow, the coloration gradually and progressively increasing 
in intensity. At an early stage of the disease the patients are liable 
to complain of an itching of the skin; and this symptom may be present 
in cases where cholelithiasis exists and gall-stone attacks have occurred 





CHOLELITHIASIS. 571 


without the development of icterus, so that it must be considered in many 
instances independent of the presence or absence of icterus, and must 
be attributed to nervous disturbances. It probably ranks with the other 
purely nervous symptoms seen in the course of most cases of chole- 
lithiasis. In icterus the stools are permanently decolorized. In cases, 
on the other hand, where the common duct is not permanently occluded, 
but where the flow of bile from the bile-passages into the intestine is 
periodically arrested, so that the bile alternately enters the intestine 
or is excluded from it, the stools are alternately colored and uncolored 
and show varying percentages of urobilin, etc. At this stage the appear- 
ance of furuncles is often noted. The frequency of the heart-beat is 
reduced and the pulse is slow. Hemorrhages from the skin and the 
mucous membranes occur very easily, so that in many cases operations 
are complicated by severe and almost uncontrollable hemorrhages 
from the cut tissues. The passage of bile into the intestine is not neces- 
sary to cause an arrest of all these symptoms. All that is needed is that 
the stasis of bile and the resulting absorption are stopped. In this way 
is explained why the passage of the bile through a cutaneous fistula 
is usually followed by a comparative amelioration of the symptoms 
enumerated. In prolonged cases it may happen that the icteric dis- 
coloration grows less intense after a time from the fact that the liver- 
cells perish in part as a result of the continued stasis of bile; or if they 
do not perish, they are at least seriously impaired in the exercise of their 
functions; consequently the production of bile is reduced or arrested 
altogether. The liver in these cases may enlarge considerably as a result 
of the distention of many of the bile-passages due to stasis of bile. It 
may even happen that the parenchyma of the liver may disappear be- 
tween the dilated passages or be present only in remnants (Raynaud 
and Sabourin). In case the tissue of the liver happened to be cirrhotic 
before, so that it was contracted, swelling of the liver as described above 
can, of course, not occur. If the cystic duct is patent, the gall-bladder 
appears in the shape of a round, tensely distended tumor at the lower 
margin of the liver. In many instances, however, the lumen of the 
cystic duct is also occluded by gall-stones, or the gall-bladder may already 
be contracted as described above, or both conditions may exist; in which 
case, of course, no tumor of the gall-bladder can be formed. The swelling 
of the liver does not cause serious disturbances in the area of the portal 
vein for the reason that no compression of the branches of this vessel 
occurs within the liver, and what little occlusion and obliteration of the 
blood-vessel occurs is not sufficient to cause symptoms of portal stasis. 
In this way it happens that the spleen is not enlarged and that ascites 
is absent; if, on the other hand, the cirrhotic changes within the liver 
assume greater dimensions, or if wide-spread cholangitis exists, some of 
the symptoms of portal stasis may appear. The common duct may 
become excessively dilated behind-the gall-stone, forming a cylindric 
or sacculated tube that may be dilated to such a degree as to contain 
as much asa liter of fluid. The same may occur in the case of the cystic 
or the hepatic ducts, so that the dilated portions of these ducts may 
* readily be mistaken for the gall-bladder. Very frequently the discovery 
is made on the operating table that the gall-bladder is small, atrophied, 
and contracted, and that the swelling that was taken for the gall-bladder 
was nothing more nor less than one of the dilated bile-ducts filled 
and distended with retained fluid. Permanent occlusion of the com- 


572 DISEASES OF THE. BILE-PASSAGES. 


mon duct may also be brought about in cholelithiasis by pressure 
exercised on it by the gall-bladder itself, when it is permanently 
dilated to a great degree following the complete occlusion of the cystic 
duct by large gall-stones. The latter are then usually found either in 
the cystic duct itself or in a diverticulum of this channel. This explains 
the observation that has been made several times that an operation 
on the gall-bladder and the cystic duct, consisting in the evacuation of 
the bile accumulated in the gall-bladder and the removal of the stone 
or stones occluding the cystic duct, was followed by the cure of chronic 
icterus without the removal of any stone or other obstruction from the 
common duct itself. At autopsy, too, occasionally nothing more is 
found to explain the occurrence of chronic icterus and occlusion of the 
common duct during life than a very much enlarged gall-bladder filled 
and distended with bile and compressing the ductus choledochus. It 
is even stated by some (Naunyn, Petit, Jakob and Cyr) that biliary stasis 
ean be produced through pressure upon the common duct by a gall- 
bladder which is completely flaccid, with reduced tonus of its walls, and 
inability to completely empty itself. 

In many cases of long-continued occlusion of the common duct in- 
carcerated gall-stones are not the only form of obstruction, as quite 
frequently we see the formation of a common annular carcinoma of the 
walls of the duct which has probably resulted from long-continued irrita- 
tion of the parts, particularly of the mucous lining of the duct. In fact 
some authors attribute most of the cases of chronic occlusion of the com- 
mon duct in the aged to the formation of carcinoma. This hypothesis, 
however, goes too far, for we know of very many cases of long- 
continued simple obstruction of the common duct without the develop- 
ment of carcinoma. Simple carcinomata of the common duct and car- 
cinomata of the head of the pancreas may also lead to chronic stasis of 
bile and to severe icterus. In these cases the gall-bladder will be found 
to be enlarged; in cholelithiasis, on the other hand, it is usually con- 
tracted and no longer permeable for bile. 

With regard to the duration of icterus in complete obstruction of the 
common duct, it may be stated that this condition can last several months, 
in rarer instances over a year, and that it can then eventually disappear 
if the gall-stone is passed or removed in some other way. Occasionally 
_ the stone escapes through a fistula, so that the orifice of the common 
duct may remain occluded. If no passage of bile occurs, death usually 
takes place after a few months,—as a rule, between the sixth and the 
twelfth month,—with all the symptoms of cholemia. 

The entrance of pathogenic microbes, notably of the pus-forming 
species, into the bile-passages in cholelithiasis is very important in view 
of its bearing on the subsequent course of the disease. As we have 
repeatedly emphasized, stasis of bile seems to favor the development 
of these germs and seems to predispose to the subsequent development. 
of severe forms of cholangitis and of cholecystitis. In exploratory 
punctures during operations for gall-stones and at postmortems, the follow- 
ing bacteria have at different times been found in the bile-passages: 


Bacillus coli, the bacillus of typhoid and the bacillus of cholera, pneumo- . 


coeci, and, finally, in combination with many other species, strepto- 


cocci and staphylococci. All these germs have been found both in the, | 


gall-bladder and in the bile-ducts. Virulent colon bacilli are found, and 
can be cultivated from the contents of the gall-bladder and the bile-ducts 


tt i i 








eee 


CHOLELITHIASIS. 5738 


(Netter and Martha, Naunyn, Levy, Dominici, and others). Dupré, Fau- 
raytier, and many later authors have found Bacillus typhosus alone in 
suppurative cholangitis, etc.; and occasionally this micro-organism has 
been associated with Bacillus coli. Pneumococci and the spirilla of 
cholera are less frequently found (Girode). Pyogenic germs have fre- 
quently been found alone or in association with bacteria of the above 
species. Cholelithiasis plays a very important réle in the causation of 
cholangitis. Dominici states that in 65% of the cases of cholangitis 
observed by him attacks of gall-stones had preceded the disease or gall- 
stones were present when the disease developed. [The rdle of gall-stones 
in insuring the retention of residual bile, as explained by Ehret and Stolz 
(see above), has a marked bearing in this connection, especially as regards 
the operative removal of gall-stones in order to avoid the danger of 
infective and dangerous inflammation of the gall-bladder and its ducts. 
—Ep.] 

It is true that in cases of typhoid fever, cholera, or pneumonia, where 
a severe attack of inflammation of the bile-passages is caused by the 
specific germ of the disease, all symptoms of this complication may be 
absent. The symptoms of the primary disease are so violent, and 
the symptoms of involvement of other organs dominate the disease-picture 
so completely, that the disturbances in the liver and its appendages 
are comparatively insignificant and are overlooked. Thus, Hagen- 
miiller found that out of eighteen cases of typhoid fever in which chole- 
cystitis typhosa was found after death, symptoms of this condition were 
present in only eleven of the cases during life. Infection with colon 


bacilli may cause suppuration and still run a purely latent course, so 


that we may be very much surprised to find pus in the gall-bladder 
and the bile-passages postmortem. 

The course of infectious cholangitis seems to be most acute in cases 
of invasion by Bacillus coli, particularly if the bacilli are very virulent. 
In infections with streptococci and with staphylococci the course of 
the disease is apt to be more chronic. In infections with Bacillus coli, 
purulent inflammation of the peritoneum is most frequently seen; in 
infection with pus cocci, on the other hand, abscess formation in the 
liver is more often encountered. The picture of insidious and slowly 
developing septicopyemia is also frequently seen. Bacillus coli may, 
however, also lead to the formation of hepatic abscesses, which, as a rule, 
develop from the bile-passages. To these symptoms of cholangitis are 
frequently added the symptoms of endocarditis (Netter and Martha, 
Mathieu, Malabran, and others). In some cases ulcerative endocarditis 
may develop. In other words, a general septicopyemia may arise in 
which the local symptoms in the liver are of such subordinate importance, 
and are so much relegated to the background, that the primary source 
of the general septicopyemic involvement is not discovered until an 
autopsy is performed and the disease-of the bile-passages is discovered. 

In many cases the occurrence of cholangitis is manifested as follows: 
After the patient has undergone one or several attacks of gall-stone 
colic, a tendency to slight febrile disturbances, an icteric color, a dull 
pain in the region of the liver, and other symptoms are observed, all 
pointing to the possible presence of some infectious process in the affected 
parts. An intermittent type of fever is frequently seen. Charcot was 
the first to describe this and to call attention to a possible connection 
between these febrile disturbances and septic processes; he designated 


574 DISEASES OF THE BILE-PASSAGES. 


this fever “‘ fiévre intermittente hépatique’’ (compare page 511). Ifa tem- 
perature curve of this kind is seen in, the course of cholangitis, it 
signifies that micro-organisms or their toxins have entered the blood 
from the bile-passages; although it is not necessary that suppurative 
processes should occur in the bile-passages themselves, for it seems pos- 
sible for pyogenic germs to pass through the bile-passages into the blood 
without infecting the former. Pathogenic germs have, in fact, at different 
times been found in the blood. The attacks of fever are liable to appear 
toward evening or during the night with chills, cyanosis, etc. The tem- 
perature may rise as high as 40°C. (104° F.). The feeling of chilliness 
may last for a short time only or it may continue for a long time, even 
lasting for two or three hours. Following this, a feeling of heat is 
complained of and the pulse grows tense and rapid. Finally, profuse 
sweating occurs, and the temperature drops back to normal. Following 
an attack of this kind, comes a period of apyrexia of varying duration, 
before the next attack begins. It will be seen that depending on the 
length of the period of apyrexia, all types of intermittent fever may 
be simulated: viz., quotidian, tertian, quartan. The sequence of the 
different attacks is not, however, as regular as in malaria. It must 
also be emphasized that in cases where the inflammatory processes 
in the bile-passages increase, or where they extend to the surrounding 
tissues, the type of fever may change and assume the characteristic 
course of a remittent or of a continuous fever. When the fever runs a 
course like this, the patient usually dies; whereas the intermittent type 
of fever seems to be less dangerous. In many of the more severe cases 
it may be found that the fever is remittent from the very beginning. 
In other cases, again, particularly in old subjects and in cases where 
the hepatic cells are very much altered, all fever may be absent; in fact, 
the temperature may be subnormal during the whole course of the attack. 
Migration of the gall-stones seems to favor the occurrence of fever. This 
is probably due to the slight injury which they always inflict on the 
mucous membrane lining the bile-passages, in this way throwing the 
doors open for the entrance of germs or of their virulent products into 
the blood. This is the reason why the fever we are discussing follows 
attacks of gall-stone colic. The intermittent type of this fever has been 
explained as follows: owing to the fluctuations in the quantity of bile 
secreted and the fluctuations of pressure to which the secretion is exposed 
during the contraction and relaxation of the walls of the bile-passages, 
the quantity of pathogenic material that can be absorbed varies, so that 
at different times different quantities of the latter products or of virulent 
germs themselves enter the blood and the tissues. 

In the urine we find, in addition to bile-pigment and urobilin, albumin 
and indoxyl. It has even been stated that tyrosin and leucin are occa- 
sionally encountered in the urine. Regnard claims that in biliary fever 
a decrease of the excretion of urea occurs; but all other investigators 
(Brouardel, Lecorché, Talamon, and others) have reported that in the 
case of this fever, as in all other forms of febrile infection, the excretion 
of urea is increased. 

In some instances the gall-bladder can be felt, palpation being, as a 
rule, easy if the organ is filled. The region of the gall-bladder is fre- 
quently sensitive to pressure. Sometimes it will be found that peri- 
cholecystitis has developed, a diffuse swelling will be felt around the 
gall-bladder, and, later, fluctuation may even be elicited in the center 








CHOLELITHIASIS. 575 


of this swelling. Death usually results in cases of this character from 
acute peritonitis. In other instances it may happen that the cystic 
duct is occluded by a gall-stone or that its lumen is completely obliterated 
by cicatricial contractions, etc. In this event, the biliary constituents 
within the gall-bladder are gradually absorbed and the fluid contents 
is converted into a thin, sanious, or serous liquid. At the same time 
the gall-bladder continues to increase in size and becomes very much 
distended, its walls growing thicker, and, finally, hydrops of the gall- 
bladder developing. The fluid contained within the gall-bladder at the 
end of this process is sterile, for the reason that all micro-organisms that 
may have been present have perished. Before the establishment of this 
stationary condition, however, various influences, as traumata, digestive 
disorders, intercurrent infections, etc., may cause a revival of the infec- 
tious germs present in the gall-bladder or may cause the entrance of 
new micro-organisms into the viscus, and in this manner produce ulcera- 
tive processes, by which the danger of circumscribed or of diffuse periton- 
itis is madeimminent. Gall-stone fistulee may also be formed as a sequel 
of such an attack of cholecystitis. 

A further complication of cholelithiasis is hepatic abscess. The 
formation of purulent collections in the liver may follow an attack of 
cholangitis, disease of the small branches of the portal vein, or infection 
of the bile-passages or the parenchyma from pus in the gall-bladder. 
If this complication occurs, the disease-picture becomes complicated; 
and the lesion exercises a considerable influence on the course of the 
disease. In the majority of cases of hepatic abscess a definite diagnosis 
of the condition cannot be made. This is particularly the case if multiple 
abscesses develop. In the latter instance the general symptoms of grave 
septicopyemia completely dominate the disease-picture. As a rule, 
furthermore, death occurs before the formation of the abscess can be 
discovered. The suspicion of abscess of the liver may be entertained if 
a pyemic type of fever develops, characterized by the alternate appear- 
ance of intermittent and of remittent temperature curves, and if at the 
same time symptoms of inflammation of the surface of the liver are ob- 
served, particularly if the diaphragm or the right pleural cavity is in- 
volved. The general loss of strength, the rise in temperature, and the 
swelling of the spleen seem to be greater in abscess than in simple cholan- 
gitis, while the fever is, as a rule, more intermittent than remittent in 
character. In the intermittent form the temperature may run very 
high and may suddenly drop to subnormal. Occasionally, the forma- 
tion of an abscess is manifested by symptoms of circumscribed perito- 
nitis. In other instances the complicating pleuritis, that may be either 
purulent or serous, may so dominate the picture that the primary cause 
and seat of the trouble are overlooked. Owing to adhesions that may 
form between the peritoneal covering of the hepatic abscess and many 
different organs or tissues, the abscess may perforate through the skin, 
the diaphragm, the intestine, etc., and in this manner the pus may be 
poured into the pleural cavity, the lungs, the bronchi, etc., and be evacu- 
ated in thismanner. It may also happen that the pus enters the peri- 
toneal cavity, an accident which is, of course, followed by most dire 
results. 

The diagnosis of abscess is established in case a protuberance develops 
somewhere on the surface of the liver, sensitive to pressure, particularly 
painful during the period of the chill (Naunyn, Osler), and later develop- 


576 DISEASES OF THE BILE-PASSAGES. 


ing fluctuation. On opening a cavity of this kind not only pus and bile, 
but also gall-stones, are evacuated. It is possible, at the same time, 
that many of the described abscesses of the liver that contained gall- 
stones, and were evacuated by spontaneous rupture or on operative 
interference, were nothing else than empyemata of the gall-bladder. 
It is a very difficult matter, and it may, in fact, be impossible, to make 
a differential diagnosis between abscess and a softened carcinoma, etc., 
in case the latter lesion develops in the course of cholelithiasis. 
Ulceration of the bile-passages may develop insidiously and in a 
latent manner, so that fistule, adhesions, etc., may develop without 
causing any symptoms. Ulcers of this kind, however, generally lead 
to formidable complications. In many instances they may cause hemor- 
rhages by eroding branches of the hepatic artery or even that artery 
itself, and permitting the occurrence of a hemorrhage into the bile- 
passages or the formation of spurious aneurysms, etc. It’ may also 
happen that some of the vessels of the stomach or the intestine are eroded 
and opened by gall-stone ulcerations, so causing profuse hemorrhages 
leading to increasing anemia, collapse, and death. Hemorrhage into the 
abdominal cavity has also been observed from time to time. Aufrecht 
reports a case of this kind in which a gall-stone penetrated the paren- 
chyma of the liver from the gall-bladder and caused so violent a hemor- 
rhage into the cavity it had formed that the blood, aside from pouring 
through the bile-ducts into the intestine, ruptured the wall of the sac 
and poured into the abdominal cavity. Following hemorrhages into the 
bile-passages, the intestine, or the stomach, blood is found in an altered 
form in the stools or inthe vomitus. The diagnosis is very difficult, par- 
ticularly if no symptoms previously pointed to the existence of chole- 
lithiasis. As a rule, the diagnosis of hemorrhage from a gastric or duo- 
denal ulcer is made. Even on autopsy it may be a difficult matter to 
completely explain the connection existing between the presence of blood 
in the stomach and intestine and the presence of gall-stones. Aside 
from hemorrhages of this kind bleeding into the stomach and the intes- 
tine is occasionally seen following severe forms of icterus, particularly 
that following occlusion of the common duct. The origin of these hemor- 
rhages must be explained from a weakening of the vessel walls as a result 
of hepatic intoxication; 7. e., of the circulation in the blood of deleterious 
_ substances absorbed from the liver. Thrombosis of the portal vein as 
a result of compression by a gall-stone in the ductus choledochus is rarely 
seen, consequently stasis in the blood-vessels of the wall of the stomach 
and hemorrhage from this source are not often encountered. The same 
applies to hemorrhages of this character from the walls of the intestine. 
In discussing abscess formation following cholelithiasis, we called atten- 
tion to the possibility of pylephlebitis and its sequel, multiple hepatic 
abscesses. It may even happen that gall-stones perforate into the portal 
vein, an occurrence indicated by a series of older reports and the de- 
scriptions of Deway, Murchison, and Roth. If this occurs, the picture 
of occlusion and inflammation of the portal vein develops, and, in addi- 
tion, we see ascites, swelling of the spleen, passive congestion in the 
stomach and intestine, and at the same time pyemia. 
*One of the most important complications of cholelithiasis is the forma- 


tion of fistulous tracts between the gall-bladder and the bile-passages, . 


on the one hand, and the intestinal tract, on the other. We have at 
different times mentioned such fistule. 


=i re a er ee ee ee 


a ap we 


Sage ee 


CHOLELITHIASIS. eure 


Concretions occasionally enter the stomach, although this accident 
must be considered comparatively rare. We are not justified in con- 
cluding that such a perforation has occurred merely because gall-stones 
are found in the vomitus, for we know that violent retching and vomiting 
may occasionally allow bile to flow backward into the stomach and to 
appear in the vomitus, and the same applies to small gall-stones during 
an attack of gall-stone colic. In the case of larger stones this cannot 
occur so readily, as these concretions can pass the pyloric orifice of the 
stomach only with difficulty. In case larger gall-stones are vomited the 
formation of a fistula must be considered. It has been definitely deter- 
mined by anatomic examination that a fistulous connection between the 
bile-passages and the stomach occasionally occurs (Cruveilhier, Oppolzer, 
Frerichs, Murchison, Jeaffreson, and others). As a rule, the evacuation 
of gall-stones by vomiting is preceded by attacks of violent pain in the 
region of the stomach, and violent and persistent vomiting of bile, 
food, etc. Sometimes several stones are vomited at the same time, 
or the vomiting of gall-stones recurs several times in the course of the 
disease. 

Fistule are most frequently formed between the gall-bladder or the 
common duct and the duodenum. There can be no doubt that our 
statistics in regard to the frequency of this occurrence are much too low. 
In many instances the fistula is mistaken for the dilated orifice of the 
common duct in old cases of cholelithiasis examined postmortem. The 
gall-bladder, the common duct, and the duodenum are situated in such 
close proximity to each other that the formation of fistulous connections 
between any two of these parts can proceed so insidiously and so quietly 
that the patient is not aware of it. In this manner the passage through 
the intestine of gall-stones that are larger than a hazelnut must be ex- 
plained. This, as we know, may occur without the developmerit of any 
inflammatory or peritonitic symptoms. Hemorrhages of varying degree 
of intensity probably occur during the passage of so large a concretion; 
but, as arule, they are overlooked unless the stools are examined carefully 
for the appearance of blood. 

If symptoms are present at all, they consist in pain, the formation 
of an exudate in the region of the gall-bladder, etc., so that a doughy, 
soft swelling is developed around the gall-bladder and can be felt in the 
region of that organ; in addition, vomiting may occur and both bile 
and blood may be raised. Icterus rarely appears in these cases. On 
the other hand, it may happen that icterus that has existed for some 
time prior to the development of the above symptoms may disappear 
because, of course, the bile that was pent up behind the occlusion can 
pass as soon as the gall-stone has dropped into the duodenum. Finally, 
the stone is passed per rectum. It may be, as we have already stated, 
that the appearance of the stone in the stools is the only symptom 
noticed. In rare instances, finally,-when the stone is very large and 
angular, occlusion of the lumen of the intestine and ileus may result. 

Among 384 cases of formation of internal and external gall-stone 
fistule (of these, 200 were internal) that Courvoisier collected in the 
literature, 108 were duodenal fistulee; and of these, 15 started from the 
common duct and 93 from the gall-bladder. According to the results 
obtained from an examination of the autopsy material investigated by 
Roth, Schréder, and Schloth, gall-bladder fistule were found in 19 


cases, and choledochus-duodenal fistule in 5 cases (Naunyn). Cour- 
37 


578 DISEASES OF THE BILE-PASSAGES. 


voisier mentions gastric fistule only twelve times, and found only one 
case among the postmortem examinations chronicled above. 

On account of the great motility of the small intestine, it rarely 
happens that a gall-stone perforates its walls. In the case of the colon 
it is different, and fistule into that viscus are quite frequently seen. As 
a rule, they start from the gall-bladder, as the fundus of this organ is 
in close proximity to the transverse colon. Adhesions are very liable 
to form between the gall-bladder and the transverse colon, and later 
perforation can easily occur. This process is, as a rule, more favorable 
to the patient than the formation of a fistulous connection between the 
gall-bladder and the duodenum, for the reason that even large gall-stones 
can pass through the colon without any difficulty, and in this way be 
evacuated with the feces without threatening to occlude the lumen of 
the intestine at any time during their transit. In cases of this kind 
the general symptoms of the formation of a fistulous connection are 
quite insignificant, and the passage of the gall-stone through the fistula 
remains altogether unnoticed. Courvoisier found 50 cases of colonic 
fistula in his collection; while Roth, Schréder, and Schloth, in their 
autopsy material, found 16 cases. Combinations of cutaneous or colonic 
fistulee with duodenal fistulae: have also been described. In cases where 
a fistula through the skin and one into the intestine existed, it might 
even be possible for some of the intestinal contents to pass out through 
the skin. If the fistula into the colon is very wide, fecal matter might 
enter the gall-bladder or the bile-passages, producing a very serious 
infection. It is hardly probable that an accident of this kind will happen 
frequently, for the reason that the fistula closes very rapidly after the 
gall-stone has passed. 

Fistulee formed between different bile-passages are of subordinate 
clinical importance. 

In the course of their wanderings through the abdominal cavity, it 
may also happen that gall-stones enter the urinary bladder. In cases 
of this kind the symptoms of urinary calculi in the bladder are produced, 
and the gall-stones can be crushed or removed just as are ordinary urinary 
stones. If concretions of this kind are carefully examined, they will be 
found to contain the calcium compound of bilirubin and cholesterin, 
these constituents, of course, distinguishing them from renal or urinary 
stones. Giiterbock has described cases of this character. I have 
also, on one occasion, examined a stone, removed by Bier from the 
urinary bladder, which consisted almost exclusively of cholesterin and 
was arranged in characteristic layers, with, in addition, a radiating 
structure. As a rule, all symptoms of inflammation of the peritoneum 
are absent. It may also happen that small stones, not larger than a 
bean, perforate the pelvis of the kidney and pass along the ureters, 
reaching the bladder in this way. Murchison assumes that this happened 
in two cases that he reports. In one of his cases some 200 small stones 
were gradually passed through the urinary bladder. Under these cir- 
cumstances the concretions may produce the symptoms of urinary colic, 
particularly if they become lodged somewhere in the ureters. In one 
or two cases they have been known to occlude the lumen of the urethra 
so’ that the operation of urethrotomy had to be performed in order to 
remove the obstruction. 

J. P. Frank describes the very unique case of a gall-stone passed 
from the gall-bladder through some adhesive tissue that had formed be- 


SM, el ol es aad #8 3 | hi 


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i 


‘ 





CHOLELITHIASIS. 579 


tween that viscus and the uterus, and voided from the vagina during 
labor. 

If gall-stones wander to the convex surface of the liver, they may 
become encapsulated in a subphrenic abscess and remain there. Under 
certain circumstances, however, they may perforate the diaphragm and 
lead to the development of empyema, pyopneumothorax, or to perfora- 
tion and evacuation of the pus into the lungs or the bronchi. 

In many cases the lung is already adherent to the diaphragm, owing 
to previous attacks of inflammation of the diaphragmatic pleura. In 
cases of this character a perforation into the tissues of the lung may 
occur without the formation of any fluid exudate in the pleural cavity. 
Within the lung, the symptoms of an abscess may develop and quantities 
of pus and bile may be expectorated for a long time. It may happen 
that the left pleural cavity is entered from the left lobe of the liver (Cay- 
ley). It has even been observed that in one case gall-stones entered the 
mediastinum (Simons), or the pericardial cavity (Legg), or that they 
wandered from the mediastinum into one of the main bronchi. Symp- 
toms of subphrenic abscess, of suppurative pleuritis, of pyopneumothorax, 
as is seen in thoracic fistulae, may all exist for a long time and still 
their connection with gall-stones remain obscure and undiscovered. 
The expectoration of bile-tinged sputum first calls attention to this 
possibility. The latter symptom is, however, still more frequently seen 
in echinococcus or in abscesses of the liver that break through into the 
lungs or pleural cavity. The diagnosis, therefore, will have to be sup- 
ported by a history of gall-stone colic, with the passage of gall-stones 
at some time in the past. In case perforation into the lungs occurs, 
the gall-stones themselves are rarely expectorated; although this did 
happen in a case reported by Vissering. 

Perforation of the abdominal walls by gall-stones has always played 
an important réle in our studies of gall-stones and the pathology of 
cholelithiasis. This accident does not occur as frequently as we might 
be led to believe from the statements made in the literature. Courvoi- 
sier, among 384 cases of gall-stone fistula reported in the literature, found 
184 in which the fistula had perforated the external abdominal wall. 
Duodenal fistule are, however, more frequent than would appear from 
statistics. This is due to the fact that they are frequently not discovered, 
whereas fistulze that penetrate the skin necessarily cannot be overlooked. 

In the production of fistule through the abdominal walls and the 
skin adhesions first form between the gall-bladder and the layers of the 
parietal peritoneum, then the peritoneum and the abdominal wall are 
perforated, the inflammatory symptoms arising incident to this process 
being, as a rule, very slight. In other cases the gall-bladder may be 
very much distended as a result of some violent inflammation, forms 
adhesions with the peritoneum and the abdominal walls, and the pus. 
that it contains finally burrows through the muscular walls of the abdo- 
men and the skin and is either spontaneously evacuated or removed 
by operative interference. As a rule, the presence of an abscess of the 
liver is suspected. When the swelling is opened, pus and sometimes bile 
are evacuated; after a time it may happen that concretions appear, and 
then only is the diagnosis in many cases cleared. The fistula is often 
situated in the region of the fundus of the gall-bladder. Occasionally, 
the inflammatory process follows the course of the suspensory ligament, 
so that the direction of the fistula is downward, in which case the abscess 


580 DISEASES OF THE BILE-PASSAGES. 


will open in the region of the umbilicus. It may even occur that gall- 
stones are evacuated to the left of the median line near the pubes, or 
in the region of the clitoris. Stones as large as a hen’s egg may be passed 
through these abnormal channels and hundreds of individual stones 
may be passed in the course of time. 

As a rule, it is not possible to follow the development of the different 
stages of the processes described. This can be done only in those ex- 
ceptional cases where the symptoms of a perforation of the gall-bladder 
appear first, followed immediately by symptoms of abscess formation in 
the peritoneal cavity, as was present in a case described by Reichardt. 
The first symptom observed is, generally, a tender swelling in the place 
where the abscess is developing. The swelling increases in size and 
occasionally gall-stones can be felt in it. In general, however, all that 
can be determined is that an abscess is forming and that the site of the 
swelling is growing redder and is gradually protruding more and more 
above the level of the abdomen. Slowly the reddened and edematous 
skin becomes thinner; and finally, unless an incision is made into the 
abscess, the pus will break through the skin. In cases where the cystic 
duct is occluded, only pus and mucus are evacuated; whereas if the lumen 
of the cystic duct is patent, bile is passed with the pus. Gall-stones, 
as a rule, do not appear in the spontaneous opening of the abscess until 
later. If the abscess is incised, the gall-stones are generally evacuated 
with the rest of the contents of the abscess cavity. They may, on the 
other hand, remain in the gall-bladder or in the fistulous passage and 
not come away spontaneously, so that it becomes necessary to follow 
the course of the fistula and to remove the stones by a special operation. 
It may also occur that the rupture of the abscess follows an empyema 
of the gall-bladder. This may be the sequel of an attack of suppurative 
cholangitis which, in its turn, was caused by the occlusion of the common 
duct by a gall-stone. In a case of this kind, of course, no gall-stones 
are found in the pus. Icterus following an accident of this character 
will be relieved as soon as the fistulous opening is established. 

The fistulous channels are frequently very long and tortuous, and 
sometimes diverticula are formed along their course that may be filled 
with mucus, pus, or bile, or may occasionally contain a gall-stone. The 
walls of these passages are often thickened by deposits of fibrinous 
material. Iven though the lumen of such a fistula appears very narrow 
on postmortem examination, this does not exclude the possibility that 
at some time there had passed through it a gall-stone larger than the 
opening appears to be. This is explainable from the fact that cicatricial 
contractions and partial obliteration of the lumen frequently follow the 
passage of the concretion. Sometimes a fistula may close and the super- 
ficial opening heal, only to be broken open again at some later time to 
allow the passage of another gall-stone. It may also happen that a 
gall-stone becomes impacted in a fistulous channel, completely occluding 
it. If this occurs and other gall-stones attempt to pass, abscesses may 
form in other places in the vicinity of the gall-bladder. Patients often 
lose all the bile through a fistula of this kind, particularly if the common 
duct is occluded by a gall-stone; but it may even occur if the ductus 
chdledochus is patent. In certain cases there has been reported a loss of 


250 gm. (9 ounces), in some cases as much as 500 gm. to 600 gm. (17.50 | _ 


to 21 ounces), or even a quart, of bile daily. Generally, this fluid is 
not pure bile; but contains also watery transudates, pus, mucus, etc. 





CHOLELITHIASIS. 581 


Many investigators have attributed the marasmus that often follows 
such a flow of fluid to the loss of bile and the deficient elaboration of 
the chyme which they claim follows the absence of bile from the intes- 
tine. This view is rendered untenable by the existence of many cases in 
which the loss of bile through a fistula was well borne for many years 
without any disturbance of the general nutrition. It is more probable 
that the marasmus is caused by the continuous formation and evacua- 
tion of pus usually observed in.these cases. 

Gall-stones that enter the gastro-intestinal tract in one of the different 
ways described may cause a variety of disturbances chiefly brought about 
by occlusion of the lumen of the intestine. It may happen that occlusion 
of the pylorus occurs. The pylorus may be compressed from without 
in case a large stone is passing through the common duct and is attempt- 
ing to perforate into the stomach or the duodenum; or, again, an ulcer 
may be discovered in the pylorus within which is seen a concretion that 
comes from the gall-bladder. Cicatricial contraction may cause traction 
on the pylorus and narrow this passage, or, finally, inflammatory swelling 
around a gall-stone may lead to traction or compression of the pylorus. 
[Fibrous bands of adhesion stretching from the gall-bladder to other 
structures may compress the duodenum or cause kinking long after the 
gall-stones have escaped.—Ep.] The natural result of all these condi- 
tions will be obstruction to the exit of the stomach-contents, with dilata- 
tion of the organ and fermentation and decomposition of the food that 
it contains. In cases of this kind cicatricial narrowing of the pylorus 
as a result of gastric ulcer is usually diagnosed; or if the gall-stone is felt 
in the region of the pylorus or the swelling caused by its presence is pal- 
pated, the diagnosis of carcinoma of the pylorus is made. Occasionally 
the gall-stone is subsequently passed in the stools or vomited, and in 
this manner the passage opened. Leichtenstern reports a case of dilata- 
tion of the stomach that persisted until on one occasion, during lavage 
of the stomach, the lumen of the stomach-tube was occluded by numerous 
gall-stones; after this the patient recovered. 

Sabatier, Boucher, and others have described a dangerous form of 
ileus following the impaction of a gall-stone, their reports dating from 
the eighteenth century. An accident of this character is particularly 
liable to happen in cases where the gall-stone perforates the walls of 
the duodenum and enters this part of the intestine. When the fistula 

opens into the colon, occlusion of the lumen of the intestine is less apt 
— to occur on account of the greater width of the canal. If the gall-stone 
becomes impacted in the duodenum, the same symptoms as those ob- 
served in stenosis of the pylorus may appear, such as regurgitation of 
bile into the stomach, dilatation of the stomach, and obstinate vomiting 
of food. More frequently, however, the gall-stone lodges somewhere in 
the lower portions of the small intestine, in the jejunum or the ileum, 
producing violent colicky pains with vomiting of food and, later, of bile- 
stained and feculent masses. Gradually the symptoms of ileus may 
increase, with the development of peritonitic inflammation in the region 
of the obstruction, followed, finally, by the death of the patient. Occa- 
sionally the obturator may be dislodged and the opening re-established. 
_ This has been known to occur during the manipulations incident to pal- 
pation. In cases of this kind the gall-stone slides along and the patients 
themselves may describe a sensation as though something were moving 
in the intestine. It may, however, happen that the gall-stone becomes 


582 DISEASES OF THE BILE-PASSAGES. 


impacted a second time either at the ileocecal valve or in the rectum. 
Obstruction in the region of the cecum and the lower part of the ileum 
is particularly to be dreaded, notably in the portion of the intestine 
situated immediately above Bauhin’s valve, as stones seem to lodge 
there with greater frequency than in other parts of the intestine. This 
may happen even if the stones are not very large. If a stone becomes 
lodged in the region of this valve, it may act as a ball-valve; in other 
words, the lumen of the intestine may be alternately occluded and 
patent; as a result the symptoms of ileus alternate with the symptoms 
of patency of the intestine. In the first instance we know that the gall- 
stone has become impacted within the valve, completely occluding the 
passage; in the second, we must infer that the stone has again become 
dislodged by antiperistaltic movements, by concussion of the body, or 
some change of position. It appears that this change in the symptoms 
occurs more frequently in cases where the occlusion of the intestine is 
due to gall-stones than in cases where it is due to other causes. Le 
Gros Clark reports a case in which the symptoms of ileus disappeared 
completely for three weeks, so that the patient’s intestinal functions 
were normal; but at the end of this time the symptoms of ileus suddenly 
reappeared and caused the death of the patient. Gall-stones situated 
in the large intestine may also occasionally act as ball-valves in the sense 
that they only allow the passage of pultaceous, soft stools. Such a 
condition is, however, compatible with many months of life. If the 
occlusion of the intestine is due to gall-stones, it appears that the pas- 
sage of flatus is less impeded than in other forms of occlusion of the 
bowels; probably from the fact that closure by gall-stones is not quite 
hermetic (Maclagan, Naunyn). This may also explain the frequent ab- 
sence of meteorism in the form of ileus under discussion. 

Gall-stones that become impacted in the intestine are usually as 
large as a pigeon’s or a hen’s egg; occasionally they are smaller. Occlu- 
sion of the intestine by conglomerations of small stones, held together 
by solid masses of intestinal contents, has also occasionally been 
observed (Puyroyer). Similar conglomerates are occasionally formed 
by masses of raisin-pips or plum-kernels. On the other hand, very 
large gall-stones have been seen to pass from the anus without having 
caused any symptoms of ileus or any other intestinal disturbance. The 
latter may be even 4 by 9 cm. (14 by 34 in.) in diameter (Blackburne). 

If gall-stones are impacted in.the ileocecal region, they may simulate 
typhlitis; and the diagnosis can in these cases be definitely established 
only by an operation (Th. Kolliker). It may even happen, in rare in- 
stances, that small gall-stones enter the vermiform appendix and produce 
appendicitis. 

In former days a great deal of significance was attached to the growth 
of gall-stones within the intestine. It has been found, however, that 
no enlargement ever occurs; if anything, the gall-stones decrease in size 
within the intestinal canal and disintegrate if they remain there for a 
long time. In rare instances, they may form the nucleus of large copro- 
liths. 

It is, as a rule, impossible to determine the exact location of a gall- 
stone in the intestine. If the patient vomits large masses of material 
tinged with bile and not mixed with feces, the diagnosis of occlusion of | 
the duodenum is very probable. In cases of occlusion of the colon it is 
frequently possible to feel the concretion per rectum. 





CHOLELITHIASIS., 583 


Even after the occlusion of the intestine has been remedied, attacks 
of ileus may recur at any time as long as the gall-stone is still within 
the intestinal canal. After the stone has been voided a series of sequels 
may remain, affecting principally the mucous membrane of the intestine 
and manifesting themselves by diarrhea, ete. 

The fatal issue is usually precipitated by exhaustion and collapse of 
the patient. Many authors emphasize the frequency with which peri- 
tonitis is seen following ileus from occlusion by gall-stones, and have 
stated that this complication is the result of perforation and inflammation 
of the mucous membrane of the intestine so often seen in cases where hard 
concretions are present. To this possibility of perforation they attribute 
the fatal issue from peritonitis occasionally seen after the occluding 
gall-stones have been removed. Other authors (Kirmisson and Rochard) 
state that peritonitis is very rare in ileus from gall-stones. According 
to the last-named authors, death occurs in 50 to 70% of the cases ; accord- 
ing to Courvoisier, in 44%; according to Schiiller, in 56%. The disease, 
therefore, is a very serious one. The duration of the disease varies, 
and may fluctuate from one to twenty-eight days. Kirmisson and 
Rochard found that the cases that terminated in recovery lasted, on an 
average, eight days; those that terminated fatally, ten days. 

As old women seem to be particularly predisposed to cholelithiasis, 
ileus from gall-stones is very frequently seen in such subjects. In case, 
therefore, an old woman is afflicted with ileus, we are always justified in 
suspecting that it may be caused by a gall-stone. Kirmisson and Rochard 
found that among 105 cases, 70 occurred in female subjects and only 
35 in males. Among 127 cases observed by Schiller, 34 occurred in men. 

Robson mentions among possible additional causes for ileus following 
cholelithiasis local peritonitis in the region of the gall-bladder, volvulus 
as a result of a violent attack of gall-stone colic, stenosis of the intestine 
following adhesions due in their turn to local peritonitis. All these 
factors are certainly less important than direct occlusion of the intestine 
by a gall-stone. 

Cirrhosis of the liver is not infrequently seen in cholelithiasis. Do- 
donzus, Forestus, and others, stated that the liver may appear indu- 
rated in cases of cholelithiasis. During the century just past, Gubler, 
Virchow, and Liebermeister, in particular, have more exhaustively de- 
scribed cases of this character. The last-named author sees a connec- 
tion between the concretions and the proliferation of connective tissue 
and the atrophy of liver-tissue observed in his case with intrahepatic 
ducts filled with stones. Hanot has written a treatise on the connection 
between gall-stones and cirrhosis of the liver. Meyer and Legg observed 
that ligation of the common duct in cats and rabbits is followed by a 
proliferation of interstitial tissue. Charcot and Gombault arrived at 
the same conclusion as the result of their experiments, but attributed 
the proliferation of tissue to the aetion of the stasis of bile. Thomson, 
also, observed biliary cirrhosis in* congenital obliteration of the large 
bile-passages. In case, therefore, stasis of bile occurs in cholelithiasis 
this may be the cause of cirrhosis (see the section on cirrhosis). In 
many cases of this kind, however, where proliferation of connective 
tissue occurs, as in the case of Liebermeister, icterus may be very slight 
or completely absent. In these cases it must be assumed that the pro- 
liferation of connective tissue in the periportal region (a proliferation 
that may extend into the region of the periphery of the acini) is a direct 


584 DISEASES OF THE BILE-PASSAGES. 


continuation of the chronic inflammatory processes prevailing in the 
bile-passages, and caused by micro-organisms and by the mechanical 
injury to which the mucous lining of the walls of the bile-channels is 
subjected. In cirrhosis of the liver following gall-stones the organ is, as 
a rule, hard, usually smooth, and easily palpated. A tumor of the spleen 
is present, but is not characteristic, as this complication may be seen 
as a result of cholangitis in any case of cholelithiasis. Ascites is rarely 
present and is only seen toward the end of the disease. Icterus may be 
absent or may be present in a mild form only, except in cases that are 
caused by general stasis of bile. Even after the gall-stones have been 
evacuated, the liver preserves its hard consistency and remains enlarged, 
owing to the fact that cirrhosis, after it has once formed, cannot re- 
trogress to any great extent. If the process is very far advanced, it 
may happen that icterus persists even after the flow of bile from the 
gall-bladder has been re-established. Frequently severe degrees of cholan- 
gitis develop in the widened channels of a liver of this kind, and conse- 
quently we see the development of multiple abscesses (Leichtenstern, 
Braubach). 


We have, in several places, mentioned the occasional occurrence of | 


carcinoma of the gall-bladder and of the bile-passages as one of the 
possible complications of cholelithiasis. We will give a detailed descrip- 
tion of the disease-picture of carcinoma of the liver in the section en- 
titled “Cancer of the Liver and the Bile-passages.”’ In this place we 
will limit ourselves to a discussion of a few of the salient features of this 
condition. If the carcinoma develops in the gall-bladder, and if this 
organ is enlarged and filled with gall-stones, a painful, nodular, gradually 
enlarging tumor can often be felt. This tumor, in the course of its develop- 
ment, may involve the cystic, the hepatic, and the common ducts, and in 
this manner compress these passages and cause biliary stasis. In many 
other cases the development of the carcinoma is so slight that it is hardly 
perceptible; or the tumor may grow exclusively on that side of the gall- 
bladder directed toward the liver, and in this way evade detection. In 
cases of this character the carcinomatous involvement of the gall-bladder 
may be completely overlooked and no diagnosis made other than carci- 
noma of the liver. The carcinomatous involvement of the whole or- 
gan may be the result of metastatic, secondary infection from the 
gall-bladder or of extension of the growth in the gall-bladder by direct con- 
tinuity of tissue. Those annular forms of carcinoma that develop around 
a gall-stone in the duct often cause such serious disturbances at an early 
stage of their development that death may result from cholemia before 
the presence of a tumor can be diagnosed. This effect is, of course, due 
to the complete occlusion of the duct and the consequent impeded flow 
of bile. It may happen, therefore, that the presence of such a carcinoma 
is not discovered until after the death of the patient, and even then a 
microscopic examination of the tissues may be necessary before the 
presence of neoplastic tissue is discovered. We may assume, therefore, 
that a good many cases of carcinoma of the gall-bladder remain un- 
recognized, and it is probable that the disease is more frequent than we 
are led to believe from our statistics. Tumor of the spleen is, as a rule, 
absent. Ascites may be present, and at the same time other transudates 


as a result of the existing cachexia; or, finally, a carcinoma of the peri- 


toneum may be present and cause ascites. Other important symptoms 
are progressive loss of strength, the cachectic appearance of the patient, 


Oe Pe ee 


a, ee eee es 


CHOLELITHIASIS. . 585 


the formation of secondary carcinomata in the liver, the peritoneum, 
etc. Only very rarely will an exploratory puncture of the gall-bladder ° 
reveal the presence of carcinoma by demonstrating small particles of carci- 
nomatous tissue in the aspirated fluid. As a rule, if carcinoma’ exists 
the aspirated fluid will consist of a mixture of an albuminous exudate 
and blood. If, in the case of old subjects, an obstinate and persistent 
occlusion of the common duct is observed, and if at the same time the 
patient grows cachectic, the probability that a carcinoma is present is 
great. In doubtful cases an exploratory laparotomy may be attempted, 
and will furnish information that is of fundamental importance for prog- 
nosis and treatment. 

Chronic peritonitic lesions are liable to develop principally in the 
region of the porta hepatis and of the gall-bladder, these locations seem- 
ing to be particular points of predilection in cholelithiasis. These lesions 
may lead to the formation of adhesions and to the development of con- 
nective-tissue strands. The adhesions may, in the first place, cause all 
the disturbances that we have described, such as compression of the bile- 
ducts with all its results; and, in addition, they may exercise traction 
on certain parts of the intestine, and in this manner hinder their free 
movement, cause stasis of their contents, digestive disturbances of various 
kinds, and particularly violent attacks of pain that usually assume the 
character of attacks of intestinal colic. An examination of the abdomen, 
as a rule, furnishes very little information, for the reason that the adhe- 
sive strands are not palpable. It is often possible to localize the pain 
and the other disturbances within a circumscribed area in the vicinity 
of the region of the fundus of the gall-bladder, this applying particularly 
to the tenderness and the spontaneous pain. If such a localization can 
be made, this may be considered a diagnostic clue of some significance. 
The suspicion will often be aroused that we are dealing with an ulcer 
or a carcinoma of this region until some serious disturbance arises that 
calls for a laparotomy, and the diagnosis is made in this way. Loosening 
of the adhesions is usually followed by a complete restoration to health; 
but unfortunately, as a rule, new adhesions form. 

It is also possible for a diffuse form of perihepatitis to develop after 
inflammation of the gall-bladder or of the intrahepatic bile-passages, 
particularly of those that are situated immediately beneath the cap- 
sule of the liver (Leichtenstern, Raynaud and Sabourin). If this occurs, 
the first symptom to be noticed will be a distinct respiratory friction 
sound; which, later, may be heard over a large area. The liver, as a 
rule, is very sensitive to pressure. Singultus may occur as a result of 
irritation of the diaphragm. Gerhardt states that he has heard the 
respiratory friction sound described above in the region of the gall- 
bladder following transitory attacks of gall-stone colic. The perihepa- 
titis under discussion ultimately must lead to a thickening and later to 
a contraction of Glisson’s capsule and of the peritoneum covering the 
surface of the liver; and, in addition, strands of connective tissue may 
extend from the surface of the organ into the interior, and in this 
manner cause atrophy of the liver (Poulin). 

Many authors consider diabetes mellitus one of the possible sequels 
of cholelithiasis, for the reason that these investigators have found sugar 
in the urine at different times following attacks of gall-stone colic. Naunyn 
has submitted these views to sharp criticism and has demonstrated that 
a clear and positive connection cannot be proved to exist in the present 


586 DISEASES OF THE BILE-PASSAGES. 


state of our knowledge between the two conditions. Most of the cases 
were probably diabetics in whom the existence of cholelithiasis had not 
been discovered because it ran its course without causing any symptoms 
or without causing any disturbances of the general health of the patient. 
Owing to the severe nervous commotion incident to an attack of gall- 
stone colic, it is possible that the excretion of sugar in cases of this kind 
became increased, and that after the subsidence of the attack the 
excretion of sugar was again reduced or disappeared altogether. In 
addition, it must be remembered that many factors that may lead 
to cholelithiasis may also cause diabetes, particularly the so-called fatty 
form of the disease. If cirrhosis of the liver is present at the same time, 
it may be that an alimentary form of glycosuria plays a certain rdéle. 
{Exner * found sugar in all but one of 40 patients with cholelithiasis, 
the glycosuria disappearing in from three to four weeks after operation. 
Zinn + found, on the other hand, that glycosuria was present in only 2 
out of 89 cases; Kausch ¢ found it in only one out of 85 cases; while 
Strauss 2 failed to produce glycosuria by feeding three cases of chole- 
lithiasis with 100 gm. of glucose.—ED.] 

If the disease is of long duration and the strength of the body is 
severely taxed, and particularly if chronic and persistent icterus is present, 
emaciation, cachexia, and anemia are seen. It has even been stated 
that the latter may assume the character of a pernicious form of anemia. 
It is probable that some of the retained biliary constituents exercise 
a deleterious effect on the blood-corpuscles. 

Finally, disturbances in the sphere of the nervous system must not 
be underestimated. They are caused mainly by the long-continued 
character of the disease, the frequent attacks of intense pain, the dis- 
turbance of sleep and of the power to move about freely, and other 
causes. In this manner, hysteria, neurasthenia, melancholia, or, on the 
other hand, states of excitement may be produced. Both the laity 
and physicians since the days of antiquity have known that such nervous 
disturbances may develop and play an important rdéle in the course of 
diseases of the liver. 

[Opie has recently been able to demonstrate the close etiologic con- 
nection between cholelithiasis and certain cases of hemorrhagic pan- 
creatitis. In the instance observed by him at autopsy a small concret 
tion blocked the orifice of the common duct and the pancreatic duc- 
showed distinct evidence of the entrance of bile into its lumen.—EDb.] 


PROGNOSIS. 


As cholelithiasis generally runs its course without disturbance, and 
only rarely causes complicating inflammation of the bile-passages and 
of the tissues surrounding them, the prognosis, as a rule, is favorable. 
Gall-stones, at the same time, always constitute a danger for the patient, 
as they may at any time begin to migrate and produce inflammatory 
and ulcerative processes which, in their turn, cause a variety of diseases. 
These appear at times when they are least expected, and may suddenly 
attack the patient and endanger his life. All this must be taken into con- 


* Deutsche med. Woch., Aug., 1898, 4p. 491. 
+ Centralbl. f. innere Med., Sept. 24, 1898. 
{ Deutsche med. Woch., Feb. 16, 1899. 

§ Berlin. klin. Woch., Dec. 19, 1898. 





CHOLELITHIASIS. 587 


sideration when making a prognosis, and even though the stones be 
perfectly quiescent, the prognosis in regard to some of the lesions com- 
plicating cholelithiasis must be guarded. In cases where icterus appears, 
or where colic and great swelling of the liver or of the gall-bladder are 
present, or symptoms appear that indicate that the gall-stone is moving, 
the prognosis becomes unfavorable. Even under these circumstances, 
however, it need not necessarily be altogether bad. 

If a violent form of intermittent or of remittent fever appears, or if 
a gall-stone becomes impacted within the common duct and causes per- 
manent obstruction to the escape of bile, the prognosis is bad. The same 
can be said if signs of circumscribed peritonitis appear, or if empyema 
of the gall-bladder, suppurative cholangitis, or abscess of the liver com- 
plicate the disease. The prognosis is particularly bad if sudden perfora- 
tion into the peritoneal cavity occurs, and if, following this rupture, 
larger or smaller quantities of the contents of the bile-passages or of the 
gall-bladder are poured into the abdomen, the contents of the bile-passages 
being, as a rule, changed and abnormal, and therefore dangerous. The 
prognosis is also very bad if a gall-stone or gall-stones become impacted 
in the intestine and cause ileus, or, finally, if the presence of a carcinoma 
can be diagnosed from the appearance of long-continued icterus, great 
loss of strength, ascites, etc. 


DIAGNOSIS. 


The diagnosis of cholelithiasis can be made from all the symptoms 
discussed above in all their essential features. 

If the gall-stones remain quiescent, the diagnosis may often be very 
difficult. In many instances an examination of the region of the liver 
and the gall-bladder will lead to the discovery of a tumor of the gall- 
bladder in which the gall-stones can be distinctly felt. This can, how- 
ever, rarely be done, and it is still more difficult to elicit the sensation 
of crepitation described by older authors. In many cases the walls of the 
gall-bladder are so thick that the gall-stones cannot possibly be felt 
through them. Nodular tumors of the gall-bladder may, moreover, be 
due to carcinoma of the viscus. In the case of the latter lesion, however, 
the further course of the disease, and the discovery of metastases, will 
clear the diagnosis. Schwartz describes the following differences between 
a tumor of the kidney and an enlarged gall-bladder: A tumor of the gall- 
bladder can be depressed or pushed into the abdomen, but immediately 
returns to its original position; a tumor of the kidney, on the other hand, 
that extends into the region of the liver, will remain in the position into 
which it is pressed until it is pushed forward again by the hand of the ° 
physician. Gerard-Marchand calls attention to the fact that tumors 
of the gall-bladder cannot be pushed upward. 

Puncture of the gall-bladder and palpation of the contained gall- 
stones is quite dangerous, although this procedure has been recommended 
by Harley and others. As we can never know, however, whether the 
contents of the gall-bladder are septic or not, it is dangerous to puncture 
the gall-bladder, as some of its contents may exude through the opening 
and, if it should be infectious, cause peritonitis. 

Gall-stones cannot be demonstrated by the Réntgen rays for the 
reason that they are permeable for these rays owing to the cholesterin 
and relatively large proportion of organic matter which they always con- 
tain, as well as to the obscuring shadow of the liver. 


588 DISEASES OF THE BILE-PASSAGES. 


In the majority of cases an attack of gall-stone colic will be the first 
positive sign that reveals the presence of gall-stones. The diffuse pain 
and the other vague and varying sensations complained of, the feeling 
of pressure in the region of the gall-bladder, etc., are all of subordinate 
importance in the diagnosis of the disease. 

It is also possible to misinterpret the significance of the attack of 
colic and to confound it with intestinal colic, cardialgia, nervous hepatic 
colic, etc. Whereas, however, in the case of peptic ulcer the pain is 
liable to occur after eating, the pain in gall-stone colic usually appears 
toward midnight; that is, some time after a meal, and particularly after 
some error of diet of which the patient has been guilty. In other in- 
stances, again, it is true, the attack of gall-stone colic may occur very 
soon after eating, and the pain may even be felt in the median line, in 
the epigastric region, so that the similarity to a case of gastric ulcer is 
indeed very great. The pain will be in this location if the gall-stone is 
impacted near the orifice of the common duct. Violent retching and 
vomiting are more frequently seen in gall-stone colic than in the other con- 
dition. In intestinal colic the pain is usually located in the right hypochon- 
driac region and is not quite so violent; and, as a rule, it disappears as 
soon as belching, the passage of flatus, or defecation occurs. Lead colic 
is a disease that causes very violent symptoms, and the painis located in 
a region so similar to that in cholelithiasis that the two may often be con- 
founded. The former is seen particularly in men, whereas the latter 
occurs more frequently in women. Certain occupations, the handling 
of lead by the patient, a blue line on the gums, the absence of pain and 
swelling of the liver and of icterus, will all speak in favor of lead colic. 
The pain of renal colic is situated more in the lumbar region, while that 
of gall-stone colic very rarely radiates into this region. The former. 
usually radiates along the course of the ureter into the bladder and the 
genitals, while this rarely happens in gall-stone colic. An attack of | 
peritonitis, particularly if it is localized in the right hypochondriac region 
and is circumscribed, may cause diagnostic difficulties. Collapse, changes 
in the pulse-beat, and sensitiveness to pressure may be observed in both 
conditions. As a rule, the pain on pressure, the frequency and the 
smallness of the pulse, and the collapse are more pronounced in periton- 
itis. At the same time, cases of inflammation of the peritoneum may 
occur in which all these symptoms are indistinct and only present to a 
slight degree, and, on the other hand, all these symptoms may be present 
in an aggravated form in attacks of gall- stone colic. \ The type of breath- 
ing, it is true, is almost always purely costal in peritonitis, while in gall- 
stone colic a distinct movement of the diaphragm will generally be seen. 
Further, large quantities of indoxyl are, as a rule, voided in the urine 
during an attack of peritonitis; this does not occur in simple uncompli- 
cated cholelithiasis. It is often possible to make a differential diagnosis 
between cholelithiasis and an attack of perityphlitis extending upward 
along the right side of the abdominal cavity (as a result of dislocation 
of the appendix) by the aid of this indoxyl reaction of the urine. 

[Mention must be made of the possibility of an attack of gall-stone 
colic being erroneously looked upon as “gout of the stomach.” The 
latter is extremely rare, and the diagnosis should never be positively | 
made except by exclusion and from the simultaneous retrocession of more 
characteristic distant uratic manifestations.—ED.] ; 

Icterus is without doubt of the greatest importance in the recognition 


ee ee 





CHOLELITHIASIS. 589 


of cholelithiasis. It is true that this valuable sign is often absent in 
cases where the gall-stones are situated in the cystic duct or in the intra- 
hepatic bile-passages, or where they pass through the common duct very 
rapidly. The change in the intensity of icterus is of particular importance 
in the diagnosis of gall-stones. In the catarrhal form of icterus, in that 
form of icterus that is the result of compression of the bile-ducts from 
tumors or some external obstruction, icterus may persist for weeks and 
months without fluctuations in its intensity. This may, of course, also 
occur if the ductus choledochus is completely occluded for a long time 
by gall-stones. This, however, rarely occurs in simple cholelithiasis; it 
is possibly more frequent if carcinoma complicates the disease. Icterus 
usually appears during the course of an attack of gall-stone colic and 
soon disappears again. As a rule, this icterus is not very severe, but 
it has a tendency to recur, and, even if it persists for a long time, con- 
siderable fluctuations in its intensity are apt to occur. At the same 
time colored and acholic stools are alternately evacuated. It is not 
at all necessary that icterus of the skin should exist. 

What can be found out in regard to the localization of the gall-stones 
—that is, whether they are located in the gall-bladder, the cystic duct, 
the common duct, etc.—has been described in the section on symptomat- 
ology; and the same statements apply to the diagnosis of ulceration, 
the formation of fistula, the entrance of gall-stones into the intes- 
tine, etc. 

From a therapeutic point of view, it is, in addition, important to 
determine whether pyogenic organisms have penetrated the bile-passages ; 
in other words, it is important to determine the presence or absence 
of suppurative cholangitis and cholecystitis. 

The chief symptom of these conditions is the appearance of an inter- 
mittent or remittent type of fever of long duration. At the same time 
a tumor of the spleen may be noticed, while septicopyemic metastases in 
other organs and symptoms of infectious endocarditis point toward the 
diagnosis. mpyema of the gall-bladder produces swelling of and pain in 
the organ. Sometimes it is possible to aspirate a purulent fluid. Puncture 
of the gall-bladder, however, is severely condemned by the majority 
of physicians, and particularly by surgeons, for the reason that great 
danger of peritonitis exists in case some of the contents of the gall-bladder 
should enter the abdominal cavity. Even if all possible precautions 
are taken,—if, for instance, very thin needles are employed, etc.,—a 
circumscribed form of peritonitis will almost invariably be produced. 
Naunyn—who, by the way, is a strong advocate of exploratory puncture 
of the gall-bladder for diagnostic purposes—makes this statement himself. 
In cases where the walls of the gali-bladder are very thin and are under 
pressure from the tension of the fluid they inclose, it will be well to be 
exceptionally careful. After the little operation, an ice-bag should be 
applied to the region of the gall-bladder and the patient kept in bed 
for at least eight hours. If the fluid that is aspirated is dark brown or 
yellowish in color and contains some of the bile-constituents but no 
micro-organisms, then we are dealing with a simple ectasy of the gall- 
bladder; if a colorless or slightly colored fluid containing mucus or squa- 
mous epithelium but no bile constituents is aspirated, and if this fluid is 
watery or viscid, then we have hydrops of the gall-bladder; again, if the 
fluid aspirated is colorless or slightly bile-stained and contains albumin, 
desquamated cylindric and squamous epithelium, micro-organisms, in 


590 DISEASES OF THE BILE-PASSAGES. 


particular Bacillus coli, we are dealing with cholecystitis seropuru- 
lenta; finally, if the fluid is purulent and contains no bile whatever, the 
case is one of empyema of the gall-bladder (Kleefeld). 

The formation of abscesses of the liver, which are as a rule multiple, 
frequently cannot be recognized. In many instances the abscesses are 
in a location where they cannot be palpated; circumscribed pain, fluctua- 
tion, etc., may be absent; while exploratory puncture for diagnostic 
purposes is as dangerous here as in empyema of the gall-bladder. (For 
details see the section on abscess of the liver.) The existence of this 
lesion can be suspected if the symptoms of suppurative cholangitis persist 
for a very long time in cholelithiasis, if the liver is painful, if symptoms 
of pyemia appear, and if purulent inflammation of neighboring parts 
can be recognized. 

In all cases of cholelithiasis the most positive criterion for the presence 
of gall-stones is the discovery of concretions in the stools. While some 
authors—as, for instance, Wolff—claim to have found them in all cases, 
still there are instances in which they cannot be discovered in spite of 
the most careful and diligent search. They may be retained within 
the gall-bladder or the bile-passages and there cause attacks of colic 
from time to time; they may also become disintegrated in the intestine 
or may be retained within the bowels for a long time even without pro- 
ducing any of the symptoms of occlusion or of ileus. For all these reasons 
it is often necessary to search the stools for days before they are found. 
It is not well to employ the old method of Prout, which consists in diluting 
the stools with water, in stirring them and then limiting the examination 
to the particles that float on top; but the stools, after dilution with water, 
should be filtered through a fine sieve and the residue washed out re- 
peatedly with water; it is not advisable during this manipulation to 
crush the stools, for the reason that the more recently formed stones are 
often very soft and may be crushed beyond recognition. If the stools 
are analyzed as above, it will often be possible to detect the presence 
of very small and quite soft stones. Gall-stones may readily be con- 
founded with all sorts of pips and kernels from berries, pears, etc.; in 
addition, small hardened masses of fecal matter, and concretions of cal- 
cium- and magnesia-soaps, that are found after an abundant ingestion of 
fat, may lead to confusion. If the masses found are carefully examined 
for cholesterin, bile-pigment, and the characteristic structure of gall- 
stones, mistakes of this kind are not liable to happen. 

[The ‘“ball-valve” stone in the common duct at times gives rise to- 
difficulties in diagnosis. The recurrence of attacks of pain, followed by 
fever and increasing icterus, make a picture easily recognized if the 
condition is borne in mind.—ED.] 


PROPHYLAXIS, 

In order to prevent the formation of gall-stones the following mea- 
sures, recommended in our discussion on the etiology of gall-stones,. 
should be employed: 

* 1. Stasis of bile should be prevented. 

2. All factors that may lead to an infection of the bile-passages,. 
and in this manner to a stone-forming catarrh, should be strenuously 
avoided. 

If sufficient care is taken that the clothing in the region of the liver 


ee se CS r 


CHOLELITHIASIS. 591 


and the gall-bladder is not too tight, congestion of these parts is not 
so liable to occur. In subjects, therefore, whose bones are slender and 
delicately constructed, who are thin with a poorly developed muscular 
system and no adipose layer, tight corsets should be forbidden; and 
they should be instructed never to wear tight skirt-bands nor to attach 
their clothing by tight bands nor to wear tight apron-bands, belts, etc. 
Women who are constructed in this way should be told to wear loose 
clothing and corsets that are made like jackets and are suspended by 
shoulder-straps and that permit the other clothing, shirts, underwear, 
etc., to be buttoned on (see page 395). If the clothing is arranged in this 
way, its weight will be brought to bear on the shoulders and not on the 
epigastric and hypochondriac regions. It is also well to advise people 
predisposed to gall-stones and of the peculiar build described above to 
loosen their clothing after eating; 7. e., as soon as the flow of bile begins. 

Physical exercise also counteracts the stasis of bile. Walking, 
gymnastic exercises, fencing, horseback-riding, etc., are efficient pre- 
ventives. Bathing, too, may exercise a favorable effect, particularly 
with swimming. In the case of those who cannot or will not persevere 
in these exercises, it may be well to advise massage of the body or medico- 
mechanical exercises. Energetic physical exercise influences the flow 
of bile not only directly and mechanically, but also indirectly by increas- 
ing the peristaltic action of the bowels and the evacuation of the contents 
of the intestine. 

Constipation must be relieved as much as possible by the adminis- 
tration of laxatives, particularly of Glauber’s and Epsom salts. In the 
same way a course in one of the bathing resorts, such as Carlsbad, Marien- 
bad, Kissingen, etc., may act in a prophylactic manner. 

Fr. Hoffmann has sounded a warning against eating at too long inter- 
vals. Frerichs has also emphasized this, for the reason that under these 
conditions the bile is retained too long in the bile-passages and the gall- 
bladder. A diet that is too uniform and that contains too much fatty 
food is also to be avoided. A régime of this kind seems to predispose 
to catarrh of the stomach and intestine, and this may readily extend to 
the bile-ducts. 

Particular care should be taken to avoid all infections of the intes- 
tine, so obviating the development of a stone-forming catarrh of the 
bile-passages. It is, of course, a difficult matter to guard against these 
infections, because a small quantity of spoiled food or any of the patho- 
genic germs may induce infectious processes of different kinds. As 
accidents of this kind are most apt to occur if the diet is too uniform 
or if too much food is eaten, so that the digestion is overtaxed in one 
or in several directions, it will be best to advise a moderate mode of life 
and the taking of a mixed and not too abundant diet. The general 
rules and regulations formulated in the paragraphs on diet in the section 
on treatment may be followed to advantage. A close observance of 
these rules will do much toward an avoidance of gall-stone formation. 


TREATMENT. 


The treatment of gall-stones will depend greatly on the presence 
or absence of complications; 7. e., whether the object desired is simply 
to remove gall-stones that may be present, and thus do away with the 
symptoms caused by their presence, or whether the disease is com- 


592 DISEASES OF THE BILE-PASSAGES, 


plicated by cholecystitis and cholangitis and it is desired to cure or relieve 
these conditions. 

In the former, the regular form of gall-stone disease, dietetic mea- 
sures, the drinking of certain waters, etc., and treatment with drugs 
must be chiefly considered. In rare cases only will it be necessary to 
consider the advisability of surgical measures from the beginning. 

In the dietetics of cholelithiasis the views of different authorities 
are in part diametrically opposed. This is explainable from the different 
views entertained by different authors in regard to the formation of 
gall-stones, the genesis of cholesterin, the importance of intestinal 
catarrhs, etc., some of these views being necessarily quite incorrect. 

Some, as Bouchard, J. Kraus, and others, debar all fatty food, for the 
reason that they believe that such a diet increases the formation of choles- 
terin. They base their view on certain investigations that seemed to show 
that the administration of large quantities of fatty food causes an in- 
crease in the quantity of cholesterin. Naunyn and Thomas oppose and 
combat this idea. According to Jankau, the introduction of cholesterin + 
itself into the organism does not increase the amount of cholesterin 
formed. The amount of cholesterin is dependent on the degree of catarrh 
present in the bile-passages. 

On the other hand, the administration of large quantities of fat, as 
recommended by Dujardin-Beaumetz, is not indicated, as the cholagogue 
action which he claims for fat is only slightly manifested; in fact, could 
not be determined at all in several investigations that were undertaken 
for this purpose. 

It seems well in the case of gall-stones to avoid the ingestion of too 
much fat, for the reason that such a diet seems to predispose particularly 
to disturbances of the gastric digestion, and may in this manner lead to 
the formation of intestinal catarrhs which, in their turn, may extend to 
the bile-passages. or the same reason the patients should be advised 
to avoid all excesses of whatever kind, including excessive eating and 
drinking, the abuse of alcohol, of spices, etc. These restrictions will be 
particularly indicated in all those cases in which disturbances of gastric 
or intestinal digestion, such as catarrhal conditions, already exist. In 
all cases of this character it will be well, therefore, to advise a very light 
and readily digestible diet, corresponding to the abnormal digestive 
conditions indicated. The most suitable diet seems to be a mixed one 
containing plenty of proteid, not too scanty or uniform, so that an abun- 
dant quantity of bile-acids is produced, and so that the flow of bile may 
be stimulated and maintained. It is a good plan to advise frequent 
meals only three hours apart during the course of the day. It seems 
superfluous to advise eating something in the middle of the night as long 
as the patient will surely eat a breakfast soon after rising. It is also 
well to advise the ingestion of an abundant amount of fluid, for while 
an abundant or an excessive amount of water does not stimulate the 
flow of bile or increase it, at the same time too little water is known to 
cause thickening of the bile, and in this manner possibly indirectly con- 
stitute an impediment to its flow.. 

‘Bramson has argued particularly against the use of water containing 
much calcareous material, as he believes. that this will lead to an in- 
creased excretion of chalky matter through the bile. Hankau, however, 
has demonstrated that the ingestion of water containing much lime 
does not lead to an increased excretion of this substance in the bile, 


i 





CHOLELITHIASIS. 593 


and that the amount of calcium excreted in the bile is independent of 
the amount ingested at any given time. 
In order to promote an unobstructed flow of bile, it is necessary to 


_ instruct the patient to wear loose clothing—a point already discussed 


in the section on the prophylaxis of gall-stone formation. For this 
reason women should be advised to wear loose, soft, and wide corsets 
attached by shoulder-straps; to these the skirts, etc., should be attached 
by buttons, and all tight belts, skirt-bands, or other supports constricting 
the waist should. be discarded. After eating, particular care should be 
taken that the patient rests quietly and that the clothing is loosened. 
Exercise favors the flow of bile, and for this reason patients who 
are lazy and fat should be induced to take regular physical exercise. 
Walking is a very good form of exercise; and, particularly in the case 
of women, long walks should be advised. Domestic duties, housework 
of all kinds, do not furnish sufficient exercise of the right kind, since 
patients in doing housework sit down or stand a great deal more than 
they realize. Other forms of exercise are also good, as, for instance, 
horseback-riding, riding a bicycle, rowing, swimming, mountain-climbing, 
gymnastic exercise, medico-mechanical exercises, etc. In the course 
of such exercises it may happen that a gall-stone becomes dislodged and 
begins to wander, so that an attack of colic is produced in this manner. 
This may happen during horseback-riding, jumping, dancing, ete. In 
case the gall-stone passes through the ducts and is evacuated, such an acci- 
dent will of course in its ultimate consequences be of use to the patient. 
On the other hand, it may of course happen that gall-stones become 
lodged in the cystic or the common duct and remain firmly impacted. 
In a case of this kind all the unfortunate results of such an occurrence 
may be witnessed—inflammatory processes may be set up in the vicinity 
of the stone, icterus may occur, or perforation of the duct with all its 


sequels may take place. It may also happen that rapid or sudden 


motions of the body may cause an impacted gall-stone to perforate the 
walls of the duct in cases where the latter had become attenuated, an 
occurrence from which serious damage may result. In uncomplicated 
cases of cholelithiasis the latter emergency will be exceedingly rare. In 
cases where the presence of ulcerative processes or of other complica- 
tions is suspected, the patient should be warned against indulging in too 
violent exercise, and should be particularly advised against performing 
sudden movements that cause a succussion of the body. Among these . 
may be mentioned horseback-riding, jumping, dancing, or such acts as 
riding in a wagon with bad springs over defective roads. 

Massage of the body acts favorably in the same sense as exercise 


of other kinds. In cases where the sluggishness of the bowels can be 


relieved by massage, the effect is especially good, as an increased peris- 
taltic action of the bowels is induced, and this is, as a rule, transferred 
to the bile-ducts, by which the musculature of the bile-passages is stimu- 
lated to increased action and the stagnation of bile counteracted and 
corrected. Direct massage of the gall-bladder rarely leads to an evacua- 
tion of gall-stones, although some cases are on record in which, following 
repeated palpation and manipulation of the gall-bladder, gall-stones 
were induced to move, entered the bile-ducts, and were finally evacuated. — 
Van Swieten long ago recommended tapping the gall-bladder with the 
fingers in the treatment of gall-stones. The employment of electricity, . 

38 


‘ 


594 DISEASES OF THE BILE-PASSAGES. 


either in the form of the galvanic or of the faradic current, has been 
advised by some authors, but is of doubtful value. 

For a great many years one of the aims in the treatment of chole- 
lithiasis has been to promote the solution of gall-stones within the bile- _ 
passages after they had formed there. All attempts in this direction 
have, however, so far been altogether unsuccessful. It may at times 
occur that a solution of gall-stones takes place. Naunyn has demonstrated 
this by introducing gall-stones into the gall-bladder of dogs. Normally 
disintegration and fragmentation of gall-stones is, moreover, quite fre- 
quently observed. The bile is a good solvent for cholesterin, but not 
to such a degree for stones that contain a considerable portion of calcium. . 
The alkaline salts of the bile-acids in particular seem to exercise this 
effect (Schiff and others). As gall-stones are soluble in alkaline fluids, 
alkalies were recommended for the treatment of gall-stones (Fr. Hoff- 
mann) even as early as the eighteenth century. Since that time their 
value in the treatment of gall-stones has become established. They are 
employed especially in the form of different mineral waters, as the waters 
of Carlsbad, Vichy, Ems, Bertrich, and many others. Warm saline 
waters have also been recommended for this purpose, as the waters of 
Wiesbaden, Soden, Nauheim, and others. Some benefit is unquestion- 
ably derived from the use of these waters. From all experimental in- 
vestigations, however, it seems more than doubtful whether these waters 
in any way influence the alkalinity of the bile and in this manner dis- 
solve gall-stones. Their cholagogue action is also doubtful and has 
not been experimentally demonstrated. Many authors attribute a 
beneficial effect to the large quantities of water that are swallowed in 
the course of such a line of treatment (Leichtenstern), and express the 
belief that the ingestion of all this fluid promotes the flow of bile and 
causes an increased excretion. Animal experiments, however, do not 
show that such an effect on the bile is exercised by excessive drinking 
of water. It is probable that the effect of large quantities of water on 
the stomach and the intestine is the chief factor and acts favorably on 
the bile-passages. Catarrhal conditions of these organs are ameliorated 
by this procedure and indirectly act on similar catarrhal conditions 
that may be present in the bile-ducts or the gall-bladder. The waters 
of those springs that contain Glauber salts act favorably on the bowels, 
promote regular evacuations, and in this manner the peristaltic action 
of the bowel musculature is stimulated, and this stimulus is transmitted 
to the musculature of the bile-ducts, causing increased peristalsis in these 
parts and aiding the passage of the gall-stone. Consequently the drink- 
ing of these waters is often followed by the passage of gall-stones. The 
use of bitter waters—a course of treatment in Marienbad and other 
places—often leads to the same result. The change in the mode of life 
of the patients during the time they are taking the course of treatment 
plays a most important réle, the regulation of physical exercise, the 
moderation and regulation of the diet, and other features explaining to 
a great extent the beneficial effects of the waters of Carlsbad, Vichy, 
and of other places. This also explains why certain patients who could 
be benefited as much if they remained at home, lived sensibly, and took 
Carlsbad waters, bicarbonate of sodium, Glauber salts, or rhubarb, never 
really notice any benefit until they go to the different watering-places 
and take the waters there. It appears to these patients that all their 
complaints are much relieved as soon as they arrive at these places, and, 


CHOLELITHIASIS. 595 


in fact, the treatment they undergo is often followed by the passage of 
gall-stones, etc. 

The different herb extracts that were formerly so popular (Hoffmann 
and others) probably act in a similar manner, the administration of 
these infusions having been based on Glisson’s observation that in cattle 
gall-stones seem to disappear in summer as soon as the animals begin 
to eat green herbs and grass. 

The administration of fats, particularly of olive oil, has also been 
recommended in order to promote the dissolution of gall-stones. It 
is doubtful, however, whether fats really enter the bile, although Virchow 
and Thoma have made statements to this effect. At all events, they 
cannot possibly exercise any effect on gall-stones that consist largely 
of chalky material. 

Durande, in 1782, recommended a remedy that created a great deal 
of interest. It consisted of equal parts of ether and turpentine. Accord- 
ing to this author, twenty to thirty drops of the remedy should be taken 
three to four times daily. In many cases the bad taste of this remedy 
makes it difficult to take (Pujol, J. P. Frank, and others), for which 
reason Durande modified his prescription and ordered a mixture of three 
parts of ether with one part of turpentine. Later Soemmering and 
others used ether alone mixed with the yolk of an egg. Of late years 
the remedy has again been recommended by Lewaschew, who bases his 
recommendation on the experiments of Botkin and on his own experi- 
ence. It is true that ether and turpentine are excreted in part by the 
bile, but in so small a quantity that they cannot possibly exercise a sol- 
vent effect. Vallisnieri recognized this quite correctly long before Du- 
rande recommended the remedy, and discovered the fact that gall-stones 
are soluble in turpentine, but refrained from advising the internal use of 
the remedy for the solution of gall-stones for the reason stated. Some 
authors (Frerichs) have attributed the favorable effect sometimes exer- 
cised by Durande’s remedy in cases of gall-stones to the calming effect 


-of the ether; while others state that peristalsis is stimulated or that efforts 


at vomiting are induced that help to expel the stone. It is known that 
ipecacuanha and tartar emetic have been employed for the same purpose. 
Dupareque has seen beneficial effects follow the administration of a mix- 
ture of ether and castor oil. 

Chloroform belongs to the same class of remedies. This drug was 
recommended by Corlieu, Bouchut, Gobley, and others. As a rule, it is 
administered in the dose of 5 or 6 drops in water or of 1 gm. in 150 of 
water, a tablespoonful being given at a time; or it may be given in cap- 
sules of 0.1 gm. Many physicians recommend the drug highly; others 
claim to have seen no benefit from its employment. It does not seem 
to possess any anodyne properties and cannot stop the pain of an attack 
of colic. If ether or chloroform is inhaled during the attack, according 
to Murchison, the effect is, of course, different. 

The oil treatment even to this day plays a prominent réle in the treat- 
ment of gall-stones. This method is of American origin, was first intro- 
duced by Kennedy, and later advocated warmly by Chauffard in France 
and Rosenberg in Germany. [Lindley Scott * found no difference in 
the solvent action of petroleum or almond and olive oil. A quarter of 
the weight of calculi was lost in twelve hours, a half of their weight in 
twenty-four hours, and all but the nucleus was dissolved in thirty-six 

* Brit. Med. Jour., Sept. 25, 1887, p. 798. 


596 DISEASES OF THE BILE-PASSAGES. 


hours.—Eb.] It is erroneous to attribute a cholagogue action to oil, as 
has been done by several writers. Rosenberg recommends the adminis- 
tration of 180 to 200 gm. of olive oil with 0.5 of menthol, 20 to 30 gm. of 
cognac, and the yolks of two eggs to be taken in one or in several doses. 
Senator has recommended the use of lipanin instead of olive oil, Blum 
advises the oleate of sodium. [Clemm * also employs the latter remedy 
in doses of 0.75 gm., and Artault + has claimed a prophylactic effect 
from the taking of 8 to 16 minims of olive oil before breakfast for ten 
days in each month.—Ep.] It is probably best to swallow the disagree- 
able remedy at one dose instead of distributing it in tablespoonful doses 
over the whole day, although the latter plan has many advocates. 
Friedr. Hoffmann, it may be mentioned, recommended almond oil for 
the treatment of gall-stones in the eighteenth century ; cottonseed oil, too, 
has been recommended. It is true that after the administration of these 
different oils gall-stones often pass. The best explanation for this is 
that the remedy, like many other drugs, acts as an emetic or a laxative, 
and in this manner promotes the emptying of the bile-passages. There 
can be no question in regard to the utility of castor oil, and this drug 
has often been employed with great advantage. Another factor must be 
remembered in judging of the value of all these oils in promoting the 
passages of gall-stones, and that is the possibility of their forming con- 
cretions of saponified oleic acid in the intestine. These masses, when 
they appear in the stools, may very well simulate small gall-stones 
(Chauffard, Dupré, Rosenberg, Prentiss, Fiirbringer, and others). Pujol 
long ago described masses of this kind formed from almond oil. Un- 
digested particles of food, pieces of pear, etc., may also lead to errors. 

Enemata of 400 to 500 c.c. (13 to 17 fluidounces) of oil at 30° C. 
(86° F.), at first reeommended by Blum, may act favorably by regulating 
the action of the bowels. They should be given at first daily, later at 
longer intervals. 

Glycerin administered with Vichy in daily doses of 15 to 20 gm. seems 
to be without value. This treatment was first recommended by Ferraud.. 

The attempt has frequently been made to introduce calomel into 
the therapeutics of cholelithiasis, as has been done lately by Sacharjin. 

Very often the physician is called while the patient is suffering from 
an attack of gall-stones, and it is his first duty to alleviate the suffering. 
He must also attempt to cut short the attack by promoting the passage 
of the stone, and, finally, avoid many of the complications, like ulcera- 
tion, inflammation of the surrounding tissues, etc., that might: follow 
impaction of the stone. 

Opium or morphin has for a long time been recommended to stop 
the pain (van Swieten, Coe, J. P. Frank, and others). These drugs 
not only relieve the great pain, but also help to relax the spasm of the 
muscles of the bile-ducts. Pujol, it is true, warns against this procedure 
because he fears that the gall-stone will remain where it is, and in this 
manner “the wolf be locked up in the sheepfold’’; but as it is known 
that the spasmodic contractions of the muscles of the walls of the bile- 
ducts are, if anything, an obstacle to the free passage of the gall-stone, 
an arrest of these contractions can only be of use. The administration 
of narcotics is therefore indicated, and is of value in promoting the pas- | 
sage of a gall-stone. At first a hypodermic injection of from 0.01 to 
0.02 of the hydrochlorate of morphin is given, or 20 drops of the tincture 

* Wien. med. Woch., 1902, No. 16. + La Med. Moderne, 1901, p. 392. 





CHOLELITHIASIS. 597 


of opium are administered by mouth, followed in from two to four hours 
by another 5 to 10 drops, the dose to be repeated every two to four 
hours. 

Belladonna has further been recommended for its antispasmodic 
action (Trousseau, Frerichs, Murchison, Stricker, and others). It does 
seem as if this drug were capable of relieving the spasmodic contraction 
of the muscles and in this manner of promoting the evacuation of the 
gall-stone. Itis best administered as the extract of belladonna in powders 
of 0.02 to 0.03 or dissolved in aqua amygdala amara (1.0 to 10.0), 5 to 10 
drops every two hours. It is well in giving belladonna to watch the 
patient carefully, for the reason that excessive doses may produce symp- 
toms of poisoning, while doses that are too small exercise no effect 
whatever. 

Antinervines, as antipyrin, phenacetin, preparations of salicylic acid, 
etc., sometimes stop the violent pain. Inhalations of chloroform should 
be administered only in cases with exceptional excitement. Chloral 
hydrate and other narcotics of this class as a rule are without effect. 
In case they do not put the patient to sleep, they are apt to produce 
great excitement, and later unconsciousness. 

Warm applications in the form of cataplasms, of dry or wet cloths, 
of poultices kept warm by means of a thermophor applied over the region 
of the liver are recommended, and seem in fact to be able to relieve much 
of the distress; but if inflammatory processes are going on in the region 
of the gall-bladder, they are frequently not so well borne. In cases of 
this kind leeches or applications of cold by an ice-bag placed over the 
painful region will often relieve. If the patient is very sensitive to pres- 
sure, the ice-bag can be suspended over the painful spot, barely touch- 
ing it without exercising any pressure (Bricheteau). In plethoric sub- 
jects, following the procedure of older physicians, blood-letting is often 
beneficial and may relieve the spasms. Drinking warm fluids, different 
herb-infusions, etc., occasionally does good. 

If it is possible to place the patient in a warm bath of about 40° C. 
(104° F.), the pain and the spasm will usually be relieved, and many 
patients are comforted if kept for a long time in a warm bath. Hysterical 
seizures, too, are best aborted and treated by immersing patients in a 
warm bath or by pouring cold water over them. 

It is advisable at the same time to procure a good evacuation of 
the bowels during the attack of gall-stone colic. This is best accom- 
plished by the administration of castor oil, Epsom salts, artificial Carlsbad _ 
salts, etc. As, however, all these laxatives are vomited in many cases, 
it is imperative to employ enemata. Large quantities of cold or of hot 
water applied in this way act very beneficially, as do also 1 to 2 liters 
of chamomile tea, or, if the stools are very hard, 200 to 300 gm. of olive 
oil injected into the rectum. If the patients are very weak and if the 
pulse is small and rapid, wine, champagne, and similar stimulants must 
be administered. Here camphor injected hypodermically in doses of 
from 0.1 to 0.2 in oil is often very useful. 

In cases, finally, where all internal medication is without avail, and 
where despite all the remedial measures employed attacks of gall-stone 
colic recur, and where the strength of the patient is being undermined, 
his nervous system shattered, and he is rendered incapable of attending 
to his affairs, surgical interference should be advised. In the present 
state of our knowledge of surgical technique and experience such an 


598 DISEASES OF THE BILE-PASSAGES. 


operation is indicated, and the patient may thus for all time get rid of 
his gall-stones. 

At the same time it must be remembered that each attack of gall- 
stone colic may be the last one, and that a permanent cure of the condi- 
tion may occur even after many severe and grave attacks of gall-stone 
colic. In some cases, too, operations have been performed at a time 
when the last gall-stone had been evacuated and passed through the 
common duct. It must also be remembered, on the other hand, that in 
cases where impaction of gall-stones occurs repeatedly the danger of 
cholangitis and ulceration with all its consequences exists, and that a num- 
ber of local changes may develop insidiously that complicate a subsequent 
operation—I refer to adhesions, stenoses, narrowing of the bile-passages, 
etc. [The danger of acute hemorrhagic pancreatitis is an additional 
reason for operative interference.—ED.] 

Operative interference should be advised at once if signs of suppura- 
tive cholangitis, of cholecystitis, or of incipient peritonitis appear. 

It is true that even in these cases recovery may occur without opera- 
tive interference; but the prospect of a cure and the general outlook are 
much better if the bile-passages are opened as soon as possible and a 
fistulous opening is created. This operation will be described below. 
Under circumstances of this kind the hepatic and the common duct 
have been drained through a fistula with good results; while in some 
instances it has been necessary to open the common ducts and to flush 
the channel thoroughly through a bent metal tube (Kehr). 

In case the operation, notwithstanding the presence of cholelithiasis, 
is not permitted: by the patient, it will be necessary to attempt to allay 
the inflammation by hot or cold applications in the shape of warm com- 
presses, the ice-bag, etc.; at the same time the bowels must be regulated 
and the feces regularly evacuated by the use of enemata, laxatives, etc., 
in the manner indicated above. Antibacterial‘remedies have also been 
recommended, such as salicylic acid and the preparations of this drug 
(such as salol), oil of turpentine, quinin, etc. The most rational method 
of administering salicylic acid appears to be in the form of the salicylate 
of sodium (four to six times daily in doses of 1.0). According to Naunyn, 
the cholagogue action of this preparation can in this way be utilized, 
in addition to its antibacterial powers. If we succeed, by the applica- 
tion of all these measures, in allaying the inflammation, and if the gall- 
stone is passed through the common duct or through a fistula, a Carlsbad 
cure or a course of some other waters should be advised, by which we 
may help remove the last traces of the inflammation and prevent a 
recurrence of attacks of gall-stone colic. 

In cases where the common duct is occluded by a gall-stone, great 
danger arises to the patient from stasis of bile, and an operation becomes 
imperative. | 

If icterus has persisted for a long time, and a tendency to hemor- 
rhage exists as a result, the operation will be fraught with considerable 
danger. Death from bleeding may occur very rapidly even if all the 
plood-vessels are carefully ligated and if all hemorrhage is stopped by 
careful packing and tamponage. It is, therefore, advisable not to 
wait too long before operating in cases that are complicated by severe 
grades of icterus. At the same time a great many operations for gall- 
stones are on record which terminated favorably despite the presence 
of icterus and the resulting tendency to hemorrhage, so that, if no other 


CHOLELITHIASIS. 599 


prospect of relief or of cure exists, the operation should by all means 
be advised. 

As soon as peritonitic symptoms appear with any degree of severity 
this should, too, be considered an indication for operation. 

The operative treatment of cholelithiasis has only been generally 
employed during the last fifteen years; and, as a result of the constant im- 
provement in the technique of operating and the introduction of aseptic 
and antiseptic methods, the results obtained have grown more and 
more favorable. 


Petit, the first surgeon to attempt opening of the gall-bladder for inflammation 
following cholelithiasis, limited the operation to cases in which he was positive that 
adhesions had formed between the gall-bladder and the walls of the abdomen. Even 
under these conditions a majority of the clinicians of the end of the eighteenth and 
the beginning of the nineteenth century condemned it. Sharp, Morand, and Haller 
supported Petit in his views during this time, and Herlin, l Anglas, and Duchainois 
attempted to demonstrate their feasibility by experimentally extirpating the gall- 
bladder from animals without detriment. Bloch went even further than Petit and 
advised the artificial creation of adhesions between the gall-bladder and the abdom- 
inal walls as a step preliminary to the operation of incision. Richter, Sebastian, 
Graves, Fauconneau-Dufresne, and others made similar suggestions. Thudichum, 
in 1859, advised sewing the gall-bladder to the abdominal walls as a preliminary step, 
and opening the viscus after six days. In 1867 Bobbs performed a cholecystotomy, 
having mistaken the tumor of the gall-bladder for a cyst of the ovary. In 1878 
Kocher performed a successful operation for empyema of the gall-bladder, and at the 
same period Sims operated on a case of cholelithiasis according to the method of 
Thudichum, with an unfavorable result. After this time Keen, Lawson Tait, Rosen- 
bach, and Ransohoff performed numerous operations for gall-stones. In 1882 
Langenbuch was the first to perform extirpation of the gall-bladder (cystectomy), 
and Winiwarter performed the first cholecystenterostomy in a case in which the 
common duct was occluded. Following these operations, Kuster recommended the 
ideal operation of cystotomy: viz., cystendesis (Courvoisier). This consisted in 
opening the gall-bladder, evacuating its contents, closing it again, and replacing it in 
the abdominal cavity. Of late years the bile-ducts themselves, in cases where the 
gall-stones were situated within these passages, were incised directly (cysticotomy 
and choledochotomy). The last operation was usually undertaken from the front 
of the body; in some instances from the lumbar region. Finally, an operation has 
been performed several times that consists in making an artificial fistula between the 
ductus choledochus and the intestine—choledochoduodenostomy and choledocho- 
peer eaee both of which operations are indicated whenever the common duct is 
occluded. 


This is not the place to describe the different operations and to go 
into the detail of their technique. All these descriptions will be found 
in the works of Riedel, Kehr, and others, and, above all, in the book 
on this subject written by Langenbuch. 

The operation is rarely performed in a typical manner, particularly 
in complicated cases. The presence or absence of gall-stones, the exist- 
ence or non-existence of adhesions, are all complications that can only 
be discovered after the abdomen has been opened, and the surgeon will 
have to be largely governed by -what he finds. In many instances the 
case will appear to be a simple one and the operation will appear easy, 
but as soon as the abdomen is opened unsuspected difficulties may be 
discovered that necessitate a complete change of plan. 

Cystotomy is the operation that: is most frequently performed. If 
several large gall-stones are present in the gall-bladder without any 
inflammatory symptoms and without any evidence of irritation of the 
surrounding tissues, and if, finally, gall-stones are absent from the bile- 
ducts, the ideal form of cystotomy, 7. e., cystendesis, may be performed. 


600 DISEASES OF THE BILE-PASSAGES. 


The gall-bladder is opened and its contents evacuated; the organ is then 
thoroughly flushed and cleansed. If it is found that the bile can flow 
through the cystic duct,—in other words, if this channel is patent,— 
and if no gall-stones can be found in the other ducts, the gall-bladder 
is closed by suturing and replaced in the abdomen. It must be remem- 
bered that whereas new gall-stones rarely form (as, for instance, around 
silk sutures, Homans), it may nevertheless happen that small concre- 
tions are left in the gall-bladder and that inflammatory symptoms may 
appear later as a result of infection of the gall-bladder. All these sequels 
and complications may endanger the replaced gall-bladder and may lead 
to peritonitis; if this occurs, the abdomen and the gall-bladder must be 
reopened. 

Cystotomy performed in the ordinary manner protects against all 
these dangers, but has the disagreeable feature that it leaves the patient 
with a bothersome biliary fistula that may call for a tedious after-opera- 
tion in: those cases where spontaneous closure does not occur. In per- 
forming the operation the gall-bladder is found, pulled as far as possible 
toward the abdominal wall, and attached to it by stitching. If the 
gall-bladder contains pus and there seems to be danger of the inflam- 
mation spreading to the peritoneum, it is best to open the gall-bladder 
at once and to evacuate its contents, the gall-stones that the organ may 
contain being removed with forceps and spoon-shaped instruments. 
In the case of old subjects, the attempt should be made to open the gall- 
bladder at once and to remove the gall-stones, as this does away with 
the necessity of a second operation (single cystotomy). 

Cystotomy in two stages is indicated in cases where the gall-bladder 
is contracted and is situated so deep down in the abdomen that it cannot 
readily be approximated to the abdominal walls. All adhesions that may 
exist are loosened and the place marked (by a thread) where it is pur- 
posed, later, to make the incision. <A cavity is formed by parts of the 
mesentery (that is pulled up for this purpose), the parietal peritoneum, 
the liver, etc., and filled with tampons. At the expiration of from 
twelve to twenty-four hours the tampons are removed, the gall-bladder 
is opened, evacuated, ete. 

Following this operation a fistula remains; through the new channel 
are poured changed contents of the gall-bladder, gall-stones, and later, 
in case the cystic duct is patent, bile. If the common duct is occluded 
all the bile is poured out through the fistula. In cases of this character 
it is frequently necessary to perform secondary operations (choledo- 
chotomy, enterostomy). As a rule, the fistula closes spontaneously, 
particularly if the flow of bile into the intestine is not impeded. 

Cholecystectomy as well as the ideal operation of cystotomy prevent 
the formation of a fistula; at the same time this operation may be more 
readily followed by disagreeable complications. The absence of the 
gall-bladder is of subordinate significance. Although it has been claimed 
that the continuous flow of bile into the intestine and the deficient re- 
tention of this excretion can produce certain digestive disturbances, 
such as emaciation, diarrhea, etc. (Oddi), all these troubles are soon 
relieved and in a measure compensated by a vicarious dilatation of the 
common duct. In those cases, however, where gall-stones are situated 
in the cystic, the common, or the hepatic duct, and are not discovered 
during the operation, it is quite possible that these concretions may 
cause much trouble, as they cannot be reached so easily as if a 


CHOLELITHIASIS. 601 


fistula had been formed, a fact constituting an objection to the opera- 
tion. Besides, the gall-bladder may be adherent to the liver and other 
adjacent tissues, and the extirpation of the organ may be very difficult 
under these circumstances. If empyema is present, it can, further, 
very well happen that the neighboring tissues become infected when it 
is attempted to loosen the gall-bladder from its surroundings. On the 
other hand, it must be emphasized that in cases where the wall of the 
gall-bladder is diseased but the bile-passages are intact extirpation of 
the organ is followed by splendid results (see Langenbuch and others). 

If gall-stones are present in the cystic duct, the attempt can be made 
to reach them from the incised gall-bladder, as they can often be reached 
under these circumstances by spoon-shaped instruments, by forceps, 
etc.; or the attempt may be made to reach them with the fingers and 
to enucleate them from their surroundings with the finger-nails; or, finally, 
it may be tried to crush them from without and to push the fragments 
back into the gall-bladder. If all these measures fail, the attempt must 
be made to find the exact location of the stone in the duct and to incise 
the walls immediately over the stone. This is often a very difficult 
procedure owing to the hidden location of the stone, and it may be im- 
possible to extract itin this manner. Too great pressure must be avoided 
in attempting to crush the stone through the walls of the duct, for the 
reason that the mucous lining of the cystic duct may be bruised, and this 
may be followed by serious complications. 

If the gall-stones are situated in the common duct, the attempt should 
also be made to reach them through the gall-bladder, to crush them 
(Langenbuch, Kehr, Credé), and to push the fragments back into the 
gall-bladder. This may succeed, particularly if the common and the 
cystic ducts are dilated, as is often seen in cases of this character. If 
all these measures fail, the attempt must be made to create a fistula 
through the abdominal walls and to allow it to remain open, or to make 
some connection between the gall-bladder and the intestine (Winiwarter). 
The latter procedures will be particularly indicated in cases where the 
general condition of the patient, severe degrees of icterus, etc., make 
it impossible to perform more radical operations, and where, at the same 
time, the outflow of bile must be established. In the last-named opera- 
tion the danger of infection of the gall-bladder from the intestine always 
exists (Dujardin-Beaumetz), and in cases where the fistula was made 
between the gall-bladder and the colon fecal fistulae have been known 
to occur (Chavasse). If icterus is very severe, it is best to wait until 
it is less intense as a result of the outpouring of bile through the external 
fistula, and then, after the tissues have recovered somewhat, the more 
serious operation may be attempted. 

Of late years the attempt has, finally, been made to incise the common 
duct and to remove gall-stones in this way (Heusner, Kiister, Courvoi- 
sier, Riedel, and others). After removal of the stone the wall was closed 
by sutures. In many cases it is a very difficult matter to feel the stones 
through the wall of the duct, and it may even happen that they are con- 
founded with enlarged lymph-glands. Those gall-stones that become 
impacted in the posterior parts of the ductus choledochus, behind the 
duodenum, are especially difficult to feel, and often cannot be found. 
Some operators have opened the common duct through an incision made 
from the lumbar region (Tuffier, Poirier) and have removed the gall- 
stone through this channel. Others, again, have made an anastomosis 


602 DISEASES OF THE BILE-PASSAGES. 


between the common duct and the small intestine (Sprengel) or the 
duodenum (Terrier, Korte, Kocher). By means of these operations the 
most natural method of cure is imitated, as even without operative inter- 
ference fistulz are often formed between the gall-bladder or ducts and 
the small intestine, and the gall-stone passed in this way. 

It is usually possible to push gall-stones that are situated in the trunk 
of the hepatic duct into the common duct. If the gall-stones are situated 
in the intrahepatic bile-ducts, they can be reached only with considerable 
difficulty. If they can be felt at all, the attempt should be made to 
slowly work them down into the trunk of the hepatic duct. - Instruments 
pushed into the hepatic duct for the purpose of grasping and removing 
gall-stones situated within the hepatic channels, as a rule, produce an 
opposite effect to the one desired, inasmuch as they only push the con- 
cretions further into the intrahepatic ducts instead of grasping them 
and pulling them out. Occasionally gall-stones within the liver have 
been found and removed in the course of an operation for abscess of the 
liver. 

Numerous attempts have been made, besides those enumerated, to 
remove gall-stones by other methods. Thus, a number of investigators 
have in vain tried to dissolve the concretions within the channels by 
injections of warm water (Taylor, Baudouin), oil (Brockbank), ether 
(Dujardin-Beaumetz), and other substances. 

The treatment of ileus from gall-stone impaction deserves particular 
discussion. If opium is indicated in any form of occlusion of the intes- 
tine, it certainly is indicated here. In the form of ileus under discussion 
the occlusion of the intestine is not necessarily due to the gall-stone 
proper, but may be due to the spasmodic contractions of the musculature 
of the intestine around the stone. Consequently the administration of 
sufficiently large doses of opium (tinctura opii 20 gtt. and 5 to 10 gtt. 
every hour thereafter) will very often relieve the ileus. High enemata 
will be of additional value. If the gall-stone can be reached from the 
rectum directly, the attempt should be made to grasp it and to extract it. 
In all other cases a laparotomy must be performed, the exact location 
of the gall-stone determined, the intestine incised, and the stone removed 
through the incision. This operation has been performed a number of 
times (Korte and others). In many cases, unfortunately, it is impossible 
to determine that the occlusion of the intestine is due to gall-stone im- 
paction, as no symptom of cholelithiasis may have preceded the attack 
of ileus; and, in addition, it may be impossible to find the location of the 
gall-stone during laparotomy. According to Kirmisson and Rochard, the 
operation of laparotomy was only successful in 20% of the cases; whereas 
of 80 cases that were not operated upon, 29 recovered and 51 died. Naunyn 
states that as many as 50% recovered after internal, non-operative 
treatment alone The best plan, therefore, will be to inaugurate a course 
of treatment with opium at first. If at the expiration of two days no 
relief is apparent, and ulceration, perforation, and peritonitis threaten, 
a laparotomy should be performed. 

The treatment of abscess, cirrhosis of the liver, and carcinoma hepatis 
following gall-stones will be discussed in the different sections on these 
diseases. 


LITERATURE. 603 


LITERATURE: 


OLDER LITERATURE.* 


Andral: “Clinique médicale,” tome 11, Paris, 1839. 

Bartholini, Th.: ‘‘ Histor. anatomic. var. Centur. 11 et Iv,” p. 335, Hafnie, 1657. 

Bianchi: “ Histor. hepatica,”’ Turin, 1716. 

Blasius, G.: ‘‘ Observat. medic. var. ’ Amstelodami,” 1677. 

Bobrzenski in Bonet: “ Sepulchret. anatomic.,” Lib. 111, Sect. xvi, p. 281, Lugduni, 
1700. 

Boerhaave: ‘ Aphorismi de cognosce. et cur. morbis,’’ Lugduni Batav., 1737. 

Coe: “ Abhandlung von den Gallensteinen,”’ from the English, Leipzig, 1783. 

Coiter, V.: “ Extern. et intern. principal. human. corpor. part. tabul. 
Norimberger, 1573. 

Craz, H.: “ De vesice fellee et duct. bil. morbis,”’ Dissertat. inaugur. Bonne, 1830. 

Dodonaei, R.: “ Medicinal. observat. exempla var. Hardervici,” 1621. 

Donatus, Marcellus: “De medica historia mirabili,”’ Venetiis, 1588. 

Ettmiller, M.: ‘Opera medica,’”’ tomus 1, pars i. p. 442, Francofurti ad Menum, 


1708. 
Fabricii, Hildani: “ Observat. et curat. chirurg. centur.,’’ Basileze, 1606. 
Fernelius: “Universa medicina. . . . Trajectiad Rhenum,” p. 141, 1656. 


Forestus, P.: “ Observat. et curat. medicin. et chirurg. op. omn.,”’ observat. XIV, Xv, 
xx1, Francofurti, 1660. 

Frank, J. P.: “ De cur. homin. morbis,” tom. v, p. 172, Florentiz, 1832. 

Glissonii, F.: ‘ Anatom. hepat.,”’ p. 38 et 265, Londini, 1654. 

Haller, Alb. de: ‘“‘Mém. sur la nature sensible et irrit. des part. du corps animal.,”’ 
tome I, p. 280, Lausanne, 1756-1760. 

— “Opuscul. patholog.,”’ p. 70, Lausanne, 1755. 

v. Helmont: “ Ortus medicine,’”’? Amstelodami, 1648. 

Hoffmann: “ Medicine rational. systematica,” 1733. 

Kentmann bei Gesner: “ De omni rerum fossilium genere,”’ p. 6, Tiguri, 1565. 

Morgagni, J. B.: “ De sedibus et causis morbor.,”’ Lib. 111, Roitols Eve p. 127, Lug- 
duni Batav., 1767. 

Miller, Godofred: “ Act. phys. med. anat.,’’ tomus v1, observat. 69, 1742. 

Paracelsus ab Hohenheim, Th. B.: “ De origine morb. e tartaro,”’ tomus I , Strassburg, 
1616. 

— “Von den tartarischen Krankheiten,” p. 282. 

Portal, A.: “Sur la nature et le traitement des maladies du foie,’ Paris, 1813. 

Prochaska, G.: “Opera minora,” Pars. 1, 11, Vienne, 1800. 

Pujol;-A,: “ Qeuvres de médecine pratique,” tome IV; “Mém. sur la colique hépat.,’’ 
Paris, 1823. 

Schurig, M.: “ Lithologia,” p. 172, Dresden-Leipzig, 1744, 

Scultet, J.: “Armament. chirurgize,” p. 300, Amsterdami, 1672. 

Soemmering: “De concrem. biliariis,’’ 1793. 

van Swieten, G.: “Comment. in H. Boerhaave Aphorismos ” § 950, Wirceburgi, 
1787-1788. . 

Sydenham, Th.: “ Praxis medic.,”’ p. 259, Lipsic, 1695. 

Tacconi: “De raris quibusdam hepatis aliorumque vise. affect. observat.,’’ Bononiz, 
1740. 

Walter, J. G. und F. A.:“ Anatomisches Museum,” 1. und 2. Theil, Berlin, 1796. 

Walter, J. G.: “Observat. anatomice,”’ Berolini, "1775. 

Wepfer, J. J.: “Histor. apoplectic . . . auctuarium,” p. 389, Amsteledami, 
1710. 


— “Histor. cicut. aquatic.,” cap. x, p. 225, Lugduni Batav., 1733. 


COLLECTIVE WORKS. 


Bouisson: “ De la bile ” Montpellier, 1843. 

Brockbank, E. M.: ‘On Gall-stones,’’ London, 1896. _ 

Budd, G.: “«Kyankheiten der Leber, ” translated by Henoch, Berlin, 1846. 
Charcot: “ Legons sur les maladies du foie,” Paris, 1877. 

Chauffard : “Traité de médecine,” vol. 111, Paris, 1893. 


* The older literature is given in full by Muleur, “ Essai historique sur l’affection 
calculeuse du foie,’’ Thése de Paris, 1884. ; 


604 DISEASES OF THE BILE-PASSAGES. 


Courvoisier: “Casuistisch-statistische Beitrige zur Pathologie und Chirurgie der 
Gallenwege,”’ Leipzig, 1890. 

Cyr: “Traité de l’affect. calculeuse du foie,’’ Paris, 1884. 

Dupré, F., in “ Manuel de médecine” by Debove and Achard, vol. v1, Paris, 1895. 

Fauconneau-Dufresne: “ Traité de l’affect. calculeuse du foie,” Paris, 1851. 

Frerichs: ‘ Klinik der Leberkrankheiten,” vol. 1, 1861. 

Harley, G.: ‘ Diseases of the Liver,’ German by Kraus und Rothe, Leipzig, 1883. 

Kehr, H.: “ Die chirurgische Behandlung der Gallensteinkrankheite,” Berlin, 1896. 

Kraus: “ Pathologie und Therapie der Gallensteinkrankheit,” Berlin, 1891. 

Langenbuch: ‘Chirurgie der Leber und Gallenblase,”’ Stuttgart, 1897; “Deutsche 
Chirurgie,” chap. 45, part 2. 

Leichtenstern: in Penzoldt und Stintzing’s “ Handbuch der speciellen Therapie,” part 
VI b, p. 28 et seq. 

Murchison: “Clinical Lectures on Diseases of the Liver,’ London, 1877. 

Naunyn, B.: ‘ Klinik der Cholelithiasis,’’ Leipzig, 1892. 

Riedel, B.: ‘‘Chirurgische Behandlung der Gallensteinkrankheit” in Penzoldt and 
Stintzing’s “ Handbuch der speciellen Therapie,” part v1 b, p. 68. 

Schippel: in Ziemssen’s “‘ Handbuch der speciellen Pathologie und Therapie,” vol. 
Viti, 1. L880. 

Thudichum: “Treatise on Gall-stones,’’ London, 1863. 

Waring, H. J.: “ Diseases of the Liver,’’ Edinburgh and London, 1897. 


SPECIAL WORKS. 


1. PatTHo.tocy.* 


Adler: “Deutsche med. Wochenschr.,’’ No. 3, 1892. 

Alison: “Contribution au diagnostic de la lithiase biliare,’’ “ Archives générales de 
médecine,” p. 141, August, 1887. 

Aubert, P.: “ D’endocardite ulcéreuse végétante dans les infect. biliaires,”” Thése de 
Paris, 1891. 

Aufrecht: “ Austritt von Gallensteinen aus der Gallenblase,” “‘ Deutsches Archiv fiir 
klin. Medicin,” vol. xLu1, p. 295, 1888. 

Bohnstadt, F.: “ Die Differentialdiagnose zwischen dem durch Gallensteine und dem 
durch Tumor bedingten Verschluss des Choledochus,”’ Dissertation, Halle, 1893. 

Bouchard: “Du mode de formation des ulcérations calculeuses de la vessie bil.,’”’ 
“ Archives générales de médecine,” p. 187, August, 1880. 

Brissaud et Sabourin: “ Deux cas d’atrophie du lobe gauche du foie,” “ Archives de 
physiologie,’’ 3d series, vol. 111, p. 345, 1884. 

Brockbank: “ Edinburgh Med. Jour.,’”’ July, 1898, p. 51; “ Manchester Med. Chron.,’ 
Dec., 1896. 

Buxbaum: “Minchener med. Wochenschr.,’’ p. 1368, 1897. 

Bychoffski: ‘“ Contrib. 4 l’étude de l’hystéro-traumatisme,” Thése de Paris, 1893. 

~ Cabot: “Medical News,” Nov. 30, 1901, p. 844. 

Cadéac: “Contrib. 4 l’étude de la cholécystite suppurée,”’ Thése de Paris, 1891. 

Cahen: “ Ein seltener Fall von Gallensteinen,”’ ‘“ Deutsche med. Wochenschr.,’’ No. 
41, 1896. 

Camac: “Am. Jour. Med. Sc.,’”’ March, 1899. 

Chauffard, A.: “ Valeur clinique de l’infection comme cause de lithiase bil.,” “ Revue 
de médecine,”’ No. 2, 1897; “Gaz. des Hép.,” 1899, No. 16. 

Chiari: “ Zeit. f. Heilk.,”’? Bd. xv, p. 199. 

Cushing: “Johns Hopkins Hosp. Bull.,” Aug.—Sept., 1899, p. 166; ibid., May, 

98 


1898. 
Cyr, J.: “Causes d’erreur dans le diagnostic de |’affection calculeuse du foie,’”” 
“ Archives générales de médecine,” p. 165, February, 1890. 
Da Costa: “ Amer. Jour. Med. Sc.,”’ Aug., 1899, p. 138. 
Dauriac: “ Les infect. biliaires dans la fiévre typhoide,”’ Thése de Paris, 1897. 
Dominici, 8. A.: “Des angiocholites et cholécystites suppurées,’’ Thése de Paris, 


1894. A 
Dréba: “ Wien. klin. Woch.,’’ Nov. 16, 1899. 


* The newer works only are mentioned here. For the very large number of 
cases we refer to the Index-Catalogue of the Library of the fied 209. Ocal 
Office, U. S. Army, under article “Gall-stones.” The collective works of Naunyn, 

’ Langenbuch, Courvoisier, Schiippel, etc., also contain many references to literature. 


—, 
— . 


LITERATURE. 605 
v. Dungern: ‘Ueber Cholecystitis typhosa,” “ Miinchener med. Wochenschr.,”’ p. 
699, 1897. 
Ehret: Abstract in. “Vereins-Beilage des Deutsches med. Wochenschr.,” May 8, 
1902, p. 143. 


Ehret and Stolz: “ Mittheil. a. d. Greuzgebeit. d. Med. u. d. Chir.,’’ 1901, Bd. v1, 

| p. 373; “ Berlin. klin. Woch.,”’ Jan. 6, 1902, p. 13. 

Exner: ‘Deutsche med. Woch.,’”’ 1898, No. 31, p. 491; ibid., March 16, 1899, 
p. 173. 

Fraenkel, E., and P. Krause: “ Zeitschr. f. Hyg. u. Infectionsk.,’’? Bd. xxx11. 

Fuchs: “ Ein Fall von acuter Cholecystitis und Cholangitis mit Perforation der Gal- 
lenblase,”’ “ Berliner klin. Wochenschr.,” p. 646, 1897. 

Firbringer: ‘‘Verhandlungen der Congresses fiir innere Medicin,”’ Leipzig, 1892. 

Gerhardt, C.: “Zur physikalischen Diagnostik der Gallensteinkolik,” ‘ Deutsche 
med. Wochenschr.,”’ p. 975, 1893. 

Gilbert: “ Arch. gén. de méd.,”’ 1898, p. 258. 

Gilbert and Dominici: ‘‘Compt. rend. de la Soe. de Biol.,” June 16, 1894. 

Gilbert et Fournier: “ Du réle des microbes dans la genése des calculs bil.,”’ “ Gazette 
hebdomad. de méd. et de chirurg.,’’ No. 13, 1896. 

— Société de biologie Paris, October 30, 1897. 

Griffon: “Calculs enclavés dans l’ampoule de Vater,” “ Presse médicale,” No. 85, 
1896; from the “ Chirurgisches Centralblatt,’’ No. 13, 1897. 

Homans: “Lancet,” July 31, 1897; ‘“ Johns Hopkins Hosp. Bull.,”” Aug.—Sept., 1899. 

Hélzl: “Darmverschluss durch Gallensteine,”’ “Deutsche med. Wochenschr.,’”’ No. 
17, 1896. | 

Hiinerhoff, H.: “Ueber Perforation der Gallenblase infolge von Ciholelthiasis,”’ 
Dissertation, Géttingen, 1892. 

Hunner: “Johns Hopkins Hosp. Bull.,”” Aug.—Sept., 1899. 

Imhofer: ‘ Prager med. Woch.,”’ 1898, Nos. 15 and 16. 

Jacobs: “Zur Kenntniss der Cholecystitis calculosa,’’ Dissertation, Miinchen, 1890. 

Janowski: ‘“ Verinderungen in der Gallenblase bei Vorhandensein von Gallen- 
steinin,” “ Ziegler’s Beitrage zur pathologischen Anatomie,” vol. x, 1891. 

Kausch: ‘ Deutsche med. Woch.,”’ March 16, 1899. 

Kirmisson, E., and Rochard, E.: “ De l’occlusion intestinale par calculs biliaires et 
de son traitement,” “ Archives générales de médecine,’”’ February and March, p. 
148, 1892. 

Kleefeld: ‘ Ueber die bei Punction, Operation und Section der Gallenblase consta- 
tirten pathologischen Verinderungen des Inhaltes derselben und die daraus re- 
sultirenden diagnostischen Momente,”’ Dissertation, Strassburg, 1894. 

Kolliker, Th.: “Centralblatt. fiir Chirurgie,” p. 1113, 1897. 

Létienne: “ Note sur un cas de lithiase bil.,’”’ ““ Archives générales de médecine,”’ p. 
734, December, 1891. 

Meckel v. Hemsbach: “ Mikrogeologie,” Berlin, 1856. 

pear daa ‘“‘Mittheil. a. d. Greuzgebeit. d. Med. u. d. Chir.,’”’ 1900, Bd. v1, p. 
307. 

Meyer, J.: “ Experimentelle Beitrige zur Frage der Gallensteinbildung,”’ “ Virchow’s 
Archiv,” vol. cxxxv1, p. 651, 1894. 

Mignot: “Arch. gén. de méd.,” 1898, p. 129. 

Miller: ‘‘ Johns Hopkins Hosp. Bull.,’’ May, 1898. 

Mixter: “ Boston Med. and Surg. Jour.,’’ May 25, 1899. 

Miyaki: “ Mittheil. a. d. Greuzgebiet. d. Med. u. d. Chir.,’’ 1900, Bd. vr, p. 479. 

Miller, A.: “Zur pathologischen Bedeutung der Driisen in der menschlichen Gallen- 
blase,” Dissertation, Kiel, 1895. 

Naunyn: “Verhandlungen des Congresses fiir innere Medecin,”’ Leipzig, 1892; 
“Mittheil. a. d. Greuzgebeit. u. d. Chir.,”’ 1899, Bd. rv, pp. 1 and 602. 

Netter et Martha: “De l’endocardite végétante ulcéreuse dans les affect, des voies 

__biliaires,’”’ “ Archives de physiolog., norm. et patholog.,” p. 7, 1886. 

Nickel: “ Zur Casuistik der durch Cholelithiasis bedingten Pericystitis vesice fellez,” 
Dissertation, Marburg, 1886. 

Niemer: “Ueber einen Fall von Gallensteinen in den Lebergallengingen,”’ Kiel, 


1894. 

Oddi: “Effeti dell’ estirpazione della cisti fell,’ from the “Centralblatt. fur 
Chirurgie,” No. 8, 1889. i fi 

Opie: “ Amer. Jour. Med. Sce.,” Jan., 1901, p. 27. 

Osler: from “Miinchener med. Wochenschr.,” p. 1125, 1897; “Trans. Associa- 
tion of American Physicians,”’ 1897, vol. x11. 

Ottiker: “ Ueber Gallenfisteln,” Dissertation, Erlangen, 1886. 


606 DISEASES OF THE BILE-PASSAGES. 


Peters, H.: ‘‘ Gallenstein-Statistik,” Dissertation, Kiel, 1890. 

Peterssen-Borstel: “Ueber Gallensteinbildung i in ihrer Beziehung zu Krebs und 
chronischer Endarteriitis,’’ Dissertation, Kiel, 1883. 

Porges: ‘‘ Wien. klin. Woch.,’’ 1900, No. 26. 

Pratt: ‘‘Am. Jour. Med. Sc., Nov. , 1901, p. 584. 

Raynaud et Sabourin: ‘‘N ote zur un cas d’énorme dilatation des voies biliares,’’ 
‘Archives de physiolog., normale et patholog.,’’ No. 31, 1879. 

Richardson: “Jour. Boston Soc. of Med. Sc. ,’ Jan., 1899. 

Riedel: ‘‘Ueber den zungenférmigen Fortsatz der Leber,” ‘‘ Berliner klin. 
Wochenschr.,”’ 577, 1888; ‘‘ Mittheil. a. d. Greuzgebiet. Med. u. d. Chir.,’” 
1898, Bd. 111, ’D. 168; ibid., 1899, Bd. Iv, p. 565. 

Robson, Mayo: Lecture on “ Diseases of the Gallbladder, ” “Tancet,” June 5, 1897. 

— “Varieties of Intestinal Obstructions depending on Gallstones, ” «“ Medic.-chir. 
Transact.,” vol. Lxxxvii; ‘ Edinburgh Med. Jour.,” September, 1899; ‘ All- 
butt’s System of Medicine.” 

Rother: “Zur Aetiologie und Statistik der Gallensteine,”’ Dissertation, Munchen, 
1883. 

Schabad: “ Ein Fall von Gallensteinen mit Ruptur der Gallenblase,” ‘‘ Petersburger 
med. Wochenschr.,’’ No. 3, 1896. 

Schloth: ‘‘ Ueber Gallensteinbildung, ” Dissertation, Wiirzburg, 1887. 

Schmitz, R.: “Intermittirendes Fieber bei Gallensteinen, ”” “ Berliner klin. Wochen- 
schr.,” p. 915, 1891. 

Schiiller: “Gallensteine als Ursache von Darmobstruction,”’ Dissertation, Strass- 
burg, 1891. 

Schwartz: “ Discuss. sur la lithiase de la vessie bil.,’”’ “ Bull. et mém. de la société de 
chir. de Paris,” vol. xxu1, p. 245. 

Simanowski, N. P.: “Zur Frage tber die Gallensteinkolik,” “ Zeitschr. fir klin. 
Medicin,” vol. v, 501, 1882. 

Souville, P.: “Cholécystite scléreuse d’origine calcul. et pericholécystite,’’ Thése de 
Paris, 1895. 

Still: ‘‘Trans. Path. Soc. of London,” 1899. 

Thomson: ‘‘ Edinburgh Hospital Reports,’ 1898. 

Vissering: ‘ Ein Fall von Thorax-Gallenfistel mit Entleerung eines Gallensteines per 
vias naturales und nicht tédtlichem Ausgang,” “ Minchener med. Wochenschr.,”’ 
p. 567, 1896. 

Weltz: ‘‘Ueber Divertikel der Gallenblase,” Dissertation, Kiel, 1894. 

Wunschheim: ‘ Prag. med. Woch.,’’ 1898, Nos. 2 and 3. 

Zinn: ‘‘ Centralbl. f. innere Med.,” Sept. 24, 1898. 


2. THERAPY.* 
(Newer Works.) 


Beck: ‘“ When shall we Operate for Cholelithiasis?”’ “‘ New York Med. Journal,”’ oe 
8, 1897. 

- Braun: “ Die operative Behandlung der Steine im Ductus choledochus,’’ Disserta- 
tion, Géttingen, 1896. 

Chauffard et Dupré: “ Note sur le trait. de la lithiase bil.,” “Gazette hebdomad.,’’ 
p. 677, 1888. 

Fenger: “ Stones in the Common Duct and their Surgical Treatment,” “ American 
Med. Jour.,’”’ February, 1896. 

Franke: “ Beitriige zur Chirurgie der Gallenwege,”’ Festschrift zur 69. Versamm- 
lung der Naturforscher und Aerzte, Braunschweig, 1897. 

Kehr: ‘ Ueber Behandlung der calculdsen Cholangitis durch directe Drainage des 
Ductus hepaticus,” “ Miinchener med. Wochenschr.,” No. 41, 1897. 

Kohler, A.: “ Beitrage zur Casuistik der Operationen an der Gallenblase, ” “ Deutsche 
Zeitschrift fiir Chirurgie,” vol. xxx1x, p, 549, 1894. 

Kiimmell: “Die ideale extraperitoneale ’ Operation der Gallensteine,” “ Deutsche 
med. Wochenschr.,”’ p. 578, 1897. 

Lange: “ Die chirurgischen Gesichtspunkte der Gallensteinerkrankungen,” “ New 
Yorker med. Wochenschr.,”’ January, 1897. 

sigs “Contrib. & étude des indic. de la cholécystotomie,” “ Revue de chirurg.,’’ 

o. 9, 1896. 


+ Leichtenstern, in Penzoldt und Stintzing’s “ Handbuch der speciellen Ther- 
apie” (Internal Therapy). Langenbuch, “Chirurgie der Leber un pplemunene, 
part 2, complete list of literature. 


ee 


HYPEREMIA OF THE LIVER. 607 


Lewaschew: “Ueber die therapeutische Bedeutung des Durande’schen Mittels bei 
der Gallensteinkrankheit,” “ Virchow’s Archiv,” vol. c1, p. 430. 

Loos: “Ueber den Durchbruch des Ductus choledochus ins Duodenum,”’ Disserta- 
tion, Kiel, 1890, 

Martig, W.: “Zur Chirurgie der Gallenwege,” Dissertation, Basel, 1893. 

Prentiss: “ Med. News,”’ May 12, 1888. 

Rosenberg: “ Behandlung der Cholelithiasis,” “ Berliner klin. Wochenschr.,” No. 48, 
1889. 

— “Demonstration von Gallensteinen, die nach Oelbehandlung abgegangen sind,’ 
“ Berliner klin. Wochenschr.,”’ p. 314, 1891. 

Roth, Th.: “ Zur Chirurgie der Gallenwege,” “ Archiv fiir klin. Chirurgie,” vol. xx, 

. 87, 1885. 

Saenie “ Berliner klin. Wochenschr.,”’ p. 604, 1891 (Calomel). 

Schréder, A.: “ Ueber die Behandlung in den Gallengiangen sitzender Steine,’’ Disser- 
tation, Kiel, 1895. 

Sendler: “ Zur pathologie und Chirurgie der Gallenblase und der Leber,” ‘‘ Deutsche 
Zeitschrift fiir Chirurgie,” vol. xt, p. 366, 1895. 

— “Beitraige zur Chirurgie der Gallenwege,” “ Deutsche Zeitschr. fiir Chirurgie,” vol. 

, XXXVI, p: 580, 1887, 

Staub: “ Divertikelbildung der Gallenblase; Cystotomie mit partieller Resection der 
Blasenwand,” “ Correspondenzblatt fur Schweizer Aerzte,” p. 1, 1896. 

Terrier: ‘Sur un cas de gastrocystentérostomie,”’ “ Bulletin de la société chir.,”’ vol. 
Xxu, p. 565, Paris, 1897. 

Trantenroth: “ Acute infectiédse Cholangitis und Cholecystitis infolge von Gallen- 
steinen; Heilung durch Operation,” ‘“ Mittheilungen aus den Grenzgebieten der 
Medicin und Chirurgie,” vol. 1, p. 703. 

Weber: “ Klinische Betrachtung der Gallensteinkrankheit vom Standpunkte der 
inneren Medicin,” ‘‘ New Yorker med. Wochenschr.,” January, 1897. 

White, Sinclair: ‘“ Lancet,” April 17, 1897, p. 1095. 

Witzel: “ Beitrage zur Chirurgie der Bauchorgane,” ‘ Deutsche Zeitschr. fiir Chir- 
urgie,” p. 159, 1884 (literature). 





DISEASES OF THE ELVER, 


HYPEREMIA OF THE LIVER. 
(Quincke.) 


THE liver, owing to the enormous development and capacity of its 
capillary system, is one of the most vascular organs of the body. If it 
is inspected during laparotomy or vivisection, it will be found that it 
presents an altogether different appearance from the organ as it is seen 
after death, and it is surprising to note the degree of turgescence of the 
liver during life and to observe how deeply it is colored. The walls of 
the capillaries are very thin and the parenchyma is very delicate; as a 
result the quantity of blood that the liver contains varies very much at 
different times. 

Many observations, chiefly alimaar seem to indicate that at the time 
of greatest functional activity,—that i is, at at the time of digestion,—and 
also under certain pathologic conditions, the quantity of blood contained 
within the liver increases. The blood-supply in the case of the liver, 
as in most other organs, is regulated by changes in the lumen of the 
afferent vessels. This is apparent from the fact that both the hepatic 
artery and the portal vein have a number of smooth muscular fibers 
within their walls. Some facts even point to the possibility that the 
capillaries of the liver are capable of spontaneously changing their caliber. 


608 DISEASES OF THE LIVER. 


The venous system of vessels within the liver is subject to many 
fluctuations from the fact that the hepatic veins enter directly into the 
lower vena cava, and as this vessel is influenced greatly by the changes 
in intrathoracic pressure caused by the respiratory movements and the 
movements of the heart, it can be readily understood why the pressure 
in the hepatic veins is constantly changing. Aside from the fluctuations 
mentioned, that must occur constantly even during complete rest of the 
body, it must be remembered that all movements of the body and 
a variety of other causes influence the blood-pressure in the vena 
_ cava. This in its turn causes the blood to flow more rapidly or more 
slowly from the hepatic veins into the vena cava. When the pres- 
sure in the caval system is increased, the flow of blood from the hepatic 
veins is slower and the pressure within the liver is increased. The liver 
during this time must be able to hold and does hold quite large quantities 
of blood. Asa matter of fact, the liver acts in this respect like a sponge, 
and is capable of absorbing and retaining much blood without detriment. 


These fluctuations in the volume of blood contained within the liver are, as a 
rule, impossible to detect by palpation. Heitler,* however, claims that he can deter- 
mine an increase of volume in the case of the liver as well as in the case of the spleen 
by careful percussion. He claims that he finds differences in the area of percussion 
dulness both in an upward and a downward direction of more than 3 em. (!), and 
states that these fluctuations can occur within the course of two minutes or even a 
shorter time. 


Of the two possible causes of pathologic plethora of the hepatic 
vessels, that which is due to passive stasis is more frequent, more im- 
portant, more readily understood, and more easily controlled than the 
one due to active stasis. This condition of passive hyperemia is, as a 
rule, caused by some obstruction to the outflow of venous blood. 

The external pressure on the liver is of some significance in bringing 
about fluctuations in the volume of blood contained within the organ. 
Tension of the abdominal walls in the presence of an abundant quantity 
of intra-abdominal fat will counteract great fluctuations, whereas flaccid 
abdominal walls and the presence of small quantities of fat in the mesen- 
tery, etc., possibly as a result of emaciation, will favor fluctuations. 

For the same reason the left lobe of the liver is probably subject 
to greater fluctuations than the right one;so that all the symptoms of 
hyperemia or stasis in the liver are clinically more apparent in the left 
lobe than in the right, from the fact not only that that part of the 
organ is more accessible to our methods of examination, but also that 
the changes are really more pronounced. This may also account for 
the observation that in atrophic and in hypertrophic cirrhosis of the 
liver the left lobe seems to reveal more pronounced changes, in the sense 
that it is more contracted in the former disease and more enlarged in 
the latter. 


PASSIVE CONGESTION. 


Etiology.—The most frequent cause of obstruction to the outflow 
of blood from the veins of the liver is insufficiency of the activity of the 
heart. This may be due either to some primary disease of the cardiac 
muscle or to some valvular disease with secondary involvement of the | 
myocardium. Those cardiac lesions in which the right heart in particular 


* Heitler, “Die Schwankungen der normalen Leber- und Milzdimpfung,” 
Wiener med. Wochenschr., 1892, No. 24. 





ee  — EE 


HYPEREMIA OF THE LIVER. 609 


is insufficient are especially adapted to cause stasis in the veins of the 
liver. Among these may be mentioned the final stages of mitral or 
pulmonary valvular disease or the sequels of tricuspid lesions. Following 
the course of these diseases and developing slowly, passive congestion 
of the liver develops in the course of many years. The acute forms 
of myocarditis following infectious diseases rarely cause the development 
of clinically recognizable passive congestion of the liver. This only 
occurs if, for instance, as in children, the organ is very elastic (therefore 
this condition is occasionally seen after diphtheria), or if slight degrees 
of stasis existed in a latent form for some time. In the new-born acute 
passive hyperemia of the stasis may follow a difficult delivery or atelec- 
tasis of the lungs. 

Certain diseases of the lungs, such as emphysema, contraction of 
lung tissue, chronic and acute bronchitis, pleural adhesions of large dimen- 
sions, act in the same manner as do diseases of the right heart. At times 
several of these conditions are present at the same time. They decrease 
the area of the pulmonary circulation and reduce the respiratory excur- 
sions, so that they finally lead to insufficiency of the right side of the 
heart. Scolioses and kyphoses of the spinal column, if they are suffi- 
ciently pronounced, may act in the same manner, as may intrathoracic 
tumors and large exudates into the pleural cavity [and pericardial syne- 
chie.—Ep.]. It happens sometimes, though comparatively rarely, that. 
the inferior vena cava alone is compressed by all these lesions in that 
short part of its course that runs between the liver and the right auricle. 
Finally, cicatricial or thrombotic narrowing of the veins of the liver 
itself may lead to hyperemia from stasis. This may also occur in some 
circumscribed district within the liver, as in the neighborhood of 
tumors, etc. 

Local hyperemia from stasis may also be seen if a lobe of the liver 
is separated from the main body of the organ by lacing. In this instance 
the veins running through the furrow between the lobe and the main 
body of the liver are compressed and cause stasis in the lobe, so that 
induration and enlargement are produced therein. General hyperemia 
of a mild degree may often be seen in a corset liver, particularly in 
those cases where the patient has a high waist or where the compres- 
sion is diffuse in the lower part of the thorax so that the vena cava is 
compressed between the liver and the spinal column. 

Anatomy.—If the flow of blood from the liver is impeded, the first 
result will be an engorgement and a dilatation of the hepatic veins. 
Following this, engorgement will occur in all the venous radicles situated 
behind the obstruction, so that in cases where stasis persists the organ 
will gradually enlarge. The dilatation of the hepatic veins then becomes 
permanent and is transmitted to the central venules of the lobules and 
to the surrounding capillaries. At+the same time the trabeculz of hepatic 
tissue situated between the dilated vessels are compressed and narrowed 
by the pressure, and finally undergo atrophic changes. For these reasons 
it will often be found that the lobules of the liver are colored dark red 
in the center, whereas the peripheral parts are much lighter in color owing 
to the many intact cells that these parts still contain (cyanotic or chronic 
red atrophy). In many instances it will be seen that those cells that 
remain in the central areas of the lobules are filled with brown pigment, 
whereas those cells that are nearer the periphery contain globules of fat. 
In cases of this character the brownish-yellow portal zone is clearly dif- 

39 


610 DISEASES OF THE LIVER. 


ferentiated from the center of the lobule, a peculiar picture to which 
the name “nutmeg liver” has been applied. The designation is hardly 
a happy one, because the majority of physicians are.probably not familiar 
with this object of comparison taken from the kitchen. 

After death the capillaries are in part emptied and the central por- 
tions of the lobules, as a result, often appear retracted on postmortem 
examination. This retraction may be apparent on the surface of the 
lobule or in transverse sections through it. The further the atrophic 
changes of the cells near the periphery have progressed, the more distinet 
will this retraction appear. In this manner it may happen that the 
surface and sections through the lobules appear finely granular. The 
individual granulations, however, are much smaller than in true cirrhosis 
—t.e., they correspond in diameter and extent to exactly one lobule, 
whereas in cirrhosis several lobules constitute one granule. On section 
the whole liver in this condition appears flaccid and tough, and if the 
organ has been allowed to lie for some time, so that much blood has 
oozed out, the liver will appear very little enlarged or even smaller than 
normal. This may be noticed even if a very short time before, during 
the life of the patient, the enlargement of the liver and the tension of 
the capsule were apparent as a result of the great engorgement with | 
blood. 

As a rule, these changes of color and consistency are not evenly dis- 
tributed throughout the whole organ, but nutmeg spots alternate with 
very red, flaccid, and completely retracted areas. Within the latter 
the liver-cells will be seen to be still more atrophied, so that nothing re- 
mains but a few scanty remnants of a brownish pigment. The surface 
of the liver in these cases presents a nodular, wavy appearance, which 
also is presented by the surface of sections through the organ. Similar 
changes, based chiefly on the unequal amount of stasis that exists in 
different parts of the organ, are also, for instance, seen in the lungs, and 
must be attributed to peculiarities in the ramification and the angles of 
division of the blood-vessels that supply the diseased areas. 

The serous covering of the liver in cases of stasis from hyperemia 
is, aS a rule, cloudy and often thickened. As the trabecule of hepatic 
tissue disappear the walls of the capillaries become more and more ap- 
proximated, until finally they come in contact with each other. The 
material situated between the lumina of the different capillaries consists 
of the thickened walls of the capillaries and of strands of connective tissue 
that are either homogeneous or striated. This connective tissue some- 
times can be traced as far as the thickened sheath of the branches of 
the hepatic veins. It occasionally shows small-celled infiltration. 

Within the connective tissue new-formed bile-channels are sometimes 
seen. These either originate from epithelial proliferation or are made 
evident from atrophy,of trabecule of liver-cells. 

In addition to intralobular new-formation of connective tissue, that 
is seen principally in the center of the lobules, connective-tissue prolifer- 
ation may occasionally be observed in the interlobular spaces in the 
vicinity of the branches of the radicles of the portal vein. Liebermeister 
appears to have encountered this condition more frequently than other 
authors. He distinguishes a circumscribed form that appears in streaks 
and a wide-spread form that appears over larger surfaces. This prolif- 
eration is followed by retraction, and in this manner adds to the atrophic 
changes that occur in the hepatic tissues. The whole picture resembles 


eS ee ll 


PLATE sil. 





HEPATIC ENLARGEMENT DUE TO CONGESTION SECONDARY TO CARDIAC 
DISEASE. OUTLINE OF CARDIAC AND HEPATIC DULNESS. 





HYPEREMIA OF THE LIVER. 611 


that of the ordinary form of cirrhosis, with the difference, however, that 
in this form the distribution of the cirrhotic areas is not uniform, but 
very irregular. 

Under conditions of this kind the granular appearance of the surface 
of the liver and of sections grows still more pronounced, and the outlines 
of the lobules of the liver seem more circumscribed and distinct from the 
fact that those parts of the lobules that are really central on first sight 
present the outline of the interlobular reticulum. 

Symptoms.—Owing to the fact that this disease of the liver develops 
very slowly, the first stages of engorgement of the organ with blood pro- 
duce no symptoms and are not recognized until after the death of the 
patient. 

If the enlargement of the liver has attained a certain degree, the con- 
dition can be discovered by palpation and percussion. The surface of 
the organ feels hard, tense, and smooth, the margin rounded and extend- 
ing as far down as the umbilicus or even further. The liver is sensitive 
to pressure. In cases of tricuspid insufficiency it may even be possible 
to feel systolic pulsations over the liver as a result of regurgitation of the 
blood into the veins. If the condition persists for a long time, the liver 
gradually grows smaller as a result of atrophy of the parenchyma, in- 
crease of the connective tissue, and a reduction in the quantity of blood 
following the general cachexia that soon supervenes. Under these cir- 
cumstances the liver does not feel so tense. . 


Immediately following paracentesis of the abdomen for the removal of ascitic 
fluid, the surface of the liver may feel nodular from the fact that the blood streams 
into the liver as soon as the pressure within the abdomen is relieved, and owing to the 
structural changes that have occurred within the organ, all parts of the surface are 
i distended with blood, and hence the ee of its surface (E. Wag- 
ner 


Occasionally the enlargement of the liver may be apparent to the 
eye from the protrusion of the hypochondriac region. 

The subjective signs of passive hyperemia of the liver vary. They are 
proportionate to the rapidity with which the condition develops more than 
to the degree of development. It may happen that very considerable 
degrees of swelling cause no symptoms whatever provided the enlarge- 
ment has developed gradually, whereas slight degrees of swelling in the 
beginning of stasis may cause a very disagreeable feeling of fulness in the 
epigastric region and may cause the patient to complain of the pressure of 
his clothing. This is particularly noticeable after eating, owing to the fill- 
ing of the stomach and the hyperemia of the liver during the period of 
digestion. At times evidence of passive congestion is noticed in the portal 
system, and is usually shown by dyspeptic and gastric disturbances and 
by swelling of the hemorrhoidal veins. 

A very mild form of icterus is quite frequently seen. As arule, it is so 
slight that it is altogether overlooked on superficial examination and is 
manifested only by the passage in the urine of a minute quantity of uro- 
bilin. Bile-pigment itself is not necessarily found in the urine. The 
most probable explanation of this icterus is that it is due to absorption of 
bile following compression of some of the bile-channels within the liver by 
dilated capillaries. Grawitz f is inclined to attribute it to polycholia, for 
the reason that he found free hemoglobin in the blood in many cases of 


* Deutsches Archiv fiir klin. Medicin, 1884, vol. xxxtv, p. 536. 
+ Deutsches Archiv fiir klin. M edicin, vol. Liv, p. 61. 


612 DISEASES OF THE LIVER, 


heart-lesions, and claims that this hemoglobin originates from the disin- 
tegration of red blood-corpuscles that are no longer as resistant as normal. 
The appearance of icterus is not universal, and its degree is variable and in 
no way dependent on the degree of hyperemia and stasis. According to 
Thierfelder, it is less frequently seen in cases where the hyperemia of the 
liver is caused by certain diseases of the lungs than when it is caused by 
diseases of the heart. I cannot indorse this view. The combination of 
cyanosis and of icterus often seen in cases of this character leads to a pecu- 
liar greenish coloration of the skin. 

In addition to passive hyperemia of the liver, a number of the other 
complications of the primary disease of the heart or lungs are noticed. 
Thus, serous exudates, edema, diminution of the flow of urine, disturb- 
ances of respiration, etc., may all complicate the lesion of the liver. It is 
very noticeable, however, that the affection of the liver seems to occupy a 
peculiarly independent position among all the possible sequels of cardiac 
and pulmonary diseases. The other complications do not appear with any 
degree of regularity, so that at one time the one, at another time the other, 
is more apparent. The hyperemia of the liver, on the other hand, seems 
to be constantly present, and when it is once fully developed it seems to 
persist until the death of the patient, varying of course in intensity from 
time to time. In fact, the swelling of the liver may be the only symptom 
outside of the affected organs themselves. It is possible that in the first- 
named group of cases the function of the liver is to act as a safety-valve by 
absorbing like a sponge all the blood that the heart cannot master; in this 
way congestion of other organs is avoided and they do not become so 
hyperemic. 

There are a number of other peculiarities in connection with this con- 
dition that merit particular mention. They refer to the swelling of the 
spleen and the origin of the ascitic fluid that is usually exuded. As arule, 
cirrhosis of the liver is followed by enlargement of the spleen. In the case 
of passive hyperemia of the liver, however, the spleen in only indurated 
but not enlarged, although in both conditions the flow of blood from the 
spleen is impeded. It is possible that the time at which the stasis de- 
velops can be made responsible for this peculiarity, or that in cirrhosis the 
frequent recurrence of hyperemia of the organ during digestion plays a 
certain réle. 

Ascites is, aS a rule, a symptom of subordinate significance in the gen- 
eral disease-picture of cardiac dropsy, and generally develops at a late 
stage of the disease, and then only to a slight degree. Ascites, moreover, 
stands in no relation, in regard to its intensity, to the degree of swelling of 
the liver that may be present. In some diseases of the heart, however, we 
_see the development of ascites at so early a period of the disease that the 
suspicion of disease of the peritoneum is created. This is partjcularly the 
case when, as so often happens, all evidence of edema of the lower extrem- 
ities is absent or is present only to a very slight degree. Continued observa- 
tion, however, will reveal the cardiac origin of the trouble, and the com- 
paratively favorable course that the abdominal lesion takes will soon ex- 
clude peritoneal disease. Ascites of this kind may not be accompanied 
by a very high degree of swelling of the liver from hyperemia or stasis. 
In some eases, it is true, cirrhosis of the liver from stasis proper or 
the induration of the organ from proliferation of connective tissue, or, 
in other instances, parenchymatous swelling of the liver, may play a cer- 
tain réle in the causation of ascites, but there are a number of cases on 


HYPEREMIA OF THE LIVER. 6138 


record in which isolated ascites of cardiac origin existed for a long time 
and finally disappeared after repeated tapping and withdrawal of the accu- 
mulated fluid. It is probable that in these instances the safety-valve 
action of the liver was insufficient, so that the congestion of the abdominal 
organs became so great that transudation of fluid occurred into the abdo- 
minal cavity or that exudative peritonitis developed. We must assume 
that the different vascular areas of the body are independent in a manner 
and that it will depend on their individual state or on individual pecu- 
liarities whether congestion, hyperemia, exudation, etc., will occur in the 
course of cardiac stasis in this or that part of the body. 

The liver, already enlarged from passive congestion, may in the course 
of a few days become still larger; whereas in the case of a healthy liver, 
acute attacks of cardiac insufficiency cause no distinct enlargement of the 
organ. In other words, if the liver enlarges rapidly as a result of cardiac 
insufficiency, we must assume that the condition of stasis was chronic, 
but that the liver was comparatively small before the acute attack, and 
that the condition of chronic stasis had in all probability existed for some 
time but had evaded detection. In the case of children this does not 
quite hold true, since here an enormous swelling of the liver may be noticed 
in the course of a few days during an attack of diphtheria. The swelling 
is caused partly by parenchymatous swelling, partly by hyperemia of the 
organ from stasis, the latter condition being the result of cardiac weakness 
combined with disease of the bronchi. We can conclude, therefore, that 
the liver in children is more elastic than in adults, or that it is rendered so 
by the acute disease. 

Diagnosis.—The most important point in the differential diagnosis of 
hyperemia of the liver from other lesions of the organ that are accompanied 
by enlargement is that a hyperemic liver constantly changes in volume, 
whereas in all the other diseases the volume of the liver remains uniformly 
large. In passive hyperemia this change is still more apparent than in 
simple congestion, because the capacity of the dilated blood-vessels 
within the liver is permanently increased in the former state. Much will 
depend onthe power of the heart to hold the blood accumulating in it and to 
propelit onward. Thecharacter of the cardiac lesion, therefore, will de- 
termine whether a decrease in the swelling will occur, and to what degree 
the size of the swollen organ may decrease; 7. e., whether the swelling per- 
sists for days, weeks, or months, or whether it disappears rapidly or slowly. 
In cases where the liver is very much enlarged a decrease in the size of the 
organ and an increase in the quantity of urine voided may be considered 
the first signs of improvement of the condition of the heart; on the other 
hand, hyperemic swelling of the liver and the consequent sensation of 
pressure may be one of the first indications that a cardiac lesion exists. 
As the distress incident to the swelling of the liver is usually increased 
after eating, the diagnosis of gastric trouble is frequently made. 

Passive congestion of the liver is also an important symptom in other 
diseases of the liver, and constitutes a frequent complication. It is found 
in the different forms of cirrhosis and in fatty degeneration of the liver, be- 
cause alcohol, the chief factor in the causation of these two diseases, affects 
the heart at the same time. I believe that this enlargement is frequently 
overlooked, and that the decrease in the size of the organ that occurs in 
the later stages as a result of the decrease in the volume of blood is attri- 
buted to atrophy of the liver. 

Treatment.—The treatment of passive congestion of the liver from 


614 DISEASES OF THE LIVER. 


stasis must be directed primarily against the cause of the condition—viz., 
the cardiac insufficiency. In cases, too, in which the primary trouble 
is situated in the lungs, it is, as a rule, easier to direct treatment against the 
complicating cardiac weakness than against the lesion of the lungs. The 
heart should be protected from excessive work, and later should be 
strengthened by systematic exercise. The quantity of fluid taken should 
be reduced; and such drugs as digitalis, camphor, strophanthus, etc., 
should be given with diuretics like calomel, squill, theobromin, and 
potassium salts. If venous plethora is very great, blood-letting may 
be indicated in many cases, the favorable effects of this procedure being 
at once demonstrated by a marked decrease in the swelling of the liver. 

The diet should be restricted, and in this manner the flow of blood to 
the intestine decreased, the radicles of the portal vein in this way being 
also freed from an excess of blood. As spontaneous hemorrhoidal bleed- 
ing is known to relieve congestion of the liver, it seems a good plan to 
produce such hemorrhage artificially, and for this purpose it was formerly 
customary to apply leeches to the region of the anus. 

A course of salines, either Glauber salts or some of the saline waters, 
is also a valuable adjuvant in the treatment of the condition under dis- 
cussion, particularly in the initial stages. Abstinence from irritating 
food and from alcohol is also indicated, and should be insisted upon for 
long periods of time. The good results obtained from these measures 
show conclusively what an important rdéle active congestion and other 
disturbances of the parenchyma of the liver play in the causation and 
the aggravation of stasis. All the measures discussed will be particu- 
larly effective in cases in which the stasis is due to pure hyperemia. 

If the pain in the region of the liver is very severe, the same measures 
should be applied as in perihepatitis, such as the ice-bag, leeches, or warm 
compresses. 

If ascites is very great, paracentesis acts both as a palliative and cura- 
tive form of treatment. It acts by lessening the impediment to the circu- 
lation of the blood within the abdominal cavity, and in this manner en- 
couraging the absorption of the transudate that has formed. It is in these 
cases particularly that a cure has actually been known to occur after re- 
peated tapping and removal of the ascitic fluid. 


ACTIVE HYPEREMIA OF THE LIVER; CONGESTION OF THE LIVER. 


We include under this heading all those forms of engorgement of the 
liver with blood that are not caused by the presence of some obstruction 
to the flow of blood from the liver. In the case of other organs than the 
liver it is, as a rule, a very difficult matter to find an adequate explanation 
for the different hyperemic states that are occasionally noticed, nearly all 
the interpretations offered being purely hypothetical. In the case of the 
liver this is particularly true when one comes to venturing explanations 
on the origin of hyperemia of this organ. In the first place, no correct or 
even approximate estimation of the quantity of blood contained in the 
organ during life can be obtained from postmortem findings. Further, 
the ,blood-supply of the liver is exceedingly complicated and intricate, 
inasmuch as blood flows into the organ from two different directions and 
from two sets of vessels—the hepatic artery and the portal vein. It is 
impossible for us to determine to what extent the one or the other set of 
vessels participates in the excessive determination of blood to the liver. 


HYPEREMIA OF THE LIVER. 615 


We know that very peculiar conditions may exist in this respect, as the 
investigations of Gad demonstrate. 


Gad allowed warm salt solutions, of the strength of 0.5 per cent., to flow through 
the liver while it was still warm, immediately after removal from the body of the 
animal. If the salt solution was allowed to flow into the portal opening alone, he 
found that more fluid percolated through the liver than if he allowed the stream to 
enter both the portal vein and the hepatic artery. It appears, therefore, as though 
the current flowing through the portal vein was impeded in its course by the current 
flowing through the hepatic artery. This may possibly be explained from the pres- 
sure exercised by the small branches of the hepatic artery on the small branches of 
the portal vein which run in their immediate vicinity. Possibly, too, the two cur- 
rents oppose each other within the capillary network where they meet. 


Our knowledge of hyperemia of the liver, from the very nature of the 
question, is based as much on general conclusions, traditions, and theo- 
retic considerations as on exact anatomic investigations; in fact, it may 
be said that we know a great deal less from the latter source than from 
the former. While it is true, therefore, that many of our conclusions are 
not grounded on a substantial basis of established facts, we are not justi- 
fied in completely ignoring them for that reason. They require, of course, 
careful and critical reviewing before we permit ourselves to constitute 
them the starting-point for further considerations. It is possible that 
many of these congestive states are due to changes in the innervation of 
the blood-vessels of the liver (both of the portal vein and of the hepatic 
artery); in other instances it is quite possible that such changes in normal 
innervation or changes in the parenchyma of the liver itself cause abnor- 
mal narrowing or dilatation of the lumen of the capillaries. 

As a rule, probably, states of congestion are accompanied by an in- 
creased flow of blood through the liver: or, again, certain external condi- 
tions may be responsible for the change i in the « quantity of blood contained 
within the liver and the amount of blood that flows through the organ in a 
given time. Whenever the abdominal cavity is overfilled (by food, feces, 
gas, deposits of fat), the current of blood passing through the liver is im- 
peded by the pressure exercised on the organ; at the same time the affer- 
ent part of the capillary area may be engorged. In case, on the other 
hand, the abdominal walls are relaxed and flaccid it may very well occur 
that an atonic condition of the blood-vessels results, and that they con- 
sequently become dilated. 

The respiratory movements are an important factor in the regulation 
of the flow of blood through the liver; and they are of more significance 
for the flow of blood than for the quantity of blood contained in the organ 
at a given time. We know from observations on peripheral parts of the 
body and from experiments on the artificial passage of currents of blood 
through different isolated organs that a change of position and passive 
movements are capable of exercising a great influence on the capillary 
blood-stream as regards the rapidity of its flow. In the case of the liver 
the movements of the diaphragm act in this way, and, in addition, deep 
inspirations cause an increased suction of blood from the hepatic veins 
into the right heart. Any impediments to normal respiratory movements 
must necessarily, therefore, cause a slowing of the flow of blood through 
the liver. From this there results an accumulation of blood in the portal 
and hepatic capillaries. 

Changes in the constitution of the blood (“thickening”) may also 
possibly play a réle. 


616 DISEASES OF THE LIVER. 


Etiology.—Among possible causes of congestion of the liver must be 
mentioned increase and prolongation of the normal hyperemia during 
digestion as a result of too copious or too frequent meals. This overfeed- 
ing is particularly injurious in still another way if it is combined with 
a sedentary mode of life and lack of sufficient exercise, for under these 
circumstances obesity may frequently be seen to develop, followed by 
the usual difficulty in breathing and in the general power of locomotion. 
These two factors, in their turn, again impede the flow of blood through 
the liver. 

The quality of the ingesta has much to do with digestive hyperemia. 
Alcohol, especially, causes high degrees of digestive hyperemia, aside from 
the hyperemia caused by food taken at the same time (v. Kahlden). 
Strong spices and coffee seem to act in a similar manner. It is also possi- 
ble that certain toxins developing as a result of putrefactive changes in 
the intestine, particularly in gourmands, lead to disturbances of digestion 
and hyperemia of the liver (Dujardin-Beaumetz’s stercoremia) (Bou- 
chard). 

Under all the conditions indicated above, other abnormal states be- 
sides hyperemia soon develop. Hyperemia is only the first stage, so to 
speak, of such changes in the parenchyma of the liver as enlargement of the 
organ, albuminous or fatty infiltration of the hepatic cells, and, later, 
proliferation of the interstitial connective tissues. Overfeeding and alco- 
holism act on the liver in the manner described and at the same time exer- 
cise their deleterious effects on other organs of the body, particularly the 
stomach and the heart, and also on the general constitution of the patient. 
It may be said, therefore, that the congestion of the liver is merely a more 
or less conspicuous part of a general disease-picture that may be called 
abdominal plethora, general plethora, or general obesity, which in its later 
stages is, as arule, complicated by gout, gravel, and glycosuria. 

If the affection of the heart is the most conspicuous symptom, passive 
congestion of the liver may develop, and in this way be combined with 
hyperemia of the organ; or it may even take the place of the latter condi- 
tion. 

Digestive disturbances and toxic agencies are by far the most impor- 
tant factors in the production of this hyperemia of the liver; all other possi- 
ble causes are far less important. We may also mention contusions of the 
region of the liver and the effect of tropical climates. } 

In the tropics hyperemia of the liver, and a number of diseases of the 
liver that develop from this condition, are frequently seen (abscess, fatty 
liver, cirrhosis), particularly in the case of Europeans, a fact that has 
been falsely attributed to the effect of the great heat. An elevation of the 
temperature alone has nothing whatever to do with it, the real cause being 
the digestive disturbances that develop at the same time in these climates, 
and certain miasmatic infections, particularly malaria and dysentery, and 
probably others of which we are ignorant. A tropical climate is delete- 
rious only in the sense that alcohol and irritating or abundant food can 
exercise a bad effect in quantities that would not be harmful in a more 
temperate climate where general metabolism is more active. 

Domestic infectious diseases, such as typhoid fever, the acute exan- 
themata, and others, can produce the same changes in the liver (hypere- 
mia and parenchymatous swelling of the organ), just as do the tropical 
miasms. Scurvy, too, according to the older observations on this disease, 
is capable of producing the same hepatic disturbances. In diabetes 


Whe, tra ee en's eee eee 


HYPEREMIA OF THE LIVER. 617 


mellitus, a disease in which, a priori, a considerable involvement of the 
liver should be expected, hyperemia of the organ has, as a matter of fact, 
rarely been observed. 

During menstruation we see changes in the liver corresponding to 
those seen in many other organs. These may consist in transitory affec- 
tions of the organ that accompany menstruation per se, or they may be 
caused by sudden interruption of normal menstruation by cold, psychic 
disturbances, etc. ‘These vicarious forms of hyperemia are transitory in 
character, but may appear for a long time during the climacteric. It is 
stated that the cessation of hemorrhoidal bleedings that once occurred 
habitually can be followed by disturbances of the above kind in the liver. 
Permanent disturbances, however, never develop from the stoppage of 
such habitual bleeding. It appears that the effect of the stoppage is ex- 
ercised on the digestive organs or other parts of the body, the latter be- 
coming congested if the plethora is not relieved by a hemorrhage, and 
becoming disordered, and thus in their turn helping to produce disorder of 
the liver. 

Other possible causes of hyperemia of the liver that have been de- 
scribed are disturbances of the innervation of the organ in the course of 
hysteria, psychic excitement, terror or fright, and excessive mental effort 
(Monneret). 

Local lesions of the liver, such as neoplasms, parasites, etc., cause an 
engorgement of the surrounding tissues with blood that may be due either 
to hyperemia or to congestion. 

Symptoms.—The symptoms of congestion of the liver, owing to the 
different possible causes of this condition, are rarely manifested in a pure 
and uncomplicated form. As in the case of passive congestion, they 
consist chiefly in a sensation of pressure and fulness in the right hypo- 
chondriac and epigastric regions that may be so intense as to amount to 
actual pain, and may be increased by movement, by breathing, and on 
occupying a position on the side. At the same time percussion and pal- 
pation will reveal an enlargement of the liver, tenderness, and an increase 
in the consistency of the organ. All these disturbances are particularly 
apparent at the time of the greatest digestive activity, and are, as a rule, 
combined with other disturbances of digestion, such as pressure in the 
region of the stomach, flatulence, heartburn, and congestive oppression in 
the head. 

In forms of hyperemia of the liver that are not of digestive origin all 
the symptoms are, in general, aggravated at the time of the greatest 
digestive activity, particularly after the ingestion of irritating food. This 
effect is more manifest in this form of hyperemia than in that which is 
dependent on lesions or disorders of the heart. In the latter no period- 
icity can be noticed, in the former a periodic aggravation seems in many 
instances to take place after eating. The general disease is, however, as a 
rule, so complicated that it.is impossible to decide in each individual case 
whether the hyperemia is mechanical or congestive in character. 

In the course of the disease, particularly if it is due to habitual conges- 
tion, icterus often appears, either following an exacerbation of the diges- 
tive disturbances or, again, without any increase in the dyspeptic symp- 
toms. It is probably due to stasis in the bile-capillaries or to catarrhal 
changes in the common duct.. This form of icterus may be very severe in 
the menstrual form of hyperemia of the liver. 

Diagnosis.—lIn the discussion of the causes of congestion of the liver 


618 DISEASES OF THE LIVER. 


we have seen that this condition, in case it attains pathologic significance, 
rarely constitutes a transitory state lasting only several days or weeks. 
As a rule, the condition becomes permanent, and frequently becomes 
aggravated, so that it may in this way predispose to more serious and 
deep-seated diseases of the liver. It is for this reason that the symptoms 
are of great diagnostic significance, even though they are not very marked 
and are not at once apparent to the physician or to the patient. In all 
cases of abdominal plethora these symptoms should be particularly looked 
for, and if they are discovered in this or similar states, it is the duty of the 
physician to institute a course of treatment directed toward their removal 
even against the wishes of the patient. In this manner it is often possible 
to avoid very serious diseases. It will frequently happen that some in- 
volvement of the parenchyma of the liver is present at the time the symp- 
toms of congestion are first discovered; but, as a rule, it is impossible to 
determine this at once, and the decision will have to be rendered later 
from the subsequent course of the disease. A valuable criterion for the 
seriousness of the involvement is the size of the liver; the less the organ is 
enlarged and the more rapidly the swelling subsides, the less danger, we 
may say, is there of extensive parenchymatous involvement, and the less 
complicated is the hyperemia. 

The prognosis, of course, is dependent on the presence or absence 
of other conditions, and on the power of the patient to abstain from 
injurious indulgences, as alcohol, or to withdraw from dangerous surround- 
ings (malaria); in other words, it is, in many instances, dependent on 
the calling and the character of the patient. 

Treatment.—The treatment of hyperemia of the liver is essentially 
dependent upon the cause of the trouble. In many of the infectious 
diseases the treatment of the hepatic complication coincides exactly with 
the treatment of the primary disease. In cases of hyperemia from 
miasmatic infection in the tropics, temporary or permanent change of 
climate is essential; and in the cases due to menstrual or vicarious con- 
gestion a regulation of the disordered functions is indicated. It may 
even be necessary to induce bleeding by artificial means. Traumatic 
hyperemia calls for absolute rest, and the local application of cold in the 
form of an ice-bag, or leeches. If the pain is very severe, the hypo- 
dermic administration of morphin or some other form of opium to 
arrest the peristaltic action of the bowels is necessary. Those forms 
of congestion that are not due to trauma are rarely so violent as to require 
antiphlogistic medication. Our chief remedy is a regulation of the diet. 
This applies not only to the majority of cases in which the involvement 
of the liver is due to digestive or toxic causes, but also to all other forms, 
for the reason that a reduction of the congestion of the liver during diges- 
tion will protect the organ from the effects of other irritants, such as 
malaria, trauma, etc. 

In the acute forms of hyperemia and in the acute exacerbations of 
chronic hyperemia the functional activity of the liver should be reduced 
as much as possible by limiting the amount of food taken, the diet being 
restricted to thin soups, water, and weak tea. The general health of the 
patient will have to be studied and these restrictions carried on only as long 
as nutrition remains fairly good, the state of the liver alone not constitut- 
ing a proper guide. It if becomes necessary to give a more plentiful 
and a more stimulating diet, the amount should be regulated by the actual 
demands of the body; but all overfeeding and the ingestion of all irritating 


HY PEREMIA OF THE LIVER. 619 


‘food should be avoided. Aside from the qualitative composition of the 
food, the latter condition can be fulfilled by causing the patient to drink 
much water. The greatest difficulty will be encountered in those accus- 
tomed to an abundant diet, and it is precisely in these cases that such 
restrictions are especially necessary; in general, although not always, 
such subjects will be found to be plethoric. All alcoholic beverages, 
irritating spices, as mustard, pepper, etc., should be completely elim- 
inated from the diet, and the amount of salt and condiments is to 
be restricted. Coffee and roasted foods are to be condemned. These 
measures alone, combined with simplicity of food, will lead to a reduction 
of the amount eaten. A mixed diet is to be preferred to a monotonous 
one, for the reason that we must take care not to stimulate the formation 
of urea alone, on the one hand, or the storing of fats and glycogen, on the 
other. These indications are, in general, fulfilled if the patient is re- 
stricted to a milk diet or to one consisting principally of soups, vege- 
tables, and fruits. In many instances the choice of foods will have to be 
governed to a large extent by the state of the stomach and bowels and by 
the general constitution of the patient. In fat subjects amylaceous foods 
will have to be restricted; in emaciated or reduced subjects fat and pro- 
teids are necessary and can be furnished by a non-stimulating diet. 

The moderate employment of cathartics has for a long time been rec- 
ognized as very useful in congestion of the liver. According to the ex- 
perience of Thierfelder, gourmandizing is less harmful if the bowels are 
frequently and thoroughly evacuated than if the reverse is the case. It is 
difficult to decide whether the incomplete assimilation of the food ingested 
that may be said to follow frequent purging is best explained on this 
ground. Such an interpretation is the first to present itself; at the 
same time, it is quite probable that the removal of putrefactive products, 
and the influence that is exercised by the increased peristalsis on the 
blood-current in the portal vein are still more important. The dietetic 
regulations formulated above are alone capable of increasing the peristalsis 
of the bowels and producing free evacuations, particularly by the fruits 
and vegetables prescribed. Saline remedies, rhubarb, cascara, senna, and 
aloes are all useful. The last-named irritating drugs should be used care- 
fully and sparingly, and certainly not for a long time, owing to the effect 
they exercise on the intestinal tract. I should hardly say, however, that 
it is best not to use them at all because they might irritate the liver, 
although the latter recommendation has been made by several authors 
(Cantani). 

The administration of saline, alkaline, and alkaline-saline mineral 
waters plays an important réle in the treatment of congestion of the liver 
and of the general disturbances of health associated with this condition. 
In choosing one or the other of these waters the general constitution of 
the patient and, in particular, the condition of the gastro-intestinal tract 
must be considered. Cold Glauber-salts waters (as Marienbad, I’ranzens- 
bad, Elster, and Tarasp) are indicated in cases of overfeeding, abdominal 
plethora, and constipation. Cold saline waters, on the other hand, should 
be recommended where plethora is less pronounced, and in all those cases 
where bathing is valuable for the treatment of complicating affections of 
the heart. Waters of the latter class are found in Kissingen, Homburg, 
Nauheim, Pyrmont, and Soden. Warm waters (such as those of Carls- 
bad, Vichy, Aix-la-Chapelle, and Wiesbaden) are indicated in those cases 
in which parenchymatous changes of the liver are already present, or at 


620 DISEASES OF THE LIVER. 


least seem to be impending. Carlsbad and Vichy waters are more effec- 
tive in the latter respect than the saline waters of Wiesbaden, Aix-la-Cha- 
pelle, and Baden-Baden. Bitter waters are less adapted for regular courses 
of treatment than of frequent use over a long time. 

Enemata are also useful in treating the obstinate constipation that 
so-often complicates this disease. It is possible that they act on the 
blood directly, by causing a larger absorption of water, and that, as a 
result, the blood is, so to say, diluted. This applies particularly to 
injections of warm water, if they are frequently employed, or to the 
administration per rectum of aromatic infusions, such as those of chamo- 
mile, valerian, etc. The old “visceral enemata of Kampf’ possibly 
fulfilled this indication. 

The French school of clinicians recommends such intestinal disinfec- 
tants as bismuth, naphthalin, naphthol, salol, resorcin, ete. 

Acute congestion of the liver accompanied by pain calls for rest; 
chronic or frequently repeated attacks of hyperemia, on the other hand, 
call for exercise. Physical exertion in the latter cases acts beneficially by 
stimulating and increasing the rapidity of the blood-stream and the gen- 
eral circulation, as well as by promoting deeper respiratory excursions. 
In this manner an auto-massage of the liver is obtained which is unques- 
tionably more effective than the external form of massage of the organ 
recommended by Durand-Fardel. It is probable that this external 
method acts indirectly through the agency of the intestine. 

Pain is rarely so severe in congestion of the liver as to call for active 
interference. In the acute forms in which perihepatitic irritation may 
occur antiphlogistics are indicated; in the chronic forms warm com- 
presses, or rarely narcotics. The latter class of drugs is particularly 
bad in this disease for the reason that they arrest the necessary peristaltic 
action of the bowels; for this reason opium and morphin should be 
given very sparingly. 


LITERATURE. 


Bamberger: Loc. cit., p. 489. 

Brieger: ‘“ Beitrage zur Lehre von der fibrésen Hepatitis,” ‘“ Virchow’s Archiv,” 1879, 
vol, Lxxv, p. 99. 

_ Dujardin-Beaumetz: “ Des congestions du foie,” “ Bulletin der thérapie,’’ 1892, vol. 
Lxxi11; “ Jahresbericht,” 1, p. 190. ; 

Durand-Fardel : “ Du massage du foie dans l’engorgement hépatique simple,” “ Bulle- 
tin de thérapie,’”’ March 30, 1881; “ Jahresbericht,’’ 1, p. 186. 

Frerichs: Loc. cit., 1, 374. 

Gad, J.: “Studien tiber Beziehungen des Blutstroms in der Pfortader zum Blutstrom 
in der Leberarterie,”’ Dissertation, Berlin, 1873. 

Hirsch: “ Historisch-geographische Pathologie,’ 1886, p. 267. 

Liebermeister: “ Beitrige zur pathologischen Anatomie und Klinik der Leberkrank- 
heiten,” Tiibingen, 1864, pp. 77-135. 

— “Specielle Pathologie,” v, p. 228. : 

Monneret, E.: “ De la congestion non inflammatoire du foie,” “ Archives générales de 
médecine,” 1861, 1, p. 545. 

Naunyn: (Lecture) “ Berliner klin. Wochenschr.,’’ 1886, No. 37. 

Potain: tt foie cardiaque et la cirrhose hypertrophique,” “Gazette des hépitaux,”’ 
1892, No. 53. 

Senator, H.: “Ueber menstruelle Gelbsucht,” ‘“ Berliner klin. Wochenschr.,’’ 1872, 
No. 51, p. 615. 

Thierfelder: Loe. cit., p. 60. 


* Herba Centaurii minoris, Rhizom. Graminis, Rad. Saponariae, Rad. Taraxaci 
aa 8.0, heated with 300 c.c. of water. To be used as a clyster. 


pepe Lf; 


HEMORRHAGE INTO THE LIVER. 621 


HEMORRHAGE INTO THE LIVER. 
(Quincke.) 


Hemorrhage into the liver is rare for the reason that there is little room 
for bleeding in the tissues around the blood-vessels. _Hemorrhages when 
they do occur are seen either in small foci distributed throughout the liver 
parenchyma or beneath the serous covering or as a diffuse hemorrhagic 
infiltration of the liver-tissue. They originate from direct or indirect 
trauma, by wounding or crushing of the parts, and may follow either a 
simple solution of continuity or an actual destruction of tissue. In the 
new-born hemorrhages usually originate from acute passive congestion of 
the liver following difficult or retarded labor. In cases of chronic conges- 
tion of the liver hemorrhages are less frequently seen, for the reason that 
the tissues of the liver in this condition are so tough. 

Hemorrhage is, further, occasionally seen in very acute cases of con- 
gestion of the organ, in tropical malaria, in mussel-poisoning, in sclerema 
neonatorum, in chronic experimental phosphorus-poisoning in rabbits 
(Aufrecht), and in carcinomatous nodule formation. Hemorrhagic in- 
farcts, following the occlusion of small branches of the portal vein, are 
a rare occurrence (Dreschfeld, Woolridge). Hemorrhages resembling 
infarcts are sometimes seen in recurrent fever and in severe forms of 
puerperal infection. [Thromboses and hemorrhages in the liver (Schmorl) 
have recently grown to constitute an important part of the pathology of 
puerperal eclampsia.—ED. ] 

If an aneurysm of the hepatic artery bursts, larger hemorrhages may 
occur. It is doubtful whether circumscribed lesions of the walls of the 
portal system of blood-vessels within the liver can lead to similar acci- 
dents because of the low pressure therein. It is possible that a number 
of obscure cases that Frerichs found mentioned in the older literature 
and discussed were hemorrhages due to disease of some of the larger 
blood-vessels of the liver. 

Symptoms.—Hemorrhage into the tissues of the liver might possibly 
be suspected in case the symptoms of hyperemia of the liver (pain in the 
hepatic region and enlargement of the organ), already present, are sud- 
denly aggravated. If the hemorrhage involves the serous covering of 
the liver as a direct result of the solution of continuity or as a secondary 
effect of the bleeding, blood will be poured into the abdominal cavity. 
An accident of this character can sometimes be recognized from the 
sudden appearance of an area of dulness on percussion, together with 
definite peritonitic symptoms and a fall of the general blood-pressure. 
The life of the patient, of course, is greatly endangered by this accident. 
The symptoms of perforation of a hemorrhagic focus into the bile-channels 
or hemorrhage directly into these passages have already been discussed 
(see page 521). . 

It may occur that liver-cells, either individually or in groups, may pass through 
_ the peat veins from a traumatic hemorrhagic focus in the liver and enter the 

general circulation; they may cause embolic occlusion of pulmonary capillaries, 
or, in case the foramen ovale be patent, may even cause embolic occlusion of some 
of the capillaries of the greater circulation in the brain, the kidneys, etc. The ~ 
formation of such liver-cell emboli is probably favored by all those conditions of the 
hepatic parenchyma that are accompanied by a loosening of the connection 


between the different hepatic cells. Such states are, for example, fatty degenera- 
tion of the liver and other parenchymatous changes. Emboli of this character are 


622 DISEASES OF THE LIVER. 


not necessarily of traumatic origin, but may occasionally be seen in necrotic lesions 
of different cause, such as puerperal eclampsia, scarlatina, and diphtheria. Jiirgens 
and Klebs assume that hepatic cells carried to the different locations enumerated 
can proliferate where they happen to be lodged, but Lubarsch contradicts this, and 
states that they may remain intact for a period of about three weeks, but that, at 
the end of this time, they are dissolved and disappear, the only damage they are 
capable of doing being to cause local thromboses. 

The diseases that lead to the formation of liver-cell emboli are all very severe, so 
pee ae symptoms are known that can be definitely attributed to this particular 
accident. 


Dreschfeld: “ Hamorrhagische Infarcte,” ‘ Verhandlungen des X. internationalen 
Congresses,”’ 1890; “ Berichte,”’ 1891, 11, p. 195. 

Frerichs: Loc. cit., 1, 395. 

Lubarsch, O.: “Zur Lehre von der Parenchymzellenembolie,” ‘ Fortshcritte der 
Medicin,”’ 1893, Nos. 20 and 21. 

Meyer, Arthur: “ Ueber Leberzellenembolie,”’ Dissertation, Kiel, 1888. 

Thierfelder: Loc. cit., p. 73. 

Wooldridge, L. C.: “On Hemorrhagic Infarction of the Liver,” “ Transactions of the 
Patholog. Society of London,” 1888, vol. xxx1x, 421. 


PERIHEPATITIS. 
(Quincke.) 


Inflammation of the peritoneal covering of the liver is always secon- 
dary, and is seen either as the result of some general peritonitic involve- 
ment or as a Sequel of a variety of diseases of the liver. The latter form is 
particularly frequent and of great clinical importance and interest. If the 
perihepatitis is acute, it may be classified in accordance with its results as 
serous, fibrinous, or purulent. In chronic inflammation the subserous 
tissues are also involved or may be exclusively affected. In the latter 
instance we see a thickening of the serosa and the formation of con- 
nective-tissue adhesions with neighboring parts; occasionally, too, the 
process extends into the liver so as to involve the interstitial connective- 
tissue structures of the organ. The process may either extend into the 
liver from the surface of the organ or from the porta hepatis, following the 
course of Glisson’s capsule. 

In general, the process follows no typical course, and the inflammation 
is irregularly distributed and varies in intensity with the primary disease 
of the liver. It occasionally happens that the whole capsule of the organ 
is inflamed so that the exudate forms a sort of capsule around the liver. 
In the more pronounced cases of the latter kind the serous membrane may 
be several millimeters thick and be of a milk-white color. In such cases 
the liver will be compressed by this covering and will be deformed, and the 
margins of the organ will be rounded (“Zuckerguss-Leber,” or “ icing- 
liver’). When we see other deformities, such as corset liver, lobulated 
liver, etc., in combination with perihepatitis, we can assume, in general, 
that the deformities of the organ are essentially the result of the direct 
pressure from without or of some disease of the liver itself. 

Etiology.—In all cases of diffuse peritonitis the covering of the liver 
is usually more or less involved. The mechanical influences that cause 
perihepatitis are, as a rule, of long duration and of moderate degree, as, for 
instance, the pressure exercised by corsets or narrow waist-bands. Less 
frequently acute mechanical influences can be made responsible for the 
occurrence of perihepatitis. In general, the former agencies produce 
permanent deformities of the liver at the same time. 


PERIHEPATITIS. | 623 


Among the diseases of the liver itself, those that involve the paren- 
chyma of the organ do not lead to perihepatitis as frequently as do those 
that involve the interstitial connective tissues, such as abscess, cirrhosis, 
syphiloma, alveolar echinococcus, carcinoma,etc. The character of the 
primary disease will, as a rule, determine the character of the inflamma- 
tion of the serous membrane. 

Perihepatitis, either purulent, serous, or adhesive, frequently origi- 
nates from the gall-bladder. The disease may also start from some of the 
organs adjacent to the liver, such as a pleuritis of the right side by exten- 
sion through the diaphragm. A simple gastric ulcer may cause peri- 
hepatitis, particularly on the lower surface of the liver and on the anterior 
margin; in this case the inflammation is generally of the adhesive kind, 
and it may happen that the ulcerative process in the stomach wall extends 
to the substance of the liver by means of adhesions between the two 
organs. 

Symptoms.—In acute cases of perihepatitis pain is a prominent symp- 
tom. It may either be circumscribed or be felt throughout the whole 
hepatic region. From the distribution of the pain clues may sometimes 
be obtained in regard to the localization and the extent of the perihepatitic 
process. The pain is accentuated by pressure from without and by differ- 
ent movements, for which reason the pressure of the clothing is disagreeable 
to the patients and they avoid lying on the right side; at the same 
time and for the same reason, respiration may be slightly impeded. The 
pain, as in all forms of serous inflammations, is, as a rule, severe and 
lancinating. Palpation and percussion of the liver are, therefore, often 
rendered very difficult. At times a friction-sound may be heard and 
a fremitus may be felt over the area of perihepatitis, generally syn- 
chronously with respiration. 

In addition, all the symptoms of the primary disease will be observed, 
whether this be in the liver itself or in some other organ. Peri- 
hepatitis rarely causes vomiting or a considerable rise of temperature. 
Icterus is sometimes seen in this condition, but it is doubtful what causes 
it. Some authors are inclined to attribute it to the reduced rhythmic 
movements of the liver following the impediment in the normal respira- 
tory excursion; but whether this theory is correct or not cannot very well 
be determined. 

Chronic perihepatitis may run its course without causing any symp- 
toms whatever, and may not be noticed by the patient until ultimately 
the symptoms caused by adhesions with neighboring organs or thickening 
of the serosa of the liver appear. Adhesions between the diaphragm and 
the abdominal walls, if they are sufficiently developed, may hinder the 
respiratory motility of the lower margin of the liver, and the condition may 
be readily recognized in this manner. 

Chronic perihepatitis may extend to the connective-tissue structures 
within the liver and in this way produce a true hepatic cirrhosis with its 
clinical manifestations (Roller, Frerichs, loc. cit., 11, p. 92). 

In rare instances chronic inflammatory perihepatitis may cause a 
metamorphosis of the inflamed peritoneal covering of the liver into tough 
contracted connective tissue, so that the liver is inclosed in a sort of 
capsule. As the covering contracts, pressure is exercised on the organ and 
the circulation of the blood is impeded in the same way as in true cirrhosis 
of the organ; consequently, a disease-picture that is very similar to the 
latter condition may be seen, characterized, in particular, by the occur- 


624 DISEASES OF THE LIVER. 


rence of ascites and the remarkable reduction in the size of the liver. 
The spleen, in this condition, is not generally enlarged, for the reason that 
this organ cannot expand owing to the callous thickening of its capsule. 
Cases of this kind have been occasionally described in the older literature* 
and have recently been studied more carefully by Curschmann, Rumpf, 
Pick, and Hiibler, and have been called ‘“ Zuckergussleber” (perihepatitis 
chronica hyperplastica) by these authors. They are differentiated from 
cirrhosis by their longer course (six, even as much as fifteen years), 
during which the condition may become quiescent at times, or, on the 
other hand, an almost incredible number of paracenteses may have to be 
performed (as many as 301 in one case). 

The capsule may be from five to ten millimeters thick, and naturally 
compresses the liver considerably. As arule, the capsule consists of thick 
fibrous tissue. ‘The size of the liver may be reduced to one-half. If the 
capsule is cut, the tissue of the liver bulges above the surface of the section. 
It is not changed in its microscopic structures and reveals no proliferation 
of connective tissue. 

The exact cause for this peculiar form of thickening of the capsule is 
not at allclear. Inthe case of Hiibler frequent and very violent attacks of 
gall-stone colic occurred and possibly constituted an irritant predisposing 
to inflammation. In other cases, again, the first remote cause of the 
trouble seems to have been an attack of pericarditis occurring long before 
the development of the capsule formation and which at the time of its 
occurrence caused obliteration of the pericardial sac. Pick mentions the 
latter possibility and calls the condition pericarditic pseudo-cirrhosis of 
the liver. 


As a matter of fact, one or several of the following conditions are found at 
autopsy in cases of this kind, in addition, of course, to the thickening of the capsule 
of the liver: peritonitis, with fibrous exudates in the upper part of the abdominal 
cavity, in the region of the capsule of the spleen and of the parietal peritoneum, 
obliteration of the pericardium, and the formation of fibrous tissue in this region, 
and cirrhosis of the liver. 

It appears, therefore, that occasionally fibrinous perihepatitis originates from 
extension of an inflammation of the pericardium or of the pleura. It seems possible 
too, that cirrhosis of the liver from stasis resulting from cardiac insufficiency plays 
a part in impeding the flow of blood through the portal system of vessels. Another 
factor that may be made responsible for the appearance of ascites is fibrinous peri- 
tonitis, a lesion which may itself lead to the formation of an exudate or, at all events, 
may constitute a serious obstacle to the absorption of ascitic fluid by the parietal 
peritoneum. 

It is also possible that stasis of lymph can help produce ascites, from the fact that 
pericarditic or pleuritic exudates, by narrowing the intrathoracic space, compress 
lymph-channels situated within the thorax. 

In a certain sense that form of circumscribed exudative peritonitis that occurs 
between the liver and the diaphragm (subphrenic abscess), and is characterized by 
the collection of pus in that region, must be counted among the manifestations of 
perihepatitis. This peritonitis may originate from a gastric or a duodenal ulcer or 
from echinococcus of the liver. Clinically, the disease simulates pyopneumothorax, 
or less often an enlargement of the liver. (This condition is discussed in detail in 
another volume.) 


The pathologic significance, therefore, of perihepatitis and the prog- 
nosis of the disease may vary as much and be as closely dependent on the 
nature of the primary trouble as is, for example, pleuritis. Another 
analogy may be drawn between the two diseases from the fact that in 


* Budd, “ Diseases of the Liver,” p. 495. Bamberger, “ Krankheiten des chylo- 
poietischen Systems,” 2d edition, p. 495. 


at a ee le ie el 


PERIHEPATITIS. | 625 


both the appearance of an inflammation of the serous membrane signal- 
izes, for the first time, a diseased condition of the organ it is covering—in 
the case of perihepatitis the lungs, in the case of pleuritis the liver. 
With the discovery of these lesions, a more careful diagnosis can be made 
and an intelligent prophylaxis instituted. 

Diagnosis.—The pain of perihepatitis may be differentiated from pain 
originating within the liver by certain peculiarities. The former is of a 
more lancinating character and is increased by pressure, the latter (as in 
abscess of the liver) is more diffuse, indefinite, and radiates particularly 
into the region of the right shoulder-blade. It is true that this differentia- 
tion cannot always be made with absolute certainty, and it is even possible 
that the symptoms enumerated as characteristic of a hepatic pain are in 
reality due to the presence of circumscribed perihepatitis on the convex 
surface of the organ. 

The liver may be tender on pressure in other conditions besides peri- 
hepatitis, as in acute swelling with a rapid increase in the size of the organ 
(acute hyperemia, phosphorus-poisoning), in cases in which the volume 
of the liver decreases rapidly (acute atrophy), and, finally, sometimes in 
gall-stone colic. In the latter disease, it is true, the pain is, as arule, more 
violent, and the tenderness, while it may extend to regions outside the 
area of the liver proper, is still by far most pronounced immediately over 
the region of the gall-bladder. In concrete cases, at the same time, a 
reasonable doubt may exist in the mind of the diagnostician whether the 
pain is attributable to the tension of the walls of the gall-bladder or to 
inflammations in and around the liver. If the pain is due to some in- 
flammatory process, it is usually of longer duration, and, finally, as a rule, 
becomes strictly localized in one place or the other. 

Treatment.—Acute perihepatitis is often accompanied by such severe 
paroxysms of pain that the latter must be treated per se. In the most 
violent attacks leeches and the ice-bag may be applied; in the less severe, 
warm Priessnitz compresses or cataplasms, with rest and, possibly, the 
administration of narcotics. If the pain persists, vesication, or painting 
the painful places with iodin may be tried. In many cases it will be im- 
possible to treat the primary disease until the pain has been alleviated and 
the acute attack has subsided. Treatment of the primary disease, of 
course, constitutes the best prophylaxis against the recurrence of attacks. 


LITERATURE. 
Bamberger: Loc. cit., p. 495. 
Curschmann: “ Zur Diagnostik der mit Ascites verbundenen Erkrankungen der 
Leber und des Peritoneums,” “ Deutsche med. Wochenschr.,’’ 1884, p. 564. 
Frerichs: Loc. cit., 11, p. 4. 
Hiibler: “ Fall von chronischer Perihepatitis hyperplastica,” “ Berliner klin Wochen- 
schr.,’’ 1897, p. 1118. 
Longuet: ‘“ Du frottement perihépatique,” “L’Union méd.,” 1886, Nos. 85 and 86. 
Pick, Fr.: “ Pericarditische Pseudolebercirrhose,” ‘ Zeitschr. fiir klin. Medicin,” 
1896, vol. xx1x, p. 388. ; 
Roller: ‘Cholelithiasis als Ursache von Cirrhosis hepatis,” “ Berliner klin. Wochen- 
schr.,’’ 1879, p. 625. 
Rumpf, H. (Bostroem): “ Ueber die Zuckergussleber,”’ “Deutsches Archiv fir klin. 
Medicin,”’ 1895, vol. Lv, p. 272. ; 
Siegert, F.: “Ueber die Zuckergussleber und die pericarditische Pseudolebercir- 
rhose,” “ Virchow’s Archiv,” 1898, vol. critt, p. 251. 
Thierfelder: Loc. cit., p. 75. 
v. Wunschheim: “ Prager med. Wochenschr.,”’ 1893, No. 15. 
Illustration in “ Rumpel’s Atlas,” D, part 1. 2. 
40 


626 DISEASES OF THE LIVER. 


ACUTE HEPATITIS. 
(Quincke.) 


Among the acute inflammatory diseases of the liver the suppurative 
forms are best understood, and their origin is most comprehensible. 
These are always, possibly with exceedingly rare exceptions, caused by 
micro-organisms. As a result, the same symptoms are produced as in 
any form of suppuration in other parts of the body. The symptoms 
that are attributable to the particular involvement of the liver are merely 
dependent on the topographic position of the organ, and have nothing 
whatever to do with its specific function. Of course, the flow of bile is 
often impeded, and this symptom may, in a sense, be designated a spe- 
cific sign of involvement of the liver. 

The diseases of the liver that are designated diffuse acute inflamma- 
tions of the organ are more important, for the reason that they are inti- 
mately connected with the specific function of the organ and involve 
principally the glandular parenchyma. 

We can subdivide acute hepatitis into acute parenchymatous hepatitis, 
acute atrophy of the liver, and acute interstitial hepatitis. 


ACUTE PARENCHYMATOUS HEPATITIS. 


Anatomy ; Etiology.—Parenchymatous cloudy swelling of the liver 
is frequently found in certain infectious diseases, particularly in septice- 
mia, puerperal fever, typhoid fever, recurrent fever, pneumonia, and ery- 
sipelas. The substance of the organ, in these cases, appears to be more 
cloudy than usual and less transparent, the organ looking “as though it 
had been boiled.”’ On microscopic examination, it will be seen that the 
hepatic cells are cloudy, as a rule contain fine granulations and, if the 
disease is of longer duration, coarser refractive granules. The latter con- 
sist of albumin, and in the later stages of the disease of fat. Sometimes 
the hepatic cells are slightly swollen, so that the liver appears anemic and 
enlarged, with rounded margins. The milder degrees of this cloudy 
swelling, it appears, do not occur during the life of the patient, but must 
be considered a postmortem coagulative change; it is more pronounced 
in the cases under discussion, however, than in normal subjects. In 
particularly severe cases, of sepsis, for instance, the intimacy of the 
hepatic cells with the interstitial tissues of the liver and their connections 
with one another are considerably loosened, so that the trabecule of 
hepatic cells are more or less dislocated (disassociated, Browicz). The 
outline of the hepatic cells becomes indistinct, necrotic changes occur 
within them, and both the nuclei and the protoplasm lose their normal 
staining properties. Similar changes are seen in malaria, but in this dis- 
ease, as well as in sepsis, circumscribed areas of necrosis may appear; it 
may also happen that in malaria and in some of the other infectious dis- 
eases a diffuse or localized collection of embryonal cells occurs which later 
become organized into connective tissue. In many of these infectious 
diseases, particularly in malaria, sepsis, and typhoid, the specific patho- 
genic organisms may be found within the hepatic capillaries. As a rule, 
however, the latter are not present in sufficient numbers to warrant the 
suspicion that they cause by a purely local action the necrotic changes 


ACUTE HEPATITIS. 627 


described. In the production of all these lesions certain chemical poisons 
undoubtedly play a réle, and such poisons may be generated in remote 
parts of the body. 

This view is strengthened by our knowledge of the fact that some of the 
known chemical poisons are capable of producing similar parenchymatous 
swelling and cloudiness of the hepatic cells. Such poisons are, for in- 
stance, phosphorus, chloroform (EK. Fraenkel, Bandler), chloral (Geill), 
and some of the mushroom poisons, as Amanita phalloides. Lupinosis in 
animals and acute fatty degeneration from unknown causes in adults and 
in children are other similar conditions. Alcohol, too, must be men- 
tioned. This drug, however, can only act deleteriously in one large dose 
provided the liver has been previously damaged by the habitual abuse of 
spirits. In all the cases enumerated the cloudiness of the liver-cells is 
accompanied by fatty degeneration, and, in the case of alcohol and of 
phosphorus, with fatty infiltration. If the poisons act for a long time, 
interstitial proliferation may supervene. 

In the majority of the cases both of poisoning and of infection 
other organs are, as a rule, involved, and frequently to a higher degree 
than the liver. This may account for the fact that in the general 
picture of these infections and intoxications symptoms attributable to 
disease of the liver are frequently absent. With the exception of phos- 
phorus-poisoning, in which the liver is infiltrated with fat and conse- 
quently very much swollen, the liver is, in general, not much enlarged. 
Consequently, the degree of parenchymatous change cannot be deter- 
mined from the degree of enlargement, but must be deduced from the 
severity of the general symptoms pointing to this condition. 


Liebermeister has attempted to attribute the parenchymatous clouding of the 
liver (and of other tissues) to the febrile rise of temperature in different infections. 
This explanation is not correct, for we learn from our observations on human sub- 
jects that the changes in the tissues are in nowise proportionate to the height of the 
fever or its duration. Animal experiments show that artificial elevation of the tem- 
perature (in the heat-box, Litten) produces a fatty degeneration of the glandular 
cells, but no parenchymatous degeneration. More recent experiments by Ziegler and 
Wernhowsky show that cloudiness, vacuolation, and fatty degeneration of the 
hepatic cells and a loosening of their connection can occur, but do not, as a rule, take 
place until the overheating of the animal has been carried on for many days. 


Those cases in which the hepatic symptoms are very conspicuous, or 
in which we obtain the disease-picture of an acute hepatitis, are rare 
indeed. This form is most frequently encountered in the tropics. It is 
impossible, in many instances, to differentiate it from the congestive 
hyperemia of the liver so often seen in this climate; in fact, a gradual 
transition can be observed from simple changes in the vascularity of the 
liver and changes in the parenchyma that follow eating and are due to 
digestive engorgement of the organ, to active congestion, and, later, to 
acute parenchymatous hepatitis. 

Malaria and dysentery are unquestionably the chief causes for this 
acute hepatitis of the tropics. Apart from these two diseases, however, the 
development of hepatitis may be seen in Europeans that migrate to warm 
climates (see page 453). This is particularly the case in young people 
during the first year or so, and at all ages until they have become accus- 
tomed to the change of climate and before they have learned to moderate 
their diet and to refrain from eating as much as they did at home, particu- 
larly if they persist in indulging in a liberal animal diet or continue to 


628 DISEASES OF THE LIVER. 


abuse alcohol. The liver in these cases is enlarged and very vascular, 
soft, and filled with grayish, more or less softened foci that exude serum 
from their cut surfaces. The immediate vicinity of these foci is more 
vascular and usually harder than the foci themselves. Later the foci turn 
yellowish, dull, and finally atrophic from degeneration of the cells and 
absorption of the debris (Cayley). It is probable that this form of hepa- 
titis owes its origin to the action of intestinal ptomains that find a suitable 
nidus for their action in the liver when it is in a stage of chronic congestion, 
and which act as irritants. According to Kartulis, pathogenic microbes 
have been seen in a liver of this character without at the same time having 
caused the formation of abscesses. In Mexico, hepatitis of this kind is 
more frequently seen in summer than in the other seasons of the year 
(Mejia). 

These acute forms of hepatitis are not found in the tropics alone. 
Kartulis has described their occurrence, for instance, in Alexandria. In 
Europe they are probably very rare. Talma claims that he has observed 
such cases in Utrecht, and several years ago described seven cases of this 
character. He quotes the rather scanty and vague statements of older 
authors. Talma is inclined to seek the primary cause of the trouble in 
the intestine, and believes that the liver is secondarily affected either 
through the blood-vessels and the portal blood or through the lymphatics. 

Symptoms.—lIn the cases described by Talma the disease usually 
begins with vomiting, followed by diarrhea, a moderate degree of fever, 
and, after a few days, pain in the region of the liver. The liver is enlarged, 
its consistency increased, and it is tender on pressure. The organ is 
greatly swollen and on its surface nodular prominences can be felt that 
may be as large as a hen’s egg. As arule, icterus is present, but the feces 
are rarely discolored. The spleen is enlarged and readily palpable. Noth- 
ing abnormal can be discovered in the thoracic organs. The sensorium 
is free. The urine contains no albumin. 

In the course of the second week all the symptoms seem to recede, the 
liver and the spleen decrease in size, and complete recovery may occur at 
the expiration of from eight to fourteen days. Talma saw a fatal issue in 
only one case, on the ninth day. 

In Alexandria the course that these cases pursue is similar, and also 
favorable, the average duration being from two to three weeks. 

The following etiologic factors have been mentioned in the production 
of the tropical form of acute hepatitis: catching cold, overfatigue, insola- 
tion, errors of diet, alcoholic excesses, and attacks of malaria. The dis- 
ease here is more violent, frequently begins with a chill, the temperature 
rises higher, and all the symptoms are more pronounced and more grave. 
The liver may be so much enlarged that it extends 7 to 8 inches below the 
costal margin. The organ may be enlarged in certain circumscribed dis- 
tricts only; for instance, toward the ribs on its anterior surface or upward 
toward the diaphragm. At the same time local pain, a feeling of pressure 
under the costal margin, difficulty in breathing, and pain in the region of 
the shoulder may be present. Icterus, as a rule, is mild. 

In malarial hepatitis the picture of acute malaria is complicated 
by*certain hepatic symptoms. The liver and the spleen generally swell 
at the time of the fever paroxysms. Kartulis discovered plasmodia, but 
no bacteria, in the blood removed from the liver by aspiration. 

In the form of hepatitis seen in the tropics the final outcome of the 
disease is favorable in those cases that are afflicted for the first time, and 


ACUTE HEPATITIS. 629 


in which the liver was perfectly healthy before the onset of the disease. 
An attack of acute tropical hepatitis, however, predisposes to subsequent 
attacks that run a less favorable course. In case the general nutrition of 
the patient is not good, abscesses are liable to form, or the liver may remain 
permanently enlarged, and possibly atrophic cirrhosis may develop later. 
In Mexico the first attack generally leads to abscess-formation, and a cure 
of the disease is seen in exceptional cases only (Mejia). 

Termination ; Prognosis.—The prognosis of the primary form of 
parenchymatous hepatitis is favorable in temperate climates. In tropical 
climates the prognosis is dependent on the primary cause of the trouble 
and on the willingness or the ability of the patient to change his mode of 
life and to live in a manner suited to the exigencies of the climate. The 
probability of subsequent attacks grows with each recurrence of the dis- 
ease, and at the same time the probability of a complete restitution to 
a normal condition diminishes. 

Frequent recurrences of the disease lead to hypertrophy of the liver, 
then to chronic inflammation, and finally to cirrhosis. In malaria local- 
ized atrophic foci develop in the liver, and, in addition, nodular hyper- 
plasias that resemble adenomata. If the disease takes this form, it is 
called by French authors hépatite nodulaire (Sabourin, Kelsch and Kiener). 

In intoxications and infections the unfavorable issue may in some in- 
stances be determined by the disorders of metabolism that follow the 
derangement of the liver incident to parenchymatous hepatitis. In cases 
of this character acute atrophy of the liver may in rare instances result. 
This disease will be discussed in the following section. 

Treatment.—lIn general, the patients remain in bed without being 
told; but complete rest is an essential part of the treatment. In the be- 
ginning of the disease purgation by calomel or salts is to be reeommended, 
while emetics—as, for instance, lpecacuanha—are less indicated. In the 
subsequent course of the disease a mild laxative treatment and “ disinfec- 
tion of the intestine” are useful (see page 464). In the beginning the diet 
should be greatly restricted and remain simple and non-irritating through- 
out the whole course of the disease, milk and gruel soups being particu- 
larly advisable. Cayley advises the administration of chlorid of ammo- 
nium at the height of the disease in the daily dose of from 4 to 6 gm. 
Later he recommends tartar emetic and nitrate of potash, aqua regia with 
gentian, and daily doses of from 0.1 to 0.3 of euonymin with a little 
rhubarb. The latter prescription is intended to relieve the feeling of 
pressure in the side. Violent pain should be relieved by blood-letting and 
by the application of compresses to the hepatic region. The diet should 
remain non-irritating for a long time after convalescence and the use of 
alcohol should be eschewed. In hepatitis from malaria quinin should be 
administered in addition to the other remedies enumerated; as a rule, the 
size of the liver will decrease in a few days after the exhibition of quinin. 

If attacks of tropical hepatitis recur very frequently, the patient should 
be advised to move to another climate. 


LITERATURE. 


Aufrecht: “ Die acute Parenchymatose,” “ Deutsches Archiv fiir klin. Medicin,” vol. 
XL, p. 620, case 2. 

— “Die diffuse Leberentziindung nach Phosphor,’”’ “ Deutsches Archiv fiir klin. Medi- 
cin,”’ 1878, vol. xxi, p. 331. 

Browicz: “ Dissociation der Leberlippchen,” “ Virchow’s Archiv,” 1897, vol. cxLv1II 


p. 424. . 


630 DISEASES OF THE LIVER. 


Cayley, H.: “Tropical Affections of the Liver,” VIII. Congress fiir Hygiene und 
Demographie i in Budapest, 1894; “ Berichte,” vol. 11, p. 695. 

Dock: “ Malarial Liver,” “ Amer. Jour. of the Med. Sci., % April, 1834. 

Erdmann, L. (Bessarabien): “Virchow’s Archiv,’ 1868, Vol. XLII, p. 291. 

Frerichs: Loc. cit., II, p. 9 

Girode: “ Quelques faits d’ictére infectieux,”’ “Archives générales de médecine,” 
1891, 1, pp. 26 and 167. 

— “Infections avec ictére,”’ “ Archives générales de médecine,” 1892, 1, pp. 412 and 
555 (mostly pyemias and septicemias with icterus). 

Hirsch: “ Historisch-geographische Pathologie,”’ 1886, 111, p. 267. 

Kartulis: ‘Ueber verschiedene Leberkrankheiten in Aegypten,’’ VIII. Congress 
fiir Hygiene und Demographie in Budapest, 1894, vol. 11, pp. 643-657. 

Kelsch et Kiener: “ Archives de physiolog. norm. et pathol.,’’ 1878, 1879. 

— “Maladies des pays chands,”’ Paris, 1889. 

Mejia (Mexico): “ L’hépatite parenchymateuse aigué circonscrite,”’ “ Verhandlungen 
des X. internationalen Congresses,’’ 1890, part v, p. 26. 

Monneret: “ De la congestion non-inflammatoire du foie,’ ‘“ Archives générales,” 
1861, 1, p. 545. 

Runge: “ Krankheiten der Neugeborenen,” p. 162: ‘“‘Acute Fettdegeneration.” 

Sabourin: ‘ Archives de physiolog. norm. et patholog.,’’ 1880, 1884. 

Talma: “ Hepatitis parenchymatosa benigna,”’ “ Weekbl. v. het. Neederl. Tijdschr. 
vor. Geneesk.,’’ 1891, No. 20; ‘“ Berliner klin. Wochenschr.,”’ 1891, p. 1111. 
Ziegler (u. Werhowsky) : “Ueber die Wirkung der erhéhten Eigenwirme auf das 

Blut und die Gewebe,”’ ‘ Verhandlungen des Congresses fiir innere Medicin.”’ 
1895, p. 345. 
AFTER THE USE OF CHLORAL. 
Geill, Ch.: “ Vierteljahresschr. fir gerichtliche Medicin,” 1897, vol. xtv, p. 274. 
Gellhorn: ‘“ Allgemeine Zeitschr. fur Psychiatrie,” 1872, vol. xxv, p. 625; 1873, 
vol. xxIx, p. 428. 
Ogston: “ Edinburgh Med. Jour.,’”’ October, 1878, p. 289. 


EFFECTS OF CHLOROFORM. 


Bandler, V.: “ Mittheilungen aus den Grenzgebeiten der Medicin und Chirurgie,” 
1896, be: 303. 
Frankel, E.: “ Virchow’s Archiv,” 1892, vols. cxxvII, CXXIX. 


ne also the literature of acute atrophy of the liver, page 647, of fatty liver, 
_and of malarial liver. 


ACUTE ATROPHY OF THE LIVER. 
(Icterus gravis ; Ictére typhoide.) 


(Quincke. ) 


Acute atrophy of the liver is in the majority of cases a sequel to diffuse 
parenchymatous hepatitis; at the same time the disease is clinically and 
anatomically so clearly characterized that it merits particular discussion 
and deserves to be ranked as a distinct clinical entity, especially since 
Rokitansky, in 1842, determined and established the anatomic character- 
istics of this condition. 

Occurrence.—Acute atrophy of the liver is a very rare disease. It is 
seen more frequently in women than in men (proportion 8 to 5); and 
about one-half of those that are afflicted, particularly among women, are 
from twenty to thirty years of age. About one-half to one-third of all 
women afflicted are in the fourth month or in later stages of pregnancy. 
The lying-in period seems also to predispose to the disease, although it is 
lessfrequently encountered at this time than at earlier periods of preg- 
nancy. 

Acute atrophy of the liver has also been observed in children; but it is 
rare. Fr, Merkel has collated 18 and R. Schmidt 16 cases that occurred 
from the first days of life to the tenth year. [A casual examination of the 


ACUTE HEPATITIS. 631 


literature since 1896 adds five new cases, with a considerable number be- 
tween the ages of ten and fifteen years, probably as a result of the atten- 
tion drawn to the subject by the article of Merkel and the monograph 
of Schmidt.—Eb.] | 

Etiology.—Very little is known in regard to the causesof acute atrophy 
of the liver. Older statements in regard to “fright, anger, abuse of alco- 
hol,” are very unsatisfactory. As the preliminary stages of the disease 
resemble catarrhal icterus, we must assume either that some particular 
cause existed for the development of this icterus into acute atrophy or 
that in the course of the ordinary catarrhal form of icterus there entered 
into the disease some new factor that led to atrophy. Some of the cases 
observed (Meder, Case III) occurred during an epidemic of icterus, all the 
other cases of which were benign, a fact that furnishes no clue in either 
direction. 

Acute atrophy of the liver has been known to follow certain infectious 
diseases: for instance, osteomyelitis (Meder), diphtheria of the stomach 
(Cahn), erysipelas (Huntermann), sepsis (Drinkler, Babes), typhoid 
(Dorfler), recurrent fever, and syphilis (twenty cases, Meder). It is pos- 
sible that in these cases the ordinary form of parenchymatous degenera- 
tion of the liver that is so frequently seen in infectious diseases attained a 
particularly severe degree and terminated in an exceptional manner. 

In the secondary stage of syphilis, particularly in the beginning, acute 
atrophy of the liver has occasionally been seen following the attack 
of icterus that is so often seen at this time (Engel-Reymers, Senator, and 
others; altogether, in twenty cases). Aufrecht observed acute atrophy 
of the liver in sclerodermia neonatorum. : 

Poisons, too, may lead to acute atrophy of the liver. This has been 
positively demonstrated in the case of phosphorus when death does not 
ensue soon after the ingestion of the poison, but when the patient sur- 
vives for some time, several weeks or more (Mannkopf, Litten, Hedderich). 
It is said that acute alcoholic poisoning (Oppolzer, Laudet) and the abuse 
of spirits in general lead to this condition. Sausage-poisoning (Wolf) and 
mushroom-poisoning (Hecker) have also been made responsible for acute 
atrophy of the liver. Bandler has recently described a case in which 
acute atrophy followed within three days after chloroform narcosis in a 
beer-drinker, causing the death of the patient. Bandler assumes that the 
chloroform was retained in the liver in large quantities and that it was 
there combined with the lecithin and the cholesterin normally present in 
the organ. He also quotes three similar cases mentioned by Bastianelli.* 

It is quite probable that intoxication by ptomains oecurs in many 
cases where the function of the intestine is deranged, and that in certain 
of the infectious diseases bacterial toxins play an important rdéle. 

Kobert + advances the theory that an intoxication by phosphoretted 
hydrogen may occasionally occur. This gas, he assumes, is generated in 
the intestine from the phosphates by the action of bacteria. He believes 
that the hydrogen compound of phosphorus acts in the same way as phos- 
phorus itself. 

Many attempts have been made to discover certain bacteria that 
could be made responsible for the occurrence of acute atrophy of the liver 
(Klebs, Eppinger, Hanot, and others). Thus, Babes found streptococci in 


* Perhaps Bamberger’s case also belongs here (“ Krankheit. des Chylopoietischen 
Systems,” 2 Aufl., S. 532). 
_ t Kobert, “Intoxicationen,” p. 416. 


632 DISEASES OF THE LIVER. 


four cases, Strobe and v. Kahlden found in the capillaries of the liver 
Bacterium coli, which had been transported through the portal vein. 
While it is possible that bacteria have a certain significance in the isolated 
cases mentioned, their importance in many other instances is exceedingly 
doubtful (Vincent, Rangleret and Mahen); in still other cases no bacteria 
whatever were found, or, if they were found, could not be cultivated 
(Kahlder, Bloedau, Rosenheim, Gabbi, Phedran and Macallum, Sitt- 
mann). 

As a rule, acute atrophy is seen in otherwise healthy livers. Occasion- 
ally, however, this condition seems to be a complication or a sequel of other 
diseases of the organ, particularly of cirrhosis, stasis of bile, and fatty de- 
generation of the liver. 

General Clinical Description.—The disease usually begins, like any 
other form of catarrhal icterus, with symptoms of an acute gastric catarrh; 
following these, icterus develops in the course of a few days or, less fre- 
quently, weeks. This first, so-called prodromal stage of the disease lasts 
for several days or weeks, in every way resembles catarrhal icterus, and 
may be so mild that it is taken for one of the very slight attacks of catarrhal 
icterus that permit the patient to be about. Suddenly, less often 
gradually, the second stage of the disease develops, with stupor, delirium, 
restlessness, and even mania. As a rule, vomiting and convulsions are 
seen at the same time. Coma increases, and in the course of a few days 
death occurs. Recovery is very rare. 

With the onset of the second stage the volume of the liver decreases, 
there is usually pain in the region of the liver, the spleen becomes en- 
larged, bloody vomiting supervenes; and epistaxis, bloody stools, hema- 
turia, bleeding from the genitals, or eechymoses in the skin are all seen. 
The urine usually contains bile-pigment and albumin, with, as a rule, 
some leucin, tyrosin, and other products of abnormal catabolism. Tem- 
perature is normal or subnormal, occasionally elevated toward the end. 

Anatomy.—The liver is reduced in size and flaccid. Its weight may 
be reduced one-half or even more, the left lobe, in particular, being 
smaller than normal. The organ is flattened, folded on itself, and situ- 
ated nearer to the spinal column. The capsule is usually wrinkled. 

In many cases the color of the hepatic substance is a dirty yellow. 
The tissue is very soft and the outlines of the lobules indistinct. Micro- 
scopically it will be seen that the contours of the hepatic cells are also 
indistinct, and that the latter are in different stages of granular and fatty 
degeneration and are stained with bile. They are least degenerated near 
the center of the lobules. In the peripheral parts of the lobules they are 
to be seen in all stages of granular degeneration, and the columns of 
liver-cells are indistinct. 

In ether, apparently more numerous cases, a red hepatic substance is 
seen in addition to the yellow tissue described. This may be present in 
small foci or may constitute the bulk of the degenerated tissue, so that 
the yellow foci seem to be embedded within the red substance. The 
former in these cases form nodules as large as a grain of oatmeal or may 
reach the size of a hazelnut. As a rule, they protrude above the level 
of the cut surface. The red substance is tough, its cut surface is smooth, 
andthe outlines of the lobules cannot be recognized. On microscopic 
examination it will be found that liver-cells are absent and that all that 
is left of the hepatic tissue is a homogeneous or striated mass of connective 
tissue inclosing detritus of different kinds. This red substance consti- 


ACUTE HEPATITIS. 633 


tutes an advanced stage of degeneration. Occasionally it will be seen 
that the center of a lobule is colored yellow and is surrounded by a ring 
of the red tissue that constitutes the periphery of the lobule. According 
to Meder and Marchand, the degeneration of the liver-cells does not always 
occur in the same manner. Sometimes finely granular degeneration is 
seen as a result of necrosis; in other cases, fatty degeneration. These 
changes are always most intense at the periphery of the acini. At the 
same time, the epithelial cells of some of the interlobular bile-passages 
perish. In the beginning the blood-capillaries are intact, although they 
may become very brittle; but later these also perish. As soon as the 
columns of liver-cells in the peripheral parts of the lobules perish, the 
bile-capillaries, too, of course, disappear; and it is possible that the in- 
terference with the current of bile in these parts is the cause of icterus. 


It may happen that so much of the yellow substance perishes that finally the 
whole liver presents the picture of the higher degree of degeneration and is flaccid and 
red throughout. 

In the beginning of the disease a certain red discoloration of the cut surface of the 
liver may be due to hyperemia, and constitute nothing more than the preliminary 
stage in the formation of the yellow substance. The latter, as we have seen, is noth- 
ing more than the conglomerate of cells that have undergone swelling and clouding 
According to this view, Frerichs designates the red parts of the liver as those that are 
least degenerated, whereas the yellow parts are those that are most atrophic. Klebs, 
on the other hand, in opposition to this view, considers the red substance alone as the 
real product of atrophy, whereas the yellow is, according to him, the expression of 
beginning regeneration. It may be conceded that in the yellow parts, owing to the 
smaller number of cells that have perished, regeneration seems to occur more ac- 
tively than in the red parts. 

According to Perls and v. Starck, chemical analysis of the liver-substance shows 
that the fat in this form of degeneration is formed from the proteid of the liver-cells. 
These investigators found an increase of the fat and a reduction in the quantity of 
dry residue that was free from fat. At the same time the water remains the same as 
normal or is slightly increased. In phosphorus-poisoning, on the other hand, com- 
plicated with fatty infiltration of the liver, fat takes the place of much water. 














Dry paid 

WATER. BAT | aoa Bo e 
Fat. 
Normal Uver 34553 vin hk ara netios ona ewe aeks 76.1 3.0 20.9 
EOP sa Cae eeu feces 87.6 8.7 9.7 
Acute atrophy | Penk) tiie siebrdy teen ag 76.9 7.6 15.5 
AS oe re 80.5 4.2 15.3 
Phosphorus-poisoning (v. Starck). ............ 60.0 29.8 10.0 
Acute fatty degeneration (v. Starck).......... 64.0 25.0 11.0 














[This question as to the production of the fat from protein must 
still be considered an unsettled one. There has been a large amount 
of work upon it recently; and, as far as experimental results are con- 
cerned, the chief of these, which were obtained by Rosenfeld, A. E. 
Taylor, and several of the Pfliiger school, indicate that the fat in fatty 
degeneration of the liver is not produced from protein. The subject has 
recently been ably reviewed by A. E. Taylor.*—Eb.] | 

* Am. Jour. Med. Sciences, May, 1899 


634 DISEASES OF THE LIVER. 


A remarkable finding in this disease is the excretion of crystals of 
tyrosin which are visible both microscopically and macroscopically, es- 
pecially if the liver is allowed to lie for some time. 

In addition to the degeneration of the hepatic cells, an increase of the 
interstitial tissues of the liver is occasionally seen. In part this increase 
is undoubtedly only apparent and relative, and its appearance is due 
to the fact that so many of the cells have perished; in part, changes of 
this character that are reported were longstanding; sometimes, how- 
ever, recent proliferation of connective tissue may be seen with small- 
celled infiltration (Riess, Meder) that may occur diffusely or in foci 
throughout the interlobular connective tissues. 

The interlobular bile-passages show progressive tissue changes in 
the form of an increase of the cubical epithelium lining them. These 
changes are more frequently seen than those described in the connective 
tissue of the liver. The cells penetrate the meshes of the collapsed tissue, 
and in this manner form new trabecule of liver-cells. Increase in the 
size of these cells and general proliferation of the cells of the liver that 
remain intact may also lead to regeneration of the liver tissue. These 
processes may be observed within the first week after the occurrence of 
atrophy, and may, in fact, lead to a real cure of the disease. The new 
liver-cells are then not arranged in the usual typical manner, and as a 
result the new-formed bile-channels are very long and tortuous. Inacase 
described by Marchand, examined half a year after the onset of the disease, 
regeneration had not occurred in a uniform manner, but nodules of hyper- 
plastic tissue about as large as lentils or peas were distributed all through 
the red substance of the liver. The yellow substance, in this case, con- 
sisted of broad tubes of cells; the red, of narrow ones. [The formation 
of new glandular cells from the epithelial cells lining newly formed bile- 
channels was clearly seen in a case described by Aly Bey Ibrahim*; the 
regenerative process taking place exclusively in the red areas.—ED.] 

Changes are seen in other organs besides the liver. General icterus, 
granular clouding, and fatty infiltration of the kidney epithelium and of 
the muscular fibers of the heart, sometimes, too, of the muscles of the 
extremities, are seen. The epithelial cells and the glandular cells of the 
stomach, and the bronchial and pulmonary epithelium, as well as the 
epithelium of the intestinal villi, may also show these changes. The 
spleen, as a rule, is considerably increased in size and is soft. In the 
intestine a catarrhal condition of the mucous membrane may be seen and 
the follicular and mesenteric glands may be somewhat swollen. In the 
majority of cases ecchymoses will be seen in the serous membranes, the 
external skin, the mucosa of the stomach and of the urinary passages, the 
connective-tissue structures of the body-cavities and of the extremities. 
The blood is generally thin. No definite changes are found in the brain. 

Symptoms.—In the prodromal stage of the disease nothing charac- 
teristic whatever is seen. Icterus usually appears a few days after the 
onset of the gastric symptoms, and as a rule becomes quite intense, the 
stools being clay-colored or colorless, and complete stasis of bile super- 
vening. With the onset of the second stage icterus increases. In ex- 
ceptional cases icterus does not appear until severe symptoms develop, or 
even after this period. Occasionally the degree of icterus, like the color — 
of the feces, fluctuates during the course of the disease, and icterus may 
even be completely absent, if the course of the trouble is very rapid. 

* Miinch. med. Woch., May 21, 1901. 


ACUTE HEPATITIS, 635 


The liver is generally enlarged during the prodromal stage, owing 
either to stasis of bile or swelling of the cells. Clinically, however, this 
condition can rarely be recognized, and the same condition is present in 
ordinary catarrhal icterus. In phosphorus-poisoning a considerable 
degree of swelling may be noticed from the very beginning, but may even 
in this condition be completely absent (Hedderich). 

Soon after the appearance of cerebral symptoms, rarely before, a de- 
crease in the size of the organ may be noticed. The liver dulness may 
completely disappear, not alone because of the decrease in the size of the 
organ, but also because of its flaccidity. The liver becomes folded and 
drops back so that it may even be impossible to palpate it. At the same 
time the hepatic region is very sensitive, and this tenderness may extend 
into the epigastric region and other parts of the abdomen. 


If the reduction of the volume of the liver leads merely to a flattening of the 
organ, the liver may still show the same area of percussion dulness, but the sound 
will be less dull and more tympanitic. This always occurs if the liver is attached to 
the anterior abdominal walls by adhesions (C. Gerhardt). 

Leube, in a case that ran a very slow course, noticed that the hepatic region was 
so doughy that the pressure of the fingers left a distinct pit in the epigastric region. 


With the cerebral symptoms vomiting occurs. The vomitus is slimy, 
sometimes bile-tinged, and toward the end bloody. Constipation is usu- 
ally present and the appetite is lost. The spleen is enlarged in about 
two-thirds of the cases. 

In the great majority of the cases hemorrhages are observed, most 
frequently as hematemesis and hemorrhagic ecchymosis of the skin. The 
vomitus is generally reddish or like coffee-grounds, large quantities of 
blood being rarely vomited. The stools may occasionally be bloody. 
Hemorrhages from the nasal mucosa, the mucous membranes of the 
mouth, or the urinary passages are rare. In pregnant women and in 
women during the lying-in period uterine hemorrhages are seen. 


Litten observed retinal hemorrhage, and in one case irregular grayish-white spots 
caused by fatty degeneration of the elements of the retina with the formation of small 
granular spheres and of small sheaths of tyrosin crystals. 


Fever is often present during the initial catarrhal icterus, but later 
the temperature is, as a rule, normal. The same applies to the second 
stage of the disease, although here it may become subnormal. Sometimes 
the temperature remains subnormal until death, while in other cases a rise 
of temperature occurs during the last two days or so and may attain very 
high degrees (42.6° C.—108.68° F.). 

The action of the heart is normal or slow in the prodromal stage and in 
the beginning of the second stage. As the general condition of the patient 
grows worse, the cardiac action becomes more rapid and weaker, the 
heart-sounds being softer and duller and occasionally accompanied ‘by a 
systolic murmur. 

The urine is, as a rule, slightly idaiiiacd and, owing to the presence of 
icterus, contains some bile-pigment and generally small quantities of albu- 
min and a few casts with fatty epithelium. The most important urinary 
constituents are a number of products of perverted metabolism, such as 
leucin, tyrosin, sarcolactic acid, oxymandelic acid (C,H,O,), peptone,* 

* It seems hardly necessary to call attention to the fact that peptone is believed 
at the present time never to appear in the urine. That substance which has been 


called peptone is in all probability always one of the various albumoses of the 
system.—Eb. 


636 DISEASES OF THE LIVER. 


and albumose. In concentrated urine a deposit of tyrosin occurs spon- 
taneously in the form of delicate needles or small bundles of needles. 

Owing to the destruction of hepatic parenchyma and the wide-spread 
degeneration of the organ, an increased excretion of nitrogen is to be ex- 
pected. As the disease runs such a peculiar course, and as the termina- 
tion is so rapid, no very careful metabolic studies have so far been made. 
Von Noorden, in one case, found the nitrogen excretion to be 10.14 gm. in 
twenty-four hours one day before the death of the patient, this being much 
more than would correspond to simple fasting. P. F. Richter found an 
average excretion of nitrogen of 9.8 gm. during the last three days of life, 
with about 3.5 gm. ingested. 

[Albu has reported * observations made upon a case studied by him 
that went on to recovery. The nitrogen output was a great deal larger 
than the amount ingested, but the urea nitrogen formed from 75 % to 
85 % of the total quantity. This he considers strong evidence against 
the formation of urea in the liver from ammonia salts.—EbD.] 

The character of the nitrogen compounds found in the urine is par- 
ticularly changed in this disease (Frerichs, Riess and Schultzen). In 
advanced cases the excretion of urea is diminished, sometimes reduced to 
nothing. In some of the cases, especially those that ultimately recover, 
an abundant quantity of uric acid is excreted. 

The ammonia of the urine is sometimes, though not always, increased. 
It is for the present impossible to determine whether this is due to the 
formation of sarcolactic acid, discovered by Schultzen and Riess, and 
the flooding of the blood with acid products of proteid catabolism, or 
whether the increase of ammonia is due to inefficiency of the liver. In 
other words, whether we are dealing with a protective process or with a 
perverted or inhibited function. 

Leucin and tyrosin were first discovered in this disease by Frerichs, 
and are among the most frequent findings in the urine of cases of acute 
atrophy of the liver. At the same time they are not always found and 
are not characteristic of the disease. The largest daily quantity of 
tyrosin found in the urine was 1.5 gm. The xanthin bodies are increased 
in many cases and on certain days (Réhmann and P. F. Richter), but 
there is no regularity in regard to the time at which this increase occurs. 
The same can be said of uric acid. 

Carbaminic acid has never been found, although its presence might 
have been postulated from the animal experiments that Naunyn has 
reported on extirpation of the liver in dogs. 

Albumoses have at times been found; but they are not constantly 
present, and when present are found in small quantities only (Thomson, 
v. Noorden). Schultzen and Riess speak of an as yet-undefined “‘peptone- 
like” body which is found in considerable quantity. 

Albumin is present only in small quantities, and as compared to 
the massive degeneration of renal epithelium, in smaller quantities 
than would be expected. Sugar is never present. 


Von Jaksch reports alimentary glycosuria (16 gm. excretion and 100 gm. inges- 
tion) in a case that recovered. 
. 


Besides sarcolactic acid, other acids have been found in different cases, 
such as oxymandelic acid (Riess and Schultzen), that was regarded as 
oxyhydroparacumaric acid, and inosinic acid (Boese). 

* Deutsche med. Woch., April 4, 1901. 


ACUTE HEPATITIS. 637 














NITROGEN. 
ACUTE ATROPHY OF THE LIVER. 
In Urea. In NH3. ae Residue. 
. eee 
Reosenhel tia: ois aes rae wae ones 81.1% 4.7% 14.2% 
MGHEOD: oo sie aa ee aie 52.4% 37% 10.59% 
WO NOOTRCN <2 0% 2 cee hee Pe es 71% 18% 172% 9.7% 
In Alloxuric 
P. F. Richter*: Bodies: 
Case 1: Ist to 12th day ....... 81.2% 8.45% 3.1% 4.6% 
13th to 14th day....... 67.5% 13% 4.3% 6.25% 
ae soso ccecras ane eta estoceen 79.6% 8.5% — 5.5% 
PHOSPHORUS-POISONING. 
Aes PEACE Vacate cece er nee ae 43.9% — — — 
PAOD it asa Bordo g, Gnd Ae arcs e | 85.6% — a — 
v. Noorden-Badt: 
CASE Miles Cobar eet oh deca ee 69.9% 7.8% 31% 19.2% 
CHSBe 2! Fon Ree A ed ear eee 67.5% 25 :8% 2.6% 4.1% 
IN ORIN Le Scars ae yar ee me ce 84-87% 2-5% 1-3% 7-10% 

















This table shows in what form 100 parts of the excreted nitrogen appeared in 
the urine in a number of cases; it will be seen that great differences exist. We will 
explain below why phosphorus-poisoning is included in this table. 


At first sight the apparent irregularity of the urinary findings and 
the inconstancy of this or that abnormal excretion in acute atrophy of 
the liver are astonishing to the observer. The explanation of this 
phenomenon, however, is readily found in the differences that exist in 
regard to the degree of the hepatic involvement; in addition, the other 
organs participate to varying degrees in disturbing normal catabolism ; 
and, finally, the rapidity with which the disease progresses must have 
something to do with the character of the excretions. 

In the second stage of the disease nervous symptoms are particularly 
conspicuous. Occasionally, in the course of one single day the tem- 
perament of the patient seems to change, restlessness, Insomnia, and 
headache appearing, to which may be added, without any premonition 
whatever, serious disturbances of the sensorium, stupor combined with 
delirium, jactitation, rapid talking, screaming, apprehension, etc., these 
symptoms sometimes being so aggravated that the picture of acute 
mania is presented. | 

In about a third of the cases in adults, and in nearly every case in 
children, convulsions occur, appearing either as regular spasms of certain 
muscular groups, or as general muscular spasms, or general clonic con- 
vulsions. . 

The pupils are generally dilated and react poorly to light. Numerous 
nervous symptoms in the digestive system appear. The vomiting 
already mentioned is, in all probability, of central origin. Sometimes 
the more serious nervous disturbances are ushered in by an attack of 
vomiting; sometimes a feeling of thirst is complained of, or ischuria, 
constipation, meteorism, and perspiration are present. The breathing 
is snoring, and occasionally irregular. 

* The average figures are calculated. 


638 DISEASES OF THE LIVER. 


All these nervous symptoms are very inconstant both as to duration 
and severity. They may disappear for a time and the patient may 
regain consciousness (particularly after child-birth), but they generally 
reappear. lIrritative and paralytic symptoms occur simultaneously and 
may be observed together. 

Duration ; Prognosis.—The duration of the disease fluctuates from 
a few days to several months. According to the figures of Thierfelder, 
50 % of all cases terminate fatally between the fifth and fourteenth day; 
30 % between the third and the fifth week. Death rarely occurs before 
the fifth day; but it may do so in pregnant women. The second char- 
acteristic stage of the disease is, as a rule, of short duration, lasting from 
one and a half to three days. It rarely lasts longer than a week. In 
the protracted cases the cerebral symptoms are less violent and all 
irritative symptoms are less severe. The second stage is of long dura- 
tion in those cases that run a favorable course. 

Certain cases that run a course of many week or months are in truth 
originally acute, and are only slow in recovering; others, again, run what 
must be called a subacute course. Leube and Wirsing report such a 
case (minimum size of the liver at the end of the eighth week, increase 
in size after three weeks, recovery after eight months). 

The prognosis of acute atrophy of the liver is in the great majority 
of cases fatal, and is more unfavorable the sooner after the onset of the 
disease cerebral symptoms appear. In the case of pregnant women 
the prognosis is particularly unfavorable, the case being here compli- 
cated by the shock and the hemorrhage of child-birth. 

In former days the possibility of recovery from acute atrophy of 
the liver was denied, and all cases that did recover were considered 
diagnostic errors. There is no reason why the damage should not be 
arrested prior to the complete destruction of the liver. We are justi- 
fied in entertaining this view because we know that even in those cases 
that terminate fatally regenerative changes can be observed during 
the first and second week. [We have already mentioned the fact that 
Albu has recently reported a case * which resulted in recovery. The 
patient was a man, thirty-six years old. Three weeks before his illness 
he had experienced great emotional excitement, followed by persistent 


icterus. He became stupid, had fever, but no tenderness or pain. The: 


liver dulness was only two finger’s-breadths in width, and later, as 
delirium came on, the dulness disappeared altogether. Large amounts 
of leucin and tyrosin were obtained from the urine. Gradual improve- 
ment, with gradual broadening of the area of liver dulness, occurred, 
until absolute recovery took place. Dobie + has also reported a case 
of recovery.—Ep.] Anatomic studies teach us this, as do also experi- 
mental studies carried on by Ponfick for the purpose of elucidating 
this very subject. In a case of Marchand’s examined postmortem, 
regeneration had occurred in the form of nodular hyperplasia. In the 
case of Bauer the patient died from miliary tuberculosis three months 
after her attack of acute atrophy, and the presence of regenerative 
changes in the liver could be verified at the autopsy. In addition to 
these instances, Wirsing has collated 16 older cases from the literature, 
and of late years Hedderich, Senator, and von Jaksch have described 
other cases. [Ibrahim’s case, previously mentioned as having shown 


* Deutsche med. Woch., April 4, 1901. 
} Brit. Med. Jour., Nov. 12, 1898. 


/ 
ot yt eee ees oe wath —_. 


ACUTE HEPATITIS. 639 


marked regenerative attempts, died between the tenth and eleventh 
weeks after the onset.—Eb.] 

It is to be expected that the clinical picture and the course of those 
cases that recover are different in many respects from cases that ter- 
minate fatally; and, while it is true that some of the older cases must 
be considered doubtful from a diagnostic point of view, we are still 
justified in assuming that in those instances where the liver decreased 
in size and remained small for a long time, and where tyrosin and leucin 
were found in the urine (Wirsing, Senator), the diagnosis was established 
with sufficient certainty. 


The following case, described by E. Wagner, is peculiar both in regard to symp- 
toms and course and in regard to the anatomic findings. The author calls it a case 
of acute red atrophy of the liver. A young girl of twenty-one had for four weeks 
vague general symptoms, for a week violent abdominal pain, and after a few days 
ascites. There was no icterus or albuminuria. There was edema of the lower half 
of the body. She died quietly three weeks after the appearance of ascites. The 
liver was somewhat smaller than normal (1500 gm.), tough and vascular. On the 
surface of the organ there were adhesions and a number of nodules of the size of a pea. 
The portal vein was thickened from the hilus to the smallest peripheral branches 
The cut surface of the organ showed irregular whitish streaks. The acini were 
reddish-brown, smaller than normal, and contained liver-cells in their outer third or 
fourth, these being somewhat more granular than normal. In the central portions 
of the acini nothing was present but connective tissue and red blood-corpuscles that 
were found lying within the columns of degenerated liver-cells. Interlobular con- 
nective tissue is present only in the vicinity of the portal branches, and somewhat 
increased in these localities. Wagner does not favor the diagnosis of pylephlebitis 
with secondary atrophy of the liver, but considers the latter as the primary condition. 
At all events, the presence of ascites points to a considerable obstruction to the flow 
of blood through the portal capillaries. 


Nature.—Acute atrophy of the liver occupies a peculiar position 
among the diseases of this organ from the rapidity of its development 
and the degree of change present in typical cases. The position of this 
disease is anomalous not only for the liver but for every other organ of 
the body from a general pathologico-anatomic point of view. It is 
variously considered as a peculiar form of acute diffuse inflammation 
that runs a particularly rapid course, or, again, as a retrogressive form 
of metamorphosis, or as a wide-spread necrosis of the cellular elements 
of the liver-cells. If the anatomic findings alone are considered, the 
initial stages of acute atrophy are most similar to parenchymatous 
swelling and inflammation of the liver (Busse, for example, describes a 
case of the disease with enlargement of the organ). Interstitial pro- 
liferation, it is true, is not a constant finding, but is in many cases present 
at an early stage of the disease. 

The nature of the noxious agent and the manner and the rapidity 
with which it exercises its effect on the liver may account for the differ- 
ences in the reaction. We have analogous conditions elsewhere, and it 
is readily understood why the acute effect of a large quantity of the 
poison, whatever it may be, will cause a complete destruction of the 
glandular parenchyma before reactive processes can develop. We will 
include these forms of the disease under the general heading of inflam- 
mation in the broader sense, and will refrain from looking for anything 
else in the whole process than an inflammation which differs from the 
ordinary forms of inflammation only in a quantitative sense. 

How can we explain the wide-spread changes seen in other organs, 
such as the heart, the kidneys, etc.? Are they the result of the disease 


640 DISEASES OF THE LIVER. 


of the liver, or are they caused by the effect of the same noxious agent 
that affects the liver? I am inclined to the latter belief, for the reason 
that changes in the other organs are sometimes seen when the disease of 
the liver is very little developed. The lesions in the other organs closely 
resemble those seen in acute phosphorus-poisoning and in so-called ‘‘acute 
fatty degeneration.” The latter disease is anatomically identical with 
phosphorus-poisoning and is seen sometimes after mushroom-poisoning 
(by Amanita phalloides, Scharer-Sahli), and frequently originates from 
unknown causes. All these conditions cause the fatty clouding and the 
parenchymatous degeneration of numerous glandular and muscular cells 
in common, as well as fatty infiltration of many of the epithelial cells 
and of the capillaries and a hemorrhagic tendency. At the same time, 
it is true, certain differences can be found. In poisoning and in “acute 
fatty degeneration,” the fatty degeneration and the hemorrhages are in 
general more wide-spread, the accumulation of fat in the liver, in par-- 
ticular, sometimes assuming such dimensions that the organ swells 
greatly; and we must assume that an infiltration of fat from other parts 
of the body occurs (compare the experiments of Rosenfeld on page 410). 
Severe cases of acute phosphorus-poisoning die at this early stage of the 
disease. At this time the liver is enlarged and the general disease- 
picture is in some respects different from that of acute atrophy of the 
liver, the same disorders of metabolism not being found and some of 
the other symptoms not being identical. On the other hand, there are 
certain cases on record that finally lead to the genuine clinical and 
anatomic picture of acute atrophy of the liver. Hedderich has collated 
33 such cases. In the majority of these cases atrophy began at the 
beginning of the second week, sometimes earlier; in three of the cases 
it was present from the very beginning of the disease; in only one-half 
of the cases was atrophy preceded by enlargement of the liver lasting 
about one week. Death occurred in the second week, generally within 
twenty-four hours after the beginning of atrophic changes. In three 
cases recovery from phosphorus-atrophy of the liver ensued. 

These facts teach us that the symptoms and the anatomic changes, 
particularly in the case of the liver, may vary greatly even in so simple 
a form of intoxication as that by phosphorus. The factors that deter- 
mine these differences are, in the first place, the absolute quantity of 
poison taken, then the rapidity with which it is absorbed, and finally 
the formation or non-formation of certain compounds of phosphorus in 
the intestine. Other factors to be considered are the possibility of the 
absorption of other substances at the same time arid the general condition 
of the liver and of the system at the time of the poisoning. 

We can draw cértain conclusions from these considerations in regard 
to acute atrophy of the liver. First, a purely chemical poison (alone 
or aided by certain concomitant factors) can produce acute atrophy 
of the liver; and this poison does not act on the liver alone, but also 
affects other organs, so that the general disease-picture of acute atrophy 
of the liver cannot be deduced from the hepatic changes alone, but must 
be evolved from the lesions known to exist in other organs as well. It 
appears that certain other poisons, such as chloroform, alcohol, and 
chloral, may occasionally act in the same manner as phosphorus, since all 
of these can lead to parenchymatous hepatitis with acute degeneration. 
As acute atrophy of the liver is frequently ushered in by certain gastro- 
intestinal disturbances, we are possibly justified in assuming that there 


ACUTE HEPATITIS. 641 


may at times be generated in the intestine certain organic poisons which 
exercise on the liver parenchyma an effect similar to that produced by 
the poisons enumerated above. We must think in particular of bacterial 
toxins and of ptomains, and possibly, also, of the higher derivatives of 
the albumin ingested, such as the albumoses, some of which are known 
to possess highly toxic properties. 

In the second place, the relationship between phosphorus-poisoning 
and acute atrophy of the liver throws some light on those cases of acute 
fatty degeneration that have been seen to follow mushroom-poisoning 
or that were caused by unknown agencies. The same noxious principles 
may cause these cases; and possibly several poisons may act at the same 
time and cause a more intense form of poisoning (?), so that they produce 
acute swelling of the liver and infiltration of the organ with fat to such 
a degree that death ensues very soon. In less intense forms of poisoning, 
on the other hand, or owing to other causes, the primary swelling of the 
liver is not produced, and, as is sometimes seen in the case of phosphorus, 
atrophy alone is present from the very beginning. 

From all that we know in regard to acute atrophy of the liver we can 
conclude that we are not dealing with a uniform clinical entity, but that a 
variety of noxious agencies may affect the liver and at the same time some 
of the other organs as well. This factor and the varying intensity of the 
poisoning explain the different forms of the disease and the different ana- 
atomic findings. All the forms have in common the great disturbance in 
general health naturally following in the path of wide-spread destruction 
of liver parenchyma, and present a most pronounced picture of so-called 
“hepatargy”’ (see page 458) and of the autointoxication that is the result 
of this perversion. In view of the manifold functions of the liver in gen- 
eral metabolism, these changes are necessarily varied in quality and in 
severity, and we can readily understand why the urinary constituents 
are different from those excreted normally both in quantity and char- 
acter, and also that they show certain peculiarities not constant and not 
typical of the disease. This is also due to the fact that the number 
of liver-cells that have perished may vary, and that, in addition, the 
function of the surviving cells may be impaired in different ways. In 
other words, we cannot draw any conclusions in regard to the nature of 
the functional disturbances that existed during life from the size of the 
organ after death. In addition, the lesions of the heart and the kidneys 
necessarily lead to certain disturbances of the circulation and of the ex- 
cretion of urine, so that the latter is no index alone of purely metabolic 
perversions within the organism, for the reason that the excretion of some 
of the most strikingly abnormal products may be prevented. As an 
example of this, the discovery of tyrosin in the blood (Schultzen and 
Riess), the liver, and the retina may be mentioned. 

The most conspicuous disturbances are the perversions in nitrogen 
metabolism, the decreased excretion of urea, the increased excretion of 
-ammonia, and the appearance in the urine of such intermediary bodies as 
leucin and tyrosin. The increased excretion of nitrogen can be explained 
from the death of so many liver-cells, and at the same time the increased 
catabolism of the nuclei of these cells may explain the increase of uric acid 
and of the alloxuric bodies. Disturbances in carbohydrate metabolism 
are, as a rule, not perceptible, because the amount of food ingested is so 
much reduced. : 


The absence of the ‘‘detoxicating” function of the liver may also 
41 


642 DISEASES OF THE LIVER. 


become apparent in acute atrophy, so that ptomains formed in the intes- 
tine are allowed to enter the general circulation and there exercise their 
deleterious effects. 

As in other toxic conditions (uremia, diabetes), the general symptoms 
of intoxication are not constant, and vary according to the nature and 
the composition of the complicated poisons concerned. 

As the etiology of acute atrophy was so obscure and the symptoms of 
the disease are so violent, it can be readily understood why the disease was 
considered an infection, particularly as at the time of its discovery the 
trend of medical thought was in that direction. We have learned, how- 
ever, from our discussion that it is to be considered an intoxication, in 
which chemical damage to the liver as well as other organs is the essential 
feature. The most frequent poison appears to consist of certain sub- 
stances that are formed within the intestinal canal and are absorbed and 
act on the liver; in other words, we are dealing with a form of bacterial 
dyspepsia or of intestinal autointoxication. In cases in which acute 
atrophy of the liver follows osteomyelitis, erysipelas, or some other in- 
fectious disease, the bacterial toxins possibly are formed in some other 
organ and are carried to the liver by the blood. 

In a minority of the cases the liver may be damaged by the local action 
of certain bacteria. The latter may enter the liver either in the blood or 
through the bile-passages. The cases of Babes, Strébe, and v. Kahlden 
furnish examples of the former kind. Here masses of streptococci or of 
Bacterium coli were found in the capillaries of the portal vein, so that the 
suspicion is justified that these organisms produced their toxins in these 
localities and acted deleteriously on the neighboring hepatic cells. 

The assumption that bacteria can invade the liver through the bile- 
passages is supported by our knowledge of certain cases of infectious 
icterus in which this has been known to occur. This is the most probable 
explanation, particularly of those forms of acute atrophy of the liver that 
begin with catarrhalicterus. The anatomic findings in many of the cases, 
the irregular distribution of the different foci throughout the organ, the 
variety in the changes of the parenchyma seen in different localities (re- 
sembling bronchopneumonia), all point to the bile-passages as the point 
of entrance. 

Finally, I would like to call attention to another possibility that has 
so far never been mentioned. When we cansider that the ducts of the 
liver and of the pancreas enter the intestine through a common opening, 
it might well be possible, in case this opening becomes occluded, for some 
of the pancreatic secretion to enter the liver and there to digest the liver- 
cells; this would be particularly the case in those parts of the organ where 
trypsin penetrates as far as the capillaries. Whether this hypothesis is a 
correct one can be determined only by experiments performed in this 
direction; as a single observer will rarely have occasion to study clinically 
many cases of this character, I will content myself with formulating this 
hypothesis. [This theory receives some support from the analogous 
result upon the pancreas from the entrance of bile into the duct of Wirsung 
as discovered by Opie. Our views concerning the nature of acute yellow 
atrophy, as well as of phosphorus-poisoning, must be largely influenced 
by the recent work on autolysis of the liver. Salkowski’s original work 
upon the latter question has lately been repeatedly confirmed, and was 
very strikingly extended by M. Jacoby,* who demonstrated very definitely 

* Zeitsch. f. physiol. Chemie, Bd. xxx. 


ACUTE HEPATITIS, 643 


that the liver after death, under aseptic conditions, shows very marked 
proteolytic digestive action. He also showed that in acute phosphorus- 
poisoning this proteolysis is very largely increased. He considers that 
this definitely confirms the idea that phosphorus-poisoning is closely 
related to ferment action, and is, indeed, apparently in large part, really 
increased ferment action; although what the actual cause of the i increase 
is cannot as yet be definitely stated. 

A. E. Taylor * has recently studied elaborately a case of acute yellow 
atrophy from this standpoint. He found large amounts of leucin and 
asparaginic acid in the liver, but, strangely enough, hexon bases were 
apparently absent. Still it has become increasingly probable that the 
chief process in acute yellow atrophy may be a pathologically active 
and rapid autodigestion, although if this be true it cannot yet be stated 
what the cause of the increase in the autolytic process in the liver is due 
to. It seems likely that it is set in motion at times by bacterial, at 
times by enterogenous or other metabolic toxic substances.—ED. ] 

A review of all the factors enumerated leads us to the conclusion that 
acute atrophy of the liver may not only be: due to a great variety of 
causes, but that the pathologic processes that ultimately lead to atrophy 
may be different in themselves. This will also explain why the course 
of the disease may be so varying and still lead to the same final con- 
dition. 

We are stimulated, therefore, particularly in those cases that recover, 
to direct our attention, for the sake of study, to those diseases from which 
it originated or to which it is related. Among these may be named: 
parenchymatous hepatitis, catarrhal icterus, particularly those cases that 
may be classified separately as infectious icterus, and, finally, those in- 
fectious diseases that are accompanied by parenchymatous changes in the 
liver and serious cerebral disturbances or icterus. It is probable that in 
many of these diseases cases will be found in which the liver shows changes 
similar to those found in acute atrophy, and that would have led to the 
development of this disease had the patient lived longer. The develop- 
ment of atrophy occurs only in the great minority of cases—namely, in 
those cases where the disturbance of the hepatic function continues for a 
long time or where certain concomitant features are apparent. In the 
majority of cases, however, death occurs before the development of 
atrophy, or before the damaged parenchyma undergoes regeneration. It 
is possible that even under these circumstances some of the liver-cells 
perish, but the number of cells that are destroyed is not great enough to 
cause a decrease in the size of the organ or to cause intoxication. It is 
probable that the surviving cells engage in compensatory activity. At 
the same time there are to be noticed in all the conditions enumerated a 
number of cases which ultimately run a favorable course, but which for a 
time develop such serious symptoms.-that they resemble the syndrome of 
acute atrophy of the liver. These are probably abortive cases. 

We will attempt to explain the symptoms and the course of the disease 
by the theoretic views developed. It seems hardly probable that the. 
serious anatomic changes seen postmortem and the atrophic process 
leading to them began only when symptoms of the disease assumed so 
grave a character. Particularly in those cases that run a less acute 
course, and in which there is a prodromal stage of from eight to fourteen 
days, atrophy unquestionably must have begun during this time. At 

* Zeitsch. f. physiol. Chemie, Bd. xxxtv. 


644 DISEASES OF THE LIVER, 


this period, however, compensation was sufficiently active to prevent the 
most serious symptoms, as compensation does not fail until atrophy and 
disturbance of function have reached a certain degree. At this time the 
severe symptoms appear so suddenly that they seem to be caused by some 
acutely acting agency; whereas in reality they have been preparing for a 
long time. The conditions observed here are the same as in other forms 
of autointoxication, such as uremia and diabetic coma; in all of which it is 
the last drop that causes the cup to overflow. 

The decrease in the size of the liver that appears at the time of the 
development of cerebral symptoms is usually explained by the assump- 
tion that at this time a large portion of the degenerated parenchyma is 
absorbed. Hirschberg assumes that a decrease in the quantity of blood 
flowing into the liver may also be in part responsible for the decrease in 
size, and that the liver looks so very small because after death the vol- 
ume of blood is still less. 

Icterus is probably caused in several different ways in this condition. 
In the beginning of the disease, when the stools are clay-colored, we must 
assume that some occlusion of the larger bile-passages exists. In the 
atrophic stage of the disease we believe that the interlobular passages are 
occluded by desquamated epithelial cells or that the passages are collapsed 
or twisted in the same manner as the intralobular channels. This is due 
to a destruction of parenchyma that robs them of support and direction. 
The central cells of the lobules are better preserved and still contain bile- 
pigment, and this has been adduced as an argument in favor of the above 
explanation. It is true that the larger bile-passages contain a colorless 
fluid devoid of all pigment; at the same time, it is possible that diapedesis 
of bile (Minkowski) occurs—in other words, that the damaged liver-cells 
allow the bile to flow both into the bile-ducts and into the blood-chan- 
nels. This is a theory which has, of course, not been proved. 

The old theories that explained the cerebral symptoms on the ground 
of inanition or the absorption of bile-products possess historic interest 
only. There can be no doubt that these symptoms are the result of in- 
toxication by products of perverted metabolism; but no one, as is the 
case in uremia, has so far succeeded in demonstrating any one substance 
that can be made accountable for these symptoms. The intoxication fol- 
lowing inhibition of the hepatic function must be considered as a very 
complicated one, and the toxic agent is a mixture of poisons of varying 
composition. 


It is impossible to decide whether leucin and tyrosin belong to these toxic sub- 
stances. Panum * and Billroth f injected large quantities of these bodies into the 
blood of certain animals without producing any damage and without the appearance 
of nervous symptoms. At the same time, this does not exclude the possibility that 
in acute atrophy of the liver these substances exercise a deleterious effect, for the 
reason that in normal animals they are possibly rendered harmless by the liver, 
whereas in the disease under discussion the liver has lost this power. The same 
reasoning applies to sarcolactic acid and other bodies, which the liver can no longer 
_ oxidize. 

As tyrosin is one of the aromatic group, and as these bodies are otherwise pro- 
duced only by bacteria, the suspicion has been created that the tvrosin found in acute 
atrophy owes its origin to the same source. The statement has been made that it is 
generated either by bacteria in the liver or by putrefactive organisms in the intes- 
tine. It has, however, never been demonstrated that this is the only source of 


* Schmidt’s “ Jahrbiicher der gesammten Medicin,”’ 1858, vol. ct, p. 215. 
+ Langenbeck’s “‘Archiv,’’ vol. v1, p. 396. 





ACUTE HEPATITIS. 645 


tyrosin in the body, and it is not excluded that metabolic processes play an important 
role in its formation. 

The hemorrhages in this disease, as in other similar conditions, can best 
be explained from the general disturbance of nutrition. It is possible that 
fatty degeneration of the vessel-walls has some influence. In the intesti- 
nal area a possible adjuvant is stasis in the portal system due to collapse 
of intrahepatic capillaries. The swelling of the spleen can be explained 
on the same basis. ) 

Diagnosis.—As acute atrophy ofthe liver is relatively rare in those 
diseases in which it could occur, it would be a very interesting and useful 
task to examine all the cases in which this complication threatens as soon 
as possible. Unfortunately this is not always possible; at the same time, 
particularly severe disturbances of the general health or the occurrence of 
certain unusual symptoms should arouse our suspicion as to the possi- 
bility of atrophy. Possibly quantitative analyses of the urine would 
enable us to detect the condition in its prodromal stages. In a practical 
sense, the first available symptoms are the nervous disorders, which some- 
times are mild and hardly noticeable, while in other cases they appear so 
rapidly as to take us by surprise. 

The decrease in the size of the liver is usually not noticed until the 
following day, rarely before. It may be well to mention again that tym- 
panites or coils of intestine situated between the liver and the abdominal 
wall may simulate a decrease in the size of the organ, and that, on the 
other hand, atrophy may not be discovered in case adhesions fix the 
liver in certain positions or if the organ is enlarged or very resistant from 
the presence of other older disease, such as cirrhosis. 

The determination of perversions of metabolism by urinalysis is of 
great diagnostic importance. The presence of tyrosin and leucin is easy 
to discover because these bodies are either precipitated spontaneously or 
crystallize as soon as the urine is concentrated. On the other hand, it is 
true that these bodies are not always found in acute atrophy, and that, as 
a rule, they do not appear until late in the disease. 

Typical cases of atrophy can usually be diagnosed as soon as the symp- 
toms of the second stage appear; but the diagnosis may be difficult if the 
cases are seen for the first time after the patient has relapsed into stupor, 
unless a history of the case can be elicited, or if the patient is a sufferer 
from some chronic disease of the liver. 

Severe cerebral symptoms as well as icterus may be due to a variety 
of causes. If the two appear together there is created a very striking 
picture to which the term zcterus gravis has been applied. This name 
explains nothing whatever; but it has a certain value as a descriptive 
term because there are, in fact, a number of cases whose course, origin, 
and pathologic anatomy remain unexplainable. The term, at the same 
time, includes a great variety of known pathologic conditions (sepsis, 
puerperal fever, pneumonia, yellow fever, recurrent fever, Griesinger’s 
bilious typhoid, peritonitis, chronic alcoholism), which can appear as 
icterus gravis in the same manner as in the case of icterus infectiosus, 
phosphorus-poisoning, or acute atrophy of the liver. Since we have learned 
to isolate the last-named disease from this group, it is not practicable to 
follow the example of Dupré and to reserve the name icterus gravis for 
this condition alone. 

Mossé distinguishes: (1) Ictére typhoide ou grave primitif (ictére grave proper) ; 
(2) ictéres graves secondaires (insuffisance hepatique) ; (3) ictéres aggravés. i 


646 DISEASES OF THE LIVER. 


division, captivating as it may seem on first sight, is neither correct nor practical, 
for many cases of acute atrophy would have to be ranked with the cases of ictére 
agegravés of the third category, and, besides, many of the cases that Mossé designates 
as ictéres graves primitifs would certainly not be cases of acute atrophy. 

Boix formulates the following division, not limiting icterus gravis to acute 
atrophy, but extending it to other diseases: 


TEMPERATURE. 
. : PHOSPHORUS! ese ese Ba wyae es Subnormal. 
Specific and Ee ES Ee Be Sralcar hd) ee ee ae Febrile. 
Due to staphylococcus 
“streptococcus Retple 
Non-specific and always secondary.... ‘¢  pneumococcus ria ; 
‘‘ proteus, ete. 
* - Bacillus coli. so7.544.: Subnormal. 


It may be a difficult matter to differentiate acute atrophy of the liver 
from some of the other conditions enumerated above; but, as a rule, it 
can be done. Symptoms in favor of the diagnosis of acute atrophy are 
the intensity of the icterus, the small size of the hepatic dulness, the ab- 
sence of fever in the majority of cases, and the serious cerebral symptoms 
that are changeable, and in which symptoms of irritation alternate with 
symptoms of paralysis, and, further, the appearance of leucin and tyrosin 
_in the urine. Although, as we have stated, phosphorus-poisoning may 
ultimately lead to acute atrophy of the liver, the differential diagnosis 
between the two conditions will sometimes have to be made in cases that 
are acutely seized and are seen for the first time after severe icterus has 
developed. This is particularly necessary if no definite information in 
regard to the swallowing of phosphorus can be obtained. For these cases 
the following points in the differential diagnosis may be given. As in the 
case of many other diseases, they are not altogether reliable in cases that 
run an atypical course. 


AcuTE ATROPHY OF THE LIVER. 


Preceded by an extended period of ill- 
ness (one to two weeks) and icterus. 


Icterus as a rule more intense and older. 
Liver sensitive, reduced in size. 


Cerebral symptoms appear suduenly 
(combination of excitement and de- 
pression), appearing one or two days 
before the end. 

In the urine: 

Oxymandelic acid. 
Leucin. 
Much tyrosin. 


ACUTE PHOSPHORUS-POISONING. 


Gastritis immediately after poisoning, . 
icterus on the third day following a 
pause of two days. 

Icterus recent, less dark. 

Liver sensitive after the beginning of 
the third day and enlarged. 

Cerebral symptoms corresponding to 
general prostration, more of a de- 
pressive type, appearing toward.the 
end, 

In the urine: 

Much sarcolactic acid. 


(In both, peptone, sarcolactic acid, tyrosin.) 


Hemorrhages smaller, fewer. 
Duration several weeks. 


Hemorrhages large, wide-spread. 
Duration shorter, less than a week 


Treatment.—In the prodromal stage of the disease something may 
possibly be expected from treatment. As danger of infection of the bile- 
passages and of “intestinal mycosis” is present in every case of catarrhal 
icterus, every such case is threatened with acute atrophy of the liver. 
This should be remembered whenever threatening symptoms or abnormal 
signs of any kind develop in the course of icterus, particularly if the disease 
is present in women and, above all, in pregnant women. In cases of this 
sort the patient should not be allowed to be out of bed, the diet should be 


ACUTE HEPATITIS. 647 


very plain and moderate, and care should be taken that the bowels are 
regularly evacuated. Asepsis of the intestinal tract is a great desidera- 
tum, and may be attempted by the administration of small doses of calo- 
mel, bismuth, salol, naphthalin, etc., frequently repeated. At the same 
time, enemata and laxatives should be administered from time to time to 
insure evacuation. The latter remedies cause increased diuresis, and 
special drugs should be given to encourage copious urination, as the 
poisons are to a great extent removed from the body by this channel. 

In the second stage the same principles hold good, and in those cases 
that have terminated favorably it appears that a good share in this happy 
result must be attributed to the administration of purges, notably calomel. 
In this stage the treatment must be essentially symptomatic. For the 
restlessness, bromid of sodium, lukewarm baths (narcotics are not so 
good); for the vomiting, ice pills, cocain, extract of nux vomica, small 
doses of morphin; for coma and collapse, stimulants. 

In cases where no fluid is absorbed from the stomach and the rec- 
tum, subcutaneous infusions of physiologic salt solution should be at- 
tempted. 

Where phosphorus-poisoning cannot be altogether excluded, drastic 
purges and antidotal treatment with old oil of turpentine are indicated. 
Traces of phosphorus, according to my own observation, may still be 
present in the intestine on the fourth day of the poisoning. 


LITERATURE. 


Babes: “ Ueber die durch Streptococceninvasion bedingte acute Lebererkrankung,”’ 
“Virchow’s Archiv,” vol. cxxxvI, p. 1. 

Bamberger: Loc. cit. .D. 527. 

Bauer (recovered case) : : “Verhandlungen des Congresses fiir innere Medicin,’”’ 1893, 


Bloedau: “Ueber acute gelbe Leberatrophie,”’ Dissertation, Wurzburg, 1887. 

Boix, E.: “ Nature et pathogénie de l’ictére grave,” “ Archives générales de méde- 
cine, ”? 1896, 11, p. 77, 202 (literature). 

Buss: “ Beginnende acute Leberatrophie,” “ Berliner klin. Wochenschr.,’’ 1889, p. 
975. 

Favre und Pfyffer: “ Weitere Mittheilungen iiber die Genese der acuten gelben Leber- 
atrophie,”’ eas eae s Archiv,” vol. cxxxrIx, p. 189. 

Frerichs: Loe. cit., 1, p. 204. 

Gabbi: “ Sperimentale, ”” Y892, 111, p. 232. 

Gerhardt, C.: “Verkleinerung der tome bei gleichbleibender Dampfung,” “ Zeitschr. 
fiir klin. Medicin,” 1892, vol. xx1, p. 374. 

Hanot: “Contribution a la pathogénie de Victére grave,” “Bericht des 
VIII. internationalen Congresses fiir Hygiene in Budapest,” 1894, vol. 11, p. 623. 

— “De l’ictére grave hypothermique,”’ “ Archives générales de médecine, id ‘August, 

1893. 

v. Haren-Noman: “ Ein Fall von acuter Leberatrophie,” “ Virchow’s Archiv,” 1883, 
vol. xct, p. 334. 

Hirschberg: «Drei Falle von acuter gelber Leberatrophie,” Dissertation, Dorpat, 
1886. 

v.J se (recovered case): “ Alimentary Glycosuria,” “ Prager med. Wochenschr.,”’ 

ay, 1895. 

v. Kahlden: “Ueber acute parenchymatése Leberatrophie und Lebercirrhose,’’ 
“‘Miinchener med. Wochenschr.,”’ 1897, No. 40. 

Kahler: “ Prager med. Wochenschr., 1885, Nos. 22 and 23. 

Klebs: ‘‘ Handbuch der pathologischen Anatomie, ” 1, p. 417. 

Lewitsky und Brodowsky: “Ein Fall von acuter Leberatrophie,” “ Vitthow's 's 
Archiv,” 1877, vol. Lxx, p. 421. 

Litten: “ Augenveranderungen bei acuter Leberatrophie,” “ Zeitschr. fiir klin. Medi- 
cin,” 1882, vol. v, p. 58. 


648 DISEASES OF THE LIVER. 


Marchand, F.: ‘‘ Ueber Ausgang der acuten Leberatrophie in multiple knotige Hy- 
perplasie,” “ Ziegler’s Beitrage,” 1895, vol. xvu, p. 206. __. 

Meder, E.: ‘‘ Ueber acute Leberatrophie mit besonderer Beriicksichtigung der Regen- 
eration”’ (literature), ‘‘ Ziegler’s Beitrage,” 1895. vol. xvu, p. 143. 

Nepveu et Bourdillon: “ Bactérie dans l’ictére grave,” “Gazette méd. de Paris,” 
1892, No. 41. 

v. Noorden: “ Pathologie des Stoffwechsels,”’ p. 290. 

Perls: “ Zur Unterscheidung zwischen Fettinfiltration und fettiger Degeneration,’ 
“‘Centralblatt fiir die med. Wissenschaft,’ 1873, No. 51; “ Allgemeine Patholo- 
gie,” 1877, p. 171. 

Phedran and Macallum: “The Lancet,’”’ February, 1894. 

Podwyssotzky: “Petersburger Wochenschr.,”’ 1888; “Centralblatt fiir die med. 
Wissenschaft,” 1889, p. 173. 

Ranglaret et Mahen: “ Recherches sur un microbe nouveau de l’ictére grave,” “Ga- 
zette hebdomad.,”’ 1893, No. 32. 

Richter, P. F.: “Stoffwechseluntersuchungen bei acuter Leberatrophie,” “ Berliner 
klin. Wochenschr.,’’ 1896, p. 453. 

Riess: ‘‘ Eulenburg’s encyklopddische Jahrbiicher,” 1897, 1, 177. 

— “Charité-Annalen,” 1864, vol. xu, p. 141. 

Rosenheim: “ Zeitschr. fiir klin. Medicin,” 1889, vol. xv, p. 441. 

Schultzen, O., und Riess, L.: “ Acute Phosphorvergiftung und acute Leberatrophie,’’ 
“ Charité-Annalen,”’ 1869, vol. xv. 

v. Starck: “ Deutsches Archiv fiir klin. Medicin,” 1884, vol. xxxv, p. 481. 

Stroebe: “ Zur Kenntniss der acuten Leberatrophie mit besonderer Beriicksichtigung 
der Spitstadien,” “ Ziegler’s Beitrage,’’ vol. xx1, p. 379. 

Thierfelder: Loc. cit., p. 215. 

Wagner, E.: “Die acute rothe Atrophie der Leber,” ‘“ Deutsches Archiv fir klin. 
Medicin,”’ 1884, vol. xxxtv, p. 524. ; 

Wirsing, E.: ‘Acute parenchymatése Leberatrophie mit gimstigem Ausgang,” 
Dissertation, Wurzburg, 1892. “ Verhandlungen der physikalisch-med. Gesell- 
schaft zu Wtrzburg,”’ 1892, vol. xxv. 

Zenker: ‘Zur pathologischen Anatomie der acuten Leberatrophie,” ‘‘ Deutsches 
Archiv fir klin. Medicin,” 1872, vol. x, p. 167. 

Illustrations in the works of Zenker, Riess, Marchand. 


CASES IN CHILDHOOD. 


Ashby: “ British Med. Journal,’’ November, 1882. 

Aufrecht: “ Acute Leberatrophie bei Sclerema neonatorum,” “Centralblatt fiir in- 
nere Medicin,” 1896, No. 11. 

Cavafv: “The Lancet,” July 17, 1897. 

Lanz: “ Wiener klin. Wochenschr.,’”’ 1896, No. 39. 

Merkel, Fr.: ‘‘ Miinchener med. Wochenschr.,”’ 1894, p. 89. 

Schmidt, R.: “ Ein Fall von acuter parenchymatéser Leberatrophie,”’ etc. (collection 
of 16 cases of new-born up to 10 years), Dissertation, Kiel, 1897. 


FOLLOWING SyPHILIs. 


Engel-Reimers: “ Jahrbiicher der Hamburger Krankenhiuser,’”’ 1889, 1 (three cases). 
“Monatshefte fir Dermatologie,” 1892, vol. xv, p. 476. 

Goldscheider und Moxler: “ Fortschritte der Medecin,” 1897, vol. xv, Nos. 14 and 15. 

Naunyn, Fleischhauer: “Congress fiir innere Medicin,”’ 1893. 

Neumann: “Syphilis,’”’ Nothnagel’s Encyleopedia, vol. xxi, p. 411 (literature 
list pp. 412 and 413, Remarks). 

Senator: ‘‘ Congress fiir innere Medicin,”’ 1893, p. 180 (two cases). 

— “Charité-Annalen,” 1893, p. 322. 

Talamon A ; Médecine moderne,” February, 1897; ‘“Centralblatt fiir Dermatologie,” 
I, p. 25. 


As to Various OrHuer DISEASES. 


Bandler, V.: “ Ueber den Einfluss der Chloroform- und Aethernarkose auf die Leber,” 
Poe i arnt aus den Grenzgebieten der Medicin und Chirurgie,” 1896, 1, p. 

Cahn: “ Acute Leberatrophie nach Diphtherie des Magens,” “ Deutsches Archiv fir 
klin. Medicin,”’ 1884, vol. xxxtv, p. 113. : 

Dinckler, M.: ‘“ Ueber Bindegewebs- und Gallengangsneubildung in der Leber bei 


ACUTE HEPATITIS. 649 


chronischer Phosphorvergiftung und acuter Leberatrophie,”’ Dissertation, 
Halle, 1887. 

Dorfler: “ Acute Leberatrophie nach Typhus,” “ Miinchener med. Wochenschr.,” 
1889, p. 878. 

Hecker: ‘‘ Acute Leberatrophie nach Pilzvergiftung,’”’ “Monatsschr. fiir Geburts- 
kunde,” vol. xx1, p. 210. : 

Hedderich: “‘ Acute Leberatrophie bei Phosphorvergiftung” (literature), ‘‘ Minch- 

‘ ener med. Wochenschr.,’’ 1895, p. 93. 

Hiintemann: “ Acute Leberatrophie nach Erysipel,’’ Dissertation, Wiirzburg, 1882. 

Scharer und Sahli: “ Vergiftung mit Amanita phalloides,” “ Correspondenzblatt fiir 
Schweizer Aerzte,” 1885, No. 19, p. 464. 

Wolf: “Acute Leberatrophie nach Wurstvergiftung,” “ Memorabilien,”’ 1876, No. 3; 
Virchow-Hirsch’s “ Jahresbericht,’’ 11, 216. 


ACUTE INTERSTITIAL HEPATITIS. 
(Quincke.) 


Small-celled infiltration and proliferation of connective tissue have at 
different times been described as occurring in parenchymatous hepatitis 
and in acute atrophy of the liver (Riess and others).* This condition 
is found particularly in those cases that are examined postmortem after 
the disease had lasted for a long time; and also in cases of phosphorus- 
poisoning. 

Sometimes the hyperplasia of connective tissue is more conspicuous 
than the parenchymatous changes, or the latter may be completely ab- 
sent. Such cases have been called “acute cirrhosis,”’ the condition being 
called acute from the appearance of the new tissue and the short duration 
of the pathologic process. Both these criteria are, however, very uncertain 
and misleading; we shall see, for instance, in the case of chronic hepa- 
titis, that a’condition of this kind may be present in a latent form for a 
long time and cause no symptoms until the disease has advanced to a 
complicated stage. Many of the cases with an acute course are unques- 
tionably old cases of interstitial hepatitis (ordinary cirrhoses) that have 
become complicated by fresh proliferation of connective tissue with an 
increase of the cellular elements and cell infiltration, or by parenchymatous 
changes that finally lead to acute atrophy. 

An example of the former combination is a case reported by Eichhorst, 
that terminated fatally within two weeks; of the latter are the cases re- 
ported by Clarke + and Richter. 

In a few cases it is possible, however, that we are dealing with a true 
acute interstitial proliferation leading, secondarily, to atrophy of hepatic 
cells (Obrzut) or appearing simultaneously with parenchymatous changes 
(Debove, Polgéure, Blocq, and Gillet). 

It is not possible to estimate the duration of the process from the ana- 
tomic findings. It is true that we know, from the experiments of Hoch- 
haus with cold applications, that small-celled infiltration may occur in the 
course of from two to three days, but at the same time other observations 
teach us that this condition may persist for months without leading to 
further changes. 

Since in chronic cirrhosis recent increase of connective tissue is found 
principally in the interstitial tissues between the lobules, or even in the 
interior of these parts, we cannot attach any particular significance to the 

appearance of the one or the other form of distribution. 


* See Meder’s arrangement, p. 182. + British Med. Journal, 1890, 1, p. 1000. . 
t Richter, “Schmidt’s Jahrbiicher,” 1858, vol. xcviu, p. 181. 


650 DISEASES OF THE LIVER. 


The same causes are given for interstitial hepatitis as for the paren- 
chymatous forms—chemical irritants coming from food-stuffs and con- 
diments, intestinal ptomains, and bacterial toxins. Whenever bacteria 
lodge in the capillaries of the portal vein, small-celled infiltration may take 
place around them. This is particularly so in the case of tubercle bacilli, 
in which case so many single foci develop that an increase in the size of the 
liver may be brought about. To aslighter degree staphylococci, typhoid 
bacilli, and the malarial parasite can exercise the same effect. All these 
germs, as well as syphilis, may cause acute proliferations, which, however, 
persist for a long time. 

In one case reported by Dreschfeld interstitial proliferation was com- 
plicated by thrombosis of small branches of the portal vein with hemor- 
rhagic infarcts. 

Symptoms.—The symptoms of acute interstitial hepatitis resemble 
those of the parenchymatous form and of acute atrophy. Possibly 
icterus in these cases is a little more pronounced in the beginning, and the 
onset and the course are not so acute. The duration of the disease is 
several weeks, occasionally several months. One group of the cases 
(malarial and syphilitic) becomes chronic and leads to the ordinary pic- 
ture of cirrhosis. Those cases in which a considerable degree of degenera- 
tion of liver-cells occurs (Blocq and Gillet) have been called cirrhoses 
graisseuses; but other authors have used this designation for a disease of 
altogether different origin (compare page 732). 

In typical cases the picture of parenchymatous and of interstitial 
hepatitis is widely different; there are, however, a number of cases that 
constitute intermediary forms in which the sequence of events, and conse- 
quently the classification, becomes doubtful. The same statements apply 
to these diseases of the liver as to the same conditions in the kidney. In 
the latter organ the attempt to distinguish strictly between interstitial 
and parenchymatous nephritis, as we know, fails in many instances. The 
differentiation of the clinical picture of these diseases in both the liver 
and the kidneys is still more difficult. This cannot surprise us when we 
remember how similar are the primary causes of the two diseases in the 
case of both organs. The symptoms, therefore, are exceedingly similar, 
with this distinction—that the course of those cases where interstitial 
changes predominate is less violent. 


Blocq et Gillet: “Des cirrhoses graisseuses considérées comme hépatites infec- 
tieuses,’’ “‘ Archives générales de médecine,” 1888, 11, pp. 60 and 181. 

Carrington: “Transactions of the Patholog. Society,’’ 1885, vol. xxxv1, pp. 221-224; 
“ Jahresbericht,”’ 11, p. 201. 

Debove: “De la cirrhose aigué du foie,” “Gazette hebdomad.,”’ 1887, No. 30; 
“‘Jahresbericht,” 11, p 278. 

Dock: “ American Journal of the Med. Sciences,”’ April, 1894. 

Dreschfeld: “ Ueber eine seltene Form von Hepatitis interstitialis mit himorrhag- 
ischen Infarcten;”’ ‘ Verhandlungen des X. internationalen Congresses,’”’ 1890; 
“ Berichte,” 1891, 11, p. 195. 

Fichhorst: ‘Ueber acute Lebercirrhose,” ‘ Virchow’s Archiv,” 1897, vol. cxivu11, 
p. 339. 

Gastou: “Le foie infectieux ’’ (illustrated), literature, Thése de Paris, 1893. 

Obrzut: “Chronische gelbe Leberatrophie oder acute Cirrhose?” ‘Wiener med. 
Jahrbiicher,”’ 1886, New Series, 1, p. 463. 

Polguére: “Cas d’hépatite graisseuse primitive,’ “Gazette méd. de Paris,” 1887; 
“ Jahresbericht,”’ 11, p. 278. 


ABSCESS OF THE LIVER. 651 


ABSCESS OF THE LIVER. 
(Hoppe-Seyler.) 


ETIOLOGY. 


The chief cause of abscess of the liver is the entrance of pus-forming 
_ micro-organisms (bacteria, amebze) into the parenchyma of the liver. 
The paths that these organisms travel are various, and from this fact, 
and because of the differences in species and virulence of the different 
germs, the varieties of the clinical course and the localization and dis- 
tribution of the purulent foci must be explained. 

The following germs have been found in abscesses: streptococci (Kir- 
misson, Pantaloni, Kruse, Zancarol, and others), Bacillus coli (Ewald, 
Pantaloni, Achard, and others), Fraenkel’s pneumococcus (Hermes), 
bacilli resembling typhoid germs, Bacillus pyocyaneus, actinomycosis, 
etc. Kruse, Kartulis, and others have found amebe, and Grimm has 
found flagellated organisms. Experimentally, abscess can in many in- 
stances be produced by the injection of these germs. 

As carriers of these infective organisms we may have foreign bodies, 
such as fish-bones, parasites (ascaris), etc.; such bodies have often been 
found in abscesses of the liver. 

A distinction has always been made between primary and secondary 
abscesses of the liver. Among the former are those that are caused by 
injuries and by the extension of ulcerative processes from neighboring 
organs, as from the gall-bladder and the bile-passages. In the secondary 
forms infection occurs through the blood-stream. In many instances this 
differentiation is not possible. Sometimes the liver is ruptured without 
contusion or laceration of the overlying parts. If the abscess develops 
under these conditions, we must assume that infection occurred through 
the blood, and that germs contained in the blood-stream found a suitable 
nidus in the wounded hepatic tissue. On the other hand, primary trau- 
matic abscesses may follow gunshot or stab wounds in case bacteria enter 
the wound through the channel so created. 

Gastric ulcers, particularly peptic ones, may extend to the liver after 
adhesions have formed between the two organs, and may lead to suppura- 
tion. An extension from an intestinal or peritoneal purulent focus is not 
so often encountered. 

Ulcers of the gall-bladder and of the bile-passages may perforate the 
mucosa and produce suppuration in the hepatic parenchyma in all cases 
in which pyogenic germs are present. In this manner abscesses are formed 
between the wall of the bile-passages on the one hand and the hepatic 
tissue on the other, or abscesses may be formed that are situated within 
liver tissue but communicate’with a bile-passage filled with pus. In these 
foci there are often found gall-stones or parasites which ultimately lead to 
occlusion of bile-ducts and inflammatory irritation, so that the develop- 
ment of the bacteria in the retained bile is favored and the organisms can 
easily penetrate the injured mucosa. In addition, the retained bile ex- 
ercises a deleterious effect on the parenchyma of the liver, so that, in com- 
bination with the action of the bacteria, necrosis and disintegration of the 
tissues (hepatitis sequestrans) are produced. This condition can be ex- 
perimentally produced by the injection into the bile-passages of. certain 
bacteria, such as staphylococci, streptococci, pneumococci, bacillus of 


652 DISEASES OF THE LIVER. 


typhoid and cholera, Proteus vulgaris, etc. In the course of a suppura- 
tive cholangitis the walls of the interlobular bile-passages may become 
softened and inflamed, this process extending to the surrounding tissues 
‘(suppurative pericholangitis) and leading to purulent disintegration of 
neighboring parts of the hepatic parenchyma. In this manner there 
originate some of the confluent multiple abscesses of the liver called 
abscés aréolaires by Charcot. 

In the majority of cases the pyogenic organisms penetrate the liver by 
way of the blood-channels (secondary abscess of the liver). This may 
occur by the following three channels: (1) through branches of the hepatic 
artery; (2) through branches of the portal vein; (3) through the radicles 
of the hepatic vein. | 

Infectious germs gain an entrance into the hepatic artery in general 
pyemia, in ulcerative endocarditis (endocarditis ulcerosa), in suppura- 
tion and gangrene of the lungs, and in purulent and putrid bronchitis 
(bronchiectasis). In connection with these processes numerous meta- 
static purulent foci are formed in the liver, following the transporta- 
tion of infected emboli and bacteria from the heart or other sources. In 
infected wounds combined with septicopyemia, abscess of the liver occurs 
in 15% of the cases, according to the statistics of Barensprung in the 
Berlin Pathologic Institute. .This form was seen more frequently in 
former days before the introduction of asepsis and antisepsis. It 
plays a subordinate réle clinically, for the reason that in pyemia the 
disease in general is so violent that the abscesses are not discovered, 
particularly as they develop slowly and at a late stage of the disease. 
Death as a result occurs before typical symptoms point to an involvement 
of the liver. Abscess of the liver is, therefore, in these cases generally 
found unexpectedly after the death of the patient. 

If the liver, on the other hand, is infected through the portal vein, 
there generally appear very distinct clinical symptoms which allow us to 
diagnose purulent hepatitis. Abscess of the liver originates most fre- 
quently in this manner. 


Morgagni long ago called attention to the possible connection between abscess 
of the liver and disease of the portal system. Dance and Cruveilhier elaborated this 
idea upon the discovery that operations on the rectum and operations for hernia at 
times led to abscess of the liver. Experimentally this was corroborated later by 
injecting mercury into the radicles of the portal vein, an operation that was followed 
by the formation of abscess of the liver containing globules of mercury. Ulcerations 
of the intestine in particular favor the entrance of pathogenic organisms into the 
portal vein. Dysenteric ulcers are the principal cause for this accident. In the be- 
ginning of the nineteenth century certain authors saw a connection between dysentery 
and abscess of the liver, and since the writings of Budd this view has found many 
adherents. It is even stated that dvsentery is one of the most prolific causes for that 
form of abscess of the liver so frequently seen in the tropics. Paine. Abercrombie, 
and Annesley in the first half of the nineteenth century found abscesses in dysentery, 
‘but they could not decide whether dysentery was the result or the cause of the abscess 
of the liver. Budd believed that dysentery was the cause of the abscesses even in those 
cases where the latter appeared before the former. He assumed, in these cases, that 
dysentery was present for some time, but had not been discovered. He opposed the 
view of esley, who claimed that the purulent secretion of an abscess of the liver 
was so irritating as to cause dysentery, and strengthened his argument by demon- 
strating that the dysenteric process left the duodenum and the jejunum free. In 
later years the views of Budd have been sharply antagonized. Fayrer, Sachs, and: 
others attributed tropical abscesses to certain climatic influences (heat, deficient oxy- 
genation, etc.) and to an irrational mode of life. They designated those abscesses 
that appeared in the course of dysentery or that followed trauma as septico-pyemic 
forms. Statistics collated since those days all speak in favor of Budd’s views. RRelsch 


ABSCESS OF THE LIVER. 653 


and Kiener, for instance, found dysentery in 260 cases among 314 cases of ab- 
scess; that is, in 75%. Zancarol states that 59% of his cases had dysentery. 
Waring, in 300 cases of abscess, found dysentery in only 27%. According to Mur- 
chison, 51 cases in which intestinal scars were present were seen among 204 cases of 
abscess of the liver; that is, in about one-fourth of the cases. While, therefore, 
dysentery is not found in all the cases of abscess of the liver, and is not the only 
etiologic factor, it certainly plays an important rdle in the causation of this disease. 
The fact that there are seen a great many cases of hepatic abscess in which no symp- 
toms of dysentery preceded the disease, and the knowledge that many autopsies are 
performed in tropical hepatic abscess in which no traces of dysentery are discover- 
able, does not militate against this statement. In India, Algiers, and the south of 
Russia it is generally accepted to-day that dysentery is etiologically related to ab- 
scess of the liver (Maguliés). If it is argued that there are certain regions, such as — 
Cayenne, in which dysentery is very frequent, but where abscess of the liver is very 
rare, this argument does not invalidate the position taken. In our discussion on the 
rdle of dysentery we will show that dysentery alone cannot produce abscess of the 
liver, but that certain other factors are brought into play, particularly the mode of 
life, and that damage to the liver in other directions creates the necessary predispo- 
sition to abscess. The argument, too, that in the dysentery of temperate zones 
abscess of the liver is not frequent is not valid, for, in the first place, this form 
is different from the tropical form, and may even be due to another causative 
factor; in the second place, climatic influences do not exercise their deleterious 
effects under these conditions; and, in the third place, a number of cases are on 
record in which abscess of the liver did follow dysentery in subjects that had 
never lived in other than a temperate climate (France, England). 

The fact that thrombi have been of rare occurrence in the portal vein in cases of 
abscess of the liver following dysentery is not a forcible argument against the exist- 
ence of a connection between dysentery and hepatic abscess, since other diseases 
are known in which pyogenic organisms are carried through the veins without 
causing thrombosis. Even though a tropical abscess is found in the liver, and if 
ulcers and cicatrices are not present in the intestine, it is still possible that the specific 
virus of dysentery may have caused the abscess; for it may have penetrated through 
some slight abrasion of the intestinal mucosa, that healed later without leaving any 
trace. Unfortunately, the etiology of dysentery is not quite clear. Certain amebe 
(as Amoeba coli felis—Quincke), Bacillus coli, streptococci, etc., have all been 
credited with the causation of dysentery; it has also been held that the disease is due 
to the combined action of different germs. All the germs enumerated have been 
found at various times in abscesses of the liver. Amebe have been found in hepatic 
abscesses by Osler, Kruse, Kartulis, and others, and are looked upon especially by 
Kartulis as the cause of the dysentery. [Osler has recently reported five cases of 
hepatic abscess of amebic origin. In all, the symptoms were obscure and latent. 
Osler calls especial attention to the absence of leucocytosis in three of these cases. 
In one case there was no ulceration of the intestine, though the history admitted 
the possibility of dysentery months previously.—Eb.] Kruse found amebe in 
every case that was preceded by dysentery or in which dysentery was present at the 
time. Other pathogenic bacteria were also frequently found, though there are many 
cases on record in which amebe alone were present (Kartulis, Kruse and Pasquale). 
Kartulis believes that amebz are of themselves capable of producing suppuration. 
Other authors assume that the amebz act as carriers of bacteria, as do the distoma, 
the ascarides, etc., and that, owing to these bacteria, suppuration is produced. It 
must be remembered that although abscesses containing only amebze seem to 
demonstrate that these organisms alone can cause suppuration, the possibility 
cannot be excluded that other bacteria were present but perished in the fluid. 
In the tropics certain forms of abscess are seen the pus of which is sterile and in- 
capable of producing suppuration in the pleura and the peritoneum in case per- 
foration occurs into these cavities (Tuffier, Peyrot, Windsor, and others). This 
seems to be due to the fact that the medium upon which the bacteria have developed 
gradually becomes exhausted and insufficient for their support. In certain cases, 
however, bacteria could be cultivated from the pus (Achard); in such cases we can 
neither assume that the medium was exhausted nor that a complete destruction of 
the germs had been accomplished by some toxic substance in the pus. It is 

ossible in any: event that the bacteria are not very virulent, and an argument in 
favor of this supposition is supplied by the fact that serious complications are absent 
in the case of many of these abscesses. Thus, although amebz play an important 
part in dysentery, and in the abscesses that occur in this disease, this does not ex- 
clude the possibility that occasionally other germs (streptococci {Zancarol], staphy- 


654 DISEASES OF THE LIVER. 


‘lococci, colon bacilli) may cause an abscess in the course of an attack of dysentery 
‘ without any action on the part of the amebe themselves. All of the germs named 
are constantly present in intestinal ulcers, and may penetrate the connective tissues 
and thus reach the liver even before the amebe. [Through the portal vein—Eb.] 
It is also possible to discover amebz deep down in the layers of the intestinal wall, at 
the bottom of the ulcers, so that it seems very probable that they also may enter 
the intestinal veins. 

[In the light of the recent work of Shiga in Japan, Kruse in Germany, and Flexner 
in the Philippines and in America, there 1s now no question that at least a large per- 
centage of all cases of dysentery are directly due to the influence of a specific bacillus, 
of the typhoid group of organisms, but differing in many respects from the typhoid 
bacillus. The cases in which this bacillus has been isolated have been almost invariably 
of the acute variety, a class in which hepatic abscess is a rare occurrence. Nearly 
all of the typically chronic cases have appeared to be due to Amoeba coli. Notwith- 
standing this seeming exclusion of the dysentery bacillus from the number of organ- 
isms that cause hepatic abscess, it seems likely that cases will be found that will give 
unmistakable evidence of the presence of this organism, in the same manner that 
the typhoid, and many other bacilli and cocci, have been found to be causal factors. 
The lesions of the form of dysentery due to the specific bacillus differ somewhat from 
those that are seen in amebic dysentery, but they none the less consist of typical 
serpiginous ulcers, and offer a seemingly ready source of infection for the portal cir- 
culation, and through the latter for involvement of the liver parenchyma.— ED. | 

It would be a very prejudiced view that assumed that all abscesses occurring in the 
tropics or after return from the tropics are attributable to dysentery. The appearance 
of so-called idiopathic abscesses in the complete absence of a history or of symptoms 
of dysentery may well be attributed to the entrance of bacteria that perforate the 
intestinal wall through lesions other than those of dysentery. [J. Alison Scott has 
recently reported a case of hepatic abscess in which there was no antecedent history 
of dysentery. Evacuation took place suddenly into the right pleural sac, with signs 
of acute hemorrhagic pleurisy and the development and subsequent disappearance 
of pyopneumothorax. The pleural fluid was brownish-red, with a heavy flocculent 
brownish sediment containing fatty leucocytes, resembling liver-cells, also bile- 
pigment and fat crystals. A culture from this fluid proved sterile. There was 
present a very old lesion in the colon. Amebez were not found in the pleural fluid, 
but were later demonstrated by Flexner in the scrapings from the abscess wall.— Ep. ] 
The fact that climatic and other injurious influences also render the liver a suitable 
nidus for the development of the different germs greatly favors such an invasion. In 
such cases Kruse has found only bacteria, and no amebe; in all cases that were pre- 
ceded by dysentery, however, amebe were invariably present in the hepatic abscess. 


We have repeatedly intimated that in order to explain the occurrence 
of tropical abscess of the liver in isolated localities and among such various 
classes of people we must assume that other factors are at work reducing 
the natural powers of resistance of the liver, and thus favoring the origin 
of abscess. 

[Robinson’s paper upon tropical abscess of the liver covers thoroughly 
the course and behavior of this condition in the Philippines and Cuba. 
He states that in the First Reserve Hospital of Manila there were in one | 
year 2251 cases of diarrhea and 1391 of pronounced dysentery, following 
in the main in the course of the rainy season. Manson (quoted) reports 
3680 autopsies made on dysenteric patients in various tropical countries. 
Of these 21 % showed abscess of the liver. In 96 dysentery autopsies 
made at the above station in Manila in 1899, abscess of the liver was 
present in over 12 %. This forms the average percentage for Europeans 
in tropical countries. The part played by the amceba coli has not yet been 
determined. It was always present in the stools, but only in five of these 
cases in the abscess, and most of these were cases of long standing.—Eb.] 

In Egypt, India, and in certain other localities the female sex is rarely 
involved, notwithstanding the fact that women are frequent sufferers 
from dysentery. Sachs found only 6 cases in women among 113 cases of 
abscess of the liver, Rouis only 8 among 258 cases, and Waring only 9 


ABSCESS OF THE LIVER. 655 


among 300 cases. The latter two series are of less value than those of 
Sachs, however, for the reason that they are obtained from localities with 
an overwhelmingly military population. 

Europeans are more liable to develop abscess than the natives. 
Negroes, Fellahs, Hindoos, etc., are rarely afflicted with abscess, although 
they are frequent sufferers from dysentery. 


Fayrer states that from 1888 to 1892, out of 1000 men in the Indian army 0.97 % 
to 1.24 % of the European soldiers and 0.03 % to 0.1 % of the native soldiers died of 
abscess of the liver; of the Europeans, 0.45 % to 0.81 %, and of the natives 0.85 % to 
1.11 % died of dysentery. Cayley corroborates these figures. Among the European 
troops in India from 1880 to 1889, 26.8 % of abscess occurred among every 1000 men, 
with 1.34 % of deaths; in the preceding decade the proportion was still worse. Of 
the native Indian troops, only 0.05 % were afflicted during this period and only 
0.03 % died (Davidson). 


Nearly all authors attempt to explain this striking fact by the assump- 
tion that the use of alcohol predisposes especially to suppurative hepatitis. 
Those soldiers who were abstainers were afflicted far less frequently than 
those who were not. In the French possessions in India, for the same 
reason, diseases of the liver are less frequent than in the English ones, 
owing to the simpler mode of life of the inhabitants. Europeans, par- 
ticularly the English, were in the habit some years ago, and are still to-day, 
of indulging in large quantities of alcoholic beverages, spices, coffee, tea, 
ete., and of living luxuriously; the natives, on the other hand, particu- 
larly the Mohammedans, are very frugal in their habits. It is generally 
recognized that alcohol, spices, improper diet, etc., exercise an unfavor- 
able effect upon the liver (compare page 454). It is also probable that food 
that is too abundant, or nourishment that is too rich in proteids and in 
fat, undergoes abnormal changes in the intestine, which result in the 
formation of toxic products. These enter the portal vein and reach the 
liver, where they are capable of exercising a deleterious effect. It is also 
possible that in the tropics the bacteria that inhabit the intestine are 
of a different nature from those found in more temperate zones, and that 
the products of metabolism are, as a result,so different as to exert a dis- 
tinct influence upon the parenchyma of the liver. It is remarkable how 
few cases of alcoholic cirrhosis of the liver are seen in tropical and sub- 
tropical climates, as compared with the many cases of liver abscess. 
Even if, moreover, by the mode of life and the influence of the climate the 
parenchyma of the liver is so predisposed to the development of suppura- 
tive processes, we are not justified in stating, as is sometimes done, that 
the climate, the nourishment, imperfect metabolism in the lungs, an 
improper diet, hyperemia of the liver, etc., are the only causes for the 
formation of abscess of the liver. 

It appears that sudden changes of temperature, traveling from a 
cold to a warm climate and vice versa, exert an important influence upon 
the development of abscess of the liver. A blow, or some other injury in 
the region of the liver, seems also to predispose to the disease; this seems 
quite plausible in the light of all that has been said above. 

When we consider all the etiologic factors enumerated, we can readily 
understand why the female sex, which is less given to excesses in alcohol, 
and the Mohammedan natives, who lead a frugal life, are attacked rela- 
tively less frequently. As soon as the natives or the women begin to 
indulge in alcoholic excesses, they also fall ready victims to the disease. 
The fact that the Antilles and Cheyenne do not seem to have as many cases 


656 DISEASES OF THE LIVER. 


of abscess of the liver, notwithstanding the presence of much dysentery, 
may be accounted for by the equable character of the climate. 

It appears that no direct connection can be traced between the disease 
under discussion and malaria, although for a long time a relationship was 
claimed between the tWo. It is, however, easy to understand that an 
attack of malaria may inflict such damag® to the parenchyma of the liver 
that it becomes a favorable soil for the lodgment and development of 
bacteria, amebe, etc. 

In colder climates, as we have already stated, abscess of the liver is 
seen as a sequel of dysentery in relatively few cases. Typhlitis and 
perityphlitis are the two chief diseases that seem to produce abscesses 
of the liver with or without thrombosis of a branch of the portal vein. 
Together with the abscess following gall-stones, this is the most frequent 
form of the disease encountered in our part of the world. The explanation 
is simple, inasmuch as inflammations and ulcerations are relatively most 
frequent in this particular part of the intestine. Korte believes that the 
suppurative process travels through the retrocecal tissues to the liver, 
and deduces this view from the fact that the portal vein shows no evidence 
of inflammation. It is much more plausible, however, to assume that 
the process is similar to the formation of metastases elsewhere, and that 
the infected particles travel very rapidly through the blood of the portal 
vein without being arrested and that they do not become lodged until they 
reach the narrower channels of the liver. Abscess of the liver is quite 
frequently seen in otherwise benign forms of typhlitis. 


Einhorn, in 100 autopsies on cases of inflammation of the vermiform appendix, 
saw 6 cases in which infection of the portal vein and the liver had occurred; Lang- 
feld, among 112 cases, saw pylephlebitis in 4 and abscess of the liver in 2 cases. 
Reginald Fitz saw pylephlebitis and infection of the liver in 11 cases out of 257 cases 
of appendicitis. In actinomycosis of the liver, too, the primary focus of the trouble 
will in general have to be sought in the region of the cecum and appendix (Barth, 
Langhans, Lubarsch, Partsch, Ranson, Samter, Schartau, Uzkow, Vassiliew). 


Many case reports in regard to the etiologic réle of appendicitis have 
been published. It may happen that the appendicitis is cured, and is 
causing no symptoms of any kind, when an abscess of the liver develops 
as the result of the primary condition. [Dale has recently reported a case - 
of multiple abscesses of the liver following latent appendicitis.—ED. ] 

Gastric ulcers, either peptic or carcinomatous, may also, apart from 
direct extension, in rarer instances, render possible the transference of 
infectious germs into the portal vein, and in this manner cause the forma- 
tion of abscess (Andral and others). Duodenal ulcers may result in the 
same misfortune (Reinhold, Romberg, and others). Simple catarrhal, 
typhoid, or tubercular ulcers (Andral) rarely lead to this complication. 
In the case of a: tubercular condition this is probably due to the fact that 
there is present a tendency to obliteration of the blood-vessels, which acts 
as a hindrance to the transference of infectious germs to the liver (Chauf- 
fard). Actinomycotic foci of the liver may originate from ulcers of the 
small intestine (Zemann, Vassiliew), or of the colon (Bargum and Heller, 
Hoeffner, Kimla, Liining and Hanau, Ullmann, Uzkow), or of the rectum 
(Samter). Ulcers of the rectum, degenerating carcinomata, hemorrhoids, 
and purulent inflammation of the same tract, when operated upon may 
easily lead to the formation of abscess of the liver, as has been known for 
a long time (Morgagni, Cruveilhier, Dance, Arnaud, et al.). 

Inflammatory processes in the bile-passages may also occasionally 


ABSCESS OF THE LIVER. 657 


lead to a more or less pronounced inflammation of the portal vein and to 
the formation of hepatic abscess, since the blood-vessels of these passages 
enter the portal vein. In this manner infectious material may be carried 
from ulcers of these ducts into the parenchyma of the liver (Geigel). 
Gall-stones situated in the cystic or the common duct may also cause 
compression of the portal vein, so that inflammatory processes may ex- 
tend to the latter vessel, causing thrombosis and phlebitis followed by 
suppurative processes in the liver (Klesser). In the new-born, infectious 
germs sometimes penetrate the portal vein through the umbilical vein in 
cases of infection of the umbilicus; these, entering the liver, cause abscess. 
Inflammation of the splenic vein in cases of abscess of the spleen, abscess 
of the pancreas, and purulent pancreatitis, may all rarely produce abscess 
of the liver. Owing to the anastomoses existing between the pelvic veins, 
inflammations of the uterus may occasionally be the starting-point for 
the entrance of infectious organisms into the portal system and the liver 
(Handford, Roughton). In pyemia infectious thrombi may form in 
abnormal conditions of the veins of the pelvis or the mesentery (varicose, 
etc.), and from these the liver may again be infected via the portal vein 
(Virchow). Finally, circumscribed peritonitic exudates (7. e., between 
the pancreas and the liver, Beveridge) may cause pylephlebitis and ab- ° 
scess of the liver. 

Any form of pylephlebitis may lead to abscess of the liver. Thus we 
sometimes see the disease after injuries of the portal vein followed by 
infection of the vessel, as, for instance, in a case in which a fishbone pene- 
trated the vessel from the intestine (Winge). 

Inflammations of the liver starting from the roots of the hepatic vein 
have often been observed, and are characterized by the development of 
microscopically determinable changes around the vena centralis of each 
infected lobule. The process extends to neighboring parts, and, generally, 
a number of small abscesses are formed that later become confluent. 
This variety is not easy to explain. As a rule, it is assumed that infec- 
tious germs penetrate the hepatic vein from some primary focus in one of 
the lower extremities, the uterus, the adnexa, or neighboring parts. The 
infectious agent probably first enters the vena cava inferior, and as soon 
as a retrograde flow of blood occurs (following stasis or forced respiratory 
movements) it is forced into the hepatic veins and its branches. 


That this can and does occur has been demonstrated by Heller, who noted the 
formation of a metastasis in a branch of the hepatic vein from a carcinoma of the 
abdominal lymph-glands; he also proved the occurrence experimentally. Infection 
may also enter the hepatic veins from the superior cava, providing even a minute 
quantity of the blood from the superior cava that pours into the right auricle is forced 
by the contraction of the right ventricle into the inferior cava (Diemer has demon- 
strated this in the rabbit). In this way it may be carried into and infect the hepatic 
veins. Ever since the days of Hippocrates a connection has been formulated 
between injuries of the head and abscess of the liver. Ambroise Paré encouraged 
this belief; Morgagni, on the other hand, discredited it. To-day we have less faith 
in a connection of this kind, and it is more than probable that in the days before 
antiseptic treatment of scalp wounds was inaugurated injuries about the head led to 
general pyemia more frequently than they do to-day, and that as a result the liver 
was more frequently involved. Langenbuch has thoroughly discussed this question, 
one particularly interesting to surgeons, and has shown that there is no apparent 
connection between abscess of the liver and injuries of the head. 


It would appear that infection of the liver by way of the hepatic veins 
occurs primarily in the presence of some weakness of the heart, so that 
stasis of venous blood occurs. Thierfelder, in a case of purulent throm- 

42 


658 DISEASES OF THE LIVER. 


bosis of the subclavian vein, noted multiple miliary abscesses of the liver 
that originated from the center of the acini and were due to infection of the 
organ by pus germs via the right auricle and the hepatic vein. 

The bile-passages exert in many respects the same influence as the 
blood-vessels. Such germs as streptococci, staphylococci, Bacillus coli, 
Proteus vulgaris, and other bacteria, may penetrate deep into the tissues 
of the liver through the fine divisions of the veins in the interlobular tissue, 
and lead to the formation of abscess (Chauffard, Gouget, and others). 

Abscesses may originate in the bile-passages in three different ways: 

1. By direct extension to the hepatic tissues from ulcers due to gall- 
stones (compare page 651). 

2. By extension of a purulent cholangitis or pericholangitis to the 
interlobular tissues and the subsequent formation of tiny multiple ab- 
scesses. 

3. By the entrance of pathogenic germs into the blood-vessels of the 
mucosa, and thence into the portal vein (compare page 657). 

Suppurative processes are rarely noted in the liver as the result of 
infection via the lymph-channels. In cases of perihepatitis an abscess 
may occasionally develop beneath the surface, but clinically such an 
* occurrence assumes little, if any, importance. 

Finally, the echinococcus may appear as the cause of hepatic abscess; 
in such cases the cysts become purulent as a result of secondary infection 
following trauma or inflammation of the bile-passages. This subject is 
discussed in detail under Echinococcus of the Liver. 

With regard to the frequency of the various forms of non-tropical 
abscess of the liver, the following statistics may be given. Barensprung 
observed 108 cases (among 7326 autopsies), of which 11 followed ulcera- 
tion of the bile-passages, and 18 followed ulceration in the territory of the 
portal vein. The latter included 8 cases of affection of the cecum and 
appendix, 5 of carcinoma ventriculi, 1 of carcinoma of the pancreas, 3 of 
carcinoma of the uterus or the vagina, 4 followed gangrene of the lung or 
abscess of the lung, and 55 followed injuries of other parts of the body. 

Luda (unpublished communication) in the Pathologic Institute of 
Kiel found only 29 abscesses of the liver among 10,089 autopsies (0.28 %). 
Of these, more than half were due to pyemia (55 %), and 31 % were due 
to disease of the portal system. 

[Oddo cites nine recent cases of traumatic abscess of the liver in chil- 
dren. The symptoms in some cases appeared at once, in others only after 
a latent period. The liver abscess seemed sometimes to be affected 
primarily by the trauma, and occasionally it seemed to be secondary to 
injury of some other portion of the abdomen. Four of these cases died.— 
Ep.] 

A summary of the principal etiologic factors leads us to conclude that 
life in the tropics is the most frequent cause of hepatic abscess, and that 
an attack of dysentery or an improper mode of living is usually the ante- 
cedent condition. Typhlitis and perityphlitis, and then cholelithiasis, 
together with the suppurative processes that accompany this condition, 
must then be considered. Direct injuries in the region of the liver are less 
frequent causal factors, as are also the entrance of foreign bodies, ulcera- 
tion of the gastro-intestinal tract, purulent infection of echinococcus 
cysts. General pyemia of varying origin is finally to be looked upon as 
one of the most frequent causes. This form of abscess of the liver is of 
subordinate clinical interest. 


ABSCESS OF THE LIVER. 659 


PATHOLOGIC ANATOMY. 


The anatomic picture presented by the liver in purulent hepatitis 
varies decidedly, not only with reference to the stage of the disease, but 
especially with regard to the nature of the infectious agent, the virulence 
of the germ, and its mode of entry. In this manner the differences can 
be explained that are seen on examining the liver in a case of tropical 
abscess and in one of general pyemia. The differences are by no means so 
pronounced between some cases of multiple tropical abscess, on the other 
hand, and certain abscesses that are seen in temperate climates following 
infection via the portal vein from an intestinal ulceration, pus accumu- 
lation in the peritoneal cavity, the mesentery, etc. This is particularly 
apparent if the reports on the different forms of tropical abscess are com- 
pared, and is readily explainable when we remember that tropical ab- 
scesses owe their origin to the entrance of infectious material through the 
portal vein. Consequently no sharp distinction can be drawn between 
acute multiple tropical abscesses and those that occur in colder climates 
as the result of infection through the portal vein. In the case of trau- 
matic pyemic abscess, abscess from gall-stone infection, and chronic 
tropical abscess, such a distinction is possible. 

Little need be said in regard to traumatic abscess. The condition is 
either one of an injury of the abdominal or even the thoracic wall, accom- 
panied by trauma of the liver, as the result of which the parenchyma 
undergoes a process of disintegration and of suppuration; or the substance 
of the liver may be ruptured within the organ itself and this accident be 
followed by inflammation. In the affected portion of the organ we find 
actual destruction of tissue, the formation of pus, hyperemia, later the 
formation of a pyogeriic membrane and the encapsulation of the abscess 
within a connective-tissue covering. Microscopically, we can see the 
leucocytes passing from the wound into the interlobular tissues, and 
making their way between the columns of hepatic cells. Sooner or later 
the liver-cells undergo coagulation necrosis and degenerate into fat and 
detritus. In this manner the process extends to the center of the acinus, 
ultimately destroying even this portion (Koster). The result is the 
formation of an irregular cavity containing sero-purulent masses, disinte- 
grated liver-cells, fat-droplets, leucocytes, etc. The wall of. the cavity 
in the beginning is formed by the parenchyma of the liver; later by a dis- 
tinct pyogenic membrane. In case the abscess is formed near the sur- 
face of the liver, perihepatitis will as a rule be observed. 

If abscess of the liver is caused by infection through the hepatic artery 
or the portal vein, the enlarged organ is riddled with many diminutive 
abscesses, so that its surface often appears mottled by prominent, soft, 
yellowish spots corresponding to the pus foci. On transverse section the 
liver appears hyperemic and cloudy; numerous abscesses, varying in size 
from that of a millet-seed to that of an apple, are seen in different stages 
of softening and disintegration. If of long standing, they pour out a 
purulent fluid mixed with particles of disintegrated tissue. The pus may 
be either serous, creamy, bloody, or bile-tinged. Occasionally it is very 
offensive, and particularly if the abscess has had its origin in intestinal 
ulcers, or from gangrenous cavities in the vicinity. The abscesses are 
often of a bright yellow color from the presence of bile-pigment, which is 
known to have particular staining affinities for necrotic tissue. Occa- 
sionally a dark green zone will be seen around the abscess, owing to the 


660 DISEASES OF THE LIVER. 


action of bacteria and their products on the surrounding liver-tissues and 
to discoloration by the hemosiderin contained in the liver-cells. In many 
instances the formation of pus does not occur, nor is there any destruction 
of tissue; instead we see numerous dark spots on the cut surface of the 
organ; this is particularly the case where the infection has originated in 
the intestine, and especially when the subject has succumbed very rapidly 
to the disease. 

On microscopic examination an accumulation of bacteria will be seen 
in the dilated capillaries between the liver-cells in the vicinity of the 
abscess, and, in addition, numerous leucocytes in the interlobular tissue. 
If infection has occurred through the portal vein, the leucocytes will be 
seen particularly around the branches of this vessel. Leucocytes also 
accumulate around the vena centralis, and in dense plugs fill the spaces 
between the columns of liver-cells. Later changes take place in the liver- 
cells, their nuclei stain poorly, the protoplasm undergoes granular degen- 
eration, and coagulation necrosis gradually occurs. Ultimately nothing 
remains but undefined masses and fat-globules, which, together with the 
leucocytes and the bacteria, form the essential contents of the abscess- 
cavity. Abscesses that originate from the bile-passages may, apart 
from such as are due to gall-stones which have ruptured the bladder-wall, 
entered the liver-tissue, and caused suppuration (these abscesses have been 
described in detail in the section on cholangitis), be caused by pericho- 
langitis. In the latter case the abscesses resemble those that are caused 
by infection through the blood. In the beginning numerous miliary 
abscesses form around the bile-passages. These may vary in size from 
that of a millet-seed to that of a grain of hemp; at the sami time the walls 
of the bile-passages become infiltrated with round cells, as is also the case 
in their immediate vicinity. This area of infiltration soon assumes the 
character of a purulent focus and invades the parenchyma of the liver 
and the branches of the portal vein, destroying liver-cells and causing a 
pylephlebitis. Peritonitic inflammation often begins on the surface of 
the liver. Such a picture is seen particularly in cases in which stasis exists 
in the bile-ducts. 


Chauffard distinguishes a particular form of abscess that he calls abscés aréo- 
laire. He believes that these are always caused by infection from the bile-pas- 
sages. Multilocular abscesses of this kind were observed even before his day as 
the result of inflammation of the vena hepatica, and especially following disease 
of the portal vein. Quite often they occurred in connection with disease of the 
vermiform appendix. These abscesses are tharacterized by their resemblance to 
infarcts. On the surface of the liver there may be seen a circular area, somewhat 
raised above the surface of the organ, and of a different color from the rest of the liver. 
If this portion is incised, it is seen to constitute the base of a wedge-shaped lesion 
the apex of which is directed toward the center of the liver. On transverse section 
the abscess presents the appearance of a spongy mass filled with numerous pus 
cavities that communicate with one another. These cavities originate from the 
confluence of the many acini that have undergone purulent degeneration; they 
form multiple round abscesses that are in contact with each other, gradually unite, 
become confluent, form a hive-like structure, and usually contain a large cavity 
in the center. In older cases the mass is surrounded by a pyogenic membrane 
that may become converted into a connective-tissue capsule. In portions more 
recently affected, near the edge of the abscess, changes are seen in the lobules, 
also round-cell' infiltration in the interlobular tissues around the branches of the 
portal vein, and cholangitis or pericholangitis is present; in some cases thrombosis. 
of the central vein and necrosis and destruction of the surrounding parts are ob- 
served. This form of multilocular abscess seems to owe its origin to the infection 
of some one of the larger blood-vessels or bile-passages. Bacillus coli, strepto- 


cocci, and staphylococci have-all been found in the pus. 


ABSCESS OF THE LIVER. 661 


Actinomycotic foci may appear in any part of the liver either singly or in 
multiple form. Sometimes they penetrate from without by extension of a peri- 
tonitic abscess or of a phlegmon in the posterior abdominal wall. These foci present 
the characteristic structure of actinomycotic eruptions, 7. e., exuberant granulation 
tissue, covered with a pus that contains the characteristic radiating fungi. Older 
foci may have a fan-shaped structure. Perforation through the diaphragm into 
the pleura or the lungs may occur, and often metastases are present in the lungs, 
the brain, etc., at the same time. | 


Tropical abscesses usually run a more chronic course, and are, as a 
rule, surregunded by a firm capsule. Usually they are single and leave the 
rest of the liver intact. 

Rouis has collected the statistics obtained from 756 autopsies on this disease, 
and has found the abscess located as follows: in 53 cases it was near the upper 
surface, in 39 in the anterior portion, in 46 in the inferior, in 47 on the right border, 
in 36 on the posterior surface, and in 67 cases in the interior of the liver. We 
learn from this that the abscess is in many cases situated, for instance, in the upper 
portion of the organ, or in other parts where it is not accessible to palpation. The 
right lobe seems to be a place of predilection. According to Rouis, the abscess 
was found 154 times in the right lobe, 33 times in the left lobe, and 9 times in the 
lobus Spigelii. The abscesses may even occupy an entire lobe, and the latter may 
constitute one large abscess-cavity. [Manson’s report of 3680 autopsies has already 
been referred to. He found that 21 % of all dysentery patients had abscess 
of the liver. The right lobe was most often affected, in one series of 13 cases, 
only two presenting an abscess of the left lobe. Sometimes patches of necrosis 
were present, but no pus. Had the patient lived these also would probably 
have formed abscesses.—Ep.] In 75 % of the cases quoted by Rouis the abscess 
was single. A good idea of the size of these abscess cavities may be obtained 
from the amount of pus contained, varying from 20 to 4500 ¢.c. Corresponding 
to the amount of pus, the liver is enlarged to a greater or lesser degree. In 101 
autopsies it was found that the liver was enlarged in 70 cases, normal in 28, and 
decreased in size in 3 instances. 


In those forms of tropical abscess that run an acute course the tissues 
rapidly undergo extensive softening, with round-cell infiltration of the 
lobules and the surrounding area, as well as coagulation necrosis of the 
liver-cells, as is the case with other metastatic abscesses. Sometimes 
death occurs before a true abscess has formed. In the early stages and 
before the appearance of true suppuration, the liver is very hyperemic, 
deep red on transverse section, and soft (Davidson). In the tissue 
grayish-white spots are visible that exude a serous fluid on section. Later 
on, the parenchyma becomes brittle, grayish-yellow, exudes droplets of 
pus on the cut surface, and shows microscopically a marked round-cell 
infiltration and fatty degeneration. 

If the abscess forms more slowly, more characteristic pus-formation 
occurs. The wall of the abscess consists of the liver parenchyma, and is 
later lined by a pyogenic membrane; this is a layer of young connective 
tissue that soon becomes covered with fibrin, leucocytes, bacteria, amebe, 
etc. From this wall there extend into the interior of the cavity processes 
consisting of more or less altered liver-tissue covered with the membrane. 
This abscess-wall may subsequently become so much thickened as to 
assume the consistency of cartilage and in it proliferation of the bile- 
passages may occur. The surrounding parenchyma is usually more or 
less hyperemic, and the liver-cells are sometimes atrophic and spindle- 
shaped. In other cases the abscess consists of a perfectly dry mass of 
leucocytes. Abscesses of this kind offer the most favorable opportunity 
for a spontaneous cure by contraction and cicatrization. On the other 
hand, the fluid from a young abscess contains leucocytes, necrotic liver- 
cells, fat-droplets, amebee, and bacteria. If an abscess of this kind is 


662 DISEASES OF THE LIVER. 


incised, or if spontaneous evacuation of the pus occurs externally, a cure 
usually results with the formation of a firm cicatrix, the site of which is 
marked by a depression in the tissues; sometimes calcification occurs. 
Occasionally, calcareous cicatrices of this kind have been found in the 
liver that have pointed to the existence of an abscess at some time. It 
has also been observed that tiny new abscesses may form in the walls of 
an old one, even after all the pus has been evacuated. 


Kelsch and Kiener draw a distinction between the foregoing and fibrous ab- 
scesses. The latter, even when they are small, are invested with a firm capsule 
of connective tissue. This capsule consists of fibrillar connective tissue containing 
spindle cells, while around it is a zone of granulation tissue with round papille, 
and around this again there is a layer of flat cells, filled with fat-globules; these 
cells are the transformed round cells which furnish the contents of the abscess. 
According to the writers, a nodule of connective tissue is formed which breaks 
down in its center, and thus creates the picture as described. These abscesses 
may be single or multiple; occasionally they resemble a degenerating gumma. 


The tissues surrounding an abscess may become necrotic or even 
gangrenous, particularly after the abscess has been opened. As a rule, 
the arteries in the walls of the abscess are obliterated and appear as fibrous 
cords; the branches of the hepatic veins are especially liable to occlusion 
by thromboses. Often the latter undergo suppuration and form small 
abscesses that later communicate with the cavity of the main abscess. 
Usually the bile-passages remain patulous and the blood-vessels, with the 
exception of those in the immediate vicinity of the abscess, as a rule, show 
no changes. In rare instances only have abscesses been found that have 
broken into the branches of the hepatic vein, and in the same manner 
perforation into the bile-ducts may occur. | 

Peritonitis and perihepatitis with the formation of adhesions to the 
parietal peritoneum are seldom seen in tropical abscesses, even though 
the abscess may be situated near the surface of the organ. In cases in 
which perforation of the liver capsule threatens, however, adhesive in- 
flammation of the serosa usually develops. For this reason an abscess 
is rarely seen opening into the abdominal cavity; such an accident prob- 
ably never occurs except as the result of trauma. It is much more likely 
that perforation will occur into the peritoneal cavity at some point from 
which the capsule has been previously removed; thus a pus collection forms 
in the abdomen which may rupture again externally, into the bowel, etc. 
Perforation into the right lung has been described very frequently. This 
may happen if adhesions form with the diaphragm, and if the inflamma- 
tion extends through the diaphragm to the right pleura. Inflammatory 
adhesion of the pleura with the base of the lung occurs, then more or less 
extensive infiltration of the involved portions of the lung. If the pus 
then burrows through the diaphragm, it may empty directly into the lung, 
or into a bronchus. In this way an abscess of the lung may be formed. 
Often, however, the evacuation of pus may be so complete that entire 
healing occurs. It may also happen that a subphrenic abscess develops, 
and leads to purulent pleuritis, the empyema finally perforating the lung. 
Cases are also described in which empyema has occurred without perfora- 
tion of the diaphragm; in such instances pus-producing organisms have 
penetrated the diaphragm and caused the inflammation in the pleural 
cavity. There is found in such cases merely a thin membrane in the place 
of the diaphragm, between the abscess and the empyema. Serous pleurisy 
may also originate in this manner. 


ABSCESS OF THE LIVER. 663 


Perforation into the pericardium is rare, and usually results in early 
death, so that no characteristic changes are to be seen in this membrane. 

It may also happen that adhesions form with the abdominal wall, and 
that the abscess perforates these parts, evacuating itself through the skin. 
In these cases fistulous passages of greater or less length are present, and 
lead from the inguinal, the axillary, or other regions of the body to the 
abscess. 

On rare occasions perforation into the colon, the duodenum, the stom- 
ach, the bile-passages, or the inferior vena cava, is seen postmortem. It 
may also happen that an abscess, in case it is situated in close proximity 
to the right kidney, may form adhesions with this organ; the pus may 
then perforate the renal parenchyma and be evacuated through the pelvis 
of the kidney. 

The abscess may discharge itself into other parts of the body, and can 
easily make its way into the circulation and thus give rise to metastatic 
foci in the brain, the spleen, etc. 


COURSE. 


The course and the general symptom-complex of abscess of the liver 
vary decidedly according to the origin of the disease and the nature of 
the infectious agency. We may differentiate acute, subacute, and chronic 
abscesses. It is, however, hardly possible to draw sharp distinctions, for 
the reason that an abscess that may have been latent for a time can 
suddenly become active, owing to some intercurrent disease, trauma, 
etc. In this manner a serious condition may be produced that will present 
all the symptoms of acute abscess. On the other hand, an acute suppura- 
tion may gradually become encapsulated, and in this way be converted 
into a chronic abscess. 

Traumatic abscess is really a surgical condition. At times, however, 
the traumatic origin of the abscess is so remote that it can be established 
only with difficulty, and the impression is then created that the abscess 
owes its origin to some internal cause. 

An open wound may extend through the skin and fascia to the liver, 
and through suppuration this may become still more extensive, until it 
involves the parenchyma of the liver. Under such conditions the pus 
will contain particles of liver tissue and some bile; by scraping the base of 
the pus-cavity liver-cells will be obtained. Under such circumstances a 
large abscess-cavity may be formed and the same picture be present as in 
suppurative processes of the liver following contusion or internal tearing. 

In certain cases of contusion of the liver (a fall, crushing, or a blow in 
the region of the organ) the symptom-complex of hepatic abscess may 
develop in the absence of a penetrating wound. 


Statistics show that abscess is not a frequent sequel of such traumata. Dudly 
analyzed 28,034 autopsies in Ziirich and failed to find a single case of traumatic 
‘abscess of the liver. Christianson had the same experience in another series of 
2450 autopsies. In America it seems to be more common; Dabney found 12 
cases due to trauma among 110 abscesses. Thierfelder found only 11 cases in the 
literature of thirty years, and Langenbuch failed to find more than 39 cases in the 
whole literature. [Attention has already been called to Oddo’s series of nine cases 
of traumatic abscess in children, all of which ended fatally.—Eb.] 


The great majority of cases of injury of the liver go on to healing 
without suppuration, unless the patient dies in consequence of profuse 
loss of blood. 


664 DISEASES OF THE LIVER. 


If an abscess forms, we see an enlargement of the liver, pain in the 
region of that organ, signs of peritonitic irritation, icterus as a result of the 
compression of bile-passages, etc. These symptoms, however, are not 
pathognomonic of abscess of the liver. The diagnosis cannot be made 
until the symptoms that are indicative of all the forms of abscess of the 
liver appear: viz., fever, pain in the right shoulder, a fluctuating tumor, 
etc. The subsequent course of the traumatic abscess resembles that of 
the other forms. It usually appears singly. The resemblance between 
the pictures of traumatic and non-traumatic abscesses can readily be 
understood, since both owe their origin to infection, from some outside 
source, such as the bowel, or the outside air, and the trauma is only a 
predisposing factor. | 

In cases of general septicopyemia or of ulcerative endocarditis the 
presence of an abscess is, as arule, not discovered. Other symptoms are 
so prominent that those about the liver are obscured; the disturbances 
of the heart, the circulation, the inflammatory processes that develop in 
serous cavities, the symptoms of involvement of the central nervous sys- 
tem, etc., dominate the scene. If pain is present in the region of the liver, 
it is usually attributed to some other cause, for the reason that no fluc- 
tuating abscess of the organ develops, since death ensues too early in the 
course of the necrosis and destruction of the liver. The type of fever is 
dependent upon the nature of the general infection. Pain in the shoulder 
is often attributed to an involvement of the joint. In very rare instances 
it is possible to feel fluctuating spots or prominent areas on the surface of 
the liver or to find places that seem painful on pressure. In some 
instances, however, in the course of pyemia, pain appears at localized 
points over the liver, the organ seems enlarged, without exhibiting the 
hardness of an enlargement from stasis, and here and there peritonitic 
friction sounds may be heard. As arule, however, no diagnosis can be 
made during life, and the hepatic abscess is first found at the postmortem 
examination. 

The diagnosis of those abscesses that develop slowly and are due to 
infection from the intestine is generally much simpler. This is particu- 
larly the case in tropical abscesses. On the other hand, it may also hap- 
pen that the development of the abscess is altogether latent, and the pa- 
tient may have an abscess of the liver containing as much as two liters 
of pus and not become aware of the fact until some intercurrent affection, 
trauma, etc., causes the condition to be recognized. 

In many of these abscesses the clinical development can be studied. 
The symptoms of some intestinal trouble, dysentery, typhlitis, perityph- 
litis, may precede the abscess-formation or exist simultaneously. The 
first symptoms that point to an involvement of the liver are pain in the 
region of the organ, and hepatic enlargement, as well as a dull feeling of 
discomfort or pressure in these parts. Pain is felt particularly in the right 
hypochondriac region. The liver dulness is increased, and sometimes 
more in an upward direction than downward, if the suppurative process 
is developing in the upper part of the liver; in this event the character- 
istic outline of the organ is revealed with the upper margin bent convexly 
upward. The appetite becomes poor, often nausea and vomiting are. 
present, the stools become thin, and often the patient is constipated. 
Pain is often noted in the right shoulder. Icterus israre. A continuous or 
a remittent type of fever develops. The pleura may be irritated at an 
early stage of the disease, and as a result a dry cough may appear. The 


ABSCESS OF THE LIVER. 665 


patient always appears to be very sick, usually lying on the back or turned 
a little to the right, with the legs flexed. 

This inflammatory stage, which is usually supposed to last a week in 
tropical abscess, may terminate favorably in cure of the disease. This is 
stated to be the case particularly in the tropical form of hepatitis. We 
must assume that in these cases the process is arrested before the devel- 
opment of true suppuration, and that the inflammatory products are 
reabsorbed. It is a difficult matter to prove that this takes place, though 
we are justified in assuming that it can occur from analogous conditions 
observed in other organs. 

The symptoms of suppuration soon appear; the pain becomes more 
localized in the affected part, and in most cases active shoulder pain de- 
velops. The temperature curve is decidedly that of a septic condition, 
rising to a high point with chills, and falling again with a sweat; in general, 
however, the attacks of pyrexia are not so severe as in pyemia. Loss of | 
appetite and intestinal disturbances are present, as well as vomiting, if 
pressure is exercised over the stomach or intestine. Respiration is more 
and more impeded by the abscess and the consequent swelling of the 
liver. If the abscess is situated so that it can be palpated, distinct fluc- 
tuation will, as a rule, be felt. Neighboring organs are next involved; 
peritonitis, usually localized in character, inflammation of the pleura, 
more rarely of the pericardium, and pneumonic infiltration of the right 
lower lobe, may all appear. Perforation may also occur, either through 
the lungs into a bronchus (in which case pus may be expectorated for 
months), or externally through the abdominal walls, or into the intestine; 
in the latter case pus will be found in the stools. Perforation may also 
occur more rarely into the peritoneal cavity, the pericardium, the right 
kidney, the inferior vena cava, etc. 

If the abscess becomes indolent in consequence of encapsulation, as is 
the case quite frequently in the tropical form, the liver remains enlarged 
and a feeling of oppression or of pain persists in the hepatic region. The 
patient emaciates more and more, the skin turns yellowish-gray, the 
strength gradually fails, and a cure can be brought about only by 
operative interference, or by spontaneous rupture of the sac and evacua- 
tion of the pus through the lung, the intestine, etc. Resorption or calci- 
fication occurs only in very rare instances. . 

The duration of the disease varies from three weeks to six months. 
If the walls of the abscess are very dense, it may persist for years. In 
these cases some intercurrent disease or trauma may cause rupture of the 
abscess into the peritoneum and death. 

Actinomycotic abscesses usually develop very slowly, and with very 
slight inflammatory symptoms; or all symptoms of a metastasis in the 
liver may be absent if the process develops in the interior of the organ. 
In general the symptoms are the same as in the case of any abscess that 
owes its origin to infection of the portal system from the intestine with or- 
ganisms of slight virulence. Later in the disease metastases may develop 
in the lungs or general pyemia may supervene (Beari). 


Now that we have given this brief description of the course of a condi- 
tion which, as we have said, may vary decidedly under different circum- 
stances, we will discuss individual symptoms and explain their signifi- 
cance. 


666 DISEASES OF THE LIVER. 


SYMPTOMS. 


General Symptoms.—A sufferer from abscess of the liver always ap- 
pears to be a very sick person, even in the absence of marked symptoms 
of suppuration or of inflammation, and even though fever and local 
symptoms are lacking. This is the reason why errors in diagnosis are 
so frequently made in a condition in which little or nothing seems to point 
to the liver as the seat of the trouble, and the patients are often considered 
sufferers from phthisis, carcinoma, malarial cachexia, etc. The great 
psychic depression that is generally present is also misleading. 

The color of the skin is usually a grayish-yellow, the sclera are yellow- 
ish, but icterus is, in general, absent, for the reason that no compression 
of bile-passages occurs; if present at all, it may be looked for in the first 
stage of the disease. If icterus is very pronounced, the suspicion is 
aroused that the condition is complicated by some such disease as chole- 
lithiasis, that leads to stasis of bile. As a rule, the tension within the 
abscess is not sufficiently strong to cause symptoms of pressure on sur- 
rounding parts; it rarely develops in the region of the porta. The color 
of the skin recalls that of cirrhosis. In subjects suffering from septico- 
pyemia, or from very acute forms of abscess, this color is, of course, not 
seen. After the abscess is cured this color disappears from the skin, 
which very slowly resumes its normal tint. 

Owing to the destruction of much of the parenchyma of an organ that 
is So important in all the processes of life, and that plays such a large rdéle 
in the regulation of the composition of the blood, anemia is frequently 
quite pronounced. 

_ Fever is almost always present, at least for a time; in the beginning 
it is usually continuous or remittent, until the development of suppura- 
tion. It may be absent in the period preceding suppuration or may be of 
an intermittent, and sometimes an altogether irregular type. During 
the period of suppuration chills occur, followed by sudden rises of tem- 
perature, and then a rapid fall, with the breaking-out of a severe sweat. 
This has been denominated septic fever, and is not characteristic of 
abscess of the liver. The rise of temperature usually occurs toward 
evening, and the fall with sweating during the night, so that the sleep of 
the patient is often disturbed by dreams, etc. The intermittent type of 
fever may resemble the hectic type of tuberculosis, or the type of malarial 
fever, and consequently lead to confusion with these two diseases. It is, 
however, distinguished from malarial fever by its more irregular character 
and, in addition, by remaining uninfluenced by the administration of 
quinin. It may happen that this fever, after having persisted for some 
time, suddenly ceases, owing possibly to an arrest of the suppurative 
process; at the same time it may rise again in these cases and usher in 
the perforation by the pus, and death from exhaustion. The pulse 
during the fever is rapid, tense, and later is small. The sensorium 
is in many cases clear until death, notwithstanding the pyrexia. Some- 
times, however, typhoid symptoms develop: stupor, restlessness, delirium, 
etc., that may lead on to the death of the patient. Abscesses have been 
reported in which all fever was absent; this seems to be particularly the 
case in those forms that are surrounded by a dense capsule and in which 
the symptoms of cachexia, etc., are prominent, and in which pain, in- 
flammation, and swelling are slight. On the other hand, local symptoms 
may be altogether absent, though the fever-curve points to the presence 
of some pus-focus that is not discovered until after death. 


ABSCESS OF THE LIVER. 667 


[Leucocytosis, if present, may prove a valuable differential sign, and 
especially if the observer is fortunate enough to have begun a series of 
examinations at the beginning of pus formation. If a leucocytosis then 
forms, there will be a distinct gradual increase in the total numerical 
count. Osler has, as already noted, reported a series of cases in which 
there was no evidence of a leucocytosis, and in many cases it is un- 
doubtedly absent. In his, as in nearly all reported cases, no differential 
count of the leucocytes was made.—ED.] 

The prominent symptoms relate directly to the involvement of the 
liver, and particularly the pain in the liver region. In the beginning 
there is a feeling of weight and oppression, generally in the right hypo- 
chondriac region, but occasionally extending to the epigastrium, or the 
region of the left lobe. This feeling sometimes slowly, sometimes sud- 
denly, merges into positive pain radiating into different areas of the body, 
according to the location of the abscess. It may be dull or crushing, but 
can also be cutting, stabbing, tearing, or boring. Its intensity varies 
greatly in different cases; it may be exceedingly severe or very mild. 
Much will depend on the location of the lesion. If the abscess is situated 
deep down in the organ, no pain may be felt until the abscess reaches 
the capsule which has a rich nerve-supply. If the abscess develops 
near the periphery, pain is an early symptom, owing to the irritation 
of the integument of the liver. Movements of the body, respiration, 
arecumbent position on the left side, all cause an aggravation of this 
pain, in the latter case because the inflamed suspensory ligaments of the 
organ are put on the stretch. Pressure on the liver and even percussion 
increase the pain. A throbbing, pulsating, pain is rarely complained of. 
As asrule, the pain is not continuous, but varies in intensity; there may 
even be periods in which all pain is absent; these alternate with periods 
of excessive distress, as is readily explainable from the irregular progress 
of the suppurative process. In this manner a remitting or intermitting 
type of pain-accession may occur, similar to the course of the fever. 
Later, and especially if the abscess becomes encapsulated by fibrous mem- 
brane, all pain may disappear; if trauma supervenes and the process 
again becomes acute, the pain returns. 

Pain in the shoulder has for a long time been considered a particu- 
larly characteristic symptom of abscess of the liver. This pain is gener- 
ally felt in the region of the right shoulder, in the cucullaris muscle, the 
scapula, the upper arm, more rarely in the left shoulder, or on both sides. 
Its origin may be traced to the distribution of the branches of the right 
phrenic that extend to the capsule of the liver. If the capsule is inflamed, 
the branches of this nerve are irritated, and the stimulus is transmitted 
to the fourth cervical, which anastomoses with the phrenic. As the 
fourth cervical nerve sends sensory branches to the shoulder, the pain is 
transmitted to this portion of the body (compare page 456). In isolated 
cases atrophy of the deltoid has been seen (Rouis), pointing to a neuritic 
process. That the pain is less frequently felt in the left shoulder is readily 
explained from the relatively rare involvement of the left lobe of the liver, 
and from the fact that this lobe is supplied by a very small branch from 
the phrenic. In 17 % of the cases Rouis found this symptom pronounced ; 
Sachs, among 36 cases, found it twenty-five times. As a rule, the pain 
appears synchronously with the beginning of suppuration, more rarely | 
before or after; it also appears simultaneously with the pain in the liver, 
seldom after, and very rarely before. The pain may either be very slight 


668 DISEASES OF THE LIVER. 


or most severe; it may be that of oppression or may seem as though the 
shoulders were being torn apart. 

Swelling of the liver is usually an early symptom. The liver is, 
as a rule, fairly soft in the beginning, but the enlargement can be clearly 
felt, and if the degree of swelling is considerable, can be seen to cause 
bulging of the right hypochondrium. The ribs protrude, and the 
intercostal spaces disappear or become enlarged. Sometimes a distinct 
bulging corresponding to the liver can be seen underneath the costal 
arch in the epigastric region. Usually the appearance is disguised 
by the contractions of the abdominal muscles, particularly of the right 
rectus. The margin of the liver, if it can be grasped, appears rounded. 
The superficial abdominal veins over the liver are often dilated. Per- 
cussion furnishes definite information. It is stated that the dulness 
extends more in an upward direction than downward, and this is con- 
sidered characteristic. As a rule, however, the boundary between the 
liver and the lung is not regular, but is indented so that the upper boun- 
dary forms a convexity instead of the normal concave line. Frerichs 
has described this phenomenon as a semicircular protrusion of the 
lung-liver boundary. In abscess this line is not so angular as in echino- 
coccus disease, and the decline on either side of the greatest concavity 
is more gradual in the case of hepatic abscess. The concavity can be 
determined between the parasternal and the mammillary lines or in the 
axillary region or even more posteriorly. Enlargement of the liver 
in an upward direction is especially apt to occur in case adhesions exist 
with the anterior abdominal wall or with the costal arch, so that the 
organ is prevented from enlarging downward. In large abscesses 
of the liver containing several liters of pus the dulness may extend 
upward as far as the apex of the right lung and downward as far as 
the crest of the ilium. The right lobe may also push the left far to 
one side, so that a distinct enlargement occurs toward the left. At 
the upper margin of the liver dulness respiratory excursion of the lower 
edge of the liver is generally absent or at best very slight. This im- 
paired excursive power of the lungs is in part explainable by the pain 
that is caused by the slightest respiratory efforts. Sometimes symptoms 
of compression may be elicited at the margins of the lung. 

_ Circumscribed bulging is produced if an abscess develops on the 
anterior surface of the liver or if a large abscess situated posteriorly 
or deep down in the organ grows to such a size as to press the liver 
forward as the result of the resistance offered by the ribs, the spinal 
column, etc., to the posterior surface of the liver. Such protuberances 
are most often found underneath the right costal arch, or they may 
be below this line, or in the epigastrium. If the abscess is near the 
surface of the liver, distinct nodules may be felt or even seen; and if 
suppuration is far advanced, it may even be possible to elicit fluctuation. 
Even a circumscribed edema of the abdominal wall is sometimes seen 
over the abscess. The patients are usually found lying on the back 
in order to decrease the tension of the liver capsule caused by traction or 
pressure. Some observers state that the patients usually flex the right 
legsin order to decrease the tension of the abdominal walls; also that 
they turn a little to the’right with the same object in view. Others, 
as Pel, claim that this position causes the ribs to press against the liver, 
and that consequently these patients never occupy it. Pel, Sachs, and 
others attach no importance to the tension of the right rectus (a symptom 


ABSCESS OF THE LIVER. 669 


which Twining mentions as characteristic), for the reason that this 
symptom is seen in other conditions, as gall-stone colic, intestinal colic, 
etc. 

Disturbances of the digestive tract are frequently associated with 
abscess of the liver. As already mentioned, dysentery may be one 
of the causes of the disease, and this condition may either persist after 
the abscess has formed, or it may become chronic, so that diarrhea 
and constipation are alternately present. Symptoms of typhlitis, gastric 
ulcer, etc., may also complicate the condition. Obstinate loss of appe- 
tite, sometimes alternating with a sensation of hunger, vomiting, a 
coated tongue, etc., may, however, be ascribed to the influence of the 
abscess itself. If the liver is very much enlarged, the ingestion of food 
may be disagreeable, owing to the pressure exercised on the liver as 
soon as the stomach becomes distended. There may be quite obstinate 
vomiting of mucus or of bile-tinged masses. This symptom, according 
to Maclean, is seen particularly in those cases in which the abscess de- 
velops on the concave surface of the liver, and presses upon the stomach 
and intestines. It is possible that the fever and the absorption of septic 
material into the blood are concerned in these digestive disorders; dis- 
turbances of the bile secretion are probably of less active importance 
in this respect. 

Ascites may appear as the result of the general cachexia, together 
with anasarca, hydrothorax, etc.; or it may be the result of direct com- 
pression of the portal vein by the abscess itself. Circumscribed peri- 
tonitis and perihepatitis follow superficial abscesses, and often manifest 
their presence by friction sounds on breathing; in rare instances in- 
flammatory sero-fibrinous exudates form within the peritoneal cavity. 

In pyemia of the liver the spleen naturally is enlarged; in the more 
chronic forms of tropical abscess, however, this is said not to be the 
case unless malaria has preceded the abscess. Amyloid degeneration 
of the organ may occasionally be the result of chronic suppurative pro- 
cesses, and in this way lead to a dense tumefaction of the spleen. 

Owing to the facility with which inflammations that involve organs 
beneath the diaphragm may extend to the pleura and lungs, respiratory 
disturbances are often noted in abscess of the liver. The right pleura 
and lung are involved with especial frequency. At an early stage a 
dry cough may develop, as the result of irritation of the diaphragmatic 
pleura; or a purely nervous cough may be complained of, as the result 
of the peripheral irritation of certain nerve-fibers in the liver which 
act reflexly on the central nervous system. This has been described 
by many authors. Active excitation of the pleura is followed by 
serous pleurisy, a condition manifested by dulness, reduced breath 
sounds, etc. Pleuritic friction sounds are not frequently heard. This 
is probably due to the fact that the fibrinous exudate occurs chiefly 
in the diaphragmatic pleura, and in a locality removed almost beyond 
our range of observation. Empyemata may appear as the result of 
microbic invasion, and for this to occur it is not necessary that the dia- 
phragm be perforated; the same physical signs are seen in this condition 
asin serous effusions: Exploratory puncture will best reveal the nature of 
the inflammation. Dulness on percussion, with reduction or absence of | 
the normal breath sounds, is most likely to occur if the liver enlarges 
upward to such a degree as to compress the lung. This compression 
may be so considerable as to cause a tympanitic percussion dulness 


670 DISEASES OF THE LIVER. 


and weak breathing over the right apex. Loud crepitant rAles are 
heard on inspiration at the same time at the lower margin of the lung. 
As a result of the upward pressure of the diaphragm, dyspnea becomes 
more or less evident, particularly upon violent effort, exercise, ete. 
This symptom may appear even in slight cases of hepatic suppuration, 
owing, even in such conditions, to impairment of the movements of 
the diaphragm, (1) because of the enlargement of the liver; (2) owing 
to the pain that is caused by the pressure of the diaphragm upon 
the surface of the liver; and to the friction between the liver and the 
abdominal parietes during respiration, particularly when perihepatitis 
is present; and, finally, to pleuritic inflammation; (8) because of adhe- 
sions between the liver and the abdominal walls. 

Pneumonia may also occur, particularly in the right lower lobe, 
by direct extension of the inflammation from the diaphragmatic pleura 
to the lung. 

The outcome of these processes, as we shall show more in detail 
below, may be a perforation into a bronchus and the evacuation of 
the abscess by this channel; healing of the abscess cavity may follow. 
Kelsch and Kiener describe certain forms of pneumonia which, as in 
the case of malarial processes in the liver, are occasionally seen in abscess 
of the liver, and involve both the right and left lungs; such pneumonias 
are probably due to infection of the lungs through the circulation. 

The circulatory apparatus exhibits the changes seen ordinarily 
in pyemia: emboli and consequent abscess formation in the lungs and 
other organs, endocarditis, etc. If the suppuration persists for a long 
time, symptoms of myocarditis develop, dilatation, irregular and weak 
heart action, and anemic murmurs. At the same time edema of the 
dependent regions of the body, the feet, the lumbar region, etc., de- 
velops. Abscesses in the left lobe of the liver displace the heart up- 
ward; in abscess of the right side the heart is much less frequently pushed 
to the left. The pericardium is very occasionally involved by direct 
infection through the diaphragm from an abscess in the left lobe, and 
a serous or purulent pericarditis may develop. Perforation of the ab- 
scess itself into the pericardium is exceedingly rare. 

In a few cases aneurysmal dilatation of the branches of the 
hepatic artery in the walls of the abscess cavity has been noted. If 
these rupture, a severe and usually fatal hemorrhage is the result. The 
blood pours into the cavity and, if this already communicates with 
some outside part, or if it ruptures as a result of the increased pressure, 
the blood passes out from it; in one case, reported by Irvine, it ran 
into the intestine, so that blood was vomited, and enormous quantities 
were evacuated in the stools. 

No characteristic changes are to be observed in the urine in abscess 
of the liver. Bile is seldom present. The urine is often colored red 
from urobilin, and in case there are fever and sweating, urates are de- 
posited in quantity. 

Parks states that a decrease in the quantity of urea passed is characteristic 
of the beginning of suppuration; other investigators deny this. Lecorché and 
Talamon found an increase of urea during the stage of inflammation, also an in- 
crease. of the uric acid and of phosphoric acid, and a decrease of all those substances 
as soon as the abscess had formed. Kelsch, however, was not able to corroborate 
these statements. In these investigations much may be learned from careful 


determination of the nitrogen supply, and these studies are not always carried 
out with sufficient care. It is possible that in large abscesses with much destruction 


ABSCESS OF THE LIVER. | 671 


of liver tissue a decrease in the output of urea may be noticed. This decrease may, 
however, also be due to deficient assimilation, and a reduction in the amount of 
food owing to digestive disturbances. On the other hand, an increase may be 
due to increased proteid catabolism as a result of the destruction of tissue, or 
as a direct result of the fever, etc. 


Disturbances of the central nervous system may be the result of 
the fever, of the cachexia, or of exhaustion. Delirium, insomnia, stupor, 
etc., are occasionally observed, and in rare instances these conditions 
may be due to the formation of secondary abscesses in the brain. 

Perforation of hepatic abscess.—Descriptions of the different 
methods of perforation through the skin, or into internal organs, occa- 
sionally in several directions at the same time, are to be found scattered 
in numerous reports throughout the literature; particularly in English 
writings. The works of Rouis, Murchison, Thierfelder, Davidson, 
Langenbuch, and others give detailed accounts of this occurrence, and, 
particularly as they are of special interest from their surgical aspect 
only, it will be impossible at this time to enter into a discussion of all 
the symptoms. 

Perforation through the skin usually occurs in such a manner that 
adhesions first form between the liver and the parietal peritoneum; 
the fibrous tissue thus formed is perforated and the pus burrows through 
either the soft tissues of the abdominal wall, the lower intercostal spaces 
on the right side, or the tissues of the lumbar region, until it finally 
reaches and ruptures the skin surface. At the point of perforation a 
doughy swelling is noticed, which gradually extends, bulges, and the 
skin becomes edematous. The parts become red, and present the 
feeling of a hernia-sac; on pressure a dull feeling of oppression is felt 
in the hepatic region. Soona softer portion of the swelling becomes ap- 
parent, surrounded by more solid tissue, and often distinct fluctuation 
is present. If an incision or puncture is made, vesicles form on the 
surface, the skin ruptures, and necrotic portions of the skin are cast off, 
the contents of the abscess evacuating through the opening. The 
fluid is often tinged with blood, and resembles a fat emulsion; frequently 
it contains pieces of necrotic liver tissue and shreds of connective tissue. 
Sometimes the fluid is viscid and stringy, at other times creamy or 
purulent. In cases of actinomycosis it contains the typical granules 
that represent aggregations of the fungi. Occasionally necrotic por- 
tions of the soft parts, particles of muscle, pieces of rib, etc., are ex- 
truded through a considerable opening. The pus is often malodorous, 
as, for instance, in cases of infection following an attack of typhlitis 
or some lesion caused by the colon bacillus. The opening of the abscess 
does not always correspond to the exact location of the latter, and 
it is possible that a long fistulous passage may lead to it. Abscesses 
have been known to perforate-in the neighborhood of the spinal column, 
on the inner surface of the thigh, in the inguinal region, etc.; they may 
even perforate in the region of the umbilicus if the fistula follows the 
course of the suspensory ligament. 

The pus is often evacuated by means of a fistula formation through 
the lung, especially the right, and by the discharge of the pus through 
the bronchus. Cases of this kind that have recovered have been re- 
ported since the last century, and the literature is full of such instances. 
As a rule, the occurrence is not preceded by symptoms on the part of 
the pleura; the evacuation of pus is preceded by the expectoration 


672 DISEASES OF THE LIVER. 


of bright red (bloody) sputum (Budd, K6llner, and Schlossberger), 
though only very slight pneumonic symptoms appear. The latter con- 
sist of dulness over several of the intercostal spaces, crepitation, and 
possibly bronchial breathing. Suddenly the patient is seized with a 
coughing spell, and a large quantity of pus.is raised by coughing; this 
is usually more or less bloody, sometimes bright red, and occasionally 
brown in color. Often it is partly seropurulent and sometimes con- 
tains shreds of liver and lung tissue. It may also contain bile, and 
subsequently, following the evacuation of the pus, bile may be coughed 
up and expectorated for a considerable time. The quantity expectorated 
is often very large, sometimes as much as one liter ina fewhours. Felt- 
ham states that in one case 500 c.c. of pus were expectorated daily. 
This may continue for several weeks, and has been known to last even 
for the space of a year and a half (Pel). In the majority of cases the 
expectoration of pus gradually stops, the pulmonary symptoms sub- 
side, and the patient recovers. In other cases the abscess does not 
heal, owing to the formation of adhesions or to the stiffness of the cap- 
sule, so that the abscess cavity cannot close; or, again, infection of 
the lung may have occurred with the formation of abscesses of that 
organ. These may continue to spread until they may involve the 
greater portion of the lower lobe. This condition is recognized by 
symptoms of cavity formation in the affected portion. In all such 
instances the cough and the expectoration continue, the fever remains 
high, hemorrhages occur from time to time, the patient grows cachectic, 
and ultimately dies. Thierfelder’s statistics show the frequency of 
perforation into the lungs. In 170 cases perforation occurred into 
the bronchi 74 times, into the right pleura 26 times, the intestine 32 
times, the abdominal cavity 23 times, the stomach 13 times, the peri- 
cardium 4 times. According to a table by Cyr, perforation into the 
lungs was the most frequent accident among 563 cases of spontaneous 
evacuation of pus. 

If perforation occurs into the pleura, empyema results. Some- 
times the opening through the diaphragm is very small, so that empyema 
develops slowly with increasing dulness and diminution of the breath 
sounds over the lower part of the right lung. Purulent pleuritis occurs 
more frequently in this manner than by infection through the diaphragm, 
without perforation. The pus often forces the liver downward (in case 
it is not adherent), compresses the lung, and pushes the heart to the 
left. Dyspnea increases gradually. The pus may now be expectorated 
through a bronchus after penetrating the lung, or it may burrow through 
the chest-wall and be evacuated externally. Occasionally pyopneumo- — 
thorax is seen (Northrup). Only rarely does perforation occur into 
the left pleura. 

If an abscess of the left lobe perforates into the pericardium, severe 
pain is felt in the cardiac area as well as a sense of oppression and 
dyspnea. Collapse and death occur in a short time, and prior to the 
development of symptoms of pericarditis, except a marked increase in 
the heart dulness. Graves, in one case in which a communication 
existed between the pericardium and the stomach, heard a metallic 
sound with each heart-beat from the presence of air or of gas in the 
pericardium. 

Abscesses of the liver are emptied not rarely into the intestinal 
tract, and with particular frequency into the stomach, the duodenum, 


ABSCESS OF THE LIVER. 678 


and the colon. If the abscess is situated on the lower surface of the 
liver, it is very liable to perforate in this manner. If perforation occurs 
into the stomach, a large quantity of blood-tinged fetid pus is suddenly 
vomited, and a portion may be passed in the stools. More rarely vomit- 
ing does not occur at all, and all of the pus passes per rectum. In the 
Same manner, when perforation occurs into the duodenum, usually 
through adhesions or through the bile-ducts, a portion of the pus is 
vomited, though the greater part is intimately mixed with the intes- 
tinal contents and is, passed in the feces. Under these circumstances 
it is often difficult to recognize the pus in the stools. There is a sudden 
collapse of the hepatic tumor, often with the feeling that something 
has ruptured within the body; copious‘diarrheic stools then supervene. 
If this occurs, we are justified in assuming that the pus has perforated 
into the intestine, although it is impossible in the event of a recovery 
to state into what part of the intestine the perforation has occurred. 
If the abscess perforates into the colon, the contents appear in the stools’ 
almost unchanged, distinctly purulent, serous, of a brick-red color, 
and containing small particles of gangrenous tissue. If the opening 
remains patulous, some of the gastric or intestinal contents, especially 
gas, may enter the cavity in the liver and UES cause a tympanitic 
percussion note, splashing, etc. 

Perforation into the free peritoneal cavity is rare. It is said to 
occur especially after trauma in cases in which the abscess is not adherent 
to its surroundings, or in which the adhesions have been torn (Davidson). 
The result is the appearance of a free exudate in the abdomen, accom- 
panied by violent pain, collapse, weakness and rapidity of the pulse- 
beat—in short, all the symptoms of a diffuse peritonitis, to which the 
patient succumbs in a short time. 

More frequently we see a sacculated form of peritonitic exudate 
in cases in which the perforation takes place slowly. Subphrenic ab- 
scesses may develop in this way, and cause a bulging of the diaphragm 
upward; later, perforation occurs into the pleura and the lungs. Or 
an abscess may be formed in the mesentery which is subsequently evacu- 
ated into the colon or through the abdominal wall. Abscesses may 
also develop between the coils of intestine in the posterior abdominal 
wall, and either be evacuated into neighboring organs, or burrow through 
the inguinal canal into the scrotum, etc. 

It may also happen that the abscess perforates into the portal vein, 
resulting in an acute pylephlebitis. The symptoms are so obscure 
that a certain diagnosis cannot be made. If the pus enters the inferior 
vena cava, the right heart and the pulmonary artery are filled with 
purulent fluid. The result will be rapid death with symptoms of as- 
phyxia, as in all forms of embolism of the pulmonary artery. 

Very rarely perforation occurs into the right kidney, and into the 
pelvis of the kidney; cases ofthis kind have been reported by Huet, 
Annesley, Naumann, Roughton, and Hashimoto. The urine contains 
pure pus, and possibly blood and liver-cells, and is brown-red in color. 
After a time the urine may become clear and the condition pass on to 
recovery. 

The frequency with which the different possible forms of evacuation 
of an abscess of the liver occur may be learned from the following figures 
collated by Cyr from all the cases discovered by him in the literature: 
Of 563 ae 311 (55 %) found no opening whatsoever; 83 (14.9 %) 


674 | DISEASES OF THE LIVER. 


were operated; 59 (10.5 %) perforated into the lung; 39 (7 %) into 
the abdomen; 31 (5.5 %) into the pleura; 13 (2.3 %) into the colon; 
8 (1.4 %) into the stomach or the duodenum; 4 (0.7 %) into the bile- 
passages; 3 into the vena cava; 2 into the kidney; 2 through the ab- 
dominal walls; 1 into the pericardium. Thierfelder quotes similar fig- 
ures (see page 672). 

If several abscesses are present, they may either become confluent 
and be evacuated together, or each one may make its own passageway. 
It has also occurred that one abscess has burrowed:in various directions; 
e: g., into the pleura and the lungs (Hames, Peacock), pleura and abdo- 
men (Haspel), pleura and pericardium (Legg), pericardium and colon 
(Marroin), bronchi and intestine (Janeway, Depesselche, Webb), stomach 
and abdominal wall (Budd, Krieg, and Goodwin), duodenum and peri- 
toneal cavity (Juhel-Rénoy), colon and abdominal walls (Domenichetti), 
colon and duodenum (Bristowe), etc. 

Amyloid degeneration of the liver may complicate the condition 
if hepatic abscess persists for a long time, and also cause changes in 
the kidneys, spleen, and intestine, that will be discussed in the proper 
section. The appearance of septicemia is particularly alarming; this 
condition may be present if pus or pus-producing organisms enter the 
hepatic circulation. In cases of tropical abscess the lesions of dysentery 
or its traces can often be seen in the bowel. Finally the symptoms 
of malaria may occasionally complicate those of abscess of the liver: 
viz., dense tumefaction of the spleen and liver, fever, ete. 


PROGNOSIS. 


The prognosis in abscess of the liver is. always uncertain with regard 
to recovery. Pyemic abscesses are probably always fatal. Traumatic 
abscesses, and those that follow acute infection through the portal vein, 
are also, as a rule, unfavorable in their outlook. Only such abscesses 
as occur singly, and contain no very virulent germs, go on to recovery 
after evacuation of the pus by operation or perforation externally. 
Such a recovery occurs quite frequently in abscesses following gall- 
stones. Tropical abscesses seem to offer the most favorable prognosis, 
for the reason that their contents seem to be less toxic, and may even 
be sterile. The more chronic forms of this type of abscess frequently 
perforate the intestine, the skin, and especially through the lungs, and 
are cured in this way. In cases of perforation into the lungs the prog- 
nosis appears to be by no means a bad one; Ughetti, for example, met 
with only 14 % of fatalities after this accident. If the abscess is incised 
or aspirated in the case of these subacute and chronic suppurations 
of the liver at an early stage, the prognosis becomes still better. In 
rare cases only do we see absorption of the pus, and cicatricial obliteration 
of the abscess-cavity. It may happen that an abscess that has been 
successfully aspirated recurs after many years (fourteen years in a case 
of Rebryend), and it becomes necessary to evacuate the pus a second 
time. In making the prognosis the following features must be con- 
sidered: whether septic or pyemic symptoms are present; whether the 
pleura, the lungs, the pericardium, the peritoneum, etc., are involved; 
and whether amyloid degeneration or other intercurrent diseases are 
present, reducing the vital forces of the patient. These factors, if 
present, render the prognosis very doubtful. 


ABSCESS OF THE LIVER. 675 


DIAGNOSIS. 


The difficulty of the diagnosis of abscess of the liver has already 
been emphasized. The older authors have called attention to this, 
and consider it a rare event indeed if the diagnosis is made at all. 

Multiple abscesses, such as follow septicopyemic conditions, acute 
cholangitis, or pylephlebitis, are generally not recognized intra vitam. 
They can only be suspected if the region of the liver is:acutely painful, 
and particularly if the painful area is circumscribed. 

Solitary abscesses, on the other hand, following life in the tropics, 
or dependent upon gall-stones, perityphlitis, and traumata, can be 
diagnosed. The chief symptoms of these conditions have been enum- 
erated above, the most important diagnostic signs being pain in the 
region of the liver, enlargement of the organ in an upward direction, 
pain in the shoulder, septic fever, circumscribed bulging, and, eventually, 
fluctuation over the liver. In pyemia a tumor of the spleen is usually 
present; its absence in the last-named forms of abscess is said to con- 
stitute a point in the differential diagnosis between this condition and 
malaria in cases where intermittent fever is present. If the abscess 
develops in the superior portion of the liver, the condition may be mis- 
taken for pleuritis or pneumonia. The convex outline of the dulness, 
the pronounced bulging (circumscribed, as a rule) of the lower costal 
area, the absence of a distinct hepatic enlargement downward, usually 
indicate the presence of an abscess. Exploratory puncture may render 
important aid in the final decision. It may, of course, happen that 
both a pleuritic effusion and a hepatic abscess are present; in such 
an event the diagnosis, of course, becomes very difficult. [The Rontgen 
rays have in certain favorable cases given valuable aid in differentiating 
between localized conditions, and extensive effusions. IF. H. Williams, 
in an excellent series of studies has shown that certain pathologic pro- 
cesses result in products which appear as dark areas when reproduced 
upon the negative. Purulent fluids are included in this class, owing 
to their great density, and these, by obstructing the passage of the 
rays, throw a shadow upon the otherwise clear area. Williams has 
demonstrated distinctly in this way the extent and locality of an em- 
pyema, and a number of observers have demonstrated the presence of 
abscesses in the lung. The procedure is of less value in the case of 
a localized collection of pus in the liver, owing to the density of the 
organ itself, but may at times be of signal service. The position of 
the liver in the body, requiring the passage of the rays through its longest 
diameter, also offers a hindrance to the success of this method.—Eb.] 
The differential diagnosis from subphrenic abscess is also a difficult 
one, though, as a whole, the history of the case will lend material aid. 
Softened carcinomatous nodules of the liver have been mistaken for 
abscess. As a rule, however, the course of malignant disease is without 
marked fever, and ‘usually evidence of carcinomatous growths will 
be discovered in other portions of the liver and of the body. It may, 
of course, happen that infection of the liver occurs from some carcin- 
omatous ulceration of the intestine, and that in a case of this kind the 
patients are very cachectic, but do not develop any fever. 

Suppurations posterior to the liver, as, for instance, paranephritic 
abscess, have simulated abscess of the liver, and the diagnosis has only 


676 DISEASES OF THE LIVER. 


been assured upon the passage of pus in the urine, or of uriniferous 
pus from the incision. 

Abscesses of the left lobe may be mistaken for carcinoma ventriculi, 
particularly if inflammatory symptoms are absent, and gastric symp- 
toms are prominent. The age of the patient, the history, and a careful 
examination of the stomach-contents will render the diagnosis clear. 
Abscesses of the liver have also been taken for aneurysm of the aorta, 
owing to the fact that the pulsations of the aorta are transmitted to 
the abscess; the pulsation will, however, be found to occur in one direc- 
tion, usually from behind forward, and is not expansile in character. 

Empyema of the gall-bladder is often mistaken for liver abscess; 
the situation of the pus-sac and its contour offer the most certain pro- 
tection against error in this regard. 

Echinococcus cysts develop more slowly and without any inflam- 
matory symptoms; they are hard, tense, and elastic; they do not show 
distinct fluctuation, and are characterized by a thrill on percussion. 
Exploratory puncture will decide the question as to their nature. The 
tumor present in hydronephrosis and pyonephrosis is not palpably 
movable with respiration; it is situated behind the colon, and may 
decrease in size coincidently with the passage of large quantities of pus 
or of urine. | 

Cysts and inflammations of the pancreas may also simulate sup- 
puration of the liver. The stomach should in such cases be distended 
with carbonic acid gas or with air, and it will then be found that the 
tumor is situated behind the stomach; the outline of the pancreatic 
tumor is, moreover, elongated and situated transversely across the 
epigastrium. 

The seat of. the abscess may sometimes be determined upon the 
following considerations: if the convex surface is involved, the liver 
is enlarged in an-upward direction, there is pain in the shoulder, dyspnea, 
and bulging of the right hypochondrium. If the tumor is in the interior 
of the organ, no characteristic signs are present and there is only general 
enlargement and pain. If the tumor is on the under surface of the 
liver, pressure is exercised upon the stomach and the intestine, and, 
as a result, distress after eating, nausea and vomiting, etc., occur; icterus 
may also appear. 

After perforation the purulent collections formed by lodgment of 
the pus in different localities may lead to confusion with psoas abscess; 
or they may appear at the inguinal ring and create the impression that 
a cold abscess of the spinal column exists; it is necessary, therefore, 
to examine both the vertebre and the liver carefully. Perforation by a 
hepatic abscess into the lung may rouse suspicion of perforating em- 
pyema; the anamnesis and a careful examination of the liver should, 
however, clear the diagnosis. 

Exploratory puncture is of paramount importance in rendering 
judgment upon the presence or absence of an abscess of the liver, its 
location, the character of its contents, and of the micro-organisms causing 
it. Especially in the case of tropical abscess, in which the contents 
of the cavity are usually non-virulent, puncture is a harmless procedure, 
even if frequently repeated. 


The operation is performed as follows: Puncture is made in the suspected 
area with a fine needle or with the fine trocar of the apparatus of Potain or Dieu- 
lafoy. The skin is first disinfected, the air evacuated from the apparatus, and 


ABSCESS OF THE LIVER. . 677 


the sterile needle inserted; the cock of the apparatus is opened as soon as the 
needle enters the soft parts; this is done in order that pus may be aspirated as 
soon as it is reached; and in order that it may not pass alongside of the needle. 
If pus is found, the needle should be removed and a note should be made of the 
distance to which the needle penetrated; the cock should be kept open so that 
aspiration is continuous. Sometimes the cannula becomes occluded, and in this 
case the puncture must be repeated. Occasionally a Pravaz needle ‘is employed, 
but it is less suitable for the purpose because the point of the needle is likely to 
make large excursions that may tear the abscess-wall. Sometimes, however, no 
other instrument can be obtained; if, therefore, this syringe is used, the needle 
should be pushed into the soft parts ‘and the plunger pulled out when the point 
of the needle enters. The respiratory movements should be followed as soon as 
the needle enters the liver, it being possible in this way to aspirate the pus without 
doing any harm. The small wound should be closed with cotton, iodoform collo- 
dion, a suitable plaster, ete. 


Sometimes it becomes necessary to perform puncture in different 
places before pus is obtained. 

Peritonitic irritation is rarely seen after this trifling procedure, 
and it has repeatedly been found on autopsy that the puncture did 
no harm. As the walls of the abscess are not so tense and rigid as in 
echinococcus, the small opening closes rapidly and does not permit 
any of the fluid to ooze out. The needle may also be inserted through 
the lower portions of the thorax, without fear of harmful results. 

In contradistinction to an empyema of the pleura, the pus of a sub- 
phrenic abscess shows an increase of pressure during inspiration and 
a decrease during expiration, so that more pus flows out during in- 
spiration than during expiration; in purulent pleuritis the reverse is 
the case. 

A careful study of the aspirated pus will reveal the presence or ab- 
sence of micro-organisms, etc. 

It should be noticed whether particles of liver tissue, echinococcus 
hooklets, actinomycosis granules, etc., are present; the odor of the 
fluid should also be determined to see whether it is fetid or pure. At 
the same time the exploratory puncture gives a certain direction to 
subsequent surgical procedures, as we shall see below. 


PROPHYLAXIS, 


In order to prevent the formation of liver abscess, such diseases should 
be guarded against as may lead to the entrance of infectious material 
into the liver, and especially dysentery and typhlitis. If such diseases 
are present, everything should be done to promote as rapid a cure as 
possible. Care should also be taken that the liver, particularly in hot 
climates, is not abused, so that there may be no predisposition to the 
formation of abscess. 

The treatment of tropical dysentery, both by dietetic and medicinal 
measures, should, therefore, be begun at once; people living in regions 
in which dysentery is prevalent should take exceptional care not to 
acquire the disease. Suitable internal treatment of typhlitis from the 
very beginning, the careful treatment of recurrences, and, if necessary, 
prompt surgical procedures for the relief of disease of the appendix 
are all powerful preventives against abscess of the liver. 

People living in the tropics should observe every care in avoiding 
the abuse of spirits, condiments, and indigestible food, as all these factors 
reduce the resisting powers of the liver. 


678 DISEASES OF THE LIVER. 


These precautions will be particularly necessary if disease of the 
intestines is already present or has been present; this applies as well 
to inflammations of the bowels in our own climate. If some injury of 
the liver has been sustained, the condition of the bowels and general 
dietetic measures should be considered in addition to surgical procedures, 
in order to prevent the entrance of infectious germs into the diseased 
liver-substance. 


TREATMENT. 


Abscesses of the liver are rarely presented for treatment in the stage 
of inflammation preceding the formation of pus. As a rule, there is 
already a distinct accumulation of pus in the organs and the problem 
is to remove the pus as soon and as completely as possible. Conse- 
quently the treatment is almost exclusively surgical. Some abscesses 
cannot be treated at all. Such are pyemic abscesses, and the smaller 
pus foci that are seen in certain intestinal diseases, or that follow chol- 
angitis with or without cholelithiasis. They are not recognized, and, 
even though suspected, may be so numerous or so small that they baffle 
all attempts at treatment. 

If a patient presents himself for treatment at a time prior to the 
development of the abscess, but when evidence of a circumscribed 
inflammation of the liver is already present, antiphlogistic measures 
should be employed. The patient should remain in bed, a light and 
digestible diet (milk, gruel, meal- or milk-soups) should be given, and 
all spirituous liquors avoided. An ice-bag should be placed over the 
liver and leeches (as many as 12) may be applied over the affected region; 
these may also be placed around the anus in order to relieve the engorge- 
ment of the portal system. Blood-letting, formerly a favorite measure, 
is useless even in robust individuals; in anemic subjects it may do harm. 
[Remlinger has reported four cases of apparently acute hepatitis, with 
symptoms strongly indicating the presence of abscess of the liver, in 
four cases of dysentery. Exploratory puncture gave exit to a quantity 
of blood, but no pus was found. In all four cases the local blood-letting 
was followed by immediate relief and subsequent continued improve- 
ment in the hepatic symptoms.—Ep.] The application of vesicants to 
the abdomen has also been recommended; it is better, however, not to 
employ this measure in view of a subsequent operation. ‘Tincture of 
iodin does no harm if the case is a protracted one. Internally, laxatives 
should be given, and particularly calomel (1 gm. divided into three or 
four doses); vegetable purges may then be used, such as rhubarb, senna, 
castor oil, etc., in order to insure copious stools. The long-continued use 
of calomel is, however, bad (Rouis), because this treatment weakens the 
patient, particularly if poisoning occurs, rendering him less fit to undergo 
a subsequent operation. Emetics, such as ipecac, tartar emetic, sal 
ammonia, etc., are useless, and are not employed as much as formerly. 

In some cases a change of climate does good; in others the develop- 
ment of an abscess is observed as soon as the patient returns from a pro- 
longed sojourn in the tropics. 

Formerly considerable time was wasted with these preliminary meas- 
ures.. To-day the most important point is considered to be the earliest 
possible discovery of the abscess by exploratory puncture, and, as soon 
as its position is determined, immediate evacuation. This marks a great 
advance in treatment, as formerly an operation was not undertaken 


ABSCESS OF THE LIVER. 679 


until rupture externally was threatened; multiple incisions were then 
made and a cure often followed. At the present time, owing to the 
danger known to exist of perforation into other organs, sepsis, etc., such 
delay is not tolerated. 


It will be, of course, impossible to describe all the different operations, or to 
outline the measures that have to be adopted to suit the location of the abscess, 
the complications, etc. A detailed description of all these matters will be found 
in Langenbuch’s hand-book, and in other text-books of surgery. 


Aspiration by means of the trocar comes first into consideration. It 
consists in evacuating the pus through a hollow needle or a trocar or with 
one of the instruments designated for the purpose by Potain or Dieulafoy. 
The procedure is the same as that described as exploratory puncture, 
except that now the attempt is made to evacuate the pus as completely 
as possible. In this manner complete cures have been brought about 
(Cameron, Dieulafoy, and others). Sometimes puncture must be re- 
peated; in one case it was performed twenty-four times before the 
patient was cured. Certain cases at least demand incision and drainage. 
Tropical abscesses, owing to the non-virulent character of the pus, are 
particularly adapted to treatment by aspiration; the metastatic forms 
of abscess of our climate, on the other hand, do not act favorably under 
such treatment. As the result in the latter cases is, therefore, always 
doubtful, the method will probably never be extensively employed; 
and, particularly in those cases that can be treated in a hospital with 
all aseptic precautions, incision is much to be preferred. On the other 
hand, puncture has the advantage of being so simple of execution that 
it can be performed in private practice; moreover, it gives the physician 
a convenient means of evacuating an abscess, even in the upper part of 
the liver, by puncturing through the pleural space and the diaphragm 
without necessitating a major operation. 

Puncture combined with drainage is also a valuable form of treatment. 
This operation is performed with a thick trocar, the cannula being re- 
tained in the wound until adhesions have formed or until a fistula has 
developed; it is then replaced by a rubber tube. 


That form of the operation is to be condemned which directs the immediate 
withdrawal of the cannula after tapping, and neglects drainage precautions. Pus 
may enter the peritoneum through the large wound in the liver, particularly if 
the abscess was large and had extended nearly to the abdominal walls, and, as 
a result, suppurative peritonitis may develop. 


If the cannula is allowed to remain, the liver tissue closes around it, 
and a fibrinous exudate, and later adhesions, form as a result of the irri- 
tating influence of the instrument; in this manner the wound is inclosed 
and separated from the peritoneal cavity. If the trocar pierces the 
pleura, the same process may occur there; the soft tissues, muscles, skin, 
etc., tightly grasp the cannula at the same time. In this manner a 
wound-fistula develops through which the pus can flow without danger 
to the patient. 


The operation is performed as follows: The skin is incised (2 to 4 cm.) over 
the point under which the abscess has been found to lie by Xo en om a puncture, 
and a trocar, about as thick as the little finger, is rapidly plunged through the 
incision into the abscess. The pus is allowed to flow out and the cannula retained 
in place; an aseptic dressing is then applied to absorb the pus that continues to 


680 ‘DISEASES OF THE LIVER. 


flow through the cannula. It is not so advisable to introduce a rubber drain at 
once through the cannula, since this has to be removed frequently, and this manipu- 
lation prevents so thorough an occlusion of the canal from the abdominal cavity; 
as a result the danger of peritonitis is greater. The cannula is attached to the 
skin by a few stitches, this being best accomplished by boring a few holes in the 
instrument to allow the threads to pass. At the expiration of two or three days 
the cannula becomes loosened, and can now be removed and replaced by a suitable 
drainage-tube. It may sometimes be a good plan, particularly in hot climates, 
to irrigate the abscess cavity with a 2 % or 3 % boric acid solution in order to 
prevent decomposition of its contents. At the same time the intestine is quieted 
by opium, and a light diet administered. If the pus is very thick, or if it contains 
shreds of necrotic tissue, gall-stones, etc., that cannot pass the cannula or the 
drainage-tube, the opening may be dilated by sponge tents or by the insertion 
of drainage-tubes of different sizes, 


The operation as described has been performed with success in 
the tropics, and also in our climate, by Renvers, Israél, Garré, and 
others. It has the advantage of being easy of execution even under 
unfavorable external circumstances; it is particularly useful, therefore, 
for the same reasons as the capillary puncture in the case of tropical 
abscess, and under all circumstances where the patient cannot have the 
benefit of hospital treatment. Physicians in the colonies employ it 
largely, and among them Cameron, Cambay, Jiminez, Ramirez, de 
Castro, and others. In Alexandria 50 % of the cases of liver abscess that 
were operated in this way terminated fatally, and of those that were 
not operated 71 % succumbed to the disease. : 

[Manson recommends a modification of this form of treatment that 
has given eminent satisfaction in his hands. James Cantlee has also 
reported a series of cases successfully treated by Manson’s method as 
follows: A trocar and cannula are first introduced. Then a large tube 
stretched upon a metal rod is passed through the cannula, and by means 
of this siphon drainage is applied. Of four cases, all operated within 
the past twelve months, three recovered and one died, the fourth case 
being moribund when operated. The chief danger is hemorrhage from 
the vena cava. These four cases completed a series of 28, all operated 
by this method, of which 24 recovered.—ED.] 

Cauterization Methods.—In order to open an abscess through a 
sufficiently large opening, without at the same time running the risk of 
entering the peritoneum as a result of deficient adhesions, a number of 
methods have been employed by which the different parts of the abdom- 
inal wall are successively perforated by cauterization until finally the 
peritoneum is reached, and this is also opened by some caustic applica- 
tion. In this manner adhesions are formed, as a result of the fibrinous 
inflammation caused by the caustic; and only when these have developed 
is the abscess incised. 


For this purpose Récamier employed caustic potash, Demarquay “Vienna 
caustic paste” (equal parts of caustic potash and quicklime). The same author 
used the chlorid of zine paste of Cauquoin (chlorid of zine with flour or starch, 
kneaded into a dough and cut into small strips). Finsen employed the Vienna 
preparation for the skin, and the zine preparation for the deeper parts. The 
abscess may then be allowed either to open by itself, or, if the adhesions are suffi- 
ciently solid, an incision may be made or a trocar inserted. 

It is probably best, in order to abbreviate the treatment, to incise the skin and 
muscles first and then to apply the zinc paste to the wound with tampons of iodoform 
gauze.» After a few days the necrotic shreds of muscle tissue are removed, more paste 
is applied, and this treatment continued until the formation of adhesions has surely 
taken place. This usually requires fourteen days. The abscess may then be care- 
fully incised, slowly evacuated, and drainage established. 


ABSCESS OF THE LIVER. 681 


This method is tedious (requiring at least two weeks), painful, and 
uncertain, and is seldom employed; in its stead the method of single or 
double incision has been introduced. 

' The method of double incision has much in common with the 
caustic method; it was introduced by Graves. An incision is made 
down to the peritoneum, and the wound is closed with tampons for a 
week or longer; the abscess is then incised. The application of the 
tampons causes inflammation of the parts and the formation of peri- 
toneal adhesions, so that the incision can be performed without danger. 
The method is safe, but requires delay, and as there is always meanwhile 
the danger of perforation of the abscess into other organs, it is not a 
practical procedure. 

The method of Récamiers and Bégins, which consists in incising the 
peritoneum directly and in tamponing the wound, is dangerous, and 
was particularly so in the days before aseptic surgery. At the present 
time, with all proper precautions, it may be allowable. 

Owing to the greater certainty of a successful issue the following 
operation of single incision is the best if carried out under strict aseptic 
methods: : 


In the beginning of the eighteenth century Horner opened the abdomen, stitched 
the liver to the abdominal wall, punctured the abscess, inserted a cannula, left it in 
place for fifty-four hours, and, finally, replaced it by a drainage-tube. His method, 
which is geserally employed to-day, could not recommend itself in his time owing to 
deficient facilities for cleanliness and antisepsis. His method was first employed in 
echinococcus disease; later Sanger employed it in abscess, stitching the abscess-wall 
to the abdominal muscles and later making his incision and evacuating the pus. 
Tait first performed puncture, evacuated the pus, and then stitched the abscess-wall 
fast. Ransohoff performed the operation with the thermocautery instead of with the 
knife. Some operators, among others Defontaine, allow the aspirating needle to 
remain in place and use it as a guide for subsequent incision. ‘The liver is exposed, 
and the pus removed with the aspirator through the needle; the liver is then at- 
tached, and the abscess opened by incision, and drained. It seems a good plan to 
allow the needle to remain in place, particularly in deep-seated abscesses; in super- 
ficial abscesses it seems better to remove it before the operation in order to prevent 
the entrance of pus into the peritoneal cavity following movements of the patient. 

The incision into the skin should be from 8 to 10cm. long. It will be well to 
aspirate the pus before making this incision, because the liver after evacuation 
changes its form and its position relative to the wound. It is best, therefore, to 
attach the organ after evacuation in order to avoid too great a tension on the stitches. 
It is also recommended to resect a semilunar piece of the abdominal wall in case the 
wound does not gape sufficiently, also to apply a ring of sutures through the capsule 
of the liver, the muscles and the fascia of the abdominal wall, and to incise the 
wall of the abscess between two forceps by a cut of 6 to8 cm. The margins of the 
liver incision, after all bleeding has stopped, are sutured to the abdominal wound. 
It is useless to curette the abscess-cavity, and harm may be done. Thick drainage- 
tubes should be placed in the wound and the cavity washed out with a 2 % solution 
of boric acid. [Thompson found amebe in the pus of a case of a liver abscess, and as 
long as boric acid solution was used to wash out the cavity living amebz could be 
found in the discharge. A solution of quinin was then substituted (1 : 1000), and 
from that time, and during the next few days, only dead amebe were to be found, 
and later none at all.—Eb. | 


This method gives good results if it is carefully performed, and seems 
to be safer than the rapid method of Stromeyer-Little: 


This operator inserts a knife directly into the abscess, beside the aspirating 
needle, irrespective of the presence or absence of adhesions. Witha broad incision, 
while the liver is being pressed against the abdominal wall, he severs the wall of the 
abscess, the peritoneum, the abdominal walls, and sometimes an intercostal space. He 

then washes out and drains the abscess-cavity. This method attracted much atten- 


682 | DISEASES OF THE LIVER. 


tion, particularly in England and France. Langenbuch has criticized it and has called 
attention to its many defects. If adhesions are present, the result may, of course, 
be good; and even if this is not the case, a cure may result if the liver is close to the 
abdominal wall, and if the pus is sterile. Oftentimes, however, the hepatic and the 
abdominal openings do not coincide after the pus is evacuated, and, as a result, pus 
enters the peritoneum, and a fatal peritonitis results. It is also possible to injure 
the gall-bladder, the large blood-vessels, the intestine, the mesentery, etc. For all 
these reasons this method should be condemned as dangerous, and the method of 
incising the abscess only after the formation of adhesions, recommended in its stead. 


If the abscess is situated under the costal cartilages on the right side, 
it is possible, according to Lannelongue, to resect the latter over an area 
that does not communicate with the pleural cavity. It may even be 
possible to push the pleural sac upward a little, to suture the peritoneum, 
and then to incise the abscess. 

In case it becomes necessary to enter the right axillary region and to 
penetrate to the abscess through the pleural space, the ribs should be 
resected, the leaves of the pleura united by tamponing or by stitching, 
the diaphragm incised, and the abscess (which is usually adherent to 
the diaphragm) opened. If no adhesions are present, the diaphragm 
must be stitched to the abscess-wall; it may also be practical to attach 
the former to the skin in order to insure perfect closure. 


Bichon’s suggestion, to evacuate the pus into the colon through an artificial fis- 
tula into that part of the intestine, appears dangerous, in that it is very possible that 
this might lead to the entrance of intestinal contents into the abscess-cavity. 


If the abscess perforates the pleura, the empyema must be evacuated 
as soon as possible by thoracentesis and resection of ribs, and drained 
in order to prevent further perforation into the lungs. If the lung is 
already perforated, it will still be necessary to evacuate the pleural cavity 
through an external incision. 

If the lung is perforated owing to adhesions with the diaphragm, it 
will be well to promote expectoration by the exhibition of expectorants, 
as senega, apomorphin, etc.; preferably, however, by inhalations of 
turpentine and of similar preparations, also by the internal administra- 
tion of these drugs and of preparations of creosote, etc. In this manner, 
too, the further development of suppurative processes in the lungs and 
bronchi may be in a measure impeded. Life at a high altitude or at the 
seashore is to be advised. If an abscess of the lungs has developed, 
pneumotomy may have to be performed; the thorax over the affected 
portion should be made more elastic by extensive resection of the ribs 
and the abscess caused to shrink in this manner. 

In case the pus is poured into the abdominal cavity, laparotomy 
must be performed at once and the pus removed; this does not often 
happen. As a rule, it occurs after some trauma, and even though the 
operation is performed at once it is often too late. If the contents of the 
abscess are sterile or not very virulent, the operation may be successful; it 
is even stated that in cases of this kind the administration of opium and 
the use of cold applications have led to a cure without operative measures. 

If the abscess spontaneously perforates the abdominal walls, thorough 
evacuation of the pus should be promoted, and, if necessary, by en- 
larging the opening, by inserting drainage-tubes, etc. 

Ifthe pus is poured into the intestine, no treatment is called for, 
unless peritonitic symptoms appear at the same time. In the event of 
some of the intestinal contents entering the abscess-cavity and causing 


ABSCESS OF THE LIVER. 683 


gangrenous inflammation, the abscess must at once be opened externally 
and thoroughly drained. 

Perforation into the pelvis of the kidney is rare, and calls for no special 
treatment. 

Frequently an operation and a complete evacuation of the pus are 
not all that is required. Fistulous openings may persist, and continue 
to suppurate; or the patient may become anemic, or his nutrition remains 
poor. It is well, therefore, to advise these patients to seek a better 
climate; to send them to sanatoria in tropical climates, in the mountains, 
to the seashore, or to send them home. In our climate [Germany] it 
will be best to send them to the seashore, into the mountains, or to advise 
a mild course of alkaline-saline waters, or of some thermal springs. 


LITERATURE. 


GENERAL ARTICLES. 


Bamberger: “ Krankheiten des chylopoétischen Systems,” ‘‘ Virchow’s Handbuch 
der speciellen Pathologie und Therapie,” Erlangen, 1847. 

Budd: “ Krankheiten der Leber,” p. 50, Berlin, 1846. 

Davidson, A.: ‘‘ Hygiene and Diseases of Warm Climates,’’ Edinburgh and London, 
1893. 

Des Portes Pouppé: “ Histoire des maladies de 8. Dominique,” tome 11, Paris, 1770. 

Frerichs:, “ Klinik der Leberkrankheiten,” 1861, vol. 11, p. 96. 

Gasser: ‘ Abscés du foie,’ in ‘‘ Manuel de médecine” von Debove und Achard, vol. 
vI, p. 188, Paris, 1895. 

Kelsch et Kiener: ‘‘ Traité des maladies des pays chauds,”’ Paris, 1889. 

Langenbuch: “Chirurgie der Leber und der Gallenwege,” vol. 1, p. 199, Stuttgart, 
1894. 

Madelung: “ Chirurgische Behandlung der Leberkrankheiten,” in “ Handbuch der 
speciellen Therapie,”’ von Penzoldt und Stintzing, Bd. 1v, Theil 2, p. 198. 

Pruner: ‘ Die Krankheiten des Orients,”’ Erlangen, 1847. 

Rouis: “ Recherches sur les suppurations endémiques du foie,”’ Paris, 1860. 

Scheube: “ Die Krankheiten der warmen Lander,” Jena, 1896. 

Thierfelder: “‘Suppurative Leberentziindung (Leberabscess),’’ Ziemssen’s “ Hand- 
buch der speciellen Pathologie und Therapie,” Bd. vi, 1. Halfte, 1. Abth., p. 78. 


Hepatic ABSCESS. 


Aubert, Th.: “ Etude sur les abscés aréolaires du foie,’”’ Thése de Paris, 1891. 

Barensprung, C.: “ Der Leberabscess nach Kopfverletzungen,” “Archiv fiir klin. 
Chirurgie,”’ 1875, vol. xvu1, p. 557. 

Bajon: “ Abhandlung von Krankheiten auf der Insel Cayenne” . . . Erfurt, 
1781. 

Bettelheim: “ Beitrag zur Casuistik der Leberkrankheiten,’’ “Deutsches Archiv fiir 
klin. Medicin,” 1891, vol. xivit. 

Blank: “On the Causes of Hepatic Abscess,”’ ‘The Lancet,’”’ February 20, 1886. 

Carl: “Ueber Hepatitis sequestrans,” ‘Deutsche med. Wochenschr.,’”’ 1880, Nos. 
19 and 20. 

Cayley: ‘Tropical Affections of the Liver,” “Verhandlungen des VIII. Cori€resses 
fiir Hygiene und Demographie in Budapest,’ 1896, vol. 11, p. 695. 

Chauffard: “Etude sur les abscés aréolaires du foie,’ “ Archives de physiologie,” 
1883, p. 263. 

Christiansen: “ Zwei Falle von Leberabscess mit Durchbruch ins Pericard,’’ “ Norsk. 
Magazin for Lager,’’ 1890, p. 211, nach “ Virchow-Hirsch’s Jahresbericht,”’ 11, p. 


259. 
eae Sear Leberabscess,” ‘‘ Deutsches Archiv fiir klin. Medicin,”’ 1893, vol. L, 
i Ola. 
Ewald : “Leberabscess nach Dysenterie,’”’ “ Deutsche med. Wochenscbr.,” 1897, p. 
67. 
Fayrer: ‘Liver Abscess and Dysentery,” “The Lancet,” May 14, 1881. 


Flexner: “ Perfor. of the Infer. Vena Cava in Amoebic Abscess of the Liver,’’ “ Amer- 
ican Journal of the Med. Sciences,’’ May, 1897. 


684 DISEASES OF THE LIVER. 


Funke: “ Zwei Falle von Leberabscess,” Dissertation, Wirzburg, 1893. 

Geigel: ‘‘ Ueber Hepatitis suppurativa,” “Sitzungsberichte der physikalisch-med.,” 
“ Gesellschaft zu Wurzburg,” 1889, p. 35. 

de Gennes et Kirmisson: ‘Note sur deux cas d’abscés volumineux du foie,” 
“ Archives genéralés de médecine,”’ 1886, tome cLv1II, p. 288. 

Gouget: “Injections hépatiques expériment. par le Proteus vulgaris,” “ Archives de 
médecine experiment.,’”’ 1. Serie, tome 1x, p. 708. 

Grimm: ‘Ueber einen Leberabscess . . . mit Protozoen,” “Archiv fiir klin. 
Chirurgie,’ 1894, vol. xLvu1, p. 478. 

Hashimoto: “ Zwei Falle von Leberabscess,” in “ Archiv fiir klin. Chirurgie,” 1885, 
vol. xxx, p. 38. 

Hengesbach: “Ueber Leberabscess,’’ Dissertation, Berlin, 1894. 

Hermes: “Casuistischer Beitrag zur Chirurgie der Leber,” ‘ Deutsche Zeitschr. fiir 
Chirurgie,”’ 1895, vol. xx1, p. 458. 

Kartulis: “‘ Ueber tropische Leberabscesse und ihr Verhalten zur Dysenterie,”’ “ Vir- 
chow’s Archiv,” 1889, vol. cxvi1, p 97. 

— “Ueber verschiedene Leberkrankheiten in Aegypten,”’ ‘‘ Verhandlungen des VIII. 
Congresses fir Hygiene und Demographie in Budapest,” 1896, vol. 11, p. 643. 

Kiener et Kelsch: “ Affections paludéennes du foie,’”’ “ Archives de physiologie,”’ 
1879, p. 398. 

Klesser: “ Ein Fall von Hepatitis suppurativa,’’ Wirzburg, 1887. 

Klose: “ Ein Fall von primarem Leberabscess bei einem Neugeborenen,” Disserta- 
tion, Wurzburg, 1893. 

Koéllner und Schlossberger: “ Beitrag zur Casuistik der Leberabscesse,” “‘ Deutsches 
Archiv fir klin. Medicin,” 1883, vol. xxxm, p. 605. 

Koster: ‘Untersuchung tber Entziindung und Eiterung in der Leber,” “ Central- 
blatt fiir die med. Wissenschaft,’”’ 1868, p. 17. 

Kruse und Pasquale: ‘“ Eine Expedition nach Aegypten,”’ ‘ Deutsche med. Wochen- 
schr.,” 18938, p. 354. 

Laveran: “Contrib. 4 l’anat. des abscés du foie,” “ Archives de physiologie,” 1879, 

. 654. 

Leyden: “Fall von multiplem Abscess infolge von Gallensteinen,” “ Charité-Anna- 
len,” 1886, p. 167. 

Mejia: “L’hépatite parenchym. aigué circonscrite,” “ Verhandlungen des X. inter- 
nationalen med. Congresses,’’ Berlin, 1890, vol. 11, p. 126. 

Menzzer: “Fall von Leberabscess infolge von eitriger Pylephlebitis,’’ Dissertation, 
Erlangen, 1889. 

Mosler: “ Ueber traumatischen Doppelabscess der Leber ” “ Zeitschr. fiir klin. Medi- 
cin,” 1883, vol. v1, p. 173. 

Monueee “Abscess of the Liver,” ‘“New York Med. Record,” February 2, 1884, 
vol. xxv. : 

Pel: “Ueber die Diagnose der Leberabscesse,” ‘ Berliner klin. Wochenschr.,’’ 1890, 


. 765. 

Rajgrodski: “ Zur Casuistik der Leberabscesse,” Dissertation, Jena, 1879. 

Ransohoff: “ Beitrag zur Chirurgie der Leber,” “ Berliner klin. Wochenschr.,”’ 1882, 
p. 600. 

Rassow: “ Zur Aetiologie der Leberabscesse,”’ Dissertation, Greifswald, 1895. 

Rebreyend: ‘‘Sur un cas de récidive 4 longue échéance d’un abscés du foie,” “ Ar- 
chives générales de médecine,” 1897, p. 226. 

Reinhold: “ Fille von Leberabscess nach veralteter, véllig latent verlaufener Peri- 
typhlitis,’”’ “ Miinchener med. Wochenschr.,’’ 1887, Nos. 34 and 35. 

Renvers: ‘“ Beitrag zur Behandlung der Leberabscesse,” ‘ Berliner klin. Wochen- 
schr.,’”’ 1890, p. 165. 

Roughton: ‘“ A Case of Hep. Abscess,” “The Lancet,” August 22, 1891. 

Sachs: “Ueber die Hepatitis der heissen Lander,” “ Archiv fir klin. Chirurgie,”’. 
1876, vol. x1x, p. 235. 

Schinke: “ Zur Casuistik der Leberkrankheiten,” Dissertation, Greifswald, 1887. 

Singer: “Zur Casuistik und Symptomatologie der Leberabscesse,” “Prager med. 
Wochenschr.,”’ 1884, No. 29-32. 

Sym: “Case of Double Hep. Abscess,” “ Edinburgh Med. Journal,’ 1887, p. 879. 

Ughetti: ‘Contrib. allo studio della epatite suppur.,” “ Riv. clinica,” 1884, No. 12, 


Vosswinkel : “Vorstellung von zwei geheilten Fallen von Leberabscess,”’ ‘ Berliner 
klin. Wochenschr.,’’ 1895, p. 419. 

Wettergren: “Hygiea,” 1880, p. 37, Nach “‘Virchow-Hirsch’s Jahresbericht,’”’ vol. 
11, p. 197. : 


CHRONIC INFLAMMATION OF THE LIVER. 685 


Whittaker: ‘Traumatic Abscess of the Liver,” ‘““New York Med. Record,” 1880, 
vol. xvil, p. 587. 

Windsor: “ A Brief Account of Tropical Abscess of Liver,” “ The Lancet,’’ December 
4, 1897, p. 1447. 

Zancarol: “ Dysent. tropicale et abscés du foie,’’ ‘“ Verhandlungen des VIII. Con- . 
gresses fiir Hygiene und Demographie in Budapest,’ 1896, vol. 11, p. 759. 


Robinson: ‘ Hepat. Abscess,” “Jour. Am. Med. Assoc.,’’ May 11, 1901. 
Scott, J. A.: “ Hepat. Abscess,” “ Proc. Path. Soc. Phila.,’’ Nov., 1901. 
Dale: “ Abscess,” ‘ Jour. Am. Med. Assoc.,’’ Mar. 23, 1901, p. 835. 
Glenard: “ Bull. d. 1. Soc. de Med. de Paris,’’ April 25, 1901. 

Oddo: “ Revue des Mal. Enf.,” Paris, Jan. and Feb., 1901. 

Osler: ‘ Med. News,” April 12, 1902. 

Willson: ‘‘ American Medicine,” Mar. 29, 1902. 

Cantlee: ‘Brit Med. Jour.,’’ Sept. 14, 1901. 

Remlinger: “ Rev. de Med.,”’ Aug. 10, 1900. 

Thompson: “ Phila. Med. News,” Feb. 3, 1894. 

Berndt: ‘ Deut. Zeitschr. f. Chir.,” vol. xi, 1894, p. 163. 

Moncorvo: “ Rev. mes. des Mal. de l’Enf.,”” 1899, xvi, p. 544. 


CHRONIC INFLAMMATION OF THE LIVER. 
(Quincke.) 


When speaking of chronic inflammation of the liver, chronic inter- 
stitial hepatitis is usually implied. If the word interstitial were intended 
to signify merely a particular kind of chronic inflammation of the liver, 
then the chronic parenchymatous form must needs also be discussed. 
This, however, is never done, for reasons that we will explain below. 
It would appear that the word interstitial is merely an explanatory 
addendum, and that every form of chronic hepatitis is necessarily inter- 
stitial. This is, however, by no means the case. In certain of the dis- 
eases that we will discuss (phosphorus- and alcohol-liver) we know that 
the parenchymatous cells of the liver are involved, and in some cases to 
a great extent; in other diseases we have every reason to assume that 
the same thing is true. In the latter class it is often difficult to prove 
that the liver-cells are primarily involved, for their appearance even in 
a normal liver is so variable, microscopically, and it is so difficult to de- 
termine the presence of disturbances of the hepatic cells during life, that 
such a task is almost hopeless. We see, therefore, that mild initial 
changes in the parenchyma can readily evade detection; whereas even 
the slightest abnormalities in the interstitial tissues are at once per- 
ceived, for the reason that this tissue is normally so scanty. 

Although in certain cases the changes in the interstitial tissues are 
primary, yet we know that they may also be secondary to primary 
changes in the liver-cells. Different investigators fail to agree with 
regard to the primary or secondary origin of the condition. 

The same difficulty is experienced in chronic inflammations of other 
organs, as in tabes, neuritis, and nephritis. A study of the latter disease 
will throw some light on the- processes that occur in the liver. For a 
long time the various authors attempted to distinguish between inter- 
stitial and parenchymatous nephritis, and to formulate certain anatomic 
types for the one or the other lesion. To-day we have learned to recognize 
that this distinction cannot be carried through, and that often paren- 
chymatous and interstitial changes are seen simultaneously, and may 
develop from one another. We know also that the same influences. 


686 DISEASES OF THE LIVER. 


(alcohol, scarlatina) can produce either or both forms of nephritis, and 
we can imagine that the quantity of poison present, the rapidity of its 
action, and its joint action with other harmful influences determine the 
cause of the various forms, as well as the course of the disease. In the 
case of the liver, too, we know that the same poisons—alcohol or phos- 
phorus—may produce either parenchymatous (fatty infiltration, as a 
rule) or interstitial changes, and that the two forms are related to one 
another; we see, therefore, that a differentiation of the two diseases is 
not justifiable either from a histologic or an etiologic point of view. 

In describing the pathologic anatomy of these diseases, the inter- 
stitial changes will be emphasized, for the reason that they are more 
conspicuous and because they are more lasting; our present knowledge 
indicates that, as a result, chronic hepatitis generally appears to be of 
the interstitial form. 

A complete description of the interstitial changes is, however, not 
possible, since the relation between the anatomic conditions and the 
clinical phenomena has not only been the subject of much investigation, 
but consequently of much discussion during recent decades. Laennec’s 
cirrhosis, the atrophic stage of alcohol liver, was for a long time the 
only form of interstitial hepatitis known, and it was in regard to this 
disease that the discussion first began. All forms of interstitial hepatitis 
that were observed later were compared with this form; some authors 
simply identified all forms with this form of cirrhosis, others attempted 
to base certain clinical differences on the anatomic and etiologic differ- 
ences that had been found. So far, however, there has been only partial 
success in this altogether warranted endeavor. 

In order to understand the present status of our knowledge on this 
subject it will be best to describe the manner in which the different 
possible causative factors can produce interstitial changes in the liver. 
Such changes are seen: 

1. In chronic stasis and hyperemia of the liver, particularly in the 
central portions of the lobules. In this location the proliferated con- 
nective-tissue structures of the vessel-sheaths extend into the acini, 
following the direction of the dilated and thickened capillaries and pass- 
ing between the atrophic columns of liver-cells. The tissue is usually 
homogeneous or fibrous, and consists in part of metamorphosed capil- 
laries (Brieger); less often there is a cellular infiltration. In describing 
congestion of the liver due to stasis we mentioned the fact that occa- 
sionally proliferation of connective tissue occurs in the interlobular 
spaces between the branches of the portal vein (Liebermeister). This 
proliferation may occur in streaks or over a large surface, so that the 
lobules become constricted and atrophic, and the occlusion of numerous 
branches of the portal vein may lead to general disturbances of the 
circulation in the liver, and to ascites. 

2. Stasis of bile from occlusion of the bile-passages. Many experi- 
ments have shown that stasis of bile may lead to the formation of foci 
of necrotic liver-cells, and to a proliferation of interstitial tissue which 
remains after the cells are destroyed; these experiments were made 
chiefly in rabbits and guinea-pigs. The proliferation begins in the inter- 
lobular spaces and penetrates the interior of the lobule from the periph- 
ery. The course of the whole process may not extend over more than a 
few wéeks (compare page 428). 

The results of these animal-experiments were applied to human 


CHRONIC INFLAMMATION OF THE LIVER. 687 


subjects by Charcot and his pupils, and in this way a distinct anatomic 
and clinical picture called biliary cirrhosis was constructed, which was 
considered identical with “hypertrophic cirrhosis of the liver” ; this view, 
as I will show, is untenable for several reasons. In other animals—for 
example, the dog and the cat—these changes are completely absent or 
very slight; here, however, a thickening of the walls of the gall-bladder 
and of the bile-passages is seen. 

In man the consequénces of biliary congestion resemble more fre- 
quently those seen in dogs than those observed in guinea-pigs. Cases 
of the latter kind do occur, however, and have been described by Janowski. 
Two weeks after the occurrence of stasis of bile (from a gall-stone) this 
author found yellow foci of necrotic liver-cells in the marginal zone of 
the lobules. These are reabsorbed; at the same time, a small round- 
celled infiltration is seen in their vicinity, and, later, cicatricial forma- 
tions occur. At the same time the epithelium of the bile-passages 
desquamates, the walls of the ducts become infiltrated, there is a forma- 
tion of new connective tissue, and a proliferation of bile-passages, as in 
the liver of guinea-pigs. A certain number of the new bile-passages 
originate from metamorphosed columns of liver-cells. 

The proliferation of connective tissue and the atrophy of the liver- 
cells may attain as marked a degree as that seen in atrophic cirrhosis; 
so that it may lead to congestion of the portal system. No characteristic 
anatomic difference can be found between cirrhosis due to biliary stasis 
and other forms of cirrhosis (Litten, Mangelsdorff, Janowski). The 
proliferation of the bile-ducts, which Charcot’s pupils consider so char- 
acteristic, is by no means specific; on the contrary, the same picture is 
seen not only.in every form of interstitial hepatic inflammation, but in 
acute atrophy as well. (Brieger has seen it in hepatic congestion.) 

Stasis of bile, therefore, while it is certainly to be included among 
the causes of interstitial cirrhosis of the liver, is not an important factor, 
because in man it rarely leads to this condition and (perhaps only in the 
presence of other influences, such as infection of the bile-passages), 
because in cases in which it does produce such changes the picture is 
dominated by the symptoms of biliary stasis. 

3. Botkin and Solowieff have claimed to have demonstrated by ex- 
periment, as well as on anatomic grounds, that stasis in the portal system 
can lead to interstitial hepatitis; this, however, has never been proved. 
Simple occlusion of the portal vein or of some of its branches leads to 
complete or partial atrophy of the liver (vide thrombosis of the portal 
vein). Inflammation is seen only when the obstruction is not a purely 
mechanical one, but contains toxins or micro-organisms that enter the 
liver at the same time. This may easily occur if the main trunk or some | 
of the branches of the portal vein become inflamed. Activity on the 
part of the different noxious agents is favored by a slowing of the blood- 
current. Only in this sense may we say that many cases of interstitial 
hepatitis start from the capillaries of the portal vein. [An instructive 
case has been described by E.- Mihel in which, in a nutmeg liver, such a 
marked deposit of calcareous salts occurred around the central veins as 
undoubtedly to cause both a mechanical pressure upon the vessels, and 
at the same time to act as an irritating foreign body in the parenchyma 
of the liver. The process was so marked that the liver grated on sec- 
tion.—Eb.] 


688 _ DISEASES OF THE LIVER. 

4, Duplaix * has observed interstitial proliferation of the hepatic 
connective tissue in arteriosclerosis and in cases of thickening of the 
smaller vessels that so often accompanies this condition. He also saw 
enlargement of the interlobular spaces and foci of embryonal cells within 
them. He compares these changes with similar but much more marked 
processes which are seen in the heart, the kidneys, and the spleen, and 
finds that they occur particularly after malaria, lead intoxication, gout, 
rheumatism, alcohol-poisoning, etc. The lesions of the liver are too 
insignificant in these cases to produce any clinical symptoms 

5. Chronic inflammation of the liver may be caused by chemical 
poisons. Alcohol and phosphorus produce fatty infiltration in man, and 
the former is also capable of causing the condition which we call cirrhosis 
of the liver. Experiments have demonstrated the latter fact. In the 
case of phosphorus-poisoning they show that the drug may produce 
not only the ordinary picture of phosphorus liver but that a subacute 
or chronic intoxication, albuminous and fatty clouding of the hepatic 
cells (Aufrecht, Ackermann), a degeneration of the protoplasm and of 
the nuclei (Kronig, Ziegler, and Obolensky), and, finally, a proliferation 
of the connective tissue, may occur. The degeneration of hepatic cells 
occurs diffusely throughout the acini, but the proliferation of connec- 
tive tissues is at first only interacinous. Gradually the latter process 
extends until it leads up to the typical picture of cirrhosis (rabbits, 
Wegner). During this process the usual granular atrophy, also a 
smooth induration, occur, and even the lobulated form of liver may 
be produced. These facts are of great importance in the understanding 
of chronic inflammation of the liver, even though chronic phosphorus- 
poisoning has as yet never been observed in the human being, since 
they show that a poison may cause isolated foci of disease, either slight 
or of excessive degree. Aufrecht’s observations appear to refute 
Kronig’s belief that the changes seen simply represent a filling-out of 
the spaces that were occupied by the destroyed parenchyma; since the _ 
former has observed proliferation of connective tissue in cases in which 
the cells were not yet necrotic, but were only slightly changed in appear- 
ance. It is impossible to state whether the diseased cells or the poison 
caused the connective-tissue changes; this question is of purely theoretic 
interest, and probably cannot be answered. Even if the proliferation 
of the cells does not coincide exactly with the changes in the liver-cells, 
this fact does not disprove the etiologic réle of the latter, since they 
may very well exercise an influence on the nutrition of remote tissues. 


Basing his conclusions upon more recent experiments with artificial chronic . 
phosphorus-poisoning in rabbits, Aufrecht arrives at the conclusion that vacuolar 
degeneration of cells and nuclear changes occur only in the periphery of the lobules. 
Some of the cells perish altogether, others merely become atrophic. The peripheral 
portion of the lobules where this occurs suggests the formation of young interlobular 
connective tissue, whereas in reality this new formation does not occur. 


Experiments with alcohol do not give such pregnant results as with 
phosphorus. Certain writers have found only a severe degree of hyper- 
emia in spite of intoxication lasting for several months (v. Kahlden) ; 
also fatty infiltration of the liver-cells (and of the stellate cells) (Ruge, 
Strassmann, Affanassiew, v. Kahlden) without nuclear or cellular degene- 


* “Contribution a l’étude de la sclerose,” “Archives gen. de. med.,”’ 1885, 1, p. 


oe Also see Eichhorst’s ‘‘ Handbuch der spec. Pathologie,” 1890, 1, pp. 391- 


CHRONIC INFLAMMATION OF THE LIVER. 689 


ration. Lafitte saw in a rabbit, atrophy of the hepatic cells and dilatation 
of the capillaries, also many punctiform hemorrhages; Affanassiew, on the 
other hand, noted collections of round cells around the bile-ducts, Strauss 
and. Blocq and Pupier made the same observation in the peripheral parts 
of the acini. Contraction and shrinking of the tissues were never ob- 
served. 

In any event it may be said that alcohol acts less energetically upon 
the liver of animals than phosphorus, but that its first effect, as in the 
case of phosphorus, is exercised on the cells of the parenchyma. The 
alcohol may itself be changed; it does not enter the bile, for Weintraud 
failed to find it there after acute poisoning. The fact that conditions 
analogous to the alcoholic liver of the human being have not been pro- 
duced may well be accounted for by the fact that the artificial influence 
has not been sufficiently long-continued, and that the single doses admin- 
istered were relatively too large. We can very well imagine that small 
doses of a certain poison frequently administered may produce purely 
functional changes in the cells that would ultimately lead to a prolifera- 
tion of connective tissue. 


_. Mertens, it appears, has succeeded in administering alcohol in sufficiently small 
doses by allowing rabbits to live in an atmosphere saturated with the fumes of alco- 
hol. Some died at the end of a few months, some at the end of a year or longer. In 
the former animals the liver was brownish-green, there was profuse ascites, and the 
liver-cells were much altered; in the latter the liver was enlarged, pale, hard, and 
the liver-cells only slightly altered, though occasionally degenerated. In all the 
cases of sufficiently long exposure the development of connective tissue was seen in 
the portal spaces extending to the hepatic veins. 


Other poisons that act similarly to phosphorus, both experimentally 
and actually, are arsenic, antimony, and, according to Langowoi,* 
cantharides. 

According to H. Mertens, chloroform acts very energetically; if injections of } to 
4 cm. were made every three to five days, the liver, at the expiraton of several weeks 
or months, was found to be harder, paler, and more nodular than usual, and the 
surface was seen to be granular; the different incisures were more clearly marked 
than usual. The liver-cells are affected first; they grow cloudy, fatty, become 
vacuolated, and atrophy. Strands of connective tissue develop, inclosing bile-chan- 
nels; these start from the portal spaces and extend to the hepatic veins. Boix 
produced atrophic cirrhosis in rabbits by administering small doses of butyric acid 
(three months), and of acetic acid (thirty-five days); the changes seen were not so 
pronounced in the case of lactic and valerianic acid. 


6. Chronic inflammation may occur around localized foci of disease 
and foreign bodies in the liver. 

Welch ¢ saw numerous foci of this kind around small particles of 
coal in a human liver. Neisser 3 injected carbolic acid solution into 
the liver parenchyma of animals and saw the development of aseptic 
foci of inflammation with round- and giant-cells. Connective-tissue 
proliferation is also seen in the vicinity of tumors of the most various 
kinds, and if there are many individual tumors the connective-tissue 
changes may be wide-spread:. It is possible that certain chemical 
agencies play a réle here in addition to the pressure of the growth. The 
extension of chronic inflammatory processes from neighboring organs 
acts in the same manner as does a gastric ulcer that extends to the 

* “Fortschritte der Medicin,”’ 1884, p. 437. 

+ Boix, “Le foie des dyspeptiques,”’ etc., Thése de Paris, 1894. 


{ Welch, “Cirrhosis hepatis anthracotica,” “Johns Hopkins Hosp. Rep.,” 1891. 
§ Neisser, quoted by Mangelsdorf, p. 561. 
4A is: 


690 DISEASES OF THE LIVER. 


liver, or a chronic inflammation of the peritoneal covering (either diffuse, 
tubercular, or simple, or circumscribed, as after lacing). The connective- 
tissue increase occurs in the interlobular spaces and involves only the 
vicinity of the inflammatory foci; occasionally it becomes diffuse and 
spreads to other parts of the organ. 


The same applies to the parasites that are so often seen in the liver of animals. 
In the liver of rabbits the presence of psorospermia or of cysticercus may cause this 
process to assume extensive proportions. In the dog Distomum campanulatum, 
which has its habitat in the bile-passages, may, according to Zwaardemaker,* cause 
a thickening of the walls of the larger and finer ducts (without icterus) ; and in other 
places circumscribed granulations, or even a connective-tissue development that 
starts from the portal branches or the branches of the hepatic veins and enters the 
acini at this point, causing destruction of liver-cells from pressure. In this manner a 
certain form of cirrhosis is produced that is not uniform, but none the less diffuse; 
it ultimately leads to ascites from stasis. 


In human beings Echinococcus alveolaris acts in a similar manner; 
also bacteria that lodge in the liver after entering the organ through 
the blood. In miliary tuberculosis of the liver especially, this form of 
proliferation assumes high degrees; in typhoid fever the development 
is scanty and the foci are, as a rule, very small. 


M. Wolff + injected saprophytic germs (putrefying blood in Pasteur’s fluid) 
subcutaneously into guinea-pigs, and observed the development of localized cheesy 
abscesses and inflammatory foci in the lungs, the kidneys, and the liver; these foci in 
the course of a few months led to a diffuse small-cell infiltration, and to the formation 
of fibrous connective tissue, a picture that greatly resembled human cirrhosis. Itis 
probable that in this case wide-spread bacterial embolization occurred, although the 
fact could not be determined owing to the imperfect methods of examination of that 
day. 

Krawkow introduced Staphylococcus aureus, Bacillus cholere, pyocyaneus, and 
saprophytic bacteria into the muscles and the stomach of birds for long periods of 
time; he observed the development of an atrophic, and more rarely of a hypertrophic 
form of cirrhosis of the liver. 


Malarial disease of the liver is probably analogous to bacterial hepa- 
titis, and to that form due to the presence of a foreign body. It is 
possible that the mechanical occlusion of the blood-vessels by the profuse 
pigment may play a rdle in the former disease. 

In some of the inflammatory processes described here the liver-cells 
sustain the first injury; in others the interstitial tissues are first affected. 
Nothing definite is known in regard to the origin of the small cells that 
are seen in these lesions; it is even uncertain whether they immigrate 
from the blood-vessels or whether they are a product of the proliferation 
of the connective tissue itself, though the latter is probably true in most 
instances. | 

The appearance on section, as well as that of the surface of the liver, 
is usually little changed, and frequently the condition is only discovered 
on microscopic examination. The initial stages may, on the other hand, 
be manifested, as in other organs, by an increase in the consistency of 
the liver or in the toughness of the tissues. In more pronounced cases 
these changes are so apparent that we may actually speak of hardening 
of the liver. . 

In addition to interlobular and intralobular proliferation of connective 


* Zwaardemaker, “Cirrhosis parasitaria,’” Virchow’s Archiv, 1890, vol. cxx, 


» ASE 
t+ Wolff, “Ueber entzunde. Verinderung. inner. Organe nach experimentel 
erzeugten subcutanen Kaseherden,” Virchow’s Archiv, 1876, vol. Lxvu, p. 234. 


CHRONIC INFLAMMATION OF THE LIVER. 691 


tissue, some authors speak of biliary, venous, portal, and bivenous pro- 
liferation, or cirrhosis. Different meanings are attached to these terms. 
Some merely indicate the starting-point of the process (periphery or 
center of the lobule); others, again, wish to show that the proliferation 
starts from the walls of the channels designated, or is due to some irrita- 
tion starting from these channels. It must be remembered that the 
use of the terms in the second sense is often based on assumptions that 
have not been proved to be correct. 

One peculiarity of all processes that are accompanied by connective- 
tissue proliferation is the development of many tortuous channels, and 
of ramified or reticulated canals of a different size; these are lined with 
epithelium of the flat or the cylindric variety. Undoubtedly these 
canals are in some way related to the finest bile-ducts, and may be 
injected from the latter vessels (Ackermann). They are not, however, as 
was formerly believed, found only in stasis of bile, but may be formed 
in the course of all interstitial proliferative processes. In cases in which 
much of the parenchyma has perished these canals may be the remnants 
of normal bile-channels that have been dislocated and approximated to 
one another by the displacement of the liver-tissues. In part (according 
to Aufrecht, exclusively) these originate from the columns of liver- 
cells that have become converted into channels and are metamorphosed 
into flattened epithelium. Thirdly, tney may be due to a true new- 
formation by branching and bulging of older channels. It will depend 
on the nature of the process which of these three procedures is the most 
concerned in the formation of new channels. 

We will.now discuss the forms of interstitial hepatic inflammation 
that are seen in man; the description of the anatomic changes will for 
practical reasons be combined with that of the clinical aspects of the 
disease. 


LITERATURE. 
EXPERIMENTAL ALCOHOLIC CIRRHOSIS. 


Ruge, P.: “ Wirkung des Alkohols auf den thierischen Organismus,” “ Virchow’s 
Archiv,’ 1870, vol. xL1x, p. 252. 

Dujardin-Beaumetz et Audigé: ‘‘ Recherches expérimentales sur l’alcoolisme chron- 
ique” (in swine), ‘‘Comptes-rendus de l’Académie des sciences,’ 1883, 
tome xcvI, p. 1557. 

Straus et Blocq: “ Etude expér. sur la cirrhose alcoolique du foie,” “ Archives de 
physiolog. normale et patholog.,’’ 1887, p. 408 (rabbits). 

Pupier, Z.: ‘‘ Action des boissons dites spiritueuses sur le foie,’”’ ‘‘ Archives de physi- 
olog. normale et patholog.,’”’ 1888, p. 417. 

Strassmann, F.: “ Experimentelle Untersuchungen zur Lehre vom chronischen Al- 
koholismus,”’ ‘“ Vierteljahrsschr. fiir gerichtliche Medicin,’’ 1888, vol. xxrx, p. 
232. 

Affanassiew: ‘Zur Pathologie des acuten und chronischen Alkoholismus,”’ Ziegler’s 
“‘ Beitrage zur pathologischen Anatomie,” 1890, vol. v1, p. 4438. 

v. Kahlden: ‘“ Experimentelle Untersuchungen iiber die Wirkung des Alkohols auf 
Leber und Nieren,” Ziegler’s “ Beitrige zur pathologischen Anatomie,” 1891, 
vol. rx, p. 348. 

Lafitte: “L’intoxication alcoolique. expérimentale et la cirrhose de Laénnec,” Dis- 
sertation, Paris, 1892. : 

Mertens, H. (Gent): ‘‘Lésions anatomiques du foie du lapin au cours de l’intoxica- 
tion chronique par le chloroforme et par l’alcool,’”’ “ Archives de pharmaco- 
dynamie,” Gand et Paris, 1895, tome 11, fase. 2; Jahresbericht 1, p. 214. 


PuospHorvus LIveEr. 


Ackermann: “Die Histogenese und Histologie der Lebercirrhose,”’ “ Virchow’s 
Archiv,” vol. cxv, p. 216. 


692 DISEASES OF THE LIVER. 


Aufrecht: “Die diffuse Leberentziindung nach Phosphor,” “ Deutsches Archiv fir 
klin. Medicin,” 1879, vol. xxi, p. 331. 

— “Experimentelle Lebercirrhose nach Phosphor,” “ Deutsches Archiv fiir klin. 
Medicin,”’ 1897, vol. Lv, p. 302. 

Kronig: ‘“ Die Genese der chronischen interstitiellen Phosphorhepatitis,”’ “ Virchow’s 
A:chiv,” vol. cx, p. 502. 

Wegner: “Der Einfluss der Phosphors auf den Organismus,” “ Virchow’s Archiv,” 
1872, vol. Lv, p. 11. 

Wyss, O.: “ Beitrige zur Anatomie der Leber bei Phosphorvergiftung,” “ Virchow’s 
Archiv,” 1865, vol. xxx, p. 432. 

Zeigler und Obolenski: ‘ Experimentelle Untersuchungen iiber die Wirkung des 
Phosphors und Arsens auf Leber und Nieren,’’ Ziegler’s “ Beitrage zur patho- 
logischen Anatomie,” 1883, vol. 11, p. 293. 


CIRRHOSIS OF ‘THE LIVER; CHRONIC INTERSTITIAL HEPATITIS. 
(Laennec’s or Atrophic Cirrhosis; Granular Atrophy.) 


Of the different forms of chronic inflammation of the liver, and of 
the different stages of this disease, that one which leads to a reduction in 
the size of the organ, and granular change in the parenchyma, although it 
was not described for the first time by Laennec, is named after him for the 
reason that he first called the disease cirrhosis. His reason for so doing 
was the fact that he observed a peculiar yellow color in the granular 
tissue. This is not a constant finding, and is, at best, one of subordinate 
importance; Laennec, moreover, considered the yellow granulations to 
be neoplasms, whereas in reality they are deformed portions of the liver- 
tissue inclosed by connective tissue. 

The name “granular atrophy” is in the majority of cases suitable to 
the last stages; but it must be remembered that not only in many cases 
does the organ remain perfectly smooth, but that, on the other hand, 
granular changes are seen in other conditions, as, for instance, con- 
gested liver due to stasis. e 

Occurrence.—Atrophic cirrhosis of the liver is seen principally in 
men of middle age, owing to its usual origin through the abuse of alcohol; 
only one-half to one-third as many women are afflicted with the disease as 
is the case with men. In children the condition is still more rare, some- 
times being caused by alcohol, and in the new-born by congenital lues 
(see page 748). 

The frequency of the disease varies according to the cause in different 
regions. 

G. Forster found the disease in 31 (1 %) cases among 3200 autopsies at the Berlin 
Pathologic Institute, in subjects between thirty and ninety years. 

In Kiel, the initial stages of alcoholic cirrhosis are among the conditions most 
frequently seen on the autopsy table. H. Lange found hepatic cirrhosis (in autopsies 
on subjects over fifteen) 43 times in 1835 men (2.34 %), in 1296 women 13 times 
(1 %). “Induration” (diffuse hyperplasia of the connective tissue) occurred in 
men 49 times (2.67 %) and in women 8 times (0.7 %). In one-half of the cases of 
both varieties of interstitial nephritis alcoholism was determined. In 16 cases of the 
first, and in 17 cases of the second category, chronic hyperemia from stasis seemed 


to be the cause. Of the 56 cases of true cirrhosis, 8 were of high degree, 32 of medium 
grade, and 16 were in the incipient stages, or were mild in character. 


Etiology.—The chief cause of cirrhosis of the .liver is continued 
indulgence in alcoholic liquors. The fact that we fail to find more cases 
of the disease, in spite of the wide-spread abuse of alcohol, does not 
signify that this abuse cannot cause the disease, but that, as Rosenstein 
says, other concomitant features must be present in this as in so many 
other diseases. 


CHRONIC INFLAMMATION OF THE LIVER. 693 


Dickinson * found 22 cases of cirrhosis among 149 men whose occupation was 
concerned in some way with the handling of alcoholic beverages; among 149 men 
whose occupation did not involve constant association with alcoholic liquors he found 
the disease 8 times. 

Charcot mentions cases of alcoholic cirrhosis in children (loc. cit.), Demme also 
describes such cases. 

[R. Abrahamsf has reported a case of alcoholic cirrhosis occurring in a baby of 
sixteen months, and Hermann Biggs f one noted in a boy of thirteen years. The 
latter had taken whisky in small quantities over a period of two and one-half years. 
His liver weighed 1430 grams.—Eb.] 


The habitual abuse of wine and beer may also produce cirrhosis, 
although not so frequently as the abuse of distilled liquors; to this I 
can testify from my own observations. We can only form conjectures 
in regard to the exact manner in which alcohol acts. According to 
Weintraud,? alcohol could not be found in the bile after experimental 
acute poisoning; and yet it is very probable that it is carried to the liver 
in the portal vein, the fact that the pathologic processes began in the 
periphery of the lobules speaking in favor of this view. The fact that 
no one has so far succeeded [wde editorial note following.—Eb.] in pro- 
ducing experimental cirrhosis in animals by the administration of alcohol 
simply shows that the duration of the intoxication and the method of in- 
troducing the alcohol are not sufficiently similar to the conditions actually 
existing; it appears that in order to cause cirrhosis alcohol must be 
given continuously every day and in frequently repeated doses. 

[Rosenfeld || has carried out a series of experiments with reference to 
the influence of alcohol upon the liver. After reviewing the work already 
done upon this subject he states that he fed twice daily through a stomach- 
tube, to dogs’that had been starved for six or seven days, 3.5 to 4 c.c. 
of 90 % alcohol in large quantities of water. The animals became in- 
toxicated. The poisoning was continued as long as practicable and the 
animals were then killed before spontaneous death took place. The 
conclusions arrived at from the autopsies were that doses of 3.5 to 4 ¢.e. 
of alcohol per kilo of body-weight, when given more than four times 
daily, result in the deposition in the liver of more than 22 % fat. The 
amount in an unpoisoned animal was about 1%. The livers of these 
animals were poor in glycogen, and in this way gave evidence that alcohol 
not only exerts an influence upon the albuminous portions of the cells, 
but also upon the carbohydrate retaining function. It was noted that 
the animals that were given a few large doses recovered if the alcohol 
were stopped. When smaller doses were given constantly, poisoning 
invariably resulted. Rosenfeld declines, however, to accept the results 
in animals as explaining all the observations in man. 

Ramond ** has, however, produced typical alcoholic cirrhosis in 
animals by feeding with alcohol in combination with various toxic sub- 
stances. His conclusions were that as a result of toxemia alone the 
liver degenerates but does not become sclerotic. He injected (1) 
alcohol; (2) toxins of bacillus coli; (3) other cultures of pathogenic 
micro-organisms, and (4) alcohol and the toxins together. The ani- 
mals from (1) gave a picture of fatty degeneration after four months’ 
feeding, but no sclerosis; (2) after seven months gave no result, if small; 


* Med. Chir. Trans., 1873, p. 27; cited by Charcot, p. 220. 

+ R. Abrahams, Pediatrics, Mar. 1, 1900. 

t Biggs, N. Y. Med. Record, Sept. 3, 1890. § Quoted by Stadelmann, page 105. 
|| Rosenfeld, Centralbl. jf. inn. Med., Oct. 20, 1900. 

** Ramond, La Presse Méd., April 21, 1897 


694 ' DISEASES OF THE LIVER. 


when larger animals were used, fatty degeneration was noted, but no 
sclerosis. (3) Gave no result except septicemia. (4) After ten months 
gave atrophy of the hepatic cells, with a granular and pigmentary de- 
generation, and at certain points fibrous tracts were in the process of 
formation. These fibrous areas almost completely encircled one or more 
lobules. 

Marckwald * has also carried out a series of experiments on the same 
line as the foregoing, but with small doses of antipyrin used subcu- 
taneously, instead of alcohol. The frogs died of malnutrition and dropsy. 
The liver-cells (and kidneys) showed degeneration but no regenerative 
processes. In small, continued doses, the drug produced hepatic cir- 
rhosis as a reactive process against the destructive process in the paren- 
chyma. Injection of large doses led to acute destruction of hepatic 
tissue.—ED.] 

We can only suggest, in the following general way, the different factors that lead 
to cirrhosis in individual cases: concentration of the alcohol, drinking on an empty 
stomach or a full stomach, taking it in one or in many doses in the day, irritation 
of the liver by excess of food, and individual predisposition. 

The other possible ingredients of alcoholic beverages are also of importance in 
this connection. These are in part fermentative products, in part artificial additions, 
and vary with the nature of the drink, its manufacture, etc. Among them may be 
mentioned amy] alcohol, and other alcohols with a higher boiling-point than ordinary 
ethyl alcohol; also the aldehyds, and the natural and manufactured aromatic sub- 
stances. 

According to Allison,f sedentary habits predispose to the disease He found 
that in field-workers alcoholic cirrhosis was present in the proportion of 1: 85; 


among city dwellers who led a sedentary life, 1 : 25; among city dwellers who in- 
dulged in much exercise, 1 : 42. 


[A considerable number of undoubted cases of congenital hepatic 
cirrhosis have been reported in the literature. In some of these there 
has been discovered a syphilitic taint in the family history, and in many 
an antecedent history of alcoholism. In certain other cases neither con- 
dition has seemed to be present in the parents and the hepatic disease 
has remained unexplained. Among the most important cases are those 
reported by Rolleston and Hayne (“Brit. Med. Jour.,”’ Mar. 30, 1901; 
no family history of syphilis), who note 59 other cases as on record; H. 
Neumann (“Berlin. klin. Woch.,” Bd. xxx, p. 445; syphilitic family 
history); Parker, Dunbar and Fisher (“ Lancet,’’ Sept. 24, 1901; several 
cases); F. X. Walls (‘“ Pediatrics,” Mar. 15, 1902). There are many 
others.—EbD.] 

Syphilis ranks next in importance to alcohol. Not only does this 
disease lead to the formation of circumscribed or multiple foci of in- 
flammation around gummata, that later are converted into connective 
tissue, but it also produces a diffuse form of interstitial hepatitis that is 
analogous to alcoholic cirrhosis. This form is found most frequently 
in children with congenital lues, not so often in adults. In the former it 
assumes the form of smooth cirrhosis, the so-called “ Feuerstein”’ liver. 

Where malaria is endemic, it frequently leads to cirrhosis of the 
liver; here, too, the duration of the primary disease and other con- 
comitant circumstances exert their influence; in southern Italy, for 
instance, malarial cirrhosis is very frequent; in other parts of the world 
(Baltimore ft), and the tropics,? it is. comparatively rare. 

* Marckwald, Miinch. med. Woch., April 26, 1901. 


+ Archiv. Gen. de Med., 1888, 11, p. 294. 
t Osler, Practice of Medicine, p. 440. § Hirsch, Pathologie, 111, p. 286. 


CHRONIC INFLAMMATION OF THE LIVER. 695 


Other possible, though not yet established, and in any event less 
frequent causes are: cholera, typhoid, and other infectious diseases 
(Botkin *), scarlatina (Osler) [Duckworth + has also reported a similar 
case.—Eb.], gout, rachitis (Dickinson{). The interstitial changes in the 
liver that occur in the course of these diseases appear clinically, as a 
rule, insignificant; this is also true of the more extensive forms of inter- 
stitial proliferation that are seen in miliary tuberculosis of the liver 
(see section on this disease and the complication of cirrhosis with peri- 
toneal tuberculosis). 

Chronic perihepatitis occasionally seems to extend to the interlobular 
tissues and in this manner to produce a pathologic picture similar to 
cirrhosis 3; in other cases there is simply a capsular compression of the 
organ, and in this way indirectly the same result is accomplished (see 
“ Zuckergussleber’’). 


Talma, || in particular, has emphasized the possibility of the development of 
hepatitis from peritonitis; this author, however, furnishes no positive proof of such 
an occurrence, simply assuming that the “causes” of the primary disease can be 
directly transferred to the peritoneal covering of the organ or can affect the liver 
through the lymph-channels, 

It is said that other substances besides alcohol may be absorbed from the intes- 
tine and produce cirrhosis; among these are mentioned certain condiments (Curry, 
Budd), drastics (Cantani **), and lead.t{ In view of the great prevalence of chronic 
alcoholism, the action of the poison can hardly ever be excluded, and it would appear 
likely that the other irritants named only aid in the production of cirrhosis. 

Many of the French authors include diabetes among the causes of cirrhosis; in 
Germany we are inclined to regard the connection of the two diseases as a matter of 
chance, or, if anything, we reverse the order of cause and effect. Hanot claims that 
diabetic cirrhosis starts from the central venules “ owing to the excessive quantity of 
sugar that passes through these channels” (! ?); Saundby ff claims to have seen 
moderate degrees of interstitial hepatitis in many (!) cases of diabetes. 

Grawitz,§§ from an isolated observation, suspects the extended use of extractum 
filicis maris of a possible influence in the causation of cirrhosis. 

Welch |||| describes a case which he calls cirrhosis anthracotica, in which the liver 
was filled with a number of circumscribed round, oval, or elongated foci of sclerotic 
tissue that were colored black by deposits of carbon. Lancereaux *** has observed 
similar cases in copper smelters. 


Sometimes several factors act together; for instance, malaria and 
whisky, svphilis and whisky, ete. 

[Longridge tt} and others have called attention to a focal necrosis that 
is found in the hepatic substance in many toxemias. Heretofore these 
foci of necrotic tissue have been looked upon as lymphatic nodules, 
commonly found in typhoid fever, eclampsia, etc. Longridge also sug- 
gests that these foci by coalescing may produce the anatomic picture of 
acute yellow atrophy. He gives an elaborate histologic description of 
the necrotic areas. It appears at least possible that such conditions as. 


* Botkin, also Laure and Honorat, Revue mens. de l’Enf., 1887; Siredey, Rev. de 
Med., v1, 1886; Bourdillon, Assoc. frang. p. Vavanc. des sci., 1891. 

+ Duckworth “The Sequels of Disease,’’ Lancet, April 4, 1896, p. 907. 

t Med. chir. Transactions, L11, p.. 359; Schmidt's Jahrb , Bd. cuiv, p. 284. 

§ Frerich, “ Leberkrankheiten,” 11, p.92. Bassi, Rev. clinica, 1889. 

|| Talma, Zettschr. f. klin. Med., 1896, Bd. xxvit, p. 14. 

** I] Morgagni, Luglio, 1890. 

+t Especially noted by French observers: Lafitte, Thése de Paris, 1892, p. 71. 
Potain, La Semaine Med., 1888, p. 230. 

tt Saundby, The Lancet, 1890, 11, p. 383. §§ Berlin. klin. Woch., 1894, p. 1173. 

|| || Johns Hopkins Hosp. Bulletin, 1891, No. 11; Yearly Report, 1, p. 194. 

*k* Tancereaux, Union Medicale, 1886. " 

ttt Longridge, Brit. Med. Jour., Sept. 21, 1901. 


696 DISEASES OF THE LIVER. 


that noted by Welch, and many other conditions of localized and focal 
sclerosis, may be the result of just such an antecedent process as this. 
focal necrosis, which, instead of going on to full degeneration, has passed 
on to cicatricial contraction and healing. In this process we may also 
have another source of chronic interstitial hepatitis —Eb.] 

There are a number of cases in which none of the causes mentioned 
can be made responsible. We must conclude, therefore, that other causes 
that are unknown to us may cause the disease; it seems probable that 
these are certain poisons that are absorbed from the intestine, par- 
ticularly toxins of bacterial origin (Bouchard). Micro-organisms may 
lodge in the liver, and start the inflammatory process. 

[Weaver * inoculated guinea-pigs with a bacillus, apparently of the 
colon group, obtained from the body of another guinea-pig dying from 
apparently natural conditions. In guinea-pigs inoculated subcutaneously 
and intraperitoneally with this bacillus there were found in one or two 
animals evidences of beginning fibrous change in the liver, and in one 
animal there was not only marked growth of connective tissue, but some 
bile-duct proliferation. 

Adami t+ reported the finding in a certain number of cases of atrophic 
cirrhosis of the liver a minute micro-organism in the liver and abdominal 
lymphatic glands which closely resembled the organism found in infec- 
tive cirrhosis of the liver in cattle. The same organism was also found 
in certain cases of hypertrophic cirrhosis. It is described as very min- 
ute, difficult to stain, and appearing as a small diplococcus which when 
grown in broth tended to assume a distinctly bacillary form. In a 
later communication in the same journal Adami reports the finding of 
this same poorly stained organism in the liver-cells within twenty-four 
hours after the injection of colon bacilli or of growths of this minute 
diplobacillus into the ear vein of rabbits. While Adami at first believed 
that in this finding he had an explanation of the occurrence of cirrhosis 
of the liver in the human being, he later modified his views after finding 
that there could be almost always found in non-cirrhotic livers the same 
organism, although in smaller number than in those with distinct sclerotic 
change. In a later communication ft he still further emphasized the 
view that this supposedly new variety of micro-organism was simply a 
changed form of colon bacillus. While the original apparent importance 
of the finding has been somewhat diminished by Adami’s further re- 
searches, his discovery is by no means without interest, although it 
cannot at the present time be determined whether the excess in the 
numbers of this bacillus has any etiologic relation to the anatomic 
change in the liver. The finding of the diplococcus form of the colon - 
bacillus in cirrhosis of the liver has, however, a considerable bearing upon 
the bactericidal function of this organ. In marked cases of cirrhosis of 
the liver this form of the colon bacillus is found in larger number and 
possesses greater staining capacity than in the normal organ. In addi- 
tion to this, Adami found that on injecting into the ear vein of rabbits 
either colon bacilli (the ordinary form) or cultures of the diplococcus 
formerly described by him, these organisms were found in large numbers 
in the liver-cells, while the bile of the animal remained sterile. The two 


jon Ader to the Science of Medicine”; Dedicated to Professor b shi 
+ Montreal Med. Jour., July, 1898, p. 485. 
t “Trans. Assoc. Amer. Phys.,”’ 1899, vol. xrv, p. 300. 


CHRONIC INFLAMMATION OF THE LIVER. 697 


facts taken together certainly point to a marked bactericidal function 
possessed by the hepatic cells.—Eb.] 

Many of the French authors also speak of the cirrhosis of dyspep- 
tics.* 

Alcoholism is so wide-spread, however, that it will be necessary to 
analyze carefully each individual case before accepting dyspepsia as 
the only cause of the disease. It is possible that morbid products of 
digestion act deleteriously in combination with alcohol, or that the 
alcohol promotes the formation of these morbid products. 

[Reference should also be made to malignant growths as a cause of 
hepatic cirrhosis. W. W. Ford, among others, reports a case of sarcoma 
of the liver, in which the liver showed a marked cirrhotic change. No 
cause was evident other than the malignant growth. A number of 
cases of the same condition (cirrhosis) associated with cancer of the liver 
were reported and discussed in a symposium before the Pathologic Society 
of London.{ Ina number of these cases, also, there was no cause evident 
other than the carcinomatous change. —Ep. ] 

As in all other diseases, individual predisposition is an important 
factor. 


Sometimes several brothers and sisters are afflicted (Staples,§ ‘children of a 
drunkard’”’). In a case of this kind that came under my own observation both 
brothers were drinkers. [Hasenclever || reports three cases of hypertrophic cirrhosis 
of the liver of the type described by Hanot, in three children of the same family, 
probably the subjects of congenital syphilis.— ED. ] 


General Outline of the Disease.—The first stages of a chronic in- 
flammation of the liver which ultimately lead to cirrhosis produce no 
symptoms for a number of years. In a small number of cases the signs 
of active hyperemia are found during this period, with a feeling of pres- 
sure in the right hypochondrium, tenderness and enlargement of the 
liver, sometimes gastric disturbances, fever, and icterus. These symp- 
toms seem to appear in attacks of short duration; they are vague, and 
by no means characteristic. As a rule, the shrinking and contraction 
of the tissues are well advanced by the time typical symptoms appear. 
These are seen in the organs in the area of the portal system, and affect 
the general health; they include disturbance of the appetite and of the 
digestion, a feeling of pressure in the epigastrium, and bloating from 
ascites. As ascites often replaces a previously fat abdomen the general 
emaciation is often not perceived by the patient; the skin grows grayish 
in color, finally light yellow; the liver will now be found decreased in size, 
and the spleen enlarged. 

In alcoholic cirrhosis the effects of the general intoxication are often 
seen in other organs besides the liver: viz., the heart and the kidneys. 
When this is not the case, the cachexia gradually increases and certain 
mechanical disturbances of respiration, circulation, and digestion follow 
the further development of ascites. As a rule, the patient succumbs 
to these disorders within a few months after the appearance of the first 
serious symptoms; in other cases hematemesis, intestinal hemorrhage, 
violent diarrhea, or an acute organic disease brings on a fatal termination 
at a still earlier period. : 

Pathologic Anatomy.—A cirrhotic liver is, as a rule, decidedly 


* Boix, Thése de Paris, 1894. t+ Amer. Jour. Med. Sct., Oct., 1900, p. 413. 


> She Transactions, 43 Lancet, Jan. 19, 1901. § Staples, "Lancet, May, 1886. 
| Berliner klin. Woch., Nov. 7, 1898. 


698 DISEASES OF THE LIVER. 


smaller than normal; this is particularly true of the left lobe. The sur- 
face presents round protuberances that are as large as a millet-seed or a 
pea; these are usually covered by a thickened layer of serosa, and con- 
sequently do not show their peculiar color so well on the surface of the 
organ as on cross-section, when they vary in color from light yellow to 
greenish-yellow and brown. They are separated from one another by a 
reticulum of whitish or reddish-gray connective tissue, the meshes and 
the single strands of which vary greatly in size. From these meshes 
single granules protrude. On microscopic examination it will be found 
that each granule corresponds to one or several hepatic lobules. The 
size of these lobules is markedly reduced and their typical structure 
changed as a result of the arrangement of the vessels. In some livers 
the lobules will be found to be of about equal size, in others of different 
sizes (monolobular and multilobular cirrhosis). Occasionally single lob- 
ules appear to be subdivided; they are sometimes outlined clearly 
against the connective tissue, and again their boundaries are indistinct. 
The hepatic cells under these conditions may be infiltrated either with 
fat, with bile-pigment, or some other brownish pigment; some show no 
changes except that they vary in size. Certain of the capillaries of the 
lobules are dilated. 

The connective tissue is principally fibrous, though in places a great 
many cells are seen and are to be traced here and there between the 
columns of liver-cells. 


According to Frerichs, and of late Hohenemser,* elastic fibers are always present 
in this connective tissue (demonstrable by orcein). The more advanced the con- 
striction, the more conspicuous these fibers. They may, in fact, constitute the 
greater portion of the connective tissue. It is probable that they originate from the 
sheaths of the smaller arteries and portal branches. 


[Flexner + has published some very thorough studies in regard to 
the nature and distribution of the new tissue formation in cirrhosis of 
the liver. He concludes that (1) in all forms of cirrhosis the white 
fibrous tissue is increased. (2) Along with this new tissue there is formed 
elastic tissue which is derived from preexisting elastic fibers in the blood- 
vessels and hepatic cells. (3) Both forms of tissue may in all kinds of 
cirrhosis penetrate into the lobules. This penetration takes place along 
the line of the capillary walls and follows the architecture of the reticulum. 
The chief distinction between the histology of atrophic and hypertrophic 
cirrhosis depends on the degree of extralobular growth, and the freedom 
with which the lobules are invaded. In the hypertrophic form there 
would appear to be less interlobular growth and an earlier and finer 
intralobular growth. (4) Alterations in the reticulum per se seem to © 
constitute a hypertrophy rather than a hyperplasia of fibers.—Eb.] 

Within the connective tissue we see numerous tortuous bile-ducts, 
arranged in a ramifying network; their lumen varies markedly in size, 
and the cells lining them are either cuboid, or flat, or resemble liver-cells. 
Their connection with the bile-passages can be demonstrated by injec- 
tion; they constitute in part efferent channels of liver lobules that have 
perished, and in part represent genuine new-formations. 

The blood-vessels that are formed in the new tissue are numerous, 
patulous, thin-walled, and resemble erectile tissue. By injection it can 
be shown that they belong to the system of the hepatic artery, and are 


* Virchow’s Archiv, 1895, Bd. cxu, p. 193. 
+ Univ. of Penna. Med. Mag., Nov., 1900. 


CHRONIC INFLAMMATION OF THE LIVER. 699 


not related, or but distantly related, to the portal system.* The inter- 
lobular branches of the portal vein show a thickening of their walls, and 
occasionally endophlebitis obliterans. 

Rather less frequently than the granular liver is occasionally seen 
the atrophic cirrhotic liver with a smooth or almost smooth surface.. 
The capsule of the organ is thickened, and has a reddish-gray color with 
a tinge of yellow. Although differing macroscopically from the granular 
form on the outside, this variety will be found to show the same micro- 
scopic changes; the difference consists simply in a more uniform prolifera- 
tion of the connective tissue, so that the lobules or groups of lobules are 
not isolated. There are all intermediate stages between these two forms, 
from the smooth and finely granular to the coarsely granular liver with 
the irregular surface. 

This atrophy of the liver with proliferation of connective tissue is 
the final stage in a process of many years’ duration. Not only in its 
initial stages, but even in more advanced periods, the process produces 
only very slight disturbances, so that the anatomy of the early stages 
can only be studied in individuals who have died of somé other disease. 
I agree, however, with Leichtenstern in saying that the opportunity to 
study this stage frequently occurs, and especially in Kiel. The inter- 
lobular connective-tissue changes may be overlooked macroscopically, 
and the only manifestation of their presence may be hardness of the organ; 
they are often determined for the first time by the microscope. 


The connective-tissue proliferation is first seen in the region of the portal branches 
either in regular distribution or particularly developed in certain interstices, so that 
later on either whole lobules or groups of lobules are inclosed within the strands of 
connective tissue (monolobular and multilobular cirrhosis). This form of cirrhosis 
is called venous by French authors, on account of its origin in the venous branches 
of the portal vein (in contradistinction to biliary). According to Sabourin, the 
proliferation often starts simultaneously from the portal and the central venules; 
such forms are called bivenous cirrhoses. In this form also proliferation may occur 
into the lobule and cause a splitting of the latter in such a manner that the different 
nodules often consist of portions of one lobule. In rare cases Sabourin claims that 
the central veins of the lobules may, even in cases of alcoholic origin, be the only 
starting-point of the cirrhotic process; there is then often combined with the latter 
a fatty degeneration of the liver. 

According to Aufrecht, no increase of connective tissue occurs in atrophic cir- 
rhosis; he claims that the disease is primarily one of the liver-cells; and that these 
undergo atrophic changes, and are converted into narrow spindles that contain no 
nuclei. [Vide foregoing editorial note quoting Flexner’s studies.—Eb. ] 


I am not inclined to believe that the proliferation of connective tissue 
per se causes an increase in the size of the liver, because of the physiologic 
fluctuation in the size of the organ, and because of the influence, par- 
ticularly in drunkards, which fatty infiltration and hyperemia (active 
and passive) exert upon its volume. These very factors help greatly to 
determine the size and the color of the organ also in the later stages of 
the disease. 

Owing to the progressive proliferation of connective tissue in the 
vicinity of the interlobular portal branches, the blood-supply of the 
lobules is interfered with; at the same time, these structures are con- 
stricted by the contracting tissues.’ In this manner atrophy of the cells 
and partial obliteration of the capillaries are brought about. The dis- 
appearance of the cells is often preceded by changes in their protoplasm, 
especially by fatty degeneration; these changes are in part passive 


* Frerichs, Atlas 11, Taf. 111. 


700 DISEASES OF THE LIVER. 


(necrobiotic), in part active, produced directly by the: action of the 
morbid agency. 


Partial regeneration of thé liver tissues, it appears, may occur in spite of and 
alongside of all these changes. This is most pronounced in the adenomatous nodules 
that are often seen in cirrhotic livers. These are as large as lentils or hazelnuts, 
yellowish-gray in color, and consist of liver-cells. The cells are arranged in col- 
umns, as in the lobules; with this difference, however, that the rows are broader, and 
the individual cells are unequal in size. Some are very large, with enormous, mul- 
tiple nuclei. These adenomata resemble active neoplasms; and are sharply out- 
lined against the surrounding tissues; they are often very numerous, and have a 
tendency to fatty degeneration. They are not found in cirrhosis of the liver alone, 
but occur so frequently that a relationship between the two conditions must be 
assumtd. They are probably the expression of some tendency to regeneration. 
The large hypertrophic oaules that are occasionally seen within the liver tissues 
in cirrhosis probably belong to the same class (Sabourin, Kelsch, Kiener, Pennato). 


As a result of the destruction of so many of the capillaries of the lob- 
ules, the total lumen of the blood-vessels within the organ is reduced, and 
we see, as a result, the effects of portal stasis; the great overdevelopment 
of the capillaries of the hepatic artery cannot compensate this defect. 
At the same time the contracting connective tissue may occlude some of 
the larger branches of the portal vein, or capillaries may be occluded here 
and there by the pressure of swollen neighboring liver-cells. The portal 
vein itself is dilated as far up as its bifurcation and the starting-point of its 
first branches; its walls are thickened by an overgrowth of endothelial 
tissue as a result of endophlebitis and periphlebitis. We will discuss the 
effect of these changes when speaking of the general symptoms of cirrhosis. 
They first become evident, in many instances, at a late stage of the disease, . 
so that granular atrophy of the liver may be found incidentally during an 
autopsy on a case that has died of some altogether independent condition. 

Symptomatology.—Prodromal Symptoms.—The initial stage of 
chronic hepatitis usually runs its course without causing any symptoms; 
when they do appear, they are, as a rule, the manifestation of some accom- 
panying disease, as, for instance, gastro-intestinal catarrh in drunkards, 
evidenced by loss of appetite, symptoms of pressure in the stomach-region, 
diarrhea, etc. The feeling of fulness in the epigastrium and the right 
hypochondrium is increased particularly after eating, in cases in which 
the liver is enlarged, or in which there is general adiposity of the ab- 
domen, as a result of fatty infiltration. Occasional brief attacks of pain 
in the liver are due to transient digestive hyperemia. These may even be 
accompanied by fever, swelling, and pain that may persist for several 
days. 

Tiver.—In subjects that are later afflicted with cirrhosis, the liver will - 
often be found enlarged for years before. As we have said, this is not so 
much due to the connective-tissue hyperplasia as to other circumstances, 
such as fatty infiltration, fluxionary or stasis hyperemia. The enlarged 
organ is more resistant than normal and more readily palpable, also more 
sensitive. 2 


The enlargement in these cases is nqt characteristic of the disease and not 
different from other forms. Borelli * claims that the upper boundary is forced 
upward partly as the result of meteorism, and partly owing to paresis of the dia- 
phragm following perihepatitis. 


* Verhandlungen der phys. med. Gesellsch. z. Wurzburg, Neue Folge, Bd. vutt, 
1875, p. 87. 


CHRONIC INFLAMMATION OF THE LIVER. 701 


A decrease in the size of the organ is more difficult to determine than 
an enlargement. The proof of the former is the disappearance of the 
lower boundary into the cupola of the diaphragm. This is no positive 
criterion, for meteorism may produce the same effect ; emphysema of the 
lungs may also aid in decreasing the area of dulness of the whole organ; on 
the other hand, adhesions may prevent the movement of the lower margin 
upward. Early atrophy of the left lobe is important and significant; if 
this occurs, the presence of the left lobe in the epigastrium can no longer 
be determined. As arule, the study of the size of the organ is performed 
by percussion, and it may happen that in cirrhosis there is no hepatic 
dulness whatsoever in the mammillary line. Palpation, for reasons men- 
tioned, is often impossible in cirrhosis; in certain other cases the nodules 
can be distinctly felt and the margin distinctly palpated. 

If perihepatitis exists, friction sounds can be felt and heard. At the 
same time, there may be local tenderness, while the other subjective symp- 
toms in the hepatic region have disappeared; particularly during the 
period of contraction. 

Icterus is not a typical symptom of atrophic cirrhosis. In many 
cases it is altogether absent, in others present to a slight degree; con- 
spicuous jaundice is rare, and usually points to some complication in the 
bile-passages. 

The results of the disease of the liver are: (1) Disturbances in the 
circulation of the portal system; (2) reduced functional activity of the 
atrophying gland; (3) secondary results of these two disturbances. 

The circulatory disturbances are the most conspicuous. As com- 
pression of the portal capillaries takes place, stasis of blood results through- 
out the portal area, and leads to congestion of the spleen and the intestinal 
tract. This may be favored by the absence of valves in the portal veins. 
The most conspicuous, though at the same time one of the latest symp- 
toms, is ascites. Hyperemia from stasis of the gastric and intestinal 
mucosa is seen at a much earlier stage and produces functional disorders of 
these organs; even in the absence of alcoholism, lack of appetite, oppression 
after eating, etc., may occur. Sometimes diarrhea relieves the congested 
capillaries, or atony exists with constipation or meteorism. Venous 
hyperemia seems to lead to a reduction of the normal secretions as 
well as to a lessening of the peristaltic activity, and absorbing power of 
the intestine. 


Fr. Miller, even in the presence of ascites, failed to find the absorption of the 
ingesta reduced; fat resorption, too, was normal, so that sufficient bile entered 
the intestine; if diarrhea was present, and as a result water absorption was reduced, 
the assimilative power was also diminished. 

Other authors, however, disagree with this statement; Fawitzky (discussion of 
the older literature) finds that nitrogenous material is poorly absorbed (in one case 
13.8 % of the ingested nitrogen in the stools) ; Miinzer, on the other hand, calls atten- 
tion to the relatively small amount of urinary nitrogen (61 %); it seems, there-_ 
fore, that in serious cases 26.9 % of nitrogen is retained (!?). Miinzer regained 
only 58 % of the nitrogen from the urine. 


Hemorrhoidal tendencies should be increased by stasis in the portal 
‘system, but are not very troublesome in this disease. 

Portal stasis produces induration and swelling of the spleen. The 
former or latter condition may predominate; if the first is present, how- 
ever, the second cannot fully develop. According to Frerichs and H. 


* Verhandlungen des Congresses fur. inn, Med., 1887, p. 408. 


702 DISEASES OF THE LIVER. 


Lange, enlargement of the spleen is seen in one-half of the cases; 
according to Bamberger, in nine-tenths. 

It seems doubtful whether the enlargement of the spleen is due to stasis 
alone; for the spleen in the congestion of cardiac disease has a different 
appearance, is more solid, is darker, and not so large as in cirrhosis. In 
the latter disease swelling of the spleen appears very early, before other — 
symptoms of stasis, and a hyperplastic condition of the pulp followed by 
a connective-tissue increase are noted (Oestreich). It appears, there- 
fore, that active processes occur also in the spleen and vary with the pri- 
mary cause of the disease. In malaria and syphilis the direct influence is 
known. It is also probable that in different subjects the spleen may show 
variations in its elasticity, so that it responds to congestion in a varying 
manner. 


Bouchard and Leudet* have reported systolic blowing over the spleen similar 
to the placental murmur. 


Ascites is one of the late symptoms of the disease, although the serous 
lining of the intestine probably is congested very early in the disease, and 
may cause an increased exudation of fluid into the peritoneal cavity. 
This exudate is, however, reabsorbed by the lymphatics of the diaphragm 
and the parietal peritoneum, which are independent of the portal systemy ; 
for this reason ascites appears only when the exudate is so massive that 
these channels grow insufficient. 


As a rule, the liver is contracted at the time of the appearance of ascites, but 
this is not always the case; it is sometimes enlarged. his may be due to com- 
plications (stasis, fatty infiltration), or enlarged liver-cells may exercise pressure 
upon the portal ‘capillaries. 


Slight degrees of ascites cause no trouble; occasionally the physician 
will be surprised to find a considerable degree of ascites, and particularly 
in patients who have habitually a large, obese abdomen. 

Less often ascites appears suddenly after some injury, as a cold in the 
abdomen (Potain).{ The fluid is freely movable, the intestine pressed 
against the spinal column, and, as a result, a tympanitic sound is only per- 
ceptible on deep percussion. 

The fluid is generally of a clear yellow color, specific gravity 1012 to 
1014, and contains albumin 0.6 % to 1.2%. Bile-pigment and sugar are 
rare; sometimes a little blood will befound as a result of the congestion. 
Sometimes the latter condition will cause a subacute peritonitis, that may 
be hemorrhagic in type; in such cases the fluid is heavier, coagulates 
more readily, contains more albumin, and possibly some blood. 

[Barjon and Henry? regard hemorrhagic pleural and _ peritoneal 
effusions as rare occurrences in hepatic cirrhosis. They report four cases 
that have come under their observation. Two cases presented both 

‘hemorrhagic pleurisy and ascites.—ED.] 

As in the case of other forms of ascites, edema of the lower extremities 
and a reduction of the urinary excretion follow the compression of the 
veins of the lower half of the body. In severe degrees the diaphragm is 
pressed upward, and respiration and heart action are impeded. If 


*Revue de méd., 1890. p. 868. 
T Quincke, ‘ Ascites, ” Deutsches Archiv fiir klin. Med., 1882, Bd. xxx. 
t Semaine Méd., 1888, p. 9. § Lyon Médicale, June 19, 1890. 


PLATE IV. 

















HIGH GRADE OF ASCITES AND ‘‘CAPUT MEDUSZX’”’ IN ATROPHIC CIRRHOSIS. 


es Pare ty 


‘ cs 





CHRONIC INFLAMMATION OF THE LIVER. 703 


ascites develops during the course of uncomplicated (!) cirrhosis, it rarely 
disappears. 


MacDonald * reports two such cases in which ascites disappeared after 31 and 
60 punctures respectively; Casati t performed puncture 111 times. [Cheadle, in 
his ace lectures (1900), mentions a case that lived eight years from the onset 
of the cirrhosis with ascites. He was tapped 19 times, the last time eight years 
before death. Another case was still living twelve years after first coming under 
observation. The last tapping was done two years before the report was made.— Eb. ] 


If stasis is very severe, the capillaries of the stomach and intestine may 
burst and cause vomiting of blood and the passage of blood in the stools; 
it may be that occasionally a gastric ulcer will develop from hemor- 
rhagic erosion of the gastric mucosa. 

As aresult of the increase of pressure in the portal system, the collat- 
eral veins are enlarged, e. g., the hemorrhoidal vein t leading to the hypo- 
gastric vein; the inferior esophageal veins that anastomose, on the one 
hand, with the vena corona ventriculi, and, on the other, with the vena 
azygos; also the vessels running in the ligamentum hepatis, and in the 
perihepatic tissue (these are newly formed vessels). The latter form a 
direct connection between the liver and the diaphragm. Within the liga- 
mentum teres a vein of some 1 to 6 mm. in diameter establishes a connec- 
tion between the portal system and the veins of the abdominal wall; a part 
of the portal blood escapes through this channel and empties itself into the 
upper epigastric veins. As a result the subcutaneous vessels of the 
abdominal wall in the vicinity of the navel are dilated and can be 
distinctly seen; at the same time the skin becomes slightly edematous. 

The shape and the caliber of these dilatations vary greatly; in rare 
cases only is the fantastic name caput meduse justified. The radiating 
group of blood-vessels around the umbilicus must not be confounded with 
the network of dilated vessels that connect the superior and inferior epi- 
gastric veins, and that are seen in every form of ascites (even though not 
of portal origin), and that constitute collaterals of the compressed infe- 
rior cava. 


Some authors consider the vein in the ligamentum teres as a rudiment of the 
umbilical vein (Bamberger,§ Hoffman, || Baumgarten**; others regard it as a para- 
umbilical vein entering into it, or as an accessory portal vein. 

It can be shown by compression that the blood flows from the navel in the 
umbilical garland of vessels; sometimes a murmur can be felt and heard in these 
vessels (Bamberger,tf loc. cit., page 519). Von Jacksch ff heard and felt a buzzing 
sound between the umbilicus and the xyphoid process, which, as the autopsy 
showed, probably originated in the dilated vena coronaria ventriculi. 

Leyden observed that the ductus Arantii had remained patulous in one case; 
Drummond,§§ in another instance, saw a communication between the paraum- 
bilical vein through an abdominal vein with the right iliac vein. 


Although these veins all help divert the portal blood, they are not 
capable (compare an Eck fistula) of carrying off all the surplus and of 
reestablishing a normal vascularity, and in this manner removing the 


* Med. News, Oct., 1889; “Jahresbericht,” 1, p. 297. 

t Il raccoglitore medico, Aug. 20, 1893. 

t Z. B. Drummond, Brit. Med. Jour., Feb., 1881; and “Jahresbericht,” 11, p. 289. 
§ “ Krankheiten des chylopoetischen Systems,” p. 520. 

|| Correspondenzbl. f. Schweizer Aerzte, 1872. 

** Bull. de ’ Acad. de Soc. Med., 1859, t. xxiv, p. 943. 

tt Koppel, Dissertation, Marburg, 1885. {{Jaksch, Prager med. Woch., 1895. 
§§ Drummond, Brit. Med. Jour., Feb. 4, 1888. 


704 | DISEASES OF THE LIVER. 


ascites.* Whenever this occurs, we must assume that the liver itself has 
become more passable to fluid. 

Occasionally, profuse, fatal hemorrhage occurs from the dilated 
esophageal veins; the blood is in such cases poured into the stomach 
(compare page 707). 

[Preble+ has analyzed 60 cases of fatal gastro-intestinal hemorrhage in 
cirrhosis of the liver. He concludes that it is infrequent but not rare; that 
in the majority of cases the cirrhosis is atrophic, but may be hypertrophic; 
that in one-third of the cases the first hemorrhage is fatal, but that in the 
remainder the hemorrhages may continue at intervals for a long period; 
that esophageal varices are present in 80 %, and that in more than half of 
these macroscopic ruptures are present; that in certain cases fatal hemor- 
rhage can occur without esophageal varices, and that in only 60 % of the 
cases with esophageal varices was the cirrhosis accompanied by typical 
symptoms and signs. He reports four new cases. Curschmann also notes 
in detail a case of fatal hematemesis in the same condition,t and mentions 
13 fatal cases observed by him. 

EK. Stein 3 cites cases of intestinal hemorrhage. Mannesse,|| Lubet- 
Barbon,** Ewald,++ and many others have noted cases of fatal hemor- 
rhage from dilated and ruptured esophageal and laryngeal veins.—ED.] 

It is stated that the congestion may be transmitted to the vena azygos 
and the intercostal vein, and in this manner cause right-sided hydrothorax4 
[Cheadle, Barjon and Henry, and others have called attention to the fre- 
quency of right-sided pleural effusion in hepatic cirrhosis. It rarely 
occurs in sufficient quantity to cause trouble. Villain|||| has observed 9 
such cases in which the diagnosis was confirmed by puncture.—ED.] 

The urine in cirrhosis of the liver is usually scanty, of a high specific 
gravity, and of a reddish color. The decrease in quantity is due to 
deficient absorption of fluid from the intestine and to accumulation of 
water in the belly during ascites. At the same time, the kidneys are com- 
pressed, and, when cachexia supervenes, the arterial pressure is lowered. 

Albuminuria may be due to alcoholic nephritis, hematuria to hyper- 
emia of the bladder (Langenbeck).*** The reddish color is in part due to 
urobilin; icterus is rarely so severe as to cause the appearance of bile- 
pigment. 


_ _G. Hoppe-Seyler t}} found an increase in the urobilin excretion to 0.24 and 0.3 
in two cases of cirrhosis (instead of the normal 0.123). In some cases the increase 
is only apparent, owing to the decreased secretion of urine. Von Noorden’s con- 
clusion that a cirrhotic liver forms abundant quantities of bile-pigment does not 
appear Justified to me. Changes in normal intestinal absorption and other cir- 
cumstances may very well lead to an increase of the urobilin excretion. 


Urea is generally reduced, ammonia increased, and sugar is sometimes 
present. We will discuss the significance of these findings in our para- 
graphs on metabolism. 


__*Monneret, quoted by Frerichs, “ Leberkrankheiten,” u, p. 40; Pel, Neederl. 
Tijdschr. 7. Geneesk., 1882; ‘Jahresbericht,” 11, p. 174. 
tAmer. Jour. Med. Sci., Mar., 1900, p. 263. 
t Deutsche med. Woch., April 17, 1902. : 
§Archiv. 7. Verdauungskr., May 6, 1899. || Gaz. hebd. de med., Jan., 1899. 
** Archiv. de Laryngol., July—Aug., 1897. 
tt Berlin. klin. Woch., 1892, No. 23. 
§§ Piazza-Martini, Rev. clinica, June 30, 1892; “ Jahresbericht,” 1, p. 195. 
Lig a Med, 1895. *k* Archiv. f. klin. Chirurgie, Bd. 1, p. 41. 
TG. Hoppe-Seyler, Virchow’s Archiv, 1890, Bd. cxxtv, p. 43. 


CHRONIC INFLAMMATION OF THE LIVER. 705 


Sometimes “peptones” [albumoses—Ep.] are found in the urine 
(Stadelmann, Bouchard), also leucin and tyrosin (?), sarcolactic acid 
(v. Noorden, Stadelmann), and abnormal amounts of volatile fatty acids 
(v. Jaksch).* 

Respiration is greatly impeded as ascites increases; this is due to 
obstruction of the movements of the diaphragm, and to the deposit of fat 
in the abdominal walls, and the mediastinum. The heart action, also, is 
mechanically impeded in ascites; in addition, the heart muscle is weak- 
ened by the alcohol and the cachexia. The pulse, therefore, grows small 
and rapid, the breathing shallow and labored, and there is a subjective 
sensation of oppression. 


_ Hypertrophy of the left ventricle, as Wagner f says, is due to narrowing of 
the arteries in the liver; its cause is analogous to that in contraction of the kidneys. 
As a matter of fact, the arteries are not reduced in size in the liver; and the con- 
dition is due to other causes, alcohol, etc. 


The temperature shows no abnormal fluctuations, or at most they are 
insignificant; fever, if present, is due to inflammatory complications 
(perihepatitis) ; in the final stages the temperature may be subnormal.t 
[Carrington% discusses the question of pyrexia in cirrhosis of the liver and 
concludes that there may be a range of temperature from 100° to 102.5° F. 
—Ep.] | 

The general nutrition and health of the patient are greatly impaired. 
Unless malaria or alcoholic catarrh of the stomach is present, the cachexia 
may not appear until late in the disease; 7. e., at the time of contraction. 
The patients look sallow and flabby, the general muscular and vascular 
tone is reduced, though, at the same time, they may be obese; soon the fat 
disappears, however, and an emaciation sets in that may be disguised by 
edema and ascites. 

The emaciation may be explained in part by the deficient nourish- 
ment, and the interference with the absorption of food. At the same time, 
the cirrhotic changes of the liver cause certain metabolic disturbances 
that also play a réle. These disturbances would be greater than they 
usually are in view of the great destruction of liver tissue, if the shrinkage 
did not occur so gradually that the organism becomes to a certain degree 
_ accustomed to it. 

The chief manifestation of this perversion of metabolism is the de- 
creased excretion of urea and the increased excretion of ammonia; this 
was first noticed by Hallervorden, later by Stadelmann, Favitsky, and 
others. It appears that the urea-forming power of the liver is still present 
to a surprising degree, even in advanced stages of atrophy, for large quan- 
tities of .ammonia salts are, under these circumstances, converted into 
urea. 


According to v. Noorden, the normal ammonia of the urine is 2 % to 5 %, 
according to Weintraud 3 % to 5 %, an average of 4.1 % of the total nitrogen. 
In cirrhosis as much as 10 % of the total nitrogen passes as ammonia, and the 
absolute quantity of ammonia in twenty-four hours may be 1.4 to 2.5 gm., according 
to Hallervorden. In less advanced cases this increase may be absent (Stadelmann). 
It is interesting from a theoretic point of view that, according to Weintraud, a 
person with cirrhosis is capable of transforming as large quantities of ammonia (ad- 
ministered as the citrate) as a healthy person, so that the proportion of ammonia- 


* Zeitschr. f. physiol. Chemie, Bd. x. t Archiv. de Heilkunde, Bd. 1n, p. 459. 
t Janssen, Deutsche Archiv. f. klin. Med., 1894, Bd. wit. 
§ “ a do Hosp. Reports,” 1884. 


706 DISEASES OF THE LIVER. 


nitrogen to total nitrogen is not increased. In the agonal period this power seems 
to be lost. The remnant of liver tissue, therefore, seems to retain the power of 
forming urea; it is even possible that death occurs as soon as this function grows 
insufficient. [It must be recalled, however, that recent experiments have proved 
conclusively that urea formation is to a large extent the function of other tissues 
than the liver. The muscles seem especially active in this direction—Ep.] Some 
facts point to the possibility that the great amount of ammonia excreted is the_ 
result of excessive acid formation (as in diabetes). Von Jaksch* found the alka- 
linity of the blood reduced, and discovered volatile fatty acids in the blood t; Sta- 
raat v. Noorden, and Weintraud discovered sarcolactic acid in the urine of 
cirrhotics. 


Chauffard observed a great increase in the urea excretion (40 to 50 gm. 
pro die) at the period of the initial congestion. 

Sugar is occasionally voided in cirrhosis, though not asarule. It may 
appear in as large quantities and as constantly as in a case observed by the 
author (100 gm.); as a rule, this occurs only after the ingestion of large 
quantities of sugar. The explanation must be sought for in the inability 
of the liver to store large amounts of sugar as glycogen; besides, a por- 
tion of the portal blood containing sugar does not go through the liver, 
but enters the systemic circulation through collateral branches. 

[In cirrhosis many liver-cells retain their reserve of glycogen intact, 
and renew this reserve even when isolated. Cells may be separated into 
groups (as shown by Brault ft) or isolated by disease, but the trabecule do 
not destroy the histochemical properties of the cells with which they come 
in contact, and especially is their glycogenic function retained. This 
glycogen integrity suggests a retention of other functional activities, and 
thus confirms histologic evidences of persistent hepatic capacity despite 
considerable cirrhosis. This explains the latent period of cirrhosis to a 
certain extent, and also those cases in which a respite from symptoms 
occurs. It also demonstrates the possibility of cure, and also of living 
with a functionally active though anatomically cirrhotic liver.—Eb.] 

French authors are inclined to attach a certain diagnostic significance 
to the occasional occurrence of alimentary glycosuria following a moderate 
ingestion of carbohydrates. 7 


Couturier made the first statement of this kind after Cl. Bernard had produced 
alimentary glycosuria in a dog by gradual obliteration of the portal vein. As 
the normal boundary for sugar assimilation fluctuates markedly (between 100 
and 250 gm.), it is not surprising to find differences in the excretion of sugar in 
a series of determinations made even by the same author. German authors (Fre- 
richs, the author, Kraus and Ludwig, Bloch, v. Noorden) all arrive at negative 
conclusions. 

In certain rare cases sugar was constantly excreted even if an ordinary diet 
was given; these possibly were real cases of glycosuria, or even of diabetes mellitus 
(Quincke, Palma). In my case 4 % to 6 % of sugar was excreted daily, although 
the total quantity of the urine was normal. Finally, both the sugar and the total 
quantity were decreased, and in the last weeks before death the sugar was no longer 
determinable. In another case, a drunkard who clinically showed symptoms 
of contracted kidney, I observed glycosuria (0.2 %); here, too, the sugar disap- | 
peared in the last weeks. 

Pusinelli observed a diabetic for eight years; in the beginning the liver was 
enlarged, but ultimately became atrophic and cirrhotic. In this case two years 
before death ascites was noticed for several months, and during the persistence 
of this condition the sugar excretion ceased; as soon as the ascites was relieved 
the sugar reappeared. It is impossible to explain the connection between glyco- 
suria and ascites in this case. 


. *y. Jaksch, Zeitschr. klin. Med., 1888, Bd. x11, p. 350. 
ty. Jaksch, Zettschr. f. phys. Chemie, 1886, Bd. x, p. 553. 
t Presse Médicale, May 29, 1901. . 


CHRONIC INFLAMMATION OF THE LIVER. 707 


[Lefas * has studied the relations of the pancreas and the liver in cir- 
rhosis of the latter organs, and has drawn some highly interesting conclu- 
sions. In atrophic cirrhosis of the liver he found the pancreas increased 
in size, with relative atrophy of the head and body. The color was 
_ yellowish-gray, and the organ appeared somewhat waxy. Its density 

was increased. The cirrhotic process, he found, might affect part only, or 
the entire organ. When the process was intense, he found proliferation of 
connective tissue around the vessels, with changes in the walls of the 
latter, and a tendency to form fibrous plaques externally. Fatty degen- 
eration of the organ was a frequent condition. Pigmentary degeneration 
was rare.—ED.] 

The appearance of ammonia and of sugar does not indicate the entire 
disturbance of metabolism caused by the destruction of so much of the 
liver tissue; sometimes, toward the end of the disease, we see serious ner- 
vous disturbances, stupor, or delirium. These symptoms recall the 
picture of hepatargy following icterus from stasis and the last stages of 
acute atrophy; they are symptoms of an autointoxication. They appear 
as soon as compensation for the disturbances of metabolism fails. They 
may be seen in the absence of jaundice, or when very slight degrees of 
icterus only are present; so that they cannot be attributed to retention of 
bile-constituents. They must be due to other products of metabolism 
that are no longer utilized by the liver. It is possible that carbaminic 
~ acid, a substance closely related to ammonia, or that abnormally formed 
acids play an important réle. 

Hemorrhages are also to be regarded as the result of general disturb- 
ances of nutrition; they may occur in the last stages of cirrhosis (without 
icterus), and are seen not only in the area of stasis, but in other parts of 
the body; as petechiz of the skin, the retina, the subcutaneous tissues, the 
surface of the nasal, pulmonary, and urinary passages, and hemorrhagic 
exudates into the pleural and peritoneal cavities. They are not so fre- 
quent in this condition as in hypertrophic cirrhosis. Death may result 
from violent epistaxis. 

Certain dyscrasias may be made responsible for some of the hemor- 
rhages in the portal area in addition to the purely mechanical factors 
(hemorrhages into the mucosa of the stomach and intestine and into 
inflammatory peritoneal exudates). At a rule, the bleeding is capillary, 
and in the case of the stomach it may lead to ulceration. Hematemesis 
in cirrhotics is usually due to rupture of esophageal veins (Litten); it 
appears suddenly without any premonitory gastric symptoms. In 
gastric ulcer such prodromata are generally present. Sometimes hemor- 
rhage relieves by disgorging the portal system; in the majority of cases, 
however, it leads to the death of the patient. 


Among 56 cases of cirrhosis Lange found hemorrhages 10 times (18 %) (stomach, 
esophagus, air-passages, and serous cavities); 37 % of these occurred in advanced 
cases, and not one case occurred in the beginning of the disease. 


Leichtenstern mentions cases~in which the clinical picture of gastric 
hemorrhage with severe anemia was simulated, and in which (possibly as 
a result of the many hemorrhages) neither ascites nor swelling of the 
spleen developed. 

[E. Stein + reports a case of cirrhosis of the liver of which repeated 


* Archiv. gen: de med., May, 1900. 
t Arch. jf. Verdauungs-krankheit., Bd. v, Heft 1. 


708 DISEASES OF THE LIVER. 


hemorrhage from the bowel was the chief symptom and was the cause of 
death. H.Curschmann* notes 13 fatal cases of hemorrhage from varices, 
from the digestive tract, etc. Webber ¢ reports a case with repeated 
epistaxis, hemorrhage from the ears, spongy and bleeding gums, and long- 
continued irregular temperature. Lubet-Barbon f{ cites a case of hemor- 
rhage from the larynx, and Ewald, Mannesse, and Miller all cases of 
fatality from the bleeding of esophageal varices. 

Carrington 3 has shown that the course of the disease may be alto- 
gether afebrile. The temperature may, however, rise as high as 100° to 
102.5° F., though it never reaches a point that could be called hyperpy- 
rexia. Increased frequency of the pulse and diminished arterial tension have 
been found in cirrhosis of the liver by Gilbert and Garnier.|| They attri- 
bute at least some of the lowering of pressure to portal obstruction, as they 
had found a corresponding decrease in blood-pressure on ligating the 
portal vein.—ED.] 


Sometimes diseases of the interior of the eye follow cirrhosis of the liver, retinitis 
pigmentosa and choroiditis atrophicans **; certain authors have attempted to find 
anatomic analogies between these lesions and the cirrhosis of the liver. 


[Hayem ++ has found diminution or absence of hydrochloric acid in 
the gastric secretion in atrophic cirrhosis, whereas in hypertrophic cir- 
rhosis an extess of acid was found.—ED.] 

Complications.—In many cases other organs than the liver are in- - 
volved in the cirrhotic process because they, too, are affected by the same 
harmful influences (alcohol, malaria, syphilis) that act on the liver; it is 

for this reason that albuminuria as a result of interstitial and paren- 
chymatous nephritis is so often seen in the course of hepatic cirrhosis. 


Jonestt found inflammation of the kidneys 26 times among 30 cases of cirrhosis 
of the liver; Wallmann§§ found it 17 times among 24 cases, Price 25 times among 
142 cases, G. Forster |||| 10 times among 31 cases. Alcohol, syphilis, and malaria 
are chiefly responsible for these changes. 


Alcohol may also cause chronic meningitis and pachymeningitis; also 
arteriosclerosis and myocarditis. Clinically, the disturbances of the heart 
become very prominent, and are manifested by the development of edema 
and of hyperemias from stasis. 

[Oestreich,*** Posselt,t{+ and Bantittt all make special reference 
to the cirrhosis with enlargement of the spleen.—Eb.] 

Complications affecting the liver itself are: fatty infiltration and 
hyperemia from stasis; both are caused chiefly by alcohol; both are, 
therefore, important because they produce an enlargement of the organ at 
a stage of the disease in which interstitial poner °F, alone would have 
led to a decrease in the size of the organ. 

Icterus, aside from the mildest degrees, is not one of the symptoms of 
atrophic liver cirrhosis per se; it may, however, be produced by cicatricial 


* Deutsche med. Woch., April 17, 1902. + Lancet, April 21, 1894. 

t Archiv. de Laryngol.,, July—Aug., 1897. § “Guy’s Hospital Reports,” 1884. 
|| Presse Médicale, Feb. 4, 1899. 

ie ** Litten, Zeitschr. f. klin. Med., Bd. v, H. 1. Baas, Miinch. med. Woch., 1894, 
0. 32. 


tT ‘Bull. M. edicale, 1898, No. 26. ti Quoted by Duplaix, p. 146. 
$$ Wallmann, Oesterr. Zeitschr. f. praktische Heilkunde, Bd. v, No 
|| || Férster, Dissertation, Berlin, 1868. 4 Virchows af te 1895. 


TTT Deutsch. Archiv. f. klin. M ed., Bd. Lxi. 
ttt Beitrage zur path. Anat. u. zur allg. secre Bd. xx1v. 


CHRONIC INFLAMMATION OF THE LIVER. 709 


compression of the finer, as well as of the larger bile-passages, and even of 
the ducts at the porta hepatis. ! 

The obstruction to the portal flow in the liver, and the cicatrices 
that are sometimes seen at the porta, all favor the formation of throm- 
bosis of the portal vein; and this, in its turn, increases the tendency 
to stasis in the whole portal area. 

Abscess, amyloid degeneration, carcinoma, and adenoma may also 
develop in a cirrhotic liver. 


In certain cases of cirrhosis there is a development of circumscribed tumor- 
like structures that are arranged like liver tissue and may be called adenomata; 
the cells of these tumors are young hepatic cells. They have been considered 
attempts at regeneration. The so-called hépatite nodulaire of French authors 
differs from this form, which is seen particularly in malaria-liver. The columns 
of liver-cells are arranged in spherical form, and the cells in the center of the nodules 
are large and contain one or more large nuclei (Kelsch and Kiener, Sabourin). 

Finally, true multiple primary carcinoma may occur in cirrhosis. It seems 
to develop from isolated aggregations of liver-cells (encapsulated, so to speak, 
within connective tissue), or from the epithelium of the finer bile-passages. Car- 
cinoma may also develop from an adenoma.* 


The rare occurrence of glycosuria as a complication has already 
been mentioned. 

The peritoneum is often chronically inflamed and thickened. This 
factor may aid the development of ascites or may lead to contraction 
and shortening of the mesentery. 


According to Gratia,t a slowly progressing, retracting peritonitis leads to a 
thickening of the walls of the intestines and to shortening of the intestine (small 
intestine, 5.8 m. instead of 8 m., the large intestine 1.5 m. instead of 1.83 m., on 
an average). In this manner it is claimed that absorption is interfered with. 
Botazzi,t too, found thickening and shortening of the intestine; he attributes it to 
some primary disease of the blood-vessels. 


Sometimes the peritonitis is hemorrhagic in character with the 
development of bloody adhesive strands of fibrin and the exudation 
of bloody ascitic fluid. Tuberculosis of the peritoneum is found 
with astonishing frequency in combination with cirrhosis of the liver. 
Aside from those rare and doubtful cases in which tuberculosis is 
the primary disease, and in which, possibly, the cirrhosis of the 
liver is caused by tuberculosis, and in this way causes secondary peri- 
tonitis, the cirrhosis is generally the primary and the more chronic disease, 
whereas the peritoneal tuberculosis is secondary and more recent. 
Brieger assumed that the reverse was the case in the instances studied 
by him; such a sequence is, however, probably exceptional. Although 
often not recognizable clinically, older tubercular foci will, as a rule, be 
found in the lungs, the intestine, ete., postmortem. 

The relative frequency with which the two diseases are seen together 
proves that certain factors must favor the development of the peri- 
toneal involvement. It is probable that the exudate forms a favorable 
nidus for the development of the bacteria that may enter it, though 
if we judge from the analogy with other organs the venous hyperemic 
condition of the intestine should, if anything, be a protection against 

* Naunyn, Reichert u. du Bois-Reymond’s Archiv, 1866, p. 725. Fetzer, Disser- 
tation, Tiibingen, 1868. Wulff, Dissertation, Tiibingen, 1876. Rohwedder, Disser- 
_ tation, Kiel, 1888. 

+ Journal méd. de Bryzxelles, 1890, No. 5. 
t Archivio per le sci. med., vol. x11, 1894, No. 3. 


710 DISEASES OF THE LIVER. 


the invasion of tubercle bacilli. In some of the cases that I have 
personally observed (autopsy by Heller) the tubercular process was 
limited to the peritoneum, so that an invasion of bacilli probably 
occurred through the uninjured (possibly edematous) mucosa of the 
intestine. 

It is very difficult to make a differential diagnosis between cirrhosis 
of the liver and tuberculosis of the intestine, and, as a result, the true 
condition of affairs frequently remains unrecognized during the life 
of the patient. There are, however, certain diagnostic clues that 
may be obtained in the course of the disease, even apart from the 
presence of involvement of the organs. The moderate exudation, 
after running a chronic course and remaining altogether hidden, sud- 
denly becomes excessive; at the same time the abdomen often becomes 
painful, and fever sets in. It becomes necessary to aspirate repeat- 
edly; and the fluid aspirated will often be found to be hemorrhagic or, 
at least, to contain more cells than the fluid of ordinary stasis ascites. 
Death occurs within a few months, after a rapid and progressive loss 
of strength. 

Duration ; Termination ; Prognosis.—Owing to the mild character 
of the initial disturbances, it is often impossible to recognize the begin- 
ning of the disease; there are many cases of contraction of the liver 
on record that have been found postmortem and caused no symptoms 
whatever during the life of the patient. It is only possible, therefore, 
to form a conjecture as to the probable duration of the disease; the 
majority of cases run a course of many (ten and more) years. 

As the disease is the result of alcohol and other poisons, it is probable 
that remissions or even a total arrest of the process may occur if abuse 
of these substances is stopped. It is, of course, hardly possible to 
prove this, because fatty infiltration of the liver and hyperemia from 
stasis develop from the same intoxications, and are diseases characterized 
by great fluctuations in the size of the liver. 


In a case quoted by Hardt,* that presented all the features of Laennec’s cir- 
rhosis, both anatomically and clinically, the liver was enlarged up to the death 
of the patient; this was due to the mass of connective tissue that had developed; 
the parenchyma at the same time was essentially intact. 


In cases in which cirrhosis can be positively diagnosed, the disease 
is, aS a rule, in an advanced stage, and death may be expected within 
a few months. 


I do not believe that cirrhosis can run an acute course and terminate in a 
few months; the nature of the process makes this improbable. Stricker,t Len- 
hartz,{ and others § describe cases of this kind; the former claims to have observed 
the transformation of an enlarged liver into a contracted one within a period of 
six weeks. In all cases of this kind I should be very much inclined to the belief 
that the case was one of fatty infiltration or of hyperemia from stasis, and that 
these conditions disappeared and caused the reduction in the size of the organ. 
In the cases described by Hanot that terminated fatally in from 2 to 6 months, 
the cirrhosis seems to have been complicated by a subacute parenchymatous hepa- 
titis with disintegration of the parenchyma. 


* “ Fypertrophische Form der portalen Lebercirrhose,’”’ Tiibingen, 1894. 

+ Stricker, Charité-Annalen, 1874, p 

t'Verhandlungen des Cong. i. inn. ML ed., 1892, p. 125. 

§ Cornillon and Scheven, quoted by Mangelsdorf, Deutsch. Archiv }. klin. Med., 
1882, Bd. xxx1, p. 519. 


CHRONIC INFLAMMATION OF THE LIVER. 711 


The outcome of a case of cirrhosis with distinct reduction in the 
size of the liver is death from general malnutrition, heart failure, edema 
of the lungs, or some intercurrent acute disease; more rarely from 
hepatargia. 

The prognosis of the atrophic stage is unfavorable. In the earlier 
stages, which can never be positively recognized, the prognosis is not 
so bad, provided we can remove the causal condition (malaria, syphilis), 
or bring to an end the chronic intoxication with alcohol. 

In those cases, too, in which ascites is already present, but in which 
the liver, though hardened, is not reduced in size, the swelling of the 
liver may sometimes recede and the ascites disappear. In these cases 
improvement may last for many years. Such a result probably depends 
upon the removal of stasis hyperemia (by strengthening the heart), 
or of the parenchymatous swelling or fatty infiltration of the liver. 

The assertion that the development of a collateral circulation in 
the veins that anastomose with the portal system can aid in reducing 
ascites does not appear to me to be very probable. It is true, how- 
ever, that a most pronounced ascites may disappear in cases in which 
peritonitis (often difficult to recognize) has existed in addition to the 
stasis. [For a discussion of operative treatment see below under Treat- 
ment.—Eb.] 

Diagnosis.—For the reasons mentioned an early diagnosis of 
chronic hepatitis would be very desirable. As the symptoms are so 
indefinite, a great deal of importance must needs be attached to general 
considerations, to the etiology, and to apparently insignificant liver- 
symptoms. Further, in making the diagnosis of such diseases as fatty 
infiltration of the liver, hyperemia, and perihepatitis, it will be well 
to remember that these conditions may be complicated with inter- 
stitial hepatitis. A tumor of the spleen that cannot be explained, but 
which appears in the very first stages of the disease, is of real diagnostic 
importance; in the later stages, when this lesion is combined with a small 
liver, it is still more suggestive. If ascites is present, it will be a difficult 
matter to recognize the presence of cirrhosis, owing to the uncertainty 
of palpation under these circumstances. All kinds of peritoneal dis- 
eases will have to be excluded, chiefly tuberculosis and carcinoma 
of the peritoneum. It is advisable, therefore, to look for these diseases 
in other organs (the lungs, the intestine, the testicles, the tubes, the 
stomach). Diseases of the peritoneum, if they develop acutely, are 
* usually painful, tuberculosis usually is accompanied by fever, and 
is characterized by nodules and strands that can be felt through the 
abdominal walls and through Douglas’ pouch. Sometimes the diagnosis 
can be aided by palpation following immediately upon the removal 
of the ascitic fluid; a particularly important point is the presence 
of a thick strand of omentum running transversely across the abdomen. 
It will also be well to remember that cirrhosis and peritoneal tubercu- 
losis may occur together. It is only in rare cases that it is possible 
to palpate the nodular surface of the liver, even after tapping. 

Definite information may be obtained by an analysis of the ascitic 
fluid. In simple cirrhosis it contains very few cells, and its specific 
gravity is not above 1014. In peritoneal disease the specific gravity 
is frequently higher, there is often more albumin, and. numerous epithe- 
lial or carcinomatous cells are found in the sediment precipitated 
by centrifuging. ‘s... : 


712 DISEASES OF THE LIVER. 


Chronic pylephlebitis and contracting perihepatitis may lead to 
the same pathologic picture as cirrhosis; the liver, moreover, may be 
small and symptoms of stasis may be present in these conditions. 
The differential diagnosis must be made from a study of the etiology 
and the course of the disease. [Colpi has reported a case * in which 
pylephlebitis was present in a typical case of hepatic cirrhosis, and 
as a complicating rather than a causal condition.—Ep.] The latter 
is, as a rule, more rapid in occlusion of the portal vein than in cirrhosis; 
in chronic perihepatitis (Zuckergussleber) it is much slower, sometimes 
lasting for years with intermissions. Sometimes pain in the beginning 
of the disease will point to the inflammatory character of the trouble, 
or, again, the whole disease may appear to start from an attack of 
pericarditis (see perihepatitis and cirrhosis from stasis). [J. B. 
Herrick + has written an instructive account of a case under his observa- 
tion in which the condition was regarded as an instance of Pick’s “ peri- 
carditic pseudocirrhosis of the liver.” The clinical picture was one 
of relatively slight edema of the lower extremities, enlarged liver, 
and rather obscure cardiac symptoms. Three similar cases described 
in 1896 by Pick showed on the autopsy table an adhesive obliterative 
pericarditis, adhesive pleuritis, and changes in the liver described as 
the nutmeg type, cirrhosis and a coarsely granular liver. From his 
studies he concludes that: this symptom-complex resembling true 
cirrhosis was caused by a pericarditis that induced circulatory. dis- 
turbances in the liver, leading to fibrous connective-tissue change. 
In this way portal stasis and ascites resulted. He emphasizes the 
importance of inquiring into the history and the symptoms for the 
presence of pericardio-mediastinitis.—ED. ] 

Treatment.—Prophylaxis would be the ideal therapy in alco- 

holic cirrhosis if it were possible to carry it out. Cases in which dys- 
peptic symptoms appear with disagreeable sensations in the epigastric 
region and the right hypochondrium are particularly suited for an 
intelligent prophylaxis, and should be advised, accordingly. This also 
applies to cases in which transitory enlargement of the liver and in- 
crease in its consistency point to an irritable state. There can be no 
doubt that a withdrawal, or at least a decided reduction in the quantity 
of alcohol ingested will arrest the progress of the disease. It is like- 
wise important to avoid other exciting factors, such as excessive eating, 
irritating food, condiments, ete. 
A simple diet will alone prevent overnourishment, and if good care ° 
is taken to treat all catarrhal conditions of the stomach and the intestine, 
the formation of irritating and poisonous decomposition products can 
to a large degree be prevented. Milk, buttermilk, gruel, fruits, and 
vegetables are all advantageous; but the selection of the diet should 
be different in each individual case, and be governed by the state of 
the intestinal tract, and of the general nutrition, since the liver is 
never the only damaged organ. In some instances a milk diet may 
be useful; the French and Italians are strong advocates of this plan. 

In the initial stages, particularly if plethora exists, the use of laxa- 
tives (salines, rhubarb, aloes), certain waters containing alkaline 
Glauber salts (Karlsbad, Marienbad, Tarasp) or saline waters (Kis- 
singen, Homburg, Wiesbaden), is indicated. The actual success at- 


*La Riforma Medica, 1900, 84-89. 
t+ Chicago Med. Recorder, p. 15, 1902. 


CHRONIC INFLAMMATION OF THE LIVER. 718 


tained by a course of these different waters suggests a direct influence 
on the liver. - 

The same can be said of iodid of: potash and of mercury, drugs 
that should be employed in cases that are not complicated by gastric 
or intestinal catarrh, also in cases of uncertain origin, and not only 
in those of syphilitic origin. 

In cases in which pain and acute swelling are noted in the beginning, 
perihepatitis is often the cause of these symptoms. Rest, the use of 
laxatives, and a restricted diet, are the chief remedies; in addition, 
local blood-letting and warm compresses may be employed. 

As a rule, chronic inflammation of the liver is seen for the first 
time in the more advanced stages; in these cases the diet (suited to 
the individual) is the most important factor in the treatment. The 
principles enunciated above cannot always be enforced owing to the 
individual appetite, tastes, habits, or the state of the patient’s nutri- 
tion; sometimes it remains necessary to give a little alcohol, and to 
allow a certain variety of food. The treatment is, therefore, essentially 
symptomatic, and is concerned with the regulation of disorders of 
digestion (constipation, dyspespia, diarrhea), and with the ascites. 

For the dyspepsia alkalies, bitter tonics, rhubarb and hydrochloric 
acid, are to be given; for the constipation the milder class of laxatives 
and enemata; for the diarrhea astringents and disinfectants (bismuth, 
salol, naphthalin, creosote). It is well not to stop the diarrhea in 
all cases, and in fact only when it interferes with general nutrition. 
The diarrhea may even act beneficially by relieving the engorgement 
of the intestinal capillaries, and in this way removing ascites. The 
same effect may be produced, provided the strength of the patient will 
permit it, by the use of purgatives; these drugs should be given in 
doses sufficiently large to insure from one to four liquid stools during 
the forenoon. 

Sometimes an increased diuresis will promote the absorption of 
ascitic fluid; this can be brought about by such drugs as potassium 
_ salts, squills, diuretic infusions, theobromin, resina copaibe (1.5 pro die, 
for from eight to fourteen days), calomel (0.1 to 0.2 t. 1. d. for three days, 
then a pause). [Apocynum cannabinum has been used recently by a 
number of observers with great success. It slows and steadies the 
cardiac action, increases blood-pressure, stimulates the kidneys (prob- 
ably by dilating their arterioles), and seems to have a tonic effect on 
the general capillary system, thus lessening the transudation of serum. 
Lloyd’s tincture is generally used in doses of 2 or 3 minims (0.12 to 
0.18 cc.) every three or fourhours. The drug is not, however, free from 
dangerous qualities.—ED. ] 


Sasaki administered for months cream of tartar in doses that insured a stool 
two or three times a day (dose 10 to 20 gm. pro die); Schwass praises the action 
of digitalis; Klemperer has recently advised the administration of urea in doses 
of 10 to 20 gm. pro die for from two to three weeks. 


The difference in the effect of certain drugs in the course of ascites 
can best be explained by the fact that ascites is not always due to com- 
pression of the portal venules alone, but may also be due to parenchym- 
atous swelling of the liver, chronic peritonitis, and cardiac insufh- 
ciency. Thus digitalis may act beneficially in some cases; and in others © 
the reduction of the fluid may be spontaneous and create a false im- 


714 DISEASES OF THE LIVER. 


pression in regard to the beneficial effect of a certain drug that happened 
to be adminstered during this time. Diaphoresis will probably be con- 
traindicated in many cases because of the reduced strength of the patient. 

Whenever the ascitic fluid exerts enough pressure upward upon the 
diaphragm to interfere with respiration and circulation the ascites 
should be removed by abdominal puncture. | 

The evacuation of the fluid acts beneficially in other ways than 
by relieving the pressure. The ingestion of larger amounts of food 
is made possible, the stools are passed with less difficulty, and diuresis 
is improved, owing to the removal of excessive work from the kidneys. 
Perhaps owing to the lessened tension of the peritoneum there will be 
a more thorough absorption of the fluid exuded from the intestinal 
serosa. These advantages, in many cases, are so considerable that punc- 
ture is followed by a prolonged improvement in the condition of the 
patient. In other cases the fluid accumulates rapidly and calls for repeated 
tapping. This procedure has among its drawbacks the loss of con- 
siderable nutritive material, and at the same time the danger that the 
sudden diminution of the intra-abdominal pressure may exert an irritant 
influence upon the peritoneum. The significance of these disadvan- 
tages and their effect on each case varies with the ordinary capacity 
for food and the condition of the peritoneum. In each individual case, 
therefore, the, advantages and the disadvantages of repeated puncture 
should be carefully weighed, and the physician must be governed accord- 
ingly. It is manifestly impossible to predict what effect puncture 
will have on a patient, and it is often necessary to perform the operation 
once or twice before deciding as to its benefits or disadvantages. 

The operation should not be performed very early in the course of 
the disease (Murchison* advises differently), and its first indication 
should be difficulty of breathing, and signs of interference with the 
circulation, or with nutrition. On the other hand, it is not well to 
wait very long. Of course, nothing can be said in regard to the amount 
of fluid that should be present before paracentesis is demanded, as this 
factor will depend upon the tension of the abdominal walls. 


Talma has proposed stitching the mesentery to the abdominal wall, and in 
this way causing an artificial collateral path for the blood in the portal system, 
allowing it to flow by this channel directly into the systemic circulation. Lens 
performed this operation, but the results are not sufficiently definite as yet to 
allow us to render judgment on the value of the procedure. 


[Since Talma first suggested epiplopexy as an operative cure for 
cirrhosis of the liver, many cases have been treated in this way, and a 
fair opportunity has been afforded to judge of the value of the measure. 

Neumann,f in a case of cirrhosis of the liver with ascites, opened 
the abdomen, curetted the parietal peritoneum and omentum, and 
stitched these two together. After many months distinct dilatation of_ 
the vessels of the abdominal wall around the navel had formed and the © 
ascites had not returned. . 

Rolleston and Turner f operated on two cases of ascites from cirrhosis 
of the liver. In one of these improvement occurred and the ascites 
had not returned for three and a half months. 

Scherweneky % has reported a successful case; Herman Kiimmell || 

* Duncan, Brit. Med. Jour., June 4, 1887. 


+ Deutsche med. Woch., 1899, No. 26. t Lancet, Dec. 16, 1899. 
§ Medicinkoie Obosvenie, Mar. 1, 1901. || Deutsche med. Woch., April 3, 1902. 


' CHRONIC INFLAMMATION OF THE LIVER. 715 


seven cases, of which two died of exhaustion (two some time after the 
operation) and three recovered, but the ascites remained as before. 
-Grisson operated upon a patient with a high grade of ascites, who showed 
such improvement as to be able to work actively for two years before 
death supervened. J. B. Roberts* reports two immediately fatal cases. 
C. H. Frazier — reports a cure. Geo. E. Brewert reports 5 cases, of 
which 4 were fatal. Of 60 cases from the literature, however, he found 
38 which recovered. Baldwin 3 reports 3 cases, of which one recovered 
completely and two died. In one of the latter cases the patient lived 
three months, and ascites did not reappear. Drummond and Morison || 
also reported a cure. 

A résumé of the modern status of the operation in hepatic cirrhosis 
may be found in an article by Packard and LeConte,** with the report 
of two fatal cases. They collect twenty-two recent cases, which they 
analyze as follows: 


Immediate déath::).4.3.0-).3:04-es:de0e8 os eine are tae oise Site eee 22.7 % 
UTD CICA UN cst eah ce ig ascatn ios eters Me rp SS OE 13.6" 
UMM PLOW cocci ye winced ctr ces nr oe OS rane aie a as 16)-" 
TM PPOVOd yatta ee ead Cha thet ee ye eke tee Cee ela eee 0.5. 
ReCOVERCE ars Wisrea se nherg eae Walt eC PO See 40.9 “ 


Many of these cases were complicated by serious independent con- 
ditions, and in some the operation certainly was performed in a faulty 
manner. Excluding such cases ‘the table would read: 


PiMB date COREO 4 ds ci a pee enh Oe eta ae ha a a tceees 7.1% 
GLO ORION Gow os cosh 516.9 repel ohn ote ie einen Salas (A es 
UWA OPO VEO ona 5 aloes arn -aiik 4.3 adn eles bie us aoe aaah eh ke Be teats 
TMPrO ved a, seek ug Saisie eles Sle Ha we as nls Ra Oe 14.3 “ 
RGCOV OLE scriay cena pak ow And cow 1a aise A aoe es 64.3 “ 


Contrasting the worst and best aspects of the operation, they conclude 
that the percentage of recoveries must lie somewhere between 41 % and 
64%. Montgomeryty{ adds sixteen cases to the above list of twenty-two. 
The whole question is one of a preference between almost certain fatality 
in the case of expectant and symptomatic treatment, and 40 % to 60 % 
of recoveries under operative measures. When cases of hepatic cirrhosis 
become bedridden, and the case is evidently hopeless unless some extreme 
and radical intervention is made, the only hope is in operation. Un- 
fortunately, the operation has been neglected until too late and until 
the reactionary powers of the patient are gone. The results, on the 
whole, have been encouraging, and even as a dernier ressort the operation 
has not proved as much of a failure as the less active medical treatment. 
—EDb.] 


LITERATURE. 


Aufrecht: Article on “ Lebercirrhose, ” in Eulenburg’s ‘“ Realencyklopidie der ges- 
ammten Heilkunde.” 

Bamberger: “Krankheiten des chylopoetischen Systems,” 2. Aufl., 1864, pp. 510- 
526. ‘ 


v. Birch-Hirschfeld: “ Leberkrankheiten,” in Gerhardt’s “Handbuch der Kinder- 
krankheiten,”’ 1880, Bd. rv, Abth. 2, D. 743. 


* Phila. Med. Jour., Jan. 26, 1901. + Amer. Jour. Med. Sci., Dec., 1900. 

t Med. News, Feb. 8, 1902. § Jour. Am. Med. Assoc., July 26, 1902. 

|| Brit. Med. Jour., Bei. 19, 1896. ** Amer, Jour. Med. Sct., March, 1901. 
tT Med. Chronicle, April, 1902. 


716 DISEASES OF THE LIVER. 


Budd: “ Diseases of the Liver,” pp. 105-132, London, 1845. 
Carswell: “Illustr. of the Elementary Forms of Diseases, ” Fasc. 10, Pl. 2, London, 


Charcot: “ Legons sur les maladies du foie,” etc., 1877. 

Chauffard: ‘“ Maladies du foie,” in Charcot, Bouchard et Brissaud’s “'Traité de méde- 
cine,” 1892, 111, p. 822. 

Cruveilhier: “ Anat. ’-patholog., * Live,12, P11, 

Frerichs: ‘‘ Leberkrankheiten, 1861, Bd. Ir, p. 19. 

Laennec: “Traité de l’auscultation médiate, ” 4. éd., tome 11, p. 501. 

Leichtenstern: “ Behandlung der Krankheiten der ’ Leber, ”” In Penzoldt-Stintzing’s 
“Handbuch der speciellen Therapie,” Bd. Iv, p. 138. 

Thierfelder: “ Leberkrankheiten,” in Ziemssen’s “ Handbuch der speciellen Patholo- 
gie und Therapie,” Bd. vir, 1, p. 148, 1880. 





Botkin: “Krankengeschichte eines Falles von Pfortaderthrombose,” ‘“Virchow’s 
Archiv,” Bd. xxx, p. 449.» 

Brieger, L.: “ Zur Lehre von der fibrésen Hepatitis,” “ Virchow’s Archiv,” 1879, Bd. 
LXXv. 

Bristowe: “ Observations on the Cure or Subsidence of Ascites due to Hepatic Dis- 
ease,” “ Brit. Med. Jour.,’”’ April 23, 1892, p. 847. 

Dieulafoy: “Les cirrhoses du foie (nimmt Uebergangsformen an zwischen der hyper- 
trophischen und atrophischen Cirrhose),” “Gazette des hépitaux,”’ 1881, 20, 39, 
40, 41, 43. 

Dujardin-Beaumetz: “ Des Cirrhoses,”’ “ Bulletin de thérapie,’’ Nov., 1892. 

Forster, G.: “ Die Lebercirrhose nach pathologisch-anatomischen Erfahrungen” (31 
cases), Dissertation, Berlin, 1868. 

Goodhart: “A Case of Cirrhosis of the Liver probably ee eae in Phlebitis,” 
“ Pathological Transactions,” 1890, vol. x1; “Jahresbericht,” 11, p. 257. 

Hanot: ‘ Cirrhose sans ascite,”’ « Archives générales de médecine, N ov., 1886. 

Janowski: “ Beitrag zur pathologischen Anatomie der bilidren’ Lebercirrhose,” in 
Ziegler’s “ Beitrage zur pathologischen Anatomie,” 1893, p. 79. 

Kabanoff: “ Quelques donné es sur la question de V’étiologie des cirrhoses du foie,” 
“ Archives générales de médecine,” Feb., 1894. 

Kiissner, B.: ‘‘ Ueber Lebercirrhose,”’ Volkmann’s “ Sammlung klinischer Vortrage, 
1877, No. 141. 

Lange, H.: “Ein Beitrag zur Statistik und pathologischen Anatomie der intersti- 
tiellen Hepatitis” (205 cases), Dissertation, Kiel, 1888. 

Liebermeister, C.: “ Beitrag zur pathologischen Anatomie und Klinik der Leber- 
krankheiten, ” Tubingen, 1864. 

Litten: “Klinischer Beitrag zur bilidren Form der Lebercirrhose,” “Charité-An- 
nalen,’’ 1880. 

Mangelsdorff : “ Deutsches Archiv fiir klin. Medicin,’’ Bd. xxx1, p. 522. 

Oestreich, R.: “ Die Milzschwellung bei Lebercirrhose, ” “Virchow’s Archiv,” 1895, 
Bd. CXLU, 2 P- 285. 

Potiquet: “ De l’albuminurie dans la cirrhose atrophique,” Thése de Paris, 1888. 

Price: “ Remarks on the Pathology of Cirrhosis” (142 cases), “Guy’s Hospital Re- 
ports,” 1884, vol. xxvir. 

Rosenstein: “Ueber chronische Leberentziindung,” “ XI. Congress fiir innere Medi- 
cin,” 1892, p. 65, und “ Berliner klin. Wochenschr.,’’ 1892, Nos. 23-26. 

Saundby: “Remarks on the Variety of Hep. Cirrhosis,” “Brit. Med. J our.,”’ Dec. 27, 
1890. 

Simmonds: “ Ueber chronische, interstitielle Erkrankungen der Leber,”’ “ Deutsches 
Archiv fiir klin. Medicin,” 1880, Bd. xxvu. 

Solowieff: “Veranderungen in der Leber unter dem Einfluss kiinstlicher Pfortader 
verstopfung,” “ Virchow’s Archiv,” Bd. txt, p. 195. 

Stadelmann: “ XI. Congress fiir i innere Medicin,’ ? 1892, p. 90. 

Steinmetz: ‘Beitrag zur Lehre von der Lebercirrhose ” (35 cases), Dissertation, 
Gottingen, 1894. 

White, H.: “ The Cause and ee dered of Ascites due to Alcoholic Cirrhosis, to 
Perihepatitis and to Chronic Peritonitis,”’ “Guy’s Hospital Reports,” 1893, vol. 
XXXIV. 


* OccURRENCE OF CIRRHOSIS IN CHILDREN. 


Taylor, F.: “Transactions of the Pathological Society,”’.1881. 
Demme: “XXII. Jahresbericht des Berner Kinderspitals,” Bern, 1885. 


CHRONIC INFLAMMATION OF THE LIVER. 717 


Hébrard: Thése de Lyon, 1886. 

v. Kahlden: ‘‘ Miinchener med. Wochenschr.,” 1886. 

Howard, P.: “ American Journal of the Med. Sciences,” Oct., 1887. 

‘Laure et Honorat: ‘‘ Revue mensuelle de l’enfance,”’ Mar. and April, 1887. 

Henoch: “ Charité-Annalen,”’ 1888, p. 636. 

Biggs, H.: “ Med. Record,” Aug., 1890. 

Target: “Med. Record,” 1890; “Transactions of the Pathological Society.” 

Ormerod: “St. Bartholomew’s Hospital Report,” 1890; Lafitte: “L’intoxication 
alcoolique expér. et la cirrhose de Laennec,” Thése de Paris, 1892 (cites 9 cases 
between 9 and 15 years of age). 

Clarke: ‘“ British Med. Journal,” June 30, 1894. 

Hall, J. G.: “ British Med. Journal,” 1893, vol. xxvu. 


HEMORRHAGES. 


Hirsch, M.: “ Ueber Blutungen bei Lebercirrhose’’ (with references to literature), 
Dissertation, Berlin, 1891. 

Lange, H.: “Ein Beitrag zur Statistik und pathologischen Anatomie der institiellen 
Hepatitis,”’ Dissertation, Kiel, 1888. 

Gaillard: ‘“ Hémorrh. pulmonaires et pleurales dans la cirrhose du foie,” “ L’Union 
méd.,”’ 1880, Nos. 155, 156. 

v. d. Porten: “ Venenerweiterungen bei Lebercirrhose,”’ ‘Deutsche med. Wochen- 

‘ schr.,”’ 1884, No. 40, p. 652. 


_HEMORRHAGE FROM THE ESOPHAGUS AND HEMATEMESIS. 


Litten: “Verhandlungen des X. internationalen medicinischen Congresses,” 1890, 
Abth. v, p. 212; “Virchow’s Archiv,” 1880, Bd. Lxxx, p. 279. 

Notthaft: ‘“ Minchener med. Wochenschr.,” 1895, No. 15. 

Wilson and Ratcliffe: ‘‘ British Med. Journal,’’ December 27, 1890. 

Reitmann: “ Wiener klin. Wochenschr.,’’ 1890, No. 20-22. 

Schilling: ‘‘ Aerztliches Intelligenzblatt,”’ 1883, No. 36. 

_ Volkel, G.: Inaugural-Dissertation, Halle, 1891. 

Ehrhardt: “Des hémorrh. gastro-intest. profuses dans la cirrhose,”’ Thése de Paris, 
1891. 

Garland: “ Boston Med. and Surgical Journal,’ 1896, No. 12; “Jahrsberichte,” 11, 


p. 199. 
EPISTAXIS. 


Verneuil: “ Bulletin de l’académie de médecine,” 1894, No. 22. 

Zarnack: “ Beitrag zur Casuistik der Blutungen bei Lebercirrhose”’ (7 cases), Disser- 
tation, Kiel, 1894. 

Garnier: “Gazette hebdomadaire,”’ 1887, No. 10. 

Bogie: ‘‘ Med. Times,” July 15, 1881. 


METABOLISM IN CIRRHOSIS OF THE LIVER. 


v. Noorden: “ Lehrbuch der Pathologie des Stoffwechsels,”’ p. 283. 

Hallervorden: “Ueber Ausscheidung von NH; im Urin bei pathologischen Zu- 
stainden,” ‘ Archiv fiir experimentelle Pathologie,’ 1880, Bd. x11, p. 274. 

Stadelmann: “Ueber Stoffwechsel anomalien bei einzelnen Lebererkrankungen,”’ 
“Deutsches Archiv fiir klin. Medicin,” 1883, Bd. xxxu11, p. 526. 

Fawitzky, A. P.: ‘Ueber den Stoffumsatz bei Lebercirrhose,” etc., “ Deutsches 
pen ES fiir klin. Medicin,” 1889, Bd. xiv, p. 429. 

Stadelmann: “Ueber chronische Leberentziindung,” ‘“ Verhandlungen des Con- 
gresses fiir innere Medicin,” 1892, p. 108. 

Aillo e Solaro: “Tl Morgagni,” 1893, Nos. 1 and 2; “ Jahresbericht,” 11, p. 273. 

Weintraud: “Untersuchungen iiber den Stickstoffumsatz bei der Lebercirrhose,” 
“ Archiv fiir experimentelle Pathologie,” 1893, Bd. xxx1, p. 30. 

Miinzer and Winterberg: “ Die harnstoffbildene Function der Leber,” “ Archiv fur 
experimentelle Pathologie,” Bd. xxx, p. 164. 


CIRRHOSIS OF THE LIVER AND TUBERCULOSIS OF THE PERITONEUM. 


Brieger: Loc. cit. ; 
Brodowski ; : Gazeta lekarska,” 1881, No. 13; Virchow-Hirsch’s “ Jahresbericht,”’ 
11, p. 189. ; 


‘ ‘ 


718 DISEASES OF THE LIVER. 


Moroux: “Des Rapports de la cirrhose du foie et la peritonite tuberculeuse” (13 
cases), Thése de Paris, 1883. . 

Weigert, C.: “ Die Wege des Tuberkelgiftes zu den serésen Hauten,” “ Deutsche med. 
Wochenschr.,”’ 1883, No. 472. 

Wagner, E.: “ Beitrag zur Pathologie und pathologischen Anatomie der Leber” (10 
cases), ‘“ Deutsches Archiv fir klin. Medicin,” 1884, Bd. xxx1v, p. 520. 

Lauth: “ Etude sur la cirrhose tuberculeuse,”’ Thése de Paris, 1888, p. 38. 


GLYCOSURIA AND CIRRHOSIS OF THE LIVER. 


v. Noorden: Loc. cit., pp. 289 and 391 (with references to literature). 

Couturier: ‘“ De la glycosurie dans les cas d’obstruction totale ou partielle de la veine 
porte,’’ Thése de Paris, 1875. 

Quincke, H.: ‘““Symptomatische Glykosurie,” “Berliner klin. Wochenschr.,’”’ 1876, 
No. 38. 

Roger, G. H.: “Contrib. 4 l’ét. des glycosuries d’origine hépatique,” ‘‘ Revue de 
médecine,” 1886, tome v1, p. 935. 

Kraus, Fr., and Ludwig, H.: ‘“Klinischer Beitrag zur alimeatiren Glykosurie,” 
“Wiener klin. Wochenschr.,’’ 1891, Nos. 46 and 48. 

Bloch, G.: ‘“ Ueber alimentare Glykosurie,” “ Zeitschr. fiir klin. Medicin,” 1893, Bd. 
XXII, p. 531. 

Casati, C. . “Ueber alimentaire Glykosurie,” “Il raccoglitore medico,” Aug., 1893; 
“‘ Jahresbericht,” 11, p. 273. 

Palma, P.: “ Zwei Falle von Diabetes mellitus und Lebercirrhose,”’ ‘“ Berliner klin. 
Wochenschr.,” 1893, p. 815. 

Pusinelli: “‘ Ueber die Beziehungen zwischen Lebercirrhose und Diabetes,” ‘‘ Berliner 
klin. Wochenschr.,’’ 1896, p. 739. 


TREATMENT. 


Lanceraux: “ Bulletin de l’académie de médecine,” 1887, No. 35. . 

Deshayes: ‘‘ Gazette hebdomad.,”’ 1888, No. 34 (milk diet and potassium iodid). 

Boccanera: “Tl Morgagni,’”’ 1888, Luglio (Milchdiat). 

Elhét, G. R.: “ New York Med. Record,” May 26, 1888 (strophanthus). 

Millard: “Trois cas de guérison de cirrhose alcoolique,”’ “Gazette hebdomad.,’’ 1888, 
No. 52. 

Schwass: “ Berliner klin. Wochenschr.,”’ 1888, p. 762 (calomel and digitalis). 

Gilbert: “De la curabilité et du traitement des cirrhoses alcooliques,” “ Gazette 
hebdomad.,”’ April 10, 1890. 

Sacharjin: “ Klinische Abhandlungen,” Berlin, 1890 (calomel). 

Frémont: “ L’Union medicale,” 1892, No. 70 (Vichywasser). 

Kramm, H.: ‘ Zur Therapie der Lebercirrhose”’ (Gerhardt’s clinic, sweat-baths used 
in every stage of cirrhosis of the liver), Dissertation, Berlin, 1892. 

Lens: “ Hechting van het omentum majus aon den buikwand bi cirrh. hep. Weekbl. 
van het.,’’ “‘ Neederland. Tijdschr. f. Geneesk.,’’ 1892,1, No. 20; “ Jahresbericht,”’ 
11, p. 197. 

Sasaki, M.: “ Ueber die Behandlung des Ascites bei Lebercirrhose und Lebersyphilis 
mit Cremor tartari in grésseren Dosen,’ “ Berliner klin. Wochenschr.,” 1892; 
No. 47. 

Casati, C.: ‘Il raccoglitore medico,” Aug., 1893 (111 tappings). 

Palma: “'Therapeutische Monatshefte,”’ Mar., 1893 (calomel). 

Klemperer: “ Berliner klin. Wochenschr.,’”’ 1896, p. 6 (urea). 


HYPERTROPHIC CIRRHOSIS OF THE LIVER. 


Anatomy.—In hypertrophic cirrhosis the appearance of the liver 
differs greatly from that of Laennec’s cirrhosis. The organ is greatly 
enlarged throughout the whole course of the disease and may attain 
a weight of from 2200 to 4000 gm. The general outline of the liver is 
preserved, though the left lobe is sometimes a little more enlarged than 
the right, and the surface of the organ is granular. The individual 
nodules on the surface do not differ in size, as in atrophic cirrhosis, and 
are, as a rule, somewhat larger (the size of a lentil or a pea). The serosa 
is usually thickened and adherent to the surrounding parts. 


CHRONIC INFLAMMATION OF THE LIVER. 719 


The liver is hard, and at the same time elastic; its surface is mottled, 
but icteric throughout, playing from yellow to green. On transverse 
section the lobules will be seen to be separated by broad, grayish or 
reddish-gray bands of connective tissue. The large bile-passages are 
completely patulous. 

On microscopic examination it will be found that the connective 
tissue consists of fine fibrils and scanty elastic fibers; these are not so 
numerous nor so coarse as in the other form of cirrhosis. Between these 
fibers are seen nests of young cells. The connective tissue stains readily 
with carmin; it is found not only in the interlobular spaces, but pene- 
trates the lobules, and runs between the columns of hepatic cells within 
the lobules. In the beginning it is said that this development of con- 
nective tissue starts from small centers situated within the lobules; 
Charcot for this reason has called the process “insular.”’ Notwithstand- 
ing the increase in connective tissue, the amount of hepatic parenchyma 
is not reduced. The trabecular structure of the lobules is well preserved, 
and the appearance of the individual cell is normal. Some of the cells 
may even be enlarged and contain nuclei with mitotic figures (Prus) ; 
Aufrecht states that all the liver-cells are enlarged and multinuclear. 
Only a few of the lobules, the bile-passages leading from which are 
occluded by bile pigment, show a disarrangement of the lobular structure 
by the invasion of strands of connective tissue; in these cases the lobules 
atrophy and become pigmented. 

Within the connective tissue the walls of the interlobular bile-passages 
are seen to be twice or three times as thick as normal, owing to the 
development of connective tissue containing many cells. The lumen 
' of these channels may be patulous, or it may be occluded by desqua- 
mated epithelia or flakes of pigment. In addition, the connective tissue 
contains numerous tortuous bile-passages like those described above, 
and, according to the statements of all authors, in much greater numbers 
than in the atrophic form of cirrhosis. In some places these channels 
are dilated and form reticula that resemble angiomata in structure; or 
they may become dilated and form cysts containing bile-tinged fluid or 
mucus (Sabourin). French authors designate these structures as pseudo- 
canalicules bilvaires, and claim that they are formed from the columns 
of liver-cells by a metamorphosis of the normal liver-cells into small 
indifferent cuboid cells; according to Hanot (I fail to see a great difference 
between the two views), the intercellular bile-capillaries simply become 
dilated. Certainly a definite proportion of these cells is formed from 
the division and budding of preformed bile-passages. 

The blood-vessels of the portal system and the hepatic artery take 
no part whatever in the pathologic process; even the smaller branches 
remain patulous and their walls do not become thickened. This can be 
readily shown by artificial injection. Only in the later stages does it 
appear possible for the connective-tissue proliferation to involve the 
vessel-walls. ; 

In 1857 Todd, in a clinical lecture, emphasized briefly the difference 
between atrophic and hypertrophic cirrhosis, and called particular 
attention to the predominance of icterus and the insignificance of ascites 
in the latter disease. Until the beginning of the seventies these state- 
ments remained unnoticed. At that time French authors began to study 
the disease; and among them Ollivier, Hayem, Charcot and Gombault, 
Hanot, and Sabourin. They described the anatomic and clinical differ- 


720 DISEASES OF THE LIVER. 


ences in contrast with those of atrophic cirrhosis. The French school 
(which has been in the habit of designating hypertrophic cirrhosis as 
Hanot’s disease) consider periangiocholitis of the interlobular bile- 
passages as the primary factor, and believe that the connective-tissue 
proliferation extends from this point to the lobules of the liver. 

So far no explanation has been given for the slight effect exercised 
by this development of connective tissue upon the parenchyma of the 
organ; sometimes the latter may even appear to increase in volume. 
Thus the main difference between the atrophic and hypertrophic forms 
of cirrhosis of the liver is the preservation of the parenchyma in the 
latter. In the last stages of the disease and when death is impending, 
fatty and parenchymatous degeneration of the liver-cells is seen. 

General Clinical Picture.—The affection begins with dyspeptic out- 
breaks, that occur at considerable intervals, and are always accom- 
panied by icterus, and a painful enlargement of the liver. At first, 
during the intervals these symptoms all disappear, but later in the 
disease the liver remains enlarged, and the icterus persists; the swelling 
of the liver may attain a very considerable degree, and there is also an 
enlargement of the spleen. Ascites is absent. General emaciation sets 
in, with a tendency to hemorrhages from various sources. Death occurs 
after several years, as the result of general exhaustion and complicating 
conditions; sometimes with cerebral symptoms. 

Etiology.—Hypertrophic cirrhosis is a rather rare condition, much 
more rare than the atrophic form. It is seen chiefly in men (ac- 
cording to Schachmann, 22 times in 26 cases), and particularly among 
comparatively young men between twenty and thirty; it is sometimes 
seen in children. 

[Among a considerable number of cases reported Mirinesca * has 
studied one of hypertrophic cirrhosis with chronic icterus in a boy of 
fourteen years; aa Gilbert and Fournier } seven cases in infants. J. T. 
Bruigier t has observed a case of acute hypertrophic cirrhosis in a boy 
of seven years, and Pierre Roy ? one in a child in whom death occurred 
after exploratory laparotomy. F. W. Jollye|| has reported two cases 
in children of the same family.—Eb. ] 

The causes of the condition are not thoroughly understood; according 
to some authors, alcohol has no influence in its production; according to 
others (P. Ollivier, observation by myself), it has. Malaria and syphilis 
are doubtful causes, and the same may be said of typhoid and cholera 
(Hayem). 

If, as it appears, alcoholism is indeed one of the predisposing causes 
of hypertrophic cirrhosis, there must be other unknown causes that 
assist in producing a type of disease that is clinically and anatomically 
so different from the usual and more frequent form of atrophic cirrhosis. 
The location seems to have something to do with its occurrence, and 
the fact that so many more cases are described in France can hardly be 
attributed to the fact that Hanot first clearly defined the disease and 
in this way called the attention of French physicians to the lesion. It 
must also in part be actually due to the more frequent appearance of 
this condition in France than, for instance, in Germany. ‘This observa- 
tion. might be adduced as an argument favoring the parasitic nature 


* Rev. des Mal. de l’Enfance, Oct., 1894. + Ibid., July, 1895. 7 
t Phila. Med. Jour., vol. v, No. 22, 1900. § Soc. de Pediatrie, Dec. 10, 1901. 
|| Brit. Med. Jour., April 23, 1892. 


CHRONIC INFLAMMATION OF THE LIVER. 721 


of the disease; it might be a primary infection of the bile-passages 
either by bacteria or by protozoa. 

Vincenzo succeeded in cultivating cocci and bacilli from a hypertrophic-cirrhotic 
liver. A guinea-pig was injected and died in forty-five days; on autopsy interstitial 
sclerotic hepatitis was found. 

[We have already (vide Atrophic Cirrhosis) called attention to numer- 
ous bacteriologic studies of the liver along clinical and experimental 
lines. There would seem, however, to be no direct constant causal con- 
nection between either form of cirrhosis and any specific micro-organism. 
The toxins produced by bacteria seem able to cause cirrhotic processes, 
not only in the liver but in the lungs, spleen, kidneys, etc., but alcohol 
can accomplish this with equal facility. It seems necessary to confess 
that at the present date we do not know the exact etiologic process 
followed in either the atrophic or hypertrophic form, and still less in the 
latter than the former.—ED.] 

Symptoms.—The digestive disturbances that usher in the disease are 
very indefinite and by no means characteristic. There is loss of appetite, 
vomiting in the morning, a feeling of pressure in the epigastrium, and 
particularly in the right hypochondrium. Icterus soon appears, and 
with it the liver enlarges and becomes painful; the other symptoms 
increase in severity until the icterus disappears, when they also disappear. | 
The liver may remain slightly enlarged. Such light attacks of icterus 
with febrile dyspepsia recur at intervals of many months, and sometimes 
of years; each attack is more severe than the preceding one, and lasts a 
little longer; at the same time the enlargement of the liver increases. 
Finally icterus becomes permanent, although fluctuating periodically in 
intensity, and at the same time the general disease-picture grows more 
pronounced. The discoloration of the skin is moderate, sulphur yellow, 
and rarely has the greenish tint that characterizes complete stasis of 
bile; enough bile always enters the intestine to give the stools their 
normal color. As a rule, the latter are pultaceous, and if anything only 
a little lighter than normal. 

The liver at the height of the disease is so much enlarged that it 
causes the right costal arch to bulge out and changes the form of the 
thorax. It protrudes below the margin of the thorax and may extend 
downward as far as the crest of the ilium. The organ is hard, its margin 
dull, the surface smooth, and appears to be irregular only here and 
there, owing to the constrictions caused by strands of connective tissue. 
The liver is sensitive to pressure and, in addition, there is a dull sensation 
of pain or of distress in the whole hepatic region. The swelling of the 
organ increases by stages; at the same time the icterus grows more intense 
and the pain more severe. The size of the organ persists until the death 
of the patient; occasionally the malnutrition becomes so marked that 
the liver shrinks a little. 

The spleen becomes enlarged in the same manner as the liver, the 
organ protruding below the costal arch. It is painful owing to peri- 
splenitis. In atrophic cirrhosis the cause of the swelling of the spleen 
was in part, at least, stasis; in hypertrophic cirrhosis the genesis of this 
enlargement is obscure. All symptoms of stasis are absent in this form, 
there is no ascites, and the collateral veins of the portal system are 
not enlarged. In those rare cases in which a slight exudate is poured 
into the abdominal cavity, the (id ate is usually due to a complicating 


peritonitis. 
46 | 


722 DISEASES OF THE LIVER. 


The loss of appetite that is so conspicuous a symptom in the beginning 
of the disease gives way to a normal appetite in the later stages, or even 
to bulimia. Notwithstanding this fact, the general nutrition of the 
patients remains low, they emaciate and feel miserable, and the enlarge- 
ment of the liver is particularly conspicuous as the patients grow thinner. 

The quantity and the concentration of the urine fluctuate with the 
condition of the digestion; as a rule, it contains bile-pigment. As soon 
as a slight improvement occurs marked polyuria sets in. 

[Minute traces of bile-acid and bile-pigment can be detected by 
means of flowers of sulphur. Avery scanty amount is powdered upon the 
surface of the urine and will at once begin to fall to the bottom if the 
slightest traces of bile are present (Hay’s test). Otherwise the sulphur 
floats upon the surface of the liquid. We have had a number of oppor- 
tunities of proving the value of this test.—ED.] 


According to Chauffard, the abundant ingestion of carbohydrates is followed by 
glycosuria, but not so readily in this form of cirrhosis as in the atrophic form. [Lefas 
has shown that in hypertrophic cirrhosis there is no increase in the size of the pan- 
creas (vide atrophic cirrhosis in contrast), but that its density is markedly increased. 
The interlobular connective tissue, especially around the excretory ducts, is in- 
creased, and there is also a certain amount of intralobular sclerosis. The sclerotic 
tissue seems to take its origin from the excretory ducts, and consists largely of round 
_ cells. The islands of Langerhans are numerous, and filled with a large number of 
cells —Ep.] Chauffard also claims that urobilin is not found so frequently (? Q.); 
both of these facts are interpreted to signify a slighter interference with the liver 
function than is true in the atrophic form. 

Myocarditis, with disturbance of the heart action, takes rank as the 
most important complication, after peritonitis. Occasionally acciden- 
tal (?) systolic murmurs are heard, particularly at the apex; the number 
of red blood-corpuscles is said to be reduced (Rosenstein), and the num- 
ber of leucocytes increased to from 9000 to 20,000 per cubic millimeter 
(Hanot, Hayem). Disease of the kidneys and albuminuria are less 
frequently encountered than in the contracting form of cirrhosis. Gilbert 
and Fournier describe a thickening of the epiphysis of the lower arm and 
the leg in children, and claim that this lesion is due to the action of a 
toxin that is characteristic of this disease. As the disease progresses, 
the hemorrhagic diathesis develops; epistaxis, hemorrhages into the 
skin, the gums, or into the intestinal tract are seen; these hemorrhages 
are, however, not so conspicuous as in atrophic cirrhosis. 

The course of the disease is slow, with many ups and downs; the 
duration, after icterus has become permanent, is on an average four to 
five years, and sometimes ten to twelve. The patients can, therefore, 
follow their calling for a long period. From time to time, and often as 
a result of dietary indiscretions that cannot always be determined, the 
above-mentioned attacks of icterus and digestive disturbances set in. 
Toward the end of the disease icterus becomes more severe, the hemor- 
rhages recur with greater frequency. At the same time, a remittent type 
of fever may appear and death occur from general weakness, from some 
intercurrent complication, or from hepatargia or hepatic intoxication. 
In the latter case a slight decrease in the size of the liver may be noticed. 
In children * physical development is impeded, and the swelling of the 
spleen becomes particularly conspicuous. The terminal phalanges of 
the fingers and toes occasionally show drumstick enlargement, and 


* Gilbert and Fournier, Soc. de biologie, June 1, 1895. 


CHRONIC INFLAMMATION OF THE LIVER. 723 


sometimes the same changes are seen in the articular ends of the long 
bones of the lower extremity. 

The diagnosis cannot be made in the beginning of the disease; it 
resembles catarrhal icterus, which also shows a tendency to recurrence. 
If the enlargement of the liver persists, the diagnosis of cirrhosis becomes 
a probability. The uniform enlargement excludes neoplasms to a certain 
extent, but may be due to cirrhosis with fatty infiltration, to venous 
hyperemia, or to chronic biliary stasis. In cases of this kind the decision 
must be based upon the constant increase in the size of the liver, and 
upon the persistence of icterus without loss of color on the part of the 
stools. In other words, the diagnosis must depend essentially upon the 
course of the disease; the most significant symptoms are the early swelling 
of the spleen, and the absence of ascites. 

[A point of much interest in relation to the disturbance of general 
health in hypertrophic cirrhosis, and one that may possibly prove to be 
of some diagnostic value in various diseases of the liver, is that recently 
recorded by v. Jaksch.* This investigator found that the amido-acid 
nitrogen excreted in the urine in two cases of hypertrophic cirrhosis 
constituted a very abnormally large part of the total urinary nitrogen. 
This is not a wholly unexpected result, since such large amounts of leucin 
and tyrosin, and perhaps other amido-acids, are excreted in acute yellow 
atrophy and phosphorus-poisoning. The increase in the amido-acid 
nitrogen of the urine was naturally not confined to hypertrophic cir- 
rhosis; it was found in typhoid fever and diabetes insipidus also, but not 
in some other conditions of importance, as, for instance, nephritis.—ED. ] 

The prognosis is unfavorable, and a cure of the fully developed disease 
has never been known to occur. A slow course is, however, a relatively 
favorable one. It.seems on its face probable that the initial stages may 
be arrested and recovery sometimes take place, though this has so far 
never been determined by exact observation. 

Treatment.—In the beginning the treatment is that of gastric and 
intestinal catarrh, of catarrhal icterus, and of congestion of the liver. 
In the intervals a non-irritating diet and complete abstinence from 
alcohol are especially indicated. It is doubtful, however, whether good 
results can be expected from any treatment after the disease is once fully 
developed. The reports of good results have been recorded in cases in 
which cirrhotic fatty liver, etc., was not excluded. 

Iodid of potash and calomel are recommended in this disease; they 
are to be given in small doses (0.06, six times a day, Sacharjin) over a 
long period. 

It is possible that even in the advanced stages a purely symptomatic 
treatment, by helping to avoid exacerbations and too many attacks, 
may do some good. 


Ackermann: “ Virchow’s Archiv,” 1880, Bd. txxx, p. 396. 

Carrington: “ Observ. on the Occurrence of Fever with Cirrhosis,” “Guy’s Hospital 
Reports,” 1884, vol. xxvu. : 

Charcot: “ Maladies du foie,”’ 1877, p. 206. 

Charcot et Gombault: “ Archives de physiologie,” 1876. 

Duckworth: “ British Med. Journal,” January, 1892. 

Freyhan: “Virchow’s Archiv,” 1892, Bd. cxxvin, p. 20; “ Berliner klin. Wochen- 
schr.,”’ 1893, p. 746. 

Gilbert et Fournier: “La cirrhose hyp. chez l’enfant,” “Revue mens. d. Mal. de 
l’Enfance,” 1895, tome x11, p. 309. 


_* Zettsch. f. klin. Med., Bd. xivu, Hefte 1 u. 2. 


724 DISEASES OF THE LIVER. 


Goluboff, N.: “ Zeitschr. fiir klin. Medicin,” 1893, Bd. xxv, pp. 353-373. 

Hanot: “ Et. sur une forme de cirrhose hyp. du foie, ” Thése de Paris, 1876. 

— “Des différentes formes de cirrhose du foie,” « Archives générales de médecine,” 
1877, tome I1, p. 444. 

— “Cirrhose hyp. avec ictére chron.,” “ Archives générales de médecine,” 1879, tome 
I, p. 87. 

— et Schachmann: “ Archives de physiologie,’ ? 1887, tome I, p. 1. 

Hayem: “ Archives de physiologie,” 1874. 

Tien! “ Charité-Annalen,” 1880. 

Mangelsdorff: ‘“ Deutsches Archiv fiir klin. Medicin,” 1882, Bd. xxx1, pp. 522-603. 

Olivier: ‘“ Mém. p. servir a l’histoire de la cirrhose hyp., ” «TUnion médicale, TASiL, 
Nos. 68, 71, 75. 

Rosenstein, Stadelmann: “Verhandlungen des XI. Congresses fiir innere Medicin,” 
1892, PP. 65 and 90. 

Senator, H. : “Ueber atrophische und.hypertrophische Lebercirrhose, ” “ Berliner klin. 
Wochenschr. ” 1893, No. 51. 

Todd: “Abstract of a Clinical Lecture on the Chronic Contraction of the Liver,” 
“Med. Times and Gazette,’’ December 5, 1857, p. 571. 

Thue: ‘ Norsk Magazin,” 1892, p. 795. 

Vincenzo: ‘‘ Lo Sperimentale,” Sept., 1889; “ Jahresbericht,’’ 11, p. 298. 


CALOMEL IN THE TREATMENT OF HYPERTROPHIC CIRRHOSIS OF THE LIVER. 


Nothnagel: “ Internationale klin. Rundschau,” 1889, Nos. 49 and 50. 
Sacharjin: “ Klinische Abhandlungen,” Berlin, 1890. 
Sior: “ Berliner klin. Wochenschr.,’’ 1892, No. 52. 


In the preceding sections the pathologic pictures of atrophic and of 
hypertrophic cirrhosis have been delineated according to current views 
on this subject. The atrophic form has been known for a great many 
years, and the later stages are fully understood; what doubt exists relates 
to the initial stages. The hypertrophic form, however, has been known 
for only twenty years or so, and has only recently become generally 
recognized, chiefly through the studies of French authors. A certain 
amount of confusion has arisen from the endeavor of Charcot and Gom- 
bault to connect the lesions of the liver that are the result of simple 
stasis of bile with the disease that Hanot has described. Moreover, the 
fact that Hanot’s cirrhosis is not seen so frequently elsewhere as in 
France prevented many from recognizing the disease as a clinical entity. 
There can be no doubt, however, that the disease called cirrhose hyper- 
trophique avec ictére is clinically and anatomically different from atrophic 
cirrhosis. At the same time, both have in common the development of 
connective tissue that for a long time was considered characteristic only 
of the atrophic form of the disease. 

In order to clear up some of the doubtful points the tables appended 
below have been constructed (see page 725), and the points in the differen- 
tial diagnosis have been contrasted. Every attempt at classification, 
however, is weak when considered from a pathologic standpoint; there 
is a tendency to consider only the extremes, and by neglecting transition- 
forms to overemphasize extreme cases and to emphasize in an improper 
manner their peculiarities, with a total neglect of the transitional forms. 
Outside of France the contrast and the identity of the two diseases has 
not been so fully recognized; even in France, Dieulafoy, by formulating 
the picture of mixed cirrhosis, has attempted to do full justice to the 
actual facts of the case. 


Eiehhorst * has recently described such a mixed case; there was a great devel- 
opment of connective tissue that was in part multilobular, containing few cells; in 


* Eichhorst, Virchow’s Archiv, 1897, Bd. cxtvm, p. 339. 


_ CHRONIC INFLAMMATION OF THE LIVER. 


part monolobular, containing many round-cells. 


725 


The liver-cells themselves were 


unchanged and neither icterus not ascites was present. 
There is a disease among New Foundlanders that can be included in this category 


of mixed cirrhoses. 


These people eat large quantities of mussels (5 to 10 kg. in a 
day) and a certain disease of the liver seems to be the result. 


It begins as hyper- 


trophic cirrhosis with icterus, and finally leads to atrophy with terminal hemor- 
rhages.* It is possible that mytilitoxin (a poison isolated by Brieger) plays a cer- 


tain réle in this connection. 


[Jakowleff + reports an interesting case of mixed cirrhosis, as does also Ullmann.t{ 


The latter ran a fatal acute course. 


At the present time the mixed form of cirrhosis 


is not looked upon as a rare occurrence.—Eb.] 


ATROPHIC CIRRHOSIS. 

Liver somewhat enlarged (?) in the be- 
ginning; later contracted. 

Connective-tissue proliferation begins 
between the lobules extralobular, in- 
terlobular, penetrates the lobules only 
in the later stages. 

It surrounds the lobules in an annular 
or capsular arrangement. 

The nodules, inclosed by connective tis- 
sue, are multilobular, rarely mono- 
lobular. 

The boundary between glandular and 
connective tissue zs distinct. 

The connective tissue is more tough, 
cicatricial, contractile. 


- The _ connective-tissue __ proliferation 
starts: 
from interlobular branches of the 


portal vein (Hanot) (venous cirrhosis) ; 
from the interlobular branches of the 
portal vein and the central venules 
(bivenous cirrhosis) (Sabourin) ; 

from the capillaries of the hepatic 
artery (Ackermann). ' 
“New-formed bile-channels” within 
the connective tissue are always 
present ; 


The capillaries of the liver lobules can- . 


not be well injected or cannot be in- 
jected at all from the portal vein; 

Liver-cells involved early in the disease, 
show fatty degeneration; gradually 
disappear. 


ANATOMY. 


HYPERTROPHIC CIRRHOSIS. 
Liver permanently much enlarged. 


Connective-tissue proliferation enters 
the lobules from the very beginning, is 
both extralobular and intralobular. 

It is “insular,’”’ and starts from certain 
points within the lobules. 

The nodules are monolobular. 


Boundary 7s not distinct. 


The connective tissue is more delicate, 
retains its nuclei for a longer time; 
resembles that of elephantiasis. 


from interlobular bile-channels (peri- 
angiocholitis) “biliary cirrhosis” — 
more correctly, cholangic cirrhosis 


(Q.); 


more abundant; 


can be well injected from the portal 
vein. 
Liver-cells remain intact for a long time. 


CLINICAL SYMPTOMS. 


ATROPHIC CIRRHOSIS. 
Liver 
smaller than normal, 
usually granular. 


Icterus 
absent or slight. 


* Segers, Semaine Med., 1891, p. 448. 


Pa Minch. med. Woch., Mar. 26, 1901. 


HYPERTROPHIC CIRRHOSIS. 


enlarged permanently, 
of great size, granula- 
tion indistinct. 


very distinct from be- 
ginning to end. 


MIXED CIRRHOSIS. 
(Secondary Contracted Liver.) 
permanently enlarged 
(contraction only mani- 
fested by symptoms of 
stasis in the portal 
system). 


absent or slight. 


+ Deutsche med. Woch., Nov. 18, 1894. 


726 DISEASES OF THE LIVER. 


CuinicaL Symproms.—(Continued.) 


ATROPHIC CIRRHOSIS. 


HYPERTROPHIC CIRRHOSIS. 


MIXED CIRRHOSIS. 


Ascites (Secondary Contracted Liver.) 
considerable. absent. (Sometimes develops gradually, not 
appears toward the end, considerable. 
but is slight.) 
Spleen 
usually enlarged. always much enlarged. enlarged. 
Hemorrhages ; 
hemorrhagic diathesis, hemorrhages seen also 
chiefly in stomach and in other locations. 
intestine. 
Onset 
imperceptible. repeated gastricattacks. 
Duration 
at most, 2 or 3 years. 5 or 10 years. 3 or 4 years. 
Death 


from complications or 


usually from hemor- 
from hepatargia. 


rhages in the _ portal 
area. 

Complications 
contracted kidney, rela- 
tively often peritoneal 


very rare. 


tuberculosis. 

Occurrence 
usually after the for- usually before the for- 
tieth year. tieth year. 

Alcohol 


not generally recog- 
nized as a_ frequent 
cause. 


a very frequent cause. 


If those cases of cirrhotic liver are excluded that develop in a latent 
manner, and that are not seen until the stage of atrophy with ascites, 
we shall find that a great many cases are left that show considerable 
variations in their course and in the anatomic changes that are found 
after death. The chronic process is seen not only in the interstitial 
tissues, but also in the parenchyma, and may attain different degrees 
of severity. In many cases other organs than the liver will be found to be 
involved; these, in their turn, exert a certain influence on the liver 
and on the general health of the patient. For all these reasons the 
so-called mixed forms of cirrhosis of the liver vary greatly, both anatomic- 
ally and clinically; they have the negative characteristic in common, 
however, that they are examples neither of Laennec’s atrophic cirrhosis, 
nor of typical Hanot’s hypertrophic cirrhosis. It should also be remem- 
bered that the latter is not the only form of hepatic disease that can 
cause enlargement of the liver; fatty infiltration, hyperemia from stasis, 
possibly, also, certain processes of regeneration, may all cause an en- 
largement of ‘the liver, though the atrophic form of cirrhosis may be 
present (see case of Hardt, for instance, on page 710). 

Thus it is seen that any and every classification of the different 
cirrhoses is somewhat forced; the only value of the different subdivisions 
consists in a certain clearness obtained and a general diagrammatic 
summary of the most important etiologic and anatomic points in the 
different forms. 


With this object in view the following classification of Chauffard may be given ; 
it is both anatomic and etiologic: 


CHRONIC INFLAMMATION OF THE LIVER. 727 


CIRRHOSES. 


I, VASCULAR? 


1. from ingested poisons, 
2. from autochthonous poisons; 
1. direct microbic infection, 


(a) toxic 


(b) infectious local, 


. hematogenous infection extra hepatic; 


a ain 
bo 


1. from arteriosclerosis, 
(c) dystrophic. 2. from venous stasis, 
3. (from portal phlebitis should be added). 


II. Bruiary: 
(a) from retention of bile; 
(b) from radicular angiocholitis 

III. CapsuLaR: 


(a) from chronic localized perihepatitis ; 
(b) from chronic general perihepatitis. 


Simmonds (and Heller) distinguish three groups, and divide them according 
to anatomic peculiarities: 

1. Cirrhosis: interlobular proliferation, early inclosure of lobules and groups 
of lobules; boundaries between connective tissue and liver-cells indistinct; 

2. Induration: interlobular proliferation without tendency to constriction (this 
form often follows malaria owing to the stasis of blood and of bile); 

3. Diffuse fibrous hepatitis: uniform interlobular and intralobular proliferation 
of connective tissue (heréditary syphilitic liver). 

Even these groups occasionally originate from the same cause and may develop 
from one another. 


It may be well to discuss certain distinct groups of cirrhotic diseases 

of the liver that can be differentiated clinically, anatomically, and 
etiologically. These forms of “special cirrhosis” are not altogether 
different from one another nor are they altogether different from 
the two principal types described. The differentiation is given for 
other reasons, and is, to a large extent, evolved from our ignorance 
of the true significance of the different groups. The groups are: 
(1) Cirrhosis from stasis of bile; (2) cirrhosis from stasis of blood; 
(3) tuberculous interstitial hepatitis; (4) cirrhose graisseuse; (5) hepatitis 
interstitralis flaccida; (6) malaria liver; (7) pigmentary cirrhosis of dia- 
betes; (8) syphilitic hepatitis. 


J. CIRRHOSIS FROM STASIS OF BILE. 


Cirrhosis biliaris. 


The French distinguish two forms of biliary cirrhosis: the one, cirrhose 
biliare hypertrophique (Hanot), caused by disease of the small _bile- 
passages, and a cirrhose biliare calculeuse accompanied by sclerotic 
thickening of the large bile-ducts. This classification is not justified, 
however, and is confusing for several reasons; above all, because the 
word “ biliare”’ in the one case is used to designate the bile as the disease- 
producing agent, and in the other to designate the anatomic significance 
of the bile-passages in the pathologic picture. 

In “hypertrophic” cirrhosis, in any event, the walls of the bile- 
passages are thickened. In case the disease really starts from these 
canals, as the French seem to believe, this form should be called cirrhosis 
of the bile-passages, cirrhosis cholangica. Cirrhosis biliaris is that form 
of cirrhosis that originates from stasis of bile; the fact that this stasis 


728 DISEASES OF THE LIVER. 


leads to thickening of the walls of the bile-passages is unimportant; 
the chief and most important factor is the action of the bile itself upon 
the substance of the liver. Cirrhosis is produced by this chemical 
irritation. 

Icterus, which is common to both forms of cirrhosis, establishes 
merely a semiotic relation between them, but does not bring them into 
pathogenetic relation, owing to the fact that the origin of icterus is 
different in each case. The atrophic form may also occasionally be 
accompanied by icterus. 

We have already described the anatomic changes that are brought 
about in the liver by the action of the bile (see pages 428, 686). Rabbits 
and guinea-pigs do not bear experimental stasis well, dogs and cats 
bear it comparatively well; in man it is borne fairly well, as in the second 
group of animals, though there are individual differences in susceptibility. 

The parenchymatous cells in the marginal zones of the liver undergo 
focalized necrosis and are separated by connective tissue; in the finer 
bile-passages epithelial desquamation and cellular infiltration are seen. 
In the larger bile-passages a thickening of the walls can also be noted, 
but the disease does not, as the French claim, start from these ducts; 
the primary focus must be sought within the numerous affected areas 
of liver-cells that can only be recognized microscopically. 

The most frequent cause for persistent stasis of bile is occlusion of 
the efferent ducts by gall-stones; it is not, however, the only cause; 
narrowing of ducts by carcinomata or by cicatrices may also lead to 
chronic stasis and to connective-tissue hyperplasia, as I have myself 
been able to demonstrate. The French designation of cirrhose bilaire 
calculeuse is therefore not the proper one. 

An important point in occlusion of bile-passages and stasis in chole- 
lithiasis is the fact that occlusion varies in degree and is frequently not 
complete, so that infection of the ducts by intestinal bacteria is rendered 
possible. The frequent presence of suppurative complicating processes 
demonstrates the frequency of this occurrence. Interstitial proliferation 
may be favored by the presence of bacteria; at the same time interstitial 
change may and does occur independently of the action of germs, as 
has been demonstrated by a number of careful animal experiments. 

In the majority of cases the interstitial proliferation remains without 
influence upon the clinical course of the disease. The condition is 
recognized on microscopic examination of the liver, but the atrophy 
of the parenchyma due to the influence of the bile is much more im- 
portant. The clinical picture is that of chronic cholemia and hepatargia; 
toward the end there is an exaggeration of the auto-intoxication. It 
cannot be shown that the interstitial proliferation exercises any influence 
on the course of the disease. 

In exceptionl cases only, that last from two to three years, granula- 
tion of the interstitial tissue is seen, and sometimes, in rare cases, a 
reduction in the size of the liver. In such cases the picture of atrophic 
cirrhosis with ascites and swelling of the spleen develops, modified 
however, by severe icterus and complete decoloration of the feces (Litten, 
J anowski). 


The microscopic appearance of the liver in a case of this kind differs in no 
respect from that of ordinary contracted liver. We see the same fibrous strands 
of connective tissue compressing the acini and ik coat them into single acini 


CHRONIC INFLAMMATION OF THE LIVER. | 729 


or into groups. Within the new tissue are the ‘newly formed bile-ducts” the 
interlobular branches of the portal vein have thickened walls and are not permeable 
(Litten). 


The essential difference lies in the appearance of icterus at the earliest 
stage of the disease; as a rule, some symptoms of gall-stones will be 
elicited from the history. 


According to v. Fragstein, icterus may disappear as soon as the stone has passed ; 
the diagnosis in the case described by him is, however, not a clear one. 


In cases in which the liver remains enlarged gall-stone cirrhosis 
to a certain extent resembles “hypertrophic cirrhosis.” In the former 
condition, however, the development of icterus is much more rapid, 
sometimes sudden, and the duration of the disease is shorter (two or 
three years, as against five and more in the hypertrophic form). Icterus 
is, as a rule, more intense in gall-stone cirrhosis, the stools are devoid 
of color, and ascites is present. The liver, too, is only moderately en- 
larged and decreases in size during the course of the disease; the reverse 
is the case in hypertrophic cirrhosis. 

Treatment, apart from that which is purely symptomatic, should 
be directed against the stasis of bile. As soon as we are convinced of 
the formation of connective tissue and of the development of atrophic 
changes in the liver following chronic stasis of bile, we should attempt 
a prophylaxis of these lesions by operative measures. The calculi 
should be removed, if possible; if not, a fistula should be made from 
the gall-bladder through the skin or into the intestine. 


Brissaud, E., et Sabourin,Ch.: “ Deux cas d’atrophie du lobe gauche du foie d’origine 
biliaire,”’ ‘ Archives de physiologie,’”’ 1884, tome 1, pp. 345, 444. 

v. Fragstein: ‘“Cholelithiasis als Ursache von Cirrhosis hepatis,” “ Berliner klin. 
Wochenschr.,”’ 1877, pp. 209, 229, 264. 

Janowski: “Beitrag zur pathologischen Anatomie der biliiren Lebercirrhose,”’ 
Ziegler’s “ Beitrige zur pathologischen Anatomie,” 1892, Bd. 1, p. 344. 

Liebermeister: “‘ Beitrag, etc., Leberkrankheiten,” 1864, p. 135. 

Litten: ‘Ueber die biliare Form der Lebercirrhose und den diagnostischen Werth 
des Icterus,”’ “ Charité-Annalen,”’ 1880, p. 173. 

Mangelsdorff, J. : ‘‘ Ueber biliare Lebercirrhose” (numerous references to literature) 
“Deutsches Archiv fiir klin. Medicin,’”’ 1882, Bd. xxx1, p. 522. 

Raynaud et Sabourin: “Un cas de dilatation énorme des voies biliares,” etc., ‘ Ar- 
chives de physiologie,”’ 1879, p. 37. 

Simmonds, M.: ‘‘ Ueber chronische interstitielle Erkrankungen der Leber,” ‘‘ Deut- 
sches Archiv fiir klin. Medicin,’” 1880, Bd. xxvut, p. 73. 

Smith, Hingleton, R.: “Case of Acute Biliary Cirrhosis Clinically Simulating Acute 
Yellow Atrophy of the Liver,” “ British Med. Journal,’’ Jan. 19, 1884. 


2. CIRRHOSIS FROM STASIS OF BLOOD. 


Cirrhose cardiaque. 


In discussing hyperemia of the liver from stasis we have already 
called attention to the fact that the proliferation of connective tissue 
that occurs in the vicinity of the hepatic veins and the central veins. of 
the lobules may occasionally involve the interlobular spaces, and in 
this manner lead to a constricting cirrhosis with narrowing of the portal 
circulation. From these lesions the picture of atrophic cirrhosis with 
ascites from stasis may develop; this may either be added to the general 
picture of cardiac insufficiency or it may overshadow this condition 
completely. 


730 DISEASES OF THE LIVER. 


According to Sabourin, a similar form of cirrhosis from stasis of blood can 
be caused by alcohol. It may start from the hepatic veins; it is said to appear in 
combination with fatty liver. 


We wish to again emphasize the fact that in cirrhosis of other organs 
than that under discussion, particularly the cirrhosis from alcoholism, 
_ the heart may be damaged at the same time as the liver, and in this 
way the microscopic picture of connective-tissue hyperplasia be modified, 
and a swelling, followed by a reduction in the size of the liver, be pro- 
duced during the life of the patient. 


Liebermeister: “ Beitrag zur pathologischen Anatomie und Klinik der Leberkrank- 
heiten,”’ Tiibingen, 1864. 

Curschmann: “ Zur Diagnostik der mit Ascites verbundenen Erkrankungen der 
Leber und des Peritoneums,”’ “ Deutsche med. Wochenschr.,” 1884, p. 564. 

Rumpf, H. (Giessen): ‘‘ Ueber die Zuckergussleber,’’ ‘‘ Deutsches Archiv fiir klin. 
Medicin,” 1895, Bd. Lv, p. 272. 

Pick, Fr.: ‘“ Pericarditische Pseudolebercirrhose,” ‘ Zeitschr. fiir klin. Medicin,”’ 
1896, Bd. xxix, p. 385. 


3. TUBERCULAR INTERSTITIAL HEPATITIS AND TUBERCULOSIS 
OF THE LIVER IN GENERAL. 


Secondary tuberculosis of the liver is a very common condition. It 
is always seen in general tuberculosis, the organ probably becoming 
infected through the blood of the hepatic artery. The foci are situated 
within the lobules, are very small, and are often recognizable by means 
of the microscope only. In chronic tuberculosis, particularly of the 
intestine, the liver is often involved; here infection occurs via the portal 
vein. 

Occasionally no inflammation is to be seen around these little foci; 
sometimes punctiform hemorrhagic spots are seen. If the process con- 
tinues for some time, small nodules are formed by interstitial infiltration 
and the development of connective tissue. If the primary foci are very 
numerous, a form of cirrhosis is produced that resembles diffuse hepatitis, 
and which, according to its origin from single foci, should be called 
“insular” (after the French type). At the same time the disease is 
“diffuse,” as it is not limited to the interlobular spaces, but also involves 
the lobules. 

New formation of bile-passages also occurs in this form of interstitial 
hepatitis. There is less tendency to contractions than in ordinary 
cirrhosis, for the reason that death ensues before high degrees of con- 
traction can develop. 

It is clear from the frequency of tuberculosis that a liver which is 
cirrhotic from some other cause than tuberculosis may be infected 
secondarily in very many cases; thus tuberculosis of the liver com- 
bined with cirrhosis may be found under these circumstances. 

Cheesy nodules of the size of a pea or a hazelnut are frequently seen, 
though not as often as miliary tubercles; the former start from the 
interlobular tissues in the. form of a periangiocholitis (Simmonds) and 
lead to the formation of small cavities containing a grumous, bile-tinged 
substance. It is possible that in these cases infection starts from the 
bile-passages, or from the lymph-vessels, whereas, in general, infection 
occurs through the blood. 


v. Lauth calls particular attention to the fatty infiltration of the liver-cells 
in the peripheral parts of the lobules. This condition is so frequently seen that 


CHRONIC INFLAMMATION OF THE LIVER. 731 


its connection with tuberculosis is doubtful, and is probably a result of the general 
phthisical dyscrasia (toxins). This is especially probable as Lauth does not make 
a clear differentiation between real tuberculosis of the liver and the fatty liver 
of a tubercular case. According to Pilliet, coagulation necrosis of the liver-cells 
is seen in addition to fatty degeneration. 


In cases in which the liver and the peritoneum are both found to 
be tubercular, the suspicion is justified that they have both become 
infected from some other organ; in rare instances the tubercular process 
may involve the liver of the peritoneum. 


Tuberculosis of the liver has been thoroughly studied in animals, both experi- 
mentally and in chance observations. The histologic picture of spontaneous 
_tuberculosis varies with the species; that of experimental tuberculosis according to 
the method of inoculation and the dose. In general, inoculation-tuberculosis runs 
a-more acute course and produces diffuse interstitial inflammation, and, in the 
case of the guinea-pig, circumscribed necrosis of the liver parenchyma. 


Symptoms.—Clinically, tuberculosis of the liver is unimportant. In 
cases of serious involvement of the liver the function of the organ, and 
even the general metabolism, may be perverted; but the symptoms of 
liver infection cannot be distinguished and differentiated from the 
general pathologic picture. In some instances the appearance of icterus 
may point to an involvement of the liver (A. Frankel). 

It is said that occasionally a painless form of ascites develops (E. 

Wagner). In children with acute miliary tuberculosis Wagner saw 
enlargement of the liver and sensitiveness to pressure, and considers 
these symptoms of value in the diagnosis of tuberculosis of the liver 
and of general tuberculosis. 
' Whether tuberculosis of the liver is really capable of producing 
cirrhosis, with contraction and subsequent symptoms of stasis, is doubt- 
ful, although Hanot and his school claim that this can occur. In the 
majority of the cases of this kind there was probably a cirrhosis of some 
other origin with secondary tubercular infection. 


: Hanot and Gilbert, in addition to latent tuberculosis, distinguish the following 
orms: 
1. Acute: Fatty hypertrophic tubercular hepatitis. 
2. Subacute: 
(a) Fatty tuberculous hepatitis which is atrophic (or without hypertrophy). 
(b) Nodular parenchymatous tubercular hepatitis. 
3. Chronic: 
(a) Tubtrculous cirrhosis, 
.(b) Fatty tuberculous liver. 
In the latter form the tubercles of the liver may be completely absent. 


TUBERCULOSIS OF THE LIVER. 


Arnold: “ Ueber Lebertuberculose,” “ Virchow’s Archiv,” 1880, Bd. Lxxxu, p. 377. 

Brieger, L.: “ Beitrag zur Lehre von der fibrésen Hepatitis,” ‘‘Virchow’s Archiv,” 
1879, Bd. Lxxv, p. 85. 

Frankel, A.: “ Klinische Mittheilungen itiber Lebertuberculose,” “ Zeitschr. fiir klin. 
Medicin,” 1882, Bd. v, p. 107. 

Hanot et Gilbert : “Sur les formes de la-tuberculose hépatique,”’ “ Archives générales 
de médecine,”’ 1889, tome 11, pp. 513-521. 

Lauth, E.: “ Essai sur la cirrhose tub.,”” Thése de Paris, 1888. 

MacPhedran et Caven: “ Diff. tub. hepatitis,” “American Med. Journal,” May, 1893; 
“ Jahresbericht,’”’ 1, p. 273. 

Pilliet: “Cirrh. tub. et la tub. diffuse dans le foie,” “ Progres médicale,’ 1892, No. 
3; “Jahresbericht,”’ 11, p. 193. 

— “Cirrhose nécrotique hypertrophique,’”’ “ Mercredi méd.,” 1892, No. 4; “ Jahres- 
bericht,” 11, p. 195. 


732 DISEASES OF THE LIVER. 


— “Et. sur la tub. expér. et spontanée du foie,” Thése de Paris, 1891. 
Wagner, E.: ‘Die acute miliare Tuberculose der Leber,” “ Deutsches Archiv fiir 
_ klin, Medicin, a 1884, Bd. xxxiv, p. 534. 


TUBERCULOSIS OF THE GALL-PASSAGES. 


Simmonds: “ Deutsches Archiv fiir klin. Medicin,” 1880, Bd. xxvu, p. 452. 
Tublet, L.: “Thése de Paris, 1872. 
Sabourin: “Archives de physiologie normale et pathologique,” 1883. 


4, CIRRHOSIS ADIPOSA; CIRRHOSE GRAISSEUSE, 


French authors, and first Hutinel and Sabourin, have distinguished 
a form of cirrhosis of the liver in which there is interstitial proliferation 
and fatty infiltration of the liver-cells; this disease they called cirrhose 
graisseuse (cirrhose avec stéatose). The liver is enlarged, and for this 
reason there is distinguished cirrhose graisseuse atrophique and hyper- 
trophique. It is found in alcoholics, and in tuberculous cases, some- 
times in combination with tuberculosis even of the liver itself. Some 
claim that the fat is present as a result of infiltration; others that it is 
the result of fatty degeneration. 

It appears to me that to emphasize this form of the disease is con- 
fusing. In the majority of cases we are dealing with cirrhosis and 
fatty infiltration, in which the latter condition appears first or in rare 
cases only after the cirrhosis. Alcoholism may produce both processes; 
phthisis of the lung may lead to fatty liver; tuberculosis of the liver 
to interstitial proliferation, and (according to Lauth) to fatty infiltration. 

Hanot, Hérard, Dalché, and Debove, have described cases that are 
altogether different, in which the cirrhosis of the liver was far advanced. 
Subsequently fatty degeneration of the cells occurred and, as a result, 
a diminution in the size of the organ. Death occurred in from four to 
six months; these were cases, therefore, of chronic interstitial hepatitis 
followed by subacute parenchymatous inflammation and death from 
atrophy. 

Blocq and Gillet, finally, include under the category of cirrhoses 
graisseuses certain cases that run a still shorter course of five or six 
_ weeks, which they attribute to infection. These cases must be regarded 
as acute parenchymatous and interstitial hepatitis. _[Eichhorst * cites 
a case in which the patient died in two days from the onset pf the evident 
disease. At the autopsy an old multilobular hepatic cirrhosis was found, 
to which had lately been added a monolobular condition, with an 
enormous increase of small bile-ducts. The hepatic lymph-glands, and 
also the parotid gland were enlarged and inflamed.: The case appears 
to have been one of acute autoinfection in which the low type glandular 
structures (parotid) were more seriously affected than the higher (liver). 
No jaundice was present.—ED. ] 


Hutinel: “ Et sur quelques cas de cirrhose avec stéatose du foie,” “ France médicale,’’ 
1881. 


Sabourin: “Sur une variété de cirrhose hypertr. du foie,’ “ Archives de physiologie 
normale et pathologique,” 1882, p. 584. 

Hanot, V.: “Sur la cirrhose atrophique 4 marche pastes ” “ Archives générales de 
médecine, ”? 1882, 1, p. 641; 11, p. 33, und 1883, tome cL, p. 33. 

Dalché et Lebreton : “ Cirrhose atrophique & marche rapide, ” Gazette médicale de 
Paris,” 1883, No. 26. 


* Virchow’s Archiv, Bd. cxivi, H. 12, 1898. 


CHRONIC INFLAMMATION OF THE LIVER. 733 


Hayem et Girandeau: “Contrib. & l’étude de la cirrhose hyp. gr.,” “Gazette heb- 
domad.,’”’ 1883, No. 9. 

Hérard : “ Cirrhose hypertr. graisseuse &4 marche subaigue,”’ “Gazette des hépitaux,” 
1884, No. 67; “Jahresbericht,” 1, p. 201. 

Bellanger, G.: “ Etude sur la cirrhose graisseuse,” Thése de Paris, 1884. 

Gilson, H.: “De la cirrhose alcoolique graisseuse,’’ Thése de Paris, 1884. 
For further discussion and references to literature see Lauth, Thése de Paris, 

1888, p. 15.) 

Debove: “De. la cirrhose aigué do foie,’ “Gazette hebdomad.,” 1887, No. 30; 
“ Jahresbericht,”’ 11, p. 278. 

Blocq et Gillet: ‘ Des cirrhoses graisseuses considérés comme hépatites infectieuses,”’ 
“ Archives générales de médecine,” 1888, tome 11, p. 60-181. 

Carpentier : “Cirrhose hépatique,” “ Presse médicale belge,” 1888; “ Jahresbericht,” 
II, p. 286. 


5. HEPATITIS INTERSTITIALIS FLACCIDA. 


Italian authors have described certain cases under the above name 
in which proliferation of the interstitial tissue occurred and the liver 
decreased in size, at the same time becoming soft, flaccid, and tough. 
It is very questionable whether this striking condition of the liver is 
always produced by the same causes. 


In the case of Ughetti, a sulphur-worker of seventeen suddenly developed 
fever and a swelling of the liver two months before death; the abdomen was en- 
larged, the liver small; there was ascites, and swelling of the spleen. Death occurred 
in stupor. The liver was reduced one-third; yellowish mottled; there were red 
and brown portions and the whole organ was softer than normal. The. surface 
was granular. Microscopically vascular connective tissue was seen, young and 
containing many nuclei; this isolated the liver-cells into lobules of various sizes, 
and even forced its way into the lobules. The hepatic cells were degenerated and 
contained fat and bile-pigment. The spleen was eight times larger than normal. 
Alcohol and malaria could be excluded. 

This case is differentiated from ordinary cirrhosis by the subacute course and 
the character of the connective tissue. The latter is embryonal, as in still another 
case described by Mazzotti in a young woman. It is stated, however, that in the 
latter case and in the case reported by Galvagni the clinical picture of cirrhosis 
was present; in the last case the liver was particularly reduced in size (870 g.) and 
pale yellow in color; the acini were rounded or oval instead of polygonal. It is 
Romeo: that in these cases an exceptionally wide-spread degeneration of parenchyma 
occurred. 


Galvagni, E.: “Sopra un caso singolarissimo di epatite interstitiale flaccida,” “ Riv. 
clin. di Bologna,” Nov., 1880. 

Ughetti: “ Archivio medico italiano,’ 1882, 1, p. 444. 

Mazzotti: “ Riv. clin. di Bologna,” 1883, No. 6. 


6. MALARIAL LIVER. 


In the type of malaria noted in Germany the liver does not seem 
to be markedly involved, and anatomic changes are hardly to be dis- 
covered in the organ. Formerly when malaria was more severe than 
it appears to be nowadays, and occurred more frequently, such lesions 
of the liver were occasionally seen. The formation of pigment in the 
blood and its deposition in the various organs, particularly the liver, 
were recognized and closely studied fifty years ago by Frerichs. The 
severe forms of malaria are to-day found only in Mediterranean countries 
and in the tropics. French and Italian physicians have, as a conse- 
quence, contributed most largely to our knowledge of these diseases. 

Acute malaria leads to the formation of pigment within the plas- 
modia, and the more severe the infection, the more pigment is formed. 


734 DISEASES OF THE LIVER. 


It is dark-brown in color and is called melanin. This pigment circulates 
in the blood, and within the leucocytes in the spleen and in the liver 
capillaries, also in the brain and the kidneys. In the liver it is found 
in leucocytes that are situated at the peripheral parts of the capillary 
lumen, and here it often leads to the formation of capillary thromboses 
or of large flakes of pigment. In addition, Kelsch and Kiener have 
described a rust-colored pigment occurring in granules or in little heaps, 
that are found in the center and at the margin of the lobules. If much 
of this pigment is present, the liver assumes a brown color that is per- 
ceptible to the naked eye; and if melanin is present at the same time, 
a dirty-grayish color. 

The older granules of this pigment give microchemic tests for iron, 
turning a blackish-green upon the addition of ammonium sulphid; the 
malaria pigment, melanin, on the other hand, is colored orange by am- 
monium sulphid and later is decolorized. Sometimes the nuclei of the 
capillaries are increased in number, and the beginning of hypertrophy 
of the liver can be seen. In severe, acute cases the liver is very vascular, 
and the excretion of bile-pigment abundant. 


Dock observed a dark green color of the liver in a fatal case of malaria of seven 
days’ duration. There were present microscopic foci of interstitial inflammation 
and (separated from these) necrotic foci in which the protoplasm was cloudy and 
the nuclei could not be stained. In the interacinous capillaries granules of pigment 
were seen. Barker, too, has pictured necrotic foci of this kind. 


The clinical manifestations of involvement of the liver in malaria 
are icterus of mild degree, bile-tinged vomit, and diarrhea, painful swelling 
of the liver, and a dark color of the urine. 

In certain forms of tropical malaria, particularly in the form of 
blackwater fever seen in Kamerun, the urine contains dissolved blood- 
corpuscles and hemoglobin during the attack; icterus is also present. 

[There is considerable discussion at the present time as to the origin 
of the pigment in blackwater fever. Karamitsao * and others believe 
that the process is entirely the result of the malarial poison. Koch, on 
the other hand, holds that blackwater fever is nothing more or less than 
a malarial infection to which quinin intoxication has been superadded. 
Sambon f{ believes that the blackwater fever and the quinin have no 
connection as cause and effect, but that coincidence is alone responsible. 
It would appear that Koch’s theory of quinin-poisoning was gaining 
ground, and that the pigment deposit is the result of the injurious action 
of quinin rather than of the malarial toxin.—Eb.] 

The changes of the liver in chronic malaria are more pronounced 
and more conspicuous. The liver is not only hyperemic, but also en- 
larged, owing to an increase in the bulk of the parenchyma. The weight 
of the organ may be from 2000 to 3000 gm.; perihepatitis is often seen. 
Microscopically it will be found that the columns of liver-cells are in- 
creased to twice their normal thickness, and that the cells are enlarged 
and cloudy with large nuclei and mitoses. In the periphery of the 
lobules are seen granules giving the iron reaction; in the capillaries, 
masses of leucocytes and large polymorphous cells are seen containing 
brown iron pigment that probably comes from the spleen; the periportal 
tissues, too, are swollen, nucleated, and contain pigment. 

This initial stage may develop in different ways as follows: 


* Wien. med. Woch., Nov. 3, 1900. t Practitioner, Mar., 1901. 


CHRONIC INFLAMMATION OF THE LIVER. 7395 


It may retrogress and lead to ischemic atrophy. In these cases 
the liver is small (700 to 1300 gm.), solid, the cut surface is smooth, light 
brown, or gray; the liver-cells are small and filled with pigment, their 
nuclei do not stain well; the tissues are dry and contain little blood; 
the bile is scanty and light in color; there is only aslight thickening of 
the connective tissue, the latter is also true with regard to the capillaries. 
melanotic pigment may sometimes be found in the spleen. It is 
difficult to inject the capillaries through the portal vein. 

In another class of cases Kelsch and Kieners hépatite parenchymateuse 
nodulaire is seen; here the liver is enlarged (to 4000 gm.), soft, and covered 
with little nodules that are visible on the surface and on cross-sections. 
The latter may be as large as a millet-seed or even as large as a pea; 
-and are distinguished by their whitish, golden-yellow color or by a 
greenish tint, and are very conspicuous objects against the red back- 
ground of the parenchyma. Within these nodules the columns of 
liver-cells will be found to be thickened to four times their normal size; 
the cells are cloudy with a large nucleus or with three or four nuclei; 
the proliferation of the cells displaces the peripheral trabeculz and 
flattens them out. The center of each one of these nodules corresponds 
to an interlobular space and the branches of the hepatic vein are found 
in their periphery; in other words, the normal arrangement of the lobule 
appears to be inverted. 

Many leucocytes are also found in the capillaries and in the nodules; 
there is thickening of the walls of the smaller bile-passages, stasis of 
bile, and yellow coloration of the cells, and the formation of microscopic 
concretions. If several of the nodules unite, peculiar structures may 
be formed that look like concrements; in these colloid or fatty degenera- 
tion may occur or they may assume the character of neoplasms; 2. e., 
of true adenomata. 

Thirdly, interstitial hepatitis may develop from the initial stage of 
hyperemic-parenchymatous swelling of the liver, which, starting from the 
interlobular spaces, assumes the ordinary type of cirrhosis. As in this 
type of the disease, certain areas of the liver are surrounded by con- 
nective-tissue strands and become isolated; these “granules” cover 
the surface of the organ, are visible to the naked eye on the surface on 
cross-section, and may be of varying size. : 

These three forms of development, simple atrophy, nodular hyper- 
trophy, and cirrhosis, may be seen side by side in the same organ, and 
in this manner very peculiar pictures are created. The volume of the 
organ may be reduced, normal, or it may be greater than usual. It is 
possible to differentiate the hyperplastic nodules from the granules of 
hypertrophic cirrhosis by the appearance of their nuclei; in the former 
the nuclei are sometimes larger, sometimes smaller, than normal, are 
irregularly distributed, and are often multiple in the single cell. In 
cirrhosis the hyperplastic nodules frequently undergo degeneration and 
atrophy. _"" 

The causes for these various forms of development of malaria-liver 
are not understood. The presence of iron pigment in the liver has 
nothing to do with it, since cases are seen in which there are great accu- 
mulations of pigment and still no parenchymatous changes or connective- 
tissue hyperplasia are observed. On the other hand, nodular hyperplasia 
of the liver and cirrhosis are often seen in the absence of pigment. It 
appears, therefore, that the accumulation of pigment in the liver and 


736 DISEASES OF THE LIVER. 


the spleen is not a necessary sequel of malarial intoxication, and that 
._ the pigment is only deposited under stated conditions after it is liberated 
from the blood-corpuscles. Further, the serious lesions of the liver 
seem to be caused by some other agent, either by the direct action of 
the plasmodia, by certain poisons, or by pigment emboli. 


The iron of the liver is often found increased to such a degree that its presence 
can be detected by chemical methods; this occurs in a variety of chronic diseases, 
and is most pronounced in pernicious anemia, a condition that is probably due 
to some miasmatic or toxic influence acting upon the blood. When I described 
this condition, siderosis, for the first time, particular attention was called to. the 
fact that the iron reaction with ammonium sulphid is frequently not found in the « 
rust-colored particles within the liver, but whether present or not it is always 
obtained with the colorless portions of the liver-cells. The colorless constituent 
that gives this reaction may be in solution or granular. In the only case of malaria 
liver that I have ever examined the iron reaction was present in the periphery of the 
lobules, and seemed to be given particularly by very fine intracellular granules, 
though these cells did not contain any brown granules. Deposition of iron seems 
to occur here, as in other places, independently of pigmentation. Examination 
of siderotic livers of ether origin than malaria shows that the presence of iron of 
itself does not necessarily imply the development of interstitial hepatitis. 


According to Kelsch and Kiener, whose description I have followed 
in the main, malaria liver is characterized by the frequent presence 
of the iron reaction and the nodular form of hyperplasia. In Southern 
Italy, I am informed by Professor Ughetti (in Cantania), no appreciable 
difference is seen between the anatomic and histologic features of malarial 
cirrhosis and those of the ordinary cirrhosis of alcoholism. It is possible 
that the unfavorable conditions of life in Sicily and a poor diet are 
responsible for the fact that no material is furnished for storing iron 
in the liver, and that consequently all the inflammatory changes are 
retrogressive. There seems to be no doubt that among these people 
the cirrhosis is produced by malaria per se, whereas among the European 
population of Algiers alcohol certainly also plays a definite rdle. 

[P. Bielfield * has made an interesting study of the contents of the 
liver-cells of healthy persons with especial reference to the presence 
of iron. He makes the assertion, as the result of his experiments, that 
former failures to find iron have been due to faulty methods. By using 
Smith’s method (removing the gall-bladder, and then cutting the liver 
into small pieces, by means of glass, scraping with a horn spatula, mixing 
with salt solution—7 : 1000—and straining through clean linen) he 
obtained a filtrate of liver-cells and salt solution. This is placed in a 
cylinder of 10 liters capacity filled to the brim, and set aside in a cool 
place for twelve hours. The liver-cells by this time subside. The salt 
solution is changed repeatedly until spectroscopic bands of hemoglobin 
fail to appear. The fluid is then decanted and the remainder centrif- 
ugated. The liver-cells he then dries and divides into two parts, one 
of which he uses for the determination of the quantity of NaCl, and the 
other for the determination of the iron. The latter portion is washed 
with hot water, filtered, and incinerated. The ash is dissolved in 
HCl, the latter evaporated, the residue treated with H,SO,, and a piece 
of zine added to reduce the iron; its amount of which is deter- 
mined by titration with a standard solution of permanganate. Biel- 
field concludes: (1) There is considerable variation in the amount of 
iron present in the hepatic cells during health. (2) The average amount 


* Russk. Arch. Patholog. klin. med. Bact., March, 1901. 


CHRONIC INFLAMMATION OF THE LIVER. 737 


of iron present in a healthy liver is about 0.19 %. (3) There is more 
iron in the liver of the male than the female. (4) The amount of iron. 
in the hepatic cells increases with age. (5) The amount is less between 
the ages of twenty and twenty-five.—ED.] 

Symptoms.—When only parenchymatous hepatitis and nodular 
hyperplasia are present, the symptoms are limited to the appearance 
of slight degrees of icterus and a feeling of pain or of heaviness in the 
right hypochondrium. At times there are attacks of congestion of the 
liver with polycholia. The liver is slightly enlarged. 

In typical cirrhosis ascites develops, the spleen is enlarged and painful 
from perisplenitis, the skin is sallow or icteroid. Loss of strength pro- 
gresses rapidly as the combined result of the malarial cachexia and the 
disease of the liver. 

In the less frequent form of ischemic atrophy the liver is small, 
there is much ascites, and the fluid returns rapidly after aspiration. 


Frerichs: ‘‘ Leberkrankheiten,”’ Bd. 1, p. 325; Atlas, Taf. 1x—x1. 

Chauffard: “ Mal. du foie,” loc. cit., p. 886. 

Auscher: “ Manuel de méd. de Debove et Achard,’”’ tome vi, p. 119. 

Kelsch et Kiener: “ Des affections paludéennes du foie,” “‘ Archives de physiologie,”’ 
1878, tome x, p. 571, 1879. . 

— “Maladies des pays chauds,” Paris, 1889, pp. 420, 547, 684, Table v, v1. 

Véron: “Cirrhoses pseudo-alcooliques,”’ “Archives générales de médecine,” Sept., 
1884, p. 308. 

Pampoukis: “ Bulletin de la société anatomique de Paris,’ June, 1889. 

Barker, L. F.: “Johns Hopkins’ Hospital Report,” vol. v, 1895. 

Bordori: “Lo Sperimentale,” 1891, No. 21. - 

Cantani, A.: “Il Morgagni,” Luglio, 1890. 

‘Dock: “ American Journal of the Medical Sciences,” April, 1894. 

Jacobson, O.: ‘‘ Malaria und Diabetes,’”’ Dissertation, Kiel, 1896. 

de Renzi: “ Riforma medica,” 1890. 

Rubino, A.: “Giorn. internaz. di science mediche,’”’ Napoli, 1884. 

Ughetti, G. B.: “Archivo medico Italiano,” Dec., 1882, 1883. 

— “Giorn. internaz. di science mediche,”’ Napoli, 1883. 


7. PIGMENTARY CIRRHOSIS OF DIABETICS. 


Cirrhosis of the liver may occur in combination with diabetes. Their 
simultaneous appearance seems to be rare in Germany, more frequent 
in France and England. This fact of itself suggests that particular 
conditions must be held responsible for the occurrence, and I assume 
that coincidence plays an important rdéle, rather than that there is any 
more serious connection between the two conditions. As often as the 
attempt has been made to discover a relation between the two diseases, 
there have been some authors that have called the one, and some the 
other, the primary disease (compare page 706). 


In some of the cases sclerosis of the pancreas may have been the cause of diabetes ; 
at least this condition has been found accompanying pigmentation in a number 
of cases of diabéte bronzé (Achard). ~. 


Hanot and Chauffard, in 1882, described a special disease-picture 
under the name of cirrhose pigmentaire hypertrophique in diabetes mel- 
litus; they stated that it was characterized by great pigmentation of 
a cirrhotic liver and by melanodermia. Other similar cases with slight 
variations have been described since then, particularly by French authors. 
Trousseau, it appears, described a case of the kind in his day (loc. cit.). 

47 


- 


738 DISEASES OF THE LIVER. 


[Condon,* in reporting a case with autopsy, mentions three theories 
relating to the nature of the condition: (1) That itis a distinct pathologic 
entity—advanced by Marie, Hanot, and other French writers. (2) 
That the primary condition is a diabetes mellitus, and that the poisons 
of the diabetes are responsible for the hemachromotosis, cirrhosis of 
the liver, pancreas, etc.—supported by Letulle. (3) That hemachromo- 
tosis is the primary condition, and that the deposition of pigment causes 
the hypertrophic cirrhosis of the liver and pancreas; the diabetes resulting 
only when the pancreatitis reaches a certain stage. This view is ad- 
vanced by Opie.—Eb. ] 

The cases are, as a rule, afflicted with diabetes of medium degree, 
but are at the same time very cachectic; they may be alcoholics or 
tuberculous cases. The disease often sets in with disturbances of the 
appetite, diarrhea alternating with constipation, and other gastric dis- 
turbances. There is a feeling of pressure in the epigastrium, great. 
polydypsia, polyphagia, and progressive cachexia. Later ascites ap- 
pears, with edema of the legs, and a recession of the diabetic symptoms; 
the liver is usually enlarged. 

With the onset of diabetes the skin usually turns a uniformly dirty 
brown color, and hence the name diabéte bronzé. The mucous mem- 
branes are not colored. It is said that this melanodermia is different 
from that of Addison’s disease, argyria, and carcinomatous cachexia; 
the tint is said to approach a sooty shade (bistre), and resembles chronic 
arsenic-poisoning more than any other condition. The discoloration of 
the skin may be of many different degrees of color, and may even be 
completely absent. The disease lasts for nine months to one year, 
and at the end of this time the patients die of cachexia, usually in coma. 

[Anschutz + has published a comprehensive review of the subject of 
cirrhosis with pigmentation, as has also Futcher t¢ at a still more recent 
date. Both point to the fact that pigmentation occurs rather with 
the hypertrophic form, and almost never with the atrophic cirrhosis of 
Laennec. Tl utcher notes‘a case occurring in the Johns Hopkins Hospital, 
which he claims is the fifth to be reported in this country (America), - 
two having been noted previously by Opie (1899), and Adami and Abbott 
(1889-1900), and two by Osler in 1899. Nearly all recent writers look 
upon the condition as one in which the diabetes is secondary or even 
a coincident condition, the diabetic symptoms usually appearing only 
within a year of the termination of the case. Nearly all cases have been 
observed in males. The liver shows at autopsy enlargement and the 
general picture of a pigmentary cirrhosis. The hepatic cells and the 
connective tissue show a brownish pigment containing iron; this has 
also been found in the cardiac muscle-fibers and in the lymph-glands. 
—Ep.] | 

The liver is generally larger than normal, heavier, and more solid; 
it may weigh 2000 gm. or more; in one case, however, the typical picture 
of an atrophic cirrhosis was seen. The color of the organ is rusty, the 
pancreas, the abdominal and the salivary glands, and the spleen are 
solid and colored brown in the same manner as the heart-muscle; in 
some of the cases a slate-like discoloration is seen in certain areas over 
the parietal peritoneum, and on the serosa of the stomach and intestine. 

The cirrhosis may be seen microscopically to be portal or bivenous. 


* Medicine, Dec., 1900. t Deutsch. Arch. f. klin. med., Bd. Lx11, 1899. 
t Jour. Amer. Med. Assoc., Sept. 28, 1901. 


PLATE--V, 











PIGMENTARY CIRRHOSIS OF THE LIVER WITH DIABETES. MARKED HEPATIC 
ENLARGEMENT AND ASCITES, WITH BRONZED SKIN (DIABETE BRONZE). 





CHRONIC INFLAMMATION OF THE LIVER. 739 


The pigment is most abundant in the periphery of the lobules, in the 
liver-cells surrounding the nucleus, and often covering the latter; it is, 
as a rule, finely granular. Dutournier and others have designated this 
condition as “pigmentary necrobiosis’’; this name can hardly be recon- 
ciled, however, with the usual enlargement of the liver. Pigment is 
also found in the endothelia of the capillaries and in a coarser form in 
the connective tissue, the migrating cells, the fixed cells, Kupfer’s stellate 
cells, and in the glandular cells of the pancreas, the salivary glands, the 
cells of the spleen, and of the abdominal lymph-glands, the fibers of the 
heart-muscle, and the smooth muscle-fibers of the vessel walls. 

The first observers did not analyze the pigment; later ones (Gilbert 
Pottier, Auscher, and Lapicque) demonstrated the presence of iron 
with ammonium sulphid (greenish-black color). Auscher and Lapicque 
claim that colloid ferric-hydroxid is present; the blackish pigment of the 
peritoneum and the intestinal serosa is a different substance, showing 
no iron reaction, and being decolorized by reducing agents. The color 
is brought back by oxygen; the pigment is soluble in alkalies. 

According to all these findings, there can be no doubt that the brown- 
ish pigment or the brownish masses are derivatives of hemoglobin; 
v. e., of destroyed red blood-corpuscles. Different authors have assumed 
that this destruction occurs in a variety of organs, including the liver; 
others claim that the red corpuscles are destroyed in the liver alone, and 
that pigment is carried from there to the other organs. 

According to my opinion, the pathologic picture as formulated is 
not justified, particularly as it is based on so small a number of isolated 
observations. The iron pigment has been examined only in cirrhotic 
livers, whereas in reality it is found in a great many diseases of the liver 
other than cirrhosis. [Attention has already been directed to’ the state- 
ment of Bielfield that iron is to be found in quantity in normal liver- 
cells.—Eb.] 

Many years ago I described this finding and called it siderosis of 
the liver (and of other organs), and showed that not only can pigmented 
portions of the liver parenchyma but colorless portions as well give 
the iron reactions. In the more pronounced cases, it is true, the sub- 
stances that react are colored brown or blackish and are present in such 
abundant quantities that the color of the whole organ is changed. This 
deposit of iron may be present in the liver-cells without causing any 
histologic changes, and may be present in large quantities, as, for in- 
stance, in pernicious anemia. Even in cases in which there accumulate 
large quantities of coarse granules and cells the latter obstruct the 
capillaries of the liver and form circumscribed foci; cirrhotic changes 
are never produced by the accumulation of iron per se. 

Diabetes mellitus is one of the diseases that is sometimes accom- 
panied by the accumulation of iron in the liver. It was a case of diabetes 
in which I saw and described siderosis for the first time both in the 
liver, and in other organs (1877):. In this case, it is true, the interstitial 
tissues were slightly increased, but not to such a degree that it could 
be called cirrhosis. I have since then seen the accumulation of small 
quantities of iron in diabetic livers in several cases, and without a trace 
of cirrhosis. This condition, it may be stated, was present only in 
the minority of the cases of diabetes that were examined. [Teleky * 
reports two cases of men, fifty and fifty-one years of age, in 

* Wien. klin. Woch., 1902, No. 29. 


740 DISEASES OF THE LIVER. 


both of whom the first pathologie symptoms were those of glycosuria. 
In both cases antidiabetic diet failed to cause the disappearance of the 
sugar from the urine. In both also, after a few weeks, marked icterus 
appeared, the sugar disappearing from the urine at once, and permanently, 
notwithstanding'a diet that was finally constituted almost entirely of 
fats and carbohydrates. The assimilation of the ingested fats was very 
limited. The icterus persisted until death took place. In both cases 
the autopsy showed marked changes in the pancreas, and an almost 
normal condition of all the other organs. The cause of the icterus ap- 
peared to be a narrowing of the ductus choledochus, dependent upon 
pathologic changes in the pancreas. In the second case cholecystentero- 
stomy was performed with one of the coils of the jejunum, and the point 
of anastomosis sutured to the mesocolon. Death followed on the Bourse 
day after the operation.—ED.] 

Siderosis appears, therefore, to be a fairly: frequent occurrence in 
diabetics. The same accumulation i is, of course, seen if the case happens 
to be afflicted with a cirrhotic liver ; it appears that these cirrhotic livers 
have interested French authors more than the non-cirrhotic ones. 


Siderosis is of frequent occurrence in pernicious anemia. Quite recently, and 
for the first time, I saw cirrhosis in combination; the patient, age 52, was cachectic 
and icteric when he was admitted and had some gastric disturbances; the first 
diagnosis was carcinoma ventriculi with secondary carcinoma of the liver. From 
the blood-picture and the absence of all changes in the liver, pernicious anemia 
was diagnosed later on. The patient died cachectic and without ascites. At autopsy 
the liver was found to be slightly decreased in size, cirrhotic, and brown. The 
microscopic picture was that of diabetic pigment-cirrhosis. The iron reaction very 
pronounced; it was present also in the spleen (that had remained small owing to 
thickening of its capsule), and in the convoluted tubules of the kidney. The cirrhosis 
was apparently of long duration prior to the development of pernicious anemia 
(instead of diabetes). The only symptom of the cirrhosis was a moderate icterus. 

Marchand has described a case of siderosis with hepatic cirrhosis in a tubercular 
case. 


Very striking is the frequency with which French investigators have 
found the complication of diabetes with cirrhosis. It is possible that 
in France an unusual number of the diabetics are constant drinkers, 
and that the deposit of iron produced by diabetes occurs more readily 
in a liver that is cirrhotic, and persists in such an organ after the deposit 
has once occurred. 

It appears that the cases described as diabéte bronzé are similar to 
the disease hemochromatosis v. Recklinghausen has described; further 
communications in regard to the latter disease must be awaited. 

The discoloration of the skin—which, by the way, is not constantly 
present—remains unexplained; it is not stated that the pigment found 
in these cases contains iron, nor is it probable that it does. It is quite 
probable that the cases reported were simply cachectic, and that par- 
ticular attention was directed to the color of the skin owing to the pig- 
mentary anomalies observed in the internal organs. It is also possible 
that an icterus levissimus modified the cachectic color of the skin. 

[A case of bronzed diabetes mellitus with cirrhosis of the liver and 
pancreas and hemochromatosis has been reported by Condon.* Gilbert, 
Casteigne, and Lereboullet + look upon the diabetes as the result and 
not the cause of cirrhosis, and believe that it is due to a hyper-function 
of the liver-cells—“ hyperhepitization.”” Their views are based on two 


* Medicine, Dec., 1900. + Gaz, Hebd. de Méd. et de Chir., 1900, No. 39. 


CHRONIC INFLAMMATION OF THE LIVER. 741 


observations: The hyperactivity of the liver they believe to be shown 
by the parallel appearance and increase of glycosuria and azoturia. Osler * 
has reported two cases of hypertrophic cirrhosis of the liver with hema- 
~ chromatosis without glycosuria. 

Opie + gives a full account of a case of hemochromatosis without 
glycosuria. He draws attention to the two kinds of pigment—hemo- 
siderin, containing iron, and hemofuscin, not containing iron. The 
absence of pigmentation from the skin in some cases is also noted. 
He says, as does Anschutz, that no case of hemochromatosis or of bronzed 
diabetes has been observed in the female. He believes that the hemo- 
siderin must be derived more or less directly from the hemoglobin, and 
draws attention to the iron-containing liver of pernicious anemia. He 
speaks of the fact that the deposition of iron-containing pigment in the 
liver and other organs has been experimentally produced by the injection 
of toluylenediamin in animals through destruction of the red blood-cells, 
but that the pigmentation is never such as is seen in hemochromatosis. 
Opie believes that the diabetes seen in some of these cases is secondary 
‘ to the hemochromatosis. He believes that the diabetic condition is of 
pancreatic origin and appears when the pancreatitis has reached a 
sufficient intensity. In Opie’s own case intercurrent typhoid fever 
killed the patient before the chronic interstitial pancreatitis had reached 
a degree sufficient to produce glycosuria. He arrives at the following 
conclusions: (1) There exists a distinct morbid entity—hemochromatosis 
—characterized by the wide-spread deposition of an iron-containing 
pigment in certain cells and an associated formation of iron-free pig- 
ments in a variety of localities in which pigment is found in moderate 
amount under physiologic conditions. (2) With the pigment accumula- 
tion there is degeneration and death of the containing cells and conse- 
quent interstitial inflammation, notably of the liver and pancreas, 
which become the seat of inflammatory changes accompanied by hyper- 
trophy of the organ. (3) When chronic interstitial pancreatitis has 
reached a certain grade of intensity diabetes ensues and is the terminal 
event in the disease. 

In further studies of the relation of pancreatic disease to diabetes 
Opie and others have found that disease of the islands of Langerhans, 
certain collections of round cells differing from the pancreatic cells proper, 
plays a most important réle in the development of diabetes. When 
these islands are spared, diabetes does not occur.—ED.] 

Chauffard groups diabetic cirrhosis and malaria cirrhosis as cirrhoses 
pigmentaires. The above discussion will show that the author cannot 
indorse such a classification. The presence of pigment has nothing to 
do with the cirrhosis; it can be seen in the absence of cirrhosis, and, on 
the other hand, cirrhosis may occur without pigmentation. 

A typical pigment is, moreover, seen only in malaria; and iron- 
containing pigments are found more frequently in other diseases than 
in cirrhosis. [We have already noted a number of cases in which typical 
iron pigment was present sufficient to show that at the present time 
this statement cannot be considered as generally accepted. Hemo- 
siderin undoubtedly occurs in most of these cases as the prominent pig- 
ment.—Ep.] (Compare the paragraph on “siderosis of the liver” and 
“pigment liver.’’) 

* Brit. Med. Jour., Dec. 9, 1889. 
t Trans. Assoc. Am. Phys., 1899, vol. xiv; p. 253. 


742 DISEASES OF THE LIVER. 


Auscher: in Debove and Achard’s, ‘‘ Manuel de médecine,” v1, 105. 

— et Lapicque: “ Recherches sur le pigment du diabéte bronzé, Société de biologie, 
May 25, 1895. 

—_—— “ Accumulation d’hydrate ferrique dans l’organisme animal,” “ Archives de 
physiologie,”’ April, 1896. 

Achard, E. A.: ‘Contribution 4 |’étude des cirrhoses pigmentaires,’’ etc., Thése de 
Paris, 1895. 

Barth: “ Bulletin de la société d’ Anatomie,” 1888, p. 500 

Brault et Gaillard : “Sur un cas de cirrhose hypertroph. pigmentaire dans le diabéte 
sucré,” “Archives générales de médecine,”’ 1888, tome cLXx1, P. 38. 

Buss, W.: “Diabetes mellitus, Lebercirrhose, Hamochromatose,” Dissertation, 
Gottingen, 1894. 

Chauffard: in Charcot, “Traité de médecine,” 111, p. 891. 

Dutournier, A. : “ Contribution a l’étude du diabéte bronzé,” Thése de Paris, 1895. 

Hanot et Chauffard: “Cirrhose hypertroph. pigmentaire ‘dans le diabéte sucré,” 
“Revue de médecine, ”” 1882, p. 385. 

— et Schachmann: “Cirrhose pigmentaire dans le diabéte sucré,’’ “ Archives de 
physiologie normale et pathologique,”’ 1886, tome xviu1, p. 50. 

Kretz: “ Hamosiderin-Pigmentirung der Leber und Lebercirrhose, ” “Beitrige zur 
klin. Medicin und Therapie,’ No. 15, Wien, 1896. 

Marchand: “Siderotisch-cirrhotische Leber bei ’Phthisis,” “Berliner klin. Woch- 
enschr.,”’ 1882, p. 406. 

Minkowski: “ Stérungen der Leberfunction,’’ Lubarsch und Ostertag’s “ Ergebnisse 
der allgemeinen Pathologie,” 1897, p. 721. 

Quincke, H.: ‘‘ Ueber Siderosis,”’ Festschrift zum Andenken an Albrecht v. Haller, 
Bern, 1877. “Deutsches Achiv fir klin. Medicin,”’ Bd. xxv und xxvi1, 1880. 

v. Recklinghausen: “ Ueber Haimochromatose,”’ “‘ Bericht der Naturforscher-Ver- 
sammlung zu Heidelberg,’”’ 1889, p. 324. 

Saundby: “ British Med. Journal,” 1890; ‘‘The Lancet,” 11, p. 381. 

Trousseau: “Clinique médicale,” 4. éd., 11, p. 780 


8& SYPHILITIC HEPATITIS, 


The interstitial changes produced in the liver by syphilis differ as 
to location, nature, and extent; in many cases their genetic relationship 
is not recognized until late in the disease. The formation of connective 
tissue containing many cells is common to all syphilitic processes in the 
liver; this tissue consists of round and spindle cells, and is either con- 
verted into cicatricial tissue, or it may undergo fatty degeneration and 
be absorbed. We will discuss separately the lesions seen in adults after 
acquired syphilis, and those that occur in the hereditary form of the 
disease. 

In adults acquired syphilis may appear in the diffuse or the circum- 
scribed form, the former being identical with the ordinary interstitial 
hepatitis that we have described under the caption cirrhosis. The 
interstitial proliferation is chiefly interacinous, but seems to penetrate 
between the columns of liver-cells more frequently than in alcoholic 
cirrhosis; just as in the latter, it may lead to contraction, and cannot 
be distinguished from it; in fact, the two diseases are occasionally seen 
together. 

The circumscribed form of syphilis of the liver is more clearly char- 
acterized and probably occurs with greater frequency; it is called the 
gummatous hepatitis or syphiloma. In this condition a few, or per- 
haps very many, single foci are seen, varying in size from that of a millet- 
seed to a walnut. They are reddish-gray to white in color, radiating in 
structure, and are of an irregular form, more or less differentiated from 
the surrounding liver tissue. In their centers are seen yellowish-white 
cheesy or dry masses that form irregular figures on transverse section, 
and by this appearance recall the centers of cheesy, tubercular nodules; 


CHRONIC INFLAMMATION OF THE LIVER. .: 743° 


at the same time they differ from the latter in that they are much more 
solid. These foci are found principally on the surface of the liver, and 
particularly near the suspensory ligament. If seen in the interior of 
the organ, they follow the periportal connective tissues, Glisson’s capsule 
(pertpylephlebitis syphilitica, Schiippel). The more recent proliferations 
consist of round and spindle cells, embedded in a homogeneous matrix; 
they are reddish-gray in color; the cheesy portions are yellow and inclose 
globules of fat. 

In addition to these gummatous nodules, there are often seen true 
cicatrices that start from the surface of the organ and penetrate the 
liver as deep furrows. It is probable that these scars originate from the 
first-named foci in such a manner that a portion of the cellular tissue is 
converted into connective tissue, and another portion undergoes fatty 
degeneration and is absorbed. In some cases only a few of these scars 
are seen, and these may or may not inclose cheesy portions. Again, 
the form of the liver may be considerably changed by these scars; there 
may be appendices to the organ consisting of pieces of the liver paren- 
chyma that have become separated from the main part of the organ; 
these may be as large as nuts or apples, or the whole liver may appear 
to be made up of such fragments. The round shape of these lobes can 
only be explained by the great elasticity of the liver tissue; it is possible 
also that a process of vicarious hyperplasia has something to do with 
their formation. | 

In gummatous hepatitis the capsule is always thickened and adherent. 
The adhesions vary in extent and character and may reach beyond the 
area of the scars proper, and in this way they are usually developed to 
a greater extent than in any other form of liver disease. 

Miliary syphilomata are less frequently seen and produce less striking 
deformities than the form described. The large foci are not present in 
great numbers, whereas the miliary areas are seen in enormous numbers 
and are disseminated all through the liver like tubercles, or neoplasms. 

Occasionally gummatous, deforming hepatitis is combined with the 
diffuse interstitial form; sometimes the normal liver tissue between the 
cicatrices undergoes fatty or amyloid degeneration; or, again, there may 
be disease of the bile-passages, with the formation of concretions. 

In hereditary syphilis the reverse is the case. The circumscribed 
form is rare, and the diffuse form frequent. The condition is found as 
early as the sixth month of fetal life or even in the new-born. It may 
also develop in the first weeks or months of life, and in the latter case 
appears in the form of hypertrophic induration of the connective tissue. 
The liver is enlarged and heavy (according to Birch-Hirschfeld, 6 % 
instead of only 4.6 % of the body-weight). Its color varies from a 
grayish-red to dirty brown (“Feuerstein,’’ Gubler), and in mild cases 
is brownish or mottled. At the same time the liver-substance is hard 
(“like sole-leather,”’ Trousseau), contains little blood, and the outlines 
of the lobules are indistinct. According to Hutinel and Hudelo, the 
microscopic picture is that of hyperemia with dilatation of capillaries, 
accumulation of leucocytes, and proliferation of the endothelium of the 
capillaries. Round cells are seen later in the broadened interstices of 
the lobules, which are inclosed in new-formed fibrous tissue. These cells | 
are also seen in the interior of the lobules between the capillary walls 
and the columns of liver-cells. They are, finally, also seen in the walls 
of the blood-vessels, extending as far as the intima. In the course of 


744 DISEASES OF THE LIVER.. 


time, connective tissue takes the place of the round-cell infiltration. In 
the beginning the hepatic cells show nuclear mitoses; later their form 
changes, their protoplasm becomes transparent, and they disappear. 

Although the connective-tissue proliferation is in general diffuse, it 
may, in certain places, be circumscribed and focalized. 

As a rule, the liver of a new-born child will be found enlarged if it is 
afflicted with indurative syphilis; this is due to the fact that the chil- 
dren do not live long; in the further course of the disease smooth atrophy 
or granular atrophy of the organ may develop. If hereditary syphilis 
leads to the formation of gummatous nodules, these usually assume the 
form of miliary nodules, that are disseminated throughout the liver in 
large numbers. 

[Obendorfer * has reported the case of a child who died of hereditary 
syphilis when about sixteen months old. The liver showed a marked 
and characteristic hypertrophic cirrhosis with much destruction of 
hepatic tissue and a replacement by connective tissue. The arteries 
were normal in part, and in part almost obliterated by hyperplasia of 
the intima. The adventitia also showed round-cell infiltration in places. 
The veins were even more extensively involved than the arteries, their 
walls being full of newly forming connective tissue. The biliary channels 
showed proliferation, and were surrounded by newly formed connective 
tissue. In the areas of connective tissue many nodules with central 
caseation were seen surrounded by nuclear remnants and round cells. 
The normal and pathologic tissues were distinctly demarcated, and over 
the diseased areas the capsule was thickened. The lesions, contrary to 
the usual diffuse process, were localized to the anterior surface, and 
its lower portion. Usually the lesions are most marked at the trans- 
verse fissure, but in this case the tissues in the neighborhood | were free 
from the process.—ED. ] 

The lesions of syphilis of the liver greatly resemble the lesions of the 
same disease in other organs, as the meninges, the testicles, the heart- 
muscle, the bones. Proliferation of the connective tissue occurs and 
occupies an intermediate position between new formation and chronic 
inflammation. The newly formed tissue shows a tendency, on the one 
hand, to degeneration, and to the formation of molecular fatty detritus 
that may be absorbed; and, on the other, to the formation of cicatricial 
tissue. 

In the newly born syphilis produces a number of other pronounced 
lesions in different portions of the body; as, for instance, tumor of the 
spleen, cicatrices of the placenta, general atrophy, etc. In the adult 
the hepatic lesion may be the only manifestation of the disease. 

Occurrence.—Syphilitic hepatitis appears in the tertiary stage of 
the disease, and at approximately the same time as gummata in the 
meninges, the bones, the mucous membranes, etc.; in general, therefore, 
it is noted a number of years after infection. As the development of 
the different lesions of lues fluctuates greatly in regard to time, it may 
be that the lesion under discussion may occasionally develop earlier in 
the disease. Key + and Biermer have reported cases in which the 
interval between infection and the development of hepatitis was only 
six and nine months; these cases, however, are not above criticism. 

In acquired syphilis the liver is one of the most frequently affected 


* Centralbl. f. allg. Path. u. i Anat., Mar. 15, 1900. 
ft Schmidt’s “ Jahrbiicher,”’ Bd. cux1, p. 142. 


CHRONIC INFLAMMATION OF THE LIVER. 745 


organs; in hereditary syphilis, possibly after the lungs, the liver certainly 
is the most frequently involved organ. The disease may begin during 
fetal life and is seen in the prematurely born, in the still-born, and in 
children that die at the age of a few weeks or months. 


The frequency of the disease may be learned from statistics that Hofmeister 
and Feige have gathered from autopsies performed from 1873 to 1885, and from 
1886 to 1895, in the pathologic Institute of Kiel. Among nurslings under six 
months, 123 and 189 were syphilitic; a record of 20.1 % and 16.5 %. Of these 
syphilitic children, 48 and 123 (39 % and 65 %) showed evidence of interstitial 
hepatitis. The lungs were frequently involved at the same time; less frequently, 
the bones and the skin. 


Symptoms.—In the adult the circumscribed form of syphilis of the 
liver rarely produces any conspicuous symptoms, and is usually found 
by chance at the autopsy. As the serosa is frequently involved, pain 
in the liver region may be felt, or there may be friction sounds present. 

Fresh gummata may be felt as nodules on the margin or on the 
convex surface of the organ; the cicatricial deformities are more fre- 
quently felt. Pieces of the liver as large as a hazelnut or an apple may 
become separated from the main body of the organ by scar tissue and 
may give the impression of independent tumors, or may lead to con- 
fusion with floating kidney. These separated parts remain in a stationary 
condition for a long time, or at least are little changed; gummata proper, 
on the other hand, often undergo retrogressive changes. Oppolzer and 
Bochdalek * mistook such softened gummata for cured liver carcinomata. 

The perihepatic adhesions frequently anchor the liver to the anterior 
abdominal wall and interfere with the respiratory motility of the organ. 

Notwithstanding all these lesions, the general health may remain 
unimpaired, provided the healthy portion of the organ continues to 
functionate properly; if disturbances occur, they usually originate from 
the portal vein, and occasionally from the bile-passages. 

If there is compression of the portal vein, and the picture of stasis 
of this system appears with ascites, the disease may resemble cirrhosis, 
particularly as a swelling of the spleen may develop both as a result of 
stasis and of amyloid degeneration, or of syphilitic hyperplasia. Icterus 
from compression of bile-passages is less frequently seen, and still less 
frequently a congestion of the liver from occlusion of the hepatic veins. 

In some cases the course of the disease is fatal, as in cirrhosis. If 
antisyphilitic treatment is instituted at the right time, all the symptoms 
may recede. Sometimes recurrences and exacerbations occur, and this 
very protracted and varying course of the disease may aid in differentiat- 
ing the condition from alcoholic cirrhosis: 

Diffuse syphilitic hepatitis in adults may, in fact, at the beginning, 
lead to an enlargement of the liver more frequently than alcoholic in- 
toxication. The onset has appeared to me to be somewhat more sudden, 
and the course of the disease more rapid than in the latter condition. 

If syphilitic hepatitis is present in the new-born, the children show 
signs of bad health within a short time after birth; they are emaciated, 
flabby, and do not thrive. The abdomen protrudes, the liver can be 
palpated as a large, smooth, and hard tumor, and, in addition, ascites 
is present or soon develops. The spleen is usually enlarged to several 
times its normal volume and can be readily palpated. Icterus is not a 
constant symptom, and if present varies in intensity. Children afflicted 


* Prager Vierteljahrsschr., 1845, Bd. 11, p. 59. 


746 DISEASES OF THE LIVER. 


in this manner die in spite of all treatment, usually with diarrhea, cachexia, 
or peritonitis. Lesser degrees of hepatitis, that cause no symptoms in 
the beginning, are compatible with longer life, and develop into those 
cases that show all the characteristics of Laennec’s cirrhosis in the later 
years of childhood, without revealing any clue to their origin. 

Many of these cases of late syphilitic hepatitis run an atypical or 
irregular clinical course, but are characterized anatomically by the 
uneven distribution of intralobular connective tissue. Occasionally 
miliary, cheesy foci, or amyloid areas will be seen in these cases. 

The older the child in which hepatitis develops, the more difficult 
will it be to determine whether the case is one of retarded hereditary 
syphilis or of acquired infection. Barthélémy has collated some 30 cases 
of this kind; showing that they occur most commonly between the sixth 
and thirteenth years, but may be seen as late as the twentieth (a case of 
Ebermaier) year. The mildest cases are not very characteristic, and 
have been termed congestive cases (Barthélémy). They show some 
dyspeptic and intestinal disturbances and an enlargement and sensitive- 
ness of the liver. In more pronounced cases the liver is large and hard 
and there is ascites, and a collateral venous network on the abdomen. 
There is also a tumor of the spleen; in rare instances the liver is small or 
deformed. Icterus is rare. 

Sometimes acute parenchymatous hepatitis may develop in an organ 
that is affected with such an hereditary cirrhosis. If this occurs, the 
picture of icterus gravis and of acute atrophy appears, and death ensues 
in a short time; the same complication is occasionally seen in hyper- 
trophic cirrhosis. A case from the Kiel clinic, described by Thielen, 
belongs to this category. 

Diagnosis.—In the new-born the diagnosis of syphilitic hepatitis is 
comparatively easy, because the organ can be readily palpated and no 
other disease has to be considered. The diagnosis of hereditary syphilis 
is not so simple in the later years of childhood because this disease pro- 
duces only vague symptoms; sometimes it is necessary to await the 
results of antisyphilitic treatment before rendering a decision. 

In the adult the diagnosis will have to be made between ere 
hepatitis, and carcinoma, or alcoholic cirrhosis. It is an easy matter 
to confound gummata with cancer nodules; both are capable of retro- 
gressive changes. In the case of gumma, however, this process is, as a 
rule, more complete, whereas carcinomatous nodules soften in the center 
only and form central delle; at the same time new nodules may appear. 

Separated portions of the liver may simulate neoplasms; they are 
distinguished by their smooth surface, their spherical shape, tense con- 
sistency, constant size, and by the lack of pain. A large palpable tumor 
of the spleen and albuminuria speak in favor of hepatitis syphilitica. 
Cachexia is not so severe as in cancer. 

In contradistinction to ordinary cirrhosis, gummatous hepatitis has 
larger nodules, of varying size, a larger tumor of the spleen, and, in 
general, less constant symptoms. Even ascites may disappear, and 
there may be long periods of comparative well-being. If these changes 
in the condition of the patient can be traced back for a period of years, 
this speaks in favor of gummatous hepatitis. 

Perihepatitic adhesions are, in a measure, characteristic of syphilis 
of the liver, and especially if they are wide-spread and to be noted in 
many places. Similar symptoms may, it is true, be caused by gall- 


CHRONIC INFLAMMATION OF THE LIVER. 747 


stones, as pain, fever, etc., so that the diagnosis must be made between 
these two diseases.* 

The anamnesis is of subordinate value for the diagnosis, because 
other diseases of the liver may be present, even in the presence of a 
history of luetic infection; objective symptoms in other organs are more 
important, as, gummata or scars of the skin, of the mucous membranes, 
or of the bones. 

It must be remembered, finally, that even ordinary lacing may cause 
the separation of a ball-shaped piece of the liver from the lower 
margin, that may resemble similar masses of syphilitic origin. The 
lobe produced by lacing is, however, always single or indentated by the 
incisure of the gall-bladder, and is always situated in the mammillary 
line, and at the lower margin of the right lobe of the liver. 

Treatment.—As in other organs, provided an early diagnosis is made, 
antisyphilitic therapy will lead to the disappearance of the gummatous 
process. ‘Treatment directed primarily with reference to other organs 
may, it appears, cause cicatrization and the formation of scar tissue 
in the liver that is seen by chance only postmortem. Specific treatment 
may only act symptomatically and temporarily; in many cases, par- 
ticularly those in which the diagnosis is positive, no success is obtained 
by the treatment because the process is already arrested and the cica- 
trices cannot be influenced by iodin or mercury any more actively than 
upon the skin or the pharyngeal mucosa. 

Even if the diagnosis is not positive, antisyphilitic medication is 
justifiable. As in the case of involvement of other organs, the diagnosis 
can sometimes be made only from the positive or negative results of 
specific treatment. 

If there is painful gummatous perihepatitis, sodium or iodid potas- 
sium should be given. The same drugs are employed in diagnostic 
treatment or in cases in which mercury, for one reason or another, cannot 
be given. More permanent results and a prophylaxis against further 
complications are obtained by a thorough course of mercury lasting 
over a period of six to eight weeks. Inunction is probably the best 
method from a practical point of view, although theoretically the internal 
administration of calomel seems indicated, because the drug is neces- 
sarily absorbed in the intestine and carried directly to the liver. The 
dose should be 0.05 twice daily in the beginning, increasing gradually 
to 0.4 or 0.6 per day. 

In addition to specific treatment, some of the complications and 
symptoms call for attention, and are provided for by the measures 
advocated for this purpose in the section on Cirrhosis and Perihepatitis. 


Barthélémy, M.: “Syphilis héréd. tardive. Lésions du foie,” (Mit Literaturan- 
gaben), “ Archives générales de’médecine,”’ 1884, tome cui, pp. 513, 674. 
Biermer: ‘Ueber Syphilis der Leber und Milz,” “Schweizerische Zeitschr. fir 

Heilkunde,” 1862, 1, p. 119, 2 Tafeln. ; 
Bristowe: “ Observ. on the Cure and Subsidence of Ascites due to Hepatic Diseases,” 
“British Med. Journal,” April 23, 1892, p. 847. , 
Dalton, N.: “Infiltrating Growth in Liver and Suprarenal Capsule,’’ “Transactions 

of the Pathological Society,” 1885, vol. xxxv1. 
Dittrich: “ Prager Vierteljahrsschr.,” 1849, Jahrgang 6, 1, pp. 1-33. ‘ 
Ebermaier, A.: “ Ein Fall von Syphilis hereditaria tarda,” Dissertation, Kiel, 1888. 
Feige, E.: “Ueber die Todesursachen der Sduglinge bis zum sechsten Lebens- 
monate, Dissertation, Kiel, 1896. 


* Compare, Riedel, Archiv jf. klin. Chir., 1894, Bd. xix, p. 206. 


748 DISEASES.OF THE LIVER. 


Gubler: “Gazette médicale de Paris,’ 1852, p. 262; ‘“Memoire de la société de 
biologie,” 1852. 

Haas, G.: “ Beitrag zur Lehre von der diffusen congenitalen Lebersyphilis,” Dis- 
sertation, Kiel, 1891. ' 

Hochsinger, C.: “ Eine neue Theorie der congenital-syphilitischen Friihaffecte,’’ 
‘Wiener med. Wochenschr.,” 1897, No. 25-27. 

Homeister, F.: “Ueber die Todesursachen der Sauglinge bis zum sechsten Lebens- 
monate,”’ Dissertation, Kiel, 1886. 

Hutinel et Hudelo: “ Etudes sur les lésions syph. du foie chez les foetus et les nous 
veaunés,” “ Archives de médecine expérimentale,” 1890, p. 509. 

Cedac: ‘‘Cirrhose hépatique d’origine syphilitique,”’ etc., “ Progrés médicale,” No. 

2 


22. 

» Thielen, A.: “Ueber Lebercirrhose bei Kindern durch congenitale Syphilis,’ Dis- 
sertation, Kiel, 1894. 

Wronka, L.: “Beitrag zur Kenntniss der angeborenen Leberkrankheiten,” Dis- 
sertation, Breslau, 1872. j 

Baumler: “Syphilis,” in Ziemssen’s “ Handbuch der speciellen Pathologie,” 1886, 
Bd. 11, 1, pp. 187-193. 

Neumann, J.: “Syphilis,” in Nothnagel’s “Specieller Pathologie und Therapie,”’ 
1896, Bd. xxi, pp. 407-435. 

Thierfelder: Loc. cit., p. 198. 

Frerichs: Loc. cit., Bd. 11, pp. 69 and 152; Abbildungen, pp. 73, 80, 163, und Atlas, 
Heft 2, Taf. rv und v. 

Budd: Loe. cit., p. 328. 


NEOPLASMS. 
(Hoppe-Seyler. ) 


FIBROMATA. 


Fibromata are benign tumors consisting of dense connective tissue, 
and are quite frequently found in the liver. As a rule, however, they 
are so small that they cause no symptoms during life, and are only 
found at the postmortem examination. On section they appear as 
small yellowish-white solid nodules embedded in the liver tissue. They 
vary in size from that of a pinhead to a pea. 

If multiple fibroneuromata develop in the body, they may form upon 
the branches of the sympathetic nerve within the liver.* They rarely 
cause any disturbance. 

Chiari + reports a large fibroma which was situated in the under sur- 
face of the right lobe of the liver to the right of the gall-bladder, and was 
7.5 em. long and 4.5 cm. wide. The growth was found at the autopsy, 
and it is not stated whether it caused any disturbance during life. 

The majority of fibromata are not dangerous, and their presence 
interferes in no way with the health of the patierft. The following 
case, however, observed by Quincke, in Bern, shows that if the tumor 
is large and unfortunately situated it may even endanger life: 


The case was that of a boy, two and a half years old, who was received in the 
Inselspital on June 19, 1873. In the fall of 1872 icterus had appeared, and in the 
beginning of 1873 enlargement and tumor formation had been noted in the middle 
of the abdomen. Fever was present on admission, the patient showed marked 
icterus, the stools were discolored, the right lobe of the liver was greatly enlarged, 
extending from the sixth rib to the crest of the ilium. The left lobe could not 
be palpated distinctly. The liver was hard, and protruded distinctly; the gall- 
bladder could be felt, and consisted of a spherical, tensely distended swelling, about 
as large as a pigeon’s egg, and fluctuating. At the same time a splenic tumor was 


* Ziegler, “Lehrbuch der path. Anat.,” Bd. 11, p. 599. 


: i Chiari, Wien. med. Wochenschr., 1877, p. 16; Langenbuch, loc. cit., Bd. 1, 
p16 


NEOPLASMS. 749 


felt, there was bile-pigment in the urine, itching of the skin, and slowing of the 
pulse. Ascites was not present. The temperature was elevated toward evening 
(38° to 39° C.), in the morning it was normal. The liver was punctured several 
times, but nothing except blood and liver-cells was aspirated. The condition 
remained unchanged for several months. In October the patient contracted 
whooping-cough; and then became so emaciated that the liver could be palpated 
without any difficulty. The size of the organ was unchanged. The gall-bladder 
was very prominent, and assumed the shape of a conical cylindric body, whose 
diameter was 3.5 cm., the axis running in an antero-posterior direction. The 
fundus was soft, the deeper parts hard and uneven. To the right of the gall-bladder 
a nodular, round tumor was felt, on the lower surface of the liver. The symptoms 
as described remained stationary for months, a slight attack of bronchitis being 
the only additional feature. The icterus persisted. In April, 1874, a swelling of 
the parotid and of the lymph-glands of the neck occurred, hemorrhages from the 
nose and the mouth appeared, and on the 19th of April, 1874, the patient succumbed 
to the disease. 

At autopsy (Langhans) nothing abnormal was found about the heart. The 
lower lobe of the right lung was hepatized, there was general icterus, and slight 
congestion of the kidneys. The spleen was swollen and hard; the follicles numerous, 
and somewhat opaque; the pulp was brownish-red. 

The liver was 24 cm. long, 6 cm. wide, and 3.5 em. thick; tough (though not 
inflexible), icteroid, and showed no clouding. The left lobe was very small. On 
the under surface a round tumor about as large as a hen’s egg was found. Its 
color was reddish, and its consistency hard. The tumor merged directly into liver 
tissue, and was found to be a fibroma. The gall-bladder was very much distended, 
and contained a gelatinous, clear, transparent fluid. The common duct was not 

atulous. . 
3 In addition, there was swelling of the parotid and of the lymph-glands of the 
neck and mesentery. 


In this case the tumor, owing to its size and its position, probably 
led to compression of the bile-passages and complete exclusion of the 
bile from the intestine, so that death occurred from hepatargia (cho- 
lemia). 

In similar cases, should they be observed in future, the tumor might 
be removed by operation, and a cure of the disease be reached in this 
manner. This has been done successfully in the case of sarcomatous 
tumors. It is necessary, of course, that the diagnosis should be made 
early, and possibly with the aid of exploratory laparotomy. 


ANGIOMATA. 


(Cavernoma. Telangiectasis.) 


Angiomata of the liver are, as a rule, clinically insignificant, and 
are found most often at the postmortem examination. In rare in- 
stances, however, large tumors develop, consisting of cavernous tissue, 
and produce certain disturbances in a mechanical way; 7. e., by limiting 
the interabdominal space, and by exercising pressure on neighboring 
organs. 


v. Eiselsberg reports a tumor of this kind weighing 470 gm., and situated at 
the margin of the right lobe. Rosenthal observed a fibrous angioma of the lobus 
Spigelii, and succeeded in removing it. : 

Birch-Hirschfeld reports an angioma of the liver that was partially extirpated 
by Hagedorn. It was as large as a pregnant uterus, and completely filled the 
abdomen. 


The majority of angiomata do not protrude above the surface of 
the liver. They are usually found in old people, and more frequently 
_ in men than in women. They develop by taking the place of the liver 


750 DISEASES OF THE LIVER. 


tissue, and consequently do not produce any symptoms of compression. 
In the vicinity of a recent angioma fatty degeneration or brownish atrophy 
of liver-cells can sometimes be seen near the margin of the tumor. 

[Schmieden* reports his study of 32 cases of hepatic cavernomas, and 
of 13 livers that presented appearances of angioma-formation. He dis- 
cusses the various theories of causation,—primary proliferation of the 
connective tissue, congestion, primary atrophy of the liver-cells, ob- 
struction to the flow of bile, hemorrhage, etc.,—and states that none 
of these theories is tenable. He believes that cavernomata of the liver 
should be ascribed to a local transposition or constriction, or segmen- 
tation of tissue, or a defect in the arrangement of the liver tissue. Evi- 
dences of the latter he claims are to be detected in the newborn. In 
short, they correspond to aberrant “rests,” and take on tumor forma- 
tion through secondary changes and alterations. They are distinct 
from cavernous angiomata of the organs, or of the skin, which are true 
blood-vessel tumors. He suggests as a better name than angioma 
“neevus cavernosus hepatis.”” These growths may occur at any age and 
have been noted in the embryo; they show little tendency to a sudden 
increase in size.—ED.] 

In general the tumors are wedge-shaped, with their bases at the 
surface of the liver, underneath the capsule. They resemble infarcts 
in this respect. They appear as circumscribed reddish or black spots 
on the surface of the organ; these may be as large as a pinhead or a 
nut, and on superficial inspection look like hemorrhages. On transverse 
section they present the appearance of spongy tissue, consisting of 
numerous vascular spaces intercommunicating with one another, and 
separated by septa of connective tissue. (Virchow found some smooth 
muscle-fibers.) Sometimes the septa are thickened; and in such cases 
we speak of a fibrous angioma (Bottcher). Occasionally the tumors 
are inclosed in a dense capsule, though, as a rule, they are not so sharply 
separated from the parenchyma. If the blood-vessels that lead to 
these angiomata become occluded, cystic metamorphosis may occur 
with exudation of serous fluid into the cavity. Occasionally dark pig- 
ment is deposited in the septa and in the neighboring liver tissue con- 
stituting the so-called melanotic angioma (Hanot and Gilbert). Quite 
frequently angiomata are found co-existing in the kidney, just as cysts 
are found in these organs together with cysts in the liver. 


The cavernous tumors have usually a distinct connection with the branches of 
the portal vein; at the same time it is possible to inject them from the hepatic 
artery, as branches of this vessel supply the septa. Some authors (Birch-Hirschfeld, 
Hanot and Gilbert) believe that they originate in ectases of capillaries, combined 
with atrophy of the columns of liver-cells. Other authors believe that they are 
the result of senile marasmus, and that they represent circumscribed atrophy of 
liver-cells, and secondary ectasy of capillaries (Ziegler). Still others, like Virchow, 
claim that they develop from dilated branches of the portal vein, secondary to a 
primary inflammatory proliferation of connective tissue. Lilienfeld, working under 
Ribbert, arrives at the conclusion that they are formed from the interacinous 
vessels; in the beginning, from branches of the portal vein alone that become dilated 
to cavernous spaces and later in the disease the smaller vessels that originate from 
these spaces participate in the process; finally, the capillaries of the acini are also 
involved. In this manner inflammatory processes take place in the interacinous 
tissues around the vessels, so that their elasticity is reduced, and they become 
dilated as a consequence. The liver-cells atrophy, and are frequently found very 
narrow in the immediate vicinity of the cavernous tissue. An abnormal number 


* Virchow’s Archiv, cLx1, 373, 1900. 


NEOPLASMS. 751 


of leucocytes is found in the blood of these cavernomata; free liver-cells are also 
seen. Ribbert has lately arrived at a conclusion that is similar to that of Virchow 
and Rindfleisch—namely, that. newly formed connective tissue penetrates the liver 
substance, and that this tissue is later filled with vascular spaces. He believes 
that the first cause of a cavernoma consists in a small independent area inserted 
atypically into the liver-tissue, where the process develops independently. 

Virchow’s view that a chronic inflammatory process plays a role in the forma 
tion of multiple angiomata appears to be the most plausible one; at the same time, 
it is possible that dilatation of capillaries together with secondary atrophy of liver- 
cells may produce the tumor, while, at the same time, in other cases the degenera- 
tion and atrophy of the liver-cells may be primary. Beneke, for instance, describes 
a case in which capillary ectasis developed in a wedge-shaped area of the liver, 
combined with atrophy of liver-cells. In the apex of this cone-shaped district was 
found an obstructed bile-duct (as a result of a tubercular process), and Beneke 
draws the following conclusion: At first there was obliteration of the bile-duct, then 
stasis of bile, followed by degeneration and atrophy of the liver-cells, and ultimately 
dilatation of capillaries. 


Congenital angiomata must be distinguished from this acquired 
form. Steffen describes a solitary tumor of this kind that was as large 
as an apple. Chervinsky saw a large number of cavernomata in the 
enlarged liver of a child of seven months; these growths made the sur- 
face of the liver nodular. They resemble the cases of v. Eiselsberg and 
Rosenthal that were described above, and appeared to be genuine tumors 
and not the result of interacinous inflammation. Pilliet thinks that 
they are fetal inclusions of mesenchyma similar to the vascular nevi 
of the skin and fissural angiomata. 

The diagnosis of cavernoma can probably only be made during 
life by an exploratory incision in those cases in which a large tumor 
is present causing distress, and calling for an operation. In all other 
cases the presence of cavernomata will remain unrecognized. 

The prognosis is favorable. 

Treatment of the condition is unnecessary in the ordinary form 
of multiple angioma, as these forms are harmless. In the case of large 
solitary tumors the advisability of resection must be considered. This 
operation is very bloody, but usually successful. 


Beneke: “ Zur Genese der Leberangiome,” “ Virchow’s Archiv,’ Bd. cx1x, p. 54. 

Birch-Hirschfeld: ‘‘ Lehrbuch der pathologischen Anatomie,”’ Bd. 1, p. 615. 

Bottcher: ‘‘ Virchow’s Archiv,” Bd. xxvitl, p. 421. 

Chervinsky: “Archives de physiologie normale et pathologique,” 1885, tome un, 
p. 553. 

v. Eiselsberg: ‘ Wiener klin. Wochenschr.,”’ 1893, No. 1. 

Frerichs: ‘‘ Klinik der Leberkrankheiten,” Bd. 1, p. 210. 

Hanot et Gilbert: ‘ Etudes sur les mal. du foie,” 1888, p. 314. 

Journiac: “‘ Archives de physiologie normale et pathologique,” 1879, p. 58. 

Langhans: “ Virchow’s Archiv,” Bd. Lxxv, p. 273. 

Lilienfeld : “ Ueber die Entstehung der Cavernome in der Leber,” Dissertation, Bonn, 
1889. 

Pilliet : ‘‘ Verhandlungen der Pariser anatomischen Gesellschaft,’ July 3, 1891. _ 

Ribbert: “ Ueber Bau, Wachsthum und Genese der Angiome,” “‘ Virchow’s Archiv,” 
Bd. cui, p. 381. 

Steffen : “ Jahrbuch fiir Kinderheilkunde,” 1883, Bd. xix, p. 348. 

Virchow: “ Virchow’s Archiv,” Bd.-v1, p. 527. 


CYST s. 
(Cystoma, Cystadenoma, Cystic Liver.) 


Cavities filled with fluid may originate in the liver in different ways. 
The most important examples of this nature are echinococcus cysts ; these 


752 DISEASES OF THE LIVER. 


we will discuss in another place. The bile-ducts may become occluded 
by tumors, scars, parasites, etc., or gall-stones, so that the bile and 
the mucous secretion of the bile-duct epithelium -is retained; cavities 
may be formed in this way that may be single, or may ramify in different 
directions through the tissues of the liver. Dilatation of the gall-bladder 
by stasis, the so-called hydrops of the gall-bladder, may also be seen; 
or tumors may soften and form fluctuating swellings. Of all these 
conditions we will speak in other sections. 

We limit our discussion at present to those cavities that are 
filled with fluid, and to such as originate in the liver independently 
of any of the above-mentioned causes. Among these we must distin- 
guish two classes—namely, first, simple (usually solitary) cysts that 
represent, in the main, malformations; and, secondly, multiple cysts, 
disseminated throughout the liver, and in this way causing more or 
less serious damage (cystic liver, cystadenoma, cystic degeneration of 
the liver). The former type is usually observed at birth, or perhaps 
at the postmortem examination. Cystic liver, on the other hand, is 
a pathologic process intimately related to tumor formation in the liver, 
and forming a distinct transition toward those neoplasms which we 
usually designate as adenomata, and which in many instances are 
malign. Some authors believe that the formation of multiple cysts in the 
liver may also be congenital, and it is possible that this is occasionally 
the case; it is, however, striking that so many cases of cysts that develop 
later in life show some proliferation and the same histologic structure 
as the congenital type. Cystic degeneration in the liver is often accom- 
panied by the same process in the kidneys, the ovaries, the broad liga- 
ments, or in other organs of the body. Cystic liver is a condition that 
progresses rapidly, and causes serious disturbance in a short time; this 
statement does not, however, apply to the first category of cases. 

Simple cysts of the liver of the first class often show in a most pro- 
nounced manner that they originate in malformations; this applies, 
for instance, to the hepatic cysts described by Witzel, Sanger and 
Klopp. 

These growths were so large that they obstructed the delivery of 
the child. 


In the case described by Sanger and Kloop a pedunculated cyst was observed 
in the liver, in addition to a marked ascites. The cyst contained a third of a liter 
of a cloudy, dark, yellow, slimy fluid, containing mucin, bile-pigment, albumin, 
squamous and cuboid epithelial cells. It was surrounded by a capsule of connective 
tissue, in which were found clumps of liver tissue inlaid with flattened cells. In 
another case liver tissue was found embedded in the wall of the cyst. The two 
authors consider the first cyst as an accessory liver with an accessory gall-bladder; 
the second case appeared to present an accessory liver with a cyst of an accessory 
bile-duct. In addition, a number of cysts were found in the vicinity of the stomach 
and intestine that also contained liver tissue in their wall, and which were con- 
sidered accessory livers developing from Meckel’s diverticulum. Other authors 
(Morgagni, Wagner, Gruber) have also described accessory livers. Occasionally 
the gall-bladder may be divided into two parts, situated next to or behind one 
another (Ahlfeld and others). In the monster described the spleen was also divided 
into numerous single spleens; there was also a transposition of the viscera, hemi- 
cephalus, etc. 

In Witzel’s case three liters of fluid were evacuated from the cavity before 
birth could take place. The cyst occupied both the left and the right lobe of the 
livery and‘communicated with the common duct, which ended in a culdesac in 
the region of the duodenum; this, too, was a monster, with transposed viscera. 
The kidneys ,were filled with numerous cysts. 


NEOPLASMS. 758 


A number of other cases have been described in which cysts were 
found in the vicinity of the suspensory ligament, and which caused no 
disturbance during the life of the patient. 


Friedreich describes a cyst that was as large as a hazelnut, and was connected 
with the liver by loose connective tissue; ciliated epithelium were noted on top of 
a layer of round embryonal cells. The fluid contents were viscid, yellowish-gray, 
and slimy. Eberth describes a similar case. We owe the most careful description 
of cysts of this kind to von Recklinghausen, who notes a cyst of the size of a hazelnut 
containing a thick pasty mass, with granules of albumin and mucin; the epithelium 
was long and ciliated, and was placed upon an embryonal layer of cells. In those 
cases in which the cells were not so long the second layer and the cilia were lost. 
This cyst communicated with a mucous gland in the hepatic wall, which was dilated 
and cavernous, and apparently manufactured the contents of the cyst. In addition, 
numerous canals were found in the wall, which Friedreich considered as lymph- 
spaces. Von Recklinghausen, however, believed them to be bile-passages, vasa 
aberrantia, and observed hyaline metamorphosis of their epithelium. He attributes 
the formation of these subserous mucous cysts to an isolation of bile-passages, and 
believes that mucus, formed by the glands situated in the walls of these bile-passages, 
is retained within these canals. Waring has described two similar cases of cysts 
in the lower margin of the liver, and has made drawings of them. Virchow has 
described structures of this kind containing mucus or colloid, and situated near 
the surface of the liver; one of these was situated in the suspensory ligament. Vir- 
chow is inclined to the belief that it was formed by the isolation of vasa aberrantia. 
It can very well be understood why these cysts contained no bile, as such passages 
are not connected with secreting liver tissue. The ciliated character of the epi- 
thelium lining these cysts need not surprise us, for we know that the form and the 
size of the epithelial cells vary with the conditions of nutrition, in the same manner 
as in ovarian cysts, cysts of the glands of Bartholini, etc. Von Recklinghausen 
considers the cyst formation to be the result of a myxadenitis, in combination with 
isolation of bile-passages. 

Zahn, on the other hand, considers cysts containing ciliated epithelium to be 
fetal growths of organs that have nothing to do with the liver; he bases this con- 
clusion upon the fact that in all cases observed by him he found the cysts always 
in the same location—namely, the vicinity of the suspensory ligament between the 
peritoneum and the membrana propria of the liver. He believes that they are the 
remnants of some organ that is present in the embryonal stage and disappears 
subsequently. Another case, reported by Girode and published by Hanot and 
Gilbert, belongs to this class. This was a cavity lined with ciliated epithelium and 
situated in the vicinity of the suspensory ligament. The growth was found by 
chance at the autopsy. 


We are probably justified in including certain cysts of the liver, 
treated surgically, among these congenital structures. These cysts 
were very large, but were similarly situated. No general cystic de- 
generation of the liver or the kidneys appeared to be present. 

As these cases recovered after the operation this question could 
not be decided. 


~~‘ 

A case reported by Winkler must be included in this category. He describes 
it as a cystoma of the ovary, but found later that it was connected with the lower 
margin of the liver; not, however, until he had evacuated some eight liters of a 
yellow, brownish-red fluid, alkaline in reaction, of a specific gravity of 1014, and 
containing much albumin and mucin, a little bile-pigment, much cholesterin, and 
colloid round structures that were about as large as a leucocyte. The wall of this 
cyst contained no epithelium, but consisted exclusively of connective tissue. After 
the operation a bile-tinged, and later a mucopurulent fluid, continued to ooze from 
the wound. It is possible that this was a congenital cyst that later became inflamed 
so that an abundant secretion occurred into the cavity, or that it was a mucous cyst 
which had originated in a vas aberrans as a result of inflammation of the mucous 
membrane and occlusion of the duct. v. Recklinghausen describes a cyst of this 
kind in a case which he reports. 

AGO oS 


- 754 DISEASES OF THE LIVER. 


The other category of cysts of the liver—namely, multiple cysto- 
mata, or cystic liver, cystic degeneration, etc.—has an intimate con- 
nection with the bile-passages. These cases, and others that were less 
carefully investigated, presented tumors that were probably mucous 
cysts developing from vasa aberrantia or bile-passages that did not 
end within the liver tissue, but ended blindly in the region of the sus- 
pensory ligament. In the cases now to be discussed the intrahe- 
patic bile-passages developed into cysts, probably in a manner 
analogous to the development of cysts from urinary tubules 
within the kidneys. Older authors (Rokitansky) believed that these 
cysts developed from blood-vessels or lymph-channels; more recent 
investigators, however, have demonstrated that they develop from 
bile-passages, and particularly from ducts formed during certain 
pathologic conditions. They are related to adenomata; and the 
cystadenomata form a connecting-link. These cysts show a ten- 
dency to rupture into blood-vessels in the same way as do bile-duct 
adenomata (v. Hippel). . 

As a sharp differentiation cannot be made, we will describe cyst 
adenomata and the so-called cystic degeneration as one and the same 
condition. Cysts hold their place among the tumor formations of the 
liver. Coexisting cirrhosis has frequently been observed and some 
authors have even expressed their belief that the cirrhotic process 
has a decided influence upon the development of the cysts. Thus, 
Sabourin states that they develop from the new bile-passages that 
are seen in interlobular cirrhosis, that these canals become dilated, 
and form a cavernous network (angiome biliatre); that they then de- 
velop further, become confluent, and in this way form a cyst inclosing 
several biliary cavities. Juhel-Rénoy, in his case, observed new-forma- 
tion of bile-passages in the condensed interacinous connective tissue, 
and in these canals signs of cholangitis and pericholangitis; further, 
dilatation and the formation of cysts; all these conditions he ascribes 
originally to the occlusion of these bile-passages. Rolleston and Kan- 
thack describe dilatation of bile-passages in the newborn in cases com- 
plicated with portal cirrhosis. On the other hand, cases have been 
described in which cirrhotic lesions were absent, or present only to a 
very slight degree, so that it can hardly be assumed that cirrhosis is 
concerned etiologically in the formation of these cysts. The new- 
formation of bile-passages which precedes the development of the cysts 
apparently is not only a result of proliferation of interlobular bile- 
passages and budding of these canals into the acini of the liver, but 
also a result of the metamorphosis of columns of liver-cells into canals 
that contain rows of cells similar to the epithelia of the bile-passages. 
We will describe the development of this process when discussing the 
genesis of adenomata and adenocarcinomata (compare page 765). 
Naunyn describes a case of cystadenoma which he calls a cystosarcoma, 
in which the transition of bile-passages into cysts is noted. This author 
shows how buds are formed on these passages, and how these again 
become dilated and increased by new cells until, finally, a cavity results 
that continues to enlarge. v. Hippel, Manski, and others have also 
described the formation of cysts from bile-passages, some of which 
sent dendritic ramifications into the acini (v. Kahlden). In the bile- 
passages of the liver cholangitis, thickening of the walls, and occlusion 
of the lumen by desquamated epithelium is frequently seen; the fully 


NEOPLASMS. 755 


developed cysts have a cylindrical or cuboid epithelium, or a squamous 
polyhedric epithelium. In the larger cysts the epithelium is lower 
and flatter than in the small variety, owing to the stretching of the 
cyst-wall by the fluid. In the largest cysts cells may be completely 
absent owing to atrophy or desquamation; hemorrhage, too, may cause 
separation of the epithelium. Occasionally the walls are folded, and 
show connective-tissue processes; in other cases the walls are smooth. 
In the manner described cysts may be formed that contain many liters 
of fluid, and these may be seen side by side with cysts that are no larger 
than a pinhead. The contents consist of a more or less albuminous 
fluid containing mucin and peculiar colloid structures; further, epithe- 
lium, leucocytes, red blood-corpuscles, granular masses of albumin, 
crystals of hematoidin, and cholesterin. As a rule, bile-pigment is 
absent; traces of phosphates and chlorids are found. The color is 
usually watery, or yellowish-brown, or chocolate color; the latter is 
seen particularly in cases where hemorrhages have occurred into the 
cyst. 

Sometimes a process of repair may be observed in these cysts, con- 
sisting of a proliferation of connective tissue in the wall, that gradually 
fills the cavity. The liver tissue is often atrophic and degenerated; 
the columns of liver-cells are flattened, and remnants are occasionally 
seen in the wall of the cyst. Branches of the portal vein may show 
cavernous dilatation. Macroscopically a liver of this kind presents a 
very peculiar picture; large and small cysts form dark and light pro- 
trusions on the surface and the transverse section of the organ. The 
interior of the liver is converted into a series of innumerable 
cavities varying in size from a pinhead to a child’s skull; between 
these cavities a little of the liver substance may be seen. Some 
of the cysts are so large that they inclose several liters of fluid (Manski) ; 
at the same time stasis of bile or of blood may be present and give the 
organ a still more peculiar aspect. Occasionally the liver is hard and 
cirrhotic and only slightly or not at all enlarged; in the majority of 
cases, however, the organ is soft and very large, so that it weighs as 
much as 10 kg. (Dmochowski and Janowski). Stasis may be present 
in the portal vein and lead to ascites, swelling of the spleen, and con- 
gestive catarrh of the stomach and intestine. 


Terburgh describes peculiar round, protoplasmic bodies with a radiating striated 
zone; and other bodies that are inclosed in a radiating striated shell, and contain 
granular masses and sometimes nuclei resembling the eggs of tenia. These were 
found in the fresh fluid aspirated from the cystic liver; the author believes it likely 
that psorospermia were involved in the cyst formation, particularly as in rabbits 
the presence of this parasite often causes the formation of large cavities in the 
liver filled with a thick whitish mass. He was not enabled to examine these struc- 
tures carefully. Gubler found a number of spherical tumors in the liver of a man 
of forty-five, containing a viscid, slimy substance in which psorospermia were 
present. Leuckart also describes a similar case (see page 789). We expect that 
further investigation will throw more light upon this subject; it is necessary, how- 
ever, that analyses should be made of fresh material, as Terburgh reports that he 
ar es longer discover the structures he has described if the fluid was allowed 

o stand. 


[Shupell called attention in December, 1900, to a case of simple 
retention cyst of the liver. He was led to look upon the case as one 
of that nature because of the histologic formation, the fact that it was 
full of bile, and because of the total absence of hooklets. A similar 


756 DISEASES OF THE LIVER. 


case has recently been reported by Israel Cleaver * that again brings 
up the question of origin of these cystic growths. His specimen ob- 
tained at autopsy measured 124 inches in width, the left lobe 4 inches, 
the vertical length 8 inches, and the thickness 54 inches. A large cyst 
projected above the surface measuring 74 inches in circumference, 
occupying the under surface of the right lobe, and crowding the gall- 
bladder, which was itself much enlarged. There was also a second 
cyst, walnut-sized, sessile, on the upper margin of the left lobe, and 
four more of the size of hulled shellbarks on the surface of the same 
face, but to the right of the large cyst. Sections of the portions of the 
organ not involved by the cysts showed no parenchymatous change. 
The gall-bladder contained 26 calculi. He refers to similar cases reported 
by Roberts} and Robson.t No hooklets were found in the fluid from 
any of the cases. The symptoms were invariably such as to lead to the 
diagnosis of distended gall-bladder.—Ep.] 

Symptoms.—Congenital cysts, like those described by Witzel, Sanger 
and Klopp, may be so large as to cause ascites, and constitute 
an obstacle to the delivery of the child. If the tumor is perforated 
or tears, the fetus dies. It may, however, not be so large as this, and 
may remain latent during the life of the subject and be found at autopsy ; 
or it may continue to grow owing to some irritant influence, the origin 
of which we do not understand, and later on form a large cystic tumor 
that will endanger life. 


Bayer reports a case in which a large, rapidly developing cyst was found, and 
in which he assumes that the growth was the result of an inflammatory process in 
the bile passages. It is possible, however, that this was a congenital cyst that 
later became inflamed and hemorrhagic. 


A cyst of this size may fill a large part of the abdomen, may push 
the diaphragm upward, compress the right lung, lead to icterus from 
stasis, and cause swelling of the liver and of the gall-bladder. All of 
these conditions I have observed in the following case: 


A girl of four years was admitted on the 19th of July, 1895; during the six weeks 
preceding this date she suffered from diarrhea, loss of appetite, emaciation, and, 
later, fever, icterus, and itching of the skin. A tumor was felt that was evidently 
connected with the liver, fluctuated, and extended below the navel. On July 21st 
Neuber performed a laparotomy, and it was found that the intestine was situated 
in front of the swelling, that the liver was pushed upward, the gall-bladder filled 
and resting on the tumor. Violent parenchymatous hemorrhage occurred, and for 
this reason the cyst was not opened, and the wound was closed with tampons. 
The child died from collapse a few hours after the operation. It was found that 
the cyst contained over a liter of a mucous, clear fluid, was situated between the 
kidney and under surface of the liver and the intestine, and was connected with 
the liver in the region of the porta hepatis; in addition there were peritonitic adhesions 
existed to neighboring organs. Thecyst had compressed the bile-passages at the 
hilum, principally the common duct, and for this reason there was stasis of bile in 
the liver and the gall-bladder, the latter viscus containing about 100 cm. of a bile- 
tinged fluid. The cystic duct was dilated, and also filled with bile. The wall of 
the cyst could be divided into two layers, the inner one of which showed the struc- 
ture of mucous membrane. Unfortunately a more careful microscopic examina- 
tion was not undertaken. 


It appears that ascites does not occur as frequently in the case of 
these cysts as in general cystic degeneration, probably because the 
isolated form of cyst develops near the anterior margin of the liver 


*Phila. Med. Jour., Dec. 28,1901. ft Annals of Surgery, vol. x1x, p. 251. 
t ‘‘ Treat’s Annual,” 1895. 


NEOPLASMS. 757 


and increases in size toward the open abdominal cavity, and, therefore, 
does not compress the portal vein. Another reason may exist in the 
fact that in multiple cystic degeneration changes are frequently ob- 
served that are not present in the case of other cysts. 

Multiple cysts of the liver are frequently unexpectedly found at au- 
topsy, as they may produce no symptoms during life. Cystic degeneration 
of the liver, however, is more frequently diagnosed than the same con- 
dition in the kidneys, principally because the former organ is more 
accessible to palpation, and because the nodulated surface, with fluctua- 
tions here and there, is to an extent characteristic. If abundant ascites 
is present, this peculiarity may be masked, as the ascitic fluid will push 
the liver upward, and also cover its surface; if the fluid is evacuated, 
the change of form can usually be recognized. Sometimes exploratory 
puncture of a fluctuating tumor may establish a diagnosis; as, for in- 
stance, the presence of albumin and mucin, the absence of hooks, sco- 
lices, shreds of membrane, will help differentiate the cyst from echino- 
coccus. It is necessary, however, to proceed very carefully, and with 
all aseptic precautions, as purulent infection of the cyst may occur. 
In addition to ascites, a considerable degree of edema of the lower ex- 
tremity may result from compression of the inferior vena cava. Other 
symptoms of condensation of peri-portal connective tissue, hemorrhages, 
catarrh in the intestine, may be seen as in typical cirrhosis; sometimes, 
but not frequently, icterus develops. Changes in the kidneys are 
particularly important, and modify the course of the syniptom-complex, 
particularly cystic degeneration of these organs, a condition that is 
so frequently seen together with cystic degeneration of the liver. The 
symptoms of chronic nephritis or of contracted kidney frequently com- 
plicate this form of degeneration, so that patients in whom a diagnosis 
of cystic degeneration of the liver was made during life, or in whom 
this condition was found postmortem have died of albuminuria, sup- 
pression of urine, uremia, and coma. 

Prognosis.—The prognosis of solitary cysts of the liver and of 
cystic degeneration of the organ depends very much on the involvement 
of the bile-passages, the portal vein, or of other organs. If the kidneys 
are diseased, or if cirrhosis of the liver is present as a complication, 
the prognosis becomes graver. 

Treatment is of little avail in multiple cyst formation, and consists 
exclusively in aspiration of the ascitic fluid or drainage of the lower 
extremities in case of compression of the vena cava. The renal con- 
dition will require the greatest amount of attention. If large solitary 
cysts are present, an operation may be necessary. Such growths have 
been successfully extirpated (Hueter), and others have been sutured 
to the abdominal wall and drained (Winckler). 


Bayer, C.: “Ueber eine durch Operation geheilte, mannskopfgrosse Lebercyste,”’ 
“Prager med. Wochenschr.,’’ 1892, p. 637. 

Chotinsky: Dissertation, Bern, 1882: 

Dmochowski und Janowski: “ Ein seltener Fall von totaler cystischer Entartung 
der Leber,” “ Ziegler’s Beitrige,’’ 1894, Bd. xv1, p. 102. 

Frerichs: “ Klinik der Leberkrankheiten,” Bd. 1, p. 216. 

Friedreich: ‘“Cyste mit Flimmerepithel in der Leber,” “Virchow’s Archiv,” Bd. 
XI, p. 466. 

Hanot et Gilbert: ‘ Etudes sur les mal. du foie,” 1888, p. 295. - 

v. Hippel: “ Ein Fall von multiplen Cystadenomen der Gallenginge,” “ Virchow’s 
Archiv,” Bd. cxxi, p. 473. 


758 DISEASES OF THE LIVER. 


Hueter: “ Ein grosses Cystom der Leber,” Dissertation, Gottingen, 1887. 

Juhel-Rénoy: “Observation de dégénérescence kystique du foie et des reins,” 
“ Revue de médecine,” 1881, p. 929. 

v. Kahlden: “Ueber die Genese der multiplen Cystenniere und der Cystenleber,”’ 
“ Ziegler’s Beitrage,’’ Bd. x11, p. 291. ; 

Manski: ‘‘ Ueber Cystadenome der Leber,’ Dissertation, Kiel, 1895. 

North: “Case of Cystic Tumor of the Liver,” “ New York Med Record,” Sept. 23, 
1882, p. 344. 

Opitz: ‘ Ein Fall von Leber- und Nierencysten,’”’ Dissertation, Kiel, 1895. 

v. Recklinghausen: “ Ueber die Ranula, die Cyste der Bartholin’schen Driise und 
die Flimmercyste der Leber,” “ Virchow’s Archiv,” 1884, Bd. Lxxxitv, p. 473. 

Rolleston und Kanthack: “ Beitrige zur Pathologie der cystischen Erkrankung der 
Leber im Neugeborenen,” “ Virchow’s Archiv,” Bd. cxxx, p. 488. 

Sabourin: “Contribution 4 l’ét. de la dégénérescence kystique des reins et du foie,” 
“ Archives de physiologie,’’ 1882, tome 11, p. 63. 

Sanger und Klopp: “ Zur anatomischen Kenntniss der angeborenen Bauchcysten,”’ 
“ Archiv fur Gyniakologie,”’ 1880, Bd. xvi, p. 415. 

Siegmund: ‘Ueber eine cystische Geschwulst der Leber,” “Virchow’s Archiv,” 
1889, Bd. cxv, p. 155. 

Terburgh: “ Ueber Leber- und Nierencysten,” Dissertation, Freiburg, 1891. 

Virchow: ‘‘Geschwilste,”’ Bd. 1, p. 256. 

Waring: “ Diseases of the Liver,” p. 148. 

Winckler: “ Zur Casuistik der Lebercysten,” Dissertation, Marburg, 1891. 

Witzel: ‘Hemicephalus mit grossen Lebercysten,” ‘‘Centralblatt f. Gynakologie,” 
1880. 

Zahn: ‘Ueber die mit Flimmerepithel ausgekleideten Cysten . . . der Leber,” 
“Virchow’s Archiv,” Bd. cxit, p. 170. 


CARCINOMA, SARCOMA, ADENOMA. 


As a rule, carcinoma and other malignant neoplasms of the liver 
are discussed apart from a connection with similar growths of the gall- 
bladder and the bile-passages. The clinical picture, however, does not 
admit of a strict differentiation, for the reason that a primary carcinoma 
of the liver may be complicated by a secondary carcinoma of the gall- 
bladder or bile-passages; and because, inversely, a carcinoma of the 
gall-bladder may make its way into liver tissue, and develop princi-. 
pally within the liver substance. Finally, carcinomata of intrahepatic 
bile-passages act just as do primary growths of the liver parenchyma. 
For all these reasons we will discuss these different forms of neoplasms 
together. 

Etiology.—The nature of the virus of carcinoma is so obscure that 
we will not discuss it. If we assume that such a virus exists, we must 
also admit that it must enter the liver through the blood in cases of 
primary carcinoma; and we will have to assume that this occurs through 
the portal vein, as in the case of all other diseases-producers that become 
localized in the liver (animal parasites, etc.). In other words, the virus 
must come from the intestine, pass through the venules into the portal 
vein, and thus be carried into the liver. Secondary carcinomata of 
the liver certainly originate in this manner. In cases of carcinoma 
of the stomach, the intestine, the rectum, and the pancreas, carcinoma- 
tous involvement of the liver is often seen, and may develop into a 
larger tumor than the original focus. Such a growth in the liver was 
at one time looked upon as the primary tumor with greater frequency 
than to-day, because the larger tumor was, as a rule, considered to be 
the primary one, and, moreover, the general examination of the abdomi- 
nal organs was often imperfect. It is also possible for metastases to 
develop in the liver by means of the general circulation through the 


NEOPLASMS. 759 


hepatic artery, as, for instance, after carcinoma of the breast, and other 
neoplasms in remote organs. In carcinoma of the female genitals, 
particularly in cancer of the uterus, the infection probably enters the 
liver from certain portions of the body the veins of which anastomose 
with the portal system. 

Primary carcinomata of the bile-passages and of the gall-bladder 
from the intestine through the ducts, may very possibly result from 
infection from the bowel through the ducts. Secondary growths of 
these parts may come from the liver, or especially from carcinomata * 
of the lower abdominal organs. 


A certain amount of importance has been attached to heredity in the case of 
carcinoma of the liver. Up to this time writers on this question have offered little 
that is convincing. Paget and West state that hereditary predisposition exists 
in 17 % of all cases; Lebert finds it in 14 %, Sibley in 11%. Leichtenstern, who 
has summarized these and other statistics, finds a hereditary predisposition in 192 
out of 1137 cases (17 %). 

It may also happen that several individuals are afflicted with carcinoma in the 
same house, and all contract a carcinoma of the liver and die from this lesion (D’Arcy, 
Power, Scott, Langenbuch). 


Carcinoma of the liver is less frequent than carcinoma of the uterus, 
the stomach, or the breast. 


According to Leichtenstern, out of 10,007 cases of carcinoma, 31 % were of 
the uterus, 27 % were of gastric carcinoma, 12 % of breast carcinoma, and 6 % 
of liver carcinoma. 


Carcinoma of the liver is particularly frequent in advanced age, 
after forty. 


According to Leichtenstern, 7.8 % of all cases were found between twenty 
and thirty years, 12.9% between thirty and forty, 53.1% between forty and 
sixty, 19.3 % between sixty and seventy, and 6.9 % above seventy. In children 
carcinoma is rare, but does occur. Thus, it has been found in the new-born (Siebold) 
and in a child of six months (Bohn). Farré found a secondary carcinoma in a child 
of three months, and in two children of two years and a half. Wulff saw carcinoma 
of the liver in a child of three years, Kottmann in a child of nine years, Deschamps 
in a child of eleven years, and Roberts in a child of twelve years. Leichtenstern 
and Langenbuch have also seen carcinoma of the liver in children. 

[A considerable number of cases of primary carcinoma of the liver in children 
have been reported within the past few years, of which the most interesting were 
those noted by Descroizille * and 10 cases noted by Schlesinger.t The ages ranged 
from four to eleven and a half years.—Eb.] 


The female sex is afflicted more frequently with secondary carcinoma 
than the male, this being due to the great tendency to primary car- 
cinoma of the breast, the uterus, and the ovaries. Primary carcinoma 
of the liver is more frequent in men because male subjects are more 
frequently afflicted with cirrhosis, and because this disease seems to 
favor the development of carcinoma. It is stated that malaria and 
the abuse of alcohol are predisposing factors. 

[This latter belief is of especial interest in view of the recent attempts 
to cure carcinoma by producing a malarial infection (Ld6ffler f). 
The procedure has since been proved to be an absolute failure as re- 
gards the cure of the cancerous growth.—Eb.] 


* Rev. mens. des Mall. de l’Enj., June, 1894. 
+ “Jahrbuch. f. Kinderh.,”” March, 1902. 
¢ Deutsche med. Woch., Oct. 17, 1901. 


760 DISEASES OF THE LIVER. 


Traumata of the liver may have something to do with the formation 
of carcinoma, just as we sometimes see the development of neoplasms, 
parasites, and the lodgment of infectious material in other parts of the 
body following slight injury. 

Chronic irritation seems to be an important factor in the etiology 
of carcinoma of the bile-passages and the gall-bladder; for this reason 
we see this form of tumor quite frequently in cholelithiasis. Courvoisier 
found carcinoma of the gall-bladder in 2.7 % of cases with gall-stones; 
Siegert found gall-stones almost without exception (95 %) in primary 
carcinoma of the gall-bladder; in secondary carcinoma they were rarely . 
found (15 to 16 %). It seems natural, then, that carcinomata of this 
character are more frequently found in women than in men, because 
the former are more frequently afflicted with gall-stones. It may be 
that lacing, which is made responsible for the frequency of cholelithiasis 
in women (Heller, Marchand, and others), exercises a pernicious effect 
on the gall-bladder, and thus favors the development of carcinoma. 


Tiedemann has collated 79 cases of carcinoma of the gall-bladder, and found 
that 11.3 % were in men, 88.7 % in women, and that gall-stones were present in 
79.7 %. Siegert mentions 99 cases of primary carcinoma of the gall-bladder, of 
which 15 % occurred in men, 82 % in women, and in two no statements are made. 
Musser found carcinoma of the gall-bladder in women three times more frequently 
than in men; Kelynack four times more frequently. ; 


The view that carcinoma of the bile-forming organs leads to stasis 
of bile, and in this manner favors the development of gall-stones, seems 
less justifiable than that carcinoma is the result of the action of gall- 
stones. 

The effect of gall-stones on the epithelium of the mucous membrane 
is to convert it into a horny flat epithelium, and as this is the same 
tissue as that seen in carcinoma, we may have here an argument in 
favor of the réle of gall-stones in the formation of carcinoma. Willigk 
has stated that stasis of bile in the bile-passages may be the cause of 
carcinoma even in the absence of gall-stones. 

In contradistinction to primary carcinoma of the liver, a condition 
that is often seen at an age when carcinoma elsewhere is rare [vide fore- 
going exceptions—ED.], primary carcinoma of the gall-bladder is chiefly 
seen in old age. Tiedemann states that sixty is the average age for 
carcinoma of the gall-bladder; whereas Leichtenstern states that in 
primary carcinoma of the liver the average age is below forty. 

Carcinoma of the gall-bladder is the most frequent of the primary 
carcinomata about the liver. Genuine primary carcinoma of the paren- 
chyma of the liver is rare. Primary carcinomata of the bile-passages 
are very rare. Among 258 cases of carcinoma of the liver in the Berlin 
Pathologic Institute, Hansemann found 25 cases of primary carcinoma 
of the gall-bladder, 6 true primary carcinomata of the liver, 2 of which 
were indefinite, and 2 primary carcinomata of the large bile-ducts. 

The rare cases of primary sarcoma of the liver that have been 
reported are usually seen in persons still younger than those afflicted 
with carcinoma; they are seen more frequently in childhood. Some 
observations seem to indicate that cirrhotic changes in the liver predispose 
to the development of this form of tumor, but this has not been proved. 
[Axtell ‘reported a case of primary sarcoma of the liver in a child,* as 


* N.Y. Med, Jour., March 3, 1894, 


NEOPLASMS. 761 


did Samuel West.* The latter case was fifteen years old. Williamson t+ 
reports 11 cases of melanotic sarcoma of the liver, in 3 of which melano- 
gen was twice found in the urine. Hamburger also reports 2 cases 
of melanosarcoma of the liver following sarcoma of the eye; in the urine 
of these cases also melanin was found. Pepper has recently reported a 
case of congenital sarcoma of the liver and suprarenal capsule.{—Eb.] 
Secondary sarcomata are also found in young persons, and may 
originate from sarcomata in various parts of the body by metastasis. 
This is particularly the case in melanotic sarcomata of the choroid and 
of the skin. The causes of malignant adenoma are obscure; it seems 
that cirrhosis of the liver favors their development. 

Pathologic Anatomy.—Primary carcinoma of the liver: Within 
the last decade it has been shown that primary carcinoma of the liver is 
of rare occurrence compared with its secondary occurrence, and as 
a result great care has since been taken to exclude the presence of car- 
cinoma in other organs. The anatomic conditions were soon better 
understood, and it became possible to differentiate between primary 
and secondary tumors of the liver, and to-day it seems fair to draw 
a conclusion from histologic examination of the liver whether the me- 
tastasis is from the stomach, the intestine, the uterus, or whether the 
tumor is a primary growth of the parenchyma of the liver. The inves- 
tigations of Naunyn, Waldeyer, Schiippel, and of his pupils; also those 
of Weigert, Hanot and Gilbert, Hansemann, Siegenbeck van Heu- 
kelom (dissertations published from the Pathologic Institute in Kiel 
by Rohwedder, Nolke, and others), as well as numerous other publi- 
cations, give us a clear insight into the structure and genesis of primary 
carcinoma of the liver. 

Some points are not clear, and are still the subjects of controversy. 
This is particularly the case in regard to adenomata of the liver, of 
the kind first described by Rindfleisch and Griesinger; also of carcino- 
mata. Occasionally adenomatous and carcinomatous growths are seen 
side by side in the liver, so that the suspicion seems somewhat justified 
that the one may merge into the other. Naunyn believed that there was 
no difference between the two diseases, and Schiippel expressed the 
opinion that nodular hyperplasia, adenoma, and carcinoma form a 
chain. The adenoma, according to his view, persists for a long time, 
or permanently, owing to its histologic structure as a typical new-forma- 
tion of glandular epithelium. Under certain circumstances, however,— 
in case, for instance, irritation sets in,—the tissues are stimulated to 
increased growth, and may develop into an atypical carcinomatous 
form of growth. Hanot and Gilbert, also Siegenbeck van Heukelom 
(adenocarcinoma of the liver), are in favor of this view. Rindfleisch, 
Simmonds, Kelsch and Kiener, Sabourin, and others, differentiate the 
two diseases. Clinically no difference can be formulated between an 
adenoma that is complicated by cirrhosis and a carcinoma with cir- 
rhosis, and for this reason we will discuss them as one condition. 

Primary carcinoma may appear in various forms. It may be solitary 
or multiple, and with or without proliferation of interstitial connective 
tissue. The parenchymatous cells of the liver and the epithelium of 
the bile-passages may participate in the formation of the neoplasm. 
In this manner totally different pictures are created. 


* Brit. Med. Jour., Oct. 25, 1902. + Lancet, Dec, 2, 1900, 
Amer. Jour. Med. Sci., Mar., 1901. 


762 DISEASES OF THE LIVER. 


The following constitute the three principal types: 

Tirst, massive carcinoma. In the interior of the liver, and usually 
surrounded by healthy liver tissue (almond-carcinoma), there appears 
a round, rapidly developing tumor that later on sends metastasis into 
the liver parenchyma. The organ is much enlarged, with a smooth 
surface, or with a surface that is covered with large flat ridges in case 
the neoplasm penetrates far into the liver. These spots appear pale, 
whitish-yellow, or grayish, and are clearly differentiated from the rest 
of the liver tissue. Occasionally the capsule is thickened, but never 
adherent to the parietal peritoneum. On transverse section the differ- 
ences in color are very apparent. The healthy liver tissue shows no 
cirrhotic induration, and the cut surface of the carcinoma no distinct 
softening, because there is very little tendency to degeneration of a 
primary carcinoma of the liver. Numerous strands of connective tissue 
are seen on the cut surface; these are white, in part transparent, and 
inclose nodules of carcinomatous tissue which are as large as a cherry, 
and appear softer in the center than at the periphery. The neoplasm 
is distinctly demarcated from the normal tissue. Metastases are found 
in the lymph-glands of the hilum, and less frequently in the peritoneum, 
the kidneys, and the lungs. 

Second, nodular carcinoma. The appearance of the liver resembles 
that of secondary carcinoma. There are numerous whitish-gray or 
yellowish nodules throughout the liver and protruding above the surface. 
There is usually no depression in the center as a result of softening. 
The liver is not as large as in the preceding case; generally, there is 
wide-spread cirrhosis, and consequently a contraction and induration 
of the parenchyma. Sometimes one large and numerous small nodules 
of carcinoma are found, so that it appears as though the latter originated 
from the former. ‘Transition stages between massive and nodular car- 
cinoma are also seen. 

Third, infiltrating carcinoma. This consists of a diffuse carcino- 
matous degeneration of liver parenchyma. The liver is uniformly 
enlarged, the capsule cloudy and frequently thickened, and occasionally 
adherent to other organs. The surface of the liver shows flat ridges 
and nodules, as large as peas or cherries. On transverse section the 
outline of the lobules can be seen as in cirrhosis; the nodules are, how- 
ever, considerably larger than normal liver acini, and are colored whitish- 
yellow, or grayish. The connective tissue between them is usually 
reddish in color owing to its greater vascularity. The lobules will be 
found to be masses of carcinoma of a fibrous. structure, from which 
a considerable quantity of carcinoma juice can be expressed (Fetzer). 


Hanot and Gilbert differentiate between massive cancer, nodular cancer, and 
cancer with cirrhosis. The first two correspond to the two forms we have discussed 
above; the last corresponds to adenocarcinoma as described by Siegenbeck van 
Heukelom and the adenoma of the liver described by Kelsch and Kiener, Sabourin, 
and others. 

In addition to numerous connective-tissue new-formations, a number of acinous 
neoplasms are seen that merge into masses of carcinoma; the liver is enlarged and 
cirrhotic; on transverse section numerous nodules are seen which when young 
appear yellowish and dry, and when old are softened and juicy; some of them are 
indented. 


The histologic picture is, in many respects, more varied than the 
macroscopic picture. Frequently cirrhotic changes and proliferations, 


NEOPLASMS. 166 


particularly of the portal, and sometimes of the intralobular, connective 
tissue are seen. Connective-tissue strands pass between the columns 
of liver-cells from the condensed interlobular tissue, and extend 
as far as the central veins, which are also surrounded by connective 
tissue. In other rare cases cirrhosis is absent, particularly if there 
is only one carcinomatous nodule. Sometimes the cirrhotic changes 
are so conspicuous that the carcinomatous element is not discovered. 
For this reason some authors (Perls, Thorel) speak of carcinomatous 
cirrhosis. Cirrhosis may be due to different causes in carcinoma of 
the liver; generally it is the result of the same agent that causes the 
formation of carcinoma, so that it originates at the same time. It 
is possible, however, that in some cases it precedes the carcinomatous 
change, as in drunkards and in stasis of bile following occlusion of the 
common duct. Such cases have been reported by Naunyn and Thorel. 
That cirrhosis, as Laveran assumes, is the result of carcinoma does 
not seem probable, although proliferation of connective tissue is occa- 
sionally seen in the vicinity of carcinoma. The origin of cancer-cells 
in primary carcinoma of the liver is also subject to controversy. Naunyn 
in his case saw the transition of bile-duct epithelium into carcinoma- 
cells; he saw the entrance of connective-tissue strands, between which 
bile-duct epithelium was placed, into the acini, and some of the newly 
formed rows of cells merged into rows of liver-cells. During this transi- 
tion into carcinoma-cells the protoplasm becomes clear and the nucleus 
enlarges. It is possible that in cases of this kind a primary carcinoma 
of the smaller intrahepatic bile-ducts has existed that has grown into 
the acini of the liver, a condition similar to that seen in tubular ade- 
nomata. Naunyn was not able to arrive at the definite conclusion 
that liver-cells become transformed into cancer-cells; in other cases, 
however, this is distinctly so. Schiippel and his pupils observed that 
liver-cells became enlarged, that the protoplasm of several cells became 
confluent and inclosed the nuclei of all the cells; and that, following 
this, mitosis of the nuclei occurred, while the protoplasm became clear 
and surrounded the new nuclei. He also saw a circular arrangement 
of the new cells around a lumen, and in this way, by atypical proliferation 
of cells, the formation of alveolar carcinoma. The capillaries situated 
between the columns of liver-cells form the fibrous stroma of the car- 
cinoma together with the strands of connective tissue that surround 
them. A portion of the columns of liver-cells becomes atrophic from 
pressure of the carcinomatous growth. Rohwedder, Siegenbeck van 
Heukelom, and others have also seen the formation of multinuclear 
clumps of protoplasm during the genesis of cancer; many authors have 
not been able to demonstrate this intermediary stage. Some observers 
have noted the fact that the transformation of liver-cells into cancer- 
cells occurs at the margin of the cancer nodule, and in the following 
way: From the tumor a round-cell infiltration starts and makes its 
way between the different columns of liver-cells. The round cells com- 
pletely surrounded the liver-cells, new connective tissue is formed, 
and in this way the surrounded liver-cells are isolated from their acinus. 
These cells then become converted into cancer alveoli, there is a clearing 
of the protoplasm, an enlargement and mitosis of the nuclei, and con- 
sequently a formation of new cells. In this manner the acini are partly 
destroyed from the periphery. Thorel describes a peculiar extension 
of the columns of liver-cell into the condensed intralobular connective 


764 DISEASES OF THE LIVER, 


tissue; at the same time he saw a metamorphosis of the cells into cancer- 
cells, later isolation of these cells within connective tissue, the formation 
of nests and of alveoli. In many instances the liver-cells will be flat- . 
tened, narrow, and elongated in the immediate vicinity of carcinoma 
nodules. These elongated cells radiate at a tangent to the 
periphery of the tumor; in these radiating stripes some authors, as 
Siegenbeck van Heukelom, have noted the metamorphosis of cells 
into cancer elements; other authors describe atrophy and fatty de- 
generation of these parts. Some of the nodules are surrounded by a 
solid capsule of connective and fatty tissue, and are necrotic in their 
center. Septa originate from the condensed connective tissue around 
the capillaries of the acini and from the intralobular connective tissue; 
these impart a peculiar fan-like shape or fibrous structure to many 
carcinomata that may be seen with the naked eye. We have already 
mentioned the fact that the color and the granular consistency of normal 
liver protoplasm are lost when the metamorphosis into cancer-cells 
occurs. Any pigment granules that may be present disappear, or 
congregate near the periphery of the cancer, or may even be carried 
off by the blood-vessels. This separation of pigment from the remaining 
protoplasm has been described in detail by Harris. In addition to the 
metamorphosis of liver-cells, proliferative processes are seen in the 
bile-passages, which form buds and branches, and sometimes penetrate 
between the columns of liver-cells of the acini. Their epithelium under- 
goes proliferation, and is changed from cylindric to cuboid or irregular 
forms. As a result of the abundant new-formation of cells, the lumen 
is filled with young smooth cells, dilatation occurs in this manner, and 
the tubular form develops into an alveolar structure. Cystic dilatation 
may also be seen, and in this event the wall is covered with a cylindric 
or cuboid epithelium similar to that of cystadenoma (von Hippel and 
others). Within the cirrhotic connective tissue situated between the 
acini, new-formations are often seen developing from bile-passages; 
they usually have a trabecular structure, and consist of numerous tor- 
tuous bile-passages, with well-arranged symmetric cylindric epithelium. 
In other words, they have all the characteristics of that form of adenoma 
that has been described by Rindfleisch. Sometimes collections of small 
liver-cells are seen within the intralobular connective tissue. Heller 
regards these as vicarious processes of regeneration intended to com- 
pensate for the loss of such liver-cells as have perished by cirrhosis 
or tumor-formation, and he believes that they may easily be 
converted into carcinomatous alveoli. Hansemann finally describes 
certain cavernous capillary ectasies that originate from compressions 
of blood-vessels by contracting connective tissue. In many instances 
hyperplasia of the liver parenchyma has been seen, principally in the 
form of small nodules. Occasionally the tumor masses grow into 
branches of the portal vein or of the hepatic veins, and in this manner 
long fibrous structures are formed. In case the carcinoma is of an 
adenomatous structure these strands protrude from the branches of 
the hepatic artery and travel for a long distance in the lumen of the 
latter vessel or of the inferior vena cava. In the portal vein they grow 
against the blood-stream and lead to the formation of metastases in 
other, parts of the liver. These metastases, in secondary carcinoma 
of the liver, develop from a cancerous thrombus of a small branch of 
the portal vein. Metastases do not occur so frequently in the lungs 


NEOPLASMS. 765 


and other organs as the result of transportation of cancerous material 
from the hepatic vein. Secondary cancer of the gall-bladder is seen 
relatively often; the tumor may also grow into the bile-passages, and 
in this way form a tumor mass that extends to the large bile-ducts and 
involves the intrahepatic passages, thus leading to occlusion and to stasis 
of bile. Sometimes this condition of biliary stasis may aid in the devel- 
opment of cirrhosis (Claude and Gilbert). Cancerous degeneration of 
the lymph-vessels and metastases to the portal glands are seen very 
frequently, the latter in this case becoming enlarged. 


A differentiation of the various forms of carcinoma of the liver, based on the 
shape of the tumor-cells, has been attempted by Hanot and Gilbert. The attempt 
is interesting anatomically, but can have no clinical significance. These investigators 
distinguish the ordinary form of epitheliome alveolaire, and subdivide it into (1) 
that with polymorphous and (2) with small polyhedric cells. They also designate 
tumors that contain giant and cylindric cells as unusual forms. 


As we have mentioned above, a number of authors, as Rindfleisch, 
Kelsch, and Kiener, draw a sharp distinction between adenoma of the 
liver (adenoid) and carcinoma, notwithstanding the fact that in pro- 
nounced cancer-formation many places are seen in the liver that are 
constructed like trabecular adenomata. These adenomata have the © 
appearance of tubular glands, and consist of numerous solid or hollow 
cylinders similar to the convoluted tubules of the kidney. These cylinders 
originate as the result of a metamorphosis of columns of liver-cells result- 
ing in a lining of the former by rows of cylindric cuboid cells. The illus- 
trations prepared by Kelsch and Kiener clearly. show the transition 
of liver-cells into these atypical forms. Hanot and Gilbert, therefore, 
call this form of adenoma trabecular epithelioma, and differentiate 

between it and the above-mentioned alveolar cancers. They also de- 
scribe a case of this kind that presented the appearance of a massive 
carcinoma, but in its interior showed a lobular structure. The cells 
within the growth were arranged in columns, as in.the normal paren- 
chyma, though with this difference, that the liver-cells had been con- 
verted into tumor-cells. 

Adenomatous nodules originate within the acini and gradually 
enlarge at the expense of the parenchyma, which can sometimes be 
seen to one side, presenting the appearance of a semilunar remnant, 
and usually in a state of brown atrophy. At the same time there is 
more or less cirrhosis, particularly of the interlobular type. The ade- 
nomata usually appear as numerous icteric nodules, varying in size 
from a pinhead to a pea; solitary neoplasms of this kind are also seen. 
They resemble the adenomata of the breast, and, like these also run 
a more benign course than typical lobular cancers. They too, however, 
show a tendency to degenerative change if they persist for a long time. 
At first they undergo fatty degeneration, and later cheesy or colloid 
transformation of the central portion develops. 

[W. H. Porter and W. T.. Brooks have within the current year * 
reported a case of primary adenocarcinoma of the liver, with metastases 
in the choroid, lungs, spleen, and kidneys.—Eb.] 


Cheesy necrosis is seen when the single tubules are so close to one another 
that the already scanty circulation of the blood is occluded; a cheesy mass results, 
_ surrounded by the connective-tissue capsule of the tumor nodule. 


* Postgraduate, June, 1902. 


766 DISEASES OF THE LIVER. 


Colloid metamorphosis occurs in the neighboring cylinders in the following 
manner: As long as the circulation of the blood is sufficient, or even overabundant, 
the cells swell, and later become soft, and are converted into a shiny mass in which 
fat-droplets and large round cells with vacuolated nuclei are seen. In this manner 
cavities may be formed, filled with blood or a serous fluid or with a purulent brownish 
substance. These cavities are also surrounded by the connective-tissue capsule 
of the tumor nodule. 


As the adenomata spread and disintegrate they gradually cause 
severe disturbances within the liver, impeding the circulation and secre- 
tion of bile, destroying liver tissue, and appearing to exercise a toxic 
influence on the whole body, causing cachexia, like typical carcinomata. 
It appears, however, that they rarely form metastases, even though 
they are known to proliferate into the hepatic veins and into the branches 
of the portal vein. 


It is not at all clear why in certain cases these adenomata should become con- 
verted into typical carcinomata of an alveolar structure, and in other cases retain 
their tubular structure until death occurs from cirrhosis or from a destruction of 
liver parenchyma by direct displacement. Our knowledge, however, is very deficient 
in regard to the formation of cancerous tumors, and the causes of the various struc- 
ture of these tumors even when found in the same organ. 


We must differentiate between benign tumors and more or less ma- 
lignant adenoid growths of the liver. In the benign growths the cells 
differ in no way from those of normal liver parenchyma. 


Sometimes only a single tumor is present (Rokitansky, Klob, Hoffmann, 
Mahomed, Simmonds, and others). 

The tumors may be congenital, and have been considered as accessory livers 
by Klob. They may be situated upon the surface of the organ or in its interior. 
Occasionally they are encapsulated, in other cases they are not. The connective- 
tissue stroma is frequently increased, the veins dilated; there may also be a central | 
cyst formation so that the whole process appears as a cavernoma or a cyst of the 
liver. These structures do not participate in the performance of the functions of 
the liver, and if the latter are perverted as a result of stasis, corresponding changes 
will not be seen in the new-growth. Benign tumors, consisting of tubules lined 
with epithelium, occur in a solitary form in the liver, and have been described by 
Wagner, Greenish, and others; they have never, however, been studied with scientific 
care. We have already discussed the cystadenomata that belong to this class. 

There is another form of growth which may be characterized as a multiple 
nodular hyperplasia; it is seen in livers that are altered pathologically, and par- 
ticularly in those that are cirrhotic (see page 700). They are not encapsulated, 
show no proliferation of connective tissue in their interior, and must be regarded, 
possibly, as compensatory structures intended to assume vicariously the function 
of those liver-cells that have been destroyed by the primary disease. The liver- 
cells in these hyperplasias are enlarged, and hyperplastic rows may be in direct 
connection with atrophic ones. Sometimes a proliferation of the cells, less frequently 
a softening of the tissue, is seen (Kelsch and Kiener, Kelynack). The nodules are 
usually as large as hazelnuts, and can be seen with the naked eye on the surface of 
the liver. The organ usually is reduced in size from cirrhosis. The nodules pro- 
trude, and appear, on transverse section, as yellowish-gray or brownish structures 
that are in part confluent. Cases of this character have been described by Fried- 
reich, Willigk, Birch-Hirschfeld, Simmonds, Kelynack, and others. Kelsch and 
Kiener have described similar hyperplasias in diseases of the liver that follows 
intermittent fever (hépatite parenchymateuse nodulaire) (see page 735). This multiple 
nodular form of hyperplasia shows a greater tendency to degeneration and pro- 
liferation, and, according to Schiippel (see above), it is possible that malign adeno- 
mata and carcinomata may occasionally develop from these nodules. 


Secondary cancer of the liver may often be distinguished macro- 
scopically from the primary form by the greater enlargement of the 
liver, the formation of nodules on its surface, a greater tendency to 
degenerative change, and, therefore, to the formation of depressions 


NEOPLASMS. | 767 


in the nodules. The tumors are usually light in color, whitish-grayish 
or greenish, and are clearly outlined, both on transverse sections, and upon 
the surface of the organ, from the rest of the normal liver substance. 
As a result of compression of blood-vessels stasis may occur here and 
there, and as a result reddish hyperemic portions are seen between 
the light carcinomatous masses. In other cases stasis of bile occurs, 
and an icteric color develops; the picture consequently is very varied. 
The cancer masses may fill the liver to such an extent that hardly a 
trace of normal parenchyma is visible. The organ may weigh 8 kg. 
and more. Sometimes degeneration of the carcinomatous tissue leads 
to the formation of cavities with a serous content (cystic carcinoma) ; 
hemorrhages may occur into these cavities, which may rupture and 
blood be poured into the peritoneal cavity. This is seen particularly 
in metastasis of the fungus hematodes, a great development of 
blood-vessels occurring in the connective tissue of the carcinoma. 

In many cases of secondary carcinoma of the liver cancerous thrombi 
are seen in the portal vein or in its branches. 


In rare cases it may happen that carcinomatous infiltration of the liver tissue 
occurs, particularly in many primary cancers of the liver. Schiippel describes 
this event in a gelatinous carcinoma that penetrated the liver from the peritoneum 
via the subserous lymph-passages, followed the lymph-channels of the vessels into 
the organ, and developed there. The lymph-vessels of the surface of the liver 
formed a gelatinous network, becoming more and more condensed, and were ul- 
timately converted into plates. At the same time the intrahepatic lymph-channels 
became cancerous, pushed the parenchyma aside, continued to proliferate, and in 
this manner filled the entire interior of the organ without changing its form. Litten . 
describes a similar infiltration in a secondary carcinoma of the liver, the primary 
seat of which was in the pancreas. Carcinomata of the gall-bladder may also 
grow into the liver by forming a massive growth in its interior similar to primary | 
carcinoma. At the same time they do not change the outward shape of the organ. 


The histologic findings vary according to the origin of the cancer. 
In general, the capillaries of the portal vein are filled with cancer masses 
of a characteristic structure. From these vessels proliferation takes 
place into the surrounding liver tissues; the liver-cells are compressed, 
and become atrophic. Later, colloid degeneration, fatty changes, or 
cheesy degeneration are seen in the central portions of the new tissue. 
Naunyn, Fetzer, Perls, Rindfleisch, and others have recorded a number 
of observations, according to which the liver-cells, and also the epithelia 
of the bile-passages and the endothelia of the blood-vessels, do not 
always atrophy, but, on the contrary, seem to proliferate and by altera- 
tion of their contents aid in the development of cancer. 

In secondary carcinoma, also, cirrhotic changes are seen, as is the 
case in primary cancer. This may be due to the action of the cancer 
nodules in penetrating the branches of the portal vein, and thus acting 
as foreign bodies. In this manner an irritation of the surrounding 
tissues is produced that leads to the new-formation of connective tissue. 
In addition, just as occurs in ulcerative carcinoma of the stomach, 
intestine, etc., micro-organisms and toxic material may be carried with 
the cancerous masses and cause round-cell infiltration and later pro- 
liferation of connective tissue. Finally, in some cases stasis in the 
bile-channels must be regarded as a possible cause, particularly if the 
primary focus is situated in the common duct, at the orifice of this channel 
into the intestine or in the head of the pancreas, constituting in this 
manner an obstruction to the outflow of bile. 


768 DISEASES OF THE LIVER. 


Carcinoma of the gall-bladder and of the bile-passages may be either 
secondary or primary. It may be secondary to carcinoma of the stomach, 
the intestine, and the pancreas, or it may extend from the pancreas 
or the duodenum by direct continuity of tissue. Less frequently it 
extends from the stomach to the common duct, and thence to the 
bile-passages in the liver and the gall-bladder. Sometimes primary 
cancer of the liver may send metastases to the gall-bladder or extend 
to the intrahepatic bile-passages and spread along their course. In 
this way different forms of cancer are developed, depending upon the 
form of the primary growth for their type. 

Primary carcinoma of the gall-bladder is a more frequent occur- 
rence than cancerous involvement of the bile-passages. As we have 
already stated, it usually follows cholelithiasis, and is the direct result 
of the irritation exercised by the concretions on the walls of the gall- 
bladder; a change in the structure of the wall is the first sign. 


There is a marked development of fibrous tissue, hypertrophy, and later oblitera- 
tion of the musculature, ulceration, and the formation of cicatrices in the mucous 
lining, and a loss of or transformation of the epithelial lining into layers of flat 
cells. At the same time, as in cholelithiasis, numerous glands of the mucosa atrophy 
and perish as a result of the sclerotic processes of the wall, and the proliferation 
of connective tissue. These glands may, on the other hand, enlarge by sending 
out processes, and in this manner possibly compensate the loss of destroyed glands. 
In other cases certain of the glands may be separated by connective tissue, and this, 
according to Ribbert, may cause the development of cancer. Those parts that are 
inclosed within connective tissue may, as in the case of ulcer of the stomach, undergo | 
carcinomatous degeneration by a metamorphosis into cancerous tissue of the cells 
' that constitute the glandular tubules. This leads to proliferation of the epithelium 
and to an obliteration of the lumen by young cells. In these cancerous alveoli 
mucoid degeneration of the cells is occasionally seen; the protoplasm swells and 
' perishes and the picture of a gelatinous carcinoma is created; or, on the other hand, 
a scirrhus may develop with abundant proliferation of connective tissue. Some- 
times large villous tumors are formed with numbers of soft cancerous alveoli; these 
readily undergo degeneration and form a cancerous ulcer. Owing to the trans- 
formation of the glandular epithelium into cancer-cells, and the metamorphosis of 
thé cylindric cells of the gall-bladder wall into flattened tumor-cells, the alveoli 
may assume the shape of a flat-cell epithelioma—~.e., with the characteristic 
onion-shaped configuration. Some authors have even described a metamorphosis 
of the cells of the gall-bladder and also of the cancer into horny cells. 


In carcinoma of the gall-bladder the latter organ appears as a large 
nodular tumor; at times it is embedded in cancerous tissue that extends 
underneath the liver; in the latter instance the gall-bladder is not seen 
until the growth is divided. In other instances the gall-bladder is 
small and may be contracted around a gall-stone; from the organ can- 
cerous tissue may extend far into the liver. As a rule, concretions will 
be found in the bladder; in other cases the stones will no longer be 
present, but their former existence be revealed by the discovery 
of scars and ulcerations, or there may be evidence of their passage, 
such as adhesions with the intestine or lesions of the cystic and common 
ducts. At times the cancer is limited to a small portion of the gall- 
bladder wall while the rest of the organ is found to be intact; at the 
site of the cancer a scar or some proliferation of tissue will usually 
be seen. A cancer of this kind, although small, may be the starting- 
point of a large growth of the liver. Quite frequently a diverticulum 
will be seen at the fundus in which are contained one or several gall- 
stones; this is usually separated from the rest of the organ by a dense 
ring. Cancer develops in this ring with great frequency. 


NEOPLASMS. _ 769 


The cancer spreads from the gall-bladder to the surrounding liver 
tissue and forms a tumor that appears like a primary carcinoma; atrophy 
of the parenchyma occurs and the tumor finally occupies a large part 
of the organ. Cancer of the gall-bladder also shows a tendency to 
travel along the lymph-channels, and in this way to infect the peri- 
toneum; it may also travel along the lymph-channels of the cystic 
duct and by this path involve the common and the hepatic ducts. As 
a result of this malignant growth a tumor is formed in the region of 
the porta hepatis that compresses the bile-ducts and the portal vein 
and causes stasis of bile as well as congestion of the portal system. 


In some cases the process extends to the smaller intrahepatic bile-passages, 
so that on transverse section these channels appear as cancerous rings. Starting 
from these new bile-passages are tubules filled with cylindric epithelium extending 
into the acini; these cause atrophy of the columns of liver-cells. Occlusion of 
bile-ducts may also result from thickening of their outer walls; the bile may in this 
manner be retained, so that cysts form that are lined by the epithelium of the 
bile-passages. 


Carcinomata which develop as primary growths in the walls of the 
bile-passages usually start from a proliferation of the mural glands 
at some point at which a gall-stone causes, or has at some time caused, 
irritation of the mucosa; these concretions produce lesions and cicatricial 
tissue, and cause general irritation of the mucous membrane with prolifera- 
tion of the epithelium. Such cancers may be annular (Willigk, Deetjen), 
or polypoid, and their malignant character may be recognized only 
on microscopic examination. In the center of these growths a gall- 
stone is sometimes found. Such a stone need not be very large in order 
to cause serious disturbances and death in a short time, particularly 
if it is situated in the common duct or in the stem of the hepatic duct, 
and in order to rapidly lead to retention of bile and cholemia. If it is 
situated in the cystic duct, the common and the hepatic ducts are soon 
involved, and in this way there is soon produced a complete occlusion 
of all the ducts with stasis of bile and all that this entails. If the cancer 
is situated at the orifice of the common duct (Marfan, Deetjen),. it may 
cause very serious disturbances even if it be very small. It can be 
readily determined microscopically that these cancers originate from 
glandular epithelium; that they proliferate and send out tubules filled 
with epithelium into the muscularis and the subserous tissues; and 
that these canals continue to enlarge dnd in this way produce a carcinoma 
of alveolar construction. 

Sarcoma of the liver is not seen as frequently as carcinoma. Sar- 
comata are also usually secondary, although it is often a difficult matter 
to discover the primary focus. It may be a small sarcoma of a muscle 
tendon, or a growth in the choroid that is no larger than a hop-seed. 

For a time the existence of primary sarcoma of the liver was denied, 
but we have to-day a number of well-authenticated cases. The tumors 
are, as a rule, spindle- or round-celled sarcomata (cases of Hérup, Lance- 
reaux, Arnold, Windrath, Waring, v. Kahlden, and others). 


These growths usually start from the region of the branches of the portal vein, 
and generally from the walls of the smaller vessels; the latter show characteristic 
sarcomatous proliferation. At the same time old cirrhotic changes are seen in 
age cases (v. Kahlden). . 

ometimes they appear clearly differentiated from the healthy liver tissue, 
which b by the tumor and undergoes atrophic degeneration, and finally 


770 DISEASES OF THE LIVER. 


disappears. Sometimes, indeed, extensions are sent off from the margin of the 
tumor that enter the liver tissue in such a manner that the cells of the sarcoma 
penetrate between the columns of liver-cells, and cause these to atrophy or separate 
some of the cells from their attachments. They penetrate the blood-vessels and 
fill the capillaries of the acini, exercise pressure on the liver-cells, and cause their 
disappearance. In this manner the alveolar structure can be explained; in some 

cases the construction of the tumor is per se alveolar. : 


In rare cases it appears that melanosarcoma can appear as a 
primary tumor; this is shown by a case of Block, in which a distinct 
alveolar arrangement of pigmented epithelial cells could be seen. 
Belin, too, has described a primary melanosarcoma of the liver. In 
another similar case of Frerichs only a partial pigmentation of the 
cells was observed. These sarcomata can grow to considerable dimen- 
sions, as shown by a case of Bramwell and Leith; here the tumor con- 
tained numerous blood-vessels and cavities with hemorrhagic contents. 
Occasionally, the tumors are situated altogether on the surface of the 
liver, or may even be pedunculated, as in a case of sarcomatous fibro- 
myoma reported by Sklifosowsky. 

Secondary sarcomata constitute especially large tumors. They may 
occur in two forms; either as nodular neoplasms disseminated through 
the whole liver or as diffuse infiltrating growths. In the infiltrating 
form, however, small nodules are seen, as a rule, within the sarcomatous 
tissue; and in the nodular form a diffuse sarcomatous infiltration of 
the adjacent portions of liver tissue is noted near the periphery of the 
tumor. 


Particularly in the case of pigmented sarcomata (pigment-cancer), which are 
usually metastases from choroid tumors or from pigmented nevi of the skin that 
have undergone sarcomatous degeneration, infiltration of liver tissue occurs at the 
periphery. Dark masses of tumor tissue penetrate the liver; from the portal or 
hepatic veins extension occurs into the intra-acinous capillaries, and at the same 
time the liver-cells of the affected areas undergo atrophic changes and disappear. 
In this manner there is produced a peculiar configuration of the transverse section 
through the organ resembling granite. In addition to these changes (in some cases 
without other change), dark-pigmented nodules are seen in which the cells con- 
taining melanin are arranged in an alveolar manner. These peculiarities have given 
this form of tumor the name of pigment cancer. 

In addition, numerous spindle-cell, round cell, and lymphosarcomata are seen, 
less frequently chondro-, cysto-, myxo-, and leiomyosarcomata. Osteosarcomata may 
also send metastases into the liver; here they are osteosarcomata without bone- 
formation. Lymphosarcomata of the liver consist of numerous miliary cavities 
filled with a serous fluid and lined by endothelium; they usually originate from the 
periosteum or the bone-marrow. Bizzozero, in one case saw a metastasis of a 
gliosarcoma. 


In general it may be said that all these tumors are differentiated 
from the tissue in which they are embedded by their light color; par- 
ticularly as the neighboring parts are usually compressed and of an 
icteroid color from stasis of bile, or are hyperemic. On the surface 
of the organ the tumor masses form large or small elevations that are 
rarely indented or hollowed, owing to the fact that sarcomata do not 
show as great a tendency to degeneration as carcinomata. 

In cases of infiltrating sarcoma, as in infiltrating carcinoma, the 
form and size of the liver are not very much changed; the organ is 
often somewhat enlarged, however, and the surface is irregular from 
the presence of flat ridges. 

In some cases it has been possible to trace the path by which 
sarcomatous material is carried to the liver; this may be either 


NEOPLASMS. - - Tih 


the portal vein or the hepatic artery; in the former instance the spleen 
is frequently involved at first and the material is then carried into the 
liver. 

Symptoms and Course.—The symptoms and the course of malig- 
nant neoplasms of the liver may be very various, and will depend on 
the starting-point of the tumor as well as upon the individual tendencies 
of the growth to extension or to degenerative processes. The relations 
of the tumor to neighboring blood-vessels and bile-passages must 
also be considered, and, finally, the nature of the growth, 7. e., whether 
a carcinoma, a sarcoma, or a malignant adenoma, and whether primary 
or secondary. The presence or absence of cirrhotic changes in the 
liver, and of gall-stones, is also important. 

-We may say that the symptomatology of carcinoma of the liver 
and of similar neoplasms is composed in the main of the following fea- 
tures: 

1. Carcinomatous cachexia. This is frequently the first symptom, 
and may remain the chief feature throughout the disease. 

2. The development of a tumor either within or upon the liver. Some- 
times we see a uniform enlargement, more frequently the formation 
of nodules on the surface and margin of the organ. 

3. Symptoms of compression by the neoplasm: (a) of blood-vessels 
(portal vein and vena cava), (b) of bile-passages. 

4. The development of metastases in the peritoneum, in the pleura, 
the lungs, etc. 

5. Cirrhosis and its consequences. This lesion may be caused by 
the cancer, or it may exist before the advent of the growth. 

Certain forms of cancer of the liver may remain altogether latent; 
especially is this true of metastases of carcinoma or sarcoma from other 
organs. This is likely to be the case if the growth develops in the interior 
of the liver or on its upper surface underneath the diaphragm. Primary 
carcinomata that develop in the form of massive cancers cause an increase 
in the size of the liver; but the presence of carcinoma may remain un- 
recognized for a long time. Adenomata have frequently been found 
in the liver postmortem without having caused any symptoms during 
life. 

In general the course of a carcinoma of the liver is the following: 
At first disturbances of appetite and disgust for meats and fats appear; 
the patient begins to emaciate even if he forces himself to take suffi- 
cient nourishment; he grows pale, the skin becomes dry, fragile, wrin- 
kled, and sallow, sometimes icteroid. He complains of pressure and 
a sense of fulness in the right hypochondrium; later of pain, radiating 
to the abdomen, the breast, the right shoulder, etc. On examination 
the liver will be found enlarged, sensitive to pressure, and usually nodular. 
Following these symptoms we usually see icterus as a result of com- 
pression of bile-passages, and ascites from compression of the portal 
vein or occlusion of the vessel by carcinomatous thrombi. These symp- 
toms do not always appear, but are usually present, and particularly 
in primary carcinoma and sarcoma. Finally, general edema appears, 
and the formation of carcinomatous metastases, as, for instance, car- 
cinomatosis of the peritoneum and the pleura. The patient finally 
dies of cachexia and heart failure. Sarcomata run a similar course. 
In adenomata and other neoplasms that are accompanied by cirrhosis, 
ascites appears earlier in the disease, the liver is harder, the course 


712 DISEASES OF THE LIVER. 


more protracted, and the disease, which in rapidly developing massive 
primary carcinomata lasts a few months, may, in these cases, persist 
for many years, and finally terminates in a cachectic condition. 

The course and the symptomatology differ according to the nature 
of the tumor. We will refer to these differences in detail at a later 
point in the discussion. 

In secondary tumors of the liver the duration and character of 
the disease will often be dependent upon the character of the primary 
tumor. In other instances the nature of the tumor is comparatively 
unimportant, and the primary tumor will be so insignificant that no 
light is thrown upon the condition until the autopsy is performed. 

Carcinoma of the gall-bladder and of the bile-passages does 
not usually cause such distinct symptoms of cachexia or of digestive 
disorders. Often the symptoms of the condition are gradually added 
to those of cholelithiasis. Sometimes a characteristic tumor develops 
in the region of the gall-bladder. Icterus soon appears, owing to com- 
plete occlusion of the biliary passages. The tumors of the hepatic 
and common ducts rapidly close the lumen of the latter and cause 
the gall-bladder and the cystic duct to become involved early in the 
disease. Ascites also develops soon because the carcinomatous infil- 
tration at the hilum of the liver usually involves the portal vein. This 
form of cancer usually ends with symptoms of hepatic intoxication 
(cholemia), particularly if it starts from the common duct. Occasionally, 
however, in cancers of the gall-bladder that grow into the liver tissue 
an altogether different symptom-complex is seen, similar to that of 
genuine carcinomata of the liver. 

The disturbances of the general health, of the blood, and of the 
nutrition of the body, included under the name of carcinomatous 
cachexia, are probably due to the action of toxic substances produced 
by malignant tumors, such as carcinomata, sarcomata, and malignant 
adenomata. The symptoms have a definite relation to the size of the 
- tumor and the rapidity of its development. The more rapidly the tumor 
spreads, the more deleterious the influence of the growth upon the 
general health. Many observations point to the formation of toxic 
substances in malignant growths, as, for instance, the increased toxicity 
of the urine (Gautier and Hilt, Moraczewski, and others), and the destruc- 
tion of proteid tissue as manifested by an increased excretion of nitrogen 
as compared to the small amount ingested (IF. Muller, Klemperer, and 
others). We know nothing, however, of the nature of these substances, 
as no one has so far succeeded in isolating them, or in determining their 
properties. For this reason we cannot say what rdéle poisons of this 
kind play in the causation of carcinomatous cachexia. 

There can be no doubt that in extensive carcinomatous processes, such as are 
usually seen when the liver is involved, the general metabolism is influenced not 
only by the supply of nourishment, but also by the direct effect of the neoplasm 
upon the proteid constituents of the organs. This is manifested by a loss in volume 
of the muscle tissues, and by atrophic processes in other organs containing much 
proteid. This occurs even when the nutritive supply is ample, the analyses of F. 
Miiller, Klemperer, and others showing that more nitrogen is excreted than in- 
gested. A decrease in the quantity of chlorids excreted in the urine has frequently . 
been observed; this is due, in part at least, to the ingestion of small quantities 
owing to the lack of appetite; it may also be due in part to a retention of the chlorids 
in serous transudates, as ascites, anasarca, etc. Occasionally, in carcinoma the 


amount of phosphorus excreted is increased in proportion to the nitrogen. The 
occurrence would seem to point to nutritive disturbances in the bones. 


NEOPLASMS. Ul 


In carcinoma of the liver Sjéquist found a distinct increase in the excretion of 
ammonia and of other nitrogenous substances, as compared to urea. This can be 
attributed to a decrease in the urea formation in the liver. According to Topfer’s 
analyses, the proportion of nitrogenous substances excreted is as follows: urea 65.2 % 
to 79.4 %; nitrogenous extracts 13 % to 23%. In the normal subject the corre- 
sponding figures are 84.9% to 96.2 % of urea nitrogen, and 0.6 % to 0.8% of 
extractive nitrogen. If catabolism of the proteids is very great, acetone and 
diacetic acid, also 6-oxybutyric acid, are excreted, as in certain other diseases. At 
the same time the alkalinity of the blood is reduced, and coma may appear, as 
in diabetes mellitus. v. Noorden states that in a case of carcinoma of the stomach 
with extensive metastases in the liver, lactic acid was found in the urine, and he 
attributes its presence to involvement of the liver. 

Other changes in the blood condition, aside from the decreased alkalinity, are 
a decrease in the red blood-corpuscles and the hemoglobin. The blood becomes 
watery, and its specific gravity is lowered. The number of leucocytes, on the other 
hand, is relatively and absolutely increased. There is sometimes an increase of the 
blood-sugar (E. Freund), although this is not a constant occurrence, and is seen 
in other serious diseases. 

v. Moraczewski found the phosphorus of the blood decreased in carcinoma, 
the conditions being similar to those present in the blood in anemia. He also 
found an increase of the chlorin and nitrogen. 


As a result of the disturbances of nutrition and the destruction of 
protoplasm, as well as owing to anemia and hydremia, edema develops, 
with exudation of serous fluids into the body-cavities and the subcuta- 
neous cellular tissues, particularly of the dependent portions of the 
body. In this manner the accumulation of fluid in the abdominal 
cavity may sometimes be explained, although, as a rule, it is dependent 
upon an extension of the cancer to the peritoneum, or an occlusion 
of branches of the portal vein. The color of the skin grows pale-yellowish 
even in the absence of icterus; the skin becomes atrophic, dry, and 
desquamates, owing to a deficient secretion of sweat and sebaceous 
material. 

It is possible to raise the skin in large folds. The adipose layer 
disappears rapidly, and remains intact in rare cases only (Frerich, Op- 
polzer). The patient may become fatigued, dyspneic, and complain 
of palpitation; others become irritable, and cannot sleep well even 
though pain is absent. Their mental faculties become impaired, they 
slowly relapse into stupor, and die in coma. 

On physical examination the chief symptoms of the disease will 
be discovered in the liver. With few exceptions, the organ is enlarged 
in part or as a whole. If the tumor develops in the interior, or on 
the diaphragmatic surface of the liver, it cannot be palpated; in the 
latter case the tumor may, however, protrude below the costal arch 
on deep inspiration, and in this way be detected. Occasionally a general 
enlargement of the liver can be determined, and presents a smooth surface 
of increased resistance to the*touch. This occurs particularly when | 
the tumor is situated in the interior of the organ, as is frequently the 
case in infiltrating carcinomata and sarcomata. In massive carcinoma 
the liver is usually as hard as a board. If many nodules are present 
the surface is rough, as, for instance, in those forms of carcinoma and 
adenoma that develop near the surface. In cases of this character 
the margin is not sharp and clean cut, but nodular, thickened, and 
projecting. This is seen especially in secondary tumors, but may also . 
occur in primary carcinomata, and especially adenocarcinomata. De- 
pressions in the nodules are rarely determinable, but sometimes the latter 
show a varying consistency according to the character and stage of devel-- 


vig DISEASES OF THE LIVER. 


opment; thus, primary carcinomata are usually denser than secondary 
carcinomata. The latter, if they are of the scirrhous type, may also 
feel very hard; more frequently, however, they are metastases from 
medullary or gelatinous carcinomata, or lymphosarcomata, etc., so 
that they feel softer than the surrounding tissue, and may even simulate 
fluctuation. The latter sensation is also experienced if softening of 
metamorphosis into cavernous tissue occurs, or, finally, if hemorrhage 
occurs and leads to the formation of cavities filled with blood. As 
a rule, the nodules are of different size, sometimes large and constituting 
the primary foci, while around will be found a large number of smaller 
nodules. In enlargements of the liver without change of its form, as 
well as in that enlargement that occurs with the development of nodules, 
large tumors are found that extend deep into the abdomen, below the 
umbilicus and as far as the crest of the ilium, or even to Poupart’s liga- 
ment, and very far toward the left. They may fill the greater part 
of the abdomen. In slight degrees of development the diaphragm 
is pushed upward so that on percussion the margin of the lung will 
be found higher than normal. The latter is particularly true in cases 
in which the tumor is very large, and cannot expand into the abdomen; 
also if ascites is present. Meteorism may occasionally cause the same 
picture. In one case that I observed the margin of the liver barely 
protruded below the costal arch in the mammillary line, while there 
was at the same time a large area of dulness in the lower part of the 
thorax on the right side, that extended very far upward. The reason 
for this was an adhesion between the lower margin of the organ and 
the parietal peritoneum. The adhesive bands consisted of connective 
tissue, infiltrated with the carcinomatous growth. 

In secondary carcinomata very large livers are often felt, covered 
with many soft nodules. In massive primary carcinoma and sarcoma, 
and in infiltrating carcinoma and sarcoma, the liver is usually large 
and smooth. In those forms of carcinoma and malignant adenoma 
that are complicated by cirrhosis the liver is not very much enlarged, 
but very nodular. 

Sometimes the enlargement of the liver can be seen. The right 
hypochondrium may bulge and protrude, and the outlines of the liver 
may be determined through the thin abdominal walls; occasionally the 
nodules even may be distinguished. On palpation (which should be 
carried out as described on page 390) the outline of the tumor can usually 
be distinguished more distinctly than by percussion, and the single 
nodules may be felt. At the same time the character of the pain which 
carcinomatous nodules often give on pressure should be noted; the 
peculiarities as to consistency, fluctuation, etc., should be determined. 
Occasionally respiratory friction sounds or grating may be heard by 
means of the stethoscope placed over the liver, a frequent complication 
of-carcinoma of the liver. It is also stated by some that the nodules 
give this peculiar grating when they are palpated. 

In carcinoma of the gall-bladder and the bile-ducts the liver 
is also generally enlarged. The surface is smooth, particularly if biliary 
stasis is present. The liver enlarges as a result of the dilatation of the 
intrahepatic bile-passages, and if the condition exists for a long time, 
the consistency of the organ increases, owing to the development of 
biliary cirrhosis. As a rule, the organ is not large, as in cancer of the 
liver. In the place of the gall-bladder a large, nodular, sensitive tumor 


NEOPLASMS. 775 


is often felt protruding below the margin of the liver, particularly if 
gall-stones or hydrops are present. In other cases it is difficult to palpate 
the tumor, owing to its situation beneath the liver. If the abdominal 
walls are very much relaxed, however, it is usually possible to feel it. 
Tumors of the common and hepatic duct cannot be palpated. In case 
of occlusion of the former, the bile accumulates in the gall-bladder 
so that this viscus can be felt as a dense, elastic fluctuating mass. In 
addition to the tumor of the gall-bladder, metastatic nodules are fre- 
quently felt in other parts of the liver. Occasionally a large nodular 
or flat, ridge-like tumor starts from the gall-bladder. 

In the event that ascites is present, the palpation of the tumor, 
whether it is a neoplasm of the liver or of the bile-passages, is difficult. 
Palpation, however, is possible if the patient is instructed to lie on 
the left side, or if the ascitic fluid is first evacuated. Sometimes it 
is possible to distinguish the presence of a tumor by ballottement, when 
only a thin layer of fluid is present. 

From the beginning of the trouble, or possibly soon after, the patient 
complains of pain in the liver, frequently preceded by a feeling of pressure 
and fulness in the hepatic region. This pain may appear spasmodically 
or may be continuous. It radiates from the right hypochondrium or 
epigastrium into the chest, the abdomen, or the back. Pain in the right 
shoulder is also complained of. Skorna describes a case of primary 
cancer of the liver in which pain was present only in this location. [A 
case has been reported by Mackenzie * of a woman, aged twenty-four, 
suffering from carcinoma of the liver. One of the prominent symptoms 
had been neuralgia of the right arm, which Mackenzie attributed to 
the anastomotic connection between the phrenic and the fourth and fifth 
cervical nerves, branches from the latter of which supply the shoulder 
and upper arm.—Ep.] Spontaneous pain, as well as pain on pressure, 
is observed particularly in cases in which the cancer is situated on the 
surface of the organ, and thus irritates the peritoneum and the nerves 
of the liver capsule. Tumors situated in the interior of the organ may 
also cause pain by irritation of the nerves that enter the liver with the 
arteries, or by causing rapid enlargement of the organ, and a consequent 
tension of the serosa. Pain of this kind may be very annoying to the 
patient, rob him of his sleep, and in this manner hasten the general 
collapse. 

Symptoms of compression and obstruction may be subdivided into 
those that occur in the bile-passages and those that occur in the blood- 
vessels. Occlusion of bile-passages is particularly seen in carcinomata 
that start from the common, hepatic, or cystic ducts, or from the gall- 
bladder. Intrahepatic tumors may lead to this obstruction either by 
occluding a large number of bile-passages, by compression, or by direct 
growth, or by infiltrating the porta hepatis, causing cancerous degen- 
eration of the glands of the hilum; or, finally, by compression of the large 
bile-ducts on the lower surface of the liver. Such a condition always 
results in icterus. At first there is a yellowish discoloration of the sclera, 
and later an icteroid discoloration of the skin and mucous membranes 
that lead to the black-green color of melas icterus. The urine contains 
bile-pigment, bile-acids, and albumin, as in other forms of icterus from 
stasis. If the cancer is situated in the common duct, complete occlusion 
of bile usually occurs. None of the bile consequently can enter the in- 

* Brit. Med. Jour., Feb. 2, 1901, 


776 DISEASES OF THE LIVER. 


testine, and characteristic clay-colored, whitish or gray, stools are the 
result. These are frequently covered by icteroid mucus. This may also 
be the case in cancerous involvement of the root of the hepatic duct. If, 
on the other hand, the bile-passages are not completely compressed or 
occluded, or if only one of the larger branches of the hepatic duct is closed, 
icterus of the skin and mucous membranes will yet occur, and bile- 
pigment will be found in the urine; but the stools will not be devoid of 
color. In addition to bile-pigment, I have repeatedly found urobilin in 
the urine, even if the bile was not completely excluded from the intestine. 
If the occlusion is complete, large quantities of urobilin are voided. 
Some carcinomata and sarcomata never produce icterus, particularly 
primary massive carcinomata; at the same time, however, there may be 
an abundant excretion of urobilin, which is reduced later, owing to the 
cachexia, deficient nutrition, and the decrease in the formation of bile. 
It seems possible that the excessive urobilinuria is due to a rapid dis- 
integration of red blood-corpuscles. [An interesting case was seen during 
the past year which presented a high degree of cachexia, deep jaundice, 
emaciation, rapid loss of weight (from 120 to 96 pounds within a few 
weeks), and an entire absence of bile and biliary acids from the urine. 
There was constantly present, however, a marked urobilinuria. The 
liver seemed normal in size, and a few days before the operation the gall- 
bladder appeared to be palpable. On incision the liver was found to be 
normal, while the gall-bladder contained a number of small hard calculi. 
Impacted in the cystic duct was a large single stone. There was no 
malignant growth evident either in the liver or in the gall-bladder, the 
latter being subjected to a thorough microscopic examination. The 
patient recovered from the operation, and both the jaundice and the 
urobilinuria promptly abated, and soon disappeared.—Ep.] Sometimes 
in the intrahepatic form of tumor icterus is so slight that it is not recog- 
nized; only in the presence of a yellowish or brownish color of the skin, 
and especially of the sclera, or in case bilirubin can be detected in the 
newly voided urine, can stasis of bile be diagnosed. An intense form 
of icterus may, on the other hand, be caused by the simultaneous presence 
of gall-stones and the development of carcinoma of the liver. Such an 
occurrence is by no means rare, and is seen especially in combination 
with tumors of the bile-ducts. | 

Neoplasms that cause a complete retention of bile, particularly those 
that develop in the common duct, sooner or later lead to hepatargy, 
(cholemia), ‘characterized by hemorrhages into the skin and mucous 
membranes, epistaxis, hematemesis, bloody stools, etc. The patient 
becomes exhausted and even more anemic than can be accounted for by 
the deleterious action of the bile-constituents on the blood. As a result 
of the damage to the liver-cells due to the biliary cirrhotic change the 
secretion of bile is diminished, consequently the icteric color becomes 
less intense. Death usually results, less as a consequence of the malig- 
nant cachexia than from the disturbances within the liver parenchyma. 


In carcinomata situated near the orifice of the common duct, the duct of Wir- 
sung may be occluded, and in this manner the pancreatic juice may be excluded 
from the intestine. Further, there will be dilatation of the pancreatic duct and 
a proliferation of the connective tissue of the pancreas. Similar conditions may 
be caused by a carcinoma of the pancreas which develops in the head of the organ, 
involves the papilla, and occludes the common duct secondarily. The occlusion 
of the common duct leads to defective intestinal digestion, and consequently to 
deficient assimilation of fluid. In this way it will accelerate the death of the patient. 


NEOPLASMS. Lid 


Neoplasms of the liver may involve the blood-vessels, and among 
them the portal vein, the inferior vena cava, the hepatic vein, and, rarely, 
the hepatic artery. The portal vein may either be compressed by tumors 
of the liver, its branches being individually involved, or the capillary 
system; or it may be occluded by means of the formation of a new- 
growth which may penetrate the walls of the vessel. Finally, carcino- 
matous masses may develop at the hilum of the liver and there occlude 
the vein. The result of all these occurrences is stasis in the portal system, 
evidenced by ascites, less frequently by tumor of the spleen, icterus, and 
hemorrhages into the intestine. Sometimes ectasies of collateral venous 
branches occur. Certain cirrhotic changes may also be concerned in the 
occlusion of the portal vein. Among these are the processes which we 
have already described, including such forms of cancer of the liver as 
adenocarcinoma, carcinomatous cirrhosis, etc. Ascites soon results from 
all these conditions, so that the diagnosis of simple cirrhosis may be made; 
particularly is this true in the case of malignant adenomata. Analogous 
changes in the inferior vena cava lead to stasis in the veins of the legs, 
anasarca, and dilatation of the subcutaneous veins of the abdomen (which 
act as collateral paths). The portal vein is usually involved at the same 
time. If occlusion or compression of the hepatic vein occurs, the stasis 
of blood will extend to the portal system, and there cause the symptoms 
enumerated above. Symptoms of stasis in the portal vein are particu- 
larly apparent in cases of carcinoma of the liver that are complicated 
by weakness of the heart, for in these cases the flow of blood to the heart 
and the lungs is insufficient. 

If malignant growths make their way into the vena cava or the hepatic 
veins, metastases are frequently formed in the lungs and in other organs 
as aresult. The appearance of metastases in remote parts of the body 
is comparatively rare in primary carcinomata of the liver, particularly in 
the massive forms that run an acute course. This also applies to the 
cases of malignant adenoma that are complicated by cirrhosis. In the 
nodular form of carcinoma, however, metastasis is a frequent occurrence, 
and secondary tumors of the liver, in particular, show a tendency to 
spread by way of the blood- and lymph-channels. Secondary more 
frequently than primary cancers of the liver are carried to other organs 
through the blood. Primary growths seem to have a predilection for 
the lymph-channels at the hilum, so that carcinomatous infiltration of 
portal lymph-glands or of mesenteric and retroperitoneal glands fre- 
quently occurs. . 

Extension of the cancer to the peritoneum occurs particularly in 
secondary growths; only the nodular form of primary cancer seems to 
bring this about. Thus ascites, which is so frequent in secondary carci- 
noma, may be explained, for we often see the development of small cancer 
- nodules all over the peritoneum, or a cancerous infiltration of the mesen- 
tery. The exudate may be so abundant that aspiration becomes neces- 
sary. In the fluid will be found leucocytes and large cells whose proto- 
plasm gives a glycogen reaction. Red blood-corpuscles are also fre- 
quently found. In fact, the whole fluid may be hemorrhagic from small 
hemorrhages that originate in the nodules of neoplasm. The percentage 
of albumin and the specific gravity of the exudate vary greatly; if the 
carcinomatosis and the chronic inflammation of the peritoneum are the 
primary causes of the exudation, or if there is congestion of the portal 
vein, general dropsy will complicate the condition. If icterus is present, 


778 DISEASES OF THE LIVER. 


the ascitic fluid, of course, contains bilirubin; urobilin may also be found 
in the effusion. If cancerous nodules upon the surface of the liver degen- 
erate, severe hemorrhages may occur into the abdominal cavity, so that 
it is sometimes found filled with blood. In addition to other symptoms 
of exudate and the characteristic signs of adhesions between abdominal 
organs, ete., cancerous masses may frequently be felt in the peritoneum. 
They present the sensation of nodular masses, sensitive to pressure; the 
mesentery may be converted into a nodular strand running transversely 
across the upper portion of the abdomen. Peritonitic friction sounds 
may be heard and felt at the anterior surface of the liver provided the 
organ is not separated from the abdominal wall by fluid. Adhesions with 
other organs, particularly the intestine, are also found in carcinoma. 
In carcinoma of the gall-bladder the fundus may be adherent to the 
duodenum and lead to twisting and stenosis of the intestine, causing 
symptoms of gastric ectasy (Ewald). In secondary carcinoma adhesions 
frequently form with the diaphragm, which becomes perforated. In 
this way a right-sided pleurisy may develop. The inflammation may be 
serofibrinous or complicated by carcinomatosis. A serous exudate is 
formed that compresses the’ lung and causes dulness, dislocates the heart, 
produces dyspnea, ete. The most dangerous exudates are those that are 
caused by the perforation of a gangrenous carcinoma nodule into the 
pleura. ; 

Leichtenstern has called attention to a swelling of the jugular gland 
that is occasionally observed. In primary carcinoma this sign is not 
always present. [Jarchette* details two cases of carcinoma of the liver 
in which an early sign was enlargement of the supraclavicular and cer- 
vical glands. He found that the enlarged inguinal gland in two cases of 
abdominal carcinoma did not show any metastasis, merely a sclerotic 
change, consisting in a substitution of connective for the adenoid tissue. 
He concludes (1) that enlargement of the left supraclavicular gland is an 
occasional sign of carcinoma of the abdomen and should always be looked 
for; (2) this enlargement may occur in carcinoma of other abdominal 
organs than the stomach; (3) its appearance may be early enough to be 
an aid in diagnosis; (4) the appearance of a metastasis in the supra- 
clavicular glands is readily recognized without a microscopic examination ; 
(5) slight enlargement of the supraclavicular and cervical glands, and 
increase in their consistency, are frequently observed in cancer, but are 
usually not due to metastasis, and are not of diagnostic importance.—ED. ] 

If marked cirrhotic changes are also present in the liver parenchyma 
symptoms of stasis in the portal system make their appearance: ascites, 
tumor of the spleen, hemorrhages into the stomach and intestine, and 
occasionally profuse diarrheas. The liver is not much enlarged,—in fact 
it may be smaller than usual,—and is hard and nodular; sometimes it is 
possible to feel smaller nodules that correspond to the cirrhotic areas and 
larger areas that correspond to the carcinomatous nodules. 

The symptoms presented by disease of other organs are primarily 
caused by the main complications of carcinoma as described above: 
cachexia, enlargement of the liver, stasis of the blood and biliary circu- 
lations, metastases of the neoplasm, ete. General disturbances of health, 
such as weakness, emaciation, and anemia, may be caused by the cachexia 
and by the deficient assimilation or ingestion of food, or may be the result 
of loss of blood. 

* Deutsch. Archiv f. klin. Med., Bd. uxvit. 


NEOPLASMS, 179 


In some cases fever is seen. This may be either remittent, intermit- 
tent, or irregular. It may be due to complicating inflammations, par- 
ticularly to cholangitis; this is noticed with particular frequency in 
carcinomata of the bile-passages. [Hawthorne mentions * a case of 
carcinoma of the liver with distinct febrile reaction, and points to the 
fact that this sign is not therefore distinctive of impacted gall-stone, 
abscess, and other inflammatory conditions. A diagnosis based chiefly 
on the existence of fever is, he insists, always open to error.—ED. | 


Achard, in a patient with fever suffering from hepatic carcinoma, found Sta- 
phylococcus albus in blood aspirated from the liver. Hanot found streptococci 
in a case of secondary carcinoma of the liver with cholangitis that was complicated 
by fever and icterus. 


In some cases a long-continued fever is seen that cannot be traced to 
any inflammatory cause; here the rise of temperature must be due to the 
rapid proliferation of the tissues and the formation and absorption of 
large quantities of toxic material. This type of fever is frequently 
seen in cases of primary carcinoma that grow rapidly, and in 
extended metastases in the liver. Sarcomata, too, show a chronic type 
of fever, particularly lymphosarcomata; Ebstein has called the fever in 
the latter form chronic recurrent fever. 

In the blood a decrease in the number of red blood-corpuscles will be 
seen; their number may be reduced even to 600,000. At the same time 
there is a corresponding decrease of the blood-pigment, of the specific 
gravity, and of the alkalinity. The white cells may be increased in 
proportion to the red cells; occasionally they are absolutely increased. 
Poikilocytosis is seen in the severe cases. Rarely there is a concentration 
and thickening of the blood owing to impoverization of the water-supply 
of the body following deficient ingestion or profuse diarrheas (Leichten- 
stern). 


In the region of the heart the signs of dilatation, of exudation into the peri- 
cardium, or anemia are occasionally detected. The heart action is weak toward 
the end of the disease and the pulse correspondingly small, rapid, and irregular; 
edema may appear in the dependent parts of the body. Sometimes thromboses 
form in the femoral veins. 

The respiration is sometimes affected by the development of a right-sided 
pleuritis following perforation of a carcinoma through the diaphragm or by the 
development of metastases in the lungs following the entrance of tumors into the 
hepatic vein or the inferior cava. Finally, hypostatic pneumonia and hydrothorax 
may occasionally develop. 


The disturbances of the organs of digestion are particularly important. 
The appetite is. lost at an early period of the disease and the secretion 
of gastric juice, particularly of the hydrochloric acid, is reduced. Some- 
times vomiting occurs as a result of irritation of the peritoneum or as a 
result of irritation of the nerves of the liver ; it may also be due to 
traction or irritation on the pylorus by adhesions. Intestinal digestion 
is also disturbed, particularly if the bile cannot enter the duodenum or 
if an insufficient quantity of bile is formed in the liver. As a result 
there are decomposition of the intestinal contents, meteorism, and the 
passage of disagreeable gases; undigested food is passed in the stools; 
these contain very little bile or none at all, but much of the calcium and 
magnesium salts. As a rule, the patients cannot digest meats and fats 
as well as milk and carbohydrate foods. 

* Brit. Med. Jour., Mar. 16, 1901. 


780 | DISEASES OF THE LIVER. 


In the beginning the bowels are constipated, this condition perhaps 
being due to stasis in the portal system; later in the disease diarrhea and 
constipation alternate. At the same time the symptoms of a severe 
catarrh of the colon develop, accompanied by ulcerations of the mucosa. 
Death may be hastened by the profuse diarrheas that follow the devel- 
opment of these lesions. 

The spleen in many cases is small and atrophic, especially if there is 
an absence of stasis in the portal system. In the forms of cancer that 
develop slowly the organ may be swollen, particularly if the cancer is 
complicated by cirrhosis of the liver. In many cases the size of the spleen 
remains normal. Metastases are rarely found in the organ. 

In case there is ascites, or if too little water is taken, or if there are 
profuse diarrheas, the urine may be much reduced in quantity; only half 
a liter may be voided per diem. The color is dependent upon the presence 
or absence of bile-pigment and of urobilin; these bodies are often excreted 
in large quantities. Urobilin is excreted in those cases of carcinoma that 
develop and disintegrate rapidly or in those that are complicated with 
cirrhosis; bile-pigment is found whenever the bile-ducts are occluded 
by the tumor. The bile constituents irritate the kidneys so that a little 
albumin is often passed, also a few tube-casts and epithelial cells. In 
melanosarcoma melanin is found in the urine, coloring it dark brown; or 
it may be present in its leuco-combination, and may be converted into 
melanin by contact. with oxidizing substances such as bromin-water. 
If decomposition in the intestine is very great, the aromatic substances 
of the urine are increased; in such cases indoxyl, phenol, and the ethereal 
sulphates in general are found in considerable quantities. The total 
daily excretion of nitrogen and the quantity of urea appear to be dimin- 
ished. 

The disturbances of the nervous system are caused in part by the 
neoplasm; pain in the region of the liver is caused directly by irritation 
of the nerves; pain in the shoulder is caused by radiation along the path 
of the phrenic and the cervical nerves. Sometimes attacks of hepatic 
colic are seen that may be due to the impaction of gall-stones or of tumor ° 
masses in the ducts, or to irritation of these passages by such bodies. 
The patient becomes irritable, there is loss of sleep, a decrease in the 
mental faculties and powers; later there is stupor, delirium, and possibly 
coma, (cancer-coma or cholemia). 

_ The skin is a pale yellow in simple cachexia, yellow to blackish-green 
in icterus. In the latter case there are scratches and small hemorrhages. 
As a rule, theskin»is flaccid, dry, and peeling. Decubitus may develop, 
and toward the end edema may supervene. ; 

According to the localization and the nature of the tumor, the patho- 
logic picture may vary greatly. It is probably carrying subdivision too 
far, however, to formulate a dyspeptic, an icteric, a cachectic, even a 
painful form, as has been done by Hanot and Gilbert. 

Prognosis.—The prognosis is absolutely unfavorable, except in those 
rare cases in which a neoplasm is so situated on the surface of the liver 
that it can be removed by an operation and the disease cured in this way 
(Sklifosowski, Bardeleben, and others). 

In massive carcinoma, sarcoma, and those forms of nodular carcinoma 
that increase and develop rapidly, the course is very rapid, and leads to 
death within a few weeks or months. In adenocarcinomata complicated 
by cirrhosis the course of the disease is slower. 


NEOPLASMS. ; 781 


Diagnosis.—It is often impossible to determine the nature of the 
neoplasm. We will frequently have to content ourselves with estab- 
lishing the presence of a tumor. 

In the case of carcinomata and sarcomata which produce a large and 
smooth swelling of the liver, hypertrophic cirrhosis of the liver, amyloid 
degeneration, deep-seated echinococcus disease, or abscesses will have to 
be considered as well as occlusion of the common or the hepatic duct by 
a gall-stone, leukemia, and other conditions. The rapid loss of strength, 
the age of the patient, the absence of biliary stasis and such etiologic 
factors as alcohol, malaria or syphilis, tuberculosis, persistent suppura- 
tion, gall-stone colic, ete., will all speak in favor of tumor of the liver; the 
blood picture, the rapid growth of the swelling without fluctuation, or 
the aspiration of a characteristic fluid, will all assist in arriving at a con- 
clusion. 

In nodular carcinoma and sarcoma a primary focus is sometimes pres- 
ent. If no such focus can be found,. echinococcus cysticus or alveolaris 
(particularly the latter), cystic liver, cysts of the bile-ducts following 
intrahepatic cholelithiasis, syphilis, abscesses, etc., must all be consid- 
ered. In echinococcus the age of the patient, local conditions, fluctua- 
tion, exploratory puncture, the hardness of the tumor (echinococcus - 
alveolaris), will enable us to make the differential diagnosis. Cystic 
liver is usually a chronic condition that produces few symptoms. Occa- 
sionally attacks of colic precede the formation of cysts of the bile- 
passages and give a clue. Syphilis of the liver is principally found in 
young individuals in whom a history of specific disease or some typical 
symptoms will aid in making the diagnosis. Abscesses can also be diag- 
nosed from the history, and the appearance of inflammatory symptoms, 
and from an examination of the aspirated fluid. 

It is often difficult to differentiate simple cirrhosis from cirrhosis 
complicated by cancer. The rapid loss of strength, the nodular char- 
acter of the liver surface, and the absence of a tumor of the spleen will 
enable us to make this diagnosis. 

Sarcomata of the liver are to a great extent secondary growths. In 
melanotic sarcoma the characteristic primary tumor will usually be found 
in the choroid or the skin; in other forms the primary tumor will be seen 
in other possibly more accessible parts of the body, as the muscles, bones, 
etc. Their malignancy is established by a rapid growth, and by the rapid 
loss of strength suffered by the patient. In melanotic tumors the exam- 
ination of the urine will yield positive information. 

Neoplasms of the gall-bladder may be confounded with stagnation 
of bile due to gall-stones, hydrops of the gall-bladder, and filling of the 
bladder with calculi. Here again the age of the patient, the symptoms 
of general carcinomatosis, the nodular consistency of the tumor, the ex- 
tension of the growth to the liver and the bile-passages, the resulting 
icterus, and carcinomatosis of the peritoneum will assist in the diagnosis. 

Carcinoma of the ductus choledochus and the hepatic ducts may 
be confounded with simple impaction of gall-stones. In this condition, 
however, the exclusion of the bile from the intestine is not so complete; 
besides the long duration of the occlusion and its persistency, the age of © 
the patient, the presence of metastases, ascites, and cachexia all speak 
for cancer. The question whether or not a cancer of the pancreas is 
closing the orifice of the common duct is a difficult one to answer. Ina 
case of this kind the absence of pancreatic juice from the intestine would 


782 DISEASES OF THE LIVER. 


be manifested by deficient lipolysis; this finding would not, however, 
decide positively in favor of such a diagnosis, for it would be equally 
possible for a carcinoma of the common duct to occlude the exit of the 
pancreatic duct secondarily. From the ecoenont of treatment this 
question is an insignificant one. 

Examination with the Rontgen rays may give some information in 
regard to tumors that are so situated that they cannot be palpated. This 
method will show the exact location and the size of the tumor. 

Treatment.—Treatment of a malignant tumor, as a rule, can only be 
palliative. In exceptional cases surgeons have succeeded in extirpating 
a growth that was situated favorably for operative interference and in 
removing all diseased tissue so completely that there has'been no re- 
currence. 

I must refer to the monographs of Langenbuch and von Madelung for 
the description of the different cases that are on record, the methods of 
operating, ete. 

Hochenegg and von Heidenhain have extirpated a carcinomatous 
gall-bladder together with a piece of carcinomatous liver tissue for 
cancer of this viscus. P. Bruns removed a carcinomatous nodule from 
the liver and reports that the wound healed rapidly; the nodule had been 
removed for diagnostic purposes: Liicke probably was the first to 
remove a large cancer nodule from the liver; during this operation he also 
removed a cancerous lymph-gland and cured his case. Very few success- 
ful operations of this kind have been performed since this occasion. 
Several surgeons have removed adenomata with success (Keen, Fr. 
Schmidt, v. Bergmann, Grube, Triconi); all the cases published were not 
malignant. 

Sklifosowski removed a pedunculated sarcomatous fibromyoma; 
v. Bardeleben, a sarcoma of the abdominal wall that had grown into 
the liver; Israel (angiosarcoma) and d’Urso have published similar 
cases. 

We know from the experiments of Ponfick, and from clinical observa- 
tion in destructive lesions of the liver, that life can be carried on even 
though large pieces of the liver are removed, and that a process of regen- 
eration and of hyperplasia soon replaces the loss. We may hope, there- 
fore, that with a perfection of surgical technique it will soon be possible 
to extirpate larger tumors of the liver, such as solitary carcinomata and 
sarcomata, and in this way to cure many cases. [Kimmell* extir- 
pated successfully a hazelnut-sized sarcoma of the liver, situated near the 
gall-bladder. He also removed a large wedge-shaped piece of liver tissue 
with the growth, then closing the wound.—Ep.] The most popular 
method so far has been to excise the tumor by a wedge-shaped incision 
and to suture the edges of the wound to the abdominal wall. The tumor 
has also been first attached extraperitoneally and extirpated in the course 
of a second operation. As sepsis seems to occur more readily if the tumor 
is situated extraperitoneally, it is best to close the wound after resection, 
possibly with the aid of the mesentery, and then to replace the parts. 

It is, however, not always possible to operate, and treatment must be 
directed toward making the patient as comfortable as possible. If pain 
is very severe, warm or cold compresses should be applied; if peritoneal 
irritation appears, counterirritants in the form of liniments, tincture of 
iodin, etc., or narcotics must be employed. For the sleeplessness chloral, 

* Aerztlich. Verein in Hamburg, Oct. 16, 1894. 


NEOPLASMS. 7838 


sulphonal, etc., can be given; the appetite can be stimulated by hydro- 
chloric acid, tincture of cinchona, pepsin, etc. These remedies will at the 
same time aid digestion. The administration of alkaline waters, usually 
indicated in affections of the liver, should be avoided (Karlsbad, Ems, 
Faching, Vichy) and constipation should be treated by vegetable laxa- 
tives, such as rhubarb, senna, aloes, etc., rather than with sulphates. 

Very much will depend on a rational regulation of the diet and the 
mode of life. In addition to warm bathing and rest, particularly in 
icterus, the patient should be kept on a diet that does not tax the digestive 
organs too much. Milk is the best food in this respect, together with easily 
digestible amylaceous foods, as soups, gruels, etc. Large quantities of 
milk should be avoided, because they may cause the formation of large 
lumps of casein in the stomach and hinder digestion in this way. The 
milk may be improved by the addition of cream, or may be given as 
koumiss, buttermilk, or sour milk. Patients, as a rule, have a disgust for 
meat, and it does not agree very well with them. In case of great de- 
composition of the intestinal contents milk again is the best remedy, as it 
seems to check the putrefaction of proteid material. The preparations 
of peptone and meat extracts are not so suitable. They may, however, 
be given in small quantities together with such preparations as somatose, 
eucasin, ete., as they stimulate the patient, and, owing to their ready 
assimilability, aid in maintaining his strength. Fats are usually not well 
tolerated. Food should be administered in small doses and frequently; 
z. e., about every three hours. 


LITERATURE. 


Achard: “ Verhandlungen der anatomischen Gesellschaft in Paris,” April 10, 1896 
(Fever in Carcinoma). 

Ahlenstiel: “ Die Lebergeschwiilste und ihre Behandlung,” “ Archiv fur klin. Chi- 
rurgie,” Bd. Lu, p. 902. 

Arnold: “ Zwei Falle von primarem Angiosarkom der Leber,” “ Ziegler’s . Beitrage,”’ 
1890, Bd. vit, p. 123. 

Benner: “Ein Fall von Gallenstauungscirrhose mit primérem Adenocarcinom 
im Ductus choledochus,”’ Dissertation, Halle, 1892. 

Birch-Hirschfeld: ‘‘ Lehrbuch der pathologischen Anatomie,” Bd. 11, p. 617. 

Bohnstedt: “Die Differentialdiagnose zwischen dem durch Gallensteine und dem 
aaue Tumor bedingten Verschluss des Ductus choledochus,”’ Dissertation, 

alle, 1893. 


Bramwell and Leith: “ Enormous Primary Sarcoma of the Liver,” “ Edinburgh 
Med. Journal,’”’ October, 1896, p. 331. 
_ Brissaud: “ Adénome et cancer hépat.,” “Archives générales de médecine,” 1885, 


tome cLVI, p. 129. 

Brodowski: “ Ein ungeheures Myosarkom des Magens, nebst sec. Myosarkom der 
Leber,” ‘‘ Virchow’s Archiv,” Bd. Lxvi1, p. 227. 

Brunswig: “Ein Fall von primairem Krebs der Gallenblase,’’ Dissertation, Kiel, 


1893. 

Budd: ‘“ Krankheiten der Leber,” German translation by Henoch, Berlin, 1846, p. 
341. 

Deetjen: “Ein Fall von primarem Krebs des Ductus choledochus,”’ Dissertation, 
Kiel, 1894. 

Eberth: “ Untersuchungen iiber die normale und pathologische Leber, Adenom 
der Leber,” “ Virchow’s Archiv,”’ Bd. x11, p. 1. 

Ewald: “Ein Fall von Carcinom der Gallenblase, ”” “Berliner klin. Wochenschr.,”’ 
1897, p. 411. 

Feickert: “ Beitrag zur Genese des metastatischen Lebercarcinoms,” Dissertation, 
Wirzburg, 1892. 

Frerichs: “Klinik der Leberkrankheiten,”’ Bd. 11, pp. 271 and 454, 1861. 

Gilbert et Claude: “Cancer des voies bil. par effract. dans le cancer prim. du foie,”’ 
“ Archives générales de médecine,” 1895, tome cLxxv, p. 513. 


784 DISEASES OF THE LIVER. 


Grawitz: “ Klinische Beobachtungen itiber den Krebs der Gallenblase,” “ Charité- 
Annalen,’’ Bd. xx1, p. 157. 

Griesinger: ‘‘ Das Adenoid der Leber,” “ Archiv der Heilkunde,” 1864, Bd. v, p. 385. 

Hanot et Gilbert: ‘“ Etudes sur les maladies du foie,’ Paris, 1888 (complete 
bibliography of liver tumors). 

Hanot: ‘‘ Note sur le modification de l’appétit dans le cancer du foie,” “ Archives 
générales de médecine,’”’ October, 1893. 

—‘Verhandlungen der anatomischen Gesellschaft in Paris,’’ Mar. 27, 1896 (fever 
in cancer). 

Hansemann: y Ueber den primiren Krebs der Leber,’”’ “ Berliner klin. Wochenschr.,”’ 
1890, No. 16. 

Harris: “ Ueber die Entwickelung des primiren Leberkrebses,”’ ‘ Virchow’s Archiv,” 
1885, Bd. c, p. 139. 

Hartmann: “ Ein Fall von primérem Gallenblasenkrebs,” Dissertation, Kiel, 1896. 

Held: “Der primaire Krebs der Gallenblase,’’... Dissertation, Erlangen, 1892. 

Holker: ‘ Ueber carcinomatose Lebercirrhose,” Dissertation, Freiburg i. Br., 1898. 

Howald: “ Die primaéren Carcinome des Ductus hepaticus und choledochus,”’ Dis- 
sertation, Bern, 1890. . 

Index-Catalogue of the Library of the Surgeon-General’s Office, vol. vir, p. 285 
et seq. (literature). 

v. Kahlden: “Ueber das primire Sarkom der Leber,” “ Ziegler’s Beitrige zur 
pathologischen Anatomie,” 1897, Bd. xx1, p. 264. 

Kelsch et Kiener: “Contribution 4 Vhistoire de l’adénome du foie,” ‘ Archives 
de physiologie normale et pathologique,” 1876, p. 622. 

Kelynack: “ Edinburgh Med. Journal,” February, 1897. 

Kuznezow and Pensky: (resection of the liver) “Centralblatt fir Chirurgie,” 
1894, p. 978. 

Langenbuch: “Chirurgie der Leber und Gallenblase,” 2. Theil, p. 32. 

Laveran: ‘ Observ. d’épithel. 4 cellules cylindr. prim. du foie,” “ Archives de phys- 
iologie normale et pathologique,” 1880, p. 601. 

Leichtenstern: ‘‘ Klinik des Leberkrebses,’’ “ Ziemssen’s Handbuch der speciellen 
Pathologie und Therapie,”’ Bd. vi, 1. Abtheilung, p. 315. 

Litten: ““Ueber einen Fall von infiltrirtem Leberkrebs,” “ Virchow’s Archiv,” 
1880, Bd. LUxxx, "pi. 269, 

Madelung: “Chirurgische Behandlung der Leberkrankheiten” in Penzoldt und 
Stintzing’s “Handbuch der speciellen Therapie,’ Bd. 1v, Abtheilung vib, 
p. 198. 

Marckwald: “Das multiple Adenom der Leber,” “ Virchow’s Archiv,’ 1896, Bd. 
CXLIV, p. 29. 

Murchison: “ Diseases of the Liver.” 

Naunyn: “Ueber die Entwickelung des Leberkrebses,” “Archiv fiir Anatomie 
und Physiologie,” 1866, p. 717. 

Nélke: “ Ein Fall von primaérem Leberkrebs,” Dissertation, Kiel, 1894. 

Oberwarth: ‘ Ein Fall von primérem Gallenblasenkrebs,”’ Dissertation, Kiel, 1897. 

Ohloff: ‘Ueber Epithelmetaplasie und Krebsbildung an der Schleimhaut von 
Gallenblase und Trachea,” Dissertation, Greifswald, 1891. 

Perls: “ Histologie des Lebercarcinoms,” “ Virchow’s Archiv,” 1872, Bd. Lv1, p. 

— 448 


Rindfleisch: “ Mikroskopische Studien iiber das Leberadenoid,” “ Archiv der Heil- 
kunde,” 1864, Bd. v, p. 395. 

De Ruyter: “Congenitale Geschw. der Leber,” ‘ Archiv fiir klin. Chirurgie,” 1890, 
Bd. xu, p. 95. 

Rohwedder: ‘Der primaire Leberkrebs und sein Verhalten zur Lebercirrhose,” 
Dissertation, Kiel, 1888. 

Schmidt: “ Ein Fall von primirem Gallenblasenkrebs,” Dissertation, Kiel, 1891. 

Schrader: “Noch ein Fall von Exstirpation einer Lebergeschwulst,’’ “‘ Deutsche 
med. Wochenschr.,’’ 1897, p. 173. : 

Schreiber: ‘ Ueber das Vorkommen von primiéren Carcinomen in den Gallenwegen,”’ 
“ Berliner klin. Wochenschr.,”’ 1877, No. 31. 

Schiippel: “Pathologische Anatomie des Leberkrebses,” “ Ziemssen’s Handbuch,” 
Bd. vitt, 1, 1, p. 284. . 

Siegenbeck van Heukelom: “Das Adenocarcinom der Leber mit Cirrhose,’”’ Ziegler’s 

_ “Beitrage zur pathologischen Anatomie,” Bd. xv1, p. 341. 

Seigert: “Zur Aetiologie der primiren Carcinome der Gallenblase,” ‘ Virchow’s 

Archiv,” 1893, Bd. cxxxu, p. 353. 


NEOPLASMS. 785 


Siegrist: “ Klinische Untersuchungen tiber Leberkrebs,’’ Dissertation, Ziirich, 1887. 

Simmonds: “ Knotige Hyperplasie und Adenom der Leber,” ‘ Deutsches Archiv 
fiir klin. Medicin,” Bd. xxxiv, p. 385 

Sjoquist: “ Nord. med. Arkiv,” 1892. , 

Skorna: “ Ein Fall von Carcinoma hepatis idiopathic,’ Dissertation, Berlin, 1895. 

Thorel: ‘‘ Die Cirrhosis hepatis carcinomatosa,”’ Zeigler’s “ Beitrige zur pathologis- 
chen Antomie,”’ Bd. xvi, p. 498. 

Tiedemann: “Zur Casuistik des primidren Gallenblasenkrebses,’” Dissertation, 
Kiel, 1891. 

“Traité de médecine” (Charcot, Bouchard, Brissaud), tome 111, p. 962. 

d’Urso: “ Endothelioma prim. del. fegato,” “Centralblatt fiir Chirurgie,” 1897, 
No. 13. ® 

Wagner, E.: “Zur Structur des Leberkrebses,” ‘Archiv der Heilkunde,” 1861, 
Bd. u1, p. 209. 

—“Zwei Falle von Neubildung von Lebersubstanz im Lig. suspensor. hepat.,’’ 
ibidem, p. 471. 

—‘Drisengeschwulst der Leber,” ibidem, p. 473. 

—‘‘Primidrer Krebs der Gallenblase,”’ ibidem, 1863, Bd. Iv, p. 184. 

Waldeyer: “Die Entwickelung der Carcinome,” ‘“ Virchow’s Archiv,” 1872, Bd. 

LM Ped bd 

Waring: “ Diseases of the Liver,’”’ Edinburgh and London, 1897, p. 182. 

Weber: ‘Ueber ein Plattenepitheliom der Gallenblase,” Dissertation, Wurzburg, 
1891. 

Weigert: “Ueber primires Lebercarcinom,” “ Virchow’s Archiv,” 1876, Bd. Lxvu1, 


p. 500. a 
Willigk: ‘Beitrag zur Pathogenese des Leberkrebses,” ‘ Virchow’s Archiv,” 
1869, Bd. xuviit, p. 524. 
—‘Beitrag zur Histogenese des Leberadenoms,” ibidem, 1870, Bd. 11, p. 208. 
Windrath: ‘Ueber Sarkombildungen der Leber,’ Dissertation, Freiburg, 1885. 
Zenker, H.: “Der primaire Krebs der Gallenblase,’”’ Dissertation, Erlangen, 1889. 
Zinsser: ‘‘ Beitrag zur Aetiologie dse Krebses,’’ Dissertation, Kiel, 1895. 


LEUKEMIC AND LYMPHOMATOUS ‘TUMORS OF ‘THE LIVER. 


The lesions of the liver seen in leukemia and in pseudo-leukemia are 
related to the lesions seen in tumor formation. This is, however, not the 
place to discuss the course of these diseases nor their treatment. We will 
therefore limit our discussion to a description of the lesions caused by 
these conditions and found in connection with other diseases of the liver. 

Leukemia is to-day divided into two forms, the acute and the chronic. 
There are transition stages between the two, though etiologically we are 
as yet unable to differentiate them. Pathologic germs have so far not 
been found, although many features of the disease, as the fever, the dis- 
tribution of the lesions throughout the body, their starting-point in the 
fauces, etc., point to a parasitic origin. [Boinet* has reported several 
cases of leukemia that point to an infectious etiology. In two of these 
cases there was a general glandular enlargement, and in one case bacteria 
were obtained from the glands.—Ep.] The acute form is variously 
described; A. Frankel states that it has a duration of from two and one- 
half to sixteen weeks; others state that it lasts much longer. According 
to Frankel, the changes in the blood consist chiefly in an increase of the 
mononuclear leucocytes, and constitute a lymphemia or a lymphocy- 
themia; others claim that the principal abnormalities consist in the ap- 
pearance of marrow-cells and of polynuclear elements. 

In the acute forms, at all events, there is an abundant new-formation 
of leucocytes and a flooding of the blood with young cells resembling 
lymphocytes. 

In the chronic forms there is also an abundant formation of white 

* Wien. med. Woch., Nov. 3, 1900. 
50 


786 DISEASES OF THE LIVER. 


blood-corpuscles; in this case the older forms, the polynuclear and the 
eosinophilic cells, are more numerous. Different authors (H. F. Miiller, 
Hindenberg) have shown that in the liver capillaries a proliferation of 
leucocytes, with the formation of mitoses, occurs; this is usually ex- 
plained from the fact that in these channels the blood and its elements 
are, comparatively speaking, at rest, and that in this way the develop- 
ment of cell division is favored. In addition to the elements named, 
the so-called myeloplaques, giant-cells, are found; their origin is obscure. 

The pathologic-anatomic finding in the liver is usually that of general 
enlargement of the organ. «The surface is usually smooth, and occasionally 
the peritoneal covering is roughened from infiltration with leucocytes. 
The outline of the organ is not changed; its consistency is dependent upon 
the degree of infiltration and its weight may be as much as 7 kg. On 
transverse section a lobulated configuration is seen; between the lobules 
are wide, swollen bands that correspond to the periportal tissues; in 
other cases grayish-white, soft nodules are seen that contain leukemic 
lymphomata. These white spots are sometimes very well developed, 
and form white plates on the surface of the organ, from which white bands 
penetrate the interior of the organ; these processes may also start from 
the portal branches, shooting out from them into the liver tissue and 
forming a system of arborescent ramifications through its substance. 

The portal lymph-glands are frequently enlarged. At the same time 
characteristic changes in the spleen, the bone-marrow, and the lymphatic 
apparatus are seen. 

Microscopically, the most characteristic feature is the accumulation 
of leucocytes in the periportal connective tissues, extending from there 
between the columns of liver-cells into the acini. Round cells fill the 
capillaries within the liver and distend them. This process is first seen 
in the periphery near the branches of the portal vein and gradually 
advances toward the center of the acinus. Some investigators claim that 
the cell-columns are hyperplastic; liver-cells are seen that are larger than 
normal. If the infiltration with leucocytes occurs in this manner and 
reaches a considerable degree, the liver-cells become compressed, nar- 
rowed, and undergo atrophic changes. In addition, venous stasis occurs 
in the center of the acini, and as a result there is atrophy of this area. 
The hepatic cells, as a rule, contain a large quantity of iron pigment and 
present the picture of siderosis; this is due to the great disintegration of 
red blood-corpuscles that takes place toward the end. Simultaneously 
may be seen, in many chronic cases, round areas of leucocytes 
between the liver-cells, the so-called leukemic lymphomata. They 
consist of a fine network of delicate connective-tissue fibers, inclosing 
numerous leucocytes of various forms. In the acute cases this is not so 
prominent a feature. These nodules, in contradistinction to tubercles 
and other small tumors, show neither a tendency to necrosis nor to 
suppurative degeneration. The bile-passages are, as a rule, not involved, 
so that icterus usually does not appear. Similar accumulations of leuco- 
cytes are also seen in typhoid fever. 

In pseudoleukemia the liver shows similar changes. Here, however, 
the portal lymph-glands show a greater tendency to enlargement, and, as 
a result, icterus from stasis and compression of the portal vein are more 
frequent. The whitish-yellow lymphomata are also larger than in 
leukemia; they may be as large as nuts, and appear with particular fre- 
quency in Glisson’s capsule. From this point they send out processes 


NEOPLASMS. 787 | 


into the acini that show a drumstick swelling at their distal extremity. 
They are also seen underneath the peritoneum. [Crowder * records a case 
of generalized tuberculous lymphadenitis simulating the clinical and 
anatomic picture of pseudoleukemia. The postmortem examination 
showed general glandular hyperplasia, and the appearance of lymphoid 
nodules in the liver, spleen, and lung. The latter, on microscopic exam- 
ination, however, were seen to be tubercular foci. There seems to be no 
doubt that many of the so-called cases of pseudoleukemia are tubercu- 
lous.—Ep.] Sometimes cirrhotic changes may be seen in the intra- 
acinous connective tissue, causing the surface of the organ to become very 
rough. If the intra-acinous connective tissue contracts, the liver is 
diminished in size, and the symptoms of ordinary cirrhosis may appear 
—namely, ascites, etc. At the same time the hepatic cells are often 
infiltrated with fat. Some authors (Klein) believe that cirrhosis de- 
velops at the same time as the pseudoleukemic process, and that both 
diseases can be attributed to a common cause. 

Symptoms.—tThe liver is enlarged in more than one-half of all cases 
of leukemia, and, as a rule, a tumor of the spleen will be felt at the same 
time; the latter is only rarely absent in acute leukemia. 

If the liver is very much enlarged, certain subjective symptoms 
appear, as a feeling of pressure, less frequently pain in the right hypo- 
chondrium, and a feeling of fulness even after the ingestion of small 
amounts of food. Schultz attributes the pain in the sternum, so fre- 
quently observed in leukemia, to the pressure of the enlarged liver. 
The organ can be easily palpated, its consistency is increased, it may 
even be extremely hard in severe cases. It is smooth, not very sensi- 
tive to pressure, the margin is not indentated, and is fairly sharp.. In 
cases of great infiltration the liver may extend as far down as Poupart’s 
ligament, or may be in contact on the left with the enlarged spleen. In 
other words, it may almost fill the abdominal cavity and cause the abdo- 
men, and particularly the right hypochondriac region, to bulge. Icterus 
is hardly ever present. Ascites is not seen in the beginning; only toward 
the end of the disease may a slight exudate be poured into the abdominal 
cavity. 

The liver shows similar changes in pseudoleukemia. Here, however, 
icterus is more frequently <een as a result of compression of the common 
duct by glands near the portal orifice. The surface of the organ is not 
so smooth, and the margin is indented owing to cirrhotic changes in the 
liver and the formation of lymphomata in the capsule. 

In leukemia the general symptoms of the disease are also seen. Thus, 
in addition to the lesions of the liver there are swelling of the spleen and 
of the lymph-glands, muscular weakness, leukemic retinitis, edema, and 
hemorrhages, the latter principally toward the end of the course of the 
chronic form, and in the beginning of the acute form. There may also be 
ulcerations in the mouth, the pharynx, and the intestinal canal, besides 
a characteristic increase in the leucocytes, both relative and absolute. 
In the urine large quantities of uric acid and xanthin bodies are found; 
this is particularly the case if a rapid disintegration of leucocytes occur, 
as, for instance, in bacterial disease, miliary tuberculosis, septicopyemia, 
ete. Atsuch times there may seem to be an improvement or a cure of the 
disease. Even the tumors of the spleen and the liver may appear to 
decrease. 

* Wien. klin. Woch., Dec. 6, 1900. 


788 , DISEASES OF THE LIVER. 


In pseudoleukemia also there is an increase in the uric acid and the 
xanthin bodies; also of nucleo-histon. 

The diagnosis of leukemic liver must be made from the characteristic 
changes in the blood, and from the swelling of the spleen and lymph- 
glands. The pseudoleukemic form is recognized by the appearance of 
numerous lymphomata, a tumor of the spleen, and the course of the fever 
(chronic recurrent type) ; [also by the absence of the blood-picture typical 
of true leukemia.—Ep.]. The tumor of the liver itself is not character- 
istic, and may be caused by fatty liver, amyloid liver, or congestion of 
the liver from stasis. 

The prognosis of leukemia is unfavorable; less unfavorable in pseudo- 
leukemia only in those cases that are not very cachectic. 

The treatment of these diseases consists principally in the adminis- 
tration of iron and arsenic, and in the regulation of the mode of life. 


LITERATURE. 
OLDER LITERATURE TO 1892. 


Hoffmann: ‘Lehrbuch der Constitutionskrankheiten,” Stuttgart, 1893. 

v. Limbeck: “Grundriss einer klin. Pathologie des Blutes,” Jena, 1892. 

Mosler: “‘ Ziemssen’s Handbuch der speciellen Pathologie und Therapie,” Bd. 
vil, 2. Halfte, p. 155. 

Rieder: “Beitrag zur Kenntniss der Leukocyten,” Leipzig, 1892. 


Newer Works. 
Askanazy: “Ueber acute Leukimie und ihre Beziehung zu geschwir Processen 


im Verdauungscanal,” ‘‘ Virchow’s Archiv,” 1894, Bd. cxxxvu, p. 1. 
Dausac: “ Leucocythémie suraigué,” “Gazette hebdomad.,”’ p. 116. 
Ebstein: ‘‘ Beitrage zur Lehre von traumatischer Leukimie,” ‘‘ Deutsche med. 


Wochenschr.,”’ 1894, p. 589. 

Frankel, A.: “ Ueber acute Leukimie,” ibidem, 1895, p. 639. 

Hindenburg: “ Zur Kenntniss der Organverinderungen bei Leukimie,” ‘‘ Deutsches 
Archiv fiir klin. Medicin,” 1895, Bd. tiv, p. 209. 

Hintze: “ Ein Beitrag zur Lehre von der acuten Leukimie,” ibidem, 1894, Bd. 
LI, 377. 

Lannois et Regaud: “ Coexist.de la leucocythémie et d’un cancer epithél.,” ‘Archives 
de méd.-expér.,”’ 1895, tome vu, p. 254. 

Klein, St.: “ Ein Fall von Pseudoleukimie nebst Lebercirrhose,’” “ Berliner klin, 
Wochenschr.,’”’ 1890, p. 712. 

Schultze: “Ueber Leukamie,” ‘Deutsches Archiv fiir klin. Medicin,’” 1894, Bd. 


Lu, p. 464. 
Zielenziger: “ Kin leukimisches Lymphom der Leber,” Dissertation, Wurzburg, 
1892. 


PARASITES OF THE LIVER. 
(Hoppe-Seyler. ) 


(A) COCCIDIA. 


Coccidia (psorospermia) are very frequently found in the liver of 
animals, particularly of rabbits. In man they are not found frequently, 
although some investigators claim that carcinoma and other malignant 
tumors are caused by these parasites. : 


. In a few cases coccidium oviforme has been found in man. Gubler reports 
a case in a man who suffered from loss of appetite, pain in the right hypochondriac 
region, cachexia, and anemia. The liver was enlarged and there was a nodular 
tumor in the region of the gall-bladder. Icterus was not present. Later there 


PARASITES OF THE LIVER. 789 


was fever, bile-colored vomit, prostration, dyspnea, and death followed. On 
autopsy numerous tumors were found in the liver, some of them as large as a hen’s 
egg, and resembling medullary carcinomata. In addition, there was a cyst from 
12 to 15 cm. in diameter containing slimy masses mixed with blood. The tumors 
were soft, gray in the center, and translucent near the periphery. A creamy sub- 
stance could be scraped from their surface, in which epithelial cells from the bile- 
ducts, liver-cells that had undergone fatty degeneration, fat-droplets, etc., could 
be seen, and, in addition, certain cells that were four times as large as the largest 
liver-cell, egg-shaped, had a double outline, and were finely granular. These 
bodies were also found on the intact portions of the liver surface. Gubler con- 
siders them to be the eggs of distoma, while Davaine and Leuckart look upon them 
as examples of coccidium oviforme infection. Dressler, Sattler, Perls, and Silcock 
have also described instances of coccidium infection in human livers. They produced 
either cysts or cheesy degeneration. Sattler found them in dilated bile-passages. 
It is reported that coccidium perforans is also sometimes seen in the liver of 
man. Exact research with reference to this parasite has never been undertaken. 


Braun: “ Die thierischen Parasiten des Menschen,” 2. Aufl., Wurzburg, 1895, p. 77. 
- Davaine: “Traité des entozoaires,”’ 2. Aufl., Paris, 1877, p. 268. 

Gubler: ‘Gazette médicale de Paris,’”’ 1858, p. 657. 

Leuckart: “Die menschlichen Parasiten,” 2. Aufl., 1, Abth. 1, 1879, p. 281. 
Schneidemiihl: “Die Protozoen als Krankheitserreger,” Leipzig, 1878, p. 36. 


(B) ECHINOCOCCUS CYSTICUS (HYDATIDOSUS). 


The most important animal parasite found in the liver of man and 
capable of causing pathologic changes in this organ is the echinococcus. 
We will not attempt to describe the natural history of this organism in 
this place. In another volume of this series exhaustive attention has 
been paid to the subject (‘‘Animal Parasites,” by F. Mosler and E. 
Peiper); also in a monograph by Neisser; and in the works of Siebold, 
Kichenmeister, Leuckart, Davaine, and others. Echinococcus cysticus 
has of late been discussed separately from echinococcus multilocularis 
or alveolaris; for while these two conditions are intimately related, they 
still show essential differences in their pathologic nature, their sympto- 
matology, and their geographic distribution. 

Etiology.—According to the studies of Siebold, Kichenmeister, 
Leuckart, and others, echinococcus disease develops from eggs deposited 
in the intestinal tract of the dog, the wolf, or the jackal, less often in other 
animals. The parasite that lays these eggs is Tenia echinococcus, a 
small tapeworm 1.5 millimeters in length. From the intestinal tracts of 
these animals the eggs are carried to the stomach and the intestine of man; 
here a greater proportion, probably the majority, perish. Occasionally, 
however, the shell is digested and the embryo penetrates the intestinal 
wall, enters the portal vein, and in this manner penetrates the liver; 
here it becomes lodged, and is converted into an echinococcus cyst. 
At the same time, though less frequently, embryos enter the lymph- 
channels and the greater circulation. The method by which these 
embryos enter the intestinal wall. is unknown. Some investigators 
(Neisser) assume that the organism is perfectly passive,—for instance, 
like a particle of silver,—and-~is simply passed through small spaces 
in the intestinal wall; others believe that it penetrates the wall owing 
to its motility. Leuckart, at all events, in his animal experiments, 
has found embryos within the roots of the portal vein, thus readily 
explaining why this parasite is found so frequently in the liver. Some 
authors have formulated the hypothesis that echinococcus enters the 
liver through the bile-ducts in the same manner as many other 


790 DISEASES OF THE LIVER. 


parasites. If this were the case, they should also be found in the pan- 
creas, where echinococcus growths are exceedingly rare. The bile- 
current impedes the advance of the echinococcus, which is very sensitive 
to the action of this fluid. This is shown by the fact that the organism 
dies or becomes impaired in vitality if bile enters the echinococcus cyst. 
No anatomical connection can be found between bile-passages and 
recent echinococcus cysts; the latter develop in the interlobular con- 
nective-tissue structure of the liver. Naunyn* has also demonstrated 
a frequent connection between the smaller cysts and the vessel-walls. 

It is said that trauma of the liver or of other organs favors the devel- 
opment of echinococcus (Boncour, Danlos, Duvernoy, Kirmisson, Soko- 
low, von Bramann, and others). A positive conclusion seems hardly 
justified in view of the scanty observations that are on record. It is 
possible, however, that an embryo might find a suitable nidus for its 
development in a portion of the liver that has been altered by trauma. 

The echinococcus soon becomes converted into a nodule resembling 
a tubercle, and develops very slowly. Around its thick cuticle a capsule is 
formed from the hepatic connective tissue containing numerous wide bile- 
passages and blood-vessels, which provide nourishment for the parasite. 
Nutritive material particularly suitable for the parasite penetrates the 
cuticle; noxious substances, on the other hand, seem to be withheld. 

As a rule, tiny scolices soon develop in the wall, and from these 
endogenous cysts, or secondary hydatids. In man the exogenous forma- 
tion of daughter-cysts is rare. In sheep, however, this is frequently 
seen, and buds appear on the outer wall of the cyst. These daughter- 
cysts, the exact formation of which we may not discuss in this place, 
are sometimes sterile. J*requently they too contain scolices and tertiary 
hydatids, and granddaughter-cysts may be developed from them. As 
a rule, from twenty-five to fifty daughter-cysts are seen in one cyst. 
Some echinococci are altogether sterile; that is, they form no scolices, 
but only growths on the inner surface of the cyst-wall that may contain. 
some calcium and fat. These so-called acephalo-cysts grow very large, 
and consequently produce more serious pathologic changes. 

Sometimes several years pass before echinococcus disease causes 
symptoms. ‘This is due to the fact that the organism develops so slowly 
that the changes in the liver proceed imperceptibly; symptoms appear 
as soon as pressure is exerted on surrounding organs, or if some trauma 
injures the cyst, such as a blow or a fall, infection with pus organism, 
or perforation. We can thus readily understand that the disease is 
frequently not recognized during life and only discovered at autopsy 
or in the course of an operation. As a great many of these parasitic 
growths, therefore, are never recognized for the reason that the indi- 
viduals are not examined postmortem, it is a difficult matter to give 
reliable statistics on the frequency of their occurrence. | 

There can be no doubt that the disease is frequent is Iceland, although 
older statements, that from one-seventh to one-sixth of the population 
are afflicted, seem to be exaggerated. Twenty-eight per cent. of the 
dogs seem to have the tenia. In Australia the disease is frequent 
wherever sheep culture is carried on. In Germany, certain parts of 
Mecklenburg and Pomerania are particularly afflicted.t According to 

“* Naunyn, Archiv fiir Anatomie u. Physiologie, 1863, p. 921. 


+ Madelung, “Beitrige mecklenb. Aerzte z. Lehre von der Echinococcus- 
krankheit,”’ Stuttgart, 1885. Mosler, Deutsche med. Woch., 1886, Nos. 7 and 8. 


PARASITES OF THE LIVER. 191 


Peiper, 68.58 % of the cattle, 51.02 % of the sheep, and 4.93 % of the 
hogs are afflicted with echinococcus disease in the neighborhood of 
Greifswald. In other European countries, France, England, etec., echino- 
coccus is quite frequently encountered, also in Algiers and Egypt. In 
Asia and Africa the disease seems to be rare. [W. J. Buchanan * states 
that hydatid disease seldom or never occurs in the natives of India. He 
reports as a medical rarity a case occurring in a native of Bhagalpur.— 
Ep.] The etiology is important for the diagnosis of echinococcus, be- 
cause intimate contact with dogs (keeping them in the same room, allow- 
ing them to lick up the food from the plates, etc.) and extensive sheep 
culture create favorable circumstances for infection with this disease. 
It is said, for instance, that in Iceland one-third of the sheep are afflicted 
with echinococcus. [Kokall + considers at length the occurrence of 
echinococcus disease in Briinn, as indicated by the hospital statistics. 
Between 1881 and 1895 there were treated 104,366 cases of all kinds, 
and in 10 of these (0.009 %) a diagnosis of echinococcus was ventured. 
Many more were found at the autopsy table; 6943 autopsies were per- 
formed, and 24 cases of echinococcus (0.34 %) were discovered. In 
men it occurred 9 times, in women 15; in the liver 19 times, in the lower 
lobe of the right lung twice, once in the spleen, once in the muscles of 
the lower limbs, and once beneath the diaphragm. In only two cases 
was the cyst multilocular.—Eb.] 

It is a peculiar fact that echinococcus disease seems to attack the 
female sex oftener than the male, though no adequate explanation for 
this phenomenon has been offered. Among 255 cases reported by 
Finsen, 191 were women. Neisser in his statistics saw a proportion 
of 148 men as against 210 women. 

Pathologic Anatomy.—The echinococcus is found more frequently 
in the liver than in any other organ; in fact, nearly one-half of the cyst 
parasites attack this organ. Other parts of the body may also bé attacked 
at the same time. If multiple echinococcus infection is present, the liver 
is almost always infected. 

As a rule, only one echinococcus cyst is found in the liver. There 
may, however, be two or three, sometimes more; occasionally as many 
as twelve have been discovered. 

The echinococcus cysticus is inclosed in a solid wall, the cuticle. 
On transverse section this membrane is seen to be striated in a charac- 
teristic manner, and, according to Liicke,t to consist of chitin; on 
boiling with sulphuric acid it yields dextrose. The clear contents con- 
tain no albumin, have a specific gravity of 1009 to 1015, frequently 
contain succinic acid (Heintze, Boedeker), inosite, dextrose (Cl. Bernard, 
Liicke), and occasionally leucin, tyrosin, etc. The chief mineral con- 
stituent is sodium chlorid. | 

Certain poisonous substances are also found in the fluid that cause 
collapse if injected into animals (Humphrey); these are probably pto- 
mains (toxalbumins ?), according to Moursson and Schlagdenhauffen. 
Brieger succeeded in isolating’ a body that was rapidly fatal for mice 
in small doses.% 

The whole bladder is surrounded by a connective-tissue capsule 


* Lancet, July 7, 1900. 

+ Wren. "klin. Woch., 1901, No. 4. 

t Liicke, Virchow’s ‘Archiv, Bd. xrx, 8. 

§ Langenbuch, “ Chirurgie ‘der Leber, e Bd. es S. 109. 


792 DISEASES OF THE LIVER. 


that is formed from the liver tissue by atrophy of parenchymatous 
cells. Nothing therefore remains but connective tissue, blood-vessels, 
and bile-channels. The latter do not seem to proliferate; at the same 
time certain inflammatory processes are present. 

Cysts may appear in any part of the organ. They are chiefly found 
in the right lobe because the right branch of the portal vein is wider 
and is straighter, consequently the embryos enter it more readily than 
the left branch. , 

The form of the liver is altered according to the location of the echino- 
coccus cyst. If the cyst develops centrally,—for instance, in the interior 
of the right lobe,—it may grow very large without producing any change 
in the outline of the liver; it will simply lead to a general enlargement 
of the organ, so that during life, and even postmortem, the presence 
of echinococcus cannot be even suspected without incising the organ. 
If the development of the cyst proceeds very rapidly, it may reach 
the surface and form a prominent hemispheric tumor, or may convert 
the whole lobe into a large round cyst. If this happens, the liver tissue 
is pushed aside and may be converted into a thin shell around the cyst. 

If the cysts develop near the surface, they protrude at a much earlier 
stage of the disease, and become noticeable in this way. They usually 
have a broad base, though they may be connected with the organ by 
a narrow pedicle; they may, however, be connected with the liver simply 
by a more or less long stem. 

If the tumor originates from the convex surface of the liver, it enlarges 
upward and may dislocate the diaphragm, the mediastinum, or the 
right lung. It may happen that the cyst reaches even the first rib, 
and compresses the right lung into an airless lobe. Under these cir- 
cumstances the lung may be compressed either toward the spinal column 
or laterally toward the chest-wall, depending upon the direction of 
growth of the echinococcus, either along the anterior chest-wall or into 
the mediastinum. The heart, at the same time, may be pushed toward 
the left into the axillary region. In large cysts the right lobe of the 
liver is pushed downward so far that the horizontal diameter of the 
liver becomes vertical; the right lobe is beneath and the left lobe above. 

Kchinococcus cysts of the concave, lower surface of the liver enlarge 
toward the abdomen, and may occupy a large part of the abdomen, 
extending as far as the crest of the ilium or even into the pelvis. If 
they are situated very superficially, they may be found reaching down 
into the pelvis, and attached to the liver by a long pedicle, so that during 
life they appear as tumors of the abdominal organs. They may also 
be found in the region of the spleen, and may even penetrate this organ. 
If the cyst develops downward, the liver occupies a more horizontal 
position, is compressed, and may become atrophic. Large cysts usually 
cause the right hypochondrium to bulge; if the part of the liver that 
is situated in the epigastrium is involved, round protuberances may 
be seen in this region. The development of the cyst into the thorax 
causes compression of the lung. Growth into the abdomen does not 
cause compression of neighboring organs like the stomach or intestine, 
because there is room for them to move. Compression of the larger 
bile-passages, combined with icterus from stasis, is rare (Finsen saw 
it only 7 times among 167 cases, Neisser 20 times in 388 cases). Com- 
pression of the vena cava and of the portal vein is also rare. 

We have already mentioned the fact that the liver tissue is com- 


PARASITES OF THE LIVER. 793 
e 
pressed by the cyst. It becomes atrophic, and covers the echinococcus 
in a thin layer only. At the same time, compensatory hypertrophy 
of other portions of the liver may occur (Ponfick, Dirig, Fléck, Holle- 
feldt, Reinecke). 


If one lobe is so completely filled by a cyst that it becomes converted into 
a shriveled-up mass as soon as the fluid is evacuated, a considerable enlargement 
of the other lobe will be seen, and microscopically an enlargement of the liver- 
cells with abundant mitoses. In may happen, therefore, that the weight of the 
organ, even after evacuation and contraction of the cyst, may be greater than 
normal. The remnants of the liver tissue that are still present in the place of 
the cyst often show hypertrophic change, in addition to a proliferation of connective 
tissue, so that nodular protuberances are formed (Reinecke). 


Rarely gangrene of the liver may occur in the region of the echino- 
coccus. On the other hand, if pressure is exercised on the liver by a 
pregnant uterus, or if certain disturbances of the circulation or of nutri- 
tion supervene, changes are seen in the fibrous capsule, consisting in 
fibrous degeneration, changes in the vessels, etc. 

In cases of this kind a cheesy mass is formed where the capsule and 
the cuticle are in contact. Owing to this surrounding area of nonvascular 
tissue, the nutrition of the echinococcus is impaired, the fluid becomes 
cloudy and gelatinous, later milky and purulent; at the same time 
the cyst. contracts, the contents thicken, and finally a mortar-like 
mass is found containing large quantities of carbonate and phosphate 
of calcium, and cholesterin; all that testifies to the former presence 
of scolices is the resistant hooklets. The puriform mass that is some- 
times found in these cysts contains no pus-corpuscles; it is frequently 
malodorous, and is acid in reaction. The daughter-cysts, as a rule, 
also perish. They contract and undergo the same changes as the mother- 
cysts; it rarely happens that they perforate the latter and continue 
to develop independently. + Another change that these cysts cart undergo 
is purulent degeneration following some injury or wound. It may 
develop in the absence of such traumata in case bacteria—as, 
for instance, streptococci (Riedel)—enter the liver, penetrate the cuticle, 
and lodge in the interior of the cyst. Suppuration occurs especially 
if a communication is formed between the bile-ducts and the echino- 
coccus cyst. The bile kills the parasite; and bacteria, frequently found 
in the bile-ducts, develop in the cyst, and in this manner form an abscess 
of the liver. In such a cavity contracted hydatids, dead scolices, fat, 
and bilirubin are found. Sometimes nothing is found but the hooks. 
In the bile-tinged fluid leucocytes in all stages of fatty degeneration, 
fat-globules, etc., are found. 

Sometimes, as a result of trauma or of punctures made for 
diagnostic purposes, abscesses develop in the neighborhood of the cyst, 
and, again, cause the death of the parasite. 

The tendency of echinococcus cysts to perforate into other organs 
is clinically of even greater importance. | 

Perforation occurs relatively frequently into the right half of the 
thorax; the diaphragm becomes atrophic from the pressure of the tumor, 
and is finally perforated, either gradually or following some sudden 
concussion. The pleura may be perforated at the same time. Finally, 
the cyst bursts, and its contents are poured into the right pleura. The 
fluid may then penetrate the lungs and destroy them, or produce an 
abscess, and in this way enter the right bronchus. As a result of the 


794 DISEASES OF THE LIVER. 


communication between the pleural cavity and the lung or the bronchus, 
air may enter the latter and lead to pyopneumothorax. 

In many cases the base of the lung becomes adherent to the dia- 
phragm, so that the cyst opens directly into the lung, and lies, as a result, 
in a cavity which it forms by dislocation of the lung tissues. If per- 
foration occurs, the fluid, containing hydatids, is suddenly poured into 
the bronchi, and may so overflood them as to lead to suffocation. As 
a rule, the material is expectorated. A large cavity is then present, 
filled with air and a fluid that soon becomes purulent; such a cavity 
may be called a pneumocyst. It may also happen that the lung becomes 
adherent to the diaphragm, and that the cyst ruptures directly before 
it has penetrated the pulmonary tissue; this frequently leads to the 
formation of abscesses. As a rule, however, a fistulous passage is formed 
leading from the echinococcus sac, through the infiltrated lung tissue, 
into the bronchi. If under these circumstances a communication exists 
with the bile-passages, a biliary fistula may be developed. Report has 
also been made of the occurrence of a pleural exudate, in a patient in 
whom an echinococcus cyst was adherent to the diaphragm and per- 
forated the lung without becoming mixed with the exudate (Trousseau). 

Perforation into the pericardium is rare. Sometimes, however, even 
this sac becomes filled with cystic contents (Wunderlich). 

In many cases echinococcus cysts evacuate their contents into the 
intestine. It may happen that rupture takes place into a large bile 
channel, and that the contracting hydatids with the fluid contents 
may enter the duodenum through the common duct. If this happens, 
stasis of bile and dilatation of the bile-ducts occurs, and as a result in- 
flammatory organisms or gangrenous material may enter the echinococcus 
cavity, causing suppuration and putrescence. Cysts may develop on the 
concave surface of the liver, and become adherent to the stomach or 
intestine as a result of adhesive peritonitis. Through such an adhesion 
perforation may occur, and the contents of the cyst may be poured into 
the intestinal tract. If the opening is small, it may close, the cyst 
walls contract, and cure take place. Neisser observed this occurrence 
37 times in 43 cases. On the other hand, intestinal contents may make 
their way into the cyst cavity and cause gangrene with all its conse- 
quences. 

Echinococcus growths of the liver may also penetrate the urinary 
passages. This occurs as the result of the formation of adhesions with 
the pelvis or the right kidney, perforation occurring with evacuation 
of the cystic contents through the urethra; or a deep-seated pedunculated 
cyst may become adherent to the urinary bladder and perforate into it. 

If perforation occurs suddenly into the free peritoneal cavity, a serious 
diffuse peritonitis may be caused, provided the contents of the cyst are 
infectious or purulent. If the fluid is sterile, irritation of the peritoneum 
is the result; even here, however, daughter-cysts may develop in the 
peritoneum (Volkmann, Krause,* and others), as is proved by the experi- 
mental work of Lebedeff and Andrejew, who transplanted echinococcus 
cysts into the abdominal cavity of rabbits. They state that the hydatids 
continue to grow and form endogenous daughter-cysts. Peiper, 
however, performed similar experiments with fresh material on rabbits, 
dogs, and sheep, and could not discover any development in the ab- 
dominal cavity. 

* F. Krause, “Sammlung klin. Vortrige,” No. 325. 


PARASITES OF THE LIVER. © 795 


If perforation occurs into a sacculated cavity, which is itself the out- 
come of a previous circumscribed peritonitis, the sequele are not so 
serious, and the fluid may be evacuated through the skin or into some 
other organ. This occurs usually, if the cavity is situated near the dia- 
phragm, into the pleura and the lungs; or if it is near the intestinal tract, 
into the intestine. 

Cases have also been noted of perforation into the portal vein, followed 
by pylephlebitis and the formation of an abscess of the liver. 

If perforation occurs into a hepatic vein, embolism of the pulmonary 
artery or of its branches may develop, and be followed by general pyemia. 
Evacuation into the lower vena cava has been known to lead to complete 
occlusion of the pulmonary artery and to rapid death. A branch of the 
hepatic artery has been found eroded, the accident leading to the pouring 
of blood into the echinococcus cavity, and to the death of the parasite. 

Perforation may also take place through the abdominal wall, just as 
in the case of an abscess of the liver. At first adhesions form with the 
abdominal wall, then suppuration occurs, and perforation of the different 
layers of the abdominal parietes is the final result. In rare instances a 
long fistulous passage is formed that penetrates between the different 
layers of the abdominal muscles. 

Symptoms.—If the cyst remains small and develops in the interior 
of the liver it causes no symptoms, or only such slight ones that its pres- 
ence is not suspected. Cysts as large as a fist may remain altogether 
latent. This is explained by the slow method of growth of the parasite, 
the slight inflammatory reaction that it produces, the yielding character 
of the liver tissue, and the vicarious hypertrophy assumed by contiguous 
parts of the parenchyma. It has also been stated that certain urinary 
abnormalities can be found in echinococcus disease (Potherat); this 
assertion has, however, not yet been verified. It is further claimed that 
the absorption of certain toxic substances from the cyst may lead to 
urticaria (Dieulafoy, Debove,* Achard f+), to certain digestive disorders, 
to a repulsion for meat and fatty foods that may be so severe as to cause 
vomiting, or to diarrheas immediately after or during eating (Bouilly). It 
cannot, however, be proved that these symptoms are primarily due to this 
cause, and the same may be said of the psychoses that are occasionally 
observed in the course of echinococcus disease (Nasse ft). Of all the 
symptoms enumerated, urticaria appears to be the only one that we are 
at all justified in attributing to intoxication with certain ingredients of 
the cystic contents, since this symptom has been seen after bursting of 
the veins of the cyst-wall (Davaine), in perforation of the cyst into the 
abdomen, and following evacuation of the fluid into the latter cavity or 
into the vena cava, or the hepatic vein. The remaining symptoms can 
probably be explained by the mechanical pressure exercised by the 
tumor on the gastro-intestinal organs at a time when it is still so small 
that it cannot be detected by physical examination. They certainly 
are not characteristic. t 

At the same time, a feeling of fulness and heaviness is often com- 
plained of in the hypochondriac region; pain on pressure or motion, on 
the other hand, is comparatively rare. 

It is owing to the vague character of these symptoms that echino- 

* Debove, Gaz. hebdomadaire, 1888, No. 11. 


+ Achard, Arch. gen. de. med., Oct., Nov., 1888, T. cux11, p. 410. 
t Nasse, Allgem. Zeitschr. f. Psychiatrie, 1863. 


796 | DISEASES OF THE LIVER. 


coccus disease so often remains unrecognized. According to Frerichs, 
11 cases out of 23 that were found:at the autopsy were not discovered 
during life; according to Bocker, 13 out of 22; and Neisser, 31 out of 47. 

The appearance of a palpable tumor in the liver region or the appear- 
ance of symptoms of dislocations of other organs leads to the discovery of 
the disease. Sometimes the tumor is discovered by chance without hav- 
ing caused any disturbances. Such tumors as are situated on the ante- 
rior surface of the organ in the epigastric region are, of course, discovered 
early in the course of the disease. Those that are located underneath 
the costal arch or on the upper or the lower surface of the organ may 
remain unrecognized for a long time. If they continue to develop, they 
may attain a great size before they are discovered. 

If the tumor develops within the organ, a general enlargement of the 
liver into the abdominal cavity may be observed, and the impression 
may be created that the swelling is due to some other cause. 

_ If the tumor develops in the epigastrium,—e. g., in the left lobe,—a 
flat or hemispheric protuberance is felt that remains quite hard as long 
as the normal tension of the sac is maintained. If several cysts are pres- 
ent, several protuberances will be felt. If the tumor develops on the 
right side of the liver, the ribs of the right side are pushed out; if the 
tumor is situated in a corresponding position in the left lobe, the ribs of 
the left side may be pushed out, or the spleen may be compressed. At 
the same time, the tumor continues to grow downward, particularly if 
it is situated on the lower aspect of the organ, in the same manner as 
other cysts that are similarly located. A cyst of this character may 
extend as far as the pelvis or the crest of the ilium, so that the lower 
border cannot be palpated. Under these circumstances diagnostic errors 
may. occur and the growth be taken for an ovarian cyst, ete. 

Kchinococcus cysts that are accessible to direct palpation feel hard 
on account of the tension of their walls, and do not, as a rule, fluctuate. 
Sometimes a characteristic vibration, the hydatid thrill, may be felt on 
percussion; the percussion sound over the tumor is dull. 


The hydatid thrill was first described by Blatin *; its diagnostic value empha- 
sized by Briancon, Piorry, and von Tarral; and its origin studied experimentally 
by Davaine and others. Cruveilhier and others attribute it to the collisions between 
the daughter-cysts, and deduce the presence of secondary cysts from the presence 
of the thrill. Occasionally, however, the symptom is noticed in sterile cysts, and 
experiments with rubber sacs showed that daughter-sacs played no rdle whatever. 
Kuster ¢ formulated the theory that the thrill denoted the presence of a second 
cyst in the vicinity of the first one in those cases where daughter-cysts were absent; 
this view, however, is also erroneous. In order to elicit the phenomenon, the 
wall of the cyst must be in a state of tension and the fluid contents of the cyst 
must be under high pressure. These conditions are fulfilled in such cysts as those 
of the ovary, the mesentery, etc., in hydronephrosis, in simple ascites, and in cysto- 
sarcoma of the liver (Landau), and the thrill has been discovered in all these con- 
ditions. Some authors claim to have felt it only exceptionally in cases of echino- 
coccus. Létienne in two cases was enabled to elicit the thrill only after aspirating 
a small portion of the fluid; in other words, after reducing the pressure a little. 
It appears, therefore, that too high tension causes rigidity of the membrane and 
a cessation of the vibrations, so that the phenomenon disappears. 


The thrill can be elicited in various ways. Frerichs advises com- 
pressing the swelling lightly with the two fingers of the left hand and 


* Quoted by Davaine, loc. cit. 
‘ | Kuster, Deutsche med. Woch., 1880, No. 1. 


PLATE VI. 














ABDOMINAL VARIX IN ECHINOCOCCUS CYST OF THE LIVER. 





- 


PARASITES OF THE LIVER. ; 197 


tapping quickly with the right; Tarral advises leaving the finger in con- 
tact with the pleximeter for some little time after the percussing. 


Davaine allows three fingers of the left hand to rest on the cyst and percusses ~ 
the middle one only; the other fingers feel the tremor. Després places one finger 
on a tumor and taps it quickly, withdrawing the percussing finger as rapidly as 
possible. 

Piorry has described the sensation as being similar to the feel of a repeater 
watch that is tapped while held in the hand; he has also compared it to the vibra- 
tions felt in gelatin. According to Davaine, a similar sensation is experienced 
by tapping the seat of a sofa that is upholstered with springs. 

Lobel * describes a crackling sound elicited on palpation of a case of a large 
echinococcus cyst with atrophy of the surrounding tissues; he attributed the 
sound to peritonitic friction. On autopsy no peritonitic involvement was found, 
though the peculiar sound could be heard over the cyst even after death. 


Cysts arising from the lower surface of the liver extend into the ab- 
dominal cavity. The liver protrudes as a hemispheric swelling that 
may occupy the whole right side of the abdominal cavity or its entire 
space. As a result, pressure is exerted on neighboring organs, so that 
constipation and diarrhea, and, in rare cases, even occlusion of the intes- 
tine and ileus, are seen (Reichold). If the cyst is connected with the 
liver by a bridge of connective tissue, the impression may be created that 
the tumor does not originate in that organ. There is dulness on percus- 
sion above, then a loud tympanitic sound, and further down again dul- 
ness over the cyst. The pedicle may beso long that the cyst is situated in 
the pelvis and simulates a tumor of that region. Compression of the 
common duct, of the vena cava, and of the portal vein may be caused by 
a cyst situated at the lower surface of the liver. 

Following pressure upon the portal vein ascites is sometimes observed, 
rendering it difficult to outline the tumor. There may also be a tumor 
of the spleen and a dilatation of the venous collaterals. The vena cava 
inferior may be compressed to such a degree that its walls are in contact, 
and the vessel may be completely obliterated. This is followed by serious 
interference with the circulation in the lower parts of the body, particu- 
larly of the legs, with edema, venous dilatation, etc. Icterus is rare, as 
the common duct is not often completely compressed; albuminuria may 
bé present, but depends almost exclusively on the amount of pressure 
exerted upon the kidney. Its degree may fluctuate with the position of 
the patient. 

Echinococcus cystic involvement of the upper part of the liver en- 
larges toward the thorax; it causes the diaphragm to bulge, and may 
even produce atrophy of the latter muscle. The upper percussion 
boundary of the liver, therefore, is often curved convexly upward, par- 
ticularly in the axillary line. This is never seen in pleuritis, and is a 
feature in the differential diagnosis; in pleural effusion the upper line 
of dulness descends from behind forward, and is concave upward. If 
the cyst develops near the spinal column, there will be a similar conforma- 
tion, and the diagnosis may become very difficult. In general, the cyst 
causes more protrusion of thé ribs and less lengthening of the thorax 
than pleuritis. 

Pressure on the diaphragm causes pain and a dry cough, later dyspnea, 
particularly after exertion. This is due to a decrease in the size of the 
thorax, cyanosis, palpitation, etc. If the tumor grows still larger, there 
will be compression of the right lung, and atelectasis may follow. 

* “Bericht des k. k. Rudolfspitales in Wien,” 1869. 


798 DISEASES OF THE LIVER. 


In such cases the left lung and the heart are also affected; the lung 
is compressed and the heart pushed to the left into the axillary region ; 
in a case of this kind described by Frerichs, death occurred suddenly 
from asphyxia. 

More frequently even than these purely mechanical injuries to the 
thoracic organs, caused by the pressure of a gradually enlarging cyst, is 
an inflammation of the pleura diaphragmatica, which usually results in 
adhesion between the two layers, and less frequently in exudation. If 
the cyst perforates the atrophied diaphragm and the adherent lung under 
these conditions, there will be hemoptysis, percussion dulness, and a 
reduction in the intensity of the breath-sounds over this area. The 
upper boundary of the dulness will be convex. The thorax will protrude 
over the cyst. It rarely happens that trauma, a fall or a blow, will cause 
the cyst to penetrate the pleural cavity after rupturing the diaphragm, 
which is already atrophic from pressure. In a case of this character the 
same symptoms will be observed as in perforation into the lung. As a 
rule, the sac will rupture and the cystic contents empty into the pleural 
cavity. 

Suppuration of the cyst is seen most frequently in cases in which a 
communication is established with the biliary passages, so that bile 
containing bacteria enters the cyst cavity. The tenia is killed by the 
bile, but the bacteria continue to vegetate, and eventually may produce 
suppuration and gangrene. The process may in this way lead to the 
formation of an abscess. In the event of suppuration in some other part 
of the body, especially if it is located in the portal area, or in general 
pyemia, or, finally, after puncture of the cyst, suppuration often occurs. 
The pathologic picture under these circumstances is that of hepatic 
abscess. There is remittent fever, a chill, disturbance of the general 
health, localized pain radiating from the affected portion of the liver 
toward the shoulder. Although in ordinary echinococcus cyst peritoneal 
inflammation is not frequent, in case of suppuration perihepatitis is often 
seen. The pus may perforate into neighboring organs as in other forms 
of abscess, and may in this way lead to very dangerous lesions. Sup- 
puration of an echinococcus cyst, as a rule, leads sooner or later to death, 
and usually with the symptom-complex of a general pyemia. 

Rupture of echinococcus cysts and the evacuation of their con- 
tents into other organs of the body are very important events from a 
symptomatologic point of view. 

If rupture occurs within the liver substance into the bile-passages, 
the parasite is, as already stated, usually killed by the action of the bile, 
and suppuration of the cystic contents takes place. Often the cyst is 
simply evacuated and undergoes contraction. If the biliary passage is 
small, the fluid will be poured from the cyst into the intestine wa the 
bile-duct, and the daughter-cysts will remain behind because they cannot 
pass through the narrow channel. Sometimes these continue to vege- 
tate; as a rule, however, they also disappear. If communication is 
established with a large passage, such as the main branch of the hepatic 
or the cystic duct, or with one of these canals themselves, the hydatids 
may pass into the intestine without causing any symptoms, and the 
cyst will collapse. Occasionally these structures, which are shriveled 
up and appear like raisins, can be found in the ’stools, together with 
shreds of membrane. Charcellay reports certain tubular, pseudomem- 
branous casts of bile-channels in the stools. The hydatids may also 


PARASITES OF THE LIVER. 799 


lodge in the bile-passages, or may become impacted in the narrow opening 
of the common duct into the duodenum, and, like gall-stones, cause 
icterus from stasis, acholic stools, and catarrhal and purulent cholan- 
gitis. Attacks of colic may be produced; if repeated series of daughter- 
cysts attempt to pass, there may be repeated attacks of colic (Wester- 
dyk).* In this way the picture of cholelithiasis may be simulated. 
Sometimes rupture takes place into the gall-bladder, and the latter is 
filled with fluid from the echinococcus cyst. This is then passed by the 
natural route, or an abnormal passageway is created into the duodenum. 
[A case was recently observed at autopsy at the Pennsylvania Hospital 
in which the entire left lobe of the liver had been replaced by an enormous 
echinococcus cyst, full of semi-purulent fluid containing hundreds of 
secondary cysts. The gall-bladder was intact, and was also full of tiny 
cysts full of scolices and hooklets. The cystic duct contained a few, and 
the common duct many intact cysts. The symptoms had been those of 
hepatic abscess, and at no time was there any evidence of stoppage of 
the bile-ducts. Death occurred from pyemia.—ED.] 

Frequently a bile-passage will rupture, and yet the cystic contents 
be poured out by some other way, 7. e., into the intestine, the peritoneal 
cavity, the lungs, etc. In cases of this kind the bile-tinged color of the 
fluid, particularly of the hydatids, will indicate such an occurrence. Or 
the bile may be evacuated in its totality through this abnormal channel, 
and be expectorated, or passed in the stools, or it may be poured into the 
pleural or the peritoneal cavity. . 

Particularly those cysts that are situated on the under surface of the 
liver perforate into the stomach and the intestine, and in the same manner 
as abscesses of the liver that are similarly situated. As a rule, adhesions 
form first. 

If perforation occurs into the stomach, an abundant quantity of a 
watery fluid containing hydatids is vomited; a part or all of the fluid may 
enter the intestine and be passed in the stools. Sometimes the perfora- 
tion is preceded by pain in the stomach region as a result of peritonitis. 
If the opening is large, the symptoms are very acute; if it is small, the 
contents of the cyst may be evacuated so slowly as to cause only very 
slight symptoms. 

If perforation occurs into the intestine, the accident is usually pre- 
ceded, as above, by signs of circumscribed peritonitis; then the tumor 
suddenly collapses, there is a watery stool, occasionally mixed with blood, 
and numerous hydatids are passed. If the opening is large, serious 
symptoms appear, because the contents of the intestine enter the cystic 
cavity and cause gangrenous inflammation. If the opening is small, 
this does not occur so easily. The perforation is closed and some adhe- 
sions between the liver and the intestine may persist. Later peristalsis 
may cause a separation of these adhesions, so that a cavity remains in 
the liver, and contain fecal matter. This cavity is in no way connected 
with the intestine (F. Krause) ; we have, however, a fecal abscess with all 
its dreaded consequences. ‘ 

Perforation into the peritoneal cavity occurs quite frequently. As 
echinococcus cysts do not show as great a tendency to the formation of 
adhesions as abscesses, just so the contents of the cyst are frequently 
poured into the free abdominal cavity. This is particularly liable to 
happen after trauma, contusions, a fall, etc. .Following the evacuation 

* Westerdyk, Berlin. klin. Woch., 1877, No. 43. 


800 DISEASES OF THE LIVER. 


of the fluid, shock becomes apparent and may lead to the death of the 
patient (Achard).* There will be seen a rapid pulse, costal breathing, 
violent abdominal pain, and the patient will be anxious and complain of 
a feeling as though something had given way in the belly. He 
feels that he is sick unto death, he may faint and lie perfectly still; his 
face is drawn and pale. Many recover; urticaria may then appear from 
the absorption of the toxins of the fluid, and nothing may remain but a 
freely movable fluid in the abdomen. The peritoneum seems to learn 
to tolerate this fluid, and it can either be removed by aspiration or may 
be spontaneously absorbed; it may perhaps even perforate into the 
urinary passages and be evacuated in this way. In rare cases daughter- 
cysts have been known to develop in the abdominal cavity (Volkmann, 
Krause). If the cystic contents are mingled with bile, the bacteria 
contained in the latter may cause peritonitis; this must be treated by 
operative measures, and may occasionally be relieved in this way. If 
purulent cysts burst into the peritoneal cavity, death results from sup- 
purative peritonitis. 

If the cyst bursts into some preformed peritoneal pocket, the prog- 
nosis is more favorable, as these cases are more accessible for operative 
interference. The fluid in these cases is not so freely movable, and will 
be discovered localized in a small painful area of the abdomen. The 
general symptoms are less pronounced, and there is less interference with 
the action of the heart. The peritoneal fluid can be evacuated through 
the skin or into the intestine without causing any very severe disturb- 
ances. 

Perforation of echinococcus cyst of the liver into the urinary passages 
is rare. If it occurs, it usually leads, because of occlusion of the urethra 
with retention of urine, to renal colic and hydronephrosis. Numerous 
daughter-cysts colored by bile are passed in the urine and reveal their 
origin from the liver. If a rupture into the bile-passages occurs at the 
same time, bile may enter the urinary passages from the fistula. 

If the echinococcus penetrates the thorax from the upper surface of 
the liver, the diaphragm may be torn, as previously mentioned, so that 
the cyst enters the pleural cavity, ruptures, and evacuates its contents. 
Perforation into the thoracic cavity may occur in still another manner; 
the echinococcus fluid may be poured into a cavity formed of peritoneal 
adhesions, and a subphrenic accumulation of fluid be formed, which, 
secondarily, perforates the diaphragm. The presence of fluid in the 
pleural cavity causes the ordinary symptoms of serous pleurisy and 
hydrothorax; namely, an increase of the diameter of the thorax on one 
side, obliteration of the intercostal spaces, retraction on respiration, 
dulness on percussion, reduction of the breathing-sounds and of the 
fremitus. The lung is compressed upward and backward against the 
spinal column, unless it is anchored anteriorly by adhesions. Bronchial 
breathing is heard over the lung; the heart is dislocated toward the left. 
On aspiration a fluid is obtained that may perhaps contain some albumin, 
or none at all. Scolices and shreds of membrane are usually found. If 
the exudate is pleuritic, the fluid will contain albumin. 

Rupture of the cyst is accompanied by the feeling of a sudden tear in 
the chest; there is oppression, dyspnea, and a feeling of anxiety. The 
pulse is rapid and weak, and death may occur rapidly with all the symp- 
toms._of collapse and asphyxia. In other cases suppuration occurs, and 

* Achard, Archiv gen. de méd., 1888, p. 410. 


PARASITES OF THE LIVER. 801 


empyema is formed, which may either: perforate the skin or the lung, 
unless opened early by thoracentesis. Sometimes circumscribed pneu- 
monia develops, with fever, sudden cough, and the expectoration of large 
quantities of purulent fluid containing hydatids. Complete evacuation 
of the fluid and a cure of the disease may be brought about in this manner; 
or, on the other hand, the lung tissue may undergo purulent degeneration 
and form an abscess. The latter usually causes death. Perforation of 
the lungs allows the entrance of air into the pleural cavity, and may cause 
pyopneumothorax. In some cases a pleuritic exudate may be present 
before the cyst ruptures the diaphragm, so that when the rupture occurs 
both fluids may be mixed. In other cases adhesions exist between the 
lung and the diaphragm, and the contents of the cyst may penetrate the 
lung without coming in contact with the pleural exudate (Trousseau). 

If the cyst as a whole enters the lung without bursting, pneumonic 
symptoms appear; later, weakness of the breath-sounds and dulness. 
Finally, the sac ruptures and its contents are poured into the lungs and 
bronchi; this causes a sudden flooding of these parts. It may be impos- 
sible for the patient to get rid of the fluid and the hydatids quick enough; 
consequently he becomes asphyxiated, and drowns (as it were) in the 
cystic fluid. If the evacuation occurs slowly and in small quantities, a 
cure of the disease may be brought about. If a cystic cavity is present 
in the lung, a large space will remain with bronchial breathing, resonant 
and metallic sounds, ete. Cavities of this kind, or the remnants of 
abscess-cavities, gradually contract and heal. Sometimes it, is necessary 
to open them from without, to drain them, and in this manner to produce 
cicatrization. 

The sputum may remain purulent for a long time, or may contain bile 
if bile-passages have ruptured at the same time. 

Perforation from the left lobe into the pericardium is rare; a few cases 
are on record (Wunderlich). The pericardial sac becomes rapidly dis- 
tended with fluid, and the patient dies in a very short time from heart- 
failure. 

If a communication is established between the portal vein and the 
echinococcus cyst, the branches of the portal vein become obstructed, 
and multiple abscesses are formed. Occasionally a branch of the portal 
vein will be punctured during exploratory aspiration. Toxic material 
may enter the blood in this manner and produce symptoms of poisoning, 
—namely, urticaria (Bouchard),—or such severe Symptoms of intoxica- 
tion that death may occur (Bryant). 

If the lower vena cava is perforated, fluid and hydatids reach the 
right heart, and are forced into the pulmonary artery and occlude it. 
The patients die rapidly with symptoms of dyspnea and pulmonary 
edema, similar to those seen in embolism of the pulmonary artery follow- 
ing the lodgment of marantic thrombi. If perforation occurs into the 
hepatic vein, embolism of branches of the pulmonary artery, hemorrhagic 
infarcts, suppuration in the lungs, and general empyema result. Entrance 
of the cystic fluid into the veins is usually manifested by toxic symptoms, 
as, for instance, reddening of the face, pain, loss of consciousness, vomit- 
ing, spasms, or sudden stoppage of the heart. 

Erosion of a branch of the hepatic artery—for instance, by trauma— 
may cause a large quantity of blood to enter the echinococcus cyst, and 
in this manner the parasites are killed. 

Perforation of the echinococcus through the abdominal wall probably 

51 : 


802 DISEASES OF THE LIVER. 


only occurs in cases of suppuration, and the same symptoms are produced 
as in perforating abscess of the liver; namely, circumscribed peritonitis, 
inflammatory swelling of the abdominal wall, later fluctuation, thinning 
of the skin, bursting of the integument, and evacuation of the contents 
of the cyst through the fistula. [Posselt * has published a detailed 
discussion of echinococcus of the liver, chiefly in relation to the symp- 
toms and diagnosis. He considers the most important sign to be the 
enlargement and alteration in the form of the liver. Enlargement is 
usually confined to the right lobe. The liver is hard, and pain and 
tenderness are elicited if the cyst is near the surface. Pain is, however, 
not a constant feature. There is usually marked jaundice, and frequently 
ascites. Often there is free sweating. The patient is usually consti- 
pated, and occasionally may show blood in the stools. It is noteworthy 
that the bodily weight seldom decreases to any marked extent, an im- 
portant point in the diagnosis of this condition from carcinoma and 
hypertrophic cirrhosis, in both of which cachexia and loss of weight are 
extreme. Cachexia in echinococcus disease is a late phenomenon. 
There is usually no fever, and no enlargement of the spleen. Polyuria 
is frequently seen, due (according to Posselt)to functional hypertrophy 
of the kidneys. He has found the disease to be common in Bavaria, 
Austria, Switzerland, and Wirtemburg, and rare elsewhere over the 
globe. ’Renon + describes a case of multilocular echinococcus of the 
pleura and right lung in a man of thirty-six. He considers this the first 
case of the disease in man to occur in France.—EbD.] 

Prognosis.—Echinococcus cyst of the liver may persist for a long 
time without causing any symptoms or disturbances, and even large 
cysts may fail to affect the general health of the patient. Their presence 
may be manifested by slight symptoms of dislocation of other organs. 
At the same time, the presence of the parasite is always dangerous, and 
such accidents as rupture into neighboring organs, inflammatory processes, 
suppuration, gangrene, etc., must always be feared. An echinococcus 
cyst may exist in an active condition for twenty years and more. A 
fall, a contusion, or a concussion is dangerous, and may lead to the rup- 
ture of the cyst. Spontaneous cures are rare; they may be brought 
about by the death of the parasite, or by cheesy degeneration or calcifi- 
cation of the cyst tissues. A natural cure by evacuation of the contents 
into the intestine and bronchi, etc., is quite frequently seen. In the > 
majority of cases, however, the skill of the surgeon must be employed 
to remove the disease. 

Suppuration and gangrenous degeneration of the echinococcus, as 
well as rupture into the blood-vessels (the vena cava, etc.), the perito- 
neum, etc., are dangerous. 

Cyr has formulated the following statistics: Death occurred in 90 % 
of cases from rupture into the peritoneum, in 80 % into the pleura, in 
70 % into the bile-passages, in 57 % into the bronchi, in 40 % into the 
oe in 15 % into the intestine, and in 3 % through the abdominal 
wall 

If suppuration occurs, the prognosis is probably the same as in a 
virulent abscess. 

The prognosis, therefore, of echinococcus of the liver will only be 
favorable in the absence of fever and suppuration or of all symptoms 


* Deutsch. Arch. f. klin. Med., Aug. 18, 1899. 
+ Compt. rend. de la Soc. de Biol., Feb. 17, 1900. 


PARASITES OF THE LIVER. : 803 


that point to a threatening perforation; or if the cyst is favorably situated 
' for operation, as, for instance, on the anterior surface of the liver. Thanks 
to the perfected technique and the methods of aseptic surgery, sub- 
phrenic echinococcus is now accessible for operation. As long as the 
cyst is intact, the prognosis is favorable. 

Diagnosis.—A small cyst can be recognized only if it is situated on . 
the anterior surface of the liver immediately underneath the abdominal 
wall, and only if it is prominent. A cyst may be very large and still 
evade detection if it develops in the anterior of the liver, and only causes 
a general enlargement of the organ. Subjective symptoms may be 
completely absent or misleading. It has happened that tumors as large 
as a child’s head have been present, but have passed unnoticed by the 
patient. 

The anamnesis is important, and it is well to determine whether the 
patient comes from a region that is noted for echinococcus disease, also 
whether the patient has associated much with dogs, etc. It is well also 
to examine for tenia the stools of the animals that the patient has been 
in contact with; if necessary, after the administration of a vermifuge. 

The following points will speak in favor of echinococcus as against 
other tumors of the liver, abscesses, etc.: Absence of pain or the presence 
of very slight pain, a tense elastic tumor (hydatid thrill) with a round, 
smooth surface, the absence of fever and of inflammatory symptoms in 
the neighborhood of the tumor (peritoneum), only slight disturbances of 
the general health, and a slow growth of the swelling. 

If the echinococcus develops on the anterior surface of the liver, the 
diagnosis can frequently be made from the above symptoms. Very 
frequently, however, the condition is confounded with other cysts of the 
liver or with a chronic abscess that is unattended by inflammatory 
symptoms; in such cases the diagnosis is not made until an operation is 
performed. Other forms of cysts resemble the echinococcus cyst in 
shape only rarely, and if they are present, the two conditions cannot be 
distinguished. 

Chronic abscess of the liver is usually found in subjects who have lived 
in the tropics; it does not present so tense a resistance to the hand in the 
afebrile stage as do echinococcus cysts. Other abscesses are char- 
acterized by fever and severe disturbances of the general health; they 
can only be confounded with an echinococcus cyst that has undergone 
purulent degeneration. Malignant tumors are frequently tense and 
elastic, but are generally nodular and painful; they cause greater cachexia, 
and develop more rapidly. In addition, primary tumors can frequently 
be found in other regions of the body. 

The Réntgen rays frequently aid in determining the gradual enlarge- 
ment of the liver by echinococcus, and the procedure promises to be of 
value in the diagnosis, particularly in distinguishing subphrenic cysts. 

Exploratory puncture is of great diagnostic value. Récamier was 
the first to execute this procedure in echinococcus disease, and Cru- 
veilhier recommended it after him. The operation is performed in the 
Same manner as in abscess of the liver. It is well, however, to select 
a thin cannula in order to make the hole in the cyst-wall as small as 
possible; this is necessary on account of the tension of the cyst-wall, 
that may readily cause a rupture and an evacuation of the cystic con- 
tents into the peritoneal cavity. The puncture should be made diagonally 
through the cyst-wall, preferably with the apparatus of Dieulafoy or 


804 DISEASES OF THE LIVER. 


Potain, rather than with a Pravaz needle. The cannula can be closed 
with wax or with a cock, and left in place for a little while; an inflamma- 
tory exudate is formed around the puncture, closing it still more effectu- 
ally and preventing the entrance of cystic fluid into the abdomen. If 
the echinococcus cyst is healthy, a clear fluid is obtained in which no 
. albumin will be found; there will be a few shreds of membrane, scolices, 
and hooklets. Cysts of a different character are usually filled with 
a fluid containing albumin, mucus, bile, etc. In abscesses, pus is found, 
and if the abscess is in reality an echinococcus cyst that has undergone 
suppuration, shreds of membrane, scolices, hooks, etc., will also be 
found. 

The puncture may be followed by disagreeable or even dangerous 
results, because the wound may gape, if the walls of the cyst are fragile 
or rupture (Segond), and allow the escape of cystic fluid. This is par- 
ticularly dangerous in purulent or gangrenous echinococcus cysts; such 
an accident is frequently followed by peritonitis, Just as in abscess of 
the liver. If the cystic contents are not degenerated, intoxication of 
the whole organ may occur from the toxic products of the parasite. 


The most frequent symptom of this intoxication is urticaria (Monneret, Rendu, 
Ladureau, Harley, Murchison, Dieulafoy, Finsen, v. Volkmann). In subsequent 
punctures this symptom does not seem to appear, possibly because the first one 
confers immunity. Severe poisoning has also been observed, attacks of fainting, 
dyspnea, nausea, vomiting, hiccup, rapidity and weakness of the pulse, signs of 
collapse, in some cases even death. Jenkins, Martineau, and Bryant observed 
death in such cases. Achard reports 8 cases of death. Fever, arthritic pains 
(suppuration of joints, Verneuil), diarrhea, and insomnia have all been seen. 

The danger of localization and the multiple development of daughter-cysts 
in the abdominal cavity need not be feared, although Langenbuch, basing his 
statement on the experiments of Volkmann and others, calls attention to this 
complication. As a rule, these cases are due to the rupture of large cysts. 


Sometimes puncture is performed in vain, as when the cannula 
becomes occluded by hydatids or by calcareous material from the wall 
of the cyst. 

Puncture is hardly ever dangerous, though everything should be in 
readiness to perform a laparotomy and to remove the cyst by surgical 
procedures. | 

Sometimes the gall-bladder may be distended by stasis of bile or 
by hydrops, and lead to confusion. Here the position and outline of 
the tumor, a history of cholelithiasis, or symptoms of this condition, 
and the character of the aspirated fluid will decide. The contents of 
such a swelling are bile-tinged, or, if not, at least mucoid and albuminous. 
In very rare cases, it is true, a large quantity of a watery, clear, colorless 
fluid has been aspirated from a hydropic gall-bladder (one liter, Tuffier). 

If the cyst is present on the lower surface of the liver, and the 
portal vein is compressed so as to cause ascites, the position of the liver 
may be altered by the transudate; it may become retroverted and 
lead to confusion with cirrhosis. Other general enlargements of the 
liver, as fatty liver, amyloid degeneration, etc., are simulated by echino- 
coccus only in those cases where the parasite develops in the interior 
of the organ. 

Cysts of the pancreas resemble those of the liver, and, owing to 
the.close proximity of the two organs, must sometimes be differentiated. 
If the stomach is distended with air, the pancreatic cyst will be found 
behind this organ and will be clearly distinguished from the margin of 


PARASITES OF THE LIVER. 805 


the liver, which moves up and down over the cyst on inspiration. Cysts 
of the mesentery and of the ovary are more readily distinguished. If 
the former are very large, so that the liver is pushed up into the thorax, 
the diagnosis may be rendered difficult. Even simple meteorism has 
been taken for echinococcus cyst (Simpson), also cold abscesses of the 
abdominal wall on the right side (Trélat, Langenbuch). 

If hydronephrosis of the right kidney exists, a round, tense, elastic 
tumor is present, which pushes the liver forward. The protrusion of 
the lumbar region, even in the knee-chest position, the motility of the 
tumor, the fact that it is situated behind the colon, will decide in favor 
of hydronephrosis. Exploratory puncture or catheterization of the 
ureter may give important information. 

If echinococcus cysts are situated immediately in front of the abdomi- 
nal aorta, the growth may pulsate, but in this case the pulsations are 
not expansile, but antero-posterior. Occasionally a cyst has been mis- 
taken for an aneurysm (Neisser, Hayden). 

Cysts of the spleen may be mistaken for echinococcus of the left 
lobe of the liver. A cyst situated in the left lobe may force its way 
into the spleen, or, on the other hand, a cyst of the spleen may be so 
close to the left lobe of the liver that it is impossible to distinguish the 
two organs. The diagnosis will in such cases have to be reserved for 
exploratory laparotomy. 

The diagnosis of a subphrenic echinococcus cyst is particularly diffi- 
cult. There will be dulness in the lower half of the right side of the 
thorax; this portion of the chest is expanded, breath-sounds are weak or 
absent, and there is pectoral fremitus, so that the diagnosis of a pleural 
exudate or of a subphrenic abscess may seem warranted. The general 
outline of the percussion dulness, the more circumscribed protrusion of 
the lower ribs, the absence of fever and of a history of inflammatory 
symptoms in the lungs or the pleura, above all, the results of exploratory 
puncture, must decide against a serous exudate in the thoracic cavity, 
and the entire absence of inflammatory symptoms in the abdomen will 
decide against subphrenic abscess. If the echinococcus cyst is situated 
beneath the diaphragm and is gangrenous, it cannot be distinguished 
from pyopneumothorax subphrenicus. The treatment of both conditions 
is the same, so that it is not essential to make a clear differential diagnosis. 

If an echinococcus perforates into the pleural cavity, the symptoms 
will be so violent and so sudden (there will be collapse and a general 
intoxication) that even without examination of the fluida pleurisy with 
exudation can be excluded. 

It is said that echinococcus involvement of the pleura can be dif- 
ferentiated from a subphrenic echinococcus cyst by the fact that the 
former forces the diaphragm and the liver downward, and on inspiration 
the liver moves downward. In echinococcus of the liver, on the other 
hand, the diaphragm is forced upward, becomes paralyzed and atrophic, 
and for all these reasons the lower margin of the liver is not found so low 
as in echinococcus of the pleura; finally, on inspiration the liver moves 
upward. 

It is sometimes difficult to decide whether the echinococcus cyst has 
developed primarily in the lower lobe of the right lung, or whether it was 
primary in the liver, later penetrating the lung. 

The diagnosis of the rupture of an echinococcus into the different 
organs can be made from the symptomatology outlined above. 


806 DISEASES OF THE LIVER. 


Prophylaxis.—In order to prevent echinococcus disease, all measures 
should be employed that will prevent infection of human beings by the 
eggs of the tenia. The following rules should be observed in regions 
where the parasite is common: 

I. The number of dogs should be decreased as far as possible (by 
means of a dog tax), and those that have no masters should be caught 
and confiscated. 

II. There should be a careful meat inspection for echinococcus, and 
all infected meat should be rendered harmless. Above all, it is important 
that no such meat should be fed raw to dogs. 

III. Peopleshould be warned against very intimate contact with dogs, 
against petting and fondling them. This is particularly necessary in 
the case of children. After handling a dog the hands should be washed 
as soon as possible. 

IV. In order to remove tenia the dogs should undergo a tapeworm 
cure about once a year, and the following prescription is useful: Flores 
kooso, 2.0 to 15.0 gm.; extr. filic. mar., 1.0 to 4.0 gm.; areca nut, 0.5 
to 2.0 gm. of the scraped or pulverized nut on an empty stomach, 
followed, possibly, by 10 to 30 gm. of castor oil in two or three 
hours, etc. 

V. All vegetables should be thoroughly cleaned, particularly if they 
are eaten raw, as is salad, for instance. 

Treatment.—The attempt has frequently been made to treat echino- 
coccus with drugs. Formerly emetics were given with the purpose 
of causing a rupture of the sac and the evacuation of the cyst into the 
intestine, the peritoneum, etc. This procedure, of course, is so dangerous 
and so uncertain that it is altogether to be condemned. 

For a time ordinary salt, sometimes in combination with other salts, 
was recommended both for internal and external use, in the shape of 
compresses and baths. This treatment was based on an observation by 
Laennec, who saw that animals suffering from this disease were cured 
if they were put to pasture on a salty soil, and a few cases have been 
described (Laennec, Oppolzer, Bamberger) in which a decrease of the 
cyst was brought about by this treatment. As a rule, however, the 
method is fruitless. 

Anthelmintics, as turpentine, Dippel’s oil, and kamala, have been - 
administered internally. Hjaltelin recommended tincture of kamala, 30 
to 40 drops, three times a day; and Bird claims to have seen a quicker 
cure of the echinococcus after puncture and evacuation of the cyst 
when kamala was used in combination with bromid of potash. These 
remedies are probably useless, and the same can be said of inunctions 
of mercury ointment, or the internal administration of calomel. 

Iodid of potash was popular for a long time, and has been given 
in these cases in considerable doses (Havkis, Wilkes, and others). Budd 
advises the administration of iodid of potash, together with inunctions 
with an iodin salve. Frerichs examined the cystic contents for iodin 
after this treatment, but failed to find it. Other investigators, as Mosler 
and Peiper, succeeded in demonstrating its presence. 

In any event the results of internal medication are very uncertain, 
and the condition of the patient frequently calls for a prompt removal 
of the parasite. In the days before antisepsis the fear of operation 
was justified in echinococcus disease, because even a simple puncture 
sometimes led to suppuration. At the present time, however, it is 


PARASITES OF THE LIVER. 807 


possible to terminate the disease rapidly and safely by surgical inter- 
ference. 

This is not the place to discuss the different methods that have been 
recommended. A detailed description will be found in the work of 
Langenbuch. The following brief description is largely based on this 
work. 

For the general practitioner puncture is the most important pro- 
cedure. 

Electro-puncture is no longer employed, although the method was 
used with some success in Iceland, particularly by Durham and Fagge. 
Two steel needles are inserted into the cyst and connected. with the nega- 
tive pole of a battery, the other electrode terminating in a moist sponge 
applied to the skin. Hydrogen develops in the cyst and forces the fluid 
through the puncture into the abdomen. Even repeated sittings may 
not succeed in destroying the parasite, and unless asepsis is rigorously 
carried out suppuration may occur. 

The dangers of puncture have already been discussed in our section 
upon exploratory puncture. If, later on, symptoms appear that can 
-be referred to the peritoneum or to other organs, the cyst should be 
thoroughly removed by laparotomy. 


Evacuation of the cystic contents by puncture is an old procedure. Hippoc- 
rates and his pupils have described the difficulties incident to this operation owing 
to occlusion of the cannula by hydatids. 

As the cyst usually collapses after the evacuation of the fluid, and the disease 
is thereby cured (Hulke, Borgherini, Mosler, and Peiper), the idea suggested itself 
to remove only a small quantity of fluid with a fine cannula (Hulke, Savory). This, 
however, is rarely successful. Sibson attaches a tube to the cannula and allows 
it to remain in place so as to remove as much as possible of the contents. 


In general, trocars of medium caliber should be employed and as 
much of the contents evacuated at one time as possible. In this way 
echinococcus disease has frequently been cured, sometimes after one 
puncture, in other cases after repeated attempts. During this manipula- 
tion, particularly if it is not carried out with aseptic precautions, purulent 
infection may occur; and it is indeed possible that in such instances the 
death of the parasite has been brought about by the entrance of bacteria 
(Kussmaul, Wright, Brodbury, Fuller, and others). Another danger 
is rupture of the bile-passages and blood-vessels in the walls of the cyst. 
This may cause the entrance of bile and blood into the cavity, and the 
death of the seolices; or, again, the membrane may become separated 
from the connective-tissue capsule, and in this way the death of the para- 
site be brought about by interference with its nutrition. | 


Harley reports 34 cases of cure out of 77 cases in which puncture was per- 
formed; Murchison, 80 cures in 103 cases. The latter advised allowing the fluid 
to flow into the abdominal cavity, and claims that it is absorbed there. Such 
a procedure, of course, is fraught with danger, owing to the possibility of intoxi- 
cation and infection. : 


Puncture and aspiration: As the entrance of air into the cystis to 
be dreaded, and as, formerly, suppurative processes were attributed to 
the presence of air, the older operators began to devise methods of remov- 
ing the cystic contents, and at the same time of aspirating the air. Budd 
was the first to advise the employment of a suction apparatus. Dieulafoy 
and Potain both invented apparatus of this kind and recommended this 


808 DISEASES OF THE LIVER. 


method of treating echinococcus cysts. A great many cases have been 
treated in this manner. The walls of the cysts, it is true, are frequently 
hard and inelastic, and under these circumstances it is impossible to 
remove all the fluid and to cause the collapse of the cyst. In case the 
cyst is sterile a cure may be obtained; but if it is not sterile, or if the 
parasite has not been killed by suppuration or by the entrance of bile, 
the fluid will collect again, and it may be necessary to repeat aspiration 
many times. There are cases on record in which this operation was 
performed as often as 300 times. After aspiration a tympanitic sound 
will often be heard over the cyst as a result of the dilution of the gases 
contained in the cavity. Pain, nausea, vomiting, and urticaria have 
all been observed after evacuation. Sudden death is reported in a few 
cases (Guyot, Martineau, Moissenet). According to Braine, the mortality 
from the operation is as high as 15 %. 

As simple aspiration has not led to the desired goal in cases in which 
the cyst has not been sterile, the attempt has been made to destroy the 
parasite by the injection of certain substances into the cyst. 


As early as 1851 Boinet injected tincture of iodin, and his example was followed 
by Velpeau, Richard, Weber, Aran, Demarquay, and Chassaignac, Schroetter, and 
others. A few successes are on record, but the operation was again uncertain, 
was very painful, and in one or two cases was followed by the death of the patient, 
so that it was soon abandoned. 

Filix mas (Pavy), ox-gall (Dolbeau and Voisin, Landouzy, and others), and 
alcohol (Richet) have all been employed for the same purpose, and have all been 
abandoned. 


Injections of solutions of corrosive sublimate and thorough irriga- 
tion of the cyst have been more successful, and promise good results 
as soon as the technique is further perfected. 


Mesnard probably was the first to inject a solution of this substance into a 
cyst; this was followed by an increase of the suppuration; he injected more sub- 
limate and thoroughly flushed the cavity with the drug; this, finally, led to a cure 
of the case. The strength of the sublimate solution was one pro mille, and injection 
was followed by irrigation with alcohol. 

Sennet and Baccelli removed a small quantity of the cystic fluid (2.5 to 30 (!) gm.) 
and injected the same quantity or a slightly smaller quantity of sublimate solution 
(1 to 2 pro mille) and obtained good results. Dujardin-Beaumetz and Blumer 
proceeded in the same way, and report the contraction of an echinococcus cyst 
after one injection, and the cure after two injections of 20 to 30 gm. of a one pro 
mille sublimate solution. Cimbali saw death occur after this operation; the case, 
however, was hardly a suitable one. Kétly saw fever following the injection that 
persisted for 20 days; at the end of this time, however, the cyst had disappeared. 
After another period the fluid again accumulated. Sublimate was again injected 
and the cyst disappeared again; he does not state whether the disease was finally 
cured. Chauffard and Widal state that 36 c.c. of a one pro mille solution of sub- 
limate are sufficient to sterilize an echinococcus cavity of 2 liters; according to 
other statements, the cyst should contain as much as 1 or 2 cgm. of sublimate. 

Debove advises as complete an evacuation of the contents as possible, and 
the injection of 100 c.c. of a one pro mille solution of sublimate; this is to be re- 
moved by aspiration after ten minutes. Terillon removed 450 c.c. of fluid, injected 
100 ae of sublimate of the above strength, and left it in the cavity; the case was 
cured. 

__ Langenbuch states that among 16 cases that were treated with injections 
of sublimate 14 recovered, 1 died, and 1 showed no improvement. 


A.5 % solution of copper sulphate has also. been employed for this 
purpose (Debove). Chauffard succeeded in causing the disappearance 
of a cyst by the injection of 150 c.c. of a 0.5 % solution of #-naphthol. 


PARASITES OF THE LIVER. 809 


In many cases puncture and drainage have been employed, as in 
abscess of the liver. 


Owen Rees, and later Boinet and Verneuil, operated as follows: A thick trocar 
was inserted and allowed to remain in place for several days, until it became loose; 
a little fluid then oozed out. The walls of the parietal peritoneum were adherent 
by this time. A drainage-tube or a double catheter can be inserted, or the opening 
can be dilated with laminaria, sponge tents, etc.; and in this manner the evacuation 
of shreds of membrane and of hydatids is made possible. As suppuration and 
gangrene may readily occur during this operation, abundant drainage should be 
provided and care should be taken that the cavity is frequently irrigated with 
antiseptic solutions. Jénassen, Harley, and others have treated many cases by 
this method. If the skin is thoroughly disinfected and the trocar is sterile, the 
operation promises good results. While the cannula is in place, opium should 
be administered. The sac should be frequently flushed and thorough drainage 
secured, so that the danger of suppuration and of gangrene is minimized. Gradual 
and complete collapse of the cavity will occur; a biliary fistula may persist for 
a long time afterward in case some of the bile-passages rupture into the cyst-cavity. 


This method is particularly adapted for the general practitioner. 
Reclus states that the mortality is 28 %, but this is due to the fact that 
in many cases rigid antisepsis has not been observed. 

In order to obliterate the cyst and to prevent oozing of its contents 
into the peritoneal cavity, several methods have been employed; among 
these were the insertion of a small cannula and allowing it to remain 
in place until adhesions had formed, application of cauterizing pastes, 
etc. At the present time the leaves of the parietal peritoneum are sutured 
together prior to making the large opening that is considered necessary 
and expedient. 


Simon inserted two thin trocars two to three centimeters apart and allowed 
them to remain in place for two weeks. As soon as it could be assumed that ad- 
hesions had formed with the peritoneum (reduced mobility of the needles on respi- 
ration, oozing of pus or fluid, etc.) an incision was made between the two needles. 
Boinet inserted a curved trocar and pushed it through the cyst in such a manner 
that it protruded again; this he left in place for some time, and then made his 
incision. Bégin and Trousseau inserted several needles, Hirschberg as many as 
five, in order to cause the formation of adhesions. As this method can produce 
suppuration if it isnot carried out with all aseptic precautions, and as, on the other 
hand, it fails to cause the formation of adhesions if it is carried out altogether asep- 
tically, it is not a useful procedure and has been discarded. 


In the seventeenth century Mayley and Dodard attempted to bring 
about adhesions between the surfaces of the peritoneum by the applica- 
tion of certain pastes that were at first applied to the skin and later to 
the deeper tissues. 


Recamier in particular was responsible for this method. He used caustic 
potash; Demarquay “yee abi “Vienna paste,” or chlorid of zinc. Finsen has 
cured many cases in Iceland by applying caustics to the incision through the skin 
every three days; in this manner he has worked his way down to the cyst. The 
latter finally ruptures and is evacuated spontaneously; sometimes the cyst-wall 
is incised. Many modifications of this method have been reported. Sometimes 
an incision has been made down to the peritoneum and caustic paste applied to 
the latter. In this way it has been found possible to open the cyst within a few. 
days. Graves simply packed the wound, thus bringing about adhesions between 
the folds of the peritoneum. 


If this operation is well performed it is free from danger, and a wide 
gaping wound is produced through which the cystic contents can be 


810 DISEASES OF THE LIVER. 


thoroughly evacuated. The method is, however, painful and tedious 
(two weeks to six months). 

In place of the foregoing appeared the method originally recom- 
mended by Recamier and Bégin, consisting in a broad incision through 
the abdominal walls and the peritoneum (about 10 cm.) and the use of 
tampons, which are left in the wound for a week or so. The incision is 
then completed. Without rigid asepsis this method meets with poor 
success, but with aseptic precautions Volkmann found it very valuable. 
According to the statistics of Langenbuch, some 48 cases have been cured 
by this method of double incision. 

Of late years the single incision has been more universally employed; 
by this operation the echinococcus sac can be opened, the cavity emptied, 
and the parasite permanently removed at one stroke. 


Lindemann reports several successful operations of this kind; before him 
Schmidt chronicled several failures. The former operator opens the peritoneum, 
incises the cyst, and attaches the margins of the incision to the abdominal walls. 
Sanger sutured the cyst before incising. Landau and others first evacuated the 
cyst by puncture and aspiration, or through a thick trocar. Other modifications 
have been described, but need not be discussed here. 


The method of operating by one incision has given good results and 
has been responsible for the death of the patient in rare cases only. It 
is performed as follows: 


A large incision is carried through to the peritoneum; if the wound does not 
gape sufficiently, a portion of the abdominal wall is resected. The peritoneum is then 
incised and the wall of the cyst sutured to the abdominal wall. The fluid is now 
aspirated, the sac opened, the margins of the wound inverted, and sutured to the 
abdominal wall, and the cavity flushed with water sterilized by boiling. If the 
. walls of the cyst are soft and fragile, if the cyst contains pus, or if the patient is 
very restless, it is probably better to perform the operations by two incisions. 
The cyst-wall is in this event attached to the abdominal wall by stitches, the wound 
is tamponed for several days, and a second incision into the cyst, followed by evacua- 
tion of its contents, is performed at the expiration of this time. 


If the cyst is already adherent to the abdominal wall, it is sometimes 
possible to operate by a single incision, to evacuate the fluid, and to cure 
the disease. In cases of echinococcus cyst that have not undergone 
purulent degeneration it is rare, however, for adhesions to form, and 
dangerous to assume that they are present. It has happened that such 
an error of diagnosis has been made and the peritoneal cavity inad- 
vertently opened. Rare cases are also reported in which the cysts con- 
tained pus, which burrowed through to the lumbar region. The cyst was 
opened here by a single incision, the pus evacuated, and the case cured. 

After opening the cyst an attempt should be made to remove the 
membrane as completely as possible. Sometimes the cysts are found to 
be pedunculated, and in such cases it is an easy matter to ablate the whole 
growth. In other cases the cyst has been enucleated with its capsule 
(Pozzi, Beckhaus). In the case of some of the larger cysts it has been 
found necessary to resect a part of the cyst-wall in order to bring about a 
cure. [Deve * states as the result of his experience: (1) that hydatid 
cysts can develop from daughter-cysts and scolices; (2) that cysts of 
the subperitoneal cellular tissue may give rise to various echinococcus 
growths (cysts, daughter-cysts, proligerous cysts, and scolices), which 
may in this way enter the peritoneal space. He suggests, therefore, 

* Gaz. hebdom. de Méd. et de Chir., Feb. 7, 1901. 


PARASITES OF THE LIVER. 811 


that there is a necessity of protecting the tissues from the vesicles and 
from the invisible scolices, by injecting some teniacide before opening the 
mother-cyst, and thus destroying the sources of new infection.—ED.] 

If the contents of the cyst are purulent, the same rules apply as in 
abscess. The operation is usually more difficult than in abscess because 
adhesions are not always formed, and because it is necessary to remove 
daughter-cysts, shreds of membrane, etc. Moreover, the walls of the 
cysts are usually rigid, so that the cavity does not collapse so readily. 
On the other hand, the prognosis is more favorable because the cavity is 
walled in by a dense membrane that is usually in an accessible location; 
pyemia does not result as often as after abscess. 

The treatment of cysts that are situated in the upper portion of the 
liver underneath the diaphragm is more difficult. Occasionally they 
become accessible from the abdominal cavity after forcing the liver 
downward (Landau), or after resection of the anterior portions of the 
eighth to the eleventh costal cartilages (Lannelongue). If this can be 
done, a Single incision will cure the disease ; in other cases it becomes neees- 
sary to open the pleural cavity and to reach the cyst by resection of the 
ribs, and by incision of the diaphragm. 


Roser was the first to suggest this method, and Israel and Volkmann carried 
it out. Sometimes the operation was performed at one time. The leaves of the 
pleura were sutured together and incised at once; or the pleura was entered (Israel), 
tampons were put in place for several days, the diaphragm was then incised, and 
after a few days the cyst was opened. Subphrenic cysts have also been treated 
by simple puncture and by injections of sublimate without an operation. Cysts 
that enter the pleural cavity are treated as above, 1. e., resection of ribs, suturing 
the cyst-wall to the pleura, incision of the cyst, and evacuation. If such a cyst 
ruptures into the pleural cavity, thoracentesis with resection of ribs is all that is 
needed. 


Cysts that penetrate the lungs are best reached via the pleura, even 
if they pour their contents into the bronchi. Again the cyst-wall should 
be attached to the pleura and the cyst opened- and drained. Pus- 
cavities in the lungs or gangrene must be treated by pneumotomy. 

Cysts that rupture into the peritoneum may be treated by simple 
puncture and evacuation of the fluid; or the latter may even be spontane- 
ously absorbed. 


The fluid has also been removed by incision (Roux and others); Langenbuch 
advises flushing the abdominal cavity with a 0.7 % solution of common salt fol- 
lowed by one liter of sublimate solution of the strength of 1: 5000 to 1: 20,000; 
he then removes all traces of the sublimate by renewed washing with salt solution. 

Rushton-Parker saw general peritonitis and the formation of a purulent exu- 
date follow puncture; all this happened within twenty-four hours. He immediately 
opened the abdominal cavity, drained thoroughly, and the case recovered. 

[Von Bokay * has reported an echinococcus cyst of the pleura in a boy five 
years of age. This case and three others of echinococcus disease of the liver, all 
in children, were treated by Baccelli’s method (aspiration, and injection of bichlorid 
of mercury). Shrinkage of the cyst soon followed, and none of the cases showed 
a relapse.—ED.] : 


Perforation into the stomach and the intestine is only recognized in 
purulent or gangrenous cysts; the only treatment consists in laparotomy 
and evacuation of the cystic contents. 


* Jacobi, Festschrift; Phila. Med. Jour., May 26, 1900. 


812 DISEASES OF THE LIVER. 


LITERATURE. 


Achard: “De V’intoxication hydatique,” ‘“ Archives générales de médecine,” 1888, 
tome cLxu, p. 410. 

Baccelli: “‘ Berliner klin. Wochenschr.,’’ 1894, p. 302. 

Blumer: ‘‘Correspondenzblatt fiir Schweizer Aerzte,” 1894, p. 216. 

Bokay : ‘‘ DerWerth des Bacelli’schen Verfahrens bei Leberechinococcus des Kindes,”’ 
“ Archiv fur Kinderheilkunde,” 1897, Bd. xx1u1, p. 310. 

Braune: “Beitrag zur Casuistik iber den Echinococcus der Bauchhoéhle und ihrer 
Organe,” Dissertation, Marburg, 1897. 

Budd: ‘ Krankheiten der Leber,”’ pp. 90 and 425. 

Cobbold: ‘“ Parasites,”’ p. 112, London, 1879. 

Davaine: ‘ Traité des entozoaires,’’ Paris, 1860 and 1877. 

Delbet: “Sur un traitement des kystes hydatiques de l’abdomen,” “ Gazette heb- 

| domad.,’’ 1896, No. 15. 

Diirig: ‘Ueber vicariirende Hypertrophie der Leber bei Leberechinococcus,”’ 
“ Miunchener med. Abhandlungen,”’ 1. Reihe, 13. Heft. 

Frerichs: ‘“‘ Lehrbuch der Leberkrankheiten,”’ Bd. 1, p. 218. 

Heller: ‘‘Ziemssen’s Handbuch der speciellen Pathologie und Therapie,” Bd. 
vu, 1. Abtheilung, p. 429. 

Huber: “ Bibliographie der klinischen Helminthologie,”’ Heft 1, ‘ Echinococcus 
cystic,’ 1877-1890. 

Humphrey: “The Lancet,” 1887, vol. 1, p. 120. 

Index-Catalogue of the Library of the Surgeon-General’s Office, vol. vi11, 1887, 
p. 264 (literature). 

Kahn: “La régénér. du foie dans les états pathologiques,”’ Thése de Paris, 1897. 

Kétly: “ Berliner klin. Wochenschr.,’”’ 1897, p. 1082. 

Krause, F. : Ueber den cystischen Leberechinococcus,” ‘‘Sammlung klin. Vortrage,’”’ 
1888, No. 325. 

Kichenmeister: ‘‘ Die in und an dem KG6rper des lebenden Menschen vorkommenden 
Parasiten,” p. 169, Leipzig, 1855. 

Lebedeff and Andrejew: ‘‘ Transplantation von Echinococcusblasen vom Menschen 
auf Kaninchen,” ‘‘Virchow’s Archiv,” 1889, Bd. cxvi, p. 522. 

Langenbuch: “Chirurgie der Leber,” 1. Theil, 1894, p. 36 (literature). 

Létienne: in ‘‘ Manuel de médecine,” tome v1, p. 210, Paris, 1895. 

Leuckart: “ Die menschlichen Parasiten,” 1. Auflage, 1863, Bd. 1, p. 328, 2. Auflage, 
1879, bis 1886, Bd. 1, Abtheilung 1. 

Madelung: ‘‘Chirurgische Behandlung der Leberkrankheiten,” ‘‘Penzoldt und 
Stintzing’s specielle Therapie,’’ Abtheilung v1 b, p. 178. 

Mosler and Peiper: ‘“Thierische Parasiten.”” This work, vol. v1, including the 
latest bibliography. 

Mourson and Schlagdenhauffen: ‘‘Comptes-rendus de l’académie des sciences,” 
1882, tome xcv, p. 791. . 

Murchison: “ Diseases of the Liver.” 

Neisser: ‘‘ Die Echinococcenkrankheit,”’ Berlin, 1877 (literature). 

Peiper: “Zur Symptomatologie der thierischen Parasiten,”’ ‘ Deutsche med. 
Wochenschr.,”’ 1897, p. 765. 

Reichold: ‘ Fall von Ileus, bedingt durch Echinococcen der Leber,” ‘‘ Miinchener 
med. Wochenschr.,”’ 1897, p. 17. 

Reinecke: ‘‘ Compensatorische Leberhypertrophie bei Syphilis und bei Echinococcus 
der Leber,” “ Ziegler’s Beitrage zur pathologischen Anatomie,” Bd. xxim, 


p. 238. 
v. Siebold: ‘Ueber die Band- und Blasenwiirmer,” Leipzig, 1854. 
Terrier: “Kyste hydatique d. foie,”’ “Gazette hebdomad.,” 1896, No. 18. 
Waring: “Diseases of the Liver,” p. 125. 
Westerdyk: “ Berliner klin: Wochenschr.,” 1877, No. 43. 


(C) ECHINOCOCCUS ALVEOLARIS (MULTILOCULARIS). 


This form of echinococcus differs so essentially from the more frequent 
cystic form in regard to its pathologic anatomy, its geographic distri- 
bution, and, above all, its clinical manifestations, that it may be de- 
scribed as a clinical entity. 


PARASITES OF THE LIVER. 813 


Ruysch (in 1721) was the first to observe such a case, and after him 
Buhl and Luschka reported similar growths in the liver. They con- 
sidered them to be alveolar, colloid, or gelatinous forms of cancer. Zeller 
found the hooks and_ scolices, and Virchow first recognized the parasitic 
origin of the tumor, and gave it the name “multilocular ulcerative 
echinococcus-tumor,”” Although the symptoms produced are different, 
and although the geographic distribution and the form and structure 
vary considerably, yet this form of echinococcus was until recently con- 
sidered to be identical with the form described above. The differ- 
ences observed were attributed to the location of the swelling and to 
other anatomic conditions. Kichenmeister, it is true, had already 
assumed that there were several forms of echinococcus, and Vogler had 
called attention to certain differences in the form of the hooklets ; but all 
this was denied by Leuckart and others, particularly after Klemm 
claimed to have produced typical echinococcus disease in a dog that he fed 
with multilocular echinococcus; unfortunately the animal was not ex- 
amined for tenia before the administration of the multilocular echino- 
coccus. Feeding experiments by Mangold also showed the presence of 
tenia; these, as in the case of Vogler, had longer and less curved hooks 
and longer roots with a knob-shaped protuberance. Fully developed 
specimens, moreover, had a ball-shaped accumulation of eggs that were 
never seen in the last links of tenia of echinococcus cysticus. Mangold 
- also succeeded in inoculating a hog with these tenia and in producing 
typical young multilocular echinococci in the liver. Miller compared 
and corroborated these morphologic differences (compare also v. Bider). 

An argument in favor of the difference between the two is found in the 
fact that metastases from the two varieties are different and growths 
similar to the primary form always being produced. 

It is also remarkable that in certain regions only echinococcus alveo- 
laris is seen, and that in other regions, again, where there is much echin- 
ococcus cysticus disease (Iceland, Mecklenburg, Pomerania), the former 
is rarely or never seen. 

Among a number of regions in which the alveolar form is prevalent are: 
Southern Germany, Austria, Switzerland, and southeastern Russia.* 
The cases seen in other countries are usually in people that come from one 
of these four countries. 


Vierordt has named the following German districts as prolific in echinococcus 
alveolaris infection; Southern Bavaria, southern Wiirtemberg (Black Forest and 
the Danube counties), Switzerland, and the German Tyrol (Posselt). Within 
these regions certain localities seem to be particularly exposed: Munich, the vicinity 
of Memmingen, the lower valley of the Inn and its surroundings, and the entrance 
to the Puster Valley. Here several cases are often found in the same hamlet or 
even in the same family. Both of Morin’s cases, for example, came from Villeret 
(in the Jura), and two cases from the little village of Oberzell. The disease is 
so frequent that the people are struck by its occurrence and have given it special 
names, as “Gilm” or “black jaundice,” in the Tyrol. In these localities echino- 
coccus alveolaris is by far the most frequent form of the two; also in the Tyrol 
the proportion of the cystic to the*alveolar form is as 11 to 26, and it is worthy 
ep vo oe) nearly all the cases of the first category come from Wailsch Tyrol 

osselt). 


The disease is found especially in the middle years of life, between 
twenty-seven and fifty; more rarely cases are also seen in younger or in 
older subjects. There is no appreciable influence exerted by the sex; or, 

* Tokarenco, Dissertation, St. Petersburg, 1895. 


814 DISEASES OF THE LIVER. 


if so, itis more apparent than real. It would appear that men are infected 
a little more frequently than women, about as 3:2 (Vierordt). ; 

The origin, the mode of entrance, and the entire pathogenesis of the 
echinococcus alveolaris are still comparatively obscure, and many experi- 
ments will be required before these matters are thoroughly understood. 
No positive statement can as yet be made as to whether cattle-raising, 
which is so extensively carried on in the regions named, has anything to 
do with the disease. 


In cattle this form of echinococcus has often been observed (Huber, Bollinger, 
Perroncito, Harms, and others), but no reliable statistics exist. It would appear 
that the disease is frequently confounded with tuberculosis (Miller). 


People of the lower classes, peasants and other country folks, are 
most frequently affected (in Tyrol, Posselt). It is probable that the 
occupation of these people, and their uncleanliness, have something to 
do with this fact. 

Pathologic Anatomy.—An alveolar echinococcus is distinguished 
from the cystic form by the following peculiarity: The cystic variety, as 
we have seen, often develops daughter-cysts within the cavity of the pri- 
mary growth; the former variety, on the other hand, does not possess this 
power, but forms exogenous cysts, one cyst seeming to bud from the other. 
The mechanism is, in fact, a process of budding, either within the cuticle 
of the parasite (Morin, Leuckart), or in some portion that has become 
separated from the main body (Klebs, Leuckart, Prougeansky). Other 
distinguishing features are its greater tendency to perish from slight causes, 
and the formation of cysts containing no hooks and no scolices. The 
parasite irritates the liver tissues and causes an abundant proliferation of 
connective tissue. The center of the growth disintegrates readily and 
large cavities filled with debris are formed. The parasite, moreover, has 
a marked tendency to advance into healthy tissue in a manner that may 
be compared to the growth of a neoplasm: It involves bile-passages, 
blood-vessels, such as the portal vein, the vena cava, and the hepatic vein, 
also lymph-channels, and may even extend to neighboring organs, as the 
diaphragm. Metastases may form in the lungs, the lymph-glands, etc., 
in the same manner as in carcinoma or sarcoma. 

The original seat of the echinococcus is obscure. Virchow and Klebs 
believed that it first became localized in the lymph-vessels; Friedreich, 
Schroeder van der Kolk, and Morin claimed the same for the bile-passages, 
Lguckart for the blood-vessels, and Heschl for the acini of the liver. The 
question is a difficult one to decide in the absence of animal experiments; 
in well-developed cases numerous organs are usually involved, so that it is 
difficult to find out which one was first affected. The opinion of Leuckart 
is the only one that we can accept in the light of our present knowledge; 
namely, that the parasite may infect any of these organs. 

The macroscopic picture of the growth varies, of course, according to its 
age and its location. The outline of the liver need not necessarily be 
changed if the tumor develops in the interior of the organs; on trans- 
verse section a great development of the echinococcus will often be seen, 
even though its presence was hardly suspected. Sometimes small or 
large nodular protuberances are seen on the surface of the liver, or little 
bodies that are clearly defined as cysts; as a rule, they are found in the 
right: lobe. Occasionally cicatricial contraction will be noticed. The 
consistency of the liver is increased, and the organ may be as hard as stone, 


PARASITES OF THE LIVER. 815 


owing partly to fibrous and partly to calcified connective tissue. In rare 
instances a softening of the echinococcus occurs so that fluctuation is 
noticed. The margin of the tumor, however, remains hard even if the 
center fluctuates. The liver often reaches a very high degree of enlarge- 
ment; in small and young tumors the ehlargement may not be so consider- 
able. Griesinger reports a case in which the sac was as large as two adult 
heads, and Posselt describes a case from which over 7 liters of fluid were 
evacuated during an operation. At the same time there may be vicarious 
hypertrophy of the liver; in another case of Posselt the left lobe of the 
liver was 35 cm. long, 20 cm. broad, and 10 cm. thick. 

The color of the tumors is different from that of the liver tissue; they 
are easily distinguished on transverse section. ‘The tumor mass is whitish 
or bile-tinged, whereas the parenchyma is darker and occasionally also bile- 
tinged. Several tumors are often seen at the same time. On cutting, 
the tumor tissue gives a grating sound, and, owing to the cicatricial and 
the calcareous character of the tissue, it is often a matter of considerable 
difficulty to distinguish between the growths. The transverse sections 
appear as a vacuolated, alveolar structure similar to brown bread, cheese, 
honeycomb, or a sponge. 


These peculiarities have probably earned for this parasite the name of alveolar 
echinococcus, and the name is better than the one more generally employed of multi- 
locular echinococcus. For several echinococci of either form would constitute a 
multilocular cyst, whereas a single one of the alveolar form is indeed alveolar in 
the arrangement, and different in this respect from the cystic form. 


The alveoli differ greatly in size; they may be punctiform or as large 
as peas. Between the single cysts bands of connective tissue are seen that 
may be broad or narrow. Occasionally the alveoli are not spherical, but 
are distorted into different shapes, owing to the pressure of the connective 
tissue and to the confluence of several cysts. In this manner the periphery 
of such an accumulation of cysts may appear gyrated and contain numer- 
ous varicose passages and cavities. The contents consist of a gelatinous, 
translucent, yellowish mass, that may become thickened, dry, grayish- 
yellow, cheesy, or mortar-like, from the admixture of calcium salts. The 
formation of cavities as a result of necrosis and degeneration is a conspicu- 
ous characteristic of the older cysts. These older cysts may develop to 
enormous sizes, aS we have seen; they may fluctuate distinctly, and reach 
as far as the periphery of the organ. The walls have ridges containing 
blood-vessels. Several large cavities from different tumors may now 
coalesce. In such cases the walls are covered by bile-tinged or brick- 
red masses of bilirubin or remnants of blood. The contents of these 
old cysts consist of a puriform, creamy, brownish, viscid, and occasionally . 
a bile-tinged mass containing chalk concretions, crystals of cholesterin, 
remnants of membrane, precipitates of bile-pigments, and crystals of 
hematoidin. In one case a sequestrum of liver tissue weighing 17 gm. 
was found floating in the cystic fluid (Kranzle). Albumin, bile-pigment, 
bile-acids, and fat are found. The cyst is not encapsulated so completely 
as in the cystic form of the disease and not so distinctly separated from 
the liver tissue. The connective tissue of the periphery is thicker and 
contains ridges, but liver tissue is mixed with it, and, on the other hand, 
the connective tissue sends processes into the parenchyma of the organ. 
In the latter new echinococcus alveoli are found. At the same time, 
cirrhotic changes are occasionally seen in other parts of the liver. 


816 DISEASES OF THE LIVER. 


The bile-passages are often involved, either by compression or by in- 
closure in the tumor mass, both accidents leading to a closure of their 
lumen. Thus the common duct may become occluded by an echino- 
coccus that develops near the porta hepatis and all the bile be excluded 
from the intestine. The cystic and the hepatic ducts may be occluded 
in the same way. This will lead to stasis of bile in the gall-bladder or to 
dilatation of the smaller bile-passages, and as a result we will have hydrops 
of the gall-bladder or of the smaller bile-passages. Concretions may 
develop as a result of stasis. The tumor grows into the walls of the gall- 
bladder, into the cystic and the hepatic ducts and their branches, and leads 
to similar lesions. Occasionally, when the tumor begins to soften, larger 
bile-ducts become eroded and in this manner communicate with the 
central cyst-cavity. The latter becomes filled with bile, or the contents 
of the cyst may be poured into the bile-passages or into the gall- 
bladder. 

If the portal vein becomes occluded or compressed, stasis in the region 
supplied by this vessel supervenes, and is followed by a swelling of the 
spleen and occasionally by ascites. The vena cava has been found flat- 
tened and obliterated by the pressure exercised by the tumor. Following 
this there was edema of the lower extremities, dilatation of the abdominal 
veins, etc. Posselt describes a case in which a communication was estab- 
lished between the vena cava and the cyst-cavity, and in which death 
occurred from hemorrhage. 

The lymph-channels are quite frequently involved, and appear in the 
region of the tumor as rosaries, the single beads of which consist of small 
echinococcus cysts. Sometimes they form thick strands that run toward 
the porta hepatis and the abdominal aorta, or form a network of threads 
from 2to 3mm. thick. The portal lymph-glands are frequently swollen, 
and contain echinococcus cysts. 

Metastases are often found in the lungs. These may be in a state of 
cheesy degeneration, particularly if they are situated in the lower lobes. 
Sometimes occlusion of the branches of the pulmonary artery takes 
place. Bosch and Morin have reported eruptions upon the diaphrag- 
matic pleura, in the mediastinal glands, and even the formation of large 
alveolar echinococcus tumors containing scolices in the latter. Metas- 
tases have even been found in the endocardium of the right side of the 
heart in a case in which the lower vena cava was embedded in tumor masses 
(Buhl). Large strands and single cysts may often be found in the peri- 
toneum. . 

Among other symptoms that may be traced to the complete obstruc- 
tion of bile-passages are hemorrhages, fatty degeneration of the heart- 
muscles, the kidneys, etc. Tubercular foci have also frequently been 
found at autopsy; these, of course, have nothing to do with the dis- 
ease. 

Histologic examination of alveolar echinococcus cysts reveals strands 
of connective tissue and a fibrous meshwork consisting of coarse fibers of 
elastic strands, which may be tinged with bile, and contain amorphous 
pigment, fat-globules, chalk concretions, ete. These different accidental 
admixtures are seen chiefly in the vicinity of the central cavity. Within 
this reticulum the alveoli are seen surrounded by a structureless, wavy 
membrane which gives the impression that the cysts are held in close con- 
tact by pressure, or suggests that the latter have attempted to grow and 
have been prevented from doing so by the connective tissue. * In the inte- © 


PARASITES OF THE LIVER. 817 


rior the granular layer of parenchyma will be found. The whole tumor, if 
still young, is translucent, colloid, and can be readily enucleated from its 
capsule of connective tissue as a round gelatinous lump. In some cases 
hooks and scolices will be found; in others they have been searched for in 
vain; in other cases they have been found in the lymph-gland metastases, 
but not in the primary tumor. As the tumor grows older the originally 
clear contents become cloudy from the admixture of fat-globules, pigment- 
granules, crystals of hematoidin, and fatty acids. In large cysts a network 
of stellate bodies will be seen in the parenchymatous layer; these bulge at 
the crossing-points, but have very thin connecting processes (Virchow). 
Here and there they are broader and contain granules and calcareous 
bodies that show a laminated structure. The chemical properties of the 
sac-wall are the same as those of the cuticular layer of the cystic echino- 
coccus, and consist essentially of chitin. Within the dry, cheesy, mortar- 
like paste that is found in older cysts, numerous chalk-granules, cholesterin, 
shreds of echinococcus membrane, etc., arefound. Calcified scolices may 
also be found. The purulent mass often found in cysts consists largely 
of cholesterin needles, pieces of cuticular membrane, chalk concretions, 
granules of bile-pigment, crystals of hematoidin and of cholesterin, scolices 
and an amorphous detritus containing no pus-corpuscles. In the paren- 
chyma of the liver hyperplastic processes are occasionally seen if the 
echinococcus grows very large. There may also be fatty degeneration of 
the hepatic cells and proliferation of the interstitial connective tissue in 
the vicinity of the tumor. 

Symptoms.—Echinococcus alveolaris develops so gradually that the 
condition often causes no symptoms and may be diseovered only at the 
postmortem. 

The first symptoms usually are, however, a feeling of pressure and 
distention, pain in the hypochondriac and epigastric regions, disturbances 
of appetite, nausea, and vomiting. Fever is sometimes present, but may 
be absent. Ifthe tumor develops in the neighborhood of the large biliary 
passage, icterus may be the first symptom. Constipation and diarrhea 
may be complained of. The patient grows weak and emaciates. The 
liver is enlarged, its margin protrudes below the costal arch, and the 
hepatic dulness reaches further upward than is normal. The motility of 
the diaphragm is impaired above the tumor. The consistency of the liver 
is usually increased. If the tumor is not hidden beneath the ribs of the 
diaphragm, a hard nodular mass will be felt that can be distinctly outlined 
and distinguished from other organs. Occasionally it can be felt at the 
margin of the liver, and is then lost beneath the costal arch. The liver is, 
as a rule, freely movable unless adhesions anchor it. The organ may also 
be diffusely enlarged and hardened, so that it feels like a cirrhotic liver. In 
the portions involved by the tumor the margin is hard and nodular; it may 
also be hard and rounded in other parts, owing to compensatory hyper- 
trophy of the liver. Later, the center of the tumor may soften and fluctuate 
while, at the same time, the tumor decreases in size and the symptoms of 
oppression decrease. Generally, the tumor is not painful to pressure; if 
the disease is, however, complicated by perihepatitis, it may become sensi- 
tive, and even the pressure of the clothing may distress the patient; 
there may also be pain when slight pressure is exercised during palpa- 
tion. The liver continues to increase in size. Very large tumors may 
result, which extend laterally as far as the ilium and to Poupart’s liga- 
ment, and toward the middle line as far as the umbilicus. Sometimes 

52 


818 , DISEASES OF THE LIVER. 


they contain several liters of fluid. It is probable that such a cavity can 
evacuate its contents through the bile-passages, but no positive evidence 
of the passage of the fluid contents of one of these cysts via the rectum has 
so far been reported. [W. Althaus,* Clayton,} and others have recently 
described cases in which large echinococcus cysts compressed and finally 
discharged their contents through the biliary passages. In Clayton’s 
case daughter-cysts were discovered in the bowel movements.—ED.] 
Buhl observed a case in which bile-tinged masses mixed with chitinous 
membrane were expectorated, but no fistulous channel was discovered 
postmortem. Sometimes it is possible, in cases in which the cystic or the 
common duct is compressed, to palpate the gall-bladder as a fluctuating 
tumor at the side of the echinococcus cyst. 

Icterus from stasis is an important symptom. As a rule, icterus 
develops early; in certain cases, however, it may be a late symptom or 
may not appear at all, notwithstanding a rapid development of the cyst 
(Posselt). The intensity of the icterus generally remains constant. If 
the tumor undergoes softening, however, and in this manner relieves the 
pressure on the ducts; or if the intensity of the catarrh of the bile-passages 
is reduced, the icterus may grow less decided. For the same reasons it is 
occasionally noticed that acholic stools alternate with those which again 
temporarily contain urobilin (case of Erismann). In many cases icterus 
is due to partial occlusion of one of the larger ducts within the liver so 
that an abundant quantity of bile enters the intestine; in other cases, 
again, there is total retention of bile from compression of the common 
duct. [L. Ferralesco t reports a case in which a large cyst compressed 
and totally occludegl the main biliary passages—Ep.] In these cases 
the highest degrees of icterus may be seen, blackish-green color of the 
skin, itching, furunculosis and ulceration, and large quantities of bile- 
pigment may be noted in the urine. The latter, in such cases, may also 
contain urobilin, and as a result of the irritation of the kidneys, albumin 
and nucleo-albumin, and, owing to the decomposition of the intestinal 
contents in the absence of bile, indoxyl. Sometimes there is polyuria, 
and the urine has a low specific gravity, so that the patients complain of 
thirst. Hepatargy (cholemia) may appear; there may be a tendency 
to hemorrhage, epistaxis, bleeding from the mouth, the gums, from 
carious teeth, from the alveoli after extraction of teeth, hematemesis, 
passage of bloody stools, hematuria (from hemorrhage into the bladder), 
and hemoptysis. Any small wound of the skin may be followed by 
severe bleeding (razor-cuts, leech-bites, scratches, etc.). Petechiz ap- 
pear and intracerebral hemorrhages have been reported. The number 
of blood-corpuscles is reduced, but the blood is not otherwise affected 
by the disease. 

The hemorrhages must be attributed to the retention of bile. A 
few cases, however, have been reported in which there was no icterus 
of long duration, and in which, nevertheless, severe hemorrhages ap- 
peared, as in a case described by Bauer, in which there was degeneration 
of the liver parenchyma and incipient acute atrophy of the liver. In 
some cases xanthopsia and hemeralopia are seen. 

In the majority of cases severe icterus causes death. It may, how- 
ever, occur that an echinococcus cyst grows steadily until it assumes 


* Mtinch. med. Woch., 1900, No. 33. 


t Lancet, Sept. 15, 1900. 
t Gaz. degli Osped., July 19, 1900. 


PARASITES OF THE LIVER, | 819 


enormous dimensions without causing icterus. In cases of this kind 
the disease usually runs a more protracted course with the formation 
of large cavities in the liver and softening of the parenchyma. 

Griesinger reports a case in which a remittent form of icterus existed 
for six years. As a rule, the time is shorter and the average case lasts 
for several months, although cases lasting over a year are by no means 
rare. Much will depend upon the completeness of the occlusion of the 
ducts, and as to whether some bile enters the intestine or none at all. 

Narrowing or occlusion of the portal vein by the tumor is manifested 
by ascites and other symptoms of stasis. Ascites may be so intense 
as to interfere with respiration, causing dyspnea and cyanosis, and calling 
for puncture. The fluid is serous and bile-tinged. The splenic tumor 
that is occasionally seen must be attributed to stasis more than to 
the effect of toxic or infectious agencies. 

# The lower vena cava may be occluded and may even become totally 
obliterated (Buhl, Carriére); if this occurs, a collateral circulation is 
established from the inguinal through the epigastric veins to the axilla 
(vena axillaris) and to the sternum (vena mammaria interna); besides, 
there is usually edema of the lower extremities. In one case reported 
by Posselt the echinococcus cyst degenerated, perforated into the vena 
cava, and produced a fatal hemorrhage. 

There is nothing characteristic about the fever which sometimes is 
seen; the temperature usually fluctuates irregularly and may depend 
on the presence of complications. 

Intestinal disturbances are frequently seen, as meteorism, and diar- 
rheas that undermine the strength of the patient. The appetite and 
general power of assimilation may remain good for a long time; in fact, 
there may be polyphagia. As a result the patient is able to attend to 
his affairs for a considerable period; later the appetite is lost, there is 
deficient power to assimilate the food, etc., the general strength is re- 
duced, and nutrition becomes altogether inadequate. 

Hypostatic processes and infarcts are seen in the lungs, and the dis- 
ease may be complicated by tuberculosis of these organs. In rare in- 
stances an echinococcus cyst has been known to rupture into the lung 
(Predtetschenski). 

The heart is not directly affected though occasionally it may be 
dislocated. The pulse is slowed as a result of the icterus. 

Death occurs from collapse; toward the end there is edema and 
general loss of strength. The fatal issue is accelerated by obstinate 
hemorrhages, diarrhea, lack of assimilation, and deficient nourishment. 
It is possible that certain toxic substances play a réle, as in the case of 
other parasites. 

The disease usually lasts for several years. No definite length of 
time can be given, because the process remains latent and is unrecognized 
for a long time. Cases in which the tumor develops in a marked manner 
from the beginning in the vicinity of the large bile-ducts, and in which, 
as a result, icterus appears early, are more rapidly fatal than those in 
which the bile-ducts are involved at a later stage of the disease. 

Prognosis.—Almost all of the cases of echinococcus alveolaris that 
are on record have terminated fatally. It is, however, to be hoped 
that, with a better knowledge of the pathologic picture and of the fre- 
quency of its occurrence, we shall soon be able to recognize the disease 
in an earlier stage and to extirpate the tumor completely, together with 


* 


820 DISEASES OF THE LIVER. 


some of the surrounding liver tissue, and in this way cure the trouble. 
In cases in which the tumor is situated near the margin of the liver this 
will be particularly easy. If, on the other hand, the tumor is very 
large when it is discovered, or if it develops in the interior of the organ, 
at the porta, or in some inaccessible part of the liver, such measures 
will be inapplicable. 

Diagnosis.—The diagnosis of alveolar echinococcus is by no means 
easy. In many cases it is altogether impossible to state positively 
that we are dealing with such a condition. 

The course of the disease is similar to that of carcinoma of the liver, 
and more closely similar to this disease than to cystic echinococcus. 
The nodular tumor, the symptoms of stasis, the cachexia, and the biliary 
stasis may be very misleading. As a rule, it is true, the patient is 
young, and evidence of primary tumors in the stomach or the intestine 
is absent; these growths are, as we know, the chief source of cancer of 
the liver. The geographic location is of paramount importance, and 
many diagnoses of echinococcus have been made rather upon a geographic 
than a elinical basis. [L. Renon * reports a case of multilocular echino- 
coccus of the pleura and right lung in a man of thirty-six years. He 
claims that is the first case of the disease in man in France.—Ep.] In 
short, if the patient comes from a region in which a case of alveolar 
echinococcus has been previously found, the diagnosis is made in favor 
of this disease rather than of cancer. The course, too, is more pro- 
tracted than that of cancer, the latter rarely existing longer than a 
year; whereas echinococcus may easily last for a longer time. The 
patient, moreover, is able to attend to his affairs for a longer time and 
is not incapacitated by pain; he does not become reduced in strength 
until icterus appears in a severe form. The nodules of echinococcus 
are usually as hard as stone, whereas cancer nodules are softer. Tumor 
of the spleen is a frequent complication of echinococcus, and is rare in 
cancer; the same applies to the fever. If cancer tumors begin to soften, 
a feeling of fluctuation may sometimes be imparted, though indistinct; 
in echinococcus there may be such widespread disintegration that fluctua- 
tion is very distinct, and, in addition, a tympanitic sound may be heard 
over the cavities on percussion (Griesinger). 

The following features, therefore, must be considered in the differen- 
tial diagnosis between echinococcus alveolaris and carcinoma of thg 
liver: the age of the patient, the location from which he comes, the 
duration of the disease, disturbances of the stomach and intestine, the 
presence or absence of a splenic tumor, and fever. 

The differential diagnosis from malignant adenoma may also be 
difficult. This lesion is, however, rare. It is characterized by nodular 
tumors, icterus, tumor of the spleen, and resembles echinococcus in 
the duration of the disease. Leichtenstern has reported a case that 
was very similar to echinococcus in its whole clinical course. 

Exploratory puncture does not furnish very important information. 
Sometimes analysis of the aspirated fluid is of no value at all. It is 
impossible in many cases to find hooklets and scolices, and they should 
hardly be expected. Occasionally shreds of membrane are found, and 
crystals of hematoidin, fat, fatty-acid needles, cholesterin, pigment- 
granules, chalk concretions, red blood-corpuscles, occasionally also a 
few pus-corpuscles and isolated liver-cells. Chemical analysis will reve 

* Deutsch. med. Woch., April 26, 1900. 


PARASITES OF THE LIVER. 821 


the presence of albumin, bile-pigment (fat often in abundance), and 
salts. Hufner analyzed the fluid from a growth of this kind and found: 
Urea, 0.014%; chlorid of sodium, 0.003 %; chlorid of potassium, 
0.7 12 %; albumin, 0.2 %; fat, cholesterin, and bile-pigment, altogether 
0.1%. Phosphoric acid, magnesia, and calcium were absent. The 
absence of the latter was noteworthy because in other cases large quan- 
tities of calctum have been found in the fluid. | 

It is probable that the cystic contents vary in different cases accord- 
ing to the presence or absence of communications with bile-passages, 
blood-vessels, or lymph-channels. The fluid always contains albumin, 
in contradistinction to the fluid in the other form of echinococcus. Ex- 
ploratory puncture seems to be well borne in all cases and not to cause 
symptoms of peritonitic irritation. 

Of late years exploratory laparotomy has been performed in a number 
of cases. A small portion of the tumor was excised and examined 
microscopically; after the diagnosis was made in this way, the cavity 
was opened and the tumor excised. 

The disease may be taken for hypertrophic cirrhosis of the liver if 
the tumor develops in the interior of the liver or on its lower surface. 
In this condition, however, icterus is not so severe and the enlargement 
of the liver and the splenic tumor appear earlier. In contradistinction 
to syphilis of the liver, the liver in echinococcus alveolaris is harder, 
larger, and less indentated. 

It is distinguished from the cystic form by its nodular surface (even 
in the stage of softening), by the greater frequency of icterus and 
splenic tumor, and by examination of the fluid contents. 

Abscess of the liver and amyloid degeneration need hardly be consid- 
ered. Gall-stones are readily differentiated by colic, the passage of con- 
cretions, etc. 

Treatment. —Until very recently we were powerless to treat echino- 
coccus alveolaris even if the condition was recognized early and the 
growth was small. Within late years, however, the attempt has been 
made to eradicate the condition by operative treatment. ‘Terillon re- 
moved a piece of the liver that contained several cysts (probably cystic 
echinococci). Bruns cured a woman by excising an alveolar echinococcus 
from the liver. 

The cyst-cavities have also been punctured, but without good results; 
the method of the double incision has also been tried; the cavity has been 
scraped and cauterized. Brunner claims to have cured a case in this man- 
ner by operating through the pleural cavity. In other cases success has 
not been chronicled because it was impossible to remove all of the dis- 
eased and infected tissue; thus, the parasite began to grow again from 
the periphery. Bobrow has recorded such an experience. Predtet- 
schenski opened a swelling which he took for an abscess of the lung, 
and the case seemed to get well. Later the patient died from pneu- 
monia and nephritis, and in -the scar tissue of the lung were found 
echinococcus cicatrices. Large cavities may develop so near to im- 
portant blood-vessels that fatal hemorrhage into the wound may occur. 
Nicoladoni (quoted by Posselt) reports a case of this kind in which the 
bleeding occurred from the vena cava. 

It might be a useful procedure to attempt the destruction of the para- 
site by injections of sublimate in the same manner as described in the 
treatment of echinococcus cysticus. 


822 DISEASES OF THE LIVER. 


LITERATURE. 


Bider: “ Echinococcus multilocularis des Gehirns, nebst Notiz iber das Vorkommen 
von Echinococcen in Basel,” “ Virchow’s Archiv,” Bd. cxu1, p. 190. 

Bobrow: “ Alveolire Echinococcen der Leber,” “Die Chirurgie,” 1897, Heft 1 
(Russian); ‘‘Centralblatt fiir Chirurgie,” 1897, pe 11S: 

Brunner: “Ein Beitrag zur Behandlung des Echinococcus alveolaris hepatis,”’ 
““Munchener med. Wochenschr.,”’ 1891, No. 29. 

Bruns, P.: Leberresection bei multiloculirem Kchinococcus,” Bruns’ “‘Beitrige zur 
klin. Chirurgie,” Bd. xv1t. 

Buhl: “ Zeitschr. fiir rationelle Medicin,” 1854, Bd. rv, p. 356. 

—Ibid., 1857, Bd. vii, p. 115. 

Friedreich: “ Beitriige ‘Zur Pathologie der Leber und Milz,” “Virchow’s Archiv,” 
1865, Bd.>xXxxiit, p10. 

Griesinger: “Zur klin. Geschichte des vielfacherigen Echinococcus,” ‘‘Archiv der 
Heilkunde,” 1860, Bd. 1, p. 547. 

Huber: “ Zur Diagnose des Echinococcus multilocularis,”’ “Deutsches Archiv fir 
klin. Medicin, % 1865, Bd. 1, p. 539. 

—“in Fall von Echinococcus multilocularis der Gallenblase,”’ ibidem, Bd. xivm1, 

432. 

rae “Zur Kenntniss des Echinococcus alveolaris der Leber,” Dissertation, 
Munchen, 1883. 

Leuckart: Loc. cit. 

Lowenstein: ‘ Multilocularer Echinococcus,” Dissertation, Erlangen, 1889. 

Luschka: “Gallertkrebs der Leber,” ‘ Virchow’s Archiv,” 1852, Bd. Iv, p. 400. 

—‘“‘Zur Frage der Echinococcenkrankheit der menschlichen Leber,” ibidem, 1856, 
Bd. x, p. 206. 

Mangold: “Ueber den multiloculiren Echinococcus und seine Taenie,” Dissertation, 
Tubingen, 1892; and ‘Berliner klin. Wochenschr.,’”’ 1892, pp. 21 and 50. 

Morin: “Deux cas de tumeurs a échinococques multiloc., ” Dissertation, Bern, 1876. 

Mosler and Peiper: ‘‘Thierische Parasiten,’’ Bd. v1, Nothnagel’s Encyclopedia. 

Miller: “Beitrag zur Kenntniss der Taenia echinococcus,” ‘“Miinchener med. 
Wochenschr.,”’ 1893, p. 241. 

Nahm: “ Ueber den multilocularen Echinococcus der Leber,” ibidem, 1887, p. 674. 

Peiper: in “ Ergebnisse der allgemeinen Pathologie und pathologischen Anatomie,” 
1896, p. 40. 

Predtetschenski: “Ein aus vielkammerigem Echinococcus entstandener, in die 
rechte Lunge durchgebrochener Leberabscess,”’ “Med. Rundschau”’ (Russian) : 
1895, No. 10, from “ Virchow-Hirsch’s Jahresbericht,” 1895. 

Posselt: “Der Echinococcus multilocularis in Tirol,” ‘Deutsches Archiv fiir klin. 
Medicin,” 1897, Bd. urx, p. 1. 

Prougeansky, M.: “ Ueber die multilolcudre ulcerirende Echinococcusgeschwulst in 
der Leber,’ Dissertation, Zurich, 1873. 

Reiniger: “Multiloculirer Echinococcus, Dissertation, Tiibingen, 1890. 

Schiess: “Zur Lehre von der multiloculiren ulcerirenden Echinococouswevenwraite 
der Leber,” “ Virchow’s Archiv,” 1858, Bd. xiv, p. 371. 

Schwarz: “Ein Fall von Echinococcus multilocularis hepatis,’”’ “ Deutsches Archiv 
fir klin. Medicin,” Bd. 11, p. 616. 

Tokarenko: “ Ueber Bcninessenis multilocularis hominis,’ Dissertation, St. Peters- 
burg, 1895, from “ Virchow-Hirsch’s Jahresbericht, » 1895, 

Tochmarke: “ Fin Beitrag zur Histologie des Echinococcus multilocularis,” Dis- 
sertation, Freiburg, 1891. 

bec as oS der physikalisch-med. Gesellschaft zu Wurzburg,” 1856, 

VI, p. 84. 

Vierordt, H.: “Ueber den multilocularen Echinococcus” (a monograph with 
complete references to cases and the literature), Freiburg, 1886. 

—‘“‘Der multiloculaére Echinococcus der Leber,” ‘“ Berliner Klinik, ” Heft 28. 
Vogler: “Correspondenzblatt fiir Schweizer Aerzte, ” 1885, pp. 191 and 587. 
Waldstein: “Ein Fall von multilocularem Echinococcus der Leber,” “ Virchow’s 

Archiv,” 1881, Bd. uxxxiu, p. 41. 


PARASITES OF THE LIVER. 823 


(D) ASCARIS LUMBRICOIDES (SPULWURMER). 


Ascarides enter the bile-passages from the duodenum, developing first 
in the intestine from eggs that are introduced per os. They do not seem to 
develop within the bile-passages, though it is possible that sometimes they 
enter the ducts when they are still young, and continue to growthere. As 
they seem to have the power of crawling through wire loops and glass 
rings (pearls), it is possible that a fully developed parasite may push its 
conical head through the orifice of the common duct and gradually work 
its way into the gall-bladder, or the hepatic duct and its branches. Many 
clinical and anatomic observations speak in favor of this possibility. It is 
not correct, of course, to assume that ascarides enter the gall-bladder and 
the bile-passages during life in every case in which these parasites are 
found in the bile-channels at the autopsy; nor are we justified in basing 
our interpretation of the disease to which the case has succumbed, upon the 
presence of ascarides in this abnormal location. In very many cases they 
have probably entered the ducts postmortem. 

All cases of hepatic disease, icterus, swelling of the liver, etc., that 
seem to recover after the passage of ascarides in the stools must be care- 
fully analyzed before any réle in the causation of the condition is attrib- 
uted to the parasites. A duodenal catarrh, for instance, due to the pres- 
_ ence of ascarides, may cause the icterus, etc. ; or, again, the treatment may 
have caused the evacuation of the ascarides, although the latter had 
nothing whatever to do with the production of the lesions that were being 
treated. In certain cases, however, icterus has been seen to disappear at 
the same time with the passage of an ascaris per rectum that was bile- 
stained at one extremity only. In a case of this kind we are probably 
justified in assuming that there has been a causal connection between the 
presence of the ascaris and the icterus. 

When these parasites enter the bile-passages, they may irritate the 
mucous membrane, may occlude the ducts, or may carry intestinal bac- 
teria into the liver. The ascarides as foreign bodies cause stasis of bile, 
and the bacteria find.thus a suitable nidus for their development in the 
dilated channels, filled with bile, and can penetrate the mucous mem- 
brane more easily because it is in a state of inflammation. In this way 
they may penetrate the liver parenchyma, and cause single or multiple 
abscesses. 

Pathologic Anatomy.—Often no changes will be found in the liver and 
the bile-passages, so that the conclusion seems justified that the parasites 
enter the latter after the death of the patient. Only such anatomic 
changes can be utilized as point directly to the action of ascarides during 
life; such as stasis of bile in the liver, the gall-bladder, and the bile-pas- 
sages; distention of these channels with thickened bile in cases in which 
the common duct is occluded by the parasite; and distention of the gall- 
bladder if the worm is situated in the cystic duct. Often there is cholan- 
gitis in the locality in which the parasite is found; also ulceration of the 
mucosa, formation of cavities originating from the bile-channels and filled 
with pus, eggs, or ascarides. Further, abscesses of the liver may be pres- 
ent containing a macerated worm, or metastatic foci in different places of 
the parenchyma, and originating from suppurative cholangitis, which in 
its turn owes its origin to anascaris. Finally, the formation of a gall-stone 
around an ascaris has been observed. 


824 DISEASES OF THE LIVER. 


Broussais, Wierns, Lieutaud, Buonaparte, Treille, and others have reported 
cases in which the worm occluded the common duct but had only entered the channel 
half-way, so that one-half was found protruding into the intestine. In the cases 
reported by Lobstein numerous ascarides occluded the common duct. An ascaris 
has been seen in the interior of a gall-stone that was impacted in the orifice of the 
ductus choledochus. Davaine quotes a case in which a large number of worms 
were found in the bile-ducts, and had made pockets in the walls of the passages 
extending for a varying distance into the liver tissue. Bourgeois reports a similar 
case. Laennec saw a case in which a communication existed between the common > 
duct and the stomach and in which ascarides were present in the gall-bladder and 
in the bile-passages. The walls of the bile-passages were reddened, thickened, 
eroded, or destroyed, and cavities were formed in the liver, as large as almonds 
and filled with worms. Laennec attributes such a destructive action on the part 
of ascarides to suction performed with their mouths. Davaine believes that sup- 
purative processes have a causal connection. 'Tonnelé describes a case in which 
pus was found around an ascaris, and in which there were several abscess-cavities 
in its immediate vicinity. Pellizari determined that two abscesses, found on the 
surface of the liver (in a shoemaker), contained ascarides and were in reality dilated 
bile-passages; after the worms were removed they were found to communicate 
with the hepatic duct and to contain pus-corpuscles, ascaris eggs, and bile-duct 
epithelia. Forget found an ascaris in the common duct and one in the hepatic 
duct; in addition, he found a cavity as large as a walnut filled with pus, which 
represented a dilated bile-passage and contained a dead worm in a state of macera- 
tion and decay. Further, there were found ten abscesses varying in size from 
a pea to a chestnut. The walls of these cavities were covered by a thick pseudo- 
membrane and were surrounded by a hyperemic liver tissue. In a case of Lebert 
numerous worms were found in the bile-passages, and a number of small abscess- 
cavities varying in size from a pea to an apple, all through the liver tissue. The 
abscesses did not communicate with the portal vein; some of them, however, ° 
communicated with bile-passages and some of them contained macerated ascarides. 
One of the abscesses had perforated the diaphragm and had entered the lung, 
so that pneumothorax was present at the same time. Lobstein also describes 
multiple abscesses of the liver, one of which penetrated the lung; he attributes 
all the lesions to the presence of ascarides. These worm-abscesses may also per- 
forate the skin, such an occurrence having been seen and reported by Kirkland. 
Kartulis found 80 ascarides, some of them alive, in a liver filled with small pus- 
cavities. Of late, Hoehler has furnished a description of multiple abscesses 
of the liver, caused by an ascaris which was found in one of the ‘pus-cavities. 
Réderer and Wagler describe a case in which an ascaris was found within an echino- 
coccus cyst; it appears doubtful, however, whether this worm entered the cyst 
during the life of the patient. 


In all the cases described the worms were situated with their heads 
toward the liver and their tails toward the intestine. Only in the gall- 
bladder does it appear that they can turn around and crawl out. again. 
Some of the worms were adults, some of them (particularly in the ab- 
scesses) young ones. Occasionally a large number of ascarides will be 
found together; Vinay, for instance, saw 20 lying together near the orifice 
of the common duct. It is probably owing to the protected and hidden 
location of the orifice of the common duct that invasion of the liver by 
ascarides does not occur more frequently. | 

The symptoms of ascarides are so indefinite and so little characteristic 
that a diagnosis of invasion of the bile-passages or the liver by these para- 
sites can hardly be made. If the common duct is occluded (Broussais, 
Lieutaud, Buonaparte), the liver and the gall-bladder swell, and there will 
be intense icterus, and discoloration of the feces. The patients complain 
of fever and of violent pain in the liver region. Sometimes icterus does 
not appear because the worms crawl through the duct too rapidly to cause 
stasis of bile; in such cases the temperature is usually high, there is pain in 
the liver region, the organ will swell, there is lack of appetite, vomiting, 
diarrhea or constipation, and ultimately the symptoms of cholangitis and 


PARASITES OF THE LIVER. 825 


of abscess of the liver appear. The patient usually dies in a short time. 
In the case of children, there may be convulsions, coma, great weakness, 
and serious disturbances of the heart-action before death terminates the 
scene. If the worms penetrate the lung, symptoms of pneumonia or of 
pulmonary abscess develop; pneumothorax is also occasionally seen. In 
Kirkland’s case the abscess broke through the skin at the level of the last 
false rib on the right side, and the worm was evacuated with the pus. As 
the fistula continued to secrete bile for a long time thereafter, it is probable 
that a connection existed with a bile-duct or with the gall-bladder. 

We must be very skeptical as to all reports of cures of ascarides 
infection of the liver. It is true that many cases have been described 
in which certain liver symptoms disappeared after the passage of ascar- 
ides, but in these cases a simple duodenal catarrh may have been caused 
by the parasites, and cured as soon as the worms were removed. 


The following case reported by Mallins can hardly be interpreted to signify 
anything else than the presence of ascarides in the common duct: An officer com- 
plained for three months of icterus and there was complete absence of bile from 
the intestine; at this time an ascaris was passed, one-half of which was bile-tinged; 
as soon as the worm was removed, icterus disappeared, bile appeared in the intestine, 
and the case was cured. 


It is possible that cases of this kind occur more frequently, but we 
must not forget that the worm, if it has once succeeded in engaging its 
head in the common duct, will certainly have a tendency to progress, 
and will try to penetrate the liver as it penetrates other organs and 
cavities. It will not, naturally, show a tendency to work its way back 
into the duodenum. Only in the gall-bladder might the worm possibly 
turn around, and, finding no other exit, slip back into the intestine 
through the cystic and the common duct. 

In general the prognosis is unfavorable if the worm penetrates branches 
of the hepatic duct, and cholangitis, abscess, etc., seem to be the in- 
evitable consequences of this occurrence. 

The only internal therapy that can be employed must be directed 
to that portion of the worm that is still dangling in the intestine. Laxa- 
tives, as castor oil, etc., and santonin should be given in order to induce 
the parasite to leave the choledochus. If the worm has entered the 
gall-bladder or if it has crawled into the common duct so that no part 
of its tail-end protrudes into the intestine, surgical measures are the 
only ones that promise any relief. A laparotomy will have to be per- 
formed, the affected parts exposed, and examined for worms; the bile- 
passages should then be opened and the parasites removed in the same 
manner as gall-stones. 


Davaine: Loc. cit., p. 156. 

Hoehler: “Ein Fall von Leberabscessen, verursacht durch einen Spulwurm,” 
Dissertation, Greifswald, 1895. 

Kartulis: “Ueber einen Fall von Auswanderung einer grossen Zahl von Ascariden 
in die Gallengiinge und die Leber,” “Centralblatt fiir Bakteriologie und Para- 
sitenkunde,” Bd. 1. 

Langenbuch: Loe. cit., p. 167. 

Leuckart: Loc. cit., Bd. m, p. 236. 

Schiippel: “ Krankheiten der Gallenwege,” in “ Ziemssen’s Handbuch,” 1880, p. 171. 


Anguillula (Leptodera) stercoralis, also called Rhabdonema strongyloides, 
is a parasite that is found in the intestine in Cochin China diarrhea. It is usually 
present in large numbers, and occasionally enters the bile-passages and the gall- 


826 DISEASES OF THE LIVER. 


pladder without causing any symptoms during life that indicate its presence. 
Its pathologic significance is not very great. 


Cobbold: Loe. cit., p. 234. 
Davaine: Loc. cit., 2. Aufl., p. 966. 


(E) DISTOMATA. 


Distomata of the Bile-passages. Distomum s. Distoma hepaticum, lanceolatum, 
sinense, conjunctum, crassum, felineum. 


In the bile-passages and in the gall-bladder liver flukes (German, 
Leberegel; French, douve) are occasionally found; not so frequently, 
however, as in sheep, cattle, and other animals. The disturbances seen 
in man are not so serious as those seen in sheep; of the latter a great 
number perish every year from this disease with the symptoms of severe 
cachexia, anemia, and hydrops. These cases are, as a rule, due to 
Distoma lanceolatum and hepaticum, both of which are usually present — 
at the same time in the same animal. 


These flukes vegetate in the bile-passages of the animals and produce dilatation 
of the bile-ducts, cholangitis, and pericholangitis. The dilated bile-passages are found 
incrusted with chalk; the connective tissue around the ducts then becomes inflamed, 
interstitial hepatitis develops, followed by contraction and, later, ascites. General 
edema and anemia are then seen. In cattle the disease runs a less severe course. 

Distoma hepaticum is a leaf-shaped trematode about 25 to 30 mm. long, and 
when fully developed 8 to 12 mm. broad. The anterior portion of the body is 
only 4 or 5 mm. long; here are seen two suckers, and longitudinal and circular 
muscle-fibers. This part of the body is covered with rows of chitinous scales turned 
posteriorly. 

The worm enters the bile-ducts in the following manner: The wedge-shaped 
head and the first millimeters of the body enter the common duct as the result of 
attachment of the suckers when the body is fully extended. The muscles of the 
body then contract and cause the worm to become thicker, and in this way to dilate 
the passage. Finally the sucker situated on the abdominal side is pulled in and 
attached to the mucosa. At the same time, the scales of chitin become wedged 
against the walls of the duct, and a position is thus occupied that offers resistance 
enough to allow the parasite to push its way further into the duct. The flat pos- 
terior end of the worm is usually rolled up and wrinkled so that the parasite re- 
sembles a faded leaf; owing to its brown color, it may easily be overlooked. 

Distoma lanceolatum appears very similar; it is narrower and shorter, how- 
ever—7. e., 8 to 9 mm. long and 2 to 2.4 mm. broad; its surface is smooth. 

The eggs of Distoma hepaticum are 0.13 to 0.14 mm. long and 0.075 to 0.09 
mm. broad; they have a flattened anterior pole covered with a lid-like structure, 
and a pointed posterior pole. The eggs of Distoma lanceolatum are smaller, 
0.045 mm. long and 0.03 mm. broad, have a thicker shell, and a more flattened 
knob-shaped extremity. 

The eggs of distoma are passed out of the bile-passages together with the bile, 
enter the intestine and are evacuated with the stools; in this manner they may 
infect the pasture. As soon as the embryo (in the flagellated stage) comes in 
contact with water its covering separates, it is liberated, and enters the body of 
certain water-snails, particularly Limneus minutus. It enters the respiratory 
cavity of the latter, forming a sporocyst; later these develop caudate cer- 
ceria. These are either eaten by the sheep with the grass on which they are 
lying, or the body of the snail is injured and the parasite liberated in this way; 
in the latter instance the worms become attached to water plants, grass, etc., to 
which they are glued with a gummy substance. 

They are eaten by different animals with grass, or are swallowed with the 
water of pools and ditches. After entering the stomach and intestine, they 
penetrate the bile-ducts or may reach the liver by way of the portal vein. 


_ Infection probably occurs in the lower animals and in man in a 
similar manner. An argument in favor of this view is the fact that this 


PARASITES OF THE LIVER. 827 


form of parasite is usually found in human subjects who have been 
known to quench their thirst by drinking well- or ditch-water, or who 
have eaten water-cress, etc. 


This, for example, was the case in a patient of Kirchner (quoted by Leuckart), 
a Shepherdess who had been in the habit of drinking the water of aswampy meadow, 
and of eating the water-cress that grew there. In Bastroem’s case the patient 
was a laborer, working near the Main-Danube canal. Baelz reports that in Japan, 
particularly in the neighborhood of Okayama, distoma is frequently found in human 
subjects. This is a swampy region that has been reclaimed from the sea; similar 
conditions exist in Katayama. He distinguishes two species of liver-flukes, Dis- 
toma hepaticum endemicum s. perniciosum and Distoma hepaticum innocuum. 
Leuckart, however, has shown that the two are identical and are both members 
of the family, Distoma sinense s. spathulatum. The peasants in the region 
named used the dirty water of the ditches for washing their kitchen utensils, etc., 
and in this manner, it is said, some 20 % are afflicted. 


In tropical regions distoma infection is frequently seen and is 
‘due, in all probability, to the use of dirty water. Bierner, McConnell, 
Carter, McGregor, Chester, and others have reported cases that seem 
to demonstrate this fact. The parasite was named by Cobbold Dis- 
toma sinense, and by Leuckart Distoma spathulatum; it was first 
found by McConnell in a Chinese, who died of a severe affection of the 
liver. Blanchard has found many of these worms in the livers of soldiers 
in Anam. Jjima found the parasite in cats in Japan. 


The worm is 10 to 13 mm. long and 2 to 3 mm. broad. Its cuticle is smooth, 
and its eggs are from 0.028 to 0.03 mm. long and from 0.016 to 0.017 mm. broad, 
brown to black in color, with a thin shell and a small lid at the narrower end. There 
is occasionally a knob at the dull extremity. 


Another kind of fluke has been found in the bile-passage of Moham- 
medans in Calcutta (McConnell), and in the livers of Indian dogs (Lewis 
and Cunningham), called Distoma conjunctum and resembling Dis- 
toma sinense. This worm is distinguished from the other species by 
certain fine processes and by the presence of hairs on the cuticle. It is 
possible that certain forms of severe cirrhosis of the liver that have 
been described by Ghose and Mackenzie in India are due to distoma 
infection. 

In isolated cases Distoma crassum, a worm 4 to 6 mm. long and 
1.7 to 2 mm. broad, has been known to cause serious disturbances in 
man. This organism was first described by Busk in the duodenum of 
a Lascar; in this case it was not found in the bile-passages nor in the gall- 
_ bladder (Budd). Cobbold and Johnson also found it in a missionary 
and his wife and child. It appears that the last-named three had be- 
come infected during a sojourn in China (Ningpo), possibly from eating 
oysters. 

Winogradoff saw a form of distoma in Siberia which he called Dis- 
toma Sibericum. Braun claims that this form is identical with that 
seen in Europe in cats, and called Distoma felineum Rivolta. 

Pathologic Anatomy.—Sometimes distomata produce only very 
slight disturbances. They have often been found first at the autopsy, or 
they are discovered in the stools, and in the absence of symptoms (Pallas, 
Fortassin, Wyss, Virchow, and others). On the other hand, fatal and 
severe diseases have been known to follow their entrance into the bile- 
ducts. Wherever they lodge, inflammation and dilatation of _ bile- 
passages occur, so that cavities are often formed as large as a walnut 


828 DISEASES OF THE LIVER. 


and resembling cysts. In cases in which the distoma is present in 
large numbers, as in the Japanese form, the bile-passages are uniformly 
dilated and may contain hundreds of worms. The walls of the ducts 
are usually thickened and the liver tissue in their vicinity atrophic (vide 
the Siberian form), or cirrhotic changes may occur and be followed by 
ascites (Winogradoff). If the cysts are very superficially situated, they 
may burst and cause death from bleeding into the peritoneum (Chester). 
Or the distoma may lodge in one of the main stems of the bile-ducts 
and cause ulceration by the combined action of the suction it exercises 
and as a result of the pressure of the chitin scales on the membrane 
lining the duct, particularly if violent contractions occur. Bostroem 
has shown that in cases of this kind the walls of the bile-passages become 
thickened; there is atypical proliferation of the epithelium, and hyper- 
trophy of the musculature; the parasite may completely occlude the 
lumen of the duct, causing retention and absorption of bile. 


In the vicinity of the worm there was in this case newly formed connective 
tissue which led to occlusion of the cystic duct and to hydrops of the gall-bladder. 
In the contents of the latter distomata were found, a proof that the worms were 
there before the cystic duct became occluded. Thus the conclusion seems justified 
that the parasites were the direct cause of the occlusion of the channel. In the 
case reported by Biermer, there was cicatricial occlusion of the hepatic duct at 
its point of division, and below the scar a distoma was found. In this instance 
the bile-passages were filled with a clear, slimy substance. Distoma hepaticum 
may also be found in the gall-bladder (Partridge). Duval claims to have found 
several large distomata in the portal vein and in the hepatic branches of this 
vessel. Miura reports numerous nodules in the peritoneum containing distoma 
eggs; these seemed to be connected with lymph-channels. They were found in 
a Japanese who had died of beri-beri, and in whom during life no symptoms at- 
tributable to involvement of the liver were observed. In distomiasis the spleen 
is usually enlarged. 


_Symptoms.—The pathologic picture is usually quite indefinite, and 
often there are no important symptoms to be observed. In other cases 
(Baelz, Biermer, Bostroem, Kirchner, and others) there are pronounced 
symptoms which point more or less definitely to the liver as the chief 
seat of the trouble. 

There may be pain in the region of the stomach and the liver, loss 
of appetite (or, on the other hand, bulimia—Baelz), thirst (Sagarra), 
and constipation, all of these being initial symptoms. Later, there will 
be a feeling of pressure in the epigastric and the hypochondriac regions 
as a result of the swelling of the liver. Then vomiting and diarrhea, 
with the passage of bloody masses, weakness, and lassitude; on the other 
hand, the general health may remain good for many years (Baelz). 
In cases in which the hepatic duct becomes occluded (Biermer, Bostroem),’ 
icterus develops; in all other cases it is absent, or present in a mild form 
and of varying intensity. The liver usually enlarges, becomes hard, 
smooth, and rarely nodular. The gall-bladder may also appear to be 
enlarged. A tumor of the spleen is, as a rule, present. In the serious 
cases that end fatally there is cachexia and anemia, due in all probability 
to hemorrhages from the mucous membranes caused by the parasites. 
The worms seem to thrive on the bloody masses with which the bile- 
passages are lined. In some cases the disease is cured; this may even 
occur after the evacuation of bloody, slimy stools containing large 
numbers of the worms (Mehlis, Prunac, Wilson, and others). Distoma 
Sinense in particular seems to produce a pathologic picture that resembles 


PARASITES OF THE LIVER. 829 


the same infection in animals, including enlargement of the liver, fluc- 
tuating icterus, an exhausting bloody diarrhea, ascites, edema, and 
cardiac weakness. Cases reported by J. P. Frank and Kirchner demon- 
strate that the European species of distoma can also produce a similar 
picture. 

Distomiasis in Siberia resembles the course of cirrhosis of the liver 
(Winogradoff) ; in the event that the parasites are evacuated, it is asserted 
that the disease can be cured. 

The discovery of the eggs is diagnostically important. They are 
passed with the feces and may be found there on microscopic examina- 
tion, as has been shown by Bostroem, Perroncito, and Baelz. 

Prophylaxis consists in the avoidance of unboiled water for drinking 
purposes, especially such as comes from pools or ditches, and in ab- 
stinence from the use of raw water-cress, particularly in regions where 
distomiasis is frequent. 

Treatment consists essentially in the administration of laxatives and 
of anthelminthics. Prunac gave extractum filicis maris, and Sagarra 
castor oil, and both witnessed the passage of distomata as the result 
of the exhibition of these remedies. Bitter-waters and alkaline-saline 
waters (Karlsbad, etc.) may also be useful. . 

If the parasite occludes the hepatic duct, operative interference should 
be considered in order to remove the worm and to reestablish the flow 
of bile. 


LITERATURE, 


Aschoff: “ Ein Fall von Distomum lanceol. in der menschlichen Leber,” “ Virchow’s 
Archiv,” Bd. cxxx, p. 493. 

Braun: “ Die thierischen Parasiten,’? Wurzburg, 1895, p. 119. 

Budd: Loc cit., p. 444. 

Baelz: ‘‘ Ueber einige neue Parasiten des Menschen,” “ Berliner klin. Wochenschr.,”’ 


1883, p. 234. 

Blanchard: “ Note sur quelques vers parasit. de l’homme,” “ Comptes-rendus de 
la société de biologie,’’ tome vu, Paris, 1891. 

Bostroem: “‘Ueber Distomum hepatic. beim Menschen,” ‘Deutsches Archiv fur 
klin. Medicin,” 1883, Bd. xxxin, p. 557. 

Braun: “ Ueber ein fiir den Menschen neues Distomum aus der Leber,” ‘‘ Central- 


blatt fir Bakteriologie und Parasitenkunde,” 1894, p. 602. 

Chester: ‘ British med. Journal,’’ October 16, 1886. 

Cobbold: “ Parasites,” p. 14, London, 1879. 

Davaine: “Traité des entozoaires,’”’ 2. éd., Paris, 1877. 

Frank, J. P.: “De curandis hominum morbis,” vol. v, Liber v1, pars 111, p. 113. 
Florentiae, 1832. 

Ghose-Mackenzie: ‘‘The Lancet,” 1895, February 2, p. 321. 

Humble: “A Case of Dist. Hep. in Man,” “British Med. Journal,” July 16, 1881. 

Kichenmeister: “ Die Parasiten,’”’ Abtheilung 1, p. 179, Leipzig, 1855. 

Leuckart: “Die menschlichen Parasiten,’”’ 1879-1886, 2, Aufl., Bd. 1, pp. 94 and 
355. 

Miura: “ Fibrése Tuberkel, verursacht durch Parasiteneier,” “ Virchow’s Archiv,” 
Bd. cxvi, p. 310. 

Mosler and Peiper: “Thierische Parasiten,”’? Nothnagel’s Encyclopedia, Bd. v1, p. 
169. 

Prunac: “ hi la douve ou dist. hép. vhes Vhomme;’’“ Gazette des hépitaux,” 1878, 
p. 114 

ner “Un caso de dist. hep. en el hombre,” “Rey. de med. y chir.,” 1890, vol. 

v, p. 505; nach “Centralblatt fiir Bakteriologie und Parasitenkunde, ” 1891, 
Selivnbe’ “Krankheiten der warmen Lander,” Jena, 1896, p. 261. 


Distomata Inhabiting the Portal Vein. Distoma Hematobium 
(Bilharzia sanguinis).—This fluke is found in the portal vein, and 


830 DISEASES OF THE LIVER. 


may cause marked lesions of the liver. These have been observed 
with particular frequency in Egypt where the parasite is common. 


For the morphology and the habits of life compare Loos and the text-books 
of Leuckart, Davaine, Cobbold, etc. The male is 12 to 14 mm. long and 1 mm. 
broad. The larger and also thinner female is often found (16 to 18 mm. long, 
0.13 mm. broad, within the canalis gynekophorus. The eggs are 0.12 mm. long 
and 0.04 mm. broad and have a tiny prickle at one end; occasionally the latter 
is seen on one side. 


The worm enters the intestine with contaminated drinking-water 
which contains the embryo. Thence it makes its way into the portal 
vein. [A new appearance (Bilharzia hematobia) has been met with in 
the larve of the bilharzia by Lazarus-Barlow and Douglas,* and com- 
mented upon in a recent preliminary note. It would appear that in 
the case of certain larvee, while still living, there occurs a formation of 
spherical bodies, ‘‘ with double contour and provided with long cilia.’’ 
The spheres exhibit an intense vibratile movement of protoplasmic 
granules. The cilia also have been observed in active motion, though 
usually motionless. The spheres are able to carry on an independent 
existence. Many authors have described non-ciliated spheres, though 
none have called attention to the ciliated forms.—Ep.] The 
pathologic process is usually more pronounced in the kidneys and 
the bladder, and the patient usually succumbs to lesions of these 
organs. Eggs are often deposited in the liver and cause inflammatory 
processes. Even when there is no deposition of eggs circulatory dis- 
turbances may be produced. The greater the number of parasites 
present in the portal vein, the more violent the signs of inflammation. 
Kartulis, among 22 cases of Bilharzia liver, found hypertrophic cir- 
rhosis 12 times, atrophic cirrhosis twice, fatty degeneration twice; 
in one case there was an abscess following dysentery. In all other 
respects the microscopic appearance of the organ was normal. ‘The 
liver is, as a rule, enlarged, hyperemic, and shows proliferation of 
the connective tissue in the neighborhood of the portal capillaries, 
round-cell infiltration, and dilatation of the bile-capillaries. The eggs 
are found in the capillaries or free in the tissues in the periphery of 
the acini, usually surrounded by round-cells. Sometimes the central 
portions of the acini will be found degenerated, and the walls of the 
capillaries thickened, even in the absence of eggs. It is possible that 
these disturbances are due to the lesion of the kidneys and of the 
urinary passages. It may also be true that metabolic products of 
the parasite present in the portal vein are carried to the liver and exercise 
their toxic effect on the capillaries and the surrounding tissues. 

It appears that the parasites can leave the liver by way of the bile- 
passages. Gautrelet, for instance, found eggs of Bilharzia in a gall- 
stone that was passed with the symptoms of colic (following a course 
of Vichy water) by a patient of Willemins, twenty years after a two- 
year sojourn in Egypt. The eggs were also found in the liver tissue; 
they were impregnated with bile-pigment and incrusted with car- 
bonate of lime. 

In many cases of Distoma hematobium no hepatic symptoms are 
apparent since cirrhotic changes are absent or only mild. Occa- 
sionally the patient complains of indefinite pains in the liver region. In 


* British Med. Jour., Jan. 3, 1903. 


PARASITES OF THE LIVER. 831 


more pronounced and well-developed cases the organ is enlarged, and 
presents the picture of hypertrophic cirrhosis. Icterus and ascites 
are rare. Atrophy of the liver has been reported by Kartulis in 
cases in which there were very many parasites. If concretions form 
in the bile-passages around the eggs, the symptoms of cholelithiasis 
may appear. 

The diagnosis is based on the presence of characteristic lesions 
in the urinary organs, hematuria, the passage of eggs in the urine, and 
of the liver symptoms described. 

Treatment is limited to care of the diseased urinary passages, to 
the administration of a nourishing and strengthening diet, and to the 
exhibition of iron, etc. If possible, a change of climate should be ob- 
tained. 


LITERATURE. 


Lehrbiicher von Cobbold, Davaine, Leuckart, Mosler, und Peiper. 

Chaker, Mahomed: “Etude sur ’hématurie d’ Egypte,” Thése de Paris, 1890. 

Kartulis: “Ueber das Vorkommen der Eier vom Distomum haematobium in den 
Unterleibsorganen,”’ “ Virchow’s Archiv,” 1895, Bd. xcrx, p. 139. 

—‘ Ueber verschiedene Leberkrankheiten in Aegypten, : “Verhandlung des vIiti. 
Congresses fur Hygiene und Demographie in Budapest,” 1896, p. 650. 

Loos: “Zur Anatomie und Histologie der Bilharzia heamatobia, »°« Archiv fiir 
mikroskopische Anatomie,” 1895, Bd. xvi, p. 1. 


(F) PENTASTOMUM DENTICULATUM AND CONSTRICTUM. 


Pentastomum denticulatum is the larva of Pentastomum (lingua- 
tula) tzenioides, a parasite found in the nasal cavities, the frontal sinus, 
the ethmoidal sinus, and in the larynx of the dog, the wolf, and, less 
frequently, of the horse, the mule, and the sheep. Occasionally it 
enters the liver of man. The eggs of the parasite are swallowed and 
the embryos are liberated in the stomach; infection of human beings 
usually occurs from dogs, the embryos penetrating the liver after per- 
forating the walls of the intestinal tract. They are found with par- 
ticular frequency in the left lobe of the liver because they can get there 
by the shortest route after perforating the stomach wall (Zenker). 
Here the parasite becomes encysted and forms a larva, having numerous 
prickly processes and rings of chitin, also claws in the region of its cephalo- 
thorax. In general these animals, despite their formidable appearance, 
produce very slight disturbances. This may be due to the fact that 
they produce no toxic products, and also because they leave the intestinal 
tract as very small embryos and consequently cannot act as carriers 
of bacteria. . 

Laudon reports the case of a man who complained of pain in the 
liver, icterus, and gastric disturbances, epistaxis, and pain in the left 
nasal cavity for many years; finally he passed a female Pentastomum 
tenioides. It is a difficult matter to establish a causal connection 
between the liver affection and the presence of the parasite in this case. 

Pentastomata are frequently first found during autopsies. Zenker 
found the worm 9 times in 168 autopsies performed in Dresden; Heschl 
5 times in 20; Wagner once in 10. According to Sievers, they were 
found in the Pathologic Institute of Kiel 22 times in 3066 autopsies; 17 
times in the liver. 

Pentastomum constrictum is more dangerous (Linguatula constricta). 
Pruner found this parasite in the liver of a negro in Cairo (identified 


832 DISEASES OF THE LIVER. 


as Pentastomum constrictum by Bilharz and v. Siebold, from its difference 
from Pentastomum denticulatum—larger and more prickly). Bilharz 
in many cases found it in the liver and the lungs of negroes, and Aitken 
mentions two cases of encysted Pentastomum constrictum in the liver 
and the lungs. It would appear that this parasite can produce peri- 
tonitic irritation, but does not cause any symptoms that point directly 
to the liver. 


Bilharz und v. Siebold: ‘ Zeitschr. fiir wissenschaftliche Zoologie,”’ Bd. tv, p. 63. 
Cobbold: Loc. cit., p. 259. 

Laudon: “Berliner klinische Wochenschr.,’’ 1878, No. 49. 

Pruner: ‘‘Krankheiten des Orients,” 1847, p. 245. 

Sievers: “Schmarotzerstatistik,’’ Dissertation, Kiel, 1887. 

Zenker: “ Zeitschr. fiir rationelle Medicin,’”’ 1854, Bd. v, p. 224. 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 


(A) HYPERTROPHY OF THE LIVER. 
(Hoppe-Seyler.) 


Just as all lesions of the liver that lead to a decrease in the size of 
the organ are termed atrophic, so all processes that cause an increase 
are called hypertrophic. A great variety of such pathologic processes 
may be responsible for an increase in the volume of the organ, as, for 
instance, proliferation of interstitial tissues, the development of neo- 
plasms, the deposit of fat, of amyloid, etc., also an increased vascularity 
and, finally, the liver-cells themselves may enlarge or proliferate. Only 
that increase in the volume of the liver which is due to an increase in the 
size and number of the cells is properly called hypertrophy, or hyper- 
plasia, and only this form of enlargement will be discussed in this section. 
The words hypertrophy and hyperplasia are employed interchangeably, 
and no distinct difference between the two can be formulated from an 
anatomic point of view. In general, hypertrophy means enlargement 
of the volume of individual hepatic cells, hyperplasia an increase in the 
number of these cells. In all processes of this kind, however, that occur 
in the liver the two conditions are found coexisting. 

We distinguish further between circumscribed and general hyper- 
trophy. The former may be a vicarious or a compensatory enlargement 
of certain parts of the liver, to take the place of other parts that have 
been destroyed or have become functionally inactive. Again, the en- 
largement of the liver may be due to a benign, and ffequently to a con- 
genital tumor. The so-called vicarious hypertrophy corresponds to 
those processes that Ponfick and others have noted in animals after the 
experimental extirpation of large portions of the liver (compare page 
408). There occurs in this way a substitution for the missing tissue, so 
to speak; the acini enlarge, and there is an abundant new-formation 
of liver-cells, bile-passages, etc. The same thing occurs in echinococcus 
sritaiia abscess, or destruction of the liver tissue by trauma, syphilis, 
etc. 

Heller has noted a case in which the right lobe of the liver was almost 
completely destroyed by a cystic echinoccocus, and in which the left 
lobe enlarged until its size was as great as that of the right one. Diirig, 
Reinecke, and others report similar cases. Sometimes the lobus Spigelii 


eh ll 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 888 


and quadratus also become hypertrophic. The echinococcus alveolaris 
quite often causes hypertrophic enlargement of those portions of the 
liver that are not involved by the primary disease, and particularly of 
the left lobe (Posselt and others). Heller saw a vicarious hypertrophy 
of the left lobe following (probably) traumatic destruction of the greater 
portion of the right one. Virchow, in a case of tertiary syphilis, in which 
a large portion of the liver was destroyed, saw enlargement of the acini 
as well as of the individual cells of the portion of the organ that remained 
intact. Reinecke made the same observation. The nodular form of 
hyperplasia often seen after cirrhosis of the liver is well known; this, 
too, is a compensatory process, intended to replace destroyed cells. 
N odules of this kind may be as large as an apple though, as a rule, they 
are no larger than a pinhead or a pea. Kretz describes several larger 
tumors of the liver of this character, in which a distinct enlargement of 
the acini and an increase in the volume of the cells were seen. Sometimes 
structures of this character form transition stages to malignant adeno- 
mata, and to certain forms of carcinomata of the liver (Schuppel). Kelsch 
and Kiener have described similar processes in the liver following malaria. 

In certain cases of partial hypertrophy there are benign tumors, often 
congenital, which probably belong to the class of malformations. Roki- 
tansky, Hoffman, Klob, Mahomed, Simmonds, and Beneke have de- 
scribed tumors of this kind in which the acinous structure was indistinct, 
and which did not seem to participate in the functions of the liver. How- 
ever, they were not involved in the diseases of the latter organ. Occa- 
sionally these growths are separated from the parenchyma by a connec- 
tive-tissue capsule; in other cases they are not distinguishable from their 
surroundings. They have been discussed at length in the section on 
tumors (compare page 766). 

General hypertrophy and hyperplasia of the liver is seen in very 
vigorous people that are addicted to the abuse of alcohol. In cases of 
this kind the organ is usually very vascular and contains much secretion 
in the bile-passages; the acini are not enlarged, but are more numerous 
than normal. No changes are seen in the cells of the liver. 

The margin of the organ is rounded, and the liver is more solid than 
normal. In diabetes mellitus, also, the liver may present a similar 
appearance to the naked eye. On microscopic examination it will be 
found that the liver cells are filled with glycogen. As a result they are 
distended and rounded; their protoplasm is shiny and slightly granular. 
On the addition of a solution of iodid of potash in iodin the cell-contents 
are colored red. As the amount of glycogen in the liver-cells varies in 
different cases of diabetes, this change may be absent, and, in fact, is 
absent in the majority of cases, particularly if they are examined in the 
later stages of the disease. Under different circumstances the liver may 
be atrophic, flaccid, or tough, and the cells may be angular, not enlarged, 
and in a state of fatty degeneration. 

In the case of people who make-their residence in the tropics the liver 
is frequently found to be enlarged very soon after their arrival; and as 
soon as they remove from the tropics a reduction in the size of the organ 
may take place (Heymann). This enlargement has been termed hyper- 
trophy in cases in which no abscesses, etc., developed, and where all in- 
flammatory symptoms were absent. It seems probable, however, that 
changes of this character are to a large extent due to inflammatory pro- 
cesses, hyperemia of the organ, etc., and are due to the absorption of 

53 


834 DISEASES OF THE LIVER. 


toxic substances from the intestine, the blood, etc. With respect to this 
point we would refer to the sections on hyperemia and hepatitis (com- 
pare page 614 and page 626). 

In leukemia and pseudoleukemia there is a general enlargement of 
the liver and an increase in the size of the majority of the liver-cells. 
Infiltration of the connective tissue, however, and distention of the cap- 
illaries with leukocytes, as well as the formation of lymphomata, all play 
their part in the process, and it is therefore more practical to discuss this — 
form of hypertrophy in a separate paragraph in the section on tumors. 

The symptom-complex of simple hypertrophy eventually consists in 
the presence of a hepatic tumor, which may cause a feeling of pressure 
to the patient, but otherwise gives no evidence of its existence. 

In circumscribed hypertrophy or hyperplasia round tumors may oc- 
casionally be felt, of medium consistency; this is especially true if they 
happen to be situated in a portion of the surface that is accessible to 
palpation, or upon the margin of the liver. They may easily be con- 
fused with malignant tumors, though the absence of cachexia and metas- 
tases, the fact that the tumors develop slowly or do not grow at all, that 
they show no tendency to degeneration, etc., and finally exploratory 
incision, will prevent such an error in the diagnosis. Congenital tumors 
of this nature are very rare. In nodular hyperplasia the signs of cir- 
rhosis are usually quite pronounced, and sometimes the vicarious en- 
largement of a lobe to replace the diseased or absent portions of the organ 
can be determined both by percussion and palpation. 

General hypertrophy is manifested by an enlargement of the organ 
that can easily be determined by palpation or percussion. Often the 
liver is more resistant than normal. Symptoms of stasis in the portal 
system and in the bile-passages are altogether absent. Sometimes it 
may be possible to discover an increased production of bile, with an in- 
creased quantity of urobilin in the urine and in the stools. 

There is no need of any special therapy in simple hypertrophy, either 
of a local or a general kind. The removal of hyperplastic hepatic tumors | 
of the liver is of no avail, and the treatment of diabetes is not modified 
in any way by the presence of an enlarged liver. 


(For nodular hyperplasia, hypertrophic hepatic enlargements, see Tumors, p. 783.) 

Dirig: “Ueber vicariirende Hypertrophie,” “Miinchener med. Abhandlungen,”’ 
1, Reihe, 13. Heft. 

Frerichs: “Klinik der Leberkrankheiten,” Bd. 1, p. 201. 

Heller: “‘ Mangelhafte Entwickelung des rechten Ticheclag eas ” “Virchow’s Archiv,” 
1876, Bd. LI, p. 355. 

—Ziemssen’s “Handbuch der speciellen Pathologie und Therapie,’ Bd. vin, 
1. Halfte, 1. Abtheilung, p. 431. 

Heymann: “Ueber Krankheiten in den Tropenlaandern,” ‘Verhandlungen der 
physikalischmed. Gesellschaft in Wurzburg,” 1855, Bd. v, p. 40. 

Klebs: “Handbuch der pathologischen Anatomie,’ 1869, Bd. 1, 1. Abtheilung, 
p. 370. 

Ponfick: ‘ Experimentelle Beitrige zur Pathologie der Leber,” ‘‘ Virchow’s Archiv,” 
1895, Supplement zu Bd. cxxxviu, p. 81. 

Posselt: “Der multiloculare Echinococcus in Tirol,” ‘Deutsches Archiv fir klin. 
Medicin,” 1897, Bd. trix, p. 1. 

Reinecke: “ Compensatorische Leberhypertrophie,” Ziegler’s “ Beitrage zur patho- . 
logischen Anatomie,’ Bd. xxi, p. 238. 

Rindfleisch: “Lehrbuch der pathologischen Gewebelehre,” p. 411. 

Thierfelder : “‘ Ziemssen’s Handbuch,” 1878, Bd. vir, 1. Halfte, 1, Abtheilung, p. 377. 

Virchow: “Ueber die Natur der constitutionellen syphilitischen Affection,” ‘ Vir- 
chow’s Archiv,” 1858, Bd. xv, p. 281. 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 835 


(B) FATTY LIVER, 
(Hoppe-Seyler. ) 


We include in the term fatty liver all processes in the organ that 
are characterized by an increased presence of fat. Under normal con- 
' ditions the amount of fat present in the liver varies, and is dependent 
upon the character of the food. An abundant ingestion of fat increases 
the fat in the liver a few hours after eating, so that the peripheral cells 
of the acini contain more fat-globules at this time than several hours 
later. With regard to the physiology of this process we would refer to 
our introductory discussion on page 414. Under certain pathologic condi- 
tions we sometimes see a constant presence of 40 % of fat in the liver, 
instead of the normal 3 % to5 %. 

An abnormally large quantity of fat can usually be discovered in the 
liver from the naked-eye appearance. Such an appearance may, how- 
ever, be the result of an increased imbibition of the parencyhma of the 
liver with fat, in the absence of any pathologic fatty change in the pro- 
toplasm of the hepatic cells; or, again, the accumulation of fat in the 
liver-cells may be present at the same time with lesions of the cell-con- 
tents, as, for instance, degeneration of the protoplasm and of the nu- 
cleus, necrobiosis, and fatty degeneration of the parenchyma. Clinically 
these two forms of fatty liver should be distinctly separated. If the 
parenchyma of the liver is affected, and is involved in a degenerative 
process, and can no longer functionate normally, the disturbances will 
be considerable. If, on the other hand, the parenchyma is not degen- 
erated and merely contains a little more fat than normally, general symp- 
toms will seldom be observed, because the functionating power of the organ 
remains intact. For this reason fatty degeneration is chemically to be 
differentiated from fatty infiltration. It has been shown, however, that 
these two conditions may be present in combination, and that there 
may be an imbibition of fat (as in simple infiltration) in addition to a 
degeneration of the liver-cells with a disappearance of their protoplasm 
and replacement of the latter by fat. Also that as soon as the liver-cells 
become infiltrated with fat to such a degree that the function of the 
cells is damaged, a degeneration of protoplasm will occur that resembles 
closely the primary degeneration described above. 

Formerly the difference between fatty infiltration and fatty degen- 
eration was considered to be the following: It was believed in the first 
place, that in fatty infiltration the fat was derived from the food, or 
from the fat deposits throughout the body, whereas in degeneration it was 
formed from the dying protoplasm and the proteid constituents of the - 
cell itself. These views were founded chiefly upon the teaching of Voit, 
who stated that the fat of the body, provided it was not introduced with 
the food, was chiefly formed from albumin; Liebig, on the other hand, 
believed that it was derived from the carbohydrates. This view was the 
dominant one for many years, notwithstanding the objections formu- 
lated by F. Hoppe-Seyler. After Pfliiger, however, in a series of care- 
fully executed metabolic experiments, had reasserted the correctness of 
Liebig’s view, considerable discussion arose, and to-day the proteid of 
the protoplasm is no longer considered to be the source of fat in fatty de- 
generation, and it is believed that this fat comes from the subcutaneous 


836 DISEASES OF THE LIVER. 


adipose tissue, etc. The experiments of Lebedeff and Rosenfeld lend 
strong support to this theory. 


The latter was able to demonstrate that even in the form of hepatic degenera- 
tion produced by phosphorus, the large quantity of fat found in the liver-cell is 
carried there mainly from the other fat deposits of the body. Thus in dogs 
fed with mutton fat until the greater part of their fat consisted of the latter, and 
then starved and later poisoned with phosphorus, the liver-cells were found dis- . 
tended with fat, and this fat was mutton fat. 

Lebedeff even before this time had called attention to the fact that the fat 
of the liver and of the adipose layers was always the same, and that after feeding 
linseed oil to a dog that had been poisoned with phosphorus, foreign fat was found 
in the liver, and that consequently the fat of the liver could not have been formed 
from proteid but must have come from the adipose layer of the body. 

It was also shown that in the case of chickens, starved until there was no 
more fat present in their bodies, fatty liver did not occur after phosphorus-poison- 
ing. In such cases the fat had plainly not been formed from the proteid of the 
liver-cells. 


It would be too radical, however, to disclaim the possibility of the 
formation of fat from cellular proteid under certain pathologic condi- 
tions. That this can occur is indicated by the fact that carbohydrate 
is readily formed from proteid, and, as we know, fat can be formed from 
carbohydrate. The presence in certain cells of lecithin also signifies a 
fat-forming process within these cells (Heffter). 

Previous analyses had already shown that in phosphorus liver the 
amount of fat present did not correspond to the amount of proteid lost 
(v. Starck and others); and that for this reason the greater part of the 
fat found in the liver must be derived from the fatty parts of the body. 
Thus in addition to a degeneration, an infiltration had to be assumed. 

Infiltration of the liver-cells with fat is also found in degeneration 
of their protoplasm, such as is seen in phosphorus-poisoning. Degen- 
eration of the protoplasm can, of course, be determined by the increased 
nitrogen excretion in the urine. 

For all these reasons it is impossible to draw a sharp distinction be- 
tween fatty infiltration and fatty degeneration of the liver. 

The appearance of fat and the disappearance of the cellular elements 
of the liver parenchyma is probably analogous to the formation of fat 
in contraction of certain organs, as the kidneys, the pancreas, and the 
muscles. : 

All that we can really say is that a pathologic accumulation of fat 
may occur in the liver without degeneration and without functional im- 
pairment of the cells; and, again, that it may equally well occur with 
serious alterations of the cell protoplasm. Clinical symptoms are slight 
or altogether absent in the event of the function of the liver-cells remain- 
ing intact, even though the fat deposit may be great. Distinct symptoms 
appear, however, if the protoplasm and nucleus of the cell itself are 
affected. We may say, therefore, that in fatty liver the fat itself plays 
no essential réle in the causation of the clinical pathologic picture, not- 
withstanding the fact that it is the most conspicuous feature, both macro- 
scopically and microscopically. The chief point is the condition of the 
cell-contents. 

Etiology.—A marked deposit of fat in the liver may be the result of 
anomalies in the mode of life, in the general constitution of the patient, 
and in the quality and quantity of the food. 

If a diet rich in fat and carbohydrates is taken for a long time, the 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 887 


quantity of fat in the liver-cells increases as well as in all parts of the body. 
The liver in this case acts as a reservoir; for this reason the livers of 
children who drink very much milk, and of adults who eat large quanti- 
ties of fatty and carbohydrate food, contain very much fat. 


In fattening animals food containing an excess of carbohydrate is given (e. g., 
maize or noodles in geese), and a fatty liver is produced in this manner. Also when 
the yolk is absorbed, the chick embryo shows an accumulation of fat in the liver 
which disappears later on. If dogs are fed with large quantities of fat, fatty liver 
is developed (Magendie, Frerichs). 


The tendency to such an accumulation of fat is encouraged by lack of 
exercise, of bodily and mental activity, by life in small, warm rooms, be- 
cause under these circumstances metabolism is not active, and oxidation 
processes are less thorough. Under these circumstances the carbohy- 
drates are not completely decomposed into carbonic acid and water, and 
instcad, owing to deficient oxygenation, fat is formed from them. For 
this reason fatty liver is seen in people who do not exercise very much, 
who shirk mental effort, and like to sit still in warm rooms. In 
prisoners, or in people who have to remain in bed for a long time (rest- 
cure), in paralyzed people, etc., an enormous deposit of fat may occur. 
Animals that are to be fattened are kept in narrow, warm stables for the 
same reason. 


It still appears to be questionable whether the acute fatty degeneration of 
the new-born can be attributed to anomalies in the supply of nourishment. A 
similar condition is seen in lambs and hogs (Furstenberg, Roloff), developing during 
fetal life. It is attributed to deficient exercise and to a deficient ingestion of salt 
by the mother, followed by an excessive production of fat, and consequently by 
an abnormal quantity of fat in the blood. The milk of these animals also contains 
more fat than normal, Birch-Hirschfeld attributes the condition in men partly 
to umbilical infection, which naturally would first involve the liver. In other 
words, he considers the condition as an infectious form of fatty liver. Infections 
of the body that start from other points—for instance, the intestinal tract—must 
also be prominently considered. 


In obesity proper there seems to be on the part of the tissues a par- 
ticular tendency to the formation of fat that has never been explained. 
Such phrases as reduced vitality, deficient oxidation-powers of the cells, 
etc., have been employed, without offering anything new in the way of 
an explanation. Obesity and fatty liver undoubtedly occur in many 
families. The condition is particularly frequent in the middle years of 
life, and is seen more frequently in women than in men, and particularly 
in the former after the menopause. The same result is brought about by 
castration, and disturbances of the thyroid gland are also said to favor a 
deposit of fat.. That all these unexplained processes play a réle in the 
formation of fat is certain; yet people are seen who indulge in a diet con- 
taining abundant fats and carbohydrates, who do not exercise the body 
or the mind, and whose digestive organs are perfectly normal, and who, 
nevertheless, do not grow fat; whereas, on the other hand, certain people, 
although they eat very little, grow very corpulent. 


That there must be some hereditary, racial peculiarity is indicated by experience 
in cattle-raising also (English hogs, certain forms of cattle, etc.). : 

It has been claimed that in obese subjects there is a deficient secretion of bile, 
and as a result a decreased elimination of fat by these channels from the liver, 
so that ultimately there is an accumulation of fat. This view, however, is purely 
hypothetic, since we are as yet unable to measure the quantity and the composition 
of the bile secreted by the liver during life. 


838 DISEASES OF THE LIVER. 


The process of oxidation in the tissues is, of course, seriously dimin- 
ished if there is a deficient supply of oxygen, such as may be due to a lack 
of hemoglobin in the blood. For this reason an abnormal deposit of fat, 
particularly in the liver, readily occurs in anemia (chlorosis, leukemia, 
pernicious anemia). Moreover, a large proportion of obese people, 
particularly women, are anemic. If blood is repeatedly withdrawn from 
animals, the fattening process is aided; this procedure corresponds to the 
processes that take place in certain intoxications that lead to fatty liver. 
The fatty liver of consumptives has been attributed to lack of oxygen 
following a decrease in the breathing-space of the lungs. In other 
diseases of the lungs, however, as in emphysema, pneumonia, contraction 
of the lungs from pleurisy, etc., fatty liver is not found, so that we must 
assume that in the former disease other factors are concerned. Dis- 
turbances of the circulation, as in congestion of the liver and in tumor- 
- formation, frequently lead to a fatty degeneration of the liver-cells. 
Thus fatty change of the peripheral portions of the acini is seen in venous 
stasis, forming the well-known picture of nutmeg liver. The red center 
of the acini is clearly distinguished from its yellowish periphery. In 
carcinomata and other tumors a zone of fatty tissue surrounds the 
growth. 

Intoxications of varying kind play a very important réle in fatty 
degeneration of the liver. The action of such a poison may consist in a 
direct effect upon the protoplasm of the cell, causing degeneration 
and a replacement of the destroyed protoplasm by fat; or the effect of 
the poison may be exercised upon the blood, causing a destruction of 
hemoglobin, and consequently a reduction in the oxygen-carrying func- 
tion of the blood. Here we see the same conditions as in anemia (vide 
above). Our knowledge in regard to these different factors is too slight 
to allow us in any given instance to determine which effect of the poison 
has produced the changes in the liver. 

Phosphorus-poisoning is probably the most important of this class, 
and has been made the subject of the most careful investigation. Von 
Hauff was the first to call attention to the hepatic changes in phosphorus- 
poisoning. His experiments, however, and those of others, as Kohler 
and Renz, combined with numerous clinical observations, do not enable 
us to say in what manner phosphorus-poisoning acts upon the paren- 
chymatous cells of the liver. There can be no doubt that oxidative 
processes are reduced, that hydrolytic processes (particularly in nitrogen- 
metabolism) are increased, that the syntheses, which occur with the 
elimination or the formation of water, are hindered. No changes can be 
demonstrated in the red blood-corpuscles; in fact, they may be increased 
in the beginning (Taussig, v. Jaksch). In intoxications that do not end 
so he the first few days the amount of hemoglobin is gradually 
reduced. 

Lack of oxygen as a result of destruction of hemoglobin can, therefore, 
not be regarded as the cause of this anomaly of metabolism. The dis- 
turbance of the heart and circulation may, however, be made responsible. 
In pbosphorus-poisoning the amount of oxygen consumed and of carbon 
dioxid given off are both decreased (Bauer and others), the amount of 
carbon dioxid in the blood being also reduced (H. Meyer). On the other 
hand, in cases lasting over a long period, which do not terminate fatally 
within the first few hours or days, an increased excretion of nitrogen is 
discovered that must be due to an increased disintegration of proteids 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 839 


(Storch, Bauer, and others). The urea is often increased. In many cases 
ending fatally the ammonia-excretion is enormously increased (Englien, 
Miinzer), and there is a corresponding relative decrease in the output of 
urea. This is due to a disintegration of cells, and to the formation of acid 
products (lactic acid—Schultzen and Riess, Araki, and others) that require 
alkali for their neutralization. Minzer’s experiments demonstrate that 
the increased excretion of ammonia is due to an increased formation of 
acid, and is not a manifestation of the disturbance of the urea-forming 
function of the liver. This investigator determined that the administra- 
tion of alkalies decreased the excretion of ammonia, but that in rabbits, 
which do not possess the power of forming ammonia in acid intoxication, 
no such increase occurred after phosphorus-poisoning. It may be 
assumed, therefore, that acid intoxication plays a certain réle in such 
cases, and manifests itself by a decrease of the alkalescence of the blood, 
Occasionally tyrosin or leucin appears, and indicates a disintegration of 
proteid combined with an insufficient oxygenation of catabolic products 
(A. Frankel, Beaumann, and others). Peptone (Schultzen and Riess, 
Robitschek, and others) or a body similar to it (Harnack) may appear 
in the urine. These products are, however, only rarely found. As a 
result of the breaking-up of lecithin, usually after the first stage of the 
poisoning is over (twenty-four hours), there may be an increase in the 
excretion of phosphates (Miinzer). Nuclein catabolism does not seem to 
play any rdéle in this increased excretion of phosphoric acid, as is deter- 
mined by the absence of an increase in the uric-acid excretion. Sugar 
has also occasionally been found in the urine (Bollinger, Huber, Araki). 
At first there is a decided fatty infiltration of the liver-cells, beginning 
a few days after the intoxication with phosphorus, and rapidly leading 
to a distention of the liver-cells with fat. This may be so intense that 
nothing can be seen of the nucleus or the protoplasm; these structures, 
however, remain well preserved, and reappear when the fat is removed. 
At the same time there is a decrease in the quantity of lecithin present in 
the liver (Heffter), so that we may assume that a portion of the fat.is 
formed from this substance. This fact is in harmony with the increased 
excretion of phosphates already noted. At the expiration of a few days 
signs of disintegration of the parenchyma appear, manifested by the 
above-mentioned disturbances of metabolism. In poorly nourished 
individuals and in such as have only a slight adipose fatty covering, fatty 
degeneration of the liver develops in phosphorus-poisoning from the very 
beginning; thus a picture of acute atrophy may be created which ordi- 
narily would not appear before the second week. If death does not occur, 
as usual, by the end of the first week, atrophy of the liver may 
take place later on, and, as a rule, in the first half of the second week 

(Hedderich). The quantity of fat decreases, the liver-cells perish, and a 
symptom-complex develops similar to that observed in acute yellow 
atrophy (compare page 641). 

* Arsenic and antimony poisoning may lead to similar fatty degener- 
ation of the liver, as may also intoxication by copper, mercury, and alu- 
minium. Certain mineral acids, as hydrochloric, sulphuric, and nitric, 
may also cause moderate degrees of fatty liver. Other substances that 
may cause the condition are carbon monoxid, petroleum, chloroform, iodo- 
form, ethyl-bromid, nitrous oxid, carbolic acid, phloridzin, ricin, abrin, 
chronic morphin-poisoning, poisoning with fungi (mushrooms), certain 
meat-, fish-, and mussel-poisons, spoiled maize (pellagra), etc. In addition 


840 DISEASES OF THE LIVER. 


to the direct effect on the liver-cells, many of these substances destroy | 
hemoglobin and diminish oxygenation, a process that is often manifested 
by an increased excretion of lactic acid. Thus in poisoning with many 
substances that lead to the destruction of hemoglobin fatty degeneration 
of the parenchyma may be seen. It may be noted, finally, that extensive 
burns may be responsible for these changes in the liver in the same way. 

Fatty degeneration of the liver is especially frequently seen in drunk- 
ards. Chronic alcoholism leads to deficient oxidation of both the ear- 
bohydrates and fats, in that alcohol reduces oxygenation by using up a 
large proportion of the oxygen for its own combustion. This has been 
determined from the decrease in the power of assimilation of oxygen, and. 
in the excretion of carbonic acid. Asa result there is a great accumula- 
tion of fat in all parts of the body, and also in the liver. This condition 
may be combined with the cirrhotic changes so often produced by alcohol, 
and thus the picture of cirrhotic fatty liver may be created (Sabourin, 
Garel, Merklen). Fatty liver is found in the majority of drunkards who 
die in delirium tremens (Frerichs, Murchison, and others). Pupier, Mag- 
nan, Strassmann, Sabourin, and others have succeeded in causing fatty 
degeneration of the liver experimentally by the administration of small 
doses of alcohol over a long period of time. Affanassiew and v. Kahlden 
administered ethyl-alcohol (the first-mentioned author mixed it with 
amyl-alecohol) during a long period, and observed a consequent infiltra- 
tion of the stellate and hepatic cells. They did not, however, succeed 
in producing cirrhosis of the liver, and other authors (Siegenbeck van 
Heukelom) also failed in this attempt. [Vzde Cirrhosis for a qualifi- 
cation of this statement by subsequent experimental results.—Eb.] 

Ungar, Strassmann, and Ostertag have noted fatty degeneration of 
the liver following prolonged administration of chloroform, though it does 
not appear from their examinations of the tissues whether the cell paren- 
chyma became fatty or whether there was simply a fatty infiltration. 
A. Frankel, on the other hand, observed well-developed necrosis of the 
liver-cells after narcosis of long duration. Certain of the cells were in a 
state of fatty degeneration. 

From a clinical standpoint phosphorus- and alcohol-poisoning furnish 
the most interesting toxic forms of fatty liver; all the more rare forms 
of poisoning present conditions in which the general disease-picture is so 
severe that fatty degeneration of the liver is comparatively of no impor- 
tance, and is often completely overlooked. 

Infectious diseases may also produce fatty liver. Fatty degeneration | 
of the liver-cells occurs chiefly owing to the presence of toxic substances 
that are produced by bacteria, and act in a similar manner to mineral or 
vegetable poisons, damaging the protoplasm and perverting nitrogen 
metabolism. We see fatty liver in septicopyemic diseases, particularly 
if they are of long duration; for instance, in puerperal fever, osteomyel- 
itis, severe cases of syphilis, prolonged suppuration, etc. The liver in 
such cases often has fatty degeneration that can be detected with the 
naked eye; the organ is large, soft, frequently fragile, and of a distinct 
yellowish color. .Charrin and others have succeeded in producing fatty 
degeneration of the liver in animals by injecting cultures of Bacillus 
pyocyaneus. In many cases there is so much hyperemia in the infectious 
form of fatty liver that the fat cannot be recognized with the naked eye, 
and only microscopic examination reveals its presence. Fatty degener- 
ation is also seen in smallpox, in severe cases of diphtheria and scarla- 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 841 


tina, and occasionally in typhoid, cholera, pneumonia, and eclampsia, 
though it is not clinically significant. In diphtheria it is probably ex- 
clusively due to the actions of toxins. 

Certain diseases of the digestive tract may also lead to fatty degener- 
ations of the liver; as, for instance, chronic dysentery, and in children 
catarrhs of the gastrointestinal tract. [A thorough study of the changes 
in the liver in gastroenteritis of infancy has been published by Lesle and 
Merklen.* They found no specific changes, and in the main an epithelial 
degeneration or sclerosis or simple congestion, according to the duration 
of the disease. Glycosuria they found sometimes to occur in the ehronic 
but not in the acute forms, and ascribed its occurrence to faulty hepatic 
action.—Ep.] It is possible that the fatty liver frequently seen in rachitic 
children also belongs in this category. 

In infectious diseases inflammatory processes are frequently though 
not always seen, coexistent’ with degenerative changes. This feature 
distinguishes such a fatty liver from that seen after pure intoxications, the 
characteristics of which we have described in another place in the section 
on hepatitis as well as those of fatty degeneration of the liver parenchyma 
in acute yellow atrophy and in pernicious icterus. 

Finally, it should be observed that fatty liver is often seen in phthisis. 
In cases of this kind fat is frequently found in the blood, and may be 
present in such abundance as to give the serum a milky appearance. We 
are justified, therefore, in assuming that the fat found in the liver is de- 
posited there from the adipose tissues of the body which are in a state of 
rapid dissolution. For this reason fatty liver is more frequently seen in 
tuberculous women than in men, since the former have, as a rule, larger 
fat deposits. When fatty liver is found in men, it is usually observed 
that the subject has been well nourished previously. Certain toxic sub- 
stances that are formed in tuberculous foci, particularly in the presence 
of a mixed infection or in autointoxications, and other toxic principles 
formed in the intestine, may also play a réle. Drugs, especially such as 
are destructive to the hemoglobin; certain narcotics which are frequently 
administered in large quantities; and, finally’ the overabundance and 
the fatty character of the food usually given to phthisical subjects 
(cod-liver oil, alcohol); may all be concerned in the process. 

_ Fatty liver often develops in subjects suffering from carcinoma or 
other malignant tumors. Here the condition is probably due to a rapid 
loss of the adipose layer and the transportation of this fat to the liver. 
The reason for this occurrence we understand all too imperfectly. To 
what extent the rapidly appearing anemia, or how far the toxic products 
that are formed in the neoplasm or as the result of micro-organismal 
action, play a réle, it is difficult to state. 

The etiology and pathogenesis of fatty liver are still obscure. We 
know too little of the processes that occur in a cell during fatty degenera- 
tion; moreover, the causes of fatty infiltration have been so imperfectly 
studied, owing to the complicated processes in the liver, in which degen- 
eration and infiltration are so closely related and so often coexistent, that 
it is difficult even to speculate as to the probable sequence of events in 
the hepatic cells. [Freeman}t has made an extensive study of fatty liver, 
and finds that it occurs with considerable frequency in infants and chil- 
dren. The general condition of the child, as measured by the body fat 


* Revue Mens. des Med. de l’Enf., Feb. 1, 1901. 
t Archives of Pediatrics, Feb., 1900. 


842 DISEASES OF THE LIVER. 


seemed to have no relation to the fat deposit in the liver. He also found 
that fatty liver occurs rarely in the following wasting diseases: Mar- 
asmus, malnutrition, rachitis, syphilis, unless an acute disease be super- 
imposed. In tuberculosis he finds it not more frequent than in other 
diseases. Most often it was found to be associated with acute infectious 
diseases and gastro-intestinal disorders.—ED.] 

Pathologic Anatomy.—A fatty liver in which there is simple infil- 
tration is usually increased in all diameters, and may weigh as much as 
4kg. It has a low specific gravity, however, and will readily float in 
water. In anormal liver there is from 1.8 % to 5 % of fat, and 72% 
to 78 % of water; in fatty infiltration there is from 19 % to 43 % of fat 
and only 62 % to 43 % of water (Perls). In phosphorus liver there is 
from 17 % to 32% of fat, and only 66 % to 57 % of water (Perls, v. 
Hoslin, Lebedeff, v. Starck). 

The margin of the organ is usually rounded, and its surface is smooth 
and shiny except in those cases in which cirrhotic processes such as are 
due to alcoholism (cirrhotic fatty liver) cause retraction of tissue and 
granular protuberances. The liver is usually of a yellow color, and some- 
times the small veins may be seen arranged in little stars through the 
surface. The outlines of the acini are clear, but often not as distinct as 
in the normal organ. The consistency is usually increased, at least in the 
dead; this may, however, be due to a solidification of the fat following 
postmortem cooling. A fatty liver that is warmed to the body-temper- 
ature is usually much softer and the imprint of the fingers can be clearly 
seen on its surface. In the dead the vascularity also appears to be less 
than is actually the case. Although during life the cells are distended 
with fat, and as a result the blood-vessels are somewhat narrowed, still 
this distention is not so great as it appears in the dead organ; thus it may 
be said that stasis seldom occurs in the portal area as a result of uncom- 
plicated fatty liver. On transverse section the yellow color and the slight 
vascularity are conspicuous features. The blade of the knife is covered 
with grayish-white fat; the acini usually protrude somewhat over the 
cut surface. If, at the same time, there is stasis as a result of deficient 
heart action or of some obstruction in the lesser circulation, the middle 
of each acinus will be reddish, and the multicolored picture of nutmeg 
liver will be presented. 


In cases in which there are present fats with a melting-point higher than the 
ordinary, as the glycerids of stearin and palmitin, the liver appears more trans- 
lucent and whitish, like wax, or somewhat yellowish in color. It is less dense if 
more oleic acid is present (Rokitansky). 


Icterus is absent in that form of simple fatty infiltration which is 
found in obese, in phthisical, in cachectic, and in anemic persons. It has 
been stated that the bile is scanty in these cases, and that, when the pro- 
cess is severe, it contains no pigment; the foregoing is true probably in 
exceptional cases only, in which other pathologic processes are actively 
present in the liver at the same time. 

The microscope reveals an enormous number of large and small fat- 
globules in the acini; these may be so numerous that nothing is seen of 
the cells. This appearance is particularly striking in the periphery of 
the acini. If the fat is extracted, it will then be found that the proto- 
plasm and the nuclei of the cells are well preserved, and that both can 
be demonstrated with the ordinary stains. | 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 843 


Occasionally fatty infiltration appears in the form of small fat nodules near 
the edge of the acini. This is often seen in phthisis (Sabourin. ) 


A similar picture is seen in cases of marked fatty degeneration of the 
liver following intoxications, for instance, during the first week of phos- 
-phorus-poisoning. The contour of the organ remains the same, but the 
abundant deposit of fat is shown in the color and in the greasy coating 
on the section knife. In cases of this kind icterus usually appears after 
a few days, so that the surface as well as the transverse section of the organ 
appear saffron yellow. 


In experimental phosphorus-poisoning the fat is seen in the liver-cells, and 
also in Kupffer’s stellate cells. At the same time, degeneration of nuclei and vacuoli- 
zation of protoplasm are frequently noted (Ziegler and Obolenski, and others). 
Sometimes focal necrosis is seen. In arsenic-poisoning very similar changes are 
seen in the parenchyma, though of not quite so pronounced a type (Ziegler and 
Obolenski, Wolkow, and others). 

Here and there small hemorrhagic foci are observed in the liver tissue. In the 
biliary pasages and in the gall-bladder there is a pale, slimy bile. In the first 
stages of poisoning, when icterus is absent the bile in the passages contain more 
bile-pigment than normal owing to irritation of the liver-cells. Icterus is probably 
due both to an occlusion of the small bile-passages, and to injury of the cell pro- 
toplasm, so that the bile constituents are no longer excluded from the blood (see 
page 426). 


In cases of intoxication that terminate fatally within a few hours fatty 
degeneration is absent. If the intoxication is not so severe, however, 
and if death fails to occur within the first few days, atrophy is sometimes 
seen aS early as the second week; the liver then decreases in size and 
grows soft and flabby, and small reddish areas are seen in a yellowish 
matrix. In the reddish portions the liver parenchyma is found to have 
disappeared. 

On microscopic examination of an ordinary case of phosphorus intox- 
ication the liver-cells will be distended with fat, whereas the majority 
show no changes of their protoplasm or their nuclei. In the bile-passages 
will be seen a scanty amount of slimy, colorless bile. In cases that persist 
for a long time, necrosis of the liver-cells is observed in the center of the 
acini, so that nothing remains but fat-globules, granules, and detritus, 
all of which are bile-tinged. 


In cases of this kind the similarity to acute yellow atrophy is so great that 
some authors have identified the two conditions. A careful histologic examination, 
however, reveals the distinct differences (compare page 633). 

Mannkopf and others have described an interstitial proliferation of connective 
tissue between the acini combined with round-cell infiltration. This condition 
is not found in many cases of acute phosphorus-poisoning, though if the intoxication 
is carried on with small doses and over a long time (Wegner, in rabbits) these changes 
are indeed seen (Weyl, Aufrecht, Ackermann, and others). 

Other authors, again, have failed to find such interstitial changes under the 
same conditions (Krénig, Dinckler, Ziegler and Obolenski). 

In pregnant women the effect of acute phosphorus-poisoning is manifested in 
the liver of the fetus, which may be found in a condition of fatty degeneration 
(Friedlander, Miura). 

Alcoholic fatty liver differs in no way from that seen in obesity, cachexia, 
etc. Here, too, proliferation of the interstitial tissues is occasionally seen, par- 
ticularly around the branches of the portal vein (Sabourin and others). The liver 
is large and hard, and the contractions on its surface and on transverse sec- 
tion result in distinct cicatricial indentations where the intra-acinous tissues 
existed. These cases probably consist of fatty liver complicated by cirrhosis; 
possibly both conditions originate at the same time. They are seen particularly 
In subjects that are obese. In the ordinary form of alcoholic cirrhosis of the liver 


844 DISEASES OF THE LIVER. 


such a picture is rare; in the atrophic form of cirrhosis there is a slight fatty degen- 
eration of the liver-cells, but here we are dealing with nutritive disturbances caused 
by. the contraction of connective tissue and by compression of blood-vessels. In 
the cirrhotic hypertrophic form of fatty liver the fat may come in part from the 
fatty layers of the body. Tuberculosis is frequently seen in combination with 
cirrhotic fatty liver (compare pages 730, 732). 


As in the case of phthisical subjects, the blood-serum of alcoholics is 
frequently chylous owing to the abundant quantity of fat suspended 
in it. 

The livers of persons who have died from prolonged chloroform- 
narcosis show, besides an extensive fatty degeneration of the cells, a 
cellular necrosis (E. Frankel). 

As the poisons reach the liver from the hepatic artery or the portal 
vein, the first changes of the parenchyma are usually seen in the periph- 
ery of the acini; even later on the lesions are all most pronounced in this 
location. 

In many intoxications, and particularly those that are produced by 
blood-poisons, there is an alteration of the protoplasm together with the 
formation of fat in the cell; in other words, a fatty degeneration. This 
_may be very slight and be noted at the autopsy merely as an accidental 
finding of no great import. The chief lesions are usually found in the 
heart or the kidneys, and have more significance with respect to the course 
of the disease than the fatty degeneration of the liver. 

In infectious fatty degeneration of the liver, distinct symptoms of 
inflammation are often observed that are more appropriately discussed 
under Hepatitis than in this condition. Only in septicopyemic forms of 
hepatic disease do we witness such an enormous accumulation of fat as 
in the forms discussed above. Here, too, the liver may be yellow and 
soft, and very much enlarged. Gastro-enteritis in children frequently 
leads to fatty degeneration of the liver, starting, as a rule, from the per- 
iphery of the acini, and only producing a local injury to the cells as 
manifested by deficient staining properties of their nuclei. In rare cases 
there is fatty degeneration, and the cells are completely involved; the 
process in such case is not only that of degeneration, but of infiltration as _ 
well (Thiemich). We may assume that certain metabolic bacterial pro- 
ducts exert a toxic action, although the bacteria themselves still are 
present in the liver-tissue. If certain pathogenic micro-organisms (strep- 
tococci, staphylococci, etc.) make their way into the liver, there will be 
found localized areas of fatty degeneration resulting from necrosis and 
fatty degeneration of the parenchyma, in addition to round-cell infiltra- 
tion. Such lesions may precede abscesses of the liver. Circumscribed 
fatty infiltration is, however, rare (Sabourin). Other changes in the 
liver parenchyma seen, at the same time with fatty degeneration, in 
cholera and typhoid, we will not discuss in this connection. In certain 
cases of fatty degeneration due to infection the condition cannot be rec- 
ognized owing to the marked hyperemia, and can only be discovered 
microscopically. 

Symptoms.—In ordinary fatty liver, such as occurs in obesity, anemia, 
cachexia, phthisis, etc., also, as a rule, in alcoholism, the organ is soft, . 
and often extends well into the abdomen, though its outline can be de- 
termined better by percussion than by palpation owing to the softness of 
the tissue. Especially in obese people are the outlines of the organ very © 
difficult to determine, and it may be impossible to palpate the margin. 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 845 


In carcinoma and phthisis where the adipose layers and the muscles 
are reduced, the enlarged liver may be seen as a prominent tumor, and 
can usually be readily palpated. In such cases, also, the soft character 
of the liver is conspicuous, and the feeling is created that the organ might 
be indented by the pressure of the fingers. Amyloid liver appears of the 
same general form as fatty liver; it is, however, if anything, harder than 
normal, and can thus be readily differentiated. The surface of simple 
fatty liver is smooth, the margin is rounded, and the general contour 
unchanged, despite the enlargement. 


If the fatty layer disappears, small fat-nodules frequently remain in the sub- 
cutaneous tissue, and may simulate small nodular protuberances on the surface 
of the liver. This occurs particularly often in cachexia. If the patient is instructed 
to breathe deeply, it will be found that these nodules do not move with the liver, 
and alter their position only slightly. 


Percussion dulness extends further down into the abdomen than nor- 
mally; as a rule, its area is not increased upward. The liver is not painful 
to pressure, and the patient does not complain of spontaneous pain; fre- 
quently there are no subjective symptoms whatever. Occasionally the 
patient will complain of a feeling of pressure and fulness in the right side 
or in the epigastric region. In uncomplicated fatty liver symptoms of 
portal stasis are absent. Ascites and splenic tumor are never seen as 
the result of simple fatty degeneration of the liver. If such symptoms 
are present, they indicate a complicating cirrhosis. There may also be 
present carcinomatous and tuberculous lesions of the peritoneum or the 
spleen may be enlarged from some previous disease, or may be another 
symptom of the primary disease (as, for instance, leukemia) which is the 
cause of the fatty liver. It is possible that in severe degrees of fatty 
liver there may be, after all, a slight hindrance to the flow of portal blood 
as manifested by chronic catarrh of the intestinal tract. There may also 
be gastric disturbances, lack of appetite, a tendency to meteorism, flatu- 
lence, constipation, slimy stools that occasionally become diarrheic, and 
hemorrhoids, all symptoms attributable to the congestive catarrh. 
These symptoms can, of course, also be explained by the improper mode 
of living that is so frequently seen in obese subjects who live an easy life. 

Icterus is not a symptom of fatty liver, owing to the fact that the fat 
cannot compress the bile-passages and lead to icterus from stasis; also 
because there are no disturbances of the cell protoplasm to favor the 
entrance of bile-products into the blood. The production of bile may 
be so slight in many cases that very little enters the intestine. This is 
particularly true in cases of deficient feeding, or in cases of reduced 
digestive and assimilative powers, as, for instance, in carcinoma, phthisis, 
anemia, etc. In diseases of this character the secretion of bile will be 
diminished, and consequently the production of bile-pigment; so that 
an analysis of the urine may even reveal a decrease of urobilin. If there 
is marked disintegration of blood-pigment, or if there are hemorrhages 
in the internal organs, the quantity of urobilin will appear to be increased ; 
but later, even under these circumstances, it may be decreased. If the 
biliary secretion is deficient, the stools assume a whitish-gray color and a 
clay-like consistency ; in other words, they become acholic. 

The appearance of the patient and the condition of the other organs 
will naturally depend upon the primary disease; thus, the fatty covering 
and the large limbs of obese people and of alcoholics are in distinct con- 


846 DISEASES OF THE LIVER. 


trast to the excessive emaciation and the loss of muscle-tissue as seen in 
phthisis, carcinoma, etc. In the first category, the vascularity of the 
skin and the mucous membranes is increased, and there is frequently 
some disturbance of the action of the heart, so that cyanosis appears; 
whereas in the latter form of diseases the skin is pale and vellowish-white. 
There are no characteristic lesions of the skin, as claimed by Addison and 
others. The latter is fatty and oily in some cases of obesity and alco- 
holism; in cachexia, however, it is very fragile and dry, shows a tendency 
to desquamate, and is a true pityriasis tabescentium. Occasionally 
edema and anasarca are seen; they are due to some primary disease, and 
are not, as has been claimed by some, the result of fatty liver. Anemia 
and cachexia are frequently found at the same time, in the same 
subject. 

The changes in the liver exert scarcely any influence upon the course 
and the outcome of the disease. Disturbances in other organs, particu- 
larly in the heart, are much more important. The patient may die after 
weeks or months or years, as might be expected from the primary disease ; 
or he may succumb to heart failure following myocarditis, or fatty de- 
generation of the heart muscle, or to some intercurrent disease, to maras- 
mus, severe anemia, apoplexy, kidney lesions, ete. 

Toxic fatty liver, as, for instance, that of phosphorus-poisoning, has 
an important bearing with reference to the subsequent course of the dis- 
ease. Here, too, however, the degeneration of the heart muscle is the 
chief cause of death. In the first stage, that lasts only twenty-four 
hours, no hepatic symptoms are noticed. The chief symptoms of this 
stage are gastro-intestinal; there is vomiting of masses containing phos- 
phorus, pain in the epigastric region, etc. Death may occur if large 
quantities of poison are introduced in a readily absorbable form; such 
cases are, however, rare. On the other hand, if the poison is ingested in 
a form that is only slightly soluble, or not soluble at all, or in case vomit- 
ing occurs, or lavage is instituted, the disease may be cured without having 
caused any other symptoms than the gastric disturbances described. 
The patient usually feels better before entering upon the second stage. 
This period of comparative well-being lasts two or three days, so that the 
impression is created that the case is cured. During this time there are 
usually a slight loss of appetite, pain in the region of the stomach, and 
constipation. On the third or the fourth day of the disease, rarely sooner, 
sometimes a few days later, icterus of the skin and mucous membranes 
appears, combined with other symptoms of absorption of bile-constituents 
in the blood; 7. e., the presence of bile-pigment in the urine, decoloration 
of the feces, and sometimes urticaria. The icterus increases rapidly in 
intensity, more rarely it creates only a slight yellowish discoloration of 
the skin. At this time a feeling of tension and pain appears in the liver 
region, the organ may be enlarged, sensitive to pressure, and feel tougher. 
The surface remains smooth. The enlargement is usually uniform, and 
is rarely seen in one lobe only. In the course of the following days the 
volume of the organ continues to increase. 


_ Imrare cases there is not only no enlargement, but a gradual decrease in the 
size of the organ. (For definite instances see Hedderich.) 


Other symptoms are painful vomiting, and frequently of bloody 
masses. The pulse is at first slow, and later, shortly before death, is 
very rapid, and at the same time small and weak. The heart is dilated, 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 847 


the sounds not clear, and there are blowing murmurs at the orifices. 
Bloody diarrhea and hemorrhages into the skin and the mucous mem- 
branes may be seen, and occasionally there is rise of temperature. Just 
before death the temperature may either become subnormal or may be 
very much elevated. Death usually occurs at the end of the first week, 
and frequently sooner, occasionally during the second week. In many 
- cases a decrease in the size of the liver is noted before death as a result of 
the disintegration of the liver substance. This is seen particularly in 
cases that live into the second week. (Compare Hedderich.) The mental 
faculties remain clear until the end. Death either occurs rapidly in 
collapse; or there may be delirium, coma, or convulsions, as in other 
forms of typical hepatic intoxication (cholemia). 

If the disease persists for more than a week, the case may recover, the 
icterus decrease, and the liver regain its normal size. Even if a certain 
amount of atrophy has occurred regeneration seems possible, and the 
organ gradually grows, the appetite returns (in fact, the patient may be 
very hungry), and the case recovers. Convalescence is usually very 
protracted, and may extend over many weeks. 


West describes the case of a woman who recovered from phosphorus-poisoning 
but who, several weeks after recovery, suddenly developed icterus and a swelling 
of the liver, and died six days later. He attributes this to the disintegration of 
the liver-cells following the intoxication. It is possible that there is a connection 
only in the sense that the liver was already diseased, and that an intercurrent 
infection destroyed the patient. As the bile-passages frequently contain bacteria, 
especially if the secretion of bile is deficient, it is possible that many cases of atrophy 
of the liver and degeneration of the parenchyma are caused by the action of these 
germs. Experimental investigations in this respect are not extant. [Vide Experi- 
mental Procedures, under Alcoholic Cirrhosis.— Eb. ] 


There are marked changes in the quantity and the composition of the 
urine. Bile-pigment and bile-acids are present, and, in severe cases, 
lactic acid, peptone [albumoses.—ED.] and, rarely, tyrosin. Urobilin is 
often present in abundance; it may then disappear, but reappears dur- 
ing convalescence (Riva, Lanz). The excretion of nitrogen and of phos- 
phoric acid and the marked amount of ammonia have already been 
discussed. The excretion of chlorin is decreased as a result of the small 
ingestion of food. Sometimes, in the earlier stages, or, in certain cases, 
toward the end of the disease, albumin may appear in small quantities; 
also casts or bile-tinged kidney epithelium in a state of fatty degenera- 
tion. There may also be blood-corpuscles, crystals of hematoidin, etc., 
in the sediment. Sugar is rarely excreted. The quantity of urine is 
decreased as the disease progresses, and may even lead to complete anuria 
shortly before death. Re-establishment of the flow of urine is a good 
prognostic sign. During convalescence there may be great diuresis. 

Alcoholic fatty liver corresponds to the picture described under ordi- 
nary infiltration. 

If fatty liver and cirrhosis are combined, the condition is manifested 
by the increased resistance of the organ on palpation. The latter is 
enlarged, and its surface is smooth, as in simple fatty infiltration. If the 
cirrhotic process assumes such a degree that the circulation is interfered 
with in the intra-acinous connective tissue, symptoms of stasis of the portal 
system appear, such as tumor of the spleen, ascites, congestive catarrhs, 
and collateral venous enlargements. The consistency of the liver is 
increased, and the surface may appear nodular as a result of the contrac- 


848 DISEASES OF THE LIVER. 


tion of connective tissue and a protrusion of the parenchyma between the 
cicatricial depressions. The increased quantity of fat in the superficial 
layers and ascites may render the recognition of these surface peculiari- 
’ ties difficult. The course of the disease corresponds to that of alcoholic 
cirrhosis (see pages 700, 732). In many other forms of intoxication fatty 
degeneration of the liver may be produced, and in the same manner as 
by phosphorus and alcohol, though not in the same degree, and yet no 
clinical hepatic symptoms may appear. If the organ were carefully 
examined, it would probably be found enlarged, but as other symptoms 
about the heart, the kidneys, also the intestines, and the central nervous 
system, are convincing, and much more prominent, fatty degeneration 
of the liver is frequently overlooked. 

The same statement may be made with regard to infectious diseases, 
in which the hepatic involvement plays a secondary réle. If there is 
actual inflammation of the organ, there may result an abscess of the 
liver, necrosis, or acute atrophy. The symptoms that may appear under 
these circumstances correspond to those already described as belonging 
to these conditions. 

Diagnosis.—If the organ is only slightly enlarged, it is impossible to 
diagnose fatty liver, and for this reason slight degrees of this condition 
are not discoverable. 

Pronounced cases of fatty liver, as in obesity, alcoholism, phthisis, 
etc., are easily recognized. The condition is to be differentiated from 
amyloid liver by the softness of the fatty organ; from hyperemia also by 
the softness and by the absence of pain. Leukemic and pseudoleukemic 
tumors are harder. The smooth surface and normal contour, the absence 
of indentations of the margin, the absence of symptoms of stasis of the 
portal system, are all characteristic. The existence of some primary 
disease that would be likely to cause fatty liver is also important. 

If cirrhosis is combined with fatty liver, as in alcoholics, the organ is 
enlarged, and more dense than is the ordinary fatty liver, but not as 
resistant as that of hypertrophic cirrhosis. There may be irregularities 
on the margin and the surface, and occasionally symptoms of stasis in the 
portal system. 

The differential diagnosis of phosphorus liver, from parenchymatous 
hepatitis, also from acute yellow atrophy, will be discussed in the appro- 
priate sections. 

Prognosis.—The prognosis is dependent upon the primary disease. 

Treatment.—The treatment will also depend upon the primary 
cause. In obesity it is necessary to withdraw fats and carbohydrates 
and to decrease the formation of fat by other measures. Alcoholic 
beverages should be forbidden, and metabolism stimulated by exercise 
in the open air, by gymnastics, ete. We cannot, however, enter into the 
details of these measures, and refer to the discussion of the treatment 
in the article on “ Obesity.” 

In the case of fatty liver in phthisical subjects it will be well to limit 
the ingestion of large quantities of fat, cod liver oil, etc. In cachexia 
there is no satisfactory therapy. With regard to the treatment of fatty 
degeneration following intoxication with phosphorus, etc., and resulting 
from infectious disease, we must refer to the works on poisoning, and 
infectious diseases, and to the sections on inflammation and atrophy 
of the liver. 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 849 


LITERATURE: 


Afanassiew: ‘“‘ Zur Pathologie des acuten und chronischen Alkoholismus,”’ Ziegler’s 
“Beitrage zur pathologischen Anatomie,” 1890, Bd. vu, p. 443. 

Araki: “ Beitrag zur Kenntniss der Einwirkung von Phosphor und von arseniger 
Sadure auf den thierischen Organismus,” “ Zeitschr. fiir physiologische Chemie,” 
Bd. xvu, p. 311. 

Ackermann: “ Virchow’s Archiv,’ 1889, Bd. cxv, p. 216 (phosphorus). 

Aufrecht: “‘ Experimentelle Lebercirrhose nach Phosphor,” ‘“ Deutsches Archiv 
fiir klin. Medicin,”’ 1887, Bd. tv1u1, p. 302. 

Badt: “Kritische und klin. Beitrige zur Lehre vom Stoffwechsel bei Phosphor- 
vergiftung,’’ Dissertation, Berlin, 1891. 

Birch-Hirschfeld: “‘Gerhardt’s Lehrbuch der Kinderkrankheiten,’ Bd. Iv, 2. 
Abtheilung, p. 772. 

Béhm, Naunyn, and Bock: “ Handbuch der Intoxicationen,” ‘“ Ziemssen’s Hand- 
buch,” Bd. xv, Leipzig, 1876. 

Budd: “ Krankheiten der Leber,’ deutsch von Henoch, 1846, p. 248. 

Cohnheim: ‘ Vorlesungen tiber allgemeine Pathologie,’’ Bd. 1, p. 536, Berlin, 1880. 

Ebrle: ‘ Charakteristik der acuten Phosphorvergiftung des Menschen,” Tubingen, 
1861. 

Ewald: Artikel: “Fettleber,’’ in Eulenburg’s “ Realencyklopiidie.” 

Frankel, E.: ‘ Ueber Chloroformnachwirkung beim Menschen,” “ Virchow’s Archiv,” 
1892, Bd. cxxix, p. 254. 

Frerichs: “ Klinik der Leberkrankheiten,” 1858, Bd. 1, p. 285. 

Friedlinder: ‘Ueber Phosphorvergiftung bei Hochschwangeren,’” Dissertation, 
K6onigsberg, 1892. 

Furstenberg: “ Virchow’s Archiv,” 1864, Bd. xx1x, p. 152. 

Garel: ‘‘Cirrhose hypertrophique graisseuse du foie,” “ Revue de médecine,” 1881, 

. 1004. 

Hie “ Berliner klin. Wochenschr.,’”’ 1893, p. 1138. 

Hecker: ‘‘ Ueber einen Fall von acuter Fettdegeneration bei einem Neugeborenen,”’ 
“Archiv fiir Gynakologie,”’ Bd. x, p. 537. 

Hedderich: ‘‘ Ueber Leberatrophie,”’ ‘‘Miinchener med. Wochenschr.,”’ 1895, p. 93. 

v. Héslin: ‘ Deutsches Archiv fur klin. Medicin,”’ 1883, Bd. xxx111, p. 600. 

v. Jaksch: “ Die Vergiftungen,’’ Nothnagel’s ‘‘Specielle Pathologie und Therapie,” 
Gs i: 

—“ Beitrag zur Kenntniss der acuten Phosphorvergiftung,” “‘ Deutsche med. Woch- 
enschr.,”’ 1893, p. 10. 

v. Kahlden: “ Experimentelle Untersuchungen tiber die Wirkung des Alkohols 
auf Leber und Nieren,” Ziegler’s “Beitrage zur pathologischen Anatomie,” 
1891, Bd. 1x, p. 349. 

Kroénig: “‘ Die Genese der chronischen interstitiellen Phosphorhepatitis,” “‘ Virchow’s 
Archiv,” 1887, Bd. cx, p. 502. 

Lafitte: ‘L’intoxication alcoolique expérimentale,’’ Thése de Paris, 1892. 

Lanz: “Berliner klin. Wochenschr.,’”’ 1895, p. 879 (phosphorus). 

Leyden: “Deutsche med. Wochenschr.,” 1894, p. 475 (phosphorus). 

—and Munk: “Die acute Phosphorvergiftung,’’ Berlin, 1865. 

Lebedeff: “Woraus bildet sich Fett in Fallen der acuten Fettbildung?’’, “ Pfliiger’s: 
Archiv,” 1883, Bd. xxx1, p. 15. 

Leo: ‘Fettbildung und Fetttransport bei Phosphorintoxication,” “ Zeitschr. fiir 
physiologische Chemie,” Bd. rx, p. 469. 

Liebermeister: “ Ueber Leberentziindung und Leberdegeneration,” ‘‘ Deutsche med. 
Wochenscelr.,’’ 1892, p. 1181. 

Litten: ‘ Ueber die Einwirkung erhéhter Temperatur auf die Organe,”’ ‘‘ Virchow’s 
Archiv,” Bd. uxx, p. 10. 

Magnan: “ Afchives de physiologie,”- 1873, p. 115 (alcohol). 

Merklen: “Sur deux cas de cirrhose hypertrophique graisseuse avec ictére,” “ Revue 
de médecine,” 1882, p. 997. 

Meyer, H.: “ Arch. fiir experimentelle Pathologie u. Pharmakologie,”’ Bd. x1v, p. 313. 

Minzer: “ Der Stoffwechsel des Menschen bei acuter Phosphorvergiftung,” ‘‘ Deut- 
sches Archiv fiir klin. Medicin,” Bd. tm, p. 199. 

Ostertag: “Die tédtliche Nachwirkung des Chloroforms,” “ Virchow’s Archiv,’ 

1889, Bd. ecxvut, p. 250. 

Perls: “ Zur Unterscheidung von Fettinfiltration and fettiger Degeneration,” ‘“‘ Cen- 

tralblatt fiir die med. Wissenschaft,” 1873, p. 801. 


54 


850 : DISEASES OF THE LIVER. 


Pilliet: Sitzungsbericht der Pariser anatomischen Gelleschaft vom 26. Januar und 
22. December, 1894. 

Platen: “ Virchow’s Archiv,’”’ Bd. Lxxtv, p. 286 (phosphorus). 

Pupier: ‘‘Comptes-rendus de l’académie des sciences,” 1872, 17, May (alcohol). 

Renz: “Toxikologische Versuche tiber Phosphor,’”’ Dissertation, Tiibingen, 1861. 

Riess: Article “ Phosphorvergiftung,”’ in Eulenburg’s “ Realencyklopadie.” 

v. Recklinghausen: ‘Handbuch der allgemeinen Pathologie des Kreislaufes und 
der Ernahrung,”’ ‘‘ Deutsche Chirurgie,’”’ Lieferung 2 und 3, p. 377. 

Robitschek: “‘ Deutsche med. Wochenschr.,’’ 1893, p. 569 (phosphorus). 

Roloff: “Die Fettdegeneration bei jungen Schweinen,” “Virchow’s Archiv,” Bd. 

XXXII, p. 553. 

Rosenfeld: ‘‘Gibt es eine fettige Degeneration?” ‘‘ XV. Congress fiir innere Medi- 
cin,”’ 1897. 

—“Die Fettleber bei Phlorizindiabetes,” ‘ Zeitschr. fir klin. Medicin,” Bd. 
XXVIII, p. 256. 

Rothhammer: “Ueber einen Fall von acuter Phosphorvergiftung,” Dissertation, 
Wirzburg, 1890. 

Sabourin: ‘“Cirrhose hypertrophique graisseuse,” “‘ Archives de physiologie,” 1881, 

. 584. ; 

Bohetder: “Hinige experimentelle Beitrage zur Phosphorvergiftung,” Dissertation, 
Wirzburg, 1895. 

Schultzen and Riess: “ Ueber acute Phosphorvergiftung und acute Leberatrophie,”’ 
“Charité-Annalen,”’ 1869, Bd. xv. 

Schiippe]: “Fettleber,” in “ Ziemssen’s Handbuch,” Bd. vu, 1. Halfte, 1. Ab- 
theilung, p. 389. 

Stadelmann: “ Der Icterus,” 1891, p. 176. 

v. Starck: “Beitrag zur Pathologie der Phosphorvergiftung,” ‘Deutsches Archiv 
fir klin. Medicin,” 1884, Bd. xxxv, p. 481. 

Storch: ‘Den acute Phosphorforgiftning,’’ Dissertation, Copenhagen, 1865. 

Strassmann: “ Vierteljahresschr. fiir gerichtliche Medicin,’”’ 1888 (alcohol); ‘ Vir- 
chow’s Archiv,” Bd. cxv, p. 1 (chloroform). 

Straus and Blocq: “ Archives de physiologie,”’ 1887, 2. sémestre, p. 409 (alcohol). 

Thiemich: ‘“ Ueber Leberdegeneration bei Gastroenteritis,” Ziegler’s “ Beitrage zu 
pathologischen Anatomie,” Bd. xx, p. 179. 

Thiercelin and Joyle: ‘“Sitzungbericht der Pariser anatomischen Gesellschaft,” 
June 1, 1894. . 

Ungar: “ Vierteljahresschr. fiir gerichtliche Medicin,”’ Bd. xtvi1, p. 98 (chloroform). 

Wagner, E.: “ Zur Kerrtniss der Phosphorvergiftung,” ‘Archiv der Heilkunde,” 
1862, Bd. 111, p. 359. 

West: ‘ Phosphorus-poisoning,”’ ‘‘The Lancet,” 1893, February 4, p. 245. 

Wolkow: “Ueber das Verhalten der degenerativen und progressiven Vorginge 
in der Leber bei Arsenikvergiftung,” ‘ Virchow’s Archiv,” Bd. cxxvn. 

Ziegler and Obolenski: ‘‘ Experimentelle Untersuchung iiber die Wirkung des Ar- 

seniks und Phosphors auf Leber und Nieren,’”’ Ziegler’s “ Beitrage zur patho- 

logischen Anatomie,” Bd. 1, p. 291. : 


(C) CHRONIC ATROPHY, 
(Hoppe-Seyler.) 


By the term atrophy are characterized all hepatic conditions that 
are accompanied by a decrease in the size of the liver. 

If only a portion of the liver is reduced in size, we speak of circum- 
scribed atrophy ; this may be due to a congenital anomaly of development 
or to some pressure effect exercised by neighboring organs that have 
become enlarged; e. g., a dilated intestine (Frerichs), pleuritic and peri- 
tonitic exudates, hypertrophy of the heart, and tumors of neighboring 
parts. Other compressing factors may be lacing, corsets, straps, or 
deformities of the thorax (kyphosis and scoliosis). Circumscribed 
atrophy is also seen in the vicinity of tumors of the liver (echinococcus, 
carcinoma, etc.), or after occlusion of certain branches of the portal 
vein; also in cirrhotic and syphilitic processes that lead to a contraction 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 801 


of the interstitial connective tissue; in amyloid degeneration, congestion 
of the liver, etc. Occlusion of the bile-passages (Brissaud and Sabourin) 
may be congenital (Lomer), and may lead to atrophy. In all the con- 
ditions enumerated there will be seen contraction of the liver, charac- 
terized either by a simple reduction in the size of the cells, or by their 
destruction by fatty degeneration and necrosis. All these changes 
have been discussed under the headings of the different diseases of the 
liver or in the section on the abnormalities of the form of the liver (corset 
liver, congenital anomalies, etc.). In many of these lesions compen- 
satory processes will be seen in other portions of the organ. 

General atrophy is, as a rule, the effect of diffuse processes in the 
organ. A general reduction in the size of the organ may be seen after 
certain degenerative processes following icterus, phosphorus-, arsenic-, 
antimony-, or chloroform-poisoning, or following general cirrhosis, diffuse 
perihepatitis with thickening of the capsule, and occlusion of the portal 
vein or some of its branches. Frerichs has called particular attention 
to the simple atrophy of the columns of liver-cells that follows the ob- 
literation of capillaries, or thickening of Glisson’s capsule around branches 
of the portal vein. In the different sections that treat of these various 
lesions atrophy will be or has been discussed. 

There is left only one form of general chronic atrophy, that which 
is seen after inanition, marasmus senilis, cachexia, etc., and is charac- 
terized by a wide-spread decrease in the size of the hepatic cells, involv- 
ing the whole organ, and without any disintegration of the protoplasm 
and without any changes in the interstitial connective tissue. We will 
limit ourselves, in this section, to a discussion of this simple chronic 
atrophy of the liver. 

If nutrition is deficient, or if too little food is taken, the volume of 
the liver will decrease; if the inverse conditions obtain, the organ will 
enlarge. This dependence upon the food is particularly pronounced in . 
animals, and depends essentially on fluctuations in the size of the cells. 
In the case of well-nourished animals the latter will be seen to be large, 
rounded, and with distinct nuclei; in starving animals they will be found 
small, angular, granular, and with small indistinct nuclei. If nutrition 
is poor, the amount of glycogen, too, will be diminished, or may be com- 
pletely absent, causing a reduction in the size of the cell. In inanition 
the liver also loses water, and later some albumin. In this manner the 
volume of the liver may be reduced two-thirds. 

The same statement may be made as to human beings if nutrition 
is poor or if assimilation from the intestine is deficient; no degenerative 
or necrotic changes are seen in the cells during this process. Such de- 
ficient nutrition may be the result of poverty, or may be due to certain 
disturbances of the nervous system that cause the patient to refuse 
nourishment (psychoses, anorexia, coma, etc.), or may be due, finally, to 
certain lesions that prevent deglutition, such as paralysis, stenosis of 
the esophagus and cardia, ulcers of the pharynx and larynx (tubercu- 
lous, etc.). Severe vomiting, stenosis of the pylorus, strictures of the 
intestine, may all be at times responsible for the deficient ingestion of 
food. All chronic disturbances of nutrition following certain gastro- 
intestinal lesions must be ranked with these agencies: for example, ca- 
tarrhs following ulcers and tumors, both of the stomach and intestine 
and of the large glands of digestion. Long-drawn-out febrile diseases 


~ 


852 DISEASES OF THE LIVER. 


may bring about the same result, as phthisis, malignant neoplasms, 
syphilis, chronic nephritis, anemia, diabetes, etc. These will all lead 
to disturbances of metabolism, deficient assimilation of food and an 
abundant destruction of body tissue; ultimately they lead to atrophy 
of the liver. In senile marasmus this condition is also seen; the liver, 
as well as the heart, the spleen, the musculature, etc., shows signs of 
brown atrophy when old age comes on. 

Pathologic Anatomy.—Chronic atrophy does not, as a rule, develop 
uniformly throughout the organ, but is usually more pronounced at 
the sharp margin than in the interior. 

The volume and the size of the liver are greatly reduced, and may 
be only one-third of normal. The organ is more flaccid, darker, and 
drier. It is a little more solid owing to the disappearance of soft paren- 
chymatous tissue, and the simultaneous preservation of the more dense 
hard connective tissue. The transverse section is non-vascular: it is 
brownish in color, and shows a great reduction in the number of acini. 
The lower margin of the liver may be translucent and tough owing to 
the complete disappearance of parenchyma. 

Under the microscope the cells will be found to be small and ee 
and to contain small nuclei; sometimes granules of brown pigment will 
also be seen. The interstitial connective tissue is intact. In these 
cases, where the parenchyma is completely destroyed, some connec- 
tive tissue will be seen in the location-of the acini consisting of collapsed 
capillaries, and all around it is more solid periportal tissue with well- 
preserved capillaries and bile-passages. The latter may even be increased 
in number (Ziegler). 

The amount of water in the liver is reduced, and later on its albumin 
may also be diminished. Glycogen can be detected only in traces. 

Symptoms.—The chief feature of the clinical picture is the progressive 
reduction in the size of the organ. This process is slow and gradual, 
and may extend over many weeks or months. As arule, the liver cannot 
be palpated; the area of dulness is decreased in all directions. The 
dulness extends neither so far down into the abdomen, nor so far to 
the left as is customary. Often, especially in cases of meteorism, it may 
be difficult to determine any dulness whatsoever. The surface of the 
organ is not sensitive to pressure, and is smooth. 

At the same time other symptoms of deficient nutrition will be seen; 
- the skin will be flaccid, the cutaneous fat will be gone, the spleen is small ; 
atrophy and disappearance of the muscular tissue may all be noted. 
Occasionally there will be cachectic edema, particularly in the dependent 
parts of the body, the legs, the lumbar region, etc.; later there may even 
appear ascites, hydrothorax, etc. The ascites cannot be due to stasis 
in the portal system, because the portal branches in the liver are neither 
occluded nor compressed in simple atrophy. At the same time, there 
will be disturbances of appetite, and of the stools, all of which may be 
attributed to the primary causal condition. 

There is usually little bile in the stools. They are clay-colored, 
owing to the fact that the atrophic cells of the liver produce little bile. 
The urine, for the same reason, is pale and contains little urobilin. In 
a man with carcinoma of the stomach, who took very little food, I found 
daily only 0.039 gm. of urobilin, and another time only 0.043 gm., whereas 
the normal amount should be from 0.09 to 0.15 gm., an average of 0.12 
gm. This man was very cachectic and his liver was reduced in size. 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 853 


In cases of inanition resulting from pyloric stenosis, and in disturbances 
of nutrition following tuberculosis, I found a minimum excretion of 
urobilin.* . 

The disease may be very protracted. Some of the digestive dis- 
turbances may be due in part to the lack of bile. The duration and 
the course of the illness are largely dependent upon the primary disease. 

The prognosis also is dependent upon the latter. If there is a dif- 
ficulty in the way of ingestion of food that can be removed, or if the 
patient is suffering from some digestive disorder that can be cured, the 
liver will also recover and return to a normal condition. 

Treatment can only be directed toward the latter object. An esopha- 
geal or pyloric stenosis may have to be cured, even by a gastric fistula; 
if necessary, neoplasms that affect the nutrition and the general strength 
of the patient will have to be removed; and disturbances of the gastric 
or intestinal functions must be relieved. The food should be very 
digestible, consisting chiefly of milk, etc. Iron, and cinchona, arsenic, 
etc., may be administered for the improvement of the general health, 
and may be useful in this capacity. 


Afanassiew: ‘‘Ueber die anatomischen Verinderungen der Leber wahrend ver- 
schiedenen Thatigkeitszustandes,” ‘“ Pfliger’s Archiv,” Bd. xxx, p. 385. 

Birch-Hirschfeld: ‘‘ Lehrbuch der pathologischen Anatomie,” Bd. 11, p. 613. 

Brissaud and Sabourin: “Deux cas d’atrophie du lobe gauche du foie d’origine 
biliaire,” ‘Archiv de physiologie,” 1884, 3. Serie, tome 1, p. 345. 

Frerichs: ‘“ Klinik der Leberkrankheiten,”’ 1858, Bd. 1, p. 257. 

Kux: ‘‘Ueber die Verinderungen der Froschleber durch Inanition,’”’ Dissertation, 
Wirzburg, 1886. 

Lomer: “ Ueber einen Fall von congenitaler partieller Obliteration der Gallenginge,”’ 

, “Virchow’s Archiv,” 1885, Bd. xcrx, p. 130. 

Thierfelder : ‘‘ Krankheiten der Leber,” “ Ziemssen’s Handbuch,” Bd. vit, 1. Halfte, 
1. Abtheilung, p. 270. 

Ziegler : “ Lehrbuch der pathologischen Anatomie,” Bd. 11, p. 573. 


(D) AMYLOID LIVER. 
(Hoppe-Seyler.) 


Amyloid degeneration is probably never limited to the liver. The 
process may be localized in the liver, but it usually involves other parts 
of the body at the same time. The primary disease, moreover, rarely 
develops in this organ itself, but usually in some remote part of the body, 
later involving the liver also. 

The physicians of two centuries ago were acquainted with this lesion 
of the liver, as it is sometimes very conspicuous; they did not, however, 
have a clear conception of its significance. Rokitansky was the first 
to describe the exact anatomic changes seen in amyloid degeneration 
of the liver and of other organs, and to call attention to the relation 
between this state and wasting diseases. He called it lardaceous liver; 
other investigators used the term waxy or colloid. Virchow, later, 
discovered the characteristic iodin-sulphuric-acid reaction and called the 
new substance amyloid; hence the names amyloid liver and amyloid 
degeneration. He believed that the amyloid substance was related to 
the carbohydrates; but the investigations of C. Schmidt, Friedreich, 
Kékulé, Kiihne, Rudneff, and others, demonstrated that it contains 
nitrogen, and that it is related to the proteids. For a long time it was 

* Virchow’s Archiv, 1891, Bd. cxxiv, S. 30. 


854 DISEASES OF THE LIVER. 


still believed that amyloid substance at least contained a carbohydrate 
body, but recent investigations by Grandis and Carbone seem to refute 
this. 

Krawkow believed that amyloid substance was related to chitin, but 
this has not ‘been proved. Oddi succeeded in obtaining chondroitin- 
sulphuric acid from an amyloid liver, and believed that this substance 
(which, according to Schmiedeberg, is a product of cartilage) was related 
to amyloid substance. The exact connection between the two has, 
however, not yet been established. There appears to be some relation- 
ship with hyaline substance, and it appears that amyloid can be formed 
from this substance. Rahlmann states that he has observed this pro- 
cess in amyloid degeneration of the conjunctiva. Tschermak supports 
this view. Amyloid substance, according to these writers, is related to 
coagulated albumin. v. Recklinghausen believes that hyaline change 
is a precursor of the amyloid process, and the investigations of Stilling, 
Hansemann, and Lubarsch support this view. The latter was enabled 
to show by his experiments that at first there was hyaline change only 
in the spleen, and that later the amyloid transformation appeared. The 
histologic findings favor the view that proteid material is gradually 
converted into amyloid. 


It would appear that the so-called amyloid is not a homogeneous substance. 
This is demonstrated by the different color reactions; sometimes it is colored by 
iodin but not with methyl-violet; in other cases the reverse is true. The iodin- 
sulphuric acid reaction is often not obtained at all, or it may be atypical; 7. e., give 
a reddish-brown or a blue or green color. 

The following diseases have for a long time been recognized as the chief causes 
of amyloid degeneration: protracted suppuration, phthisis, neoplasms, malaria, 
syphilis, leukemia, and pseudoleukemia. 

The ultimate cause of amyloid degeneration, however, remained obscure, and 
only recently have experiments thrown light on the subject. Animals were in- 
fected with bacteria, and a general chronic pathologic condition was produced, 
with marked emaciation, amyloid degeneration of the spleen, and of the liver, etc. 
Birch-Hirschfeld observed amyloid degeneration in a rabbit with a long-standing 
suppurative process; and Bouchard and Charrin have occasionally noted amyloid 
deposits in the kidneys of animals that had been injected with pyocyaneus and 
tubercle bacilli. Czerny produced amyloid degeneration in a dog by causing sup- 
puration with long-continued injections of turpentine; and also found a body giving 
similar reactions in the pus-corpuscles. Krawkow especially, and later Davidsohn, 
succeeded in producing a deposit of amyloid material around the vessels of the 
spleen and the liver by repeated injections of staphylococcus cultures, Lubarsch 
obtained similar results by artificially inducing suppuration. Gouget injected 
proteus cultures into the vena porte and the common duct; Candarelli injected 
Bacillus termo, and both obtained amyloid degeneration. Carriére saw the same 
procedure after injections of tubercle bacilli. Petrone believes that it is due to 
an impregnation of the vessel-walls with perverted blood-pigment; this would seem 
to explain the appearance of amyloid material after chronic suppuration of the 
bones and of the soft tissues, following tubercular processes, staphylococcus infec- 
fection (osteomyelitis), etc. The appearance of amyloid in pulmonary phthisis 
may also be due to infection with staphylococci. Amyloid degeneration is seen 
with particular frequency after ulceration of the intestine, the trachea, and the 
larynx. In primary urogenital tuberculosis, and in other unmixed forms of tuber- 
culosis, the condition is not frequently seen provided the foci remain closed off; 
as soon as such a focus is exposed, however, amyloid degeneration may appear. 
Among 48 cases of amyloid degeneration in tuberculosis, 42 were combined with 
some tubercular lesion of the intestine. 


_ Suppurations of bones demand particular attention in this connec- 
tion, in that they are difficult to cure and persist for a long time. Caries, 
psoas abscesses, necrosis of the bones, combined with suppuration, as 


PARENCHYMA TOUS CHANGES AND DEGENERATIONS. 855 


in complicated fractures, osteomyelitis, etc., and all suppurative forms 
of arthritis; also chronic leg-ulcers, chronic empyema, bronchiectasis 
(with abundant production of pus), chronic liver abscess, purulent pye- 
litis, ete. A few cases are on record in which amyloid degeneration has 
followed gastric ulcer or chronic dysentery. 

In syphilis such cases seem particularly to lead to amyloid degenera- 
tion as are complicated with suppurative lesions and ulcerative pro- 
cesses. In hereditary syphilis the condition is frequently seen, and 
it has even been claimed that an amyloid condition may be congenital 
(Rokitansky). 

The role played by malarial cachexia, by gout, and by rachitis is a 
doubtful one. The statement has also been made that mercury-poisoning 
may cause amyloid degeneration; this is probably not: the case. 

In the presence of tumors amyloid degeneration is not so frequently 
seen as with suppurative conditions and tuberculosis. The slow-growing 
tumors predispose more actively to this condition than those that develop 
rapidly and lead to the death of the patient in a short time. Thus gelat- 
inous carcinomata, scirrhus, etc., are more apt to cause amyloid de- 
generation of the organs than other forms. Neoplasms that are com- 
plicated by ulceration of the stomach or the uterus, for instance, seem 
to create a particular predisposition to amyloid degeneration. In many 
cases the cause of the degeneration cannot be determined; a thing that 
is not surprising when we remember that many bacteria (staphylococci), 
etc., develop in a latent manner and escape recognition. 


Phthisis is the most frequent cause of amyloid degeneration. Hoffmann found 
it in 67.5 %; O. Weber in 40.5 %; Wagner in 56.25 %; Wicht in 50 %; then suppu- 
ration of bones and chronic suppuration (Hoffmann 7.5 %, Weber 38 %, Wagner 
23 %, Wicht 22.8%). Men seem to be more frequently afflicted than women. 
The age of twenty-one to thirty seems to offer the greatest susceptibility. The 
kidneys and the spleen are more frequently involved than the liver. If the liver 
is involved, the two former organs are usually also involved. 


Pathologic Anatomy.—Slight degrees of amyloid degeneration can 
only be recognized by means of the microscopic examination. If the 
process is well developed, the whole organ enlarges and may weigh as 
much as 5 or 6 kg. The surface is smooth, the margin rounded, and 
occasionally sharp; the contour remains unchanged. The organ grows 
harder; its tissue becomes translucent and appears like yellow wax or 
boiled bacon; for this reason the degeneration has been called waxy 
or lardaceous (“‘ Speckleber’”’). This appearance is in part due to the 
small amount of blood contained in the organ. If, on the other hand, 
there is a considerable quantity, the organ looks like raw ham. The 
outlines of the acini are, as a rule, indistinct; though a point in the center 
and a fine line at the periphery will designate the old location of each 
acinus. This appearance is due to the fact that the process of degenera- 
tion is less complete at the periphery and in the center. If Lugol’s 
solution is poured over the transverse section of the liver, the latter is 
colored mahogany brown. Under the microscope it will be seen that 
changes have occurred in the intra-acinous capillaries. The endothelium 
is fairly well preserved; and exterior to it will be seen a thick, trans- 
lucent, shiny mass that is colored brown by iodin and red with methyl- 
violet and similar stains. The same thick layers are seen around the 
capillaries in some of the experimental investigations (Krawkow, David- 
sohn), with the production of artificial amyloid degeneration by the 


856 . DISEASES OF THE LIVER. 


injection of cultures of staphylococci, etc. The walls of the blood- 
channels are thickened and between the latter the atrophied liver-cells 
are seen; they are either in a state of brown atrophy or of fatty degenera- 
tion, and finally seem to perish completely. The theory has been held 
that in cases of this kind the shiny masses consist of transformed liver- 
cells. From Bottelier’s and others’ studies it appears not impossible 
that amyloid degeneration occasionally occurs in the cell protoplasm. 
Certainly it is seldom distinctly evident, and is of comparatively slight 
significance as compared with the deposit of amyloid substance in the 
vessel-walls. This same deposit may sometimes be seen in the media 
of the branches of the hepatic artery, which run in the interacinous 
tissue. The middle zone of the acini seems to be the most affected, 
the center and the periphery being less involved. As a rule, the de- 
generation is uniform throughout the organ, circumscribed foci being 
rarely seen. 

The bile-passages do not, as a rule, participate in the process, and 
present an absolutely normal appearance. 

Marked amyloid changes are generally seen also in the other organs, 
as the spleen, the kidneys, the suprarenal capsules, and the intestine. 

Symptoms.—Experimental investigation has shown that amyloid 
changes may take place in the liver within the course of a few weeks. 
Before the process assumes such dimensions as to be evident clinically, 
however, more time must elapse. 

Slight degrees of amyloid degeneration cannot be detected, owing 
to the fact that neither the size nor the consistency of the organs involved 
is changed. 

Only such involvement as is diffuse throughout the liver can be 
recognized with any certainty. In such cases the whole organ is enlarged 
and extends in the right mammillary line a hand’s-breadth below the 
costal margin. Its margin is frequently sharp, occasionally somewhat 
rounded; it is indentated only in cases that are complicated by cirrhosis 
or syphilis. The surface is usually smooth; even in cases of extreme 
enlargement no pain is felt. There is a marked resemblance between 
this form of degeneration and fatty liver, particularly in its contour and 
in the character of its surface and margin; amyloid liver is differentiated, 
however, by its extreme hardness. The organ, at the same time, is 
by no means as unyielding as in cirrhosis, but retains more of its elas- 
ticity. There is no sign of stasis,in the portal system in spite of the 
marked involvement of the vessels; this is due to the fact that the amyloid 
change develops in the vessel-walls, and grows outward, so that it thickens 
the walls of the vessels without narrowing their lumen. The pressure 
exercised in this way upon the surrounding tissues causes atrophy of 
the liver-cells. At times there will be a serous exudate into the peri- 
toneum, dependent upon the primary disease. There may be a cachectic 
transudation, or the effusion may occur in combination with edema in 
other parts of the body; it may also be due to tubercular peritonitis. 
Splenic tumor is often associated with amyloid liver, and is caused by the 
same changes that are operating in the liver; it is characterized by its 
extreme hardness. Albumin, casts, and renal epithelium are often 
found in the urine, as accompanying symptoms of amyloid kidney. Albu- 
minuria may be absent, however, despite the existence of severe grades of 
amyloid change. If diarrhea now supervenes, with the passage of slimy 
stools, the probability of amyloid degeneration of the intestine is great. 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 857 


At the same time, various processes, purulent, syphilitic, tuber- 
culous, etc., may be present in different parts of the body, and may 
modify the pathologic picture; usually they play the most important 
part in the disease. 

The function of the liver, apparently, remains intact for a long time. 
Marked degrees of amyloid degeneration and the disappearance of con- 
siderable parenchyma involve a decreased secretion of bile. The stools 
lose their color, and the urine contains little urobilin, being light in color. 
The excretion of urea is decreased, owing, probably, to the deficient 
assimilation of food that is so often observed in cachectic conditions. 
Icterus is absent, unless the disease is complicated by some other condi- 
tion that leads to stasis of the bile. 

Until recently amyloid degeneration was considered an irreparable 
condition. This view was based upon the great resistance offered by 
amyloid substance to the action of chemical and physical agencies. Of 
late years a number of reports have been published from which it appears 
that amyloid processes may recede. Thus, it has been ascertained 
that amyloid substance, when incorporated into the body of animals, 
may gradually become absorbed. Lubarsch extirpated a portion of the 
spleen from one of his animals four weeks before death, and found dis- 
tinct amyloid change; when the animal died, amyloid material could 
no longer be discovered even in the vicinity of the scar. Rahlmann, 
finally, has noted the disappearance of amyloid degeneration of the 
conjunctiva, after the condition had been positively diagnosed by micro- 
scopic examination of a small excised portion of the growth. 

It would appear, therefore, that amyloid liver may recover, if the 
primary cause can be removed; e.g., if a suppurative bone lesion, em- 
pyema, etc., can be cured by operative interference. 

The prognosis is dependent upon the curability of the primary disease. 

The diagnosis rests upon the character of the liver, already described, 
upon the absence of symptoms of stasis in the portal system, and upon 
the demonstration of amyloid degeneration in other organs. Particu- 
larly important is the presence of such a condition as suppuration, which 
predisposes to this form of degeneration. 

Treatment.—Prophylaxis is important. Suppurative processes should 
be removed as early as possible, particularly if they involve bones or 
joints; old syphilitic lesions should be carefully treated; phthisis should 
be handled by nourishing the patient and regulating his mode of life, 
and all tubercular foci should, if possible, be removed, while secondary 
purulent infections must be cured. 

Even after the disease has developed hope should not be given up. 
A rational and thorough treatment of the primary disease may often 
lead to a cure. The patient should receive a diet rich in proteids, and 
readily digestible, such as milk, easily assimilable meats, eggs, digestible 
cereals, etc. Arsenic, iron, and potassium iodid have been recommended. 
Particularly in cases resulting from malaria or syphilis are these drugs 
useful. Amyloid degeneration of the intestine and the kidneys should 
be regarded and treated according to the etter principles enunciated 
in the appropriate volume of this series. 


For the earlier literature of the subject vide Schiippel: “ Amyloide Entartung der 
_ Leber,” in Ziemssen’s “ Handbuch der speciellen Pathologie und Therapie,” 
1878, Bd. vii, 1. Halfte, 1. Abtheilung, p. 359. 
Index-Catalogue of the ee of the Surgeon-General’s Office, 1887, vol. vim, p. 241. 


858 DISEASES OF THE LIVER. 


Bouchard et Charrin: ‘‘Comptes-rendus de la société de biologie,” tome xu, p. 688. 

Carriere: ‘ Archives de médecine expér.,”’ 1897, tome Ix. 

Czerny: “Archiv fiir experimentelle Pathologie und Pharmakologie,” 1893, Bd. 
xxxI, p. 209; “Centralblatt fiir allgemeine Pathologie,” Bd. vit. 

Davidsohn: “ Ueber experimentelle Erzeugung von Amyloid,” “ Virchow’s Archiv,” 
1897, Bd: ci; p: 16, 

Gouget: “ Archives de médecine expér.,”’ 1897, 1. série, tome Ix, p. 733. 

Krawkow: ‘‘ De la dégénérescence amyloide,” ibidem, 1896, 1. série, tome vit, p. 
107. 

Litten: ‘‘ Veber Amyloiddégeneration,” ‘‘ Deutsche med. Wochenschr.,”’ 1888, No. 24. 

Lubarsch: “ Zur Frage der experimentellen Erzeugung von Amyloid,” “ Virchow’s 
Archiv,” 1897, Bd. cu, p. 471. 

Oddi: “Ueber das Vorkommen von Chondroitinschwefelsiure in der Amyloid- 
leber,” “ Archiv fiir experimentelle Pathologie und Pharmakologie,” Bd. xxxu11, 

: ors 

Petrone: ‘‘ Recherches sur la dégénérescence amyloide expérimentale,” ‘“ Archives 
de médecine expér.,’’ 1898, 1. série, tome x, p. 682. 

Rahlmann: “ Ueber hyaline und amyloide Degeneration der Conjunctiva des Auges,”’ 
“Virchow’s Archiv,’”’ Bd. Lxxxvil, p. 325. 

Tschermak: “Ueber die Stellung der amyloiden Substanz unter den Eiweisskor- 
pern,” “ Zeitschr. fiir physiologische Chemie,”’ 1895, Bd. xx, p. 343. 

Wicht, L.: “Zur Aetiologie und Statistik der amyloiden Degeneration,” Disserta- 
tion, Kiel, 1889. 


(E) SIDEROSIS OF THE LIVER. 
(Iron-Liver.) 


(Quincke.) 


In the normal state the liver contains more iron than any other organ 
of the body. The absolute quantity is 30 to 90 mg. in 100 gm. of dried 
liver substance in normal animals, and 80 to 200 mg. in man (Oidtmann, 
Stahel, Granboom). Under certain pathologic conditions the amount 
of iron may markedly decrease, or, especially if iron is administered, 
increase. 


Exact determination of the amount of iron present in the liver after incinera- 
tion is possible in animals only when all the blood has been washed from the organ 
with normal salt solution. Zaleski, Gottlieb, and others have made such deter- 
minations. In human livers it is impossible to remove all the blood, and the results 
obtained are therefore not uniform. For this reason, and because pathologic changes 
cannot always be excluded, so-called normal figures are uncertain as far as the human 
liver is concerned; the figures given by Stahel are, however, probably too large (see 
table, pages 865, 866). 


Occasionally it is possible to determine the differences in the quan- 
tity of iron present from the intensity of the reaction given with am- 
monium sulphid, a simpler method than that of estimation by weighing. 
Small pieces of the organ, particularly if they are finely cut (and conse- 
quently as free as possible from blood) and prepared for the microscope, 
usually appear green to the naked eye when treated with ammonium 
sulphid; with a little practice it is possible approximately to estimate 
the quantity of iron from the shade. In the dead body this reaction 
occasionally takes place as the result of the generation of sulphuretted 
hydrogen in the intestine. A green color is to be seen in portions 
of the surface of the liver that are in contact with the loops of intestine. 
_ Microscopie examination with a high-power lens shows that the 
liver-cells are normally diffusely colored; but that under certain condi- 
tions, and especially when pathologic changes are present, the peripheral 
portions of the lobules show more intense coloring, and that small granules 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 859 


of pigment, almost blackish-green in color, are situated in this location. 
As a rule, these granules are found, either in the main or exclusively, in 
the axis of the columns of the liver-cells. They are usually fine (not 
more than 2 » in diameter) and are surrounded by a greenish areola. 
Iron can also be demonstrated microchemically in the capillaries. Here, 
too, it is more abundant in the periphery of the lobules, and consists 
of little lumps that are composed of fine and coarse granules. The color 
of these granules, which are 6 » and over in diameter, is made darker 
by ammonium sulphid, indicating a greater amount of iron. [C. Biel- 
feld * has analyzed many livers with the aim of discovering free iron in 
the hepatic cells. He now asserts that preceding failures have been 
due to faulty methods. He used Schmidt’s method, and arrived at 
the following conclusions: The average amount of iron present in a healthy 
liver is about 0.169 %. There is more iron in the liver of the male than 
the female. The amount of iron in the hepatic cells increases with age. 
The iron becomes less between the ages of twenty and twenty-five.— 
Ep.] The clumps are frequently seen within the leucocytes; others, as 
Kupffer has recently shown, are found in the endothelium of the vessels, 
and some are free in the lumen (Kupffer). If the capillaries contain 
iron, the reaction may be obtained in Kupffer’s stellate cells, in the 
connective tissue, and in the vessel-sheaths. 


The iron reaction is not usually seen in the capillaries of the healthy human 
liver. In the dog there are always certain isolated cells that become dark when 
treated with ammonium sulphid; in the rabbit they are also found, but are not 
so numerous. 


Chemical analysis will reveal the total quantity of iron present in 
the liver; microchemical reactions will indicate the distribution of iron 
in different tissues. The two methods supplement one another. 

The intensity of the green coloration by ammonium sulphid may be 
utilized as a measure for the determination of the quantity of iron present. 
It must be remembered, however, that not all iron compounds react to 
ammonium sulphid, as, for instance, hemoglobin. The most important 
iron compound found in the normal liver is Schmiedeberg’s ferratin; 
this is a ferri-albumin acid of a light brown color containing about 6 % 
of iron, soluble in weak alkalies, and colored dark by ammonium sulphid. 
The reaction does not occur at once, but requires several minutes; 
after the reagent has acted for a little time the substance becomes 
darker and then gradually a dark green. Even after several days no 
sulphid of iron is found. Ferratin may be dissolved by boiling fresh 
liver pulp with three or four volumes of water. The decoction is filtered, 
and the ferratin precipitated as a brown sediment upon the addition 
of a small quantity of tartaric acid. The fresh liver of a healthy animal 
contains from 0.15 % to 0.3 % of ferratin (Vay). The amount of ferratin 
seems to correspond to the general state of nutrition, so that in the ma- 
jority of human livers there is only a comparatively small quantity. 
Vay succeeded in extracting some 60 % of the iron of the liver in the 
form of ferratin. Of the other iron compounds a small portion is dis- 
solved in the fluid over the ferratin sediment; this also gives a reaction 
with ammonium sulphid. The remainder of the iron is insoluble in 
water, and is probably present in various combinations. One of these 
has been obtained by Zaleski by extracting the liver-cell pulp repeatedly, 

* Russian Archiv. Patolog. klin. Med. Bakt., March, 1901. 


860 DISEASES OF THE LIVER. 


and subjecting it to artificial digestion; this was accomplished by dis- 
solving the residue in ammonia solution, and precipitating by alcohol. 
The substance obtained was called hepatin, and is a nucleo-compound 
containing 0.0176 % of iron. It does not give an iron reaction with . 
ammonium sulphid. Woltering has demonstrated the presence of a 
similar nucleo-proteid. The other iron-containing substances of the 
liver are not thoroughly understood, especially those which will be dis- 
cussed below, which give an ammonium sulphid reaction, and are found 
in the liver after the administration of large quantities of iron, and in 
certain pathologic conditions. The liver, when it contains much of this 
substance, is colored a deep blackish-green. This tint can be recognized 
microscopically and macroscopically, and points distinctly to the presence 
of a large quantity of iron. This condition I have called siderosis of 
the liver. It may be called pathologic siderosis in contradistinction to 
the physiologic siderosis mentioned above. In marked degrees of sider- 
osis the liver appears rust-colored to the naked eye, and reveals micro- 
scopically a number of brownish granules within the liver-cells and 
capillaries; less frequently there is present a diffuse brownish coloration 
of the cell protoplasm. 


Kunkel first regarded the rust-colored pigment found in the lymph-glands 
after extravasation of blood asa “ ferrioxyhydrate,” and later Auscher and Lapicque 
looked upon the peculiar ochre-colored pigment of the siderotic liver as a special 
ferrioxyhydrate, Fe,03.3H,O. In my opinion the iron is more probably combined 
with certain organic substances, and this combination was destroyed by Auscher 
and Lapicque by boiling with sodium hydrate solutions. 


While the iron reaction is obtained with particular intensity in these 
brownish masses, it is not seen in these alone. A large portion, and 
possibly the greatest part, of the substances (both in the cells and the 
capillaries) that give the iron reaction are not colored brown. 

The iron found in the liver may come directly from iron compounds 
absorbed from the intestine. In a series of experiments a number of 
animals were all fed with a special diet, and at the same time certain of 
them received a certain amount of an iron salt; others that did not receive 
the iron were used for comparison. Kunkel, for example, administered 
a meat diet to two dogs, and gave one of them, in addition, the chlorid 
of iron. In the liver of the latter animal he found 51.2 mg. of iron, in 
the control animal 16.5 mg. In another series of experiments he fed 
young dogs with milk, and performed venesection several times. One 
of the dogs received liquor ferri albuminati. The liver of this animal 
contained 22.2 mg. of iron, that of the control animal 2.9mg. We find, 
therefore, that the proportion of iron was as 1 to 7 in the liver; at the 
same time, it was only as 5 to 8 in the blood. 

Gottlieb fed his animals with an abundant meat diet, and found that 
when iron was administered at the same time 46.7 mg. were found in 
these dogs, and only 20.2 mg. in the control animals. Samoiloff per- 
formed similar experiments on rats, and found that 100 gm. of dried 

substances contained 70 mg. of iron after the administration of, oxid of 
iron, whereas the control animal furnished only 45 mg. Hall fed mice 
with carniferrin, and found 199 mg. of iron, and only 62 mg. in the control 
animal. Woltering obtained similar results. 

Animals fed with iron gave a more intense ammonium sulphid reac- 
tion with the liver substances (Kunkel, Woltering, Filippi, Quincke and 
Hochhaus, Hall). 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 861 


Délépine claims to have found an increase in the microchemic iron reaction 
of the liver eight to twelve hours after an ordinary meal. 


If the metal is given in the form of the vegetable acid salt, subcu- 
taneously or intravenously, the accumulation of iron is still greater. It 
is well known that these salts produce a fatal result in a very short time; 
in the case of a rabbit death can be accomplished with 25 mg. of iron 
pro kilo of body-weight, and in a dog with 20 to 50 mg. 


Gottlieb, Jacoby, and Zaleski injected the tartrate of iron and sodium into 
the blood, and obtained the following figures upon analysis of the liver: 








LIVER. 
TARTRATE OF IRON 
AUTHOR. ANIMAL. AND SODIUM CORRE- ; : ae 
SPONDING TO 10 MG. Fx.| Examined Contains mg. Fe | Contains of the 
after Last in 100 gm. of Fe Intro- 
Injection : Dry Substance: duced: 





Gottlieb .| Dog. 100 to 200 mg. in | 1to4 days. 210 to 420 mg. | 20% to65%. 
divided doses. 








Jacoby ..| Dog. 200 mg. 14 hours. | 105 mg. 40%. 
Zaleski ..| Rabbit. | 9.6 mg. 3 hours. 172 mg. (nor- 
. Cat. 56 mg. 3 hours. mal 99). 
89 mg. (nor- 
mal 43). 




















Laevecke injected the citrate of iron subcutaneously into rabbits, giving a dose 
of 15 to 176 mg. of iron pro kilo. Microchemically the liver-cells gave a distinct 
iron reaction that was stronger and more persistent in the peripheral part of the 
lobules, and disappeared in the course of the second day. Iron was passed in the 
urine within half an hour, and was found in the bile from the fourth to the sixth 
hour in a form that gave a direct reaction. When the ureters were ligated, the 
iron reactions of the liver and the bile were particularly intense. 

Noélke injected citrate of iron into rabbits daily or every other day for from 
one to five weeks. The animals bore 5 mg. of iron very well, and 10 mg. not so 
well. As long as the doses were kept small only a slight iron reaction was elicited 
from the kidney, though the metal accumulated in the liver, the spleen, and the 
bone-marrow. The liver showed a very intense iron reaction, particularly in the 
cells, and less so in the capillaries. In two animals cellular siderosis of the liver 
was found four months after the administration of iron; in a third animal, treated 
in the same manner, it had disappeared at the end of seven months. 

Very insoluble iron preparations, such as ferric oxid and ferric hydrate, are 
absorbed, and may lead to siderosis of the spleen, the bone-marrow, and the liver. 
I have verified this personally by injecting these substances into the subcutaneous 
connective tissue of dogs, rabbits, and guinea-pigs. The iron is deposited chiefly . 
in the liver-cells and to a lesser extent in the capillaries. 

When pure hemoglobin is injected under the skin, there is an accumulation 
of iron in the liver. v. Starck and Schurig performed experiments of this kind in 
dogs and rabbits, the latter especially administering small doses frequently and 
for a long time. A portion of the injected hemoglobin (usually from the horse) 
was decomposed in the cellular tissues in such a manner that two (v. Starck) or 
four (Schurig) days after the injection the iron could be demonstrated directly. 
Another portion of the hemoglobin was absorbed as such, and entered the circu- 
lation, of thel atter, a portion was excreted in the urine, but only when the quantity 
injected exceeded 1 gm. pro kilo of body-weight. A small quantity of hemoglobin 
was excreted by the bile; the rest was elaborated, and in part formed bilirubin, 
and in part was converted into substances that will be mentioned presently. Stadel- 
mann and Gorodecki found that from 30 % to 40 % of the quantity injected was 
converted into bilirubin, and caused a pleiochromia of the bile. 


862 DISEASES OF THE LIVER. 


Both the iron that is separated in this process, and the iron that is obtained 
from other decomposition of hemoglobin, is to a great extent retained in the body 
and can be demonstrated microchemically in the spleen, the bone-marrow, and the 
liver. In the latter organ the peripheral portions of the lobules show a distinct 
iron reaction. Schurig found that in certain instances more iron was deposited 
in the leucocytes of the liver capillaries, and in other exactly similar experiments 
more in the liver-cells: it did not appear to be clear what caused these variations. 
It has been shown also that pigeons, in the experiments of Laspevres, tolerated in- 
jections of equine hemoglobin only so long as the quantity did not exceed 0.3 gm. 
pro kilo of body-weight. The conversion occurred a little more rapidly, and up 
to the third day an intense iron reaction was elicited in the splenic pulp and in the 
liver-capillaries; the iron was usually seen in the shape of large granules, whereas 
from the sixth day on it was found almost exclusively in the liver-cells in the form 
of fine granules. 

In the minority of the experiments mentioned above the substance within the 
cells that reacted to iron was colored brown. Sometimes it had no color. It is not 
certain how much of this iron is formed in the liver, the spleen, and the bone-marrow, 
from hemoglobin brought there unaltered; and how much of it is carried to this 
organ in the form of decomposition products from the hemoglobin of the body. 
It is remarkable that (according to Schurig) the iron reaction could not be deter- 
mined before the fourth day, whereas an increase in the formation of bilirubin (ac- 
cording to Stadelmann) begins within ten to twelve hours. It would appear that 
the iron radicle must be present in an unknown form for the first three days, and 
is then converted into a compound that gives the iron reaction. 


The question of the origin of iron in the liver becomes still more com- 
plicated if the blood of an animal of the same species, instead of a solu- 
tion of pure hemoglobin,* is injected into the blood-stream or the peri- 
toneal cavity. It is possible that the artificial plethora causes a portion 
of the hemoglobin to be dissolved in the serum, and it is certain that 
a number of blood-corpuscles are taken up by the leucocytes and the 
marrow- and pulp-cells while they still contain hemoglobin. They are 
found in the spleen, the bone-marrow, and the liver-capillaries, and are 
here altered in such a manner that positive iron reactions become ap- 
parent. The capillaries of the periphery of the liver lobules contain a 
great many of these iron-holding leucocytes. If artificial plethora is 
induced by repeated injections of blood, the liver-cells themselves may 
contain iron.t 

Moreover, if the blood of the animal is injected subcutaneously, the 
consequences are only slightly different. A partial exosmosis of hemo- 
globin occurs at once, so that results are seen similar to those observed 
after injections of hemoglobin. Here, too, we see siderosis of the spleen, 
the bone-marrow, and the liver-capillaries, and to a slight degree of the 
liver-cells, whereas the renal epithelia show a slightly increased iron 
reaction, just as in intravenous injections. | 

Similar conditions are sometimes seen in man when large extrava- 
sations of blood occur into the abdominal cavity or into the cellular 
tissues. In such cases siderosis of the liver and of other organs develops 
(Hindenlang). 


_ I had the opportunity recently of observing a case that was very remarkable 
in this respect. A young man, previously in perfect health, suffered from a twist 
of the mesocecum and mesocolon, and died within six hours. Owing to the torsion 
of the vessels the whole duodenum was filled with bloody infarcts, and contained 
free blood. There was a pronounced siderosis of the liver, but a positive iron reac- 
tion was obtained only from the liver-cells. It would appear, therefore, that this 
condition of hepatic siderosis occurred within six hours by the absorption of hemo- 
globin from the wall and the lumen of the intestine. 


* Quincke, Deutsche Archiv. f. klin. Med., 1880, Bd. xxv, 8. 580. 
{ Ibid., 1883, Bd. xxxm, S. 22. 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 863 


Siderosis of the liver and of other organs which follows poisoning 
with arseniated hydrogen (Naunyn and Minkowski), and with toluylene- 
diamin (Stadelmann, W. Hunter, Biondi), is of complicated origin, 
for under these conditions not only is hemoglobin present in solution in 
the blood, but remnants of red corpuscles which still contain hemoglobin 
(as in artificial plethora) circulate in the blood, and are gathered up 
by the colorless cells. 


Other blood-poisons (compare page 496) act similarly, as, for instance, a poison 
found by Schaumann and Tallquist in Bothriocephalus latus. Destruction of red 
blood-corpuscles followed by siderosis of the spleen, liver, etc., may also be due to 

oisoning by carbon disulphid or carbon oxysulphid (Schwalbe, Kiener, and Engel). 
tt appears, however, that the pigment that gives the iron reactions in this case is 
of a different nature, being brown-black in color, and yet seemingly originating 
within the blood-corpuscles. 


From all these experiments and observations we must form the 
conclusion that the liver as well as the spleen and the bone-marrow is 
a depository in which iron (in a form that gives positive iron reactions) 
is arrested. It is immaterial whether it is introduced from without 
or whether it enters the blood-stream from other organs, particularly 
from red blood-corpuscles that have perished. It seems, therefore, that 
the liver performs a similar [storage.—Eb.] function with regard to iron, 
as is the case with fats and carbohydrates. When needed, this reserve 
store of iron is reabsorbed and utilized. 

A number of physiologic and pathologic facts corroborate this view. 
Gottlieb has seen the iron of the liver increase to five times the normal 
amount (from 30 to 170 mg.) in a dog, after a period of starvation ex- 
tending over eighteen days. Guillemonat and Lapicque, it is true, 
found no differences after fifteen days of fasting. In certain hibernating 
animals an abundant quantity of iron is found in the liver-capillaries 
(Quincke), and, according to Kriiger, the liver of the fetus of cattle con- 
tains much iron (up to 300 mg.). This is also true of new-born animals 
(cattle 180 mg., Kriiger; dogs 390 mg., Zaleski), a condition of affairs 
which is probably intended to compensate for the small amount of iron 
present in the milk. After a few weeks the quantity of iron is reduced 
to the level of the adult animal. 


Westphalen subjected the livers of a small number of human fetuses to micro- 
chemical examination, and found that the quantity of iron in the organ, as well 
as in the spleen, was greater in the earlier months of intrauterine life than at a later 
period. 


In animals in which artificial anemia has been produced the color 
reaction with ammonium sulphid is less marked (Quincke, Schmiede- 
berg). In man, if there has been much loss of blood, so that anemia 
supervenes, either no iron reaction, or only a slight one, is obtained in 
the liver, the spleen, or the bone-marrow (Stiihlen and Quincke, Stock- 
mann). In cases of this kind we must assume that the iron has been 
lost from the system. ; 

On the other hand, the liver of human beings may be found to contain 
much larger quantities of iron than normal. Normally large quanti- 
ties are rarely found, because the absorption from the intestine is regu- 
lated by the demand. If iron has accumulated under pathologic condi- 
tions, it is usually derived from the blood, although some of it may come 
from other organs. This condition, therefore, might very well be called 











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867 


868 DISEASES OF THE LIVER. 


hemosiderosis (in contradistinction to pharmacosiderosis, Naunyn). The 
débris, consisting of used-up red blood-corpuscles, is probably carried to 
the liver in the plasma, partly in the form of hemoglobin in solution; the 
old red blood-corpuscles are also taken up by the pulp-cells of the spleen 
and enter the liver-capillaries while still within them. Still another portion 
may lodge within the liver-capillaries, and be taken up by the lymph- 
corpuscles and the endothelial cells of the vessel-walls. From these 
cells iron may be passed on to the liver-cells either in the form of hemo- 
globin or of some iron compound that reacts to ammonium sulphid. 
[Minkowski * has described a curious affection, apparently heredi- 
tary, in which there was chronic icterus, urobilinuria, enlargement of 
the spleen, and siderosis of the kidneys. Several members of the 
family had congenital icterus lasting for years. Two brothers, aged 
forty-two and fifty years, were distinctly icteric, with enlargement of 
the spleen. The children of both of these brothers also had the same 
association. Previous generations were also said to have had the same 
jaundice and dark urine, and in spite of these conditions lived to an 
advanced age. There was no evidence of malarial poisoning, nor was 
there any tendency to hemorrhages. The examination of the blood, 
made wherever possible, showed nothing unusual. In the only case 
in which autopsy was performed there was neither cirrhosis of the liver 
nor obstruction of its ducts. Even on microscopic examination there 
was nothing abnormal found in the liver except an abnormal pigmenta- 
tion of the cells in the center of the lobes, this pigmentation not showing 
the reaction for iron. The pigmented kidneys, however, gave an intense 
iron reaction, and the ash of one kidney yielded 1 or 2 grams of iron. 
Minkowski looks upon the affection as unique and evidently dependent 
upon a hereditary defect, probably an anomalous transformation of 
the blood-pigment, perhaps due to primary splenic trouble.—Ep.] 
The hemoglobin of the red blood-corpuscles may be disintegrated in 
different ways. We learn this from the behavior of extravasations 
into connective tissue, where we see both bilirubin and hemosiderin 
deposited, the latter giving ammonium sulphid reactions (Langhans, 
Quincke). 
In certain pathologic conditions the amount of iron present in the 
liver is very frequently increased, as may be demonstrated both by 
chemical analysis and by macroscopic and microscopic reactions. 


Frequently only the liver-cells show an increased iron reaction (I will designate 
these cases as A), while in other, rarer instances the liver-capillaries alone give the 
reaction (B). Occasionally iron reactions are present in both the cells and the 
capillaries (C). 


A most conspicuous increase of iron is found in pernicious anemia 
(A, C). This may be so considerable that the rusty color of the liver 
is evident to the naked eye. Sometimes as much as 1800 mg. of iron 
are found (vide table), and the total quantity in the liver may amount 
to 7 gm. of the metal. Similar conditions are found in bothrioceph- 
alus anemia (Stockmann). [Vide editorial note with reference to 
anemic hemolysis.—Ep.] Siderosis of the liver is further found in 
many acute and chronic conditions, in acute enteritis of children (A, 
Peters), in typhoid and other acute febrile diseases (A, Quincke), in 
phthisis (A, C), in leukemia (A, Quincke, Stockmann), diabetes (A, C, 

* “ Verhandlungen des Cong. f. innere Medicin,’’ 1900, p. 316. 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 869 


Quincke), congested liver (Peters), chronic diarrhea (A, and atrophy, 
C, Quincke, Peters), in malaria (A, Kelsch and Kiener), in granular 
atrophy of the kidneys (A), in artificial plethora (A, C, Quincke), and 
also after large subcutaneous extravasation of blood (A, C, Quincke), 
in massive cellular hemorrhages (Hindenlang, Auscher, Lapicque), in 
cirrhosis of the liver (Hanot and Chauffard, Gilbert, Kretz, and others). 
The largest quantity I have ever found was in a case of diabetes mellitus 
(38600 mg., total quantity 27 gm.). 

The origin of hepatic siderosis is in certain of these cases fairly clear. 
In cases of tissue-waste a large number of red blood-corpuscles are de- 
stroyed, as in hunger and in hibernation; iron is at such times deposited 
in the liver for future use. The same principle applies in the case of 
blood extravasations (including congested liver), and of artificial sub- 
cutaneous injections of blood into the circulatory stream or the peri- 
toneal cavity. In leukemia the red blood-corpuscles perish, while the 
white ones enormously increase in number. The manner of destruction 
is not always the same; sometimes the solution and diffusion of hemo- 
globin in the plasma are more in evidence (hemolysis) ;in other cases there 
is partial destruction of the erythrocytes (rhestocythemia), their frag- 
ments being taken up by the leucocytes in the various organs. Of the 
blood-poisons that have been subjected to experimental tests, some act 
in one, some in another manner, this fact accounting for the various 
pictures presented by poisoning with different toxins. The variations 
depend altogether upon the blood-dissolving or blood-corpuscle-destroy- 
ing properties of the different substances. In certain cases, as in the 
acute enteritis of children, and in the above-mentioned case of volvulus 
of the intestine, the hemoglobin seems to be dissolved with great rapidity. 
The fact that in some instances the liver-cells alone become siderotic, 
and in others only the capillaries, can only be explained on the basis 
of differences in the action of the various toxins, which are as yet un- 
intelligible to us. Thus, we have observed that in experimental injec- 
tions of hemoglobin at one time the capillaries, at another time the cells, 
show the greater deposits of iron. Other factors must cooperate in the 
process of hemolytic siderosis, possibly differences in the excretion of 
iron from the colon (or the bile?); we assume this from our knowledge 
of the fact that the condition of siderosis is neither proportionate to 
the amount of iron that is consumed nor constant, even though the 
pathologic process remains the same. 

Several investigators have assumed (and Kretz recently) that a 
functional weakness of the liver-cells favors the deposit .of iron. Such 
a weakness is not a necessary condition, however, inasmuch as experi- 
ments by Quincke, Nélke, and Schurig have demonstrated that the 
deposit may occur in healthy animals. In pernicious anemia we must 
assume that a particularly active destruction of red blood-corpuscles, 
hemophthisis, occurs. In the beginning there is probably a compensa- 
tory replacement of the erythrocytes as a result primarily of an increased 
activity of the bone-marrow; and the iron required is probably obtained 
by increased absorption. This excess is, however, immediately destroyed, 
and iron accumulates more and more in the liver. Owing to excessive 
overwork, the blood-forming powers of the bone-marrow decrease, and 
progressive anemia results in the same manner as in repeated losses. of 
blood, with the difference, however, that in the case of such an internal 
hemorrhage the iron is deposited in the liver and the spleen. The clinical 


870 DISEASES OF THE LIVER. 


picture and the microscopic blood-findings may be the same in either 
case. 

[Auschiitz * considers especially the etiology of cases of cirrhosis 
with pigmentation. He finds that they do not occur with the atrophic 
cirrhosis of Laennec, but mainly with hypertrophic cirrhosis. Fletcher t¢ 
also notes 8 cases of hypertrophic cirrhosis of the liver, of which one 
presented a remarkable grade of bronzing of the skin. The clinical 
symptoms are known as the condition diabéte bronzé, and are quite 
similar in all cases. The liver showed at autopsy the features of a pig- 
mentary cirrhosis. It is enlarged, and the cells and connective tissue 
contain a yellow, ochre-colored pigment, containing iron. The pigment 
may also be found in the muscle-fibers of the heart and in the lymph- 
glands.—Eb.] 

In a certain number of cases of diabetes conditions similar to those 
observed in pernicious anemia seem to obtain. I have frequently seen 
siderosis (chiefly cellular) of the liver in cases of diabetes. There was 
not so much iron as in the other conditions, and here and there siderosis 
was completely absent. In cases of acute enteritis in children, and in 
cases of chronic diarrhea, we must assume that ptomains are formed 
in the intestine that act as blood-poisons. In malaria, the finely granular 
dark-brown, iron-free pigment, which is formed in the red blood-cor- 
puscles, accumulates in the liver-capillaries. The iron-containing por- 
tion, which is split off, is dissolved in the blood-plasma and reaches the 
liver-cells in this way. In contracted kidney deposits of iron are often 
seen in the liver and the spleen. In typhoid and phthisis a pronounced 
siderosis of the liver may occasionally be present. 

Only a few diseases lead to the deposit of large quantities of iron in the 
liver. This is seen particularly in diseases that are complicated by the de- 
struction of large numbers of red blood-corpuscles. It will depend upon 
the intensity of the disease whether or not siderosis occurs, and the con- 
dition may be seen in certain stages of the disease and be absent in others. 

Siderosis of the liver is in this respect similar to fatty liver. The 
accumulated material is held in the liver for future use; and occasionally 
the amount is so large that it can no longer be regarded as reserve mate- 
rial, but must, in part at least, be considered as permanently placed out 
of circulation. This applies more to the case of iron than to fat. It is 
possible, too, that a large quantity of iron is deposited in a form that 
is indifferent and not readily acted upon by ordinary agents. 

Siderosis of the liver was first described by me in 1877. Mild degrees 
are frequently seen, if they are only looked for (discoloration of the adja- 
cent intestine, and the ammonium sulphid reaction). In very pronounced 
cases the liver is rust-colored; but, as I have repeatedly emphasized, not 
only the brown parts of the protoplasm, but the colorless ones may give 
an iron reaction. There can be no doubt but that there is a great variety 
of possible iron compounds; this is clearly demonstrated by the differences 
that are seen in the ammonium sulphid reaction, both in regard to the 
rapidity with which the color change appears and the shade of the color. 
The nature of these various iron combinations is not well understood. 
Ferratin appears to be the most important one found in normal livers, 
though even it probably participates only to a slight extent, and pos- 
sibly not at all, in the development of pathologie siderosis. 


* Deutsch. Arch. f. klin. Med., Bd. ux11, 1899, p. 411. 
| Jour. Am. Med. Assoc., Sept. 28, 1901, p. 815. 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 871 


Little attention has been paid to siderosis of the liver, owing to the 
fact that no anatomic changes are seen other than an excessive deposit 
of iron and an enlargement of the organ. Clinical symptoms are not 
caused by the condition. The deposit of iron may, of course, occur in 
a liver that is already pathologically altered, just as a deposit of fat may 
occur under these conditions. As livers of this kind have been examined 
more frequently than normal ones, many investigators have called atten- 
tion to the excess of iron and the rusty color in various lesions of the 
organ; in fact, French authors have formulated a distinct clinical entity 
which they call pigment cirrhosis, and claim that the deposit of iron is 
etiologically related to the proliferation of connective tissue. I have 
already called attention to this idea (see page 739), and have demon- 
strated that it is false. In pernicious anemia the liver may be very 
siderotic and still show no changes whatever in its connective-tissue 
structures. If such changes are present, they are, as a rule, due to some 
other factor. In experimental siderosis (Schurig, injections of hemo- 
globin, and Nolke, injections of citrate of iron) no connective-tissue 
changes were noted. 


I have already mentioned the fact that siderosis may be seen in malaria- 
liver, when malaria pigment is deposited in the capillaries. Peters found an abun- 
dant quantity of iron that gave the iron reactions in the capillaries of amyloid livers; 
I have found it in acute fatty degeneration with icterus.* I have frequently ex- 
amined livers in cases of icterus from stasis of long duration, but (maybe by chance) 
have never discovered the iron reaction. There seems to be no connection between 
stasis of bile and siderosis. Délépine, in a case in which one of the smaller ducts 
was occluded, could elicit an intense iron reaction in the immediate vicinity of the 
area of stasis, in the cells, and in the capillaries. 


Symptoms.—Although the diseases that lead to siderosis are im- 
portant for the very reason that they withdraw iron from other parts 
of the body, no symptoms are caused by the deposit of large quantities 
of iron in the liver per se. It might be assumed that icterus, when it 
is seen in pernicious anemia, is an icterus polycholicus, and is due to 
the increased disintegration of red blood-corpuscles, and is in this manner 
related to siderosis of the liver. In view of the fact, however, that icterus 
may be due to so many different causes, this symptom can hardly be 
utilized in making the diagnosis. 

The size and the consistency of a siderotic liver are not increased. 
We are unable, therefore, to diagnose the condition. That the condition 
is present may be suspected, however, when some of the diseases that 
can cause it, as diabetes, pernicious anemia, etc., are present. Stihlen 
has shown that pernicious anemia and that form of severe anemia that 
is caused by great loss of blood differ chiefly in that in the latter condi- 
tion less iron is contained in the affected organs. It might be of value 
from this point of view to recognize the existence of siderosis of the 
liver during the life of the patient. It might even be useful to attempt 
exploratory puncture of the liver during life in order to examine the 
aspirated material for iron. 

The treatment of the primary disease should prevent or hinder the 
formation of hepatic siderosis. In cases in which the primary cause is 
known, as in certain forms of anemia, in absorption of intestinal ptomains, 
etc., the diet may be regulated, the bowels may be thoroughly evacuated 
‘and disinfected, and such drugs as calomel, bismuth subnitrate, tannin, 

¥ Vv. Starck, Deutsch. Archiv f. klin. Med., 1884, Bd. xxxv, p. 484. 


872 DISEASES OF THE LIVER. 


salol, naphthol, benzonaphthol, yeast, etc., administered for this pur- 
ose. 

2 According to the animal experiments of Nolke with citrate of iron, 
artificial siderosis can recede, the iron stored in the liver probably being 
eliminated through the intestine and the kidneys. It is probable, there- 
fore, that pathologic siderosis of the liver, as seen in human beings, can 
also be cured. It is possible that the elimination of iron can be stimu- 
lated by the administration of an abundant quantity of water, by 
vegetable acids, and by the salts of these acids (sodium citrate, bitar- 
trate of potassium) and by natural acid fruits. 


The liver, it appears, possesses the power to store other metals in the same 
manner as iron; statements to this effect have been made in regard to lead, copper, 
bismuth, arsenic and antimony. In cases of poisoning with these metals they have 
been looked for in the liver and have been found there. As a rule, the quantity 
discovered in the liver is very small, and in the case of arsenic and antimony other 
changes in the organ will be found. There are not many careful quantitative records 
extant in regard to the exact amount of these metals found in the liver; the ma- 
jority of the statements refer to lead-poisoning, but it does not appear that the 
liver, as in the case of iron, is capable of storing so much more of the metal than 
any of the other organs.* 


(F) PIGMENTATION OF THE LIVER. 
(Quincke. ) 


Substances are quite frequently found in the liver that influence the 
color of the organ, and are usually in such cases present in the liver-cells; 
they are more often granular than diffuse in character. The following 
substances may be mentioned: 

1. Normal liver pigment, consisting of yellowish-brown granules 
found in a small number of cells, either near the periphery or near the 
center of the lobules. This pigment is not constantly found, and is 
present especially in old people, and in cases of atrophy of the liver. The 
intensity of the color and its shade are variable, and the chemical nature 
of the coloring substance is not accurately known. Probably there are 
several substances which owe their origin to more or less pathologic 
processes not yet thoroughly comprehended. One of these is possibly 
hemofuscin (see below). — 

_ 2. Bile-pigment, usually bilirubin, more rarely biliverdin. Normally 
these are found only in the bile-passages; in cases of occlusion (and some- 
times in the absence of this condition) the biliary pigments may stain | 
the liver-cells, as well as the interstitial tissue, yellow. The greatest 
intensity is noted in the cells near the center of the lobules, and in the 
large and small granules within the cells. When the color is less intense, 
there is a slighter, more diffuse staining of the whole protoplasm. Ne- 
crotic foci are stained very intensely; the latter are often observed in 
this condition following the experimental production of biliary stasis 
in rabbits and guinea-pigs (Steinhaus and others), or following similar 
experiments in dogs (Pick and others) (compare page 429). 

With the microscope it is usually possible to recognize bile-staining 
from its peculiar yellowish tint. On the addition of nitric acid Gmelin’s 
color, reaction is characteristic in the different tissues. It must not be 
forgotten, however, that if the tissue is hardened with alcohol, the bile- 


* Vide Kobert, “ Intoxicationen,” p. 140. 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 878 


pigment is in great measure dissolved; whereas if the organ is hardened 
in sublimate or formalin it is much better preserved. 

3. Rust-colored iron pigment. I have discussed this pigment in 
the preceding section. It is found principally or exclusively in the 
periphery of the lobules, and may be present in the liver-cells as a diffuse 
or a granular stain. Sometimes it is seen in the other tissues, and usually 
in the form of coarse granules or collections of granules. This is par- 
ticularly the case within the capillaries, in which the leucocytes and 
epithelial cells inclose the iron granules. They may also be seen in the 
large cells that come from the spleen. In rare instances they may be 
found within the leucocytes in the lumen of the veins, a fact from which 
we must assume that they are present occasionally in the free blood- 
stream. Granules are also found that give the iron reaction in Kupffer’s 
stellate cells, in the vessel-sheaths, and in the interstitial connective 

‘tissues. Some of the colorless constituents of the protoplasm also give 
the iron reaction; these substances, as well as the iron compound, are 
probably combinations of iron with organic bodies, the iron being present 
as the ferri-ccompound. According to Auscher and Lapicque, they are 
a colloidal ferri oxyhydrate, Fe,O,, 3H,O (? Q.). The brown pig- 
ment is usually found in conditions in which large quantities of blood 
are destroyed, either by extravasation or within the blood-stream, so 
that its hemoglobin or its iron compounds are in solution; damaged 
blood-corpuscles themselves may be carried, as such, to the liver. 

4. Brown pigment is seen in venous hyperemia, chiefly in the center 
of the lobules and within the liver-cells (Perls); sometimes it responds 
to iron reactions, and may be identical with the pigment last considered. 
Sometimes it is not changed by the action of ammonium sulphid. It is 
probably derived from the red blood-corpuscles that make their exit 
through the stomata of the distended capillaries, and are altered in the 
interstitial tissues, as is the case in other extravasations. 


In a case of aneurysm of the hepatic artery that ruptured into the bile-passages 
I found isolated red blood-corpuscles in some of the acini within the liver-cells. 
Their form and color were not markedly changed. The hemoglobin had in part 
been converted into a brown pigment that gave a reaction with ammonium sulphid. 
In this instance the pressure of the blood had forced a few of the red blood corpuscles 
through the bile-capillaries directly into the liver-cells. 


5. Malaria pigment. The finely granular dark brown or black pig- 
ment that is formed by the plasmodium malariz in the circulating red 
blood-corpuscles, and which is later found floating free in the blood- 
plasma, is arrested in the most various capillary areas, particularly in 
the spleen, the liver, and the bone-marrow. This process is analogous . 
to the arrest of injected cinnabar. In the liver this pigment is never 
found in the granular cells themselves, but exclusively in the capillaries 
near the periphery of the lobules, and in the connective tissue of the 
blood-vessels. Jacobson has also observed it in the lumen of the hepatic 
veins. This brown-black malarial pigment is distinguished from the 
brown iron pigment of the liver by its color and by the uniform size of 
its granules. It does not give iron reactions, is insoluble in concen- 
trated acids, but disappears in potash solutions and in solutions of chlorid 
of calcium (Neumann). Ammonium sulphid converts it into a reddish- 
brown or orange-colored pigment, which ultimately becomes colorless. 
This can be seen in microscopic preparations (Kelsch and Kiener). 

6.. The pigment of melanotic sarcomata. This pigment colors thick 


874 DISEASES OF THE LIVER. 


masses of the tumor black, though microscopically it is yellowish-brown. 
It forms granules of various sizes within the sarcoma cells, and remains 
behind as a granular mass after the cells have perished. A portion of 
these granules may be carried off by the blood-current, and lodge in the 
liver, the spleen, and bone-marrow, just as do malaria pigment and 
cinnabar. In contradistinction to malaria pigment, sarcoma melanin 
appears to be particularly soluble in the blood-plasma (possibly after 
undergoing some modification). Within the liver this pigment is found 
exclusively in the capillaries and the interstitial connective tissue; never 
in the liver-cells. Sometimes it is present in such enormous quantities 
that the liver appears characteristically colored to the naked eye (com- 
pare Nélke and Hensen, case from the clinic in Kiel). 

The pigment deposit changes the color and the markings of the liver. 
If bilirubin is present, the general shade of the liver will be bile-yellow 
or -green; if iron pigment is present, it will be rust-colored; if malaria’ 
pigment is present, chocolate-colored. The outlines of the lobules are 
usually more distinct because the pigment is not evenly distributed; 
thus the bile-pigment and pigments formed by stasis are found near the 
center, malaria and iron-pigments ‘near the periphery of the lobules. 
Occasionally several pigments are present at the same time, as, for in- 
stance, bile-pigment, together with malaria pigment, or pigment from 
stasis; malaria with iron pigment. If the vascularity of the organ is not 
uniform and the deposit of fat varies in different parts, and if, finally, 
there is a development of interlobular connective tissue, the picture 
may be very interesting. 

In view of their various origin the significance of the different liver 
pigments varies. These differences are not sufficiently appreciated. We 
must not forget that the color of the organ is only one of the many ex- 
ternal symptoms, and may be the same when caused by different sub- 
stances. The damage caused in the liver by pigment deposits is apparently 
also various. When the deposit is bilirubin, it is greater than if it consists 
simply of iron (whether owing to the bilirubin or to other bile-constitu- 
ents?). The deposit of pigment in the capillaries, as seen, for instance, in 
malaria or in melanotic sarcoma and siderosis, constitutes a mechanical 
obstruction to the blood-stream, interferes with the nutrition of the liver- 
cells, and hinders the circulatory stream in the portal system. Of much 
greater importance is it to determine whether, in addition to the deposit 
of pigment, the parenchyma has suffered injury, or whether changes 
have occurred in the interstitial connective tissue, as is the case especially 
in malaria and chronic stasis of bile. 

Many clinicians include in the term “pigment liver” only the pig- 
mented malaria liver, the so-called “melanemic” liver. This is not 
only a one-sided view, but an incorrect and confusing one, because rust- 
colored pigment is frequently found side by side with the brown malaria 
pigment. And yet the former is found in altogether different diseases, 
as, for instance, in pernicious anemia and diabetes. Many, if not all, 
of these forms of pigment are related to hemoglobin. In the case of 
bilirubin, malaria brown, and of the rust-colored iron pigment, this 
relationship has been established. In addition to the pigmentation of 
the liver, other organs are also found to be stained, so that in an attempt 
to explain the pathogenesis of this condition the liver should not be 
considered alone. Experiments have been directed with a view to ex- 
plaining the conversion of the blood-pigment in extravasations, in arti- 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 875 


ficial plethora, and following the ingestion of hemoglobin, and appear 
likely to throw some light upon this question. 


Hemoglobin may be disintegrated in several ways so that different substances 
are generated: (1) Bilirubin, which is formed in blood-extravasations as well as 
in the liver (Langhans, Quincke). (2) Malaria brown, which is formed within 
circulating red corpuscles, and enters the plasma as soon as the latter disintegrate. 
Neither pigment contains iron; the iron is separated, dissolved, and is in part carried 
to a distance from the focus of pigmentation. (3) Yellow and brown pigments of 
different shades. These have been found particularly in spontaneous blood-ex- 
travasations, and after the injection of blood into the subcutaneous cellular tissues 
(Langhans, Quincke); also in the lungs (M. B. Schmidt). These pigments fre- 
quently appear as granules, particularly within the leucocytes or fixed connective- 
tissue cells. Sometimes they seem to be formed directly from red blood-corpuscles, 
and in other instances hemoglobin in solution is taken up by the cells and stored 
as a granular material (M. B. Schmidt, Schurig). In certain stages these granules 
give a reaction with‘ammonium sulphid; one which may, however, also be obtained 
with certain colorless granules, with the colorless protoplasm found at the point of 
extravasation, and with splenic cells, marrow-cells, liver-cells, leucocytes, and the 
connective-tissue cells of the liver. Some of the masses that give iron reactions 
are rust-colored. Neumann has grouped all these derivatives of red blood-corpuscles 
that give iron reactions under the name of hemosiderin. If the point of extravasa- 
tion is examined, it will be found that the iron reaction does not appear for several 
days, and that later it then decreases in intensity (M. B. Schmidt); so that in the 
beginning very many, and later an increasing number of brown and yellowish granules 
are found that do not give the iron reaction. M. B. Schmidt also found that the 
iron reaction decreased in intensity some nine weeks after the injection of blood 
into the lungs. It is probable that by this time the iron is dissolved from the golden 
yellow and reddish-brown granules that are seen. During the period of transition 
—that is, during the time in which iron-containing masses appear and disappear— 
the intensity of the iron reaction is slight in the protoplasm granules, and may vary 
in shade from a very light-green to black-green. It appears, therefore, that a 
considerable number of substances are formed in blood-extravasations, and that 
these differ not only in color, but in the intensity of the iron reaction. The same 
observation can be made in the case of the pigmentary substances found in the 
spleen, the bone-marrow, and the liver, and of the colorless ones that are present 
and give an iron reaction in these organs.* 

Recklinghausen’s hemofuscin belongs to this group; it does not respond to the 
iron reactions, but is found together with iron-containing brown pigments in many 
ee thus presenting the condition that Recklinghausen has called hemochroma- 
tosis. 

v. Recklinghausen found iron pigment only in the glands and stellate cells 
of the liver, in the connective-tissue cells of the synovial membranes of the joints, 
in serous and subserous tissues, in superficial cartilage cells, in lymph-glands, and 
vessel-sheaths; but not in the glandular cells of the salivary glands, the gastric 
and intestinal glands, the mucus- and sweat-glands, nor in the small muscle-fibers 
of the intestine, the blood, or the lymph-vessels. All the latter tissues contained 
hemofuscin. Other observers (Quincke, Hintze, Buss) have seen the iron reaction, 
in addition to hemofuscin, in the heart-muscle, the glandular cells of the pancreas, 
of the salivary glands, of the hypophysis, the prostate, the thyroid, the epithelium 
of the choroid plexus, and, to a slight degree, in the small muscle-fibers of the vessels. 
Hintze calls attention to the fact that pigment granules sometimes give a weak iron 
reaction, and that here, as in the extravasations, transition stages are seen be- 
tween the two pigments; for this reason Recklinghausen’s strict distinction between 
hemosiderin and hemofuscin cannot be maintained. I am personally very much 
in doubt whether the last-named substance is a distinct substance of itself, or whether 
it is a collective name for a variety of Substances. While local staining with hemo- 
fuscin may be due to extravasation of blood, we are not justified in always attri- 
buting general hemochromatosis to the hemorrhagic diathesis, as does v. Reckling- 


* The pigment granules of the liver stain well with methyl-violet, though not 
all with equal intensity, and form a dark blue color. The iron-bearing leucocytes 
are of a dull grayish-blue, and the splenic granules (pigment) garnet-red (Quincke). 

+ Hemofuscin is very stable, alcohol, ether, chloroform, and strong acids 
exerting no influence or change upon it (Buss). 7 


876 DISEASES OF THE LIVER. 


hausen. The latter condition probably originates from a long-continued process 
of destruction of red blood-corpuscles, during which the derivatives of hemoglobin, 
whether they contain iron or not (whether they are pigments or chromogens), are 
dissolved in the circulation, and thus reach the cells of the various organs, where 
they are precipitated as a finely granular deposit. In slight degrees of this hemo- 
lysis the deposit of the colorless irqn as well as of the brown pigment occurs only 
in the liver, later in the spleen and bone-marrow; in the more severe degrees, hemo- 
siderin or hemofuscin may be found in the other tissues. _ 

The deposit of iron and of pigment usually occurs simultaneously, but not 
necessarily so, and the deposits of the two substances do not follow a parallel. The 
degree of hemolysis can, therefore, only be determined by estimating the quantity 
of both pigments. 


The deposit of pigment in the liver is a very conspicuous symptom. 
It is impossible, however, to estimate its significance correctly with- 
out determining the nature of the pigment, and without studying all 
changes that occur in the body as well as those that take place in the 
liver. 

What we have already said with regard to the diagnosis of siderosis 
applies also to the diagnosis of pigment deposits during life, and to the 
significance of the accompanying changes in the size and the consistency 
of the liver. 


LITERATURE. . 
DEposits OF IRON AND PIGMENT IN THE LIVER. 


Auscher and Lapicque: “ Accumulation d’hydrate ferrique dans l’organisme animal,” 
‘“‘ Archives de physiologie,’”’ 1896, tome vin, p. 399. 

Biondi, C. :  Experimentelle Untersuchungen tiber die Ablagerung von eisenhaltigem 
Pigment in den Organen infolge von Himatolyse,” Ziegler’s “Beitrage zur 
pathologischen Anatomie,” 1895, Bd. xvi, p. 174. 

Buss, W.: “ Ein Fall von Diabetes mellitus, etc., mit allgemeinerHaimachromatose,”’ 
Dissertation, Géttingen, 1894. 

Délépine: “On the Normal Storage of Iron in the Liver,” “The Practitioner,” 1890, 
vol. xiv, No. 2. 

de Filippi: ‘‘ Experimentaluntersuchungen iiber das Ferratin,’’ “ Beitrige zur patho- 
logischen Anatomie,” 1894, Bd. xv1, p. 46. 

Frerichs: “ Leberkrankheiten,” Bd. 1, p. 324, Tafel 9, 10, 11. 

Glaeveke, L.: ‘ Ueber die Ausscheidung und Vertheilung des Eisens im Thierkérper 
nach Einspritzung von Ejisensalzen,’’ Dissertation, Kiel, 1883; und “ Archiv 
fiir experimentelle Pathologie,’ 1883, Bd. xvu, p. 466. 

Gottlieb: “Ueber die Ausscheidungsverhiltnisse des Eisens,” “ Zeitschr. fir physi- 
ologische Chemie,”’ 1891, Bd. xv, p. 371. 

Guillemonat: “ Recherches anatomo-patholog. et expérimentales sur la teneur en 

. fer du foie et de la rate,’’? Thése de Paris, 1896. 

— and Lapicque: “‘Teneur en fer du foie et de la rate chez homme,” “ Archives 
de physiologie,”’ 1896, tome vu, p. 841. 

Hall, W. S.: “Ueber die Resorption des Carneferrins,” “ Archiv fir Anatomie und 
Physiologie,’ Physiologische Abtheilung, 1894, p. 455. 

— “Ueber das Verhalten des Eisens im thierischen Organismus,”’ “Archiv fur 

_ Anatomie und Physiologie,’ Physiologische Abtheilung, 1896, p. 49. 

Hindenlang, O.: “ Pigmentinfiltration von Leber, Lymphdrisen,” etc., “ Virchow’s 

_ Archiv,” 1880, Bd. Lxxrx, p. 492. 

rent “Ueber Hamachromatose,” “Virchow’s Archiv,” 1896, Bd. cxxxrx, 

Hochhaus and Quincke: “ Ueber Eisenresorption,” etc., ‘Archiv fiir experimentelle 
Pathologie,”’ 1896, Bd. xxxvu, p. 159. 

re: if 3 “The Pathology of Pernicious Anemia,” “The Lancet,” 1888, 11, pp. 

Jacobi: “Ueber das Schicksal der in das Blut gelangten Eisensalze,” “Archiv fir 
experimentelle Pathologie,’ 1891, Bd. xvi, p. 257. 

Jacobson, O.: “Malaria und Diabetes,” Dissertation, Kiel, 1896. 

Kelsch and Kiener : “ Maladies des pays chauds,”’ Paris, 1889, pp. 414, 550; table 111, 
figure 4; table v, figure 2. . 


re) 


PARENCHYMATOUS CHANGES AND DEGENERATIONS. 877 


Kiener and Engel: “Sur les altérations d’ordre hématique produites par le sulfure 
de carbone,” ‘Comptes-rendus de l’académie des sciences,’ 1886. . 
Kretz: “ Hamosiderinpigmentirung der Leber und Lebercirrhose,” “ Beitrage zur 
klin. Medicin und Chirurgie,” No. 15, Wien, 1896. 

Kriiger : “ Ueber den Eisengehalt der Leber und Milzzellen in verschied enen Lebens- 
altern,’” “ Zeitschr. fiir Biologie,’’ 1890, Bd. xxv, p. 439. 

Kunkel: “ Zur Frage der Eisenresorption,”’ “ Pfliiger’s Archiv,” 1891, Bd. x. 

— “Blutbildung aus anorganischem Eisen,” “ Pfliger’s Archiv,” 1895, Bd. ux1. 

Langhans: “ Virchow’s Archiv,’’ Bd. xu. 

Naunyn: “Siderosis der Leber bei Diabetes,” Nothnagel’s “‘Specielle Pathologie 
und Therapie,” vol. vir, 6, p. 240. 

Neumann: “Beitrag zur Kenntniss der pathologischen Pigmente,’’ ‘“ Virchow’s 
Archiv,” Bd.cxt. 

— “Notizen zur Pathologie des Blutes,” “ Virchow’s Archiv,” 1889, Bd. cxv1, 
p. 318. 

Peters, E.: ‘Ueber Siderosis,’’ Dissertation, Kiel, 1881; und ‘“ Deutsches Archiv 
fur klin. Medicin,” 1882, Bd. xxxu, p. 182. 

Quincke, H.: “Ueber pernicidse Andmie,’”’ Volkmann’s ‘Sammlung klin. Vortrige,” 
1876, No. 100. 

— “Ueber Siderosis,’”’ Festschrift, Bern, 1877. 

— “Ueber Warmeregulation beim Murmelthier,”’ ‘Archiv fiir experimentelle 
Pathologie,’ 1881, Bd. xv, p. 20. 

— “Zur Physiologie und Pathologie des Blutes” “ Deutsches Archiv fiir klin. Medi- 
cin,” 1880, Bd. xxv, xxv; 1883, Bd. xxx111. 

— “Bildung von Gallenfarbstoff in Blutextravasaten,” “ Virchow’s Archiv,” 1884, 
Bd. xev, p..125. 

— “Ueber Eisentherapie,’’ Volkmann’s “Sammlung klinischer Vortrage,’’ Neue 
Folge, 1895, No. 129, pp. 5 to 13. 

v. Recklinghausen: “Ueber Hamachromatose,” “Bericht der Naturforscher-Ver- 
sammlung zu Heidelberg,’ 1889, p. 324. 
Samoiloff: “ Beitrag zur Kenntniss des Verhaltens des Eisens im thierischen Organ- 
ismus,” “ Arbeiten des pharmaceutischen Instituts zu Dorpat,’”’ 1893, p. 1. 
Schaumann and Tallqvist: “Ueber die Blutkérper auflésende Eigenschaft des 
breiten Bandwurms,” “ Deutsche med. Wochenschr.,”’ 1898, No. 20. 

Schiippel, O.: “ Ziemssen’s Handbuch,” Bd. vim, 1, p. 420. 

Schurig: “Ueber die Schicksale des Himoglobins im Organismus,” ‘“ Archiv fir 
experimentelle Pathologie,” 1898, Bd. x11, p. 29. 

Schwalbe, C.: “Die experimentelle Melanimie durch Schwefelkohlenstoff und 
Kohlenoxysulfid,” “ Virchow’s Archiv,’’ 1886, Bd. cv, p. 486. 

Stadelmann and Gorodecki: “Ueber die Folgen subcutaner und intraperitonealer 
Hamoglobininjectionen,” ‘ Archiv fiir experimentelle Pathologie,’ Bd. xxvu, 


p. 93. 

Stahel, H.: “ Der Eisengehalt in Leber und Milz nach verschiedenen Krankheiten,”’ 
“Virchow’s Archiv,” 1881, Bd. Lxxxv, p. 26. 

v. Starck: “Ueber Hamoglobininjectionen,” ‘ Miinchener med. Wochenschr.,’’ 
1898, Nos. 3 und 4. 

Stockmann, R.: “Remarks on the Analysis of Iron in the Liver,’ etc., “ British 
Medical Journal,’’ May 2, 1896. 

Stithlen, A.: “Ueber den Eisengehalt verschiedener Organe bei animischen Zu- 
standen,” “ Deutsches Archiv fiir klin. Medicin,” 1895, Bd. trv, p. 248. 

Vay, Fr.: “Ueber den Ferratin- und Eisengehalt der Leber,’’ “ Zeitschr. fiir physi- 
ologische Chemie,” 1895, Bd. xx, p. 377. 

Westphalen: “Ueber den mikrochemischen Nachweis von Eisen im fotalen Organis- 
mus,” etc., “ Archiv fiir Gynikologie,’’ Bd. xi. 

Woltering : “ Ueber die Resorbirbarkeit der Eisensalze,” “ Zeitschr. fiir physiologische 
Chemie,” 1895, Bd. xx1, p. 186. 

Zaleski: “Zur Pathologie der Zuckerharnruhr und zur Eisenfrage,” “ Virchow’s 
Archiv,” 1886, Bd. crv, p. 92. 

— “ Hiesngee der Leber,” “Zeitschr. fiir physiologische Chemie,” 1886, Bd. x, 


p. 6. 

— “Zur Frage tiber die Ausscheidung des Eisens aus dem Thierkérper,” “ Archiv 
fiir experimentelle Pathologie,’ 1887, Bd. xx11, p. 317. 

— “Das weg Mice Organe bei Morbus maculosus Werlhofii,’? Ebendaselbst, Bd. 
XXIII, p. 77. 


878 DISEASES OF THE LIVER. 


FUNCTIONAL DISTURBANCES OF THE LIVER. 
(Quincke.) 


In view of the numerous functions performed by the liver, the com- 
binations of these different functions must vary greatly even under 
physiologic conditions. In the light of the conditions that influence 
these functions, moreover, how great must these variations be? The 
amount of food taken, the character of the diet, rest and exercise, are 
probably the main conditions. In addition, the different ingredients of 
the food, alkalies, acids, ammonia salts, spices, alcohol, etc., must all 
be considered ; also an increase or a decrease in the biliary secretion. Any 
one of the functions may be excessive or may be reduced, may be stimu- 
lated or depressed. 

We may assume that deviations from the normal in the different 
liver functions occur under the following conditions: (1) After anomalies 
of gastric and intestinal digestion. Anomalies of this kind will influence 
biliary secretion and internal metabolism. (2) General metabolic 
anomalies, overfeeding, plethora, diabetes, obesity, gout, as well as 
anemia and cachexia, for instance, after carcinomatosis, may any or all 
produce qualitative and quantitative changes of the liver function. (3) 
All febrile and many infectious diseases. (4) Psychic and other nervous 
influences. 

In the last three groups the functional disturbance may be of hepatic 
origin, but may be also in part due to deviations from normal metabolic 
processes in other organs, owing to which the liver is secondarily in- 
fluenced. As usual it is difficult to draw a strict distinction between 
physiologic variations and pathologic disturbances. Functional dis- 
turbances usually precede anatomic changes, and play a definite réle 
in the etiology of many diseases of the liver that have been discussed 
above. They must be considered in the prophylaxis, the treatment, 
and the after-treatment of these conditions. There are always transi- 
tions from purely functional disturbances of the liver to congestive 
hyperemia, hypertrophy, and fatty degeneration; in considering these 
anomalies the purely functional disturbances of the early stages of the 
condition have also. been considered. : 

In the treatment of gastrointestinal diseases, as well as in that of 
diseases of metabolism, functional disturbances of the liver will have 
to be considered with reference to therapeutic principles. 

We will only refer to these functional disturbances of the liver and 
to their significance. As a matter of fact, we have little to aid us in 
their recognition, aside from slight changes in the composition of the 
urine and the stools. Formerly, and even to-day, in the English and 
French literature, certain symptoms have been directly attributed to 
disturbances of the hepatic function, Among these are a yellowish, 
sallow complexion, a feeling of pressure and fulness in the epigastric 
and right hypochondriac regions, a thick yellow-coating of the tongue, 
a bitter taste, bilious vomiting, flatulency and heart-burn, irregularities 
of the stool, the passage of very light-colored or very dark feces, and of 
dark urine which forms a large sediment. In addition, there may be 
headache after eating, psychic irritability, ete. ) 

_ None of these symptoms, however, demonstrates conclusively that the 
liver is involved, although it is true that they are also observed in many 


NEURALGIA OF THE LIVER. 879 


diseases of the liver, and also in many other pathologic conditions that 
may and do lead to involvement of the liver. It is confusing, however, 
to teach old theories or old hypotheses that have been constructed on a 
false basis, and it is not proper to look for functional disturbances of the 
liver in every case in which there are digestive disorders. On the other 
hand, of course, we cannot insist on a purely anatomic classification 
of diseases. It is just as erroneous to recognize nothing else than a 
catarrh of the stomach and intestine, and to discard all the older diag- 
noses of gastricism, weak stomach, dyspepsia, and diarrhea, as to look 
for functional disturbance of the liver in every case of catarrh. It is 
probable that catarrhal conditions are present in many cases, but we 
are not as yet able to recognize them in every instance. 


Murchison: “ Functional Derangement of the Liver,’’ London, 1874. 
Cayley, in Davidson: ‘‘ Diseases of Warm Climates,” 1893, p. 637. Vide also sections, 
General Etiology, p. 451; Hyperemia, p. 607; and Fatty Liver, p. 835. 


NEURALGIA OF THE LIVER. 


(Nervous Liver Colic.) 
(Quincke.) 


The term neuralgia of the liver is applied to the occurrence of violent 
spasmodic pain in the region of the liver which cannot be explained on 
anatomic grounds. The pain resembles gall-stone colic, is as violent, 
and may last from half an hour to several hours, or even several days. 

The patient is prostrated by the pain, very much excited, restless, 
pale, and collapsed; the pulse is small and irregular, but may either be 
accelerated or retarded. The pain starts in the right hypochondriac 
region, and may either remain localized strictly in the region of the liver 
(Furbringer) or may radiate like the typical colic. It is usually increased 
by pressure on the liver. In the case reported by Talma pressure over 
the region of the gall-bladder only was painful. Sometimes other pres- 
sure-points are also painful—the ovary, the kidneys, the uterus, the celiac 
plexus. During the spasm of pain vomiting often occurs, though never 
chills or a rise of temperature. Icterus and enlargement of the liver, 
which are often present in cholelithiasis, are also absent in hepatic neu- 
ralgia. When they are reported as appearing in isolated cases, suspicion 
is always aroused that the case was not purely of nervous origin. 

The attacks of pain are frequently periodic, and may occur shortly 
before menstruation (Frerichs), during menstruation (Pariser), every . 
night, every six weeks, or every three months (Fiirbringer). Cyr observed 
a cycle of attacks occurring twice a day on the first, second, third, eighth, 
and fourteenth days, first and sixth months. The cause of the attack 
is usually not discovered; in other instances menstruation, psychic ex- 
citement, social excesses, or, in some people, the abuse of alcohol, strong | 
spices, mustard, pepper, vinegar (Beau), or tea (Cussak) can be made 
responsible. | 

In the intervals between the attacks there is usually, though not 
always, an absence of pain. 

Frequency of Occurrence.—Nervous hepatic colic is found exclu- 
sively in hysterical, nervous, and usually anemic individuals, conse- 
quently most often in women, and particularly in young girls. In cases 


880 DISEASES OF THE LIVER, 


of this kind other symptoms of a nervous character are usually present, 
as intercostal neuralgia, or facial neuralgia, and these may alternate 
with the liver colic, or may later take its place entirely. The patellar 
reflex is frequently exaggerated. Spasms of different kinds may appear 
independently, or together with attacks of liver colic. 

Nature of the Disease.—The pathogenesis of these pains is as obscure 
as in other forms of neuralgia. They have been attributed to irritation 
of the hepatic plexus originating in the abdominal sympathetic and 
following the course of the hepatic artery; they have also been ascribed 
to spasms of the bile-passages. This would be analogous to muscular 
spasm of other hollow organs. This view is strengthened by certain 
peculiarities we know to exist in gall-stone colic. If this explanation is 
the correct one, the appearance of a slight icterus, or a partial obstruction 
to the flow of bile, or a transitory enlargement of the liver, might still 
be considered symptoms of purely nervous colic. The connection of 
the attacks with the ingestion of certain substances may indicate an 
idiosyncrasy, with analogies in the cardialgia following ingestion of 
lemons, asthma after ipecac, urticaria after crabs. 

Vasomotor disturbances, spasm of the vessel-walls, particularly of 
the hepatic artery, must also be considered, and are analogous pictures 
to that of migraine. It may also be true that sensory, motor, or vaso- 
motor nerves may be involved, as in other organs. 

Diagnosis.—While the existence of nervous colic of the liver is un- 
questionably established as a fact, the diagnosis of this condition must 
be very carefully made, and particularly when we remember the manifold 
appearances that an attack of gall-stone colic may present. Several 
authors (Beau, Cyr) have apparently not drawn a sufficiently sharp 
distinction, so that for a time the symptom-complex of nervous colic 
was either forgotten or its existence denied. __ 

The differential points between gall-stone colic and this condition 
may be enumerated as follows: the disposition of the patient; the above- 
mentioned primary causes of the attacks; the absence of icterus, of swell- 
ing of the liver, and of concretions in the stools; the periodicity and 
limitation of the pain to the liver region. As we have stated above, 
none of these symptoms is absolutely diagnostic (a nervous woman may 
be afflicted with gall-stones, etc.). If several of these factors, however, 
are present together, the disease is probably a nervous one. Sometimes 
the diagnosis will have to be deferred until treatment has been instituted 
for cholelithiasis, without effecting any result. As the pain in gall- 
stones is only partially nervous and to a great extent inflammatory in 
_ character, the absence of all inflammatory symptoms in a given case 
may be of value (a palpable or percussible tumor, and the persistence of 
pain in the gall-bladder in the interval between the attacks). 

Treatment.—The treatment of neuralgia of the liver should be di- 
rected with a view to improvement of the general health, and an ameliora- 
tion of the general nervous condition. The mode of life and the occupa- 
tion should be regulated, and bodily exercise and the diet supervised. 
It is necessary to particularize, especially in warning against the different 
factors that may cause an attack. Thorough regulation of the intestinal 
functions is invaluable; massage of the hepatic region and of the abdomen 
is sometimes useful. In treating the attacks the selection and dosage 
of narcotics must be governed by the general condition of the nervous 
system. In gall-stones an operation is indicated; in neuralgia of the 


DISEASES OF THE PORTAL VEIN. 881 


liver it should of course be avoided, and the diagnosis is particularly 
important in view of rendering a decision in regard to the necessity of 
operative interference. In doubtful cases an operation has been per- 
formed, but the possible nervous origin of the colic should be remembered, 
so that if the operation reveals negative conditions it can be stopped 
in time. 


LITERATURE. 


Beau, J. H. L.: “Archives générales de médecine,” 1851, tome xxv, p. 397. 

Cyr, J.: “Sur la périodicité de certains symptomes hépatiques,”’ “ Archives générales 
de médecine,” 1883, 1, p. 539. 

— “Causes d’erreur dans le diagnostic de l’affection calculeuse du foie,’’ ‘ Archives 
générales de médecine,” 1890, 1, p. 165. 

Frerichs: Loc. cit., 11, p. 526. 

Firbringer: ‘ Zur Kenntniss der Pseudogallensteine und sogenannten Leberkolik,”’ 
“Verhandlungen des Congresses fiir innere Medicin,”’ 1892, p. 313; 1891, p. 55. 

Naunyn: “ Klinik der Cholelithiasis,”’ p. 86. 

Pariser, C.: “ Beitrag zur Kenntniss der nervésen Leberkolik (Neuralgia hepatis),’’ 
“Deutsche med. Wochenschr.,’”’ 1893, p. 741. 

Talma, S.: “Zur Kenntniss des Leidens des Bauchsympathicus. Leberschmerz,”’ 
“ Deutsches Archiv fir klin. Medicin,” 1892, Bd. xix, p. 233. 





DISEASES OF THE VESSELS OF THE LIVER. 


DISEASES OF THE PORTAL VEIN. 
(Quincke.) 


THE portal vein has an important réle in the genesis of many dis- 
eases of the liver in so far as it carries many noxious agencies to the 
organ; among the latter portions of the ingesta, products of intestinal 
decomposition, and also bacteria. This probably explains why so many 
diseases of the parenchyma of the liver begin in the periphery of the 
acini, where the branches of the portal vein dissolve into capillaries. 
It also explains why so many diffuse diseases of the liver begin in small 
circumscribed foci in the interlobular spaces. In so far as other diseases 
than those of the liver are caused by the absorption of poisonous prod- 
ucts from the intestinal tract, the portal vein really serves as the entrance 
gate for all these toxic substances, so that Stahl’s old proverb, “ Vena 
portarum porta malorum,” is justified, even though originally it was 
based upon theoretic speculation. 

Although the portal vein is the main channel for the entrance of 
disease-producing agencies, it is itself comparatively seldom affected, 
at least to any marked extent. It is possible that certain functional 
disturbances occur, and escape recognition owing to the protected position 
and the difficulty of observing lesions of this vessel; and that such dis- 
turbances are of greater significance with respect to diseases of the abdo- 
men than we know. Certain facts seem, indeed, to indicate this as true. 


The portal vein and its branches are devoid of valves, but contain a strong 
internal circular musculature, as well as external longitudinal muscle-fibers. In 
the long and short intestinal veins there are valves, and the circular musculature 
is predominant. The latter fibers decrease in number as the veins converge to 

56 


882 DISEASES OF THE VESSELS OF THE LIVER. 


form the portal vein, and ultimately disappear altogether in the ramifications of 
the portal vein within the liver, so that the latter vessels only have a longitudinal 
musculature (Koeppe). The muscles of the wall of the portal vein are supplied 
by the splanchnic nerve. After ligation of the lower thoracic aorta in a dog, so 
that the amount of blood present in the portal system was reduced, P. F. Mall has 
observed a narrowing of the portal vein and a complete disappearance of its lumen 
if the splanchnic nerve was irritated. 

Kronecker determined the amount of blood in the portal vessels of the intes- 
tinal canal in rabbits (colorimetrically). If the aorta was occluded and the intestine 
massaged gently, and then the portal vein ligated, only 1 to 2 cm. of blood were 
found. If, on the other hand, the portal vein was ligated first and the aorta not 
closed until the animals had begun to grow weak, the vessels of the intestine con- 
tained from 14 to 24 em. of blood; that is, ten times as much. About the same 
amount of blood remained in the liver after ligation of the portal vein. 

These experiments, and the well-known changes in the vascularity of the whole 
intestinal blood-vessel system during hunger and during digestion, demonstrated 
that both the capacity and the lumen of the total portal system are subject to great 
variations. To what degree this change actually occurs and what role it plays in 
the causation of abdominal disturbances of a nervous character, and what sig- 
nificance it has in certain diseases of the liver, we do not know. It would be a very 
interesting and important matter to determine this point. The experiments of 
Asp and others demonstrate that irritation of the splanchnic nerves causes a rise 
of arterial pressure, but this can only in part be attributed to an increased filling 
of the arteries following the emptying of the portal system; in part they must be 
explained by an increase of the general tone of the arteries from reflex irritation 
of the splanchnics. 

Experiments carried on by the Ludwig school (F. Hofmann, Tappeiner, and 
others) show that rabbits die a few hours after ligation of the portal vein. 
first this was explained by assuming a plethora of the portal system; the theory 
was formulated that the animal bled to death into the portal vein. This was not 
tenable, however, because Hofmann found only 30 % and Tappeiner only 10% 
of the total blood in the roots of the portal vein. Kronecker added the amount 
of blood present in the liver, but even with this the amount of blood withdrawn 
from the general circulation is not sufficient to explain death after ligation of the 
portal vein. Possibly there is a paresis of the general arterial tree from reflex irrita- 
tion; or an intoxication following the obstruction of the circulation and the result- 
ing interference with the nutrition of the parts. 

I refer to the experiments of Nencki and his associates on page 406 to demon- 
strate how complicated and obscure the results of any change in the portal blood 
may be. These experiments consisted in allowing the portal blood to flow into the 
lower vena cava. 


In the light of our present knowledge we can group the diseases of 
the portal vein as follows: First, disturbances of the blood-stream follow- 
ing occlusion and narrowing of the stem of the portal vein or of its 
branches; second, inflammation of the walls of the portal vein. 


OCCLUSION AND NARROWING OF THE PORTAL VEIN. 


This condition may be caused by: 

1. Diseases of the wall of the portal vein. Acute and chronic in- 
flammations of the vessel-wall, or the extension of a neoplasm by con- 
tinuity, alter the endothelium and cause the formation of a wall-thrombus 
which may narrow or even occlude the lumen of the vessel. It may 
develop rapidly or slowly, or it may dissolve away, or it may become 
thoroughly organized. If the latter process takes place, the occlusion 
of the vessel may become permanent (pylephlebitis adhesiva). This 
disease of the venous wall is analogous to arteriosclerosis, but not as 
frequent as the latter; the investigations of Sack and Wehnert demon- 
strate that it is not as rare, however, as is generally believed. The 
resulting thrombi and vessel-occlusions in other venous areas do not 


DISEASES OF THE PORTAL VEIN. 883 


produce any serious consequences when there are free anastomotic chan- 
nels. It is a different matter in the case of the portal vein, in which 
chronic phlebitis seems to be the chief cause of occlusion of ‘the vessel 
(see statistics of Borrmann of cases quoted by Gintrac, Balfour and 
Stewart, Raikem, Morhead). This endophlebitic thrombosis may begin 
in the main trunk of the portal vein itself or may originate in the splenic 
or mesenteric veins. Occasionally the phlebitis is of syphilitic origin. 

2. Compression from without. This may be brought about by 
tumors, particularly carcinomata, starting from the stomach, the pan- 
creas, the mesentery, the retroperitoneal glands, or the liver ‘itself. It 
may also be due to enlarged portal lymph-glands lying in close proximity 
to the vessel. These glands are frequently involved in cases of neoplastic 
growth in their neighborhood (carcinoma or tuberculosis). Gall-stones, 
too, may compress the vessel, if situated in the hepatic or the common 
duct (Key and Bruzelius). Cicatricial inflammation in the neighbor- 
hood of the portal vein accomplishes the same result; this condition 
is frequently caused by syphilis, and starts in the liver with gumma 
formation. The syphilitic process may involve the wall of the vein 
itself. Chronic peritonitis may also cause the formation of compressing 
adhesions, particularly in tuberculosis of the peritoneum (Achard), 
duodenal ulcers (Frerichs), or infarction of the spleen (Osler). Some- 
times these circumscribed inflammations of the peritoneum are caused 
by concretions situated in the gall-bladder or the large bile-ducts. The 
very nature of these lesions renders it probable that, in addition to pressure 
upon the venous wall, alterations should occur in its structure, and in 
this way cause the complications of thrombosis. 

’ These lesions are generally seen in that part of the portal vein that 
is outside of the liver; less frequently in one of its main branches, or its 
roots, the mesenteric and the splenic vein. 

3. Slowing of the blood-current, as in the case of other veins, aids 
in the formation of thrombosis. As narrowing of the lumen may cause 
a slowing of the blood-stream, it constitutes of itself a cause of throm- 
bosis. Cirrhosis of the liver also causes slowing of the blood, which 
in this case is due to a narrowing of the capillary area (possibly this is 
the cause in Case 2 of Nonne). A general lack of circulatory power 
rarely is the cause of the above-named lesions in the portal area, though 
it is well known that in the veins of the lower extremity such a weak- 
ness may lead to marantic thrombosis (Auréol; Case 1 of Nonne is very 
questionable). It is possible that the portal vein is so often exempt 
because it is never at rest, there being a constant variation in the swift- 
ness of the current and in the fulness and position of the vessel, owing 
to the continual peristaltic action of the intestine. 

4. Changes in the contents of the portal vein. It appears that the 
parasite which lives in the portal system, Distoma hematobium (see 
page 830), possesses very little coagulative power. At the same time, 
the parasites occasionally occlude one or the other branch of the portal 
vein by mechanical obstruction followed by coagulation. Inflammatory 
lesions situated in the portal area may pour their products into the por- 
tal vein, and in this way increase the coagulability of the blood; such an 
increase in the coagulability is apparently present in pyemia and other 
severe diseases. We do not understand the exact cause of this condition, 
and it is quite possible that it forms the basis of some obscure cases s 
portal thrombosis whose etiology is unknown. 


884 DISEASES OF THE VESSELS OF THE LIVER. 


Experiments by Wooldridge are worthy of mention., This investigator suc- 
ceeded in causing coagulation of the blood by the endovenous injection of a peculiar 
proteid body, obtained from the thymus. In rabbits such an injection caused 
death at once; in dogs, however, coagulation seemed only to occur in the portal 
system; if the occlusion is complete, death will of course occur. If smaller quan- 
tities are injected, a partial coagulation is the result, followed by certain lesions of 
the liver which will be discussed presently. 


5. It need hardly be stated that in many cases of thrombotic occlu- 
sion of the portal vein the cause remains unknown (see above). 

Anatomy.—Narrowing of the portal vein may vary from one of a 
slight degree causing no symptoms to complete occlusion. Compression 
is frequently associated with the formation of thrombi. The thrombi 
show the well-known changes in color, consistency, laminated structure, 
etc. Unfortunately their character does not admit of our drawing any 
conclusions with regard to their age, this fact rendering the pathogenetic 
interpretation of the individual case extraordinarily difficult. If the 
thrombus becomes organized, and particularly if there is plastic inflam- 
mation of the vessel-wall, complete organic occlusion of the vein may 
result. On the other hand, the clinical course of some cases, as well as 
analogous findings in other veins, indicates that an occlusion may retro- 
gress, and that reabsorption and contraction of the thrombotic material 
may occur. 

Softening of the thrombus is observed with particular frequency in 
inflammation of the roots of the portal vein. The contents of the latter 
may themselves form a thrombus, or small particles of a softened throm- 
bus may be carried on into the liver, and cause embolic occlusion of 
large or small branches of the portal vein within the organ. Even if the 
thrombus does not undergo softening, certain mechanical influences 
may cause a transportation of coagulates from the splenic veins (Frerichs) 
or the hemorrhoidal veins (IxGhler) to the liver. If a carcinoma per- 
forates the wall of the portal vein, numerous carcinoma nodules may be 
formed in the liver. In other cases degeneration of the carcinoma does 
not occur, growth taking place within the lumen of the vessel, and ul- 
timately filling it; then following on into its ramifications, and in this 
manner producing very peculiar pictures. 

Whenever thrombosis is present, there is a tendency for it to extend 
within the vessel. This, as a rule, occurs more readily, and to a greater 
extent, from the roots and the stem than backward from the branches 
into the stem. 3 

Any or all of the changes described, however, may be found either 
in the main portion of the vessel or in its roots or branches. 

Other processes are frequently seen in the liver associated with occlu- 
sion of the portal vein. Among them may be a proliferation of the 
connective tissue, either circumscribed (cicatrix) or diffuse (in the form 
of Laennec’s cirrhosis). There may also be atrophy of the liver tissue; 
this also may be diffuse, or limited to one lobe, if individual branches 
of the portal vein are alone occluded. In the latter event the atrophic 
changes are often severe. The changes in the liver may either be a 
result of the occlusion of the portal vein, and may be directly due to 
disturbances of nutrition; or extensive narrowing of the liver-capillaries 
may occur as a result of the cirrhotic process, leading to secondary nar- 
rowiig or thrombosis of the large afferent vessel. Both interpretations 
have been advocated, and it is probable that in certain cases the first 
and in others the second theory is the correct one. 


DISEASES OF THE PORTAL VEIN. 885 


The following statistics have recently been collected by Borrmann and v. Ber- 
mant. Cases in which the liver has undergone simple atrophy as a result of occlu- 
sion of the portal vein have been described by Gintrac (three cases), Bertog (two 
cases), Leyden and Waldenstrém; others with cirrhotic atrophy by Gintrac (two 
cases), Botkin and Carson. If only single branches of the portal vein are occluded, 
focal lesions may develop, which resemble the hemorrhagic infarcts of other 
organs, in that the current within the hepatic veins runs backward, so to speak, 
causing hyperemia in the affected area. The foci are wedge-shaped or oval, and 
usually extend to the surface of the organ; they vary in size from that of a hazelnut 
to a whole lobe. - In the beginning they are distinguished from their surroundings 
by their dark red to brown color, and are outlined clearly by a distinct jagged line. 
Generally they are soft (Koehler-Orth, two cases; Rattone, Dreschfeld). Later 
these areas are depressed as a result of the decrease in size of the liver-cells. They 
grow pale and undergo cicatrization (Rattone). In one case, reported by Bermant, 
the whole right lobe had disappeared, and in its place was seen a cicatricial mass 
about as large as a hen’s egg. 

Oré, and later Solowieff, caused experimental narrowing of the portal vein, and 
produced contraction of the liver, a decrease in the size of the hepatic cells, as well 
as an increase of the connective tissue. If the occlusion of the portal vein was 
brought about suddenly, death occurred in from four to twenty-two hours. The 
liver was found engorged with blood, its cells enlarged and cloudy. In some of 
the branches of the portal vein coagula were found, and the surrounding liver tissue 
was seen to be infiltrated with leucocytes. + 

Other observations seem to show that occlusion of the portal vein is not fol- 
lowed by these results. Asp, for instance, experimented on dogs, and found that. 
after ligation of the portal vein the secretion of bile was decreased but not stopped; 
so that it appeared that the amount of blood carried into the liver through the 
hepatic artery was sufficient to maintain the secretion of bile. Cohnheim saw 
nothing but hyperemia of the center of the acini in a case of diabetes with chronic 
thrombosis of the portal vein. This hyperemia was limited to the areas of the liver 
supplied by the obstructed portal branches. Cohnheim and Litten attempted to 
produce artificial embolization in the liver and succeeded in obtaining only a 
natural injection. They found that the hepatic artery supplies the vessels of the 
bile-ducts, the walls of the portal vein, and the hepatic veins, as well as the con- 
nective tissue of Glisson’s capsule; that the veins gathered from these capillaries 
pour their contents into the interlobular branches of the portal vein; and that there 
is only a slight communication between the arterial capillaries and the capillaries of 
the portal vein. This finding was opposed to that of Chronchzewsky, who claims 
that the periphery of the lobules is supplied by the portal vein, the center by the 
hepatic artery. When arterial blood was excluded from the whole liver or from a 
lobe by ligation of the hepatic artery, or of one of its main branches, necrosis of the 
liver and of the lobe occurred. This was an indirect process following the death of 
the wall of the portal vessels and the disturbance of circulation that naturally 
resulted therefrom. (These experiments cannot be carried on in the dog owing to 
certain anastomotic connections, but they are possible in rabbits.) After necrosis 
of the lobe had occurred the animals survived for two or three days; in necrosis of the 
whole liver, for twenty hours. Cohnheim and Litten did not succeed in observing 
any consequences of ligation of a lobar branch of the portal vein. Litten, it is 
true, states in a subsequent publication that he observed the following changes in 
the liver after he had produced embolic foci by the injection of chromate of lead. 
The cells lost their nuclei, and here and there atrophy of the lobules could be seen. 
Notwithstanding the embolic occlusion of small portal branches within the liver, 
and a deficient filling of the capillaries in these areas, changes in the liver-cells 
themselves could not be seen. Rattone ligated the hepatic artery, and produced 
embolization of branches of the portal vein. He noted the development of foci 
in the liver, which at the expiration of four hours appeared pale, and after seven 
hours red, and resembled hemorrhagic infarcts. No liver structure could be 
recognized in these areas. Rattone, therefore, from his injection experiments 
recieobay that the hepatic artery also supplies the capillaries of the periphery of the 
obules. ; 


There can be no doubt, therefore, that occlusion of the portal vein 
or of one of its main branches is of great significance to the entire liver 
or to a single lobe, and we see that atrophy may result, leading even to 
complete destruction of the glandular tissue. The connective tissue in 


886 DISEASES OF THE VESSELS OF THE LIVER. 


the affected area seems to be increased. This is, however, probably a 
relative increase, while as a matter of fact it merely does not disappear 
as rapidly as the parenchymatous structures; in other cases, possibly, 
there may have been some proliferation before the vessel lesion occurred. 
Cohnheim’s apparently contradictory observations cannot invalidate the 
positive results obtained by him. The obstruction of circulation which 
he produced was not of sufficiently long duration, and was too circum- 
seribed. Occlusion of small branches of the portal vein that supply only 
a few lobules will allow capillary anastomoses, so that the nutrition of 
the parts may be maintained. If large branches are occluded, however, 
this process is insufficient. It may also be true that defective nutrition 
is withstood for a certain length of time, but ultimately slowly leads to 
atrophy, with a simple reduction in the size and the number of the hepatic 
cells. 


It is possible that the case of E. Wagner mentioned on page 639 is one of atrophy 
following disease of the portal vein, though the author rejects this interpretation. 


Connective-tissue proliferation will be more readily produced in an 
organ that is not sufficiently nourished than in a healthy one. The 
direct cause of this proliferation may be some one of the many noxious 
agencies that are carried to the liver from the intestine. It will depend 
on the character of the anatomic changes whether occlusion of the vessel 
occurs rapidly or slowly, and whether collateral branches shall assume 
the nutrition of the affected areas or not. It is not yet determined to 
what extent the capillary areas of the hepatic artery communicate with 
those of the portal vein, and to what extent, therefore, arterial blood 
can, under certain circumstances, take the place of portal blood. 


Heidenhain mentions certain earlier cases reported by Abernethy and Lawrence 
in which collateral passages were formed. . 

In one case mentioned by Cohn the arterial stem had become dilated, so 
that a sufficient amount of blood was carried to the liver by the hepatic artery, 
maintaining the nutrition of the gland, and, to a certain extent, the secretion of 
bile. 

It is also possible that in certain cases of occlusion of the portal vein itself Sap- 
pey’s so-called “accessory portal branches,” which empty into the right main branch 
of the portal vein, carry blood to the liver. 


If a large branch of the portal vein becomes suddenly occluded, 
hemorrhagic infarction may be the result. At the same time, it. seems 
that in the liver, as in other organs, the backward current from the veins 
which is necessary to produce a hemorrhagic infarct occurs only under 
certain conditions. One of these is the simultaneous occlusion of the 
hepatic artery (Dreschfeld, Koehler). Necrosis and cicatricial forma- 
tion may undoubtedly occur without the existence of a hemorrhagic 
infarct. The case reported by Bermant demonstrated that occlusion 
of one of the main branches of the portal vein is sufficient to cause com- 
plete atrophy of the glandular tissue; in this case the branch of the 
hepatic artery leading to the area was patent. 

Above the occlusion or stenosis the portal vein is often dilated, or 
the vessels may be dilated and there may be hyperemia in the area of 
the portal roots, so that the spleen is enlarged and even indurated. Fur-_ 
ther, there may be parenchymatous or surface hemorrhages in the 
mucous membrane of the stomach and intestine, or even hemorrhagic 


DISEASES OF THE PORTAL VEIN. 887 


infarction of the intestine. The latter lesions occur particularly in cases 
in which the occlusion occurs rapidly. The thrombosis extends back- 
ward into the mesenteric veins. 

Symptoms.—Thrombotic narrowing of the portal vein may lead to 
acute symptoms, which are either superadded to those of some prior 
disease (cirrhosis of the liver, chronic peritonitis, tumors of the abdo- 
men), or may appear suddenly, while the patient is apparently in per- 
fect health, owing to the fact that the disease of the vessel-wall has 
remained latent up to then. The most important symptom is the 
sudden appearance or the rapid increase of symptoms of stasis in the 
area of the portal roots. The disease is sometimes ushered in and char- 
acterized by the appearance of sudden epigastric pain followed by vom- 
iting and diarrhea, and the passage of blood from the mouth and bowel. 
Ascites and swelling of the spleen may develop in the course of a few days. 
~The former condition causes distention of the abdomen, edema of the 
lower extremities, and a dilatation of the cutaneous veins of the abdomen. 
Sometimes a venous network and edema are seen to surround the umbil- 
icus. If the ascites increases too rapidly, puncture may be necessary. 
The fluid, however, reaccumulates with great rapidity. If in spite of the 
ascites it is possible to examine the liver, and if the organ was not pre- 
viously diseased, it may sometimes be determined that the liver decreases 
in size as the disease progresses. 

Icterus is sometimes present, and may be due to an obstruction of 
the flow of bile owing to compression of the bile-ducts by the throm- 
botic and inflamed vein, or to pressure from without, together with that 
exerted by the vein. 


In isolated cases icterus may be due to more remote causes. Frerichs has formu- 
lated a hypothesis according to which narrowing of the portal vein causes a fall of 
blood-pressure in the hepatic branches, favoring a diffusion of bile into the blood- 
vessels. Theoretically, this is possible; it is doubtful, however, whether as a 
practical thing these circumstances can lead to icterus, and the hypothesis is ren- 
dered still less probable by the rare occurrence of jaundice when narrowing of the 
portal vein is known to be present. 


We have no means of estimating the decrease in the biliary secretion 
that probably occurs. Possibly the reduction in the degree of icterus 
seen in the later stages of the disease can be attributed to this factor. 
If hemorrhages occur into the intestine, secondary arterial thrombosis, 
hemorrhagic infarcts of the intestinal wall, and peritonitis may occur. 
The pathologic picture then assumes the features of acute peritonitis, 
or of occlusion of the intestine (case reports, Boucin). 

In some instances the symptoms of narrowing of the portal vein which 
set in so acutely gradually subside, only to reappear at a later period. 
These changes are probably due to variations in the size of the thrombus 
which are caused by partial resolution and contraction, followed again 
by new deposits. 

In other cases of narrowing-of the portal vein the symptoms of stasis 
develop slowly and progressively, so that the disease resembles cirrhosis. 
A differentiation may be particularly difficult, since both conditions may 
lead to a reduction in the size of the liver, and also because such a reduc- 
tion need not necessarily occur in cirrhosis. The only symptoms that 
are fairly characteristic of occlusion of the portal vein, in contradistinc- 
tion to cirrhosis, are the magnitude and the obstinacy of the gastroin- 
testinal hemorrhages, and the rapid formation of ascites. 


888 DISEASES OF THE VESSELS OF THE LIVER. 


We must remember, however, that ascites may be. absent even in complete 
occlusion of the portal vein. This is the case in the event of abundant and repeated 
hemorrhages, when there is no increase of the pressure in the portal area (Jastro- 
witz, Borrmann); or when collateral branches develop and carry the blood into the 
systemic veins. The same vessels are concerned in the latter process as in cirrhosis 
of the liver. As compared with other veins, these vessels are not so abundant, nor 
can they be so readily dilated. The principal system, the hemorrhoidal plexus, 
communicates, on the one hand, with the portal vein through the superior hemor- 
rhoidal vein, and, on the other, with the vesical plexus through the middle and ex- 
ternal hemorrhoidal vein; the latter communicates with the hypogastric vein. An- 
other anastomotic connection is the rudimentary umbilical vein, and its branch the 
paraumbilical vein, which pass along the ligamentum teres and communicate with 
the vessels of the abdominal wall. There is an anastomosis between the coronary 
vein of the stomach, and the esophageal and diaphragmatic veins of the gastro- 
epiploic vein, and between the mesenteric vein and the renal veins; also, though 
not constantly, there is an anastomosis of the lumbar and renal veins. Finally, 
there are the so-called accessory branches of the portal vein (Sappey), which run 
from the porta hepatis through the suspensory ligament to the diaphragmatic and 
epigastric veins. 


The digestive functions, even aside from the effect of the hemorrhages, 
are disturbed. There is loss of appetite, deficient assimilation, and either 
retention of feces, or a watery diarrhea that often relieves the engorge- 
ment of the portal system. 

Owing to the slight absorption of fluid and to the transudation into 
the peritoneal cavity, the urine is decreased, and it is stated, particularly 
by French authors, that it occasionally contains sugar, as in cirrhosis 
(glycosurie alimentaire). This is due to the fact that a part of the sugar 
ingested is carried past the liver by the collateral veins (see page 706). 
The occlusion of a branch of the portal vein, even if it leads to complete 
atrophy of the portion of the gland supplied, may not cause any symp- 
toms, because the remaining portions of the liver may hypertrophy and 
may vicariously assume the functions of that which is destroyed (Ber- 
mant). 

The condition may last for'a few days or a few years. If there is 
profuse hemorrhage and rapid disintegration, the disease will be of short 
duration; the more rapidly occlusion occurs, the more rapidly will the 
disease progress. Occlusion of the portal vein never occurs as rapidly 
in human subjects as in experiments on animals; the clinical course of 
the disease is likewise never so rapid. 

It appears that moderate degrees of narrowing, developing slowly, 
can be well borne for some time, even though they ultimately lead to 
complete occlusion of the vessel. Striimpell mentions a case that lasted 
for six years and in which fifteen punctures were performed; Leyden 
and Alexander report similar cases. A large number of instances are 
on record in which the course of the disease showed variations; these 
occupy an intermediate position. 


The following case reported by Dreschfeld is a very peculiar one: There was 
pylephlebitis portalis in a man of forty-eight, which led to the formation of hemor- 
rhagic infarcts. The disease lasted for five weeks, and was characterized by the 
appearance of icterus, fever, chills, ascites, diarrhea, and vomiting of blood. I 
assume that syphilis of the portal vein and of the portal cellular tissue was the cause 
of the trouble (Q.). 


The prognosis of portal narrowing is always unfavorable, although 
it is not absolutely bad. Cases that are due to the presence of syphi- 
litic gummata or to pylephlebitis syphilitica may be cured; it is also 
possible that such cases as are due to intestinal ulceration, cholelithi- 


DISEASES OF THE PORTAL VEIN. 889 


asis, or inflammatory compression may be relieved by treating the pri- 
mary disease. | 

Treatment is, as a rule, palliative and directed toward removing some 
of the consequences of portal narrowing; it is similar to the treatment 
of cirrhosis of the liver in this respect; it is possible to relieve the engorge- 
ment of the portal system by well-selected laxatives and purges; ascites 
can be relieved by puncture. It is well, however, to postpone the latter 
operation as long as possible, because in this disease the ascitic fluid has 
a great tendency to return within a short time. 

In syphilitic cases a course of iodin, and especially of mercury, should 
be instituted, and an amelioration or a cure of the disease be attempted in 
this way, so long as gummata or gummatous inflammations of the walls 
of the vein are present. If the occlusion of the portal vein is due to an 
organized cicatricial mass, treatment will, of course, be altogether in vain. 


INFLAMMATION OF THE PORTAL VEIN. 
Pylephlebitis. 


1. Chronic Pylephlebitis——The wall of the portal vein, as of any 
other vein of the body, may undergo a degeneration similar to that of 
arteriosclerosis in the arteries; it is characterized by a thickening of 
the intima with impairment of its elasticity and degeneration and cal- 
cification of the media. Phlebosclerosis of this character frequently 
develops from unknown causes; it may be the starting-point of throm- 
botic occlusion of the portal vein, as described in the preceding section. 
Chronic inflammatory thickening of the walls of the portal vein has also 
‘been found in cases in which some inflammatory process, caused by the 
presence of gall-stones, has extended into adjacent tissues, or in which 
the inner surface of the vessel is irritated by the Distomum hematobium. 
This parasite is frequently found within the portal vein and in large 
numbers (see page 829). Syphilis may also cause changes in the walls 
of the portal vein, consisting in circumscribed gummatous inflammation. 
In the new-born, syphilis frequently causes stenosis of the umbilical 
vein from endophlebitis (Oedmannsson, Winckel); or there may be pyle- 
phlebitis and thickening of Glisson’s capsule around the larger branches 
of the portal vein within the liver that leads to narrowing of the lumen 
of the portal vein, of the branches of the hepatic artery, and of the bile- 
ducts (Schtppel). Weigert has described tuberculosis of the walls of 
the portal vein. 

All these diseases of the portal vein lead to a decreased elasticity and 
to an impairment of the vasoconstrictor and dilator powers. They 
frequently cause the formation of solid mural thrombi, which may be- 
come organized or enlarged, and either reduce the lumen of the vessel 
or bring about complete occlusion (pylephlebitis adhesiva). We have 
already discussed the symptoms: of this chronic form of inflammatory 
stenosis. 

2. Acute Pylephlebitis. — (Pylephlebitis Suppurativa, Ulcerosa.) 
Acute inflammation of the main trunk of the portal vein may, in rare 
cases, be caused by the presence of some sharp foreign body that pene- 
trates the wall of the intestine, and, entering adjacent tissues, reaches 
the portal vein (fish-bones, Lambron, Winge; wire, von Jau). The 
‘inflammation may extend to the stem of the portal vein from an en- 


890 DISEASES OF THE VESSELS OF THE LIVER. 


capsulated purulent exudate (Schonlein), or from a lymph-gland that 
has undergone purulent degeneration. ‘ 

More frequently the inflammation starts from the roots of the portal 
vein, or from suppurative foci, or from ulcers in the intestinal tract. 
Typhlitis and diseases of the appendix are particularly important in 
this respect. Further, the different forms of ulceration of the colon 
(dysentery, typhoid, tuberculosis), diseases of the rectum and of its 
vicinity, as hemorrhoids, carcinoma, fistula, mechanical injuries in- 
flicted during the administration of an enema, and during operations 
in this region. Pylephlebitis may also start from the venous plexuses of 
the bladder and the uterus. Ott describes a case of this kind occurring 
during the puerperium. Gastric ulcers are rarely the starting-point of 
pylephlebitis, notwithstanding their situation (Bristowe, West, Son- 
sino). This is probably due to the fact that they rarely suppurate. 
Frerichs (11, page 394) and others have seen pylephlebitis start from 
an abscess of the spleen, Leudet from a glandular abscess of the mesentery, 
Chvostek from a purulent pancreatitis. In the new-born infection of 
the portal vein sometimes starts from the umbilical vein after it is cut. 
Focal diseases of the liver may extend by direct continuity to neighboring 
branches of the portal vein and cause inflammation, for instance, abscess, 
or ulceration of the bile-passages as a result of concretions. 

Anatomy. —The suppurative processes that cause inflammation: of 
the portal vein are probably without exception of bacterial origin. They 
extend to the outer surface of the wall of the vein, usually first involving 
a small intestinal or mesenteric vein. The vessel-wall becomes thickened, 
injected, and infiltrated with cells; finally, some small area in the intima 
is perforated, or thrombotic occlusion of the vessel occurs, followed by 
bacterial disintegration of the thrombus. By continuity, or by diffu- 
sion of bacterial products, the thrombus may extend centrally up the 
lumen of the vein, and in this manner reach the stem of the portal 
vein. Or, on the other hand, fragments of the softened thrombus may 
become loosened, and may be carried centrally until they lodge at some 
point in the portal vein, or in some intrahepatic branch of this vessel. 
Wherever these embolic masses lodge, they form the starting-point of 
new thrombi and new suppurative processes. The latter do not involve 
the thrombus alone, but extend to the inflamed and thickened vessel- 
wall, and further into the surrounding tissues. In this manner it may 
happen that the roots, the stem, and the branches of the portal vein 
are filled over large areas with pus; that their walls are thickened and 
infiltrated with pus, and, may become ulcerated or even perforated. 
These portions of the vessel are separated from others that still carry 
blood by a solid thrombus that is attached to the vessel-wall. In the 
case of smaller veins this occlusion near the primary disease focus may lead 
to organization and to definite occlusion. Cases of this kind are never 
recognized. In the majority of cases this protective wall will only partly 
and incompletely fulfil its mission, so that coagulation proceeds from 
this point; the puriform softening, with loosening of embolic fragments, 
continues. If fluid pus enters the blood, the inflammatory material 
is more finely distributed, becomes lodged in the capillaries of the liver, 
and in this manner causes the formation of numerous small abscesses; 
larger emboli, on the other hand, usually cause the formation of a solitary 
abscess. According to the character of the primary focus, the secondary 
ones will be purulent or gangrenous. 


DISEASES OF THE PORTAL VEIN. 891 


Acute pylephlebitis beginning in the branches or the stem of the 
portal vein rarely shows a tendency to form thrombi in a direction opposed 
to the blood-stream. 

Symptoms.—As long as the inflammation is limited to the wall of 
the vein, no other symptoms except those caused by the primary disease 
are noticed. As soon as the thrombus forms, or as soon as it begins 
to soften, symptoms appear. Mechanical disturbances following occlu- 
sion of the vessel are ‘not important in acute pylephlebitis, and may 
be altogether absent. The general symptoms of pyemia are particu- 
larly conspicuous—namely, an irregular fever with high excursions, 
chills, sweats, collapse, and temperature remissions below normal. As 
in other forms of pylephlebitis, these general symptoms do not appear 
for some time after the inflammation of the vessel has occurred. This 
rule also applies when symptoms are present of softening of the thrombus, 
and in secondary suppuration in the liver. 

Occasionally local symptoms in the abdomen designate the origin 
of the pyemia; thus there may be pain in the region of the cecum or 
the spleen. If this was present before the other symptoms apneared, 
it may become exacerbated as soon as pylephlebitis occurs, probably 
as the result of slight peritonitis. The spleen is usually enlarged as a 
result of inflammation, as in any case of pyemia; occasionally there is 
hyperemia from stasis, particularly if the portal vein is extensively 
occluded. There may also be parenchymatous swelling of the liver, 
with enlargement of the organ; or, in cases that last long, there may be 
abscesses. These may either be numerous and small, so as to cause a 
uniform enlargement of the organ, or single large abscesses and cause a 
circumscribed swelling. 

Icterus is not constantly found in pylephlebitis. If it is present, its 
intensity varies, and its pathogenesis varies in different cases. Some- 
times it is due to pyemia; at others it is due to stasis from compression, 
or from inflammatory swelling of the bile-channel walls. There is gener- 
ally some disturbance of digestion, lack of appetite, vomiting, or diar- 
rhea. If these symptoms are not caused by the primary disease, they 
may be considered the results of pyemia, or of the interference with the 
blood-current in the portal area, or of peritonitis. The latter complica- 
tion frequently develops from an extension of the inflammation by direct 
continuity from the portal vein. Peritonitis is localized in the beginning, 
but may become general as the disease progresses. 

Owing to the rapidity with which the disease begins and develops, 
the purely mechanical results of disturbances of the portal blood-stream 
are rarely seen, as, for instance, ascites, and dilatation of the veins in 
the umbilical region. Toward the end of the disease there may be bloody 
evacuations as a result of infarction of certain portions of the intestine. 

The urine is scanty and may contain albumin or indoxyl. 

Course.—It is probably impossible to determine the true beginning 
of the inflammation of the vein during life. The first symptoms that we 
notice are those of the general infection, which may develop either spon- 
taneously, or be consecutive to the primary local disease of the cecum, 
etc. In many instances the primary disease seems to be cured, and 
symptoms of pyemia fail to develop for several weeks, lasting usually 
from two to-six weeks; less frequently for several months. 

Diagnosis.—The pathologic picture of purulent pylephlebitis corre- 
sponds, on the one hand, with that of pyemia; on the other, with that 


892 DISEASES OF THE VESSELS OF THE LIVER. 


of abscess of the liver. As a rule, only the diagnosis of pyemia can 
be found from the objective symptoms; its origin, however, remains 
obscure, or can only be guessed at from the history. In other instances 
the primary focus is still demonstrable, or can be determined, on careful 
examination, by such symptoms as local pain, etc. 

It is impossible to formulate a clear distinction between abscess of 
the liver and this condition, either diagnostically or pathogenetically, 
owing to the fact that every metastatic abscess of the liver is caused 
by a perforating inflammation of a small vein. It is due to this that 
we see transitions from simple hectic pus-fever to most pronounced 
pyemia. The source of the latter is, however, always anatomically 
demonstrable in the region of the portal vein. Secondary pus foci are 
rarely found in the greater circulation, because the liver forms a pro- 
tecting wall against the transportation of pus. 

Local hepatic symptoms are less frequently seen in the very acute 
cases than in the slow chronic variety. 

The prognosis of pylephlebitis, when once distinctly diagnosed, must 
usually be a fatal one. At the same time, it is possible that an acute 
nongangrenous inflammation of the stem of the portal vein might be 
relieved, in case the primary focus of inflammation should subside and 
the thrombus be reabsorbed. It is even possible that purulent embolic 
phlebitis of a branch of the portal vein might be cured in the same manner 
as dysenteric abscess of the liver (a condition genetically related to this 
condition), provided the primary focus—as, for instance, an inflamma- 
tion in the region of the vermiform appendix—is treated surgically and 
in good time. 

Treatment.—From a prophylactic point of view the correct treatment 
of all diseases that may lead to pylephlebitis is important, as, for in- 
stance, the early opening of pus foci in the region of the vermiform ap- 
pendix, and of periproctic abscesses, the careful treatment of hemor- 
rhoidal phlebitis, strict asepsis of the umbilicus in the new-born and in 
all operations of the rectum. It is certain that many cases of phlebitis 
have of late been prevented by these precautionary measures. 

Even when pyemia is already pronounced these precautions should 
not be neglected. Ifthe primary focus can be removed, and the secondary » 
abscesses in the liver incised and evacuated, some cases may be cured, 
as in other instances of pyemia. Treatment, of course, can only be 
palliative and symptomatic; drugs belonging to the class of roborants, 
excitants, and narcotics should be used. I think that the old-fashioned 
decoction of Peruvian bark is more useful in these cases than quinin, 
antipyrin, and similar febrifuges. | 


oe other pathologic changes of the portal vein may be men- 
tioned: 

Dilatation of the stem of the portal vein has been. noted above an 
old stenosis that has not completely obliterated the vessel (Virchow *); 
in this case the wall was thickened, and.the involved area resem- 
bled an arterial aneurysm. The portal vein may be dilated to its 
roots, and the vessel may be tortuous. Cirrhosis may also cause dila- 
tation of the vessel from stasis. Sometimes this condition will lead to 
collateral dilatation of the esophageal veins, and the formation of sub- 


* Virchow, Verhandl, der phys.-med. Gesellsch. zu Wiirzburg, Bd. vir, p. 21. Ex- 
tracted by Schiippel, loc. cit., p. 781. 


DISEASES OF THE PORTAL VEIN. 893 


mucous varices. The latter may burst and cause fatal hemorrhages (see 
pages 707, 708). . 

Varicose dilatation of the submucous veins of the intestine (Rokitan- 
sky,* Thierfelder,t Neelsen,t and Koster 2). These were as large as 
grains of wheat or peas, or even cherries, and sometimes resembled 
mulberries, owing to the tortuous character of the veins. Sometimes 
they were gathered in bunches of dozens or hundreds, and usually were 
limited to certain portions of the intestine, either the colon, the jejunum, 
or the upper part of the ileum, and, in one case, the whole intestine (here 
they were smaller). Koster reports two cases of subserous varices in 
small areas of the colon, and in the pyloric end of the stomach. Gee 
describes varicose veins of the gastric mucosa as thick as a goosequill, 
and some of them thrombosed.|| There was no obstruction of the blood- 
stream in any of these cases, so that it is probable that they were formed 
by local disease of the walls. Neelsen believes that the lesions were due 
to atrophy from inactivity of the musculature of the veins following 
some disturbance in its innervation. These varices caused no clinical 
symptoms, but occasionally produced hemorrhages. 

Rupture of the portal vein,** either of its stem or of one of its main 
roots, may occur spontaneously, and, of course also as the result of trauma. 
It is probable that in such cases there is some circumscribed lesion of 
the wall. Frerichs in one case (a drunkard) saw fatty degeneration of 
the wall; Vesal in another case perforation of the vessel by an abscess 
of its wall. Perforation occurred either into the abdominal cavity or 
between the layers of the mesentery, sometimes immediately after a 
meal. Sometimes the patient has complained of a sensation as if some- 
thing had torn in the upper region of the abdomen. If perforation 
occurs into the peritoneal cavity, death follows rapidly from internal 
hemorrhage. If rupture occurs between the layers of the peritoneum, 
the patient may survive for two days. 

For parasites of the portal vein see page 829; for carcinoma, see page 
777. Either condition may result in the occlusion of the blood-stream 
and cause various disturbances. 


A remarkable anomalv has been reported by Abernethy +f occurring in a child, 
the portal vein entering the lower vena cava in the neighborhood of the right renal 
vein. Aside from the fact that the stem of the portal vein is absent, this anasto- 
mosis corresponds to Jacobson’s vein in birds, and to the so-called von Eck fistula 
that Pawlow, Nencki, and their associates created experimentally. 


LITERATURE. 


Achard: “ Archives de physiologie,”’ 1884, tome xvi, p. 484. (Compression durch 
tuberculése Peritonitis.) 

Alexander: “ Berliner klin. Wochenschr.,” 1866, No. 4. eee 

Asp: “ Zur Anatomie und Physiologie der Leber,’ “ Arbeiten aus dem physiologischen 
Institut zu Leipzig,” 1873, Bd. vu, p. 136; “Bericht der saichsischen Gesell- 
schaft der Wissenschaften.”’ ‘ 


* Rokitansky, “Lehrb. der patholog. Anatomie,” 1844, 1, p. 672. 

+ Thierfelder, Archiv der Heilkunde, 1873, p. 83. 

t Neelsen, Berlin. klin. Woch., 1879, p. 449, 470. 

§ Koster, Berlin. klin. Woch., 1879, p. 634. 

|| “ Bartholomew’s Hosp. Rep.,”’ 1871. Jahresbericht 1, p. 189. 

** Frerichs, 11, p. 382. ‘ ; 

+t Abernethy, Philosoph. Transactions, 1793, 1, p. 61. Quoted by Heidenhain; 
Hermann’s “Lehrbuch der Physiologie,” v, 1, p. 237. 


894 DISEASES OF THE VESSELS OF THE LIVER. 


Auriol, L.: “ Contribution a l’étude de la thrombose cachectique de la veine porte,” 
Thése de Paris, 1883. 
Bermant: “ Ueber Pfortaderverschluss und Leberschwund,’’ Dissertation, Kénigs- 

berg, 1887. (Literature.) ; wae 

v. Birch-Hirschfeld: “ Beitrag zur pathologischen Anatomie der hereditaren Syphilis 
Neugeborener,”’ “ Archiv der Heilkunde,” 1875, Bd. xvi, p. 166. 

Borrmann: “ Beitrag zur Thrombose des Pfortaderstammes,” “Deutsches Archiv 
fiir klin. Medicin,” 1897, Bd. urx, p. 283. (Literature.) 

Botkin: “ Fall von Pfortaderthrombose,” “ Virchow’s Archiv,” 1864, Bd. xxx. 

Boucey, H. O.: “Des lésions intestinales consécutives a la thrombose de la veine 
porte ou de cas branches d’origine,” Thése de Paris, 1894. 

Budd: “ Diseases of the Liver,” 1845, p. 136. 

Chauffard: in Charcot’s ‘“ Traité de Médecine,” tome 111, p. 816. 

Chvostek: ‘‘Krankheiten der Pfortader und der Lebervenen,”’ “Wiener Klinik,’ 
1882, Heft 3. (Literature.) 

Cohn, B.: “ Klinik der embolischen Gefasskrankheiten,” p. 490, Berlin, 1860. 

Cohnheim and Litten: “Ueber Circulationsstérungen in der Leber,’’ “ Virchow’s 
Archiv,” 1876, Bd. Lxvul, p. 153. 

Couturier : “ De la glycosurie dans les cas d’obstruction totale ou partielle de la veine 
porte,” Thése de Paris, 1875. 

Dreschfeld : “ Ueber eine seltene Form von Hepatitis interstitialis mit hamorrhagi- 
schen Infarcten,” “ Verhandlungen des X. Internationalen Congresses,’”’ 1891, 
Abth. v, p. 184. . 

Ewald: in Eulenburg’s “ Realencyklopadie,” Bd. xv1, p. 286. 

Frerichs: “ Leberkrankheiten,” 11, p. 363. (Casuistik.) 

Gintrac: “ Journal de médecine de Bordeaux,” 1856, Jan.—Mar.; “ Journal de l’ana- 
tomie et de la physiologie,”’ 1864, 1, p. 562. 

Goodridge: “The Lancet,” June, 1887. (Injury to the portal vein, due to cica- 
tricial bands.) 

Jastrowitz: “ Deutsche med. Wochenschr.,” 1883, No. 47. (Thrombose aus lue- 
tischer Ursache.) 

Koehler, B.: “Ueber die Verainderungen der Leber infolge des Verschlusses von 
Pfortaderisten,” “Arbeiten aus dem pathologischen Institut in Gottingen,” 
Berlin, 1893. 

Koeppe, H.: “ Muskeln und Klappen in den Wurzeln der Pfortader,” “ Archiv fir 
Anatomie und Physiologie,” 1890, Supplement, p. 168. 

Kronecker: “Ueber den Tonus des Pfortadersystems,” “Bericht iiber die Ver- 
sammlung deutscher Naturforscher und Aertze,’”’ 1889, p. 311. 

Lambron: “ Observations d’inflammations: 1. de la veine porte, 2. des veines sus- 
hépatiques,” “ Archives générales de médecine,” p. 129, June, 1842. 

Leyden: “ Falle von Pfortaderthrombose,” “ Berliner klin. Wochenschr.,”’ 1866, No. 
13. : 

Mall, F.: “ Archiv fir Anatomie und Physiologie,” Physiologische Abtheilung, 1892; 
1890, Supplement, p. 57. 

Nonne, M.: “ Zur Aetiologie der Pfortaderthrombose,” “ Deutsches Archiv fiir klin. 
Medicin,” 1885, Bd. xxxvu, p. 241. 

Oré: “ Journal de l’anatomie et de la physiologie,”’ 1864, tome 1, p. 565. 

Osler: “Case of Obliteration of the Portal Vein,” “Journal of Anatomy,” p. 208, 
January, 1882; Jahresbericht, 11, p. 178. 

Ott, vu “Zur Casuistik der Pylephlebitis,” “Prager med. Wochenschr.,” 1883, No. 


Pippow, R.: “Ueber die Obturation der Pfortader,” Dissertation, Berlin, 1888. 

Quincke: “Krankheiten der Gefisse,” in Ziemssen’s “Handbuch der speciellen 
Pathologie,” 2. Auflage, 1879, Bd. v1, p. 574. 

Sack: “Ueber Phlebosklerose,” “Virchow’s Archiv,”’ Bd. cx1t. 

Seniff, M. :“ Ueber das Verhiltniss der Lebercirculation zur Gallenbildung,” “ Schwei- 
zer Zeitschr. fir Heilkunde,” 1862, 1, 1. 

Schiippel : in “ Ziemssen’s Handbuch,” Bd. vii, Anhang, p. 269. 

— “Ueber Peripylephlebitis syphilitica der N eugeborenen,” “ Archiv der Heilkunde,”’ 
1870, Bd. 1, p. 74. 

Solowieff: “‘ Veranderungen der Leber unter dem Einflusse kiinstlicher Verstopfung 
der Pfortader,” “Virchow’s Archiv,” 1875, Bd. uxu, p. 195. 

Sonsino : “Lo sperimentale,’”’ 1888, Ottobre. (Pylephlebitis following gastric ulcer.) 

Stahl, G. E.: “ De vena portae, porta malorum hypochondriaco-splenetico-suffo- 
cativo-hysterico-colico-hamorrhoidariorum,” Halae, 1698. 


DISEASES OF THE HEPATIC ARTERY. 895 


Striimpell: “ Lehrbuch der speciellen Pathologie,” 5. Auflage, 1, p. 783. 

Tappeiner : “ Ueber den Zustand des Blutstroms nach Unterbindung der Pfortader,”’ 
“ Arbeiten aus der physiologischen Anstalt zu Leipzig,” 1872, Bd. vu, p. 11. 

West: “Pylephlebitis suppurativa durch Magengeschwiir,” “Transactions of the 
Pathological Society,” 1890; Jahresbericht, 11, p. 261. 

Winge: “ Pylephlebitis durch Fischgrite,” “ Norsk. Magazin f. Lageridensk.,’’ 1880; 
Jahresbericht, 11, p. 197. 

Wooldridge: “On Hemorrhagic Infarction of the Liver,” “Transactions of the 
Pathological Society of London,” 1888, vol. xxx1x, p. 421. 


DISEASES OF THE HEPATIC ARTERY. 


Aside from aneurysms of the hepatic artery, which are compara- 
tively rare, we know very little of the pathology of this vessel. We 
have already discussed the peculiarities of the blood-stream within the 
liver (see page 615), and especially in cases in which the portal vein is 
diseased (see page 885). The latter vessel and its capillaries may be 
termed a functional system, whereas the hepatic artery furnishes blood 
for the nutrition of the connective-tissue structures, the walls of the 
blood-vessels and the bile-passages. Wherever there is new formation 
of connective-tissue the capillaries of the hepatic artery are implicated. 
This is particularly the case in cirrhosis (Frerichs). The hepatic artery 
also sends vessels into neoplasms, so that in large carcinomata there may 
be dilatation of the main stem of this vessel (Frerichs). 

As we have demonstrated above, the capillary blood of the hepatic 
artery may act vicariously for the portal blood in case the latter vessel 
is obstructed. This can only occur in an imperfect degree, and if large 
areas of the portal system are occluded the compensation is altogether 
inadequate. In cases of this character, also, Cohn has seen a dilatation 
of the stem of the artery. Spontaneous disease, sclerosis of the hepatic 
artery and its branches, is rare in comparison with its frequency in other 
vessels. Duplaix claims that the thickening of the smallest arteries is 
an important factor in the development of interstitial connective-tissue 
proliferation (see page 688). 

If the main stem of the hepatic artery or one of its main branches 
is occluded in rabbits, necrosis of the connective tissue will follow, and 
as a consequence, indirectly, of the whole liver or of one lobe. In dogs, 
however, this does not occur, owing to the existence of so many arterial 
_ anastomoses (Cohnheim and Litten). It is not known what occurs in 
occlusion of the main stem of the hepatic artery in man (after excluding 
anastomosis with right coronary arteries of the stomach and the gastro- 
duodenal artery), because only one such case is on record (Ledien), and 
here the occlusion by an aneurysm developed so slowly that there was 
plenty of time for the formation of anastomoses. 

If a branch of the artery is occluded within the liver, in the course 
of animal experiments, no circulatory disturbances are evident owing to 
the numerous anastomotic connections that are formed. 

We know nothing of the results of embolic occlusion of the hepatic 
artery in man, though it is probable that such embolic occlusion may 
lead, for instance, to verrucose endocarditis. If in cases of this kind we 
see no local involvement of the liver, nor any cicatrices of the organ as in 
the case of the spleen, we can only assume that in man the collateral 
circulation is sufficient to compensate such a lesion. If there are infec- 
tious arterial emboli, general pyemia and abscess of the liver will result. 


896 DISEASES OF THE VESSELS OF THE LIVER. 


ANEURYSM OF THE HEPATIC ARTERY. 


Aneurysm of the hepatic artery is not frequent. Mester, up to 1895, 
found 20 cases in the literature, 11 of which were studied clinically. In 
16 cases the aneurysm started from the main stem or from one of the 
two main branches (in the case of Standhartner there were aneurysms 
of both branches), once from the cystic artery (Chiari); in 4 cases the 
aneurysm was situated outside of the liver. The extrahepatic aneurys- 
mal sacs may become as large as a goose-egg or a child’s head; the intra- 
hepatic sacs remain small, and are never larger than a hazelnut. They 
are usually true aneurysms, their walls being formed by the layers of the 
artery. These aneurysms may perforate into the bile-passages, the gall- 
bladder, the duodenum, into the stomach, through an abscess to the 
lower surface of the liver, into the peritoneal cavity. Generally, there 
are several hemorrhages. Ledieu, in one instance, found an aneurysmal 
sac that had healed spontaneously by coagulation. 

Etiology.—In one case a traumatic origin was established, the lesion 
following a kick in the abdomen by a horse (Mester); in another case 
(Borchers) traumatic origin was probable. In the case of M. B. Schmidt 
and Chiari the aneurysm resulted from injury to the wall of the artery 
from without by a gall-stone. In Irvine’s case the hepatic artery was 
eroded by an abscess of the liver, in the same manner as occurs in pul- 
monary cavities. In the case of Uhlich the wall of the artery was sclerotic. 
. In the majority of the cases the cause of the aneurysm is obscure. 

Of recent years syphilis has been recognized as an important etiologic 
factor, and a history of syphilis has probably not been elicited in all 
the cases in which it actually played aréle. Here and there the existence 
of some infectious disease, as typhoid, pneumonia, osteomyelitis, is men- 
tioned as preceding the formation of aneurysm; it is doubtful, however, 
whether such a history is of any significance. The majority of the cases 
have been under forty years of age. 

Symptoms.—If any symptoms indeed are recognized during life, 
the three following are the most important—namely, pain, hemorrhage, 
and icterus. 

Pain, when present, is localized in the epigastric or the right hypo- 
chondriac region, and once it was noted, in an aneurysm of the left branch, 
in the left hypochondriac region (Irvine). The origin of the pain in 
extrahepatic aneurysm is probably pressure on the hepatic plexus which 
surrounds the vessel; in intrahepatic aneurysm, local distention of the 
capsule of the liver, adhesive inflammation in the vicinity of the aneurysm; 
and in perforation of the vessel, distention of the bile-passages by the 
blood that is poured into them. In the latter instance the pain may 
be spasmodic, as in gall-stone colic, and may be accompanied by other 
symptoms of this condition. 

Hemorrhage, as in other forms of aneurysm, is the most frequent 
cause of death. Sometimes the first hemorrhage is copious and at once 
fatal, the blood pouring into the abdominal cavity or into the intestines ; 
in other instances several (sometimes a dozen) hemorrhages occur with 
intermissions, so that anemia from hemorrhage occurs. The patient 
in the intermissions may recover from the effects of the bleeding. The 
latter. form of hemorrhage is seen particularly in cases in which the 
aneurysm perforates the bile-passages, for as soon as the latter be- 
come distended with blood the pressure becomes so great that the bleed- 


DISEASES OF THE HEPATIC ARTERY. 897 


ing ceases; thrombotic occlusion of the tear in the aneurysm may thus 
occur. 

The blood may enter the intestinal tract through the bile-ducts, or 
if the perforation occurs in some other place by another channel, but 
always in the first portion of the intestine. The greater portion of 
the blood is, therefore, passed in the stools, and only in rare cases does 
a portion of it enter the stomach so as to be vomited. As a rule, the 
quantity of blood poured out is large, so that the presence of blood can 
be readily detected in the intestinal evacuations. In one case observed 
by the author the blood coagulated in the intestine and formed casts of 
the folds of Kerkring, proving that the hemorrhage had occurred in the 
uppermost portion of the small intestine. 

Icterus is present in the majority of cases, either because of direct 
aneurysmal pressure or owing to changes produced by the tissues causing 
an obstruction to the flow of bile. The icterus may be intermittent, as 
in the cases of the author and of Lebert and Mester, and be due to the 
temporary distention of the bile-passages with blood. If icterus is com- 
bined with paroxysmal pain, the picture of hepatic colic may be simu- 
lated. In the author’s case most of the attacks were accompanied by 
a rise of temperature, and sometimes by a chill. In the same manner 
as the concretion is passed in the stools after an ordinary attack of colic, 
blood is passed within the next twenty-four hours. It is probable that 
the latter flushes the larger passages of bile so thoroughly that the second 
_ portion of blood is coagulated. In cases of this kind the attack of colic, 
of course, will be very severe, and it may even occur that casts of the 
bile-passages are found in the stool. 

Enlargement of the liver is rarely observed; this, as we know, is 
variable also in stasis of bile. In a case reported by Stokes the left 
lobe was pressed against the abdominal wall by the aneurysm, so that 
an enlargement of this portion of the organ seemed to be present. In 
a few cases there has been an enlargement of the gall-bladder, due, as in 
the case of Niewerth, to hemorrhage into this viscus. 

A pulsating tumor, as yet, has never been felt; but it is quite probable 
that such a lesion occurs, although it cannot be determined. In a few 
instances a systolic murmur has been heard (Rovighi). 

Course.—Some cases run a very acute course, and lead to the death 
of the patient from hemorrhage into the stomach, the intestine, or the 
peritoneal cavity. Others run a longer course; Mester’s statistics give 
as the average duration four and a half months. Pain is the first symp- 
tom to appear, and is soon followed by repeated hemorrhages, with 
icterus; this picture is characterized by remissions, and lasts for several 
months. The patient usually recovers during the intervals, and death 
finally results from exhaustion or some complication. 

Diagnosis.—A diagnosis cannot be made in cases that end suddenly 
with hemorrhage. In others there is repeated hemorrhage into the bile- 
passages, and the diagnosis can-then be made from the combination of 
symptoms of duodenal hemorrhage and biliary colic. If a great deal 
of blood is passed in the stools and there is only occasional vomiting of 
blood, the former possibility can be suspected. As a matter of fact, the 
diagnosis of duodenal ulcer is frequently made. If casts of Kerkring’s 
folds are found, the intestinal hemorrhage can most certainly be located 
in the small intestine. : 

It is possible that the duodenal ulcer may be complicated by icterus, - 

57 


898 DISEASES OF THE VESSELS OF THE LIVER. 


because there may be cicatricial contraction in its vicinity with torsion 
‘and occlusion of a bile-duct. Such a complication will, however, never 
produce paroxysmal icterus, or attacks of colic. Aneurysms of the 
hepatic artery have been seen, associated with cholelithiasis, and the 
latter disease may also be complicated by hemorrhages * (from ulcers, 
fistulas, or chronic icterus). The large quantity of blood that is poured 
into the intestine is of some significance in the diagnosis of aneurysm. 

Treatment.—Internal treatment of an aneurysm of the hepatic 
artery promises very little. Syphilis rarely plays a rdéle, so that the 
treatment of this taint will lead to no results. If the diagnosis can be 
made, operative interference is Justifiable. As a preliminary step it 
will be necessary to determine how well human beings tolerate ligation 
of the hepatic artery. 


In three cases operative treatment has been attempted, although for other 
indications; namely, in two cases reported by Mester and Sauerteig for ulcerative 
internal hemorrhage, in one case retorted by Niewerth for threatened Ileus. In 
all of these cases such severe hemorrhage occurred during the operation that it 
could not be finished. 

Marion describes erosion of the hepatic artery by a carcinoma of bile-duct. 
Fatal hemorrhage rapidly ensued; the blood was poured into a cavity near the gall- 
bladder and through a duct that communicated with the duodenum into the intes- 
tine. 


LITERATURE: 


Duplaix: “ Contribution 4 l’étude de la sclérose,”’ “ Archives générales de médecine,’ 
1885, 1, p. 166. 

Frerichs: Loc. cit., p. 353; Atlas 11, Tafel 111, rv, v. 

Langenbuch: Loc. cit., 11, p. 67. 

Marion: “ De la mort par hémorrhagie dans la lithiase biliaire,” ‘“ Mercr. médical,” 
1894, No. 51; Jahresbericht, 11, p. 223. 

Quincke: ‘“ Krankheiten der Gefisse,’”’? in Ziemssen’s “ Handbuch der speciellen 
Pathologie,” Bd. v1, p. 547, 422. 

Schiippel: Loe. cit., p. 325. 


ANEURYSMS. 


Borchers: Dissertation, Kiel, 1878. 

Chiari: “ Aneurysma der Arteria cystica,”’ ‘ Prager med. Wochenschr.,’’ 1883, No. 4. 

Hansson, A.: “ Hygiea,” 1897, 1, p. 417; “Centralblatt fiir die Grenzgebiete der 
Medicin und Chirurgie,” 1, p. 299. 

Irvine: “ Transactions of the Pathological Society,’’ London, 1878. 

Lebert: “ Anat. pathologique,” tome 11, p. 322. 

Ledien: “Journal de Bordeaux,” 1856; “Schmidt’s Jahrbiicher,” Bd. xcrt1, p. 56. 

_ (Verschluss durch Aneurysma.) 

Mester, B.: “ Zeitschr. fir klin. Medicin,” 1895, Bd. xxvim, p. 92. 

Niewerth, A.: Dissertation, Kiel, 1894. 

Quincke, H.: “ Berliner klin. Wochenschr.,” 1871, p. 349. 

Rovighi: “ Riv. clin. die Bologna,” 1886, No. 52. 

Sauerteig: Dissertation, Jena, 1893. 

Schmidt, M. B.: (Aneurysma durch Gallensteine.) “Deutsches Archiv fir klin. 
Medicin,” 1894, Bd. x11, p. 536. 

Wallmann: “ Virchow’s Archiv,” Bd. xrv. 


DISEASES OF THE HEPATIC VEINS. 


Dilatation of the hepatic veins is frequently seen, particularly in dis- 
eases of the heart and the lungs that lead to an engorgement and an 
insufficiency of the right side of the heart. Dilatation of all the finer 
branches and the capillaries is observed in the center of the lobules, and 

* Arndt, E., Dissertation, Strassburg, 1893. 


DISEASES OF THE HEPATIC VEINS. 899 


is usually combined with thickening of the vessel-wall. The consequences 
and the symptoms of this condition coincide with those of hyperemia of 
the liver from stasis (see page 608). 


NARROWING AND OCCLUSION OF HEPATIC VEINS. 


Narrowing and occlusion are found less frequently than dilatation of 
one or several of the branches of the hepatic veins. This condition may 
be due to: 

1. Compression by tumors or cicatrices, particularly gummata that 
develop within the liver and extrahepatic tumors, as, for instance, lymph- 
glands. The latter usually compress the vena cava at the same time. 

2. Disease of the vessel-wall. These are rarely primary, and 
usually originate in the adjacent liver tissues and extend to the thin 
vessel-wall by direct continuity. There may be a new-formation, or, 
more frequently, chronic inflammation, with a development of connec- 
tive tissue starting from the capsule of the liver (Frerichs, Hainski) or 
from interstitial hepatitis (Brissaud and Sabourin *). Many of the latter 
forms develop from the central veins of the lobules. This has been 
particularly emphasized by French authors. Some of the larger veins 
of the liver may also be narrowed in interstitial hepatitis, and if the 
hepatitis is of syphilitic origin, the proliferative changes seem to involve 
the walls of the veins, or they may even start from these walls (as in the 
case of the portal vein). Whenever perihepatitis involves the liver veins, 
the right pleura and the pericardium are usually the seat of chronic 
adhesive inflammation. | 

3. Thrombosis. This is often a complication of the above-men- 
tioned diseases of the vessel-wall; the subsequent changes of the thrombus 
are determined by the character of the disease; 2. e., whether there is 
new-formation of connective tissue, purulent degeneration, or carci- 
nomatous development. Marantic thrombi rarely originate in the liver 
veins, probably because the right heart is so near this organ that the 
current of blood is maintained; the cardiac action is, moreover, aided by 
the constant movement of the diaphragm. In a case of hyperemia from 
stasis I was enabled to diagnose thrombosis of the hepatic veins during 
life and to corroborate my diagnosis postmortem. It is possible that in 
this disease thrombosis is more frequent than we suspect (see below). It 
may occur secondarily after occlusion of the stem or branches of the portal 
vein, followed by a general obstruction of the blood-current in the liver. 

Schuppel reports a case in which the coagulability of the blood seemed 
to be increased, a factor which appears to play a certain réle in the forma- 
tion of the thrombus. 

4. Embolic occlusion is quite frequently seen in the area of the liver 
veins when the blood-stream is reversed (Heller). It will depend on the 
nature of the embolus whether simple occlusion, suppuration, or tumor- 
formation occurs. " 

The forces that cause a reversal of the blood-current are gravity, 
contraction of the right heart, particularly of the auricle, coughing and 
other violent expiratory efforts. 


Cohn and Arnold noted simple coagulates within the liver veins that were pro- 
pelled there from the heart, and originated in the spermatic veins. The last-named 
author also saw an embolus at the bifurcation of one of the hepatic veins. Heller 


* Archiv. de physiologie, 1884, p. 444. 


900 DISEASES OF THE VESSELS OF THE LIVER. 


found small tumor particles that came from the lower vena cava; and Bonome saw ~ 
tumor fragments that were carried through the heart-blood into the hepatic veins. 

Frerichs, Heller, Arnold, and others, have attempted to study the conditions 
obtaining in these lesions by animal experiments. It was found that mercury, 
oil, and air did not form suitable emboli because their specific gravity differed from 
that of the blood. The majority of their experiments were performed by injecting 
wheat-grits into the veins of different parts of the body. If sufficiently large quan- 
tities were injected, the pulmonary blood-vessels were occluded over large areas, so 
that respiration was seriously interfered with and the action of the right heart was 
impaired. In cases of this character emboli may be carried backward as far as the 
crural and cerebral veins, and into the liver as far as the central veins of the acini 
and their surrounding capillaries (Arnold). If less was injected, the granules were 
surrounded with a thin layer of fibrin and moved along in the peripheral layers of 
the blood-column, hugging the walls of the blood-vessels. These particles were 
hardly moved by the fluctuations of the blood-current caused by the respiratory 
movements; they were propelled, however, by the more sudden waves that started 
from the heart (Arnold and Ribbert). These heart-waves propelled them against 
the blood-current either in stages or in jerks. Some of them entered the central 
blood-current and were carried along in the direction of the blood-current; others, 
again, became lodged in the narrow venous branches. We may consider the move- 
ments of the heart, therefore, as the principal force that causes recurrent embolisms. 
It is probable that violent expiratory efforts play a certain réle within the area of 
the upper vena cava and the lower extremities, but with respect to the hepatic 
veins and the abdominal cavity they seem to be of no significance. This is due to 
the fact that these portions of the body are exposed to the same pressure as the 
thorax, so that only in exceptional cases can material be forced from the vessels 
of the thorax into those of the abdominal cavity. Factors, on the other hand, that 
hinder normal respiration may aid in the formation of embolism of the hepatic veins 
by causing distention and increased activity of the right heart. 


Anatomy.—Occlusion of isolated central lobular veins causes a 
reversal of the capillary blood-stream in these lobules, but owing to the 
abundant capillary anastomoses this occurrence is not followed by any 
serious lesions. The same principle probably applies to the smaller 
branches of the hepatic veins. The anastomoses here are, however, not 
so abundant as in the case of the portal branches, and occlusion of large 
venous branches is followed by hyperemia and congestion in their roots. 
If this condition develops slowly, atrophy of the columns of liver-cells 
occurs as a result of pressure, and the hepatic cells may disappear com- 
pletely. If the occlusion occurs more rapidly, there will be complete 
stasis of blood in the distended capillaries, and hemorrhagic infarcts with 
bloody infiltration, coagulation, necrosis of glandular tissue, and forma- 
tion of connective-tissue cicatrices take place. The first stages of these 
venous infarctions have never been studied anatomically. It is probable 
that their outline is not so regular as that of portal vein infarcts, because 
the hepatic veins are less regularly distributed. 

Cicatrices formed by occlusion of hepatic. veins may be of various 
shapes, and follow the course of the branches of the hepatic vein; they 
are seen with particular frequency in the region of the posterior margin 
of the liver, sometimes in the interior of the organ. Occasionally they 
enable the investigator to recognize venous walls that have become glued 
together, or a thrombus in the lumen of the vessel and in different stages 
of organic metamorphosis. Heller and Lange saw an annular arrange- 
ment of the thrombus, which was pierced by a narrow canal; this lesion 
was the result of chronic endophlebitis. 

Owing to venous congestion the liver is enormously enlarged during 
life. “At the autopsy, however, the organ will be found normal, or even 
smaller than normal. On transverse section it will appear like a con- 
gested liver, 7. e., flaccid and slightly nodular (both on the surface and 


DISEASES OF THE HEPATIC VEINS. 901 


transverse section), as a result of the above-mentioned irregular develop-. 
ment of cicatricial tissue. It is possible that some of the strands and 
layers of connective tissue that have been described in congested 
liver by Liebermeister are due to thrombi of the hepatic veins. The 
capsule of the liver is usually thickened in the region of the cicatrized 
veins, particularly at the posterior margin of the liver. Adhesions may 
exist with neighboring organs, and the thickening may involve large 
portions of the surface of the liver. In addition, as in ordinary congested 
liver, there may be wide-spread inflammatory thickening of the peri- 
toneum, and, here and there, the formation of cicatrices, as, for instance, 
in the covering of the spleen or in the peritoneal layers of the pelvis. 


In a case reported by Barth (occlusion of a vein by a gumma) stasis and en- 
largement were seen only in the left lobe; the right lobe was no larger than an adult 
fist, and atrophic, probably as a result of infarction. In a case reported by Hainski 
a number of small nodular hyperplasias (cSmpensatory?), which varied in size from 
a pin-head to a pea, were disseminated throughout the liver. 

Eppinger reports a case in which the liver cicatrix extended to the wall of the 
vena cava, and occluded this vessel. In one of my own cases this scar extended 
into the vena cava and caused the formation of a mural thrombus. 


The anatomic picture resembles that of ordinary congested liver; it 
simply constitutes a more advanced stage of this disease. 

When thrombosis and occlusion of the hepatic veins is found, in 
combination with diffuse or cicatricial interstitial hepatitis, the symp- 
toms of stasis are not so pronounced. Moreover, the rédle played by the 
occlusion of the hepatic veins in the causation of the liver lesions is not 
always a certain one. 

When carcinomatous nodules of the gland penetrate the hepatic veins, 
the blood-current is only slightly interfered with. The carcinoma in 
such cases shows a tendency to proliferate along the vessel, and through- 
out its lumen, and in this manner material is furnished for the formation 
of carcinomatous metastases in the lungs. It would appear that emboli 
are not often formed from simple thrombi of the hepatic veins. 

When the total lumen of the hepatic veins is diminished, the trunk of 
the portal vein is usually dilated, and its walls thickened. If the former 
is completely occluded, thrombi may form in the portal vein. 

The spleen is large and indurated as a result of the stasis. Its cover- 
ing is frequently fibrous. The gastric mucosa shows ridges and wart-like 
thickening (Maschka). 

Symptoms.—Occlusion of single branches of the hepatic veins is not 
recognized during life. The resulting circumscribed swelling of the 
hepatic tissue remains unrecognized, as a rule, because of its situation at 
the posterior margin of the organ. It is possible that this condition is 
responsible for the exacerbations and the attacks of pain in congested 
liver and in interstitial, particularly syphilitic hepatitis. In extensive 
involvement and occlusion of the hepatic veins, engorgement and en- 
largement of the liver result. The organ can be readily palpated over 
large areas, and is hard; its shape, however, is not changed. Occasionally 
its margin is perhaps more rounded, and, if the disease is acute, palpation 
is painful. The symptoms of occlusion of the blood-stream in the liver 
are those of atrophic cirrhosis and occlusion of the portal vein—namely, 
ascites and enlargement of the spleen. As in thrombosis of the portal 
vein, ascites seems to recur more rapidly after puncture than in cirrhosis, 
because obstruction of the blood-stream is more complete. In two cases 


902 DISEASES OF THE VESSELS OF THE LIVER, 


observed by me there was from 3.5 % to 5 % of albumin in the ascitic 
fluid; this is a very large proportion. In another instance the fluid was 
milky. If ascites is present, palpation of the liver naturally becomes 
difficult; as a rule, however, the organ, as in simple stasis, is not much 
enlarged. Occasionally the enlargement of the liver diminishes, either 
because the blood-stream is re-established in certain areas of the organ, 
or because a portion of the liver parenchyma undergoes atrophic changes. 

Icterus is never seen in thrombosis of the hepatic veins. 

The spleen is often very much enlarged, so that it can be readily 
palpated. As arule, it is hard, and sensitive to pressure. 

As in other cases of ascites, there is a partial suppression of urine, and 
there may be edema of the lower extremities. Both are the result of 
pressure on the kidneys and the lower vena cava. 


I have personally studied three cases of occlusion of the hepatic veins. The 
first case has been described by Lange, and occurred in a working-woman of thirty- 
nine. Nine months after the birth of a healthy child the abdomen began to enlarge. 
While the case was under clinical observation the liver was found enlarged and re- 
sistant; its surface in the beginning smooth, and later nodular. There was much 
ascites (circumference 119 cm.). Aspiration was performed four times in eight 
weeks. The fluid was cloudy (in later aspirations still more so), and deposited 
a thin, whitish, creamy layer consisting of small granules that seemed to be albu- 
minoid in character, but from which fat could be extracted by ether (quantity 7000 
to 14,000 c.c.; pressure up to 47 cm.). It was impossible to decide during life 
whether this was a case of carcinoma of the liver and the peritoneum, or of syphilis of 
the liver. Death occurred half a year after the beginning of her symptoms. 

The second case was that of a merchant, forty-one years old, who was a sufferer 
from chronic heart lesion. (On section myocarditis and pericarditis were found.) 
Four years before the death of the patient a sudden exacerbation of his symptoms 
appeared; there was rapid enlargement of the abdomen, so that puncture had to 
be performed three times. I saw the patient with his physician, Dr. A. Bockendahl, 
and I could palpate the liver very well, notwithstanding the great amount of ascitic 
fluid. The organ was large and hard (formerly had been still larger), the spleen 
was enlarged, occasionally painful, and the lower part of the body edematous. 
Digitalis, which up to this time had helped the case, became inefficient. I sus- 
pected the presence of thrombosis of hepatic veins, possibly complicated by exuda- 
‘tive peritonitis, particularly because stasis in the upper part of the body was slight 
as compared to that in the abdomen. The treatment seemed to corroborate this 
diagnosis, for after the exhibition of senna, diuresis and diarrhea occurred and the 
edema disappeared. Later on, it was found, similar conditions could always be 
remedied by the same treatment. The volume of the liver decreased, although 
the organ was never reduced to its normal size. The patient was able to attend 
to his office-work for many years, and finally died from an embolism of the 
brain. 

The third patient was a working-woman of thirty-two. Two weeks after de- 
livery her abdomen began to enlarge, though there were no othersymptoms. Three 
months later a diagnosis of peritoneal tuberculosis was made, and a laparotomy 
performed. The peritoneum was found normal. Ascites returned, and had to 
be aspirated five times in the three months that elapsed between the operation 
and the death of the patient. The circumference of the abdomen was 125 cm. 
The liver was examined four months after the beginning of the disease, and was 
found to be palpable and hard, but only slightly enlarged; its surface was somewhat 
uneven. Following later punctures, the organ was found to be smaller, less hard, 
somewhat nodular, and lobulated. The spleen was enlarged and palpable. Death 
eeourTeS after six months. During life a diagnosis of syphilis of the liver had been 
made. 

The last two cases have been described in a dissertation by Thran. 


Course.—The anatomic beginning of narrowing of the hepatic veins 
cannot be recognized clinically. As in the case of other obstructions of 
the hepatic blood-current, a diagnosis is possible only after the lesion has 
reached a certain grade, and caused ascites, It appears that in persistent 


DISEASES OF THE HEPATIC VEINS. 903 


occlusion the disease lasts only from three to six months. Thedominant 
symptom is ascites, so that tuberculosis, or carcinomatosis of the perito- 
neum, or hepatic ascites, is usually diagnosed. . 

My second case demonstrates the fact that the obstruction of th 
blood-stream and the enlargement of the liver, as well as the ascites, may 
diminish. This occurrence may be due to the development of collateral 
channels in cases in which the occlusion occurs gradually. The blood is 
carried through the coronary and suspensory ligaments, or through 
adhesions between the liver and the diaphragm, or between the liver and 
the anterior abdominal wall. 

The veins of the diaphragm and the right internal mammary vein have 
been found dilated (Gee). 

Diagnosis.—Thrombosis of the hepatic veins has up to this time been 
studied chiefly from an anatomic point of view. My Case II shows that 
the condition can be diagnosed from the occurrence of hepatic ascites, 
with the simultaneous and uniform enlargement of the liver. 

The enlargement of the spleen is important in the recognition of the 
lesion, since it seems to be particularly pronounced in this condition. 
Another important point would appear to be the rapid development of 
ascites after puncture. It is possible, also, that a large quantity of 
albumin and a milky clouding of the ascitic fluid, if present, is significant. 
The absence of microscopic tumor elements may be of value. 

The enlargement of the liver may be due to other factors, as, for 
instance, primary carcinoma or one of the forms of cirrhosis; the history 
of the case and the symptoms in other organs will have to be carefully 
considered with this in view. Absence of icterus, which is more fre- 
quently seen in carcinoma and cirrhosis, is also important. The uniform 
enlargement of the liver, the absence of nodules, the rapidity with which 
the swelling of the liver and ascites develop, and, finally, the occasional 
reduction in the size of the liver in later stages of the disease, are all 
significant. In cases of the latter variety, flat, ridge-like irregularities 
of the surface of the organ may be palpated. A secondary reduction in 
the size of the organ is also seen in many cases of cirrhosis, but does not, 
as a rule, occur so rapidly. The general appearance of the organ is 
similar to that of hyperemia of the liver from stasis in heart lesions. 
Cardiac involvement, however, is rare in thrombosis of the hepatic veins. 

When such a lesion is present, the enlargement of the liver is more rapid, 

more considerable, and more persistent; and there is less fluctuation in 
the size of the organ than in simple hyperemia from stasis. The en- 
gorgement of the liver, moreover, is out of proportion to the symptoms 
of stasis in other parts of the body. 

The only case in which a genetic relationship between syphilis and 
obliteration of the hepatic veins has been established is that of Maschka. 
In two of my own cases (I and III) is it quite probable that lues played 
a réle, and in my other cases also the character and the multiplicity of the 
scars, and their relation to the vessel-walls, make it probable, from an 
anatomic point of view, that syphilis was concerned in their formation 
also. It will be well in future to remember this point, and possibly to 
utilize it in the diagnosis. 

It is remarkable that in my Cases I and III, and in Maschka’s case, 
the symptoms of the disease appeared several weeks or months after 
delivery. Future cases will decide whether this was a coincidence or not. 

Prognosis. —The prognosis of occlusion of the hepatic veins is usually 


904 DISEASES OF THE VESSELS OF THE LIVER. 


bad if the larger branches are involved. In rare cases, and particularly 
if heart lesions coexist, the condition may be cured, and some of the 
sequels of the lesions may be compensated. 

Treatment.—When the primary cause of the disease is known, the 
attempt should be made to remove it. Cardiac disease should be treated 
with digitalis, diuretics, baths, etc.; syphilis with iodin and mercury. 
For reasons mentioned above, it will always be a good plan to try anti- 
syphilitic medication in cases of which the etiology is obscure. 

Repeated aspiration of the ascitic fluid will be necessary ; occasionally 
drastics administered over a long period are beneficial in relieving the 
engorgement of the portal system. By decreasing abdominal pressure 
such drugs exercise a beneficial effect indirectly, inasmuch as they help 
to re-establish the normal flow of urine. 


INFLAMMATION OF THE PORTAL VEINS. 


Chronic inflammation of the walls of the veins, analogous to arterio- 
sclerosis, is occasionally seen. There is generally some local thickening 
of the wall, and the inflammation is carried into the liver tissue or the 
interstitial connective tissues of the organ; syphilis is probably a prolific 
cause of this condition. Following these changes in the vessel-walls, we 
see thrombosis and narrowing and occlusion of the lumen (adhesive 
phlebitis), the results of which we have discussed in the preceding para- 
graph. 

Acute purulent inflammation of the hepatic veins is more frequent 
than chronic inflammation, and, as a rule, the former condition originates 
in some pus focus within the liver. It may happen, therefore, that in- 
fection occurs from an abscess, in its turn produced by pylephlebitis; 
purulent cholangitis and a suppurating echinococcus cyst may also 
cause suppurative inflammation of the hepatic veins. The walls of these 
vessels are very thin and favor the entrance of pus into the vessel, either 
by permitting perforation or by favoring the formation of a purulent 
thrombus that later undergoes degeneration. From the hepatic veins 
pus emboli may be carried to other organs and produce abscesses in the 
lungs, or of other parts of the body. . 

It would appear that purulent inflammation of the hepatic veins 
occurs, and by no means seldom, as the result of infection from an em- 
bolus carried in a direction opposed to the blood-stream. This will 
explain the occurrence of secondary pyemic abscesses in the liver alone 
when there is a primary pus focus in another organ. Wagner, for ex- 
ample, mentions two cases of this kind in which infection of the liver 
originated in a thrombus of the jugular vein due to an operative lesion 
of that vessel. [Lubarsch * calls attention to emboli formed entirely 
of liver-cells. They are principally of traumatic origin. These emboli 
have been observed by others in the pulmonary and hepatic capillaries, 
especially after puerperal eclampsia.—Eb.] 


Th. Aubert claims that many of the areolar abscesses of the liver start in the 
veins. He believes that the central vein of the lobules is thrombosed, undergoes 
puriform softening, thus leading to the destruction of the adjacent tissues. The 
areolz formed are of different size, some as large as millet-seeds, others as large as 
peas; they may then become confluent and in this manner form cavities that are 
as large as a hen’s egg or even larger. They are always wedge-shaped with the 


* “ Zur Leber von der Geschwiilsten,’’ 1899. 


DISEASES OF THE HEPATIC VEINS. 905 


base near the surface of the liver. Occasionally phlebitis of the wall of the gall- 
bladder is the starting-point. 


Suppurative phlebitis hepatica causes no recognizable symptoms, 
although it must invariably have existed in cases in which suppuration 
in the portal area leads to general pyemia. We can be certain of its 
presence when abscesses of the lung follow abscesses of the liver. 

The diagnosis of embolization against the blood-stream may also be 
made if an abscess of the liver develops from a pus focus situated in the 
periphery of the body; e. g., in the region of the neck. It is hardly prob- 
able, however, that an hepatic abscess of this nature can develop and 
attain such large dimensions that it can be clinically recognized without, 
at the same time, leading to the formation of secondary abscesses in other 
organs. | | 


LITERATURE. 


Aubert, Th.: “ Etudes sur les abscés aréolaires du foie,’ Thése de Paris, 1891. 

Barth, H.: “France médicale,” 1882, citirt bei Barthelémy, “Archives générales 
de médecine,” 1884, tome 1, p. 527. (Verschluss durch Gumma.) 

Budd: Loe. cit., p. 146. 

Chvostek: “ Krankheiten der Pfortader und der Lebervenen,” “ Wiener Klinik,” 
1882, Heft 3. 

Cohn: Loe. cit., p. 484. 

Eppinger: “ Prager med. Wochenschr.,” 1876, No. 39, 40. 

Frerichs: Loc. cit., 11, pp. 92 and 408. 

Gee: “Complete Obliteration of the Mouth of the Hepatic Veins,” “ Bartholomew’s 

Hospital Reports,’ 1870, vit; Jahresbericht, 1, 159. 

Hainski, O.: “ Ein Fall von Lebervenenobliteration,” Dissertation, Gottingen, 1884. 

Lambron: “ Archives générales de médecine,” June, 1842, p. 129. 

Lange, W.: “ Ein Fall von Lebervenenobliteration,’”’ Dissertation, Kiel, 1886. (Lit- 
eraturangaben.) 

v. Maschka: “ Vierteljahresschr. fiir gerichtliche Medicin,” Bd. xii. 

Quincke: Loc. cit., p. 568. 

Rosenblatt: Dissertation, Wurzburg, 1867. 

Schippel: Loc. cit., p. 323. 

Thran: Dissertation, Kiel, 1899. 


RECURRENT EMBOLISM. 


Arnold, J.: “ Riicklaufige Thrombose.” (Literature.) “Virchow’s Archiv,” Bd. 
CXXIVv, p. 385. 

Bonome: “ Archivo per le scienze mediche,”’ 1889, vol. x11. 

Diemer, L.: “ Ueber Pulsation der Vena cava inferior,’ Dissertation, Bonn, 1876. 

Heller, A.: “ Zur Lehre von den metastatischen Processen der Leber,’’ ‘ Deutsches 
Archiv fiir *klin. Medicin,” 1870, Bd. vu, p. 127. 

Ribbert : “ Ueber den riicklaufigen Transport im Venensystem,”’ “Centralblatt fur 
allgemeine Pathologie,”’ 1897, p. 433. 

Scheven: Dissertation, Rostock, 1894. 

Wagner, E.: “ Allgemeine Pathologie,’ 6. Auflage, p. 263. 











INDEX. 


ABDOMINAL organs, disturbances of, in 
Addison’s disease, 347 
Abnormalities of development in supra- 
renal capsules, 310 
of excretory ducts of pancreas, 25 
Abscés aréolaires, 652, 660 
Abscess of liver, 651. See also Liver, 
abscess of. 
pancreatic, 122 
in diabetes, table, 70 
Absolute liver dulness, 384 
Accessory duct of pancreas, 20 
pancreas in stomach, 24 
in wall of duodenum, 24 
of ileum, 24 
of jejunum, 24 
Acholia, 440 
Acne pancreatica, 189 
Acute hemorrhagic pancreatitis, 116. 
See also Hemorrhagic pancreatitis, 
acute. 
Addison’s disease, 333 
and diseases of suprarenal capsules, 
diagnosis, differential, 351 
changes in skin and mucous mem- 
brane in, 340 
condition of blood in, 345 
of urine in, 350 
course, 336 
diagnosis, differential, 351 
disturbances of abdominal organs 
in, 347 
of circulation in, 344 
of nervous system in, 343 
pathogenesis, 364 
pathologic anatomy, 333 
prognosis, 362 
symptoms, 336 
treatment, 362 
Adenoma of liver, 758 
malignant, 761 
of pancreas, 176 
Akathectic jaundice, 427 
Albumin, faulty digestion of, as symp- 
tom of diseases of pamcreas, 91 
Albuminous bodies, changes of, by 
trypsin, 32 
Alcohol, abscess of liver and, 655 
effect on liver, 693 
Alcoholism, chronic 
creatitis from, 139 
fatty liver and, 840 
Aluminium, fatty liver and, 839 


indurative pan- 





Amyloid degeneration complicating ab- 
scess of liver, 674 
of pancreas, 265 
liver, 853 
diagnosis, 857 
pathologic anatomy, 855 
prognosis, 857 
prophylaxis, 857 
symptoms, 856 
treatment, 857 
Anemia in abscess of liver, 666 
pernicious, siderosis of liver in, 740 
Aneurysm of hepatic artery, 896 
of aorta, abscess of liver and, 676 
Angiomata of liver, 749 
Angiome biliaire, 754 
Anguillula stercoralis in bile-ducts, 825 
Anomalies of pancreas, 23 
Anteversion of liver, 385 
Antimony, fatty liver and, 839 
Apoplectic cysts of pancreas, 186 
Appendicitis, abscess of liver and, 656 
Arsenic, fatty liver and, 839 
Arteries of pancreas, 20 
Ascaris lumbricoides, 823 
pathologic anatomy, 823 
symptoms, 824 
Ascites in abscess of liver, 669 
in passive congestion of liver, 612 
Asparagic acid, 32 
Aspiration in abscess of liver, 679 
Atrophic cirrhosis, 692 
Atrophy of liver, acute, 630. See also 
Laver, atrophy of, acute. 
chronic, 850. See also 
atrophy of, chronic. 
circumscribed, 850 
general, 851 
granular, 692 
of pancreas, 262 
in diabetes, table of, 58 
of suprarenal capsules, 311 
Azotorrhea as symptom of diseases of 
pancreas, 91 


Liver, 


Biz, cirrhosis from stasis of, 727 
disturbances in canalization, 473 
formation, 414 
influence of, om trypsin, 31 

arapedesis, 427 

Bile-ducts, anguillula stercoralis in, 825 

carcinoma, occlusion of passages, 775 


907 


908 


Bile-ducts, carcinoma, symptoms of, 774 
distomata in, 826. See also Disto- 
mata. 
leptodera stercoralis in, 825 
Bile-passages, carcinoma, 
772 
catarrh, 476 
cirrhosis, 727 
diseases, 469 
fistula, 523 
hemorrhage into, 521 
inflammatory processes in, abscess of 
liver and, 656 
narrowing, 473 
occlusion, 473 
perforations, 522 
symptoms, 522 
treatment, 523 
rupture, 522 
solutions of continuity, 522 
Bile-pigment in liver, 872 
Biliary cirrhosis, 727 
Bilirubin in liver, 872 
Blood, cirrhosis from stasis of, 729 
condition of, in Addison’s disease, 345 
extravasation, jaundice after, 494 
Blood-vessels and organs of posterior 
abdominal wall, relation of pancreas 
to, 29 
chronic indurative pancreatitis from, 
5 


symptoms ; 


disease of, pancreatic hemorrhage 
from, 209 
of pancreas, 20 
Bronzed diabetes as symptom of diseases 
of pancreas, 96 
Bullet wounds of pancreas, 269 


CaLCULI, pancreatic, 223 
chemical composition, 224 
color, 224 
consistency, 224 
diagnosis, 231 
frequency, 228 
in diabetes, table, 65 
number, 224° 
pathogenesis, 225 
pathologic anatomy, 227 
seat, 224 
shapes, 224 
sialangitis in production, 226 
size, 224 
statistics, 228 
symptoms, 229 
treatment, 232 
weight, 224 

Garbohydrate metabolism of liver, 408 

Carcinoma of gall-bladder, 768 

of liver, 758. See also Liver, carci- 
noma, 
of pancreas, 148 
course, 170 
diagnosis, 164 
duration, 170 
etiology, 153 





INDEX. 


Carcinoma of pancreas in diabetes, table, 
68 


pathologic anatomy, 150 
prognosis, 170 
seat, 150 e 
size, 151 
statistics, 153 
symptoms, 153 
treatment, 170 
variety, 151 
Catarrh of bile-passages, 476 
Catarrhal cholangitis, 476 
jaundice, 477 
anatomy, 480 
course, 478 
diagnosis, 481 
etiology, 477 
pathogenesis, 480 
prognosis, 481 
sequels, 479 
symptoms, 477 
treatment, 481 
pancreatitis, 116 
Cavernoma of liver, 749 
Celiac neuralgia, 167 
Chauffard’s classification of cirrhosges, 
726 
Cholangitis, catarrhal, 476 
suppurative, 508 
course, 512 
diagnosis, 512 
etiology, 509 
occurrence, 508 
prognosis, 512 
symptoms, 511 
treatment, 513 
Cholecystitis, 515 
symptoms, 516 
treatment, 517 
Cholelithiasis, 525. See also Gall-stones. 
Cholemia, 440 
Chronic indurative pancreatitis, 134. 
See also IJndurative pancreatitis, 
chronic. 
obstructive jaundice, 473. See also 
Jaundice, chronic obstructive. 
Circulation, disturbances of, in Addi- 
son’s disease, 344 
Circulatory disturbances of suprarenal 
capsules, 312 
Cireumscribed indurative’ pancreatitis, 
chronic, 142 
Cirrhose avec stéatose, 732 
biliare calculeuse, 727 
hypertrophique, 727 
cardiaque, 729 
graisseuse, 732 
atrophique, 732 
hypertrophique, 732 
hypertrophique avec ictére, 724 
pigmentaire hypertrophique, 737 
Cirrhoses graisseuses, 650 
pigmentaires, 741 
Cirrhosis, acute, 649 
adiposa, 732 
and diabetes mellitus, 740 


INDEX. 


Cirrhosis, biliary, 727 
Chauffard’s classification, 726 
cholangica, 727 
from stasis of bile, 727 
of blood, 729 
of bile-passages, 727 
of diabetics, pigment, 737 
of liver, 692. See also Liver, cirrhosis 


of. 
Cloudy swelling of liver, 626 
Coccidia in liver, 788 
Copper, fatty liver and, 839 
Congestion of liver, active, 614 
passive, 608. See also Liver, con- 
gestion of. 
Corset liver, 390 
_ diagnosis, 393 
symptoms, 392 
treatment, 394 
Cystomata of liver, multiple, 754 
Cysts of liver, 751. See also Liver, cysts. 
of pancreas, 180 
amount of fluid in, 191 
apoplectic, 186 
complications, 195 
diagnosis, 201 
duration and course, 205 
etiology, 195 
in diabetes, table, 69 
nature and development, 181 
pancreatic hemorrhage from, 213 
pathologic anatomy, 189 
prognosis, 206 
shape, 189 
situation, 193 
statistics, 197 
symptoms, 197 
treatment, 206 
proliferation, of pancreas, 185 
retention, of pancreas, 181 


DEGENERATION of liver, 832 
Detoxicating function of liver, 411 
Diabéte bronzé, 738, 740 
Diabetes and glycosuria as symptoms of 
diseases of pancreas, 39 
bronzed, as symptom of diseases of 
pancreas, 96 
experimental pancreatic, 41 
indurative pancreatitis in, table, 62 
mellitus, cirrhosis and, 740 
liver in, 739 
pancreas in, abscess, table, 70 
atrophy, table, 58 
calculi, table, 65 
carcinoma, table, 68 
changes, 56 
cysts, table, 69. 
fat necrosis, cases, 72 
fatty degeneration, table, 61 
hemorrhage, table, 71 
microscopic changes, table, 72 
necrosis, cases, 72 
normal, table, 80 
pancreatic, experimental, 41 





909 


Diabetes, pigment cirrhosis with, 737 - 
relation of pancreas to, 56 
siderosis of liver in, 870 
total destruction of pancreas without, 
table, 81 
Diarrhea, pancreatic, as symptom of 
diseases of pancreas, 99 
siderosis of liver in, 870 
Diffusion icterus, 427 
Dilatation of gall-bladder, 518 
prognosis, 521 
symptoms, 519 
treatment, 521 
Displacement of pancreas, 268 
Distomata in bile-ducts, 826 
pathologic anatomy, 827 
symptoms, 828 
in gall-bladder, 826 
Diverticulum of Vater, 19 
Duct of Santorini, 19 
of Wirsung, 18 
Ductus choledochus, carcinoma, diag- 
nosis, 781 
Dujardin-Beaumetz’s stercoremia, 616 
Duodenum, wall of, accessory pancreas 
in, 24 
Dysentery and abscess of liver, 652 


Dyspeptic disturbances as symptom of 


diseases of pancreas, 104 


Ecurnococcus alveolaris, 812. See also 


Multilocularis. 

cysticus in liver, 789. See also Hy- 
datidosus. 

cysts and abscess of liver, differentia- 
tion, 676- 


Emboli, liver-cell, formation, 621 

Emotional jaundice, 484 

Empyema of gall-bladder, abscess of 
liver and, 676 

Epidemic jaundice, 501 

Epiplopexy for cirrhosis of liver, 714 

Endarteritis obliterans, chronic indura- 
tive pancreatitis due to, 135 

Excretory ducts of pancreas, 18 

abnormalities, 25 

Experimental pancreatic diabetes, 41 

Exploratory puncture of liver, opera- 
tion, 676 

Extirpation of pancreas, effect produced 


Extravasation of blood, jaundice after, 
494 


Fat metabolism of liver, 410 
necrosis as cause of pancreatic hemor- 
rhage, 212 
of pancreas, 244 
diagnosis, 260 
etiology, 248 - 
experimental, 251 
frequency, 258 
in diabetes, cases, 72 
pathologic anatomy, 246 


910 


Fat necrosis of pancreas, statistics, 258 
symptoms, 259 
Fatty degeneration of liver, 640 
of pancreas, 263 
in diabetes, table, 61 
infiltration of pancreas as cause of 
pancreatic hemorrhage, 211 
liver, 835 
alcohol and, 840 
aluminium and, 839 
antimony and, 839 
arsenic and, 839 
carcinoma and, 841 
copper and, 839 
diagnosis, 848 
etiology, 836 
gastro-enteritis and, 844 
infectious diseases and, 840 
intoxications and, 838 
mercury and, 839 
pathologic anatomy, 842 
phosphorus-poisoning and, 838 
phthisis and, 841 
prognosis, 848 
symptoms, 844 
toxic, 846 
treatment, 848 
stools and diseases of pancreas, clin- 
ical experiences, 85 
concurrence, 85 
experimental results, 84 
as symptom of diseases of pancreas, 
83 


diseases of pancreas without, 87 
without alteration of pancreas, 88 
Ferments of pancreatic juice, 30 
fate of, in the organism, 35 
Feuerstein liver, 694 
Fever as symptom of diseases of pan- 
creas, 104 
pancreatic secretion in, 37 
Fibromata of liver, 748 
Fistula of bile-passages, 523 
Floating liver, 395. ‘See also Liver, 
floating. 
Foreign bodies in pancreas, 270 
Function, detoxicating, of liver, 405, 411 


GALL-BLADDER, carcinoma, 768 
diagnosis, 781 
symptoms, 772, 774 
dilatation, 518 
prognosis, 521 
symptoms, 519 
treatment, 521 
distomata in, 826. See also Disto- 
mata. 
inflammation, 515 
symptoms, 516 
treatment of, 517 
Gall-stones, 525 
classification, 531 
complicated by irregular cholelithia- 
sis, 569 
complications, 569 





INDEX. 


Gall-stones, course, 554 
diagnosis, 587 
history, 525 
origin, 536 
pathologic anatomy, 548 
prognosis, 586 
properties, 531 
prophylaxis, 590 
symptoms, 554 
treatment, 591 
weight, 533 
Gastric ulcer, abscess of liver and, 656 
Gastro-enteritis, fatty liver and, 844 
Glycosuria in cirrhosis of liver, 706 
and diabetes as symptoms of diseases 
of pancreas, 39 
Granular atrophy, 692 
Granulation tumors, infectious, of supra- 
renal capsules, 314 


HEMOGLOBIN injection, siderosis of liver 
and, 861 
liver pigmentation and, 875 
Hemoglobinemia, jaundice after, 495 
Hemorrhage into bile-passages, 521 
into liver, 621 
symptoms, 621 
pancreatic, 207 
course, 221 
diagnosis, 222 
disease of blood-vessels as cause, 209 
etiology, 209 
fat necrosis as cause, 212 
fatty infiltration of pancreas as 
cause, 211 
from disintegration of neoplasms, 
213 


from embolism of pancreatic artery, 
13 


from inflammations of pancreas, 214 
from pancreatic cysts, 213 
from trauma, 213 
in diabetes, cases, 71 
pathologic anatomy of 215 
symptoms, 219 
treatment, 223 
Hemorrhagic pancreatitis, acute, 116 
Hepatargy, 440, 641 
following neoplasms of liver, 776 
Hepatic artery, aneurysm, 896 
diseases, 895 
ducts, carcinoma, diagnosis, 781 
veins, occlusion, 399 
diseases, 898 
inflammation, 904 
narrowing, 899 
anatomy, 900 
course, 902 
diagnosis, 903 
from compression, 899 
from disease of wall, 899 
from embolism, 899 
from thrombosis, 899 
prognosis, 903 
symptoms, 901 


INDEX. 


Hepatic veins, narrowing, treatment, 
904 
Hépatite nodulaire, 629, 709 
parenchymateuse nodulaire, 735, 766 
Hepatitis, acute, 626 
interstitial, 649 
etiology, 650 
symptoms, 650 
parenchymatous, 626 
anatomy, 626 
etiology, 626 
prognosis, 629 
symptoms, 628 
termination, 629 
treatment, 629 
tropical forms, etiology, 628 
chronic interstitial, 692. See also 
Liver, cirrhosis of. 
gummatous, 742 
interstitial, tubercular, 730 
in malaria, 735 
interstitialis flaccida, 733 
sequestrans, 651 
syphilitic, 742 
ascites with, 745 
diagnosis, 746 
hereditary, 743 
occurrence, 744 
perihepatitic adhesions in, 746 
stasis with, 745 
treatment, 747 
syphiloma, 742 
Hydatid thrill, 796 
Hydatidosus, 789 
cysts of spleen in, 805 
diagnosis, 803 
electro-puncture in, 807 
etiology, 789 
evacuation of cell contents, 793, 798 
hydatid thrill in, 796 
operating by one incision, 810 
pathologic anatomy, 791 
perforation in, 793, 798 
prognosis, 802 
prophylaxis, 806 
puncture in, 807 
and aspiration in, 807 
rupture of cells, 793, 798 
symptoms, 795 
treatment, 806 
Hydronephrosis, abscess of liver and, 676 
Hyperemia of liver, 607 
active, 614. See also Liver, con- 
gestion of. 
Hypertrophy of liver, 832 
of suprarenal capsules, 311 


IcING-LIVER, 622 
Ictére typhoide, 630 
Icterus, 423. See also Jaundice, 
diffusion, 427 
gravis, 630, 645 
Indurative pancreatitis, chronic, 134 
circumscribed, 142 
course, 147 | 





911 


Indurative pancreatitis, chronic, diag- 
nosis, 147 
duration, 147 
from alcoholism, 139 
from blood-vessels, 135 
from closure of the excretory 
ducts, 141 
from endarteritis obliterans, 135 
from excretory ducts, 140 
from syphilis, 137 
pathologic anatomy of, 134 
prognosis, 147 
symptoms, 144 
treatment, 148 
in diabetes, table, 62 
Infectious diseases, jaundice in, 500 
granulation tumors of suprarenal cap- 
sules, 314 
jaundice, 503 
nature, 506 
occurrence, 505 
symptoms, 504 
treatment, 507 
Inflammation of gall-bladder, 515 
symptoms, 516 
treatment, 517 
of pancreas, 116 
pancreatic hemorrhage from, 214 
of suprarenal capsules, 313 
Intestine, submucous veins, 
dilatation, 893 
Tron in liver, 864-867 
Tron-liver, 858. See also Liver, siderosis. 
Islands of Langerhans, 22, 23 


varicose 


JAUNDICE. acute, febrile, 503. See also 
Weil’s disease. 
after extravasation of blood, 494 
after hemoglobinemia, 495 
akathectic, 427 ° 
anatomic-histologic changes in other 
organs in, 432 
and urobilin, relation, 445 
as symptom of diseases of pancreas,101 
eatarrhal, 477. See also Catarrhal 
jaundice. 
chronic obstructive, 473 
anatomy, 475 
diagnosis, 475 
duration, 475 
etiology, 473 
prognosis, 475 
symptoms, 475 
course, 442 
diagnosis, 448 
due to polycholia, 493 
emotional, 484 
epidemie, 501 hyeas 
in new-born infant, 489 
pathogenesis, 490 
in pregnancy, 485 
in syphilis, 487 
pathogenesis, 488 
infectious, 503. See also Infectious 
jaundice, 


912 INDEX. . 


Jaundice, menstrual, 486 
starvation, 486 
symptoms, 433 
toxic, 496 
urobilin, 445 


LAENNEC’s cirrhosis, 692 
Langerhans, islands of, 22, 23 
Lardaceous liver, 853. See also Amy- 
loid liver. 
Leptodera stercoralis in bile-ducts, 825 
Leucin, 32 
Leucocytosis in abscess of liver, 667 
Leukemia, liver in, 785 
symptoms, 787 
treatment, 788 
of liver, 834 
Lipomatosis of pancreas, 264 
Liver, abscess of, 651 
actinomycotic, course, 665 
alcohol and, 655 
amyloid degeneration complicating, 
674 
and carcinomatous nodules, differ- 
entiation, 075 
and paranephritic abscess, differ- 
entiation, 675 
anemia in, 666 
aneurysm of aorta and, 676 
antiphlogistic measures, 678 
appendicitis and, 656 
ascites in, 669 
aspiration by trocar in, 679 
cauterization treatment, 680 
central nervous system in, 671 
circulatory apparatus in, 670 
circumscribed bulging in, 668 
course, 663 
cysts of pancreas and, 676 
« diagnosis, 675 
differential, 675 
Rontgen rays in, 675 
digestive tract in, 669 
disease of portal system and, 652 
double incision for, 681 
due to infection from intestine, diag- 
nosis, 664 
dysentery and, 652 
echinococcus cysts and, differentia- 
tion, 676 
empyema of gall-bladder and, 676 
etiology, 6 
exploratory puncture and, 676 
fever in, 666 
fibrous, 662 
frequency, 658 
gastric ulcer and, 656 
hepatic veins and, 657 
hydronephrosis and, 676 
ice-bag in, 678 
incision for, 681 
indolent, course, 665 
inflammation of pancreas and, 676 
inflammatory processes in bile-pas- 
sages and, 656 





Liver, abscess of, leucocytosis in, 667 


location, 661 
malaria and, 656 
microscopic appearance, 660 
multiple, diagnosis, 675 
open wound and, 663 
pain in liver region in, 667 
in shoulder in, 667 
pathologic anatomy, 659 
perforation, 671 
into inferior vena cava, 673 
into intestinal tract, 672 
into pericardium, 672 
into peritoneal cavity, 673 
into portal vein, 673 
into right kidney, 673 , 
perityphlitis and, 656 
pneumonia in, 670 
primary, 651 
prognosis, 674 
prophylaxis, 677 
pulse in, 666 
pylephlebitis and, 657 
pyonephrosis and, 676 
respiratory disturbances in, 669 
secondary, 651 
sensorium in, 666 
solitary, diagnosis, 675 
spleen in, 669 
Stromeyer-Little’s treatment, 681 
subphrenic abscess, differentiation, 
675 
sudden changes of temperature and, 
655 


swelling of liver in, 668 
symptoms, 666 
traumatic, 663 
treatment, 678 
tropical, 653 
pathologic anatomy, 661 
typhlitis and, 656 
urine in, 670 
wound-fistula in, 679 
adenoma, 758 
course, 771 
histologic picture, 765 
malignant, 761 
symptoms, 771 
treatment, 782 
alcohol and, 693 
amyloid; 853. See also Amyloid liver. 
anatomy and histology, 401 
topographic, 383 
angiomata, 749 
anteversion, 385 
atrophy of, acute, 630 
anatomy, 632 
bacterial course, 631 
decrease of size in, 644 
* diagnosis, 645 
differential, 646 
duration, 638 
etiology, 631 
general clinical description, 632 
icterus in, 644 
nature of disease, 639 


INDEX. 913 


Liver, atrophy of, acute, occurrence, 630 


pancreatic digestion and, 642 
phosphorus-poisoning and, differ- 
entiation, 646 
prognosis, 638 
* red, 639 
symptoms, 634 
acute, 630 
anatomy, 632 
symptoms, cerebral, 644 
treatment, 646 
urine in, 635 
chronic, 850 
pathologic anatomy, 852 
prognosis, 853 
symptoms, 852 
treatment, 853 
circumscribed, 850 
from narrowing of portal vein, 885 
general, 851 
bacteria in, 642 
bile-pigment in, 872 
bilirubin in, 872 
carbohydrate metabolism, 408 
carcinoma, 758 
blood in, 772, 779 
course, 771 
diagnosis, 781 
differential, 766 
digestive disturbances, 779 
etiology, 758 
extension to other tissues, 777 
fatty liver and, 841 
fever in, 779 
health in, 772 
hepatargy after, 776 
histologic picture, 762 
infiltrating, pathologic anatomy, 
762 


massive, pathologic anatomy, 762 
nervous system in, 780 
nodular, pathologic anatomy, 762 
nutrition of body in, 772 
pathologic anatomy, 761 
primary, pathologic anatomy, 761 
prognosis, 780 
secondary, course, 772 
symptoms, 772, 774 

skin in, 780 
symptoms, 771 
treatment, 782 
urine in, 780 

cavernoma, 749 

changes in form, 390 
in size, 388 

cirrhosis of, 692 
afebrile course, 708 5 
ascites in, 702 : 
bivenous, 699 
circulatory disturbances, 701 
collateral veins in, 703° 
complications, 708 
diagnosis, 711 
duration, 710 
epiplopexy for, 714 
etiology, 692 

58 





Liver, cirrhosis of, focal necrosis and, 695 


frequency, 692 
gastro-intestinal hemorrhage in, 704 
glycosuria in, 706 
health in, 705 
hemorrhages in, 707 
hypertrophic, 718 
anatomy, 718 
clinical picture, 720 
course, 722 
diagnosis, 723 
etiology, 720 
prognosis, 723 
symptoms, 721 
treatment, 723 
malaria and, 694 
malignant growths and, 697 
micro-organisms and, 696 
monolobular, 699 
multilobular, 699 
nephritis with, 708 
new tissue formation, 698 
nutrition in, 705 
occurrence, 692 
outline of diseases, 697 
pancreas in, 707 
pathologic anatomy, 697 
peritonitis with, 709 
predisposition, 697 
prognosis, 710 
prophylaxis, 712 
respiration in, 705 
spleen in, 701 
symptomatology, 700 
syphilis and, 694 
termination, 710 
treatment, 712 
tuberculosis of peritoneum with, 709 
urine in, 704, 705 
cloudy swelling of, 626 
coccidia in, 788 
congestion, active, 614 
_ diagnosis, 617 
in menstruation, 617 
in tropics, 616 
prognosis, 618 
symptoms, 617 
treatment, 618 
etiology, 616 
passive, etiology, 608 
anatomy, 609 
ascites in, 612 
diagnosis, 613 
spleen in, 612 
symptoms, 611 
treatment, 613 
corset, 390 
diagnosis, 393 
symptoms, 392 
treatment, 394 
cysts, 751 
multiple, 757 
prognosis, 757 
symptoms, 756 
treatment, 757 . 
degenerations, 832 , 


914 


Liver, detoxicating function, 411 


disconnection, 405 
diseases, 383 
diagnosis, 383 
auscultation in, 387 
general, 460 
inspection in, 387 
palpation in, 386 
percussion in, 384 
etiology, general, 451 
prognosis, general, 461 
symptoms, general, 455 
treatment, general, 462 
dulness, absolute, 384 
echinococcus i in, 789. See also Hyda- 
tidosus. 
epitheliome alveolaire, 765 
fat metabolism, 410 
fatty, 835. See also Fatty liver. 
degeneration of, 640 
fibromata, 748 
floating, 395 
diagnosis, 398 
etiology, 396 
frequency, 396 
symptoms, 397 
treatment, 398 
functional disturbances, 878 
functions, 405 
hemorrhage into, 621 
symptoms, 621 
hyperemia, 617 
active, 614. See also Liver, con- 
gestion of. 
hyperplasia, multiple nodular, 766 
hypertrophy, 832 
icing-, 622 
in diabetes mellitus, 739 
in leukemia, 785 
symptoms, 787 
treatment, 788 
in pseudo- leukemia, 785, 786 
inflammation, chronic, 685 
from alcohol, 688 
from chemicals, 688 
from chronic stasis, 686 
from foreign bodies, 689 
from hyperemia, 686 
from parasites, 690 
from stasis of bile, 686 
of portal vein, 687 
iron in, 864-867 
lardaceous, 853. See also Amyloid 
liver. 
leukemia, 834 
malarial, 733 
marginal position, 385 
melanemic, 874 
melanosarcoma, 770 
multiple cystomata, 754 
neoplasms, 748 
neuralgia, 879 
diagnosis, 880 
frequency, 879 
nature, 880 
treatment, 880 





INDEX. 


Liver, nitrogen metabolism, 407 
parasites, 788 
parenchymatous changes, 832 
pathology, general, 400 
pentastomum constrictum in, 831 
denticulatum in, 831 
phlebotomy, 467 
phosphorus poisoning, 640 
atrophy and, differentiation, 646 
physiology, general, 400 
pigmentation, 872 
brown, 873 
hemoglobin and, 875 
malaria, 873 
melanotic sarcomata, 873 
normal, 872 
rust-colored iron, 873 
position, 383 
marginal, 385 
pseudo-leukemia, 834 
psorospermia in, 788 
retroversion, 385 
sarcoma, 758 
course, 771 
diagnosis, 781 
frequency, 769 
primary, 760 
prognosis, 780 
secondary, 770 
symptoms, 771 
treatment, 782 
siderosis, 740, 858 
diarrhea in, 870 
in diabetes, 870 
in malaria, 870 
in pernicious anemia, 868 
injections of hemoglobin and, 861 
insoluble iron preparation and, 861 
pernicious anemia with, 740 
symptoms, 871 
size, 383 
changes in, 388 
syphilis of, 742. See also Hepatitis, 
syphilitic. 
thickening of capsule, in perihepatitis, 
624. 


topographic anatomy, 383 

tuberculosis, 730 

vessels, diseases, 881 

axy, 853. See also Amyloid liver. 

Liver-cell emboli, formation, 621 
Liver-cells, iron in, 736 
Lymphomata, leukemic, 786 
Lymph-vessels of pancreas, 22 
Lysatinin, 32 
Lysin, 32 


MauaRrtiA, abscess of liver and, 656 
acute, liver i in, 733 
chronic, liver i in, 734 
cirrhosis, liver and, 694 
interstitial hepatitis i in, 735 
liver i in, 733 
iron pigment and, 735 
aympions, 737 


INDEX. 


Malaria pigment in liver, 873 
retrogressive stage, liver in, 735 
siderosis of liver in, 870 

Manson’s treatment of liver abscess, 680 

Melanemic liver, 874 

Melanosarcoma of liver, 770 

Menstrual jaundice, 486 

Menstruation, active congestion of liver 

in, 617 

Mercury, fatty liver and, 839 

Metabolism, carbohydrate, of liver, 408 
fat, of liver, 410 
nitrogen, of liver, 407 . 

Metamorphosis from perihepatitis, 623 

Miliary syphilomata in liver, 743 

Milk-coagulating ferment of pancreatic 

juice, 35 

Multilocularis, 812 
age and, 813 
diagnosis, 820 
icterus in, 818 
pathologic anatomy, 814 
prognosis, 819 , 
symptoms, 817 
treatment, 821 


NARROWING of bile-passages, 473 
Necrosis, fat, as cause of pancreatic 
hemorrhage, 212 
of pancreas, 244 
diagnosis, 260 
etiology, 248 
experimental, 251 
frequency of, 258 
pathologic anatomy, 246 
statistics, 258 
symptoms, 259 
classification, 233 
diagnosis, 244 
experimental, 241 
from disease in vicinity of pancreas, 
238 
from diseases of pancreas, 233 
from indefinite causes, 239 
in diabetes, cases, 72 
pathologic anatomy, 240 
symptoms, 243 
Neoplasms of liver, 748 
disintegration, pancreatic hemorrhage 
from, 213 
of pancreas, 148 
of suprarenal capsules, 314 
Nephritis with cirrhosis of liver, 708 
Nerves of pancreas, 22 
Nervous system, disturbances of, in 
Addison’s disease, 343 
Neuralgia, celiac, 167 
of liver, 879. See also Liver, neural. 


gia. 

Newthonn infant, jaundice in, 489 
pathogenesis, 490 

Nitrogen metabolism of liver, 407 


OBSTRUCTIVE jaundice, chronic, 473 
anatomy, 475 





915 


Obstructive jaundice, chronic, diagnosis, 
475 
duration, 475 
etiology, 473 
prognosis, 475 
symptoms, 475 
Occlusion of bile-passages, 473 


PANCREAS, abscess, 122 
accessory duct, 20 
in stomach, 24 
in wall of duodenum, 24 
of ileum, 24 
of jejunum, 24 
adenoma of, 176 
amyloid degeneration, 265 
anatomy, 17 
anomalies, 23 
apoplectic cysts, 186 
arteries, 20 
atrophy, 262 
blood-vessels, 20 
bullet wounds, 269 
calculi, 223. See 
calcult, 
carcinoma, 148. See also Carcinoma 
of pancreas. 
course, 170 
diagnosis, 164 
duration, 170 
etiology, 153 
pathologic anatomy, 150 
prognosis, 170 
seat, 150 
size, 151 
statistics, 153 
symptoms, 153 
treatment, 170 
variety, 151 
consistency, 18 
cysts, 180 
abscess of liver and, 676 
amount of fluid in, 191 
complications, 195 
diagnosis, 201 
duration and course, 205 
etiology, 195 
nature and development, 181 
pancreatic hemorrhage from, 213 
pathologic anatomy, 189 
prognosis, 206 
shape, 189 
situation, 193 
statistics, 197 
symptoms, 197 
treatment, 206 
destruction, total, without diabetes, 
table, 81 
disease in vicinity of, necrosis of pan- 
creas from, 238 
diseases of, abnormalities of stools 
as symptom, 104 
clinical experiences, 85 
concurrence, 85 
experimental results, 4 


‘also Pancreatic 


916 


Pancreas, diseases of, bronzed diabetes 
as symptom, 96 

changes in urine as symptom, 92 

diabetes and glycosuria as symp- 
toms, 39 

diarrhea pancreatica as symptom, 
99 

dyspeptic disturbances as symp- 
tom, 104 

emaciation as symptom, 99 

etiology, general, 105 

fatty stools as symptom, 83 

faulty digestion of albumin as 
symptom, 91 

fever as symptom, 104 

glycosuria and diabetes as symp- 
toms, 39 

nausea as symptom, 103 

necrosis of pancreas from, 233 

pain as symptom, 101 

pathology, general, 37 

pressure on adjacent organs as 
symptom, 103 

resistance as symptom, 100 

sialorrhea pancreatica as symptom, 


statistics, general, 105 
symptoms, general, 37 
treatment, general, 108 
tumor as symptom, 100 
vomiting as symptom, 103 
without fatty stools, 87 
displacement, 268 
excretory ducts, 18 
chronic indurative pancreatitis 
from, 140 
closure of, chronic indurative 
pancreatitis from, 141 
extirpation of, effect produced by, 41 
fat necrosis, 244. See also Necrosis, 
fat, of pancreas. 
fatty degeneration, 263 
infiltration, as cause of pancreatic 
hemorrhage, 211 
stools without alteration, 88 
foreign bodies in, 270 
hemorrhage into, 207. See also Pan- 
creatic hemorrhage. 
in cirrhosis of liver, 707 « 
in diabetes, abscess, table, 70 
atrophy, table, 58 
calculi, table, 65 
carcinoma, table, 68 
changes, 56 
cysts, table, 69 
fat necrosis, cases, 72 
fatty degeneration, table, 61 
hemorrhage, cases, 71 
microscopic changes i in, table, 72 
necrosis, cases, 72 
table, 80 
inflammations, 116 
abscess of liver and, 676 
pancreatic hemorrhage from, 214 
' jaundice as symptom, 101 
lipomatosis, 264 





INDEX. 


Pancreas, lymph-vessels, 22 
necrosis of, 233. See also Necrosis of 
pancreas. 
neoplasms, 148 
nerves, 22 
parvum, 17 
prolapse, 268 
proliferation cysts, 185 
relation to blood-vessels and organs 
of posterior abdominal wall, 29 
to diabetes, 56 
to other organs, 26 
retention cysts, 181 
rupture, 265 
course, 268 
diagnosis, 267 
symptoms, 267 
treatment, 268 
sarcoma of, 174 
structure, 22 
syphilis, 179 
topography, 25 
tuberculosis, 176 
veins, 21 
Pancreatic abscess, 122 
calculi, 223 
chemical composition, 224 
color, 224 
consistency, 224 
diagnosis, 231 
frequency, 228 
number, 224 
pathogenesis, 225 
pathologic anatomy, 227 
seat, 224 
shapes, 224 
sialangitis pancreatica in produc- 
tion, 226 
size, 224" 
statistics, 228 
symptoms, 229 
treatment, 232 
weight, 224 
diabetes, experimental, 41 
hemorrhage, 207. See also Hemor- 
rhage, pancreatic. 
juice, effect of temperature on, 32 
ferments, 30 
fate, in organism, 35 
from ‘permanent fistula, physical 
characteristics, 30 
from temporary fistula, physical 
characteristics, 30 
milk-coagulating ferment, 35 
physical characteristics, 29 
secretion, 36 
effect of different foods on, 37 
in fever, 37 
: innervation, 36 
Pancreatitis, acute hemorrhagic, 116 
catarrhal, 116 
chronic circumscribed indurative, 142 
indurative, 134 
course, 147 
diagnosis, 147 
duration, 147 


INDEX. 


Pancreatitis, chronic indurative, from 
alcoholism, 139 
from blood-vessels, 135 
from closure of excretory duct,141 
from endarteritis obliterans, 135 
from excretory ducts, 140 
from syphilis, 137 
pathologic anatomy, 134 
prognosis, 147 
symptoms, 144 
treatment, 148 
indurative, in diabetes, table, 62 
primary suppurative, 123 
- diagnosis, 131 
etiology, 125 
pathologic anatomy, 123 
prognosis and course, 132 
statistics, 128 
symptoms, 129 
treatment, 132 
secondary acute suppurative, 133 
suppurative, 122 
history, 122 
varieties, 116 
Paranephritic abscess, and abscess of 
liver, differentiation, 675 
Parapedesis of bile, 427 
Parasites of liver, 788 
of suprarenal capsules, 316 
Parenchymatous changes in liver, 832 
Pentastomum constrictum in liver, 831 
denticulatum in liver, 831 
Perforations of bile-passages, 522 
symptoms, 522 
treatment, 523 
Perihepatitis, 622 
chronica hyperplastica, 624 
diagnosis, 625 
etiology, 622 
metamorphosis from, 623 
prognosis, 624 
symptoms, 623 
thickening of capsule in, 624 
treatment, 625 
Peripylephlebitis syphilitica, 743 
Peritonitis with cirrhosis of liver, 709 
Perityphlitis, abscess of liver and, 656 
Pernicious anemia, iron in liver in, 868 
siderosis of liver i in, 740 
Phlebotomy of liver, 467 
Phos horus-poisoning, fatty liver and,838 
of liver, 640 
atrophy and differentiation, 646 
Phthisis, fatty liver and, 841 
Pigmentation of liver, "872. See also 
Liver, pigmentation. 
Pneumonia in abscess of ‘liver, 670 
Polycholia, jaundice due to, eg 
sBgee* s ae We disease of, abscess of liver 
van, changes i in contents, 883 
compression from without, 883 
dilatation of stem, 892 
diseases, 881 
inflammation, 889, 904. See also 
Pylephlebitis. 


~ 





917 


Portal vein, narrowing, 882 
anatomy, 884 
prognosis, 888 
symptoms, 887 
occlusion, 881 
rupture, 893 
slowing of blood-current, 883 
wall, diseases, 882 
Pregnancy, jaundice in, 485 
Primary suppurative pancreatitis, 123. 
See also Pancreatitis, primary oue 
purative. 
Prolapse of pancreas, 268 
Proliferation cysts of pancreas, 185 
Pseudocanalicules biliaires, 719 
Pseudoleukemia, liver in, 785, 786 
of liver, 834 
Psorospermia in liver, 788 
Pylephlebitis, 889 
abscess of liver and, 657 
acute, 889 
anatomy, 890 
chronic, 889 
course, 891 
diagnosis, 891 
prognosis, 892 
suppurative, 889 
symptoms, 891 
treatment, 892 
ulcerosa, 889 
Pyonephrosis, abscess of liver and, 676 


RANULA pancreatica, 189 
Retention cysts of pancreas, 181 
Retroversion of liver, 385 
Réntgen rays in diagnosis of abscess of 

liver, 675 
Rupture of bile-passages, 522 

of pancreas, 265 

course, 268 

diagnosis, 267 

symptoms, 267 

treatment, 268 


Sonne duct of, 19 
Sarcoma, melanotic, pigment in liver, 
873 
of liver, 758 
primary, 760 
of pancreas, 174 
Sclérose periacineuse, 136 . 
Secondary acute suppurative pancrea-~ 
titis, 133 
Sialangitis catarrhalis, 226 
pancreatica, 140 
in production of pancreatic calculi, 
226 
Sialorrhea pancreatica as symptom of 
diseases of pancreas, 99 
Siderosis of liver, 740, 858. See also 
Liver, siderosis of. 
Skin and mucous membrane in Addison’s 
disease, changes in, 340 
Spleen, cysts, h datidosus and, 805 
in abscess of liver, 669 


918 


Spleen in cirrhosis of liver, 701 
in passive congestion of liver, 612 
influence of, on formation of trypsin, 
33 
Spulwirmer, 823 
Starvation jaundice, 486 
Steapsin, 33 
Steatorrhea and diseases of pancreas, 
clinical experiences, 85 
concurrence, 85 
experimental results, 84 
as symptom of diseases of pancreas, 83 
diseases of pancreas without, 87 
without alteration of pancreas, 88 
Stercoremia, Dujardin-Beaumetz’s, 616 
‘Stomach, accessory pancreas in, 24 
Stools, abnormalities, as symptom of 
diseases of pancreas, 104 
fatty, and diseases of pancreas, clinical 
experiences, 85 
concurrence, 85 
experimental results, 84 
as symptom of diseases of pancreas, 
83 


diseases of pancreas without, 87 
without alteration of pancreas, 88 
Stromeyer-Little’s method for abscess of 
liver, 681 
Subphrenie abscess and abscess of liver, 
differentiation, 675 
Suppurative cholangitis, 508 
course, 512 
diagnosis, 512 
etiology, 509 
occurrence, 508 
prognosis, 512 
symptoms, 511 
treatment, 513 
pancreatitis, 122 
history, 122 
primary, 123 
diagnosis, 131 
etiology, 125 
pathologic anatomy, 123 
prognosis and course, 132 
statistics, 128 
symptoms, 129 
— treatment, 132 
secondary acute, 133 
Suprarenal capsules, abnormalities of 
development, 310 
anatomy and histology , 307 
atrophy, 311 
circulatory disturbances, 312 
degenerations, 312 
diseases, 307 
diseases of, and Addison’s disease, 
diagnosis, differential, 351 
symptomatology, 332 
embryology, 309 
hypertrophy, 311 
infectious granulation tumors, 314 
inflammations, 313 
neoplasms, 314 
parasites, 316 
pathologic anatomy, 310 





INDEX. 


Suprarenal capsules, physiology, 316 
removal, effect produced by, 319 
extract, action, 322 
therapeutic properties, 330 
Syphilis, chronic indurative pancreatitis 
from, 137 
cirrhosis of liver and, 694 
jaundice in, 487 
pathogenesis, 488 
of liver, 742. See also Hepatitis, 
syphilitic. 
of pancreas, 179 


TTELANGIECTASIS, 749 
Temperature, effect of, on pancreiie 
juice, 32 
on trypsin, 32 
sudden changes of, liver abscess and, 
655 
Toxic jaundice, 496 
Trauma, pancreatic hemorrhage from, 
213 
Trypsin, 30 
changes of albuminous bodies by, 32 
effect of temperature on, 32 
formation, influence of spleen on, 33 
influence of bile on, 31 
Tuberculosis of liver, 730 
of pancreas, 176 
of peritoneum with cirrhosis of liver, 
709 
Tumor as symptom of diseases of pan- 
creas, 100 
infectious granulation, of suprarenal 
capsules, 314 
Typhlitis, abscess of liver and, 656 
Tyrosin, 32 


ULcER, gastric, abscess of liver and, 656 
Urine, changes in, as symptom of dis- 
eases of pancreas, 92 
condition of, in Addison’s disease, 350 
in abscess of liver, 670 
in acute atrophy of liver, 635 
in cirrhosis of liver, 704, 705 
Urobilin and jaundice, relation, 445 
jaundice, 445 


VaricosE dilatation of submucous veins 
of intestine, 893 
Vater, diverticulum of, 19 
Veins of pancreas, 21 
portal, inflammation of, 904 
Vomiting as symptom of diseases of 
pancreas, 103 


Waxy liver, 853. See also Amyloid 
liver. 
Weight of gall-stones, 533 
Weil’s disease, 503 
nature, 506 
occurrence, 505 
symptoms, 504 
treatment, 507 
Wirsung, duct of, 18 
Wounds, bullet, of pancreas, 269 


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be used independently of the practical exercises, which constitute an important 
feature of the book, and aims at being a complete exposition of the subject, adapted 
to the requirements of the student of medicine. In the present edition the book 
has been thoroughly revised and in parts rewritten. A considerable amount of 
new matter has been added, especially to the chapter on The Central Nervous 
System, the rapid advances in the knowledge of this subject demanding extensive 
alterations and additions. The additions in the other parts of the volume have 
been balanced, for the most part, by the omission of some passages and the 
abridgment of others, so that its bulk is only slightly increased. 





OPINIONS OF THE MEDICAL PRESS 





British Medical Journal 
‘Of the many text-books of physiology published, we do not know of one that so nearly 
comes up to the ideal as does Professor Stewart's volume.” 


Philadelphia Medical Journal 

“Those familiar with the attainments of Prof. Stewart as an original investigator, as a 
teacher and a writer, need no assurance that in this volume he has presented in a terse, concise, 
accurate manner the essential and best established facts of physiology in a most attractive 
manner.” . 


The Lancet, London uae 
“ It will make its way by sheer force of merit, and amply deserves to do so, It is one of 
the very best English text-books on the subject.” 


BACTERIOLOGY AND PATHOLOGY. II 





Eyre’s 
Bacteriologic Technique 





The Elements of Bacteriologic Technique. A Laboratory Guide 
for the Medical, Dental, and Technical Student. By J. W.H. Eyre, 
M. D., F.R.S. Edin., Bacteriologist to Guy’s Hospital, London, and 
Lecturer on Bacteriology at the Medical and Dental Schools, etc. 
Octavo volume of 375 pages, with 170 illustrations. Cloth, $2.50 net. 


FOR MEDICAL, DENTAL, AND TECHNICAL STUDENTS 


This book presents, concisely yet clearly, the various methods at present in 
use for the study of bacteria, and elucidates such points in their life-histories as 
are debatable or still undetermined. It includes only those methods that are 
capable of giving satisfactory results even in the hands of beginners. The excel-. 
lent and appropriate terminology of Chester has been adopted throughout. The 
illustrations are numerous and practical, the author considering that a picture, if 
good, possesses a higher educational value and conveys.a more accurate impres- 
’ sion than a page of print. The work is not intended for the medical and dental 
student alone, having been designed with the needs of the technical student gen- 
erally constantly in view, whether he be of brewing, dairying, or agriculture. 





_ Warren’s 
Pathology and Therapeutics 





Surgical Pathology and Therapeutics. By JoHNn CoLLINs WARREN, 
M.D., LL.D., F.R. C.S. (Hon.), Professor of Surgery, Harvard Medical 
School. Octavo, 873 pages, 136 relief and lithographic illustrations, 33 
in colors. With an Appendix on Scientific ‘Aids to Surgical Diagnosis 
and a series of articles on Regional Bacteriology. Cloth, $5.00 net; 
Sheep or Half Morocco, $6.00 net. 


SECOND EDITION, WITH AN APPENDIX 


In the second edition of this book all the important changes have been em- 
bodied in a new Appendix. In addition to an enumeration of the scientific aids to 
surgical diagnosis there is presented a series of sections on regional bacteriology, 
in which are given a description of the flora of the affected part, and the general 
principles of treating the affections they produce. 


Roswell Park, M. D., 
In the Harvard Graduate Magazine, 


‘I think it is the most creditable book on surgical pathology, and the most beautiful medical 
illustration of the bookmakers’ art that has ever been issued from the American press.” 


12 SAUNDERS’ BOOKS ON 


Diirck and Hektoen’s 
Special Pathologic Histology 








Atlas and Epitome of Special Pathologic Histology. By Dr. H. 
Dirck, of Munich. Edited, with additions, by Lupvic HEKTogn, M. D., 
Professor of Pathology, Rush Medical College, Chicago. In two parts. 
Part I.—Circulatory, Respiratory, and Gastro-intestinal Tracts. 120 
colored figures on 62 plates, and 158 pages of text. Part I].—Liver, 
Urinary and Sexual Organs, Nervous System, Skin, Muscles, and 
Bones. 123 colored figures on 60 plates, and 192 pages of text. Per 
part: Cloth, $3.00 net. J Saunders’ Hand-Atlas Series. 

The great value of these plates is that they represent in the exact colors the effect 
of the stains, which is of such great importance for the differentiation of tissue. 
The text portion of the book is admirable, and, while brief, it is entirely satisfac- 


tory in that the leading facts are stated, and so stated that the reader feels he has 
grasped the subject extensively. 


William H. Welch, M. D., 
a ku of Pathology, Johns Hopkins University, Baltimore. 


“T consider Diirck’s ‘Atlas of Special Pathologic Histology,’ edited by Hektoen, a very 
useful book for students and others. The plates are admirable.” 


Sobotta and Huber’s 
Human Histology 








Atlas and Epitome of Human Histology. By PrivarpocenT Dr. 

J. Soorra, of Wiirzburg. Edited, with additions, by G. Cart Huser, - 

M. D., Junior Professor of Anatomy and Histology, and Director of the ° 

Histological Laboratory, University of Michigan, Ann Arbor. With 

214 colored figures on 80 plates, 68 text-illustrations, and 248 pages of 
text. Cloth, $4.50 net. Ju Saunders’ Hand-Atlas Series. 


INCLUDING MICROSCOPIC ANATOMY 


The work combines an abundance of well-chosen and most accurate illustra- 
tions, with a concise text, and in such a manner as to make it both atlas and text- 
book. The great majority of the illustrations were made from sections prepared 
from human tissues, and always from fresh and in every respect normal specimens. 
The colored lithographic plates have been produced with the aid of over thirty 
colors, and particular care was taken to avoid distortion and assure exactness of 
magnification. The text is as brief as possible, clearness, however, not being 
sacrificed to brevity. . 


BACTERIOLOGY. — 13 





Levy and Klemperer’s 
Clinical Bacteriology 





The Elements of Clinical Bacteriology. By Drs. Ernst Levy and 
Fevix KLEeMpPerER, of the University of Strasburg. Translated and 
edited by Aucustus A. Esuner, M. D., Professor of Clinical Medicine, 
Philadelphia Polyclinic. Octavo volume of 440 pages, fully illustrated. 
Cloth, $2.50 net. 


This book represents an attempt to group the results of bacteriologic investi- 
gation from a clinical point of view. Bacteriology has become more and more an 
indispensable aid to medical art. It has enlarged our comprehension of the nature 
of infectious diseases, and it has established their prophylaxis, diagnosis, and treat- 
ment upon a broader basis. The work shows how useful to the physician in his. 
capacity of counselor of the well and coadjutor of the sick are bacteriologic thought 
and action. 


S. Solis-Cohen, M. D., 
Lecturer on Clinical Medicine, Jefferson Medical College, Philadelphia. 
‘‘T consider it an excellent book. I have recommended it in speaking to my students.”’ 





Lehmann, Neumann, an? 
Weaver’s Bacteriology 





Atlas and Epitome of Bacteriology: IncLUDING A TExT-BooK oF 
SPECIAL BacTerioLocic DiAcnosis. By Pror. Dr. K. B. LEHMANN and 
Dr. R. O. NEuMANN, of Wiirzburg. From the Second Revised and 
Enlarged German Edition. Edited, with additions, by G. H. WEAVER, 
M. D., Assistant Professor of Pathology and Bacteriology, Rush Medical 
College, Chicago. In two parts. Part I.—632 colored figures on 69 
lithographic plates. Part II1—511 pages of text, illustrated. Per part: 
Cloth, $2.50 net. Jz Saunders’ Hand-Atlas Series. 


INCLUDING SPECIAL BACTERIOLOGIC DIAGNOSIS . 


This work furnishes a survey of the properties of bacteria, together with the 
causes of disease, disposition, and immunity, reference being constantly made to 
an appendix of bacteriologic technic. The special part gives a complete descrip- 
tion of the important varieties, the less important ones being mentioned when 
worthy of notice. 


The Lancet, Londor 


‘We have found the work a more trustworthy guide for the Seon of unfamiliar species 
than any with which we are acquainted.” 


14 SAUNDERS’ BOOKS ON 


Raymond’s Physiology 


Human Physiology. By Jos—EpH H. Raymonp, A. M., M. D., Pro- 
fessor of Physiology and Hygiene, Long Island College Hospital, New 
York. Octavo volume of 668 pages, with 443 illustrations. Cloth, 
$3-50 net. | 

SECOND EDITION, ENTIRELY REWRITTEN AND ENLARGED 


In its present form the book has been entirely rewritten and very greatly en- 
larged. Although intended more especially for students’ usé, the book will be 
found particularly well adapted to the needs of physicians, since it brings out very 
fully the application of the science of physiology to practical medicine. 


The Lancet, London 


“The book is well gotten up and well printed, and may be regarded as a trustworthy guide 
for the student and a useful work of reference for the general practitioner. The illustrations are 
numerous and are well executed.” 


Senn’s Tumors 


Pathology and Surgical Treatment of Tumors. By NicHOLAs 
SENN, M.D., Pu. D., LL.D., Professor of Surgery, Rush Medical Col- 
lege, Chicago. Handsome octavo, 718 pages, with 478 engravings, 
including 12 full-page colored plates. Cloth, $5.00 net; Sheep or Half. 
Morocco, $6.00 net. | 

SECOND EDITION, REVISED 


The author spent many years in collecting the material for this work, and has 
taken great pains to present it in a manner that should prove useful as a text-book 
for the student, a work of reference for the general practitioner, and a reliable, 
safe guide for the surgeon. 














Journal of the American Medical Association 


“The most exhaustive of any recent book in English on this subject. It is wellillustrated, and 
will doubtless remain as the principal monograph on the subject in our language for some years.” 


Stengel and White on Blood 


The Blood in Its Clinical and Pathologic Relations. By* ALFRED 
STENGEL, M. D., Professor of Clinical Medicine in the University of 
Pennsylvania; and C. Y. Wuire, Jr., M.D., Instructor in Clinical 
Medicine in the University of Pennsylvania. Ju Preparation. 








ITS CLINICAL AND PATHOLOGIC RELATIONS | 


__ This work will deal with the blood in its clinical and pathologic relations. It 
will be heautifully illustrated, and will represent the latest knowledge on the sub- 
jects, concisely and clearly expressed. 


BACTERIOLOGY. 15 


Gorham’s Bacteriology — 


A Laboratory Course in Bacteriology. For the Use of Medical, 
Agricultural, and Industrial Students. By FrEpeEric P. Goruaw, A. M., 
Associate Professor of Biology in Brown University, Providence, R. I, 
etc. 12mo volume of 192 pages, with 97 illustrations. Cloth, $1.25 net. 








This volume has been prepared as a guide to the practical details of laboratory 
work. It is intended to present the subject in such a general way as to lay a broad 
foundation for later specialization in any branch of bacteriology. By a judicious 
selection the course can be made to conform to the requirements of medical, agri- 
cultural, or industrial students. 


American Journal of the Medical Sciences 


‘One of the best students’ laboratory guides to the study of bacteriology on the market. ... 
The technic is thoroughly modern and amply sufficient for all practical purposes.”’ 





Stoney’s Bacteriology and Technic 





Bacteriology and Surgical Technic for Nurses. By Emity A. M. 
Stoney, Superintendent of the Training School for Nurses at the Carney 
Hospital, South Boston. 12mo volume of 200 pages, profusely illus- 
trated. Cloth, $1.25 net. 

This work is intended as a modern text-book of Surgical Nursing both in hos- 


pital and private practice. The first part of the book is devoted to Bacteriology and 
Antiseptics ; the second part to Surgical Technic, Signs of Death, and Autopsies. 


The Trained Nurse and Hospital Review 


“ These subjects are treated most accurately and up to date, without the superfluous reading 
which is so often employed. . . . Nurses will find this book of the greatest value.” 


Clarkson’s Histology | 


A Text-Book of Histology. Descriptive and Practical. For the 
Use of Students. By ArTHUR CLarkson, M.B., C. M. Edin., formerly 
Demonstrator of Physiology in the Owen’s College, Manchester ; late 
Demonstrator of Physiology in the Yorkshire College, Leeds. Octavo, 
554 pages, with 174 colored original illustrations. Cloth, $4.00 net. 








The first chapters of this work are devoted to a consideration of the general 
methods of histology ; subsequently, in each chapter, the structure of the tissue 
or organ is first systematically described, the student is then taken tutorially over 
the specimens illustrating it, and, finally, an appendix affords a short note of the 
methods of preparation. 


New York Medical Journal 


‘The volume in the hands of students will greatly aid in the comprehension of a subject 
which in most instances is found rather difficult. . . . The work must be considered a valuable 
addition to the list of available text-books, and is to be highly recommended.” 


16 " BACTERIOLOGY, PHYSIOLOGY, AND HISTOLOGY. 
Ball’s Bacteriology Fourth Edition, Revised 
ESSENTIALS OF BACTERIOLOGY: being a concise and systematic intro- 
duction to the Study of Micro-organisms. By M. V. Bat, M. D., Late 
Bacteriologist to St. Agnes’ Hospital, Philadelphia. 12mo of 236 pages, 
with 96 illustrations, some in colors, and 5 plates. Cloth, $1.00 net. Jz 
Saunders’ Question-Compend Series. 


‘“The technic with regard to media, staining, mounting, and the like is culled from the 
latest authoritative works.’’— 7he Medical Times, New York. 


Budgett’s Physiology 
ESSENTIALS OF PHysioLocy. Prepared especially for Students of Medi- 
cine, and arranged with questions following each chapter. By SIDNEY 
P. Bupcerr, M. D., Professor of Physiology, Medical Department of 
Washington University, St. Louis. 16mo volume of 233 pages, finely 
illustrated with many full-page half-tones. Cloth, $1.00 net. lz 
Saunders’ Question-Compend Sertes. 





‘‘Contains the essential facts of physiology presented in a clear and concise manner.” — 
Philadelphia Medical Journal. 


Leroy’s Histology Second Edition, Revised 
ESSENTIALS OF HistoLocy. By Louis Leroy, M.D., Professor of 
Histology and Pathology, Vanderbilt University, Nashville, Tennessee. 
I2mo, 263 pages, with g2 original illustrations. Cloth, $1.00 net. Jz 
Saunders’ Question-Compend Series. 


‘“‘ The work in its present form stands as a model of what a student's aid should be; and 
we unhesitatingly say that the practitioner as well would find a glance through the book 
of lasting benefit.’""— Zhe Medical World, Philadelphia. 


Bastin’s Botany 
ILABORATORY EXERCISES IN Botany. By the late Epson S. Bastin, 
M. A., Professor of Materia Medica and Botany, Philadelphia College of 
Pharmacy. Octavo, 536 pages, with 87 plates. Cloth, $2.00 net. 


“It is unquestionably the best text-book on the subject that has yet appeared. The 
work is eminently a practical one." —Alumni Report, Philadelphia College of Pharmacy. 


Frothingham’s Guide for the Bacteriologist 
LABORATORY GUIDE FOR THE BACTERIOLOGIST. By LANGDON FROTH- 
INGHAM, M. D.V., Assistant in Bacteriology and Veterinary Science, 
Sheffield Scientific School, Yale University. Illustrated. Cloth, 75 cts. net. 


American Pocket Dictionary Third Edition, Revised 

DorLand’s PockeT MepicaLt Dictionary. Edited by W. A. NEw- . 

MAN Dor.anp, M. D., Assistant Obstetrician to the Hospital of the 

University of Pennsylvania. Containing the pronunciation and defini- 

tion of the principal words used in medicine and kindred sciences, with 

64 extensive tables. Handsomely bound in flexible leather, with gold 
edges, $r. oo net; with patent thumb index, $1.25 net. 


“ I can recommend it to our students without reserve. "—J.H. HOLLAND, M.D., Dasa 
of the Jefferson Medical College, Palaeriphia. 








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