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iiiiiiiiiiiiiiiiiiiif ' . '") 




Professor of Clinical Medicine, UniYersity of Pennsylvania ; Physician to the Penn- 
sylvania, University, and the Philadelphia Hospitals 

"Witb 399 f Uuetratione in tbe XLcxt, mani^ oX tbem in Colore, and 
7 tulUpage CbromolitbO0rapbic platee 




Set up electrotypcd, printed, aod copyriKhted September, 1898. Revised, reprinted, and 

recopyrighted March. 1899. Reprinted August. 1899: November, 1899. Revised, 

reprinted, and recopyrigfated October, 1900. Reprinted July, 1901; 

September, 1903. Revised, reprinted, and recopyrighted July, 1903. 

Reprinted March, 1905. Revised, reprinted, and 

recopyrighted September. 1906. 

Copyright, 1906, by W. B. Saundbrs Company. 




Ik the revn^ion for tiie prei*ei>t eclition the author has felt it 
ij^-eessary to reconstruct a large part of tht* si'ctiniis dealing with 
(reneral Pathology, The chapters on Intlanunation, Iramnnity, 
imd Animal ParaRites liave l>een extensively revised and somewhat 

It has been difficult to esca|>e tlie teniptatiou lo intrtKhice new 
matter under the headings of Pathologic Physiology, but the 
author has decided that ftir the purposes which liis hook is intended 
to fidhll, sufficietit had been introduced in previous editions, and 
that only such revision as increased knowledge required was desir- 

The volume has been increased in size, but the general characs- 
let of the work — that of a text-book for students and practition- 
ers — has been retained. It is a pleasure ti> acknowledge the 
courteous eo-operation of Messrs, Saunders Com|Mny and their 
generous willingness tn rce^ist plates and otherwise spare no ex- 
pense in making the present i'ditic»ii wliat the author desired, 

I*I1J1^A11ELPM1A» ^ptanher, 1906. 



In writing this book the author has tried to pre.seiit the sub- 
ject of Pathology in a>? practiriil a form as possible, and ahvays 
from the point of view of the clinical pathologist. Con.s^iderable 
parts of the book were tiryt prepared and used as the basis of 
demonstrations npni clinical pathology for studcntjf of medicine ; 
prominence is thcrefure given to puthologie physiology, and dis- 
cursiveness and citation of authorities are avoided. 

Except in a few instances, disensston of methods of examina- 
tion has l>een omitted, because it seemed unwise to iJi crease the 
size of tlie book with matter that is ajipropriatcly presented in 
special works on teeliniqne. For similar reasons the author hajs 
decided to exclude the pathology of the i>kin and of the organs 
of special sense. 

Controversial matter lias Ix^en avoided as much as possible, 
excepting in certain parts of the sections on General Bacteriology 
and on Neuropathology , in which it seemed proper to discuss 
conflicting theories. 

Full use has been made of w^orks on pathology and of special 
monographs in English ixs well as in French and Germau, 

The author is greatly indebted to Dr, Samuel »S, Kneaj5S and 
Dr* Alonzo E. Taylor for assistance in tlie sections on General 
Bacteriology and the Degenenitiuus in Part I,, and especially 
to Dr. Joseph Sailer, who prei^ired ahnost wholly the sections 
on Neuropathology, Acknowledgment is also due Mr. Thos. 
F. Dagney, of Mr. Saunders' editorial office, i\\v his uniform 
courtesy and assistance in many ways, and >Ir, R, \\\ Greene 
for the preparation of the Index. 





The EnoixMjY of BiJseAfie IH 

TmunrntiKiTi, U* — Physical nindition«, 20 — Pobofu^ 24 — Vegetable 
and Aninml Paraj*itt*i^ ^iL 

tllAr'TER II , 

Di^RBEKS OF Nutrition and Mltabqi.ism . . . , 33 

Foodj 33 — IHminLHhtNl Supply of FfKxl^ 33-— Increased Supply of 
Food, 33— Exce*«ive TiK^iie-desi ruction, 35 — Add*mlfiiication, 35 — 
Foroialion of Albumcwea, 38— Alio x in BasHw and Uric Acid, 3S— Gout, 
39— Glycosmrm, 40— Diabet€f«, 41— Ft^ver^ 4*5, 


DusriTRBANCES OF THE i 'iRCll.A TltiN OF THB BlXK>D .......*. 48 

Oentml DistuplMiiices, 48— I^»cal ny}K*rt*iTimj 50— Local Anemia, 52 — 
Hernrrrrhage, 52— EmMiKiti, t>(i Infuniicm^ 57^Thrombo8ifi, 5^— 
Edeioii, (14. 


Retrogressive PR(.M?EtiSES , ...,,.. 68 

Atrophy^ 68 — The iJegeneralioiLs, 70— CIikhIv dwelling, 70— Fatly In- 
filtration, 72— Fntty Degeoenition, 74"'The AUMiniinoid iX^generationK, 
77 — Amyloid Dtxt^nemlioo, 78 — HyuliiULi l>egeneralion» 80— Mucoid 
Deg<?nemtion, 83^Colloid iVgencnitlon, 85 — iilycojienic Inliltiiition, 86 
^Dro[>»iical Infiltration, 87— Ca lei lien t ion, 88 — Owilirtition IN) -llratic 
Infiltration^ 1*0 — PignH*nl^in*»ti, W— Xe^Ttt^is, !**"» — ( na^ulution-necrtjflis, 
98 — Liquefactitm-neerosis, ?Hi^( 'a^^t^ntion, KHl— Fal-nerroj^is, lOl^IlLniol- 
ysb, 102 — Gangrene, 102— Cell y la r Necrosis, l(>i— Piwt-nioiteni Altera- 
tions in r«ll Nut'lei in Necrosis, 105— AlleraliimH in the Fonn of Celln 
in NecroHiH, 105— Alttrwi Karyokine.siw in Necrotic Cells, 106— Post- 
mortem Alterationt^ 100. 


Inflammation and RBt#ENERATitiN 107 

Inttumnmlion, 107 — Regeneration, 128 — Metaplasia, 134. 


PRtKiRESFlVE TlSSUtK^ANriES , , , . . 

Hypt'rtrophy, 134— Tniiiorfs i:^— Fibwrnia, 146— Myintna, 150— Li- 
pomn, 152 — Xanthoma, 153 — Chomlronia, 153 — CMleomii, 157 — Lymph- 
angiornaf 159 — Ileniantfioina, 151) — Lyniphadenoma, 16* — Myeloma, 165 
-Sarcoma, 166 — 8pitidle-celle<l tsurconja^ 160 — Round-celled Sarconia^^ 




170 — Angio6anx>ma, 172— Cylindroma, 173 — Melanoearcoma, 174 — 
Giant-celled Sarcoma, 175 — Mixed Tumors, 177— Chloroma, 177 — 
Psammoma, 177 — Mycosis Fung^ides, 178 — Endothelioma, 178 — Glioma, 
180 — Neuroma, 183 — Leiomyoma, 184 — Rhabdomyoma, 186 — Papilloma, 
187 — Adenoma, 188 — Carcinoma, 192 — Epithelioma, 201 — Glandular 
Carcinoma, 203— Colloid Cancer, 204 — Syncytioma Malignum, 206 — 
Cysts, 207— Teratoma, 210. 


Bacteria and Diseases Due to Bacteria 212 

Classification, 212 — Morphology, 214 — Biology, 216 — Functions and 
Products of Bacteria, 217— -The Local Eflfects of Bacteria, 222— Effects 
of Toxic Products of Bacteria, 223— Immunity, 224. 

Diseases Due to Bacteria, 239— Suppurative Diseases, 240 — (ronor- 
rhea, 246 — Croupous Pneumonia, 248— Other Forms of Pneumonia, 251 — 
Rhinoecteroma, 252— Diphtheria, 252— Typhoid Fever, 256— Bacilli Coli 
Communis, 263 — Dysentery Bacillus, 265 — Cholera, 266 — TuberculosL**, 
270— Smegma Bacillus, 281— Fowl-tuberculosis, 283— Pseudotuberculosis, 
284— Leprosy, 284— Glanders, 288— Malignant Edema, 290— Anthrax, 
291 — Infectious Emphysema, 294 — Tetanus, 295 — Actinomycosis, 298 — 
Mycetoma, 302 — Relapsing Fever, 303 — Influenza, 304 — Bubonic Plague, 
306— Thrush, 307— Pharyngomycosis Leptothricia, 308— Syphilis, 308— 
Soft Chancre, 314— Yellow Fever, 315— Measles, 317— Scarlet Fever, 
318— Mumps, 318— Whooping-cough, 318— Variola and Vaccinia, 319— 
Typhus Fever, 319 — Rabies, 319 — Proteus Infection, 321 — Hemorrhagic 
Diseases, 321— Rheumatism, 322— Malta Fever, 324— Beri-beri, 324. 

ANiMAii Parasites and Diseases Caused by Tiiem 325 

Protozoa, 325— Amoeba Dysenteric, 325— Amceba Coli, 326— Other 
Ameba?, 327 — Cercomonas Hominis, 327— Cercomonas Coli Hominis, 
327 — Trichomonas Intcstinalis, 328— Trichomonas Vaginalis, 328 — 
Other Fonns of Trichomonas 328 — I^niblia Intcstinalis, 328— Trypano- 
some, 329 — Parasites of Malaria, 331 — Coccidium Cuniculi, 335— Cocci- 
dium Bigeminum, 336 — Eimeria Hominis, 33() — Sarcosporidia, 336 — 
Balantidium Coli, 337 — Balantidium Minutuni, 337 — Animal Parasites 
and Molluscum Contagiosum, 337 — Variola and Vaccinia, 328— Vari- 
cella, 340 — Measles, Scarlet Fever and Other Diseases, 340. 

Cestodes, or Tape- worms, 340— Ta?nia Solium, 342— Taenia Sagin- 
ata, 344 — Hymenolepis Nana, 345 — Ilymenolepis Diniinuta, 346 — Dipy- 
lidium Caninum, 346 — Davainea Madagascariensis, 346 — Twnia Ech- 
inococcus, 346 — Dibothriocephalus I-^itus, 349— Dibothriocephalus C'or- 
datus, 350 — Bothriocephalus Mansoni, 350 — Diplogonoporus CJnindis, 350. 

Nematodes, or Round-worms, 350 — Ascaris Lumbricoides, 350 — 
Ascaris Canis, 351— Ascaris Maritima, 351— Oxyuris Vonniciilaris, 351 
— Trichinella Spiralis, 352 — Ankylostomum Dmxlenale, 353 — Unoinaria 
Americana, 354 — Stix>ngyloides Intcstinalis, 355- Trichocephalus Trich- 
iurus, 356 — Filaria Medinensis, 357— Filaria Bancrofti, 358 — Other 
Forms of Filaria, 359 — Echinorrhynchua (iigns, 360 — Eastrongylus CHgas, 
360— Strongylus Apri, 360— Strongylus Subtilis, 360. 



Trematodes, or Flyk«-wornia, StUj— FuH'ioIa lI(?iMitiai, 361-^ 
Dicr«jc<jL4mni Lanceaniiu, liHl— npisihorthU FelinenN. 'Ml — < Jni«tbor- 
chis Sineiihiis 362 — SchUt<is<iiiimii Ik-iimtobidin, ^iH2 — 8t'hirtl(js<tmuiii 
Jaimnic^ini, Mli — Piirag<jnimus \\V'»leniiaijni, J^63 — (JtbL*r Fluke- worms, 

Annelides 364. 

Athrapodia, *ir"4~Lingimlula RKinunsi, 3iM— Pni\»cf>j>liiiltis (Vm- 
BtiictLL8, 3Llt> — \f jiuhif*, 305. 




DlBEAS£4 OF THE BloOD 806 

Annlotny, 3«W^ — BJtKxI'foritisiliitti, 371— Putholo^ic Clmn^rfs in Ktd 
Cor|»us(j^lt^ 372 — Futholo^ic l/Juin^es in Loukcjcytes, 375 — Fatlicilogic 
Change?* in Pbisfiia, 375 — Pk*thani, 37*>— Oligemia, 377— Hydremia aaJ 
Arihydremia, 377 — Li|M?mia, 378 — Mclaneiiiiii, 378 — Heajncytolvbis and 
HeTiioghibJneniia^ 378 — Pulycy ihtmia, 380 -LeiikcxytoHLs, 380— Ilvfrn- 
leukocytLwi-'S 383 — Anenun, 3S3— <_'lik>ro8i% 38*i — Progresisivc Pemiinoiitj 
Anemia, 388— Aplastk* Anemia, 3'.K) — Leukemia, 300 — HodgkinV J>i?*- 
eaae, 394- Pseudoleukemia Infajitiiiii, 395— Foreign Bodies and iVra- 

sites, 305. 


DlBEA.«E£9 OF THK LVMIMIATK^ Tl?<-<r4iS 30l) 

Spleen, 306 — Abnormal I ^uvrloiiment and Situalion, 397 — CircHlatory 
Disturlxinrt*v 307~liifiammatioii, 3i*8 — Atrr>jdiy and rk'geaemtion, 401 
— T»jmoi> and ParjsiteM, 40^— Infectious Disea»e?s 403. 

Lymphatfc Otands, 404— Atmpliy, 404— Hypertrophy, 404~De- 
genenitiiins, 4U5 — inliannmiljon, 4Ul) — InftM-tious Ilineast's, 408 — Tumom, 

Bone-marrow, 413— I>egenenitions, 413- Alropby, 413 — Hyi^er- 
trtipby, 413— Marrow in Infet-tions, 414 — Inflamniati^m, 414 — InfectioUH 
DiM'Ji.^s a n d Tn m o rs, 4 1 5. 

Thymus Gland, 41 i. 


DliSKAJ'ES fiF THE ClR< rLAIXlRY 8Y5«TKM - . 4]tl 

Heart, 4Ui- (Vmgeuital Dincasew and Ih-foriinties, 4H>— Cirfulaton- 
Di.-'lurhftneeA, 420— /C*M/of«rJ{Mm, 422 — Kndm'anlitis 422—CirL'ulaton' 
DiHturbanec!*, 4IM) — Dei^L-nenitions, 430— lnflanimati«m, 435 — HypL»i>lasia 
and Atrophy, 441— Hyf^rtropby and Diliitiilion, 443— Anenryj<Tri, 440— 
Wounds and Ruptnrt% 44^— Tnrertioiis Dist*ases, 447 -Ne^v Hmwilis and 
Parasites, 'm—Frnfartlium, 447 -Circulatory I>iHiurK'tm-<»s, 4 48^ In- 
flammation, 448 — lnfectiouH Diseases, 452 — Tuniontaiid Pa^^^iles, 452— 
PoeumopcHcaiTliiim, 4*^2, 

Arteries, 453— Cbnpretiit;d ncfet!ts4r>3— HyiM^rtropby, 4r):i- Atrophy, 
453"Degeneration8, 4M— Inflammation, 455— In feet io us Dis^euHeH, 4iH)— 
Aneurysm, 460. 

12 V0NTE2fTS 


Veins, 467— Circulatory Disturbances, 467— Degenerations, 468— In- 
flammation, 468— Dilatation, 470— Tumors, 471— Infectious Diseases, 471. 

Lymphatic Channels, 471— Inflammation, 471— Dilatation, 472— 
Infectious Diseases, 472— Tumors, 472 — Parasites, 473. 

Thoracic Duct, 473. 

Diseases op the Respiratory Syotem 474 

Nasal Cavities, 474— Congenital Abnormalities, 474— Circulatory 
Disturbances, 474— Inflammations, 474— InfectiousDiseases, 475— Tumors, 
475 — ^Parasites and Foreign Bodies, 476. 

Larynx, 476 — Congenital Abnormalities, 476 — Circulatory Disturb- 
ances, 476— Inflammation, 477— Infectious Diseases, 478— Tumors, 479— 
Parasites and Foreign Bodies, 480. 

Trachea, 480— Malformations, 480— Circulatory Disturbances, 480— 
Inflammation, 480— Infectious Diseases, 481 — Tumors, 481. 

Bronchi, 481 — Congenital Malformations, 481 — Circulatory Disturb- 
ances, 481 — Inflammations, 481 — Stenosis and Obstruction, 484 — Dilata- 
tion, 484 — Infectious Diseases, 485— Tumors, 485 — Parasites aud Foreign 
Bodies, 485. 

Lungs, 486— Congenital Defects, 487— Circulatory Disturbances, 487 
— Hypertrophy and Atrophy, 491 — Emphysema, 491— Atelectasis, 495— 
Inflammation or Pneumonia, 497 — Gangrene, 514 — Tuberculosis, 515— 
Syphilis, 527 — Glanders, 529 — Actinomycosis, 530 — Tumors, 530— Para- 
sites, 533. 

Pleura, 533— Circulatory Disturbances, 534— Inflammation, 535— 
Infectious Diseases, 539 — Tumors and Parasites, 539. 

Diseases of the Gahtro-intestinal Tract 541 

Mouth, 541— Congenital Abnormalities, 541— Circulatory Disturb- 
ances, 542— Inflammation, 542- Atropliy and Degeneration, 545 — Infec- 
tious Diseases, 546 — Tumors, 548. 

Teeth, 548. 

Pharynx and Tonsils, ")50— Circulatory Disturbances, 550 -Inflam- 
mation, 550 — Pressure-necrosis, 553 — Infectious Diseases, 554 — Tumors, 

Salivary Qlands, 556. 

Esophagus, 557— Congenital Defects, 557— Circulatory Disturbances, 
557— Inflammation, 557 — Stenosis, 558— Dihitation, 558— Perforation and 
Rupture, 559 — Infectious Diseases, 559— Tumors, 559. 

Stomach, 560— Congenital Defect-s 560— Circulatory Disturbances, 
560— Inflanmiation, 561— (Jastric I'lcer, 564— Atrophy and Degenera- 
tions, 566— Alterations in Position and Size, 567— Infectious Diseases, 568 
— Tumoi-s, 568 

Intestines, 572— Abnormalities, 572 - Intestinal Obstruction, 575— 
Prolaj>seof Rectum, 577— Atrophy and Degeneration, 577— Circulatory 
Disturbances, 577— Inflammation, 579— Inflammation of Special Parts, 
.581__Infectious Diseases, 585— Tumors, 591— Para.sites, 594— Intestinal 
Rupture and Foreign Bodies, 595. 



Liver, 596^Malf<*nuatiuiiH and t'tiaagesi of roHidoii^ oitti— Cin'ulatory 
Bibtiirlmnctt*, «597 — Atrophy and l>eg^^nejiition,s, 59^)— iiiflannmition, tj04 
— UyjMjrtrophy, &01* — Kuptitre, i>lO — Jnfccdoiis Diseases, 610 — Tuuiorj, 
512— Pani«iti34, 015. 

Biliary Ducts and Gall-bladder, tJ17— liiflnnimation, (U7— iSteiitwls 
and DibuilJon, BlH—i iiilJ-sUmcN^ i'lKdelithiiiijiH, fJU* — Tumc^in, ti'ill — 
Jaimdit^, 620. 

Ptmcreas, 621— Congiimtul AbnoriniiUtiea, 021— Circnlatorv Umui1>- 
ances, 621 — Ahx>iihy anrl lA^jMjtinfnitioii.s, 622 — lntIiiiiMuatlon,623 — Infec- 
tious Disease*, 625 — Tuiiiors» 025— l'aDci*oatic Duct, 626. 

Peritoneum* 627— i-'ongt^nitul Abnonnalitiew, 627— < •ircuhilan- I)i^ 
turbiiiiLfis 627^1iiHammiition^ 6211 — Infeclious Diseases, 633 — ^Tuinoi's, 
633— Poni!iite*,6:M. 


IhaKAJSlSH OF THK DlXTLESS (JLANt*H ... - 6;^') 

Th y r O id Gland , i >;i.3 — ^C* h igen U« I I H.*f ec b<j 635— Distii rl»i nte.'i i »f C ir- 
culation, 6^V>— Iiiflammation, i^'M'^ — Stniimi orGoitei'j63tt — lnftH.*tiouHi Dl**- 
eoseSj 631* — Til iiK JIN and Para-situ^, 640— Gen em 1 Ki-sidLs of Th/roid Di^ 
eaee, 640, 

Suprarenal Bodies, 642— Congenital AnonmUeH, 642 — Degeneni- 
tions, 642 liifot'tinnH Discii-s^?^, 64 '1 — drciilfitory Disturhinct'M, 64:^ — 
Inflaniiimtion, 644 — Tuinurs, 6-14— 4ieiiend KfleetH of Supnirenal Dlii- 



Kidneys, 645— Congou (Ui I Annfuulies, 645— Cbanges of Position, 646 
Ciifulatoiy DUturbance;*^ 646 — InHaiiiniatioii, 648 — Nephritw, 648 — 
CJironic NcphritLs 653— Chnmic Parent hymaloiis Nephritic', 659^^ 
Climnic Inleretitial Nephritic* 655 — Atrophy and Hyi>ertrophy, 663 — 
Degenerations, 664^-0 mrreliont* in the C'rinilemtLH Tubnlesj 668 —Infec- 
tious Diseases, 6tiK — Tmnors, 66l>~Par-iisitesj}73. 

Pelvis of Kidney and Ureter, 674— rongenital and Ac-rjnired Mai- 
fonnariunsj 674— ('jik-uhiH, 674 — Inflammation, 675 — Infeetious Diseases, 
676 — Tumors^ 677 — Panisitpf^, 677. 

Urflaary Bladder* 677— Malforaiations 677— rimngef^ of Position, 
678— Rupture, 678— Circjilaltjn' DLstnrlian« e«, 678— Iiittainmation, 679 
—Infectious DiseafH?**, 681— faltnili and ForeiKn Bmiies 681— Tn morn, 
683— Abnormal Conditions of the rdne, 684 — Chemical Changes and 
St^iiments of I'rine, 61*0. 

Urethra, 6*>;i—<W,UP,Utn I AbnomialitiPR 693— Inflamnmlion, 693— 
I^nries, 696— InfeelitHH Dii4ea»<es, 696— Tunioi-s, 697. 


J^BASm or TUT. RKPRoinrrTJVt: DiuiANs , , . , ♦ 697 

Uterus, 697— Dcvelojuiient and Anatoniy, 697 — (*ongi:*nital Abnor- 
tnali ties, 698 — Altera I ions of Pti^itioii, ti98— StenoMs, Dilatation, and Rtip- 
loTC, 701 — Cirenlnlory Di.stiirhanre?*, 702 — ^Inilannnation, 703 — lnfeetiou>i 
Di^en^ea^ 707 — Atrophy an*! Degenerations, 710 — Hypertrophy, jokI 
Hyperplasia, 710— Tiinitjrs, 711^Pantsite?«, 716. 


Ovaries, 716 — ^Development and Anatomy, 716 — Congenital Abnoi^ 
malities, 717 — Changes in Position, 717— Circulatory Disturbances, 717 — 
Inflammation, 718 — Infectious Diseases, 718— Tumors, 719— Cysts of the 
Parovarium, 722— Cysts of Kobelt, 723. 

Fallopian Tubes, 723— Congenital Abnormalities, 723— Changes of 
Position, 723— Stenosis, 724— Dilatation, 724— Circulatory Disturbances, 
724 — Inflammation, 725 — Infectious Diseases, 727 — Tumors, 728 — Extra- 
uterine Pregnancy, 729. 

Vagina, 731— Prolapse of Vaginal Wall, 731— Stenosis, 731— 
Wounds and Fistuke, 731 — Qrculatory Disturbances, 732 — Inflamma- 
tion, 732 — Infectious Diseases, 733 — Tumors, 733. 

Decidua, Placenta, and Fetal Membranes, 734— Anatomic Con- 
siderations, 734 — Abnormalities of Development, 734— Circulatory Dis- 
turbances, 735^Inflammation, 735— Infectious Diseases, 736— Hypei^ 
plasia, 736. 

Vulva, 738— Wounds, 738— Circulatory Disturbances, 738— Inflam- 
mation, 738 — Infectious Diseases, 739— Tumors, 739. 

Penis and Scrotum, 740— Congenital Abnormalities, 740— Inflam- 
mation, 740 — Infectious Diseases, 741— Tumors, 741 — Injuries, 742. 

Testicles, 742— Congenital Abnormalities, 742— Atrophy and Hyper- 
trophy, 742— Degenerations, 743— Circulatory Disturbances, 743— Inflam- 
mation, 743— Infectious Diseases, 746— Tumors, 748— Parasites, 750. 

Prostrate Qland, 750— Inflammation, 750— Atrophy and Degenera- 
tion, 751— Concretions, 751— Infectious Diseases, 751— Ilyiwrtrophy and 
Tumors, 752. 

Cowper's Glands, 754. 

Seminal Vesicles, 754. 

Mammary Qiands, 755— Congenital Abnormalities, 755 — Circula- 
tory Disturbances, 755— Inflammation, 756— Ati-ophy and Hypertrophy, 
757— Degenerations, 757 — Infectious Diseases, 757 — Tumors, 758. 


Diseases op the Bones 761 

Anatomy and Development, 761— Rickets, 762— Regeneration of Bone, 
764— Circulatory Disturbances, 767— Inflammation, 767— Hypoi)la8ia 
and Atrophy, 771— Degenerative Conditions, 772— Infectious Diseases, 
774— Tumors, 777. 


Diseases of the Joints '^*^ 

Luxation and Ankylosis, 779- Distortion, 779— arculatory Disturb- 
ances, 779— Inflammation, 780— Infectious Diseases, 784— Tumors, 785 
— Tendon-sheaths and Bursa*, 785. 


Diseases of the Voluntary Muscles 786 

Hypertrophy, 786— Circulatory Disturbances, 786— Inflammation, 787 
—Atrophy and Degenerations, 789— Infectious Diseases, 791— Tumors 
and Parasites, 792. 





Dora Mater, 793— CinHjlsUory IHstiirbttiices, 793— Idfljimmalion, 793 
— I n fet^tioujs 1 >i st'ases, TIM — T 1 1 rm >rH, 7^.*t>— CysL^ 7 9/>. 

Pia and Arachnoid, 7i*t> — Circulm^jiy DisturUiiiceh, 79l>— liitlaiiuua- 
tion, 797 — Infections Disea^^ets 800— Tutiu>j-s, S02» 

BraJilt 804 — DevelopiuLMit and Anutomy, H04'-tkjiigeniuil Abnomiali- 
ijes, 810— Po6t-niniitiiti DegenenitJVe Conditions, 8Ui— GeneRiI Putlio 
logic Anatoraj t>f the NervoiH System, 814 — The Blood-vessels, 826— 
Circulatory Disitirbjince**^ ^-*^ — inflanuDation, 837 — liyuncR to tVntrai 
Nervous System, 845 — Ijifectious Disease*^, H4t> — Tnmom. K47— Chomid 
Plexus, 850 — Ventricles, 85:^ — Htuit.iry Body, or Hypoidi^-wjK Ceivbri, 
8d6^Piiieal Gknd, or Epiphysis Cerebri, 860. 


OF THE SpiNAl. i\mi> AXI> ITS MeMBBANBR .-.,.,.*. 861 

Dura Mater, 8*) 1 —Fa t ly I n ii 1 1 ra i i on , 8f > 1 — He m nrrha ge, 861 — Tn bei^ 
crjUisi-s 861— Syphilis, 862 -Tumors, 8<>2. 

Pia And Arachnoid, 862— Cirtndatory IHsturbinres, 862— Dcgenera- 
lion.s, 862^ In Ha mm all on, 863^ — Infeclious Disea^s^ 863. 

Cord« Stj4 — Anatomy of the Corrl, 864 — Om^niuil Abnormalities, 864 
^Ilydroniyelia iind Syrin^iriiyeliiiT 8<>7 — Cirmdatory Disturlitinees, 871 — 
Inflammjition, 873 — Primary I >egenL rations, 879 — vSecoiadary Degenera- 
lion^ 887— Tumors, 889. 


Di!^EAt4i2^ OF THE Peripheuai, Nervoi^ SY!?rEM * . 889 

Ganglia of the Cranial Nerves, 889. 
Qangrlia of the Spinal Nerves, 8^10. 

The Nerves, 890— Circulatory DiHtiirlmnee**, 890— Alnrpliy ujid IV 
genemtion, 890 — Regeneration after Injury of Nerve, 891 — InllammotJon, 
893— Infectious Diseases, 896--Tuinot^ 896. 


Patbolo^c Technique, 807 — Examination of Fresh SjKwimens, 897— Fixing 
ami tlartlenin^', 898— Ik*«iIcit5^>j»tion, »0O^Enit»edding, 902— Stains, 90^^— 
« 'leaning and Mounting, 909 — Steps fur Tiiejiting Sections to lie Stained with 
Eosin-hematoxylin, 910— Examimilimi of SjK?cial Tissues, 910^Metbmls of 
Examining Nervous TiBwnes, 9U^-Metbods of Examining the Blood, 918 — 
<ir(J€» Pathologic Specimens, 921^Anim!il Panisiteji, 922. 

Bacteriolo^c Technique, 923— Prei^n ration of Tube*^, 923— Culture- 
media, 923 — Bai'tericdrtf,oc ExaminaliMiiH, 927 — Examination by Culture, 931 
— Ijolation and Identification of Bacteria, 932 — Widal Reaction, 93:i— Deter- 
miimtion of Baotena in the Circulating Blood, 933— Cultivation of Anae- 
robic Bacteria^ 934* 



A Text-Book of Pathology. 



Pathoi/>gy h the gcien<'e tluit deah with disoajie in n\\ its 
aspei'ts* It iQclmles the study of the ouu^ies, the nianitestatioiis, 
and the re,5iilts of disease. 

Three iraportant subdivisions of the j^tndy of patluil^jrry are 
recognized, viz., efiofor^tf, or t!ie study of the e.niseis of disease; 
morbid or pathokfgic anafouttf, the study of the stnietnnil i-Jian^es 
in disease ; and morbid or puihohgh' pbifHtohf/if, the stuily of 
disturbauees of funetif>n. In the latter group is ineluded jtathf/- 
logk chani^trif, as uiurljid eheniieal aetiun and its results are the 
outcome of disturbed function. 

Pathology' may be divided into fjemral and iiprnal pathology. 
The former treats of causes af dist^ase an<l pathologic processes 
irrespective of any imUvidual part; the hitter deals with the causes 
or processes in individual diseases^ orgtms, or jvarts. 

Disease itself may l>e defined as abuHrniality in structure, in 
function, or in botii condiined. It is doubtful uliether alteration 
of function can occur without some altenition in structure, but it 
frequently hap|jens that fruictional disturl>au('es are present though 
no structural alteratiuns are discoverable even by the most j>reeise 
methoils of investigation, 

The ffi/mptoms of dismsc are the expressions oi' abn(*rm:d finic- 
tional activity, and aR* therefore properly discussed under the 
head of pathohigtc physiology ; but they are so iniportiint from a 
pructieal standpoint, and funn so extensive a suljjeet of inves- 
tigutiuu, tiiat they are usually euusidered apart from patliolt>gy, 
ID spei^ial treattsea dealing with diugnofiiis and the practice of 

2 17 




The causes of disease may be classified as predisposing and 
determining. The former prepare the system or part by rendering 
it weaker and less resistant ; the latter are the immediate or spe- 
cific causes of disease. 

Predisposing Causes. — The normal system is abie co cope 
with the determining causes of disease to a certain point by its 
general vitality and regulative functions. Thus heat and cold 
may prove harmless if not too intense or prolonged. In the case 
of exposure to heat, the superficial capillaries become dilated, 
sweating increases, and there is increased heat dissipation fipom 
the surfece at the same time that increased respiratory function 
occasions evaporation and loss of heat through the lungs. In 
the case of exposure to cold, increased muscular exercise leads to 
greater heat production, while contraction of the superficial blood- 
vessels restricts the elimination of heat. When, however, a cer- 
tain point of intensity is reached in the case of heat, cold, or other 
causes of disease, the normal organism is unable to oppose suffi- 
cient resistance, and disease or injury results. The degree of 
resistance differs in different individuals, in different races, or 
people living under varying climatic conditions, etc. In some 
the degree of resistance may be so great that certain diseases are 
never contracted. The term immunity (q. v.) is applied to this state. 
In other persons there is a recognizable w^eakness of resistance in 
one direction or another which constitutes a definite predisposition. 
The latter may be either hereditary/ or acquired. Acquired pre- 
disposition results from previous disease, vices of living, and like 

Heredity as a predisposing factor in disease is probably less 
important than was formerly believed, but undoubtedly plays a 
part in many conditions. By hereditary predisposition is desig- 
nated abnormal weakness of resistance transmitted from the mother 
or father to the offspring. There may be congenital weakness 
that is not definitely hereditary, as it is more or less accidental — 
that is, not the outcome of tendencies of the same kind (latent or 
active) in the parent. Heredity may be direct or immediate — 
that is, from the parent (himself or herself presenting the condi- 
tion) to the offspring— or remote^ as in cases in which the hereditary 
trait is latent in the parent. One or several generations may thus 
he free fn)m certain diseases or tendencies which reappear in 
later generations. This return to conditions present in remote 
ancestors has been likened to atavism in the Darwinian sense. In 
some cases hereditary traits are conveyed from the male parent to 
the male children, or from the female parent to the female off- 



spring ; in other cases there is crossed transoiissioii. A peculiar 
form of heredity is seen in iieniophiliu iiml some ythcr tliseases, 
which are transmitted through tlio I'eniule irK*ml>ers of a family, 
who fifenerally remain Tuiatfectetl, to tlie male offspring. Heredi- 
tary toaits sometimes predispnjTe to a nuinlier of allied afleetioos. 
^ This is partieularly striking in the ease ot* tlie nenrupathie heredity, 
in which various f{>rms of nervous disease may a|»pear alternately 
or irregularly in members of an atl'ected family* 

A number of theories have been cniiHtructed lo explain the mechanism 
of heredity, Darwin in his hypothesis of |»angeneais suggested that minute 
tiarticles are ^iven off from all of the cells of the body ; these are collected 
m the reproductive cells» which in consequeuce represent all of the bodily 
characteristicH, hereditary aad acquired. Weismann denied the transiaiis- 
sibility of acquired characterii^tics, and holdi* that in the process of reproduc- 
tion a certain amount of ** gcrm-pla»m " passes froai the parent cell into 
the offspring, where it remains, and is in turn passed ou to succeeding genera- 
tiond, ifiux perpetuating iinrc^stral characteristicH, 

Determining Causes. — Among the im mediate or deter- 
mining eaiijics i>\' disease ait^ those whieh originate outside tlie 
body and thi>se whielj are generated within the liody. Athou^ 
the former are ineluch'd traumatism, heat, eold, and other physieal 
agents, poisons, and living organisms, ineludiug haeteria and va- 
rious animal parasites. The causes of diseavse originating within 
the hody itseH are less definitely known, but it Ims been ibnnd in 
eheraiail studies tliat variuns prodoets of normal nietulM>lism when 
aeeumuhited lualmormal quantity, <)r prodnets of tlisturbcd nietab- 
oli^^m, may oeeasion Im'al or widespreiui disease t*l' various sorts. 
This self- poisoning is designated aiito-intoxieation. 

The term "aato-intoxic^tion '* is frequently applied to poisoning by 
products of intestinal putrefaction. This application of the terra ia not, 
strictly speaking, correct. The same poisons might have been produced by 
putrefaction of furxl outside the body, when the use of the narneauto-intoxi' 
leatioD would be niauifestly absard. If poisona are produced by imperfect 
digestion, and these sifTeet the organi:§ni| the condition contd properly be 
termed auto-intoxication. 


Traumatism, or nieehanieal injury, may be of various sort.% 
gradual or siid<hMi, suuill or large ; and the etfeets are fiependent 
upon the form and severity of the injury* Presmwe brouglit tcj 
bear upon a part h^ads todistnrivanees of the circulation and more 
or Ies6 direct injury of the eeHuIar elements. When the pressure 
ii* gnidiuil true atrophy of the ]iart may oeeur, as in the case of the 
atrophic liver resulting frtmi lacing. Whcu the pressure is greater 
and the circulation is eomplefely arrested more destrnetive change 
may result, such as necrosis or gangrene. This is seen in the 
ntfcrotic atrophy of l>one resulting imm the pressure of aneurysms, 


or the gangrene of extremities resulting from ligation. Wounds. 
— Frequently, inflammatory reaction occurs in the surrounding 
tissues when traumatic injuries have been sustained. This is 
illustrated in all forms of wounds, and it is through the inflam- 
mation and subsequent regeneration of tissue that the areas of 
destruction are restored. In eases of injury by fine particles, as 
in powder-marks of the skin, or the surface injuries sustained by 
miners and metal-workers, or in individuals inhaling shaq) par- 
ticles like coal-dust, marble-dust, or steel-filings, small injuries of 
the tissues result. The foreign bodies may be subsequently dis- 
charged, leaving a focus of infliimmation, or the inflammation may 
surround the particle imbedded in the tissue, and encapsulation by 
fibrous-tissue formation may occur. Large injuries in which the 
tissues are contused or broken may lead to extensive inflamma- 
tion, in part the result of the direct injury to the tissues and in 
part the result of injury of the blood-vessels. 

Gross traumatism of the body as a whole, as in falls, crushing 
injuries, etc., causes various disturbances according to the part 
mainly involved. Rupture of the viscera, as the lungs, heart, 
liver, spleen, stomach, or intestines, may occur. When the head is 
violently struck, unconsciousness is common as a consequence 
of either disseminated punctiform hemorrhages, large focal hem- 
orrhages, or obscure and possibly only functional disturbances. 
Commotio cerebri^ the condition occurring in sucih cases, may be 
fugacious or may lead to permanent disonler dej>endent upon 
organic changes in the brain. Spinal symptomi^, met with after 
railway injuries and like accidents, may be due to hemorrhage 
and secondary morbid processes in the cord, or may be due to the 
uncertain pathologic conditions constituting hysteria. 


Heat. — High temperatures pnxluce local or general results 
according to the mode of api)lication and degree of heat. 

Local cxcesH of heat produces various lesions. Moderate excess 
leads to relaxation of the walls of the blood-vessels ; with increas- 
ing grades of tem])erature there is in addition necrotic change in 
the cells of the part, and exudation of serum causes vesicle for- 
mation. Still higher grades of temj)erature j)ro<luce immediate 
destruction, perhai)s with charring, of large or small areas, while 
the surrounding tissues suffer from reactive inflammation and 
hyperemia. Extensive burns involving one-third or more of the 
surfa(;e of the body frecpiently cause death. Tn these cases it is 
likely that poisonous proilucts are formed, either directly through 
tissue- and blood-destruction, or indirectly through disturbances 
of the functions of the skin or internal organs. The immediate 
maimer of death is often in the form of shock ; when the termi- 



Dadon is more ilelaveil various vasrnhir, lieniir, and tisKiie-<:li.s!urb- 
unces may uoriir. TiitrnviiM-iilar magiikition is not iiiUK-^iiaU and 
is not improbably the rej?iilt ol" the liberntioii into thf bUnMl of 
tissTie-elements set free in the areas of local destrnetion, or to 8iib- 
st^inecs pro<liicc(l by tlireet (Ic^tnietion of tixe lilood. The siiine 
sub*itanecs iiiiiy aeeouut fi)r tin* existence of ivvvv f ferment intoxi- 
cation)* The intmviisi'ular eoa^ulation eaused in this or other 
ways may indnee venons ,<ti\i^\s and Inealized liniinrrhatrej^. Ffieiil 
necrosis or degeneration of the tissues of various tnpms, snt-h as 
the liver* kidneys, or the nnieous and serous memhnines^ may be 
due to tltronibotie oeehision of vessels, or to the inflnenee of cir- 
culating pHsons without tlirciiidiosis, or to both. Marked changes 
are found in the lyuiphatii- jL!;lund> as wull as in the Malpiglnan 
botlies of the spleen and in the bone-marrow* These chantj:;es 
present themselvt-s as arras of leukueytic degenemtion containing 
actively phagocytic endothelial cells and surrcumded by a zone of 
lymphocytic invasion, Tlie lesions are not unlike those produced l>y 
abrin, riein,and haeterial toxins. Duodenal ulcer is oiten referred 
Xa) as an m'eiLsional result of extensive liurns. The blood itself 
may present evidence of disease in the form of degenerations of 
tile corpuscles, in the rctluetion of their number and of the amount 
of coloring matter; while regenemtive changes frequently present 
themselves some time lattir (iiue!eatj(Hl red eorpnscles). Changes in 
the urine mav nr-eur in (*ases of extensive luirus, in consequence of 
the tissue-dest ruction (hemoglobinuria, albumosuria)* 

Exposure to genera! high (emperatHre varies in its eflects accord- 
ing to the manner of exposure (dry air, steam, etc.). An animal 
€X{)OBed to a constant temperature somewhat aliovc the usual 
surrounding tempemture [>resents a slight increase of its body- 
heal, which is eom|H'usaled Jur l*y increase in tlie respirations 
and pulse-rate* Mueh higluT temperatures may cause death 
by C04igulation of the tissues ; n<»tal)ly, the muscular struct- 
ure of the heart or the respinitnry nniselcs. liefore this extreme 
is reachetl, however, it nuiy be fniind that the consumption of the 
tissues^ of the hmly is greatly in excess, thougli the respinitory 
quotient is altered in fav(U' of the amount of air inhaled, ('(in- 
tinuous ex{>osure to cx(*cssive lu'at fretpiently causes peculiar dis- 
turbances in man, known as heatstrokes sunstroke, or insolation 
and heat-exhaustion. In these i'(Hiditiuns hyjKTemia and edema, 
or even inflammation of the meninges, may occur. These lesions 
are sometimes supjxjsed to be the result of the direct effect of 
the heat ; but there is reason to beheve that tliey may be ot*ca- 
sioned by pasouous substiuices produced within tlie body by dis- 
turbe<l metabolism, as a result of the heat. One evideiu'e of the 
effect on the blood of continued elevation of tempemture is the 
appeaninee in the red blood-coqiusch.^s of basophilic gmnules — 
granular degeneration of Grawitz, (See chapter on BIocmJ.) 


A portion of the body, as an arm or a leg, may be exposed for a 
limited time to excessive temperatures (300*^ to 400° F.) in dry 
air without injury. The general temperature is slightly elevated, 
but metabolism is practically unaffected. 

The effects of general or local heat are much increased when the organ- 
ism as a whole or in the part involved is below par. A paralyzed limb is 
burned or scalded at comparatively low temperatures. 

Cold. — Exposure to extreme degrees of cold may cause results 
quite similar to those produced by heat. Exposure of the skin to 
liquefied air, solidified mercury, or other substances at excessively 
low temperatures produces vesiculation and necrosis of the tissues 
like those produced in bums. 

Exposure of the body to greatly reduced but bearable tempera- 
tures of the surrounding atmosphere causes vascular disturbances 
followed by necrosis of the tissues and inflammatory changes. 
The parts so affected are the extremities or projections of the 
body, like the toes and fingers, nose and ears. The primarj"^ 
result of cold is vascular constriction and local anemia. These 
serve the purjwse of preserving the body heat by preventing heat 
radiation ; later the blood-vessels are paralyzed and extreme hyper- 
emia results. Then cellular exudation and necrosis may occur. 
These changes are well seen in the condition termed chilblain. 
In prolonged exposure to cold there are a gradual reduction in 
the activity of the various organs and a gradual obtunding of 
the sensibility till the patient becomes comatose. The retention 
of excrementitious products of metabolism, or the formation of 
products of abnormal metabolism, may be important in causing 
this condition. 

Exposure to cold plays an important part as a clinical cause of 
disease. Various forms of pharyngitis and coryza or bronchitis 
so frequently follow such exposure that the term " cold '' is gener- 
ally used. Other conditions, like rheumatism, pleurisy, pneumonia, 
and the like, bear a similar relation. It is now recognized that in 
most of these cases cold is merely a predisposing cause, the imme- 
diate cause being in many, if not all, cases specific micro-organ- 
isms. The mode of action of the exposure is uncertain ; probably 
it causes a reduction in the resisting powers of the organism and 
thus favors the activity of bacteria. In some cases it may be that 
the cold alters the fluids of the body in such a way as to permit 
increased virulence of micro-organisms already i)resent, or to pro- 
mote their entrance into the system. 

Increased Atmospheric Pressure. — Exposure to extreme 
pressure of several atmospheres may occur among deep-sea divers, 
or in men working in caissons used in bridge building. But little 
disturbance may be caused at first, or for a long time ; but on 
return of the workmen to the usual atmospheric conditions synip- 



tonis make their appearance (caisson disease)* Among these symp- 
toms are bleeding fruni the nasal or other mucous membranes, 
great depression, delirium, and pandytic eonditiuns. Congestion, 
degenerations, and vacuolations in the spinal cord have been dis- 
covered in some ca^^es. 

Decreased Atmospheric Pressure.— Effecti^ of decreased 
presi-itire are seen in inhabitants of high altitudes and in persons 
ascending in baUoons. Marked excitement of tlie vascular system, 
hemorrhages, somnolence, weakness, vomiting, and similar symptoms 
are observed ; in less marked cases a general excitement of the 
nervous systc»m, sleeplessness, etc., occur. These symptoms have 
been attributed to hick of oxygen, and compressed air and oxygen 
have been successfully used to combat them ; but experiments 
sliow tliat the air-pressure may be as low as 400 mm, of mercury 
without interference with the respiratory exchange of gases. To 
a certain extent the symptoms are prohalily mechanical and due 
directly to the reduced pressure on the exterior. Recent studies 
show that the blood contains greatly increased numbers of red 
corpuscles in a given volume, and the j>ereentage of hemoglobin is 
correspondingly inrreastcL This is probably due, to a large extent, 
to disturlxujce in tlie ilistriliutirm of the fyrpusrles with stagnation 
in the pcriphenil vt^ssels (see Diseases of the Blood), 

Instifficiency of Respiratory Air. — A certain amount of 
air is necessary Uir the c^mtinuance of Ilea It li or life. Insutticieney 
may be due to iliseases which olistruct the air-passages or affect 
the puhnonar\' tissue itself, and to foreign l>odies (solid Ijodies, water 
in drowning) within the a ir-))assa ges, Cliang4's in the atmosphere 
or gases taken into the lung may cause insufiieiency in the supply 
of oxygen, notal>ly in C'0-pois(ming, in wliich the foreign gas enters 
into firm combination with the hemoglobin of the blood and thus 
excludes oxygen. 

Moderate decrease of the supply of air causes labored and rapid 
breathing, more or less cyanosis, depression, and stupor. This 
condition is termed a.'iphi^xia, Oimplete lack of air causes increase 
of these symptoms and death by Hiiffhitition. In tliesc cases the 
blood is exceedingly dark and fluid, and hemorrhages may be 
found in various situations. TIjc latter result frrjm excessive IdotKl- 
pressure during tlie death aguiiy. L4>ng-ri>ntinueil insufficiency 
of oxygen may directly or indirectly oecasion degenemtive dis- 
eases of tlie tissues* 

It has often been aaserted that anemia caasea many of iU symptoms and 
results because the hiaod ia incapable of carrying Hufficient oxygen in its 
reducfKl state. As a mutter of fact, however, nhysiolngic experiments 
hare demonstrated that the respiratory exchange (nihalation of oxj'gen and 
exhalation of earbonic acid gas) is biit little affected and is as frequently 
tDcreasei jls decreaied. 


Blectric Influences. — The eflTects of powerful electric cur- 
rents and discharges on the tissues resemble those produced by 
bums. Locally a dry, crisp, excavated lesion is produced. Later 
hyperemia and appearances resembling moist gangrene develop. 
The underlying muscles are more or less paretic. Uhanges in the 
blood-vessels and a fluid state of the blood, extending to some 
distance from the local lesion, have been observed. Very power- 
ful and fatal discharges in some cases produce hemorrhages in the 
floor of the fourth ventricle and petechiae in the serous membranes 
and elsewhere. Death seems to be caused by powerful inhibition 
of the heart. 

^fleets of X-rays. — Exposure of healthy or unhealthy 
tissues to X-rays causes cellular degenerations and necroses with 
secondary inflammatory reaction. The skin — being most im- 
mediately exposed — is the most susceptible of normal tissues ; but 
diseased tissues and new growths are still more readily affected, 
probably because of their less stable condition. The epithelial 
cells of the skin suffer first and most intensely, the glandular 
cells of the skin are less prone to degeneration. Swelling and de- 
generation of the endothelial and other cells of the blood-vessels 
and thromboses may in part account for some of the results of 
X-ray exposure. 


Definition. — The term poison may be applied to substances 
which when introduced in relatively small amounts into the living 
organism disturb its structure or functional activity. 

The Action of Poisons in General. — Gaseous poisons act 
primarily ujx)n the respiratory mucous membranes with which they 
come in contact, or after absorption into the blood disorganize this 
fluid or lead to disturbances of the nervous system. Liquid poi- 
sons are generally absorbed through the gastro-intestinal mucous 
membrane, but may be received directly into the tissues by injec- 
tion under the skin. They are rarely absorbed through the skin. 
Solid poisons must in all cases first be dissolved, and are then ab- 
sorbed like the liquid poisons. They may by their strong attrac- 
tion for water absorb the latter directly from the tissues, and by 
this process alone may bring about imjx^rtant changes. 

The lesions due to a poison may be entirely local, as in the 
case of certain corrosives or caustics ; in other cases the point of 
entrance is unaffx?cted, the pathologic manifestations being en- 
tirely due to the changes in different parts of the body, or to ner- 
vous disturbances resulting from the circulation of the poison in 
the blood. 

The fate of poisons after ingestion is very different in dif- 
ferent cases. Some poisons circulate with the blood and are 
eliminated unchanged. Others may suffer chemical change within 



the stomach or other cavities ot th^* bwly before absorptioo^ and 
may be either completely TientraliztMl, or may he converted into 
forms which are ^miiisequciitly slowly aljsorhed* After absorption 
into the ld<MHl other chemical reactions may occur, and t!ie pojsim 
may lie more (ir less nciitndizfd, tlic system then s^ntlonnt;: either 
fnjin the rcsultino; coinp(»unds or frmn the clmn)^ed eoaditions (*f 
the lilorHh Active destruction of the ikhsou may occur in the 
blood or in the various ortrans, espeiidly the liver. In these 
processes.^ however^ the glandular ortraus may stiffer seriously, 
various fonns of degeneration or necrosis rcsultinji. Certain pcji- 
gODs^ like the toxins, enter into clicurical eunibiuation with cells 
of the body, and remain fixed in this way. (For further details 
see Imnuuiity,) 

The effect of poisons depends upon tlie dose as well as upon 
the nature of the sulistanec^ and also upon the imlividuaL The 
repeater! ingestion of certain |ir>isons, such as arsenic or opium, 
may generate a considerable degree of immunity or tolemnce 
(Mithridatization). Similar immunity may he clianicteristie of a 
given indi vidual or of chis,ses or species. Susccptibi lity to the action 
of |K>isons is further intbienced by age and constitutional vigor. 
Chikln^n hear certain poisons better, com j)a rati vely speaking, than 
adults, while the reverse is true of other substances. Sotnetimcs 
there are idiosynenisics which learl to peculiar results not observed 
in the average indi%-iduaL In coasccpicnce of this, substances ordi- 
narily not toxic may l)c extremely injurious to certain jiersons. 

8otiietiiued poisons are comparatively iDnocuoiis when administered in 
one way, tlioiigti powerfully toxic to tlie saine auiami when otherwise intro- 
duced. Thus in dogs intravenous injeclion of atropin is very slightly in- 
jurious, but injection into the spinal cord of minute doses causes rapid 
{yoisoDing. Borne reeent experiments indicate that the leukocytes are capa- 
>le of fixing inorganic pokons and thuis afting aw defensive agencies. Non- 
fatal doeeii of poisons (arsenic) cause iirst diminution of the polymorphonu- 
clear leukocytes, followed by hyi>erleukoeyt(jsis ; and the poiBon is found in 
abundance in thef^e lenkoeytes. Fatal doseB are unattended w^ith the 
secondary stage of leukocytosis or the leukocytic fixation of the pois§on* 
The«e resulte need further eontirmation. 

£limmatioil. — ^The excretion of jmisons may tiike place 
thront^li the kidneys, Innt^s, the mneous menibmne of the i^^stro- 
intestinal tract, the mammary |l:;1ihkIs, or through the skin. In 
some instances a poison is eliminatcfl without change in the 
excreta ; in oilier cases it sntfcrs complete ehange, and is not 
present at all in the excretions. The nite of elimination varies 
greatly, and is nn>rc or less dc]>endcnt upon cunilitions of the 
system. Some poisons, as phosphorus and nicrcniy, may he stored 
up within tfic hmly for a considerable period, subsequently sutler* 
iog sh»\v elimination. 

ClESSification, — The number of suhstinees wfiieh may act as 
poii^ms is very great, and the manifestatioiis are cd' veiy different 


sorts. Classification of poisons is therefore difficult and not en- 
tirely satisfectoiy. We may crudely distinguish between gaseous, 
liquid, and solid poisons ; between animal and vegetable, organic 
and inorganic, and the like; but these classifications have no 
scientific value. 

From the point of view of the action of the poisons we may 
distinguish corrosive poisons, or those which have a local action ; 
organic or parenchynia-poisons, or those which act less strongly at 
the point of application than upon the various organs to which 
they are conveyed through the blood; blood-poisons, or those 
which exercise their effects primarily upon the blood; and the 
nerve-poisonSj or those which disturb the functional activity of the 
nervous system without producing definitely discoverable lesions. 

Oorrosive Poisons ; Escharotics ; Caustics. — Under this heading 
are included various acids, alkalies, and mineral poisons, such as 
sulphuric, nitric, oxalic, carbolic, and hydrofluoric acids, caustic 
potash or soda and ammonium, and gases like chlorin and bromin. 
Nitrate of silver, bichlorid of mercury, sulphate of copper, and 
other inorganic compounds have a similar action, and certain 
organic bodies, such as cantharidin and croton oil, belong to the 
same class. 

All these poisons exercise a destnictive effect upon the cells 
with which they come in contact, partly by abstraction of water 
and partly as a result of a coagulating power or similar action. 
The acids and mineral caustics usually produce dry and more or 
less discolored areas of necrosis ; the caustic alkalies cause a sort 
of gelatinous change or a saponification of the tissue. The degree 
of injury jdepends upon the poison and the amount in contact with 
the tissues. There may be only a superficial injury of the outer 
layer of epithelial cells, or extensive destruction. Reactive inflam- 
mation is almost always present, and often, especially in the mucous 
membranes, the inflammatory reaction is extensive though the cor- 
rosive action of the poison is limited in depth and extent. The 
affected part may present slight areas of necrosis with reactive 
hyperemia and inflammation beneath and around them, or deep 
eschars, vesicles, or large bullae. In the process of healing 
extensive scars may form, and these may be serious in their effects, 
as in the case of strictures of the esophagus. 

Organic Poisons; Parenchsrina-poisons. — This large group in- 
cludes many metallic compounds that have a local corrosive or 
escharotic effect, but which may in smaller dose gain entrance to 
the blood and cause extensive organic lesions. It also includes 
poisons of vegetable origin and products of bacterial growth. In 
general these poisons have a similar action. The kidneys and the 
mucous membrane of the intestines are especially active in their 
elimination and suffer most seriously. Degenerations of the epithe- 
lial cells of various sorts are met with, such as nuclear degenera- 
tionsj coagulation necrosis, fatty degeneration, and even calcifies- 


tion. The changes \i\\\\ he diffus*^ cw may ouvwy m small focL III 
the latter c^^e small areas of trnmiilar appearanco, having a lighter 
color than tlie syrruimdhig tissiieSj are seen ; and on sUiining tlie 
cells are iVnind to eolor poorly or not at all, the nuclei often slew- 
ing this cliange first. Nitelear degenemtions (fnignientation, liypcr- 
chroniatosis, etc.) are ohserved, and in sftnie instances niarkeil tatty 
degeneratiLm of the eetls oeeurs. Around the foci of degeneration 
tliere is more or leas ronnd-cell infiltnitiun (polymoiphornicvleiir 
cells), and to a less degree the tlegenenitetl area itself is intiltmted. 
In rases in which dift'use ehange occurs there is eqnally diffuse 
round-cell intiltmtion. After the acute process has snlvsiVled 
hyperplasia of the connective tissues may oeeur and the ailected 
part heeomcs more or less sclerotic or indurated. Regeneration 
of the parenehynia-ecUs is less apt to occnr. 

Some of tlie more important of the poisons of tlie group may 
now be separately considered. 

PhoBphorus is a poison of cousiderahle activity in the yellow 
form ; the red variety is ijiert. Worknicu in match factories are 
the most frequent victims of this Jbrni of intoxication, but oeca- 
sionally accidental j>oisc»ning l>y swallowing occurs. In the latter 
the manifestations are acute. The [lathologic changes are catarrhal 
inflammation of the g:istro-intcstinal nuieous mi'mhrane and more 
or less widespread fatty degeneration of various tissues and otgraos* 
The liver sutlers most severely, being enlarged, light yellow or 
reddisli in color, and friable or tloughy, Mi(*rosco|iica!ly the liver- 
cells are fonnd extensively degenerated (fatty). Sinu'hir hut less 
inarkeil fiitty degeneration is foiuid in the renal tubules, gastro- 
intestinal epithelia, and heart-nujsch:', and in the iutima of the 
blood-vessels. Extensive jaundice is frcfjuent and numermis 
hemorrhages mayrx'cnr. In tln" more chronic j>i>isoning of mateh- 
makers the |>oison enters tlirough the inoutli and respiratory pas- 
gages, being inspired as dust, Chronic eatarrlud inflanrmation of 
the respiratory tract may occur and a peculiar form of neci'osis of 
the bones (see Hones) is met with. 

Arsenic is poisonous in certain forms (wliite arsenic, arsenous 
acid) and inert in other forms (the sulphids). Acute jKHSiUiiug 
occurs when toxic forms are swallowed in large doses ; the chronic 
forms of poisoning result i'rom gradual ingestion or the inhalation 
of dust containing arsenic. Cases of the latter sort occur when 
wall-|>aper, hangings, and the like, colored with arsenic-pigments, 
are used, Tlie lesions in acute arsenic-poisoning resendile those 

i)rr»duced l>y phosphorus. The gastro-intestinal inllammatiou is, 
lowever, miire seven* ; while t!ie fatty degeuenition of the organs 
is less marked. In chronic arsenic-jMiisoning clituiges in the 
peripheral ner\'es (degeneration and inflammation) are most ira- 
[K>rtant. It is likely that focal or diffuse myelitis may likewise^ be 
caused by tliis poison. Chronic in Ham mat ions of the gastro-intesti- 
oal or respinitory mucous membranes are met with in some cases, 



Tnflanioiatory lesions and pigmentation of the skin may oeonr. 

Lead. — Amon^ the eoniponnt].H luading to acute or siihaente 
poisoning the ehroniate, the acetates, the carbonate, and oxid are 
most important, t'liroiiic poisouin^ oeeurs in workmen in iMiirii 
munnfaetories and anmn^ painters, ajid in persons drinkinj^ certain 
waters that luivo licen eoialueted throriirh h^ad ]iipcs. Less rarely 
the nse of eosnu Hes, dyestulfs, etc, eontaininf; leatl cinises elironic 
poisoning. In the acute forms of lead-pois<ming moiierate gastro- 
enteritis oeeurs. In tlie chronic form changes in the ners'ous rvs- 
tem aiT most important. Peripheral neuritis is the most frequent 
lesion, but eliangcs in the larjj^e gtuiglionie cells of the gmy matter 
c^f the cord have sometimes hrvti fimnd. Dilfuse pclern^is of the 
hlood-vessels, iuterstitiiil nepliritis, and the lesiems of gont may be 
present. Atrajihy and fatty degenemtiou of the mnsele-tiher'^ are 
less imiH>rtant lesiuns. A bhie line on tljc gums at tlie junction 
with the teeth (due to dej^osit of sulpliid of lead) is a lesion of 
clinical importaure. A constant ami. alninst path^»gnonionic 
clumge is found in a peeuliar degrncratioii (basic degeneration)' 
of the erythrocytes. (See eluipter un lihiod,) 

Mercury ^^ — Poisoning with mercury may be acute, subacute, or 
ehmnie. The first is tine especially to the corrosive elilorid and 
other mercuric salts; the second to calomel or small doses of those 
of the former grou]*, Chronic poisoning tieeurs as a result of inhala- 
tion II f fimu s or tlust containing mereury, and is seen in w*n'kmen 
in mirror manufactories. In the acute cases violent inHammatorv 
and necrotic lesions of the gastro^intestiual tnu't are seen. Paren- 
ehynuitous degenerati^ui, tatty chrmgc, and even ealeification of the 
renal epithelium may occur; and fatty degenenition in other 
orir^ms inny sometimes lie met with. In sul>acutc eases miirke4l by 
ptyalism snuic change is doubtless present in the salivary glands, 
l>ut tiie Utiturc of tliis has mit bei-u detirmincd. 

Ergot.— Ergot is a poison capalilc of pro<lnt^ing intense toxic 
results. It contains tw*o important toxic principles, spliacelinic 
acid and an alkah)id, eornutin. Acute piusouing s^mietimes re- 
sults from y venl usage ; while chronic iutoxieatiun m^eurs fnau 
the use of atfectt'd grain, piu^tieularly in famine years. Wide- 
spread jM>isoning of conruiunities has sonu'timcs resulted. The 
lesions prmlueerl are not definite or uniform, tfastro-intestinal 
inflammation and erosion of the mucous nuanbrane have been ob- 
served, bat are not habitual ; sclerotic change in the spinal cord 
lias been found in a few eases, (tangreue is a frequent lesion, 
profjably resulting from vascular obstruct ion due to eon traction 
of the blood-vessels. Enlargement of the spleen has sometimes 
been noted, 

Toxalbumins from Plants. — Certain vegetable bfidieSj like 
ricin fieri v^d fn uii tiie castor bean and abrin derived from 
jerpiirity bean, are exceedingly toxic, acting in part as blood- 
poisons but also as parenchyma-poisons. Injected into animals 



these substaoces cause violent intoxication, ami focal areas of 
neorosis in various situations, notably in the liver. In part tlioi^e 
lesions result from vascular thronilwrsis ; in part from din'^t ac- 
tion. The study of the actinn of these pois4)iis is of partieuhir 
interest from the reseuiblanee of the le.sioib? to those caused by 
certain bacteria and bacterial [)oisi>ns. 

Toxic Products of Bacteria.— In the grrowth and nndtiplica- 
tiou of various bacteria detinitc toxic substunces are nroduced, 
ami tlirouj^h tlic latter the lesions of infection arc to a larii:c ex- 
tent prodLieeil. Sucii poismious iMxlies may l>e j^enemted \n the 
growth of the bact^^ria outside of the body, as well as within the 
body. In the latter case the patlioloirie lesitius at the point of 
infection raay be the fi>cus of ori»,dn of toxic substances which 
are then distributed throutj^hout the liody in the blood. This is 
eminently true of tetanus, and to a iarjii^e detj^ree of diphtheria* 
In other eases the bacteria tljemselves arc tmusported to various 
parts of the body, ami finding lodirement in the tissues set 
up changes by wdiieh their toxic products are evolved. The 
latter increase the lt)eal foci of ]>atholo.irie chanfje and then 
5prt^ad in the circulatiuu and cause (general intoxication. Fur- 
trier reference to these p<»isoris will be made when discussing the 
individual bacteria. 

The venom of serpents and of various insects contains 
toxic biKlies, some of which are albununous in nature. These vary 
ill their action, being to some extent bl(KHl'poisous, but nuire par- 
ticularly parenchyma-poisons. The lesions produced an.^ local and 
^^ncrah Locally thi're are intense' iuHammatory reaction and 
edema amund an area of cell u hi r necrosis ur di 'struct ion where tfie 
pois<jn has come in immediate contact with the tissues. Tlie blood 
i^eems to suffer great disorganizatirm and corpuscular change. 
Petechial hemorrliage ami foci of cellular necrosis f>ccur in various 
organs ; and eclcma of the luui,^?^ is freipiently prciient. The action 
of the venom of di iTerciit animals varii'S in kind and intensity tii 
a certain extent » but is in general of a simihir type. 

Blood-poisoEs.^ — ^ Various liquid or gaseous substances are termcil 
l)hKKl-|Mjisous Ijecause of their esiK'cial action upon this liquid. 
The blood-poisons may be classified as (a) those which combine 
nith the hemoglobin without changing the corpuscles ; (b) those 
which alter the red corpuscles and the coloring matter ; {c) tliose 
which alleet the bloud as well as tlie tissues generally ; and (d) 
tho^ which eiiuse changes in the hlood-plasmaj iucreasing or de- 
crtiiasing the tendency to clotting, 

(a) Among tlie poisons wliicliact Ijy entering into combination 
Mith the hemoglobin withtmt clianging th<' e<u'puscles» carbon 
moDoxid, cyanogen, and hydrogen sulphid ar*' important. In 
earbon-monoxid [xasoning, which often results from iidialatiou of 
the funiee of charcoal burning with insidlicient air» the IjIocx! has 
a light color au<l light iM^techial <liscolorations mny be seen in 


various parts of the body. In cyanogen-i)oisoning the blood is 
similarly light in color ; while in HjS-poisoning the blood is often 
dark, sometimes quite black. 

(6) Among the poisons which disorganize the blood-corpuscles 
and later the hemoglobin are a large number of chemical agents 
used in medical practice or in the arts, including potassium chlo- 
rate, nitroglycerin, anilin, nitrobenzol, various coal-tar derivatives, 
and arseniuretted hydro^n. Certain poisonous plants (toadstools) 
act similarly. These poisons lead to a reduction of the hemoglobin 
with formation of methemoglobin and at the same time destruc- 
tion of the corpuscles themselves, with release of the hemoglobin 
into the serum. The altered condition of the blood often induces 
secondary changes, such as fatty degeneration and hemorrhages in 
various organs. The blood-corpuscles are found in variously de- 
generated conditions, showing microcytosis and poikilocytosis in 
particular. Nucleated red corpuscles may be present as in other 
conditions of blood-destruction with attempted regeneration. 

(c) Among the poisons which disorganize the blood and at the 
same time cause cnanges in the parenchyma of organs, reference 
has been made to abrin and ricin. In addition to the organic 
changes, these substances cause certain alterations in the blood 
itseli, increasing the coagulability and thus inducing thrombosis. 

id) Various substances introduced in sufficient quantity are 
capable of affecting the plasma of the blood or the corpuscles in 
such a way as to affect its coagulability. Calcium salts, carbonic 
acid gas, and fibrin-ferment arc active in this way, but the last 
alone produces toxic results through this function. Ferment-in- 
toxication may occur in consequence of various other intoxications, 
when corpuscular or tissue-^lestruction has liberated the ferment. 
Among the poisons which decrease coagulability peptone (albu- 
mose) is imiK)rtant. 

Nerve-poisons. — This grmip contains a large number of sub- 
stances capable of producing violent symptoms and even death 
without definite change in the tissues of the bo<ly. Recent inves- 
tigations showing certain alterations in the finer structure of the 
nervous system in disease and in cases of intoxication suggest that 
histologic changes in the central neurons may be found to result 
from poisoning by these substances. Changes of this kind 
(changes in size and form of the cell and nucleus, thickening, con- 
traction, or disappearance of dendrites, alterations in the chromo- 
philic bodies, etc.) have been described in the gray matter of 
animals poisoned with alcohol and certain toxins of bacterial 
origin. It is not unlikely that similar changes will be found in 
other conditions. 

Among the nerve-poisons are alcohol, chloroform, ether, and 
various alkaloids like morphin, atropin, etc. In this same group 
might be included some of the poisons contained in the venom of 
serpents and other animals, but these usually cause definite 


lesions in the blocMi or tissues of the bcxly. Another irroiip of 
ptiisoDi? i>f siiniilar netiou are those protltieeit within the Imdy by 
piitrt'lhetive act if ►n or in various foodsliiti*? before iiigestioiu Fre- 
quently cast's have been observed in svliieh all tlie meniliers of a 
family or even large nimibers of petypk* liave been poisoned by 
eating certain meats, sausages, iee-ereum, and other foods. In 
some of these eases it has been found that the toxic element was 
a basie eom pound resembling the alkaloids in ehemieal strneture. 
To tliese putrefactive eomjHHUids the name pfomain h given. 
One of these co[ni)ounds, wliicli occurs in cheese, and occasion- 
ally in milk, has been termed tyrotoxieon* Intoxications of 
this class must be distinguished from infections resulting from 
the use of ff»od contaminated with miero-<irganisms. The symp- 
toms may be so rapidly developed (absence of inenbation pericHl) 
and so immediately generalized that the distinction can l>e 
arrive<l at clinically, but the absolute diagnosis is made liae- 

A considerable number of ptomains have been s£*panited» in- 
ehiding neurin, ol>taine<l from putrid flesh ; nuiscarin and i*thy- 
lendiamin^ derived fmni decayed fish ; mydalein., an<l niydatoxin. 
Scmie of tlii'se substances produce toxie results indistinguishable 
clinieally fn>rn those produced by certain alkaloids. This fact has 
liecome one of great importance iu medicolegal investigations, 


Vegetable parasites are by far the most important causes 
of disease. The belief in a living cause or eontagium vivum is by 
no means a recent acquisition, Imt the actual demonstration that 
diseases may be eauseil by minote living organisms has only 
recently been reached. The miero-organisma in question (bac- 
teria) belong for the most part to the vegetable kingflom and con- 
stitute t!ie lowest orders of fungi. Their biologic cliaracters and 
tlicir relations to special diseases will be describetl in a subsequent 

Etiologic EelatloBship of Bacteria to Disease. — It is ditlicult to 
prove the specitic relation of bacteria to disease. Koch has laid 
down four impoi-tant laws which must be conformed with before 
the etiologic im|>ortanee of a bacterinni is admitted. These are: 
(1) the bacterium must be found iu the diseased person ; (2) it 
must be cultivatal>le upon media outsi<lc the bcMLly ; (3) pure 
cultures introduced int^^ a healthy animal must produce the dis- 
ease in the anima! ; and (4) the bacterinni must be recoverable 
from the body of the animal. In a number of diseases micro- 
organisms have been prfjved to be the specitic causes according to 
the requirements of Kocli's rules. In other diseases it has not 
hei»n possible to furnish absolute [jroof, thongh the presump- 
tive e\"idence, furnislietl by constant occurrence of the bai'tcria, 
s^iiggei=tive ass<jciation with the lesions of tiie disease, absence of 


the bacteria in other diseases, etc., is sufficient to satisfy all but the 
most sceptical. 

Olassiflcation of DiaeaseB due to Bacteria. — ^The general term 
infectious disease is applied to all such as are caused by bacteria. 
In some cases the diseases are readily communicated from person 
to person, even though contact has not been immediate. These 
are termed contagious diseases^ while the term noncontagious is 
given to those in which such ready transference is not obser\'ed. 
As a matter of fact, the distinction is artificial. Any infectious 
disease may be communicated from the diseased to the healthy if 
the germs or bacteria are transferred. In some diseases this trans- 
ference readily occurs, even through the air and at considerable 
distances ; in others actual contact is necessary ; while in still 
others secretions or excretions of the diseased must be conveyed 
to the healthy. Contagiousness is therefore a matter of degree 

Infectious diseases may at times spread in communities, affect- 
ing large numbers of people. Such a dissemination is termed 
epidemic, and the disease an epidemic disease. When the disease 
spreads over large areas, as a whole country or continent, the term 
pandemic disease is applied. Other infections are constantly 
present in a locality; for such the terms endemic and endemic 
disease are used. Some endemic diseases are restricted to certain 
localities and seem in some measure dependent upon local con- 
ditions (of atmosphere, soil, etc.) for their continuance. These 
are called miasmatic diseases. 

Infectious diseases are frequently described as loccd or general. 
Local infections are those that present specific pathologic change 
in a restricted part of the body ; the general organism suffers more 
or less in consequence. Examples of this are erysipelas and diph- 
theria. General infections are marked by an immediately gen- 
eralized disease, as in typhus fever or plague. Strictly speaking, 
most if not all of the so-called general infections are at first local. 
Among purely local infections might be named the diseases of the 
skin due to vegetable micn)-organisms. 

Entrance of Micro-organisms into the Body. — Bacteria may be 
inhaled or swallowed, may enter through abrasions in the mucous 
membranes or skin, and may be transferred in utero from the 
maternal to the fetal blood. The mode of entrance in individual 
diseases depends upon the nature of the bacterium, its habitat, and 
surrounding conditions. Some may enter in but one way ; others 
gain access in any of the different ways. Details reganling this 
sul)j(»ct will be given in the discussion of special infections. 

Animal parasites of various kinds act as causes of disease. 
This grouj) of diseases is termed the parasitic diseases or invasion 
disen^es. In some instances the clinical course is similar to that 
of infe(itious diseases (malaria, dysentery, trichinosis) ; in other 
cases the manifestations bear little resemblance to infections. 





Food, — In tlie lifi' of th*^ orgaui^in eortain substances are 
^ needed for the repair of tissues eoiiriiuiied in tfie wear aufl tear of 
' life and to supply heat mid other enerijy. Among these foods are 
proteids, carhtilml rates, fats, inorgiinie salts, and water. A con- 
tinuance of normal existence rcrpiires more or less definite propor- 
tions of the first three and at least a sufficiency of salts and water. 
The amount of food and the exact projxirtions vary somewhat iti 
individual eases and under var}'ing circumstances. Volt found 
that a lahorin«^f man under onlinary conditions ret|nires 118 j^. of 
proteid, 06 g* of fats, and 500 g, (»f carho hydrates. The protei^ls 
of the diet are nec-essary to restore tissue- waste, since the organ- 
ii?m cannot build up proteids from simpler compounds. This con- 
aumeB jwirt of the nitrogenous fouilstuJIs. The rest, with most of 
the fats and carbohydrates, is mainly useful in contributing 

Diminished Supply of Food ; Inanition ; Starvation. — 
KitluT the want of tuod or disorder of the gastro-iutestinal tract 
niiiy lead to insufficient uourislunent. Tliis causes a hiss of ijody 
weight, as the neeessiiry heat-]>mdueing au<l energy-giving sub- 
i-Btanccs must be snpjdied to muijitjiin life, and the tissues are con- 
Bunied for this purpose. The tiits suffer fii>t and most profoundly , 
then carljohydrates (giyct»gcn of liver and musclts); unimjiort- 
ant [^rts are reduced l)eforc the vital structures aix^ attacked. 
The subcutaneous and other adi|wse tissues an<l the nnis€'les first 
waste, then the liver, bones, heart, etc. ^Nitrogenous elimination 
is reduced, thougli it still indicates a degree of tissue-waste bewar- 
ing approximately the normal ratio to the weight of the l>ody, 
Tlie eldorids in the urine arc regularly dimiuislu'd, while calcium 
sak.H are increased in correspondence with the tlestruction of osse- 
ous ti^ue. 

The functions of various organs suffer greatly : the respirations 
and heart-action are weak, mustndar exertions arc reduced to a 
miniaumi, the enduranee and nervous force decline, the Ijody- 
temperature sinks, and finally death nu*y occur from exhaustion or 
secondary affections consequent upon the disturbed nutrition (see 
Acid-iutoxication). The blood in starvation preserves its corpus- 
cular richness surprisingly, even after prolonged iRistinenee. This 
h doubtless due to loss or evaporation of liquid ; the actual num- 
ber of corpuscles probably suffers reduction. 

Increased Supply of Food ; Overfeeding,— The effect 
of this depends upon individual conditions, such as the amouut of 
exerci^, the surrounding temperature, and less easily demonstrable 


peculiarities of the individual. Ad excess of proteid food leads 
to increased excretion of the end-product of its metabolism — urea. 
Experiments have shown that a reser\'e amount of albuminous 
tissue may be built up by excess of proteid food. This, however, 
probably rarely occurs in health. Great excess of proteid eventu- 
ally disturbs digestion and leads to its own discharge with the 

The carbohydrates and fats are broken up in the body and ex- 
creted mainly as carbonic acid and water. An excess of these 
foods tends to cause increased dej)08ition of reser\'e fat and gly- 
cogen, which may be called upon at subsequent times of need. 
This deposition is a normal or physiologic process and has the 
distinct purpose just indicateil. Exceptionally in the condition 
called obesity the storing up of fat is inordinate and probably 

Obesity. — The origin of fat is still a subject of controversy 
among physiologists. According to the oldest view, which, how- 
ever, is still adhered to bv some, and has indeed been strongly 
defended, the fat of the body is derived from that of the food, and 
the possibility of this has actually been demonstrated. Under 
ordinary circumstances, however, only a part of the fat is so pro- 
duced. Another school of physiologists maintained that the pro- 
teids of the food break up into a nitrogenous and a non-nitrogenous 
part, the former being finally excreted as urea and other substances 
or repairing the tissue-waste, the latter part contributing energy 
or forming fat. At the present time it must be admitted that 
though proteids may possibly form fat in this manner, the actual 
demonstration is still wanting. The main source of fat is cer- 
tainly the carbohydrates and fats of the food. 

Causes of Obesity. — Excessive ingestion of food by persons 
having active digestion and leading sedentary lives may occasion 
unusual deposition of fat. It is difficult, however, to determine 
the limits between physiologic and pathologic fatness. In some 
cases patients assert that the amount of food has not been exces- 
sive, and this may be actually true. Obesity in such individuals 
is undoubtedly pathologic and due to some inherent abnormality 
of metabolism. A further proof of the existence of such a ten- 
dency is seen in certain families, in which excessive fatness is 
common, even in childhood. The nature of this metabolic dis- 
order is obscure. It has often been held that the power of oxida- 
tion is lacking, and, as a matter of course, the amount of oxygen 
consumed is d(^cient in comparison with the amount of food in- 
gested. This must be true, or the fat could not accumulate ; but 
it remains to be shown whether the diminished oxygen-consump- 
tion is the primar}' cause or only an incident in the disease. Ex- 
perimental investigations in cases of obesity have sometimes 
shown slight reduction in the consumption of oxygen but con- 



sidering the amount of inactive tissue (adipose) in siieli persons 

the retlucti<in has not been ^uffieient to pi'ove siiboxidation the 

f cause of the disease. It must, h<*wever, be adioitted tliat very 

Islijrht reductions (even so sli£j;bt as to escape detect i tin owing to 

"the ranire of error in oljservations) may in tlie course of time cause 

aceumuhition of fat. Some of tlie experiments seem to indiciite a 

retarded oxidatinu if not a final reduction, 

Patholoiric Anatomy, — Tlie excessive adipose tissue in this 
Ldisease is found m tlw skin and siilx'utaueous tissues, in the umcn- 
■tum and [>critoneuui, around tlie kithieyi^T heart, and mediastinal 
tissues, in the liver, and less commonly elsewhere. The amount 
varies from slight excess to monstrous deposits. Secondary changes 
in the org^ans (notaljly the heart-muscle) may be thie to pressure 
or functional inactivity. 

Associated Conditions.— Fatness is more or less closely re- 
lied to certain other diseases of nu'taholism, sueh as diahetcs aud 
rjpoiit. Anemia is frequently present and has simuiimcs been re- 
ganleil as a catise, ojKTating by reducing oxidation. The occur- 
reuce of fatness in eertain nervnus diseases in idiocy, at the meno- 
pause, and after east rat ion is signilicant of nutritional ilisordcr 
ic^Ksildy (it* neurutic origin. ( Further discussion of this subject is 
Lieluded under Fatty Inliiimiiou.) 

Excessive Tissue-destrtictioti.— This has l>eeu nferred to 
in connect iim with inanition ; but it may ix-cur as a condition in- 
dependent of the amount of tbod ingested. Among the ctinditions 
in whicli this is observed may he mentioned fever, iidections ttr of 
other forms; e!ir«>nic iufectiotis diseases, with iir without fever; 
tujuors, especially carcinoma ; int*ixieatic»ns of various sort^ ; some 
rases of Graves' disea>se, etc. In all of these conditions the fats 
f*f the bo+ly may waste as in simple inanition ; but there is an early 
and marked tendency to consumption of the nmre important pro- 
teid structures. This hitter eonsumptiiui may proceed ahuig 
f)hvsiologie lines, or tlicre may Ijc ilistiuctly pathologic niodifica- 
tiou-s sonietimcs teadiug to serious results (sec Aeid-iutoxicatiou). 
The nature of the nu^tabolic distnrliauces in these cases i8 ob- 
scure, though it is likely that toxic substances of various sorts are 
the direct causes. This is most probable in the aise of direct in- 
toxications (phosphorus), but is also likely in other cases. In 
Graves^ disease and carcinr»ma, as well as in fevers, there are 
I doubtless poisonous substances in the IdcMid, but wlietlier these are 
rthe causes of the nietiibolic changes or not requires further study. 
The fact that thyroi<l extract is capable of eansing excessive de- 
struction of tissue in normal or obese persons is significant in this 

Add-itltoxication. — In the final metabolic transformation 
Pof proteids there arc produced ammonium, urea, kreatiniuj aud 
other nitrogenous substances. The formation of urea is still 


.' -^ ::v in ?. ■::!•> j<inioiilai>. It i> oirtain tliai a large jiart is 

rr:o:':»f*l ia the liver, and ii i? pn»lKi}>le that i^^me is formed in 

z'zr: n ^T^.^.e?- The inieniievliaie ?ir^j« in the manufacture of urea 

zji i I'l r-een drdnitfiy dtitrmini-tl. luii it is known that the liver 

ir :-sziz.''\r -i LVUvtrniiiiT ammonium >alis dirtvtiy into urea, and it 

if rr '^■^''\-ir :ha: amm-'iiium is an im|^inauT intermediate pnxluct 

: ZT- 'rii :ra::^:-.rma:ion. An t-x*>-*- if aoiJ? in the l>xly ('either 

I :r.:r.«iuo::' :: ir«^m without or pr'*Iuo:i«»n in the Ixnly) is in 

I rsin r.r MTnliZi^i by alkaline lus^^^^ in th-.- l»K>xi and tissue-juices, 

izi :r. :>ir: ':y an:nioa:um. In ivn-^e^juence of this c«>n^umption 

:' inzi L:.:r- ::.e iinea ot the urinv ti'vre-a-es anil the ammonium 

?;i.i? jr*r :z-::v-a?^>l. The quantity ••!* suoh salt.s is therefore in a 

.1 n-e-jLjurv i- :r.'i:oati'»n of th^ ^'"•nditiou which ha* l>een termed 

' i . :-'":■ x: ti:: >n. Wh^n thv t:x"I alkalies sodium and potassium) 

lt '.-i r. :> :: f -r n».utni'.:7a:i"!i «t* ai i«i<. the alkalinity of the 

■'. ••". "i '. v.^.:. For:'.:r.iit« ly ti;:-. i-i usually pn-v.-nteil hy the 

I 1 .1-.- •:' :i!::aiiMi:is::'.. "'.t in txtriuu i^ii^'.s of aoid-intoxieatitni 

j "L_- i-„:_:.-.!.::ii «irs iwz s-.::tiv*r-. 

Ei7*riz:en?al acid-intoxication i- •:i-!'-y rn^hutHl in aninuil> liy 

■ :— • J : -".; w ::h :--^is «l»:>r*v»/il .■:' :-.*.k;i'.::i- Jas«:s or hy •lin'Ct 

i : _ •:-••.:: a -f a. -'is. li\ tiiv f-Trurr -us^- :ho acids isulphuric 

:> .-ri •-- -:>•':: ir '■:' :i:?»::r/.::v'^:- f--l : ;:::.'• i.:..>si.horic from the 

-.1 -• r> > -i'.:':.^ t'r :v :~'V-r- :::ia:: :i -f rV*-! and tissues must 

-»: i- --...'. 1--: • y :*:>: a'.k.-*!' - ••:' :::- : ":> M\d :l.o ammonium pn>- 

: — . - -. - • 7-«>>- :' :r*a-:''r:v.:-:i :: .:■. ::> livrr : in the latter 

•L— -: -- - i-7 • : • x.->-"f aoi«i. S . .i :•:-::. :.'xi«.':i:i« mi is readily 

-.:■•'. .-. . -.7 :: r > air. :. ■..".!-. : - : .- ;r.v. ■•.:": "f pnneitl f«>o«l 

- - - : •. ■ : -r . :- ::^v I :: ".::"!• ..:..:v :::::m is pro<luce«l. 

'" - - - - - -'.:..:: :.> :•> l-'rv ■■. n> animal breathes 

-.-:.-' J- •: r.'. :■:«!. r.;*.:-. :'...r ^^ t a kt:e<s. ataxia, and 
• " "•..-": -:.-!*y ..«::::i ..r ^ *..:ip'i«^. ttmiinaie^ the dis- 
-. * 7 . • -"-.:■ :: ■ : ;\ - : ::^v ••» :i;plt:vly arrest tlie 

- • -J*--- : '. ' :\ V:'' ::. a:il :::!! r» •: "■ :: !: r::ay 'Xvur. 

A:ii-— ■:.:x::ji::cz -jz Man. — ^iv.. u .: -i'.'lar symptoms are 

■ - ■—:.":• .i"'^.— •"•'. ^^ " ■ ". .;:^^^:ls<:^^ alkalinity of 

..i - -. -•: /■■:■..:•. w •."..■.■; •.■•■.;in. with deen^ase 

- - \ - - • :■ :" : ". :' ■-:..!: 'riranic acid<. have 

• ■■ r - .;--.:::::: :: :- ^v.-r:^i!:>-il that the>e are 


' '. tiiis'^vursarefivfr, 
- • y :' tl.e liver, severe 

•i ^.i-iTr^-inttstinal disease, 
r.. .: oir.r-K? 'Xin In? detecteil 
-:r - ■Ttstiiuil dis4>i\lers are 
:" -' ".r. aoid«*si'5. Poisi^ns 
' ■:: : '.-y the metaln^lie dis- 
:• ■. '?: acids- 



Anioug these acids aR^ laotie, sacrolactic, sulphuric^ phosphoric, 
diafvtir, ami /9-c)xvbutyrie urul. These in part combine with the 
fixfnl alkalies ana with amnumiuni, and in part are excreted as 
Rucfi. 8ume, as Kircolaetie arid, usually suffer deeoiii position in 
the IkkIv, and are therefore rarely met with in tlie urine. The 
important acids arc oxybiityrie and diaeetic, and with these h fre- 
quently cond>ined aeetoue. These tiiree bodies may he derived one 
livim tlie other in the order named. None of them is in itself the 

ifij)eeit]c eause of tlie syniptoms of aeid-intoxieatiuu, nor is any 
B|M?eial acid the sole cause. The symptoms are, on the contrary, 
probably the result of tlie acidosis in general and of its direct coil- 

The origin of the acids of the fatty acid series has been the 

, snhjet^t of much enn trovers V. It has Ijeen held that oxybutyric 

' acid, diacetic acid, and acetone are derivatives of ]irtrteid decom- 
position ; and thi* fact that these bo<lics increase in the urine of 
gome diabetic patient^s when small amounts of carbohydrates are 
supplied, and decrease wlien the carbohydrates an3 increased, 
suggests that destructive deeom|Ki8ition of proteids is the irnimrt- 

'ant source, though il may not be the only or invariable source. 
Some recent investigations, however, go far toward indicating that 
tlie tats are an important source, if not the most important source, 
of the bodies in question. It was shown, for example, tliat the 
acids and acetone conhl be increased or decreased at will by giving 
or withholding fats in ihc dict^iry. Recently ^?-amidohutyric aci<l 
derived frnni destructive metabolism of tlie buity protcids das 
been regunhKl as a possildc antecedent of /s^-oxy butyric iH'i<l. It 
IS doubtful, however, whether this view will he confirmed. 

There is always reduetiou of oxidation in cases of acid-int*ixi- 
cation, l)ut it is not known whether tin's is the primary disturb- 
anee, or whether it is but an aceompauiiuent. Expcrim-^ntally it 
has been shown by several ol>scrvcrs that ihoiinution in tlie supply 
of oxygen will lead to increase of these acids. They proliably owe 
their presence to excessive prodnctitm and to the iailure of the 
normal oxidation which would reduce such bodies to simple ex- 
cretory prrnl utns. Otiier substances may result from the same 
tissue-destruction with insutlicient oxitlation. Among these are 
the amidod>odies, leucin and ty rosin, found in the urine in phos- 
phorus-poisoning and acute yellow atrophy of I he liver as well as 
in other condition^?, 

SymptomB. — The symptoms of acid-intoxication in man may 
be quite similar to those seen in experiments upon animals. 
Marked dyspnea (air-hunger), rapidity of the pulse, depression, 
stupor, and deep coma (coma carcinoniatosum, diabeticum) are 
some of the more ])ronounced nianifestations. The exphination of 
the symptoms oceurring in acid-intoxication is not entirely clear. 
The extreme dyspnea wdiieh is r*uc of the aiost characteristic 


symptom.s was first naturally referred to asphyxia ; but as it has 
been found that the blood contains an adequate amount of oxygen 
and a ^n'eatly diminishe<l quantity of COj^ this explanation cannot 
hold. It is probable, however, that the dyspnea is due to the 
inability of the blood to cany off carbon dioxid from the cells, in 
consequence of the re<luction of available alkali owing to its neu- 
tralization by the acids. There is thus a decrease of oxidation 
frr>m the accumulation of carbon dioxid in the cells, but not 
asphyxia in the onlinarj' sense of the word. Some have l)elieved 
that the symptoms of acid-intoxication are due to certain as yet 
unkufAvn toxins which are produced at the same time as the acids. 
There is no direct proof of this, and the evidence at hand would 
imlicate that the acids in themselves, by reducing the alkalinity 
of the blood and by disturbing the metabolic processes in the cells, 
arcf sufficient to cause the symptoms. 

Formation of Albtunoses. — In disturbed conditions of 
metalK>liam albumoses, or probably ver\* rarely peptone, are formed. 

The caujteji which lead to the presence of these substances in 
the blf><Hl and their excretion in tlie urine are numerous. Fever 
of all kinds may Iw attended by this condition, and it may occur 
in the course of suppurations, or other forms of tissue-destruction 
(acute yellow atrophy, phosphorus-|x>isoning). It is found in 
ulceration of the gastro-intestinal tract, and in some cases of new- 
growths. The occurrence of albumosuria in osteomalacia has long 
been recognized. 

In all cases there is rapid tissue-tlestruetion in which the albu- 
min.-* become hydrated, forming some variety or varieties of albu- 
nifKrfr^, and possibly in rare eases peptone. Formerly the term 
peptonuria was generally used to designate what is now called albu- 
nK>r-ijria. The presence of albumoses in the blooil causes no well 
recr)^ize<l results. It is known that they retard coagulability, 
and their ingestion often causes leukocytosis. It is verj' likely 
tliat they have other effects, but these are obscure. 

The term peptone is now quite generally limited to the final hydration 
product according to the definition of KUhne. The peptone of Brucke 
includeH certain bodies now recognized as albumoses. 

AUoxin Bases and Uric Acid. — The investigations of 
recent y<nr- have shown tliat these substances are derived from 
the niich-in of rellular nuclei. The xanthin bases — xanthin, 
giianin, ad<nin, and hy|K)xanthin — ^are intermediary products which 
partially or Ifir^ely become oxidized to uric acid. Normally the 
amount of iiri^r acid is far in excess of that of the bases. Some of 
the uric acid may b«'Come further oxidized, with formation of urea. 
The gn^at t^fttrtj-. of these products is cellular destruction, and 
eflp(;cially thai, of the leukrH»ytes. Abnormally large quantities are 
found in th<; iirin^ in leukemia and in some cases of leukocytosis; 


and ill a measure these sub^itaiices furnish no iiulieatimi of leuko- 
cytic destruetiun. Tht.* kiad of diet may ititlueuce the amount of 
tiie??e hcMlit*s^ aeconliii^ ns it is rirh (veal, thymus ^laml) or poor in 
cellular tissue. The attrmjit to t^stabUsli a relatiouship between 
certain disonierv (lieadaohes, migraine^ ete.) and increased prtxluc- 
tioD of alloxin bases has not as yet pro veil satisfactory. 

A theory of the etiology of gout has been proposed by Kolisch, in which 
It 18 held that the kiiioeys are maJTjIy coiieernoJ in the transformatiOTi of 
the xanthin-bases into uric acid, and that this fiiiictioti of the kidneytj is re- 
duced in gout. The exceas of xanthia-hasos re^ukino: from thia cause in 
turn acts destructively upon the kidney-sub^taTiee, which then fn\h to excrete 
the uric acid existititr in tlie blood. Tliis tlieory was ba.sed upon work per- 
formed with a faulty chemical method, and has therefore been dii^eredited. 

A diir^ease In i^ome way dependent upon or associated with ab- 
normal formation eif nrie ueid and alloxin bases is i^out* 

Gout.- — In its typieiil fnrm ^out is a paroxysmal disease 
marked by deposits of urates in the joints and other struct ores, 
and by coincident or conseijuent inflammatory disturhaneps. There 
are many varietieSj however, of irregular gout in which tlic par- 
oxysms may be |>artly or wholly wanting? and in which the disease 
' takes the form of a genenil systemic disfuxler, or of organic maki- 
dies of various sorts. 

Etiology.— Gout is essentially a hereditary affection, tlu" heredity 
(Dot rarely being iK>lymorphous. By this i^ meant that in certain 
fiuntlies gout and other diseases, such as obesity » diabetes, and 
I arterial sclerosis, may occur intcrehangeably. Gout usually de- 
velops in the hiter years of life, and among the contrihutiug i-auses 
are tlic use of alcohol, overeating, sedcntiiry life, and cl ironic lead- 

Pathologic Anatomy. — The conspicuous anate>mic lesions are 
those of the joints, and eonsist of the deposit of urate of sodium 
in the cartilages and connective tissue, and seroudary inflammatory 
changes. The latter nuiy (*ausc great di.^tiUliou and filu'ous over- 
growth. Similar urate 4l*'|M)sits may t*c(nir in the i'aitihigcs of the 
ear, eye, and ntise, and in the subcutaneous connective tissue or 
elsewhere. These depi^sits, called the gmity tophi ^ may subse- 
quently disapp<^ar by absorjxtion or by ilistdiargi ng tlirough the 
skin, Cirrh<>sis in various ivrgans and tissues of the i)ody fi\'- 
quently oeeurs in the c(*ursc ui^ gout. Aturuig these the cirrhotic 
or gouty kidney is most impiulant. Atheroma, cirrhosis of the 
liver, hypertrophy anti tibroid change in tht* heart, and chronic 
valvidar disease arc a!st) frequent. 

Pathogenesis. — For a long time some disorder in the form- 
ation and excretion of uric acid has been Indd responsible for t!ie 
manifestations of gout, 

(Ttirrod tirst demonstrate*! an excess of uric acid in the blood 
and recent exact chemical studies have confirmed this observation. 
There are, however, diseases, such as leukemia, nephritis and 


pneumonia, in which excess of uric acid in the blood oocors with- 
out any of the results seen in gout. It is possible, of conrsey that 
the accumulation in the blood may be due to different causes in 
these conditions but it is evident that other fectors beside the mere 
presence of excessive uric acid are operative in gout. 

The excretion of uric acid in the urine is found reduced iust 
before an acute paroxysm of gout, increases above the normal dur- 
ing the attack, and then falls to about the normal. In chronic 
cases without attacks the excretion is about normal. The increased 
quantity in the blood may then be due to increased production or 
to a reduced transformation to simpler metabolic products. No 
definite pn>of of either view has been obtained. The reduction of 
uric acicf l)efore attacks lias l>een attributed to the deposition of 
acid urate of soda in the joints and elsewhere. Possibly changes 
in cliet or intestinal al>sc)rption may play a part in this reduction. 

The pathogenesis of the urate deposits remains obscure. Ebstein 
first insisted that local necrosis itself perhaps the result of excess 
of uric acid in the blood, is the din*ct occasion for the deposits and 
some recent authorities believe that a primary' and essentially 
gouty l(x*al inflammation invites urate deposits, the uric acid itself 
having no importance in the first condition. Experiments have, 
however, shown that uric acid is capable of causing local inflam- 
matory lesions. Traumatism and circulator}- conditions may play 
a part in localizing gouty precipitations. 

P(jssibly the conditions in which uric acid is held in solution 
in the blood may differ in gout from those in health and other 

Studies of the general metabolism in gout show a uniform 
tendency to nitrogen retention apart from any possible reduction 
in uric acid excretion. There is also a reduction of intestinal ab- 
wjrption with increased excretion of indican. 

Glycosuria and Diabetes. — A certain amount of grape 
sugar occurs in the blood and urine of normal persons. Tne 
quantity in the blood varies from 0.1 to 0.2 per cent. Notable 
increase above these figures constitutes a pathologic condition, 
hyperglycemia . Sometimes other forms of sugar, as levulose, occur 
in the blood and urine. When there is sufficient sugar in the 
urine to be discoverable by the ordinary tests, the condition is 
pathologic and is termed glycosuria. This may be transient and 
trivial in character, or a manifestation of a definite diseased con- 
dition called diabetes. 

The di.siK)sition made of carbohydrates by the animal body is 
not definitely known in all particulars. It is certain, however, 
that these sub.stances are deposited in the liver and in the muscles 
in the form of glycogen, that they form fats, and are in part con- 
sumed by oxidation. The deposit of glycogen is of the nature of 
a peserve store, the system thus being prepared for intervals of 



abstmeoce. The glycogen is gradually *lUehargod from these 
tissues, and thus the quantity of sugar in the hloud is maintained 
at a more or less constant level. 

Alimentary glycosuria is a term applied to glyerisuria tK^cnrring 
in healthy or diseased |>ersons as a result *it"exei"ss of earbcihydmte 
foocL It is easily prod need by the administration of eonmderable 
qnantities of milk-sng^ar, levulose, eaiie-sugar, or glueose. The 
<]rinking of beer seems to aiti partienlarly in its development 
The explanation of this condition seems a simple one. The 
i>rtranism is imable to store u]\ or consnme tlie amount of earbo- 
hyd rates a*lministerefb mul the ^X(*ess is thert'fure discharged 
throngli the kidneys. The ease with wlu'eh sueh glyeosnria is 
developed difters in tliifiTent individual"*^ and researehes have been 
made to determine the runditiuns tliat favor its development. The 
liver in particular has been en spec ted as the organ most likely 
inc^ftieient in these cases, Init thus far no detinite facts have 
been learned ; and the rok of this organ has probably been exag- 

It h wortliy of attention that ahinejittiry glycosuria m pronounced io 
diabetes mellitus, and nmy be found in marked degree before contitant gly- 
cosuria m detected. The existing glycosuria in gri^atly incrc^jiaedj or, if tJie 
dUea^ie is not in an active stn^e, ghicose may jijjjiear when exct^a of sugar 
w starch ia administered, though it had not bt^ou pn^ent before, 

Experiinentftf f/itiromtiia y [irmbu'L-d liy admini.stmtion of phlorid- 
zin, otiers several puzzling faets for eonsidemtlon. It shows that 
exeens of gbieose in tljr blood (itifperf/fi/eeinia) is not a necessary 
condition for the <Mrenrrenee of glycosuria. After adtuinistration 
of phloridzin, a jL:lueosi*le which eimtains about 40 per eent. of 
sugar, there is no excess (d'snifar in the bleHxh but trlueose appears 
in the uriucj and indeed more than conld have brcn pn»iluccil by 
the entire quantity of phbtridzin administered. This shows that 
there is abstraction of sn^ar frr»rn the reserve stores in the body. 
It is not unlikely that the renal cells, by aetively eliminating: sugar 
from the l)loo<b [day a part in the occurrence of tliis unusual excre- 
tion. This fact, together with the disappearance of ir^n^AV Ivoin the 
urine in the late stages of some crises of diabeteH, when rcjial disease 
has oecurredj Ini^ snggested the possibility of renal fonm of f/iifco^ 
miriaand dinbdes. This view, however, has not yet been established* 

Clinical CaEses of Glycosuria. — Glucos<* ap^x-ars in the urine in 
many conditions, incbidiug (hetary excesses, various iji feet ions dis- 
eases, intoxications, and concussion^ injury, or disease of the central 
nervous system, espt^cially the floor of the fourth ventricle. 

Diabetes is a disease in which polyuria and glycosuria are 
markal symptoms. It is not inipmbable that the term includes 
disorders of quite different sorts, but no ditferentiation of such is 
possible at the pres-ent time, A mild and a mrvre form are dis- 
tinguished, and these present some striking differences, to which 
reference will be maile l>elo\v. 


Etiology. — Diabetes h frequently a lunvilitnrv disease, ixriirririj^ 
in fuTiiilies in which the same rliseui^e or obesity aud gout have 
occurred. The Jews seem jnirtietihirly liabb^ to it* Overeating, 
sedentary lifoj and ^out are causes of some importance^ especially of 
the milder form. Sometimes abnormal conditions of tlie nervous 
gystem may be the uii<ler!yin^ cause. AmonjiT are functional 
depressions, as in cases of cxecssivc grief; traumatic injuries with 
ooneussion of tlie brain ; and local dis(*ases at tlie base of the brain 
in the vicinity of the medulla* Disease of the jiancrcas is the 
probable cause in many cases, and may prissibly play a part in all 
causes, tbou*jh demonstrable lesions of the pancreas are not pres<:nit 
in all. Diabetes may txvur in the yotuig or after middle life, the 
milder eases more frequently ix'currin^ at the latter periotl. 

Pathogenesis. — In the milder eases of diabetes the same ex- 
planatiiin may be a}>pli(*able as that iriven for glycosuria, vi^., the 
liver and muscles do n<it stijre up the carlinhyth'ates carried to 
tlieni, aud the exeeKf* of sujjar is not Ijnrned np in the tissues, 
IIyper<^dyr{'mia with rousequent Lrlye(»suria results. In these eases 
the witlidrawal of i-arliobydrnte foiMl <>r temjKjrarv alistiuence finm 
all facHl may cause <Iisappearauce of the glycosuria. In severe 
cases this explanation is nt»t applicable, since tbeamiuint of glucose 
in the urine is often but little affected by abstinence from carbo- 
hydrate food or even by starvation. It is quite certain that in 
these severe cases the tissues, especially tlie muscles, furnish the 
sugar excreted in the urine. In normal individuals, and even in 
those sutlering w^itii inihl diabetes, the sugar thus libenUeil i^ burned 
in tlie tissues, (jlycosuria does not therefiU'e occur. Severe and 
raild diabetes differ only in degree : in one case the power to con- 
sume sugars is greatly deficient, in tlie otiier only UHMjerately so* 

The nature of the metabolic disturbances that lead to this 
inability to dispose i>f carbohydrates is still very obscure. The 
old theory^ that there is a lack of oxidizing power, is disposed of 
by the ex|Ten mental ilemonstration that oxidation may be nor- 
mally active. It is not improbable, however, that the oxidation 
of sugar is retarded l>y the iailure of certain preparatory stages in 
the decomiHisilion of the sngtir molecule^ as a result of wliicii it 
cannot be oxidized Ijy the tissues. Hie iuHueuce of the nervous 
By stem is undoubtetL RefeR'nce nuiy here be made to the occur- 
rence of diabetes after puncture of cerUun parts of the !>raiu 
(medulla). At oiu^ time puncture was tliought to act thnaigh the 
vasomotor mechanism, i.'ongeistion antl disturlianee ot function of 
the liver being regarded as the important consequence of vasomotor 
derangement. At the present time the part played by the liver is 
considennl less important. No siitisfactory explanation of tlie rdle 
of the nervous system in tlie etiology of dialvetes has been presented. 

Older pathologic studies showed that diseases of the |>ancn:'as 
are frequently ass<iciated with diabetes ; and recent experimental 
iiivestigatitms emphasize this relationship. Total extirjMtion of 



the pancreas in the lower animals eayst's diabetes. It has not, 
however, been shuwu in what way pancreatie or ablation 
acti?, though Lrtpine and i^thtTs believe tliat tlie panerens elaborates 
a ghieose-ilestroying (glycolytic) fV-nncnt, wht>se absence undrr the 
conditions named causes acconjulation of sugar in the IjIikxI and 
consequent glycosuria. Recent pathologic studies indicate that 
the pancreas elalwirates an ** internal secretion " that somehow 
affects the dis|nisal of sugar. This secretion is probal>ly made by 
the islands of Langerhans (see Pancreas), hut the evidence in the 
matter is indirect, and ]KJsitive views cannot yet be expressed. 

The view that iliahetes is due to increased formation of sugar 
has been definitely disproved. 

Metabolism in Diabetes.— The essential fact is the inability of 
the body to consume airboh yd rates for the production of energy. 
As long as excess of proteid and fatty food is taken and consume*!, 
no disturbance of the general metabolism results ; but when diges- 
tion fails or the diet is poorly regulated, destruction of the i>roteid3 
of the body with increased excretion of urea occurs. Emaciation 
may be prevented for a time by increased consumption of proteid 
food, but eventually occurs. In the destruction of the proteids 
of the food and tissues, acids are formed in excess (phosphoric from 
the phosphorus, sulphuric from the sulphur, ^9-oxy butyric and 
diacetlc from the albumins or fats), ami tlie condition termed acid- 
intiixication (see above) iTsolts. A consequence, and to some 
extent a measure, of tbis is the increased excretion of anmioninm 
salts in the urine. The uric acid of the urine is but little increased 
in diabetes, 

Patholo^c Anatomy* — Aside from tlie lesions already referred 
to as in some way rehited to the causiiti(*n of tiie disease, tlieiv are 
found patbologie changes of various kinds that residt from it. 
The lesioijs of gout (arterioseh^rosis and eirriiotic kitlnevs) may be 
of the nature of mere concomitants, or may be direct resnlts of 
diabetes. Renal diseases are of peculiar interest. Late in diabetes 
albnminnria frrfjuently develops and interstitial nephritis may fol- 
low. When this occurs tbe glycosuria and other symptoms of 
diabetes sometimes subside. The explanatfmi of this is obscure 
(see under Glycosuria)* Changes in the liver (cirrhosis) have 
often been found, and have been regarded as causative in some 
cases. A peculiar form of diabetes with hepatic <lisease and 
general ieteroid staining (heraochromatosis) of the skin and otiier 
tissues has been described under the title diabHe bronzL Skin 
eruptions (eczema, furuncles, carbuncles) are frequent in certain 
forms of diabetes, and gangrene of the extremities is common. 
Pneumonia and pulmonary tuberculosis are among tlie frequent 
developments i*f late stages of the disease. Cli runic endocartlitis, 
neuritis, and cataract are comparatively rare lesions. The blood 
in diabetes is less alkaline than normal and contains an excess of 


.^>liii matter, porticularlv when great poljuria has led to inspis- 

Ozalnna. — ^This term L>. nrictly speaking, applicable onlv to iDcrease of 
oxalio :u!iii in the arine. but U a^^uallt employeil for ca^es in which crrstals 
of oxalate *'ti lime are f'jand abandant in the urine. The normal mazimnm 
of oxalic acid ia 'if) mgr. for twentv-foar hours. True oxaluria determined 
by chemical estimation of the total excretion of oxalic acid has been 
tound in jaundice and in ;Mme cai^e:* of diabetes. The source of oxalic 
acid in the urine b still somewhat in doubt, ^veral InTcstigators claim 
to have found that the older view regarding itn presence in excess in 
the urine follow! n:^ certain kimis of vegetable diet is erroneous, and that 
there is no such thin^r as ** alimentary oxaluria.'* The weight of opinion, 
however, still favors the older view. There is some experimental evidence 
for the belief that intestinal fermentation is an important factor in the 
formation of oxalic acid. While this may be true, there seems little 
doubt but that the oxidation of uric acid" accounts for the presence of 
much of the oxalic acid in the urine, and that nucleins and nucleo- 
albumin are, therefore, important sources of derivation. The authors who 
have argued in favor of a specific disease marked by nervous symptoms 
an<i oxaluria based thf^ir observations on the presence of an excess of oxa- 
late setiimeut, rath*=T than on chemical examinations. Increased sediment 
occurs in certain iastances of gout in which the oxalates alternate with uric 
acid or coexist with this. In these cases, as in cases of oxalate calculus in 
the kidney or bladder, the important causative factor is most probably some 
alteration in the constitution of the urine, such as conversion of monosodic 
phosphate into the disodic phosphate, that reduces the solvent power of 
the urine for oxalate of lime. 

PhOffphatoria. — This term sh«^uM be restricted to increased excretion 
of phoHphi>ric acid, rather than to the prt^ence of increased phosphate sedi- 
ment in the urine. The latter may be due simply to want of acidity of the 
nrin»^. The daily maximum of phosphoric acid with ordinary diet is from 
'Vo rn 4 jr. The term phosphaturia might also l>e applied to cases in which 
rut :ihHolute excess of phosphoric acid is found, but in which this substance 
is relatively in excess when compared with the excretion of nitrogen. The 
normal pr'ffH*rtions are from 17 to 2*> parts «)f phosphoric acid for 100 parts 
of nitr'i'.'^^-n. Ph'>-pliaturia in the sense just described has been found in 
-oniir ♦'ji.-.«=7* of inanition. l)ecided increase in the phosphatic excretion, ab- 
"^oliit** ;w well as rt-lative, o<vurs in some castas of dialwtes; also in cases of 
tuberculosis and disease of the bones, such as ostitis and osteomyelitis. In 
considerinir th*? 4Ufrf>tion of phosphatic excreti^m in the urine it is important 
to rpni*-nilji-r that tlie greatest jM>rtion of phosphoric acid is derived from 
thr- iinA, only minor quantities coming from the metabolic consumption of 
tisrtu*"*. Fnrtlur, it \n\x< be remembered that much of the phosphoric acid 
of niHtaboli^rn is excreted through the bowel. Recent observations show 
that wlnn th«re is some intestinal disorder preventing excretion of calcium 
from the inti'?»tin»*s thrre may be excess 4)f phasphoric excretion in the urine 
in fonibination with <>alrium. The term dinb^frf pfiii.*phaticMh'JS been used 
by Teissi«;r for ph'Hpliaturia in the sense of increased total excretion, and 
four varieties have \u-vn describeil: (u} cases with j>olyuria and marked 
nervous symptoiuH ; if*) cum s preceding oraccomi)anying pulmonary diseases, 
es[)ecially tuberculosis; [r) eases in which phosphaturia alternates with or 
coexists with glyro^^nria; and (//) oa-*es in which oxaluria, pidyuria, and 
slight albuminuria are present and in which there is some relationship with 

The nature of the metabolic disturbances in phosphaturia are obscure. 
Sometimes the disorder of metabolism seems to be merely quantitative, in 
other cases doubtless qualitative. 




Definition,— Tt is not easy to define this term aceiirately, 
though we may reganl as fever a eandition in whieli the tempera- 
ture <*f the }>u(!y is elevated almve the norinul (*JH.G^ F, ; 37 "^ VA 
aoxl in which the tii^soe-metabolism is altered in the direction of 
inereased eoosuinption. There are easen in whieh the latter in in- 
sij^ifieant or wanting, and there are other instances in whieh the 
temperatnre remains normal or jsolinornml under influences that 
onUnarily provoke fever. It is doubtful whether mere elevation 
of temperature, .such iis occuri^ in experimental injury of eerlain 
j>arts of the hrain, eonstitutes fever; but unquestionably it would 
be improper to a|>ply this term to conditions of excessive tissue- 
destruction without elevation of temperature. 

Nature* — It is important, fir^st, to e* insider the regulation of 
tlie temperature in health. In tl»e nurmal individual heat is pnv 
duc*e<l ni th(* body by constant oxidation and other metalKjlic 
activities, and tlie exees^s is dissipated by mdiatiou from the sur- 
face and the heating (»r evapcu-atiou of excreta. These proeessf?s 
of keaUproduclLon and heid^lUsiimtton are rer^ulated in an onlerly 
manner nuderthe influence of the nervous system. Special centers 
for the pHMluetiun^ dissipation, anci regulation of heat have lieeu 
deMTibed by the physiologists, tliongh their location and methud 
of operatiou still remain in doubt. Whatever the exact mechanism 
may be found to be, it is quite certain that in some way the ner- 
vouH system exercises a control over production and discbarge of 

The excessive heat of fever may eoju'eivably lie due to (»xct>ss 
of heat-prrMluction» to diminution of the dissipation, to both of these 
conditions, or to increase of both with greater excess of produc- 
tion* In most instances of fever in man it appears that produc- 
tion and dissipation are both increased, though the latter is in- 
sufficient. At tlie on^et beat-dissipation may for a time be 
diminished. Tlie increased production results from increased 
oxidation and otiier metabolic {jnicesses. A study of the respira- 
tory excliange of g;ises shows that oxygen is consnmed in greater 
quantity than normally, and the quantity of COj is correspond- 
ingly increased. The excess may amount to as much as 20 per 
cent., but in jwirt this iricreased oxiilation is due to the stimulation 
of muscular enntractions in rigor, etc. Investigation of the ex- 
creta shows at the same time evidences of mm*e *>r less rapid and 
extensive tissue-waste. The quantity nf nitrogen eliminated is in 
excess of that Cfmsumed in the foiMl, and wasting of the tissues 
resultB. The albuminotis elements sufl^er particularly in the meta- 
bolic wasting, the decrease of fiit l>eing more es|>eeinHy dej>endent 
on insufficiency of tbod. 

Etiology. — The causes of fever doubtless vary greatly, Di- 


rect exposure to heat does not affect the temperature more than a 
fraction of a degree in healthy persons, unless the surrounding 
tem|>erature is very great. Ordinarily the heat-regulating mech- 
anism maintains a proper adjustment. Excessive heat may, how- 
ever, bring on fever, as in the case of sunstroke. Here, it has 
been held that the heat leads to direct disturbances of the nervous- 
regulating apparatus ; but recent investigations seem to show that 
there are first producetl toxic substances which secondarily influ- 
ence the heat-centers of the brain. In another class of cases still 
more direct disturbance of heat-regulation seems to occasion fever. 
Among these cases are the instances of fever in hysteria and other 
ner\^ous diseases. 

In the great majority of cases of fever it is quite certain that 
toxic substances are the cause of the febrile disturbances. These 
substances may be of quite different sorts. In the case of infections 
it is known that certain substances contained within the bacteria 
themselves may (»ausi» fever, and that products of the growth of the 
micro-organisms may have the same effect. The latter are prob- 
ably of albuminous nature. Other albuminous bodies resulting 
from normal or disturbed metabolism, independent of the action 
of bacteria, such as albumoses, peptone, tissue-fibrinogen, etc., may 
be equally potent ; and various ferments, such as pepsin, fibrin- 
ferment, diastase, etc., are known to have the same power. These 
facts explain the multiplicity of causes capable of producing fever, 
as any chemical, mechanical, or bacterial injury of the tissues may 
liberate toxic substances, which in turn act upon the nervous 
system and occasion the phenomena of fever. 

Pathologic Physiology. — Fever is accompanied by or leads 
to a variety of disorders. The appetite is lost, there is excessive 
thirst, emaciation is habitual, and the functions of the various 
organs are more or less disturbed. To a large extent these results 
are doubtless due to the presence of toxic substances in the blood 
and to other changes in this fluid. There is always a tendency to 
inspissation of the blood, the number of corpuscles being augmented 
(relatively) and the specific gravity increasing. This is not, how- 
ever, invariably the case, as destruction of the solid matters of the 
blood may exceed the loss of liquid. The alkalinity of the blood 
is more or le^is reduced by the production of various acids in the 
increased tissue-destruction. A common or possibly characteristic 
metabolic process is the hydration of the albuminous tissues with 
formation of albumoses. There is little accurate knowledge of 
the toxic substances in the blood. The original poisons that 
caused the fever may be toxic for the entire organism, and other 
poisons may be produced by the elevation of temperature and 
the disturbwl metabolism. 

Pathologic Anatomy.— Definite morbid changes may occur 
in the various tissues of the body, notably the muscles, heart, liver, 



and fcUtievfr, Among thf^se chiin^es tire oloudy t?\\Tlliiit^^ futty 
degeneration, and cr»agii!ation-necr(isi&. It is unlikely timt the*-e 
eiiatjges are the direct result of the inereaHetl temperature. More 
pr(»bably they result from the action of toxic suh^tanees generated 
in the course of the fever- 
Conservative Effects of Fever,— \\ hi le fever occasions 
many disturl>anrt -- and le:id> to various pathf^hipe eont?t:'qiuvnce??, it 
is not iniprohaljle tiiai tliere is a certain nii'asure of nsefidness in 
It. Some authors have called attention to the ftiet that nipid 
rediietion of the tempeniture under the influence of antipyretics 
is often followed by harmful coniscquences. This diM's not neces- 
sarily prove the userulness <if the fever, as tlie autipyrctics are all 
capalde of harm in thrmselves. A nionj definite pnMif of the u^vh 
of fever is that obtained Ijy subjectinfr infect e^l an i mills to high tcm- 
fjeratures or to febrile conditions, and then studying the progress 
of the infection. Ihider these circumstances it has been found 
that the course of various infections, such as with the Di]>lococeos 
pneumonias *1*<^' liacillus of typhoid fever^ and other orgtinisms, is 
nmeli milder and tlie conscouenees less serious tlian in uuimals not 
placeil under the simie conaitious. These results a^ree very well 
with exix*rimcnts with bacteria outside the animal ImkIv. For 
example, it is know^n that many of the bacteria are influenced 
unfavomblv in their growth and virulence bv excessive tempera- 
turt^s (1U4^' to 101 Ay^ V. ; 40'' to 42^ C). Whctlier in the body 
the tempeniture atfci-ts the miriT*-nrgauisms directly or ludircctly 
through the pmduetion of antitoxic substances, or in other ways, 
remains unsettled. It is not unlikely that increased circulation 
and respiration favor the elimiuation of the toxins that cause 
the fever. Increased toxicity of the urine has been found, but 
the methods employed are open to criticism. 




The circulation of the blood is maintained by the rhj'thmic 
contractions of the auricles and ventricles of the heart, aided by 
the elasticity of the arteries ; by the compression of the veins by 
the muscles ; and by the suction of the inspiratory movements of 
the chest. 

General disturbances of the circulation result from lessened or 
excessive heart-power, from arterial disturbances, or from changes 
in the quantity or character of the blood. Muscular and respira- 
tory weakness may be contributing causes. 

Weak Heart. — There are various forms of heart-disease that 
may lead to disordered circulation. The muscle itself may be 
weakened from overstrain, the fevers or other diseases, the action 
of poisons or insufficient nourishment, as in the anemias, or from 
narrowing of the coronary artery. The muscle may be soft and 
cloudy, fatty, or hardened by sclerotic changes. There may be 
no evident muscular disease, but merely functional weakness of 
the intracardiac ganglia. The valves or orifices of the heart may 
be diseased, and regurgitation or obstruction of the blood-flow re- 
sults. Sometimes blood-clots form within the heart and similarly 
cause obstruction of the current. Finally, pericardial effusions 
or adhesions or tumors pressing upon the heart may seriously dis- 
turb its action. 
.. The result of the weakened state of the heart must be the 

f| accumulation of blood in the venous system. The place of 

engorgement depends upon the |>art of the heart sjiecially weak- 
ened. If the left ventricle fails, the blooil backs into the left 
[ auricle and the lungs. As long as the right heart maintains its 

[ power the venous congestion goes no further ; but when this fails 

repletion of the right auricle and of the systemic veins ensues. 
When the right heart is first at fault general venous congestion 
is an (»arlier manifestation. In all cases the arterial pressure falls 
and the blood-current is slowed, whereas the venous pressure is 

Sudden and complete failure of the heart causes anemia of the 
brain and syncope, which mav prove fatal if not instantly relieved. 
Hypostatic Congestion. — In cases of serious weakness of the 
heart, in which it is qufte unable to maintain an active circulation, 
the blood tends by the force of gravity to sink to dependent i>arts. 
This condition is known as hy|X)static congestion. It occurs very 
frequently in low fevers and quite commonly just l)efore slow deatk 


resulting from any cause. Dilatation of the vessels from vaso- 
nintor pan\<i.s, troiipral musciilar weaknoss, and tlie Jailurc of 
vi^yort »us iiispiraturv t^fiU'ts arr secondary caus^'h. 

TUv Mood accumulates in tlic skinuf tlic liiuk, e^ipc^^ially about 
the luittocks. The skin is of a livid color, but is Idoodh'ss over 
the bony points ; the tissues tend to become sodden from transu- 
ilation of liijuid from the lihwid-vcssels. Slou^hine^ aud jr^m- 
gT*me (b^'dsorcs) may result Internally, hypostatic couL^cstiou 
affects tlic lun^ ])articnhirly, and a firm ot" pucumonia may 

Post-mortem lividity is allied to hypostatic enngcstion. Ai'ter 
death the bloo<l gmvitiites to the ilepciulent pai1:s and accumulates 
especially in the veins, as the arteries coutract as soou as the heart- 
action ceases, 

Overaction of the heart is less frequent thuu weakness* 
Temporary overaction ncrasions increased activity of tiie circu- 
lation ami elevation of blood-pressurcj sometimes sufficient to cause 
heraorrhaf^e. Mure prolontjed overaction due to overwork, to ex- 
cessive fe^xlin^, or to nervous stimidation, as iu Graves's disease, 
causes hypertrophy of the left ventricle, and later of the wliole 
organ. Iu conserpieuce the circulation may be more or \em per- 
manently ovei^active. 

Arterial Disorders.^ — Both orjiranicaml nervous disturbances 
are iruportaut. Of the on/anie di^tHrbaiuri^ the most frequent is 
scler*:)sis of the arteries, which otters a constant impediment to the 
arterial circulation. Hypertrophy of the heart overcomes the ol> 
j*taek% but when the heart tails venous ermgestions aud dropsy en- 
sue. Sclei"osis may also atfect the veins, hut much les.*? commonly* 
Local diseases of the aorta, as cimgenital narrowing, compressirm 
hy enlargmt glands or tumors, aneurysms, and l)!ood-clots may 
obstruct the flow of blood to the arteries, and thereby cause stag- 
nation 4 if the blood in the heart, linigs, and venous system. 

Vwtomotor ffiMfnrffanet'.i are ilepeudent upon the nervous system. 
Under the intlueuce of certain diseases of the nervous system or 
of poisons (as carbonic acid gas in asphyxia) acting locally on the 
vessels or uiwn the vasomotor center iu the bmin, contraction of 
tlie smaller arterioles occurs ; and iu consequence the blood-press- 
ore i^ greatly elevat<>d, the heart is impeded, and venous conges- 
tion results. On the other hand, the arterioles may distend fmm 
vasomotor paresis, the blood -pressure tallsj and unless the heart is 
active tliere is a tendency to hypostatic congestion. 

Changes in the Blood.— Increase aud decrease of the 
cpiautity of the blooil are generally merely passing conditious to 
which the circulation readily adapts itself hy clilatation or cou- 
fnu^tion of tlie vessels, Sudden losses of Idooil^ if large, may he 
fatal i>y syncope. Smaller losses are soon repaired by absorption 
of water fnjm the tissues ami by n*genen*t«on of b!o<xL Increases 



pneumonia, in which excess of uric acid in the blood occurs with- 
out any of the results seen in gout. It is possible, of course, that 
the accumulation in the blood may be due to different causes in 
these conditions but it is evident that other factors beside the mere 
presence of excessive uric acid are operative in gout. 

The excretion of uric acid in the urine is found reduced just 
before an acute paroxysm of gout, increases above the normal dur- 
ing the attack, and then falls to about the normal. In chronic 
cases without attacks the excretion is about normal. The increased 
quantity in the blood may then be due to increased production or 
to a reduced transformation to simpler metabolic products. No 
definite proof of either view has been obtained. The reduction of 
uric acid before attacks has been attributed to the deposition of 
acid urate of soda in the joints and elsewhere. Possibly changes 
in diet or intestinal absorption may play a part in this reduction. 

The pathogenesis of the urate deposits remains obscure. Ebstein 
first insisted that local necrosis itself perhaps the result of excess 
of uric acid in the blood, is the direct occasion for the deposits and 
some recent authorities believe that a primary and essentially 
gouty local inflammation invites urate deposits, the uric acid itself 
having no importance in the first condition. Experiments have, 
however, shown that uric acid is capable of causing local inflam- 
matory lesions. Traumatism and circulatory conditions may play 
a part in localizing gouty precipitations. 

Possibly the conditions in which uric acid is held in solution 
in the blood may differ in gout from those in health and other 

Studies of the general metabolism in gout show a uniform 
tendency to nitrogen retention apart from any possible reduction 
in uric acid excretion. There is also a reduction of intestinal ab- 
sorption with increased excretion of indican. 

Glycosuria and Diabetes. — A certain amount of grape 
sugar occurs in the blood and urine of normal persons. The 
quantity in the blood varies from 0.1 to 0.2 per cent. Notable 
increase above these figures constitutes a pathologic condition, 
hyper glyceniia. Sometimes other forms of sugar, as levulose, occur 
in the blood and urine. When there is sufficient sugar in the 
urine to be discoverable by the ordinary tests, the condition is 
pathologic and is termed glycomria. This may be transient and 
trivial in character, or a manifestation of a definite diseased con- 
dition called diabetes. 

The disposition made of carbohydrates by the animal body is 
not definitely known in all particulars. It is certain, however, 
that these substances are deposited in the liver and in the muscles 
in the form of glycogen, that they form fats, and are in part con- 
sumed by oxidation. The deposit of glycogen is of the nature of 
a Deserve store, the system thus being prepared for intervals of 


abstinence. The glycogen is gradually discharged from these 
tissues, and thus tlie quantity of sugar in the blood is maintained 
at a more or less cnnstaiit level. 

Alimentary glycosuria is a term apjilied to glycosuria occurring 
in healtliy or ilisease<l j»ersons as a result i»f excess of carbohydrate 
footh It is easily prmhieed hy the adiniiiist ration of eonsidenilde 

3iiantities of milk-sugar, levulose, cane-sugar, or gbieose. The 
rinking of beer seems to aid partienlarly in its (levclopnient. 
The explanation uf this I'ondition seetns a simple one. The 
orgimism is unable tr^ str^re up or consume the amount of carbo- 
hydrates administere<I, and the excess is therefore discharged 
throiigh the kiihieys. The ease with which such glyc^t^suria is 
developed differs in di tie rent individuals, a u<l researches have been 
made to determine tlu' i-imditions tliat favor its development. The 
liver in |xirticular has been suspected as the organ most likelv 
inefticient in these cases, hut thns lar nii definite facts have 
been learned ; and the rdie of this organ has pruliably been exag- 

It is worthy of attention that alinu^iitary clycosurlii is pronounced in 
diabetes mellitus, and may be tbuiid in marked degree bL^fure eoM^Uiiil gly- 
cosuria is detected. The existiag c:lycosuria is greatly increased, or, if the 
diseaae m not in an active Btas^e, glacose may appear when exceiw of sugar 
or starch is administered, tbongh it liad not been jireHcnt before. 

Ex per im *? n h li f/fif comi rhi , pn kI ueei 1 1 j y a d t n i n ist I'a t i on of ph I o ri d*- 
SEin, offers several puzzling tliets tor etmsideratiim. It sliows that 
excess of glueose in tlie hlocMl (hitpci'(f!y€€miu) is not a neeessary 
condition for the c»eenrrenee of ^lyeosuria. ARer administmtioii 
of phloridzin, a gliicoside whieli eon tains ahoiit 40 per eent. of 
sii«j:?ir^ there is no exeess of snu:ar in the iilorxl, hut ^lueose appears 
in tile urine, and indeed mnre than eonlil linve bi'en ])rodueed by 
the entire quantity of phhiridzin adniitiistered. This shows that 
there is abstraction of su^ar from tlie reserve stores in tlie Ixvily, 
It is not unlikely that the renal eells, hy actively eliniinatin^i^.siigtir 
from the l>b:MT<l» play a part in the oecnrrence of this unusual exere- 
tion. This faet, together with the disappearanee of sujirar from the 
urine in the la to stiige.s of some eases of diahetes, wdieu renal disease 
has occurred, lias suggested the possibility iy? renal fonuji of f/ftfeo- 
suria and fUfibftt'S. This view^, how^ever, has not yet been established. 

Clinical Causes of Qlycosiiria. — Ghieose apjiears in the urine in 
many conditions, inelndin^ dietary excesses, varions ijifeetious dis- 
ea^^s, intoxications, and coneassioii, injury, or disease of the central 
nervons system, esj>*:*cially the floor uf the fourth ventricle. 

Diabetes is a disease in whieh polyuria ami glycosuria are 
marked i^ymptoms. It is not impr<4>ahle that the term includes 
disorders of quite ditTerent sorts, hut no fbrt'erentiation of such is 
possible at the present time. A m'dd and a m'vej'e form are dis- 
tingiiishe<l, and these present some striking differences, to which 
reference will be made l>elow. 



Passive cfinfrfstion of any parade and stasis interfere with func- 
tional activity in two wiiys : l>y tliu rfcliu'tioii of nntrltion of tlie 
cells anil hy the jiruwriure exercised upon them by the aceumulatuig 
blooil and scrum* 


Local anemia or ischemia is the eonrlition 
tiian its proper quantity of 

in whieh a tissue 
enntains less tiian its proper quantity of hlood. Tins may l>e 
tUvM when it results from causes ol>,^truetin^ the How into the 
arteries, or eolkderal when it is dne to withdniwal of hlocKl into 
livperemie areas in other parts of the liody. Of the causes acting 
directly, pressure is the most fi-efjnent. There may he genend 
pressure upon an orLfdn or localized area of the hody, as in tiie 
applhuitiun of elastic haud:ii:i s ; r»r pressure upon the vessels 
within the tissue itself, as in amyhml disease, the amyhjid suh- 
stance compressing the arteries and ea|>illaries, or there may l>e 
direct compression of an artery hy tumors. The ciifulatiiui in an 
artery may be impeded hy schTi>sis of tlie vessel-walls and by 
euihuli or thrombi within the vt^sseh Loi-al anejuia of moderate 
or even severe grade may [>e flue to ucrveHis influences aetinjs: 
throu^li the vasimiotor system, as in the 
ea rl i < " r in a n i t es la t i o u s o f I \ a y na ud 's d i se^ise. 
Col lateral anemia is well illiistniteil by the 
anemia of the braiii *R*enrriui^ in aninuds 
iu which the sjtlauelniic nerves have been 
cut, with tliC consequent proiluclion of ab- 
doiuimd liyperemia. ^\'hcn ischemia is 
due to ol>structii)n r>f a single vessel the 
einudation is generally soon rwtoivd by 
collateral anastomosis: the collateral ves- 
sels sometimes reach cousidcrablc dinn^n- 
sions{Fig, 2). When i\n artery which has 
few auastotuoses and whieli siMtn sj^lits up 
into capillaries is obstructed the phenom- 
ena of intiUTtioii (see page 57) ensue. 

All anemic area is pale, reduced in size 
and temperature, anil functionally less ac- 
tive than norrual. l\' the condition per- 
sists, fattv degeneration ajid necrosis 
result* Ulien a severe Im^al anenn'a is 
relieved it h apt to be folhtwcd by hy|jcremia of the same ai*c^, 
due to cxliaustum or degenerative weakness of the vessel-walls* 

Fni. 2.— Aiirtstomosea three 
months aai*r UKntiou of the 
Htmural iirtf ry of a dog (Fortu). 


By hemorrhage is meant the escape of the sev*eral con- 
Btttueuts of the Idoml irom the IdoLxl-vefisels* It is aiiil to he 


arifTinl^ venom^ or capiiiffri/ according to the vessel from which 
the flow of LhxHl takers phiee, and patrm'hiimafouH when it conien 
frt»m all of the vessels, lienuirrha'^e niav occur either bv dia- 
lH*«esis and extnivasnti<m throo^rh intaet vessels {hcmorrlKrr/r per 
dmpctlv^iin) or hy nctnal rnpture <if a vesst^l (hworrhm/t' ptr rhexin). 
The former priK-ess is s<:en tmly in tlie capillaries and smaller veins ; 
the latter oerurs mainly in the arteries und veins. 

Diapedesis and Emigration* — Under normal conditions 
a certain nurnljerof white eurpusek's hy virtne of t!ieir ariiehoid 
movements es(*ape from tlie eapiHaries, and iH^eome wau(hrin*i: 
cells whieti move aliotit in the tissues or are carrietl liy tl*e lytnph- 

Fstream. This jiroeess is cidh-d niiif/ntiion. There is at tlie saine 
time some tmiisudation of plasma, whiidi, with the lenkwvtes, 
enters the lymphatic circulation. Under certain abnormal eomli- 
tions the red c<irpuseles also pass thron^rh the vessel- wall and col- 
lect in the tissues. This is ktuHvn as fffttpitlrsts (Fitj. t\). It may 
Ik* studied ver\' readtly nnch r the uu'c^roseope iu the mesentery of a 
living tixig. It is nntieed thiit the red eurpuseles apiirnaeh cert^iin 
pirti? of the wall of the capillary or vein and bec4)jue tixed ; then 
a small prtrjeetiou appears out>ide ihe vessel, opp*)Kite the corpusr- 

-de, and a^ this inereuses the eorpnscle witliin throws smaller, nntil 
be.whule body has gradually passed through, Not rarely several 

' Fie. 8.— Diapedi'Bts of the re<l Tjlood-rorpusples through a cajilijiry of a ttog-i tonjfue 

(nft^r Thcman). 

corpuscles pass through in one muss ; as has l»cen particularly 
noteil by Thoma. Outside the vessel the coqiuscle at once an- 
feiimes its ordinary sliiii>e. 

Biapedeftis was first stiulied Ly Strieker and Cohnheim. Arnold, whose 
Jttiv»tigtilioas are mcwt imjinrt^^nt, first belfeved that the emergence of the 
fed c»r[»a^cle5 takes place thrciugh orificcsor stomjita : but hiter rccc^nized, 
'ifi 15 now generally believed, that the siipposcd t^tomala jire merely accumu- 
lation** of intercellular substance ia certain filaces between adjniiving endo- 
IheliaJ CelU or at the junction of several cells. The active cause of the 
extrusion of the red corpuscles is the pressure of the blood. 

The leukocytes emigrate frnm the ve?isel iu exsietly thesatue way 
, as the red enrpu?>cde^, liiit mtiitdy hv tlieir own ameboid movements. 


At til*) saline time there is a more or loss eopjoiis overflow of jilasma. 

Diaiwdessis ih readily indnred hv^ mecliariiral compression of a 
Vf^in, wliich elevates the blood-piT'ssure ; or it niiiy follow elevation 
of bJooil-j)ressiire from any otlier eiuise. On tlie other hand, with 
Rorniiil pressure inereasetl perinealiility of the vessel-avails may 
occasion diapedesis, Sueh dei^enenitive conditions of the vessels 
may be due to tli<! actii>n of poisons, to various infeeticiiis diseast^s^ 
to rnodenite tramiiatism, or to t-emporary <>hstryetion to the flow 
of bhxKl into a eerliuii area. Pi-rtiaps also altered states of the 
blood may play a part wiien lioth the vessels and pressure are normal. 
Hemorrhages Uy diapMlrsis are generally small and puiM'tate (pe* 
teL'Idie), lint may be cpiite large, as somi'times in the eoiijiuietiva. 

Mnitipte eceiiynmscs may residt from ohstruetion of eapfllary 
or small l>h km 1- vessels. ISoeli oitstruetions oecur in the form of 
liyalin tlirondii in various infectious, as a result of burns or freez- 
ing of the skin, as well as from exogenous and emlogeuons jwjisoD' 
ing. Fat emijolisui and pmlioiism of partmehymutous cells may 
bring about the same result. 

Causes of Hemorriiage. — The ordinary form of hemor- 
rhage per rkexhi may be due to traumatism, to discuses uf tlie 
vessels, to increase of the bloo<l-pressure, anil to certain vague 
m^rvous i nfl uences. 

1. Traumatic hemorrliage may l>e due to direct laceration of a 
vessel or to contusituis which men ly weaken the vessel-wall and 
lead to 8ul)sc4pient rupture. 

2. Diseases of the blood-vessels c-ansing liemorrhage genemlly 
originate from causes within the ves.-^elj aud are due to such con- 
ditions as poisouiug, inteetious fevers, cachexias, or tfie anemias. 
Among tiu_' fl incases oi" tbe vessels are fatty degeneration of the 
intima or media, atheroma, and miliary aneurysm. *On the other 
hand, the outer coat may be eroded by surrounding disease and 
hemorrhage ensue (hemorrliage per diabrosin). This is seen in 
plitbisical cavities in tho lungs, 

fj. Increase of blood-pressure may he absolute or relative* The 
fonucr occurs from emotional excitement, Jmm byjiLrtropliy of the 
heart, iluring paroxysms of whcHiping-eougli, croup, and various 
convulsive disorders. In asphyxia there is decided increase of 
blood-pressure both from vasomotor contraction and irom the 
violent muscular etlbrts. Relative inci-ease of pressure occurs 
when the pressure external io the vessel is reduced, as in ballffl^n 
a!?cension, or in tlu' pleura in cases in which during violent in- 
spiratory efforts the air «innot enter tbe lungs, as in the fetus at^ 
tempting to breathe during labor, 

4. Neuropathic Hemorrhage. — Th^ ncrv^oiis syi^tera exercises a 
peculiar iu9ueuee ujion the vessels. lu cases of a{H)|dexy, of 
epilepsy^ and of section of the spinal cord, and in other nervous con- 
ditions, s|M>ntaneous hemorrbuges from tJienon: or stomach, or into 
the lungs, suprarenal bcHlies, aud other organs, are not infrequent. 



In thf siiiiie ^nMiji alsn an- to I to reckornMl tlio iiL-^tiiinx's of 
vicariniLs liemurrlnige due to aupproi^sioii of tlie nieiistvs^ and the 
reraarkuble eases of stigmatization. The last named is a condition 
in which under nervous exiillatioi] or livf^teria spmt^ueous hemor- 
rhages oeeur from various parts of the body, eyixvially from the 
parts wounded in tlie enieifixion. 

i'K The Hemotxhagic Diatbesis. — Certain persons present nn in* 
herked tendeney to hleed sjumtinieously or a Her very trivial injuries. 
Such ix.TMjnfc> are kmnvn as ** Ijleeders/" and the eondition as Aewo- 

£hilia. The exaet palhologic eondition whleh oeeasions the 
?iuorrhai::es is still uncertain, A Itemorrhagie diathesis nuay also 
l>e <leve!oi»ed as a result «pf various diseases, as typhua fever, 
an til rax, septieemia, or }*ht*s|)horus'poisouing. The same is ol»- 
6er\X'd in the severe forms of anemia, like progressive pernicious 
anemia and leukemia. In these eases altered blocKl states and 
disease of the vessel- walls are doubtless the eauses at \^'ork. 

Classification of Hemorrliages,^Hemorrhage may ocenr 
on ft-ee surfaces or into the tissues. In the former ease various 
name^ are applied to designate the locality, bueh as epktaxis, nose- 
bleed ; hemopti/sis^ hemorrhage frtjui the lungs ; hemfifetm'siii^ fnjm 
the stomach ; enierorrhnf^ia^ inuu the bowel ; mdmrrha(/Ui, uterine 
hemorrhage l^etween, and menofThttf/ia at, the menses. 

Hemorrhagt^s into tlie tissues take their names from the size 
and nature of the lesion. A liemorrhagic iniiltratiou l>eneath a 
surface, a^ of the skin or mucous meml>nine, is cidled an frrhiimmis, 
which if small ami well delined is a peia-hia, but if large and 
ditiuse, a mifff/iUailon or auffumm, A distinct aeeumulation of 
bloody constituting a veritable blood-tumor, is known as a heuiit^ 
icrna. Infiltrations of a peculiar sort, involving Iwali/cd portions 
of a tissue or orgjiu, are known as hanorrhfftjif iiifatriH {q, r.). 

Results of Hemorrliage, — A very large hemorrhage may 
catise sudden tleath by cerebral anejoia. IVIore tVequently the 
patient remains nueonscious for a time and then slo^^ ly recovers. 
The hemorrhage ceases spontaneously by the diminution in heart- 
action, by clotting of the blood at the point of ru|)ture, by retrac- 
tion of the elastic vessels^ and by prt^ssure of the surrounding 
tissues. Blood extni\'asated in tlie tissties ei>on coagulates and 
subsequently undcrgeies disorgiiiiization, the re<l corpuscles break- 
ing down into pigment-matter, which may be carrie<l away or 
deposited at the seat of hemorrhage. The' fluid elements may be 
completely aijsorbed, or, staineil with coloriug-matter, may remain 
^ a cyst. A Iwiis of bemfjrrhage may set up reactive inflam- 
mation and lead ro encapsulation l>y new connective tissue, .Some- 
liraes hemorrbagie aecmuukitious l>eeome inspisr^ated and undergo 
calcification. Biootl in tlie serous sacs does not readily coagulate, 
but mingles witli the normal litjuid si*eretion. It may be grad- 
ually absorbed or may undergo degenerative changes, especially 
when infected ljy micro-organisms. Large hemorrhages cause acute 



aneiTiia ; repeated sokiM extravasatiuu.^ may lead to i>mfnuiitl sec- 
ondary anemia. (These eoiKlitioii.s will be more fully discussed 
under Diseases of the Blood.) 


Btnbolism is the proee^^ in wliieh fiireiirn biidies of various 
kinds are eurried in the 1>1o(kI an*l tleposited in the smaller arteries 
or eapillaries throiitrh which their ^ize does not ]K'rnnt them to 
IxLs.s. The hodi^.s deposited are eidled rmholt. 

Sources and Nature of Emboli. — The most common form 
of eniholisrn is that in wliifli pent ions of thronild Ritnated in 
the heartj the large veins uf tlie extremities or pelvis, or nii ather- 
omatous patehes in the aorta^ are swept into the cirenlatioii and 
lodge in the smaller vesst.'ls. Softening of the original thrombus 
is generally the immeiliate cause. More nirely portions of a dis- 
eased heart- valve or of the intima of the lieart or aiteries, liver 
or placf^iital cells, or parts of tumors, are carried in the eireula- 
tion and deposit*'*! as emholi, Emhnlism of large giant-cells of 
the hoiie-ioarrnw is partienlarly eoinio*»n, and is nenrly always 
a seeondary process when there has been some other form of 
ceUnlar embolism. Disorganizatinn of the blood may cause 
embolism of pigment*particles» as in malaria, or of small liyaline 
masses, as in burns and errtain turms of pois4ining. In cases of 
fnietnre of l>ones parti*'les of Iht may be dishnlgfd fnnn the mar- 
nn\ and enter the eirxHilation, wliile in won mis of the large veins 
of tile neek or elsewhere air-embolism is observed. Finally, 
masses of bacteria, s^-olices of echinococcus, anil oilier parasites 
are a serion^: form of emboli. 

Seats of Embolism. — The tinal place of hxlgcmcnt ol" an 
cml)ohis depends mainly *in its sonree. Those derived from the 
genend veiit>ns eirenhitiun are usually carried through the right 
heart to the lungs, wlierc they oeelude branches oi' the pulmonary 
artery. Emboli in the portal cirenlation may lodge in the liver, or 
pass through the liver to the heart and lungs. 

Retrograde Embolism. ^Sometimes portions of thmmbi, 
tniiiof oi:i>ses, utlier et lluhir cinijoli, t^r micro- organisms may be 
transjH>rtetl in the veins in a direetion rvpposite to tin" normal blood 
current, Thns emboli may be carried upward in tlie inferior vena 
cava and into tin- hepatic veins and so into the liver; or from any 
of the larger veins or even from the right lieart baekwartl toward 
the peripheral veins. This eoinbtion, known as retrr^gradc em- 
bolism, is oljserved when some pulmonary disease such as whoop- 
ing cough, emphysema, etc. eanses increased intrathoracic pressure 
ami eonse^juenlly a positive instead td' negative pressure in the 
large inthrathoraeie veins. There may l>e an actual retrogadc cur- 
rent of blood or the centrifugal transportation of the embolus may 
be more gradually aceomplisbeil liy repeated imjuilses directed 
toward the periphery, eac!i of which pushes it a little further. 


Emboli cnrniiiig from the left lieart or from the aorta are dis- 
tributed in the general arteriiil eirenlation. They are most ire- 
quently found in the spleen » kidneys, and hniio. Other organs or 
tlu- periplieral vessels may likewise be atfeetedj hut the results of 
enjbolfsm are less marked in them and ^.re frecjnently overlooked. 
EniboH fniiii the veins may reiieh the general eirenlation in teases 
in which the lurarnen ovale or septum ventrienlorum is perforated 
{paradoxir eini/ofimi)^ or by being Ijroken np into smaller emboli 
in the Inngs and tlnis passing through the pulmonary eapillaries. 
Tlu* latt^^-r is not iufrr<|urut in eases of tat-emliulism of the lungs. 

Results of Embolism. — A large eudiolus may eaus** sudden 
death hy tx-eluding one of the UKiiu bnuiehes of the judmonary 
artery, one of the enronary arteries, or a hirge eerelu*id vessel. If 
the vessel m not wholly oeeluded, secondary thrombosis niay com- 
plete the obstruction atnl deatli m;iy be slow. In the case of less 
irajKJrtant vessels merely local anemia results. This may he re- 
lievcHJ by establishment of collatend cireulatiun^ or may cause more 
or less extensive necrosis if not relieved. The original end>nlus 
and the secondary throndjtis may ujuiergo softeintigor organization 
in tlie ssime manner as ordinary thrombi (//. r.). 

The results of oeclusion of smaller vessels by emboli depend on 
the nature of the emhohis. Thry are either pnrelv meehitnic(d 
when the embolus is aseptic, or fit pttc wlien the embolus contains 
micro-organisms. The important mechaincal result of small 
emboli is the pathologic condition called in/areiioTL 


Infarc'ts CKxnir in situations in Avhich there {*rc small arterios 
having only capillary ur at most very slight arterial aiuistoniosis 
with neighbnring arteries. Such arteries were called vutlurterm 
by Cohnheim, They are foimd especially in the kidney, spleen, 
lungs, retina, base of the brain, and 
pcirt^ of the heart. When one of 
these is occhuled by an emhohis in- 
farction may *>ccur. 

Infarcts? are situated in the periph- 
eral part of the organ, and arc harder 
tiian the surroumling tissue. They 
are wedge-shaped, the base being out- 
prard toward the perijihery of the 
brgnn. Infarcts may sometimes res id t 
from occlusion <if a immber of adjoin- 
^ing arterioles or capillaries, and in this 
are irregular in uutline. There 
ire two forms of iufaretinn, the red J^eru/^^'*-^" ^^'^ ^^ '^' ^^"'"^^ 
hemorrhagic, and tlie white or 
nemlc. The former are dark red in color, and have the appear- 
jice of w*cdge-sliaped areas of hemorrhage with coagulation. 

Fm, 4— Anoralt* Inflirct of the 
kdlnev: ihe cmlKjlns, orrludln^ « 
braiu'h iA the reiiiil mrtery. is shown 


Anemic or white infarcts preric^nt tfio same gi^neral features, but 
are less elevated and are yellowish or grayish in colon They are 
frerjuently surroujided by a zone of congestion or liemorrhage 
(Fig. 4). 

Formation of Infarcts. — The first effect of orc-bision of :iii 
eodartery by an ernbuhis is stoppage of the circulation beyond the 
embobis, A wedgc-sha|>ed atiemic area resolts. Tliis may renxain 
anemic and undergo coairu!ation-neero>4is, with the formation of 
an anemic orjrhtfe infnni. In oilier eases, liowever, the vessels 
of tlie occhided area, after a temporary period of anemia, hecome 
overfilled with blood, extravasation occurs, and an ftfmorrhaffic in- 
fard results. Various theories are otfcred to explain the persist- 
ence of anemia iu tlie first ease nud the overtilliuj^: with blood in 
the second. In aniMuie infart^ts the |>ersi stent anemia in some 
cases is d ue to t h I'o n i bi is i s in t ii e Vf^ n ules wl i ie h rece i ve 1 1 1 e I d< mxI 
from the oeelndcd i/ndartery and in the anastomotic capillaries. 
At times rapid swelling of tlie par<'nchymatons cells of the oi^n 
compresses the capillaries and maintains the anenna. S>me ron* 
t*.»nil that white infarcts are frequently formed by rapitl absorption 
and removal of the eoloring-niatter of the bh>oil from hemorrhagic 
infarcts* In the latter the overfilling of the vessels residts either 
fiiim a backfiinv <if bliKid froin ih*' veins (Cohnlu^im) or from free 
ca p i 1 1 a ry -a nast o 1 1 1 os is. The I a t tf r w 1 1 a 1 d 1 >e t ^s j k* c • ia 1 1 y apt to 4>ec u r 
when th*' g<juend or local Ijlood-prcssurc was previously elevated, 
or when the lodgement of the embolus caused reflex (*ontmction 
of the snrninnding vessels, and thus overflow of blood into the 
occluded area through the (^npillary-auastomoses. The hyperemia 
thus pnwluccd suon leads to extrtivasatitrn i»f l>lood, l>eeause the 
vessels II f tlie twx^l uded areas rapitlly underg^i ilegt*nrrative changes. 
Infarcts in the luugs are nearly always hemorrhagic; those in the 
kidneys and especially the sjilccn are frequently anemic. In the 
brain irregularly sliaiH'd areas of anemic necrosis (softening) are 
the usual result. 

Subsequent Changes, ^In am^mic infarcts coagulation-ueero- 
sis and caseation arc the marked degenerative changes. The l)roken- 
dowi] tissue is gradually absorbed and reactive intlammatiiin and 
organizatiiui cause cicatrization. Xot infVcqni'ntly a small amount 
of caleart'inis matter is deposited, i"Spr(*ially in intluTts of the linigs. 
In hemorrhagic iniai'^'ts the extnrvasatrd bloiwl breaks up into 
pigmcnt-mattrr aiKl the tissues suffer degrtK-rations simihu' to those 
seen in anemic infarcts. The final result in i ithcr ease is genendly 
a scar, which is pigujcntrd in cases of hcmorrluigie inlaiTts, More 
rarely infarcts undergo lit|Uefaction and <'yst-formation, rspeeially 
in the braiiu The infarct may become infected by microorganisms 
afUa* its formation and absces^s may result, as iu cases in which the 
emlx)lus itself was an infectious one. 

Infections embolism occurs in cases of purulent softening 


[ of tlinjmhr, in eases of ]o<?al sn|>j>uniti{iii or necrosis, in nicerative 
endocarditiif, ami tht^ like. The first <4Je*-t may he the formation 
oi a hemorrhiifi^ic or aneniie infarct ; hnt tlie iniero-or^tiiHsms scwin 
imiuiply ami invmle the tissm's, eausinjL^ su[t[mr4tive or g:an*^renoiis 
pnK?eH8es. il eta static aUsee.sses are [ir^HhifiHl in this manner. 
Similar rej^nlts follow \vhen an iniiiret is seeondarily infeeted. 
This is not infreqoent in the lungs, wliere the air-passages furnish 
a ready path for the entrauee of mterti-organisnis. 

Bnst-embolisin. — Small particles of coal, iron, marble, or clay entering 

t^ ' -^ in respiration may penetrate tho ti&?iieH, are largely taken on by 

I to cells, and for tfie me^t jmrt are c arried tn the branch iai lym- 

j ,..,.. V ^:and!?» If the hitter i*re nnrdiar^^'ed and «ntU ii. the ilust-particles may 

igain acce?i?» to the circulation through the efferent lyni|>h-cbannels of the 
gland or by ruptnre of the pland into nejghbf>rinir veins. More rarely dust- 

[psriicle^ may enter t!ie blood-vcMsels in the luiif^s^ directlv, by penetration. 

'AiWr their "entrance into the blood they are deposited in the capilhme-s 
And eubfltance of the liver, Hpleea, and hone-marrow; where they may re- 
Jtiain permanently, either free or enclosed in fixed cells, or whence they 
may be removed by wandering cell^; The tinal disc barge occurs especially 

k from the lungNt, the tonsils, the lympbatie structures of the int<?stincs, and 
from the livc-r in the bile. 

Air-emboliBm.— Small quantitiefl of air mav occasion no serious dia- 
tiirbancei^ ; but when larpe qnantities* enter the veins the right heart h 

I found full of frothy bbxHl and the pulinunary arterioles are occluded by 

r im&U bubbles, Sudden death in these caae?* is not uiiKsyah 8ome recent 

1 experiments in dogs !*eem to cast doubt on the HerirniMnejsS of air-emboOsm, 
but the matter is not yet settled. 

Fat-embolisin. — Sudden death may occur when a larpre number of the 
pulmonary vessels are obstructed by embolic oil-drops. Wben the proceiw 

[Js left* extenf^ive little ilisturbiOMe arbcs, as the tdl i« soon bniken up into 
droplets and passes through the pulmonary capillaries, or it may be ab- 
Borbed in the hin^s. 

P\Unwnaru in/atcU may be due to embolic occlunion of the blood-vesseb, 
but also to oostruction ot'a bronchiole. Any kind of hemorrhagic extrava- 
■ution in the lungs may asisuitie a wedge-shape, because the area infxitrate<J 
i» tli<? wedge-sha[»ed area included in the divifiions of a terminal bronchiole, 
(For details, see the chapter oo the Lung^.) 

Metastasis. — The procesi? of metastasis of tumors and of infectious 
dj9efb«es IS closely allied to that of ordinary embolism, Small particles of 
tumors in the one cai?e, or of infeeted thrombi or tissne in the other, enter the 
blo<jcl-vej*sela or the lymphatic chainiels and are carried to neighboring or 
distant parts of the body, wliere they lodge in capilbiry- vessels. In the case 
of tumorerabolism the embolus may grow an<i Oi'casion a metastatic nodule ; 
in the case of infectious proccik^es secondary foci of the infectious disease 


Throrabosi.H is the eoagtilatioii uf blood within tlie blood-ves- 
yt\& or heart during life. At the very Ix'ginnini: of the proeess 
tJje formation is not a oijugulum in the onlinury sense, hut .snbse- 
queutlvcoao^ulation is the es.'?ential feature. After death eh>t-s form 
within thr- heart and vej^^sels, as in l>hMHl removed tVom the bmly. 

Caases. — The eonditioas fevomlde to tiirombosis are alter* 


ations in the blood-current, changes in the vessel walls, and alter- 
ations in the blood itself. For the most part two or all of these 
conditions are present in cases of thrombasis. 

Alterations in the Blood-current. — Anything which slows the 
current, snch as narrowing of the blood-vessels, weakness of the 
heart, or pressure upon the vessels, favors thrombosis. Complete 
arrest of the current in a part may lead to ordinary clotting, such 
as occurs post-mortem ; but with careful precautions a vessel may 
be Hgated at two points without the occurrence of clotting in the 
occluded portion — at least for a long time. Some change in the 
blood-vessel wall is generally necessary in addition. Thrombi due 
to slowing of the current are frequently seen in the heart, the ves- 
sels of the lower extremities, and in the sinuses of the brain in 
the course of exhausting fevers or other asthenic conditions. They 
are called marantic thrombi. In many of the latter micro-organ- 
isms have important etiologic relations. 

Changes in the vessel- walls play an important part. Atheroma, 
inflammatory or degenerative changes in the vessels of areas of 
inflammation or necrosis, ligation and other traumatic injuries, and 
diseases of the endocardium are all examples of conditions leading 
to thrombosis. In many cases of thrombosis apparently due to 
slowing of the current of blood, micro-organisms have been the 
more important factors, by causing primary infective lesions of the 
endothelium. Dilatation of the arteries (aneurysm) or veins 
(phlebectasia) or of the cavities of the heart acts largely by slow- 
ing the current of blood or by producing irregular currents. 

Alterations in the Blood. — Experimentally, thrombosis may be 
induced by injection into the circulation of extracts of the thymus 
gland, the suprarenal bodies, the testicles, and other organs. 
These extracts contain large quantities of the fibrin-ferment re- 
garded by Schmidt as an essential factor in coagulation. Patho- 
logically, it is probable that the tendency to thrombosis in typhoid 
fever, sepsis, and other diseases is due to increase of similar fibrin- 
forming factors in the blood. The name ferment thrcyinbosis is 
a])plied in these cases. 

The presence of bacteria in the blood in cases of thrombosis 
and within the thrombi thcmelves indiciites a probable relationship 
of great importance. Some bacteria (especially staphylococci) 
seem particularly pQtent while others apparently liave little effect. 
The mode of action of the bacteria has not been fully established 
but hemolytic activity and injurious effects on the lining of the 
blood-vessels must be considered as probable factors. 

Hemolytic action is also the probable explanation of the fre- 
quent thrombosis met with in various mineral poisonings and in 
auto-intoxication such as follows freezing or burns. 

Recent investigatorH claim to have shown that coagulation of the blood 
results from a conversion of certain albuminous substances into fibrinogen 


which under the inflitence of a /frmrttf {filirin-fenneiit cir thnimbin) acting 
in the pTeaence of (Calcium salts [imiiucts libriri. The til>rin-tVrnieiit(throm- 
binl ia in part a derivative of an luitece^lent called prnthrombtti which occurs 
in praetieaUy all of the eelU of tht? hody except the red blood eorptisrles. 
Thrombin is, however, ako a direct product of various ceUi* of the l>odv and 
e3*|>ecially of leukocyte?* and viLscular endothelial ccll^» The conversion of 
proihnrtmbiii into thrombin \^ aceoni] dished by the action of isymopiastie 
substances found in the various celU of the body includiny^ tiie red corpuscles. 

According to these view8 the »ta^o?i in coagulation are : (ft) conversimi of 
prodirombin into thrombin l>y action of zymopliisttc Mubntancc^ ; {L) conver- 
jsion of albuminoU:^ bodien (purnglohulin) into tihrinogen and into soluble 
fibrin under the influence of thnnnbin; [c] prccipilation of inmduble 
{ibrin by calcium ^alt<*. 

Fibrin wa.s formerly thought to he a calcium compound but more 
recently the role of calcium in promoting coagulation ban been interpreted 
a.- that of ft body which stimulates the ftirmation of the tibrin ferment and 
doe-i not cuter into the chemical compoi^ition of fibrin. Recently it has brcn 
held that a substance (thrombogen ) i-* tirsl converted into prothrombin 
under the intinence of a tissue coai^ulin (Loel») or throaibokinawc (Mora- 
witzi; the [>rothrombin unites with the calcium ?*alt« to form thrombin 
(fibrin- ferment) which with tihrinogen producer fibrin. 

Pathologic Anatomy,— The apj>earam*c and eonstnietion 
of thronihi clrjjc^nd ujhui th*' niniiiier of f*)rttmtit>ti, 

When fornied id eoiiseotiencc of a 1 most cotii[)lcte ^toj){wi^e of 
the eirctilation they are rlark-<Mdored, s*>tl, ret} dofs^ .similar in every 
way to post-mortem coutjiila ; aiul under tlie mi(*n>8eope sh(»w fib- 
rillar fihriii enelosiiii^ ma inly red eurptiseles. 

Yellowish or n liite throtiibt are formed .slowly fnmr aetively 
circtdating bloml and are more eoiisistent. Their eompo.sitiiui will 
he understood from the mode of format i^tii. In the nt^rmal ciir il- 
lation the reil eorpnseles move in a eolumn in the center of the 
stream, separate! 1 frtjm tlte wail of the ve.ssel by a plasmatic zone 
in which the lenkueytes may be .seen, Wlien the eirenlation is 
slowed, [daqiies form and approaeh the vessel-wall, and tend to 
adhere in small nmsses to any point cd' disease in tlu' endothelinra 
aiKl also to each otliet\ This has Ijcen termeil vunyiHthmihrn of 
tlie blood-plaqties, 

Ka the blood- pUtjucH are probably produced by degeneration of the. red 

corpuscles, it might be expected that causer^ of Mich defeneration would 

cca^ion abundant fi^rniation of idaqucti, and vQns^ntwxly pkifiUf-thmmhi, 

T?ach, iodeed, in the ciisc, and hyaline thrombi area regular accompaniment 

of eertnin forms of iutoxication in which hemolysis occurs. 

In the ordinary thromlnis, aftf r primary eonijlntination of the 
placjnes, leukocytes are added, and red eor[>nseles in jrreat or small 
numbers, aeeonlincj to the manner of formation of the elot, w hether 
rapid or slow. White thrombi consist of eontrhjtinated phnpies, 
lenkoeytes, and fibrin. They first appear as hyaline, visei<l masses, 
hut subsequently l»econie gramdar from partial disintep'iitimh If 
the eirenlation is alternately slow and more rapid, distinct layers 
are seen in the thrombus, first dark eolored from admixtitre of red 



rorpusclus, tlicn lii,Hit*T in liuc. Sik'Ii tlirornlii are called Unttified, 
If the rirenlatinn is irregular fnuii tlilatatron of the vessels or 
from other causes, the light and dark areas of the thrombus may 
be niore irre^ridarly disposed. 

Till." throiiibtis first f*>rme<l i^ tlie primary thrombus. Siibse- 
cjiiently it extends by additicms {Htvf*n(htt^thrmnhm) in the direetion 
of the current of blood as far as the next collateral braneh ctf the 
vein or artery, into whieh tlie tliroinbus freiiiieiitly extends as a 
roimded prominence. In the ease of the veins a new thrombna 
may start from isuch projection (Fig. 5), and eventnally the clot 

Fig. 5.— Tlironibuf. in the femoral vtHn in a (ix^i^ of ph1»?Mti^ iix\*m ft efHet imen In the 
Maaeum of Uit' Pliihulelpiila Husplialy. 

may in rare eases extend as far as the heart. The thrombus may 
be lafentl — that is, when it lies atrainst the vessel-wal) — or ah^trnrt- 
ivCf when the lumen is completely oliliieralecL In the veins small 
thrombi are frequently formtHl in th<' valvidar poiiehes in maraiilic 

Tio, <l.— ThrombcMiii in curdlao 
cliaml>ers, fihowing cytMllie struct- 
ure lOrthj. 

Fk, 7.— Braneh of the bmchial arttry Alter 
amnutiition, showing vascularization of tiie 
thrombus. Th (Weber k 

enbjects. In the heart throml>i are especially common on diseased 
valves, in the anrienlar appenda^res, and in the inteilraljeeniar 
spaces. They frerpiently appt^ar as jmlypoid masses, an*l may he 
attached by slender pedicles. A eurions form, calle<l ball ihromlfi, 
is eeen in the anricles* These are ronndetl elots whollv or almost 


wholly st^paratefl from the wall, and may occasion serious obBtruc- 
tinn at the orilioeg of the heart, 

effects. — Freijuently the collateral eireulatloii is so quickly 
establiished that no uiitowanl results art^ seen. Wlien a lai*ge vein 
is obstructed venrnus eongestiori and ilrop^y nia)- fi^llow ; t^hstrue- 
tion of an artery eaust^s hx-al anemia, and subseqiientlvj if the col- 
lateral circulation is not estiiblished, degenerations or necrosis. 
Thrombotic f>bi?t ruction of t^nudl arteries may cause hemorrhagic 
infarction, Eniholism and, if the thrornhus is iufccted, general 
pyemia may result from softening of the thrr^mbus, 

Subseqtient Changes, — After their formation all thnioibi 
contract. In this way the red forms may become light colored by 
extrusion of the red corpuscles. In ^mall vessels reel thrombi often 
become light colored by removal of hemoglobin and a species of 
hyalin-transformation. These may have the ap|)earance8 of white 
tkrombi and are only disti ngu is! led Ijy careful examination. 

After the tiirombus has eontraeted it may nndergo various 
degenerative changes. Frequently tlic wfiite corpuscles, plaques, 
and fibrin are broken down into an emulsion by liquefaction- 
necrosis and fatty degeneration, and the re<l corpuscles converted 
into granular pigraent'^d masses. These s*>ftenefl portions are 
swept into the circulation and occasion emlx»lism. Frequently 
this form of nmpie sofiening occurs in the cent<T of large* thrombi 
and gives ri*««r to cyst*likc fiirmations (Fig, G). 

A more g^ritJOii fonn of softening occurs when the thrombtis is 
bv micrtHOff^ganisDiB. In this case true purulent mfiening 
pbce, and ibe wall of the bloocUveseel diares largely in 
mppontive prooeaees. This form oecuns especially in the 


i^>mbi blocking blood-vessels of suppurating or necrotic tissues. 
G^!i>enl pyemia and infectious embolism result. 

A more favorable termination of a thrombus is calcification. 
This is mo^ frequent in the clots in dilated veins, the calcareous 
dirotnbi being known as phleboliihs, Arterioliths and cardioliths 
are rarely met with. 

Organization of the thrombus may result from the irritation 
it occasions. New blood-vessels and proliferating connective-tis- 
Boe cells spring from the vasa vasorum and lining membrane of 
the blood-vessel as well as from endothelial cells covering the throm- 
bus, and penetrate the thrombus (Fig. 7). From these organi- 
zation proceeds as elsewhere, and as it advances the thrombus 
itself is absorbed. Finally, the clot is fully replaced by connec- 
tive tissue enclosing a small amount of blood-pigment or calcified 
remains of the thrombus. The blood-vessel may be converted into 
a solid fibrous cord, or may be distorted and narrowed by bands of 
connective tissue in the interior. Sometimes after partial vascu- 
larization of a thrombus small vessels running parallel with the 
lumen of the obstructed vessel become dilated and thus partly re- 
establish the channel. This is termed canalization of the throm- 
bus fFig. 8). In other cases canalization may begin as a process 
of simple softening. 


Definition. — The term edema is applied to a condition in 
which the liquid within the tissues is increased in quantity. 

Htiology. — It is primarily necessary to understand the methods 
hv which the liquids normally present in the tissues escape from 
tfie bloorl-vessels, their original source. 

?f*:vfTal processes are concerned in this escape of fluid. In the first 
pLa/r^r. the pserwure of the blood serves to cause a certain amount of direcf 
^^T'Uion, jast as liquid enclosed in tubes of permeable animal-membrane 
**^Ap*r<* when the pressure outside is less than within. In this process of 
dir<-','t filtration the state of the tissues themselves plays a t)art. If the 
aon/iai frla/iticity of the tissues and degree of pressure of the liquid in the 
iiit^r«ititial Hf^aces are lowered, liquid escapes through the capillary-walls 
v> *3grializ^ the pressure. A second process at work is that known as 
difuxifm or r^inrAvf. In this there is an exchange between the blood and 
ti**: tlff-u^r-liquid"*, Certain substances being taken into the blood in ex- 
ciunjr*: for wat^r and other constituents of the blood-plasma. The liquid 
tbuij dl'^h2Lru:<^i from the blood-vessels enters into the metabolic activity 
of xw: :i**u*r* to a greater or less degree, is somewhat altered in character, 
u^d \u»: feurpla^i is carried off in the lymphatic capillaries as lymph. Cer- 
UiJi pby<»iologi4t5 (Heidenhain et ai.) believe that there is a farther and 
r«T jfufMirtiint factor of a vital sort. This is described as an active secre- 
lofT function of the endothelial cells of the capillaries and lymphatic 
•pftcei; fo that, according to this view, lymph-formation is in a measure 
al Uuutt a direct secretion. This view, though not generally accepted, is sup- 
ported by many facts. 


Briefly, then, lympL-fonuutii-ni may be described as the escape of water 

and other substances through a more or \em permeable membrane, the 

r capillary- walla, in rrnisequeiice of direct filtration, 08mf>?iis, antl jtrobably 

'•ecretioiL The ouantity present in the tissues depends upon the quantity 

escaping from tne hlood-Tessels and the amount carried away by the 

lymphatic circulattan. 

The ainses of increased acetini illation of liquid in the tissues 
may th«^n he n^udily deterntined. Among these are (a) increase 
of blood-pressure, or (6) of tissiie-elastieity and pressure; 
(c) alterations of tlie blood rendering it more diffusible, or {</) of 
the liquids in i\\v t issues increasing thr nsniotie power of these j 
(«') iiicfeased p<^rmeahihty of tlie walls of the bluod- vessels ; (/) 
obstruetion \n tin* How in tin- lyin|>ltatic vessels. These eiuises 
will be eousidered si-parately with reference to certain well-known 
clinical types of edemii. 

(a) Increased blood-preBsure al\\'ays oeeasions ineroased eseape 
of liquid from the vessels (transudation) Jind thus incrciised ibrmu- 
tion of lymplK In active ' hy]ieremia witli exeess of pressure the 
amount of liquid ntrdy l>eeomes so ^reat that the lymphatic ves- 
sels cannot carry it otf^ and edema does not therefore occur. In 
passive congestions^ liowevcr, as in lieart-disease, pressure upon 
veins, etc., the escape of liquid becomes more ra])id and copious, 
and the lymphatic circnlatiun is insuthcieni. Edema or drupsy 
rr*sults. In tins process of direct lilt ration the transudate consists 
mainly 4>f the water ami sulinc crmstitucnts nf the plasma and to a 
relatively small ticgrcc <d" the albuinitions constituents. 

(6) Decreased tissue -elasticity and pressure is nirely a factor of 
prime innH)rtani-e, though it may be a eontribnting *'ause in manv 
cas^s. In one class of cases termed n>dema ex vacno it is the 
principal cause. In these eases litpiiti escapes from tlic blood- 
vessels to HU a space left vawuit by disease or atrtiphy ol* tissue- 
elements. This is frequently seen in the subarachnoid spaces of 
the brain and in uther parts of the centra! nervous system. 

(c) Alterations of the bloody though theoretically very intpor- 
tant as direct causes, pmbably act indirectly. It has been found 
by experiment tliai artilicial hydremia, even though cond>ined 
with consideralde increase of the l)ulk of blood, does not cause 
edema unless by some means tlie walls of the IdtMiKl-vessels have 
been injur^i'f L It is pnibable, therefore, that the edema of anemic 
and marantic persons is similarly dn^ to increased penueability of 
the vessels. Tins in itself might txx'asion cdeniaj though the 
degree is probably greater as a conseqtience of the anemic state of 
the blood. The vascular disease itself is probaldy in some way 
(w^rhans by the action of eircidating toxic substances) brought 
about by the condition of tlie l>lood. 

(c/) Alterations of the liquids of the tissues may, conceivably, 
occasion increased diffusion of liquid, Imt practicall)' little is 


known of the operation of this element. There are, however, 
certain cases in which disturbed metabolic activity of the tissues 
seems to alter the tissue liquids in such manner as to favor the 
development of dropsy. 

{e) Increased permeability of the capillary -walls is df great 
importance and probably plays a part in every case of edema. Ex- 
perimentally it is easy to prove that this factor alone may cause 
pathologic transudation. Applications of heat to a part or the 
introduction of poisons capable of causing disease of the walls of 
the blood-vessels may thus occasion edema. Clinically this factor 
is of importance in the edema of Bright's disease. Formerly the 
dropsies of renal disease were attributed to hydremia, but the 
experiments cited above show this factor to be insufficient. On 
the other hand, changes of the vascular system are known to occur 
in Bright's disease, and particularly in cases usually attended with 
marked edema (glomerulonephritis). Changes in the blood may, 
of course, contribute, as may also stasis due to cardiac weat- 

Disease of the capillary-walls is also an important cause of 
edema in and about areas of inflammation (inflammatory edema). 
In these cases the toxic causes and products of inflammation doubt- 
less attack the walls of the vessels and render them more porous. 
Such edema may occur only in the vicinity of an inflamed area, or 
may be widespread. Thus in some cases edema of the lungs and 
other internal organs may be occasioned by bacterial toxins derived 
from a distant focus of infection. 

Cases of hereditary edema have been described. These may 
owe their origin to a congenital excess of vascular permeability. 

Finally, there are cases of edema in which the nervous system 
seems to exercise an influence. Among these are the dropsies 
attending\s of neuritis, neuralgia, or organic diseases of the 
cord. In these instances changes in the blood-vessels and per- 
haps in ihit tissue-elasticity may be important causes. An inter- 
esting fiirni of this sort is that known as angioneurotic edema, in 
which l(xial edema of various forms (often as giant-urticaria) makes 
its appeamnco under the influence of nervous irritations. 

(/) Obstruction of the lymphatic circalation does not ordinarily 
occasion edema, becaase the collateral circulation is sufficient to 
carry away the lymph. When, however, a larger trunk, especially 
the thoracic duct, or numerous smaller lymphatics are obstructeii 
edema may result. This is observed in the chylous ascites due to 
obstructions of the thoracic duct and in the edema of elephan- 

Pathologic Anatomy. — Edema may take various forms 
according to its situation. In some cases it is localized, affecting 
a limited part of the Ixxly, as a single organ or member. In other 
cases it is widespread in the subcutaneous tissues and skin, when 


the term anasarca is applied. It may occur in the serous cavities 
in the form of serous transutlates (hydrothoraXj ascites^ hydro- 
pericardium, etc.). 

I The liquiil itself varies in charaetc^r aecordiog to the cau^^e. In 
the pure tniusudate.s doe to increased filtmtion the licpiid Ls waterj^, 
low in t^peeitic gravity (below 10 Hi), and eoniparatively poor in 
blood-eorpii8eles and albuminons eonHtituenis, In eases in which 
disease of the vessel -walls has playtxl a large part in the causation, 
espe<?ially in the inflaniniatory edemas, the liquid is more dense 
and contains more corpuscles and alljuininous bodies. 

The transudate first occupies the lymph-s];iaces or interstices of 
the tissues, causing a more or less uniform swelling and liogginess. 
The tissue pitis on pressure, and on section more or less abundant 
liquid exuues. The solid organs (kidneys, liver) arc lighter In 
color, less dense, and more moist oo section thaw normal ; but the 
appearances of edema are here less characteristic than in the sub- 
cutaneous or submucous tissues, or in the softer organs like the 
IiiDgs and brain. 

Mieniscopieally the tissue-elements are seen to be pushed apart 
by the transudate, and in mme eases tlie cells themselves may i*e 
diseases! (see Dn^psieal Infiltnxtion). 

Results of Bdema. — The function of edematous parts is 
necessarily impjiired. Sometimes serious consequences ensue, as 
in die case of edema of the epiglottis, tlie lungs, or the brain. 
Secondary changes may occur in [Kirts the seat of continued edema. 
Among tliese are various degenerations of the cells and a productive 
change in the connective tissues. The latter is well illustrated in 
the sclerotic change in the subcutaneous tissues of long-standing 
dropsy, elephantiasis, etc. 





Definition. — Atrophy is a condition in which a tissue or organ 
undergoes a more or less uniform diminution, without definite 
disease of its constituent parts. It is extremely difficult to draw 
a sharp line bet\\«en atrophy and degeneration. Frequently one 
of these conditions merges in the other. 

Hypoplasia. — This term is applied to a condition in which certain 
organs or tissues fail of their normal development. Thus the heart and 
blood-vessels and the internal genitalia have been found incompletely 
developed in some cases of chlorosis; and similar conditions have been 
found in other diseases or apart from manifest disease. It is difficult to 
determine in some cases whether the lack of development is purely the 
result of deficiency in the developmental processes or the result oi congeni- 
tal disease. Thus in the state called infantilism^ in which the body as a 
whole remains undeveloped, there is doubtless a relationship with cretinism, 
and primary disordered action or deficiency of the thyroid gland is the 
underlying cause. Occasionally an organ or part of the body is entirely 
wanting. To this condition the name aplasia is given. 

Btiology. — The causes of atrophy may be varied. It occurs 
as a result of want of functional demand, as in the atrophies 
affecting palsied limbs ; and sometimes as a result of disturbances 
of the trophic nervous system, as in diseases of the anterior horns 
of the spinal gray matter. In the latter instances lack of use is a 
contributing cause. In the involution processes of old age there 
is more or less general atrophy, which might be designated tia 
physiologic. Similar normal or physiologic atrophy occurs in 
certain organs before the general manifestations of old age. Thus 
the atrophy of the thymus-gland in early childhood and of the 
genital organs at the menopause are instances of cessation of func- 
tion, and consequent or concomitant atrophy of physiologic char- 
acter. Atrophy may be more definitely pathologic, and the 
result of distinct causes, such as want of local or general nourish- 
ment by occlusion of the vessels, pressure, etc. In these cases the 
process may be purely atrophic, or there may be distinct degenera- 
tive disease of the cells with diminution of bulk. 

Pathologic Anatomy. — Atrophy may be gimple or numerical 
In the former kind, to which the term true atrophy might also be 
applied, the individual cells decrease in size without manifest di»- 




Fia. 111'.— Brown atrophy ot 
the hcarMiiui'cle. 

iso ; io the latter tlie cells are reduced in number, and are usually 
Brst alterefl by fy>me form af degenerative diseas<:', s<j lliat tiie proe- 

IS not, strietlv ti)»eakiiig, true atropliy. 
The pirenchyjiiu ut' or^anw suffers first and 
most eJiardftt*ristieally, the eonnet five tissues 
remaining unaHeeted or even undeig(»ing hy- 
perplasia, lu true atropljy the eel Is luay 
present no definite alteration, exeepting per- 
haps slightly increased pigmentation. This 
is sometimes due lo the Jaet \htii the normal 
pigment of the eell does not suffer reduetio!i 
do the other eonstituents of the eel!, but 
in other eases there is actual de]M\sition of 
pigment (hematogenous). Cases of the latter 
kind arc desiguutod as brown airopfttf {Fig. 9). This ib seen most 
-Strikingly in the heart-musc^le in {uK^aneed ohl age or in persons 
'dead of some ehrouie eaeheetie disease. In some of the eonditions 
generally (h'serilR-d as atrophy the cells show degenenitions of 
various forms, such as cloudy swelling, coagulation-neerosis, fatty 
degeneration with vacuolization, and other gross alterations of 

Secondary degenerative ehanges may oeeur in the connective 

ttissues at\er the pareneliyuia-eells liave beeoine atrophic. TIuis^ 

I tftcr the physiologic atroj>hy of the thynuis-glanil has occunt^d 

the connective tissues of the gland and of the ^Turmunding parts 

iK'Come eonveiled into fatty tissue. In other •.•ases myxomat^uis 

change may be obser\^ed. 

Orgiins which have undergone arroj^hy are often quite irregular 
on the surface from unecpia! involvement t>f the flitferent i-^m- 
Ptitnents. The c<msisteney nuiy l)e little changed or nuiy l>e 
greatly reduced, particularly when some form of eell u la r degenera- 
tion is present. On the other hand, tlie organ may be hard and 
.tough from seeondary hyperptasia of the eonneetive tissue. The 
'capsule is generally wrinkled from ihe slirinkage of its contents, 
and secondary thickening is not unusual, especially in the heart 
and spleen. The color of the organ, like that of the individual 
cells, often l>ecomes darker than normal and may be decidedly 
changetl in brown atrophy. 

In cases of pressure-atrophy various distortions of th*' affected 
» organ maybe obscrvetl. Tliese are partieularly marked in the 
livers of women who have laeed cxecssively* The right h^he of 
the organ often presents a deep gniove or furrow eorresimiifling 
with the lower border of tlie ribs, and ca(*h of the ribs with which 
the organ comes in contact may cause a tlepression. 

Pathologic Physiology,— Th(^ function uf an atrophic 
organ is neces.sarily impaired. In the atrophies of iild ag*» this 
may be of little consequence, as the functi<aial demand grows leas 


and lees. In prematore atronhies general a^ well a^ local disturU- 
anoes may CKxnir. These disturbanea^ vary with the varying 
functions of the organs, and w ill be separately discussed* 


Tlie general terms degeneration and metamorphosis are applieil 

to changes in the tissues by w hifli tlieir integrity is altered in the 
direction of luwercil vitality. TbiTf may be a conv^ersion of the 
protoplasm of the cell into substances abnormal to it either in kind 
or quantity. This is termeil ikf/e iteration in a narrower sense. 
In a secfuirl class there are deposited in the cell, from the blood or 
other tiuids of the bmly, substances abnormal to the cell in kind 
or c|Qantity* Tlie name ii^Iiratiou is applie<l to tliese processes. 
In iudividual cases it is often difficult to distinguish between the 
two varieties. 


Definition. — ^Cloudy swelling, also termed albuminous infil- 
tration and parenchymatftus degeneration, may be tlefmed as an 
edema of the celhilar |U'otoplasm, with gnuinlar alteration in the 
proto|)lasmie protcid and the pnxluction of oimcity. 

Etiology. ^Cloudy swelling is an almost universal accom- 
paniuK^nt of inflammations. Cii>ulatory disturbances (anemia) 

Fio. 10.— Ooadf Bweltlog and raecrodl* of the epitbelial eelh of the ren*! tiibul£«. doe Co 
tubllmAte-polAoning (KatK &n(i Schmorl), 

were formerly supposed to be important, but arc now considered! 
to be of little significance. Fever per »e can piYRluec cloudy swell- 
ing, probably not so much the result of the simple degree of heat 
m of metabolic disturbances induct^ thereby. The most frequent 


cause of cloudy Bvvellins^ is intoxicatioD, either by l>aeterial toxins, 
as .in the various iiifeetious conditions, or by innnmenible oi^nic 
and inorganic subatanees. Cloudy swell tnjj; is also caused by nii- 
tritionul disturbanees ; .stan-ation of an organ will prcHbiee it as the 
iirst btage of atroj>hy ; and, on tlie contrary, the eelLs may in other 
cases be so overloaded with initritional substances as to become 
teniponirily transfonncd into this eonditioui as in the glandidar epi- 
tlielium of the liver during active digestion. It is further known 
that excess.! ve cellular activity may result in a cloudiness of the 
protoplasm, as in the kidney and in glands excited by nervous 
^stimulation. These latter prcH-e8Sf\s should l>c viewed as uornial 
phenomena^ analogous to the physiologic fatty degenerations* 

Pathologic Anatomy. — The swollen cells present a fine 
opacity whicli under higlj powers is seen to be due to the presence 
of diffuse refractile granules (Fig, 10), The nornuil protoplasmic 
granulations (Altmann's granules) may partly or mIioHv diwippcar; 
ill miiscle-filjcrs tlie striatJons are obscured or oblitcratetL Vaciio- 
lation may lie seen in the late stages. The cell- wall l)Cconics in- 
distinct, so that the eclls apf>ear to have coalesced. 1'lie inielei 
may be little altered but are commonly abs(?ured by the granu- 
lation. Genendly the chromatin becomes diffusely stained ; it may 
elect the aei<l-stuins or may refuse all staining. In late stages the 
entire cell may lose its Ui^rmal reactions to staining-reagents. The 
distinctive granules are not sMloble in alcohol or etlier, but are 
dissolved by acetic acid and alkalies. 

The large glandular organs, the liver and kidneys, illustrate 
the condition exquisitely. The entire organ is symmetrically 
swollen; the general consistency juTljaps a little deci*eased. On 
' gection the surface may be foimd a little moist and the jmren- 
chyma protrudes. The color is an opatpic pallor, suggesting the 
appearance of boiled flesh. 

Seats, — The glandular epitbelia (liver and kidney) and the 
muscle-fibers are the striking seats of this degeneration. 

Pathologic Physiology^^Tbe opacity seems to l>e due to 
a coagulation or precipitation of a part or all of the protoplasmic 
proteid. Some systematic wTitcrs have attemj^ted to divide it into 
two groups ; albuminous infiltration, in whieli the material has 
been deposited in the cell and then l>eeu precipitated ; and albu- 
minous degeneration, in which the inherent eellnlar proteid has 
been precipitiited. It is doubtful whether this division is justified. 
The ehemic relations are entirely oljscure. It is as yet incompre- 
hensible how bacterial toxins, themselves apparently pn:»teids, can 
precipitate other and higher proteids* In the ease of inorganic 
{joisoaing (metallic salts, acids) the process is more readily under- 
stood. The swelling of the cell is probably a simple edema » due, 
it may be inferred, to disturbed osmotic relations. 

The function of organs is more or less profoundly disturbed by 



this form of tlegeiieratioD. Complete recovery is easy and fre- 

auent. If, however, the causes jHTsitit, the cells pass into other 
egenerations, usually tatty metimorphosis. 


Definition. — Fatty infiltration is the dei>08ition of fats derived 
from the circulation in cells and tissues which normally contain 
none, or the deposition of an excess of fats in cells and tissues 
which normally contxiin such- 

Etiology. — Fatty inliltratlon may be physiologic or patho- 
logic in its origin. In conditions of gcncml ohchity the rcgtdar ' 
consumption of excessive quantities of nourisfiment m?iy h'ad 
to the most marked degit^es of fatty infiltration ; an inlieritctl 
predisposition and lack of exercise acting as contributing- causes. 
In rare instances it seems ivossililc that with the normal physio- 
logic diet persons of exceptional digestive power and living 
under conditions wliich restrict combustion may become atfected 
>vith pathologic liitty infiltration. The condition may (x*rur 
during pregnancy, and is frcijucHt at the menoimuse. In a 
large class of eases an iilinin-niul <liet, or the presence in the 
diet of substances wbi<"h tend to the formation of fats, such as 
alcohol, arc responsible for the condition. It is doubtful whether 

Fic, IL— Fauy infiltmtkm of the Uver, 

poisons prrKluce general fiitty infiltration ; they frequently, now- 
ever, indirectly pmdnce local or visccnd infiltnitions. In cachexiiis 
certain organs may l>ecome loaded with fats, as is sometimes seen 
in the liver in pbtlusis, lu carcinoma the cells of the neoplasm 
may become iutiltrated with fats. In orgjmic diseases of the ner- 
vous system accompanied by extensive disintegration of myelin^ in 



iisea^es, and even following fractiireB of or op{^ rations on 
ttones, the liberated fats are taken up l*y the circulation and 
deposited in susceptible k^calities. There is a nire form prol>ab]y 
entirely of senile origin, and also a type which appears at pul>erty. 
Of generul diseases tliat may cause o;cneml fatty infiltration, chlo- 
rosis and diabetes may be mentioned. Fats may be deposited 
locally as substitution-tissue, as in the capsnie about selerosed 
kidneys, in the place of atrophied muscular fibers^ in the bones, 
and ai>out areas of local disease. The j>rotective ureas of til^rous 
tissue whicli wall oH' pathoh^gic prn>cesses of various kinds may 
beeom e e x t e n s i v ely i n li ! t ra ted , 

Pathologic Anatomy. — The fat may be ditfuse, in localized 
areas, or in streaks aluMjLr tlie planes of fibrous tissue, Tlie ajK 
i^pc^rances naturaliy vary with the tissue aftected. Tlie connective 
^tissue mtiier tlian tiic parenchyma usually displays the disease. 
The microscopii^ picture in comiective tissues is jirccisely the 
same as tliat *)f normal adipose tissue. The dei3<jsit,s in connective 
tissue are most prominent in various fasciie and along the fibrous 
stmnds, under the eiulf>thelial mend>ninesj aliout the lymph- 
channels, between tiie musclar filirillte, and to a marked extent just 
btnieath the true skin. In the kichiey the collections are between 
tlie tubules ; in the liver, iu tlic fibrous trabeculie, but especially 
in the hepatic cells ; in the heart, undcnu/atti the siTusa and bc' 
tween the Inmdles of fibers. Within the parenchyma-cells, and 
tliis is most marked in glandular epithelial cells, the fat is seen 
as distinct drops witfiin the cell- walk The fat-drops are always 
i»f eonsidemljlH size, iuid soon run together, forming one drop, 
which pusiics the privtoplasiu ami miclens against the cell-walL 
The nuclei though tlatteued are usually normally distiuct and stain 
well; the cell' protuplasui is clear and presents its normal gnuinles; 
the cell-wall is intact, though often Indging to acconnuodate the 
exces.s of contents. In nire, prolonged, and extreme iustauces the 
bulk of the fat may be such as in interfere with the fuuctiuns ami 
nutrition of the cells, whose nuck'i :ind pmtriplasm will then show 
pathcdogic alterations. Crystalline fiiruKitious, as of margarin and 
cholesterin, and tiny balls of lecithin may be present, but are 
more often sr-en in fatty ilegenemtions. The fat may be stained 
with osmic acid or siidan III. 

Seats. — ^The favorite seat^ of fatty infiltration are the snbcu- 
t:uiei>us and subsemus tissues, tlie mesenteries and omentum, 
ahutg the fascia, l>etweeu the muscles, about the kidneys, and in 
the liver and heart. The lungs and central nervous organs are 
rarely and only slightly affected. 

Pathologic Ptysiology,— I liave attempted to define this 

Leondition rigidly as an infiltration of fat into otherwise normal 

foells or tissues, distinct from any possible foraiation of fat in tliem. 

Infiltration arises whenever there is an abnormal quantity of fat 



in the cireulatioo ; the causes of this were pointed out in the 

etiology. Infiltration into imperfect or diseased cells may, how- 
ever, occur with only norma! quantities of circulating fat ; in this 
case a distinction from fatty degenemtion may be difficult. All 
cells and tissues are not of the same degree of susceptibility ; 
when, tlierefore, is^Jlated areas occur in unusual lot^lltieg a pre- 
existing disease should be suspected. The mechanism of de- 
position is not well understood ; it is perhaps effei*ted by circulat- 
ing cellular carriers. 

Unless very extreme, fatty infiltration does not geriously em- 
barrass the functions nor threaten the existence of tissues, and 
complete recovery and restitution are the rule. It may, however, 
cause mechanical embarrassment or may lead to secondary de- 
generations, wliich, particularly in the heart, may be of serious 
consequence to the organ. 


DefimtiOM,— This is defined as a nietamoqphosis, the c^n ver- 
sion of the cellular [jrotoplasm into fat. The classic physiologic 
illustration is the fal-prcHlueticm in the secretion of milk. Here 
the nature of this process lias not, however, been determined. The 
majnrity of tlie secreting cells neither die nor show pathologic 
alterations ; while in the case i if such as are cast ^ifl^as colostrum- 
cells, it has not been shown that their fat was not an inJittnition. 

Etiology.^Fatty degt nerations frequently follow upon cloudy 
swelling, and the causes detiiiled for the one iipply also to the othen 
Of all agents, ptusons are the most imp4»rtant. These may be me- 
tallic, as mercury, arsenic, had, jjhusphurus — indeed most of the 
metals. iVimjwuuds which directly bind the hemoglobin or reduce 
it, or break up the red corpusi'les, likewise prtHluce it. Such are 
carbonic oxid, ehlonites, pyn:>gallic acid, some coal-tar compounds, 
etc. Certain pcusons, like ehlomform, ether, icxloform, and the 
acids, fH»em to act directly t>!i the cell-nutrition. In the case of 
most of these substances it seems to have been shown in m4>re or 
less accurate chemical studies that the poison acts by disturbance 
of the gaseous cellular metabolism. The tuxins ot bacteria art* 
causes of imporUmee, but their mode of action is not clear, and the 
analog}^ with the metallic poisons which naturally suggests itself 
has not been made out. In all anemias and cachexias fatty de- 
generation is common ; it is rare in uncomplieated chlorosis. The 
degeneration in these cases was ibrmerlv regarded as due to sub- 
oxidation. Since, however, it has been shown that no suboxida- 
tion occurs in sm^h chronic anemias, tlie degeneration may best be 
classed as toxic. It seems possible, however, that extreme henK»r- 
rbage can produce fatty degeneration by suboxidation. Metab- 
olic diseases can also produce it, as i» sometimes seen in diabet 



Fever can produce it, but tlie temperature must be high and 

Local fetty degenerations may be caused by local disturbances 
in nutrition, if not too sudden. This is seen in cases of con- 
gestion, thrombosis, embolism, athenima, in tumors, and in tuber- 
cular and syphilitic deposits. The fatly changes of senility are 
probably of like origin. In the involution of tissues, as in the 
thymus, corpus loteum, uterus, etc., fatty degenerations are com- 
mon. Trophic disturbances produce the degeneration, as is seen 
in the voluntary muscles. In many [jathologic processes, as in 
caseation, liquefat^tion-net^rosis, and the resolution of pnenmoma, 
this metamorphosis plays an imjmrtant r6le. In rare instunees, as 
meotionedi fatty infiltration may pass into fatty degeneration. 


1 f ^^ 

Fm. 12.— Fatty degco«niCioQ of the tipltbellum of the reuiil tubutefl; at&tned with oimlfl 

aeid (Slmmoticlii). 

Pathologic Anatomy.— Organs the subject of marked fatty 
r degeneration are often somewhat increased in size: to this, how- 
ever, tliere are many exceptions ; a notable one is acute yellow 
r«trophy of the liver. The consistency is usually lessened, though 
1i»0ciat^ fibrosis may render tfie affect e<l part abnormal ly dense* 
The specific gravity of tjjr tissue is mitalily n-duL-t-d, In the ner- 
vous system and in caseation and allied* conditions liquetaction 
may occur. Tlie color in typical instances is a pale yellow ; the 
existence and degree of congestion, pigmentation, or jaundice, will 
obviously alter the color. The areas of tiegeneration may be uni- 
Jbrm or isolated. In the heart and liver pjirticularly streaks or 
Brregular areas may pnKlucc a mottled appearance, ' On section 
free fat may drip from the knife and cut surface : in other eases 



FKi. 13.— Fatly de- 

Epnention of the 

no fat-*lroplcts can be h?<*ii mutToscopifiilly. To rare iostances 
fat-crystiiis may be visible to the nuktHJ eye, 

Micrt^»f'opic A ppfii ranees. — Tlie [«irriiehynia-<:ells are first and 
in(»^t extensively attk-ted, though (he i'oiineetive tii^i^ue may be- 
come involved. The eells are usually S4)ra€\vhat enlarged. The 
mrtiinrl gnmules of the jjrotophiKm di8ii|)pi^ii\ and 
in their .^tead are tine dark granules, which usually 
stain blaek with osmie aeid (Figs. 12, 13), and 
whieli are disstJved by alcohol, ether, etc., hut 
not by acetic aeid. A jn-cnliar reaction of the 
granules is their staining with fnehsin (fuch- 
siiiuphih' grannies). I'stially the gninuhs are 
very fine and only slightly refnietile ; they may, 
however, be large, and considerable dn^plets may 
appear or the entire cell become c>ne large fat- 
dmp^ as in fatty intiltration. The nuclei in njfiny 
eases tjf nimhnite ilegree show nu changes ; later 
in tlie [jroeess, however, the chromatin becomes 
difl'iii^cd and refuses to stain and the nnelens may entirely disap- 
pear. When the fat is dissolved out of the cell a vacuolated 
protoplasm may be observed . In early stages the protoplasm has 
been asserted to be imaltcred when thus examined. The cell- 
membnine sfx>ner or later breaks di>wn, and the fattv contents 
and detritus fill the space. i'holesterin, lecitliin, and fatty 
crystalline formatiojis are often seen. 

Seats. --Fatty degeneration occurs in nearly all tissues. The 
epithelial structures, esjieeially the liver and kidneys, the heart- 
muscle, and tlie central nervous organs are the tissues most fre- 
quently a fleeted. As before t^tated, interstitial as well as paren- 
ehvmatoiis tissues may be involvtHl. The cellular constituents of 
exudates and tniosndates are also lial>le to the change, and the 
lirpiid may thus pn'seut the appearance of an enuilsion. 

Pathologic Physiology. — Kecent investigations tend to 
destrov the old theory that fatty degeneration results from a trans- 
formation of the pn»toplasni of cells into fat. Investigations have 
shown that the cells of many of the tissues and organs, notably 
glands, contain tat and that this is undouhtedly derived frt>ni the 
l»lof>d, also that the fat in true fatty infiltration has the same origin, 
lu both of these instances the (*ellul:ir protoplasm is not de- 
monstrably altered. In fatty degetjeration so-calle<l the protoplasm 
iH diseasi-d and in advannx'd stages completely destroyed. This 
would seem to sustain the old view of direct transformation of 
protoplasm into iat; but the most accurate chemical investigations 
do not confirm the possibility of such a transformation. Further 
when animals were poisoned with phosphorus and a fat foreign to 
the animal wasadministererl the fatty organs contained the fort^ign 
fat. These considerations have led to a quite general belief that 



fatty degenemtioii results from an infiltration of fat derived from 

the blocwi and remotely from the fat ilepc^sit^ of the Ijody or from 
food. The signifieajit ditierenee between fatty intiltmtion and 
fatty degenenition i.s thut the former is a deposition of fat in otlier- 
wise normal cells as a result of exeessive supply of fat or possibly a 
lowered metabolic activity whieb normally disposes of fat, while 
the latter represents a dei>osit of fat in a diseased eell, the disease 
inviting the tJeposition or grt^atly retluein^^ the eapaeity of the cell 
to dispose of fat even in norma! quantities. For these reasons the 
terms '^fatty infiltration*' anil "^legeiu^utive fatty iniiltratioir- have 
been suggested for the respt^etive con il it ions. 

In some recent experiments in which starving frogs were poi- 
sonetl with phosphorus the direct eonversion of protoplasm int^i tat 
seemiHl to have been denionslnited but even in tiiese experiments 
the glyeu^cn of tlie liver may have l)een the source of the fat pro- 
duetnl and besides objection has Ix'en raised against the chemical 
meiliods relied on in t!ii?se experiments. 

Fatty degeneration tends to cause secondary changes in the 
protoplasm of the affected cell or the degeneration which in the 
first instance underlies the ermdition tenrls to increase until the 
cell is practically destroyed. ( Vibdar function is therefore eventu- 
ally impaired »ir perverteib but exjKnnmeTits liave sliown that eou- 
fiiderable fatty deg(Hieration of tlu' heart muscle may exist witliuut 
impairment of the heart's power ( Romberg; Krehl). The same 
may be true of other organs. Mild grades with preservaticm of 
the nuclei of tlie cells a*lmit of recovery^ severe grades go tm to 

t*>tal necrobiosis. 


A- E. Taylor while engajred in systematic analyses nf the liver uml VU]- 
neys in fatty tlci^ont'ratiori noticed that these degenerated organs retained 
less of their fat on ethereal extraction thati do mirmal or^^aiH. He, there- 
fore, rrtrried out experiments on frogs by producing a fatly degeneration 
with phojiphorua and extracting the fat, which wa^ then compared with that 
from normal frogs. Aa a result of his experitnenti* he ofler^ the hypothesis 
that the combined fat h a metabolic constituent of the protoplaMin of the 
eell. During the course of the disease causing the fatty degenenition. this 
combination is broken after the miinner of the ttction of fi?rnienti< and the 
pre%*iously combined tat is set free when il appears as fatty granules in the 
protoplasm. Following thi^ eonies fat transportation and infiltration of the 
affected cells. The reason for Buch infiltration is, however, not understood, 


The amyloid, hyalioL^, mucoid, and colloid de^nemtions r^p* 
resent proteid metanioqdioses %\hich an^ tdosely related. In 
typical instiinces they am be quite clearly LliHerentiated i'roin each 
other, and for the sake of elearness and e<Hn enience they will he 
i separately described. It must be nn(h"i*st(KKlj ln>wever, that the 
products are eh^sely related substances whose i'hemical character- 
istics and relatif^ns are not clear, and which cannot in many cased 
be distinguished. 




i>efitiitioti. — Tbis consigt^i in the appearance in tissues of 
am yloid material j whether it is formed in loco or deposited a^; an 
infiltration is not onite clear. Amyloid seems to be a combination 
of ehondratin'sulpnuric acid with a proteid. 

Etiology- — The common conditions under which amyloid 
degcDeratioQ arisen are suppuration and ulceration. In tubercu- 
loma, especially of the lungs and skeleton, and particularly in cases 
of mixed infection, and in syphilitic ulceration are found the con- 
ditions most favorable to its production. It occurs^ however, in 

WtG. II,— Amyloid ilv^feneralion of thti ktdney, showing amyloid iubetance In Uie walU 
of the blcxjd-resielfl of the glomertiltu at b, attd hyaline tube-cftiU in Uie renal tuba!«« 
at g (Ziegicir). 

connection with ulcerations of various sorts, gastro-enteritis and 

actinomycosis. Riirely it occurs under conditions of cachexia 
without suppuration, as in cancer, malaria, leukemia. Sometimes 
it is found without any apparent cause. 

Certain local "amyloid" formiitions {rorpora oviiftaeea) are prob- 
ably in no wise conu(^Hed with tlie gene ml condition and undoubt- 
edly arc often futirely plivssiolo^ic. 

Pathologic Anatomy. — In marked instances the organs are 
enlarged, and their specific gravity increased. On section the 
tiBsue is firm ; the cut surface is smooth and neither contracts nor 
extrudes* The consistenuy varies with tlic coexistence and degree 
of fibrosis, fatty degeneration etc. Amyloid substance is more 



inelastic than any other degenerative material. The color of the 
organ is usually pale, but may obviou?iIy be altered by eougestion, 

[)ignientation, or tatty degeneration. The amyloid substance iti^elf 
las a glistening, waxy, translucent appeanince which is almost 
pathognomonic* This waxy apjx^arance is not always uniform. 
Mild or even modemte degeneration may not prCcSent maerof=w?opic 
appeamncoa ; in fact, apparently quite normal tissues may l3€ 
highly amyloid microseopieally. The special appcaninces in 
various organs will he de&cribed in the ap{»n>priatc chapters. 

jncrmcopir Appearances. — The favorite seats are the outer sur- 
face of capillary blood-vessels, and the iutinia and media of larger 
bhiod- vessels, the advcntitia being rarely ati'ecteil, the endotlieliam 
apparently never. The fixed connective tissues of the organs, 
elastic tissues, and basic membranes of glandular acini are the \\aiis 
atfected, the wandering cells and leukocytes being rarely involved. 
Muscle-cells are uuduubtcdly susceptible; but recent studies seem 
to show that glandular and lining epithelium is never involved. 
8neh cells may, and often do, show fatty or other degenerations or 
necn>sis, but the presence of amyloid substance within their pro- 
toplasm has not been sho>vn. The substance appears as irregular 
clumps or streaks in the interstitial tissues, often compressing the 
cells and blood-vessels. It presents a glistening homogeneous a {> 
peurance. The cells usually present evidences of atrophy and 
other degenerations. In the renal glomeruli and in the Malpighian 
corjmsides of tlie spleen the a|)peaniuees are perhaps most dis- 
tinctive. Without staining, amyloitl degeneration cannot always 
be distinguished tVom other degenenitions ; indeed, not always with 
staining react iems. The substance is highly resistant to bacteria^ 
decern f>osit ion and to digestion. 

Reaeiions (see also below ).-^The gentian-violet reaction seems 
to be the most invariable. In sections of tissue iixed for micro- 
scopic study gentian -violet colors the normal tissues blue ; the 
amyloid substance is a light pink or red. lodin-green gives a 
similar red reaction. A mahogany -red react iou with Lugol^s 
solution of imlin is quite constant, but fails in the isolated amy- 
loid bodies. It is easily obtained in fresh specimens. The red 
color is changed to a blue by treating with sulphuric acid or 
chlorid of zinc. 

Seats. — In the ortler of frequency amyloid degeneration affects 
be kidney, liver, and spleen, then the larger blood-vessels, the 
itestiual mucosa, the lymph-glands, the skeleton, the adrenal 
bodies, and the heart. It rarely aflects the pulmonary mucosa, the 
bladder and gein"talia, the thyroid body, the voluntary muscles, 
and, apart from the local amyloid bodies, the nervous system or 
the integument. 

Local Amyloid Formationfl. — These occur in the nervous system, 
esi)ecially in advanced years and in scleroses, grouped about the 



blood'Vesaeb and mc»«t marked hi the |x>sterior cord and in the 
brain ; in the prof^tati^ j^Iand ; about the inflanimaton* areas ; in 
infarcts; in graniilomata, especially syphilis; and in neoplasms. 
They present themselves as small round Ixxlies which usually have 
a concentric arrangement resemblinir starch-gnuudes. They do 
not usually present tlie typii-al amyloid reactions ; often they react 
more like hyaline substance, an*! indce<l the 1> I *xxl- vessels of the 
affected part seem especially affected with hyaline change. The 
special apjiearances and reactions of the amyloid hotlies of the 
n er vou s sy stem will be d es( * ri 1 ) ei I i n co n n eet i rm with n e u ropat hology , 

Pathologic Physiology- — As state*!, aniyjfml substance 
seems to be a ctjmbinatioii of cliondratin-sulphtiric acid with a 
proteid. It is composed of hydrogen, nitrogen, carbon, and sul- 
phur, and is insoluble in wc^k alkalies. Choiidratiuic acid is 
normally present in bones, eartilagt^s, and elastic tissue. It seems 
to have been shown that an amyloid-tike suljstance exists in the 
elastic c<iat of the Vilooii- vessels — jx'rhajvs a different combination 
of ehondratioie acid. Our present k now Irdge suggests that amy- 
loid substance is not entirely abnormal, but rather an abutinnul 
combination of normal substances. It seems to result fn>m (pro- 
teid alterations incoonrction with thr palliohjgic processes already 
detiiiled. That hiirterial influences are not necessary is suggc^sted, 
th<^ugh not provt*d, by the fact that aniyluiil change has lieen pro- 
duced by long-cuntiiHied aseptic suppunition induced by turpentine 
injection. Amyhml change seerns to lye an intiltration, the con- 
stituents being deposited from the blood and assiuning their 
peculiar characters locally, for amyloid is not found jirefonued in 
the blood itself Possildy local cellular eonditious tavortlnvth- 
positirm by reason of a loss of power to dispose of the constituent 
substiinees hrouglit by tin* bhxid. Hyaline degeneration seems at 
times a preliminary stiige in the process. 

Amyloid degt^neration interftTcs with functional activity by 
pressure upon the piirenehyma and by vascular disturtjances. By 
its situation in and arnnnd the blood-vessels it nuiy occasi<»u 
thrombosis. Reul>sor]ition of nniyloid substance is possible as it 
has been know n to occur ^vhen part of tlie diseased area Ims been 
extir|Kited, Sucfi reabsorption does not, however, occur when ex- 
tensive amyloid change exists. 


Definition.-^This is a retrogrt^ssive process consisting in the 
appearance of a li<*mogeneous proteid substance of obscure* nature. 
It is closely allied to amyloid, mucoid, and colloid degeneration, 
and can certainly pass into each of them. It is also related to 
coagulation necnjsis. Tlic liyaline change of epithelium of ohhT 
authors is now by genend consent classed as a mucxnd tmusfornm- 
tion. , 



Etiology, — H3*iiline degeneration occurs under the following 
pathologic eircumstanoes : in the rauseles during infections and 

fgeptic processes und following tmtiniatisni ; in intoxications, jis by 
lead ; in interstitial hemorrhages and hematoma ; in fitrunia ; in 
eieatriet's ; in the blixxl-vessels in old age, artcrioseleroeis, or aneu- 
rysm ; in all forms of arteritis, especially of the nervous system ; 
in the emJrM'ardium and i^ardiae valves in all diseases affecting 
them ; in the grannlomata ; in neoplasms, espeeially cylindromata 
and keloids ; in the hings in [vneumoiiia ; in the kielncys in nephri- 
tis ; and in all conditions of coagiilation-ne<'rosis and tilirinoiis 
exudate in, for in thesi^ processes hyaline dcgcncnition seems tc* be 
a factor. Very jirohably the prrjccss is m>t the same in ail of these 
cases hut tlie similarity of appearam^e, staining reaction and gf^nenil 
IiitthHlogieal behavior prevents a difinite diffcn^ntiatinn. 

Pathologic Anatomy. — ^Hyaliue change is not usnally mas- 
sive enough to l>e niaenjscopicalh' a]>pre(*iahle. When so, the organ 
or tissue is cnlai'ged, dense, and presents a pale, homugcneous^ 

I opaque appearance. Ui>ou the mucous and serous membranes small 
roHections may l>e readily seen, and may present either a pseudo- 
men!l>ninous appeanince or may appear as opaque plates upon or 
beneath the surtaee. MieroH/opically there are three chief sites : 
(«) In the hhxxl- vessels, where t!ie degeneration may appear 
in the endothelium^ beneath it, between the coats and tihcrs of 
the vessel, or surrounding the vessel. The wall is thickenedj the 
Innien is narrowed < ir obliterated ; the endothelium may he in a 
state of proliferation. Pcrivasi-ular hyaline change is well seen in 
certain tumors — i-yliudromata (Fig. lo)* (h) In the interstitial 
tlgg'-ies, as between the mosele-iibei*s, the hepatir ci^lls, the renal 
tnhnles, in the retieubmi of lymph-glands, in tlie retina, and in 
neophii^ms and cicatrices. It may be uniform in distribution, but 
is more often irregularly elumped or may he in euneentric whorls. 
In tnbereulous foci the reticular fihrilhe l>eenme swivlh^n and gelat* 
inous in appearance. They may swell tn su( h a degree that the 
whole foeus has a un if irmly waxy appearance, the cells enclosed in 
the meshes meantime undergoing ctmiplete necrosis. In scleroses, 
as in the liver, the newly- form ed connective tissue may assume 
a hyaline character, the fibers being so closely packed together 
and transformed that tlic mass has a homogeneous appearance, 
(c) Within the cells. This condition is probably limited to meso- 
dermic cells. It may be seen iu nius^^le- and giaut-c^ells, and in 
endothelium, leuk'K*ytes, or wandering cells to a less degree. 
Whether the epithelial cells take part in this transtbrmation in the 
coagulation -necm sis of nuicous menibraaes and in the production 
of casts in nephritis has not been deeidrHl. It has not been pos- 
isible in the intercellular or interstitial varieties to decide whether 
the substance was ffirmed there or de|>osited there ; in the vascular 
f(»rm, and es[>eciallv in coagulation-necrosis and tibrinous exuda- 
tions, it 18 more probable that it is formed in loco, 




" Hyaline-thrombi '* cannot be distin^ished iu their appear- 
ance from hyaline masses elsewhere. Whether or not they are 

exam pies of true hyaline material Is uncertain. 

Russelfa Fiu'fmn BmU^s, — These are round b<HJies, of variable 
size, situated within or between tlie cells of epithelial tumoi^ or 
Diany normal tissues. They resemble hyaline material in api>ear- 
ance and gtainmg reactions^ especially in their affinity toward acid- 

Unstained, liyaliiie siibstimee lias a tjlistening, waxy appeaninee; 
it is less trani?lueent than aniyhnd. Typically it evinces an attiii- 


Pig. 15.— CyUndromii, showing n num i»t>! <-i blood-yessela whose willf'tiave beconi« 
converted into bynlloe materiaL 

itj" for the acid anilin-stains. Stained with van Gieson^g mixture 
of picric acid and acid fuchsin, tlie hyaline substance takes on a 
brilliant red eoh^n It may or may not tiike the fibrin-stains ; it 
often tiikes basic stains in a modified manner, Ii» truth, the 
reactions of hyaline material are very uncertain and sliiftintr : in 
many instances it can scarcely be distinguished from amyloid, and 
the change is then called hyalo-amyloid ; in other instances the 
product chjsely resembles mucin {ind the colloid substance. The 
cells of affectai parts often show fatty degeneration or other alter- 

Scats. — The locations most often aflrecte*! are the muscles, espe- 
cially the i-ecti abdominalis in typhoid or other fevers, the mucous 
membranes, the liver, kidneys, ovaries, and adrenal bodies, the 
cardiovascular system, the nervous system, the serous membrane??, 



and the retina and choroid coats of the eye. The other locations 
are suggested io the clijiriission of the etiolog}\ 

Pathologic Physiology. — Von Reck iinghaiisen believed it to 
be a coagulation of normal proteid u|Km the death of tfic cells; 
this explanation is, however, iiisiiliieient. It appears more likely 
either that it corwists of prottnd m<xlitied in hvo hy disturlx'd 
action of cells, or that it is a dejxjHition by cclhilar carriers of 
insolnble material formed elsewhere. The exact nature of the 
transformation is entirely ol>scnre ; it cannot be lield analngnus 
to the coagulation of proteids by heat ; ntir to the precipitation by 
metals or salts, i?ince in these events the protcids are not usually 
rendered permanently insoluble in water and are in *Jthcr wavs 
clearly diHerent. Hyaline material can nndoul)tcdly be recon- 
vertnl, absorbed, and removed. Its presence nirely conij>rfimises 
the jmrenchymatous structures to an extreme degree. It may be 
converted into tlie other albuminoid degenemtions, and may im- 
det^ caseation and also caleareons iutxltmtion, 


Definitioil. — Theoretical ly this is tlie conversion of cellular 
pnjtoplasm into nmcin. Mucin is a glycoproteid, which contains 
no pliosphorns, ami wliich by virtue of its carbobydmte moiety 
rc<biccs cupric snl|>hatc in alkaline solution. It is cpiite insoluble 
in water, but has itself a marked cnpa*'ity ftjr taking np water. It 
is very soluble in alkaline solutions, but is pn-i-ipitated by siitura- 
tion with most neutral salts. It is prccijiitated by acetic acid from 
solutions poor in salts ; also by heat, alcohob and many of the 
metals. It does not dialyze. Tlie secretions from different classes 
of epithelium tbfler notably among themselves, and the pathologic 
mucins differ still more. 

Etiology. — Mucoid tnmsformation slioiild be distinguished 
fnini hypersecretion of mucin. Hyjiei-secretion is a common re- 
sult of inflammation or irritatinn of all sorts j it is seen in the 
pulmonarv, gastro- intestinal and orinury mucous membmnes, in 
the glands of C'owper, the gtdl -I* bidder, the salivary glands, in the 
antrum of Higlimore, in the lachrymal glanils, and in tlie testicles. 
The product of the epithelium of tlie urinary tnict and gidbblad^ 
der, usually called mucin, is more often nucleo-albumin. Mucoid 
d^*neration in tlie strict sense occum most fretpicntl}' in mcso- 
bla^*c tissues, the abnormal substance lying between the cells. 
It is in some way connected with inflammatory prticesses, as, ajmrt 
from its occnrrence in tumors, it is found only in tissues the seat of 
inflammation. Any of the connective tissues of the body may be 
affected. Widespread myxomatous degeneration of the Bubcuta- 
Dcous tissues may be seen in myxedema. In some cases of myx- 
edema^ ^leroderma, antl the other ]>achy dermic affections, mucin 
has been extracted from the skin ; other attemj)ts in similar eases 
have failed. Neoplasms comprise the third group of mucoid plie- 



nomcDii. The imnsibrmatioii occurs id sarcomata, carcinomata, fibro- 
mata, lipmiiata, chontlroniata, and especially in the myxoraata, in 
which nuicin is the r'ssential clement, wliile in the other growths 
it is an accidental ;md occasional transforniatirin. In the epithelial 
tumors the epithelial cells thcms**lves may be affected. 

Pathologic Anatomy* — The ^ross apfK^amnces may consist 
in nothing hnt the appearance of the nniein. Up<m catarrhal 
mucmis membranes is a coat of thick, tenacious nmcns, with or 
without eonj^estion or t>thcr chanji^^s. In hMndities where the 
mucin becomes pent np it swells markedly, dilates the chambers, 
flattens the epitheliimi (which may tlun atrophy)^ and later 
Wcomes converted into a simple albuminous fluicL Huch a pro 
cess is seen in the antrum of Highmore, in C'<nvper's gland.^, in 
the salivary glands, in the gall-ldadder, in the vermiform appen- 
dix, etc.; in these cases the appearances are those of a cyst. In 
mucoid degenerations in the connective tissues the appeaniuees are 
often not characteristic of mucin ; the tissues are soft and elastic 
am! tear easily. In tumors, cysts are usually formed along with 
general nujcuid infiltration. In cystic ovarian neoplasms the pro- 
ductitm is often massive, and the substance is often peculiar in 
refusing precipitation by acetic aci*!, and has tlieretore been termed 
pstnidomucin. In myxomata the sul>stance is usually much more 

MwroHCop li " A ppea ra n et\s. — In f *a ta r r ! la 1 m u eon s membra Uf *s 
the gf»hlet-(*ells are seen in excessive t|uantity. Only in extreme 
instances is tlie pr^>eess accompanied by the death of the celL The 
cells are niu<'h swollen, and the distal end is esjiecially bulged out 
with its <lrop of mucin. There is usually a siilmjucous inflam- 
matury reaction, ami pus-cells 4'ontaining mucoid matt^rial may bt- 

seen. In the euuncctive tissues it 
is seen that the mucin lies between 
the cells and that the grouud-sul)- 
stance has <lisa(*pcared — i, i\j been 
ci inverted into mucus (Fig. 16). 
The ct*lls very ran-ly pr4\srnt mucous 
change, but arc often degenerated 
in other ways. In tumors the 
change may occur in and between 
the cells and in the form of cysts, 
whose walls nuiy or may not pre- 
sent a eclbdar lining* The blood- 
vessels are nirely affected. In all 
sitmitions mast-cclIs may be seen, 
often abundantly. 

Mucin is Inst fixed with cor- 
rt>sive suldimatc. As a rule, it 
electa basic stains. It stains only moderately witli hematoxylin, 
but very well with methylene-blue and indeed with most of the 

Fi«. Ifi — Myjcomatons dcgenenitloTi 
of (i ^urt^mii, (tliowin^ sti'llate relLs 
aopamti'd by mucoid InttrrceUulax ma- 
tL'riiil (Karjf ancl Schmorl). 



basic aiiilin-stama. Thinnin antl toliiicliii-bluo are the best staius, 
giving it II pyrple-rrd col<ir. These staining rtnictioiis htp not 
entirely distnietive, :iiul it is c»fteii iniiHissible to ditlereiitiate 
nuiooid from eplioid material, ami eveji imm liyaliue- and amyloid 

Seats^ — Of normal epitlieliai tissues the mucosa of the respi- 
raton^ and gastro-iiite?^tiiial tracts, the s^iltvary glands, and the 
nt^:»riLs are m<ist often atfeeted ; any epithelium may, however, be 
involved, Tlie connective tissues have been .sutlieicntly eonaid- 
ert*d. Of nenplaisras, ovarian cyst^j al>doiuitiid eareiiiumata, and 
nie^ioblastie tumors anywhere are most lial)le. 

Pathologic Physiology. — ^Sinee the deposition of mucin 
seemn to be exeluded, the only e.xplanation is to assume the con- 
version of other proteids into nntein. The causes antl modim 
Oj/enindi are not clear ; the fatt, ho\v*'ver, that in the ey^ts the 
mucin may be reduced to simple albumin, shows the jKjssibility 
_ of sueii transformations, 
^^b Unless the disease is very prolotigctl, atfeeted mueous inem- 
^^■branes may recover. The connective-tissue forms du not oi'them- 
I selves threaten the life of the tissue ; and the deposit is often 
I removed by reabsorption. In neoplasms the degeneration seems 
L an evidence of eell-ileath. 


Definition. — This consists in the abnormal appearance of a 
substance whose prototype is the colloid material of the thyroid 
gland. It is not precipitated by acetic acid n(*r alcohol, does not 
take up water avidly, and is therefore much like the pseudorauein 
already noted. 

Etiology.— It occurs in (r< liters and in tlryroid ueojilasms, in 
the hypophysis cerebri, in the kiilneys (some cases of contjenital 
Cfvstis), and the adrenal bn4lies, in the prostate and seminal vesicles, 
in the atrophic <rastrie ruueosa, in cysts of the lips nnd Itirynx, and 
in the cervix uteri. Colloiil traostbrmation in neoi)lasms apart 
from those of the thyroid IxKly is wry rare. Colloid may arise 
from or liecome convertetl into uuu oid materiab and stands very 
close to the hyaline sulistanee. 

Pathologic Anatomy,— iV tfected organs may be enlaro-ed, and 
tnay be lianl or i|uitr s<ilh Chi section ttic cnlluiil areas appear as 
yellowish-bnjwa transliK-ent bodies; nxrcly they are arrancre*l in 
large clumps. They may be nia*-vroscopically iiivisiiile, or, on the 
entjtrar\% may f<*rm lar^e cystic collections with thin, tiattened 
walls. Colloid de^'iiemtion may be aeeorupanied by serous trans- 
mlation^ due prolnibly to vascular distnrbnnc<'s. The serous tmns- 
tldation seems to dissoh'e the colloid material^ so that finally the 
cysts form com part luents filled with a f.*hocohite-col(ired fluid'con- 
taining pus, bltMMl, and crystals of eholestcrin, sodium chlorid, 
and calcium oxalate [Fig, 17), 



Mlerosmpieidiif the material is found in the glandular acini, in 

the cells, and in the connective tissues. There are often signs of 
pressure, and, probably from the same cause, the areas are ane- 
mic and ha\^e a poor vascular supply* The arraiigenient is 
asually in balls or whorls, homogeneous as a rule, but often with 
concentric or radiating lines. The are^is often intercommunicate, 
and extensions may he traced into the adjacent tissnes. The cells 
usually show degenerative changes, and intlanimatory reactions 
are often present. Crystals of caleiimi oxalate are common* Acid 
gtains are usually elected, as in hyaline degeneration. The indefi- 
niteness of the reactions may make it im]>ossihle to exclude hya- 
line anfl mncoid chap*j''^ 

b 17.— Colloid rlcgem*r*lkiT» of tlir Uiymir! pluti 
the gljiiini atini (Kiirj? an 

of colloid matter in 

Pathologic Physiology. — This is obscure^ hut seems to be 
anali>gous t<i that ol" mucoid change. The substance is undnubt- 
eilly jjroducecl in lotm. 

Colloid is a grave degeneration, usually connected with marked 
cellular disturbances. The substance may become hyaline or mu- 
coid, or may Ije replaced by a simple or purulent exudation. 


Definition,— *This condition consists in the presence of gly- 
cogen in cells which normally contain none, or the presence of an 
excess in cells which normally contain it, as in the liver, ciirtilagc, 
muscles^ leukocytes, in the cmliryo in all tissues, and in the uterus. 
The attempt has been nnulc to separate glycogenic infiltration 
from a glycogenic degeneration, but the conversion of proto|dasnjic 
proteid into glycogen lias never been demonstrated. 



Ktioiogy. — The condition ib not infrequent. It is seen in the 
tissues iu diabeteB, eBpecially in the kidneys, muscles, liver, and 
i circulating leukocytes^ It oi-enrs io neoplasms, espeeiiilly in 
malignant growths tri" niisohliLstie origin, btiing rare in nifist earei- 
nomata. In leukocytot^is oi" different varieties the cells may con- 
tain grannies of glycogen or a suVistance resembling glycogen, and 
similar granules may Hoat free in the ]*lasnia (see lodophilia). 
In purulent collections and in iutlammatf^ry areas the cells may be 
.markedly infiltrated. The infcctians granulomata, however, seem 
'exempt. The amylaceous bodies of the prostate arc closely allied 
to glycogen. 

Pathologic Anatomy. — Tissues rieli in glycogen may pre- 
sent a hyaline apiK'anince ; usually there are no macroscopic alter- 
lations. Mieroseopieally the material is gencnilly found \\vithin 
^the cells; it may, however, be in the inten'elliilar substance, and 
may be free in the plasma of blcxid or ttie fluid of exuilates. It 
is commonly dcjx3sited as njuud balls, which may be concentri- 
cally striated. In frft>h tissues it is soluble in water, but loses its 
solubility after fixation by alcohol, etc. 

Glycogen is stained brown by iodin, but the brown is not 
ktunied blue on the application of snlphurie acid, Ptyalin or amyl- 
E opsin convertK it into sugar, with the loss of the cxiltn-rcaction. 

The pathologic physiology is obscure. In diabetes it is 
simply an expression of the general li\7>erglyeemia. In neoplasms 
and suppurations the collections arc probably deix»sitions. 


By dropsical infiltration is meant edema of the edh, the pres- 
in cells of an excess of plasma. This does not always occur 

no. 18,— Dropeical Inflltratiuii of tht epithelial ceUsof ft carciitoina of tlie breast: a. 
ordlnmiT epUheual ceUs; h, dropsical rells; c, dropsical nuclei; d» enlarged nucIeoU 

in general dropsy^ the fluid being between the cellss and often 


cxjmpreseiDg them to a marked degree. In other instances the 
cells take up the fluid. In bums and pemphigus and in other 
iikin-lesions conne<-*t<^d with vesiculution, and in variou.s influniTua- 
tionsi of organs, edema of the cells occurs. It is also a part of the 
d^eneration termed cloudy swelling. 

The cells are enlarged, often to an extreme degree, and they 
may even burst. The protoplasm stx>ner or later becomes cloudy 
an<l often presents tlegenerative changt^s — tatty metamorpliosis in 
particnian Vacuolation is frequently observed (Fig* 18). 

The conditio in is probably a purely physical phenomenon in the 
dropsies. In tlie cutaneous lesions other factors are operative. 


Definitioii. — Calcification consists in the abnormal deposition 

in tissues of ciirthy salts. The phosphates and carbonates of cal- 
cium are the chief salts concerned, the oxalates, liowever, are often 
present ; and the corresponding magnesium salts may be mixed 
with thern. The Ijest physiologic examples are the senile change 
in the vascular apparatus and the furmation of the bniin-sand 
(acervulns cerebri). Calcification of the skeletal tissues is usually 
accomplished as a physiologic process through the activities of 
special cells ; this is an essential element in ossification. 

Etiology. — The disposition genenill}' iit-curs in diseased tis- 
sues, especially in those tiie seat of vaiseutar disortlers. Ijocal 
necrosis or fibrosis antedates intereelbihir wilcifimtion, and the 
process may bti accompanied by atnusliy and absorption of certain 
cellular elements. In neoplasms abnormal cellular conditions 
certainly predisjwse ; but here, too, the vascular riOations are of 
notable importance. Hyaline and fatly degenerations often pre- 
cede or accompany calcification. 

In mre instances no lofal priM^l is posit ions can be determined. 
Cases of this kind mx*ur in old age, antl in lliese cases it is inferred 
that, owing to inrreased llnie-resorption from the skeleton, the 
system is saturat^'d to the jioint of preripitiition (metastatic ealci- 
iiciition). Similar supersatn ration of tlie lilood with calcareous 
matter may occur in i-ases of extensive disease of bones, and may 
k'ati to widespread deposit i*>n. 

v. Kossa tound that nrrn^sive sublimate, acetate of lead, copj^^r 
salts, iodin and iwloform, ail arc capable of producing calcification 

Pathologfic Anatotny. — Early in the process no macroscopic i 
signs are apparent. On micmse^opic examination the salt8 are seen] 
as fine granules scattered through the inteFt*elbdar substance, C^dl^ 
ular infiltration, however, is not uncommon, and in such instance^ 
the cells show more or less extc»nsive nuclear and protoplasmiJ 
degenerations. By the coalescence of the granules larger, ivrvgxl 



larlv spherical bodies may be forruetL These usually have a con- 
centric arrangement (psammoma bodies)* Definite erystals are rare, 
bnt may lie ^een. The next adjacent tissne may present an opaque 
appeanince. In certain localities, especially the lilood-vessels and 
serous menibrane.s ealcareons plates are formed. The depositions 
may attain a surprising size, especially in the vessels and in neo- 
plasms. The color of the deposits is usually white^ grayish, or 
vellow ; accidental pigments may, however, prwluce discolomtions. 
On staiinuj^r the depinition taken u(» Uoth carmine an<l hematoxy- 
lin, but exhibits no elective attnirtion for the anilin dyes. The 
salts are dissolved by acids, best l>y bydrtK*hloric acid ; in the case 
of carl w nates J with evolution of carlwrnic acid gas. Many oi^nic 
and inorganic acids are em|>loyed in the decalcification of tissues 
for pur|K>ses of micros<^opic stufly. Fibrosis, cellular necroses, 
and degenerations can be demonstrated in the tissues by suitable 

Seats. — ^It is in the eardiovaseular system that the condition is 
of the most importance. It often occurs as a simple senile change, 
usually connected with an atrophy of tlie elastic tissues of the 
vessel-walls, liyaline degeneratiftn oi' the connective tissue, and 
genend hijnjsis. It is almost invariably an accompaniment of 
fielerotic endocanlitis and arterioselentsis. In the endocardium the 
valves are most frequently atlct:ted ; of the vessels^ the aorta, the 
coronary arteries, and the c<UTbral vessels. The process is, how- 
ever, often universal, and the splanchnic vessels and nidial arteries 
seem ver\' susceptible. It affects eliicfly the intima an<l media. In 
the perieanlium the ilcjMJsition is uncoinmon without the prcvions 
oocurrence of jx^ricarditis ; in adherent perieanlium the heart may 
be litem! ly enclosed in a calcified sac. In the myocardiimi ealei- 
fieation is usually interfibrillar, but may involve the fibers. Large 
collections may occur in the pituitary btKly, the meninges, and in 
the ventricular plexust-s. It is conmion in the joints, uncommon 
in the pleura, rare in the peritoneum. In the musctes hx^al for- 
mations are not mrc, and usually t)ccur at the scat of previi)us in- 
jury or irritation. In the lungs and liver it is not unusual in and 
around foei of necrosis due to various causes (tnben'nlosis, parasites, 
etc.). Cicatricial tissue often becomes calcified. In the walls of 
cysts, in the biliary and urinary bladders, in the limiting wall of 
old abscesses and hcmatnmata, in thromboses, and even in tnitaneous 
ecars calcification is a eouunon iuL'idt'ut. In the kidneys infarcts 
of these salts may be forinetl. The neoplasms most subject are 
the avascular tumors : uterine fibromata, fibromata in general, der- 
moid cysts, goiters, scirrhous caRnuomata, tumors of the pituitary 
iKMlies, and especially neoplasms involving bones or ciirtilages. 
It may, howev^er, occur in the most vascular sarcomata. The 
sjjecial term psammoma (g. r.) is applied to certain calcified 
neophLsms. Lithopedia are the ealeitied fetuses of extra-uterine 
pregnancy. Afiart from neoplasms, the most striking intracellular 


cle|msitioi)s are seen in tlie gaiigl ion-cells in area^ of softc^niiig and 
in the renal cells following certain nietiillic poLsoniii^ (mercur>^)* 
It is iiitoresting to note that tlie iotestinal epithelium, which 
normally seoreten tlje larj^er part of the lime-saltft discharged from 
the body, is rarely infiltrated by tliem. 

Pathologic Physiology. — Various views are held to ex- 
plain tile d*>pt)iiition8. An excess of tlie salts in the blood or tissue- 
liqui<ls lie rare. On the one hand, it has been assunieil that 
the soluble are converted into insoluble salts, and, on the other 
hand, that the tis^^ues liave become h\sg solvent for the salts. 
T*rol>ai>ly the best e,stal)lishetl view is that the salts are precipi- 
tated as insolulile eombi nations with proteids. 

Calcareous deiwsits are prol>ably never removed, but once 
formed remain permanently. There is no doubt that they in- 
fluence the adjacent tissues, causing degenerations* 


OB»ific4ition implies the dc^ position of linie salts anfl other clmngefl' 
tl) rough the agency of ostt-ublitstic cells. It occurs in cartilages, and in 
tumors connected with the holier*, cartilages, and periosteuuL Ossification 
of the mu^les may occar ha a local process or as a widespread and progres- 
sive disease (see Myositis OssificaoA). The salts are regularly deposited 
and are usually in maases between the cells. An accurate difft»rentiation 
from calcification can in t^ome inf*ljineea be made only by the detection of 
oflleoblasts after decaleifica^tion of the material. 


DepOfiitti of urate of sodium in the cartilages and fibrous tt^ues of joiata 
and in Tarious other ailuations occur in the cour^se of gout (see Disturbaocea 
af MetAboliam and DiBeasea of Joints)* 


According to tlie origin and variety of the pigments, piginenta- 
taons may be divided into four groups : 1, thoe-e in which the pig* 
tnent^ are derived from external sources ; 2, those derived from 
the hemoglobin ; 3, those derived from the bile ; 4, those derived 
from cellidar activity ^\^thin the organism. 

PIsrtnentation from the Exterior. 

Of the first group, those censed by entrance of foreign bodies 

through the air-passages are the most important The condition 
now generally termed pneumonokoniosiS is commonly a disease 
of occupation. Coalj iron, and stone ure the most frequent foreign 
substances irdialed- Vegetable particles, as grain-dust and textile 
fibers, and aninml hairs and furs are not uncommonly the cause of 
such pigmentations. Corresponding to the agent, there are scich 



t«rms as aiithracosis (coal-dust i%rm.'ntiition)^ sidero&iB (tron), caU 
eicosis (stone), etc. (Fig, 19). InhaltMl aiibBtiinces pmbably do not 
n^i'h tJie alveoli, but are caught hy the !)ronchial cellular cilia. 
In part they are cougliiMj u[) or otherwise cawt oil' with the bron- 
chial secretions ; in part they jienetrate tlie brtmchial walls or are 
carried by plmgocytic eel in into the snbniucosa (Fig, 20), They 
may beeonie deposited jo the latter situation, or may be earried in 
the lymphatic cin^ulation to tlie peribronchial and mediastinal 
glands, the fibrous tissue of the lung, or the siibpleural tissues. In 
rare instances the pigment finally readies tlu' general tnreulation, 
following whicli it is deposited largely in tht* spleen, liver, intes- 
tinal mucosa, and kidneys. In these eases the mucous niembrane^j 
from the lips downwanl may be more or less pigmented. 

Fte. If.— TutjercuXoiiu of the lutig, Ktiuwiu^ auihruootic (^iginoutiitfoiii in tlie lower paft. 

Pigmentation thmugli the alimentary tract is be^t illustrated by 
argyria fnllowing the excessive ingestion of soluble salts of 
silver. The defwjsitions seem to consist of a redueeil form of a 
tilver albuminate. In the skin the pigment lies directly under the 
epithelial layer, betv^'een the cells, aud in the intercellular tissue 
and lymph -spaces. The gastric and intestinal walls ar<? deeply 
affected. The liver and kidneys are usually in vol veil ; in the 
former the deposition is prriportal, in the latter the glomeruli and 
the corticomedullary boimdary contain the pigment; in both the 
t^lls are free. Among the nirer sites are the choroid plexus, the 


text-book: of patholooy. 

various glaodg of the body, and the walls of the blood ves- 


Fio. 20.— PhEecKrTtic celli of tlic brnncbf^t secretion (Bpiittiiii) cotiUinitif bUck Mrtictes 
of dust ana carbon ; the celk on (he right are tUilncia wllh mctbylene^lue (JaVob). 

Pigmeiitation Ijv ciitiineous absorption iipart fnnii tattot>in|^ is 
problematical ; it lias been alleged to ix-eiir in \v(irkers in copjH*r. 

I1ematogen0us Pigmentation. 

This (?imeerns the deposition of pigments (lerived from the 
hcnio^hjbin, of whieh there are two groups, the Mtderous and tlie 
non-side pons. The ehief siderous pigment is liemosidenti, whieh 
lias, liowever, many moilifieations ; the non-siderous pigments ai^ 
derivatives of heniatin^heniatoidin, liemofusein, melanin, etc. 
In the eoui^e of time the siderous pigments may lose* their imn. 
F'robably all formation and further ehd)<jnition of these pigments 
are the result of specifie eellular uetivities. Two groups of lienia- 
togenous pigmentations may l>e *listinguished» (1 ) those in wliieh 
the heinolytie agents aet in the rireuhiting blood c*r tlie assiteiated 
organs, and (2) those in wlvieh the reduetiuns cKrur In Itveal tissu^^s, 

(1) To the first group belong the general hemolyses. In prr- 
nicious anemia and leukemia, in malaria, in severe eaeliexias, in 
occasional infeeti^ms and septic pnx^esses, in poistmings (as by pyro- 
galli<* aeid, chlorates, arseniurctted hydrogen, by some molhisks, 
by pyritlin and toluylendianiin, etc.), the hemoglobin is set free in 
the circulation* It is promptly excreted by the kidneys, and to a 
limited extent by the intestines ; mneh is converte<l into bile in 
the liver, mnw little passing into the bile unchanged. A certain 
amount is rediu'ed i)y the tissues (ap}xirently l)y the liver) to the 
two beforc^-mentionetl series of ]>ignu^uts, wfiich are then carried in 
the lympliatie and vaseuhir circulation and by means of celluhir 
carriei-s and deposit(*d in various j>laees. As time passes, these 
pigments seem to become nuhiccd, the iron being excreted l>y the 
intestine and the rcmainilt r by the kidneys as urobilin. In the 



liver the depositions are largely in the periphery of the lobule; in 
the spleen » in the ref^ions <if the fivllieles : in tlie kidney the tnost 
marked a>i lections are in untl ahout tbe glomenili and the tubules. 
In all tissues the tlejKisitioiis are both intereellnlar and intraeelhilar ; 
the cells may cither take up pigment *>r have it deposited in ihenu 

Heinochromaiosts, — Von Recklinghausen first described under 
this name a condition in which imn-contatning pigment is de- 
positeil in the epithetia of the abdominal glands, especially the 
liver and pmcreais, and iron- free pigment in the smooth-nmscle- 
fi bers of the intestines, and the walls of bhHxl-vess*:'^ and lymph- 
vessels, as well as in connective tissues. He found cirrhosis of 
the aflFected organs associated with the pigmentation. Later a 
form of wide-spreail pigmentation of the same diameter and in- 
volving the structures named, as well as other org:ins, antl notfil)ly 
the skin, and attendefl with glycosuria, was deserilied by French 
writers under the name of diubNe bronzS, In this condition there 
is pronounced elrrliosis of the liver and pancreas* and the diabetic 
ass4i<^jation is attributed to the invfilvement of the latter organ. 
Cases without piincreatic cirrhosis of a eertiun grade or kind are 
unattended with iliabetes. 

Alcoholism, cachexia, and suppositious toxemias of other sorts 

,— Pbagocytic ceUa of the spiitnm crontaJnltig blood -pigment, from & case of cardtao 
coDgi'Stioii of the Umip M^1t(>t)). 

have been regar^led as of etiologie impfjrtance. The pigment is 
certainly of hematogenous origin. The deposits in the cells cause 
degeneration and death of the latter, and eimsequential cirrhosis. 

The appeanince of organs with marketl hematogenons pig- 
meDtatioD varies with the variety and stage. A rusty -re<l color 
is the usual early apjiearance ; later a brown, then a greenish, color 
may l^ie pro<lucfMl^ and finally a dark Idackii^h-lmnvn. Tlie associa- 
tion of Jaundice, whieb is common, alters appearances verv^ much. 

(2) The two <'hief eaiisrs of iocaf pkpntnittfioit are thrombosis and 
interstitial hemorrhage and coagulation. The pigmentations .seen 
io the indurations resulting from pnjlonged venous stagnations and 


eongeistions are probably of analogous origin* Uu*If*r these cir- 
tnimstaiit-os the hemoglobin is tlift'iistnl from the blood-eells, and a 
ixirtioii passes tlirertty riito the plasniutic t^ireidatioii and isearrietl 
away to he eliminated ; soon, however, the area heeomes walled 
off antl the two sets of pigments are then formed wtthiiu Tlie 
siderons pigments are most frequently seen in small lesion.s ami at 
the periphery nf large ecehynioses ; the hematoidin series is mowt 
prevalent within the cystic eontents. The pigments change in 
color (the color-i'hanges in a bruise are due to this), and finally 
become a brownish amorjjhoiis matter, which in turn d(sapi>ears. 
Phagocytic cells take up all forms of the pigments (Fig. 21), and 
earr\^ them to various parts of the body, especially to the liver, 
hematopoietic organs, intestines, and glands; the depositions in 
them are know^n as pif/menl'mtiadanai. 


Fia. 22.-'R€'miitoldin crysttals from an uld heraorrbagic focu« (Jftkob). 

The distinctive reactions of the various pigment.s are not well _ 
known. Of hematiu and liemin it is known that they are insohi- ■ 
ble in water, alcohol, and ether; sliglitly soluble in weak accti<T 
and mineral aeids ; easily niluble in ehlor«»form and in weak alka- 
lies, ihtm which solution they are precipitatLHi on the addition of 
linje- or baryta- water. Hematoidin ditters fnuu these in being 
gijmewhat soluble in ether, but ins^dnble in weak acetic acid, ami 
gives with strtnig nitric acid the sjxH^tral play of colors. Apart 
from tlie iron reactions little is known of hemosiderin. The ir<jn 
is best demtuist rated by it.s eonvei'sion into the sulphid by means 
of ammonium sulpliid, or by the Frnssian-l)lue reaction with weak 
hydr«>eiiloric acid mul (votassium ferrocyanid* 

Mivt'oscojumfly hematogcnons pigment presents three chief 
appearances ; small needles, rhond)ic crystals, and amorphous 
masses or tine balls clum|X"d together (Fig, 22). The first two 
frirms are veiy rarely peen within cells, the last forni commonly. 
The colors vary from a pink-red to a deep rubin, from pale yellow- 
green to a deep br*iwn or absolute black. 



H e patogetious Pi g me n tot ion . 

Pigmentations derived from the bile are due to hilirninn (iso- 
meric with hc^matoidhi) and its oxidation-product, biliverdin. As 
will be elsewhere exphiined in detiiil, all jaundice is now held to 
l>e of hepatic origin ; so far as know n» only the hejKitic and renal 
cells can pnxluce l*ilirul>in from in'matin. 

The de[>osition of these pi^^mients may be either in solution in 
the tissues, in granular precipifations, or in en^stals (needles and 
rhrvndnc plates). The cerehnil substance alone seems never, ex- 
cept in the new-he >rn, in lie pitrnieoted. The liver, skin, mucous 
menilimues, the endarteriutn and other serous memliranes, and the 
glanduhir and tatty tissues are especially susceptible. The color 
is first yellow antl gradually tlecpens to a dee[) olive, tlie urine 
prei*eiitmg simihir transitions. The lachrymal and salivary glands, 
the mammsc, and the intestinal mne(js;i seem to be alile to keep the 
pigment from pissing out with their secretions* The ocular tin ids 
are coloreiL 

The pigment in sidution satumtes the tissues^ Tlie graiudar 
pigments, yellow, liruvvn^ vr greenish in color^ may l>e seen in the 
cells or in the interstitial tissues ; the ciystals, yellow or red in 
color, are usuidly extracellular. The pigment displays the spec- 
tral play of e(jlyrs on cfuitaet with strong nitric acid, and is turned 
green by weak tincture «if iodin, 

A special iVirm of deposition is the hilirnbin-intarct in the uri- 
nary tubules. These are s(*en in severe janntlice of the new-honi, 
but niay occur m deep ic terns of adults, us in a^jute yellow atrophy. 

Meta bol ic Pi ^me n tat Ion . 

The pigmentation derived inmi eellidar activity may be prop- 
erly termed metabiilic* We know isolate^l facts abnut tht' differ* 
cot forms, but there is little syslematie fnndanicutal knowledge. 
Two facts, however, seem clear : tliat thesi' pigments are formed 
by migratory and resident pigruent-buihling cells, which with 
leukocytes and plasma-rells accomplish the transportation and 
deposition of the pigments ; and that hemoglobin is in some way 
or other tlie mw matcriiil for tht ir manufacture, witli, pf^rliaps, 
the exception of some pigments in melanosarcuma, wlii(4i sei'm 
derived from protcids. 

The manifestations may be lo<*al or g4'neral, Aint^ng the former 
are the pigmentations oi' nevi and moh»s, of pregnancy, of the 
corpus luteum, freckles, some scars, certain skiiMliseases, as chlo* 
asmu and xanthelasma, of the lesions sec^aidary U> some cutaneous 
fKii- ^\ A special local type is that seen in tumors, notablv 

in III ircouiala. Li|Mimata and sarcomata (chloroniata) may 

be analogously atfeeted. 

Among the general pigmentations are those of Addison's tlisease, 
of certain severe anemias and cachexias, of tuhereulosis of the 
peritoneum, intestines^ and retroperitoneal glands, of abdominal 



neopla^tn^, and of senility. The cases associated with ahJuniiual 
leoons are held ti> be eonneote<l with distiirbances of the adrenal 
bodies or of the sjyhmelinie sym pathetic system, which lias been 
considered to have control of pigment -format ions. 

The nietaholic pigments an* very varied, and a detfiiled diseii^- 
«on of them liere won Id be mipmfitahle. They may have a hipfh 
pepcenta^ *if .^ulplnir, and may or mtiy not eontain iron. They 
wre: comtnonly dejxisited in and between the eells as grannies, but 
may be erj-stalline. lliey do not give a play of colors with nitric 
licid, and have varying .solnlnlity. 


Definition. — Necrosis may be defined as the death of tissues. 
The death uf individual eells is termed m'crobioHh ; death of tissue 
en masse ^ usually accompanied by putrefactive changes, constitutes 

Btiology.^All ela'^ses of cellular death may be brought un- 
der fotU" etiolugic gn>ups : 1, those due to nutritional and eireula- 
U)ry disturbances ; 2, those due to trophic disturbances ; -3, those 
due to |M>is<jn.H — animal, vegetid>le, bacterial, and inorganic ; and, 
4, those due to traumatism, employing the term in it*^ broadest 
sen*^*. It lias been attempted, without success in our opinion, to 
cloiiS the tropliic necmst*s as identical with those due to circulatory 
and lujtritional disturbances ; similarly the poisous and traumatism 
have b{^u eonsidere*! as acting only through the eirctdatory and 
nutritional paths, but it seems evident that in the light of our present 
knowledge the lour groups are to a greater or less degree distinct. 
The various causes do not produce eonst-int types of necrosis^ 
but oc<»iision one form in some eases, another in other c:iscs. Prom- 
inent among thes^i varying eircnira stances are tlie native health of 
tlie ti^ueft and their vital resistance, the circulatory relations of the 
part involved, the activity and duration of the causid agents the 
age of the subject, the presence of other diseases, the temperature 
of the ttifiueH, etc. It will therefore be better first to consider col- 
li*cti%*ely the caases of necrosis, and subsetpicntly detail the varieties 
of it. There can be no doubt, however, that in the direct forms 
of Q49cromi the reetiltA are Uj a marked extent individual to the 
agent; for example, cells kilh'd by the action of acids, alkalies, 
and metallic halu present ap[X'arances quite characteristic of each. 
OiiciiIaUny DerangementSa — The circulutory disturbances in- 
iude many eondi lions. Acute and chronic ischemia, however 
ifodiiced — by emlKilism, throml>osis, arteriosclerosis and atheroma, 
by extra-art/'rial presmirf*, by cardiac weakness, or by arterial 
ppaum, aii in liaynaudV disease and perhaps in ergotism^ — are im- 
pirtant conditional. Venous stagnations are respon^hle for many 
iBi^tanc4>K. Actual fnkmh due to mechanical obstructions and such 
puhsfiningA wi prodaoc c<xigulaticjns is a rare cause. Heat and 
cold act partly by drculatory disturbances^ Among the geoezal 



ilisoi-clers of circulatiuu and uutritiuii iimy lie iiieiitiouLMl tbt* 
aneoiias, tlie cachexias, senility, arnl certain metaljolic diseases, 
snvh iL« (Ualjetes. In these conditions tliere is nmrli piv>l»al>ility 
that poison iujir l»y tuetaholie priKJurt^ plays an iniportjuit part. 

Trophic Berangements.— Forms vf nurrosis due to trophie dis- 
turbances are well illiistrute<l Ijy bedsores (deeubitUB), myelitic 
i'vstitis, the ulcerations seen in trigeaiinal neuritis, and the 
arthnipathies. These forms nt' »-ell-deatii cininot be bnaii^ht under 
the eireulatory, toxic, or iraniuulii' t-la'^^iticatiou. ^Fhev can Ije 
explained only by tlie asstun[»tit*n that the biologic nieebanisni of 
the cell is disturbed, and that in eoiis(Mpieiice deatii tx*curs. 

Intoxications.— Th(* g'''*'4* ^lue to poisons is very extensive 
and the paitieuhir subdiv^isions numerous. The toxins of bacteria 
furnish many examples of direct necrosis, and act indirectly in 
cases which 8<?em circulatory or traumatic, tliough they are not 
really so, mucc these factors ordy lower the resistance of tissues, 
which then liecome siisceptible to bacterial iufection. Experi- 
mentally tlic most excpiisite forms of cell-degeneratious and necrosis 
can be ]u*oduced by tlic injection of toxins or analoircais substances 
like ricin au<l abrin. The alkaloids possess nuirked power in the 
pr<Klnction of necrosis. Acids, alkalies, metallic salt^, and innumer- 
able otlicr chemical substances may prfwluce direct necrosis, or indi- 
rect nei^msis ijy the preliminary |*ryduetion of dcLrc iKTations. The 
siime substances often cause liotb circulatory and mechanical di.s- 
turbances, which augment their direct ejects. Heat and coM act 
like chemicals; heat alters the pnjperties of prott ids ; ctdd affects 
the fluids rather than tiie pnftoplasmic substances; both also 
induce marked circulat<iry disturbanrcs. 

Mechanical Agents. — The nieclianical causes of necrosi.s are 
many and varied. Pressure per se may cause the deaHj of cells, 
hut is often aided by the circulatory disturl)ances which it occa- 
sions. Tliat tension causes necrosis is an old surgical truth, well 
iUiLstratetl by tlie results of collections of exudates below the peri- 
osteum ami l)y tlie resnUs u( strangulations. The j pressure of cal- 
culi, eoncretioiis, enteroliths, and exo-^toscs may cause ini|K>rtant 
necrotic processes, Cirt*ulatory disturbances often arc a vevy active 
fact^jr — indeed, many forms of tmumatisjnact solely through them. 

Inflammation, whatever its cmginal inception, may become so 
extreme as to lead to necrosis. Necrosisj on the other hand, often 
leads to inflammation, the dead cells constituting the primary irri- 

All forms of necrosis are accompanied to a greater or less 
extent hy the various degenerations. In particular the cellular 
alti^mtions are constantly present, and constitute the eviilences of 
morbific action. (Reference will be made below^ to tlie cellular 

There are several general forms of necrosis which, however 



proclu<^«Hl, have a siiffieifiitly clistinet pluimcter to warrant separate 
<lpR*riptioiis. They are f<wuriilati*»u-iie€T(wis, liiiuetaction-necrosis, 
frag^atiou^ fat-neerosLs, ijeiufilysis, and gangre^De, 


I>efifiitiotl. — This i.s ilcfiiied as that tbrm of death of tissue 
in which tfie pmtoid sutlers a change similar to or ideotical with 
coaofulation. It is seen only in those tissues which are rich in 
proteids. The prtjcess is partly at least a siK*eies of fibrin-forma- 
tion, and is allied to hyaline defeneration. 

etiology. — The causes of this condition are those alx»ve de- 



jxtreme periphery of ihc ilinstmUoa 

tailrjfi for fjeen>rtiH in ^nerah Cireulator}* distnrlianees, ext^pl 
ti§rttm\t*tniH or inJiiretions, play ii mini»r ntle here, Chemicail irri- 
fiit«l hi^h tcni|M'rutures frec|iiently produce it- BaeC^ml 


0imtiP» are very pixjiie to produce it, especially thi^se elaborated 
Uy flic pyo^feiii*' Iwctcria, the tubercle bacilhis, ami the Bacillus 
mytfilHrriiK. Aliout every abscess is IIiuikI inert* or IfSB Cfn^ula- 
iimMfet'timin ; it is one oi* the early changt.'S in tubeides and the 
frrfylnrrMiitu) elenif nt in tk- pn^thietion of pscuckniieBlbnMflu AH 
- • r f Tf/-^ mvl trjiiLHUiktcs are liaJile to coagulatioo. 

««rrifii4 and mucous membranes arc most $ysnr{idl4e; next 

i-Hijcs /nflien the myot^rdiuniK 

r Anatomy. — ^The tis^ie baf« a ghanl, opaqiae^ 

.1', and is firuier and paler thatl tmnmL Im blw 

«i„ ,r Ixjcumcs ^ ray and tJje tissmf inclttKS lo soAfa. 

J4, it in H*fcn that there is an exiKiatr ^hkh has beco 

,. is; fibrin is seen (with suitable ^tains> ui 

ltd fiiirils. In addition to thr 6hnm liw» ij 

,r i«fwm hooKi^encous matter (fibri»oid\ mhkh dot^ M 





s like fibrin, but which i.s neverthelesja closely allied to that 
substance. TIjc cells soon lose their ch ctioii for stains (Fig. 23), 
Early in the piYice«i8 the niiclcj miiy stain liiintly and present a 
homogeneous appenmnee ; later the cell disintegrates completely 
(Fig. 24). In muscles the st nations disappear ; and in the car- 
diac musf'le the intereellnlar ceraent-suhstanee j^eenis to be dis- 
solved, for tlie cells often lie separated and present vacnolation 
and fragmentation. I'us, lenkoeytes, and rvd hlmMl-cells in tlic 
affecteiJ areas all suffer the fate of tlie fixed tissne. The blood- 
vejkscls at the margin of the area are seen to l»e thromboi^ed. In 
the kidneys the tulades may eontiiin lirm casts. 

Morbid Physiology, — Many ehcmicids cause coagulation by 
direct action. In the larger nnmber of instances, Iiowever, it 
mubt be assnnied that the tibrinetgenetie substances vvhieb bring 
ab<iut the coagulation of the protcids an* dtrivinl troin ihe necrcH 
biotie cells in the area or are carried thither by the lymphatic 

ft ^ — CoAguUtlon necrcffiifl of the heymtic veUn in a cnae i>f piifrperal eclAmpelA 
iKarg utid SchiiiiiriL 

wIU. There is considerable evidence that bacterial products may 
ai't fibrinogeneticaliy. It has l»een contcutiiMl that coagulation 
Dtvrosis is simply a s{>ecies of inspissation of the tissues. This 
is eertiiioly not the cuse. 

An arcii of ciKigulatiMn may be east off by the )>roecss of oleer- 
ation, may undergo litpictaetinn, caseation, or suppuration, may be 
^cysteil, and apparently may l>c dissolved and reabsfjrl»ed. The 
arr-a of disease* may finally be converted into sear-tissue by 
s€iH>udary regeneration, More or less complete lusis of function 
nsulti» from this tbrni of necrosis. 


Definition. — This change e(*nsists in the <leath of tissue with 
t*«>llit|Uati<>n. It may be divided into priimiry and seeoiidan^ 
forms. St»condary litjUefaetif m-neerosis is the furm in which other 
viiriotu... i.r !nxTOsiia or degeneration are followed by li(|uefaetion. 



ThtiBi areas of coagulutiwo'tiecrosiis, elieesy necrosis*, and of iuflain- 
niation^ jran^retioiis tissu«% \uv\ tumors may boeome liquefied, 

AmoiJ|^ the .s|M'i"ial tiiruis may lie iiiciiMoiicfl vcsiele-forniation 
and the softeninc: of caseous tubeivulous h>iims. A very fr<'r|iient| 
seat of liqiiefactioii-iieerosis is tlie cn-iitral iiri'vous systt^iii, where 
the conditions are nufiivorable to eoji^ulatitrn, so that li<|uefartion 
here follows patliolcjgie conditions whieb would elsewhere proiliiee 
coagulation. Cinnilutory disturbances, traumatism, antl intoxica- 
tions all cause softening in tlic ecutral nervous system: tlie 
peripheral nerves are mneb less susceptible, 

Patholoiic Anatomy,— In the early stages the tissue is 
softer than nrtrmal and very rich in juices. Later, when the s<.)lu- 
tion of t lie fibrillar tissues is advanced, the area beeoines tilled witli a 
liquid of greater ur less consistency, d« pending npon the tissue in- 
volved. The cells hi the area arc seen in all stages *jf tlegcueration ; 
later, not iiing but detritus is visible. In some instances, instead of 
becoming more and inure tlnid/tbe ex lulate undergoes cuagnlatiou. 
The color may ix^ white, from tlie presence of an enudsion of fats; 
yellow, from tats and jjigiuents ; red and hrown, from the pivsence 
of blooil-pigment , and<leeply colored when jaundice is associated. 
The pnK'css consists in the infiltration of fluid into tis^nnes and 
the more or less coni|)lete suliUion (*f the tissue-c^lements in it. 
It haj» been compfired to the altenUiMUs of pi*oteids by digestion— 
a reasonable deduction, since enzymes are 
often elal>orated in the processes which give 
rise to liquefaction. In other res]iects the 
process resemldes the solution in distilled 
water of proteids precipitated by salt so- 

Areas of liquefaction may diseharpi 
their eou tents, may cuagnlate, nuiy be re* 
absorbed, encysted, or in uncommon in- 
stances organized. 


Caseation is the cnide name applied to 
a e^implex process whose prtxliict has a 
cfieese-Iike ap]>earanee (Fig. 25). 

Tlie condition is most frequently seen , 
in connection with tuberculosis^ although ^ 
it is found in the other gmnulomata, and 
als> in other pathologic processes. The 
preliminary eomtiiio sine tpta non of casea- 
tion is eoagidation-necrosis. 

The early tnliercle, lK?fore the oeear- 

renee of softening, has an appi\irance like 

le*- homi^treneuus and more i^ranidar (Fii:. 



26). A form of ciiseatiun qiuto similar in api>t'ii ranee occurs in 
pneumonia^ in tumor,^, an*! Lspfcially in i^yphilis. Soft caseation 
is iisnally rMmgiilatioiv-nccropis iidvaiict'il to liquefaction, tngctlier 
witli fatty mcUiniorjiliosis, so that the apiiearanccs arc thos^ of 
stiit, creamy cliecsc. The liquctaetiou-neerosis of tlic ecntnil ner- 
vous sviilem may present similar a pf»ea ranees. 

Microscopically, the tissues in caseation show no cells present- 
ing their staining-reactions ; everyllnng is converted into debris. 
Arornid the afleeted an^a is nsnally foun*l a zone of eoagnlatiou, of 
intiiuimiation, or hotli. 

Fig 2es»— l^rge tubercle 6f xhv Iniiir, .show i tig chce»y uccrogJ*. 

Tis&ncs that have undergone caseation may be east off, reab- 
80rbe*l, or encystetl ; n.*sohition is not passible. Calcification is a 
frequent termination. 


This term is now used to designate a peculiar tyjw of necrosis 
to which the fatty tissues are subject, iind is distinct from ordinary 
fatty metaniorpbosis. In human brings it is seen abuost exelu- 
f^ively in the atKlonicn, alKlominal walls, and subperitoneal fat. 
In nearly all instances it appears in connection with paucreatic 
disease — cysts, tumors, {»bstruetiou to the duct, and the various 
fonoj* of acute pancreatitis. In rare instances the ptmereas has 
not seemed es|iecially diseased. In one ease I ha\"e seen of hypcr- 
tTophic cirrliosis of the liver the omentum was affected, while the 
{lanerea^s showed notliing liut a m*)derate degree of fibrosis. 

Tlie atfected areas arc white in color, usually not larger than a 
pea; they may be st>ft or cpiite gritty, luflanmiatory reaction 
may or may not surmund them. On microscopie examinati<m 
cry&talss of tlic fatty acids may be seen together with more abun- 


dant crystals of a ooiubinatioii of liaie with the fatty aeids. Thij^ 
oomhiimtian, it a|)pears, is not a primary feature in the necrosis, 
6Ugge-.ti ng that the fatty acids are first set free and then uuUe 
with lime-salt?^. In experimental work by Hildehnin<l, VV'iUianis, 
and Flexner it seeing to have been sliown that tlie ty|>ical condi- 
tion may be the result of direct action af the fat-splitting ferment 
of tlie pjiijcreatie secretion. It is cert;iin» however, that in sorue 
cases of pancn^atic cysts containing sttiaps^in no fat-necrosis has 
occurrech Iketi-ria have been stip(>osed by some to be the essen- 
tial agents caijsing tbe change, but this has not been demoustrati^d. 

ih (rideon Wrils, after quite extensive experiments on animals, 
states that fat necrosis is merely a special form of necrosis of fat 
tissue dilfering fmm tlie simple necrosis chiefly m the sharp limi- 
tation of the affected area, nsnally by a wall of leukocytes and 
hiter by connective tissue; and the filling of the necrosed cells by 
the prodnctvS of fat splitting. 

It seems to be due to the action of one of the ferments of the 
pant^reatic juicCj raoal probal>ly lipase fsteapsin). As this ferment 
cannot be isolated absolute proof is wanting. It may be that the 
lifKise causes tlie fat splitting after some otiier ingn-dient of the 
pancreatic secretion lias injured the celL 

Lipase acting on the fat rolls splits up their coutained fat into 
glycerine and tatty acids. Glycerine diffuses leaving beliind the 
fatty acids. Tljc cells lieeome n(^er*>tic and (n*entually the fatty 
acids combine with calcium salts and are precipitated wlnlc a ir*av 
growth of connective tissue encapsulates the area and diminislies 
its size. 

Dissemination of fat necrosis outside of the alnlmuiual cavity 
has l>een observcil as early as twelve hours after intniivritoui^al 
injection in animals, the route of spreading being probably liy the 

The suggestion made at one time that bacteria might be the 
cause of fiit necrosis has been entirely given up at the present time. 


Hemolysis, or bhxxl-dest ruction, is a term lijuitHl to the red 
cells, and indicates destruction of the cell with disjK^rsiou of its 
hetuoglol>in. (The caiLses and other features are describt^ under 
Pigmentations and Di.sctuses of tlie Blood.) 


Definition,— Gangrene, furuicrly defim^l as the death of tie 
sue en mame^ is [jerhaps Ix^st detiue<l as the putrefaction of area 
of necrosis. It may be prima n/, when a particular bacteriui 
produces a gangrenous inflammation as its dirtn't result, as in 
malignant edema ; or secorviary^ when saprophytic bacteria dec«jra- 



n area alroLulv iircnxseil froru utluT eaii?5es. It may he dry 
f'^ohfy according to the hx'ation and sui>ply of fluids. It may 
furthermore S>e eircHtiutcribed^ progremve, or mdaMatic, 

Primary gangrene constitutps a specific aifectionv or nUlier a 
nimiher of sixritk: aHet^tions. Malignant edema, infectious em- 
physema, and H^me farms of antli rax may he included in this 
gmup. In thetS4-^ conditioos there i.s violent iiifccti%^e iuflammatioo 
with practically immediate g-angretie of the affeetitl parts. 

Secondary ganp'ene is niore common, and theapiM^araueeaare verj' 
varied. The essential conrlition is putrefaction of a necrosed area. 

Dry gangrene is usually tine to vascular disturljanccs. As a 
result of arterial obstruction it is seen in the cxtivniities in senility, 
and foHowiu^ arterial emholism or tliitjinljosis of whatsoever nature 
if the collateral circulation 1m* iiisutticient to nourish the part. 
Freezing may proiluce a dry form of gangrene, the vessels Ijeing 
blocked by thrombosis. Ergotism causes dry gimgrene as a rule ; 
the same may be stiid of IJayiraiaFs disens*'. Finally, dry gan- 
grene may result from tlie moist form when pTitreiactioii is slow 
and evaj)^>ration of the tin ids oc(^ui>i. The putrefiictivc proc-esses 
in the dry ty[ie arc luit marktd, and may cease entirely. Di'v gan- 
grene is generally circuniscrilxHj, and tlie end-result of a tyiiieal 
case is mummitieatioiL The color is usually dark, finally black; 
earlv it may \}e yellow nr Iutjwu ; rarely, the tissues are very pale. 
There is little toxic absorption in these cases. 

Moist gangrene presents numerous varieties. It is mrcly pro- 
duced by arterial ucclusiun, liut is the usual result of extensive 
venous occlusitm. Internal emboli, as in the pulmonary arteries 
or veiiLs or mesenteric arteries, not infrequently i^iuse gsingrene of 
this form* It al.'^> CM^nirs in the huigs as a result of inspirational 
or other pneumonias, abscess, neoplasms, Ijronchieetasis, and in 
dial)etes. It is seen as a result of trauuuitism and pressmv in 
severe contusions (t'l-^pxially with vascular injuries), in intussus- 
ception and strangulation of the l>owel j as a result of ttjrsioii in 
movable kidneys, splccnsj or tumors. It is frequcait in the ob- 
structed or strangulated vermiform appendix. Extensive moist 
gangrene of the extremities (^r other parts is not mre in connec- 
tion %vith dialx^tcs. The mucous membranes may become gan- 
grenoiLs a.s a result of various infections. A particular form is 
noma of the mouth and genitalia. It is seen its a rare condition 
in certain skin-diseases; an<l is not unusual in severe troplue 
Wtons, as decul>itus, cystitis, mal jM.'rfbraut, etc. 

In moist g^ingrtiie the consistency of the part beeomes progi'es- 
rively softer. There nuiy Iw local or widespreat! emphysema. 
The color is usually tlnrk brown, due to disorganized bltHxl-pig- 
nient ; tlie skin commonly beeomes black, and is covered with 
blebs. j\bout the arc^ tliere may be a zone of coagulation-necro- 
9JI with vascular thrombosis ; or a zone of intlanimatory reaction 



which will prtwhiw n line of *lemurkatiini. In souie cases^ espe- 
cially the *luilx'tk% iieithiT of tlwi^^ zcines is formed* 

Tho c<'lls tirst iiJUK't'iioilK Tht.^ t>rotO|iliisni aiul mirlei exhibit 
various fvicii-nces of di generation , tlie iinch^i disappearing and 
the cells becoming txtnvertetl into ^^rannlar detritus, F*at und the 
ni veil n- sheaths of nerve-hliei's iire n-duced to free fat and fatty 
cn^tals. Tlie nnisc^Ie-eells loi?<? their striations and beeome frag- 
mented ; the axis-eyUndei's of nervei^ tibriHate, Hemorrhages into 
the area are eomniuii, due eitljer to ero?^ion of vesisi'ls and expidtion 
of their thnjmbi by the preKsnreof tlie bkKxI-eurrent, or to a genu- 
ine hemorrhagic eon<btion the rcsnlt of toxemia, Conneetive tissue 
and elastic fibers resist longer than the cells, but finally become 
liquetieiL The affeet^'d area contains crystals of pigment, tatty 
acids^ cholestcrin, Icucin, tyrfjsin, plioisphatcs, and carljonates. 
Ammonia, the ialty acids, itulol and skatol, amins, sylphiirettcd 
Iiydi'ogen, carboiuc acid, and other giises, usually of pronounced 
cnlor, are formed » There is more or less toxic absorption from 
tliesc areas* 

Bnt two things can hnjypcn to an area of gangrene ; it may 
|>n:>gress and cause tlic death of the individnal^or may become cir* 
cumseribed. In dry gangrene and in tlie vascular forms of moist 
giingrene limitation is the rule; the other moist fonns tend to be 
pnigressive. In the «'ircuniseril>ed fi>rm a line of dcmnreation is 
(orined by inHammatory reaction* and the mass is^ finally east off 
as a Mphaeelus or j^loiigh if the art^a be super fieiai, or encysted if 
tlie ar'ea be intcrnaL The latter casc8 may be tbilowed by real> 
eorptioti of the contents ami calcification of the sac. 


TIr* cell a^ aa individual element is liable to pathologic processes of 
varioaa k'uuU that tuc^it brief cuiisideratiou, apart from definite fonm of 
tijwueHle^'etjeratidii aad aecrofiis. 

Etiology. ~Tli*i emise^H of cellular degeneration and necrosis are numer- 
oui*, iaclydjiig inecUanical. tberiual, electrical, chemical, and vital (trophicj 
in fit* en COM of various kinds. It is easy to demonstrate the influence of 
some of these caune** in the unicellular organisms such as amebte, and the 
changes tliUH produced may also be seen under proper conditions in the 
cellf* of the animal body, 

Fathalog'lc Anatomy.— The cell as a whole may show various forms of 
d Ik torn on, or in tern at dmnge. I nt" reaped irritability and mobiiitj' of the 
protoplasm cause the projection of psetidopodia, and these may be separated 
from the boily of tiie cell as rounded particles mure or less resembling the 
original celb This is eiwily demonstrable in red blood-corpuscles sub- 
jected to Jieat. Hiumetimes particles are discharged lTf>m the cell and 
varmdation^* kxpuUion- vacuoles J rei^uU. Certain influence^ like cold and 
mtlaliic walta or other poisons, cause a reduced mobility and general con- 
traction r»f the cell. 




L Karyorrhexis. 

H, Degeneration of tlte Cell Membrane (chromatolysis). 
fK Budding of the Cell ileoibrane, 
c. Pvkno^ii!-* 

a. Degeneration of the cell meoibrane is a regular phenomenon 
of gradual physiological eeli destruction as in the ovary, 
testis, epitheiia^ etc. The membrane thickens (hyper- 
fhromatosii^) and shows clumped areas. 

b. In the budding j>rocess the nucleus may be small and deeply 
and homogeneously stained and surrounded bv small spheri- 
cal bud- 1 ike projections or there may be very Iwrge ciub-like 
projections which extend to the piri|diery of the cell or even 
outside the celL 

c. The pykootic nucleus is sraiiller than normal, deeply Maining 
and homogeneous in charai^ti'r. Contractinn of the nucleus 
leavei^ a vacant z<»ne abont it so that it .*^eemH to lie in a 

2. Karyolysiw. 

The nucleus undergoes a gradual jaolulion.but its size and shape 

may .still be recognized by ihe delimitation of the surrounding 

f}rotnpla>im even after conmhte holutiim, 
This in contriidistinction to the variouf* types of karyorrhexis is 

essentially a postmortem change and occurs when dead cells 

are still surrounded by tissue fluids, 


In a^jM>eiation with pyknM>iw i>f the nurleus the cells shrink and become 
jagged. In condition:* in whicJi there h fluid stirrounding necrotic cells, 
the cells at tir^t swell and later contract. Varioa.s irregularities of shape 
may 'iccur. 

Among the various forms of degencrntive change in the cell preceding 
lis necrosis are vacnolizatifjn, cloudy ,'^\velling, and dropj^ical degeneration. 
\os^ of preexisting granules or granulation of previously humogeneou.s pro- 
toplof^m, pigmentation, and hyaline and glycogenic change. These de- 
gt-nerations may affect only j>art of the cell, the Hurrouncfing protoplasm 
rf^mainintr healthy. In sucli cases the ap]»earance of alien inclusions is 
given, and such areas of degeneratiou have frctiuenlly been mistaken for 
animal parasites. Rnsseirs fuchsin bodies are examides of this condition. 

Among the changes ol)*«erved alterations in the Altmann granuU>p which 
oecur in many cells, are sign iticant. These granules lirst become larger and 
more readily demonstnible, their iifRnity for acid anilin stains increasing. 

Certain methods, .such as hardening in a mixture of 2 per cent, osmic 
arid *M>liition and 5 per cent, potassium bichromate solutioiu staining in 
hot 20 percent, anilin-oil aeid-fuchsin snhition, diHbrentiation with alcohoh 

Sicric acid solution, are nect^&sary to demonstrate the granules. Jn the 
egenerated cell even the fresh tissue or that hardened in alcohol or 
ionnol and stained with acid anilin suffices. 

Next the granules b«se their characteristic arrangement; they partly 
dissolve and parti v aggregate in large spherical masaes which may ue ex- 
truded from the cells. 

In the third stage there is an altered chetnical composition evidenced by 
changed staining affinity. The granules without special preparation of the 
tissue may be stained with Weigert'B fibrin methipd or they may lose their 
iCaining capacity or in the third place acidophilic granules may become 
baiiophilic or the reverse. 



1. The chromosomes may become notably thickened especially in cases 

in which injuries are inflicted on cells already dividing. 

2. Granular fragmentation and alteration of staining reaction of the 

chromosomes. The cell itself may be vacuolated. The nuclear 
fragments become acidophilic. 

3. Hypochromatic Mitosis. The number of chromosomes may be re- 

duced to 6 or 8 or to an uneven number as 7 or 5. Such changes 
are seen in rapidly growing malignant tumors and in rapidly re- 
generating tissue acted upon by destructive agencies. 

4. Broken Chromosomes. Parts of chromosomes broken off from the 

main body are scattered about in the cell outside the nuclear 
spindle. The process seems to be one essentially affecting the 
achromatic spindle. Thickening, clumping and oxyphilic change 
of the chromosomes are associated conditions. 
S:?uoh changes have been found in cells unfavorably influenced after 
division was underway. 

5. Asymmetric Mitosis. The daughter stars may have an unequal 

number of chromosomes and thus be of unequal size. 

This has been found in carcinomata, sarcomata, adenomata and re- 
generation of the epidermis. 
G. Uy perch romatic and Multiple ^litosis. 

The number of chromosomes may be excessive and there may be 
pluripolar mitosis the number of centrosomes and corresponding 
spindles being 4-G, 8 and even 20. 


Certain changes take place after death which may suggest in their 
appearances ante-mortem disease. It is therefore necessary to recognize 
Uu»se in post-mortem examinations. The most striking change is the 
rigidity or rigor morti$, which is due to a coagulation of the muscle-albu- 
min or myosin. This occurs at different intervals, according to the cause 
and nature of death. Sometimes, as in deaths after electrical discharges, 
it occurs almost instantaneously ; more commonly its beginning is delayed for 
some ht)urs. Alter twenty-four or forty-eight hours the rigidity disappears. 
Occasionally irregular post-mortem contractions of the muscles take place, 
and distortions or oven movements are thus produced. 

Oirculatory Phenomena.— As is noted elsewhere (see Congestion) the 
blocHl-vt»ssels, ospiHMally the arteries, contract after death, and drive the blood 
into the capillaries and veins. It is then more or less free to sink to 
dependent parts through the influence of gravity, and in consequence the 
lower j>arts of the orgjins and of the body in general are congested. This 
is particularly nuirktHi in the luns^, but occurs in practically all organs. 
The bUuKl may remain entirely within the blood-vessels, but not rarely the 
i*oloring-matter ditl\isi»s it^iolf' through the tissues and causes pigmented 
areas {Jintre* mortu) that may s\»gfft»st ante-mortem bruises. 

The bhxHl in the heart and other vessels tends to coa^late, though in 
aome oase^ this is long dolayeti and remains imperfect. Usually dark red 
clots are found in the cavities of the heart and in the large vessels. Yel- 
lowish fibrinous clots an^ loss likely to bo post-mort«m, but more often occur 
in OAsi^ in which death hjis taken a lingering form. 

Po6t-moTtem Degeneration of Tissues.— Some time after death the tis- 
sues may lKHn>mo niaooratiHi and putrefactive changes may occur. To a 
Ur^ extent thost^ are duo to invasion of micro- organ bma. It has been 
found that during the terminal stages of disease various forma of infection 


f?<»pecially microcoecic) oceiir. This ttnninai Infectimi is oft en tlie im- 
mediate cause of fleath, and it is alao concerned in the post-morteni chaDge 
in the tissues, HisLoltigically, a striking peruliiirity of such post-mortem 
change is the absence of evideiues of reaction (cellular infiltration and 
proliferation)^ such as characterize the response of living tissues to irri- 

Post-mortem softening of the mucous membranes may be due to the 
action of the secretions. This is especially marked in tiie tttomacli, where 
it is common to observe a macerated condition of the mucosa of the pos- 
terior wall In this case the gastric juice \a the direct cause of the altera- 
tion in the mucous membrane. , 




Definition^ — InfliimmatioQ is a oi>nihinatioii of" puthcdijgic 
procefis<?s representing the reaetiaii of the ti.sHues to various fnrms 
of irritation ; it is t'hararteri^iHl by liypej-envia, ext^eKsive t^nuj^ratifni 
of IeMkm;yte.s ironi tlie Idootl-vessels, exudation <»f more f»r less 
alti^rtMl biood-piasrna and seooiidarily and less c.s>fentially hy ropn>- 
duetive cellular processes and l>y flegenerative changes in the 
afiet'tetl tissues. 

The relative significance of these processes will be more clearly 
appreciated when the plicnonicna of itdlannnation are separately 

No one of these conditions alone cou»tit«tes infIammatio?t though exce»- 
wve leukocytic eJui^Tation is pcrhupH more nearly re|iresentative of the 
essence of the condition than any other of tlu' processes niimid. Kveii thi;* 
is a quantitative rather tban t|iialitative criterion i^ince the leukocytcH 
traverse the wall^ of the blood-vessels and infiltrate tlic tiHsuew in health :ind 
more decidedly in s^omevvhat abnormal lojiditions t^uch u.s when blood 
pressure is excejssive or liyi^ue tone i« dfpresrstd. The pecuHarity of infltiui- 
matory emigration of leukocytes is its excessive decree. Exudation of 
p1a»ma likewise U a normal process and is excessive m various conditions 
which occasion dropsy ; hut the chtiructcr of inflannnatory exudation of 
plasma ditier;! somewhat from the normal or dropsieaL The reproductive 
or proliferative celluiar changes of inflammation differ but little from thi»i*e 
of regeneration, and indeed, it is diflicult to determine in how far these 
processes belong titrietly to inflammation rather than to a secondary re- 
generation occjisioned by the intlainmalory destruction of tissue. Finally 
tJie degenerative chanjres of inlhouniation diilbr in no ess^ential particular 
from degenerations unattended with infljinuuation iind are distinctive mainly 
on account of their close association with the other proceiwes that together 
cooHtitute the whole picture. 

ffuloricfil. — The earliest conception of inflammation was that of a 
8peci5c entity. Hubsecjuently various theorits were oflbred in explanation 
of the aeveral phenomena or ^ymptiims. First, the blood-vessels were sup- 



po*ed to be inflneiiced tbrAugh the nervous system (vofcuiar theorir^), 
S^eit, it was taogrht tliflt the inflammatory irritant exciter proliferative 
chsDges in the tiwfue» (thiit% giving ri^e to round cells), and that this stimu- 
lation of the cellular activity invites more blood to the part (hence the 
InrperemiaL This was the rffiular and attmrti/m theory of Virchow. 
Otoer*! notably Cohnheim, deatcrtbed the emigration of letUtocytes from the 
blood*Tessels, and beld this to be the essential feature of infljimmation. 
Tbifl emigration was first de^ribed by Dutrocbet (1824), Waller (1842), and 
Strieker; but Cohnheim was the first to system a tize the emigratum theory. 
According to Virchow, the first stt^p is a formative stimulation of the cell> ; 
according to Cohnheim, defeneration of the vessels leading to emigration ; 
according to Weigert^ at least in many ca-se??, the first step is necrosis of the 
p&renchynuXous cells. At the present day inflammation is generally re- 
garded as purely reactive in nature, the irriuition causing sometimes one 
And aometimes another primary lesion. 

Galen and his followers defined inflammation by giving the 
cardinal symptoms; heiit (cfihr\ redness {ntbor\ pain {doIor\ and 
swelling (tumot). To thei^e may be added altered function \Jtnidio 

Phenomena of Inflammation in Vascular Tissues*— 
These raav Ik' \v»'li strvdir>d in tlR" mesentery or tongue of a frog. 

Fw. 27p-*Ioflamtniitioii c»f tho ni<?i»enterv. showing overfilling of the bloofl-vcwelt, With 
©niigitttlon of louktjoyu^ and diA[>ecleais of red corpuaclea (Zieglerj. 

Whrn the mesentery is exposed and spread under a microscope 

and a loealizi^l nrca injured, tlie tirst visible effect is a very tempo- 1 
rary eoutrafticin «>f the arteries, whieli may 4lisai)pear before the ex- ' 
ittnination ean be made. It is followed by (blatatkm of the artrries, 
and then uf tla^ eapilhiries and veins. The tis.sne heeomesdistinetly 
more vascular thnn normal as eapillaries in which there had been 
only plasma or a fvw eorpuseles become distended with lilood and 
thendbre more visible. The bloml-eiirrent is first more rapid than 
normal, tlien slower, and may finally stoj) entirely (stasis), espe- 
ehilly in the c-apillarief? and veins in the center of the inflamed area. 
Notable ehangen are seen in the eireulating eorpnscles. It will be 
recalled tliat under normal conditions the corpuscles circulate in 

iyn heoexeratiox 

the middle* of the va^ciilur .stn^aiu, Icaviiii^ a ekar plasinatie zone 
a<lja(TUt to tho vcssol-vvall ; in this zunv iiiuy l>e ^^vvn \vukuv\ivA 
travel liug sinnewhitt tnore shm W tliaii tlie central eurpiiscnlar strmm, 
A^ the current l)ecM>nies fehnver the leukLKiytes in the pla.sniatie zon<3 
increase in ntunberaml stick U* the vessel-walU in a continuous row. 
In theoiinillaries cinnip.s of leukocytes frerjnently alternate witli 
masst*3 ot ri^l cnrpu>eh s, or i>f red and wlntc c<u'jiiiseh\s in their 
customary uroportinii, Xext, it may be ohsc rved thatthe leukocytes 
are passing through the wallsof the capillaries and veins and ifpread- 
ing in the ontsitle tissues. 8orue of these may enter the lymph- 
channels and thus return tn the cirenlntion ; others sutter degener- 
atioa ami destruction hM-ally. At tlie same timea certitin number 
of retl corpusch^s pass through the capiHary walls, and altered 
plasma escapes ami inliltmtes the tissues. In the connective 
tissues ontside the vessels proli!erati%'e changes take phire, and 
the nnmenms lymph-chanmdH of the surrounding tissues are filled 
with round cells — partly uew-formetl eonneetive-t issue cells and 
partly emigrated leukocytes. In structures in which there are 
parenchyinatous (andiililastic) cells the latter niulergii various de- 
^*neniti\^e changes, such as r-|(JUily swelling, edenuij nnir-ous de- 
g^nieratifin, fatty degeneratiou, or even necrosis. Less frequently 
prolifcmtion of the pareuchymatons cells takes ]>lace. 

Every ease of inflanunation does not prescjit all these phe- 
nomena, nor is the snbst^fpieut fate of tlH> exudate and altered cells 
always the same. 

Phenomena of Inflammation in Avascular Tissues,— 
Sora e o f t h e pr oeosses o f i n fl a m ma I i o n have 1 >ee n bes t e 1 u c i d a ted 1 jy 
experimental inflaniniation of the c^rrnea. It will V>e recalled that 
tliis stmcture is e€m|X)sed of layers of parallel fibers, the direction of 
the fillers in one layer being at angles to tl*at of the filjcrs of ad- 
jacent layers. Ana^^tomosing Ipniph-channels occupy the spaces 
between the fibers and layers, Init tliere arc no l>loiHl-vessels. A 
very slight injury of the cornea mav l)e il^llowi-d by no other re- 
sult than slight swelling td' the corneal corpuscles arouml the |>oint 
of injury, and subsecpu^ntly multiplication of these cells to repair 
the tlaraage. This slight change cannot be readily deuuinstmted. 
Usuiilly there is si*en around the injured s]>ot a hazy j^one which is 
com|»sed of masses of leukocytes that litivc liecn ntt meted to the 
center of irritation. Tiiese escape from tln^ hvpcremic conjuuetival 
vessels at the peripherv of the cornea. The alteration (clilatatinn, 
dc^j^ieration of the walls) of these vessels may be due in ]iart to 
Wfflex nervous influenees and in part to the direct action of toxic 
Ifubatances generated at the site of the primary corneal injury and 
diffu^kni to tiie surrounding tissues. 

The corneal corpuscles themselves swells undergo nuclear di- 
rUion and to some extent become free (phagocytic) cells. In more 
iij tense grades of in Ham mat ion the local degeneration of the corneal 
ei»rpusjcles causes a visible defeet (erosion, ulcer), and the surround- 



iiig zone of leukocytic invasion ia proiinoncod. In cases of nutrked 
corneal inrtammation newl>lood-ves^iplsare formed attlie sides ^f the 
cornea, ninl piislie<l into it-^ previously avascular striu-ture ; ihi" plie- 
noineiiM, then are practically the game us th*>se fonml in inflani- 
mat ion of vascular tissues. 

Id the ease of iuflainniation of the heart-valves no nngnition 
of leukocytes to the diseased focus tK*ciirs, The cn*lothelial celb 
at the point of injury (near the I'ree edge of the valve) sw('ll and 
j>res(*nt uurlrar division ainl also more or lessch^generative clian|j^e ; 
tlie tissues al the base of the leaflets becotne hypenemic and some 
emignition of Irukoeytes occurs in this s^ituatioii. Thus as in the 
case of the cornea cellular destruction and j^roHferation occurs at 
one place (the point of injury) while tlie vascular plienoriR'na and 
emigmtion of leukm^ytes are found at scmic distance. In hcfth 
cases there may eveninally bt* an ingrowth of loops of capillary 
lilo(Ml-vcssrIs fiT*m tlie vascular periphery into the avascular 
structure au<l tht'U hnal emigmtion of leukocytes from these 
capillaries may take place. 

The phenomena nn\>i mwx be separately considered. 

1. CliaBges in the Vessels* — The tirst etfcct of irritation may be 
momentary eoutraetiou of the arteries ; but this is rarely ol»served. 
Usually tlie artmes dilate at once» and dilatation of the eapiilaries 
and veins | >r oin p 1 1 v f o 1 1 o ws . T h e ca u se o f t h i s d 1 1 a t a t i o n was fo r- 
nierly hu-ated in the nervous system aud undoubtedly nervous in- 
flneneesdo play a part in some cases at least, but the more imjwirtant 
cause is prol>al>ly some defjenenition of the vessel -walls. The 
mieroscopi' does not nveal this, but some of the pheuomeua con- 
nected with exudation and thr cireulatirm of the blood show that 
the cause nmst be in the ycsm'I- walls. There ai"e certain visible 
chanties in the vessels, such as swelling of the cndf*thelial cells 
aud increase of the intercellular substance, and some nndoulited 
though iuvisilde (^hangcs, such as inereasetl adhesiveness of the 
endotbclial cells. The last-nuiitioued eondition and the swelling 
of the endothelial cells wtiieh thus eneroach u]M>n the hnnen of the 
vessels are conditions that together witli thcililatation of the blood- 
vessels occasion slowing of t!ie blood-current ami adhesion of the 
leukocytes to the vessel- wall 

In the later stages of inflammation karyokinetie changes and 
consequent multiplication of the endothebul cells of the capillaries 
are fjbscrvcd. The new-iornu d eurh^Iielial cells are ytiii;^ed in 
the proflnetiou of new bbMid-vessels (see (Jranuhitieai Tissue). 

Infiutnce of the NervoHM System, — It ia likely that the nervfius system 
throiiiih iti* vaj5omo(:nr meclianii'm plays sin imjiertant rok hoth centrally 
aiul peripherally in the vascalar ami exud*'itive phenomena of inflainaiation. 
Dilatation of the veswels may be favf)red by weaknes;* of the constrictors or 
^stimulation of the dilators. This is illustrated by the severe inflammationg 
jesultinfT from trivial rauses in paralytic partes and by the occurrence of 
sympathetic inlianmiation in one oyefolhiwing disease of the other. In the 
latter instance the trophic neives are aUo concerned. 



2. Exadatian.^ — ^As the blood-ourrent grows dont^r the leu- 
k kocytes in the plasmatic jtane of the blood^-HTvaru increase in lumi- 
' erand cling to the wall of the vessel. Thb is juirtly a nitvhaiii- 
<?al result of the slower rate of the bhxKl-current, :uul imrtly tilt 
result of the adhesiveness of the vesj^el-walls and projtvtum of th« 
endothelial eelU. Possiblj the attmctive (chemotaeiie) infliirm:^ 
of the agents causing the inflammation may play some part hy 
*lniwing the leukcK'Vtes to the walls of the vessels (see l>elow), 
FiiKi!K\ the leukocyte:* piiss throu^li the vessel-walls between the 
I'fidothelial cells and collect on the outside of the blcHxl- vessel, 
whence they more slowly miirnite through the ti>^iie (Fig. 27), 
The passage of the leiikoc_\^es through tlie vessel- wall can be 
jtudie^l in the mesentery of the fnig. At lirsl a bud-like pnv- 
jecti»»n pushes itself tliroagli the wall between th** i^udotlielial cells, 
llifn ruore and more of the corpuscle follows till the wlmh* crll hjis 
eseape<L When outside the blond- vessel thr cn-ll creeps thniuj^h 
the tissues in the intercellular spaces, often eluULTJttiug itself in 
narrow places to a line:ir turrn and again swelling to its nonnal 
rounded form where tlaid exudate has wuiened the spaces. 
This emigration of leuk<xwtes occui's to a slight extent normally, 
but is abnormal iu degree in iuflauiTuatiun. (ohniieirn ascrilnHJ it 
to disease of the vessels — increased jirnricability— the l<'uk<ieyt<*s 
hcin^ piirelv passive. Later obsorvation in4licates (hat llie c4iict' 
rdif in this excessive emignitiou must be assigned to the stimu- 
late<{ ameboid mfivements of the leukocytes. Degeneration nf 
the vessel-walls, espirially swell itjg and softening of tlir ceuji^ut- 
suhstanee between the end<»th*'li:d ci^Ils, and thc^ pn*ssnrc fif the 
hlrKwl, aid; hut onlv to a minor extent. The cauH: of this aftive 
amcbiiid moti<ui and tendency to emignition lias recivutly ht-fU 
found to be an attractive forc^e peculiar to tlie causes of inflam- 
mation. Stahb iinil later PfefTer, found that certain sub«taneeH 
exert an attractive or repellent force upon h>w forms of vegetal>le 
and animal life, u|Mjn spores of jdants, and upon harteria. To 
this force the name (*hemotHXtH has been given, and the terms ptt^i^ 
Hrf an<l mgatite eheniotojris are used to dehignate the attnu'tion 
anil the repulsion respectively* Positive c he mo taxis is an un- 
doitbl«d and aatisfectorily demonstrated force. The irritiiiit »ub- 
I stance? which directly cau«*e inflammation are positively clicmo- 
flBc?fic* in action ; and in eases in which mechanical injury cjiuh*** 
n, such suWtances first result from UM^elmnical ilr^truc- 
1 - and then incite the subs4*fpjeut phenouiena of iriflafn- 

imutKtn. The letikorytei^ that emigrate unuer the influence of a 
eh#*motactic Ji::r*nt ar** alm<ist exclusively the pfdvmoqihonuclear 
ffirms, and thesr- con«tttnt4} tlie majority of the cefls of an inAam- 
[>rr extid * slier stages. Tliey are not, howet'cr^ the 

IT form- - found in an inHammatf*r\' area. Frc-- 

utlv • i4#iup|iciar are the iMr^iuophiles. Sometime* ihtsu* 

i arv- mlanl tn the tnflanie<i \nirt. In somewliat later 


gtag"C*s lymplinoytes are tonncK In purt lliose doubtless emigrate 
from the bluod- vessels, but the greiiter nutiil>er is derived fVuin the 

lyiHiih-clmiinels ami regiuiial 
lynii>himl eolleetioiLs for ^iioh 
eiilltH'tiVm^are exeeetlingly wiile 
spread throughout varit»iis tiss- 
ues and (►rgaiis. The lympho- 
cytes are jiroiie to oeeiir in 
groups wlneii has led some 
atithorities to attrifnite their 
presence to hyjn rplasia of ex- 
isting lymphoid enlleetinns and 
to some extent to the altraetiou 
exerted on t!ie lymphoid eel Is 
of the Meigld>oring lymph spaces 
towanl t!ie existing lymphoid 
e<Jh-'(*tiuiis in tlie at! rioted art^a* 
Ptasnia-L'< lis and mast -eel Is are 
alsc* iountl^ but as thesignitieaiiee 
of these is still doulKfnl, sepa- 
rate reference will be made to 
them below. The plasma cell 
nndonl>te(lly plays an important 
rufv in some eases, as the iidlam- 
mat^iry exudate may consist al- 
most wholly of this ty]>e of eelL 
The leukoeytes are highly 
useful factors in the defense of 
tlie orgsinism agjdnst the aetion 
of irritants. In the inttam- 
matory area, the polymorphonu- 
clear cells are ai^tively phago- 
cytk% taking up bacteria ^ if these 
are not loi> highly virulent, and 
carrying them out of the dis- 
eased area. In like manner 
various kinds of d6bris are 
rcmoveiL If the bacteria are sufficiently virulent^ the leu- 
kcxiytes may be rapidly destroyed, hut in their disintegration may 
Sit fn*e milulde substances capable of destroying the bacteria. The 
part of tlie eosinophiies is not that of phagocytes, but rather of 
**ren'tintc ^'ellw that fhrow^ nut substances of l>acteriolytic character. 
Thr* h'tikoeytes arc of secondary importance in the pluigocytosis of 
inrtammation uwing largely to their early ilisappcarance and dcstriic- 
lion. Of far jnore signiHeanee in this relation arc tiie swollen and 
[»roliferut<Hl eonnective-tissue cells and the end<4helial cells. In 
elironie inthimujations, particularly those due U\ the presence of 
fori*ign bodies, giant cells are found and are essentially phagocytic. 

Fio. 2fi,— Arote Rppendfdtts. with ertea- 
ilve Fuund-oeU In Hit ration of all of the co«ti 
of Uj« «pppn4lx. 




The micmscopic appeiiraiicc of the tissues after eniiji^ratinn of 
the leukocytes is eliaraeteristtc. Tlie capilJarios aro dilated aud 
obseuretl by a mantle of exuded white eorpu^eles, and the tissue 
amurid ia lull It rated with uiigratory leukoeytes. The siib>^eqiient 
distribution wixd a{>pearauei' of the h iikoeytes ilepeuds very umeh 
upon the charaeter of the iuflanimatinn and of tiie ti-^sues in which 
it rx'cnrs. Tlje leiikoeyt<>s en^^-p through the intereellular and 
iutertibrillar spaees and iwax be ehiuirated to linear figuren or they 
nmy^ in looser tissues or when tliere is abunilauce t>i" liquid ex- 
udate distending the tissue spaees, oeeur iu their normal form 
aud in chistere<l masses. 

Plasftia'Celh. — The cell det^cribed under this tenu by U una is a nmall cell 
whose protoplasm staia;* a violetrblue with methvlene-blae. There are im 
distinct granules, thou^^h sometime?* the protoptasm iii slightly jjcranular 
The nucleus ia u.suully ecceatrieally phiced and ^^urnm tided by dart masses 
of chromatin. The cell varies In size from tliat of the nniall lymiihocyte to 
that of the lar^e mononuclear leukocyte, Karyokinesi?* has been ou»erved in 
a few ca**es. The plasma-cell is probably an altered lyuipliocyte which has 
escaped from the blood-vessels. Some hold that it is a form of connective- 
tissue cell and that it is concerned in regeneration of Ci>nneetive tissue* 
This ii unproved and unlikely. The plasma-cell h found in inHammat^iry 
exudates of all sorts and in the le.^ions of the specific infectious di'^eases-^ 
tuberculosis, lepnMy, syphilis, etc. 

The plasma-cell of WaUlcyer is diflerent from that above described. It 
is identical with the mast-cell of Ehrlich. This is a cell containing large 
basophih'c g^raiiules. (Bee Diseases of the liloodf. It occurs in intlaninia- 
tory proeesses of a chrimic character and in varions tuaiora and degenera- 
tive k'sions. Its aignilicance and nature are uueertain. 

Fide of fhtiLtmkocytm, — In onlinary(non-purnlent) iufluniniationa 
the leukocytes (p(dyniorphouiielear) soon disappear, in part l^y 
eraiirration to the snrronndinir lyinjdiatie vessels aud in part by 
their rapiil destruction. The latter proiM^ss is one of fatty defener- 
ation, nuclear fraguientation and total rrll-neerosis. In the later 
stage*^ lyraphoeytes and round or variously shaped new eonneetive- 
tissue cells are the main eonstituents of the ijiflanimatejry tissue, 
the j^Kjlymorphonnelear leukocytes beino; eonipnmtively scarce. 

Exndntion nf Lnptiflx. — Coineidcntally with leukoeytie einisrra- 
tion there is exudation of more av less altered blotwl-plasnia* The 
amount of lit|ui4l exndatioji and the eharaeter of the exudation 
vary with the nature and eonilitioii of the tissue afteeted and the 
character of I he irritant. In loose cellular tissues and in inHarn- 
mations of niornlmmcs linintc cavities larjjfe quantities of liquid are 
piuired out of the vessels, while the reverse is seen in denser parts, 
Sime intense irritants oeeasion free exudation, while others, bv 
their very ititeusity or peetdiar eharaetcrs, at once destroy the tis- 
sues^ and exudation is comparatively sli^lit* 

The exudate is rictier iu albumin aud more eougulable than 
drnpsical fluid, which is a furtlier iiulieatitui that the blood-vessels 
are more permeable in iotlamtnation ihau iu health or mere con- 
gestion. It is probable, moreover, that the capillary walls act in a 


secretory mauner, as do the walls of the lymphatic channels. This 
would in some measure explain the diiference between inflamma- 
tory exudate and dropsical liquids. The accumulation of exudate 
in the tissue may l)e so abundant that the term inflavwiatory adema 
is justified. In such cases as in all inflammations, to a less ex- 
tent, the cause of the retention of liquid in the inflammator}' area 
is a reduction of tissue-tone or elasticity which prevents the move- 
ment of the fluid toward the efferent lymph-channels. 

After its exudation the fluid exudate may undergo coagulation 
with formation of fibrin and consequent solidification of the in- 
flamed area. When inflammations effect mucous membranes there 
may be admixture of mucus which materially alters the exudate. 

The exudate plays an important rdle in inflammation. It 
serves as a diluent of noxious bodies, and brings from the blood 
substances that destroy the irritants, or takes into its solution 
similar substances from the secretions of leukocytes or from the 
products of their degeneration. Occasionally it has the unfavor- 
able action of c»arrying away and thus spreading thn)ughout the 
system the toxic causes or j)roducts of the inflammation. In the 
case of fibrinous inflammation, the fibrin serves to strengthen 
the limiting wall by which an inflamed area is surrounded. The 
highly nutritious character of the liquid is doubtless of importance 
in the proliferative processes that are presently to be described. 

DlapedeHia of Red CorpuscfcH, — Finally, a certain number of 
red corpuscles escape from the capillaries by diapedesis. This is 
a purely passive process so far as the red corpuscles are concerned, 
being due to pressure of the blood. It is particularly marked 
when stasis and consequent intra-vascular thrombosis has occurred. 
In very intense inflammation accidental hemorrhage by rhexis may 
add to the blood in an exudate. 

3. Proliferative Changes. — Sooner or later in an inflamed area, 
and especially at the peripluTy, there are evidences of cellular 
proliferation which occasions the appearance in the tissue of round 
cells closely resembling lymphocytes or mononuclear leukocytes. 
They differ, however, in beinir somewhat larger, in having a larger 
and paler nucleus, which is round or oval, and in their frequently 
exhibiting evidences of karyokinesis. These cells are direct de- 
rivatives of the fixed connective-tissue cells and of endothelial 
lining lymph spaces. The parent cells first undergo enlargement 
by swelling of their protoplasm, then mitosis of the nuclei and 
cell-division follow. The resulting round cells are those above 
described as characteristic of inflammation after the earliest stage 
of leukocytic exudation. The new-formed round connective-tissue 
cells in part bec()me wandering cells and are more or less phago- 
cytic ; in i)art they remain fixed, elongate or become polymorphous 
in shape, pro<luce intercellular substance and thus assume a purely 
regenerative ro/e. This latter type is designateil jibrch-lilaMic ceils 
(see Regeneration ). 



At tlie sxngir \wx iiu'k'r roiisidenitioa the influnied ih^ne is 
iDfiltratPtl with emignitrtl kMikoi-ytes and more purtic^yhirly with 
IvTiiphciid fxdls urid round connective-tissue cells. The appeHnince 
is ehardcteristic of the niore ailvaiioed stages of aente inHaitimation 
and of chrotijc inflaniinutioii. It is termed rtnual-edl inJiUndion 





Flu. •J.'^.—Si- 


itUfMl-Wt^vir- ami hhrMblnstlr rt'Ue in a 

begininit^' lulKeaiun of iht; pehnirilliil Inyer?. 

Vireliow hrld tlie pro- 
liferati ve elia i ig* -s t< * l>e the 
esi^ential feature in intlani- 
mation^and Ijclieved that 
all round eel Is have this 
oritrin ; ( 'ohenlieiin denied 
the oeeiirrence of pro! i fer- 
ation»antl iuscriheil to emi- 
^mtiori the essential rok. 
I^ater, it was held that the 
prolifemtive chanj^^es are 
i\ot m reality a part of 
inflammation, litit rather 
rt*irenerative and for the 
|>nrjxisr of repairing the 
tissuc'injnries after inHainniation (Fig. 29), At tlie present time we 
must roifjinl tis factors in inflammation hoth emigration and pro- 
literation, whether the latter in any individual ease is due tu direct 
stimulation of the cells, or is seeoudary to tlestruetive ehanges, or 
h merely the result of increase of nutrition from the inflammatory 
congestion. It is eonjecturt^d hy some that tinder chemotaetie 
influences the cell-«intents of fixe<l eells are incited to movem*Jits 
terminatiiti^ in karyoknu'sis, just as the whole ctdl is influenced in 
the case of movahle <!ells. The prolifer.iti*ni of the fixed eon nec- 
tiv^e-t issue cells may be an early pmeess hut does not usually occur 
until some time after tfie exiulative chana^es have taken place. 
The new- formed eells have at first the eharaeters above deseril>ed, 
hut later they become irres^ular in sha|>e antl many of them spindle 
shaped (formative cells). In chronic iuflarninations, especially such 
as surrtmntl foreiirn ImhIics, iriant-cells are fiunuL These liave 
distinct phajL^^cytic functions. They may lie formed hy conflumce 
of a numl»er i>f eidls, and when their |iurp>se is fulfilled, may 
divide into the com jxuient pnrts. Mi^rc enmmouly the ^iant-cells 
seem to be the result <d* clivision of the original nucleus, with 
growth J but nou"di vision, of the protophu^nu 

Granftftrfiftfi TAvN^/r.— When the pmliferative changes are 
active, new blond-vessels, fbrnie<l by midtiplication and lateral out- 
KTowtli of the endothc>lium nf the pri'-i-xisting vessels, are a con- 
Hpifuious feature. These, siirroimded l»y the various fivrms of 
nmnd cells alxive described^ and sometimes giant-cells, con- 
stitute gninnlation tissue (see also Repair of Wounds and Re- 
^•ui-ration). 8ueh irranulation tissue is cs|>eeially couspieiions in 


the floor of ulcers. It is more properly considered as a regener- 
ative than as an inflammatory product. 

Proliferative Changes in the Parenchymatcms Cells, — Swelling 
and later mitosis, may occur in the early stages of inflammation 
but are of slight extent. In certain chronic inflammations also, 
such as some forms of cirrhosis of the liver, proliferation of 
parenchymatous cells may be observed. In the latter instance 
the process is rather of regenerative character. The changes in 
the earlier stages of inflammation are more truly inflammatory 
though the new-formed cells unlike some of the proliferative con- 
nective-tissue cells do not migrate or take on phagocytic action. 

4. Degenerative Ohanges in the Tissnes. — The irritant which 
causes inflammation may in some cases (bacteria) contain in itself 
the agencies that excite the various phenomena of inflammation — 
vascular phenomena, exudation, degeneration, and proliferation; in 
other inflammations (mechanical, thermal, etc.) the irritant first 
causes destruction of cells which liberates substances capable of 

I)nKhicing the successive phenomena. Even in the case of oacteria, 
lowever, the primary attack on the cells and the consequent pro- 
duction of noxious bodies are important factors in the whole 
process. The first effect may fall upon the blood-vessel walls or 
upon the tissues. Weigert, Neumann, and others hold that the 
"primary effect" in inflammation is generally or always this tissue- 
tlegeneration, which excites secondary exudation and proliferation. 
This is certainly the case in many instances ; and the discovery 
that tissue-degeneration leads to the formation of substances posi- 
tively chemotactic in action would indicate the manner in which 
inflammation is brought about in these cases. The degener- 
ative r-hanges may be merely physiologic (some form of altered 
funcftional activity), or there may be structural alterations, such as 
cloudy swelling, mucoid degeneration, liquefaction, fatty change, 
c^mgulation- or other forms of necrosis. The nature of the 
difgenenition depends largely upon the severity of the irritation. 
Very jx>werful irritants cause necrosis at once, and not inflam- 
mation. It is the irritants which disonler, but do not entirely 
d<'r*troy cflls, that are especially apt to excite inflamniation. The 
rel hilar clegonerations now under discussion are entirely different 
in j»ignifir*an('(' from the more conspicuous secondary cvlhilar degen- 
eratioHH conHid<Ted below. The primary' degenerations occasion- 
oil by tli<» first attack of the irritant are often inconspicuous and 
inferential nitluT than demonstrable. The condition of general 
and local vitality is of great importance in determining the extent 
of the degenerative change in the tissues. Thus, in states of re- 
duced general vitality catarrhal inflammations with extensive 
epithelial degeneration may be very pHprsistent, and may subside 
promptly when the general health has improved. 

Secondary Cellular Degeneration. — When inflammations attack 



tissues containing epitlielia or other |>arenchyniatou8 cells the latter 
oflen sutftT ^it'euiichirv <letrt'nt'nitive ehiiiiges, cloudy swelling, fatty 
or mucoid degeneration and total neerosis. These seeondary 
celliilar changes may serve to sjnvad and intensify the origimil 
inflammation and are moreover e.s|jeeially Ijurmful to the functional 
activity of the diseased organ or tissue. The cause of tl*ese de- 
generations may be tlie same tt>xie a^ent wliieh initiated the whole 
process or on the otlier hand tlie pressure of exudates and tlie 
cireulatorv disturhauees incident tu the iuriaiiiiniitiun. 

Etiology. — Irritation by meehanieal, chemical, thermal, or in- 
fectious agents causes iuriammation wheu it is severe enough to dis- 
turb the vitality of tlie tissue and not sufficient to cause extensive 
necrosis at once. When the irritant is brought to hear upon the 
tii^ues directly, there is prob:d)ly, first, cell-degcueratioji, fVil- 
lowed by vascular disturhauccs autl emigration. Wlu^n the irri- 
tant acts through the blood, vascular discu'ders probalily, as a rule, 
precede the tissue-changes. Miero-orgruiisms may act by first de- 
stroying the cells, or may liheratc tVom tlieir sul (stance some poi.son 
(protein) whicli is irritant and elieuiotactie, 1 )isturhanees uf eir- 
cidatJon, innervation, (U* nutaltolism may h» alter cellular proceBSf^s 
as to oecasiou theprtiductiuu of irritating and chemotactic products. 

Special Forms of Inflamniatloii-^Various classifications 
may kje used in describing forms or types of inHammation. The 
most natural is tliat which fullows tlie ;ujatomieal changes. Thus 
we may disiinguish (1) txutintirt intlarnniation, or the form in 
which the fluid and eelhdar exudatifiu from the blofMl-vessels is 
the predominating element in the jiathologic process ; {!2) jmrrH' 
dii/maious or degenemtive inflammation, or the form in which 
destniction of the parenchyma cells is the leading feature ; and 
(3) proiiuiiive iutlaumiationt in which |)rolifemtioii is the striking 
characteristic . Tlic nature <if the cause, as well as the resistance 
of the orgaiusru or of the alfected part, deterniines the particular 
form in a given ease, 

A number of sub- varieties may be described, but it must always 
be rememljcretl that the three processes exudation, degeneration, 
and prol iteration are present in greater r*r Ic'^s degree in all forms. 

Types of Infiammation,— I. Edematous or seroas inflamma- 
tion is chara(*terizecl by a copious exudation of fluid with com- 
paratively little cellular matter, as iu edenui of the larynx^ sercuis 
eflFusions in the serous sacs, etc. The local forms of edematous 
or serous inflammation are usually expressiotis of intensely irritant 
causes ; the serous inflammations of serous cavities, however, are 
not necessarily of this severe grade. In<lr^( d, in many cjises serous 
inflammation niayl)e a mild, subacute iU'chronir, process, which may 
subgiide gradually, leaviug the serous membranes slightly thick* 
ened or fulherent. Tlie fluid in inflammatory exudations difl'ers 
from dropsical fluid in containing more albumin and fibrin -factors. 


2. Fibrinous Inflammation. — ^The plasmatic and cellular exudate 
may form a fibrinous membrane on free surfaces or a network 
within the tissues; this is termed fibrinous inflammation. 

In purely fibrinous inflammations of serous surfaces there is a 
whitish or yellowish-white dej)osit of variable thickness, which is 
more or less adherent to the underlying surfacie. When removed, 
there may be seen beneath it a pronounced injection of the blood- 
vessels and rouj^hness and rawness of the surface. This is due to 
b(*ginning granulations (see Repair of Wounds). Microscopically 
the fibrinous dejK)sit consists of an irregularly arranged mass of 
fibrillar, granular, or homogeneous fibrin, with leukocytes and 
endothelial cells (more or less degenerat(»d) enclosed in the dejH)sil. 
Microscopically the fibrin may be found in star-like formations 
made up of a more or less d(*generated leukocyte in the center an<i 
nidiating threads of fibrin extending from it in every direction. 
This may be signifieiint of the lib<?ration of fibrin ferment from the 
degen(;rating cell and consequent formation of fibrin about this as 
a centiT. Some authorities believe that fibrinous inflammation 
can n(»ver occur independently of destruction of fixed cells. In 
other words, they doubt that the fibrinous exudate is ever purely 
an exudate. Some exjH*rimenters have, however, described fibrin- 
ous inflammations of serous surfaces with an unbroken lining of 
endothelial cells under the fibrinous dej)osit, and have concluded 
that the fibrin is wholly exudative. Others reganl the lining cells 
as cells of lymj)h-spaces, and not the original sm-face cells ; and 
conse(jU(»ntly conchnle that cellular destruction plays a j>art in the 
fibrin-formation. Fibrinous inflammation is often associated with 
serous exudation, and the term i^rro- fibrinous is applied. In other 
cas«'s (cspcMMally in peritoneal inflammations) the exudate is likely 
to become \mr\\\vn{—fibrino'parulenf inflammation. 

Inflammations of the serous mcMnbranes are nearly always more 
or less fibrinous. 

3. Diphtheritic inflammation differs from the last in having 
associate*! with the coagulation of the exudate deci<led coagulation- 
n<!(!rosis of the cells of the part inflamed. The difference is one of 
d<»gree rather than of kind, and is largely dependent upon the 
character of the tissue in which the inflammation (x^curs. Diph- 
theritic inflammation occurs es|K»cially in the pharynx and larynx, 
wIktc it occasions j>seudomembranes (Fig. HO), This is most fn*- 
<jU(Mitly due to the sj)ecific bacillus of the disease calltMl diphtheria; 
but diphtheriti<* inflammation may result from a variety of severe 
irritants, such as other bacteria, superheateil steam, and chemical 
ag(»nts. The <liphtheritic membrane consists of a network of 
fibrin or of homogeneous or granular fibrin-masses enclosing de- 
genoratt»d <»pithelial cells and emigpatiMl leukocytes. Sometimes it 
18 quite HUj>erfiicial, involving (mly the surface-layer of epithelium; 
at other times the whole depth of the mucous membrane is impli- 



cat4?d. The farmer itn* >oiiictinies cultrd croujion- ami the latter 
diphthoritir falst* nn-mbranes. These tfrms, l»owever, arc ill-de- 
fineil and oljjeeiirnialilu, 

4. SuppuratiTe inlammatioii is i-haracttTi/ed by uDu<^ual abun- 
dance of cmi^nKt'd leukixrytes and liv (lie teiideney to lifjue- 
fuetion, Ijacleri:i are inoi^t frt'(|nently the eau>;e ; bnt it has 
Ix'en slniwn ex|K'rini(^ntally that eroton t*il, eahaiu'l, tnr|K'ntiiie, 
and othi r sulistMUris an- ea|)al>K* ni* |ini<lnriut: sn|i|iiifaticin. Of 
the bacteria, tlie romnionerft are th** HM'alle<l jnogenie staj»hylo- 
eocei and streptut^oeci ; bnt numerous forms, not ei^.sentiatly |)yo- 
gt»nie, luay oeea^sionaliy prove so. fSneh are the baeilliis of 
typhoid lev<T, the cronm*fK*eiis, the ISaeilhts eoli, and others. 

The iniplantatino of bacteria of siippiiratinn at the jH)int of dis- 
ease may take pla(*e directly throiir!:h wonnds, ur somewhat indi- 
rectly thronii;h small abrasions in the various mucous merui)ranes. 
Some local injury may t!ien serve to determine the suppurative 
inflammation at a given place, 

lieeent studies ascrilje to chemotaxis the important rdlc in the 
action of bacteria in intlammatton and supparatiou. P^ilher the 
prixlucts of the Ijacteria or sul>stauces derived from their owu 

Pi4*. aa— P»etulouifmhnuioii» hirt«imm»tloii of the iiviilut ft, iiiiu(«es of micrococci; b, 
necroUe ccUs; c, romid-ci'll iiiHltrutiotn rf, libiiM-uelwork tZie^fler). 

pnitoplasm (endogenmi!* .substances) exereiise a poweHul chcmo- 
tactic iurtuence, ami tirns occasion tlic massing ^f ruii**rnt<'d 
leukt>cytes (Fig. 31). The same or similar suljstauccs furl her 

Iinpveat tihrin-formation or eiiuse a solution of fibrin already 
brmed^ and tints tlie exudate liquefies and Ibrms pus. Tin* 
sequence of events may bt* as folh^vs: bn*'teriu directly itnplante*! 
in the tisstie or carried to th<' cripillari^'s in the bloml fu*st cause 
loi'al cellular changes (degeiieraliou or neerr^sisf ; then congestion 
an*l exudation of leukocytes anil jilasma ocvur mnaiud this foeiis, 
next mure or less Hiu-in formation results from the exutlation, and 
fimilly solteuing of the whole area anil a more or less complete Hlling 



up will» exudativa leukocytes. The softening of the degenerated cells 
and of the iibrin is pmbably tlie residt of some sort of ferment- 
activity, tlie ferments resulting from tlie aetion of tlie haeteria on the 
cells. The Hrm packing of exudative cells anfl the j pressure caused 
by vascular tnrgesceneej as well as the anemia caused by stoppage 
of circiihition by stasis and intravascular thrombosis, are» Ivnwever, 
additional factors that lead to degenerative clianges and pus- for- 
mation. The essence i>f suppurative intiammation is the excessive 
emigration of leukiM-ytes, the scdteniug of the tissues, and the 
failure of the liuid cxuthitc to coagulate and form tibrin. The exces- 
sive leukfH'ytie invasion is chargea!)le t4» inonlinatc cbcmotaxis 
due to the niieroorganismal or other causes of the inflanu nation or 
to their products. The sc^fteui ng may possibly be occasioned l*y 
tiie same suljstauccs in excess or to other sidistances eoincidently 
formed in the tissues. It is not likely that tlicM' ferment sub- 
stances are (Hajveycil in the bacteria themselves, a> non-ebemotaetie 
eliemieals may act precisely like pyogenic l^ac^teria. 

FlO. 3L— EmboUf fttiJKes* hi tin- nl>^ rjirlnj?)*. ^h-vs mil' ihdimulation of large Dumbers of 
k■ukl^cyle^ iKiirg nut] <i:hnu>Tl). 

Pus consists «if a liquid part, the /ifpior }ntrls^ a nmditied blixid- 
plasma, wliich differs from ordinary plasma in being less ccmgnlable 
and in containing notable ipiantities ofa 1 bum ose( peptone hand a eor- 
puseular part, mtisistiu^ chiefly of polvmoqdionneler leukocytes 
more or less degi'ueniteth Scnnc proHfemted connective-tissue 
cells or wandering cells ntay be added from the neigld^oring tissue, 
but these et>nstitute but a mitiority of tlie whole nund>er. The 
jms-cells present a distinctly gnmular |irotoplasm and fragmented 

Abscess. — A\nien eirenmscribrtl suyn*unition oeeiirs in the sub- 
stance of a tissue or nrgan, tlie lesion is called an ahseess. This con- 
sists of a collection of pus, which usually has a creamy yellow coh>r, 



but may be viiriou^ly altered in odor or color hy siilhsequent clianges. 
The abscess grmvii by turtherliqiii'fiicti w oliungc^s in thesurroumling 
tissues and fiirthtT attniction oi' It'iikcRn'tes fruiti the hyjicrcmic 
veiisels in llie |ji:'ripheral iatructiires. Around thu abscess the tissues 
present the jiroliienitive changes deseribrd as purt oi" inJiaui- 
raatinn. Tiiere are inmiernus nnnid cells, ilitleriiig from etnjgiuted 
lenkwytes and utteii showing niitotic figures in the nucha, and 
there are new blood-vessels and beginning organiziition (see Re- 
generation). Fibrin in tlie form oi* interlacing threads or in 
masses, the prmluet of plasmatic exudate ami of coagulation- 
ntx*n\sis, athls to tlie etabaukmeiit. In slowly iurming abscesses 
the surrounding: wall uf condensed tissue is uften quite ilnn. This 
restraining wall was formerly erroneously regarded as a pus-pni- 
ducing membrane, and tbereibre called the pffof/cnw mniii/ntne. 
Abscesses tend to soften the surrounding tissues in the direetiou 
of least resistance, and thus to break on the surface, discharging 
their contents by sinut>us tracts or sinnstH, Sometimes the pu^ of 
an abseess l>ccornes inspissated by absorption of the liquid ptu't, 
and the residue undergoes v^arious degenerative changes^, such as 
mucous, fattv, or ealcare«jus. At the sarae time the surrounding 
membrane may advance to complete organization, ami thus eneap- 
gulates the abscess, 

Phleffjttonous /^i/frtmmnfi'ofi.— Suppurative inflammation may 
have a less definitely eircuniscril>etl character than that seen in 
absi*esses. It may take the form ot*a purniint infiitration in which 
the tissues are extensivclv infiltratfd with emigrate*! leukocytes 
and mort^ or less softened by liquefactive pr^jccsses or by abund- 
ance of fluid exudate that does not coagulate. In other cases a 
nearer approach to the comlitions seen in al»scesses is observeil. 
The purulent pnK^ess spreads along planes of tissue or neighboring 
fiK'i coalesce to form a diifusc suppurative condition. To this the 
terms phlegmon and j^hirgmonom inffammafion are applied- 
Ulcer. — Suppurative inflammation with erosion of arciis of the 
skin or mucous surfaces o^'casiuns nkers. These have tli(^ same 
liii^oU>gie construction as the wall of an al>scess, the base oi' the 
ulcer being the same as the pyogenic membrane. In it nuiy be 
aeen small red poinds or gramdatiuns, wliich consist of loops of 
capillary blood-vessels surrouridcil by roimd cells* (Tlie his- 
lolngy of trninulation-tissue is more minutely dcscribeil under 

The appearance and i*athologic cowrse of ulcers vary widely. Some^ 
times rapid de*«truL'tion of the tissues eaUBi^y large and J^preadirig iilccr3» 
called phnffedenic. Otln rs extend m one dJrectiun wliile healint^ in «»tber 
pftTto, ivnd are called >*erpi(jtnoa^. The f^rarmlatiuns may be too rapid in 
|iowlh» forming red fungous inaases (proud flcRh) which fill up the ulcer. 
In other ca^ie^ the ulcer reinaiiiB dry and imioltnt, sbowiDg little tendency to 


Borne ulcers are not priraarily of inflammntory origin. For example, the 




or p^ie uleer of , the iiton]ac!h is formed bj digestion, through the 

of the gastric juice, of a purl of the dtuoiach which has become 

crwl in vitality or possibly necrotic. 8iiuilarh% the beginuin^ change in 

^itte perff/raiinff utcf^r of the i oat in tabe^* and in decubitus (bed -f*ore* and 

C€jl4*r Jornirt of pren-^ure ulceration) is not inflammatory, but mther necnitic, 

Hueondarily, however, the necrotic>ue^ become active irritaDts and oc- 

true inflammatory ulceration* 

Sappumtivc inflammation"^ of r^fTous membrane* lining closed 
cause collectit>n-< *>r ]n\i^ in the cavities. The pu.** usually 
csoatainii more or less fibi^n, and there is a fibrino-puruicnt exu- 
date on the ficrous surface, 

Supfnirutive inflammation of the .skin iind sulicutaneous tissueB 
may be Im^uHzed or difluse. Of the loea]ize<l type there are 
various juiHiuft'M^ fu ninths or hinU^ and varbnncieis, 

A furuncle is a so|)pumtive and necrotic inflammation be- 
ffinning in tuie »»f the ^wcat-glanils^ sebaceous-glands, or hair- 
iollielf5>(. A t*arliuiicle is a more extensive but similar process 
lK*^nnnifjg in several of the gr|andsor hair- follicles si multaneuusly, 
and causing cDn^-idcrablc necrosis or gangrene of the skin and 
«ulxmianei>u.<4 tis»ue. 


ii.Mi. AiuLihroiurlUitl cntoirrli, ihowlnfT the caciipe nf Iciikorytc* f^om the '•ubmuiii 

5, Catarrhal laflammatioa, — Tld.n term is used ti> designate in- 
fliHiMuunou^ *>J'muciMis inendu'ancs. Tlie character of the inflam- 
tufttion depenrls to a large extent upon the individuality of tiie 
inut?ouH nx'inbraiie aflectcd, diflering greatly in tlie nose, throaty 
litomachf bi»wi'l, etc. There is always eonsiLlerable congestion of 
the muctoKa, arul generally a great deal of serous exudation, which 



is discliartretl from the surface as a rtik% but ii^ to pome extent 
retained in the t issuer causing edeniatou>? swelling* This ia 
espeeially luarked wluii tlie Bubrnueosa is eoiisiderably implieated, 
The epithelial eells^ iA* the surtaee sutler {ItgenLTation (mucous or 
fatty) and neerosis, and are discharged with the serous exudate ; 
they may be reeogni/j/d as goblet-celis nutieous) or as granular 
cells (fatty) or as tVagmented neerotie struct ure?«. (Joineideutly 
with the serous exudation, and in greater measure after the latter 
has become less marked, leukfn:'ytes escape from the blood-vessels 
or emigrate from their re.sting-[4apes in the suhnincos^i arid make 
their way to tlsc surface between tlie e|iithelial cells ^ Fig. 32). 
When in great ainuidauce (as in some nasal calarrlis) ihe pnx*ess 
may \}Q t\ purulent or mr ppuraf ire one ; more frequently there is 
sufficient niueiis to requir*' the term muco-pHnikitL Suj^erfieial ero- 
sions «»f the ejiit helium and hemorrhages are freqnently met with, 
"Wlnvn catarrhal inflanmiations arc chrtmic, there is usually 
cousiderahle pr*Hhifiire iytjlnitiutfifitin, with cousecjucut thickenings 
and later, when the new tibrons tissue contracts^ there may be 
uniform tluuniiig of the mucosa or irregularly distributeil areas of 
liyiHTplasia intermixed with areas of thinning, lu some eases^ 
however* progressive atrophy of the nulcc^sa oi-eurs withont j»re- 
vious priKbietivc changes. This is es[»ecially marked in the ImjwcI, 
where, douliticss, constant di>tention plays an imjKirtant part. 
When ihe eont factions ot' the librous lissue are irregular, the 
mucosa between the tibrous areas may l)e elevated, especiidly if 
tliere is at the same tiiue pnd iteration of the suriace epitludiuni 
and the glandular elements in the mucosa. In such eases a 
granular surface or polypoid elevations result. These are com- 
mon in the stomach and the bowels. 

6. PareEchymatoiis or Degenerative InfiammatioE. — Tins term 
may be applied to certain intlamouitions, sueh as forms of neph- 
ritis, in which degeneration (cloudy, fatty, etc.) of the parenchyma- 
cells is more eonspicuous than the exudative prm^<*sses. The 
ciianges in the parenchyma in such cases are often seconclary to the 
inflammation, in either eases they arc precedent. Strirtly speak- 
ing the parenchymatous changes arc not essentially a part of tlie 
inflammation, but in those cases in wliich nujch degeneration of 
pftrenchymatous cells accompanies inflamniations the term paren- 
chymatous inflammation is convenient and expressive, 

7. Productive Infiammation. — lu this form the |trolifcrative 
e hanges p ret 1 ot n i n a t e u v er exm la t ion and degc n em t i < m . T h i s i n ay 
be due to tljc nature of the etif>logieal factor, to ]icculiarities in the 
tij!sue n^action, or locul conditions atl'ecti ng tlic removal of the 
irritant- In all eases in which intlamraation fi>r any of the above 
reasons becomes chn>nic the proliferative clianges in the atfected 
tissues become nu>rc or less predouunating. Sime degree of pri- 
nmry tissue destruction appears to be essential to tlie protluctive 



Fir, 33."r*<Mtt»fl of IjUxjO- 
▼esseli* in gTHnuUliull-ti!>l^tlu 
(Thiersch I. 

process, which tht^n^f^re must be regankMl as ahvavs reactive or 

The term inkrHtilial inflammation is applied to this form as a 
contrast t^CJ pfity^uchifmnfoufi hifiammafion above clerfcrihc*L Rutli 
these iiarnes are ternis nf coiivtnienee mther than i^i^oiticant of 
esse n t i a 1 1 y dl ffe re ti t pro< *esses , 

Repair of Wounds. — Prodtirtivo inflaniniatioii is well illus- 
trated in the iiealing t*f w<uiinls. If the li(>s »*f a clean, iiieiscd 
won ml are dmwn tngi^thcr at once atul 
kept c^hxsely apposi'il, rapid healing:; iM'cur.s, 
which is called hfaiinfj (tif immediate unlotK 
III these ea^ses a niier<».scoj>ie examination 
shows slight exudation from the surfaces 
of the wound an*l prolifenited connertive- 
tissue cells. The epithi'lial continuity is 
re.<t(ired hy proliferation of the oh! epi- 
tlielial cells. ShouhJ apposition be less 
ira met Hate or less accurate, the a mo nut of 
exudation is greater. If the wounded snr- 
faces are examined twenty -four hntirs after 
the injury, they are f<Kmd n*d nnd swollen 
ami soiin they hc^'omc ghized in appear- 
ance. The microsi*o|)ie features Iktc are 
the same as in the case of liealiug l>y 
immediate iuii4»n» exeeptinij the amount of exudation is gn-ater. 
Heidin*^ proereds in the sanje wav lint more e^lowly, and i^ called 
hni/tHi/ f^ti firMt Infndion. In neitiier case is thi^ir ^reat couiiestifin. 
If the wound h»* irritated hy foreign liodies or kept ex postal, tliere 
will he seen on tlie «uriaccs» after two or three days, small red el^^va- 
tions, known as f^ramdntlon^, which consist of Imtps of new- formed 
capillaries covered l>v emii^rate^I and new-formed round cells, ami 
sometimes (after hinger intervals «»f time) giant-eells (Fig* 3*i). 
When infected, the surface may be ei>vered %vith eotisiderable pus* 
The proliferated round cells gradnidly elongate ami tVtrm new 
fibrcms tissue (see Kcgenenition K wliich afterward contracts, form- 
ing ricatrirfff or scars. The epithelial continuity is rc-establislied 
by multi])lieation of the old epitlielial cells at the edges of the 
wound. Tins form of healing is called healhig by seeond inlaiHoJi 
or heaUnfj iiif f/ranulatio^hs. 

The formation of adhesions following inflammation of the 
Bemns siirfaeus occurs in nnieh the same way as wounds lieah 
The primary exudation is largely fibrinous ami causes agglutina- 
tion of neighborinjT surfaces. Kuitsef[tiently the proliferative con- 
nective-tissue cells, having l>eeome actively wandering cells, pene- 
trate this fibrinous exudate, as do newly formed bhxKl-vessels 
(Fig, 34). Tints a union of vascular channels is affected between 
the adjacent inflamed surfaces, and organization follows. 


PrecUely similar rbnnges occur in the tiw*ues Kurroiiuding a foreign 
body, a» a piece of sponge, or around a porti«m of dead tissue. In these 
cases the exudative and proliferated i ells lend t*> iienetrate into the foreign 
mass, as occurs abo in the organ izant>n r>f thrombi. There is in these 
cases a greater tendency to the fortnatioo of giunt-eelb iby confiuence of 
cells or by division of nuclei without division of the eell-bfuJvj than in 
ordinary granulations^. If the fi^reign niaHi? vnn be s<>ft«?ned i\i\i\ abi^<»rl>ed, 
this gradually oecurs. and later merely a t^ear will reniaiii; if it cannot be 
absorbed I connective tissue eventually encloses or encajisuJatcs it. 

■■■■'■' ^^ 

t 8i^Adhcstve pericardltiii. nhowiuK llbrin-defioslt, with new bl«od*Te8sela extending 
upward itito It (Peris). 

General Fibrosie. — A teiulonev Uy widespread prixlneti ve iiiflam- 
niation is noted in eertuiii iorJividii;ds. This affects the blood- 
vessels et?pet!ia!ly (general arterioeapHlar-y fibrosis, j^^eneral aiioio- 
st»lerosi8), aod alsci the liver (cirrht>sis of the liver), the kidneys 
(interstitial nephritis), and otlier organs (Fig. 35). iSome form of 
degeneration or necrosis of the |>nrcneliyniatous cells is doubtless 
the preliminary condition in all of these rases. First the endo- 
tJielia or the nmselo eells are affeeted in tlie eases of IdocwJ- 
ve.ssels ; the hepatie cells in ease of tho liver ; the epithelia of the 
tubules and glomeruli in case of the kidney, etc. The resulting 
fibrosis is, however, out of all propoi-tion to the demoustnilile 
change of parenehynia. The eanse of these cdiansfes is supposed 
to be some general intoxication — alcoholic, gouty, syphilitic, or the 

Productive inflamniatiou may eflVet other tissues than the tibrons 
connective tissues. Reference has already been made to epi- 



tlielial prrilifemtirin in the lie-aliii^^ t>f \v(hiik1s. Siitiilar opitlielia! 
processes uf ;f re liter nrtivity ur (hiriitioii iiuiy U'iu\ tu wartx i^rowths 
itf tlie skin or |R»ly|joitl oiiti^nnvths on th«' Trjiieniis menihranes, lo 
phan'Ugeal eaturrljs eoiLsitlemhle pmlitenition of tlie adenoid tis- 
sues is not iinusnal. 80 also tftiekening of *"artila^es, hones, or the 
periosteum is not ait uinisual result of inllaminatioii of these 

8. Hemorrliagic InflanLmatioii. — More or less c)iupeilesis of red 
corimsclcs generally occurs in inflanuuatiun ; l>ut souietiiues the 
irritating cause falls with such jK^c^uliar force on tfie l>loo<l- vessels, 
or the general condition of the [uitient (cancer, tuberculosis^ iiemo- 

Kick Slk-^tirouic Intentitial ncrpbrUia : ujenl increiute of eotmectire titsne urounil Ihe 
glomeruli t rvrml tubulfsA, and oltxtd-YemelB : frum a ciUio of urterlocApill&iy fibroali. 

plilliu, scurvy) is sucli that the exudate is nnusnally rich in red 
en r 1 1 « I se 1 cs. Cert a in mi < *roo rt^a 1 li s u 1 s ( o ri;a n i "^ 1 n s o t* h e ni o r r h ati i c 
septicemia) nmre or Jc>s regnlariy ciiiisc henKtrrhagic iuHammation. 
Intravascular throniliosis and obstruction of caplllurics with masses 
of micrm>rganisnis j>lay an im]H:irtant part in causing the lienior- 
rhagic exndatiniL These are always serious in Ham mat ions, and are 
to be ilistinguishcd irmn ordinary intlauimatirms in which acci- 
dental ljeraorrfiaL'<" rH/nir--. 

9, Necrotic or gangrenous inflammations likewi^ depend for their 
c»ccurrence npm the severity ^f the irritation or the state of the 
general system, 

Patholog^ic Physiology. — Inflammation represents in- 
creased an<l altered activity ot' tis^^ues as a result of irritation ; its 
primary obj^^ct is the removal of the irritant. It is a pathological 
ml destnictive pr<w*ess p*:r /te but considereil fnim tlic }>nint of view 



oiitB icnh (the remo^'al or ( 

suhiii^ twoe deatroctioo) iamammmtmrn » gaxim mMy cswrmtit^e 
and nflefoL In tUe prooese no new Ibi^ees or artirhifs are in- 
Tolved : the pbaMMDCBa wm wU dbservrA m wwnai ttasoes* tbott^ 
to a less dtgne and in moi^ orderlj bebaTior. Tli^ Itqnid aixl 
odlttlar exfadmtiaa has its pmtotype in tfa« formatioa of lTni|ih and 
in the oomnl waadeiin^ cells of the ti^^so^ ; the innwrd ^-^ 
cnlaritr h the result of inrreascd demaoil, and b abnonBal in d^ 
gree unly ; the oeilolar di'^^tnictioa is an accei^tnatioD of the ortlt- 
narr death of cells resoltiiig: fi^ioi wear and tokr^ tbciosHi the ft^rm 
of the eell-destmctmo is motv viokfit and pcvhably diflTeft^nl ; tlte 
piKst'inflaunniainrr reieaienitioo is effected hr karvokiiietic multi* 
plicataofi of oellay as m nomal tisEoesu 

In the dflstraetiiiii aad ranoval of the irritant^ phagomosis 
(a, t,)h iroportani ; it is aoeoinplisbed bv the lenkocvic^ hv en- 

ThoQgh a local proces tnflunniatioi] ha^^ often wkie<pr>pad re- 
anlta. The products of tiasoe change (|Hintarv 4^11 ular necioets, 
defeneration of the emigrated leuhorvtes, softening of the tissue 
and coagulated exudate) mar occasion fever and other evidences 
of toxemia. Seeoodaiy pai^ochvmatoass changes bv altering 
organic action may be highly injiirirms to the whcde oiganism. 

The fuDctioial activity of a part the seat of inflamination is 
oAen tnercasedy thiNigb somewhat altered. Ati inflamed gland 
may prodoeean excessive but abnormal secretion. In other cases 
functional activity 15 les^ned ; chronic inflammations admo^t cer- 
tainly lesisen functioiml action. 

Resolntiott after Inflammation. — In cages of trivial 
exudation the emi^at^J l4»uk«»c'yte^ may re-enter the bIood'<?ur- 
rent or may eei*;ap<* thniugh the lyniphaiie^. The liquid exudate 
b similarly dispcte^^l of; whil*? tJie pn>liferated conaeorive-tissye 
oeUs remain tn loco or become wandering cells. When the exu- 
date is moTQ abimdant^ the liquid elements may be removetl in the 
same way, but the wlU lir«i undergo degenerative soften ini: and 
are reduces! to the form of an emubiou, which is ^:radually ab- 
eorbed. In punileut inflammation^ the pu** may lie disehargeil 
througli exlenial openings or into cavities of the body or may 
become inspissated (see Purulent Inflammation )« The d^eneralitl 
parenchyma in inflammation may recover if the degeneration is not 
faevertf, or mav be g^iftentHj and remove*!. Phago^-ytic cell* often 
ptay a ? it part in the removal of broken-down cellular 

remain-, it-ma^^es, and the like. 

The reparative chan^r<^ i" inflammation may be s«> slight as to 
lead to no discoverable Ici^itm after the prtxess U eomp!cte<l ; 
but when large flamagc ha^ be^-ii done there is apt to be a perma- 
aeut ecar or some iitber productive lesion. 



Definition. — The term regeneration is applied to the forma- 
tion of new cells or tissues to take the place of those destroyed. 
Regeneration may be physiologic or pathologic. The former is 
that which occurs in the normal life of the organism and by which 
the cellular wear and tear is counterbalanced. Pathologic regen- 
eration is the more massive and oflen atypical reconstruction that 
follows disease or injuries. Regeneration is one of the essential 
elements in inflammation, as has been shown in the preceding 
pages, but it is not always an inflammatory process. 

Btiology. — The cause or mechanism by which normal regen- 
eration is brought about is more or less obscure. The cells have 
an inherent tendency to multiply, and this goes on to a certain 
point at which the normal development is complete. This limit is 
probably maintained by some restraining influence, but the nature 
of this is unknown. In the skin and mucous membranes, where 
physiologic regeneration is most active, new cells are constantly 
prcKluce(r and the older cast off. In what manner the balance is 
so maintained that production and destruction keep their equal 
pace is as yet matter only for speculation. The idea of action and 
reaction occurs naturally to the mind, and it seems probable that 
the rci)rodnctive processes are dependent in some way upon the 
loss oi substance. In some cases the normal restraining influence 
seems to be deficient and giant-growth results. In all forms of 
normal or physiologic regeneration the reconstructed cells are 
exactly like the pre-existing cells, and the status of the tissue is 
unaflected. In nighly-specialized cells, such as those of the 
nervous system, regeneration seems to be intracellular — that is, 
the wJIs are constantly rejuvenated by supplies of nutriment 
rather than reproduced in toto. 

In pathologic regeneration there seems to be abnormal stimu- 
lation of the reproduction of cells as well as a reduced restraint. 
It is not improbable that various toxic substances have the power 
of stimulating the formative process, though this has not been 
actually demonstrated. In all cases in whic-h regeneration follows 
mechanical, thermal, or toxic causes there is, first, destruction of 
cells, and following this regeneration. In such cases the relief 
from the accustomed pressure may serve as a withdrawal of re- 
straint, but at the same time there is doubtless augmented form- 
ative energy. The latter may result from the same agency as 
that which caused the primarj' cell-destruction, or it may be due 
to the influence of formative irritants derived from the dying and 
dead cells. The demonstration that micro-organisms are able to 
produce substances having a strong attractive or repellant influence 
upon leukocytes gives some warrant to the belief tliat similar sub- 
fUuices are at work in the regenerative changes that accompany 



bacterial diseases. In the case of tissue-destruction due to other 
causes siniiliir products possibly play a part. 

Pathologic Anatomy- — In tlic n<iruial regeneration of cells 
the prfj€Oss is one of gradual cell'muifipfi cat tort without marked 
chan^jes of any sort. Pathologic rejjeneration may be equally 
simple, but more ofYen there are eomplieated changes in the pre- 
existing tissues and new ibrniation of I dood' vessels preceiling or 
accompanying the n^genenition. The vaseidar regeneration is a 
neressar)^ preliminary, having the pui*|Hise of ^uj^plyiug abundant 
Dutriment to the tissues undergoing proliferation. 

Celt-muUiplicalion occurs in two ways^ tlie direct and the in- 
direct. The former nu^hod is <»ue of simple cleavage, l*y which 
the cell is divided into two or nu>re purts. Tliis muile of division 
is unusual. 

AmiiodM or dlnci veil illvkioji is a retrogmde process iu 
every instance. In some eases it is simply a fragmentaiiou 
of the nucleus owing to altered conditions in the cell and pn>l> 
ably not in any sense an attempt at cell division, When 
nnmenms fmgnients ure formed ^ and s(mie growth of t lie nucleus 
attends the jirocess^ giant cells may result because the protoplasm 
does not divide. 

Evidences of degeneration of the protoplasm are apt to 
be met with in such cells. Of these vacuolization^ gnmular 
or hyaline change, fatty degeneration, and even calcification may 

The common metlind is called indi reef .^erpncntatifm, kftrjiokincslM, 
or kari/omitosis. In this method complicated changes begin in the 
nucleus and fiiuilly lead to division of the cell into two or rarely 
into several parts. It is unnecessary to refer to the histologic 
stages in detail^ but in a general way we may describe the pnjcess 
as follows : (1) the uucIpus of the cell enlarges and the chrnmatin- 
fiiiers become thicker and less closely woven than normal ly ; (2) 
U->haped loops of chromatin*fibers arrange themselves around a 
central clear space or polar field to form a mofher-wrealh ; (3) these 
hiops then midergo liMigitudinal cleavage and the separated parts 
move one to one pole and tlie other to the (jpjKjsite pole of the 
cell, firming fkntf/httr-starft, which eventually Ijecome coarse and 
then fijie skeins of new nuclei ; (4) the p^^toplasm of the cell finally 
divides and the process l>eeomes complete. 

Abnormal iMl-diviaion. — Tiiere are certaiTi disorders of cen-multiplica- 
tioD that may be here deseribed. Karyokinesisp inj^tead of being a regular 
prrjcess of diviHian of the nucleus into two daughter iiucleij may proceed 
irre^larly. SometiiDcs the process is a»ijmmdric — t. c, doe^** not lead to 
equal division; in other canea it is multimkir^ several instead of two 
daughter-nil el ei resulting. Other leas definite irregularities are sometimes 
obeerved, and nome have held that cell-division may occur by a proceaa of 
tnired karyokineaia and amitosis. It is important to recognize that some 


of the forms of nuclear degeneration (karyorrhexis ; hyperchromatosis) 
may be mistaken for normal or abnormal karyokinesis. Pathologic karyo- 
kinesis is most frequently seen in malignant tumors. 

Pathological Regeneration. — In its simplest form, as for instance 
after a very slight injury to the cornea, regeneration occurs by a 
direct replacement of the injured cells by multiplication of the 
cells of the same kind at the point of injury. The intact cells be- 
come somewhat swollen, then undergo ordinary cell division and 
new cells are formed. In the reconstruction of surface epithelium 
involving to some extent the underlying tissues, as in lesions of 
the mucous membranes or skin, the surface epithelium under- 
goes the same kind of multiplication as that just described and the 
mass of new formed cells dips down somewhat into the space 
caused by the injury. In the deeper tissue new formation of con- 
nective-tissue takes place in the manner already described under 
the head of the Healing of Wounds and to be presently discussed 
more fully. In the subsequent stages, the redundancy of epithe- 
lium caused by the dipping down of the mass of new cells into 
the injured area is re<luced by condensation and gradual disap- 
pearance of some of the cells so that eventually the epiderm or the 
layer of epithelium on the mucous surfaces does not differ from 
that in the surrounding {)arts. When large areas of epithelium 
have been destroyed, the replacement of the epithelial covering 
occurs by gradual increase of the cells at the periphery of the 
denude<l area until in time the whole surface becomes covered. 
When skin grafting is practiced by the surgeon, a similar growth 
of the epithelial cells starts from each of the grafts placeil upon 
the denuded surface. 

Regeneration of Pibrons Oonnective-Tissne. — In all cases of exten- 
sive injury the connective-tissues take an active part in regener- 
ation and in the case of highly specialized tissues, new-formed 
connective-tissue takes the place of the specialized tissue which 
itself is less capable of regeneration. There is almost always an 
excess of cellular repwHluction and consequently an enlargement 
of the part aflfected by the injur}-. Subsequently the cells con- 
tract and thus the bulk of the new tissue approximates that 
destroyed. The new tissue must of necessity be more firm, as a 
larger number of cells are condense<l in tfie space previously 
occupied by a lesser number. 

The important processes in regeneration of the connective 
tissues are : swellingand multiplication of the connective-tissue cells, 
migration of the new cells into the area of injury, and the formation of 
new blood-vessels. The old connective-tissue cells increase in size 
and then undergo division by mitosis of the nuclei. As a result new 
celk of rounded outline and with rather pale nuclei result. These 



may remain at the point of their 
like leukocytes towards tlie cente 



L^hanfre of fri 

to undergo a change ol torni» uecuraing 
shaped or irregukir in outline (Fig* .^ 
36). It is these cells wliich are ac- 
tive in the hnal restoration of the 
tiasnes and the terms ** formative 
cells'* an*! '* tibro-blasts*' arc there- 
fore appmprintc. When tlie new 

Fro. 37.— Fortnutinn fkf new blornl- 
vestscb. as s>i*i*u in tlit* tail of a tadpole 

cells have been formed, increase of intercellular snbstance takes 
place. The IiIhtIs may he derived from the cells themselves by 
separation of lilanieotous prolongs tion^ growing out from the 
pointed extremities nf tlic spindle cells, or tliey may rcsnlt from a 
eleaviigc of a homogcncuus intercellular substance in which tlic 
cells an* at first imbedded. This intercellular substance doulitlcss 
is a product or a secretion of the cell. In either case tlje fibrils 
are essemtially a result of cellular activity. In the later stageg 
of connective-tissue regeneration, the fil>rils contmct and the tissue 
thus l)ecomes mure c< impact especially when the amount of iuter- 
cellular substance is excessive. The cells at the same time 
decrease in size and some are s<^> compressed as to be almost 
ohlitcrated. It is characteristic of newly ibrmcd connective-tissue, 
however, that np to the latest stages tbe tissue is more cellular 
than normal tissue. 

New-formation of blofMl-vessels is an important factor in regen- 
erations of conne*'tive-tissue when the extent of injury has been 
eonsidei-able. Kepair of very trifling injuries, sueh as an incised 
wound followed l>y a close appisition of tbe injured surfaces, 
does not involve nny new formation of blowl-vesscla thtaigh the 
pre-existing vessels lieeome somewhat hypcremic. Wheu the 
injur)' is more extensive vascularization is a necess^rv step in tlie 
repair. The new vessels result from extensions from the pre- 
exigtmg vessels. (Fig. .17.) The endothelium nf the caj>illarics 
becomes swollen and here and there processes are sent outwanl. 


These may unite with similar processes from adjacent capillaries 
or from the same one at a point somewhat distant, and central 
vacuolization may convert the loop into a primative channel which 
eventually becomes a fully formed capillary by multiplication of 
the endothelial nuclei and formation of definite endothelial cells. 
Sometimes the new vessel is formed by parallel outgrowths from 
aiJjacent endothelial cells of the parent capillar)^ leaving a space 
l>etween the new formed cellular extensions. Such new-vessels 
orx'ur around the site of injury and project in the form of loops 
int^> the area of injur)' itself, being surrounded by the newly 
form<.*<l connective-tissue cells alx)ve described. Usually the area 
of injur)' is first filled with a blood clot or coagulated exudate 
derivffd from the injured tissues. This forms a matrix in which 
the newly formed connective- tissue cells migrate and the capillary 
Kx>pH project. The clot or coagulated exudate is subsequently 
'd\}j¥}r\}in\ as the process of cellular replacement advances. The 
young <^>nnective tissue thus formed later contracts and the small 
bhKKl-vessels are largely reduced by compression so that the 
apiKTunince of the tissue may become that of a quite avascular 

In regeneration of connective tissues, elastic fibers are not 
o\mtTyiti\ in the earlier stages. Subsequently they are formed 
mon; c»r leas abundantly. 

Regeneration of cartilage and bone takes its origin from the 
IMfrichondrium in the former case and from the periosteum or 
marrow in th(» latter. In both instances embryonal connective- 
tissue such as that which occurs in regeneration of fibrous connective 
tisHUc*s is first formed. Later in the case of cartilage areas of homo- 
gen* ous intercellular substance appear and thus cartilaginous sub- 
stance? is rh»v«*loped. Very commonly, however, regeneration of 
fracturesof cartilages is mainly fibrous and there may be little if any 
true cartilage. Regenenition of bone in the case of fractures procee<ls 
in much the same fashion, an abundance of cellular tissue first 
appftaring around the fractureil ends of the bone, within the 
narrow cavity at the point of fracture, and between the broken 
ends of the brme. In this embryonal connective-tissue branching 
and Hidiating columns of rudimentary osseous tissue appear as a 
8<irt of network in which complete ossification occurs at subse- 
anent stages. Here and there areas of cartilage may also appear. 
Later much or all of the embryonal tissue around the fracture and 
within the narrow cavity is absorbed and the repair of the fracture 
18 made complete by thorough ossification of the part between the 
eoA» of the Ixme. 

Baceneration of adipose tissue begins with a formation of fat- 
finee cellular tissue. liiter the cells become infiltrated with fat. 

Segenention of Mnscle Tissue. — Striated muscle after injury or 
excision is capable of some regeneration by a multiplication of the 



muscle cells* The area of destruction is first occupied bj regener- 
atiugeonneetive-tissue into wliicli irregular ]»rotfn>lasmie projeetions 
from the emls uf the divided uuiscIl" HIuts extend, Sul)j^e(jucMidy 
thei^ elongate aud forui new innsck- iWiiT^ bnt they are apt \\\ I e 
narrow aud more or less irregularly arranged s\\ tliat the regener- 
ation is mrely complete. 

No typical regeneration of smooth nmsele takes place l>ut con- 
nect ive-ti.s.s ne fortuation (K^curs iuste:i<L 

RegcneratioE of Glandular Organs. — In epitlielial glandular 
organs, snch as the li%er, kithiey, mamuniry gluiid or sidiviiry 
glands, eoiisiderabh^ new formation of epithelial cells may take 
place. As a rule this regeneration prot*eeds frnm tlie epillielial 
ducts or canals nitlier than from the propiT tiecreting cells. In 
the liver^ there may he active prolifenitiou of e<41s and formation 
of new biliary dnets. This is sieu lu exj)erimeutal iujnries aud 
also in association with some forms of cirrhosis. The liver cells 
themselves show little tendency to regeueratiou thongh mitoses 
may commonly be found. In the case of the kitliiey, regcuenition 
mayaffet:t the cells of the stndght tuhules, while iu the mammnry 
glands, salivary glands aud the smullerglauds of mucous mend»ranes 
new formatiuu of aeiui :uul duets proree<ls from the smaller excre- 
tory ducts of the at1'eete<l glands. Iu this way an atypical gland- 
ular stnictnre may result. {This will be discntrsed under Adeuojua), 

Eegeneratioii of Nervous Tiasue* — Nerve fibers are caj>uble 
of eonsidemble rcgcnemtiou which proceeds from the sheath of 
8<*hwaun. The axis cylinder an*! medullary snl)stauce are 
differentiatKl within the sheath aud the new axis cylinder is possibly 
in a nu-asure an ontgrowth from the end of the existing axis cylinrh'r, 
Regenemtioji of the nervous fibers in the brain and ror<l takes 
place to hut a slight extent. Injuries here arc usually repaired 
by the formation *>f new connective-tissue and regenerating glia. 
The large uudtip<>lar nerve cells seem to be capable of inter- 
eellular repair after jjnrtial injuries hut complete regeneration is 
rarely if ever accomplished^ It is jiossible, however, that they 
may be ea]>able of limite^l proliferation as such cells oecur in cer- 
tain tumf^rs. 

Pathologic PliyBiology. — Regeneration is tlie more or less effect- 
ive effort of nature in rejilace iujure*l or excised tissn**. The 
restomtion is complete in j)ropurtinrj as the tissues lack in higlter 
organization aud diflereutiatiou, 1'he younger" the individual the 
more complete the regeneration of his tissues and the lower the 
type of tissue the more complete will be it.s restoration. In 
glandular organs, though some proHferation of epithelial structures 
occurs, the new formed glauchdiir elements are but little capidile 
of glandular activity. Newly deveh>ped nervous tissue is least 
capable of restoring the original functitm. 



MetaplaBia is the term applied to the transformation of one 
form of tissue into another without the intervention of a stage of 
regeneration by eelluiar multiplication. In many instances the 
change consists of a transformation of the intercellular substance, 
as, for example, when ordinary connective tissue is converted into 
myxomatous tissue, or fibrillar connective tissues are altered to car- 
tilaginous or even bony tissue. The cells themselves suffer second- 
ary changes. In other cases of metaplasia the cells may l>e 
primarily altered, as when ordinary connective tissue is changed 
to fatty tissue. 

The metaplasia of epithelial cells, as for example, a change from cylin- 
drical to squamous cells on the surface of mucous membranes has been 
doubted by some authorities. They assume that such apparent trans- 
fiirmationH are duo cither to ingrowths of the new order of cells from sur- 
rounding areas or by onlaivements of islets of mucosa covered with such cells. 
KxpcrimentM as those of Fiitterer, however, prove beyond doubt that meta- 
plasia does occur. In this process not only the old epithelia are altered by 
the changed conditions but the new formed epithelia, under the altered 
conditions of environment, develop into the new order of cells rather than 
into the parent form. 

Tho U^rm ^Wetrograde changt'* (Ribbert) has been applied to an alteration 
of cuills in which under pathologic conditions a lower order of differentiation 
is aiMumed, but in which the new order of cells do not accjuire specific 
characteristiw of a different sort Thus cylindrical epithelia of gland- 
ular tubules may be changed to cuboidal cells lacking the original func- 
tional cluiracters and not possessed of a new function such as would be the 
case with squamous cells. Similarly in the atrophy of striped muscle non- 
NtriattMl, narrow tUn^rs with abundance of nuclei give evidence of a retro* 
gradt« change toward embryonal conditions. 



TlIIH torni may Im» useil to designate pathologic conditions in 
whi(!h thort> \^ a dWided tendency to formation of new tissue. 


Defltlitlotl. — Tlie term hyj>t»rtrophy is applied to a jjathologic 
condition in whioli a ivrtiun jiart increases bevond the normal 
hIim^i without inarkiHl altoratiomi fn>m the normal stnicture. The 
term hyiM»rtrophy is frtH|nontly usoii loosely to designate enlarge- 
monta ol various kinds in which hut one tissue of an organ is 
inoroAHod, or in which then' is doj)osit of abnormal exudate. Such 
inatenoM aro not, strictly speaking, cases of hypertrophy. 




l^tiolof^. — The causes of hypertropliy arc quite Bnnifnius, 
floret.' cases there is a distinct iiiereaj^ of functional demand 
brought about in some way or ijther, a.s in the hypertrophy of the 
mu^es of athletes ; in the hyjK^rtrophy of a kidney after disease 
» removal of its feUow ; or in tlie hypertrophy of a limb after 
tnjun* to the opposite limb. The direct increased demand for 
work occasions the liyuertropliy. Sonnet ime?* there appears to be 
SL special tendency to hypeitrophy, iks is evidenced by the occur- 
rence of congenital or hereditary giant grt>wth. Most of these, 
however, are instances of p€»euliar and abnormal deveb:ipment, 
rather than of hypertrophy, the latter being a condition developed 
pathologically in parts previously well formed. Disturbances of 
the nervous system may play a part in the development of some 
hypertropliies, but these influences are obscure. Continued conges- 
tion undoubtedly stimulates tissue-growth^ but this element is the 
means wliereby hypertrophy is effected rather than the original cause. 

Pathologic Anatomy,^ Parts the seat of genuine hyper^ 
trophv are uniformly increased in size. This is well seen in the 
eondition termed giant growth^ or giganHsm, in which the bony 
faimework and other tissues may be uniformly affected ^ the indi- 
^rtduml growing to excessive size. Sometimes local giant growth 
of the skeleton and external tissues is obser%^ed, as in the case 
of one member or a single finger. This has often bcK'n found in 
eorre8i>onding members on the two sides of the body. In certain 
eases termed hypertrophy, in which this designation is more 
or less justified, kek of uniformity in the increase of the organ or 
part affected causes irregular increase iu size. 

Histologically, hypertrophy may be mmph' or fme h/pmirophyj 
and numerical (hyperplasia). In the former there is increase in 
the siJce of the individual cells ; in the latter the cells increase in 
number, though the individuals are not excessive iit size^ and 
indeed often smaller than the normal cells. In the hypertrophy 
of the uterus during pregnancy and of the heart-muscle in cora- 
fet^tLtory enlargement, simple hyj>i?rtroj>hy predominates, Hyper- 
pljuaa L«4 very commonly a factor in liypertrophy of any kind, but 
tamy be so strictly limited to one tissue of an organ, notably the 
connective tissue^ that the term hypertrophy is in no way appli- 
cable. Between these extremes there are all grades of cases, in 
many of which it is difficult to detemiine w*hether the designation 
hypertriDphy is applicable or not. In some cases the clinical desig- 
nation hypetirophic eniarf/ernfiH is used, though the condition is 
•trictly one of hyperplasia of the connective tissue, with a ten- 
denc)' rather to atn>phy than hypi?rtrophy of the pmper substance 
of the oigan. Instances *»f this are hypertrophic cirrhosis of the 
Krer, some cases of hypertn_>phy of the heart-muscle, etc. 

Pathologic Physiology,' — Hypertn>i>hy results from an 
iafjr^njed demand upon an organ or member, and leads to increased 



fiinetioriLil eapacity. Thus in tlie ciiso of a iliseased kidney the 
oppcfcsite kidney may he capalile of cotnpojisating for tht* defi- 
cieritT ; in tlif case of laborers the enhir|2;ed ninseles may meet 
every demand made upon tlteni. Tliere are oecasional inntanees 
of mtire or less genuine liypertrophy, resulting from diseased con- 
ditions, in whieh the excessive functional eapacity causes marked 
disturbances, as, for example, in case of enlargement of the tliy- 
roid gland. 


Synoii3mis. — New-growth, Neoplasm, Pseudoplasm. 

Defiuitioo. — Tn its broadest etynioiogic signiticumce the term 
tnmor designates an abnormal swelling in any part of the IkkIv. 
Thie definition, however, is not applicable to tumors in the ordi- 
nary sense. Inflammatory gmwtlis and collections, such as ab- 
»ceBseg, hyperplastic dciMjsits, and the like, are excluded. Path- 
ol ogists, Itowever, liave always found it difficult to construct an 
aeeumte definition for tumors or to draw sharp lines of separation 
between them and the inflammatory or infections swellings that 
occur in various diseascHl conditions. An attempt to establish an 
ultimate bounilar\'«line is eviilcnced by the term mdonovious nei/v 
growths applied by Thtjma. This name is used to designate the 
snpposed spontaneous origin of new-growtlisand their indi^pendenee 
of ordinary <'auses, such as nre recognized in the prfxluctiun of 
inflanrmat^jry outgrnwths and the like. It cannot be said* how- 
ever, that tnmors are ea useless, and in the discii&sion of the eti- 
ology we shall have occusinn to refer to certain definite factors 
known to aid in their prcMluctiun. It is true, however, that the 
growlh fif tumors is practically always out of proportion to the 
amount of local irritation or to the severity of other factut*s that 
may be conceivetl as |>laying some jiart in the etiology ; and in the 
great majority of cases the amses, whatever they may l)e, are 
ol)scure or unknown, A negative definition perhaps best suits for 
the delimitation of this term tumor. Thus we may exclude from 
the c^itegory of tumors all swellings in which s<jme sufficient cause 
is diseovemble, and include the ap|mreutly causeless growths 
among the true tnmors. A furtlicr eharacteristie of tumors is their 
iudependence. Excepting tiie l)lm>d supply there seems to be no 
dependence on the organism in which they oeeur and they con- 
tribute nothijig to the emiti nuance of its life and its integrity, 
N(>r is tliere any apjiarcjit restraint to the indefinite growth of the 
tumor comparable to that whic*h kecjis normal growth and even 
pathologic proeesses of other kinds withiii certain bounds. 

Despite all of these ciiaracteristics tlu^re are cases in which 
pathologists canncit determine positively whether certain growths 
are to be classified as tumors or some other conditions. 



Etiology,— A great nuojliiL'r of theories have been en tertiii tied 

to explain the causation ^if tninors. 

Among the older writers there was a disposition to attribute 
the iKHjurreUi'e oi' tmnorj? tti a nmsittHrfotud tli/sn-a^ia^ or a iliseai^cd 
state of tlie Hiiids t>f the IhmIw Tliis explanation, hc*\vever^ is 
bajsed entirely iipun s^upjnssition, and is mast unsatisthetory in that 
the as^simied ilvfecra^ra is as dirticult to explain as the tumor sup- 
pisetl to result from it. 

Recently a numl>er «>f more t*laborate theories have been eon- 
htnic'ted that resemhle this older one, in ascribing the growths to 
H>me f»rm cd" disturbance td' vital activity and v>f eell-proliicratit»n| 
witluait explaining tlu' cause of siicli ilisturbance, Fnr example, 
\vc may refer to the thenry that tuninrs result from a reirognide 
ehange in vital properties of ecrtaiu eel Is, sn that tlu^y teud toward 
the original ehamcteristies of the germ-cells ami multiply in a pur- 
jKjseless and indeterminate nianner. This theory- was bused upon 
the fact that asyuimetrie karynmitosis is iVe(punlly obHTvetl in 
tumors. It was assumed that in this uiH'i|ual divi>i<ui of the cells 
the peculiar, differentiating {puiHties of tlie cell are east of!' with 
the smaller portion causing the larger in the course of sevenil 
generations to IwH-nme ajiaphwtit* ar rvtrogrddiH], It has^ however, 
been shown that the same sort of asymmetric* mitosis also occnrg 
in non-tumorous eonditinus ; and an additinnal tketor tliat must 
entt^r into the theMry, the nature of the stimulus that eatises the 
anaplastic cells to proliferate actively, is wholly unexplained, 

^Vnother theory would explain the occurreut^e of new growths 
fiomewliat upc»n the basis of infection, assuming, instead of an 
exogenous infection witli nderoorgajnsms, an endogenous infect iuu. 
This was suggested iiy thv discovery of leukocytes within the 
tumor-cells. The nuthor uf tlris theory ixplaius that iu vou- 
fiequenee of some thernjii", chemical, or other irritation certain 
eeUs may become^ so to speak, infections, assuming the rtllr of a 
S|>erm-ccll and stiuiulating the adjacent cells to abnormal multi- 

1>lic4iti«»n. Such theories, iiowever, are entirely s|>eculative, and 
eave the etioh\gy as little settled as Iteforc. 

Virchow strongly advocated the theory of eMertufi irnfation^ 
and was aide to cite numerous examples of tunu»rs thut had arisen 
in consequence of more or less defirdte traumatism. Thus iu cases of 
f^arcinonia of the breast, in the epithelioma occurring on the lips 
in pipe-sm<^ikers» and in the epithelioma of chimney-sweeps, tluTc is 
at times a definite iiistory of unu>ual irritatirm, aud the relation of 
caus*J and effect seems easy traceable* It must b*' admitted, 
however, that there is some i'urther underlying cause which 
renders ojie individual liable to tumor-growth, while another is 
not thus predisposcfb aufi tiiough it is proljable that some tumorsi 
owe their origin to irritation as the exeiting-eanse, all cai«es can- 
not thuB be ejc plained. 



Coholieim advaocf^rl the interc^sting theon' that defepfivc devef- 
apmmt lies at the basis of tumor- format ion* Accorilin|^ to his 
theory, there are frequently einall errors of development leading 
to the inclusion or misplaeement of portions of the original blasto- 
derm in the midst of tissues deri%*ea fn>m a different layer of the 
embiyo. These inclusions or emhryonie restH are independent of 
the function of the ]>art in which they lie, and are assumed to be 
liable to subsequent sprouthig with the consequent formation of 
tumors. There is evidence tliat this theory contains a certain 
measure of trtith, and s<ime tumors, as, for example, ct^rtam 
ovarian growths, tumors of the jtarotid region, and others, seeni to 
originate in tliis way. The tlieyr)% however, is not by any means 
UDiver!!jally applicable, and it leaves unexplained the final prolif- 
eration «»f the embryonal rests that ha«l previously remained dor- 
mant. The assumption, however, that such rests wouhl quite 
readily take on active growth as a result of various simple irritations 
or wlien the vitality of tlie part was stimidated, is ha^a forced than 
that which wouhl attribute such proliferative activity to cells in 
their normal relation to surrounding tissues. Similar conditions 
may be brought about by disease or injury of various tissues. If 
certiiin cells or j)arts of tlie tissue are displaced from tlieir normal 
relations to the surrounding structures, the same conditions are 
established as by the embryonal displacement of portions of tissue. 
Xot improl^ably this sonictinu's tx?curs either as a result of acci- 
dent or of (Urease ami subsequently tlie displaced iwjrlions may 
pmve the starting point of tumor growth. liecently some 
authorities have insisted upon this as a frequent occurrence and a^ 
explanatory of many tumors. Experiments have shown that 
certain types of epithelium (epidermis) botli adult and fetal, as 
well as certain fetal connective-tissues (cartilage) nuiy be exj>eri- 
nientaliy removed from their U(>rmal j>ositi4m and implanted in 
another part of the same animal and still retain their potentiality 
of growth. Sucfi transplanted fetal tissues do not continue to 
reproduce the fetal stage but tend to reproduce the ultimate stage 
of the transphiJitcd tissue. Furthermore in no case bus there 
been found any infiltration of surrounding tissues bv transplanted 
tissue, nor any tendency U\ metastasis. All of this shows that 
there is something additional iu thedevelupment of tumors beyond 
the mere dissociation of structures from the surrounding tissues. 

Recently an tn/rrfioaii eharncfrr has been as<!ril>ed to malignant 
and benign growths, and there is no doubt that in c<*rtain respects 
tumors resemble infectious prwesses of definite! v ascertained 
kinds. Their effect u\ym the general liealth and their tendency 
to metastasis are very significant facts. Furthermore the discovery 
that various pathologic proeesst*s chartietcrized bv nodule form- 
ations resembling tumors in gross appearance are in reality infect- 
ious growths lends color to the suspicion. The resemblance of 



such growths to tumors is, however, merely HiiperfieiaL As far 
as mottiBtasis is eoiicernefl tumors differ iiotiil>iy from infections 
for, io tlie former, parts of tlie growth itself are coiiveye*! to some 
place at a distance from the starting i>oiot, tiiere to jiroliferate and 
occasion a metastatic inxhile, while in the ea^se of infections the 
mieroorgiinisms alone are earricd to the secondarv sitnation where 
they occasion clianges In the locni velis similar to tliose fbnnd in 
the original focus. 

Nunierons investigations have been made to dt^termine a possible 
connection of l»aeteria with tnmors. These have proved beyond 
tlonht that no hacterinni of ordinary sorts has any such relation. 
The possifiility of ultra-microscopic organisms and even of such as, 
through excessive pamsitic character, could not live except in 
other cells, lias been considered* 

Secondary and accidental invasions of bacteria into tumors may 
occur and sometimes confusion has been occasioned by this circum- 

Various investigatoj's since Hanan luive found it possible to 
transplant certain tumors from man to animals or from one animal 
to another This has sometimes been interpreted as an evidence 
of tlie infectiousness of tumors thongfi with dtvubtful propriety 
since tlie transplantation of the tissue from one site to another, 
like the phenomenon of metastasis, proves only the proliferative 
tendency of the cells of the growth and not of necessity any infec- 
tious origin. The transplantation of part of the tumor from one 
animal to another or from one part to another in the same animal 
d<:»cs not ditlcr from the transference ol' |>ortions of the tmnor to 
distant ])laces in ordinar}^ mc tastasis. 

In carcinomata ami «ttlier epithelial new-growths, as well as 
in sanxmiata, certain tbrnts of supposed am'mal jmrasites have been 
described. In 1889 Thonia found in the jirotoplasm and nuclei of 
carcinoma-cells iMKlies whieli he reganled as coccidia; and about the 
same time Malassez and Albarrau fonmi sijnilar structures in the 
cells of an epithelioma of the nuixilla. Darier found bodies of 
the same kind in Paget 's lUsease of the nipj^le and many sub- 
sequent investigators have described similar formations. 

Among these supposed protozoan organisms some are iidra- 
nneteat\ some extrannrkftt' and some wholly exirnrrfhifar. Among 
the intranuclear and extranuclearceil-inclosuresSjorhrijig deserilied 
round bodies whicli tend to grow and eventually sporulate, form- 
ing cystic bodies coutaiuing twent}' to thirty spores I sfvore-cysts). 
These structures resemble the parasites of silk-worm disea.^e, and 
are so classified by Sj orb ring as micn^sporidia. Sndakewitseli and 
others have descrihed bodies more close4y resend>ling coccidia in 
their sharp, double contour and the presence of peculiar, sometimes 
sickle-shaped, bo<lies within. Podwyssozki and Sawtschenko 
described forms diflVring fi-om coccidia in the absence of a distinct 



eapsiik*, and resenil*ling nitlier the amebic, such as those oociirriDg 
in the blofMi of birds and Ja malaria* The views of these authors, 
partieularly Sa\vtsuhenko» have, however, undergone some modifi- 
eatiou in tlieir several eonfrihntions. Rnt!er, Plinimeruud Walker 
deseril>ed Htruetnres oeeiirriiig only in the protoplasjo of the cells, 
and resetul>ling eoeeidia, hut forming neitln-r spores nor siekle- 
shajM'd IxMlies, hut midtipliiig hy direct division (Fig. 38). Many 

Fig. 38.— Indiislona in fancer-cells : a nnd fi. mrly stages of "puirajiitlc" bodies; f , Ute 
9it«goi(, showing diviNiou by scgmetitalkm ; ti, cHnetT-ccn conuiiuliif; leukucjles (Ruffer). 

of the investigators lay stress ii[>ou the behavior of the supposed 
parasites toward stains. Thus Uufter and his eollahorators point 
out that the nuclei of their pai'asites do not receive basic stains 
like eell-uuelei, hut the aeid stains^ and tlie body of the jmrtisite 
is scar<"ely at all stained* This point, however, lias certainly been 
overestinuitetl as an intlication of the parasitic nature of the bodies. 
Degenerated cells notoriously vary from normal ones in this 
resjT4?et, The stipp<3sed spores of Sjorbring and others are very 
probably products of degeneration, as Rufler and others contend ; 
and it is possible that some of tljese supjMisetl parasites are degener- 
ated leu kwytes or epithelial cells included witinn the eancer-eetls, 
wliile others^ if not alb are simply products of cellular activity 
(seeretious) or cell-<legeuenition. 

Siyme authorities bave advanced a theory cpnte different from 
the above, liuldiug tliat the eanec^'-celis tbemselves are parasitic 
nrganisms, Xru^otueli' distinguishes three kinds of orgmiisnis in 
04ircinonui : aniebie, eoeeidiji, au<l grcgarinidie. The anichoid form, 
wliich he calls Am*rhn enckexlcff^ Ijas a granular protoplasm an*l a 
clear nucleus. It is actively motile, antl may h^ave the e|uthe]ial 
cells to enter the eemneetive-t issue. After estal>lishing itself it 
becomes encysted, the uueleus breaking up and the proto^dasm be- 
coming more dense. Ziwids and sporozooids result, tbe former 
going on to the formation of a gregarina (Kbo)mloct phalus earei- 
noniatosus) (Fig. 30), or a c^jccitliuni, the latter forming new 
amehte. Some of the structures figured by KorotncH' are undoubt- 
edly merely cant*cr*eells. 

A few autliors claim to have found parasites of various kinds in 
the blo^id of cases of carcinoma. 

Recent investigations have brought forward a few additional 

faooassstrs nssvE-cBAxoESi 


uftUJ«iui (Korotnein. 

^'bcMfies," llie proionui omtuie of which lias been cljuim^ Uv the 
Ammgi ggy mad the etiolo^ unpoHanoe of which has berii iniijjeil 

El the abnndaiioe and distribatkNi of the bodies md some iiicoii* 
▼e cAirts at mJtivatioii and inociilAtion. A 
doee atadjr of the whole subject points to no cer- 
tain resolt. The ^tippo^^d panisites or cell-in- 
clygjoos of various kinds are doubtless in most 
eases products of cell^ctivity, while others of 
the SQ^o^ ** protozoa " are pnxlucts of cell de- 

Recently blastomycetes have ^»een thought of 
some etiolugical importance in the causation of car- 
cinoma, but a careful review of the literature is 
cooviucing that the evideuce doe^ not suffice to 
establish any such eonn*x*tion. Blastomyct^tesdo 
not constantly occur in malignant tumors, aiul vvliou 
present are not in such nunib«:»rs or in such rela- 
tion to the tissue as to establi.^h an etiolojrical 
significance. The lesions definitely known to be 
due to blastomycctes are of entirely diflennt 
character from those of tnnior growths, Ijcing strictly exudative 
and inflamniator>' with prolifenitton of eudotheliiuu and cou- 
uective-tis^ue, such as CK*c«rs in infectious inHauniiatioiis, The 
proliferation of epiderm s<on in the Ijlastoniyretic skin-Iusions of 
man is entirely secondary to the chronie inflammation of the 
und<-rlying tissues. 

Predisposing Coiiditions« — \\lmtev<T may eventually pnivf lo 
Ik? the immetliate eaiise of liiniors, it is etTtaiti that preclispnsiisg 
causes are often of great importance. Tlie ttccurreiioc tjf ecrtaiii 
forms of tumors in persons <if advanced age and in persons whose 
vitality has been reduecil hy disease gives evidence that a consti- 
tutional predis|x>sition is sometimes rotjuisite for the formation of 
the new growth. The nature of this vital defect has sometimes 
been speculated upon, and retrograde vital metamorphonis of the 
cells or other like changes have boen assumed to oceun These 
theories, however, are purely speculative. In s<nnc cases there is 
evidence of a family predisposition, and lieredity was fonnerly 
regarded as of great inifHirtancc. While this element cannot be 
entirely denird, it has certainly been over-estimated. 

The Structtire of Tumors. — In their histologic structure 
tumors do not ditfer abstjiutely from healthy tissues. In all cases 
thev conform more i^r less with the structure of some one or more 
tissues. Tlie cells eumposiiig tumors invariably represent some 
one or several types of norujal cells, though they may tlilfcr in 
being larger or smaller than the normal cells, ur in l>eit»g of eraliry- 
onal or undeveloped eharacter. 


Not infreqaentlv asymmetrical and otherwise abnormal mitosis 
of the oelLs is observed. Some reference to the varieties of such 
mitoses wiU be found in the section on ceUohir necrosis (p. 104 ). It 
is important to note that such mitoses are not confined to tumors, 
but occasionallv occur in inflammatory and infectious cellular pro- 

In the arrangement of their cells tumors differ greatly from 
normal tissues, and they may be described as being atypical pro- 
liferations as &r as their organic or tissue arrangement is con- 
cerned. The onlerly disposition of cells and stroma or intercellu- 
lar substance seen in the normal tissues and organs is wanting, 
particularly in the tumors in which organic arrangement is simu- 
lated. There may be in some cases entirely typical glandular 
acini, but the relation of these to each other and the absence of 
regularly disposed excretory ducts render the tissue as a whole 

In the histologic examination of tumors it is customary to find 
scattered through the stroma and between the tumor-cells various 
forms of leukocytes, especially the polymorphonuclear forms and 
lymphocytes. The imperfect development of walls of the blood- 
vesseU of tumors permits of ready emigration of leukocytes, and 
there is, therefore, in practically every tumor a certain amount of 
leukocytic infiltration. Sometimes leukocvtes are found in enor- 
mous numbers ; and when a tumor undergoes inflammatory change, 
massive accumulations and abscess-formations may be met with. 
Plasma-cells, which are probably altered lymphocytes, are some- 
times conspicuous, and mast-cells (basophilic granular cells of 
doubtful significance) are sometimes found in benign as well as in 
malignant tumors. They are frequently abundant near the edges 
of the growth. Eosinophilic leukocytes are occasionally quite 

The leukocytes are often found within the tumor-cells in the 
form of inclusions. These, doubtless, have been mistaken for 
parasites in some instances. 

The blood-vessels of tumors have comparatively fragile and 
poorly developed walls. In the malignant growths or rapidly 
developing tumors of any sort the vessels are mere spaces between 
the tumor-cells, with little attempt at the development of firm 

Regenerative changes are constantly met with in tumors. In 
this way the connective-tissue framework of the growth is formed 
just as such tissue is normally produced, and in this process elastic 
as well as ordinary connective tissue may be formecl. In rapidly 
growing malignant tumors the framework of the tumor is for the 
greatest part derived from the pre-existiug connective tissue of 
the affected part, and only in very small measure from regenera- 
tion of connective tissue. 


The «triicture of tumors is uhvuys closely rt4attHl \o that of 
the tiseae from which it sprioj^, a priman^ tumor invariably ^mw- 
ing in a part in which there is tissue of the typt^ simulutc tl by the 
^ tumor, and it is from this tissue, doubtless, that the tumor takc8 
'ite origin. A connective- tissue growth invariably springs fnmi 
a part in which connective tissue of some form has pn*-exist«Hl^ 
anil epithelial growths from a part in whieli then* has bin-n 
epithelium. Transtbrmatiou of one variety of tissue into anotlier 
variety, with the prcnluction of a heten>lo£^>us tumor, tkn's not 
occur, Thijs statement, thouj^li applicable also to secondary tu- 
mors, is sometinii^s ilifficnlt of dennmst ration from the fnet tlint 
the secondary grow t lis take origin from cells tnu»sjH>rtcd to the 
ftt of the metasthetic growtli, though iiot normally found in the 
"|iart in which the secondary tumors have orlseiK Th(* oeeaslontd 
dis< -overy of a primary tumor in a locality in whicli the fonn of 
tissue composing the timior tloes not occur mny he explained 
upm the assumption (based tm some actual tlemoustnitions) that 
embryonic rests had been deposited at the seat nf tht* tumor by 
faulty developrmvut 

The Shape of Tumors. — This depends to a large extent 
upon their manner of growth, their situation^ and the intluence of 
siurrounding jwrts. We may distinguish, tirst of all, between 
cirtmrnserihi'd and iiiJiHratlnf; gmwths. The J'orrm^r may Im' uf 
various shapes, but are distinguishi'd by their sharp delimitation 
and often by tlic existcnee of a distinct capsule ; the hitter are 
indeterminate J and the extent to wliieh they involve tin* healthy 
tissues cannot be accurately determined, CircumseribfHj tumors 
usually grow eentndly or in an exjmnsive nianiier, tlu* new erlls 
being produced in the interii^r and gradually pnsliing tlie oldi-r 
parts outward towanl the surrounding tissu(\'^. The iidiltniting 
growths are eccentric in development, and may ri'sult iVom a 
gradual extension of parts of the peri|»her)^ of the original j^^rowth 
or by the development of secondary nmlules in the iieighhorhmxl 
which become confluent with the original mass. f>t' the eireum- 
ccribed growths we may distinguish small mj<lules of spherical or 
ovoidal form burieil in the substance of the tisane or i»rojeetlng 
fnmi some surface as more or less hemispherit*al elevations. Tht^w 
may be large or small, and the terms milinn/^ tuljeratlary nmlular^ 
and the like are employed to designate the indiviflual gnuli^M. 
When a tumor projects imm the surface in sueli a manner that the 
projecting part is larger than the [lart between the pnjjeetion and 
tbe sor&ce of the I^kkIv or the organ involved, the term funf/ifmin 
V fimgoid tumor may be applied, while in the imn^-^ in which the 
growth is attached by a more or less narrow iiediele the name 
or jKdypmd tumor is applieable. Wart-Iike growthd an* 

„ J as verrueoAe or papUlary tumors, and tboee in which a di»- 

' tiod cdttItflower-li >rm is developed are called dtndrHic, 



The Number of Tutnors. — Prlmarif lumor.^ are iiso:iIly 
solitan^ at thtir onset, though examph's of multiple primary 
growths, such as eai-cimmia involving l>oth bivasts si mul tan eon sly, 
or sininltaneons appeanmee of eareinumata or sarcomata in differ* 
ent partvS of the oiueous memlimne or ( l^ewlicrCj may he obscrved. 
In these eases it is ofteo likely that there was a .single tumor at 
the very onset, with seeoinlary growths originating beti>re the 
primary growth had reaehe<J any ecmsirlerable magnitude. Primary 
benign tunior>? are usually s*jlitiiry» hut sometimes may Ik? found 
in eonsitlerable number, and there may be enormous numbers 
scattered in various jxirts of the l)ody. Thus in cases of mnlti|»le 
enchoiHh'oniata i>r multiple fibromata the numljcr may fntuj tlie 
6rst he very great, 

Seconda/'t/ tamom are usually multiple. In most cases the 
number of nodules found p<»st- mortem or during life is considerable, 
and sometimes they are so numerous that large }:K)rtions of the 
body may he litendly stu<lded with new-growths. This is seen 
very well in the secondary sarcomatous or carcinomatous nodules 
involving the peritoneum and the oth(^r serous surfaces, in which 
cases the degree of involvement is ^sinlulateil only by that seen in 
m i lia ry tu here u 1 1 >si s. 

Pathologic Physiology,— In most cases tumors take no part 
in the functional life of tlie part in which they occur or of the in- 
dividual. What influence they may l)car to the general nietab<>lism 
is as yet practically unknown. Cases, however, are re curded in 
which large lipomatous or other tumors liave been found to sufler 
practically no change^ while the individual in whom they occurred 
was undergoing progressive emaciation from starvation. That 
there is a certain auiouut of fnnelion, however, in some cases is 
shown by the tact that biliary pigment is detected in the cells in 
certain carcinomatous tumors of the liver, or abortive milk-torma- 
tion in cancers of the breast. It may be that the want of proi)er 
organic arrangement, and particularly the lack of excretory ducts, 
accounts for the lack of function ; but w^hatever the cause, it is 
certiiin that as a rule the fuuctional aclivity is pnictically ni/, or at 
all events j>e?r%'erted. The occurrence of large quantities of 
glycogen in certain tuuiors is perhaps of interest as indicating an 
attempt at functional activity, but is more probably significant 
only of active proliferation. With very few exceptions h may be 
said that tumors are entirely parasitic, living at the expense of the 
organism ami contributing nothing to its development or nutri- 

Certain tumors disturb the general healtli. This result may l>e 
due to secondary degencmtive or inHammutory changes deix^odent 
upon lack of nutrition or ujxm irriUition and bacterial infecti<>n ; 
or to obscure caiLses connected with the tumor-growth itself The 



progressive ciiehi^xia uf eiUTiiKmia i^ ^till nin'xpiaiiie*]* tlion^li in 
mme cases hemorrhage and interference with organic fu net I on 
pluv a part. There are probably noxious prrxlucts of some sort, 
tijoiigli tlieir nature is still entirt^ly unknown. 

Tumors nia V lie cbssitied as henu/n or mall^nanL The former 
do not affeet tlie general healtli of the patient in any notable 
di'grL-e, and are dangerous nun id y hy rt-iison of the pressure I hey 
may exert on %utal struetures or tlie seeomhiry changes (hemor- 
rhages, softening, snppuratinn) to whieh they are liable. Malig- 
nant tumors generally disturb tbegenend health from the first, and, 
in addition, tend to reenr after removal and sj>rea<l to other parts 
of the btwly (by diitvt invasion or by metastasis through tJiecir- 
enlation or lympbatie ebatmels), 

Meta.stiisis, or the transplantation of a tumor from one part of the 
body to anotiier^ may oeeur in st'veral ways. Tht^growth may invade 
gurroundiug lymphatic or venous chaimels, and extend in a linear 
manner sometimes to considerable distnnees. Tlins a growth of the 
neck may extend in tljc jugular vein and vena cava as iar as the 
right heart. More commnuly, single tunmr cells or small numbers 
are carried as emlmli ah^ng the lymphatic or venous channels to 
some new IcN'ation where a secondary growth results. A thinl 
method is that in whit-h parts of the tumor are spread over free 
surfaces sneh as the peritoneum or pleura, and thus occasions new 
foci. Sometimes, tbougli rarely, this happeos on mucous sur- 
faces also. 

Occasionally tumors that are ordinarily benign recur after re- 
moval or cause metiistasis. The fornu^r eircnmstanee is not in- 
frequent in the case of nasiil polyps and keloids of the skin ; the 
hitter in the case of adenomata of the tliynMil glanrl, ehondni- 
mata, Iciontyomata, hemangit»mata and occasionally some others. 
The nuunier of gnnvtii (eentml j>roliferationl doubtless accounts 
f^ir th<^ infrcquency of metastasis of benign tumoi*s. 

The terms prhnartf and sfrimcianf tirmors refer to the original 
and the nictastatic growths respectively. 

Classification of Tumors. — No very ^atlsfaeti^ry elassitica- 
tiou is [lossible at the present time, and it is unlikely that any will 
he constructed until more <letinitc knowledge regartling the etiology 
is obtained. The older elassi Beat ions were based upon the shape, 
the phvsieal properties, or the natun- (whether destructive or 
harmless) of various forms, Vircliow otiered a classitication liased 
on the histology of the new growths (histogenetie elassiJication). 
According to this classitication, fTl>roma, osteoma, chondmnui, 
lyniphomaj and sarcoma art- included under the hi'adiug of con- 
nective-tissue tumors or tumors reproducing m*>re or less accurately 
connective tissues. The ditt'erent forms ol" tumr>rs comprising the 
group are distinguished by their resemblance to one or another of 



the forms of connective-tissue. Among the epithelial growths arc 
papilloma, adenoma, and carcinoma, and in the same group should 
oe placed glioma, which, though it superficially resembles con- 
nective-tissue tumors and arises from the neuroglia, a tissue resem- 
bling connective tissues in function, is really an epithelial growth 
as the neuroglia is an ectodermal derivative. Among the tumors 
reproducing muscle-tissue are the two forms of myomata, the 
leiomyoma and rhaMomyoma. 

This classification is eminently satisfactory in some cases, but 
fails in the ease of mixed tumors containing a variety of tissues 
and in which the primary' or the essential constituent is not always 
obvious. Thus in papillomata it is sometimes difficult to deter- 
mine whether the growth is originally epithelial or originally of 
connective-tissue type. 

Recently it has been suggested (Mallor}^) that a more careful 
study of the histologic diiferentiation of the cells and intercellular 
substance may serve as a basis of classification of tumors. Three 
forms of fibrils called neurogliay myoglia, and fibroglia fibrik 
have been distinguished, and have respectively been found in 
gliomata of various types, in leiomyomata, and in connective-tis- 
sue growths including fibromata, fibrosarcomata, and spindle-celled 
sarcomata. The fibrils diifer sufficiently to form the basis for 
the recognition of the character of the cells from which they origin- 
ate, irrespective of the rate of growth or physic^al properties of the 

Other |)athologists liave grouped tumors according to the 
embryologic derivation of the tissues from which the new-growths 
originate or of the tissue composing the tumor. It is perhaps 
wisest to attempt no classification of any kind, and in the follow- 
ing sections I have arranged the various tumors according to their 
histologic charact<?rs without attempting to establish groups. 


Definition. — A fibroma is a tumor composed of connective- 
tissue cells and fibers resembling those seen in fibrillar tissue. 

Btiology. — The causes of fibroma are as obscure as are those 
of tumors in general. There are many facts, however, which 
point to the importance of irritation or injury as exciting causes. 
Among these may be mentioned the development of a peculiar 
form (keloids) in scar-tissue and the resemblance of these tumors 
to spontaneous fibromata, and the appearance of fibrous nodules in 
the skin at points of friction or definite pressure or in places irri- 
tated by discharges. 

It is impossible to draw sharp lines between fibromata and 
hyperplasias of connective tissue following irritation. In the 



skin and superticial tissues there ofciir hyperplastic connective- 
tisRU*^ pmc*esses, ooni^titntin^ olephuntia,<is, wliirh in Home cases 
arr ilistinrtly tlie n^'^ult «>f irritaticm and in other ra^fs ^evm 
purely spontniieoiis. Tlit* t*l( piiaiitiasis of tropica! foiintrif'^, f>ften 
due to fM'<"lusiori of the lyiojdiiitie channels hy filarial and the 
thicken ing of the pkin ami adjaeent connective tissue of the leg:i3 
around old ulcerations or eczema tons areas, are instances in which 
dii^tinet irritation is the canse. On the other hand* congenital 
elephantoid (n>n< lit ions of the skin are seeniinji^ly spf»ntaiieous or 
causeless, and sojue of the cases in later life have the siifoe ehar- 
aeteristie. The diffuse hyperplasias of the viscera, thoo^i often 
distinctly inflammatory, may afjpear without adet^uate discover- 
able cause, and, acc<u'<iinti: to the view of some authorities, are 
to be looked ujMin as diffuse fibrosis or fi luTmiato.sls, rather than 
as inflarnTuatory etniditious. In ordinary eases of scIerosi,s of 
the ortjraiis the ci»uneetive-tissue growth is entirely diffuse, but 
ihiekening-s may oeenr in certain situations, and the reseml>lance 
to tumor-formation is then mucli more striking. This is sometimes 
the case in the liver, but partieularly in the kidnevs. In tlie 
breast there are case,s in wiiieli no dividing-line can be drawn 
between ehrnnic^ interstitial mastitis and fibronuL The micro- 
scopic appearances are practical ly identical. A distinction, if auv 
ean be made, is bas<'d up<m the nodular character and sjKintaneous 
origin in t!ie one and the opposite eomlitions in the other. 

Appearance. — The nakwt-eye appearance of fibromata is 
usually quite ehameteristie. The tumor may be hard (Fig. 40) 
or soft (Fiu:* 41), aeeordin^ as it resembles hwse or dense con- 
nective tissue in stnu'ture and aeeordint^ to the amount of 
p<leniat<^«us liquid or associated myxomatous degeneration of tlie 
intercellular substance. The growth is more or less ronnderl and 
usually enclosed hi a flistinet ca|*sule. In tlie substance of organs 
it is spherical (*r tuberous, ami wfien near the surface projeets more 
t»r less. Wlien it springs from a mucous or stMXHis niemljnine or 
from the skin the weight of the tumor may gradually lead to a 
j-MiIypoid tbnuatiou. Stmie of the tibrfimata of the skin are arlKv- 
rescent or dendritic in form, and keloids are frequently irregular 
or star-like in outline. The rounded and enejipsulated tumors 
limy be lobulated, thougii more frequently they occur in a uniform 

Seats.^ — The points of origin fnmi which fibroid tumors arise 
'are very numerous, thougii they always spring iroiu pre-existing 
connective tissue. Among some of the more common hvcalities 
may \w mentioned the subcutaneous connective tissue, the sub* 
mucous tissue, the p(n'iosteiim of bones, tendons^ and tendon- 
sheaths, and the tibrons covering of nerves. Of the internal 
organs, the uterus, die ovaries, the kidneys, and heart -muscle are 



the most important. Less frequently fibromata are found in the 
serous membranes of the chest and abdomen or of the central ner- 
vous system. The fibroids of the skin, the uterus, the nerves (see 
Neuroma), and the mucous membrane of the nose are the most 
important. ' 

Fio. 40.— Hard fibroma (Warren). 

The mammary gland presents several interesting forms of in- 
flammatory or fibromatous new-growth. First, there is a diifuse 
form of interstitial mastitis in wliich the entire breast becomes 
indurated ; this is distinctly inflammatory. In other cases nodular 
or lobular areas of thickening occur, and in these the evidences of 

Fig. 41. — Soft libroma of the subcutaneous tissue. 

inflammatory action are sometimes obscure or wholly wanting. 
Some of these are certainly instances of true fibroma {fibroma 
mammce nodulum). In still another group of cases the fibromatous 
proliferation of the connective tissue projects into the tubules and 
acini of the gland, pushing the epithelium before it and sometimes 



sproiitini^f or pniliftrathig in |H)ly|vuicl form with in the tnhiiles. 
The gland in such rases may present a t^trikiug macroscopic appear- 
ance on section. Numeroii:^ eytatic forniation.s may be visible with 
projecting dendritic fonmitians within, eausin^ an aj>peanince 
somewhat like that of a !seeti^«n through a eaulitlower (Fig. 42). 
Mieroscopieallv tlie proiifemtion.s of the eouneetive tissue between 
the tubules and projecting within the tubules constitute the 
charaeferistie features. The term infraanuiik'uhr jihmma has 
been given to sneh cases, Obstr notion of the tnbulcK in certain 

Fia. 42,— IiilmcratmlirMil^ir tibruimi iTerl*), 

areas may lead to very- marked cystic distention. Combinations 
with san*oma are frequent, 

Stnicture,— The definition explainf> the structure of iibro- 
mata. On section through the body of the tumor the fil irons 
nature may be revealed by a distinct concentric or radiating 
striation, partieidarly in the ease of hard fibromata. The softer 
varieties are mueh lej^s likely to present this feature. The color 
is usually gray or whitish, and may ix* glistening when there is 
raneons degeneration, or yelhiw in the ease uf associated lipoma. 
Microscopical ly a striking feature is the conneetive-tissue cell^ 
which is rounded, star-like, and bmnching in the softer tumors, 
and compressed, spindli'-sliaped, or elongate*l in the casc^ of the 
har^l varieties. The iutereeliular substance isc(»mposed of a fibril- 
lar netwftrk ami liomogeneous or gmnuhir material traverse*! Ijv 
thin-walled l)l<HMl-vessels, ofttimes liaviug merely an endothelial 
coat. The parallel and wavy bundles of fibrils are the most con- 
gpicuous feature of hard fibrumata. In softer varieties tlie fibrils 
are less otWn in bundles, and are twisted or irregnhirly eurletb 
Tlie fibrillar substance may be so closely packed that the inter- 


r-..juiijr sIJr^^cL^>^ !SA5 a elistoniug, hyaline appearance. Thiri is 
T-*^ mLTL^i :i k-el-r-fris- S.^merinies actual hyaline change affects 
iiH iiir-.-r. \x-^^n*:<:^ dilatation and rupture of the ve»?ei- mav 
«jih^ i ii?cn^i-'C i-ci:>rrtuigic appearance of the section, bat such 

Ii ?i me rai?ef rcibrronal round cells niay be abundant and a 
dt^ini"" sLT!' am: . ^is iruistomiation of the tumor may occur. 
Tnfc. ii'v-t^-r. jr rarv^. In other instances, as has alneady been 
Teniin!L.-L n-TcaLvis tissue may be c^inspicuous. and all grades 
♦r -znnrrd rmiii* c fr»:'Ci a pure fibroma to a pure myxoma may be 
m^ vo. -r^e^iallj in the case of soft fibroma. Fattj- degenera- 
Ti'n r II*- :tI2- izd lipii-matous infiltration or associateil lip>ma 
irr- 1*^ zr-. ifrct- Thtnse forms, the myxomatous and lipomat^^us. 
itr- yasrzt-^'i.iLr.j f:v»i:ient in the submucous and subcutanei>as o^«- 
it— 1- - T:rr-i^r«?. •! al'iai^Mis degeneration occurs in laige fibrom- 
in.»i.- TiZLs rrr. rarii^Iarly in those of the uterus, and very raivly 
TTe — iTitarj.r '::iL? i>een reported. Less commonly ass-x^iarion 
•r x:r*i:ii. -rrz. :r±rtT rorms of tumor-gro^nh is touinl. Ara«T»iii: 
iitr— 11 f " r- •.''A-:,ji .jf fi bn>ma with lei«>myoma is usual in the 

X^Urt:. — FT'r-Eia is essentially a benign tumor, th^v^h 
r^niT-'ii— •■* s=-i.:-cs!> takes place after removal, this Wing par- 
Ti'/iuu-" iiK :L-r: Triih keloids and some of the polyploid :m>wths 
ii" iiiu'-'iu^ iif^-ii'-.-rine*- In •••me of these instaiKvs theiv- is 
uu(i\»iiTr,^:l; I r--r^':''.Ian«>r tu sarci>ma. if not actual <sin>.»matous 
innHTitnmni.c- A- a rule, fibroid tumors are destructive •>nly in 
-* iar H- 'irr tr* .azAble of prcJucing m^hanieal injury by pness- 
ur*. 7V r^'VTi. :' zh^ tumors is u?uallv exceedinjilv slow. 


XtadEBStaoa^ — Myxr,fna i* a timior <»mp>sed of con»et.tivt- 
tiwti» •.'•uf tui v^i inr^rrcellular substance c^^taining mucoid 
luan^frsu. tL iii'.c* •.•r 1*?^ abundaiK*- The gelatinous subfuuxt? of 
\Viia*^'»i I 'u^ vjn'r^flica! onl and the vitn^Mis hnni«>r i-kf the eye 
ai"* uytnuu. zy>rr y^:/':ii myxomata re*<^nible in their >!mct*i:y\ 

EStittik^gT, — T:jr ^risf^ ami the nature of myx^Miiaxa are 
ptvfii'.'aii* •!!*: ^^Vjr i* ihffr*' of fibn^niata. and :ntermt>liate forms 
tuiUL* f. ULfli'"..^ V/ 'Jriw a sharp line Wtwei-n the tw.x L«r?s frt- 
uiMTit'^y vL"'::rjjA'jt, ir^ sar»>»matous irp>wths with niyxoiaati>us 

JtgywglfafcCe. — A :yr>i'-al myxoma is a s^^.n. more or It-s^ dab\v 
^mwti »fii«'i'.fc^': -.-.- i 'jaf9*rj!e. anii haviuir a roiiihled •Hulme. I: 
JMir ytoj^r. irxi, \£^. i?«jriace of the b«xiy or of an onnn as a bemi- 
jMlirTi'i ejv* L- 1.'.-., /r ir:iy hanj ny a iiarr.»wt>i j^icie in the 



form of a distinct jwlyp. The latter is frequent in tlie miicotis 
metiil>niiies, but may orrur in the .^^kiu as well. Sonietiiues the 
tumor is lobulated,iuui tlw lubiile?i uuty hv vi.sible or may be easily 
felt* Oeeasionally bixunatotiiH g:rowths are (Hftuse, having no 
capsule and markrtl by no definite limitii?. 

Seats* — Among the common situations are the suljeutaneous 
and submucous tis^sucs and the connective tis.^nes of eeitain organs, 
notaldy the mammary glands. They may oecur ahuig the f'onrse 
of nerves, and in the brain or the spinal rord. They sometiuies 
spring from subserous tissues, notably from the intenuu'ieular sep- 
tum and valves of the heart. The tuuu^r may \n: solitary, or, like 
fibroma, may be met witli in numbers. (.V*ngenital myxoma has fre- 
qnently been fotuid. 

Stmcttire,^ — Mieroseopieally tlie ehameteristie features are 
stellate or spindle-sliapefl eonnretive-tissne cells whirls lie within 
a matrix of myxomatous njateria! (Fig. 43), The latter is luuuiK 
geneous or slightly granular, and somewliat rt'tmetive to light, 









Fig. 43,— Jfyxoiua. sbowing aielJatt* ceUs ei'pftruted by n gelatinous (mueoid) 
IntereeUular maleriaL 

giving the surface a glistening quality. The cells themselves may 
be entirelv normal young eoiuu^etive' tissue eells^ or they may 
present evidences of fatty tlegeneratiou. Konnd» eonnective-t issue 
cells are met with in some instances, either scattered tli rough the 
tumor or in certain areas, and may be so abnndant as to justify the 
term myxosiu-eonia. The vascular supply is usually poor, and 
the blood-vessels resendde tliose of fil^roma in being only partially 
developed. Association with tibronui and lipoma is frequent. 
Cartilagiuons tissue may be found in myxomatous tumors td' the 
parotid gland or testicle, ami in these cases the myxomatous jior- 
tion 18 rather an association than a degeneration of an original 

^iiiH]itr".ni£u KrxtiEiui&)ii» 'iRs^mscadiia -ir 'mcYiuaDiimia. 'rHB*** 
iii*iC lit^r^fyiwirij 'Vr^mfCT^i^ ami in x a*'w ixiiHiiiii!f*?f iiHyat^niww. iiai* 

A Iip>iiift ift X rsimivr '^twiiptTswi •« ♦iuit' n^soe 
Kii^ man -iC -Jii^ anmiftl ^adv^n&ftiitif^ni^ dk«iiK. Tl» •'pipuiii! j^ 

bi -A^'^oht 'irtfantp^mtHic ot tdk* cropfeiif- ai*rvi^njf -sv^cmiu w uiu* j .m^v liii 
oc^ g^>*»*> ainiijC%. Ic w 'fidbniix ;t£ rvmaM *, &> iisaw :& "iiisirD Inn? b«f- 

'i*r-tlai* -.#m:»^**^ii Iipr>oiaxa ami t^cdrriarr •5i>»sttnr. ^innt* imEvainiils 
httT* a saarkrfl Liiafcilrcy &> '!iiiit«Giixc •riV**r2rn'wm ot 2iC ai «iiiBfr»?ac 
Y^xrjt of tihff^ fjTjfij. ami the tt»nii ** I^ptMl]aE:»)»H^^ ** ^ iii>c TT.tppiJL'abie. 

Pita cirjvt^r on. an ohninint i&«iiiHii!v to a»£pi3i!«? det.'TmuiId.cii>a^ 

TruifT^ttlL-m •«t4^ixbf &> plakT w> part* dkicozii. ikcirr auiIi3r:LCi«>a:^ an> 
p<*^ini^ --> '.^n^ir AfTinruri ar»«* •>€* Eajorr oc ►fisttk?**. aiui in 'fcwHif^nireii 

Appearance — Lfpomofia anr nt^csallj e£rvMzmrf4rrtb«f^i imi *?i3r- 
f^l^Jjxrj^x V4-r.i..r* having a WmlaitHi .^iarn'trfrr. nat* LacGfr I>?mir 
^/v: jv *^r»c», of -^ifirwtrtivv* ri?«nfr- l>a the -mniu.'if ••c thje btA^Iy 
tfca'^T' apt»*^r L* *ocwrTrfaac E«rniL'?phierii.'aI vhit'ii Qi;iv 

Hc^. IckT^riii'tC of zhfi- ^jfAj, a». i?^ exanipi"?. when they :iri:?e in 
tkk^ '•iir/cr. ^-rf-cL- ^.r >ntj»'?f*r'<i& •!! -cinei^ti Vf^ tist^ce* they aj*: vtry 
frv^i-t^-nr.; >, th^in^i n^x alway?. p''lyp*>itL S-ci^rlxe^ th^y be- 
^jnv- 4«*rji(r».r.**:fi axMi may be netaitt^i in v-ae oc tfc»e -.•avitw^ ot 
r.fc^ h^irly Art rV'rKr Vjriie-. On 5e!ti«:»a the af»peaj:!tnvt L? thiit ot" 
6tfty tL^wir, 'XUi*'^i m -f-jciw: oa=<es it Ls m»>re trai rn.^ci the jj?ir4X'b- 
ti/iO ot niTirr/iirt Zki»a^-jf:^ %tA in other oace? It?*t tinii fnr-ci the nature 
tA thif: ixTxj ti;**»>^ It-^If or irom a«?»x-iatcri myx'XiLirocL'? change. 
lAVJtCiHtjk, Eoay r^ -rJitary tTim»>r?, finr then? may be many. A< a 
mie^ t:h#^ apf^r in aifialt year* •>r miJdle UtV, bac o-ngenital 
IrpocnaiA ar^ r*rjr. v-^ry rare ; ami otx^ask^oally they arv t«>un^{ to 

Stats* — \ttiif^^ th«^ .4toatioD> in which lipocuata oevur the mo^( 



common arc the subcutaneous fatty tiesue of the Imck, slioulders, 
butto(^kf^» or limbs the siilnniicoii?*, and the .sribseroiijH tissues. 
They may arise eitlier in the normal fatty tissue or in eonneetive 
tii^sue^ in which iat is not uoriiially present* Sumr authors, how- 
ever, deny the possiljilify of lipomata arising cxcepting^ from pre- 
exi?^ting fatty tissue* Of the or^.ms, the mammarj' gland and the 
ki(biey are most fre(|iiently involved. 

Structure. — Mieroscopically lijiomatous tumors resemble the 
normal fat. It is notable that the cells are larger — that is, cer- 
tain more oil^ — than the normal iat-t*ells, and this is stri kingly tlie 
case in isome instances, Ijut is not always dcnumstmble* The 
vascnlar f^npply is about the sauie as in normal fat, though occa- 
sionally large vessels with thin walls are seen. Assticiatcd myx- 
omatous or fibrous change may cause a variation of the microscopic 
app^.i ranee, 

Lipomata nuvv undergo softening from ne<'rosis, but more fre- 
cj neatly become calcareous in part or completely* 

Nature. — This m the most benign form of tumors. Recur- 
rence after more fir legs complete renmval does, however, at times 
occur, A lipoma is dangerous iuily iVom its weiglit or poi?itiun. 
It dcKvc; not contribute to the support of the systeru in ease of 


Befinltian* — This term is appHeti to two possibly distitict though similar 
forms of new growth. The jcunihotmi vftlgare occars most frecjuently in 
the eyebds and may he cenfincd to that situatioa. The growth appears in 
the form of tlat elevfttioD^s of a yellow t'olor. Generalizt-d xaiUhrana begin- 
ning about the eyes is less frequent. JCanihmmi diabeHcorum is n similar 
affection of diabetic patient^. It occurs at ii more advanced agt% is more 
dmtincfly inflammatory, the masses arc more rounded, and the eyelids and 
face arc rarely affected. 

Structure. — The histoloj^y of xanthoma is that of modified fatty tissue. 
It resemhlea embryonal adipose tissue, and there \a usually more or less 
round*cell infiltration as well. Some authors regard the latter as a tendency 
to sarcomatous change; otliers look upon it as infJammatory. 

Nature. — Xanthoma i» eminently benign. Tlie diabetic form ifi subject 
to sudden and apparently cauicless invohuion. The ordinary form may 
ftimilarly subside, though much less commonly. 


Definition. — A elioudroma is a tumor composed largely or 
entirely of cartilu|xc. It is tliiiicuU to dmw a shsirp line between 
outgrowths of cartilage ircuri cxistin^r cartilage or bone flue to irri- 
tation from definite uud independent tumor-like grtjwtbs. A 
group of cases of interuie<liarv cluinieter is that including carti- 
Jag]non.s nodules formed in teiulon^ of mus<:*les subjected to fre- 
quent iiTitation.s, as in the deltoid muscles in soldiers carrying 


heavy arms, and in the adductor muscles in the thigh in horse- 
back riders. In these cases normal connective tissue seems to be 
directly transformed into cartilage, though the influence of irrita- 
tion is undoubted. 

Btiology. — A congenital disposition, sometimes hereditary, is 
unquestionably present in certain cases. Virchow maintained that 
chondromata often spring from remnants or islands of cartilage 
left in abnormal situations, as in the midst of bone, as the result 
of imperfect fetal development. The same explanation would 
account for parotid chondromata on the assumption that parts of 
the branchial arches are misplaced and remain in the substance of 
the parotid gland. Other evidences of the truth of the theory 
are the frequent occurrence of chondromata at the epiphyseal ends 
of bones, and the appearance of such growths in early life and 
especially in rachitic individuals. 

Irritation has been referred to. Direct traumatism is some- 
times the cause of cartilaginous outgrowths from bone, particularly 
when fractures have occurred. 

Appearance. — ^Two distinct forms may be considered, and 
these are somewhat different in appearance. They are (1) carti- 
laginous outgrowths, ecchondroses or ecchondromata, and (2) carti- 
laginous tumors or chondromata proper originating in non- 
cartilaginous tissues. 

Ecchondromata present themselves as rounded or somewhat 
irregular outgrowths from cartilages. Sometimes they are "wart- 
like in form, and may occur in rows or groups. Thev may be 
firmly attached, or may be loosely united to the cartilage from 
which they spring. The most frequent (though not strictly neo- 
plastic) are the outgrowths in the articular cartilage occurring in 
chronic arthritis, particularly in rheumatoid arthitis. Occasionally 
they become detached after their formation, and in the joints may 
thus become free bodies. More characteristically tumor-like 
ecchondromata originate from the surfaces of the laryngeal carti- 
lages or from the costal cartilages. 

Chondromata proper most frequently occur in bones or the 
periosteum, and have a rounded or lobular appearance. 

Chondromata springing from the inner surface of bones (pos- 
sibly originating from the marrow itself) may grow uniformly by 
repeated or constant proliferation and lead to globular swellings 
of the affected bones (Fig. 44). The true bony covering becomes 
more and more thin until it may actually be perforated. 

The true chondromata are usually rounded bodies ; they pre- 
sent lobular irregularity when they reach considerable size, the 
lobules being separated by connective-tissue. 

All forms are hard, though secondary softening may occur. 
In cases in which association of mucous, sarcomatous, or other 
soft tissue is present the consistency is correspondingly less. In 


some eases central sofleniDg leads to cystic formation. The liquid 
in the cyst is more or less turbid and occasionally sanguinolent. 

Seats. — Ecchondroses and chondroraata, for the most part, 
take their origin from bone, cartilage, or periosteum. The 
ecchondromata originate from the perichondrium rather than from 
the cartilage itself. In some cases chrondromata originate in 
connective tissue, as that of the tendons, by a process of carti- 
laginous metaplasia. Cartilage-tumors are met with in some of 
the glandular organs, notably the parotid gland, testicle, and 

Fig. 44.~Chondroma of the thumb (Warren). 

ovarj' ; and rarely they occur in the lungs, especially at the root 
and springing from the peribronchial cartilages. 

Ecchondroses are most frequent about the long bones, as those 
of the extremities, and particularly at the epiphyseal attachments, 
where they may reach considerable proportions. Situations of 
great clinical importance are the interpubic and occipitosphenoidal 
junctions. In the former situation ecchondroses projecting inward 
may interfere seriously with labor, and in the latter place carti- 
laginous outgrowths may penetrate the dura and exercise injurious 
compression on the brain. Allusion has been made to the ecchon- 
drr>ses of the joints in arthritis. 

Chondromata proper may occur in the neighborhood of bones, 
in the muscles and tendons near their bony attachments, and in 
the organs mentioned, but in the last situation are rarely pure, 
myxoma being the most frequent associate. 

Structtlte. — Chondromata resemble hyaline, fibrous, or elastic 
cartilage, the first-named being much the most frequent. The 
tissue differs from normal cartilage in the fact that the cells are 
frequently without capsules and are much less regularly arranged 
(^^S* '*^)- The intercellular substance is more abundant, and is 
frequently g^elatinous, mucoid, or fibrous, and not rarely the differ- 



etit types of cartilage occur within mirrow limits;. AssoeiatioD 
with myxoma and surronia, or both, is common, cs]>ecially in the 
parotid and te.stieh^s, thr projioTtimi of the .sevtral in^i^rodients 
varying g^rt^atly. Tumors of this kind iire siKikin <»f as mixed 
fuumn*, Calciliration and trof ossifiration are not infrequent, par- 
ticularly in eartilairt'-tmiiars intimately ronueetcd with bone* The 
term mh'ochondmma is applied in auch ma^cs. The name fjHkoid 



Pro, 45.— Chondrtymm of the fiyalftic type. 

rhoiiiltmna h applied to ehondrc*mata in whieb tbe intercellular 
enhstance is trabeeidar in armngenient, snj^gesting bone-stnietnre, 
but ill whieb actual os^^sification luis not occurred. Such ii:ro\\lhs 
are met with abont tbe bones and, as a rule, s[>rin|r from the 

Degeuerative changes are frequent. Myxomatous de^euem- 
tinn may oeenr, though myxoma is more frequent as an assoi'iatiou 
than as a degeueration* Sofk'uiii^ uuiy occur in the center of the 
mass, and may lead to cyst-rorniation, this being particularly com- 
mon in tbe myxocbondronuila. Growths of this kind are fre- 
<|Uently c|uite vascular aud lu'UU)rrhages into tbe rysts may occur. 
Eventually such cases may show searcely any cartilage-cells, a few 
being perhaps detected in snrue |)iirt of tbe <'yst-walL A single 
bard buup may be left at one side of tbe eyyt, the rest of tbe 
tumor having softened. 

Nature. — Chondromata are usually Ijenigu, and are danger- 
ous otdy throngb tbe pressure they exert. Kcmoval iif a jxirt of 
tbe tiuuor may have a lieneficial infliienee iu causing calcitieation 
of the renraiuder. Metastasis itiay undoulrtedly oeeiir in pnrc 
chondromatu tlmjugb tmusportat ion of particles in the circulation. 



Such rarti I urinous eiiiboli have often t>eeii dt^monst rated. The 
Feeoiifliirv growths are most frequent hi the Itin^s, Metastatic 
ehoii(ironiata are, however, more frequently chondrosarconiata 
than pure chondromata* 


Definition* — An osteoma is a tumor eompoAed of osseoua 
tissue. Osteonuita are chisel y allied to eurtilagiiious tumors, and 
frequently transfnrmations *K'eur. 

Etiology. — The name diffieulty is ex|jerieneed in dintin- 
gnisliin*^: intlammatoiy outgrowtlis or exn^tose?^ fnmi true bony 
tumors, as in the of eartilaginoas growths. Enlargement 

of the facial tiones in leontia^is os^eii, of the lit>nes of the extrem- 
ities in acromegaly and bypertropliic pulmonary o^stefwtrtbrop- 
athy, and ossiHeations of the muscles hi myositis ossiticans, are 
instances of border-line conditions separating true tumors tTOm 
inflammatory hyperf*stoscs. Irritation and traumatism undoubt- 
edly play a inirt in the etiohjgy, even in neo|dasnis unattacherl to 
the bone, and in the case of l)ony outgrowths iujiu'y is generally 
the immediate cause. An underlying pre<hsp»sition uuthuilitedly 
exists, and explains the t>eeurrence of congenital multiple bony 

Appearance* — Two forms may be distinguished, as in the case 
of cliondromata ^1) outgrowths or exost<Jses an*l t)steophytes, and 
(2) the ostcouiata |jrf»pcr, or !ietcniplastie osteomata. Exostoses 
an<l ostcnpbytes aiv distinguished one ivom the otiier l)y their 
Bha|»e and appearance ntther tlian by any t ssential ditlereuee. The 
former are direct outgrowths of more or less wart-like character ; tlie 
latter are more extensive and present the a[>peanineeof bony deposits 
upon bojies, and are less closely attached (Fig, 4<i). In both i'ornis 



the surface nf tlio trniwtli h irregular, iiLwlylutecl, or wart-like 
(Fig:, -^T). Tlie L'unsiiiteney Ik that uf bone, and the giize varies 

ihun that nf s^niall oiitgrowtlis to 

inas?i(^ as? 


as a ti??t. On 

Ftiv. 47 — O«t«onift of the lower jaw 

^'etinn twij iarni!? may lie dis- 
tingui^lll'd ; the hard or oshoimt 
tin rum, a Jul tlie ,^oft *ir odmma 
Mpom/iomm. Sometimes the i^iiib- 
stance of the tinnrc h exceedingly 
<lense, and the term mleoma tbur^ 
nt urn is applii d. 

The licterf »[dastie oleoma ta, or 
those separated inmi the bone, are 
more roonded and, when of eon- 
^iderabte size, nsnally noduhited 
and hiboUitecK In the t?eroiis 
nieml>rane?^ they t>ccnr as flat 
btmv phites. 

Seats^ — Osteoniata j^prin^ from the I tone or cartilage, or from 
eonneetive tissue near the boues. More rarely they arise in other 
corineetive tissues, in the serous membmnes, or in certain organs, 
notably the testicle and jiarotid gland. 

Osteomata comic ctcd with liones are most frec|nent al»out tlie 
epiphyse*.s, at the attachments i*f nniscks, or at the scat of old 
fnictures from which al>niidant calhms has Ih^'u iiejMKsited. The 
skull-bones jnay lie atfcctetl on the outer i»r iruier surface, ami 
often an elevation is notcnl without and within at the same sjK>t. 
A iorm of clinir^al imjHirtance is that in which cxiistoses ix'cur on 
the inner aspect of tlie mctatarsid bone uf the ijreat toe irom <Mim- 
pression of ti|j:lit shoes. In the maxilliiry bones osteoniuta may 
ori^rimite about the rrMits of malfnrme<l teeth. In cases of aeeomu- 
latiou of eement-snbstance beginning at the neck of the tooth the 
term fit' nit jI osteoma is applied; these are strictly comparable to 
osteomata. In cases in which prolitenitiou of the tlental pulp 
has occurred the term otfontfmKf is apjilitnihle, and tJie tumor is not 
of osseous chamctta\ The liony joi^rowths somctiiui's seen in the 
serous smrliiees nearly always arise in areas in which th*Te has 
been tliickeniug from chronic inflammation* Tiicy are most fi^e- 
ouent in the dura mater of the bniin, particularly the falx rerehri ; 
tiiongh the memlinnics of the eonl, the jJenni, or |>erieimltum may 
be involved. 

Structure, — Microse<jpi<"ally c»stcomata rescmbli' more or less 
accurately hoiu^-t issue. They vary, tiowtver, in different areas, 
and mixtures of eartila^^^e with l>ony tissue are fre(|m^ut. Second- 
ary <legeuerativc changes (s4jfteiiing) may (K!cur and association 
witli tumors of other character are not infretjiient (^chondroma, 
myxoma, fibroma, sarcoma). 





Nature,— ThoH' growths an* eminently bonign, flo nut rt/cnr, 
and do not give rnetasttisis, Tlieir sittialiou sometimt'i!i makes 
them trouljlesome or ilangerrms. 


A lymphangioraa ig a tumor eoniposed of dilated lymph-vci^els 
or lymph-?|)aees; more frequently the latter. It is ditfieult to 
gepimite dilatations of lyniphatie ehannels due to olistruetii^n froni 
Iiyperplastie proeesses, CVmgenital enlargements of eertain [wirts 
are met with whioh seem entirely dependent n]K)n the abnormal 
development of the lymph-spaces. These efvnstitnte t!ie eondititm 
called ekphm}im,^iA coiigmita molfm^ in which the suhentaneons 
tissues are boggy or edematous, ami even distinct eystie formations 
oeeur* Coitf/ttiiiai r if stir lufgmmii Is an instance m{' dilatatifJii of 
the lymph-s{xiees* Congenital enlargerntiit of tlie tongue, termed 
nuterof/iossin ; of the lips, muerorlmila ; and of the skin, mn'toi 
fifmphaftcus; are other instances of the same process. In all of 
these, in addition to tlie dilatation of the lymphatic spaces, a 
tnarke*! proliteration of the conneetive tissues as well as the 
ninsele (in the ease of t!ie tongue) is striking; iiut tlie prcK^ess in 
all probability originates as a dilatatii>n of tlie lympli-spaees. 
The terras iifniphtjitr/fottiff etfixntoi^uin ami earernoma /t/mphafumm 
have been suggi'sted for these eases of dilatation of the lympli- 
Spaces. On ytaiuing with silver-salts the endothelial lining of the 
spaees may l>e readily demonstrated. Actual enlargement and 
varicosity of existing lyniphatie ve.^sels may wcur, but is ex- 
tremely nire in the funn of ei re luu scribed growths ; it is met with 
more irequently in association with general prc^eesses, sueh as ele- 

?>hnntiasis. Tiic bursting of dilated lymphatics may lead to 
tfmphort'hea or external dihiehargc of lyin]rh when the process 
involves the skin, or to effusiims of lymphatic ebaraeter when the 
tBtTous cavities are involved. Chylous {HTi<'arditis, jd( uritis, and 
^ascites are thus prodnecil. Ru])tin'e of dilated lynijihatics along 
the iirinarv tnict (kichit^y or l>la<ldcr) <KM'asions **hi/inria. Lymph- 
1 ftogioma is a benign prcw^ess in the patliologie sense. 


Definitions^ An hemangioma, or angioma as it is more fre- 
quently called, is a tnnior-like formation conqHised jirinci pally of 
MrMMl-vcssels. Strietly speakings many of tlu-se are not tumors, 
Keing uTerelv localized di hi tat ions and elengations of pre-cwi sting 
bhxxl- vessels. Sijnie, however, represent actual proliferations. 
Two varieties may be described, that which simulates merely dis- 
tended capillaries anrl veins (tmf/ioma tefemiffiixiaftcmn), and tiiat 
in which there are enlarged spaces lined with endothelimn 
Aan^lomtt carrrnomnn or rannioma}. In many tumors the blotxl- 
vessels are sctmewliat enlarged; these are spoken of as telean- 


Btiology. — Congenital malformation certainly plays some 
part in certain cases, as the frequency of hemangiomata in the 
new-bom and particularly at the junction of the branchial arches 
would indicate. Injur\% however, and meclianical causes gener- 
ally also play a part, and pre-existing disease, jiarticularly fibroid 
inflammatory' processes, may contribute to the subsequent dilata- 
tion and proliferation of the vessels (see below). 

Appearance and Seats. — The angioma teleangiectaticum 
may ix)nsist merely of delicate capillaries and arterioles, and in 
this case a bright-red color is observed. The tumor api^ears as a 
spot on the surface of the skin, more or less shaq>ly outlined from 
the surrounding tissue. It is not elevated and has the same con- 
sistency as the healthy parts. Usually it occurs as a multiple 
condition, an 1 the larger are often surroundeil by smaller s|)ots. 
The skin is the favorite seat; but the sul)cutaneous adipose tissue 
and sometinu*s the mucous membranes are involved. Less c»om- 
monly larger (venous) channels occur in the tumor, when a dark- 
re<l color is ol)serve<l (port-wine stains). 

If a cirL*ums(*rilKHi {)ortion of the circulation is uniformly 
involve<l, the vessels thicken and elongate, and a jKxniliar form 
of hemangioma rt»sults. In these cases the arteries are greatly 
thickeneil and tortuous, and form bunches under the skin, sug- 
gesting to palpation a bundle of i^arth- worms : while the surtaw 
of the skin presents peculiar irregular elevations without of 
necessity any change of color (aneury^nna racanosum sen cir- 
aoidenni). This is not infrequent in the scalp. A similar condi- 
tion of the vessels is observe<l in the varicosity of the l^:s, labia, 
or other parts. It is most frequent in the hemorrhoidal veins, 
constituting the onlinan* heniorrlioids. (Thc^se c*t>nditions do not 
strictly constitute tumors and will lx» more fully describeil in 
discussing the dise:ises of the vessels.) 

Cavernous angiomata present themselves a< more distinctly 
tumor-like formations of dark venous color, involving the skin or 
subcutaneous tissues, the retrobull>ar tissue of the eye, the mucous 
membranes of the nose or pharynx, and certain organs, as the 
mammie, the kidney, the spleen, but jiarticularly the liver. Like 
the other variety, they may l)e ct>ngenital, but more frequently 
arise in later life, esptvially tliat of the liver, which is most ci>m- 
nion in old persons. The ap|K»arani*e is that of a more ciivum- 
soribe<l tumor, sometimes showing a di>tinct mi^sule and \"arying 
in consistency with the degree of distention of the blood-spaces. 
In the skin it pnyects slightly fn>m the surface (iKrriw promi^ 
nciM) : in the liver the tumor does nm projivt. 

Structure. — The definition explain> the structurp in general. 
The bkHxl-vessels of leleangiwtatic anjriomata may l>e simply di- 
latiKl csipillaries with a lining of endothelium and a fibrous outer 
coating. More commonly the vessel? are considerably thickened 
and held together by a reticular connective tissue. In rare in- 

PRoanEssiVE tissue-changes. 


stances the vcsaels are 8o closely iiacked and the walls so thickened 

that wheu the blood Ls removed the appc araiice h oot unlike tliut 
of the tubules of a sweat-gland. The congeries of vesseLs of a 
leleiingiectatic angioma represents the elongated antl tortuous 

Fig, 4« — Cavernoiw AngtomA (Warren), 

vessels of the affected area, and alrio iiew-fornicd vessel'? originating 
from the former. The only connection of the angioma wifch tlie 
general circn latino is through one or a few afferent arterif^les and 
efferent veini^. The growth is not merely an enlargement of |U't.*- 
exi^ting vesj^els, but an actual new-f >rination» 

The cavernous angiumata present large spaces lined witli endoth- 
elial cells (Fig,48k Between these spaces are parallel fibers of con- 
net^tive tissue which form tlie framework of the tumor. In eases 
involving the liver the proper substance of this organ (lisapjM?ars 
eonipletcly^ leaving only anastomosing spaces with a fibrous frame- 
work. Vircliow taught that the lilirnus jimeess was ]>riiuary, and 
by traction an*l jircssure gradually inductHj dihitatifui of the vessels 
and atrophy of fhe liver-substance. Sou^e of the more recent writ- 
ers believe that tlie dilatation of the vessels is tfie primary eondi- 
tron. The capsule sometimes found snrn>nnding the cavernous 
angioma is certainly a secondary formatitai. 

Angiomata of the skin may enclose liie hair-follieles and 
swetit-glands ; those of the subcutaneous tissue fretpicntly show 
areas rich in fatty tissue (angiolii>onia) ; secondary angiomatous 


change of tumors is probably the result of dilatation of the pre- 
existing or new-formed vessels. Sometimes secondary change 
may occur in the connective tissue of the vessels of an angioma, 
as in the plexiform angiosarcomata, in which the blood-vessels are 
surrounded by ensheathing sarcoma-cells (see Fig. 48). Certain 
cylindromata have the same origin. 

Nature. — Angioma is essentially benign, and may continue 
through life without enlarging. Hemorrhage and inflammatory 
or necrotic clianges are its dangerous consequences. 


Definition. — This term is here used to designate a more or 
less malignant form of new-growth affecting the lymphatic glands 
or other lymphadenoid tissues, and having the structure of lym- 
phatic tissue. The clinical name for the condition is Hodghin*9 
DiseaHr, or Pseudoleukemia, Lymphadenomata may be considered 
as forms of sarcomata, or at least as closely allied to sarcoma. The 
term iT/mphosarcoma is sometimes applied, but is more appro- 
priately given to growths of a more definite malignant nature, 
having the reticulated stnicture of lymphadenoid tissue. Other 
names applied to lymphadenoma are malignant lymphoma and 

Btiology. — It is exceedingly difficult to establish the limita- 
tions of the term, and especially to decide whether or not certain 
cases in which definite etiologic factors have been discovered 
belong to the group under consideration or should be separate<l. 
There are cases of infectious enlargement of the glands and trau- 
matic swellings that cannot be clearly distinguished. In some 
cases even the clinical course is the same and a separation seems 
im]X)ssible. For example, the glands in a numi)er of instances of 
Hodgkin's disease (as far as the clinician can establish this diag- 
nosis) have been found to contain tubercle i)acilli. We must con- 
clude that general lymphatic tuberculosis may occur in the clinical 
form of Hodgkin's disease, but cannot assert that this establishes 
the pathologic identity. The presence of tubercle i)acilli may 
furthermore be explained as sometimes the result of secimdary 
infection. In a number of well studied cases the absence of tuber- 
cle bacilli has been ])roved by the inocuhition of animals. 

Various micrococci and bacilli have been discovered in glands 
from cases of Ho(lirkin\s disease, but their presence must be 
reganled as accidental. In a few instances bodies resembling 
protozoa have been discovered. 

Appearance and Seats. — Lymphadenomata ])resent them- 
selves as enlargements of the lymphatic glands of a single group, 
or more commonly of a number of groups in diflerent parts of the 
body. All of the glands of the group may be involved, or only 



u few. The intlividiial glands retain tlieir shajM, as there is 
usually no toiulenry to extcusion Ijeyond tlie capsule of the gland. 
In exeeptioiKil rases, however, the process is uf a more in Hit rating 
kind ami the eapsule h penetrated or destroyed- These instances 
merit tlie special term lyniphosareoma. 

Lyniphadenomata may i>e mft uv hiirdf aceording to the amount 
of connective tissue and the dens^nt's^ of tht^ celluhir infiltnitiiin 
and proliferation. ( >n section tlie tumors are found lo be grayish 
or whitish in appearance, and exceptionally may show slight areas 
f>f necrosis or softening. Extensive softening is exceedingly rare. 
The individnal glands nf the gronp may he clearly distinct, or may 

Fio. 4I>.— Lymphntlih I I ' I inf-hosarcomttt probably <>rlifiiiiitiiitr In rtuitiatit nf tbymua 
KlAlid ; the Iuiji't < - i r. ■ I the U|tfjcr xmrt **f ibe htarl hk*' a hvt^L The ilLuMrtitiun 
diows the tiimur turned upw wnl uinl exiMtaiii^ ibe ijcriuttnitma on its under surface. 

be fitted together hy interglandular eon neetive-t issue overgi^iwth 
or by the penetration nf the lympliadcnomatuus pnpei'ss thrnogh 
the capsule. 

When superficial lymphatic groups arc involvetl tumors of 
various sizes are pnMhirrfl^ and project as knohhv or rounded en- 
largements beneatli the skin. The latter is freely mnvalde nver the 
tumor nnlcKS the gntwth has penctratc<l the eapMilc or se^condary 
inflamniatory elianges lutve uceurred. In the case of internal 
glands large intnittiuraeic or ahdr*ruinal growths may l)c fr^rmed, 
and may exen^^i^^e destructive eom|iressic)n tif vital parts. 

Simihir lymphadennniat<*us gi-owths may spring fri>m the lym- 


phatic tissues of the gas tro- intestinal track — tonsils, lymphatic 
follicles of gastric and intestinal mucosa. 

Sometimes the primary gnnvth seems to l)egin in the thymus 
glancl or its remnant (Fig. 49 j. Tumors of considerable size are 
produced in these cases, and their origin is recognized by their slia{)e 
(two lateral parts united bv a sort of isthmus) and by the absence 
of the apjK?arance of a conglomeration of glands. In these cases 
the adjacent glands, and later more distant groups, an* involved. 
Jjymphadenoma may be confined to the glands, but frequently 
extends to the solid organs by metastasis. The spleen, liver, and 
kidneys are the organs most frequently affected. They become 
enlargtKl and indurated, and on section show light-colored areas of 
lymphadenoid tissue. Similar ''lymphoid intiltration" may he 
seen in the heart, lungs, or other parts. 

Lymphadenoma may affect the bone-marrow secondarily and 
perhaps primarily. (Reference will be made to this under the 
title Myeloma,) Sometimes the tumors have a yellow or green 
color and are called Moroinaia (7. v,), 

Stmcture. — Histologically the glands in the earlier stages 
show a hyperplasia of lymphadenoid tissue with predominance of 
small cells (lymphocytes). I^ter larger cells with pale nuclei 
make their appearance. These are doubtless in the main pro- 
liferated endothelial cells of the lymph - sinuses. They may 
enlarge to form mononuclear or poly nuclear giant cells, the nuclei 
dividing by amitosis. Sometimes large areas of nucleateil proto- 
plasm (syncitial tissue) are observed. Coincidently witli the 
appearance of these epithelioid and giant cells there is forme<l a 
reticular fibrous network which increases with the age of the 
process till the gland becomes quite indurated. A somewhat 
characteristic, though not constiuit, feature of the histology is 
the presence of numerous eosinophile leukocytes scattered through 
the tissue or in small mass(»s. Plasma cells and mast cells may be 
pres<'nt, l)ut are not characteristic. 

The spl(»en may show similar (.'lianges, beginning in the Mal- 
])igliiaii bodies, l)ut in many crises is affected in but slight degree 
or not at all. 

The bone marrow presents a picture of proliferation of myelo- 

The liver, kidneys, lungs, gastro-intestinal mucosji and other 
tissues may be extensively involved, ])resenting new-formations 
of the same character as those in the glands and originating from 
the lym])lioid masses normal to these parts. These lesions were 
formerly regarded by most authorities as simple metastases, but 
are now thought by many to be proliferations of existing lymphoid 
tissue. Some, as Hibbert, hold that they are metastatic and are 
due to proliferation of metastatic cells, which however are attracted 
to preexisting lymphoid coUw^tioiis by a species of chematoxis that 
seems to invite the doposit of cells in areas where similar cells exist. 

The o<:;casional ptrtbratioii l»y tlie growths of small bhanl 
vessels with proliferation witliiii the vessaels is a strong argument 
io favor of the oeoplastif nature of the procejas. 

Nature, ^Lyiuphudentmiii is varialily malijijnant. In a small 
projMjrtion of the ea?>ert this malignancy is of local rharacter— that 
is» the *,^piwth tends to invade ttie neighbi»ring pirts. In most 
instances there is rather a tendeney to general involvement of tlie 
lymphatic system^ with seetunhirv growths in various organs. To 
eases of tliis kind the terms Hodgkin's disease, psendoteukemia, 
and adenia have been given. These cases present tliemselves in 
the form of a progressive anemia {lymphatir anemia— Wilks)^ often 
with irregularly relapsing lever (ehrimic relapsing fever — Epstein), 
and especially with lymphadenonjatons tumors hi the snptrHcial t>r 
tleep lymphatic groups (axillary » cervical, inguinal, mediastinal, or 
abdominal). Tlie disease pn>gresses more or less rapidly, antl 
terminates in death from ciichexia and exluiusticm in from ime to 
tliree years. Occasionally the course is rapid, repealed hemor- 
rhages or pyrj)ura may occnr, antl a fatal termination is reaehtnl 
in a few weeks or morjths. Tlie whole conrse of the disease is 
in tliese castas suggestive of an infections process. Tlie chronic 
caset* may be infeetitnis, or due to some torm of toxemia, but 
are at present racire appn^priately considered under tiie head of 

The relation of Hodgkin'S disease and lenkeniia, especially the 
lyuipliatic tyjie, is certainly very close. The glamlular tuniurs 
and the secondary eliangi's in the organs are very similar, except- 
ing that the lymphatic glands are more prominently involved in 
ordinarv lympha<leiioma antl tlie marrow-elianges more striking in 
leukemia. The only striking difference is found in the blotxi. In 
leukemia there is marked and rharacleristic lenktwytosis; in the 
other condition this is absent. 3Iany eases huve, however, been 
observed in which ilodgkinV disease^ has become leukemia ; and 
some authors do not hesitate to speak of t!ie two diseases as 
identical and representing merely two stages of a com mem affec- 
tion. According to this view, we might classify different cases as 
either ieukemic or ainthinic ltfmf*hiftft'tiom*ifft. This view seems to 
me well grounded. 

The blood in aleukemic eases shows m*»re or less pronunnced 
reduction in the nnmber of red cells, and a normal, reciuced, occa- 
sionallv a ramlerately increased, number of lenkocytes. The small 
mononuclear lenkoeytes are sometimes in relative excess* In acute 
eases nucleated red cells may be found. 

The cau^ses and nature of the irregular tV'ver are uncertain. It 
may be «lue to an in feet ions cause, or may be the result of breaking 
up of leukm'vtes and I i Iteration of fennents. 

Multiple Myeloma, — This growth jitteeta the sternuni, rib*, vert€bT«B, 
skulh and leas freqaeutly ottipr bone^. The tumor iit tirst ^ugge^U a hyper- 


iiiji-ii'; ^y^ijdition of the marrow ; later the fruUstauce of the bone is replaced 
by tjj*r gTom-».h. whir-h luay fiDallv break throuj^h the *»hell nf bone covering 
jt and iiira'i<r tije v^Ax tii^^^ues. Metar>ta^i?« i> ver>* rare. The growth has a 
iiiotiie'i g^rayi.Ji and re^Jdish aiifM-arance and U rather soft. Microscopically 
it is coiDjKri-e*! of v^uiaW round cell?* and a vascular network of thin-walled 
Te*y*ei». The cell» resemble small myelocyters, or possibly in some cases 


Definition. — The term sarcoma is applied to tmnors composed 
of conn^-i-tive-tis^ue cells with ven* little intercellular substance. 
It ir? otun Mild tliat sarc<»ma-cells roemble those of embryonal 
connw-tive tissue : more projx^rly h|)eakin^, they may l>e likened 
U) th^f ordinary connective-tissue cell falling short of complete 
devejopini'iit. There is little tendemry in sarcoma to the forma- 
tion of fibrous int<*rcel hilar substance, but a great tendency to 
ryintinuous cell-proliferation. 

Etiology.— (>f all the tumors sarcoma furnishes the best 
ground for Cohnheim's theorj'. Its frwjuent occurrence in young 
j>ersons, the relation of melanosarcomata to congenital pigment- 
hjiots of the j^kin, and the sarctmiatous mixed tumors of the jiarotid 
and testis were citfKl by Cohnh(*im among the evidences pointing 
U> a congenital origin. Traumatism and inflammation certainly 
play some part, either in stimulating sudden growth of a latent 
san/oma or in <leveloping a l(»sion from which sarcoma s|irings. 
The i>arasitic the<jry has gained many adherents in recent years, 
though no s|>eciHc organism has been demonstrated. Experiments 
at implantation of the disease in animals have been partially suc- 
cressful, but do not establish an infei.'tious diameter as lias been 
shown in prece<ling jMiges. Recently intracellular protozoan organ- 
isms have been descTibed, but these are doubtless various unim- 
j)ortant inclusions or cellular degenerations. In some cases the 
structures dcsiTibed are certainly nuclear degenerations. It is not 
impn^baiih* that certain lymphosarcomata may be due to the action 
of iiacteria. 

In connection with the supposed infectious nature of sarcoma it is of 
intercHt tr) note that a rehitionship has been observed l>et\veen sypliilis and 
Karcoina. This is based on the fact tliat some cases disappear under anti- 
«y|)hilitic treatment. 

Appearances. — Sarcomata are generally more or less roundiKl 
tumors often enclosed by a capsule; they may, however, be irregu- 
lar, infiltrating, and therefore unencapsulated. Some forms appear 
on surfaces, spreading as flat elevations more or less irregular in out- 
line. The consistency is soft or hard according to the number of 
cells and the amount of intercellular substance, or according to 
the kind and amount of associated tissue (myxomatous, chondrom- 
atous). Typical sarcoma, as the name implies (<Tao?, fleshy, is flesh- 
like in consistency, and frccjueiitly on section the color is pink or 



of a fles!i-tint. Many nf the san*utiiMta, Imwover, are quite white 
or ^niy^ and a >vlHtisli liijuid i^xude>5 Iroui the surfaee on seetioiL 

Dilatiition of the hlcKxl-vessels may cau.^e a dceidedly hemor- 
rhiigie appearance, ond netnal hemorrhages may take phiee, oaii?4in|r 
hli>od-cyst< or, .snhsefjnently, sernns ey.sts. Other de^eiierative 
oliiio^es, such as iieerosis, mnentt] fhanjj^e, and slniph^ Ittpiefaetion- 
neen»sis^ may render ?saivuniut:i stif't and often eystle. Sarcomata of 
^landuUir orgsiUH like the lirea«t may present a eystic appearance 

TtG. ^,->8««ond*rf varcomata of the iuni;: the prhnErf growth was attaehed to Ihe 


in consequence of eompression, and suhHequent dilatation, of the 
irhinduhir dui-ts and aeini, 

Angiosiireoujata (the variety in whieh «ure<nna-c*ells spring 
from the adventitia of hlood-vesselB) present tlieni?f<'lves as more 
or letiii irregular growtlis, frequently Mattened and hmnching when 
the surfaces of organs are involved. 

Secondary siireomata are nmlular in eharaeter and nearly al- 
ways present a eajisule if the size is at all considerable (Fig. 50)* 
They are nsually white or pinkish ; rather firm on section, but 
with a t€nden(*y to eentnd necrosis or solleni ng. In some eases 
almost every part of the l)ody may be studded with minute whit<3 
s\}ot^ peareely distinguishable from miliary ttd)eix;les* This con- 
dition is called mrcomnimiii. 


8cat0. — SarciHiiata Hpring from pre-existing connective tis- 
WMfH, Hii(4i an the Bubcutaneous, intermuscular, periosteal^ or tendi- 
nous tiMHues ; bone^ cartilage^ fat, lymphatic glands, the submucous 
and serous surfaces. They may arise in the internal organs : kid- 
ney, liver, spleen, thyroid gland, testis. The individual seats will 
be further (considered under the different forms. 

Stmcttire. — The sarcoma-cell is rounded, cylindrical, spindle- 
tfhaiKid, or of ]K>lymorphous forms, the latter usually being larger 
than the round or spmdle-forms. The large number of cells in 
eomiMiriHon with the amount of intercellular substance is always 
(*()nH|)i(MiouH. The cells themselves contain rather large nuclei of 
a somewhat vesicular appearance, though sometimes quite granular. 
In nipidly growing tumors karvokinetic figures may be very 
abundant ; less frequently the cells show evidence of direct divis- 
ion of the nuclei. Nuclear degenerations (karyorrhexis, kar^'o- 
lysis, and hy|)erchromatosis) are frequent, and doubtless cause 
some of the appearances supposed to be protozoa. The arrange- 
ment of the cells in sarcomata is usually very irregular ; in some 
eases, how<»ver, particularly in spindle-celled sarcomata, the cells 
li<» in fasciculi or parallel columns. The intercellular substance 
eonsisttt of a homogeneous matrix with a few fibers in the case 
of thi» spiiulle-c^elled variety, but with few if any in other cases. 
The e(»lls may be all of one type, but more frequently different 
forms or shapes occur in the same tumor. Among tlie polymor- 
phous forms of cells may be noted large flattened cells resembling 
endothelial plates and giant-c<»ll8 resembling myeloplaques. (These 
forms will be disiMissed under the headings p]ndotheIioma and 
(Jiant-eelled SarexMua.) 

T1m» bloo(l-v(»ssi^ls of sarcoma art* usually channels line<l with a 
single eiuloth(»lial coat (see Fig. 52), but there may be more fully 
tleveloped vessi»ls. In some easels the vas(»ular network is very 
eonspi(»uous and fi)rms the skeleton of the *tumor, the sareoma- 
cvUs being nuigtnl nnuul the vessels in the form of mantlet^ and 
pn>lmbly springing fn)m the adventitia. Se<H)ndar}' changes may 
iH'cur in the i»ellular massifs surrounding the vessels, and jHTuliar 
tonus of tumors thus rt\*iult (stn* Cylindroma). 

Combinations of stiriHtnm with other forms of tumors are not 
mn\ .\11 gra(h»s betwwn the tnie sjinM>ma antl the fibroma may 
W mot with, ami it is ditfieult to draw a line of distinction. 
Whenever a tendency to tn^Uular pn^literation is conspicuous and 
the t\>rmatiou of fibn^blastic ivUs with elongateil fibrous pnyiv- 
tions is not (M*nsi>icuous it is warranteil to n.vonl the tumor as 
sjinHMuatous. Prunary fibromata may become sarcomatous, and 
sim^omattms tumors jHThajv* at times IxHxmie mon* benign by 
fibnuuatous transformation. Combinations Avith chondnHua, os- 
teoma, myxonui.and other i\>nneotivt*-tissue tumors; with adenoma, 
rlmlHlomviMua, and fibnmiyoma an* not infnHjuent. Mon* mn'ly 



the fibrous tissue of thr iMiiign tumors uiay uj^ilcrgo sarcomatous 

The structure td* individual forms of saret^ma will be separately 

Nature,— Sart^oma is es.sentially mali^uaut. It tends to I'eenr 
aftt^r r*?un>viil : it affects the ^r^nۥnll liealtli of thr^ pjitii^iit ; iiud 
metastasis is ireqiieut. Metastiisi> (K-eurs throiiirli tlie eirculatiou. 
The liegree of malii^uauey varies greatly. The small rcjund- 
celled and uielauotic varieties are the most dangerous. Some 
forms, as the giaiitH*elieil and the librosarf*omata» are eorapara- 
tively lit^nii^n, Tlie relatively heiiitrn ff>rm of timior ealled reeitr^ 
rmf fihrolff tumor \\y Pa^^et is in real it v a (ihrosanvima. The 
growth of sarcomata is usually rather mpid^autl uiny l>e(x>me very 
nipid iu eoiiserjuenee i>f irritatinu. 

S«ireomata an* injurious to the geueral health in some ohsenre 
wny. The evidenee of this is tlie anemia and hnikoeytosis and the 
irrejtrular fever i>liserved in various eases. The aniunia lua}' l>e 
trivial or severe, and may Inrome extreme, Ijeukoevtosis is fre- 
quent, hut rarely mai'k*'d. The pitlymorphous elements may l>e 
Bpeeially inereasrd, but I iiave fouiul the lympluH-ytes exeessive in 
a number of eases. Irregular iever is often noted in lymphosjir- 
eoma and general sareoraatosis. Neerotic ehange may iuert^ase 
the teudeney to fi-ver. The exaet inflnt^nee of sarcoma on metab- 
olism is unknown. 

Spindle-celled Sarcoma* 

This form may consist of eitlier large or small spindle-shaped 
cells with attenuated and sometimes l>ninchiug extremities (Fig. 
51)* Angular or stellate cells are unt iutreqneut. TIk^ cells 

Fig. W.— Cella frum u Jnrge a piodk' -celled sarcomii (Ziegter). 

be ranged in parallel eolumns, so that the tissue l)eeomes 
eomjmct ; and faseicidi ot" such r/ell-masscs may run iu diifer- 
ent directions, interlacing, and tlius giving the 8<^ciion a fibrous 
appearanee* In some cases the cells present no definite arrange- 



jiient. Spindld^eolled f^arconiatii arc harder ihim tho round-celled 
varieties iiikI iLstjally ruure «;rayi.^h or riesbH?olored. They may be 
quite soft and white or th:^*reiienited and cystic. 

The aniQiint cd* intercellular sub.stance in some eases is quite 
eoii.siilenil)le, and tiie term fibrosareoma may he justitied. ^J'he 
intereelliilar fibrils are of the fjbro<rlia iy\^^ and are indistiuirnish- 
able from tliose of fibromata. It is very diffieolt sometimes 
to deeide whether tlie tumor is sareoinatuus or purely fdjromatous, 

Spindle-eelU'd sareomata oei'ur in the dense ernmeetive tissue 
of the p-nosteum, tendons, aii<l fasi'ire ; less frequently in the 
softer tirisues. They are relatively Innii^n, some teases showing no 
tendency to metastasis, though recurring after removaL 

Ro u n d -ce 1 led 5a rco m a . 

Sarcomata may l>e eoniposed almost entirely of spherical or 
round cells, small or large in size, The dcsi<i:iiations small and 
large round-celled sareoniata arc u.seil, hut do not really define 
separate varieties. The round cells when small resendile those of 

Fio. 62,— Smtill round-ccUed ftarcama : in the center is aevn a blood-veftsel with lli irall 

of endothelium. 

Ivnqvbatic organs. There is little intercellular substance. The 
bloo(i-vessels may lie ((Uitc large and lienmrrhagi's with secondary 
changes may occur (Fig; *^2V The larger cells contain relatively 
more pmtoplasm, frequently several nuclei, and not rarely differeot 
forms of cells (spimllc-slijipeil an<l |>olyniorphous) are associated. 

The naked-eye ;q>j*earances of nuind-eelled sarcomata are usu- 
ally quite characteristic. They are luilky-white^ g'^'ty.* or pink in 
color: sometimes quite soft or cheesy in the center, and a milky 
liquid exudes. Cystic changes aud even calciticatiou may occur 
in the center. The small-eclled variety is, as a rule, softer than 
the larger, though both are soft. 

Round-eelled sarcoiuata are always malignant, tlie sraall-celled 
form being perhaps the most malignant of all varieties. 

I/jmiphosarcoma is a variety of round-celle*! sai'f^oma. The 
appearance is the same as that of the *>ther fornix, but micro* 
scopically a close resemblance of structure with that seen in lym- 



phatic glands is ilisrovmML Tlie jjriiicipiil eliuracteristic is the 
rcticuhiDi or stmma formed by IjramyiiiDg stellate cells united by 
their pro loiij^j^t ions. I a the mealies of this reticulum lie lymphoid 
round cells (Fig. 53). The stmma may not be plainly visible 
unless seetions are shaktm to rlislodge t!ie cells from the reticulum 
Lyraphu'sareomata uccor in the lytnphatie glamls and lympluid- 
enoid tij^siies uf the niuct»us menibrane><. Occasionally the thymus 
gland and other organs may be the seat. The distinctions from 

Fig. SSy — Lymphosiireomn of muni maciiUL?) m^'in>ir.itie : a> on Ivfl slda a blood^vesBel, on 
right side reticulum; b, cctlsof reticulum; c, aarcom&celU (Zfegler). 

Jymphadenoma have been discussed under that heading. The 
princj|ial feature ♦>! diHerentiution is the tendency of lymphosar- 
comata to extend beyond the normal 1 imitations of the gland or 
other structures in which they originate, whereas iymphadcnonuita 
are confiiitMj l>y tlie glandular capsule. 

Alveolar sarcoma is a sul*- variety of n>und-cellwl sarcoma, 
though there are always sjiimile-cells as well. It is tlistiuguished 
by tlie occurrence of structures suggesting aeiju and tilled with 
large round cells havuig a more or less decided cpitheliuitl aj>pear- 
ance. Tlie stroma forming the acini is computed hirgely of 
spindle-shaped cells with a certain amount of tiljrillar intercellular 
substance (Fig. 54). The blood-vessels su[»|ilyitig the tumors 
traverse these trahecuhe, Tlie rt)urKl cells within the alveoli 
may vary greatly in size, though they are usually large. The 
macroscopic ajipe^irance is ni*t sfKicially distinctive; many of the 
cases, however, are pigmented ( see beln w). Alveolar sarcoma is most 
frequent in tlie skin, where it springs from moles and warts. It 
may also neeur in the lyniphatic glands, the serous membmues, 
and tither parts. 

In some cases the alveolar appearaiicc nf the sarcoma is dtie to 
the fact that the sarcomatous prolifi-ration has occurred in the 
mivcntitTa of blood-vessels forming a plexus. In this way the 
nicslics of the vascular plexus heriunc filled with round cells 
and the alveolar appearance results. In ivthcr <*ases the alveolar 



character is due to the occurrence of sarcomatous foci of circum- 
ecribcd character in a eonaective tissue. Thej^e in their growth 
push the coDnective-tisBue elements aside and thus form alveolar 

Fio. 6|.^Alveolar sarcoma (WttrrirD) 


In this variety the sarcomatous prolifcnitiou begins in tlie ad- 
ventitious coat of blo<xl- vessels {jM^riiheiioma). Certaiu authors 
have attempted to f^how that all forrass of sarcoma originate in the 
blood-vejiaels ; tliis view, lujwevcr, caunot l>e suppt>rted, Angiosjir- 
comata are met with in theserou.s niembraues, in the skin, and espe- 
cially in the salivary glands. Very rarely they «»eeur in other parts 
of the body. The tumor is, as a ruh% tjoite vascular, but may not lie 
strikiugly so. Sometimes leleaugieetatic eliangf^ in the blood- 
vesselt? has been note<b Hi.stologieally these growths are charac- 
terizwl by round-eel I e<l masses surrounding the blood-vessels. 
The origin of thr cells from the advi'nlitia mav be evident or oli- 
genre. In east*s in which a vascular network is involved and 
each vessel lias a t*<»atiug of sarcoma-cells a plexlform apj)ear- 
ancc or arrangemi-nt results (Pkxijorm AnffimafToma), In other 
instanceB in which a network of vessels is involved the sar- 
coma-cells accumulate in the vascular meshes in the form of eell- 
ijests, and thus give rise ti» an alveolar form (Alvtofar Auf/toattr- 
mma), Snch ftirms occur in sjinunuata ^|)riuging from moles or 
warts* They are prone to melanotic changes The endothelium 
of the vessel is fjccasionally the point of f)rigin of vascuhir stircn- 
mata ; this form is a rare variety of endotbcliomu. The angiosar- 
comata an^ lialih* to degenerations, eliiefly tnvxomatous (Fig* 55) 
and hyaline, and thu:? a certaiji proportion of the cases of cylin- 




dmma (see below) have their origin, Tfie lihxjd-vessels may give 
way iim! hemorrhag'ic infihmtioii re.-^^ilts. 

'Angiusari'omatu art* in a meat>iire benign, iiietaistasis being very 
rare in the orrljuitn^ forms. The alveolar and melanotic varieties 
are highly malignant. 

iMi'-^^' ^ 

Fig. 65.— -^nulosarioma wiih luvxf^niHiUms d<."iienofnUnn ^^rylfwlroiim) r th« fipire rep- 
n»ent» one of the blood-vf^^f?*"!* with the ftarcomiitoua cells apriiigluif from ita waUb, &{ral 
oilUidc of tho«e myx^iinatouii tiit^vie. 


This term was originally applicHl by Billroth to tnmors show- 
ing gelatinons niai^se;^ or tniheeuhe traversing their snbstanee. 
Histologieally ditterent innns rd" growths may lie distinguished. 
AVe df*al here only with iSarvfmy^touH Vifihidnmniia, 

The latter may be .simjily ^jireimiata in whieh hyaline or 
myxomatous dt^genemtion has oeenrred in mon* or less insular 
fsi^hion, or in wliieli siireoiua and myxoma are* jmi^uliarly eom- 
bined. Nearly always tin re h some hyaline change wit !i the myx- 
omatous. In most cases it is th(^ angios'ircomuta that presi'nt this 
[K'culiar condition. The sarctmia-i.'ells snnitunding the bliHwl- 
vessels l)erome cuu verted into hyalomyxomatous tissue or cause 
the formatiMU of tliis, Tliere result bninehing columns of hyalo- 
rayxomatous character traversing the sixreoma. In some eases the 
walls of the 1>1o4h1- vessels themselves may lie the seat of hyaline 
change (Fig* 56), the prolifenited sarcoma-cells surrounding the 
vessel being merely piishe{l aside. Tlie term Anr/tosamomata J/^a?- 



(mJdofJts is given to these ¥tticiilar forms* CyliDdrooiata ciccor iq 
the aalivan^ glan<k, the brain, die lachrymal grlamls and rarely lu 
tbe subeutaoe^iUd Us^^ut^, lu nature they are muT^ or le^ benign. 

Fta. 10*-^UiidnMiUi thowing pr4>»(>uu4.vil l044liuc dcgynerftiion of the waUs of diA 

M e I a n osa rco ma* 

Mf?Ianoflarcoma, melanoma^ chroniatophomma or pig^mented 

fiarcomu is* a form in which the tanior presents a dark color on 
account of the presence of hiack or hrown pigment. The latter, 
acconiing to careful chemical studies of lierde/, anr) Xeneki, con- 
tain}? nr» iron, and is therefore not a simple blwKl jvitfnient but 
m'rianin, a pmiliict of cell metabolism. Iron-containing piirment 
han b<'cn foond In some tumors and sometimes in true melano- 
Hun'om;ita* It is fuiind outside the cells and is probably acei- 
dcntal, rcsidlin^ from licmorrhMgie extravasations, TIte true 
melnniu-ptt^rueutation rw-cur:* in tlie eclLs, in the ceHular pndonga- 
tioii'^ i)r the intc^reelhilar fibrilj*. It is most frequently present in 
the form i»f brovvoish black granular matter, or may oecnr as a 
d it! use ftlnin, 

Mehin^jsarciima most eomijiunly arises in the skin, especial Iv in 
pigm«*nt»'rl moles or vvuris, in the choroid coat of the eye or in the 
pia mater. Tin? growth is found to consist of cells of various 
shapes, sometimes round or irn*gular, sometimes spindle shaped, 
hut ihiTc* is u very constunl tendency, especially in the pigmented 
Bar(!*imat4 of the skin springing fmm warts^ to assume an alveolar 



arrangement* In tlies<% the cells around the periphery (*f the 
alveoli are more or let^s ?^pinille shaped, while thiise in the eetitre 
are hirge, irregular ur rouniied eell^, soEuetimes epitheliuni^Hke. 
Melanotic tareoinas ot the elioroitl are composed very ]ar|^ely of 
celU having an elongated ehar«icter with drawn out extremities. 
These resemble the normal pigment eells of the chonutl eoaL 

Melunoi^arconm h extremely malignant, recurring whm removed 
and iVequently causing extensive melastasis. The latter involves 
the local lymphatic glands in tlie fii^t place* hut later various 
organ^^ esjx'cially the liver. The metastases may he of the same 
gtrncture as the original growth, but sometinjes non-pi gniented 
metastatic tjrfjwths <ieeur in association with the pigmented ones. 
Occasionally the seeunilary <!eposits are more pigmented than tlie 
primary growth. The melanoma originates from the pigment- 
containing ceils or clinnnalfiphores of the part in which they 

Fro. 57.— MclAfiosarcotttJi, mniiily rouiniLTUcd: frum a nodule in the akin. 

originate. In t!ie skin these are found in close assoctati<ni with 
the lower layers of the epidermis, iind some authors liave insisted 
tliut tliev are essentially epithelial in origin and that the tumors 
should therefore be considered as earcinomata. There is, however, 
eonsideniljle gnauid for believing that the c^hromatnphores are 
invariably connect ive-tissne cells. Mrlanosireoniu is a thfaute 
growth and not merely a sarcoma that hajipens to be pigmented. 

Giant -eel led Sarcoma. 

This variety is rharaeterized by the presence of large multi- 
nuclear cells resembling exactly the myeloplafjues of bone. The 
remaining portions of the tumor may l>e spindltwelled or rcamd- 
celled; perhaps more frequently round arid spindle-i'ells are asso- 
ciated. The giant-<^^!ells are often exceedingly large and contain 




that they result from a fusion of cells seeras uowairanted. Ziegler 
n^aintains that the preseuce of giant-cells di>es not form an eHsen- 
tial eharacteristic of a petHiliar type of tumor * hut that it is aoci- 
dental, resulting from ("ontinued irritation. The oc^eiirrence of 
giant-cells in .sarcomata of bones would then he explained by the 
constant irritation of the bony particles, while in other cases the 
presence of masses of blood- pigment in the sarcoma accounts for 
the development of giaut-cells in the vicinity. This view i^ sui>- 
ported by considerable authority and seems reasonable. 

Giant-eel led sarcomata occur most frequently about bone, and 
I the terms odeoHarcmna and nufeloid sarcoma Ivdve l>een given in 
^ consecjuence. They may, however, occur lu other situations. 
Their nature is usualiy benign, metastasis being rare. 

The gianfc-<*elled sarcoma of bone is usually rather slow iu 
growth, and gives rise to liar<l and irreguhvr turners, firmly attached 
to the hone-strnetnr^^s. It may begin within the boneas a w7/f'Mf/- 
ejioiis form (Fig, 5H)or from tlie i^eriostenni. Secondary myxoma- 
tmiis or other change may cause more or less softening. The bone 
most frequently involved is the maxilla, the tumor known as epidls 
(sarcimia springing irom the gums or alveolar processes) being 
generally a giantrcelled sarcoma. 


All forms of connective- tissue tumors may be associated one with another; 
•wociation of several forms are known as mixed tumors. Very frequently 
there is more or leas sarcomatou!! tissue in sueh growths. With this will be 
, found myxomatoiid, fibromatoua, chondroraatou.s, or o^^teoniatous elements, 
I The varioiii* constitu«siits of the tumor are arranged with no speoial order, hut 
simply prei*ent themMelvea as masaea of cells or intercellular substance of 
' difTerent forms combined to make a heterogeneous tissue^ Among the fre- 
quent fieats of SQch mixed tumom the parotid gland and the testicle are 
most important. A not infrequent combination is tbat of sarcomatous aud 
udenomatoua tissue. Tumors of this character are supposed to develop 
from embryonal " rests," and are particuliitly common in tht^ kidney, where 
they (>fien reach large sizes. 

Adrenal "rests" in the kidney give origin to the Grawitz tumor or 
hypernephroma, a tumor largely competed of cells resembling adrenal cells, 
arranged in adenomatous faiihion. (bee Tumors of Kidney.) 


This tumor is no special form of new growth, but rather a variety of 
lymphosarcoma or round-celled sarcoma occurring with special frequency 
in the neriosteum nr the bont^ of the head aad secondarily in other parts 
of the nody. The name is applied because of the peculiar greenish pig- 
tnentation of the cells. The nature of thin pigment i-i not certainly deter- 
tnined. Clinically cases of chloroma may present aymptoma of leukemia 
or pseudoleukemia. 


This represents no distinct species of tumor-growth, but rather a pecu- 
liarity of oiflerent kinds. The name refers to tlie presence of calcareous 
matter like that of the brain-sand (acervuhia cerebri), and psaaimoma haa 



aometimeti been ciuled on^rrui/jtHa. Tlie calcareous matter oocars in the 
form of rounded maMC» or concentrically arranf^ whorls. Tbe tnmor- 
elemente themselree mar be fibromatous, gliomatous, narcomatons, or even 
adenomatous or carcinomatous. In most inntances it Is endotheliomata 
that present these appearan^.'«f^. Psammomata are met with in the mem- 
branes of the brain, tne choroid plexus, and the pineal gland. 


Mvcosis funpoides or granuloma fungriides is a pathologic condition of 
the slcin and subdermal structures having certain resemblances to sarcoma 
and to some of the infectious inflammations. 

Etiology. — Ver>' little is known regarding the causes of this disease. 
Various bacteria, principally micrococci, have been discovered in the 
lesion!?, but none of these has been shown U) be pathogenic. A few ob- 
servers have found liodies resembling prot4^>zoa; but it is not certain that 
thes^f were really animal organisms. 

Appearance. — The disease freouently presents distinct stages. Firsts 
the Ac in becrjmes sf>mewhat swollen and red aud presents eczematona 
\^vtn^. In some caAes the ap[>earance is that of an erysipelatous inflam- 
mation. In the next stage nfAlular elevations occur, and nnallv tumors of 
conhiderable -i//.', s«>metime8 a** large as an orange, and more or less fungoid 
in ap|>*raranc<'. Necro!<is ih frer^uent and watery or bloody liquid is dis- 
charg*r'i. The tumors may have an angry, red appearance, ana have been 
lik«;ne<i to tomat^>es. liapid di»ap{>earance and reappearance of the tumors 
are a pe<'uli:ir feature. 

Anv part of the b'xlv niav l>e aflected and usuallv the lesions are mul- 
tiple. ' 

Stmctnre. — Microscopically the structure of the tumors is allied to that 
of iymnhadenornata. Tnere is a proliferation of connective- tissue cells 
alxiut tlje bUKxl-ves.Hel8 and glan<ls at the bane of the papillseof the skin, 
forming a network or reticulum in which round (lymphoid) cells are em- 
bf^dded. 'i*he celU, however, may be irregular in form and size. Mytotic 
figures may l>e found. Early in the disease the new formed cells degen- 
erate considerably, but later ])niliferation predominates, and the tumor 
results. The epithelium covering the growth may be thinned to a single 
layer, ax it may »hf»w thickening. In the latter case enlarged papillte dip 
down into the round-cell collections and the sections have somewhat the 
ai)pcarance of carcinoma. Knithelioid ctOls and giant-cells may occur. 
The tumors are poorly sup])lie<l with blfK»d-vessels, and to this is attributed 
the tt^ndency to central necrosis. Inflammatory infiltration (polymorphous 
leukocytes) is not observed to any considerable degree, excepting in the 
latter stages around and in the areas of necrosis. Mast-cells are often abun- 

Associated Conditions. — In some cases enlargement of the lymphatic 
glands, liver, and spleen has been observed, and has suggested the term 
pseudoleukemia cutis. Occasionally the blood presents leukemic char- 

Nature. — ^The disease ])resents many resemblances to sarcoma or lymph- 
adenoma, and it has frequently been described as multiple sarcoma of the 
skin. In other respects it is allied to the infectious inflammations, though 
there is much less evidence of true inflammatory infiltration than in these. 
The relationship to leukemia and pseudoleukemia is unsettled. 


This tumor, which in also soniotiincs designated enddhdial 
cancer, resembles can(;er ver>' closely in histologic appearances in 



Fig. bu.— EndytlK'Momii of pleura: the pleural cAv^itv wvlh distended with eflfhaloti and tha 
lung w«a iioro pressed and invadcnl by »econdiir>' nt>dule«. 

Wn, SL— MlcroflcotUe Ret* tion from the case figured iu Fig« dO. 

some causes. It appc^ars, however, to be purely endothelial iii 
origiD, and therefore rather of the eonneetive-tisstie group ar sar- 
comata. It aflect8 the pleuni, peritoneum, aud membmnes of the 



brain most frequently, but may be found in the skin» walls of the 

blood-vessels, periosteum, bone* marrow, lymphatic glands, g^iKis, 
ovary, testicle, liverj and salivary glands. Tlie 8ert>us merabraiies 
when affectcil become greatly thickened, tough, and white in color 
(Fig, 60), and irregular elevations or nodules may occur. Metas- 
tasis is infrequent, but the adjacent organs are sometimes involved, 
and occasionally more distant structures. Endotheliomata of the 
dura mater spring from the inner surlace of that membmiie and 
have a flattened nodular character. Histologically they may pre- 
sent the concentric whorls of cells and calcilication characteristic 
of psammomata (see above). 

Histologically the tumor is cliaracteri^ed by more or legs 
tubular or aeinus-like aggregations of endothel ial cells. The latter 
vary in character from those which are distinctly endothelial 
to the most differeutiated, which may be almost typical cylin- 
drical epithelium (Fig. 61.) Between these cellular columns 
or acini the connective tissue of the part affected may be seen in a 
normal state, though it is more frequently thickened l)y prolifera- 
tion, lu the endotheliomata of serous memliranes inspection of 
the sections shows that the columns of epithelioid cells occupy 
lymph-i'hannels, and it may be possible U> demonslrate that the 
endothelium of the latter Ims been the starting-point of the cel- 
lular proliferation. In cases of carcinoma with penetration into 
the lymphatic channels it is notable, on the other hand, that the 
endothelial lining of the channels is uninvolved. Endotheliomata 
may in rare cases originate in the endothlelium of capillary blood 
vessels. In these growths anastomcitic channels linetl with enothelial 
cells, or anastomozing columns of emlothelial cells [jriK'laim the 
origin from vessels. The term hnnanriioendoth^lioma has been 
applied. A more frequent variety is that which originates from 
the endothelium surrounding IjIikxI vessels. The ^.ndothlium of 
perivascular lymph spaces proliferates to form a growth surround- 
ing the blood vessel ancf extending along the vessel and its 
branches* The term perifhrlloma is applied to this form. Muc*>id 
and hyaline dt^euenition is frequently found in such growths^ and 
the tumor known as cylindroma (see p. 17*3) may have this origin. 


Definition.— The term glioma is applied to tumors composed 

of neuroglia. It is difficult to distinguish iMween the circum- 
scribeii tumors of this structure and tlie diffuse ueurogliar h\^r- 
plasia or gliomatosis met with in certain cases. (See section on 
I)is<_^ascs of the Nervous System.) 

Etiology. ^ — It is probable that congenital defects of develop- 
ment play some part in the causation of these tumors; particularly 
in the forms more frequently spoken of as gliosis. 

Appearance,* — A typical glioma is usually a solitarj^ tumor. 



rounded in outline, though it^ limits are difficult to determine, as 
it raei^es gradually into the surrounding nervous tissue. Gliomata 

Pig. tl— Glioma of the corpora qundrigemluii (PerlB). 

are somewhat hardiT than the normal bniin-??ut)stanr!e, and oft^en 
the color is a little ditterfut, either more grayish or pink or red- 
diah* Sometimes they are quite vaseular and dark red* The 
normal shape of the part may he a little tlisturbed, or there may 
be indefinite elevation. In size the tumor varies up to massi's jis 
large as a lemon. Diffuse glioma tosis eauses a swelling of the 
affeeted parts, sometimes quitt^ regular, at other times irregu- 
lar. When the spinal eord is aifected its thickness may be con- 
fide raVily increased. On section the area of gliomatosis is rather 
iirm and grayish in color/ Nearly always there is a tendency to 
excavation or cyst-formation. In the cord this leads to the de- 
velopment of considerable cavities, as a rule communicating with 
the central canal. 

Seats. — Glinmata occur in the brain and less frequently in 
the spinal cord. In rare cases the cranial nerves have been in- 
vidved. In one case a glioma was found over the coccyx and 
sacrum, originating from the remains of the lower end of the 
neural cjinal. Glioma uf tlic eyel>all will be referred to below. 
IHtVuse gliomatosis is particularly common in tlic cord. It is 
usually met with in the vieiuity of the cavities of the brain or 

Structure. — The minute structure of glioma varies consider- 
ably according to the type of neuroglia represented. In the 
typical glioma the cells contain rounded or oval nuclei, and the 
protoplasm is scanty. Wavy intercclbilar fibrils (neuroglia fibrils) 
lying jmrallel to the axis of the cells to which they belong are 
characteristic structures. They are not prolongations of the celts, 
but merely Much the cells at their sides, the extremities of the 
fibrils being free. These fibrils are distinguishable from the finer 
fibroglia fibri is nf connective-tissue growths. The abundance of the 
fibrils varies in dilferentgliomata, but is generally a ratlier marked 
feature^ These give the section a granular ap|w?a ranee when seen 
under low magnification. In other cases the cells are of the 
ependymal type, and occasionally tiiey may be arranged around 



brain most frequeDtly, but may be found io the ^kin, walls of tbe 
blood-vessels, periosteura, bone* marrow; lymphatic g^lands, gums, 
ovary, testicle, liver, and salivary glands. The serous nierabmni'?? 
when affected become greatly thickened, tough, and white in color 
(Fig. 60), and irregular elevations or nodules may occur. Metas- 
tasis is infrequent, but the adjacent organs arc sometimes involved, 
and occasionally more distant structures. Endotheliomata of the 
dura mater spring from the inner surface of that raembmne and 
have a flattened nodular character. Histokigically they may pre- 
sent the concentric whorls of cells and ca^lcitication characteristic 
of pflammomata (see above). 

Histologically the tumor is characterized by more or less 
tubular or acinus-like aggregations of endothelial cells. The latter 
vary in character from those which are distinctly endothelial 
to the most differentiated, which may be almost typical cylin- 
drical epithelium (Fig. 61.) Between these cellular columns 
or acini the connective tissue of the part affecte<l may be seen in a 
normal state, though it is more frequently thicken*xl by prolifera* 
tion. In the endotheliomata of serous membranes inspection of 
the sections shows that the columoa of epithelioid cells occupy 
lymph-channels, and it may be possible to demonstrate that the 
endothelium of the latter has been the starting-point of the cel- 
lular proliferation. In cases of carcinoma with penetration into 
the lymphatic channels it is notable, on the other hand, that the 
eDdoihelial lining of the channels is iininvolved. Endotheliomata 
may in rare cases originate in the endothlelium of capillary blo<xl 
vefisels. In these growths anastomotic channels linetl with enothelial 
cells, or anastomozing columns of endothelial cells proclaim the 
origin from vessels. The term hernanfftoendotMiomn has been 
applied. A more fret|uent variety is that which originates from 
the endothelium surrounding bltxxl vessels. The endothlium of 
perivascular lymph spiiccs prolifenites to form a growth surround- 
ing the blood vessel and extending along the vessel and its 
branches. The term perlifieliama is applied to this form. Mucoid 
and hyaline degeneration is frequently found in such growths, and 
the tumor known as cylindrormt (see p. 173) may have this origin. 


Definition.— The term glioma is applied to tumors composed 
of neuroglia. It is difficult to distinguish between the circum- 
scribed tumors of this structure and the diffuse ueurogliar hyper- 
Elasia or gliomatosis met with in certain cases, (See section on 
Useases of the Nervous System.) 
Stiology. — It is probable that congenital defects of develop- 
ment play some part in the causation of these tumors; particularly 
in the forms more frequently spoken of as gliosis. 

Appearance.. — A typical glioma is usually a solitary tumors 



Qrionia Qaitglionare. 

DefimtioiL— This term indicates a form of mixed tumor composed of 
neuroglia and nerve-fibers with lurge fjangUonar nerve-cells. 

Etiology.— Probably congenital abnormality of development furnishes 
the gntuudwork for the subsequent development of these tumors. 

Appearance*— A ganorliQ^ar glioma may resemble the ordinary glioma, 
occurrmg m a solitarv tumor, the outlined of which are difficult to db- 
tinguLsh from tlie surVouiiding tissue. :More frequently it occurs in the 
form of multiple nodular condensations scattered through the brain or 
cord. The corjtour of the affected parts may not be iilteretl, and on section 
the j?rowth« mav be reco^niKetl only by the light-colored patcheii and areaa 
of increased density. A few casen of ganglionar gliomata of the spinal or 
sympathetic ganglia have been described. In these cases the inmora ap- 
pear a» rounded eiilar^emenLs of the aflected ganglia. Occasionally the 
nerve-roots are seats of these tumors; llie suprarenal eapsulea may also 
be affected. 

Structure. "The definition indiciitcB the usual structure. The glia- 
fibrils are generally conspicuous in number, the nuclei being comparatively 
few. Traversing the tumor there may be more or less abundant nerve- 
fiber* with or without medullary sheaths. Large ganglionar cells may be 
found in considerable abundance or in small number. The vascularity of 
the growths di Iters greatly. 

Hature, — The nature of these tumors ia the same aa that of the ordi- 
nary gliomft. 


Definition. — Strictly B|Mmk[ijg, iieiiroiua is the ienn applied 
to tiiriiors ciHiipostMl of iierve-filji*ris. (Jnliiiurily, however, tlie 
Uikuie 19 given to fil>rou.s growths .^priii^iiig from the perineiiriiun or 
endoaeiiriuTii of nerves. Tiie terms irw ami /(due ncunwui di.s- 
tiii^ni^sli between the two forms. True neuromata are exeeeil- 
ingly rarf\ 

Etiology,— Very little is known reganling the eauBation. 
Injury may phiy a paii, as in tlie ease of amjuitatioji-neuromata. 

Appearance^ — False neuromata <x^enr as ntH.lular thiekenings 
ah)ng the course of nerves. They may be fusiform or elongated, 
may extend considerable distances along the nen-es, and may 
form networks of ridges or elevations when tlje periphend nerves 
are luvolvtHl (Plexiform Xeuroma). As a ndc tlicy are midtiple, 
and sometimes iK^'ur in exci'edingly great numl>crs scattered over 
the entire bmly or involving a single pait of the body, as the 
nerves of the arm or leg. After amputations rounded thickenings 
may occur at the ends of the nerves and eau-e painful conditions 
of the stomp. 

Seats. — The peripheral nerves are most frequently involved, 
hut the ner\'es may be implicatcil near their rootis, or the terminal 
fibers witliin the organs may become ati'ected, 

Stmettire. — Onlinary false neuroma consists t>f fibrous tissue 
in the iVjrm of reticular connective tissue with greater or leas 
abundance of cells pushing a,si<le or surrounding the nerve-libers 
proper. The latt4^r are prone to degenerate in eonBequenee of the 



omxiode^ is given to the&e vascular fornii^. Cylindmniata occur in 
t!ic salivary glands, t!ic Uratn, tho laehrv nial irl^inl^ inn I ran ly in 
tlje subcutancotis ti?^siK*h. In iiuture tlicy are inr^rc tn* Ici??^ benign* 

Fio. 56»— TyllDdroma showing pmnoiiricetl hyuUuc tivgeiieratlon of the walla of the 

Me [a nosa r co m vl, 

Melanogarcoraa, inclaunma, chraniat*)phort)ma or pi^rmefiteil 
sarcoma i.^ a form in wliich tint tnnior presents a rlark color on 
account of the presence of black or brown pigment. The latter, 
according to careful chemical studies of I'erdez ami Xencki^ con- 
tiins no iron, and is therefore not a simple blood piijruent but 
nu'Iauin, a jirnduct of cell metabolism. Iron -contain ioir piirnient 
lias been fotunl \n some tumors and sonictimes in trur melauo 
sjireounita. It is found outside the cells and is prolmbly acei- 
dcntiil, resulting from hemorrhagic extmvasations. The true 
nielanin-])iL:mentatioii orcors in the cells, in tlte cellular pmlonara- 
tiuns or the intereellular tibrils. It is most frequently present in 
the torni uf brownish black granular matter, or nuiy oecur as a 
diiiuM.' stain. 

Melanosarcoina most coumionly arises in the skin, especially in 
pigmented moles or warts, in the choroid coat of the eye or in the 
pia mater. The growth is found to consist of cells of various 
shapes, sometimes roinid or irregular, somi^times spindle shnped, 
I ait tUere is a very constant tendeney, especial ly in the pigmented 
sarcomas of the skin spring* og from warts, tx> asBitme an alveolar 



arrangement. In these, the cells around the periphen^ of the 
alveoli are more «>r h ss spiriclle i^liaped, while thot^e in tlic eentre 
are hirge, irreguUir ur rnuinird cell?, ;^otuetime,s epithelium-like. 
Melanotic siirrmnas M the i4i<jroi<l ure eorapo^ed very largely of 
ceils having an elongated charactiT with drawn out extremities. 
These resemble the normal pigment eel Is of the chttroid coat* 

Melanosarcoma is extrenjeiy malignant, recurring when removed 
and frerjoently caysiiig extensive nietastasis. The latter involve.s 
the hical lyrnphatic glands in tlie tir>^t place, but later varii^nis 
orgacj5, espeeially the liver. The metastasejs may be of the same 
structure a.s the original growth, but &ometinies non-|>igmented 
metai^tatie gnjwths oeenr iu association with the pignKUted ones. 
Occasionally the Aeeondary (h-posits are more pigmented than tlie 
primary growtlu The nn:4annnia originates i'roni the pigment- 
containing cells or chrnmatoph^tres of the part iu which they 

Fig. 57.— MelAiios&rcuiiift, nminly ruuiid-CLllid : from n nodiile in the akin. 

originate. In the skin these are found in close association with 
the lower layers of the epidermis, and some authtirs have insisted 
that they are essentially epithelial in origin and that the tumors 
should t h e re fore be eon s i d c ^ re d as ea re i n o m a ta . 1' 1 1 ere is, h o wc v e r, 
considendjle ground for believing that tlie chromatupliores ai"e 
invarialily eonneetivc-t issue cells. Melano-art^oma is a drlioite 
groAvtIi and not merely a sarcoma that liappeiis to be pigmentetl. 

Qiant-ceUed Sarcoma. 

This variety is characterized by the presence of large multi- 
nuclear cells resemlding exactly the myeloj>laipies of bone The 
remaining portions of the tumor may be spindle-celled or ronod- 
celled ; {K-rhaps more ircquently mund and spinflle'f_'ell> arc asso- 
ciated. The giant-cellfet are often exceedingly large and contain 



pressure* Proliferation of the nen^e-fibers has eoinettmes been 
deBcribefl, but it ib doubtful whether such actually cxvurs* More 

Erobably the existiEg fibers increa^ in lengrtb and form a mass ^ 
y curling at the end. True neuromata of two' kinds are de- 
R^ribed : thost* composed of medu Hated and those consisting of 
nc»n-medtillated nerve-fibers. The former are called mydinicj the 
latttT amyd'mk\ 

Nature. — Neuromata are painful tumors, but benign in a 
pathologic sense. Their growth up to a certain point is often 


Defitiitioti. — Leiomyoma, or myoma tevicellulare, is a tumor 
c^>ntaining smoiith muscle-fibers. Nearlv always there is a cer- 
tain amount of fibrous tissue associateu^ and in the most com- 
mon forniy myomata of the uterus, there is always considerable 
fibnius tissue, and the term fihromyoma is appropriate. Occasion- 
ally a few unstrip'd muscle-i'ells may be seen in tumors of other 

Etiologyt— 8ome of the myomata of the uterus ejthibit 
glandular acini in the interior, which suggest their origin from 
congeni tally misplaced portions of tlie Wolfian body or duct of 
MuUer. These misplaced stnictiires are assume<l to cause an irri- 
tuition of the surrrHmdiug nuiscle cells. This, however, is by no 
means eertfiiu. In other cases there are features suggesting that 
irritatifin is the important eause^ though this also remains to be 

Appearance. — Leiomyomata are usually rounded growths, 
varying in size from minute nodules to huge solid masses weighing 
aa much as sixty to seventy pounds. The largest (heaviest) solid! 
tumor I have ever seen was a degenerated fibromyoma weighing 
eighty pounds, Leiomyomata are surrounded by a capsule more or 
less well developeHl and are generally quite hartl, though secondary 
degeneration at times altet's the consistency, making the tumor quite 
ftoft in the case of mucous transformation, or stony-hard wlien cal- 
cification has occurred. On section through the growths the 
stratified or fascieulated arrangement of the cells is visible to the 
naketl eye. Concentric layers may be apparent, or a more wavy 
irregularity may be seen. They are grayish or flesh-colored, or in 
rare instances quite red (myoma cavernosum) in consequence of en- 
larged vascular channels/ Central softening may lead to cystic 
change (myoma cysticum). 

When the myomata spring from the submucous or subserous 
tissues they may become polyixiid, hanging from a {KJint of attach- 
ment by a narrow pedicle. In rare instances the latter is 
eevered and the tumor becomes a free body* Submucous myo- 
mata of the uterus may thus eventually be discharged after a 
spurious labor. Subserous myomata may become free in the 
peritoneal caWty. 


Myomata of the utoriis nuiy htive three Hituatiotis — subnuicoiis, sub- 
serous, or intenstitiaL In the latter, the tuuior occupies the wall of 
the uterui without any tendency to project ifarticularlv toward either sur- 
face. Uterine myomata are usually multiple, occur during the third and 
fourth decades of life, continuing their growth until the menopause and 
usually decreasing after that epoch. They endanger life by their pressure 
and by the copious uterine hemorrhages which they occasion. Very fre- 

3uently salniugitis is associated, and recently attention has been called to 
egenerated conditions of the myocardium in patients ^ufiTering from uterine 

Myomata of the skin occur in younger patients, even in childhood, and 
are generally nmltiple and often painful (tnhercula dolorosa). 

Seats. — The common situations are the uterus, the gastro- 
intestinal tract, and the ovaries; the less common seats are the 
walls of the blood-vessels, the skin, and the nipple. In all situa- 
tions the tumor springs from pre-existing un>>tnped miisele-fil>er. 
In most cases, according to some iitithors, the origin is in the walls 
of the rainote bhiod- vessel 6, but ilirect origin from the muscular 
layer of the affected organs, or from the erectores pilorum in the 

Fig. 63. — Leiomyoma of utenu. 

case of the skin, cannot be denied* Myonmtons metaplasia of the 
connective tissue, as in the ease of myomata originating in the 
areas of old pleural thickening, has been assumed, but is im- 

Stmcture* — As has been said, association with fibrous tissue 
IS usiiaL Mierosfxppically the tumor presinits a characteristic 
appearance. Bundles of muscle-cells are seen running in different 
directions. Those cut longitudinally show cylindrical nuclei as 
the moat conspicuous feature, the outlines of the cell being indis- 
tinct (Fig, 63). Where the cells are transversely cut the nucleus 
presents a circular outline with clear protoplasm surrounding it. 
The picture of a leiomyoma is often suggestive of sarcoma, hut 
may be distinguished by the greater regularity in direction of the 
cells in different bundles and by the more distinctly cylindrical out- 



line of the nucleus. The cells of loiomyornata may bo isr^hitol by 
maceration of the sections in 20 jkt eent. s<>hitioii nf nitric aeiil 
for twenty minutes, or in *10 per eent. solntiou of <^aiisrie jxitiihh 
for fifteen minutes. Tficy are spindle-sliape*! structures eoiitaining 
a oocletis about one-third tlie lengtli of the entire cell. Consider- 
able elastic tissue is fouud in some leiomyomata, especially in tJie 
J0iiiiger areas. 

Leiomyoma ta are generally poor in bh>od-vcssels, hut may 
allow a teleangiectatie condition of the vessels. The lymphatic 
apao» may similarly dilate, forming cystic spaces containing 
cpoDtaneoosIy et>agulal)le material. 

Of the degenerative changes caleific^ation is the most common, 
paitaciltariy in the uterine fibromyomata. This begins in the 
center of Uie tumor, but may eventually involve the wliole mass. 
Mjxomatoaa change may occur in myomata containing nuich 
fibrous tissue, and sarcomatous transformation has been described, 
but is rare. 

Nature. — The nature is eminently benign, Myomata of the 
digestive tract may cause occlusiou or strangulation, or by their 
weight may esen:*isc serious traction. Uterine myomata are dan- 
gerous in the ways already indicated. The gro\vtli is usually 


Definitioil,— Rhabdomyoma, or myoma striocellulare, is a tu- 
mor containing more or less striped muscle-tilicr* Usually there 
is but a small quantity of the tattler, tlie l>uik <»f the tumor l>eing 
of some other tissue, most trecpiently sarcomatous. 

Etiology.— Congenital defective development seems an im- 
portant i^siuse, as the tumors occur in early lif*^ and in situations 
in which striped mus<'le-rtl>er does not normally occur. 

Appearance and Seats. — The rhalKlomyoniata of the kid- 
ney (the most frequent seat) present themselves as large roundeil 
or irregular masses, more or less en(*aj*sulated. In the testicle 
they are similar, though of smaller size. A few eases have been 
describe*! in which irregular tumors of the retroperitoneal tissues 
have contained muscle-tibi'rs. 

Stmcture. — The mrr roscopic appearance is usually that of a 

?>indkwx'lted Harcoma, r*rintaining more or less striped muscle-fil>ers. 
hese are elongitted spindie-sliaped cells, j>artly striated, and sug- 
gesting embr>*onal muscle-tissue and rarely more iully develojied 
musi'le-fibem. Large areas of the tumor may contain no muscle- 
fiber at all; wliih" e4*rtain portions are ri<*hly supplied. Adenoma- 
tous I'lemefits are not rarely associated. The tumors of the kidney 
wliieli eontjiiti b-tri[»ed muscle-tibers ait^ in the main sarcomatous or 

Nature* — These tumors are malignant in proportion as the 
san:oniatous element in jiredominant. Metastasis is, however, 


jEfreqiiGDt. General cachexia and hemorrhages reduce the vitality 
and lead to fatal termination. 


Definition. — ^The term papilloma indicates a tumor arising 
from the surface and covered witli epithelium somewhat as the 
epi<lermis caps the jMpilla? of the iMjriuni. 

Etiology.— It is difficult to draw a line between certain papil- 
lomatous growths that are the result of chronic irritation and otiiers 
that arm* in a seemingly sjion tun cons manner. It would appear 
that irritaition is an important factor in most, if not all, cascs^ but 
there is also no donht some form of })redisposition. Whether this 
resides in structural peculiarities or not is difficult to determine. 
A peculiar form of inflamniator}^ growth resembling the sjxinta- 
neons papillonuita is that known as veneirfil warf. It (x^curs about 
the genitalia or anus and espt^cially after gonorrhea* Another 
form of inflammatory |mpillomata is that found in the mucous 
membranes surrounding carcinomata or chronic ulcerations of 
S}qihilitic or other kinds. 

AppeEUrance. — The most familiar form of papilloma is that 
which orcurs in the skin and wliich is comiiujuly called wiirt. 
Warts or papillomata may be single, but more frequently 4jccur in 
gnujj>s, and there may be many grcjwths in widely scattered areas 
of the IkrIv. a wart may l>e simply a 
smooth hemispherical ehnatifui, or it may 
have a cninlitlnwer a[>jRni ranee. The epi- 
dermis covering it is, as a rule, somewhat 
more granular or rougli than is that of the 
normal skin. The sixe of these growths 
varies from minute }K>ints to nodules as 
large as a wa 1 n u t , On t h e m u c m> u s su riat^cs ^ 

Xially wile re the epithelial covering is 
xnar, the papilloma presents itself as 
a soil and more distinctly cauliflower 
growth (Fig. 64). It is red in color, or, 
if the epithelium is str.itihcd and squamous^ 
grayish or pink. The growth is usually 
ei^nipamtively hard when covered by 
equamous epi thel ium. 

Twf> varieties are sometimes distin- 
guished. The hard papHioimda, such as Pin. r.i,-papiUoni,ua cf the 
those w^Hch occur in the skin, and the yoc«U'r.rdMfraDifl^prrimeri 

^ .„ , I /* II in the Museiiro of the Philii- 

itojt p<ipiif omnia y or the lorn» usually seen deii^hia HoBpitai). 
in the mucous membranes. 

Seats. — Papillomata occur in the skin of the neck, hands, 
back, and other parts, and in the mucous mcmbnines, particularly 
in the bladder, larynx, iiasiil chambers^ and gastro-intestinal tract. 


Small papillomatous oiiterowth? may spring from the lining mem- 
brane ot gliiniiular ducts. a;& in the breast or ovan-. These may 
lead to subsequent cystic change in the organ, or they may arise 
after cystic change has begun l)y proliferation of the lining mem- 
brane of the cyst. In a similar manner papillomatous elevations 
may •►ccur within the t^avities of cystic ailfuomata (see below i. 

Structure. — The essential parts of papilloma are the center 
or groundwork of connective tissue containing blo^xl-vessels and 
the cpitlielial covering. In the skin the gn>wth imitates the nor- 
mal papillse, all p'-rtions of the latter, however, being greatly 
exaggerated, and tlu? papilla with its covering oX epidermis U-ing 
raised alH>ve the surface instead of having its usual seat below 
the surface with theepidennal cnvering level with the surrounding 
parts. When there is ien«Iency to cauliflower apjnarance the 
papilloma shows a branehing form on vertic:d sivtion. Each of the 
branches contains a connective-tissue framework with an epithelial 
covering. The latter consists of stratitieil, sc|uamous cells and 
shows a decided tendency to horny change. Distinct ci»ncentric 
whorls «if horny epithelium, such as (.K*cur frt^juently in epiiheli*- 
niata of the skin, may b»- met with in luipilloniata. In some i.-js«- 
th«' amount of cnnne<:tive-t issue ground W(»rk in the ^tapilloma i- 
excessive; in others the new-growth consi-ts almost entirely «jr 
proliferated epithelium. In some of these latter cases the resem- 
blance to epithelioma may be rjuite suggestive, but a distincti'^n 
can bo made by r»bserving that the tumor tend> to grow outwarii 
rather than into the deejur structures, and always shows s m** 
connective-tissue stroma at least. The juipillomata of the muciMi- 
membranes ditfer acconling t«i their situation. In the lar\nx and 
other |K)rtions coven-d with squamf»us epithelium they may present 
much the siime ap|H.'arance a?? tliat seen in the skin, though the 
epithelium, as a rule, n-mains softer. There are cases, however, 
in whi<'h a di.-tin<-t pachydcnuatou- changi* is found in the epi- 
thelial coviTJngof jnipilloniata. In the gastn>-intestinal tract and 
in the Idadder papilloniatii are prone to be soft and villous in 
appearanc<: and an- r-oven-fl witli a s<;antier epithelial coating. 
Oystic! (;han;:e i- not !inii-iial a^ a result c)f degenerative proces«?es 
or of dist^-ntioii of tlie riiru-r,ii. (rjand... 

Nature. —The narun- of th*-'- tumor- is benign, but they may 
be de.struetivi- of rj,- j/i-n. rai health in c(»n sequence of repeated 
hemorrliatr|- ar bv inNrf-riutr with the function of the organ or 
part in whir I, tli^v '.xti*A\M:i\it\. In >f,me cases they are suppL»sed 
to become UinW'^unur -> ,^ ri.i- Jia. not been (h-iinitely proved. 


I Definition. -.V:..'.',-;.. .. t|„. wrm appliwl to a new-srrowth 

Wl correHjxmdjjj^i inoM v.. .«,., .,, ^^rrneture with certain epithelial 



_Hids> and therefore presenting acini or tubules containing 
glandular epithelial cells (cylindrical or polyhedral) and a reticii- 
him of ennnective tissue and blocid-vesselH. It is difficult to 
separate simple glandular hyperplatiiu on the one hand and carci- 
noma on the other hand from true adenoma. This will be die* 
cussed in referring to the structure. 

biology. ^ — The causation of adenoma is obsciu'e. In some 
ca^es congenitid misplaecnicnts of tia«3ue-elenients appear to play 
a part, as is seen in me castas of adenomata of the kidney having 
the structure of suprarenal bodies. These tumors whichj it is true, 
some authorities refuse to consider as adenomata, have a general 
resemblance to adenomata and spring fi-om remnants of suprarenal 
tissues embedded in the kidney-substance. Traumatism may be 
a factor in the etiology by exciting the prolifemtion of such mis- 
placed tissue-elements. In other cases the ordinary glandular 
struetnres seem to be stimulated to abnormal liypcrplasia and 
tumor-growth in consequence of continued irritation. Instances 
of this sort are freciuently seen in the gastro-int4?stinal mucous 
membranes, notably in the stomacli and lf>wer part of the colon 
in certain cases of chronic gastritis and old dysenteries. 

Appearance* — The appearances of adenomata vary greatly 
with their seat. On the mucous surfatn^s there may he a simple 
thickening or more or less diftuse and irregular elevation of the 
surface* or in other cases distinct jutpillomatous outgrowths and 
rarely definite no<Udar tumors. In stmie of these cases the e<)ndi- 
tion is ptirely one of inflammatorj^ hyperplasia; in otiicr eases 
there is undoubted tumor-growth. No sliarp demarcation can he 
established. In the substance of the organs adenomata (H-ctir as 
nodular tumors, usually singly and well circumscribed, and not 
rarely surnjunded by a fibrous capsule. They are moderately 
firm, and on section whitish or pink in color. Sometimes cystic 
change occurs as the result of dilatation of the glandular acini or 
in conse(|uenee of degenerative softening ; in these cases the con- 
sistence is corres{K>ndingly altered. 

Seats. — Among the situations in which adenoma is frequent 
may be mentioned the mucous meml>ranes, the skin, and certain 
organs, notably the mammary' ghind, liver, kidney, suprarenal 
bodies, thyroid gland, and ovaries, Clinically important seats are 
the pylorus, tlie duoilenal papilla, tlie rcetum, and the uterus. In 
these situations adenouKita .spring from the epithelial tubules or 
mucous glands. In tlie skin the points of origin are the sebaceous 
and sweat-glands. 

Stroctfire* — The definition in general indicates the structure 
of these tumors. They are more or less typical ; that is to say, 
there are acini of normal appearance presenting a single layer of 
columnar epithelium, with perhaps in places a tendency to heaping 
up the several rows of epithelial cells. These acini are well in- 


closed by a snrrounding connective-tissue reticulum^ and the 
appearance of normal gland-tissne is thus produced. Unlike 
normal glands, there are no excretory ducts, or at most imper- 
fectly developed ducts. 

Two varieties of adenoma are sometimes distinguished, the 
tubular and the racemose or alveolar. In the former the glandu- 
lar system is simple and consists of tubular formations lined with 
columnar epithelial cells ; in the latter the appearance is that of 
more complicated glands with closely aggregated acini of circular 
outline containing columnar and often cubical or polyhedral cells. 
The number of varieties may be carried further, however, for in 
the liver the adenomata resemble the normal liver-structure rather 
than the ordinar}^ glandular formation above described, while in 
the suprarenal capsules and kidney the appearance is that of 
slightly atypical suprarenal structure, or in other cases that of 
embryonal renal tubules distended to form considerable cystic spaces 
with partitions and inwardly projecting papillomatous elevations. 

With the further growth of adenomata the appearance may be 
little changed. In other cases considerable variations occur, and 
there is a tendency*, more marked in some situations than in 

Flo. 4&,-.I>«fttructive adenoma (Beyea). 


<)tlitTs,U> active proliforation of the epithelium, which may cause ^ 
consi(l(frablo alt<»ration in the liistology f»f the tumor, and event- 
ually transformation into i\(^ti\\\Ut carcinoma. The terms adeno- 
carcinoma, (IcKtniftivff adenoma, and malignant adenoma are 
sometimes applied in hucIi im^. The same names, however, are 



given to a type of adenoma charaoterized by the formation of 
abumlant anastomosing or sepanite<l tubules and acini with com- 
paratively little reticular tissue, and by the tentleney to rc]>etitioo 
of the same structure in the local extensions from the origin 
growth and even in metastases (Fig, Bo). 

The CrOnnective-tissue stroma of adenomata may be nif>derate 
in quantity or may be con^iiderable. In some adenomatous 
proliftTationj^ of the mucous menilvranes the number of gland- 
acini or tubules may be relatively small j while the interglandnlar 
connective tii*sue shows active round -eel I intiltrntion to a very 
coa«idenible degree. iSometimes the iuterglandular tissue is dis- 
tinctly sarcomatous (adenosarcoraa). In other instances the bulk* 


FlO, M.*'Aa«ncim»of the mominitry Klaini, with ryaik efilarjjemetit of mciai and AbuBd&nt 
interglaoduliLr Eyper^ilfUiifi of Gotmeitive tiesue. 

uf the tumor may consist of connective tissue of fibrous character 
in which are endieddcd a relatively small number of glandular 
alveoli. In all of these cases it is ditticult to determine whether 
the connective-tissue process was primary and the epithelial sec- 
ondary, or the reverse. 

Secondary changes are common, the adenomata of the stom- 
ach and uterus being particularly prcme to change their char- 
acter to that of carcinoma. In these cases there may be noted 
active proliferation of the epithelial cells, sr* that the acini or 
alveoli become completely fiUe^h or that the ends of the tubular 
structures become bloc^kcil np, Tliere is a tendency to extension 


A -^pith'-iiai innltrariou lipvoncl tin* limits of the acini, 'tincermis 
.'it^-i\rrii-. rH>inir the iv^ult. In orin*r j-asi^ the maiiinuincv- r 
nrianitV-st*-fl :.y th»* exi^essivr ppitlu*Ii:il |)mlit('raiifm in the rorra •!' 
nf'.r 3/ini if irrejrjiar chararter (Fii^. Ho). Eventually the tumor 
may '>#*f.'inri** purely carr* innmuiou.*. : in othrr tnLM*3. however, i: 
'•'»ntinii»-«i :o iruTfase in siz**. always rotainine its aiieniH^airin*- 
,Ti:ittiii- i|»i>paran«!f*. but n«*vi*r hft'oniini^ typically (.arriaumacous. 
r^*irtTi»'ratIv»» ohantrf^s may 1)h niK witli ils in other tumors, 
fiv'iiiin* tran-itorniation or pnviur'tion of hyaline or myxomatous 
ri-«-i!i** "n tiiH stroma may 2'iv«» thi» tumor an appe:irance justifying 
•h** vrn ■• ^y:In«iri»ma'' or *' cylin<ln>-a«l»*niima.'' Such oaaes an? 
mrr-. \f ■.•\-umatoMsan«l evt^n <'al«»an'oiis «'hanffe may S4imetimes i>e 
►ns*-rv.-si. Til*- «'onnt*fnivi»-tissiie stroma may proliferate actively 
irifi i--Jiin*'-ar- iTnatous app»»aranfe — aili*no*arr»oma. Cystic oJums** 
Ti.'iy r-^iiit rVim jnnhial ililauuion of tli«' irlam hilar acini or from 
li-'.-itlon if rn.r-nal 'luots or alv«Hili of the ^rlanfi in which the 
^.,\r^i>r i^-^ur*. In thi'sp i^asi*s the t«*nn <'ystic adenoma or cyst- 

Nature. — ^A"i»Miomara are l)oniirn tumors. In isome oaa»»?. 
■»..'v-' T. I r>«ir* ^{•^n«)ma may iriv** ri-f r«» motasta.'iis. Tliose "f 
•:m' ■■•r. r'*r ••x.impli'. not nin^ly <*an-»f» stM-ondar}' ilt*i)«)sit$ in ttu' 
-r*'»'--i It'-j-* ir'-'|ii»'ntly ♦»U»»wh«Ti'. Tht» ailenomata of the 
♦ii-T.'-l s\'Mv\ -i mi la fly ransf^ nirtastasi-^. tlmuffh their structure 
{«>'-■ .11 .t ill i:iy way suif'i'est maliirnant ;jrrowths. Di^mictive 
rnii'n*.»n:iM '*r iil'-ivxriiroinomata an* maliL^nant in pmportitm to the 
■wno'j-ir if .-ap.'i noma tons rnnstnrmarion «)n thi* on«* haml or i>f 
rit-.':.i.-i. /!:jnijii!ar [iroiif-rarinn on tht* "thiT lian«i. 

Tij" "tr-r-t of a«l«'no!ii:ira *^n rii»- ir'-mrnl ln-alth is vanahlt*. 
T;i«-' f\*i nut ^onrril*iit»' to th,. ._r.'n»T:ii mi-raWoIism a:? far as i? 
K'n-.-vn. ttiMiij"J» M«fa-!i»iiaily liiiiary piu^Tii'-nt.itinn of tiie adenomata 
'.:' r\\(' li/.-r. arnl ^'v.-ti -rf rh»'ir nvra-ra.-t-. Miiij the s«fn*tion <»f 
rnilis-lik'- rfniil in m:itn:n:irv :i'l«-nniii:ir:i 'viili-nre the partial 
[»r- -'Tvitliin of t'linr-tion i>y rin- i-»-I;-. Tin- L'"»"n«-r:il ht^alth maybe 
nniiiV'ir.iJil/ in{iii«'n«-«''l bv aili-nnmata of rl.o miii'on> surlacf* in 
.-. iii-:ifi'i«'nii- 'it* *b»'ir inr.'r?"'-r'-ii'-»- with nunnal f jn*-ti«*ns i>r in con- 
-'■.,M»ii !' -i-'"'i:nl:irv !ii«-*T:irinn :jn<l ln-soorrba-.^*'. 


Definition. Ilf •••nn '-ar in'.n.M ..r 'an'^T may beapplie*! to 

'.i.iM.i-. M « 'I'l-li ■■iiiTfi«!!:il pp.iil'-r.'iti'iii- in rlii- form of s«iliil bliM'ks 
,r ..«i»M!i- 'i'- In f|i«- I'.ri;. ot" :ir'. |ii«:ii ;n-ini, -•■paniriil by mon- **v b-ss 
•...i.u-. li ■ •i-.ii«-. pp -« lit rinTii-. 1-.'-. rh" '-jiirh'Tlial prolifonition 
-i.o-«''i._r I -..ririi.,,! Ui t<u\x*\ iM-.'.ii-l iiiirmal anatomic limitji. 
,'■ ^ ■.•ir...,,r ! ■ IliVn 'li^ fo #ori-^ri!T ;i ibrinition that will Iw 
ifii-- ■• ,ii.- i»,.,iii- »!,!«. S«,tii*- \\A\'r p'/anb-tl riie trn«lenoy of the 
•»'»b«-'-il j»»-.i* !«ri!if,Ti ?i, bnuk rfiroii.rb tlir normal limits and 




extend beyond the confines of the epklieliiil structun^'S from whirh 
it rises, as the important fnndiiniontal element of eairinoma. 
Others have hehl that there is a peeuh'ar atypieal oliaraet4:*r in the 
epitJielial cells tlicniselve^s sliown l)y irrcji^nlar cell-division, hyper- 
chroma tosis, and otiicr features. The older authors lielieved that 
[Mplymorphisni ami rertaiii irrcgnlarities of cell-( ontonr snttiee to 
♦listinguish car<*inon)a-eeIls from normal cells or those of other 
tumors : hot this polymorph is tn is now recotrnizcd to he the result 
entirely of compression in the growth of the tumor, and to be 
therefore accidental. Some have believed that tlie term car- 
cinoma should inelndc all epithelial tnmors g'iving rise to metas- 
tasis, but this ncccssiirily restricts tlie term too frreally t>n tlxe one 
hand, and, on the otiier hand, incluflcs ciTtain tumors probably 
purely adenomatous, I pn^fer to regard as caiviuoma any 
epitlielial growth atypically reproduciug certain glau<lular or 
other structures and showing a manitest tendency to irregular 

Stiology.^ — The causes and nature of carcinoma are still 
obseui'c. A number of theories liave been offered. These have 
been referred to in the tliscussion of tlie etii dtigy of tmnoi-s in 
•nemL A l>rief ret *insidcratiou tnay be useful in this place. 
(a) Congemtal Theory. — The theory of Cohnheim regarding the 
etiology of tumors iu general is less applicable to ciiuccr than to 
certain other growths. There ar*^ a few examples, h*»wevcr, which 
wfudd seem to prove that nrisphuxni epithelial cells undergo ear- 
ci nomat 011-5 pro Mferat ion ; Ibr example, there are eases of appar- 
ently primary carcinoma springing from bones whieli would seem 
to require this explanation. It is not always certain, however, 
that such cases are aettially jjrimary. They may represent metas- 
tases from small primary growths which have escaped noti<*c. 
The rarity of eareiuouiata in early life would seem to neg^Uive 
the congenital theory, and at all events wouhl show that otiier 
kiHuences of importance are recjuisite. Of late, a number of 
hypotheses that in a meiisure contain the idea of congenital 
origitj have been put forwanl to explain the formation of ear- 
cinotna. In these it has been assumed that there is some peculiar 
irregularity iu cell-mnltiplieation and a teudeney to iudetermiuate 
prolitcratiou supposed to originate in faulty development. These 
hypotlieses are vague an*l nneertain. 

(//) Traumatic Tbeory. — Clinicians are inclined to give great 
weight to this. A single traumatism profnibly has little import- 
ance, I hough women fref|ueutly state tliat they recall distinct 
injuries from which earcinomata of the breast have seemed to 
originate. It must l»e recalled tiiat such injuries are sustained by 
practically every woman, and the preseuee of earcinotna would 
readily lie attributed to a preceding hurt. In eases of epithe- 
lioraata of the lip iu pipe-sniokcrs, in the earcinomata of the 


«crr>tiiin and lim}>!9 in chimney-sweeps and paraffin-workers, and 
in cai«es of uterine careinomata following laceration of the cervix, 
the effect of chronic irritation would seem to be important. The 
frerjuent association of gall-stones with carcinoma of the gall- 
bladder has often been considered in the same light. 

fc) InfiMtioiis Theory. — The peculiar growth of cancer, its 
destnictiveness of the general health, and its metastasis readily 
Hiiggest an infective origin. Bacteriologists sought to isolate micro- 
organi-^ms without success ; later investigators have turned their 
attention to low forms of animal life, protozoa. (For further dis- 
cus<«ion, see p. 138.) A few successful experiments have been 
made at implantation from man to animals, or from one animal 
to another ; but as Hanau, one of the few successful exj>erimenters 
in this work, himself states, these experiments do not prove infect- 
iousness. The secondary growths in the second animal may be 
simply of the nature of metastasis, due to implantation of the 
i^ancer-cells followefl by their proliferation. 

A renewal of activity in the study of the etiology of cancer 
during recent years, and with all the advantages of modern 
rnetlKxls, has thus far led to no positive result. Statistical evidence, 
the probable cases of accidental infection in surgeons and others, 
the more or less suggestive results of experimental inoculation, 
and the distribution of cancer — lend some probability to the 
infectious thef>ry, but it must be confessed that the evidence is far 
from {Mwitive. 

Anionj^ vegetable organisms to which etiologic significance has 
been attributed are the blastomycetes, which some investigators 
(;laim to have found in every cancerous growth examined, and the 
assnriKMl irnporUuice of which is further based upon the results 
of experimental infections with cultures of the organisms. The 
invariai)le occurrence of blastomycetes has, however, been disproved, 
and the e\j)(»ri mental lesions are not really analogous with 

(al) Tumor-dyscrasia. — This indefinite term is supposed to indi- 
cate that certain peculiarities of the liquids of the l)ody occasion 
the tendency to cancerous growth. Xo proof of the existence of 
any <lefinit(; dyscrasia has ever been furnished, though it is not 
unlikely that some form of disposition to this jrrowth acts as the 
|)re(lisposii)g cause, (»ven if traumatism, infection, or other factors, 
are the immediate cause. 

Age plays an important part in the formation of carcinoma, 
as this tumor is essentially one of advanee<l years. Among 275 
cases collected by Lubarsch, ofj.O per cent, occurred between the 
ages of forty-five and sixty-five. There were a few instances in 
childhood and early life. Between fourteen and nineteen there 
were 1.4() |)er cent.; between twenty and twenty-five, 1.8 jier 
cent.; between twenty-six and twenty-nine, 1.1 per cent. The 



frequency in later life was fornierly aserihed to some altemtion in 
the vitality of tlir epitlielial eolls» rcticlcrini; iheiTi more lial>le to 
abnormal prolifenition. Tlir n^iture anil cause of sueli alteration, 
ho\^evei\ remain of»seiire anil ther>retieal, tlnnj^h tliere is certainly 
a greater tendeney to eaneer-frrowtli us a^e inerea^es. 

Heredity was formerly regarded as of great impLirtance, Cer* 
tainly in t?ome eases there seems to be hereditary transmission of 
the tentlency to develop eareinoma. 

Appearance, — Cart^inomata differ coni^iderably in ap|K'arance 
in different parts of the body. Those of the surfaces present 
themselves as more or less nodular, flat elevations. In the skin 
the nodules may remain hani and rather smooth, or they may 
soften upon the surface, fljrming nnsightly ulcerations. In the 
mucous membranes th<' growths are mrtre freqtiently siift and poly- 
pe »id or eanliHower-exereseenees (Fig. fi7). Ulceration may occur 

Fl». 67.— Caftltiouia nf ihc duodenal paplUa (raodlflcd Ttom Kiutt and Runipel). 

on tlie surface of such elevations, or from the fir^t the tumor may 
be of nkerative eharaeter, causing spreading excavations limited 
by tliickened projecting edges, Carciiionuila of the giantlnlar 
orgaas form more or less nodular tumors or irn*gular infi It rations. 
These varv greatly in cnusistcney, s(jme being almost .^tituy hard, 
others soil in ('onsec(uence nf tlieir ]u*cpunderaiijig cellular eliar- 
ncter of secomlary degeneratitms. Du brctiou the tniiior is found 
to Ix? white or grayisli in culor, generally somewhat tnnislueent 
and glistening; milky liquid may cxize from the surface. ^**'P~ 
tit dt*- formation is rarely seen, though in occasional instances tfie 
normal connective tissue of the organ is pressed outward by the 
growth of the tumor, au<! thus forms an imjierfect capsule. The 
primary growth is generally solitary. Oceasiunally instances are 
oliserved in wliich two separate masses develop .simultaneously and 



apiKirenlly intlejH'ntk'iit nf riieh other: a.s in the two breasts. 
Mi)re frequontly iipjKirent multiplicity is caused by tlie early apjn^ar- 
ance and rapid ^rovvtli of metastases. 

Secondan' careiiif^mata are nodular in character and nearly 
always nioltiple. T!ie larger are often dislinetly encai>sulattHl. 
Centnil softening nr eontmetion «tf t'(mneetive tis*ne may give tlie 
surface t>f the uodiile an umbilicatetl ebameter (Fig. 68). The 
number varies greatly, fnun a few large or small nodules to innu- 
nieralde tulK^nde-like forms in f/etieral atrcinomattjgi^!. In some 
situations, as in bones, secondary cart*inoraa lias an infiltrating 

Fifi. iA.— MtrtAsUtirr tuidnlef of c«rdDoijia on tbe EtirfiU'e of the 1- 

Seats. — The situations in which earcinomata occur art xtry 
numerous ; they invariably arise from pre-existing rpitbetial 
structures* In the rare instances in wliich a presumably priimfT 
c^an-inoma has occurred in Ixme or other connective 
presumption is warranted tliat the tumor originated fkwn 
of epithelial tissue left by faulty development. Among the 
fluent plaec-s i if origin the 'most important are the uterus, tfcej 
the gnstro-inti'stinal tract, particularly the esophagus, pyknts^aiMl 
rectum, tiie mammar>' gland, the ovaries ; less frequently the It^g 
kidney, thyroid gland, pnj^tate, or testicle may he the -^ — '^ — 
point, Secondary earcinomata curiously do not often I ^ 
in which the primarv^ growth is frt^juent. Of the i 
of siiondan' careimwiiii, the lympliatie glands, the Urrr. i , 
Imig^, heart, and serous membnines are the nic^l iinpcjflMit. Si 
oiulary cjirciufima of the l>«jncs is Miecially frequent after cmwi 
of the breast nr the thvrrmJ gland. 

Structure. — The hii»tiflog>^ of carcinoma varies grt^tly 



fcrent situations awl in (liferent ftirins. Thore are two distinct 
elements involvt'4 — viz., ^J^^ith€4iai valh iuid a t'onnective-tif^sne 
stroma. The epithelial eells are [iiedium-isized or large, and have a 
rather largo and elear nueleus ; tiie sliape nf the eivll, however, differs 
\v id ely . I n e|) i 1 1 1 1 ' I i u 11 1 at a t ) t" t h e s Iv i n t lie ee 1 1 s a r e la r ge a iid u sua 1 1 y 
of a squamous variety. In eareiuomata of mueous membranes they 
are more often cylindritMi (ireuluinnar,and there is a tendency to the 
formation of euhoidul or jiolyhedral epithelinm. The last-named 
forms are habitually present in the eaneers ctf glandular organs. 
The mutual eompression exercised may occasion a polymorphous 
character, and the older writers wrcingly regardtnl thiB as a feature 
hv which a carcinoma-cell con Id he reeogniztrd as such. Secondary 
change^ may oet^asiun wide variations in the ap|>earance of the cells ; 
thus the epithelia of cancers of the akin tend to become arranged in 

Flo. 6M.— EpftbeUomji nfskin. ^howitig couceotrlc arrHngcmeiU aud dei^ncmtlon of oellA. 

Concentric whorls an<l at the «ujie time to become somewhat 
glistening from Imrny tmnsfnrmation (Fig- 61*). The nnelens 
may be clear and f|uite atruetureless, or may show a distinct 
nneleolus and a definite chromatin network. Karvokinetie fig- 
ures may be quite abnn<lant and are frec|iiently atypieal. Degen- 
erative changes (dropsical iiitiltration, myxi*oiatous change, fatty 
degeneration) may alter the nucleus as well as t!ie ImhIv 4»f the 

The epithelial cells are usually grouped as cylindrieal and 


lirimchiiig i»r anastoiiin.siii^ CHjloimi-i, ot as irregular tuliular forma- 
tions, the tubules being of varying lengths. Tbt* explanation of 
the struetnre of the columns or tubule.s is that they are f(>nneil by 
tlie exteu,sion of the musses of proliferated cancer cell? along the 
lymplj channels mid spaces of the tissue. Very often the section 
shows all the tul>ules cut tmusversely, and thus the appearance of 
glandular acini is given» In some cases the tubules are short ;uid 
aeinuB-like ; as a rule, however, the appeamnee is only due to the 
mjinner of Bcetion. The acini differ strikingly from those of 
ad en on i a in si lo w i ng 8e v e ra I or ma ny I ay e rs < >f w 1 1 s i n stead of on e, 
and tliere is the further ditlereiice that cellular outgrowths may be 
seen at the periphery of tlie aeiiii.the cells Iiaving broken through 


tliC retaining wall (basement-mend >rane) and prolifenitcil outside 
to form new ehmips (Fig, 70). On examination of the epitlielia 
within the acini it is found that those of the peripheral layer 
frequently retain the columnar character seen in theuomud alveoli 
of the gland from which the tumor springs. The connective- 
tissue etrfjmaof carcinoma is more or less dense, but practically is 
always of fibrous clmractcr. It is arranged in such manner its 
to form lioilowcd s|Miees or eolmiins in which the epithelial stnu-- 
tun»s already descriljcd are embedded. Kecently attentiun has 
been K^\\VA to the fact, that elastic tissue is ibrmed in the sirH.*ma 
of the tumor in vrirving abundance. Frequently infiltniting 
leukocytes and plasmanvlls or niast'Cells are seen witinn the 
strotnn, and die latter also bears the vascular channels that supply 
the tunior. 

PHoanESsrvE tissue-cha noes. 


TliO altovt' clestTi])tioii a[>|>lie?? to the imlinarv carcinoma of 
*:l:mdiiltir oi-^iis. Sonic tlitlcrcnoe \h ohservahlc in tlie cancers n[' 
the skill and otiicr external surfmces. In tlie^c the stnicture i8 
rather that of nil trh cnlarsfed im|iil lie penetnitin^' int(» the deeper 
tissues?. The cells in their tnirly staples are similar to tho&e of the 
deeper layers of tlic^ skin, arc lar^rcr than tho,se fd' crlandular (*an- 
eers, and more translucent. Snbseqiieiitly the cells tend to l)ecoTne 
uf tlic sfpiuniou.s type and nndcrgu more or less horny change. 
Hollow alveoli and acini are nn usual in cancers of the skin, 
tlion^xh such gtructnn^s may occur in mme eases. 

Degenerative Changfes.— Carcinoma ta are quite prone to 
de|^eneraticais» In nearly all cases in which the tumor liu:^ reached 
e^:jnsideral>lc size more m* less fatty tlcgcncration Mf the cells 
becomes apparent. Preceding this or associated with it may be 
cloudy swelling or ilropsical inliltratimi of t!m trells, iviiderin^jj the 
nuclear outline less distimit and s<unetimes causing vaeuolations. 
Irregular and multiform nucli-ar degenemii^ms are met with, and 
prt*baldy occasion some at least of the structures known as para- 
sites of cancer. The cpitlicliomata nf the skin arc particnlarly 
prone to a horny transf<trmation, this occurring first and most 
prominently in tlie concentric wliorls already described. lu the 
adenocarcinomata of the ovaries and other genital organs of women 
the degenerated epithelial cells frecpu^ntlv undergo calcareous iufll- 
tnition, and psmnmomata arc thus formctk Colloid degeneration 
of the epithelial cells is a rare event, ant 1 the term colloid cancer is 
generally a misuomer, the real degeneration in most of tliese being 
myxomatous, affecting the connective tissue principally* though 
the epithelial cells are to a certain extent involved. Coniplctc 
degeneration hy myxomatous or associated myxomatous and fatty 
change niaydestn*y all of the characteristics of the original tumor. 
In mmc cases cystic transformation occurs in organs the seat of 
cancer, or in the cancer itself. This may l)e due to (x;clusi<ju and 
Bubsequent dilatation of the ducts of the orgiui or of the acini in 
the tumor, the cystic spaces becoming tilled with mucoid or 
gelatinous material. In some instances cystic can^iuoniata are 
secondant^ developments originating in cystic adenomata. Hyalin- 
change and pigmentation are rare in cani-er. 

luflammatnry processes are ([uite common. Cancers on free 
sui*faees are proue in undergo ulceration in eonsecpieuce of irrita- 
tion and infection. Aninng the nnVpi-organisms discovered in 
such instances the staphylococcus and streptoccx'cus are conspicn- 
OUfi. A distinct erysii>elatous inflammation may ix^cnr io cancers 
88* in other structures. Invasion of tubercledjacilli and the 
dejKjsit of nxiliary tubercles in carcinoma arc rare events, tlmugh 
they sometimes occur. Associations of carcinoma auil tuberculosis 
or syphilis may in other cases result from the seconilary growth 
of cancer in pren^xisting gummatous or other syphilitic lesions or 



la Iripii*. Prai*ri»ally all •?arv:Ln«>CLuini -tii.'W ^jm*t [•rak'>:yrio infil- 
trarii-«n. The amormc of this. fai>wev.rr. vari»-> orr»?atIy. 

Natnre. — ^'.'^rMiwaja L* trs^sentiaily mali;rniint. th«* dejrpei? *^f 
maii^^naoiy Jepeniiing, h»> wever, opoa the ?ejt am i iipoa oertain 
pei?uliaricies of the :ndivil:iaL S-merinitjs & small growth mav 
remain pracd'SilIv Lit«rQt t»>r a l«>ac time 'in*:! a«?i*iiien*al oircum- 
*tani>r!s. like traumatism. inten.*um?nt lii^ease. pr-^nanoy. or rhe 
like, 5timalate active gr»>wxh. 

<_ar^ia''rria exhibit* all the elemears "i sialUr^^ac^'y : the ten- 
•ir-ni*v :■. r^'-uraiirr prmoval. ui»-ta-tasis. aii«i ^.iiTnil dr:tt.n««rdtit»[i 
of the health. Rctriirreat^e aner removal is nii>?t iva-iily explaiaeil 
up«>a the a-rinrnptii-n that the rndre ^rp^Hth has n«>t been re- 
nii'Vei. \[:«r«'S4»'pi'' -t!j»iies sfai-w tliat the j.pra '.'f iaairrat:«»n is 
iL-iijally rani.-h :r^^ra^-r rhan thr nakel-^ye apj-earant.'e^ w.-cld in«ii- 
•^te. and this ♦rxplain-r why the suive«.'n oann».'C wdl remi-ve the 
whole dir^a-s^. Metastasis, as a nil^r. fallows the lymphatic ohan- 
n»rl-. an<l thus primarily involvr> the lymphatic glanvis in the 
n»^iirhr»rh«*-I ot" th*:- :iP>wth. The ppx'ess may b*^ rx plainer i as 
f .ll..u>: -«.rue rt thf '-■pirhelial Ctrl Is in rhtir ailvan-cin^r pp ^litV* ra- 
ti- ^n penetrate the lymphatic chann»:Is an«l art '.arriel in the 
lymph-rtream i** the n^trarest lymphatic gIan«L whrre th«:y a^ain 
pP'lifrrar- an-i r'-rm si•*>■n•lar^■ n«*iiues : rp?ni ::.•:<♦; a -iraihir 
extension i^vurs. antl trvt^ntiially wi.Uspread metastasis Prsults. 
Less nvi^ii^-ntiy the primar%- ijp^wth {.>fn«etnite< the walls "t a vein 
an^I metastasis irorurs thp.'iixh the circulari«'n. This is 'juite o>m- 
m^n in the oase "f «*an».^r* of the sti*maoh i-r :ntr-stia«rs. The 
metastatic vmyl fir^t sprta«l thp.Hi^h the pi-rtal cip -illation t*-* the 
liv.;r. In -till other instan^.'es j*;ci.*n«lari- gn.nvths pfsiiit fp^ra 
met?hiini' al transp^.^rtativn in thr ni»''vemeuts oi th«f t^Jy: thus 
in eap^inomata "f the aNl^minal "rrans the {vri^taltic m«ive- 
mt-nts may transi'-rr particles t*.* tli fit rent parts »•*" th^- ai-^k'niinal 

Patholo^c Physiology. — The c?iniral hralrh . f patir nt? suffer- 
ing with 'ripini'ma is afftr'tt^l v^ry pP'i'HUniiy. :h'V.i;;h the tu:in- 
n*T in whi-.h this ♦xviir? rt^niiiin- oi»5<'tiP:-. It w...-.:M ?<^m t»» be 
«'f th- niit'ir^ of a :<'Ximia. Emaoiitti'-ri a:i«l l-^ss ■ ■ ' ?tP:-nirth are 
habitual. th-rJirh •-■::«fii. lyrliaps, in Lir-jv par: rht r:si:l: ••f inter- 
f-p^n'-e ^virii •■r^'' fuucti«'ii-. a-r. rVr r xaiLi'lv, ::i ..up^iu'^nia y'^f 
tri- *r«'niL':« h. Pp-j:Prs>ivv anemia :-:ay make i:^ :ipr*arance. the 
p-*l •■■r]i- :**"■'> :-.1■«•nlin^: k->s abundan: an«i :;.-■ t,i:aut::y ot hemi>- 
;:i' I ' i ri r- 1 ! '. in:; * 1 --•; i • I-« i !y . Tl ■ * p: is •i^! la 1 ly ii r.;- ■• 1-. nut an lount of 
l'-';kt-.y:..-i-., th- lur^K- ni-'n-'nu-'lvar t'Tni> ir-.-r-a^ir.;; particularly. 
To'.v:inl th- ^n»l *'X lif- tri- ti-'r-'i'--b.-rr.;' ::• :i in'-PLav.s ::Piat!y, 
th'-jh the ►:X';p:«-n- pp-»li:«.ts --t* -^ may I'l--: : •. ::• rably in- 
• ■ rr-ii - -^ 1 : n r i ; '■' r x ■ ■ p.- : i ■- n ■? i n • ■« ■ ii -. * j iw n • ■-. • ■ :" ::i : 1 : ii :i •• : p.. • : lat ion ami 
inip-nV- 1 p-nal fTin«t:"n. At thi- -tairv :hv i-.vv.r/.iila::- n *A' such 
pp-i'i'-r- in til- ^I'-^l may I-:id :•• -'I'l'i^n «I'.a:h rp'-:r. ■ ^^nui *see 


AciJ-iiitoxiciiti*»n). HoniorrlmgiA^ aiicl ulcerations may also con- 
tribute to the iiiipairnit'iit uf liralth in eases of cancer. 

Varieties of Carcinoma. 

Thfrp are srveml forms of ram'i'r sufliriently different to re- 
quire sepiimte (leseriptiun. The elassifiration of these is generally 
baset] upon the eluiracter and'ment of the epithelium. We 
mav distinguish (1) (*areiiionuita ei^mposed 4if snrfa<'e-epithehijm, 
either (tt) sfjnamous or (A) eylindrieal, and (2) jLrhnididar canMncH 
mata, Itaving i4ther{^f) mure or less distinct adeiionKitons structure 
or (b) solid phiirs or eolunuis of *'pithelial cells, or (c) a mixture 
of acini and soliil columns. 


This form, wljieli consists of surface-epithelium, is of two 
varieties, tlir s^juajoMus and the cylindrical. 

Squamous epithelioma occurs in the skin or mucous mem- 
branes, wliert* s<piiiun>iis epithelium exists normally. Among the 
frequent seats are tlie lips, the esojiluifriis, the larynx, and tlie cer- 

Fto. 71.— Squ&motja cpiUieUotna, showlnjy wborls of t'piUiellal v.eUs with centra] ilegCQ- 
enitiofi <frniii a photograpli liy J^r, W, M, <jriiy), 

vix Uteri, Occasionally squamous epithelioma arises in |)arts nor- 
mally covered hy other kinds of e[iithelium ; as, for exarjiple, in 
tlie fundus of the uterus. In tliesc instances there is probably a 
primary metaplasia of the epithelium followed by carcinomatous 
• Ifrowth. Kven in eareinonnita of the breast some of the acini 
nay present metaplasia of the cells to the squamous type. 
k[uamous epitlicliomata present themseh'es as inMlukir, wart-like 
elevations of the skin or inucrais membrane* tending to become 
Itllccnited on the surfiice. Those of the nuieous surfaces are more 
^elevate<l and sot\cr. Histologically there arc seen Ijranching col- 



iioin.'^ o^ epitiioliul oells extcnJing dou award irnm tlu' jKipillm of 
tliL" skin into tht- derper stnR'tin\?j^. Tlie,se cuiislst uf large truus- 
lucent .squamoirs cf lis wliich bIiow a tendenfy to arrangt^ tlieni- 
selves in certain places concentrically to form epiihelial /mv7*x 
The latter frequently underjiri a lutrny transfurniiition and sonir- 
times even calccrons rlianc^e. (Fig* 71 K The same structures 
occasional I y occur in jiapillomatajuit much less frequently. Metas- 
tasis is frcfpumtly seen in the ncighl)i*rintf lymphatie glands, but 
the malignaiH-y is less marked than in glandular carcinon^ata. 

Some authors have described as a separate form skin cancers 
(^om|M)se*l of cuboidal or polvniorphons cells resembling those of 
tlic basid layer (Malpigliian layer) of the skin and their cmtirynnal 
equivalents. As a nuittcr of fact all chancel's of the r^kiu originate i 
imm these ccllsj and the special variety alluded t<» ditlers from the 
ortliiiary type only in the fact tiiat the cells du not become trans- 
formed, as hi the normal gn»wth of skin and in ^u^dinary e])ithelio- 
niata into squamous cells. 8uch ibrms originate from the hair 
tbllieles, sweut-glamls antl sebaceous glands, as well as from the 
basal layer of the epiderni* 

^•6. 72.— Cylinilric&l epUheilomji of the lubeRtlae (Ferlfl^ 

Cylindrical Epithelioma,— Tins form is composed of co- 
lumnar or cylindrical epithelium. It is frequent in the mucous 
membranes, especially in the gastro-intestinal tract and the uterus. 
The epithelial cells of the tubular glands or sometimes tboddi 
of the surfaces form the start ing-jwint of the growth* More' 
or less acu3Lu»-like tubular structures, conijio^iied of a layer of 



epithelial cells, or more frcquently of a number of layers of epi- 
thelia, the outer layer being ufteii distinetly uolntiiuur, eunstitiite the 
e ba me terijstie feature of the tumor (Fijj:. 72). fu th«^ luU'r stuges 
tlie acini beeome fiOed with prHliferaUMl u^nthelial eel Is f»f various 
sliapes autl tlie eylimirieal or tubular eliaraeter of the ueini is hrst, 
C'areinoinata of iUv kidney, liver, aud mammary gland, though nut 
originating i'rom surtaee-epithtdium, strietly speaking, mny br of 
the cylintlricai form, ( ylindrical epithehi»mata more ni-arly re- 
semble tilt* glanduhir careinoiuata iu their malignaney ajid general 
behavior thau tvc^uamyus variety. 

Glandular Carcinoma. 

This term includes the caret noniata that have a resemblaDce 
to raeemnHe glands in their histologic j^trueture. They consist 
of aeini or alve*jli 4"ontiiining epithelial cellrr, usually in several 
layers or completely filling the lumen, and a stnjnia of eonneetive 
tissue. Some authors ilistingiiisli three forms : the fihttplr, the 
medaUary^ and the schrhunti. These are sinjply variations of tlie 


Fio» 7S.— Medullary ciircinomn of breast 

[le tumor. In the simple form there is a comlunation of epi- 
thelium and stroma in about the proportion seen in normal glands. 
The tumor Is tlierefore neither strikingly hard n«u" soft. In the 
ine<hillary or soft carcinoma the amount of epithelium is excessive 
and tlic tumor lias a soft cliarai'tcr (Fig. 7rJ) ; while the scirrhous, 
or hard, cancer is an indurated form, due to excess of fibrous tissue 
and deficiency of the epithelium (Fig* 74), 

The glandular cancers are mure or less no<lidar or infiltrating 
growths varying in consistency in different cases, but having on 


section a glistenini^ white ct>lor with a certain amount of translu- 
ceiiey. Milky li(|ii!d exudes from the snrface on section. This 
is composed ni aibmninoiis floid containing degi*nerated epithe- 
lium and iree oil-dn ►plots. Among the seats in which these ibrms 
(lorur the mu^i im|x»rtant are the pylorns anfl other mucx>iis snr- 
luces, the mammary glan<l, the jmiirrea>» kidneys, ovaries, and 
testieh'S- WidcT^pread metastasis and other featurt^s of malignancy 
arc noted. In the case of the scirrhons form the primary tumor 

f'jf, 7< — s*cirrti*mB caneer of bremtt ( Warren). 

may be Btrikingty email in comparison with the amount of meta- 
i<tatic deposit* 

Colloid Cancer. 

This term h iiMiially a rniM)r»mer, as most of the coHoid cancers 
contain tvt colloid mati^rinl. Th*- mime gelailnon^ would be more 
appropriate, bat liax not \ti*i*n generally aeeeptetl. Colloid canoere 
are met with in the t^ti^mafh and inttstinal tract, in the mammaiy 
ghuiil, and in the ovari<*«, Thf tnnjor lias a peculiar tnmspjirent* 
i^list^^ning apiKaran**^. The entin* mass maybe uniformly jelly- 
like, or ordy jiortionH of it are alfected. Microscopittilly macoiis 
degonenition of lb** c/itinrvHive tissue as w^ell as of the epithelial 
cells Ik di«ov«*r*^l < Kit* Ih), In wnne eases no trace of c^rcinom- 
atouH tiy vembb*, thi* whole tumor having undcs*- 

goni* Aix urn*-?* tin* proriss involves the epithelitaa 

mtliir than \iw eiiwiM-<'t* vi' timme. ( 'olloid cancers frequently spread 
by direct ejctenhion, aiAil ibe HJtire alidominal cavitv raav wxtA 



filled with ^olatiTioiis material representing de;^enerated secondary 
growtlis. Oecasionatly the s;*nie kind of peritonesd growths seem 

L 7o.--" Collwid cancer" of tht? breiUit,sTu>wlnK tnyxoninlrtua ilmuigf in thir scromft&Dd 
filtty degeueratJott und i^urtiul dLsappvArancu uf the epithelitirt'eU^ (Perls). 

to originate primarily in the peritomiim, springing from fetal rem- 
nants of epitlielial tisstie {Fig. TH). 

Fig. TB,— Colloid carmur of the peritoneum uuodined from liirch-llinichfeld). 

Tnte eoliohl en n err' — that i.s, eareinoma with ^'olloid degenora- 
tirm of the epitlielinm — h sonietiine.s seen, tliongh it is very nxre. 
It rR'casionally eanses a i^ross iip|iea ranee r»'semh!ing that uf sar- 
comatous cylindroma, and the term rarriimmalom cylindroma has 
been applicxl. 




This term is applied to a form of tumor originating at the 
placental site during pregnancy or the puerperium. It has also 
been called deciduoma malignum, -sarcoma deciduocellulare, 



Fio. 77.— a. Fibrin, with numerous small round cells caught in the meshes : 6, cella 
resembling decidual cells, probably a proliferation of the Langhan's cells; d, protoplasmic 
masses containing large f^ee nuclei. 

destructive epithelial tumor of the placental site, and chorion- 

The tumor occurs as a hemorrhagic infiltrating growth, some- 
what resembling placentiil tissue in gross appearance, and fre- 
quently causes metastasis by breaking into the blood-vessels. The 
metastatic nodules are found in the external genitalia, frequently 
in the lungs, less often iu the liver, spleen, or other organs. The 
growth is rapid, the uterine wall being quickly invaded and met- 
astasis occurring iu a short time. 

The nature of this tumor is still the subject of some contro- 
versy. Two types of cellular elements are recognized in its struc- 
ture. One of these consists of irR'gular masses of protoplasm 
containing dark nuclei (syncytial tissue). The nuclei probably 
multiply by direct division. These protoplasmic masses are 
arranged in islands or in branching columns which form a network. 
In the meshes of this network are l)lood-spaeescontiiining thrombi 
or masses of l)l()od-corpuseles. Sometimes masses like those above 
(le.seribed are found within the blood-spaces. The second form of 
cells consists of smaller irregular-shaped elements, which are 
unusually rich in glycogen, and in which cell-division by karyo- 
kinesis is observed. These cells lie in masses, of greater or less 



81 ge, between and beside the larp^er prntoplasraic areas before 
describcH^I, In the later stiigt^s of the ^^rowtfi obtiterative throm- 
bosis of the vessels leads to nerrosis of the e*'lliil:ir eon.stituents, 
partieularly of the coliirims <^f lar^c epithelium-likr etOLs. These 
are eunverted into hoinuguneons librinous masses, and even the 
thronihi theniBelves may degenenite. The view of Marehanrl 
reganlin|!; the nature of these tumors is most wiilely aeceptcd. He 
holds that tlie lartr^'r eellsarederivativt^s of thi' syneytium (astriK*- 
ture rompjse^l of epithelial eells, prolmhly of ft-tal oritrin), while 
the smaller ei-lls are formed from the epithelial eoverrng of the 
chorion villi (Lan^hans's eells), Thetniiior, therefore, is epithelial 
in nature, and it lian malignant jin>perties. It ditflrs, however, 
from ordinary epithelioma and from earcinon^i in its peculiar 
structure antl in its eliniad course and disseminati<iiL 


Defimtion.^This term inelurles pathologic formations of 
varit^I eharaeten Some are true tumors; others are of quite dif- 
ferent nature. 

The term cyst is applied to patliologir^ formations consisting of 
a more or less well-defined wall and en<dosing liipiid or semiliquid 
contents of different character from the surromiding parts. This 
definition is not entirely appliet4bh\ as certain structures that do 
not present a definite capsule are stmietimes termed cysts. Ac- 
cortlingly we may itistinguish between (nw rifsta ami eyst-like 
formations or cifi^toklK^ the former being enclosed by a capsule 
lined with epitlielium or end<>thclium ; the latter merely present- 
ing a eircuniseribcd eullection of softened materiab 

Classification,— A eeonliiig U> the methtHl of formation, wc 
distinguish rrtention^eysts, scdtciiiitgHTsts, eysls due to the pres- 
ence of foreign Iwdies, and prf>lifenition-cysts. 

Betentioii- cysts are fnrmed when the exeretory ducts of a gland 
become occluded and the secretions aci!Umulat(* and cause disten- 
tion <>f the acini or t»f |>arts (d* tlie duct* Among such cysts may 
be nanuHl the distended sebaceous glamis of tlie skin in the ibrma- 
tions cjdled ircfia ; the cysts of the sidivary or small mucous 
glands or ducts under the tonguCj called /vf/i re/a?; retention-cysts 
formed In the uriniferous tubules, tlie tul>iite8 of the ovary, or in 
the parovarium, in the acini and tlu<'ts of the mamiuie, pauen^as, 
and other glands. An entire organ may bet'ome converted into a 
cyst, as in ciiscs of ilistcution of the kidney (hydi'oneplirosis) from 
obstnictton of the ureter. 

Tliese cysts an* distinguished by the fact that they have a dis- 
tinct connective-tissue wall lined with epithelium or endothelium. 
The c>ontent8 of the cyst depend upon the part in which the Ibrma- 
tion has taken plac<^* 



Softening-cysts occur in consequence of degenerative softening 
of normal or pathologic tissues. They are not rarely the result 
of hemorrhage, the blood-clot first becoming inspissated and then 
serous exudation occurring in the area of hemorrhage. Softening- 
cysts are very common in tumors of difierent kinds. 

Cysts due to foreign bodies are in part softening-cysts. The 
tissues in the immediate vicinity may be injured and undeigo 
necrotic soft;ening, while connective-tissue reaction produces a 
capsule. This form of cyst is most frequently the result of in- 
vasion of parasites, and the cyst-contents may be composed of 
the parasite or the parasite and tissue-elements more or less 

Proliferation-cysts. — This term is applied to formations more 
closely analogous to true tumors than those mentioned before. 
They merit more extended description than the other forms of 
cysts, and may be designated as epithelial cysts. 

Epithelial Cysts. 

Definition. — In certain glandular organs, notably the ovary 
and mammary gland, cystic formations occur which present strik- 
ing appearances ; and thougli perhaps they represent adenomatous 
or carcinomatous new growths, are so striking as to deserve special 

Fig. 78.— Papilliferous adenocystoma of the kidney (Karg and Schmorl). 

Btiology. — These growths, in part at least, result from ob- 
struction of excretory duct« and subsequent irritation by retained 
secretions. Congenital abnormalities of structure may possibly 
play a part in their causation. 

Appearance. — Cvstomata may be single or multiple, the 



entire tiiraor bi'inj>f fompo&cMl i^ither of a gintrlf ev\«it orof one larjj^e 
cyst subdivided into many ^smaller, or again of numerons .separate 
and uiiconnectol cysts uf varying sizo. On section the cystic 
cavities are found to contain more or Icsrt seroui? or .gelatinous 
liquid J and t^ometinu'S lieniorrhagic fluid is observed. Most fre- 
quently the liquid is tr<iIatinous or ro]iy, and is comiuonly sjjuken 
of as colloid material. Tlie inner lining of the cyst may be 
smooth, like a siTous or mucous Burface, or elevatetl irregularly in 
the form of polypoid out^^rowths into the cavity of the cyst. The 
entire cyst may thus l)e tilled with papillomatmis elevations from 
the epithelial lijiing. The term papifitftrouH or proiifn'tttirf 17/x/- 
omata h given to these forms (Fig. 7H). The tiize of cystomata 
varies from minute tumors not larger than a pea to enormous 
masses weigliint^ as much as sixty or eighty [jounrls. Si'condarv 
degenerations may m'eur in the form of softening, liemorrhage^ or 

Seats,— The manmiary glan<l and ovary are the principal 
Bituations in which tumors of this deserijvtiou are met with, but 
analogous growths may make tJieir aiqiearanee in any of the 
glandular organs. 

Structure* — M!en>sco|)ieally these grciwths present cystic 
eavities line<l with typical or mrKlitied c ulumnar epithclinm and a 
stroma or ivticulum of eonueetive tjssiu'. The auiotmt of the 
latter and the ap[>earauce of the cysts themselves vary in ditlcrcnt 
cases. At ti tues tlie stroma is very aliuutlant tunl takes tlie tbrui 
of weU-«>rgauized fibrous tissue, while the cysts and acini are small 
and few in muiiber, In these causes the apjx^a ranee snggests a 
primary prolitemtive connective-tissue j>ro(*ess with secomlary 
implication of the epitlieliul elements. Sueli eases (x^'ur particu- 
larly in the mammary gland, and there is difficulty in seiiarating 
them sharply Trt^m instances ot" chronic inter^jtitial mastitis or dii- 
fnse fibroma. In other instances the process numifestly begins 
with the formation of epitlielial acini, and the hyperpla.sia of 
the connective tissue is certiiirdy secondary. The acini in these 
cases present themselves as holh>w spaces of varying sliajie and 
size, often branching, and lined witii columnar epithelium in a 
single layer or sometimes with several layers of more 4)r less dif- 
ferent i a t eel cf ) 1 u uma r epithelium. 

Nature. ^ — These cystic growths often have a decided tendency 
to malignancy. They may remain benign thmugliout ; l>ut fre- 
quently they undergo carcinomatous change and spread widely or 
give rise to metastasis. The malignancy is generally in prop*»r- 
tion to the amount of the epithelial proiiferati«m and f>apilliferous 
change, but there are instances in wliieh metastasis occurs fn>m 
adenrK'VStomata having regular gland*acini lined with single layers 
of typical columnar cells. The cystonmta <*f the ovary not rarely 
extend to the surface of tlie organ, l)reak through the capsule, and 


present upon the surface as papillary growths, and frequently 
they extend to the peritoneum and neighboring structures. The 
entire alxlomen may be involved. At the same time, or in other 
cases independent of such direct extension, metastatic deposits 
may l>e seen in nearby lymphatic glands. Somewhat the same 
conditions may be observed in cystoma of the breast, but in this 
situation the tumor is much more frequently confined within the 
capsule of the organ. 


Definition. — The term teratoma is applie<l to tumors of pecu- 
liar mixcil character, representing different elements of complex 
tissues or structures in a situation in which these do not normally 
occur. For example, the most frequent form of teratoma contains 
various epidermal structures, such as hair, teeth, etc., and occurs 
in internal organs. 

Btiology. — The causation of teratoid tumors or teratomata is 
to Ix^ s^ju^ht in congenital misdevelopments. We may, with Klebs, 
distinguish enflogenouH forms, in which inclusions of superficial 
tissues are retained in internal |)arts by a pnx'css of constriction ; 
and fHf^/enouM forms, in which a separate fetal de[)osition is the 
origin of the tumor. The latter form represents a separate and 
ill-develoj>eil fetus within the develojKKl or^iusm—SL fcetus in foetn, 
A regular gradation may be traced fn)m distinct teratoid tumors 
having irregular mingling of tissue-elements, to malformations in 
whirli a more or l(»ss systematic outgrowth, somewhat approaching 
double monstrosities, (K'curs. Of the distinct teratoid tumors the 
most fn»quent is the dermoid cyst. 

Dermoid Cyst. 

This tumor |)res<Mits itself as a cystic formation with a con- 
ne<*tive-tissue membrane and an inner lining resembling the skin. 
This may present all the elements of the skin, such as stratified 
epidermic, a jxipillarv layer, and even subcutaneous connective 
tissue. Hair-follicles and sebaceous glands are frequent, and 
habitually long, light-colored hairs are found within the contents, 
and tietli may be found in the lining membrane or free in the 
content- of tl/e cyst. The cyst is filled with a semifluid, cheesy 
mass consisting of epithelial cells, fiitty matter, and other detritus. 
()ccasi«»nally dermoid cysts may contain nerve-tissue, muscle, 
thyroiil ii>-iu', (►r structures resembling intestine. 

The dermoid cysts vary in size from minute bodies no larger 
than a jK-a to huge masses, the latter being most frequent in the 
ovaries. Amrmg the situations in which dermoids occur the 
ovaries are most common ; less frequently they are found in the 
testicles, in the peritoneum, in the membranes of the brain, about 
the eye, in the neck, fi(K)r of the mouth, and elsewhere. Growth 
i« very slow, and they may remain practically latent through life. 



Theniitiiro of iIk^s** tiirnors i,s tisiially benign, though carcmom- 
atoiiR change may occur, anfl in thi* (* varies cystoma is prone to 
. be asfiociate<l, and the latter may hi- malignant. 

Other Teratoid Tumors. 

NofUihir nmsseja may apjitiir ahont tlie head or neck or in vari- 
ous parts of the body, consisting of mingleil tissues of various 
kinds, such as glandular tissues, eonnit'tive tissues^ nerve» mus- 
cle, etc. These can he i-lnsr^iticd ns tenitoid growths. Sometimes 
they resemble some definite organ, as in t!ic ease of growths 
appearing at th<' umbiliejis nf tlie new-born and simuhiting the 
structure i»f normal intestine. 

In the neek there are Hinietimes seen more or less cystic 
grf>wths lined witli epithelinm aud having in their walls miisele- 
fibers, lymplmid tissue, cartilage, etc. These growtlis probably 
sjiring from remnants of the endjrvonal branchial clefts, 7^he 
mixed tumors of tlic piirotid gland (see Sarcoma) are allied to these. 

Plfi. 79. — rtioleBtoatoinii rrom thf ni«iiibranfB of tlir hmin. 

Cholesteatoma. — Thi.s tumor ischamcterized by glistening, whit- 
ish, »»r jjearly luwbcs eompt»sed of concentric layers of cells resem- 
bling epithelium (Fig. 7JI). Sometimes crystals <>f eholestcrin are 
fountl in the cent<'r nf these bodii s, whence the name choleS' 
t^atoma. (Iiolcstcatomata aiv f*iuji*l in the membranis or sub- 
stance of the brain, and present tiii^msclves as single or nmltiple 
nodulcg. They arc usually soft and glist*'uiiig in appearanee, 
8om«' authors consider them end*itheliimmta, but Ziegler hag 
fomid bair-folliehs arul luiirs in certain speeinitns, and from this, 
as well as iroio tlic horny change to winch t!ic cells in the pearly 
hodies are prone, classifies them among the teratcpid growtlis. 
Thev probably originate in ectodermal fetal inclusions or rests. 

Somcwhat'similar tinnors ocenr in the pelvis of the kidneys^ in 
the testicles, parotid glands, ovaries, and noddle or extcrnnl car. 




History. — Although for many centuries there had existed the 
idea that disease and decay are due to the action of minute or- 
ganisms, it was not until the use of the lens enabled the Dutch 
naturalist Leeuwenhoeck actually to demonstrate their presence in 
water and in human intestinal contents that the h>7)othe3is of a 
" contagium vivum " l>ecame more than mere guesswork. He 
discovered, even with his imperfect instruments, short rods, curved 
and straight, and describe<l their motility. Muller (1785), by the 
use of the compound microscope, attempted a more systematic 
classification of these micro-organisms, and from that time many 
investigators liave added much to our knowledge of microbes, 
that gniup of organisms which had been denominated by Linmeus 
by the term Chaos. To the German Henle is due the credit of 
having first intnxluced an idea of order into this disorder. He 
held that fermentation was the result of organic life, and that the 
action of a contagium was analogous to that of a ferment. The 
earliest systematic <'xp(*ri mental work was that of Pasteur, in 
which Ik* <.stablishe<l beyond doubt this relation between fermenta- 
tion and the life and development of bacteria. The first definite 
idf-as of th(? physiol(»gj' of these micro-organisms are found in his 
experimfiit.s on lactic-acid fermentation, and the j>athogenesis of 
niirrfwirgaiiisms was established by his demonstration of the 
etiology of the silkworm-<lis<'ase (1869). Davaine and Rayer 
fiU)fit the s'lrn^ time Chtablished the causal relation of a bacillus 
foTind in \\\f- \)\<y*A of a sheep dead of anthrax to that disease. 


V^ri/n^ ^iichizr)niy(*etes, or cleft fungi) is the name given to a 
bfar>/ r» '»( i\if' hiwe-it and simplest of the orders of the v^:etable 
kluy'\',(ft, 'Jb'-y are small, unicellular organisms, generally free 
'/j ' r»,^r.pri/II, find colorless; they possess a cell-membrane albu- 
j/»i ;*'/.'] Hi rounffr^.U\(tu and homogeneous protoplasmic cell-contents. 
^fift* •.;;ri''t.<-^ art- iiiotih*. Nu<;l(?i are absent, though in the opin- 
ion hi ^fth* »h«r whole IkkIv mav be regarded as a nucleus. Bac- 
t/'ria iii'.i^\y\y \r/ c<'ll-<livisioii, s(?xual distinctions being absent 
In tuiiW; j-j/<' i'-s-. n-i-i-tant i'ornis — six)res — occur. 

'1'1j<' »rJiijj/J' iUuit'uUwy forms that (xjcur are of three kinds: 
the ^AM-rMt^j \iit l/;i/'illiir, ;in(l the spirillum (Fig. 80). 

Coccui^, Thi.^. in. a Hplxrical cell, varying in size up to 1 /u in 
diariM'tt^r. li lafe**', iIm* anilin-stains readily. Spore-formation 
and uu^iWiy aiv mr*-. When tho cocci are found in groups, the 



mclivuluals Ijeing eiitirely separate, they are termed staph ylot^cci, 
frnm the n^semlilance of tlie groups to a hunch of gnipes ; wlien 
' in pairs, diplm-ooci ; wlieo in eliains, strcptocoeci ; when in groups 
of four, tetnidj^, ut memraopedia ; when in packets, sarcina?. 

ml U 3^ 

Fna, 80.— ViMifrtM formi of bnfftcHa : 1 diif! 2. rnrnid anil oval microi-cwa : % <ltp!r>cf>pci ; 
\ 4, totmeoLci, or tHmrls; '». i*trf ptoru^^ci ; 6. tutcIUi ; 7, bacilli in vbaitia, the lowtr showing^ 
l#|K»n^-formatkm: », bacilli ahuwiriB sporeii, forming dry niatickB and clostndiii; « and 10, 
fipinlla; H, BfijrueheUe. 

BacilluSp— A n id-shaped, eylinilriral eell of varying length 
and tliiekneRs. Spore-formation ami motility are eonimon* Most 
of the group stain easily with the aiiiliii tlyes, hut some require 
special metliods of staining, 

Spirillmil. — X eylimlrieal, rwUshaped cell, curved or spiral, 
sometimes motile. It stiiins readily. 

Many other classifications, all of them being to a certain extent arti* 
ficial, have been made by different aatlion*. Probably one of the most 
ifal and actentifie in tliat of Migula: 

L CoQcaceffi* — Spherical cells dividing in one, two, or thre^ directionB. 
Endosporet* rare. 
L Sirepi4>coccm.—\MvMciu in one direction, the individuals cohering 
to form chain?*. Motility absent. 

2. Mierococcus, — Division in two directioiia, the individuals whea 

coherent forming groujiM of four. F lamella absent. 

3. Sarcina, — Division in tliree directions, fonning packets of eight, 

twenty -aeven, or more cells. Motility abisent 

4. PfanoefHjcitii, — Division in two directions, as in the micrococcas. 

Motility present, 

5. Pfanosarcina. — As the sarcina. Motility present, 

II* BacteriacesB,— Rod-like, cylindrical cellB, dividing at right angles to 
the long axis. 

1. Baderium, — Cells without tlagella^ often with spore«. 

2. BaciUm.—Celh with peritrichous fla^ella, often with spores. 

3. /V^wffo'W«>«aJ^.— <]Iells with pobir H age 11 a; spores rare, 

HI. SpirillaceaB.^Cells eyliiulrical, curved, bent, or spiral. Division as 
in IL 
i. SiHrftmm/t.*'—C^]h ripd, without flaj::ella, 

2, MietOJtpirtL — Cell** rigid, with one, rarely two or three, polar tJagella, 

3, ♦Wn7/«/«,— Cells rig^id, with five to twenty polar Jhigella, 

4, Spirochcta.—CGlh tlexible, motile, but without liagella: perhaps 

possessing an undulating membrane. 
IV. ChlamydohacteriaceEB. — Cell?* united in a simple unbranched fila- 
ment, Divitiion in one direction. Forms non-motile; conidia. 

1, Stre/jfothrijr, — Cells united in a simple unbranched filament. 

Division in one direction, P'orms non-motile; conidia. 

2, C/adothrix. — Cells uniti^l in a filament, with a false branehing. 

3, Crenothrix. — Cells united in an unbranched filamentj and dividing 
in three directions into small rounded cells. 


4. Phragmodwthriz. — Cells at first united in an unbranched filament, 

and dividing in three directions. Later the separate cells break 
through the thin membrane and grow out as branches. 

5. Thiofhrix. — Cells united in an unbranched filament contained in a 

thin membrane. Division in one direction. Cells contain gran- 
ules of sulphur. 

V. Beggiatoacese. — Cells united in a filament without sheath. Motile, the 
movement being due to an undulating membrane. 


Cell-contents. — The body of the organism in unstained con- 
ditions ap]>ears as a perfe<.'tly homogeneous protoplasmic mass. On 
staining with anil in dyes a granular appearance is often observed, 
which under high powers is resolved into a hyaline mass contain- 
ing numerous chromophilic granules. Vacuolations also are often 
present. Some modem observers (Butschli et al.) have made out a 
network immediately within the membrane and surrounding a 
central body which readily stains with the nuclear dyes. This 
latter they regard as a nucleus. Others, however, affirm that this 
ai)ix?a rauce is due to a concentration of the cell-protoplasm (endo- 
piasiu), the result of the rather complicated method of staining. 
The question of the i)resence or absence of a nucleus is still an 
o|)en one. In many organisms, as the Bacillus diphtherise from a 
blood-serum culture, for example, there exist certain transparent 
refractive bodies which stain differently from the rest of the 
microbe. These metachromatic lx)dies, as they are called, are 
regarded by Ernst as nuclear in character. Others look upon 
them as possibly the primary stiige of spore-formation. 

Spore. — The sjiore is a non-vegetative resistant form that the 
microbe assumes when the conditions for growth are unfavorable. 
The endoplasm seems to concentrate and bec<mie a small, oval, 
highly refrac'tive body, separat(*d from the bacterial protoplasm by 
a membrane of its own. It is generally of the same diameter or 
somewhat smaller tlian the l>acillus itself, and is situated either in 
the middle (equatorial) or at the end of the microbe (])olar sporej. 
It may be larger in diameter than the microbe and cause a swell- 
ing at that ])oint. When in the center of the ro<l this gives rise 
to the \\)V\\\ known as Clostridium ; when polar, to the so-called 
drumstiek-lbrm (as in the Bacillus tctani). 

Such intracellular spores <u* endospores occur among many 
bacilli. Among the micrococci they ar<' rare; but it is supposed 
that certain individual c(K*ci l)ccome larger and more refractive in 
appearance and assume the spore-state. These* are called artliro- 
ffponx. Whether these can l)e regarded as true spores is still 

The spore is extremely resistant to conditions to which the 
vegetative form readily succumbs ; to the action of certain chemi- 


cTil n^ageiits, liglitj licat^ etc. Bacteria that are grown on media 
fMKJT in nutrient material teml to become asporo^enotis, A rertatn 
tempemtnre is also iieeessarv for spore^formation. Thus, alth*ni|>:h 
tlie authrax Imciihis develops well at a temperature of 14*^' C\ 
(r)7° F.), it dtK'i^ not form s|)f»n^s lu'low 18^ V. (IH^ R). To obli- 
gate aerobes oxygen is ne*'essnrv fur their ilevelopoient, and anat3- 
robic eidtnres present them only in the absence of tliat gas. 
Placed under eoixditions faviiralde to its vegetation the i^porci loses 
its elij^rness, al>sorl»s water, and swells. A small ]>rominenre pre- 
sents at the side or end, whifli irnuliinlly lengthens and develops 
into a young bacillus. The niemliraue (»f this new niieTobe is 
formed iVom the inner layer of tlie s|jore-membrane (r;if7ox^>o/'^*i/?/*), 
while the f*uter layer {t.vfmjiorium) is east off. In not all of the 
varieties of bacilli docs sporulatit*n take place, and even where it 
does (jceiir there may, under certain conditions avS in growth at 
high temperatnres, arii^e niees which liave h)8t this piwer (aspo- 
R>geiious races). 

The spore dues nut stain readily witli the unlinary anilin 
stains, ami speeiai metlHHls have been devised fur euloring it. 

Cell-meiiibraiie. — Surroundingeaeli organism is a menibmne 
(e€toplai<m) denser am] mure highly refractive than the eell-eun- 
lenta (endffp/asm). In sunie thin is not to be dilbrentiated 
from the cndoplasm ; hut in others it is larger, and imxler certain 
conditifuis beeoines a gehitinous mass. In this ease it is easily 
seen, especially after apjin^priate staining. This is eddied the 
cajmih'. Ill gene ml this ocelli's oidy when the bacteria develop 
within the animal orgtuiism, and not ii|K>n artificial eidturc-mcflia. 
It is pr*)bable that the eetuplasm is not a mere protective envelop, 
but iias to do with the fimetional activity <*f the ba<'teriuni. The 
fact that tlie Hagclla, to which is due the motility of eertain mi- 
crobeSj are directly continuous with and are simply prf)longations 
of this membrane, points to this view. 

1'he cell-nienil>rane is not easily cohered by ordinary methods. 

Flagella, — ^lotibty is often a (intperty of bacteria. It is 
manifested in dilfcrcnt ways, and is often ivharacteristic of the 
several varieties of liaetcria. Some move slowly forward across 
the Held, others with great nipidity ; othei^ again dart hither and 
thither, slowly or m quickly as to be with difficulty obs<U'ved, 
Tliey may at the sime time have a rotaiy movement around their 
long or their short axes* 

After appropriate staining the cause of this motility is seen to 
be the presen<'c of slender, wliijHlikc |irolongations, originating 
directly fmin the ectojilasm (Biibes). Tliey may be twenty times 
as long as the hotly of tlie bacterium, and are arranged in tlie dif- 
ferent species in flitferent Avays, I^acteria that jiossess no flagella 
are termed (Tymnubacteria ; those that have these organs, 
Triehobacteria. There may be Imt unc Hagellum, situated at the 



pole (monotrk'hous)^ or a number may be present {hphotrichotts). 
When they are situated at botli poles the microbe h termed amphi- 
irichou^ ; when distrilnited over the %vIiole luxly of the bacteria, 
perifnelmm. The preseiiee tind the aetivity cif Hagelhi depend on 
many faetors : on the eomlition of the meilium, baeteria grown from 
litpiid me<lia being more active than those fnmi ^5olid ; on tem- 
perature ; on prf.':fenee of air ; on light ; and on the age of tlie 
eoltore. They are easily broken off from the microbe, aod care 
mnst he rised in staining them. A speeial method is employed. 

Involution-forms. — Ify invohition-form is meant the irrc^g- 
ular appea ranee a mierobe often assunjes when its eotiflitions of 

i growth are unfavorable, Nnmerout^ baeteria melt together and 
)ecome irregolar chains, or they apjjear pear- or club-shaped. 
The protoplasm becomes retracted and irrt^gidar staining takes 
place. Sometimes the miemijes lose all ehanieteristic appearances. 
Sometimes forms with l>ranehing projections are diBcovered. 
Tiiesc have often lieen ilcscril>ed as in volution- forms, but are now 
more commonly reg:»rded as normal, tbougfi unusual, stnietnres. 
This appbes to tuljcrcle Imcilli, diphtheria bacilli^ and some 
others. This true bmnehing{diehotomy) must not be confomided 
with false or pseudodiehotomy, due to niere apjKisition of si'jtamte 
organisms, as seen in various bacilli, streptococci, cte., and habitu- 
allv in the eladoth rices. 

Chemistry. — The bacterial cells are of variable t^omposition, 
depending to a great extent up^m the kind of nutrient matter. It 
consists mainly of water (85 per cent.). The i-hief solid material 
is albumin. This varies according to the medium of growth, und 
has t)een given the general name of mtivftproffin (Ncncki). Kat 
is also present. The nuelcin-bases, xanthin, guanin, adenin, and 
cellulose, have been found by some. Some eojitain certain color- 
ing-matters, baeteriopurpurin and a green substance similar to 
chk»ro|jliyll. Organic acids and ferments of differt^ut kinds are 
also found, Tn some special forms— the sulphur bacteria — sul- 
phur is present. 


Bacteria may be divided intf> two great classes : those that 
live only on dead orgjinic matter are termed HaprophyieH ; those 
that develo]» in and at t!ie cx])ense of the living organism, para- 
mle^. These hitter l>y their growth cause certain pathologic con- 
ditions in the host, and are called ]Tathogenie, By obf if/ate sapro- 
phytes or parasites we mean those that can exist only under the 
conditions named ; by /oerf^M/Zcf saprophytes ami parasites, those 
that can develop under both conditions. 

Conditions of Growth.^ — <\rtain surrounding conditions 
are necessary to bacteria, and any jnarked ehaugc in them will 
inhibit the growth or totally desti*oy it. 



Mechanical Conditioiis, — A slight shaking of a liquid culture 
ficemti to help the devi-Iopoient of baot4:Tia, while a more violent 
and long-eon tinned agitation, destroys theni. 

PliyBical Ooiiditiona* — Eiectrical cufrrentn destroy the grt^wth, 
but probuhly by the action of certain products of the eleetrolvsis, 
and not by direct action. 

Light. — Diffused daylight inhibits tlie growth of bacteria: sun- 
light and, to a less extent, electric light dcBtroy them. 

Hmi.' — A certain temperature is oeccRsary, the degree varying 
with the species of microbe. Most of the Nvater bacteria and sapro- 

Ehvtes grow between O*" and ZQ"* C (32'" and m"" FX the optimum 
eing 15^-20° C {59^^68^ F,) (Psvchrophilic). The pathogenic 
flourish between 10^ and 45° C (50^-113° F.), best at the 
body-temperature, 37° (98.6^^ F,) (Mesophilic). There are some 
that develop well ut 40°-70^ C (104^-158^ R) (ThermopbilicV 
AlKJve these limits the members of the several ^oups are killed, 
and each Ijacterium has its own thorniic death-point. That of 
most of the pathogenic varieties lies between 50*^ and 60'^ C. 
(1 22° and 140° F.). Below the lower limit the growth is inhibited 
only ; ver\' low temperatures (- 250° C. ; —418° F.) having been 
used without preventing the future development of the niicmbe. 

Spores are extremely resistant to higher temperatures. While 
no bacterium can live after exposure to UX>° (\ <212° F.), the 
ispores of some of the eartli microbes are killed only after exposure 
for an hour to stiram heated to 115° C\ (239° F.)/ 

Chemical Conditioiis.— The essential substances for the growth 
of bacteria arc water, carbon, nitrogen and oxygen, an<l certain 
salts. For the carbon^ they require already prepared carbon com- 
pounds, as the sugai-s^ glucose, saccharose, laetcisey etc., maunite, 
glycerin — in fact, mf>st of such as arc* soluble in water. Most of 
the protoids ami many simpler substances, even such as ammonium 
carbonate, furnisli the nitrogen. Free oxygen is necessary for 
many microb*^s. Those lor whi^di this is absolutely required are 
termed obligate aerobic. Facultative aerobes are those that grow 
best in the presence of oxygen, but mny develop in its absence. 
Anaerobic microbes are those that grow best without oxygen and 
are also obligate and facultative. It has been found jwssible to 
pnjduce races which, altbough naturally obligate anaerobic, 
develop also in an atmosphere of oxygen* 


The study of the substances that result from the action of the 
life of bacteria and the changes that they prrMluce in their various 
media of growth is really a branch of organic chemistry. The 
function of bacteria is essentially a destructive one. They split 
ap the higher nitrogenous and non-nit rogeuous compounds into 
simpler substances. 


The various .substances that are found in the njedia of bacterial 
growth comprise : (1 ) tlie eoni|>onents of the bacterial cell proper, 
as the proteins ; (2) the secretions of the c<*ll, as tlie ferments and 
toxins ; and (3» substances that are the result of the action of 
microb(»s u|X)n the medium of growth. The toxic substances 
in bacterial cultures may be classified as (a) intracellular 
and (h) extracellular accorcling as they are contained within the 
bacterial cell or free in the culture medium. The extracellular 
substances may l>e purely products of bacterial secretion which 
have been separated from the cell, or tliey may l>e decomposition 
products derived from the culture medium. 

(1) The first group has already been spoken of (see page 214). 
The proteins may pr<Mluce suj)]>unition (pyogenic) or fever 

(pi/rof/cnic), or they may be the cause of an inflammatory pi'ocess 
( phlof/offoiic). Tlies<' subsUmccs are comparatively resistant to heat 
and are thus sharply distinguished from the ferments and toxins. 
The best kn(>wn examples are mallein, derive<l fnmi the bacillus 
of glanders, and tuberculin, from that of tuberculosis. These are 
pyrogeni<* wlien injected into animals suffering resi)ectively from 
glan<lers or tuberculosis, but have no, or at least verv' slight, effect 
uj)ou healthy subjects. Other ])roteins are shown to have similar 
effects on tul)erculous animals, l)ut not in the minimal doses which 
suffice when tul>erculin is us(»d. In ])ractice the curative effect of 
thes(» proteins has not proved of much wortli. 

(2) The second grou]) of products includes the ferments and 
possibly the toxins. 

Perments. — A ferment is a complex body al)out which we 
know but little except the effects that it prmluces. By its pres- 
ence, and probably without entering into intimate chemical com- 
bination, it j>ossesses the j)ow<'r of breaking u]) more highly organ- 
ized nitrogenous and non-nitrogenous (roiujwunds into simple, 
and more diff'usibh' molecules. They are terme<l enzymes or u/j- 
forincfl fri'iinni.^ in <-ontra<listinetion to the ba<'teria themselves, 
which are called /*o/-m<v/ or /irinf/ Jcnncnfs, That the action of fer- 
ments is not <lne directly to the micr(>be is sh(>wn by the facts that 
bactericidal >ui>stan<-e>, such as phenol (o per cent.), chloroform, 
ether, etc., Iiav<' no effect on them, and that cidtures freed from 
bacteria by filtration still jxjssess fermentative jx)wer. The 
action (►f fe^Inent.•^ is termed frtinentdfion, but this term is more 
espi'eiaily limited to the etleet of certain I'erments ujxm non- 
iiiirogenons eoinjM)nn<ls, particularly the carbohydrates. The 
result oi' ierni<ntation upon nitrogenous material is calk*d imtrc- 
jadion, which generally oeeur.> with, though often without, the 
formati(>n of (wlorous ga>es and other snbstan<*es. The intracellular 
origin of (teriain ferments has Ixen demonstrated by their experi- 
mental separation irom the bacteria when j>la<'ed uiuUt high pres- 
sures. The resulting bacteria-free liipiid possesses the same fer- 
menting qualities as the culture itself. 



The ferinenls like toxins arc of 

unknown eonijx)siti<in, iire 

highly destructiljle by clioniiral atrents and heat, eanse eifW-ts nut 
*jt* al] projHjrtion to tliuir iMilk <>r anuuint^ ancj are fnqueiitly 
rneelniniraily privipiiaUMl with various indith rnit hodir.^, "When 
injwte^I into animals Uuth aiv capal>le of uxeiting tlie formation 
of auti- bodies (auti-fennents and auti-toxine). 


\v pnncipiil bacterial ftTmerits are 
-These irans 


Proteolytic Fermenta. — l liese iranslonn ali>unyn.s intf> more 
8ohibIe and ditfiisibh^ substanees. One form very often met with 
U that which liqueties gelatin. This aets in an alkaline medium, 
and is therefun^ akin hi the animal ferment trypsin. This litpie- 
faetion o^' the gelatin affonls a means of di^^tintcnishing many species 
of mirrohe??. 

Diastatic Ferments, — Tliesi' trunsfurni the starches into sugars, 
and an^ found in many baeterial euitures, as of Baeillus mat lei , 
liafiihis pnemnouiie, ete. 

Inverting Ferments.— These ehange tin: non-fermeiitiseible sn- 
gjirs into those that under^fo direet fermentation. Such ferrnent.H 
are found, for instanee, in euUnre.s of Spirillum eholera^ and 

EmwlsiiyiBg Ferment. — This is formed by but few microbes. 
Onv examfilr is MieromK-cns (jyogenes ttjnnis. 

Coagulating Ferment.^ — One nf the means of diffen-nttation of 
bacteria is the eoagnlation of milk used a.s a enlture-inedium for 
the bacteria under observation. This eoa^^uhition is *lne not to 
acidity priHJueed in the uunlium, but tt« thr' action of a ferment. 

S<>me varit^ies of microbes priHbu-c a ferment tiiat has the 
[Miwer «»f di>sulvin|r tins edaguhim when formed (easease) ; and 
still others prochjee both ferments— -the eoa^nlaling an*l the ilis- 

Hydrolytic ferments are smdi as bi^eak u[> urea into ammonium 
carbonate and liippnrie acid into glyeocoi and henzf»ie acid. 

Fat-splitting ferments split the fats into glyeerin and the fatty 

0xidi2ing and nitrifying ferments an- otiier less important 

Effects of Ferments. — The singh' or eondnned action of 
thesi" various ferments «'auses certain special kinds i>f fermentation 
distin^ui^^iied by tlu' prinrijial substamv priKlriee<L Alc<)hoHe, 
hn'tic-acid, ami Innyric-aeid fermentatiim of the sugars, acetie- 
acid fermentation of aleuhol (^Baeillns acidi lactiei, Harillus butyri- 
Ciis, Bacillus aeidi butyriei* Haeillns acetieu^^ ete*) I eelluluse fer- 
mentation with the prudnetidu <»f earb«inic-aeid gas and anunonia ; 
iiitritieatjc»n, in which rhxidatlonof ammfunum h^ads to [)rodnetiuu 
of nitriteii (W inognid.'-ky's nitnvmonas) and sernndarily conver- 
6U)n of nitrites into nitriien (nitri>baeter) ; mucoid fermentation of 
glucose and in vert -sugar arc examples. 


Toxins. — The pathogenic bacteria pnxluee certain toxic sub- 
stances that are akin in action to the poisonous venom of certain 
serpents and other animals, and to certain poisonous principles of 
plants, as abrin and ricin. These are of indefinitely determined 
character, and act deleteriously upon the organism only after the 
lapse of a certain time — a period of incubation. They are con- 
sidered the ffjf^vific toxins of the several bacteria. According to 
some, these give all the reactions of albumin, and have been 
termed foxaihumiifM { Brieger). It is probable, however, that the 
toxalbiimin is but an impure form of the true toxin, a combination 
of it and various substances derived from the medium of growth. 
Some authors regard it as an albuminose ; others, as a peptone. 
Most recent invf.-stigators lor>k upon the toxin as akin to the fer- 
ment-. Roux and Yersin, in their monograph on the Bacillus 
diphtheriie, held this view and more recent investigators support 
the theof}'. The analogous pathologic action of tlie toxins and 
ferments, their common origin, their destruction (oxidation) in 
the presf,»nc(»of lijrht, their precipitation by alcohol, their precipita- 
tion frrmi solution?* by colloid bodies, their long and imperfect 
dialvsis, all point to this. High tem|>erature affect both sinii- 
lariy, both Ixring destroyed at from 60° to 100° C. (140^ to 
212° F.). f'hemical substances that have no effect (chloro- 
form, cihcT, etc.) on the ferments are without action upon the 
toxin-* ; and, r/Vv rerwj, those* that destroy the ferments (for- 
maldehyfl) an- al^^o injurious to toxins. Both may l>e sM-allowe<l 
with impunity, although they are pathogenic when injected sub- 
'iitari^oij-ly or intraiK-ritoneally. When the microbe is grown 
;fj -orn^r inor^^nnic medium or in a non-albuminous one (as 
f-/ Kin !■:•/'- -olijtion), the toxic principle obtained corresponds 
iu >- 'fj'»rii'?il nartions to a ferment. Most important is 
tK': f;;/r t\;ut ixinnu'W minute dos<s are effective. Fer- 
.';.'.'.*' .:/r A If hour P'lrard to the mass employed, and it would 
<^/;;, *.'.;;• •o/in- jKt in almr>st inijxmderable amounts. It has 
»/</;; '.••..';.::•-'! fti;it , ^.^'^ ,- gm. of tetanus toxin will kill a horse 
^.*:'/!..t.'/ *;V; y.'/. — IX hundred million times its weight; and 
iitii* ., /;./ hi' tij^inrnliii f-auses a reaction in a diseased man 
v,«i;/|.i/jv i/f y/ -ixty trillion times its weight. Finally, both 
;i/ f ojj, . ;)fv/ :» d<finit>* [htIo^I of incubation. Courmont and 
l)*jy,n i'nu'i Ui;jf. },y inen-asiiig the amoimts of tetanus toxin 
\u'y'U4i i,ji/, ;i /J/,// f !,<..,. vvw-re not able to diminish beyond a defi- 
niU' jlriiir fhi- l;<i> fif j^ri'^j. B1*kh1 taken from the animal during 
th'- hub.v'j'j' lit 'Ml. ijMoiis raiis<*d, when injected into another 
animal; uu iiij//i« /ji;if>- i/f;iiiif! attack. According to these authors, 
the U'nii*it\. jy/.v-ji/ly not to\i<- in itself, is capable of elaborating 
within th<- \yAy or * ijltun- iridium tlu» tetanizing substance. 

ConKiderabl« ij;/ht h;i.'. b«rri thrown upon the nature of toxins by 
the r<Mi*tiii inv« ^ii/;jr;o/i of Khrlirh and others who have followed 


him* Tlic^e invostij2:ations ]\n\'v l»t en mainly concenied Mitli {l*r 
behavior of the toxin ttnvard the antitoxin bodies. Ehrlich has 
found t!mt tlie serum contuins at least three distinct substances : 
the toxin propi_^r, toxoid, and toxone. The toxin is the active 
poisonous element; but, aside from its toxic property^ it liits a dis- 
tinct eombining abiHty, so that it enters \\\U^ condiination with 
antitoxin. A ^iven serum, however, will combine with a greater 
quantity of antitoxin than the tfixic power of the serum would 
indicate. In other w^ords, there are other eombining Iwdies which 
bav(* no toxic jmwer, or less t4>xicity than the b>xiu. A serum as 
it grows older lost*s in toxic jMnver withtmt losinp: in eond>inJMg 
power. This is due to tfie conversion of toxin into toxoid. The 
toxone has similarly the comhiuiiig power tor antitoxin, but is 
slightly toxic, l>ciu<' i^apafile, in tlie case of diphtberitie serom^ 
for example, of prod ueiug the p^jst-diphtberitic ]>anilyses. J I is, 
however, not a derivative of the toxin, Ijut results Worn a direct 
action of the bactenuiu, ami is produced simultaneously with the 
toxin. The dissmiiation of eouibiniug power ami toxic power is 
explained upon tlic assumption tliat each mohH:uk? of toxin con- 
tains a group of atoms sjiecially adapted to combining with 
vulnerable cells or with antitoxin and a toxic group. To the 
former the name hapiophore *jrtmp and to tlie hitter the term 
toTophore (jrtmp has Ijeen given. The prol)abIc nature n\^ tiicse 
will be referred to in the discussion of Ehrlich's tJicory of inunuuitv* 

It \A important to tionsider in this place certain advei-se criticisniN that 
have been made to Ehrlich^^ views regarding ihv prescnfi' cif diverge «ub- 
Btances of varitible toxic and conibiniitj^ (tower, Arrheiiins iind Madftcn 
hjiv»* i*hown tlKit ivlien sul>staiice8 i»f weak ronibinintr pinver, j^ueb atJ* bt>rii; 
acid and aninionia, are mixed the neutralization of amaiouia (und consi'- 
fluently the Iosj* of hemolytic eiiect of that ,sab?^tance, whicli is c^juivalent 
to toxic or hejaojy tie elfect-^ of toxin*) is greater for a certain amoniil of 
boric acid fir^i adde<l than for the same amr>unt Hubset^aently added* The 
resulting cyrve repre^senting lo.s;^ of hemolytic power sliows rapid redueticjn 
at first, then gradually a lenks and lesii sudden oescent of the curve. When a 
stroDg acid &s hydrochloric is used the neutralii^atioii of the ammonia is 
represcQted by a straij^ht line, which shows that the disappearance of 
ammonia and the consctimiit Io?^s of hemolytic etfcM't h in direct proportion to 
the amount of hydrochloric acid added at any stage of the experiment. They 
irijsist^ therefore, that the supposed diversity of toxic subj^tauees di^cribeil 
by EhrUch does not exiiit, but that the toxin and antitoxin stand in u 
relation of substnuces having weak combining affinity, and that the variable 
effect of addition-i of antitoxin to toxic serEni i?^ dne tc» this vvuak affuiity 
rather than to the f^resence of i^everal distinct bfrdie^s. Ehrlich later 
admitted that the vie^vs of Arrlienius and Madsen might apply to i\\v case 
of letanolysin and tetanus antitoxin (the kicterial .siibstances with whiL*b 
they worked as a control ol the etl'ects of boric atid on ammoniii). but he 
atili insists that the s^ime prineii>les do not apply to diphtheria toxin and 
antitoxin, fi>r which he claims active affinity comparable to that of ammoniii 
and hydrochloric acid. 

Fate of ToxiuK — It is certain that there exist in various cells 
of the animal organism certain oxidizing ferments by which the 


toxin is destroye<l. Not all of the toxin is thus oxidized. A part 
is eliminated unchanged through the kidneys in the urine and to 
some extent through the liver in the biliar}' secretion. Beside 
these there is still another method of defence of the organism 
against the action of toxin — the antitoxin (9. v.) 

(3) The third group of jmisons found in bacterial cultures are 
the pnKlucts of decomj)osition of the culture medium under the 
influence of the bacterial growth. They diflFer from toxins in the 
fact that their elaboration is more closely dependent on the char- 
acter of the medium than is that of the former. The toxin of 
tetanus or diphtheria may be produce<l in various, even in non- 
albuminous, media, but the elaboration of certain ptomains and 
other decomposition products is more narrowly restricted to growth 
of certain organisms in appropriate media. The substances pro- 
duced by bacteria from the culture-media and tissues are varied 
and numerous. Besides those produced by the various fermenta- 
tive processes there are : the products of digestion of albumin, 
albumoses, pe])tone, etc.; the ptomains ; nitrogenous substances, as 
leucin an(l tyrosin, metliyl-, dimethl-, trimethyl-, ethyl, propyla- 
mins ; orjpmic fatty acids, formic, acetic, propionic, butyric, mar- 
gjiric, lactic, etc. ; certain aromatic compounds, as indol, phenol, 
kresol, skatol, mercaptan, hydrochinon, etc. ; and finally, hydrogen, 
carbonic dioxid, hydrogen sulpliid, ammonium, water, etc. All 
of these are more or loss toxic and may contribute to the unfavor- 
able action of bacteria, but are not the specific toxic agents that 
occasion the ijharacteristic pathologic effects of the various micro- 

Chromogenesis. — Many bacteria form colors which give to 
the culture a characteristic appearance. Some attempt has been 
made to classify thos(^ pigments according to their solubility in 
alcohol, ether, etc. The pigment-forming Ivacteria themselves are 
called rhroniophoric when the pigment is a conii)onent of the bac- 
terial cell itself; chromoparic, when the coloring-matter is an 
excretion and the mi(Tobe remains colorless ; and parachromo' 
phoric when both conditions exist. The production of the pig- 
ment depends to some extent u])on the constitution of the medium, 
and it is possible to produce cultures and even races of pigment- 
forming bacteria by the use of appropriate media. 

Photogenesis. — The phenomenon of phosphorescence ob- 
served in decaying fish is due to the action of bacteria. This 
producjtion of light is observed in many of the cholera-group of 


These may be either (a) mechanical or (h) histologic, the me- 
chanical effects being least in importance, (a) Sometimes masses 
of micro-orgiuiisms more or less completely occlude small blood- 


vessels and otrcusion j^fc^jtKlarv rfiautri^f,' m tUv tiHBUKS in this 
mrchariifal nay. In other teases I he nljslrurtioti is iin'omplete, 
but occasions throiiibi>sis iu the blood-vessel and various conse- 
f|ueutial <li?*onler,s. {h\ Tlw histolojirie rhuoges occasioned hj 
hnvtefm art* pro/tfiratirr and (itsfnfHfrt\ among the latter being 
various dept'nemtions and necrosis. The proliferative clianges 
n*ay be iion-spe(*ifie ivr specilie^ — that is» there may be simply 
proliferation such as fuvurs from any irritation ; or there mav Ue 
speeial forms of proliferation more c»r less eha met eristic of the 
indivuUml nucnj-organism in extent^ distribution, and natnre. 
This is st^en in the pccidiar lesions of tnbereidosis, glanders, 
rhinoseleroma, etc. The eelUHar degenerations and neentses cK'cur 
coincidentally or snhse<|iieut to the proliferjitive * lianges. On the 
contrary, in many eases tlje first etleets of liaeterial invasion seem 
to be degeneration or necrosis of the tissue?* immediately around 
the organisms^. 


Bacteria usually gain entnmce iiitu the aninnd hmly through 
gome h'sic»n ot" the epithelial layer, often the result of traunuitism. 
Sometimes the micTohcs find in certain eavities of the botly favor- 
able conditions for growth, as in tiie pidmonary or alimentary 
tracts, and tliert* develop and (l:\bnrate their toxins. 

Intoxication and Infection. — In one clasr. of *hseases the 
infecting niicrohe renu»ins h>calized at ihe ]ioint oi' innt illation, anil 
is never or only exin^ptitnudly fun n*l in the tin ids cd" tlie ho*ly, the 
general symptonis of tin" <liseas»' being due to ahs«a'|Jtiou of the 
toxic protlnets. Such arc true ]nto.rir(f(ioin<. In other cases the 
microbe is fonnd einndating in tlic hluod throiighoiit tlie body 
and finds Indgrment in UK>st of llie organs, 'fht'se are t ailed ht- 
JfHtnhH in the stric^t sensu. Tcianiis is the typi- uf llie first class; 
anthrax, of the seeouih There is, liowevei% %us ilisdnrt line to be 
drawn, for the symptoms of all infections are doubtless due to 
toxins or other toxic products, wliellier proiluced hjcally at the 
jMiint of implanttitinu of the organism <>r tliroughnut tlie b<jtly 
when it is di^isenii[iated. While some bacteria always j»np<hice 
pure intoxications (trtannsK niost cd" them niay» under varying 
conditions, cans** eitiier intoxication?! or ini'eetitjiis. Thisdidbrence 
is due to a variable degree of virnleiice or to variable resistance on 
the part of the tisssue. The toxin is essentially negatively eliemo- 
taetic (see InHamniati<m), and thus preveiits the jdiagoeytic action 
of the leukocytes ; while many c^thrr bacterial priulucts and the 
bacterial proti^us ( Baehner) are pc^sitiveiy ehcuHitaetic. When a 
patliogenic ndcrobe is wanting in virulence, there is a detcrniiua- 
tion uf leukocytes to the point of inoculation, anrl Siippnrfdhn 
restdts. A virulent microbe in the strict smse^ tlien, is one that 


iuva<les the animal liodv and there produces its more or less 
pfiwerful toxin : an a virulent one produces but little, if any, toxin 
and is de?troye<l by liacteriolytic substances and by phagocytosis, 
either with or without suppuration. The number of organisms, 
a«^ well ar? the virulence, is important in determining the character 
of the effects. Knise has formulated the following scheme 
ti> illustrate this effect of small and large doses of virulent and 
le?r?? virulent organisms : 

1. Small doses cause general septicemia (general infection). 
Examples, anthrax an<l the plague. 

2. Small dr>>c*s <>ccasion local effects and metastatic foci ; large 
d'iH-«^, s<'pti^'<.'inia. Example, glanders in field mice. 

3. Small dos^'S clause local lesions ; medium-sized doses, local 
legions and metastases ; large doses, septicemia. Example, pneu- 
m</(^¥(^'\i- and streptococcic infection of rabbits. 

4. Small do-if-s cause no effi^ct, and larger doses local lesions 
'AU*\ ifj^'ta?»tatif- fVxi. 

o. I^rge doses cause* only IcK'al lesions. 

0. Maximal doses have no effect. Example, pure saprophj-tes. 

Sapremia, Septicemia, and Pyemia, — From local sup- 
purative f'Kri toxic ]>r(Klucls may be absorlx»d into the general 
cin-uJation. and a condition known as Sapremia results. The 
lui'^^Uiir bacterium itsc»lf may invade the blood-current without 
\[\\\u'^ ri-rf.' to any s^.'condar}* collection of pus. This is terme<l 
j^jAi^v-mia, When, however, the microbe is carried to various 
jiart* of th<' bo<ly and there gives rise to secondary- suppuration, 
the <^yij'iition is called Pyernin. 

T)i*' d^'-truetion of leukcx'vtes that takes place in the formation 
of ]/»j- i- pn^bably due to bacterial pn>teins in conjunction with 
th«' }>r' --ur*' due to elos<*Iy packed exudate. Fn>m this point of 
••!' V. -ijiijjiiration \> not sj>ecific, and its production by various 
*in ui'i'-A r=iib-tanc<*s proves this. 


Definition. — In the present state of our knowledge of the 
'ondition of iiinniinity it is most <lifticult to give a precise defini- 
tion of thi- term. It denotes that condition of an organism which 
'-naf^N'. it to re.-i.-t tin? attacks of bacteria and their toxic secre- 
tion-. In on<' sense it is the reverse of susceptibility. An animal 
t|i«t i- not sii!^-<)»tible to an infection is said to be immune, and 
the t^nn immuniziition is applied to the process by which an 
animal becomes thus refractory. 

Varieties. — Two principal forms of immunity, with a number 
iA' ^ulxli visions, are recognized: {(i) Natural immunity; (6) Ac- 
UnimA immunity. 




(«) Natural immmiity is the power of rosistanoe to certniii bac- 
teria and toxins niaiiitL'Sted by raet\s or classes t»f men and animals, 
or even by certain indivitinalg. It is nearly ahvay.s or always au 
inheritance from imninne ancestoi*s» We may distiiiij^iiish : 

1, Nafitrai Baderiai Jvimutut}^, — In this ease the resist-ance 
IS f life red to the specitic bacterium, Thns, nnni- of' tlie lower 
aninuils is susceptible to syphilis, measles, or leprosy ; man is 
insuseeptible to rinder(*est ; dogi? and Algerian shee|> to anthrax ; 
chickens to tetanus ; nej^nn's to yellow fe%'er ; and in epidenii<*s of 
various kinds s<inie indiviiluals regularly escape. This l>aeterial 
imnmnity is only exceptionally fibMoiufe^ a-s in the ease of animals 
to syphilis ; usnally it is merely j^ehfivfj the snseeptilnlity or 
iusnseeptibility varying with the environment or individual con- 

2. Naim^ai Toxin Immunittf, — Just as the hog is naturally 
re*?istant to snake-venom, so certain animals are immune to certain 
Imeterial toxim, Kats are resistant to <!jphtheria toxin ; chickens 
to tetaiuis toxin, etc, 

(/>) Acf^uired Immimity. — This may l>e }ta(ur€ilhf (tcquired^ ag 
when an animal has passed through an intectious disease, or arti- 
Jiciaiiii acquire*!^ when an animal or num has l^een inwulated with 
meteria or l)acterial products- We may again distingnisli two sub- 
varieties, as in the ease of natnml immnnity. 

1. Arquind Baderlai Litmirnifjf. — In this fonn the animal or 
man has been rendered immune by previous, natnrally aequired 
disease or by ino<ni!ation with tlie s|M_'eific organisms that have 
been first redueeii in virulence or killed by beating and other 
means* Acquired baeterial immunity iloes not follow all infections* 
In the ease of gonorrbea, for example, it is wanting, and in eiy- 
Bipelas there seems tn lie increased susceptibility; but in most 
of the iniectious iumiunity is produced, it is of variabh' dura- 
tion, sometimes lasting throughout life, sometimes only brief 
periodn of time* 

2. Acquired Toxin Immuniti^.^-^Jn this form the imnutnity is 
produced by the injection into animals of the toxins from bac- 
terial cultures or by injection in men or animals of sernin of 
animal tiiat have been rendered natundlv or artiticially ininiune. 

Active Immunity. — This term is apjjlied when artificial bacterial 
iminnnity or toxin immunity has been prorkieed by inoculation 
with living or dead bacteria or by injection of filtrates of cidtnres, 
because in these cases there is act ire production of the immunizing 
substances in the bcxly of the experimental animal. 

Passive Immunittf, — This term is uppbed to the protection 
aiforded by injections of serum of imninne animals, because in 
this case the ppx^ess is passive as lar as the recipient of the anti- 
toxic injection is concerned. Active inirannity is rt*latively much 
more lasting tlian passive, 



iu friany cases immunity asserts itself against both the infect- 
xkx^ fukf >lx; and its specific toxin^ as in the rat with regard to the 
-cUftSitiieria-bacillus and its toxin; but more often an animal is 
f^i:$Uirit to the infection, though susceptible to the toxin. An 
fxarnple of this is the action of the guinea-pig toward tetanus 
''X'aiJIanl). The reverse may be true, and we see an injection of 
tul>^n;ulin without effect upon a healthy animal that is very 
sut»r^'ptible to tuberculous infection. Most commonly natural 
ifijifiijiiity exists toward the infecting microbe and not its toxin. 

Theories of Immunity. — All the phenomena of immunity 
iiav<f not l>een satisfactorily explained, but the subject is at least 
jiiu<rli c'hiarer than formerly. 

Bacterial Immnnity. — Alexin Theory. — The blood plasma and 
fluidn of a naturally immune animal are capable of destroying 
the l>acteria toward which the animal is immune. Thus the blood 
of llie nit destroys the anthrax bacilhis. That tlie destructive 
ag^'ut is contained in the blood itself is shown by the fiict that 
the defibrinate<l blood and ])ericardial effusions of dogs and 
rabbits destroy anthrax bacilli outside the body. This bacteri- 
t:uiii\ a<'tJou is not, however, specific nor confined to serum from 
aniriL'il.s naturally immune to certain infections. On the contrary, 
the df'.stnictive action is manifeste<l toward all micro5rganisms in 
varying d<*^n?es, and the scnim of man or animals always mani- 
fc*ht« bact<*rici(lal power, though not always decidedly. This 
l/ax't<*ri<?idal action was attributed by Buchner to certain albu- 
iiiiiioiirt lMHli<*s which he ternu^fl alexins. These are unstable sub- 
tiUitU'i'i^ n*rt<*inbHn^ ferments in action and easily destroyed by 
li«':itiii^ iIh! s(*rum to from 55° to 60° C. It is now ouite gen- 
«nill y l><-li<;vr<l that the principal source of alexins is the leuko- 
';vii.-, \vlii(;li may either secrete the substances in question or 
Jifi* r;il<' tluMu when they de^norate. It has been recently shown 
lliiii. iIm' pn>t4*(;ti<)n in bacterial immunity is not afforded by a 
>\n'^*\t' ImmIv or alexin, but by two distinct substances, each of 
wjji' li in iM-rihsjirv. (See Ehrlich's Side-chain Theory.) 

Tltr,,rif nf Inhihiiion. — Another theory asserts that the inhib- 
i^nr, i-W't-ri oftlnj soniin causes some chan^ in the vital properties 
'A ill' l>:iit« ria. Culturc-s of bacteria in the senim from immune 
;.?i;in:ilrt M-rfii to sliow somc such inhibitory effect, but this is 
j/» '/•/;! Mv 'liii' ratlMT to the immunizing action of the serum in 
.. • ' li ill* V nn* KtispendtMl, as bacteria freed from this by filtration 
t' .. ■ .-Ijo'.v no *iii('h physiologic do<n»neration. 

t'hui/orjitoHiH. — M(»Whnikoff proposeil the very attractive theory 
//^ ^,h.r/*t*'\U}h\^. lie? holds that the destruction of the microbes in 
^^/ :iitiui\i\ hoiiy is to be explained not by the conditions of the 
f//i/ rtuidh, but by purely cellular activity. The infecting microbes 
0f^ f40h'n lip by ccTtain cells of the org:mism and are destroyed 
t^/ UtffU4'^'l\\i\€ir digestion. These cells— phagocytea — are of two 


kinds: the miemphagos, ineliidiiig the pt»]ymaq)honiiclear leu- 
kfjcytes; and the nmcrophages, int^hjtling mtirioniieloar leukot-ytcs, 
the vascular endt>thelial ceils, the cells of the borie-niarrow ;i!id 
spleen, certaiD eomiective-tisHue cells and Kupfer^s cells, and even 
those of the nerve- and nmbele-ti??sLie. The niierophages are 
mainly concerned in the aimorjjtioii and destruction of bacteria ; 
the macrophages in the destruction of cells, portions of dead tissues, 
and the like. After injectifin of a cidtiire into tlie subcutaneous 
tissueof ananimiil iiatuniily or artiticially ininiunej heuoticed that 
the bacteria wercidl taken u|> by the leukoeytcs. That these microbes 
were still living anil virident, and were not taken up as mere dead 
matter, Mct^chnikotf regards as fidly estal>Hshcd, One proof he 
cites is tite iact that an exudate containing nu free bacteria^ but all 
intracelluhkr^ is capalde of prndncing cultures on artificial metba 
and causing infection in suinceptiblc animals. 

Baderiolt/tiv Theory, — ^Pfeiffcr opposed to Metschnikoff 's theory 
the experiment of injecting cliolera vibriones into the peritoneum 
of artificially imnninized guinea-pigs. He ob.scrvcd a complete 
destruction of the microbe by the peritoneal fluid — an agglutina- 
tion into masst»s and a gradual degeneration* Thert! were feWj if 
any, leukocytes present, and he therefore claimed that such destruc- 
tion was entirely extracellular and humoral in character. This 
property of destroying or dissolving l>acteria luis been termed the 
^^ fj/mf^enk -^ action of scrum. However, if a preliminar}' injec- 
tion of some substance that determines a local leukcK^ytosis is 
made, there may occur, instead of the reaction of Pfeiffer, a true 
phagocytosis, Metsehnikoff interprets Pfeitfer's phenomenon 
as the result of a dissolution of tlie leukocytes by bacterial 
action, and solution iii the peritoneal fluid of the destructive 

While at the present time the theory of phagocytosis must be 
regarded as incapalde of explaining all of the pncuomena of the 
defense of the organism against bacterial invasion^ tliere can be 
no doubt of the im|K>rtancc of this [ihenomenon in the protection 
against invading organisms. If the Ijacteria are not too virulent » 
phagocytes are capable of alisorliing them without any previous 
action of destructive clieruical agents in the serum. As a rule, 
however, certiiin chemical substances in the serimi areopenitive in 
reducing the virulence of the organisms or otherwise rendering 
them susceptible to phagocytic destruction. 

Opsonins. — Recei»tly Wright an4l otluTs have demonstrated in 
the serum of animals certain thermolabilc bodies wluch, acting uptm 
bacteria^ sensitize them for phagocytosis. These substances which 
liave been termed opf^ontHS arc unah>gous in nmstitution to toxins 
in having a liaptopliure gnaq* l)y wl»ich they attach themselves to 
the bacteria and au opsonifenuis group, which resembles the com- 
plements, and, acting Hke a ferment, completes the sensitization of 
the bacterium. Heat is destructive to the ojisoniierous group. 


Acfr^MdiiB. — An attractive theory has been suggested by Bail 
vj f'xpLiin the unusual virulence of micro-organisms under certain 
<-irc'Ufiif^tances. It was found by Koch that intraperitoneal inocu- 
hixvm with fresh cultures of tubercle bacilli causes a rapid destruc- 
tion of tuberculous animals. Bail found that if tubercle bacilli 
with sterilized tuberculous exudate were injected into healthy 
animals, sudden death resulted. Neither the sterile exudate nor 
the tulKTcle bacilli alone had such an effect. He, therefore, assumed 
that something in the exudate increases the virulence of the micro- 
organisms and gave tlie name aggressin to the hypothetical sul)- 
8tance. The exudate found in the peritoneal cavity in these cases 
M'as found to consist solely of lymphocytes and Bail suggests that 
the aggressin acts by panilyzin<>^ the polymorphonuclear leucocytes 
and thus prevents phagocytosis. The lymphocytic character of 
tulxfrculous exudates is explained by the presence of the aggressin 
in the tul)erculous animal or man, and the consequent prevention 
of mi Juration of polymorphonuclear leucocytes. Similar phenomena 
liave iHti'W found in case of other micro-organisms. Antiaggressins 
have hiH}i\ prcxluced by repeated inoculation of animals with exu- 
date-? containing the aggressins. 

Wliile an important part must be admitted to phagocytes in 
the ultiniato destruction of bacteria, bacteriolysis may occur inde- 
jx;nd4;ntly of phagocytes. 

The bacteriolytic substance has been found to operate outside of 
the lK><ly, though not so actively as in the peritoneal cavity. When 
it Iia« b^'en partly destroyed by long standing or heat, the addition 
*A' a hfnall (juantity of normal serum from the same animal species 
n".Vfn"i th<» bacteriolytic |>ower. (These phenomena will be again 
ff'-rnrd to in the <Hscussion of Ehrlich's theory.) The sources of 
x'ii*: barNrriolytic substances are the spleen, l)one-marrow, lym- 
^A*Jix^i': j/lands, thymus gland, and doubtless other organs as well. 
l\ ,^ l^robable that the source differs in different infections. 

J/.v;ti'riolysins differ from Buchuer's alexin in being specific in 
4/^. 'ffi. and, tluTefore, operative only in the case of bacteria to which 
^^.^ >^:/:tiin\ has been immunized. The bacteriolysins are closely 
/» ♦./': t/i, if not identical with, hemolysins, substances occurring 
'. -■ . ifliftna under certain conditions and capable of destroying 
.*'.•: ,.vyJ-<j';rpuscles. (See Ehrlich's Theory.) 

/;v/ // / 1/// Atjtjlatination, — Recent investigations by Gniber, Dur- 
/'iHA'r V/</J;il, and others have shown that the serum of animals or 
,^v««*s <" h/\f'rtti\ immune (naturally or experimentally) to infection 
lf\f)^ J**»/? \/iu:\\\\ of typhoid fever, cholera, the bacillus coli, etc., causes 

]*^4miion and flocculent precipitation of the respective bacteria 
rt^f U/uillon cultures. The reaction may be obtained with 
Ivit^lli under certain conditions and even with inert matters 
nryw-J I* *rWf*wwion. (For further details see Typhoid Fever.) This 
pi^mH9*ff9fm (rerpdion of OrvJber-Wulal) has been interpreted as 



representing the mode of defence of the organisra against inf€ction, 
and the renction has therefore been considered as one of irnm unity, 
Tlie reaction, howe%'er, bears no relation to the severity of the 
inft?ction or the degree of immunity* The serum may be highly 
agghttinativc and yet have no immune properties. Some have 
thoiiglit that the agghitination is closely associatwl with bacteri- 
olysis, perhaps a% a preparatory step, but the two fimctions are 
certainly distinct. 

Recent experiraents seem to show that two substances are con- 
cerned! in agglutination — an agglutinal>le and an agglutinating 
body. The latter appears to be albuminous or related to serum- 
globulin, as it is precipitated witli the latter by magnesiura 
sulphate. It is much more resistant to heat than is alexin. 

Ferment Thmrtf, — X ferment theory has Iw^cn offercil in explana- 
tion of some of the pheuoinena of immimitVt but it is of only re- 
strieted interest or imptjrtanee. Certain bacteria, like pyocyaneus, 
typhoid, and cholera bacilli, are eapalde of elaborating ferment-like 
bodies that have been designated jtiforiiajiase^ ti^pfi(ut% and cit of erase. 
These have some baetcriulytic power, and natural immunity has 
been explained by assuming the presence in the plasma of such 
ferments. The action of these ferments is not, liowever, specific, 
and their relations to otlicr l>aetrriolytic bodies is still obscure. 

Toxm-immuiiity.— The probaldc nature of toxins has been dis- 
cussed on page 220. It is found in sijine eases tlmt an animal is 
susceptible to the action of the toxin of a cert;iin bacterium, though 
refractory tn the bacteriiun itself, and the n- verse may also oc-cur. 
It is clear, therefore, that the resistance to bacteria and the resist^ 
ance to toxins are distinct processes, though the two are in most 
instances asf?ociated in the same animal. 

Natural Toxin-immunittf. — Normally, certain classes of animals 
exhibit natural toxin-immunity Just as we have seen uatunil bac- 
terial immunity exi.-^ting in certain aninuds. The immunity of 
the bog to snakc-veuoin, of the chicken to tetanus toxin, of the 
rat to diphtheria toxin, and other examples might be cited, Tlie 
explanation of this natural invmuiiity is j^till nneertain. It is snp- 
pose<l thai the immunity, which is an heni'ditary one, originally 
o^*curred in the aueestors as a result of tlie inieetimi nv intoxi- 
cation in question. They then tnmsmitted the innoiuu'ty to their 
descendants. With the discovery of antitoxin (to be described 
below) it seemed likely that an explanation of natural toxin- 
immnnity had been discovered, but it wa^ found that, in the ease 
of the chicken and rat, not a traee of untitoxin was present in 
the l>lo<jd, though these animals are highly immune to the toxins 
of tetanus and diplitheria, respectively. It was also found that 
in these animals the introduction of the toxins, while producing 
no symptoms, rendered the serum highly toxic, and that, trans- 
ferred to other animals^ this serum produced the symptoms of the 


(iiHriiHOH iianHKi. The toxin evidently circulates in an unaltered 
Htiit4» at liMiHt for Konic time, and the immunity is not due either 
to (l(*Htruotion of the toxin or to its rapid elimination ; and as anti- 
toxin is uh8t*nt, it seems likely that the immunity rests upon 
tin uurtvoptivo ijualitv in the cells of the body. Recent experi- 
luonts h:ivo made it clear that toxins attach themselves closely to 
^vrtcUM wUs, rt^% for example, the ner\'e-cells in the case of tetanus; 
iMul \\ uiAv itisily Ih* ciuiceived that if these cells are not receptive, 
\>w i\*\M\ mi^ht oin-ulate harmlessly in the serum. Experimental 
j\»x\»f' s»r thi'i vu*\v will Ih* oiteil later. 

l*f>,* tv»iit *ntitx.\tin is applied to a substance or substances in 
bN^. «^'Miin oi" tiM iiuimal that pn>tect against the toxin of a specific 
^»i,«t ,«.««*. 

\ ,^.. ,.•/ f\rin-intmunittf, — Behring first produced antitoxin 

if :i|*]i •-». M<(. bki^ xtiKv Ills investigations antitoxins of tetanus, 

.im'v \* «».»«•». »»kI i»r x^rious infiH'tious poisons, mainly of labo- 

.^.».: % iii.M.i. I»a\c Uvn phmIucihI. The production of anti- 

u.x.i* . 4. .oiiii»l».xlK\l l»v tn^ating an animal at first with small, 

».,.: ',f. I u«ili l.»!v;%'i\ dvKM's of the toxin until the antitoxic quality 

:i *, ••|sJ V'* ii maiiiT of practical procedure in some cases 

.;i|.iiili. ii<4^ vnlturt'S that have l)een sterilized by heat or 

,:ni., . . *.iii omiiv; Uu'iiTia of low viniloncc are frequently used in 

.li . .,«:% ii»»*A noiw. and hiter, when a certain degree of immunity 

r, I >.. . ii )*i%Hiiut-J. tlie aninml is inoculated with virulent cultures 

mnioMii iH'arhes a maximum. When toxin of sufficient 

.til W i»l»lainiHl, the antitoxin can be most surely pre- 

i 1.^ n iiK- ilir toxin alone. I n the course of the immunization 

, , .1.111 tl ilir antitoxin sometimes disappears from the blood, 

,ii .... !. s^.iln»iii ;ui\ lo>s of ininiunity on the part of the animal. 

I h. j.ii lu.iiiv Moh inav he explaine<l, like that of natural toxin- 

.... ,, ui«l iLitumlbaeterial immunity, by the assumption that 

J, I! ..II ilir Olio liaiul, have IxH^onie unreceptive for toxins 
*,., I .1, H ,1,.. I.KhhI mtuiu has bm)ine bacteriolytic. 

\ .....i««l loMii inunnnity was first explained by Behring in a 
^^^ ,.,., ^ ,,,,,1 ^1 lo (lio rxplauation at that time oflfered for natural 

"!y U.OO..U \\u\i i>* '»'* taught that the tissues of the body 

I. ..u I. . »i loini'il to tlir toxin, a sort of Mithridatization. I^ter 

1^ ^ ^^^ ^ ^\ iini ilii* ix'>iMaiuv is duo to the presence of an anti- 

m llo. \\ tir.i \\a-» ivi^anled by many as an 'altered form of 
»i!xo\ ssxA o.i.'iii' oihor ox|H'riments otfered to prove this view, 
x\x\\ M .M uoi.ilioi; anliioxin in ntm by the action of either a 
vvmiuoMu . X's tiio ounv.u or a nipidly intemiptcKl direct current. 
\\\ \\ \\\ys\s how o\ or. that t ho sup|K»siHl antitoxin in this case 
ia/.tmhl^ '* »^»^»»* **•' '^*^^^'*' viruloiuv and that its seemingly anti- 
u\^v oh'utiotoi wa. ix.iUv vliio to Its ni|Kicity for developing im- 
{\,\ \\\\\\s M\|oolod into aniumls. 





Occasionally antitoxin is found in the normal animal or in man 
withont pn'vious occurrence of tln^ iufeetion under consideration ; 
thus in a uotahU' projwrtion of uonual horses diphtht'iia antitoxin 
is found in the blo^xl, and the same is true of cliildreu and of adult 
human bcins^. lu these latter, of coiir?*e^ tlic possibility of a slight 
attack of the disca^st* occurring in early life aud having been over- 
lookt^d must be considered, h\ animals, such as liorses, in which 
the disease does not o<.'eur sjxiutfineously, this explanation does not 
hold. In the light of recent knowledge it seems probable that 
antitoxin may be pro<luced by the cells under stinndation other 
than that of the specific toxin, and while antitoxins are specific to a 
very large degree, so tliat tliat of diplitheria protects only against 
the diphtheria ]>oisou and that of tetaims only against the tetanus 
p>ison, this speeifieity is \\<\i absolute. It is knnwu that<liphtheria 
toxin protects against abrin poisoning and the antitoxin of al>rin 
protects ag;iinst abrtn and ricin poisoning, while the tetanus 
antitoxin is jiartially preventive against snake-venom. Further, 
it has been shown that inject lou of various chcmotactic sul>- 
stanees, such as salt soiutinn, extracts cjf certain organs, |K:>ptone» 
cinuamie acid, etc,» are capable of pnnlnciug in the bloiMl some 
antitoxin, though they are more particularly active in generating 
bacterial immunity. These facts imlieat*' that antitoxins are not 
stru'tly specific aud that in a limited degree they may he pro- 
dueihle by otiier means than preexistiug infection or inoculation. 

Adlon of Anfifoxin. — It was tii^^t thought by Behring that the 
toxin aud antitoxin entrr into a eliemieal combination which com- 
pletely destfitys the identity of the two substances. This was 
disprovcil by the discovery tliat a mixture of snake toxin aud Its 
autitoxiu, which has no effect when injected into an animal, be- 
comes highly toxic when heated to 70"^ C\ It is known that the 
antitoxin is dcstroye<l at this tenijx'raturc, while the toxin is not. 
It IS very probable that the toxin and nnti toxin cuter into a form 
'of li.Mjse eiiemicid rombiiuitiou without h>sing their identity just 
as hydrochloric acid enters into loose combination with albumin 
in gastric digestion* 

The Chemical Nafure of Anlitoxht.^-Biit little is known regar*!- 
ing the antitoxins excepting that they are relatively resistaut to 
Iieat and other external agencies. Thus the tetanus antitoxin 
beiirs a temperatun^ of up to 70"^ C, as well as the action of sun- 
liglit, anil even |>utretaction, withont being destroyed. It seeuis 
likely that the autitoxijis are albuminous bodies or that they are 
closely associated with such bodies. 

TVammmtion of Anfiioxm, — The heretlitary transmission of 
antitoxin has been studied, aud it has been found that transmission 
takes place from the niother to the offsi>ring tlirough the fetal 
circulation or after birth through milk. There is no transmission 
from an immune male parent to the offspring. In experimental 


work the traofini^^ion of immunf- •uh-ianoe irouM not be traced 
a.- lar a» th*- s^-'^nd pfnf- ration. 

Ki'uiunfition. — Antit'ixiu ir proliably eliminatoil thn-iiiih all 
the r^-'-n.-Ton- nivan.-. It ha* ]•«-« n found in the iirint- and ti» a 
lan<'- 'XT'-nt in th^ milk. Brir^rir ami Ehrlicli ohtainni a ijuite 
Ci«n'«;iJtnjt«-<I fttrni of antitoxin liv |iivcipitatii>n i»f the caM-in by 
anirijMrjiiirii criiliiliate and puritir-sition by dialy>i>. A? in tht- t-a**!- 
of t'.xin-. the whole f*\' th*- antitoxin M-em^i to bt- c-arritil down by 
th<' jir«-'-ipitat'-<l folhijil i-a&i-in. 

All th" jdi'-miiiiena of ininiunity have been explaint-il by Ehrlieh 
in a \-t-ry eorujin-h'-n-^iv*- th«'on- t-jilh**! tlu- SkU-^'h^in Th*:onj. Tht* 
appli'-atinii- <t\ thi- v* toxin-ininiunity will be tirst con>idiTtil XT 
tli«- -ak<- oi' •iinjilii-ity. 







■ |.'.-.r 

I.. .-■ 

'A I*- 

I:i 1 . 

jt .J- ii liM* 

l.'.".'t|iJif '. . 

-lii'il- - .in'. 

'Fit' >1, II ' i.;iv«- .1 )i.i| 

iiaini-'J K» « ji-;*<- . /" ii<. fi rn, 

iinlrj'Til \i.i\\W\ .}. 1 ■..':.! 

•;,.!' !;.■■ /^ i;.'.i.j,'.r.- ;.-r ■ 

if., f..'. 
•1 ',i'i- 

rs KSjr:;. :. 

r-.;.' .r- '.f thr.- ■.rl"r«: 1. Tl:- r." ..j-T.-r ■ f :\.- *r-r ■ rS r :< 

.'.•■■. it -iiiV «,th»-r fir.'t: -ri. i m th;- ui. u:\l Ehrl:- ». -;- Ak* 

.' -1. I . - i'.h r'-'»rpt-r- !»r'.- -Ji :it ■!. i »:i •:..■ rij:.' '. i- -. :* 
Ii- i.:..T.'J A T», . 'I t.,xi!j :i. ■.:..■';:.-. »i. Jh..- latl- r ^l.-w* •/* y.?*: ! -^ ■ 
t..v..j,}...r. ::r.. jp .it «/. It i- th*.- rcc-i.t-T .f ih- TlT>t • r.^. r •■.-.: - 

:'- r.iT-.| fr-.m th- [..iP-Til .■.•:!. j. I: T'T -r^.-f ih..- ■i-«v.r.-', r'- 

- u'r-'Uii. .. anil ii zym'-ph-.r- -.'r- ■!:!•. J. Tl..- lai:- r •'* ' 
;.«• i;i|.aiiti'f . On w.,.- riL'ht hand i« Pi-en a ir-.K-fj^c 
:.« '! -a:'.:, th.- i.aj.i>.i.hi.ri; trroi:;""! tI.i- r»irj.ior. i:i Mub !».».::■ 
:- ' nil .!« t i;j,.,;i :t. Haviii- I'.t i-ii- lia|.ii-i' en;:!'. !:*.•. :: 
••■■f!;..: -•.■i-.ii.l ..r.l.r u:-. ar. :!ii:i;.K.l !:!;.U-r iJit- it :::. 



' I. 'I 


/MiJi'..- ri ami ]«rii ;j:t.jli..ii nn.- j.r.i.aL.v 
■-.••■■r- .: J:.-.. j.-..r- ..f Tl..- t;,!r.| .■r-l-.r Ki-. ^l.'lll . i a"v 
!■■ ■^•;..'.{.- ' .iri'l'/. On..' .f fin -■ i ..niliiiu* wiil, a n!« I.i r.'»- . r ri'.I ' :r 
. ].!.ir J..I- iii;;»i:ty, ai..] U.. ..i;,.-.- i-.i:j».itj».-.s \*i:!. tl...- i.aj.t. j-}.. n- tr- ;::■ ■":■:^.-.■ 
« i,iii|.;. Ui. m. /: wli;« !i whiii M. *'in,l.iii.«j. i-art aH \i]„,\\ i\„- i;...Ui i;!.- um h,.n-»l :■■ :: v 
f.i.i- f Ji.ipi'.i.h'.p; ;T'."i!. 'Mil- i'.rj.i,]»:ju.:iii ha- lu.i ;:rt.ui.B— .-i:!-. i;> l.iii.i. i-h.-ro. ft.ii::-: Ti.r 
i/lJi' !. It- /jijji.t'ixi': iif>n\i, ;. 

Ehrlich'8 Side-chain Theory. — ft. To.rhi-inninniUii, — This theory 
explains tin* fads n-ir-irdiiiL^ th*- Mrtinn nf to.\in> and tlu* f^irmatinn 
of antitoxin^ iM-lt^-r than any that h:i- Imm-ii ."-UL^^n^ted. It is ba>td 
upon tin- hyp<»lln-is lh:it harKriai toxins, like a>siniilattHl \\^n\- 
stufls I'liti-r into rhi-iniral <-oriibiii;ition with tin- *'clls tif the IhmIv. 
In this n>pi"fl toxin- diilrr fn»m rhcniical jjoisons whicli do n^'t 
enter into such coiitbinatioii, and this may <'X])lain the iailnri' of 
nil exprrinirnts at prodneiii.n of antitoxins for such poisons 
KcMne non-bactcrial |»oi>ons, sikIi a< snake- vrnoni, abrin. riein. 
ft<*., nwnible toxins in ioml>inin<: with the eells, and it is notable 
that in the ease of these |H}isons antit<»xins have been pnxlneiHl. 
Th(! mnibinution between a toxin and a e<»Il is effected bv atom 



groups or radicals (to borrow terms from organic chemistry), the 
-group of the cell entering into combination with the groop of the 
toxin. These groups wliieh effect the junction of the cell and the 
toxin are termed haptophorc r/roiips. In addition to its liaptopliore 
group, the toxhi molecule contaius a toxophorc group which car- 
ries the toxic capacities, but the toxopiuirc gnaup rannot oper- 
ate upon a cell until tlie toxin has been anchorcil to the cell by 
the juuction of the haptophorc groups (Fig. 81). When a toxin is 
introJueed into the body^ it seeks tint cells eontairiing haptuphore 
group.s having atlinity for its own haptophore gnnip. These hapto- 
phorc groups of tlie cells, fmm their receptive function, are called 
receptors^ and they an.^ specific in sc* far as tht* receptors of certain 
cells will eomluue with ihe haptHphore groups for wliich they 
have tdtinity aiul with no others. In this way it may happen that 
a highly toxic body may cireulate liarudi'ssly in the botly, as there 
are no receptors tor whii-h it has affinity. {This matt^^r was re- 
ferred to in the panigraidi on Natund Toxiii-inununity.) 

When the reeef>tors of the cells arc utilized by eombinatiou 
with the Imptophores of \Uo toxin, th*w nniy l>e reganled as 
neutralized or [vrartically destroyed, and the cell has suffered a 
** defect " which aiast be replaced by regen< rative processes. This 
usually fallows promptly according to the well-known theor}" of 
Weigcrt that destruction is followed by regenenition. In acconl- 
ance with the mme theory this regeneratinn ofl;en more than re- 
places the loss, sn that in the case under discussion there is an 
overproduction ni^ n ccptors in the cell, and some of tlit^se are 
extrutled from the cell into the blood -plasma. The actual extra- 
eioD or separation of the haptophore gronps requires the stimulus 
of the toxophorc gj-oup. The stpamted haptupliore groups now 
free in the bloud-plasnia constitute tlie anHtarh}., since they are 
now free and able to combine witli the toxins before these can 
reach cells susceptible to the action of the toxopliore group. The 
toxin thus combined with a liberated receptor (antitoxin] is inca- 
pable of harm, as its own ha|>toph(Kre grou|> is promptly joined to 
the antitoxin and cannftt, therefor*-, become anchored to a vulner- 
alde cell, which is the prerequisite for the operation of the toxo- 
phorc group upon a cell, A tier antitoxin formation has begun, it 
may continnc for some time, tausiiig successive discharges into 
the blood-stre^im of the antitoxic material. This is shown by the 
continued presence of antitoxin in animals that have been bled so 
abundantly that practically all tin? oriLdual blood must have been 

All the steps in this theory have been practically demon- 
strated. In the first place, it has been shown that the toxin eutera 
into firm combination with the cell by mixing tetanus toxin and 
ennilsioDS of normal brain tissue. Under these circumstances a 
certain proportion, or all, of the toxin unites with the nerve-cella 


PSRZ^u frv«u I2f(r oranLdiisaes «f tiM* iapK^AicR- CTcw|i^ <if the tox- 
in ToA 'S ^dut obEL SM i$ zi»d«p«MieBi <4 ibe v«x«|iliOfv gmp. 
Ttik in^ i/aoKmsaaaub^ hj prwiiiaiiE ii K T eja ei i fnfmpdfaifitT to 
fii^ ^.o:<c ^.^ Vjxis in aziiinai^ iw:<nziiiCMi vidi K<ix<«d a kodT de- 
HT'e'i fr.ffii Vjxin Un Latiii^ x»n loxic qiiilhie« ^ Ute «>xotd has 
fife*. ^asK; crjmUziioe <a|»dtr ibr rEOPfiK*^ •I'f ii»e oeU? a« fass the 
loxjs. l*aT h -amplT lac^ the toxcfiiKV^ gr^i^ips. which s«i«iiehow 
iaiTe diapfiearra or beeome alseraL In liK- experiment just 




Fi^ <S.— £ ?e&«Bfr fik-TTiar cell vixh reccyCon • e . Ooe reeeftor hw bees oorapied 
^^ A Vvxjs zaf>:>WT;> t> . Tbcs« hu z«sa]s«d a£ OT«7e:>!iQcsxo w renpioa and tvo of 
»•» ^'' zjkr^ t0ttKimt f«7Axase4 fr«c the ctll. 

//. ^.i/KSut titvwisf u.'Xin co^nzies ^ anached to free ivc«fSrcB tc^ is tbe blood. 
Tz^, v.z.^ > :&-3s pnT«iu4 frr-a anartimg iuelf to tbe xtceptoa < a of tke cell aad the 

tf¥AfA Uifrre was no trace of antiiorin in the blood : hence the tox- 
^Ad was fsnyeiA^ of causing increased prvJ notion of receptors an 
(A^ f^^ffjt hut not free in the l>loi>i as antitoxin. Other experiments 
fthow t?iat thfr stimoln^ of the t«»xophore gniup is necessary to 
^aa.-f- the r!f:paration of new-formed receptors fn.»m the celL In 
th*r thinl placfr. it has been shown that the antitoxin formation 
tak'-- plar,-^ in the fixed tissue-cells, where the toxin finds suitable 
r^*-ptor*. and n'»t in the cireulatine Mooil its*?lf. since antitoxin 
c^^uM \fH extracted with salt solution? from the blood-making or- 
'^^xit of animals that had been treated with toxin but had not yet 
any antit^>xin in the blood. Of course, the period of time during 
which -uch an experiment could succeed! must be a very brief one, 
but it has been accomplished. 

Numerous experiments have shown that the antitoxin is not 
altenr^l toxin, but a new pnxiuction. as stated in this theory. The 
larjre amount of antitoxin produced by a small amount of toxin 
alone would suflSce to disprove the theon- of transformation. 

Haptophore groups or receptors still in connection with the 



parent cell are not to be regarded as antitoxin ; rather the contrary, 

for they serve to anchor the toxin to the cell where the toxoplifire 
group is in position to injure the cell (Fig. H2.) The experiment 
quoted above showe<l this for the animal treated with toxoid de- 
veloped increased vidnembility to toxin (because of the incn_^ascd 
n u m be r o f rece p to rs ) n nd 1 1 ad n o t ra ee o f a n ti to x i n i n i ts b lof h L It 
is only liaptophore groups that are free in the cireulation, and 
therefore, capable of fixing toxin and keeping it away from the 
cells that constitute antitoxin. 

6. Baeterml'Immiinit}/, — The application of Ehrlich's theory 
to the phenomena of bacterial-immnnity is quite as witivsfactory 
as it is t4> the iV*rraatiou of antitoxins. When a bacterium is 
introdueetl into the bo«ly, the problem of the defence of the organ- 
ism against the invading bactcriuui ts mucli more complicated 
than that of tlie dt?fi:nce against a toxin, because tlie bacterium 
contains a variety of sulKstanceSj such as it.s [irotein, various fer- 
ments, and even siwx-ifjc toxin^s elaborated in tlie cidture-uiedium, 
and after its introduction into the animal organism more toxin is 
elaborated. In ecKisetpit'uce, thf d*^fenee of tiie animal orgiintsin 
against the bacterium is a complicated one» involving formation 
of antitt)xin and other antagonistic bodies, including those which 
attack the ijaeterium itS4*lf in contnidistinetion to the proilucts 
of the baeterium. The <lefeust* against the bacterium is the proc- 
ess that has l>een refcrre^l to previousiy in describing Pfeiffer's 
phenomena of bae tenolysis. Tins process, aeeonling to Ehrlich's 
investigations, is pmetically identical with that of hemolysis, 
or destruction of red corpuscles, which cx-curg when the bkiocl 
of one animal is injected into another, or when ceiiain henio- 
U'tic agents, like snake-venom, are intrrxluecd into the bltK»d. 
As the stuily of the heuiolysis is pmetically much easier than that 
of Imeteriolysis, tlie theory was elaborated on the basis of experi- 
ments in hemolysis, and twii distinct substances or bodies are 
involved in the process. One of these Ehrlieli formerly desig- 
nated as the Intrnnedtartf-bofJt/ in the ease of liemolysis, or the 
immHHr-hoffj/ in the case of bacterial -immunity ; the second is a 
coniplenientary body, and is ilesiguated the comjffemenL The 
intermediary-body, or immune-body, is a product of cell acti\^ty 
under the intlueuce of infect ions, toxic, or other agencies^ which 
in set fn*e in the same manner as is the haptophore group or re- 
ceptor in the case of antitoxin formation. It has two haptophoi-e 
groups — one having affinity for the complement, and therefore 
* designated mmpk'mentophifh: ; and the other having affinity for the 
bacterium, red corpuscle, or other cell, and therefore designated 
etftophilic. On account t>f this possession of two haptophore groups 
Ehrlich has lately designated the intcrmediary*body by the term 
nmboceptnr. It is a stable substance, not influenced by moderate 
heat. The complement^ on the other hand, is a ferment-like 


body, and is a constituent of normal blood-plasma. Its ferment- 
like character is evidenced by its ready destractibility by heat 
(55^ or 56^ C.) The complement is probably, in a great meas- 
ure, derived from the leukocytes. Without the complement the 
amlxx:*eptor is a harmless substance, and without the amboceptor 
the complement cannot affect the cells (bacteria, red blood- 
corpu&^:les, etc.). The cytophilic group of an amboceptor is more 
or lei^s specific, so that, imless the recept<»rs (haptophore groups) 
of the bacteria, red corpuscles, etc., are homologous with the 
cytophilic haptophore of the amboceptor, and the complement is 
homologTiUs with the complementophilic haptophore of the amho- 
cffptor, the three elements cannot be brought into relation — in 
other wonls, the amboceptors and complements are more or less 
F?pef;ifie and must be homologous with the receptive haptophores 
or receptors of the cells. There must, then, be a great many 
varieties of receptors — perhaps hundreds or thousands — in order 
to fix the equally numerous varieties of amboceptors, and the same 
is doubtless true of the complement. Various substances doubt- 
less act as complements. Thus in experiments on snake- venom, 
Kvi's found that lecithin is the complement. 

Tlif l^acteriolysin of Buchner called by him aleorin is according 
to nr<x*nt views a compound substance one part being the ambo- 
ceptor, the other the complement. 

Expfanation of Pfeiffer^s Phenomenon, — The phenomenon of 
Pfeiffer's bacteriolysis may be explained in the following manner: 
NVImh a bacterium, with a quantity of immune serum, is intro- 
'liic<,'d into the peritoneal cavity of a non-immunized animal, am- 
\nH'jt])t<)T^, df-rived from the immune serum attach themselves to it 
TIh' complement (ly.sin) present in the |>eritoneal fluid then be- 
comes anchored to the complementophilic haptophore group of the 
amlMK'<|)tor, and in this jx)sition is able to bring about the solution 
of {\n' \}ii('U'num and its destruction. The phenomena of hemo- 
lysis may br- explained in the same way : the aml>oceptor first 
attarjio itsflf to the rod corpuscle, and the complement (hemo- 
lysin; in turn attaches itself to the amboceptor. 

The nicfssity for two bodies in the production of these phe- 
nonii-na lias been tliorou^dily demonstrated. It is known that 
••enim eapai*lc of phmUkmii^ Pfeitfcr's phenomena in vitro loses 
tlii- |K»\ver when sul>jecte<l lor a certain length of time to heat or 
?-iinli^Hit. A prompt restoration of the ]>ower follows the addition 
of -mall quantities of normal (uiiheated) serum of the same animal 
ujK'eieu. This proves that a ferment-like body (destroyed by heat) 
is a necessary factor, and that this ferment is present in the 
normal nerum of the animal. The importance of the complement 
has been further <lemonstrated by the formation of anticoraple- 
ments, which are capable of combining with it and thus stopping 
its motion. When the; anticomplement is withdrawn, the comple- 



mcut is again eapal>le of o{>emtiiig. In a similar manner anti- 
ainljoeeptors have bet-n pruclncudt and have .sometimes heeii found 
in the blocHl of nnrnml animals. 

The following scheme represents graphically the relatit>ns i)f 
the amlxx'eptor and complement to the cell and tlie possihilitie?i of 
various anti-bodies such as the anticymplement and antiambo- 
cepti^r : 

The following tables (modified fnim Miiller) will show in a 
condensed form the varieties t>f immunity detailed in the foregoing 
paragraphs : 

A n tUoxic Im m un itu, 
h Cellular. 

A. Lack of appropriate receptors. 
(si) congeiiitiil 
(b) acquired (loss of the receptors) 

B. Lack of susceptibUity to the toxophore group 
of the toxin. 

(ii) eon genital 
(b) iict|uired (?) 

C. Attachment of the toxin tu insusceptible 

ill) congenital 
b) acquired (development of new re- 
ceptors in in»mceptible tissues) 

IL HematogeDic* 

A. Acti\*e 

(a) manifest form (abnndance of anti- 
toxin in the blood) 

(b) latent form (no antitoxin present but 
capaiity for making it quickly 
and abundantly) 


B. Ptosive, 

Antitoxin is introdnced : 

(a) through the placenta to the fetus. 

(b ) milk to the nursling. 

(c) by direct injection. 

Amtibacterial Jmmymiijf. 
L Xaxnral (congenit&l • 

a. The animal organism is an unsuitable me- 

dium for the growth of the bacterium. 

b. The organisms are destroyed at the point of 

infection by amboceptors and compl^nents 

c. Amboceptors present but no complements. 

The latter are supplied by 

1. increase supply of tissue fluids 

2. advent of wandering cells. 

d. Complement present but no amboceptom 

The latter are supplied : 

1. locally 

2. by the lymphoid blood-making orrans. 

e. Phagocytosis and intra-phagocytic bacterioly- 


U. Aniioially Increased but not 5?pecific (Piseudo im- 
iL'.ijii:y . Injection of irritating substances which 
^:a:is^ local acctimulation of phagocytes and bac- 

IIL V^tnrilly acquired specific immunity. 

IV. Ardficaliy acquired specific immunity. 

a. Active Immunity. 

1. Abundant presence of specific ambo- 

ceptors in the blood and ttsHie flnkk. 

2. No performed amboceptors bat ui- 

creased capacity to manufiicture such. 

b. Pasfiive Immunity. 

«>pecific amboceptors in the blood tderived 
from another animal). 

¥l\r/y':.'^ :h*<jr\- al^o explains certain pnicesses* soch as agglati- 
r:i*' •;.. ir*ii;:pitation. c\tolysis, etc., which an? noc actively cim- 
'■-rr.^^i .:. ::.*: pfi*-n<imeiia of immunity, but may be refrrrcJ to in 
■* * ;.:>>: .'. lififfiinx of their illustrating the af^iUcaiioos ot the 

AtCVTtrractioii. — Bacterial agglutination ( Pfeiffer-Gniber-Dar- 
:^< '■- :oi^'.f,vrry/ri i* #'xplained by Ehrlich's thei»ry 5«^mewhat in 
'li' •Ji.ij*: viv 2l. \fii('Ur\c)\\'T\< and hemolysis* In the case of 
aiijT-.nlrif.^.'f. . ':.oyk''\f'T. there is but one agent — a liberated ambo- 
'^;i:',»r. :^tv.:,.ij a haptophore group, which attaches itself to the 
\ski*'\.^rvjn> , a zymophore group, which plays a part similar to 
that of t:j^ 'f.<s.\,\t'mf:T\X in l»acteriolysis (Fig. Sl, II dL It differs 
fn.mi tli^r 'r.f:.i^,*-rri*-nt, however, in that the zymophore groap is 
an ijuiegra] yi^T'^ of the amboceptor, and not a separate loly, whkh 
attache^ \x^\{ */, the latter. A serum which has the prp^erty of 
agglutiimtiii^ t:i*- \Afrif:nsL of a certain disease (ase.^^ typiwrf fevwr^ 



contains liberated amboceptors that were set free by the cells of 
the body and that hiive the property of attaching themselves to 
the specific bacteria concerned in that disease* When so attached, 
their ferment-like group or zymophore group, which is the active 
agent, produees agglutination. (See Typhoid Biicilhis.) 

Precipitm. — Tlie phenomena of precipitiitioii of varioiie sub« 
stances tiiat have been introdueed into an animal organism by the 
action of serum derived from the blood of sueh animals liave 
l>een ascribed to speeiiic ** precii»itin8." Thus, when the bhxKj 
of liuman beings is repeatedly intrtxluced into the peritoneal 
cavity of rabbits, tlie raljbit-serum aetpiirt^s the property of pre- 
cipitating human hlo*>d. When the blood of several animals in 
succession is introdnred into an animal of a different species fn>m 
each of these, it is found that the preeipitiition is a speciiie process, 
since the 8|3ecific power to precipitate the bkxxl of each of the 
specMCs employee 1 can be successively demonstrated. Wlien albu- 
minous lifjuids or such a complex mixture as milk is introduced 
into animals, the bloo+l-sonnn uf tht* animals acquires the property 
of precipitating the albumin used (>r the milk {easeiii). This and 
other experiments show the wide nuigt* of applicability of the 
principle of preeipitation. Elirlieh explains the |mtcess of precipi- 
tation in the same way as thai of agglutiuatiou, liy the assumption 
that araboeeptors carrying hapt^>pliore groups with an afBnity for 
the j>red|jitabk' body are set free in the sernm^ and that asso- 
ciatetl as an integral jiiirt of these amboceptors are zymophore 
groups capable of producing the phenomena of precipitation or 
agglutination. The zymophore gnni|)s are destructible by heat, 
though the degree of heat is mucli higher than that required to 
destroy the complements eoneernetl in bacterial destruction and 

Cytoly Bin.— Injections of emulsions of various cells into animals 
have been fouu<l to generate destruetive substances in the serura 
of the experimental animals. These destruetive Ixxlies are speeific 
for the cells used iu the experiment. Thus spermatolysin, epi- 
tludiolysin, and hepatolysiu are substances whicli will eause 
destruction of spermatozoa, epithelia, and hejtatie celJs res|>ec- 
tively. The phennmena involved in soeh cytolysis are closely 
allie<l with those of bacteriolysis and hemolysis^ but require 
further study. 


The bacterial diseases form a large and increasing group. In 
jme cases it has been shown by the positive application of KcK.'lrs 
^iles (see page 31) that the suspected micro-organisms are the 
actual causes of the diseases under consideration ; in more numer- 


<«§ i]k«taiK«s all of die mlcs caniMC be ^iplied, bat otber < 
eia&CA* ;p> ^u- u> vanJ egtabli4iinfr the g| i eql i c natore of 
uattenk : in sdll <:Hfaer case? tbe evidence vrnmn^ a stni 
<rv>o of the ftttbr^p^nicrrr of bacteria found in eoonectioQ vitli cer- 
tain dis«L9<bs. bat there i* nothing approaching actnal demoiKtiatkn. 
DirisoD of inCwtioos diseases into those of cenain and thoee 
of anccTtain faacteriologv must cao^e difference^ c*f opinion. It is 
adopted oolj for coarenience. the merits of each individod case 
b»n? coQssderevi in the discossion of the individual diseases. 



Definiticm. — Und^r this bending we include for the present 
varioa= f^>nns of suppurative inflammation^ such as funincnloeis, 
ab=r:«::^:r-K>rmation. and allied diseases, like oeteomvelitisw endocar- 
ditis, cellulitis, etc. . 

Stiology. — ^Xomerous organisms have been found to have 
the power of prodocing suppuration. Amoi^ these the staphvlo- 
coccus group is most important. The Streptococcus pyogenes seu 
ervsipeiatis is alsri of great significance : less fineouentlv the IHp- 
krtoccus pneumanis. the Pneumobacillns of Friealander, the Bm- 
cilia* pvoryaneur. tbe typhoid bacillus, the Bacillus eoli communis 
or tbe Bacillus pyogenes fcetidus. the gonococcus. and others. 
Som^ caries of suppurative disea:!e are due to a single organism ; 
in many there is double or multiple infection. 

1. The Staph^ococcns Groop. — Among these have been de- 
scribed three important forms, the Staphylococcus pyogenes 
aureus, albus, and citreus. 

The Staphylococcus pyogenee aureus is a minute, rounded 
body aiffrnt 0.5. to 1 u in diameter, having no motility and not 
formine ^po^es. When found in the tissues the cocci are apt to 
be a'^-sociated in clusters, whence the term staphylococcus (Fig. 84). 
Sometimes they are grouped in pairs, and may thus present a re- 
semblance to gonococci. The opposed surfaces, however, are flat 
instead of concave, as is the «^se with the gonococci. The 
staphylococcus may be stained with onlinary anilin solutions anc 
is beautifully demonstrated by Gram's method. Cultures arc 
easily obtained upon the ordinary- media. The most characteristic 
gro\ith is that upon agar. Along the line of inoculation a moist • 
colf»ny develops, with at tirst a whitish but soon an orange-yellow 
CTilor. The gro^^-th in gelatin causes rapid liquefaction and the 
precipitation of orange-yellow particles. The growth Ls best ob- 
tained at oven-temperatures (25° to 35^ C.) but may be secured 
at lower degrees. 

Didribution, — The Staphylococcus aureus is frequently found 
upon the skin or in the various external secretions of healthy in- 



divitluals* It does not seem to flourisli anywhere apart, from the 
I bodies of man or aiiinials, }>iit may remain in an active state in the 
' dust of Rioms or upon clothing and the like. It lias been found 

in various lesions of the body ; notiibly, however, in furuncles, ab- 

Fio.84,— SUipbylococcu* pyogenes mlbuj (Jakob). 

Boesses, and earbuneles, and in ulcerative ennditious of t!ie exterior 
or of the raucous membnuies. It Ls also frequent in internal suppu- 
rative inHammations, such as malignant endix^arditis, osteomyelitis, 
appendieeal abscesses^ etc. In many of these lesions other organ- 
is ras may be associated. 

Pathniofjie Phfinffihf/}/. — ^Filtrates of the cidtures nm\ the 
bodies of the stajihylococci (killed by heat) contain highly toxic 
substances capable of pnxhicing intense infJammations and sup* 
puration. Certain of their pro<lucts are markedly hemolytic. 

When injeetcd into tlie subcuhnicous tissue the ,stiiphyloct>L'eu8 
produces local effects. The orgiiuisms nuiy become liljcrated, 
gain cutmneu to tlie eireulatinn, ;uid prothiee widesprea<l results; 
but it do€8 not seem to produce extra cellular toxins that cause 
generab'zed results* The effects of tlie staphyloeoeeus seem to be 
due ratlier to a certiin poisonous body contained in the organism 
itself. This has been termed the bacterial jirotein, and it has 
been thought to belong to the group of alkaline albuminates. 
This body ljy its chemotactic effect causes the leukocytic aceinuu- 
latious found in suppurative inflammations. The staphylococcus 
also leads to liquefaction in the tissues, as in gelatin^ luit whether 
directly or through tlie accumulation of botlies derived tmm leu- 
kocytes is uncertain. The defence of the orgunism against the 
staphyliX'occus is partly median ical and partly vital. Tin' leu- 
kocytes probably engli»be a certain number of organisms and 
cause their destruction, while stjluble bactericidal bodies, seem to 
be produced in the course of the infection. These have Ireen 
termed alexins (see Immunity.) 


Pathogenicity. — When virulent cultures are injected into ani- 
mals, abscesses are produced and a fatal termination may follow. 
In the latter cases diffusion through the blood is found, and 
infarcts of the kidneys, lungs and other organs caused by bacterial 
emboli are discovered. Multiple abscesses may be seen. The 
organism readily loses its virulence, as in the case of those found 
upon the skin of healthy persons and in other accidental situations. 
When rubbed in a virulent state into the skin of man it produces 
abscesses or boils. 

Staphylococcus PyogeneB Albus. — ^ThLs organism Ls practi- 
cally identical with the last-named in morphology, but in culture 
produces a w^hite instead of a yellow growth. It has been found 
as a frequent harmless parasite of the skm (Staphylococcus epiderm- 
idis albus of Welch). It occurs in abscesses and various suppu- 
rative diseases, but rarely alone. As a rule, it is associated with 
the golden staphylococcus or other organisms. It is distinctly less 
virulent than the aureus. 

Staphylococcus Pyogrenes Gitreus. — ^This form is the least 
important of the three. It is not so common and, as a rule, less 
virulent. It differs in the brilliant lemon color obtained upon 
culture in various media. 

2. The Streptococciui Pyogenes sen Erysipelatis. — Under the 
name fdreptococcas are included various spherical bacteria which, 
as a rule, divide only in one plane and form chains of varj-ing 
length. The different forms resemble each other so closely that 
tamie authors group them all, including the Micrococcus or Strep- 
t4>cocru8 ])iicurn()niae, under one general head. The latter, however, 
h>eeiii8 sufficiently differentiated to merit separate classification. 

TJie Streptococcus pyogenes was first studied by Rosenbach in 
(^ses of suppuration. A similar organism was afterward described 
as tlie Streptococcus erysipelatis by Fehleisen. It would seem, 
h(jw<fvc*r, that these two organisms are identical. At all events, 
iUcrt* are no distinguishing features which we can point out. The 
strept^)coccus is a small spherical organism of variable size (0.5 to 
1 // ) frequently associated in chains of from three to twenty or 
more individuals (Fig. 85). Not rarely it occurs in diplococcus 
form (as pairs). It is easily stained with ordinary anilin solution 
or by (iranr.s methcKl. the eoc^i are not motile. Spore-for- 
mation has not been observed, but occasionally in chains one of the 
individual members is larger than the rest, suggesting arthro- 
sjxires. lTjK)n artificial media sciuitv but rather characteristic 
growths arc; obtained. On the gelatin plate there are formed 
small, translueent, whitish or yellowish colonies of irregular out- 
line. The gelatin is not lifjuefied. Upon agar a verj' thin, trans- 
parent growth forms around the line of inoculation.' It consists 
of separate colonies which do not become confluent In milk the 
growth is usually abundant and attended with lactic acid for- 
mation and coagulation of the casein. 


The dwlribuHon of the .streptococxjus is much the same as that 
of the staphylococei, though it is less commonly discovered about 
tbe healthy body. It may, however, be foimd upon the mu- 
cous meml>ranes or in the various i^x^retions or cxeretions of the 
body. It is probably a strict parasite, multiplying only within 
the living organism. 

In disease it has been fonnd in various forms of snppurationj 
such as phlegmonous forms of inflammatioo of the subcutaneous 
nr siAmucons tis^sues, either alone or in association with other 
organisms. It r^ccun? occasionally in fix;al suppurations, such as 
abscesses, though these are more commonly due to staphylococci 

Flo, 85.— Strt'ihtiHOcriis pyogenes (Jftkob). 

alone. The streptncocens occurs at limes in uh_*erative endocar* 
ditis, not nirely iu infectious endometritis and in goueralizcd ^ep* 
ticopyeniia, Streptocin'cic inflammations of tlie thrnnt are of 
great interest. They ninv i>ccur in persons previously in good 
health, or in the cours<^ of infectious dispases, like scarlatina, 
meask'S, or influenza. To tlie clinician, tlic resulting It^sion may 
he indistinguishable troiii that of diplitherin ; baetcriolngic exami- 
nation alrme serves to establish tlir diagnosis. The streptococcus 
is found in all cases of erysipelus, in the tissues and in the serum 
or other exudations. 

Paiholoqic Plufaiolofjy and Pathogpfimiii.— The streptoerM?cus 
wcmlil seem to be more active in the pnxluction of soluble 
toxins than the staphylococci. The toxhi has been made by inocu- 
lating small quantities of bouillon witli virulent eoeci, allowing 
these to grow for seveml weeks, and then destn^ying the orgjinisms 
by heat. The injection of the toxins thus prrKluctHl leads to local 
and general reaction. While there is a certain amount of this 
extra-eel hilar toxin it seems that most of the toxie sulistances of 


streptococci are embodied in the micro-organism itself. In vinilenl 
cultures actively hemolytic bodies are often frequent and certaii 
streptococcic infections in man are attended with hemorrhages and 
evidences of hemolysis. 

Injected into animals (intravenously) virulent streptococci may 
occasion septicemia but it is notoriously difficult to obtain cultures 
of great violence and the succeeding generations soon lose their 
power. White mice and rabbits are the most susceptible animals. 
Subcutaneous injections may cause abscesses or erysipelas. 

A single attack of erysii>elas or streptococcic infection confers 
no immunity on man and similarly one inoculation occasions no 
immunity in animals. By rc()cat(nl injections, however, an anii- 
streptorocciis aerum of some potency has been obtained. Recent 
studies show that more satisfactory practical results may be obtained 
when the antistreptococcus serum has been prepared with a strain 
of organisms similar to that present in the case under treatment. 
For this reason mixtures of serum ]>repared with several strains 
are used (ix)lyvalent sera) so that in a clinical case (because of the 
difficulty in distinguishing various strains) a specifically active 
anti-senun may be administered. 

Streptococcus intracellalaris meningitidis (Weichselbaum). — This 
organism, also called vienvu/ococcu^ or Diplococciis nienijif/itidkyU 
found in the meningeal pus, nasal mucous, sputum, and urine of 
I : I individuals affecteil with epidemic cerebrospinal meningitis. This 

■ micro-orgjinism in some resi)ects resembles very closely the Pneu- 

i ' I mocxKJCUs or Streptococcus lanceolatus and in its form and intra- 

p I cellular cxxjurrence still more closely the gonococcus. 

The oi^anism appears as a biscuit-sha|>ed diplococcus, bui 
sometimes as tetrads or in clumps, a!id occasionally as short chains 
i!i which the line of cleavage between the diplococci is in the same 
direc^tion as that of the chain. The organism is Gram negative, 
but is easily staimMl with Ijoffler's methylene-blue. Some authors 
claim that it may be Gram i)ositive, but such forms are probably 
otluT associated micrococci. 

In the meningeal exudates it is usually found within l)oly- 
m()r|)lionucelear leukocytes like the g<mococcus. Some have 
described its occurreiKH? within the cellular nuclei ; this is doubt- 
Hi '"'• 

It grows well at 37.5® (\ on blood-agar, serum-agar and plain 

agjir. ( )u the latter there apjx'ar, in 48 hours, flat, grayish-white, 
faintly gnuiular and viscid colonies that do not coalesce. On 
blooil-agjir the colonies are more luxuriant. 

T1h» cultures may live for w(M»ks but often die in a few days 
and thcrcfon* recjuire fnM|uent transplantation. 

l>isfrlbntlon, — The meningococcus is found in the sero-puruleni 
exudate of epidemic cerebrospinal meningitis and is readily 
demonstrated in the fluid obtained by lumbar puncture. It has 

' I 



frecjuently been foiiuil in the nasal mucus wf patients 6ufleriiig 
tW>iii the di,seaR* aud iu ht'iihhy individuulft iiHire or less closely 
a^HX'iat^^d witii the patient. The iisMunption is, that the meningeal 
infection tjccurs by passage of the or^i^an isms frurii tlie nose or sinuses 
adjacent to the meninges througli the lyniph channels. Recent 
experiments seem to indicate tlxat the organisms may tnivel in the 
opposite direction for in monkeys infected by intradural in^>eu- 
lation, tiie orgauisnis were found in tlie nasal cavities after a short 
interval. Organisms r^^st^nd)lillg tlie nieningococcns and probably 
actuid meningofocei have Inen found in the hings in eases of bron- 
chitis and pneumonia complif*ating epidemic meningitis. The 
raeningocoeeus has been found in the blood in 10 of 40 cases of 
the disease (Elser), 

Pathologic Phtfswloffif and Pfifho(/eiie8w. — Large subcutaneous 
injections may cause death ant! intrapleural and intraperitoneal 
injections may kill animals ami cause a fibri no-purulent inflam- 
mation of the serous luemljrane. Subdural inoeuhition (spinal and 
cerebral) in dogs and monkeys have caused lesions identical with 
those found in man. 

Ofha* On/anhms in Menm^iiiK^-The pneumococcne, strep- 
toeo4"cus pyr>gcnes, staphyloeo<'ens pyogenes^ typhoid and colon 
bacilli, influenza bacillus and less commonly some other forms 
have been isolated in cases of primary meningitis or meningitis 
secondary to infection elsewhere. 

Other OrganiBms of Lesser Importance* 

The BaeiiiiiS pyocyaneu* is an occ-aaional pathogenic org-aniam found ia 
pus having a bluish or greenish color. The baeiTluH i^ small in aize^ fre- 
quently occurring in chain-formation » and is actively motile. 

Upon artificial media it produces colored growths and n soluble pig- 
ment, which gives to the culture-niediuui for some distance from the growth 
s greenish^ or in some cases a dark-blue, coloration. The organism in 
pure culture in highly virulent, producing intense suppurative mflamma- 
tiona. Occasional instances of general pyocyaoeuB infection have heen 

The opgaiiisin acts destructively upon other bacteria so that a fatal 
do»e of Bariifm artthrfieij* may he rendered innocuous by the s«iniultaneou» 
injection of /?. ptjortjauene. The destructive efTect ban been dtmonstratefl 
in vitro. It 8eem« dependent on ferments sw well as intracellular substances 
contained in the bacillus. 

The BaeiUuM pijofftntA ftrtidw^ is probably identical with the Bacillus col i 
communis, or is at least a clone relative. These organiamM, as well as the 
typlioid bacillus, the Diplococcusoneumoniie, the Diplococcus meningitidis, 
and the Pneumobacillus of Friealander, any of which may excite suppur- 
ation, are referred to elsewhere. 

Micrococcus Tttragenus, — ^This form is a micrococcus from I to 2 /j in 
diameter, and receives its name from the peculiar association in groups of 
four. It occure in the sputum and contents of cavities in pulmonary 
phthisis^ and occasionally elsewhere. It may give rise to general sepsis. 

BaeiUm LacHs Mro^fnei. — This organism resembles Friedlander's pneu- 


mobacillus quite closely. In large doses it occasions suppuration in animal 
experiments, while in man it has been found associated with purulent 
cystitis, pyelitis, and pyelonephritis. In consequence of its fermentative 
power it may occasion pneumcUuria, 

Micrococcus caiarrhalU is a micro-or^nism found by PfeifTer in cases of 
bronchitis in which there was a great deal of expectoration, and in which 
the symptoms resembled those of influenza. It is a small coccus, usually 
occurring in diplococcic form, and resembling the micrococcus of gonorrhea. 
It often IS seen within the pus-cells, and occurs in large numbers in the 
sputum and nasal secretion of individuals suffering from bronchitis. It 
does not cause the constitutional disturbance that is caused by the bacillus 
of influenza, but it is often found as an associated infective agent in cases 
of pneumonia due either to the Diplococcus pneumoniae or to the bacillus 
of influenza. To obtain it in pure culture it is best grown on blood-agar. 
It grows as sharply defined, somewhat raised, granular, yellowish, non- 
transparent colonies on the surface of agar. It resembles the Staphylo- 
coccus pyogenes aureus, but the colonies are much more raised and haraer. 
They can be picked up on the end of the needle, and are crushed with diffi- 
culty. The needle can be drawn across the culture without destroying the 
integrity of the individual colonies. After the first generation the micro- 
coccus grows well on ordinary agar, but it must be transferred every three 
or four days to be kept alive. It is decolorized by Gram's method. Its 
pathogenicity is as yet undetermined. In its behavior toward animals it 
resembles the bacillus of influenza. 


Definition. — Gonorrhea is an infectious inflammation of the 
urethral or other mucous membranes due to a specific organism, 
the Micrococcus gmiorrhcece or gonococcus discovered by Neisser in 



Fio. 86.— Pus from gonorrhea, showing gonococci (Jakob). 

Etiology. — There is no doubt that the gonococcus is the 
specific cause of gonorrhea. This organism is a micrococcus, 
usually arranged in pairs, the opposed surfaces of each being 



slightly concave. This arrangement has suggested the designa- 
tion ** biscuit-shaped " di|jkKxwH"Hs (Fig, 86). Sometimes gnrtips 
of fimr or more are found, while m otiier casi.'rt the coeei ueour 
singly. The orginiisius are ubaiulant in the pu.s of acute g^iaiir- 
rlieaj k*ss abuudiint in advanced stages, in tlie [His of goncFrrheal 
sidpingitis or other conditionH, and may not he discovered at alL 
Tliey generally occupy the pus-i^ells, lying in the protoplasm, 
either in small iniml>ers or so abumhuitly as to fill the cell 
uniformly. In tlie tissues the same iutnieellidar position is usual, 
bat here, as in the free pus, some nrgauisms may generally he 
fonml between the eells. The gouoeo€eus stains readily with 
ortlinary solutions of anilin tlyes, and is readily decolorized l>y 
Gram's method. 

Cultivation nf the gonrmmx'us is diffinlt. <iro\vths may, how- 
ever» i)e obtained at 37° (\ ufuju ag-ar-agar streaked with human 
blrM>»l or on nnMli:i prepared from hiimnn aseitic or pleuritic fluid 
or allmmiuous urine Later generations may grow well on ordi- 
nary media, but nsnally require the serujn additions. The growth 
in blooii-serum consists of small colonies cif grayish color that 
coalesce au<l form a fihn on the surface of the medium ; n round 
the colony may generally be seen an irivgidar ;iud inconspicuous 

The gi^mococeus eanuot be positively distingnisbed fiy its 
morpbology uor by the iutracellular position. Other organisms 
may in certain stages of tlieir growth slmw a typical bisiaiit-fonn 
(staplndococci and others) ; and the iutracclbdar position is not 
tarely assumed by a variety of bacteria. The failure to stain by 
Gnm^V nietliod and the failure to grow ttu ordinary media are 
strong points suggesting the gonocticcns, Typii-al cultures alone 
settle tlie diagnosis. A number of orgmiisms resembliug the gon- 
ococ<?us wen* found by Bnmrr* in the vaginal mncus. The Micro- 
coccus catarrhal also resembles it closely. No similar micro- 
coccus lias thus far been found in the nude urethra. 

Pathogenicity,— It has been demonstrated by direct implanta- 
tion of pure colonies upon the healthy uretlim that this organism 
will cause characteristic gonorrhea. Urethritis may, however, be 
due to other organisras ; the specific form termed gonorrhea is 
robably always due to the gonoci)e<:;us. Secondary lesions, such 

salpingitis, oophoritis, arthritis, peritonitis, conjunctivitis, endo- 
carditis» etc., may alsd be due to this organism, no other form of 
bacteria being present. Sometimes, however, complications, such 
as periurethral abscesses, suppurative adenitis, etc., are due to 
secondan^ infections. 

Pathologric Anatomy. — The lesions of gonorrhea will be 
considered elsewhere. Suffice it to ,say in this place that the 
lor^uism causes suppurative catarrh of the mucous surfaces with 


which it comes in contact. There is abundant cellular exudation 
and the orgtuiisnis tend to penetrate deeply into the ti^isue^. 

Pathologic Physiology. — Gonorrhea is in mo^ cases a 
purely local disease. Little is known of its power to produce 
soluble toxins* The effects art* probably due to an intracellular 
toxin. The distant lesions are in all cages, as £ar as we definitely 
know, dependent u[X)n deposit of the specific organism. These 
have been found in the effusions of arthritis and in the vegetations 
of gonorrheal endocarditis, as well as in tlie blood in the last named 


Definitioti,^ — There are a number of forms of inflammation 
of the puhnonary tissues to which the term pneumonia is appli* 
rable. The most definite form of disease is that s{x»ken of as 
croupous, fibrinous, or lobar pneumonia. In its typical form this 

FlO, 8B^a.— DI|>loeocci:i^ ^ n< 

'>ni:T- ill the 

kd »ndPfei<^r). 

is a specific and w^ell characterized disease. It is infectious, more 
or less cniitagiou-s and caused by a specific organism, 

Etiology. — The organism most frequently found in the lung 
in croupous pneumonia and donbtle^ the specific cause of the dis- 
ease in such cases is the Diploc^oceus pneumonict. It is less regal- 
ia rly the etiologic agent in broncho-pneumonia and atj^iical pneu- 
monias, but even in these cases it is found more frequently than 
other liacteria. 

The organism is also called the pneutmiCCHyni^^ the IHerwoeem 
lanceofahtSy and sometimes the SlreptococcuJi pnntmonkt »m hncfO- 
lotus. The diplocoecus of pneumonia was recognized in the saliva 
of healthy persons by Sternberg and Pasteur^ but its idalioo to 



Flo. m, 6. — Dlplocopotis 
pneuiMotilic : a. cocci, with- 
out cttpsulcs: 0, «iiiKle and 
paired cocci, wlHi capMiles: 
c, cbnin-fomi; d^ colony of 
cocci tZIegler). 

croupous pneumonia was first denujniitratoil by Fraukel, and later 

by Weichselbaum. The individual orgauisni luis a somewhat elun- 

gate^I, lanceolate shai)ej and has, therefore, been considered a baeil- 

lus, tliouc^di it does not ahvays show this pseudo-bacillary shupe 

distinctly f Fig. 86 a). In the sputum and 

lungSj and in tlie blood of inoculated ani- 
mals, it is commonly found in pairs ; the 

broader ends of the organisms adjaeent, and 

the {Hiiuted ends projecting otitward ; tlie 

group i.*5 .surrounded liy a tnmsparent cnjw 

sule, which doi's not readily take stuiiis nnd 

therefore l>eeome8 conspicuous (Fig. 8t>i). 

Sometimes the organism forms eliains in 

which however the |>ain5 f>f micrococci are 

a little distance apiiit. i'hain formation ig 

esjxx'ialiy marked when the fd'gjinjsm is 

grown in fluid media. The capsule is not 

seen when the orgiinism is obtained from culturcj^, Tlie dipk\ ocens 

does n«»t pos^sess individual motility and lias no flagella. It does 

not seem to pn>ibice spores. 

It may l>e readily demonstrated in the sputum or in the 

tissues by staining with the ordinary aiiilin dyes t>r by Gramas 


Cultivation. — The diplococcus grows readily upon oixiinary 

media, excepting jvotato. It forms eliaracteristic colonics upon 
ag-ar-agar pkites or in gelatin, Upon the surfbee of the agar there 
appear transparent dn>|>-like colonies hardly visible to the naked 
eye, %vliich under the microscope have a finely granular a]i|>ear- 
ance. I^pon gelatin plates sin^ilar gro^vths are produced, while in 
I gelatin punctures the growth occurs along tlie path of the wire as 
granular whitish spots sepsirated from each other. The addition 
of serum or ascitic liipiid to agar makes a medium in which larger 
and more conspicuous grayish colonies of circular outline appear 
on the surface. In the paler marginal zone of the colojiy diplo- 
ciK'ci or short, chains may be seen. In iMiuillon a cloudiness is 
produc»ed when the culture is from 12 to 24 hours old ; lat<^r the 
organisms precipitate^ and the bouillon becomes clear. Milk is 
coagulatetl by the pneumoem^iLs. When inulin is added to a 
senim metlium the |meumoeciecus ferments the inulin and eongu- 
lates the serunr, The organism tends to die out very readily in 
cultures* and also loses its pathogenic proi>erty when propagated 
for several generations. In solid media not containing serum and 
more particularly in fluid media the virulence may be preserved 
for a long time, sometimes for months. It is most luxuriant at 

Pathogenicity,' — The specific character of this organism has not 
be^n definitely proved according to the rules of Koch, but it is 


highly probable that it is the usual cause of pneumonia. The 
diplococcus is frequently found in the saliva of healthy persons. 
When this is introduced into animals, particularly rabbits, the 
animal dies, with evidences of rapid sepsis (sputum-septicemia). 
The post-mortem shows some fibrinous exudate and occasionally 
a little pus at the point of inoculation. The spleen is enlarged, 
and capsulatcd bacteria of distinct lanceolate form are widespread 
throughout the body. Injections of lung-tissue or of pneumonic 
sputum produce similar results, and the organism in pure culture 
likewise causes this form of septicemia. It has been sho.wn that 
injection of pneumonic exudate aspirated from the consolidated lung 
into the lungs of rabbits will produce true pneumonia. Recently 
typical pneumonia has be(»n produced by injection of virulent 
pneumo<M>cci into the lungs of rabbits previously immunized 
against the pneumococcus to prevent the occurrence of general 
pneumococcus septicemia. 

Besides the di|>lococcus there are certainly other elements 
which contribute to the causation of the disease, else the frequent 
oc(mrrence of the micro-organism in question in the saliva would 
make pneumonia a much more common affection. The nature of 
the contributing causes is, however, obscure. Exposure to cold, 
general de])ression of the system, traumatism, alcoholism, and other 
causes certainly predispose or help to determine the occurrence of 
the diswise. These causes may act by temporarily increasing the 
virulence of the diplococcus or by lowering the resistive power. 

Certiiin irregular forms of lobar pneumonia may be caused by 
strep toc(K!ci, staphylococci, the Bacillus pneumoniae of Friea- 
lander, tlie influenza bacillus, that of typhoid fever, etc.; but true 
croupfMis pneumonia is probably always due to the Diplococcus 

Pathologic Anatomy. — (Soa Diseases of the Lungs.) 

Pathologic Physiology. — The diphx^occus produces, in the 
first place, local lesions of the lungs; and in the second place, 
systemic infection and [x>ssibly also general intoxication by toxins 
of une<»rtain eliaracter. In the case of svstemic infection the 
orgtiuism itself gains access to the blocxl an^ may produce second- 
ary l(\sions in other organs. Infection with the diplococcus of 
pneiimouia causes a pn)nounce<l reaction on the part of the blood 
in the form of leukocytosis. Tliis is not invariable, ijjut is usually 
seen. After the attack of pneumonia then* is temporary immunity, 
and it has been found that animals may be immunized for consid- 
erable lengths of time by r(*i>eate(l injection of pneumococci. 
The serum of the immunized animal has a certain protective and 
curative value which has recently been attributed to the formation 
of opsonins (see Immunity\ whit^h are operative by rendering the 
pneumoc»occi liable to ra]>id ingestion by phagocytes. 

The IMplococcu8 in Other Diseases.— The Diplocoocus 


pneuinonitt* has beori fnimd in various conditions cotnplifating 
pntHinioiitUj and occa.siniuilly in legions nniissoeiatcd witli croujwns 
piieinntmia* Among other losions, Bieningiti]>?i ph^urisy, and other 
inflammations of the tierous suriiiccs,!es8es, otitis media, and 
arthritis have been found h) he due to this organism ; or, at least, 
this organism alone has been found in some of these cases, 


Amnn*r other varieties of pneuniouia may he mentioned the 
catarriial or h»l>nlar form, the tuhereuloiis form, and various irix^g- 
nlar pneumonias^ partly eelhdar, partly fibrinous, partly purulent 
or hemorrhagic. Though the piu'nnioeoecus is nK»re frequently 
present than any other single ^>rganism in lironclio-pnennuinias 
atler infections diseases like measles and diphtlieria autl in various 
irregnlar types of l)i"onehu-pneunioniu, ditierent nrganisjns may be 
found in sneh cases, and some of these may l>e of etiu logic impor- 
tance in certain cases. Not rarely the pulmonary tlisease is tlie 
result of mixed (double or multiple) inicction. 

The Bacillus Pnetunoniae of Friedlander, — ^11 us orgjinism was 
regarded at one time as the cause of crtaipous pneumonia. It 
pnibably occurs in most cases as a mixed infee*tiou, th(nigh it may 
occasionally be tlie cause of catarrhal or irregular fin'ms of pneu- 
monia or of ordinary cnjupous pncnnionia* 
The eases of pneumonia due primarily to the 
pnetmiol>acillus arc cliaracterizwl by their 
virulence and a [leeuliar viscid eliameter fd* 
the exn<!ate in the limg. Frie^llandcr^s 
orginiism ocrurs as a distinct hacilUis, usually 
in pairs and surnuindcd bv a capsule like 

that Ot the dlpiocOCCUS(r Ig. ^ibe), JSome- monlai of FriLdliuder, 

tim<^ it may form chains of three, four, or 

more organisms. It stains well witli tfjc a nil in dyes, hut is de<3ol- 
ori7e<l by Oram's meth«Kh A cliaraeteristic culture is ohtaintHi in 
gelatin. The puneturc-<;nUiU"e is tvharaetcrized by a luxuriant 
growth at the top anrl a consiih'nd>le vegetation all along the 
track. This leads to a nail-shaped growtli. The gelatin iloes not 
liquefy. Upon agar a considcmhle whitish or yellowish moist 
gr<5\vth oecurs U|>on the surfaec. There is formation of gas in 
mcilia containing gluei>se, and often also on potato. 

A number of organisms closely ndatetl to Friedlandcr's puen- 
moooc^ens have Ijccn classified under the generic name Baci/luH 
vtucomtJi ca}}mtiatitfi. Among these are the li, laethatTOf/nu-Hj B. 
fwifli hcticiy B. ozaf'tHv and /?. rhhmftohromafis. The several ty}>es 
differ somewhat in their power to ferment various carbohydrates. 

Other Organisma in PEeainoma. Among the variiuis organisms 
that have been f«»nnd in broneho-pncnmonia or less commonly 
fibrinous types of pneumonia are the SlreptoctK^cns pyt^nes, more 


rarely the influenza bacillus, the Bacillus coli communis, the 
typhoid bacillus, the bacillus of glanders, of the plague, and occa- 
sionally other organisms. In some of these cases the disease may 
be the result of double infection. 

Tuberculous Pnemnonia, in which a uniform pneumonic process 
is found in the lungs, may be due to simple infection with the 
tubercle-bacillus, or to mixed infections. 


Rhinoscleroma is a disease afibcting the skin about the anterior 
nares and adjacent parts, and probably caused by a specific bacil- 
lus. The disease h&s been especially observed in central Europe. 
It presents itself in the form of nodular thickening of the skin of 
the nose and lip, and sometimes spreads to the neighboring mu- 
cous membranes — mouth, pharynx, or larynx. In the latter situa- 
tions ulceration of the surface is frequent ; the lesions of the skin 
rarely ulcerate. Histologically the growth consists of round 
granulation-tissue cells. Frequently the c^lls sufler hyaline de- 
generation, forming rounded hyaline bodies. The bacilli may be 
found between the cells and within these, especially such as pre- 
sent hyaline degeneration. The micro-orranism resembles the 
bacillus of Friedlander, but, unlike this, ordinarily stains well by 
Gram's method, and when cultivated upon blood-serum or agar 
retains its capsule. In other respects the two forms are identical. 
Inoculation experiments have thus far failed to produce the 
disease in animals. 


Definition. — Diphtheria is an infectious and contagious dis- 
(ra,sf* raiisrfd by a specific bacillus. 

1- lo. Mi, d.-^Biicillus diphtheria: from a pure culture. 

Etiology. — TIk! IJacillus diphtheriaB was discovered by Klebs> 
and more ar^'uniU-iy Htudie<l by Liiffler, and is therefore called the 
Klebs-I>)ffl4«r liacilluH. This organism is a rod varying in length. 



from 1 to 6 //, rather thick, and with somewhat swollen ends. 
It is readily tli'inonst rated in tho \\u'i\\ lesions of the inneons mem- 
branea or skin, where it in;iy be t[Uite abinuhint • the indi- 
vidual liMeilli, liowev^er, are separate from one another. The 
organism is peeiiliar in it^ great irre^ifiilarity of shape and size, 
particularly in eulturej* (Fig, 86 f/). Seemingly lirnnebed forms 
nave been ol>served, and some i invest iffJi tors liav<' viewed the 
nrganism as a streptothrix or even as one of tlie liyiihtimveetej^. 
Frequently one end is especially large, giving a elul>-shaped 
app^amnce ; some of Uie ha(*illi are very large ; .si>me present 
munded gmnules at either eml, the so-ealled polar granules 
or Ernst bodies. The baeillns is readily staineil witli arjueous 
solutions of basic stiiins, espeeially with thos^^ rendc^red slightly 
nikalint*. (Loffler^s stiiin — siitiinited aqnervus solution of inethylene- 
blue, 30 cc, in aqueous solution of iMitassinni hydrate^ 1 : 10,000, 
100 ce. — is the favourite stain). The enlor is soau'wbat retained 
when stained by Gram's method. The stained speeimen sliows 
the morphology of tlie baeiUns very clearly. The rounded 
entls generally stain more deeply than the shaft of the haeillus, so 
that the appearance somewhat sugp^ests a diplocnccns. Not rarely 
transverse fractures give tlieorganism the appearance of disjointed 
segments. There are no flagclla, and tlie haeillus is not motile. 
8j>orcs have not been demonstrated* 

CultiTation. — The most characteristic cultures are obtained 
up<»n bloixl-semm, especially such as contain a small amount of 
glucose. Upon this medium there is fiirmed within six, twelve, or 
twenty-four hours a thin, whitish or yel hi wish -white layer of ir- 
regular outline, often showing separate smaller colonies aroon^l 
the edge. A small portion of the colony may be removed and 
stained, and the diagnosis thus estalilished with ease in a short 
time* Other organisms f(*und in the throat are slower in gnjwtb, 
and do not theret* ire interfere with the diagnosis. 

Pathogenicity,— When cultures in bfniillon are injected beneath 
tlie skin of a guinea-pig a filtrinous intlammation with more or less 
widespreatl edema results, and X\w animal dies in from twenty-four 
to thirty -six hours. Necrotic foci in tlic liver and other organs 
are found pist-morteni ; the neighboring lymphatic glands are 
enhjrged. If die animal survive, paralysis may mak** its appear- 
ance, as in human beings recovering frum the disease. The 
jKithogenieity has alsu l>cen shown by inoculation of varions other 
animals, and tirhnitcly by accidental infection of man, 

Nom-patliogeiiic diphtheria bacilli are found in the pharynx of 
healthy individuals in some eases, as w^ell as upon the hands, hair, 
or other parts of the boily* They are also found in various forms 
of rhinitis, conjum^tivitis, and iion-dipbtheritit" angina. These 
may differ from tlie virulent l)acilli in being somewhat sht^rter 
and in gn>wing more luxuriantly. Their distinctive character, 


however, is their harmlessness when injected into animals. The 
term pseudodipktheria bacUlvs is unfortunate, as it is possibly 
the same organism, but one having lost its virulence by growth 
in an unfavorable situation. The results of different investigations 
of this question have varied, and the identity or non-identity 
of the organisms is unsettled. 

Neisser has devised a staining method that has some usefulness in 

distinguishing diphtheria bacilli from the pseudodiphtheria or zeroeis 
bacilli : 

(1) Methylene-blue, 1 g. 
96 per cent, alcohol, 20 oc. 
Ac. acet. glac, 60 cc 
Water, 950 cc. 

(2) Vesuvin, 2 g. 
Water, boiling, filter, 1000 cc. 

Cover-glass preparations are stained for from one to three seconds in 
solution 1, washed, and treated with solution 2 for from three to five seconds 
and washed. 

Cultures must be made on Lbffler's blood-serum for at least nine hours, 
and not longer than twenty to twenty-four hours, at a temperature of 34"- 
36° C. (not over 36° C). This procedure, according to Neisser, brings out the 
Ernst granules in the true diphtheria bacillus, while the pseudo variety 
remain negative. Frankel holds that microbes that do not give the 
granules with this method are of the pseudo variety. 

Liiffler and others hold that while this reaction is a useful addition to the 
differential diagnosis, it must not be relied upon absolutely. 

According to Neisser, a further aid in diflferentiation is obtained by 
making impression preparations from six-hour old serum-cultures. In these, 
true diphtheria bacilli will be found lying side by side or crossing each 
other, while the pseudodiphtheria bacilli and xerosis bacilli adhere so 
closely to the culture-medium that they are not removed with the covers 

Klcbs-Loffler bacilli may be found in the pharynx of a person 
showing no indication of disease. This means that the organism 
has not iouiid a iavorable soil for its development or no abrasion 
or opening into tissues that will support its growth. The bacil- 
lus may, however, thrive and multiply for a considerable time 
u|Mni the mueons meml)rane of such a throat, as it may upon food, 
clothing, or other infected materials. 

Mind Inftu'tinn in Diphtheria. — Other organisms, notably strep- 
toeocc'i, sta|)iiyloeo(r<!i and pneumococci may he associated with the 
diphtheria haeillns, and may be actively concerned in the local or 
^^•neral patliolojric processes. The streptococcus is especially 
potent as an associated cause. The streptococcic infection may 
pn'ci'ch' or follow the diphtheritic infection. Various other 
or^ani»-tn>n of a Kipropliytic; nature may cause putrefactive changes 
in the prfijdoiiM'nibrant'. 

I'nuUHjunilmj ( 'tuLHVH, — Some predisposition is necessary for the 
developriMnt of tli#« dis<'ase. In part this is personal, some 
indivinimli-. h<inj/ hi^lily susceptible, others scarcely at all. In 
part, tii'A\u\i*HU%\ ''^mditions, sn(»h as pharyngitis, laryngitis, abrasions^ 
etc., fiiriiinh u fttv#inible op|M)rtunity for the infection. 



The fiiphihetna of bltrhy calves, and certain other animals ig 
tlistinct from the human <lisease ; and the or^j^anisms are in no 
way related. Human diphtheria may oceur in eat5, and these 
animals may propa^te epidemies. 

J*8eitdomembranoiw Jihrhiouii mjlammation is not invariably 
caused by the diphtheria baeillus (see Inflammation). Among 
the organisms capable of causing sonicwiiat similar pseudo- 
merabranes, the most frequent is the Streptoeovciis pyogenes. 
Another important *ine is the pneumfM^ocens, Recently a long 
bacillus (Bacillus of Vincent*s Angina) has been fonnd in certain 
cases of idcerative and |»seudomendininous sore throat8. This 
organism has not thus tltr been cnltivated on artiticial media. 

DistribEtion of the Bacilli, — The organisms are abundant in the 
pseudfinicmbranes of diphtheria, but are only exceptionally fonnd 
in the blood or internal urgiins. Tlie visceral or nerve-lesions are 
doe to the toxins, and not tn the bacillus. The same is true of 
expi^rimental dijditberia. The intenial lesions may be produced 
by injection of the toxin obtained by filtering a bouillon-rultnre 
thrnngh a Pasteur filten 

Pathologic Anatomy.— Diphtheria is primarily a local dis- 
ease of tlic pf larynx ( pharyngeal )» of the larynx {laryngeal), of 
tlie nose (nasiU), or of tht' skin (diTmal), The baeilliis lodges in 
the mucous membninc or skin, and produces a pseiulomemhnioe. 
Tliis consists of fibrinous exudation iu the form of fine graimlar 
material or a fibrillar network, in vvliich are embedded the cpi- 
tlielial cells and other tissue-elements and infiltrating lenktK'ytcs. 
The epithelial cells rapidly undergo eoagidation-neer<tsis or granu- 
lar degeneration, as dc> also the connective tissues when the pn>- 
cess ex^nds beneath the mueosii. The bhH«l-vessc»ls bcctjme 
obstrnctcd hy thrombosis or compression, and the tissue is there- 
fore avascular. Neiirly always the pseu4loniembrane thus formed 
is attached to tlie nnderlying tissues^ and wlien removed a raw 
and bleeding surface is ex|XKsed. The ck'pth of involvement^ 
however, varies ; sometimes the suhmuc(»sii is soon invfvlvcd ; 
more often tlie disease is practically confined to llie mncosji. 

The mat^roseopie appearan(*e is that of* a whitish, dirty-yellow- 
ish, or brownish membnine n|^M>n the mncons lining of the throat. 
This begijis as one nr several jMtches upon the tonsil, and spreadi- 
rapidly to tiie neighboring parts. In other situations the appear- 
ance is mu<'h the same. Infiainmatory swelling beneath and 
arijund the diseased area is habitual. It is of great clinical ira- 
j)ortancc to recognize that true diphtheria may occur in the form 
of typical follicnlar tonsillitis. 

liitemal or visceral lesions may occur in the course of diph- 
theria or during convalescence. They are dne to the action of tbe 
toxin, and not of the bacillus. Necrotic ft>ei in the liver^ showing 
advanced cellular degeneration of the cellw with hyperchromatosie 


of th#? nuclei, and similar lesions of other organs^ may be seen in 
th#; human IkxIv, as in animals killed with the organism or its 
f/»tin, MycK^rditis and myocardial degeneration, renal degenera- 
ti/^i find nffphritis, and, most interesting of all, degeneration of the 
yftrri\Au'.fu\ nerves and neuritis, may be met with. All of these 
#ill \hz dewsribed elsewhere. 

Pathologic Physiology. — As has been said, the disease is 
IfnumrWy local, and the bacilli nearly always remain localized in 
(t(Mr itiiiKfrficial lesions. The general manifestations — fever, pros- 
tration, and the visceral lesions — are caused by poisonous sub- 
«|iAfir'#'H i!lal)orated by the growth of the bacilli. There are prob- 
t$it\y wfveral substances o? this sort, but one in particular — the 
A/W/t — JK most important. This may be obtained by filtering 
lf^/<iillon-<*ultures through j)orcelain, and by its injection the con- 
tetitiirjonal and some of the local manifestations of the disease may 
\pi' ifidijc(*d in animals. Successive introduction of increasing 
iUmnh of toxin causes the development of antitoxic substances that 
maw finally accumulate in the blood to such extent that the ani- 
rrial iMfWiUics immune to the most virulent bacilli. The antitoxic 
teiibhliince or substances, or arditoxiny found in the blood and the 
bl'MKl-Hcnim of immunized animals, will render other animals im- 
iijijiKf for a time, or combat and overcome the disease if already 
f'xihtifig. Simultaneous injection of antitoxin and of many times 
tUi' ordinarily fatal dose of toxin or diphtheria-cultures leaves an 
animal unharmed. Later, when the immunity has passed oflT, a 
ternall dose of toxin or culture without the antitoxin will kill the 
tuiuw animal. The value of the antitoxin in animal experimenta- 
tion is beyond doubt. In the human being there is scarcely any 
d/iulit of its potency, though, of course, crucial experiments cannot 
\fi'. made. 

Af'tiT an attack of diphtheria there is temporary immunity, 
\tm this passes off and successive attacks may thus occur in the 
^uu*. |H;rson. 


Definition. — Typhoid fever is an infectious disease, with 
/:haru/.leristic lesions of the intestines, and due to a specific 
S^uWhin. It is important to recall the fact that local or general 
ffflfhf/id infection may occur without the intestinal lesions or usual 
/ lioi/'al ftfatures of typhoid fever. In su^h cases local inflammatory 
U^tttu^., Hiippurations or necroses, or septicemia have been observed. 

Rtiology. — Certain predisposing features make individuals 

Ht^m'. liable at one time than another to this disease. It occurs in 

uAfA^f^^noe and the young, though rarely also in the old. Cli- 

HHUi eonditions are supposed to play some part, and doubtless do 

'• m influence. Typhoid fever is especially a disease of the 
>mla JEones, and is most abundant in the autumn. Drainage 



and otlier conditions aflTecting the sufToiindiiigs of persons may 
influence the predii^iwsition. One attack usually confers immunity 
for the rest of life ; exeejitions, however, are met with. 

Tiie Baeillu.s. — The Baciihi:^ li/phi ah<!'munaMi<y the spccitic 
organ ii?m, was diseovered by Eberth and isolated by Gaffky. It 
is a short, bacillus, from 1 to 4 ^ in Icn^h and 0.5 to 0,8 /i in The end.s are rounded ami often f^omcwhat plump* In 
culture the*?e rods or bacilli t>cciisioually form lon^ eliaiiis, but in 
the tissues they are never su arrjingcd. The organism is actively 
motile, this being due to flajrellay of which there aix^ eighteen or 
twenty attaelied to the periphery (Fig. 87). When stained with 
alkaline methytene-blue or other stains there are sometimes seen 
dark*roh)re<l spots at the ends of the organism. Thesi* were 
formerly regarded as sfMjres, but are now recognized as areas of 
eondcnsation* Under eertain cireumstauces the eoudeusation is 
seen in the eenter and vacuole-like formations are found at the 
ends. The organisui is readily stained, hut deeoh prizes very 
eaailVt and is thercibre difficult to denmustrate in tissue. Pn>- 
longctl staining, however, and nipid (leet>1ori/4ition sometimes give 
beautiful resulti^* The bacilli are, as a rule, found in e lusters. 
These groups may, however, be few in number, and thus difficult 
to detect in the organs, 

CultiTatian. — Artificial cultures of the bacillus have been ob- 
tained from the spleen and other organs, as well as directly from the 
blo4jd, stools, and urine of patients s^iffcriug from the disease. They 
grow ven" well upon tin* ordinary eultu re-media, sui'li as agar-agtir, 
gelatin, and potato, the t( oipc^niture *if the body being most favoni- 
ble, but some growth occurring at the ordinary tempo niture of the 
room. Upon gelatin and agar there are formed irregularly whitish 
filmSt which on close inspection with the lens show a granular 
appearance. This growth, however, is not distinctive. Upon aeid 
potato a eharacteristie transparent [>elliele is Ibrmed. This may 
be invisible except to the trained eye, but on scrtiping the surface 
%vith a platinum wire the pellicle can be raised, and e>n micro- 
scopic examination it is found to he composed of baeilli. Some- 
times the pellicle is yellowish or brownish. When cultivated in 
milk there is slight acidity, but coagulation does not oc^eur. When 
grown in agar containing a little glucose practical ly no fermenta* 
tive gas results. Another feature of importance is the absence of 
indol-reaction, the addition of potassium nitrite and sulphuric acid 
to bouillon-cnltures causing no n>se color, such as ot^curs with 
some otlier organisms. Several special media liave been su^ested 
for the diffen^ntiation of typhoid baeilli from colon bacilli and 
other similar organisms. The media of Hiss have given very 
satisfactory results. (1 }., A plate medium cfjmjKjscd of gelatin 
grams 25, agar grams 10, stMliura chloride grams 5, Liebig's beef 
extract grams 5, and glucose grams 10, in 1000 ccra, of water, i* 



prepared by adding the gelatin to tlie thoroughly melted agar, 
titrating agaiiust ph*^iiolphtlialeiix a.s an indicator, and adding 
normal hydnjchloric acid or .sodium liydrat^* solution nntil the 
reaction indicates 2 jkt cent, ot* normal acid. The meiliuni nmy 
bt! cleared by adding 1 or 2 eggs in 25 cc. of water, boiling 
for 45 minntes and filti^ring tlirongh absorbent cotton. The 
ghicose is added after ck^aring, (2), The tube medium of Hiss 
contains gelatin grams 80, agar grams 6, sodium bichloride 
gmms 5j Liebig's extract grams h^ and ghicose grams^ 10 in a litre 
of water, and the reaction is 1 *5 j>er cent, of normal acid. 

Flo. 87.— BacLlluB lyph J nbdom i nn] is. 1 1 . 

SagtiUn stained by LorUera iu^lim 

' ulture six houTi old* fthovring the 
N) (Fninkel ftnd PfeilFer). 

In tlie plate medium the typhoid bacillus ff»rms colonies with 
irr<'gtihir mitgrowths and thninblikc extensions, while the colon 
gri»U|» Jbrnis larger colonies without threads. In the tubes the 
typhoid Imcilli cause uniform clouding within 18 hours at bmly 
t/*rnperatnre. The colon bacilli do not cause the uniform clouding, 
but ajijMuir a« localized growths, or, if diffuse, streaked growths 
rainrfving through tlie cloudy tubes. The presence of gas is 
Klgniiicmisi that the orgiinisni is not the typhoid hacillus, 

(Detailf iwarding these media ami others devised for tite same 
purpoie filtlirt oe obtained from hooks on bacteriology). 

Tlie dSflgnwttc features of the bacillus are plainly distinctive, 
exei*pt tbttt the Bacillus coli communis has a puzzling resemblance. 
TliP latti*r, however, grows ujKin acid ])otato as a yellowish or 
browni^ih (llm, «'4»agidates milk prfimptly and causes decided acid 
reaction, and \h an active gas-pro*lncing organism when grown in 
glQcrnieHif^ir. I'he sernn) -reaction of Widal is a recent and im- 
portant difttiuguiahing mark. The serum from typhoid patients 



must not, however, l>e relied upon absolutely, as it may contam 

suhstanees prfx!noo<l by tho Bjicilhis eo]i as well as those'prodaced 
by the typhoid germ (see Widal reaetion). 

Patliogenidty* — Aniiiial-exjierimeutation has thus far been iin- 
satisfacton*. A fmv obst^rvers have suceeeded in prcxlufing intes- 
tinal lesions and ilhiesi? l>y fl/edin^j animals witli typhoid cultures, 
particularly atler the stomaeli nnd intestine,s liave Iwen rendered 
alkaline witli j?o<ia and peristalsis has been checked with opium. 
In most cases injection of th*^ typlioid bacillui^ has produced sep- 
ticemic manifcsfcations. The constant i>ccurreuce of tlie ^erm, its 
absence from other conditions, and the alisence of any other germ 
as a constant aeeonipaniment of typhoid fever, have led to the 
general acceptation of tlus as the sjM?cific cause. Moreover, its 
properties are such that the spread of the disease in the ackuuwl- 
edged ways is entirely compatible with the acceptance ot* the 
bacillus as the si>ccific cause. 

Distribution, — The ty|)hoid bitcillus tK-curs botli witliin and 
without tlic human Iw^dy, and doubtless multiplies gn^atly in tfie 
ext-ernal world when tlie conditicMis are favorable. It occurs in 
the h'sious of the iutestiiiL's and in the int<'stinul contents, esi>e* 
cially < luring the second and third weeks nf the disease. It is 
usually less abundant^ but often i>rcsent in the spleen, liver, and 
kidneys; it may *x*cur in cunsidembtc abundance in these organs 
when there :rn* loi-al compHeatitms. It is almost always present 
in the gall l>Iadder in eases oi* typhoid fever, and fre*juently 
occasions chohfcystitis and not nirely initiates thi' iVmnation c>f 
gtdl-s tones. It also occurs in tfje lungs, in the parotid gland, and 
m other organs, and ]>ost-tvphoidaI abscesses may contain the 
or^nism in abnodance. Complicating lesions of other organs 
may be dependent solely opdu the s[>ecitie bacillus, tliis being 
capable even of acting as a pyogenic orgtmism, or they may be 
dependent upon secondary or mixed infections. Tlie bacillus may 
be found in the blood quite regularly. 

The typhoid bacillus is p<x'uUarly resistant, and may thrive 
upon clothing, in soil, and in water for a long time. Cold has no 
effect, the germ being virulent after freezing and thawing several 
times. Carbolic acid in strengths that prove destructive to most 
organisms has little effect on this germ. These features explain 
the spread of the disease and its general prevalence. The organ- 
isms are discharged from the body of a patient suffering from the 
disease mainly in the stools, but in part also in the urine, sweat, 
and other excreta. If they are not at once destroyed, contami- 
nation of clothing, soil, water, etc. may uccnr, and subsequent 
infection of susceptible individuals takes place through drinking- 
water or food with which the infected water or other matters have 
come in contact. It is possible that infection may occasionally 
take place through the lungs by inhalation of dust. This must be 



highly probable that it iHi the usual cause of pneumonia. The 
tliplococcus is frequently fouud in the Huliva of bealtliy pernons. 
AVlieu this is introtlueed into auiiiials, paitieuhu'ly rabbita, the 
animal dies, with evidenees of rai>id .sepsis (s|Jutinu-septicemian 
The post-mortem shuws some tibriutnis exudate ami ocejLsitJually 
a little pus at the point of inoeulation. The spleen is enlarge*!, 
and eapsulated bacteria of distinct laueeolate form are widespread 
thn>ughout the body* Injections of lung-tissue or of pneumonia 
sputiuu produce simitar results, and the organism m pure eiilture 
likewise causes this form of septicemia. It has l^een sliowu that 
injection t»f pneumonic exudate aspirated from the consolidated lung 
into the lungs of rabbits will i>rochiee trite pneumonia. Recently 
typical pneumonia has been produced by injection of virulent 
pneumoeoeei into the lungs of nibbits previously immunized 
against the pneiunrn'oeens to ]>revent the occurrence of geneml 
puei I niococcus sept icemia. 

Beside:^ the dlpUxniccus there are certainly other elements 
which contribute to the eausation of the disease, else the fn-quent 
occurrence of the micro-organism iu qtiestirm in the sidiva would 
make pneunnmia a much more common affection. The nature of 
the eontribntiug causes is, however, obscure. Exposure to cold, 
general de])ression of the system, tranmatisni, alcoholism, ainl other 
causes ccitainly predisixtse or help to determine the oeeurren(*e of 
the disease. These causes may act by tem[>omrily increasing the 
virulence of the diplococcua or by hnvering the resistive ji+nvcr. 

Certain irregular forms of lobar pneumonia may be caused by 
streptococci, stapliylococci, the Bacilbis pneumoniae of Fried- 
liinner, the influenza bacillus, that of typhoitl fever, etc.; but true 
croupous pnoumojiia is pmbably always due to the Diploeoocua 

Pathologic Atiatomy, — (See Diseases of the Lungs.) 

Pathologic Physiology, — Phe diploeoecus produces, in the 
first place, local lesions of the lungs ; and in the second place, 
systemic iuicction 'And possibly als<> genenil intoxication by toxins 
of uncertain character. In the ease of systemic infection the 
organism itself gtiins access to the l>lood and may ]u^k1ucc second' 
ary lesions in other oi^gans. Infection with the diplocm^ens of 
pneumonia (pauses a pronounced reaction on the part of the blood 
iu the ibrm of leukt>cytosis. This is not invariable, lyit is usually 
seen. After the attack of pneumonia then^ is tcmporarv inmumity, 
and it has Ijccn f[>nnd that anin^als may l>c inununized for eonsid* 
enable lengths of time bv repeated injection of pncumoco(^ci. 
The serum of the immunized animal has a eei-tain pniteetive and 
curative valne which has recent! v been attrii)uted to the formation 
of opsonins (see Iniuumity), wliieli are operative by rendering the 
pnenmo<?occi liable to rapid ingestion !w phagocytes. 

The Biplococcus in Other Diseases.— The DiplocoocuB 



pnFumoniie haa Ixm^ii foimd in various coiiditioiis coriiplicatiiig 
piieiinionia^ and occasiniially in lesions unas.soeiated with crnii]K)us 
jMieiimQiiia, Among other lesions, meningitis^ pleurisy, and other 
inflammations of tlie semus surfaces, absi-esses, otitis media, and 
art [iritis have been fuund Uy he due to this orgtxnism ; or, at, 
this organism alone has been found in «ome of these cases. 


AuHinir other varieties of pnemiionia may be mentioned the 
catarrhal or loljnlar form, the tuberculous form, and various int^g- 
u!ar pneumoniasj partly cellular, partly filirinons, partly puruleut 
or heniorrhagie. Though the pueumoeoecus is nu»re frequently 
present than any other .^iu^le organism in broncho-pneuiuonias 
after infectious diseases like measles and diphtheria and iu various 
irregular types of broneho-pneiunouia, diOereiit organisms nuty be 
found in such crises, and some of these may be of etit^logie inipor* 
tance iu certain casi's. Not rarely the pulmonary disease is the 
result of mixed (double or nuittiplc) irdVetion. 

Tlie Bacillus Pneimioniffl of Friedlander* — This orgimism was 
regarded at one ti nu> as the cause of cmujwius ]uieiUuonia, It 
probably occurs iu !uost cases as a nuxed infeetiou, though it may 
occasionally be tlie cause of catarrhal iw irregular ff)rms of jmeu- 
nionia or of ordinary croupous pneumonia. 
The cases of |nieumonia due primarily to the 
pueumobaeillus are characterized Ity their 
virulence and a peculiiu' viscid ehirraeter i>f 
the exu<late in the lung. Fried liinder^s 
org:uusm occurs as a diiftinct liacilius, u.sually 
in pairs and ^urnnmdcfl by a capsule like 
that of the diplocoeeus(Fig. >?G e), Some- 
times it may form chains of three, four, or 

more organisms. It stains well witii the anilin dyes, hut is decol- 
orized by Ciraui's method. A cha met eristic culture is obtained in 
gelatin. The puncture-culture is characterized \iy a luxuriant 
growth at the top and a consitlerable vegetation all alf»ng the 
track. Tins leads to a nail-sha])ed growth. The gelatin does not 
liquefy. Upon agar a considerable whitish or yellowish moist 
growth occurs up>u the surfnee. There is fornuition of gas in 
media contaitdng gbieuse, and often also on [lotatn. 

A nnnd>er of organisms closely related to Fried liinder^s pneu- 
inoco<'cns have been {-lassified under the generic name BucMuh 
muromfJt cfjpmdaiuM. Among these are the B, ktdhaerogruritj B, 
arifli htdlri^ E. ozof^wr aud Pk rhlnoxchrnmnfis. The several ty|>es 
differ somewhat in their power to fenuent various carbohyd rates, 

Other Organisms in Pneumonia. Among the various organisms 
that have been found in broncho-pneumonia or less commonly 
fibrinous types of pneumonia are the Streptococcus pyogenes, more 

Fiu. Srt, f.— BaeiUiH pinj^u- 
moniiB of Fried litiHU'r. 



has a relation with globulin. It can be precipitated by mag- 
nesium sulphate. It k dt-stroyed by heating t€ 70^ C. (\b%^ FT). 
The reactiuii i.s regarded by some German authors an being anal- 
ogous to the phenomenon oi' coagulation, since tlie presence of 
salts is necessary. 

This reaction was found in 2283 cases of typhoid fever repf»rtetl 
by variotis writers, and was absent in 109 cas<'s of typhoid fever. 
It was alisent in 1365 nou-typboid cases, and pix*sent in 22 non- 
typhoid patients. It was therefore foimd in St5*o per cent, of tlie 
typhoid eases, and was absent in 98.4 per cent, t^f the uon-typhoid 
easels ; or, taking the entire 3779 cases, the correct result for 
diagnosis was arrived at in 96*5 per cent. The reaction some- 
times persists for some years after the attack of typhoid fever. 
Siimetimes it fjceurs in cases in which there is typhoid infection 
without typlioid fever in the onlinary sense. These facts may 
exjilain s<ime of tixe positive results obtained in non-typhi>id exM^^. 
The serum nuist be diluted with nineteen parts or more of water. 
Reactions witli stronger serum or partial reactions may be decep- 
tive. (See also Jmmuniiij,) 

Paracolon Infection; Paratyphoid Infection. — Gwyn, Schott- 
in idler, Kurlh, < 'ushiug, and others have rejiurtetl cases resembling 
typhoid fever clinically^ hut in which the \Vidal reaction was per- 
sistently akseut and in which bacilli closily resembling the typhoid 
or colon bacilli, though ditlering in some essential ]>articalai*s, 
were isolatetJ from the hiood and tissues. The intermediate 
organisms here referred to difter from the V)acillns of typlioid by 
their ability to prorluee g;is in glucose-ei>ntaining mediii, ami to pn)- 
duce an alkaline reaction in nutrient media. They ditVer from the 
Bacillus i'oli conununis l>y not coagulating milk, not fermenting lac- 
tosCj and l>y failing t*! form iutlol. The group f^f intermediates has 
been divi(h*d into a paracolon group and a paratyphoid aei/ording to 
the closer resemblauee to the colon group tm the one hand or the 
typlioid bacillus nu the other. Members of the paracolon group 
are less chjsely related as for example iu tlu' matter of inter-agglu- 
tinatitui than are those of the paratyj^hoid group. 

The inttTUMHiiati'S ai'celosely allietl to the Ea<"illuspsittac*osisof 
Nocanl, the B. ieteroi<les of Sanarelli, the bacillus of liog cholera, 
the Kacillus euteritidis of Gartner (meat-poisoning bacillus) and the 
B. dysenteria? of Shiga. The Bacillus ikecalis alkaligenes of Pct- 
rnshki is nearly rehit<"(l and sometimes causes typhoid-like infec- 
tion but it does not lielonii' to the group, 

PaifiokKfh Amdrmy.—U. G. Wells and I.. O. 8ct>tt (1903) 
summarize the pathologic findings in five cases of fatal para- 
typhoid infection, the cases of Strong, Longcopc, Sion and Negel, 
Lucksch and their own. The most constant change is splenic 
enlargement which is in all rcs|>ects the stime as that of typhoid 
fever or septicaemia. Tlie endothelial cells are loaded Math pig- 


nieDt evidently the result of the hemolysis of the disease* 

Ini^'stinal Le^iom, — In Laiigcop^^'s and Strong's cases, the 
intestines were i|nite iiniitfected ; in tlie other three, uleenitions 
resembling those of dyi^tnterv nit tier than tliose of typhoid fever 
were discovered* Peyers patehes iuhI the Bolitary i'ullieles were 
pnietically unatfected ns were nUo tiie meBenterie glands. In no 
was there generalized ghindnlar hypeq>lasia. 

In Ijongcojie^s and llieir own case, foeid iieeroses in the liver 
Kffering from thowe uf typhoid in Ui*i eontaining endothelial eells, 
were found. The elianges of ]>rolilenuion and phagorytosis 
deseribed by Mai lory for tyi*h<ml it'Vt-r were almost entirelv absent 
in tlie intestinal lesions and very slight in tlie jnescnteric glands, 
not being more eonspienous in their own ease than what may be 
seen in simple enteritis. 

The anatomic picture was that <tf a septicaemia with splenic 
enlargement and occasionally non-^j>ceitie nleeration in the intes- 
tines. The eseape of layer's patches suggests an essential if 
obscnre biologic difference between the typhoid and paratyphoid 

Nature of Paraii^phoid Jiifection. — The tendency of most 
pathologists at the present time is to r*'gard paratyphoid infection 
as distinct in a baetcrinlugie sense rather tlian in a clinical or gen- 
eral patliological sense, in the samt^ way as jinenmonias of varying 
bacteriology are distinguished only etiologically. 

It ciinnot be denied that there are decided imthologic differences 
but tbc practical clinical identity and the near relationship of the 
bacterial agents warrants the elassilieation of i>anityphoid inteetion 
as a sub variety of typhfiid infeeti<>n nnd the rejection of the term 
** paratyphoid fever '^ as significant of a separate disease. 


Sy^onj^tnS. — Bjieterinm coli commune. It is customary to 
speak id' the ** colon group'* since it ha^ been reaignizcd that 
several anfl perhaps many slightly varying tl»rms have been 
classe<l under the name Bacillus coli Cijmmunis. A luimber of 
organisms descril>e*l under ditfcreut names arc prolmbly identical. 
Among these are Bacillus Ncajjolitanus of Emmerich ; Bacillus 
pyogenes ftetidus of l*asset. Severjl t4her organisms are either 
closely allied or i<lcnfifaL 

Morphology.— The Bacillus coli communis is an organism 
almost exactly like the typhoid bacillus in appearance. It is rod- 
shaped^ but sometimes ehnigated an*l fi lauu^ntous, at other times 
(young forms) short and mther roundcHl — coccus-like. It is 
actively motile, and has fl a gel la attached to the periphery of the 
bacillus. The flagella are shorter, more slender and less numerous 
than are those of Eberth's bacillus (three to ten), and the motility 



of the organism is less uniform and at^tive. It may be stainetl by 
ordinary s<^lutions of aiiiliii i\yi*i^y (Kirtictilarly with alkaline or 
earbolized solutions. It i?5 decolorizeil by Gram's staining-niethod. 
Thestaineil baeilhis shows light-eolored or unstained portions like 
those of the typboitl baeilliis. True spores have not l>e4'n dettx-ted. 

Cultivation* — The organism grows Inxiniantly njKin ordinar}'' 
media. The most dislinetive growlb is obtainetl np*>n acitl [M>tato. 
An elevatetl l>rou'niHh eolony is prodtieed, wbieh is usually easily 
distinguished frurn the typhoid eulture in the same medium. 
When euitivated in gelatin or agar etmtaining ghieose active gae- 
pnuluetinn results. In liquid media (bouillon) a iKHiviiliar odor is 
devehvped. Addition of nitrites and pun* hyib^oehlorie or sul- 
phurie acid causes a rose-reil en lor — indr4-rraeti*m. Milk is 
readily eoagulated partly as a result of aeid lorn Kit iun and jjartly 
by tile elaburatiim of a roagulating fermeni:. 

Distrlbutiati and Pathogenicity,— The eolon baeilhis is a 
normal inhabitant of the gastru-intestiual traet. It seems to 
exen-ise a benettoia! efleet in restraining (l>y its own active growth 
and aeid formation) the growth of putrefaetivLvinid possibly patho- 
genic organisms. In certain ijiHammatory cbscases of the intes- 
tines, Iiowever, it seems to increase in munbers and ilonbtless also 
in virnlenee. The organism may be found outside the body in 
various sittuitifuis, particularly in water. 

The bacillus eoli is eiipable of producing inflammatory' eondi- 
tions in diHerent situations. Injeeted into tlu' peritoneal cavity 
of animals it gives rise to acute tiininopurulent peritonitis, and in 
other parts of tite borly hits anah^goiis effects. 

It has been found in various diseases of the gastro-intestinal 
tntet, of the biliary jmssages, of the urinary system, and of other 
part>s, and is doubtless the direct cause of some of tliese, as the 
conditions present are practically the siime as those proiJuced by 
experimental iucwulation of pure eultun^s. 

Among the gtistro-intestinnl troubles it has been foimd in sns- 
pieious abundaui-e in various forms of enteritis, in the distended 
anil sup{>urating appendix, and even in Asiatic cholera. It is 
known that the strangulation ijf a knuckle of intestine by a liga- 
ture leads to rapid inerease of virulence of the contained baeilli. 
It is possible that in a[i[M^ndicitis and in otlier intestinal diseases 
similar conditions lead to increased infectivity, and thus cause an 
onlinarily ban n less organism to become virulent. In tfie eases of 
Asiatic eliolera in which tliis organism has been tVnmd the specific 
germ of cholera has |)robably been overlooked or ha.s disajjpeared 
during the rapid multiplication i>f the saprophytic IJaeillus coH, 

Peritonitis may result fnun escape of the l)acillus thrtjugh a 
ruptured intestine or directly tlirougli the wall of the bowcL The 
latter is particularly prone to oet^ur in cases of strangulation of the 



Various ioflamniaton' of the urinary- tract, sueh as 
cy«^titis, pyelitis^ mid pyelonephritis, arc c>ccasioned by this i^rae 
g^rm, which first rear^hes the bladder through the urethra or by 
penetration of the wall of the Ixiwel and then of the liladder, or 
in other cases, infects the kidney primarily, having been carried 
there by the blood. 

Finally, there are causes of peritonitLs secondary to enteritis^ 
plenrtsy^ eDdocarditis, and other iiiflatiiniator)" diseaaes^ apjiareutly 
catised by this organism, 

Patliologic Physiology.— Little is known of the toxic 
effects of coli-intection. Some toxic substance is doubtless 
produced. A reaction similar to the Widal redaction obtainetl 
with the t}"phoid germ lias been found to cKXJur when 
cultures of the eoli bacillus are subjected to the action of serum 
from an animal inoculate^l with this organism or from a person 
suffering with appendicitis or other diseases, either due to coli- 
iniection or acconipaniefl by 8Uoh. Occasionally the coli bacilli 



^6^ tt.— SptriUam of Asiatic cholen. fmrn a bouliion-cuUure three weeks old, tbowtnc 
nambers of long aplml^ : ■' I**** ( Frankel and Pfeiffer). 

agj^lutinate and their motility is checked by typhoid serum* The 
explanation of this may be that in certain oases of typhoid fever 
the coli bacillus is also active in the intestines, and in conse- 

aiience a mixed form of infection is present. In part it is also 
le result of the presence of ij;nnip agglutinins that art on diftcTent 
bat allie<i organisms* 


Certain types of dysentery in the tropics and of acute dysen- 
tery' of temperate climates are aceonipanied by liacilli, first recog- 
ni/id by Shiga, and afternanls htutlied by Flexner, Park, Kruse, 
and others. 



The organisms resemble thosi^ of the colon groop, being non- 
motile baeiUi with few^ if any, flagella. 

In gelatin culture, the colonies reaemble those of typhoid 
bacilli more closely than tliost^ of tlie colon group* In bouilhm a 
diffuse cloudiness without production of iudol is observed, lu 
glucose bouillon the bacillus drM?8 not prtxhice gas nor acid. Tlie 
organisms, as observed by different ubiscrvers, have differed in 
some particulars. The original form recognized by Shiga dws 
not ferment mannite, maltose or saccharose* fcJome of the later 
types liave been found to ferment mannite and to proihice indol^J 
while still others actively ferment mannite and also maltose and ' 

Animal cxpt^rimeuts have given certain suggestive results and 
the serum of inoculated animals contains agglutinating and 
iraoiuue bodies. 

The pathological anatomy anil physiology of dysentery will be 
conmdered in the section on Ifn^easm of the Infesiints, 


Sefiiiitioti* — -Cholera is an acute infectious and contagious 
disease caused by a spirillum or vibrio. 

IStiolog^* — The specific cause of chi>lcni is the Spirillum or 
Vibrio cholene Asiaticfp. This organism is frequently spoken of 
as the comma-baeillus of Koeli. It is a short rod, from 0.8 to 
2 fi in length, and usually siimewhat i-nrved. The tt^rni comma- 
baeillus is ap|ilied to it ou account of the latter fact* It is found 
abundantly iu tfic rice-water discharges of choleraic [)atient^, and 
is not nirely arranged in nnvs, themgh the vibriones are not actu- 
ally attached Ut one another (Fig. 88). It is motile, the mrnility 
being due to a single flageltum attjiched at one end* In artiticial 
cultures the (»rg:inisms are actually joinctl to form spinils of greater 
or less length, aJ»d these may present a ra |>id rotary movement. 

The demonstration of the cholera-spirillum is usually easy, as 
ordinary stains color it intensely. Even the Hagellum may be 
stained by the ordinary stains, though more definitely show*n by 
special methods, 

Ciiltivation* — The cultivation of the spirillum is usually easy* 
Cultures may be obtained upon agar-agar, blood-serum, or other 
media, but the gelatin-culture is most characteristic. In puncture- 
cultures the growth occurs along the entire length of the puncture, 
but particidarly at the top, where the supply of oxygen is abun- 
dant; and the gelatin beeoraes liquefied. This gives rise to a 
peculiar nail-shaped or funnel-shaped forniation (Fig. 89). In 
plate-cultures the growths first appear in the lower strata of the 
gelatin as small gramdar whitish spots which extend toward the 
surface, liquefy the gelatin, an<l tlnis produce excavations* The 



urC'Culttir« in gcl> 
atiii of spirillum of 
cholera; sixty hours 
old (Shakespeare ^ 

^^^ irance to the naked eye suggests small air-Liilihlps m the 
^teledia. Under low powers of tbe microseoije the cnhure is seen 
to be coarsely gniniilar, the size of the granules 
varying with the age of the culture. The Itotttun 
of the growth presents an appearance like tiiat of 
a Burfaee sprinkled with [Miwdered glass. 

When grown in houi Hun or other liquid media 
the cholera-microbe prixltieea nitrites and iudo!, 
so that the addition of a little pLirt* sulphuric aeid 
or hydrochloric aeid leads to a reddish eolomtion 
(indol). This may be cxtracteil with chloroturni 
or benzol, and '^^holera-red'' nuiy be thus obtained. 
The indol reaction is not absolutely diagnostic 
since other spirilla may cause it. Negatively, 
however, the test is extremely useful since its 
absence exelndes the ebnlera gcrui. A definite 
quantity of [x^ptone is ncces.s;iry to make the 
test reliable, Tbei-elore, instead of Ijouilhrn an 
alkaline 1 per cent, peptone solution containing 
0,5 per cent, of sodium chloride is preferable 

The cultures of eholeni grow best at a temper- 
ature about that of the budy, l)Ut they nuiy thrive 
at mneh lower degr^'cs e^f heat. Exposure to a temperature of 
52° C. (125.6*^ F.) for four minutes nuiy cause their destrnetiou, 
but ten or fifteen minutes' ex[>osure at 65^ C. (131^ F.) does not 
always })rove destruetive. They may thrive in distilled water, 
or m water containing saline matter ; in or upon various forms 
of foml ; up<)U clotJiing ami the like. The resistance, however, 
is not very great, and this has been urged as an objection to the 
likelibf>od (*f the organism being the cause of a disease liaving such 
evident tenacity. 

Distribution, — The cholera -spirillum is found only in the 
intestinal contents and mucosa. The orgtUiism has never been 
found in the blood nor in any organ or tissue except the gastro- 
intestinal tract. 

Fathogemcity.—Thc pathogenicity of the cholera-spirillum is 
now admitted universjilly. Injcctetl into the {x^ritoneum of ani- 
mals it causes a rapid fall of tcmpcnitnn^ abdominal tenderness, 
and cfiUapse, The jicritoneum shows signs of begijining inflain- 
^ination, and the organisms are found in abundance within the 
cavity. It has been possible also to produce intestinal changes 
almost, if not, identical with tiiose of human cholera in animals by 
arresting the peristalsis of the intestines with injections of opium, 
rendering the liquids of the stomach alkaline with sodium carbonate, 
and then feetling cultures. In man a few autoinfections have 
been practised, the experimenter swallowing cholera-cultnres. In 



one case at lea^t typical cholera was admittoLl by Pettenkofer, the 
most important opponent of the acceptanee of tliis germ as the 
specitie cause. The celehrated case of Dr ( )ergt:4 who dieil as a 
rei^iilt of hihoratory autoHiociikition seems pnietically conclusiv^e. 

Otlier Causes Operating in Cholera. — Certain climatic conditions 
favor tlie devehipinent of the disease, ThoK it is constant in cer- 
tain regions of ludia^ untl spreails thence when the conditions 
become favoniljle. The evidence shows that the genn is carried 
by individuals, or by infected food and tlie like. The disease 
Hourishes in warm seasons of the year, and an epidemic is usually 
brought to a close by winter frosts* 

Individual disjKJsition plays a part in the occurrence of the 
disease, for the gemi is easily destrovcfl l>y the acid gastric secre- 
tions, and infection is there lore most likely to occur when gastro- 
intestinal derangements furnish a favorable predisposition. 

Pathologic Anatotny,— The lesions of this disease are 
found in the intestinal tract, and will be described in the ajtpro- 
priate section. 

Secondary lesions of other organs are met with in sevei*er 
cases, anil result from the circulation of toxic substances produced 
by the bacillus. 

Pathologic Physiology*^ — A munber of toxins have been 
isolated from the blood of cholera-|jatients and ironi cultures. 
The exact nature of these and the relations uf the seventl forms 
remain to be determined. It is certain, however, that toxins pro* 
dneed in the intestinal tract ^ive rise to many of the symptoms 
of the disease. Injection of the filtrate of cultures causes collapse 
and Mther synipttjuis lilve those of tlie algid stage of the disease. 
The principal toxic substance seems to be closely attached to the 
organism itself (endotoxin] hut a secreted toxin may also be found 
in the culture fluid when the organisms are enclnscd in a collodion- 
sac. The human itr animal organism in gome way develops 
immunizing or protective substances in the course of infection, and 
it has been found jxissible by a process of vaccination with cul- 
tures of gradually increiusing virulence to protect animals and 
human beings from tlic disease. Hairkine's protective vaccination 
of human l>eings yielded very encouraging results. He inoculated 
200,000 pCTsons in Indiii, Pfeifter found that the serum of animals 
so vaccinated had a distinct action njion cholera-spirilla, causing 
their agglutination or destruction, and possibly in this way exer- 
cising a protective influence. This, or a similar, reaction has 
DOW been perfecte<l in the case of typhoid bacilli, and forms the 
basis nt" the well-known Widal test. The same test is applicable 
to Asiatic cholera. 

The rapid and copious intestinal discharges of cholera lead to 
considerable inspissatifin of the blootl, and doubtless contribute to 
the causation of some of the symptoms of the disease. Examination 



of the blood during the lieight of the raalady may show greatly 
increased numbers of the red blood-corpuscles. 

Organisms Resefnblini^ the Cholera-vibrio. 

Spirillum of FinMer and Prior. — This organism was discovered 
by the investigators, whose names it bears, in the stools of a i-ase 
of cholera nostra.s. It resembles the vibrio of Asintic ehoh^a in 
its sliape and .somewhat in its nianner of growth and its prociue- 
tion of the iudol-reiiction. It dillerj?, liowever, in heiug somewhat 
longer and more slender and in coagulating milk when this is used 
as the culture-mediunk The growth upon gelatin is more rapid, 
so that within twenty-four hours in the ease of a puueture-eulture 
the liquefaction has proceeded so far all along the puncture that an 
elongated sac-like exenvation is formed, in which turbid liquid is 
contained. It lias not yet been proved that this organism has an 
etiologic relation to cholera nostras ; its pathogenicity is im- 

Spirillum T3rT0fenicum.— ^This is an organism dis<"overed in old 
cheese by Dcnceke. It resembles the last-named variety very 
closely, and dit!ei*s from the viln^io of cholera in li{juefying gelutin 
quickly, though the ra])idity is not so great as in the ease of the 
Finkler and Prior organism. 

Spirillum Metschuikowi, — This organism M'as discovered by 
Garaalcia in the intestines of chickens affected with cholerifonu 
disease. It is somewhat shorter and thicker than the cholera- 
spirillum. In culture it resembles the vibrio of cholera very 
closely, thougli the trained bacteriologist can easily distinguish 
them. The organism is non-jiathogcnie for man, but ehiekeus, 
pigeons, and guinea-pigs are highly susceptible. 

Besides these spirit hi or vihriones which have been discovered 
in %"arious diseases, a number of <>rgauisms that resemble closely 
the spirillum of eh<ileni have been ftumd in the water of streams 
supplying the drinking-water of cities. Among these Neisscr 
deseribeir the Spirillum Bertjliuensis, obtained fmm the water of 
the Spree in 1893. Duuhar and Oergcl isolated a similar organ- 
ism from the water of the El lie, and a nund>er ot* others of like 
character are known. The relations, however, of the (lifterent 
ibniis to each other and tlie ditfercntiatit>n of these varieties have 
not as yet been detinitely deternnned. 

PatJiogenicity.^ — Stjme of the forms dr^st*ribed produce violent 
gastro-intestiual disturV»ance and death in a certain proportion of 
animals prepared l>v injection of opium and alkalinization of the 
intestinal tract witli smla and then fed with pure cultures of the 
orga.nisms. They are evidently highly irritating Imcteria, and 
9ome remote relationship seems to exist between them. This, 
however, cannot be positively asserted. 




Definition. — The term ' tuberculosis refers to various condi- 
tions due to infection with the tiibercle-baeilluSj no nuitter what 
the form or individual peculiarities of the case. The name was 
originally employed betiause of the occurrence of small nodules 
or ^* tubercles.*' It must be remembered^ however, that other 
diseases ghow small miliary nodules, perhaps imlisting^uisljable to 
the naked eye from miliary tubercles, and that tuberculosis some- 
times occurs without a single definite tubercle. 

Etiology.—Tuberculosis is infectious and contagious, the ba- 
cilli being transferred by the secretions and excretions from dis- 
eased |>ersons to a susceptible individual through the air, food, 
drink J or in other ways* The infectious cha meter of the disease 
was long suspected » but was definitely ]>ri>ved by Villemin in 
1865, and in 1882 Kocli succeeded in isolating the infective ba- 
cillus. Predisposing causes are of some importance. Formerly 
family susceptibility was thought an all -important cause, and the 
disease was supposed to be transmitted directly in families. At 
the present time we recognize the transmission of susceptibility^ 
and very rarely transmission of the disease itself^ from parent to 
child. Susceptible persons fre^piently show delicate organization 
with poor development of the body, particularly of the chest. 
Besides inherited susceptibility^ acquired predisposition may result 
from occupations which lower vitality, from grief, prolonged ner- 
vous strain and exhaustion ; and some one of the organs may be 
Bpeei«illy predisiKised by injuries, as in cases of tuberculosis occur- 
ring in the lungs of those inluiling sharp particles of metal, coal, 
and the like. Such mechanical lesions prepare a place of lesser 
resistance, and tubercle-bacilli more easily gain a footing than in 
normal tissues. Continued local anemia seems to predispose. 

The kuman Itditreie fxtcillnJi is a rod-shapeil orgiuiism, 1.5 fi to 
3,5 n in length and from 0.2 ft to 0.5 /i in breaiith. 8onietimes 
it is even longer, especially after cultivation. It oileu occui^ in 
pairs or in groups arranged end to end, but not overlapping, and 
evidently not attached the *me to the other. It also occurs either 
straight or more or less curved, and may njften be found S-shape<i 
or in branching fornis. When staineil, it may either appear uni- 
formly colored or nniy present a beaded appeamnee. The latter 
condition is caused liy the alteration of pt^rtions well stained and 
intervening ptuts with little or no stain (Fig. 90). These light 
areas were fonnerly regarded as sjwres (Koch), but are now oe- 
lieved to be the result of fragmentation of the bacillus and retrac- 
tion of the substance of the *>rgauism causing vacant art»as. In 
other words, the light areas are tlue to degeneration. They are 
certainly not spores. There appears to be a narrow capsule closely 



applied to the organism and the capsule seems to contain in 
especial abundance the wax-like substance that occasions the pecu- 
liar staining properties of tlie bacillus. The bacillus is non-motile 
and does uot have flagella. It is, therefore, transported by out- 
side agencies entirely. 

The tubercle bacilli fijnnd in man, cattle, and fowl exhibit 
fitrnctuml and oultnml differeoi^es, tlnjugli thiy are probably the 
same bacilli exhil>iting different i-haracteristics caused by their 
growth in different environments. 

The bovine baf^illus is mnch shorter and thicker than the human 
bacillus, being from L5 fi to 2 ft m length and of an oval shape, 
the length being not more tfian double the breadth. It is straight^ 
and dfies not exhibit the curved and liranehing forms of the linman 
bacilli. When stained, it is uniforndy colored^ tlie beading being 
markedly absent Cultures of the bovine organism in glycerin 
broth are at first acid but become alkaline while those of the 
human species never become alkaline* Tuberculin made from the 
bovine species is alkaline ; that from the human species highly 

The avian tuhrrrh* haei/htJt differs from the human bacillus in 
that it is more nfteu club-shaped and branetii ug, und that it gmws 
more luxuriantly upon glycerin agar and bloml-sennnj and at a 
nmeh higher tempcnitnte— 45^ C\ (113° F.). It will also grow 
on ordinary agar, but not on potato. It is much more resistant 
to heat, especially as regards its virulence. 

JflO. so,— Tabenile-bAcUli Jei tha ipuium ; SSelu'a homo;. Immerelon ^, Oc. 4 ; magtilAed 

about lOOa diAm, 

Artificial culture of tlie Bacillus tuberculosis was first success- 
fully accomplished by the use of blofxbserum as a me<linm. 
The baciUus grows very slowly ; after ten days or two weeks 
the surface of the medium shows dn^ flakish deposit^s, somewhat 
resembling the scales in certain skin-diseases (Fig. 91). The 



edges of tbe^ flakes tend to elevate themselves a little, nrnl the 
substance of the growtli has aonmibled appearance. Placed under 
a cover-glass in muss and exam intni uiih tla- mk-ruscop^- these flak i^s 
are found to be eomjK>sed of rontorttd nuus??^^ at' bacilli (Fig. 92). 
Pure cultures are »>btaiurd from the lymphatic glands «»f ani- 
mals artitically infected and dcstruyed before the tuberculous foci 
have ad%^anced to the stage of necrotic change. Cultures may be 
obtiiiued with some ditticulty from the sputum or otiicr excreta. 
At the present time bhKMl-scrum is h'ss frequently 08*^1, as it has 
been found tluit agar-ag-ar slightly aeidulatcd and CHtUaining a 
large proportion of glycerin, and bonilhin containing glycerin, serve « 
as useful media. The original culture is still, as a rule, olitaineil in 
blood serum or coagulated egg. Even potato and other simple 
substances are foimd to be satisfactory media. The bacillus re- 
quires a rather even temperature for its growtli ; it flourishes best 
at 37.5° a ( 99.5^ F, ), and dws not grow below 29^ C. ( 84^ 1^ ), 
or above 42° C\ f 107.6^ F, ). Exposure to higher tempcnitnres 
(75^ C. )(1<>7° F. ) mpidly destn>ys it; and strong sunlight is 
destructive. It refpiires considerable air and always grows ujion 
the surface of the medium in which it is cultivated. Prolonged 
cultivation upon artiiieial media lessens its virulence. 

DemonstratioE. — Tiie demonstration of the tulxTclc-bacilbis by 
stain ing-methods is extremely easy and satisfactory. It has \>een 
found that this organixsm, Hke that of lepra and the smcgraa-bacil- 
lus, does not readily stain, but after receiving a stain retains it 
despite the action of strong mincnd acids. Upon this principle 
the methods of sUiiniugart* based. Kcwli useil as a stain a geutian- 
violet solution containing anilin-oib the latter playing the part of 
a mordant or an agent in fix the sUiin in resistant bacilli* The 
specimen was then decoh»rized by treating it with a siilution of a 
mincnd acid, which removes the stain from everything but the 
tnbercle-haeillus. A counter-stain might then be used Uy render 
the detection of tlie Imcilli more easy. 

The most convenieut method is the following : sputum is spread 
in a film u|)on tliin eover-glasses or slides. These are allowed to 
dry in air and then thoroughly tixed by drawing the speeinien 
through a Buuscn flame three times ; a dr<jp or two of Zichl's 
solution of carliol-fochsin (see Appendix) are addtn] an(i heated 
until the liquid steams. After two or three minutes the stain is 
washed off with water and a few drops of Gabbett's sobition 
(methylcnc-bluc, 2 ; sulphuric acid, 25 ; water, To) placed upon it 
ami allowed to remain a minute or two. The specimen is again 
wjishcd witfi water, and should then l>e uniformly blue; if not, a 
little more (iabbett's solntitm is addtnl as Ix'tbre. In this metliLKl 
the earbobfuehsin stains everything, including the tubercle-bacil- 
lus ; the sulphuric acid of the second solution decolorizes everv- 
thiog but the tubercle-bacillus ; and the niethylene-blue at once 



Stains the cells and other element^?, leaving the bacilli dark red. 
Even more satisthctory resultrt may be obtainHl by allowing the 

c^rljol-fuchsin t*» ntain at onlinary temperatures tor twelve hniirn; 
and in the staining of bu<'iUi in tiss^iies this prolongt*d cold staining 
is particularly desirable, (rram's metluxl i^ives jKisitive results. 

Distributioii of tlie Tubercle-bacillus .^Tii is organism is prob- 
ably a pure parasite, occ 11 rri 11^ and inuhiplying ojdy in the limly 
or excreta of diseased indiviiluals, hiuaan nr animal* Spnta or 
other excreta containing tlie Imi^lhis may tlry and retain the 
bacilUts in a dormant tliongh still potential form tor long pt rio<ls 
of time, ont^ide the body. Mnltiplieatit^n 
of the organism, however, probably very 
nirelym*enrs, except within the ImkIv. The 
bacillus is fonnrl iii the lesions of all j>arts 
of the ImmIv. 

Modes of Infection.— The bacillus niav 
7^ #"ii gain access to the b^nly citlnT by direct in- 

',J ^ iJ oculation, bv the inhalation iir swallowitig 

Fig. 91.— Ctiltiirp «f tubciTl*> 
tiACini oil f^XyrijTin-aent, four 
wi*«lcj aid ( Frill It V I a ntf Pfe lin-r ) 

k1ji«i!« prcptirHiinti rrtun u fniirteen-diiy-old blood' 
aeniiu culiufc; • UH) iFrunki4 ftu4 Pfelffer). 

of the gcrni^, or by tiufa-utcrinc iransferrnce thivnigh iIuj placenta. 
Direct inficulation through external wounds is jxrhaps move tre- 
cjuent than is Ijelieved. Definite lesions of the skin have been 
caused by vaeeiiiation, and arc not infrcqiictit upon the Imntis of 
anatomists, in the form of the B(x*allc(l anatomic tul>erclcs. In 
some of the cases of scrofulous ^*r tubrivuhtus glands «»f tlie 
neck in children, it is likely that the bacillus gains entrance 
through abnisions f»f the >kin or nf the miicnns mcmbnmt* nf the 





motith cir pharviix, Gi^oital tuber* "U Ins is Ia quite pLissibly fro* 
cjuently proflueetl bv direct impiimtation. The eommon 
iorni of iiiffctioD is thronj^h the ins|iin*d air. The breath of 
phthisical patients does not ortlinurily contain bacilli, but the dust 
of n Kirns in wliiefi tuberculous jiatii^nts have lived may contain 
numerous iiaeilli in a tlry state, and these readily become mixed 
with the air and are thus inhaled* Tuberculosis of the lungs, nr 
more rarely of otlier parts of the respiratory tract, is thus produced 
in susceptible persons* The swallowiutr (jf tuberculous material 
may lead t<* tul>ercuIosis of any part of the gastro-intestinal tract 
by the direct iuoculation that results. Thus intestinal tuberculosis 
in piirticular is producetb Sometimes, liowever, the bacilli pass 
through the wall of the iutestine auil cause a primary lesion in the 
lymphatic glands of the abdonien, and it is nut improbable tliat 
even the mesenteric lymphatic glands may escape without dis- 
coverable lesicm or wholly and the final lodgement of the iufcctiug 
organism luay l>e the lungs. Tlie lincilli are swallowed witli milk 
or meat, or they may gain access to the mouth, in the ibrm of ibhst 
or particles of various kin<ls, autl lie swallowed with the saliva. 
The milk aud meat of infected cattle frequently contain bacilli, 
and uudr»ul>ted instances of infection in this way have occurred. 
Tlie prm>f of this is that in some cases of abdominal tuberculosis in 
yoimg children the organisms obtained in culttnvs have shown 
the clianicteristics of the lx>viue species. Tlie intra-uteriue trans- 
mission of tuberculosis is Kire, but does occur. Most of tlie cases, 
howeverj of tuberculosis in earlv life may be explained as post- 
natal infections thnaigh milk, inspired air, etc. Some recent 
authorities assume that a few^ tubercle bacilli tninsferred from the 
iiHtthcr to the fetus may lie dormant in tlic fetus and cliild atid 
later cause active infection. This liypothesis rests u|>cui no demon- 
strated facts. 

Relation of Human to Animal Tuberculosis*— Tul>erculosis attacks 
the lower animals with varying frccpieucy. It is n^ost eommon 
in cattle, aud iMcaust* of the pcculianties of the bacilli and lesions 
this form of the disease is termed '* bovine tubereul<Ksis." Slany 
expertriM-nts !iave been made to establisli the rclatictn existing 
bet\v»*eu the Ijovine nud human forni,'^ of the disease, and Koch, 
in VM}\, made the statement tiiat the two were ilitierent dis- 
eases antl probably w^ere not intercom muuical)le. Kavenel dia- 
[)roved dii.-^ asM-rtion by proihicing the disease in cattle with 
mcilli obtained frotu luuiiau sources^ altluuigh the animals exhib- 
ited a high grade of resistauce t4i sueli au infcetum. At tire same 
time lie reportetl 4 cases of accideutid IcK^al infei-tiou in man with 
the iHiviur- bacillus, lie, theretbre, nutiutains '* that human and 
bovine tuberculosis are bul f tightly different manitcstations of one 
tttid the same disease, and tiuit they are interec»mnumicable,^' Less 
frequently tulicR^ulosis occurs in hogs, goats, horst^s, dogs, cats, 




slieep, rats guiiieii-pig.s, and rabbits. All these animals are more 
ftiii^eeptible wbeii kept in eonfincineiiL Captive monkeys are 
highly suseeptible. In all ttiese iinirnals tlie rliseaM' i,s proluibly 
iiitereoniniitniealile with tninian tuljerciilosis, but the lesions are 
not alwavs identieal with tliose foiuid in ihe latter lUsease, Binls 
and fowl of various kinds are suseeptible, tliongh the disease is 
somewhat diifrreut in them from that seen in man (see Fowl- 
Tubereijlosis). Ttiljercnlosis of eold-i*hKMled animals has also 
bf en reeogrvized. Tlie form cd" disease in the latter is atypieal, and 
tlic> baeilhis shows peculiar ebanieteristies, but tends to upproaeh 
the form of the In i man bacillus by successive passag^e through 

Animals may become infected from man^ and may further 
spread the infeetion by their diseluirges and exeretions. In the 
case of eattle tlie ilanger of <lissemi nation is jiartieularly great, 
because <»f the danger to man of infection tli rough tlie diges- 
tive tract by means of tuberculous milk or meat insufficiently 

Aceording to the best testimony available at the present time it 
seems likely that the Iioman» bovine, avian, and otlieranimal species 
nr<' simply variations of one common bacterial organisnj. Not 
improbably the peculiar I'haraeteristics may l>e ai'fpiired in the 
human bo<ly or the animal after tlie tjriginal infection. Thus the 
proof of the original scnirce of the infection may be lost. 

Pathologic Anatomy.^Tubereulosis is characterized by the 
erupti<*n of sujall nofhdes v^irying in size from one or two mi 1 li- 
me ters in diameter to that of a small pca» These are known 
as miliar f^ titfMiX'h\s. As already mentioned, tlie tatter in gro^s 
appearanee are not distinctive of tnbercuh»sis, as similar hckIuIcs 
are met with in othcT diseases. Besides the tubercle there are 
inflammfttorif kmonj< occurring between the tul>ercles and varying 
with the anatomic i*haraeter of the organs affected. Thus in the 
bmgs tile tubercle may be inconsjMeuous, whereas the pueumonic 
infiltration nf the Inng-t issue surrounding the tubercles and tilling 
in the s{>aces between them gives the organ its most striking 
anatomic characters. There are instanc*'s of tnbeivulosis in which 
the whole i>rcx'ess nms its course withotit the development of any 
definite tuWrcles, For example, in the Inngs the inhalation of 
tubende-bacilli in considerable nuudK r may be followed by rapid 
tuliereidous pneumonia without flelinite tubercles, and in other 
sitnations similar results may be produeed. In the further prog- 
ress of a case of tuberculosis eaM'om change is important. This 
may present itself in the form of areas of considerable size having 
a dull, opatiue, luster less, grayish or whitisli charactcT, and not 
inaptly likeneil to the appearant^e of eheese. Tiu^se centers of 
wiseons necrosis may finally iK'conie liquefied, and cavity-forma- 
tions may n!sult. These clianges are particularly frequent in 



tulieruulosk of tlM- luopi. len^ freqiK'iJt in tiotDes, ddn, glands 
kidii^}>:. Ld wttinw^taon "witij ral^erpuloa* of bones there nunr 
be formed «iiuiU or lai^ ^iviti^ filled with liqoefi«d csdecmfs 
or purifrinii materiaLl. Tbe*ie may JDvolve the si2iTomidiii«: ti^ 
Hue*- a*- \\*f\\ tu!^ tbe \Mjiatf^ tbemftelves. Tbe term ocJd abf^^eaf^ 
it applied tc» tbem. Small tul>ert-ular area^ and dometniDeB <*v«i 
lanere loci are pfjue tt* Ix* «urn>m>ded by reacitive fibtxwiMassDe 
IrypHr^JaKia. auo tiiuf^ a <ir>mplete eDcapsulatkiD may resoll. fimall 
i'o<;i may Ijf- iuuii'«.tfiuJy traiifdR^rwed by organizatioD of prcilifenitiiig 
coiiue«.n.jve tJ*s*iue aud may Ix- tbu^ entirely beakd. li cnber cae^e* 
simiile ^JU'^apHuiatioD Ofx-urr-, tbe tuljerculous mas^ m-hbin pc-Aajif 
miaer;yr'.»iii^ *^dii*^ali^jii. Tbeee changes will be m<a>e parDcolarly 
rderred lo belov . 

>i'.. K..->!.:iu'-y lu-j 

pan*, t] 

'JuUnuloU'- ]«-Hon«rof tlie muam.^ membraDe> iVinjuenily Ix^in 
MJtlj t]j«- ionjiatiojj of dirrtiurt tiib^-n.-k^ *.»ivni>yinir the deeper 
layers of thi- njii<r»-ia or the ^ubIlJ^l<^•^a. Thtx- hv ix>nflut'nce may 
i'onu <^>ij»-i<ierable anrsir of tuln reulou- di^<«se. while at tbe same 
liuie n^tiv*;- iuflamniation of the .-ummndintr tis>iu^ add> to the 
man^. S>r»ij<-r or later ulrx-rative eli:nij^t^ ii|H»n tho Mirfac'e make 
their api>earane«,- and irn^gtilar. iiion- or U'>> necn>tii*, ulcers iv- 
Buit. I'lie iHi.^HyM'!^ api>ea ranee f»f these and the ixvuireiK^ of 
dibtinct tul>erf.*le« in the Mires or ha^ manifest the character of 
the pnxj^ftK. 

Stnicture and ETolntion of the Tnbercle. — When the tubercle- 
bacillus b receiveid into any tissue or organ its fii^t effect, acciml- 
iog to the investigation-? of Ikumtrartenris to stimulate or irritate 
tbe fixed connective-ti-srue elenu^nts an*! endothelial cells and 



cause a pmliferatinn nf roiuid cells, which resemble in their hIjuji- 
dance of pn>t(i|)liii?ni tlie epithelial cells,anil are t f if re fu re known as 
epithelicml cells. These [jave tisiially a sin^^le nueleiis, nf nuher 
ek'ar vesicular appearaneL-, not deeply stainingj ainl a relatively 
targe amount of prtJtupla^m. They may be pnuluced in greater or 
less abuniiancCj us the first reactive change of the tissues t*j the 
irritati^ju t>f the tuberele-haeilli. Next there follows an infiltration 
with h/tikocytes from the ^nrromuiing l>looi!-vessels or lymplioid 
collei'tifins euniniuM to all tissues; anil the fotnis at irritation thus 
Ijecoine^ surrtmnded with numerous small round eel Is mostly 
moiionnelear, with darkly staining nucleus and a email pmtophtsmic 
b<Hly ( Fig. 93 )* In more acutely formed lesions poly morpho- 
imelear leukocytes are more ahundant. This lenkncytic infiltratit>n 
represents the reaction c>f the vasenlar system to the tuberculoviB 
irritation uv infeetion. The number of small round ceils varies 
greatly in tliffercnt instances. Sometimes, as in certain tubercles 
of lymphatic glands, they may he relatively few, while the epitlie- 
lioid cells are present in ahundimee. In other cases the leukoeyteg 
are go tpnekly attract cd and in snch nnndiers that tlic tnltcrcle 
seems composed <pf these ( ells ahine, no epitliclioic] cells ajipearing 
in view. These tnherehs art* known as tlic lymplioiih In the 
later stages the nnuid cells may disappear by degeneration, exj>os- 
ing the previonsty Ijidden f^|)itheHoid vvWs to view. 

At tlie stage of the tubercle when it is composed mainly of 
epithelioid and lymphoid cells it ajipears to the naked eye as a 
gRiyisii, somt^what tninshic»ent p<'arly lnMly, It is avascular, no 
tendency toward fi*nnation of nt w blfjotl- vessels being apparent. 
In the further evohition of the lesion <lcgenerative clnmges take 
place* These are hyaline degeneration, coagulation-necrosis, fatty 
change, and eventually a transformation into cheesy material, 
the S(>ealle<l caseous necrosis. These changes result* from the 
specific action of the living tubercle-bacilhis, though in part 
also from the avascular cunditii>u of the tissue. Avascularity 
alone, however, is not the cause of caseous necrosis. One 
of the first changes noted is a granular change in the cell- 
protoplasm which lessens the affinity of tlie cell-protoplasm 
ami of the nucleus for t>rdinary stains. There mny he 
seen among the cells of the tubercle here and there indi- 
viduals which show this l>eginning necrosis. These are usually 
grouped in the center of tlu^ tuhercle, though at times also at dif- 
ferent points* The outlines of these cells become less <listJiiet and 
they are progressively less deeply stained, imtil with advant^ed 
necrosis the cell is broken down into parti<'les or debris (Fig. 94). 
In the early staercs of necrosis tlie c[i!tlielioid cells tend to form 
giant cells eitlicr by <'iialcsccuce of neighhoring epithelioid cells or 
by division of the nuch-us without division of the cell-body. The 
gmnt-cell i§ not characteristic oi' tuberculosis, as it may be found 



iit riiaiiy of the specific inflammations aad aLso in foci of chronic 
innliiti{jii due to fon'i|T;n bodies, as well as in tumors. In no con- 
dilion, hovveve?*, are they so abundant or so eonspieuous as in 
tnbtrenlosis. In sihoo eases they niay not be seen in tiie tnben^le.s 
at iuiy stage, fu otlier eases tboy are very nunierons, Tl*e giant- 
cell falls an early victim to the advancing neerosis. Perliaps in 
fliet the formation of the giant-i'ell is an evidence of beirirmin^ 
nef^rosis and the division of nuclei without division of the cell is 
an (>vlih*nct^ of the *h'irenerative ehaii|jje. As nerrosis of the cell 
advaneeh the protoplasta becomes granular and opaque, and event- 

^ flPBfcW— I^rgii lutMfrelt^ of the liui^, showing cheesy iKtrt>sia fti the center; the epitb^ 
lioid uinl Ik' in lit -I'd Ls Jirouiid the ch«?e«y center are morti or leiis dc^e tie ruled. 

nally breaks down t^onipletcly. This change usually occurs at the 
opptxsitc side tjf the cell from that in which the nuclei are jjathcrcd ; 
or in rrascs in whiefi the nnelei are near the ]jeripliery of the cell 
the neiTc^tie eban^es licijin in ihe cenlcr. Finally^ a tuljcrcle 
undergoes alniost complete necrosis antl is transformed into a 
cheesy mass, the snrronnding coinicctivc tissue perhaps still show- 
ing proliferative changes which may eventually cjuisc enca]»sida- 
tionofthe tubercle. Calcitication may ensue in the cheesy masH 
and thus lead to pennauent arrest of activity in the no<hdc. 

In the growth of tuberculosis tht* normal tissne-elenients of the 
part affected are pushed aside, or may lH^M>ftenetl and de?^troycd by 
the disease-pnxvssis. Tlie connective-tissue iil)ers of the jxirt, 
however, are longi'st ivtained, and remain as a reticulum or tuber- 
cle-etroma h>ng afVer tin- other elements ot the ti*ssue have dis- 
appeared or bt'cn pushed aside. 

Tnl>creles t**ud to «H>alesee, forming larger tubercular musses, 
and sometimes ilistinct tubertrulous turaon^ are sti produced. In 



tli(^ lower ;»iiimaLs» pnrtiruliirly in nittle, such tuhereular tumors 
of the sen>us i^u^faee^5 are nut uiieonim<ni. They may simply 
stud the niembmiies, or they may hang as |>c>lypoid masses ; the 
term '^|warl disease'* is applied to tliese^. SomeAvhat similar 
tubereuhir tumors are met with in Imman tuhereulosis, especially 
in tlie liraiu. A?? a rule, ln^never, increasing areas 4jf tubei^culous 
disease of organs are only partly eom posed of tiibereles, the bulk 
of the disea^seil area presenting evidenees of ordinary t»r peculiar 
inflanTmatory changeH to wbieh the j>re,sence oC tin' tn!>errles has 
stimulated the tissues. 

Fio. 95.— GL&rit-cen eontaitiiUR biwillt {fyom a photograph mi44e by l>r. Win M. flmy). 

The tuberele-baeilli iu the earliest stages of the tube re*! e may 
be seen lying in the tissue and perhajjs lietween the epithelicHd 
cells first funne<l. \\'itlj the evolution of the ilisease they are 
more and more abundant, are largely within the eelLs^ and tlie 
giant-eells in j>articular may contain large nninbcrs (Fig. SJ-")). Ai* 
tlie necrotic elianges increase the bacilli become less couspicnons, 
and eventually none may be visible. The existence of the bacilli 
or their sjMires, however, cannot be <loul*te(b since injection of 
pirtions of sueb tnlHTcles jinKluccs the disease in giiinea-pigB. 

After the establishment of the local lesion of tul»er<'nlosis in 
any part of the body two opposing ti'udt^ncies struggle for supreni- 
ajcy\ the tendency *»f the tuberculous disease to spreati and the 
tendency of the normal tissues to encapsulate or limit the spread 
of tiie invading disease. lo most eases the f(»rmcr suc<*eeds and 
the si'eoiidary tu!>ercles first appear in adjaecut parts, the tninsfM^r- 
taticm of the bacilli trom the primarv to the sc<>undarv focus being 
accomplished either t>y the flow of the lymph or juiees of the hoily, 
or by the phagocytic activity of lenkm\ytes. Tlu^ latter take fnjm 
the tnlges of the tubcnde some of the bacilli and transport tliem 
either by their own amebnid activities or in the lympb-sti'eain to 
neighboring parts, where tlu-y thi'inselves fall victims to the organ- 


Lsms they have appropriated^ and thus deposit the germs of new 
foci of disease. The dissemination of tubercles to more distant 
parts may occur in various ways. In the case of tuberculosis of 
the mucous membranes bacilli may be cast off from the surface 
and spread to other parts of the mucous tracts with the contents 
of these, as in the case of tul>erculosis of the gastro-intestinal 
tract. In the case of pulmonary' lesions the ulcerative processes, 
or attacks of coughing, may loosen infected particles from lesions 
of the bronchi, and the deep inspirator^' efforts following the 
cough, or the ordinary inspirations, may carrj' the bacilli into 
the finer bronchioles, where new foci arise. If the tubercular 
lesion involves the walls of the lymphatics, particularly the larger 
lymph-channels, like the cervical or thoracic ducts, bacilli may 
gain access to the lymph-stream and thus be transported to the 
venous circulation, and then through the heart to the lungs or 
perhaps to other organs. When the tuberculous lesion invades the 
wall of a vein the dissemination of the bacilli is even more rapid 
and widespread, as the organisms find their way to the heart by a 
more direct route. In rare instances an artery* is invaded and the 
organisms are scattered through the terminal distribution of this. 
Upon surfaces the disease may spread by direct continuity or by 
the movements of the body. Thus lesions of the peritoneum may 
become almost universal in consequence of the peristaltic move- 
ments, though more frequently the extension occurs along the lym- 
phatic channels. 

The condition which results from general infection and forma- 
tion of tubercles in various situations is kno^Ti as miliary tubercu- 
losis. In these cases the progress is usually rapid and a fatal 
termination is not long delayed. The tubercles therefore remain 
small, and at autopsy are still typically gray miliarj' tubercles. 
Sometimes, however, miliar^' tul>ereulosis may assume a more 
chronic form, perhaps in consequence of the gradual admission of 
bacilli to the circulation and the formation of small crops of 
tul>ercles during a considerable periixl of time. 

Miliary tulM^rculosis may be local or general. In the former 
case the bacilli are admittetl to the vasinilar distribution of a re- 
stricted art*a only ; in the latter widespread dissemination through 
the bIcKxl occurs, and practically all jxirts of the body may be in- 
volveil. Lineal izeil miliary tuberculosis is most frequent in the 

Seats of Tuberculosis. — Among the frequent situations 
in which tuberculosis makes its ap[X»arance are the lungs, the 
lymphatic jrlands, the Inmes and joints, the muc<nis membranes, 
particularly those of the larynx and intestines, the serous mem- 
branes, the pn>state, testicle, ovaries, Fallopian tubes, kidneys, 
utenis, snpran^nal capsules, brain, liver, spleen. In some of these 
situations the lesions are pnictically always sei'ondarj', as, for ex- 




ample, in the liver ami .spleen. In others tliey are mo^t IVequeiitiy 
primary, as in the liin^s. The ^Mvurretiee of jirimary tuberculosis 
in the internal ort^ans may he ilifficiilt to explain. It is possihle, 
however, fur the haeilli to piin aeress to tlie lymphatic i»r bhwHl- 
einajlation without causing a It^sian at tfj*' point tit' entnincc. Their 
dep<^si. in some intrrmil or^^nn tlien ^wH'asitais tlie iirst or |>riniary 
focn^ of tli.sease. Thns [trimary taherenlosis of ttn* nt(^M ntene 
glamU of the lymphatie t^lamls of the iieek, or of the post- 
hn^nehial glands, may o(*eur willmut [>rimary f>f the intes- 
tine:?, of the miuith or skin, rtrof tlie lm*^s in the several instaners. 
Similarly primiiry tohereuhisis r*f tla* kichnn^ or of tlie snpmrenul 
e^psnle may oeeur witiiout any evidence of the point of entrance* 
of the miero-4jr^ni8ms. In some e^^^es, of eourse, the primary 
lesion may be &o small and in sneh a hidden situation that it 
escapes notiee. 

After the dii^ieovery fif the tubenjle-baeilhis a minibiT of ihse^jses 
not previously rei!Ognize<l as tuberculous beeanie identified as 
forms of this disease. Among tliese is Lupus Vuff/ariH of the skin. 
The histologic examination shows numerous tubenndous granula- 
tionSj sometimes arrangcnl in striate fashion altmg the small bliKid- 
vesjiels of the skin and eoataining epithelioid and lymplioid cells 
and giant-eel Is. The presence of tiic bacilli and the proved infee- 
tionsness of the tissue, with the histologv, render the riature of this 
disease certain. The warty formations treqnently acquired by 
anatomists at points of injury have likewise been sliown to be in 
many eases due to tuberculous infection, Sorofufa^ which was 
formerly regarded as a special cruiditinn pivdisposing strongly to 
tnbereidosjs, is mnv regardc^d as tubeivnlosis oc(*urri ug in (liferent 
forms and situations. The scrofulous glands of the neck consti- 
tute tuberculous adenitis, the iutection in matiy cases gaining 
aceess through the mucous membranes of the month ami pharynx 
or through the skin. SiTofulous rhinitis ami sinuses have simi- 
larly been shown to Vjc feuius uf tubcnndous disease. Manv enses 
of JointHlisease reganled as scrofulous or otherwise an* depentlent 
npon the action of the tuberele-baeilhis. 

The Smegma Bacillus.— A Imcitlua quite closely resembling the tuberele- 
bacilluB woj^ discov<.«riHl in the smegma and hiter an the akin of varhiua 
parts of the body. It not only rewembles the tuberch^-baciniis morpho- 
logicallj, but behaves in a similar manner toward stains. In particular this 
bacillus holds its stain when attempts are made t«i decoloriste with acids. 
The bacillna is treqnently found in urine, and thus may cause an ermnceius 
diagnosis of tuberculosis of the kidney or bladder. It may u^sually, though 
not certainly^ be distinguished by its easy diseolori^tiou with absolute 

Other Acid-proof Bacilli.— Severr^l other bacilli that are refractory to 
decolor! ziiti on with acid ♦tr nlrohol have been discovered in milk and butter^ 
in «puta, and in iiurulent or piiigrenou^ collectionH in the lungn and elne- 
where. Injections cd' pure cultures of tiomc *»f these cause hhrinous in- 
flammations* in the peritoneum of uuinea-pi^!* and rabbiti^, or p^eudotuber* 
culous formations, but not the specific lesions of tulicrculosiH. 



The lesions resaltine from inoculation with acid-fast bacilli show a 
striking resemblance to tnose of tobercalosis, and only a careful microscopic 
examination senrers to di^ttinguish them. Examined with a microscope, the 
lesions of this spurious tuberculosis present a more inflammatory appear- 
ance and show a tendency toward abscess-formation. In very rare instances, 
however, an approach toward the typical histologic conditions of ^nuine 
tuberculosis, cnaracterized by the formation of giant-celU, epithelioid cells, 
and caseation, is seen in thb form of pseudotuberculosU. 

Latent TaberenloaB. — A tuberculous lesion may become encap- 
sulated and limited in its extent before it has invaded tissues 
widely, and may so remain for years without giving rise to mani- 
fest clinical symptoms. Subsequently, however, the encapsulating 
membrane may be penetrated and widespread infection, local or 
general, may occur. Such latent tuberculosis is particularly fre- 
quent in the p>st-bronchial glands. These glands are often found 
enlarged at autopsies in which no tuberculoa< disease of other 
organs Ls found. Injections of emidsions of such glands in a nota- 
ble proportion of cases produce tuberculosis in guinea-pigs, and 
thas it has been determined that the glands in question are fre- 
quently the seat of latent tuberculous disease. The existence of 
such lesions explains the cases of sudden generalized miliary 
tul>erculosis, in which no primary- focus of the disease was recog- 
nized during life. 

Pathologic Physiology. — The effect of tuberculosis upon 
the general health varies greatly. Uiidoul)teilly the bacillus con- 
tains or is capable of producing toxic substances that have an 
eff<*ct upon the general organism ; the naturt* of these, however, 
still remains undetermined. The tuberculin of K<x*h, a glycerin- 
extnurt from cultures of the tubercle-bacillus, produces fever with 
the general symptoms characteristic of pyrexia and local reactive 
cliangf*s in existing tuberculous lesious. Among the latter 
nxlness or iucreaseil vascularization of the tul>ercles, and soften- 
ing or ncrrosis of the cells surrounding the bacilli, are most 
important. The last-named change deters the growth and mul- 
tiplication of the bacilli themselves, but at the same time makes 
their escajKf from the focus of disease more easy and thus 
exposes the individual to the liability of gtMioral infection. The 
active substance contained in tuberculin is probablv a protein. It 
dfx*s not act ujK)n the tubercle-bacillus direi'tly ana is not an anti- 
toxin. In addition to this the tubercle -bacillus in its dead state 
contains some bixly or lK)dies capable of influencing the organism, 
as was shown by the experiments of Prudden and Hodenpyl, who 
were able to pnxluce nodular lesions by injecting dead bacilli into 
the circulation of animals. These lesions, of course, are not 
strictly tulK^rculous, though they possess some elements of the 
natural tubercle. It is altogether probable, however, that in 
addition to the tuberculin of Koch and the cheniotactic substances 
oontaineil in the body of the tubercle-bacilli, there are other 


I>oisonons siib^binees prmluce<l by the growtlr ami rnnlti plication of 
the liu<:illi ii) the tir^sups, tluit k'lid to a (^iiirnil tjrtori(*ratiorj in the 
ln^alth i>f victiiim of thiis <lis( usr, Trudoau, Ftjarsnii amf <iilliluntl 
and iithtTs havr been abh^ to itnnurnixo aniinaU liy nuputed iiUM-iila- 
tions with Imrilli of lowiTctI viralenee. A form of imniiinity calleJ 
"i^opiithic" (Bchriojj;) i.s tliii?? prodncod. Tfie mr^x of siich 
immunized atiimuLs i.s nut ]>rut<^etive or eurativr U\ otlirr anttimls. 
Xone of the sopjioscd *■* antitoxic " Ht^ra thns fnr prudiieeil ba;^ 
been pruved to hrive antitt>xje or ininiunizint^ power. 

Tnbereidosis is primarily a h>eal j»mee.'^<, but influences the 
general organism by its tHreet efft^et upon the organ ie function:^ of 
the piirts in wldeh it is hieated by tlie dovelopmc^nt of tliese as yet 
unknown toxie substances^ and later by the wiilrspread infection 
of the organisUK The mechanism of defcn<'e agiunst tubereidosis 
i8 oidy partly kniiwn. In the ease of hx-al lesiims of the lung>^ or 
other parts the reaction of tire tissues probably resulting from the 
activity of ehemotactic substances in the body of the bacilli them- 
selves, or of similar substances pHxluced by the ccOlular necrosis, 
leads to the formatiruj of an em bai dement of celbdar or fibrous 
tissue that serves in Iiold tfie disease in < beeh. SubM ([ucntly the 
disease may l)e wholly eradicated by degenenitive changes termi- 
nating in calci Heat ion. That such favorable results are not 
uncommon is proved by the frequent occurrence at autopsies of 
small sclerotic or calcareous areas in the lungs. Tuberculosis is 
frecjuently cured in tliese early stagers, but after it has reaebed the 
degree of intensity f«r the widespreod character that makes it reeog- 
nizaljle by our present methiMfsof pliysieal examination, the reactive 
prt>cesses arc* usually no longer able to co[ie with its progress. 


Tuberculosis in various forms of fowl and birds (avian tubei-- 
cnlosis, tuln-reulosis gidlinanuo) is a disease sijuilar to, but nt^t 
identical ^^ith, human tul>i'reulosis> Tlie sjHiutaneous disease of 
birds wjcnrs most freipiently in the liver, the lunt^s Ijeing never 
primarily involvetl. In the liver are found notlulcs composcnl i)f 
roimd-eells, l»ut showing little tendency to coaguhitir»n-neerosis or 
to the format irni of giant-eel U. The structural and eultund dif- 
ferences of tlie hntuan antl avian bacilli have been disensscd on 
]>age 270. 

Ex|XTimeutal inoculations of bacilli isolated from the sponta- 
neous dise^ase will pnxluce the same disease in birds; but if animals, 
sueli as guinea-pigs or dogs, whieii are very siisceptilde to human 
tubereidosis, are iuoeululedj they frecjueutly resist inieetion, though 
they occasionally sueeumb. In the latter case tulnrehs iire usually 
alfgent, l>ut large unndH^rs of bacilli an- finuKl in the orgjins and 
in the abscesses which result at the point of inoeuhition. Accord- 



ing to Noeunl, rabbits show a marked degree of etisceptibility in 
this form of tuberciiloBis. 

Although tliere iy no doubt but that fowl in sonie instances 
have Vjeconie jnfertod tiirou|rh iHinuin sources, yet ex peri men tally 
they ex hill it a very higli degree of resistanee to linman baeilli. 
If, however, the human hac^illi are piissefl throtigh birdn IVir three 
or four genenition.s, or are plaeed in tlie [teritoneura of fowl in 
colkKJion sacs for the wime length of time, the virulence to birds 
is not only heightened, l*ut the liaeillus ehauge.s in its structural 
and enltund ehanieteri^stieH, asf^umiug those of the baeilbis isulatt'd 
from spontaneous avian tubercnhisis. Tlie same is true <if avian 
bacilli wlii-u thehe are iuoculatetl in animals susceptibh' to human 
bacilli. With each passige through sneli au animal the virulence 
of the haeillus is increase<I and the form and cultural ehanicter- 
istics become more and more like tliose of the liuman haeillus. 
Fr<im these experiments it ajipars that tlu^uian tulMTcle V)acilhm 
is only a ni(Mlifi(*atH>n of the ordinary tubercle l>aeil]us caused by 
Jt« growth in the tissues of the binh 


This name has been applied to conditions occasionally met 

with in which nrvdular lesions resembling tubercles, but containing 
micro-organisms of different kinds, have been found in the liver^ 
kidneys, and other orgatis. Pseudotubercid(Ksis is not a specific 
disease, as a number of distinct infections assume this imtliologic 
character. Among the organisnis isolated are various strepto- 
thrices and acid-proof bat-illi resembling the tubercle bacillus to 
some extent ( see pages 281 and ^l(Xi). In the lower animals, and 
very ran^ly in man, certain animal parasites cause lesions of the 
sanxe kind, 

PttntmonomycmiM Aj*pergiiiina.—Jii man and in animals pulmonary infec- 
tion with forma of asperirillus, eHpecially A. ftjmifjfitw!, may occur in a 
pseudotubercuioiiH form. The leMions are exadative and prrdiferative, and 
central cas^eation may be conmdcutiUs. The fungi which beloni^ to the 
prouf) of hyphmnyf^ten ur*? readily distiiipuiahed by the abundant myi'tdial 
threads ana the eonidia. Infection «f other orgaas may occur stfionta- 
neously or experimentally. 


Definition -^Leprosy I Lepra» or Elephantiasis Grtecornin, is 

an infect ioiis and mildly eonrxigi<nii5 di-ease eaused by ii specific 
bacillus, the Bacillus leprie, discovered by ILmseM. 

Etiology. — The essential cause of leprosy is a bacillus which 
closely resembles the tubercle*bacillus, though it ib less frequently 
curved and U somewliat more easily stained. Fnrther, it diflers 
in its grouping in ihe tissues and iu its failure to grow satisfac- 
torily on artificial media. The orgniiism i^ usually found in large 



numbers iu the Iqirous lesions and in the Bnml mucus, wlietlier 
there he definite lepmus ulir rat ions in the nose i>r not. In the 
tissnes the baeilli are tVnnid within large cells ot' tlie spi-ritie gimi- 
u latino tissue ( lepra-eells ). In the auiesthetie form il is tinmd in 
the nerves and centra] ncrvnus tissues. The c^rgunism lias ln'cn 
denionstnited in the hhxMl in certain eases of tlic tuiKrculnr ty}M\ 
It is readily stained by any of the methods npplieable for the 
tuberele-baeiUi or by Gram's method. It frequently shows light 
ureas like those of the tuhc^rck-baeillus ; these have been re- 
^ardcil as spores, but are int>re probably priKlueed by fmgmcnta- 
tions, as in the ease of the tnlterele-baeillus. Attempts at etilture 
have thus far been unsucees>ful, though Ncisser claims to have 
obtained cultures on blood-serum containing gelatin and on coagu- 
lated egir-albu(niu. Others have claimed detiuite residts with 
similar medisi^ l>ut euUivation at the present time is not ordinarily 

The s [>ec i fi c na t u re o f 1 1 ir bae i 1 1 ( i s h a s m it b eei i d c in oust ra teil , 
as it is almost, if not entirely impossible to produce the disease 
in animals. 8onie suggestive reisults liave been obtained by 
inoe (dating portions of lejirous tis.sue in the anterior chamber of 
the eye or otln-r part.s of anijuals; l)ut definite generalized leprosy 
lias not Ijeen thus far produei'd. In one ease the disease has l)een 
given to a condenimxl criminal by direct iiuM'ulation. 

Besides tlte specific bacillus other conditions are important io 
the etiology. Thus the disease flourishes in eertain hx-alities 
extensively and little in other places. It Is uncomnujn in the 
United States, liut simw of the (iulf States, piirti*'ularly Louisiana, 
have eonsideralilc colonics^ and in the Xortlnvt^st antl on tlie Pacific 
Coast it is met witti aniong tit* Norwegian and Chinese immi- 
grant's. In Mexico, South America, Norway and Sweden, India, 
and other Asian eon n tries it is common, and the Siindwieh Islamls 
are parti(*ularly at!crtcd. During the Middle Ages it finurished in 
Europi* as a uni versed seonrge, unsmiitary conditions ])rnbai)ly 
acting as the predisposing <"au.s«\ Certain articles of cliet are 
believed to oceai?ion it^ jiartieularly fisli ; this view, however, lacks 

The dijseai?^ must be regarded as contagions, though less so 
than tubereulosis. Intimate ass+iciation fur a long time seems to 
he neeessan" Inr its t ransfe renee. It is iJi-ubably traitstnittcil from 
|>iirent to utfsjiritjg in rare instances* 

Pathologic Anatomy. — Leprosy pre*4ents itself in two 
forms, the Utherimkir and tlic fittrfifhrtlr form. In ttie former there 
are developed in the skin of the taee, tlie extensor surfaces of the 
elbows and knees, alxait the liantls, or less frequently else where, 
small or large niwlular i'levations. These at first are re<lflish in 
cole»r, with apparent intlammatHry rr action. Later they lr»se tlieir 
redness and ii^niain a> indolent lesions that grow very slowly or 



rt'main ^tatiimarv. They mny break do\m, funning ulecrations 
whieh do not nudily heal, or they may he ^^rmlrially {converted 
into fibrous eieatrieial tissue^ eausiug im?^iirhtly deformities of the 
s^kin. The appumnee of the fmtieiil's faee is hisrldy eharaoteriiitie, 
ami is known as (eoniiui<h leprom (Fig. 9G). The miieous niem- 
braiK's and some of tlie internal organs may l»e involved. The 
auestlietie form is usimlly marker I by les.s eonsi>ieiious lesions, but 
subjective .symptoms, snch a^^ hypereBtliesia and neuralgie pains, 

in;, ^V— Nciiiular leproay ((.♦olilschrnifltl. 

and later ulcerations partly tr iplnc in nature, may make it a more 
serious variety. In the skin there ai*e found whitish or brownisli 
spots, slightly if at all t*levated or altenni in eonsistency. Later, 
ulremtions may ajijR'ar. Very eomnionly the anestlietic and 
tiibenndar varieties are coexistent. 

The mwlules oceniTing in tht^ liv(*r, spleen, and testes in this 
disease aR* admittetl to be siniilnr to the nrxlules of the skin j 
those found in the lun^s, kidneys, and Intestines, as well as those 
of the H'rous surfaees, are lielieved by many to be tuberculous and 
the re&nlt of seeondary infection. These two diseases are certaiirly 



frf'fjueotly associated ; jirHlmliiy 40 per ceut* of the eases of lepra 
become tiiherealoiis. 

Other f(*rins of secondarv' infection occur, tlius injuries of 
pujierlieial lesirms may allow pyo^enie infection, and extensive 
ulcerations ami g-an^renons necrosis may ent?ue. The terms hpra 
madia iis and itj/ni fjatif/ntnosa arc applied to sui^h ; ao<l various 
niicrwH>cci and sapn»[>liytic orgiiuisnis have l>een disco verc^d in 
such ca^^s, 

Stnicture of the Leprous Lesions.— The nmltde or lepronia is a 
soniewliat indurated ^rrouth resemijling the tubercle, but differing 
from it in its greater vascularity atid in the absence of the ten- 
den ey to cheesy necrosis. Microscc*piealIy it is com|xised very 
largely of proliferated eonneetivc-tissne cells of different fonu.s, 
and leukocytes. New blood-vessels are disco vere*! in more or IcSvS 
aliundanee, an*l a tendency to complete orgimization witli the 
iormation of tibrons tissue may be seen in the character of the 
cells and tlie presence of liiirous iutcrcelbilar material. The 
bacilli occur vvitiiin the ecUs and possibly also between tliem. 
They are always ibimd in gron^js and usually in large numbers. 
They multiply witlun tlie cells, tfie j>rotoplasin oi" the latter at the 
same time uoilergoing a process of swelling and degeneration. 
This at first spares the nueleus, but finally the nucleus itself is 
broken down and the cell is thus converted into a sac containing 
degenerated protoplasm an<l alnuKlant bacilh (Fig, 97). Tlie term 
hftnt-t^'U has l>een given to these. Ctiant-cclls may be formed, 
tliongh they are not frequent and are rarely typical. S(K'ondary 
infections or injuries may lead to snppurative or other forms of 
soften in ST. nnd tlu' finai terminatirm sillier with or without previous 
softening nuty be eicatrization. The lesions of the internal organs 
met with in s^uru' leprous eases^ notably those of the hnigs, intes- 
tine, kidney, and m rcujs surlin-es, arc avascular, show more tciutency 
to necrosis, and euiitaiu more giant-cells; in some cases inocu- 
lation has showed that the Icsious con- 
tained tnliercle-baeilii. Whether they are 
strictly tnbereles^ or wiiether they are 
leproiuata with seeon<larv in fed ifiii with 
tnberele-bat^JHi, cannot be deciilecb Tficy 
are certainly not pure leprosy, aiul more 
prcjliably are purely tuberculous. 

The anesthetic areas and pignicnted 
or light-eoloD d spots of the anesthetic 
fJirm |>rescut somewhat the same his- 
tologic featiiiws as the lepmus nodule, 
thongii in a diffuse form. Formerly 
these lesions were cousidereil entirely the 
result of trophie changes. In these eases the more eonspicyous 
h^siou is that of tfic nerves. These may show nodular tliickening 

1 JG. i>T,— lA'pm-ljrtctlll in * 

It-pm fell (Ktiri? and Sehtiiorl). 


of the ])crineurium with inflammatory and degenerative changes 
of the nerve itself The bacilli are i)resent in these lesions. 
Changi»s in the spinal cord have occasionally been discovered. 

Pathologic Physiology. — Infection with the lepra-bacillus 
leads to local rather than g;enepal disturbances. The toxins of the 
disease, if such there l)e, are not of great virulence, and constitu- 
tional symptoms are therefore wanting as a rule. In the later 
stages lever and other systemic disorders may be occasioned by 
secondary infections. A supposed antitoxic substance has been 
prepared and has been largely used. It is impossible to claim or 
dis<*laim the; antitoxic nature of this, as no toxins have as yet been 
isolated or obtained in any form, and the supjwsed antitoxic sub- 
stances cannot therefore be tested. 

In the anesth(»tic form it was formerly cnstomar}* to regard the 
pigment or light-i'olortMl sjK)ts as a result of trophic disturbance, 
an<l more* destructive lesicms, such as ulceration and gangrene, 
received a similar explanation. Recent investigations, however, 
8et»m to show that in thest» eases there is usually from the first a 
leprous ehangt* in the tissues, and that secondary infections fre- 
quently i)lay a jwrt, though trophic disturbances must still be 
admitti'il to a certain extent. 


Definitioti. — Glanders is an infivtious and contagious disease 
of horst*s and asst»s, st)metimes (H>mmunieateil to other animals and 
to man, and caustni bv a siH^cifie bacillus. 

Etiology. — The bacillus mallei was first isolated by IaM^v 
ami 8i*hiitz. It is an <)npinism resiMubling the tubercle-bacillus, 
though somewhat slu>rter and thicker. In cultures it may grow to 
long filaments and not ran^Iy it brt^aks up into <\Hvus-like frag- 
ments. It oiMMirs in the lesions of the disease singly or in clumi>s, 
and has Inon found in the blo^Ml. The baeillns is non-motile and 
d«n»s not pi>ssi'ss rtagella. Staineil s|KH'imens show |\:irts that do 
not nveive the stain. These have Ihmmi reganUn^l as siH>n^s. but 
an^ mon\$^Mierally thought to In^an^isivf clegeneration. Onlinary 
solutions of anilin dvi»s, and rs|HviaIly alkaline solutions, stain the 
orgsmism vofa* wt'll. The dcnitmstration of the bacillus in the 
tissues n'<juin»s pn>longeil staining and rapid dtri>loriz:ition. 

Cultivation.— C'ultun^ an* Ivst obtaimnl from M>t\en(Hl iki<1uU*s 
of guinea-pigs imvulatiHl with intW'tiHl pus. or t*n>m the testicles 
after injt\*tii>n o( inftvtive matter into the ivritom'al I'iivity. The 
otyanism grows quite rt^adily ujxm onlinarv nu'<lia, but the most 
charaeteristio eulturi' is s<Y*n ujwn Ix^ihnl }^>tato. The ix>lony 
first apjx^irs as a honey-like layer, whirh lHHH>nu^ bn>wnish in 
etJor. The i»tato itself lKH\>mes gnvnish-bn>wn lH*ni»:ith and 
around the iH^lonv. The cultivation is most >ut\vsstiil Unween 
30^ and 4tV^ C. «S«S aixl U>4-" Yx 



Drying :iih1 rlivtUod tcmpcTiitnres nqiidly dtstrnv the organ- 
Ism, aiul mitis(*j»tt(*s kill it \\\\\Xv yvim\\\\\ T\\v IkmHIms is a jvuro 
pamsite, JmiltipJyiiig unly in th(* IkkIv (»r info-ti'il aiiimals or 

Pathogenicity* — The specific character of the ijaciHiLs is uncjues- 
tionahh', Ijinciihition of <jjuinea-pi;is, ral>hits^ fiehlHiiicf, ur rither 
iiniraals \x\{\\ miWivi] jms ur with purr cultures leads to n*Kliilur 
lesions vtt the piiiit of introtluctiou, with suhseipn-nt softeuint: and 
nleeratinii. SiM'ondarily tin' lyrnpfiatic jrlands tiilarge and after 
from 2 to 4 w< ( k> sup|iiiniti'. In male guinea-pigs a practically 
pathngiinnionic conditirtn (great en large me lit of the testicles) is ob- 
served within two ur tlirce days after intrajieritoneai iiineulatiun 
with pure eiiltiires ur exn<lute fmni the lesions of the disease. 
After death ii«idu)es are tonnd in the liver, sjileen, kidneys, or 
other organs, and tliese contain the haeilH, In horses and ansen 
ehanicteristie lesions of tlie nineons nn'nihranes have been [im- 
dnced experimentally ; while in man aeeidental infection of hostlers 
or others ermiing in contat^t with di*irased animals^ iunl t>i bacteri- 
ologists working with enltnn'S, have l»een rejieat^^dly ol>s4'rveiL In 
one case in my nwn knowledge a man was inieeted in a stable in 
which a ghinih'rei! horse was kept, and the Imeteriohigist wlio 
isolated the organisms from the patient accidentally infected him- 
self witli tlu^ en It ares. 

Patholog^ic Anatomy.— In hoi-s^s ghindcrs [presents charac- 
teristic h'sions i>f tiic mneusa of the* nose. At tirst tliiTe are found 
slightly eli'vatcfi nodules, wliieh iiuve a marked tendency to soften, 
forming irregidar nlcerations tliat hecome ctmfluent. Ttie floor 
and edges of the ulcers are y el h) wish and mx-rotic in appearance, 
and diseharge more or less pnndcnt matter. The lytnpliatic glands 
of the neek and elsewhere enlarge and may snppnrate. In the 
skin th(* lesiojis arc much the same, bnt more shiggish. Xodules 
are not rarely met with i]i the Inngs, These are grayish t^r ]>ink- 
isli in color, and tend to rapid necrosis. ]More rarely nodules or 
ulcers are tbond in the nincosa of the gastnj-intestinal tnict. 

In man sinular n{3<hdes and nieerntions may he iV»nnd in the 
nose, larynx, nv tiiH-hea ; and external hsions resembling small or 
large carbuncles are i'onnrl, 

Histohigieally the lesietns <jf glanders consist of aggregations 
of round ceils of lymjilmid or polynior|>linnuelear type. ThiTc i^ 
a marked t+'ndt ney to supjKU'ative wv neurotic softening, and s<jine- 
times lienmrrliagie in lilt rat ion may Ije ])n>nouneed* 

Pathologic Pliysiologry.— A toxie sidjstanee called mafkht 
ill hacterial jirotein) iias hei ii obtained from cultureMif the bacilli. 
Injecte<! into infectetl animals this acts somewhat as doe> tnlwrcn- 
lin in tul*erenlosis. A special toxin is probably active in the pro- 
duction of the general symptoms of the disease* By repeato<l 


dr>6a^c with mallein it is claimed that immunity may be con> 


Definition. — Malignant edema is a form of intense infective 
inflammation and necrosjis observed in certain animals and in man, 
and is due to a specrific micro-organism. The condition has fre- 
quently been describecl by clinicians as gaseous gangrene, traumatic 
gangrene, gangrene foudroyante, etc. Infectious emphysema (9. t?.) 
has doubtless often been mistaken for this disease. 

]Btiology. — The micro-organism of malignant edema was de- 
Hcrilxnl by Pasteur and named the Mbrion septuple. Koch showed 
that it dcK^s not flourish in the blotnl, and that the name given by 
Pasteur is therefore not appropriate. He therefore named it Ba- 
cillus (cdemath maligni. This organism is widely distributed. It 
is very commonly present in the soil, particularly in garden-earth, 
ami is often found in dust and in the intestinal contents of animals. 
Introduced into the subcutaneous tissue of animals it multiplies 
greatly and sets up a violent local process. The bacilli are readily 
ol>taiiie<l from the diseased area, and may be stained with the 
ordiiiar)' aniliu dyes, but not by Gram's method. The bacillus 
n-M,'ijibies the anthrax-bacillus very closely, but is somewhat-more 
<^lefMler. It is prone to occur in pairs or in chains or long fila- 
UK-^iitrf, the sevenil bacilli being joined end to end. Movement of 
tiifr or/ani?5m.s is frequently observt*d, and lateral flagella are found 
hy 2i{>propriate stains. In the snore-formation the center of the 
4/s^«i«>Mi -wells and the spore isdevelopeil within. 

OihiratioiL — The cultivation of this organism is generally easy. 
W^>^ fuu-*: or «»ther susceptible animals an* first infecteil by intro- 
'f-^ift/ (j^>wden'<l garden-earth into a suln^utaneous sac. Direct 
Cfi-ifr'n,n of the open wound will not succetxl, as the organism is 
<f r rttl y ^n;i *'• rol ur, 

f'V^iffi f.h^r pus in the sul>cutjuuHnis tissui»s gn>wths may be ob- 
o.i^i fl [ifir,ri the surface of gelatin in an atnuvphere of hydrogen, 
'-.f Jrt fiunrf.unr-cultures in gelatin trvnu which oxygen has been 
^*u'r.)nfU'ii. (hi the surface of the g^»Uitin arv formed small grayish- 
%h.ii- ntftiit'^., which incre:ise in sii^* with advancing age. Portions 
.^/M.u,»''ii from these and staimxl siiow masses of iKicilli in the 
(^r:n ^»f lon<r filament?. In the v:vUiii>-tube there are formeii 
•hifmh *ph^ri*^^I colonies of ;i >K»tu^whai cloudy appearance. 
Th#*'^ r.f,nA:*t of a turf>id H^ut^I. the gelaiiu undergoing lique- 
fc#»t.r,n. Th^re is als4> s<>me g»s-|>rv\luctk>n. the ga:> formed haying 
* jVruil^ and impleasani i^kV. Tbr^ i:^ marked when the medium 
<iAtltJUr)x jfliicr>?re ( Fig. J*^\ 

ftiiniiiHiiiii — The iKK'aiiei \^' maiijciiaiit edema occurs only in 
jmh#^itanef>iis tis^w* XKUt iW point of inocubtion, in the 



muscles, ami in the peritoneal cavity at the time of death. It 
does not invade the iduot], as the amount of oxygen there present 
prevent.s Iti^ j^nnvth, and it tlnnrishes iu the sub- 
cutaneous tissue bfcati^e this is l(*ast accessible 
to oxygen. In bfidic-s dead some time tlie 
oi^nism may spreuil to the blood an* I the 
ors^^ans of the body. The tli^tribution of the 
orjjr;iiu'snis outsi<le the body has lieeii re ferret! to. 

Pathogenicity.' — The bacillus of niulit^qiant 
edema is undoul*tedly the (*ause of tlir disease 
in (|uestion, a8 has been proved l>y ioiieidations 
upon mice, guinea-pig, and other animals. Cata 
and ilogs are les.^ susceptible tlian i>ther ani- 
m a! s ; 4^a tt ! <» s* -e m to 1 )e a \int )s t w 1 1 o I ly i a j lu u n i\ 

Pathologic Anatomy. — The lesions uf 
muli^jnaut edema consist itf \*arituis tonus uf 
nipid suppuration and necrotic intlamtnatinn of 
the subcutaiie<)us tissues. There may rapitlly 
form emphysematous and frangrenous altera- 
tions of the sulicutaneous tissues, with some- 
tiines pns fr>rmatton, at othfT times extensive 
h e rat tr r luigic i n ti 1 1 ra ti o n . 

Patliolog:ic Physiology • — Toxins are 
douhtl^^ss frtrme^l, but these hav<* not as yet 
re< 'ei ve< 1 speeia 1 at tcMi tion. Art i tici id i jnm nn i ty 
has been svn^ureil by injectinns tit' sterilized cul- 
tures of th(? bacilhis in bouilliin, and by other 
m*_-thods» A few cases of niirlitrnaut edema 
have been reported in man, some following injec- 
tion of musk in the course of typhoid fever, 
, aome occurring in the puerperiuni, and some apparently without 
Bxterual injtiry. Infection in the latlt/r probahlv oct*nrn'd from 
the mucous surfaces. In all eases the general vitality of the 
patient was reduced by some previous disease. 

Fio !W, — Bur 11 Ins 
ivf [nnUgnaiit cdtTiia 
irrtnu ing 111 slur'<^>i<?- 
Mn" In till (Kraiikcl iiiid 


Definition. — Anthrax is a specifie infection due to a charac- 
teristic bacillus. It occurs most frequently in cows and sheep ; it 
may affect other animals and man. Dogs, cats, birtls» and cold- 
blocxled animals iirc *pute immune. In animals it is called splenic 
fever; in man, malignant pusttde and wool-sorters^ disease. 

Ktiology, — ^The Bar iff us fuifhrfirh was first observed l»y 
Pollrnder in 1840, and sIkvwu tn be the spccifiiM^ausr of anthrax l>y 
Davaine in 1863. In 1879 Koch, Pasteur and others suceeedrd 
in making pure cultures and in demonstrating their pathogenicity. 
It was therefore the first pathogenic <trganism definitely isolatcth 


The anthrax bacilhis is a non-motile rod-shaped organism that has 
a decided tendency to form long chains. The individual bacillus 
is from 5 to 20 /i in length and from 1 to 1.25 [i in thickness. The 
chains appear as threads with often a little thickening at the ends 
of the individual bacilli showing the points of contact. The ends 
are squared or often slightly concave. In artificial cultures in the 
presence of oxygen spores are formed within the bacilli. These 
are elliptical or oval in shape, and do not alter the configuration of 
the bacillus (Fig. 99). 

Fig. 99.— BacilluB anthracis. staiued to shuw the spores (FrSnkel and Pfeiffer). 

The organism is easily stained with the simple anilin dyes, and 
may be demonstrated in the blood or the tissues by Gram's or 
Weigert's stains. There arc no flagella. 

Cultivation. — The anthrax-bacillus may be obtained in pure 
culture from the diseased organs \\\y}\\ various media. The cul- 
ture in gelatin is most characteristic. Upon plates there are 
formed whitish colonies, which under low powers of the micro- 
scope sho\v a tufted, irregular character at the edges and upon the 
surface, suggesting bunches of twisted wool-fibers. The gelatin is 
slightly liquefied. The tufts may be removed by pressing a cover- 
glass agjiinst the surface of the colony, and when stained are found 
to of curved parallel chains of bacilli. In puncture- 
cultures filaments project at right angles to the puncture toward 
the sides of the test-tube, and the growth at the surface, where 
oxygen is abundant, is luxuriant, while that in the depth is com- 
paratively sparse. 

Pathogenicity. — The infectiveness of the bacillus is undoubted. 
A small portion introduced into a susceptible animal gives rise to 
marked symptoms in twelve or twenty-four hours, and death soon 



follows, TItr lia<'illi may be (lernoJi^trattH! in the IiIockI and in 
variu^is orinnis in gnat alinmliim^e, \^'lJrn tlie barilhis is killrd 
and the s]w>n> are intruiliu'ed into the body j^ioiilar n'.sults follow. 
The sporei^ arc* highly resistant anrl may preserve their virulenee 
for years. Sj mi relets varieties of anthrax l>aeilli have lieen en- 
countered and lia%'e iuen prodneed hy eultivation nn<ler tnifinorahle 

DistriMtion,— The aiithraxdmeillus oeeni^* in all of the Inral 
lesions^ and from these h earned into the bin* id and the orphans, 
partienlarly the ^ph'en, liver, kidneys, antl luntjsi, wliere it is found 
in the eapillaries in bnniense nii miners. The «t met are of thcf^e 
ort^ans in, as a ride, little afl^eted, jm*l>ahlv lieean^^e death 04'eurs 
before changes ean take place. The orginiisnis may \>v present in 
otdy Piiial! nnnihc/rs in the Idood of the general ein-nlation wiren die 
rapillaries of the various organs are tilled with them. The 
orgimismsaredischargeil from the body in the stools, urine, and other 
disehurges, and are thu.s e(»nveyed to other animals. At one time it 
was sa[>po>ed that they vveiv seattered abmit by earth-wnrnis ob- 
taining I hem from eadavers. This is searefly pnilialile. Multipli- 
oatiun of the organisms outside the bndy durs not oeenr to any ex- 
tent, but the nrgani^ms, and partienlarly the spores, may live a 
long tinK% and may be conveyed to great distances in infet ted 
materials, partietdarly w^ool, hides, bristles, and the like. 

Mode of Infection, — In animals infe<'tion most frei|uently «>eeur?i 
through the gastro-intestinal tra(*t, tlu^ Imcilli Ijeing swallowed 
with fodder that has been eituta ruinated. The organisms may, 
however, gain entranee through the lungs or through external 
abrasions. The latter form of infection is most common in 
man ; thougli gastro-intestiual and pnlmonary infection sometimes 

Pathologic Anatomy. — The lesions produced l>y anthrax 
are more itr less lot^iil, but occastou general septicemia. In man, 
alter infection of the skin through abnisions in persons handling 
the hides or w*ool, or other materials from dis(*ased animals, a 
swelling of greater or less size develops. This is intensely in- 
flammatory', often covfTcd aiul siirmnndetl by slight bidlous vesi- 
cles, and attended with cousin lerable edejna. Erosion of tiie snr- 
taee may take jdace aitd siniions liquid may be ilisehargeit, with 
the formation ai' crnsts. Histologically the pro<'ess eonsist^s of 
rapid intiltration of the (*onum and papillary bodies with h'uko- 
cytes. The bacilli an> found in alumdauce between the cells, and 
hemorrhagic infiltration and sero*sanguin«>leut edema are observed. 
Necrosis subsequently oi-cnrs, though not to a considerable extent. 
When infection takes place through the gastro-intestinal tract, as 
is sometimes observed in man atid very conmionly in animals, 
lesioiLS somewhat like the above are formed in the mncosti 
and ,9ubinueosa of' the small iutcstinCj less frequently of other 



parts. At first tlu-se k'sious appear as hemorrhagic extra vasa- 
tiuii-s, then swelling follows, and finally the surface lilcemtes, leav* 
mg irregular excavations with bltxnl -stained bases and edges. 
Profuse diarrhea with hlfKKly discharges may occur. Infection 
thnnigh the lungs m!curs in men engaged in handling infected 
\\€M>1 (wrM>l-s<irters' disease), and in jKirson^ working in paper-lac- 
tories, when? infected rags carry the germs. In these instances 
the Imeilli hwlgt:* in tlie alveuli of the lung's, causing rapid cellular 
exudation with eonsiderablc edema and hemorrhagic infiltration* 
The process is lobular in elmraeter, but large areas of the lungs 
may Ik* simultaneously involved, Serosanguiunlent pleorisy, swell- 
ing rpf tlie ly in] Jill tic glamls of the mediastinum, and iiemnrrhagie 
extra \*a sat ions nf the nK*diastinum are not unusual. 

Pathologic Physiology-— Thu presence' of tlie anthmx- 
bacillus leads to the formation of toxic materials in the blood, and 
a |K>ii5«jnous albumose has been obtained from cultures. The 
general symptoms, however, are pmbably in large measure tfie 
result of dissemination of the bacilli themselves and their !tx*al 

It has been found possible l>y eultivati*tn at high temperatures 
and by intrculucing the organisms into insusceptible animals, and 
also byaddiug chemical agents to cidtni"es, to alter the pathogenie- 
ity of the bacillus to such an extent as to make it li a mil ess, even 
to white mice. By introduction of such cultures anil subsequent 
sneccssivc inoculation with cultures of iiicreasing viridence \nx}- 
tection has been afforded. Antitoxic suljstauces have been obtained 
from the bloml of protectee! animals, but the method of successive 
vatvinatious rather than the use t>f antitoxic sernni is at pi'csent 
rclii'd upon to eotubat the diseasi\ 


Definition*— This term is |>ruvisionally applied to a form 
Ai{' infection that has been described under various names, such as 
gaseous gangrene, gas-plilcgmon, em(>liyseniatous necrosis, and the 
like. Undoubtedly it has Ih'cm mistaki-n \\yv malignant edema in 
certain cases. Th(^ disease is caused by the Bacillus aerogenes 
eapsulatus of Weh*li au^l Nuttall. 

Btiology,— The bacillus in question is a nou-nu)tile organism 
of variable size, 3 to ^i fi in length and about the thickness of an 
anthrax bacillus, with adjacent ends slightly rounded or square 
cut, and occurring singly, in pairs, clumps, or s*)inetimes in short 
chains. Very rarely it occurs in long threads. It is easily stained 
with the ortlinarv anilin dyes or (irauvs stain. A capsule is some- 
times demonstrable in specimens obtained from the bodV or 
from agar-eul tares. The bacillus does not form spores. It La 
probably identical with the Bacillus phlcgmones emphysematosie 
of FriinkeL 



Cultivation. — The organism is anaerobic, tio growth occurring 
on the surface of ^olid media in the presence of oxygen. In 
media containing fermentable material ga:?-fi>rmation is regularly 
observed* The colonic!^ in ag-ar are grayish- white or slightly 
brownish ; those in the deptli appearing as small spheres or ovals 
slightly flattened, with knob*like or feathery projections. The 
cultures in gelatin show slight and slowly developing liquefac- 

Pathogenicity, — By ex]>erinicr)ts on animaU exactly the same 
lesions are prmluced as those ibimil in man. 

Patliologic Anatomy.^The lesi*ms of this infection are 
widespread. At the j)oint of inoeiilatiou tliere may be found 
edematous intiltration, with blooil -stained fluid, and emphysema 
due to ^s-fonnation. Rapid necrosis or gangrenous soften- 
ing of the tissue may ix^cur. The entire surface of the body 
soraetinies becomes emphysematous, ami at the autopsy the organs, 
especially the myocardium, kidneys, liver, ami spleen, present a 
characteristic apiK*amuce. They are lighter in c(4or, and on in- 
spection are finind to be tilled with minute Mieuoles or gas-buli- 
bles* The blood of tlie heart and vessels |>resents a foamy eondi- 
tiou, due to the gixs-f u^mation. Practically any of the tissues of 
the body nmy be affected . Micrfiseopieallv, the oct-urrenee of gas- 
vesicles with numerous bacilli in their walls is the most striking 

Regarding the nnxle of infection, it seems likely that in all 
cases the orgtmisms enter through some injury or abrasion con- 
nected with the external world. Some cast-s have followed trau- 
matic injuries, otiiers occur in eonucctiuu with itisease marked by 
ulcL^rations of the surface of mucous meml)raues, and at least one 
instimce has been carefully studied iji which the disease occurred 
during the puerp^^rium, pnvbahly due tt> uterine infection. It is 
not improl>aljle tfiat uuuiy of the eases of supposed air-embolism 
from douching <>f the uterus after labor are in reality eases of 
this Ibriu of iufection. 


Definition, — Tetanus is an acute infectious disea^ due to a 

•specific bacillus. The l>acillus i>f tetanus was discovered by Jfico- 
laicr and isolated by Kitasatn, 

Etiology,^ — The bacilii <x*cur in the form of cylindrical nxls, 
whieli are frequently swollen at oue end, due t*^ the presence of a 
rounded spore (Fig. 100), They are slightly motile in the absence 
of air, and tliev may have flagella. They nsnally occur singly, 
though oct%-isioJial!y a few nuiy l»e seen end tn end. They 
occur in the luoal lesions frnm which traumatie tetanus takes its 
origin, ami nuiy sometimes bt- readily dcmonstratril by spreading 
some of the pus or exudate U|Km a cuver-glass and staining with 


the ordinary anilin stains. They also stain by Gram's method. 
The bacillus does not diffuse itself through the body, but in a few 
eases it has been found in the central nervous system. The organ- 
ism is readily destroyed by heat, but its spores are quite resistant. 

Otiltivation of the tetanus-bacillus is difficult. It is obtained 
from garden-earth or the pus of infected wounds by submitting 
the material to sufficient heat to destroy other organisms, even the 
bacillus of tetanus itself, leaving the spores uninjured. With thif 
material animals are inoculated, and from the products of the local 
lesions or directly from the original material cultures are made in 

The organism is strictly anaerobic. The typical culture is 
obtained in the depth of gelatin. Deep beneath the surface there 

■ ' \ 

^ y-' 



Fir.. l<<).— Bacillus letaiii ; x 1000 (Frdnkel and Pfeiffer\ 

are foniu*d along the line of puncture pointed processes stand- 
ing out at rijirht angles fn)m the punctnn\ After a week lique- 
faction of the gelatin occurs, and an accumulation containing 
grayish-white turbid liquid is formtHl. When thegn>wth is formed 
on tin? surface of gelatin in an atmosphere of hydnigen a similai 
radiating structure is found in the colonics, the centers of whicli 
are rather dense. Liquefaction of the gelatin subsequently takes 
place, (^'onsiderable gas with a pungent oilor is prouuceil in tht 
growth of this bacillus. 

Distribution. — The tetanus-bacillus is found very frequently in 
garden-<!arth, in the intestinal dischargt»s of animals, and upou 
various articles al)out stables. Infection otrui's in human beings 
or animals through punctures made by nails, splinters, and the like. 

Pathogenicity. — The bacillus placet! ujK>n an open wound niaj 
not give ris<» to the disease, from the fact that the presence 



of oxygen (jrevents it^ growtlh Suhcutuuettus iimculatioiij how- 
ever, eaujie.s rapid clc^stnirtion of aiihnals witli t\ i)i<.'al symptoms. 
The |MTi(Hl of incubation may l>e only a few hours, or one or two 
days, nr it may he several weeks. The assot^iation of etfrtaiii 
other or<ranisms, sueli as tlxe pns-prn<lnein^ t»r<^auismS| seeniH^ to 

fixvor thr <1( veh: 



ivor thr development ot the disease liy prt'vriitm^ pJia^>cyt 
aetion of Irukorytf s, or by inmsuming oxygen and tlins ailowing 
tiir^ t»-tnniis-l>aeilhis to flonrisli. 

Pathologic Anatomy. — No eharaeteristie lesions are fonml 
in this (lis4'iise. Local ly a wonnil or injury throuj^li which ijioeu- 
Iiition lias taken place ma ' be discfivered ; l)ut tliis is only execp- 
ti*»nally exti-nsive, Sinnctinies my lot a I injnrv can he *liscovr red^ 
and it is su|i|Hiscd tliat infi'ctifai at times occurs thnni^li tliet^astro- 
inttstitial tract, or tlirongh other nineous meinhmucs. Intense 
congestion uf parts of the ntTvotis system may be found at the 
autopsy, but this is nut ciiaracteristic. 

Pathologic Physiology, — ^Tm'o distinct toxins have been 
recoii^iiizcd — ftianf^sptt^ntitu whicli is tlic )nvdunHnant poison and 
that whirh caiisi^^ the spa.sms, and fifatif*if/^'itN a hcin*ilytie stibstance 
of uncertain iiu[>ortan<'e* The toxin of tctiiotis is alnidst iu(*on- 
eeivably p>is*)noni^, a fact wliieh acctMuits for the dcvplojiment ol' a 
fatal clisetLse in cases in which the innnhcr of harilli is minimah 

Tht* spasnimlie seisiu res first atf'ect tlie muscles near tl\e point of 
in«M*u[ation and in mild infc<lions may he contiufcl to these 
nnisclcs* This has been explnuc*! by the rcccJit ex[K'rimcnt*s of 
Mever and Ranisoin and others wIki showed that the toxin n-aela s 
the nerve cells ot" tlic spinal eord by traveling from tlic niuscidur 
end-plates of tlie motor nerves tlirougli the axis cylinderB to ttie 
cord. The toxin iujcctetl into the bhioddois not passilirectly to the 
nerve centres but always travels ap the motor JU'rv*"^ as ilescriljed. 
The p:trts first affected liy spasm are therefore those about the 
point of ino^'uhition ajid of elaburatiun of tlic toxin. 

Tetanus antitoxin has l>cen obtained hy snccessive inoculations 
of animals with the toxin and in laboratory expei*iments hag been 
tband specific and exact in its antagonism fo the toxin. In treat- 
hi'j^ the disease in manor animals the re^^ults have been dlsappoint- 
ini^ hut this is jiow known to he due to the maimer in wliich the 
toxin and antitoxin arc respectively distributed and absorlved and 
t*i the fact tliat the toxin has usually reached tlic vubienible nerve 
centres at the time wdien the antitoxin is injeeted. The antitoxin 
must be first alisorluHl by the lymjOiatics and carried to the l^IiKwl 
witli which it is distributed to the Huids nf th*^ Ixtdv whence it is 
again abscu*bed l>y the nerves. It is not tidceu up <lireetlv fnmi 
the bhx»*l by eitlier tlie central or peri[ihend la^rvous tissue. For 
these reasons the sulicntancons injection of aniJtoxin fails to efTcet 
the neutralization (jf mueh <if the toxin since the latter is ([uickly 
absorbed hy the peri|»heml nerves. Intravenous and intradural 




(spiual) ijjjectioiis are more rapid iu their effects and therefore pre- 


Defitlition- — ^At^tiiMniiyrosLs is a ilironir "mfeivtiaus pnK'css 
chara^t^^rized hy ititlaiiiiiiutory reaction oi' the tissues with a ten- 
denty to the foriTiation of auj»punttive foci, and due to the sj>eeitic 
aotinn of a rnicro-organisra, the Adinomyea* bovis. 

etiology,— = A r^tinnmvroriis is a disease of cattle, horses, swine, 
sheep, the Iknia, the elepliant, deer, dog, and iKX-asionally ijf man. 

The s|>ecific caiK^e of the disease is an organism which (jeeiii^ 
in the tissues in the form of clusters having a radiate structure, 
and it has therefore been termed t!ie ** ray fungus.** These 
clusters may be so small as to be invisible to the naked eye, or 
they may reach considerable tlimensions by their growth and 
aggregation. The central part of the chister frequently has a 
granular apjx^a ranee, suggesting a mass of mierococci. Keachiiig 
out from this may lie seen more or less rcguhirly diverging striae 
or rays, ami the periphery is composed of wliat appear to be 
bulbous extremities of tite rays (Fig. 101). 








• \M 




^t't V 

4 ij^^Q 

I ^, 




^^r^R<» _ • •* •' 




.- ••.•'•''^■ ■ 


Fia. 101. AcUuoiayttij* elu^vler (K^irg aud SctiEaorl). 

Bostroem in 189nan<l WoltTand Israel in ]H91 pufdisiied not- 
aljle articles on actinomycosis and rc>i>ectively isolated an aerobie 
and an auaerr»bie growth. Tlie relation tif the former to actinnmy- 
cosi^ has, however, been disproved while the anaerobic growth aloue 
is important* The aeroljc of Bostroem was apjvanutly a contami- 
nating or^iuism relate<l to the liranching organisius which weur 
in the outer world, and that have been varii>u.sly classified as strep- 
^i)tlu'ix, cladotbrix, etc* As these occur on various grains and on 
the spears of t lie i>at seed, etc., Bostroem believed tliat the organism 
was derived from such sources. More recently accurate studies 
like those of Wright (Journ. ^\mA. Itesearch, Jlay, 1905.) seem to 



have disproved the coiiiieetion of the aerobic oi^nism and to have 
established the iiirlependencf of tiit'^ true at'tiiKnjiyccs from the 
group of hniuehing orgtuiiHiiit^ rfffrred to. Wright insists that 
these* sliould be elassitied as a se[jiirate genus uiitler the name uf 

Cultivation of the Orfjanlsm. Growths have been obtained 
upon sugar agar, in bonillon, and various other niHlin. Suspen- 
isiun eultun^s in dextrose or glucose sugar show in the eoui-se of 2 
to 4 days seattered colonies in tlie dt^jitli of tlie agar an<l a very 
few within 5 to 10 nuni, of the surface* A shallow zone of closely 
set colonies giving tlic appearance of a dense cloudiness in the 
media and about 2 to 4 wide is generally tbund at a point 
about 5 to 10 m.m. lx4ow the surface. Kelow this zone tlie c*>l' 
onies are more st^attereiK 

The growths are essentially auai'rolu'e ; an<l grow l*est at body 
temperature. Under tlie micro>copc the smaller colmues ai*e 
found to be spherieul masses of bmnching filaments mdiating from 
the centre. The braueliiug is tnie bninrhing and increases as the 
colony grows older. 

In stab cultui'cs in sugar agar the growth appears as a dense 
gray streak or line of small Tiodides in the drepcr parts uf tlie stab. 
No growth ot;curs near the .^uriaee. 

Ill l>onillon solid wliitc nnisses ibrtii al the bottom of tlie IuIm* ; 
none appear Jiear tire suHaee. In bonillon the growths occur lj(»th 
under aerobic and anaerobie eonditiuns, Init in the case of the 
former Wright suggests that on accyinit of tlie ennipaetness of the 
masses there are really anaerobie conditions within tlie colony* 

liccently Wright has itbtainetl juire cultures ejf hriniching tila- 
mentons organisms agreeing with one another, in 1»] ca^cs of 
actinomycosis in man and 2 cases in cattle. 

The cuUivatiiUi of this organism presents unusuid difficulties 
owing chieMy to tljc frei|ucnt pnst nee of other bai^teria in tlie 
lesions which usually grow mon^ rapidly aud more luxuriantly than 
does tiic speeiijc organism. 

In a IW cases pure cultures were obtained by phmtiug the 
granules directly in iKiuillon. In some instances of contamination, 
by allowing the tube to stand tor sevend days, the contanduatiug 
organisms died out and transplants then yiehled pure cidiures. 
Generally sugar ngar was the ujc<liuni e^niployed ibr isolatif^n of 
the micro-organism. It grew well only in ngar and bouillon cul- 
tures and in the inenhator at 37 '^' C In the other usual cultural 
media and at room tem|)eniture, it grew very pfKU'ly or not at all. 
It was essentially an anaerobe ; ami did not form spore-like 
reproductive elements. In cidtures its eolonies wire similar in 
character to those in the lesions. The vitality of the micro-urgan- 
ism was varialde. In g*^neral it did not seem to survive as loug 
in cultures as w4ien dried on the sides of test tubes. It was killed 


by exfxjsure to a temperature of from 00° to 64° C. for ten minutes. 
The micro-organism stained well by Gram's method the clubs los- 
ing the stain and taking the contrast stain ; it is not acid fast to 
Gabl)et's decolorizing solution after staining with carbol fuchsin. 

The filaments of colonies immersed in animal fluids such as 
blo<xl S(;rum and serous pleuritic fluid may under certain unknown 
conditions become invested with a layer of hyaline eosin-staining 
material of varying thickness and the filament may then disappear. 
Thus <tnictures are produced that seem to be identical with the 
characteristic "clubs" of actinomyces colonies in the lesions. 

Pathogenicity. Inoculation experiments on animals with cul- 
tures of the micro-organism resulted in producing in the tissues of 
the inoculated animal characteristic "club*' bearing colonies. This 
club formation Wrigiit is inclined to Ixilieve represents a kind 
of protective membrane for the mass of the colony against the 
destructive action of the juices and cells of the tissue. After the 
int)culation of animals nodular lesions and in some instances rela- 
tively ext<?nsive lesions were produced. They, however, showed 
little tendency to progress and only in a few cases did multiplica- 
tion of the oriranism in the body of the animal seem probable. In 
other words thrse results simulate closely the negative or ambig- 
uous results olitained by other observers who inoculated animals 
with the lesions of actinomycosis. It would seem, therefore, proln 
able that the micro-organism in the cultures was identical with 
the micro-organism in the lesions. 

Wright rwognized but one micro-organism as the characteristic 
infectious agent in typical actinomycosis and applies to it the gen- 
eric and specific name of Arfinoini/crs hovis as given by Bollinger 
and Harz. There is not sufficient difference between the actino- 
myces from the human and bovine cases to justify their classifica- 
tion ii< separate species. 

The mannor of inf(»ction with the actinomyces is not com- 
pletely determined. Formerly it was thought that the parasite was 
carried to the tissues by various vegetabhi substances, j>articularly 
the spears of the oat-seed an<l other grains. Sometimes these have 
b(*en found enibed<led in the lesions ; in other eases splinters of 
woo<l have been discovered. The fact that the organism is a rigid 
anaerobe an<l grows only at body temperature tends to disprove 
this view and it is likely that the actinomyces is a normal inhabit- 
ant of the mouth and gastro- intestinal tniet and always derived 
from these sources. Carious teeth and lesions of the mucous mem- 
branes may play a part in the etiology. 

Pathologic Anatomy. — The pathologic changes induced by 
the actinomyces consist of round-celled infiltration and prolifera- 
tive changes in the ermnective tissue surrounding the parasite, and 
sometimes secondary softening, necrosis, or sup])iiration. The 

Actinomj'cods nf tin* jaw-lMjnc nf nn ox. Tlie dark arfn?* ntu\ t]w bnikon- 
down piirt iu the ceiiitr of th« picture are foci of ibii dkeit^*'. The whit|« fiono 
I 10 eotargi'd. 



granulation ti-sMK- iif ai'thiutDyc(Ji?i.s is espceiully ricli in leucueytos, 
ami not iiit're(|iiiMUly the.^e fiu'tn ikiir>e iiK."i, wliicti later devi?lr»p 
puriiitint col l*rt ions, lu rattle the disLase utlet*ts the lower jaw, 
leas frequently the upper jaw or other l)oneri ; the tissues of the 
neck, the tongue, and other jitiits. In man it is met witli in the 
ginns, tlje eheekj^, and Hoor ot' tlie mouth, in tlie hingt^, intestines, 
and other intiTual organs. Tlie nuked-eye appearanee of the lesions 
may tirst l>e simply that of a hard red papuhir tormatiou, witli more 
or ies5 induration surroinidiug it ; later this tends to iucreiise io 
size and may hn^ak tlown, forming necmtic or suppurative exea- 
vations. The pnvcess of repair or cieatrization may proceed in 
some parts to the extent of almost complete repair, while tlie sup* 
pnrative or necrotic change advances in other directions, and thus 
cavities antl irregular communicating sinuses arc estahlished. The 
so-calle<l sulptmr granules or aetinoniycos btxlies arc found in tlie 
pus diseharged from the sinns or still retained. The part in which 
the disease exists may be considerably distigurcd and ninch enlarged. 
Tlie pus or necrotic material witliiu the lesions contains peculiar 
granular boilics, the *' sulphur grannhs '' or actinomycosis-bodies. 
The s:ind4ike or sulphur grannies measure O.'i to 0.6 to at times 
1*2 mm. Tlicy arc of a gray, yellow, green, to red cf»lor When 
young soft, when oldei% much tonglicr in consistency. Occasion- 
ally ealciticatiou of the dis^^asetl area may Inke [ylaoe. Whr^n the 
jaw-boue is aflW'tcd the disease, ns a rule, begins abont curious 
teeth, tistida; communicating witli the roiits of teeth. 

In the citse of disease f^f tlie lung's smue have f observed a pre- 
liminary eatarrlnd iiiHammation of tlie linmehi. More fVri|Uently, 
however, there are fnmi th*' first innlular anas of bronchopiieti- 
mtmia, which tend to undergo elianges similar to tlnrse already 
descrilietl. The siirroiuidiug lung-tis,snc frctjUf^ntly iHM^omes indn- 
ratcd from interstitial pncnmrmilis. Ext<iision may ticeur to the 
pleura, pericardium, and n^ediastiual tissU(\*i. 

In the case of actinomycosis of the intestinal tract there are 
first elevations of the nmcons membrane, the disea^se involving the 
mucosa and tlie sulmiucosa. 8ubscf|uent softening of tlii^se leads 
to tlic formation (»f nh erations. Extension to l\\v peritoneum and 
tt> tlie other organs of the abdomen may take place. 

In any case of actinomycosis a j>cnctnition of the bhwid-vessels 
or lymph-cli:inuels m:iy lead to mt^tastascs. Thus in aetbiomyeo 
sis of tlu' abdmninal cavity the liver is frequently involved; and 
other parts of the limly may be similarly affected. Actinomycotic 
lesions of the brain (abscesso) are sometimes seen in such in- 
stances. In ivther (*ases of cen'hnil iuv<ilvcmcnt there mav be no 
evidence of the original 1<m'!i> or point of entivince u\^ the germ. 

Microscopically tlic characteristic feature of this disease is the 
parasite itself snrronnded by lymphoid cells in considerable num- 
bers, with some epithcboid cells and occasionally giant-cells. 



When the process tends to n fiivomhle termination hvcinatrization 
fibrons-tissye fur mat ion proi'tMHk in the iisiuil nuitmer. 

Pathologic Physiology. — The aetinomyees is mainly active 
as a Ifieal |iiirdsite, i\\Q genemi (listiirhiinces of health bein^ com- 
jKjrntively slight. There is a market! tendency to linn'tation or 
retardation ot* the disease, and sonH^tini* s this is etfeeted eoni- 
plett Iv. 


Mycetoma, or .Xfaduni-luot, is an infectious disease occurring in 
India and elsewhere, and caused l>y an iirganism (»f an uncertain 
hiolugie class. The disease is not infrequent in Aladuni, Delhi, 
and (»thcr parts of India, and has lieen observed in Africa, 8<juth- 
em Europr, nnd Americii, 

Etiology and Pathologic Anatomy, — As its name indi- 
cates, the disease affects the fr»nt,and usually fullows injuries, joar- 
ticularly tliorn- wounds. In rare i-ases the hands or other parts 
arc affected . At first there is nodiihir inflammatf»ry swelling* be- 
ginning on the plantar surface or dorsum of the foot and spread- 
ing to the sides. These swellings 
arc hnrti ami paiidess. Ljiter, 
softening occurs and rupture 
takes phxce. Thin, M'ater\* pus 
is dischargetl, and this contains 
grayish or reddish granular IkkI- 
ies or black gnuiules resciniiling 
|>artic'lf's of" giuipt»wder. In tlie 
former eaM' thi- term pale myce- 
toma is applied ; tlie latter vari- 
ety is called bhick or nielanold. 
In the lat( r stages of" the disease 
disrlmrgiug simises may remain, 
wiiih' newer niMhdes in turn are 
inrninl and soften. Finally, the 
memlier affected iRt'omes greatly 
deff»rmed, thi* jxirtions not in- 
vtilved growing thin, while the 
dj>cased part iuereases in size. 
I)( ath fH'curs from exhaustion or 

UhifJoyieuHy the nothdes re- 
semble hirge tubercles, but are 
wu. ur> «♦„.* .1 . *. I - highlv vascular. The bulk of 

uon of tamHiiwMt tiMur <vinrotit). tnc growtii eonsists nt granula- 

tion-tissue cells, those in the cen- 
ter being nmalb those near the outer edge o^en large and contain- 


In th 

e center 

ing two iir murv mielei. True giant-cells are mvt\ 

loiiv Im' tbiifid 31 brauehing mit*n>-organism, called SfirpifjUirix }fa* 


dnrff (Vincent ). This stain,s hy (intm\« iiiL'thorl, find sometimes 
shows somewliut liiill>uus t; welling; <it' the ends uf the tijreuds and 
their branches (Fig. 102}. The niyrelia of tho blaek variety of 
myeettmia are descrihed \>y Laveran as tliieker and fo;irstr than 
thoso of the pah^ form, ami he believes the orjiranij^ms are distinet 
varieties of a species, Aronnd tlie or^-^nism may he seen an area 
of degeneration, having a .'striate arrangement suggesting that 
seen in aetinomyeosis. Extensive degenenitinn mid pns-formatit^i 
oceiir in the center of the diseased areas in the hiter stages; and 
hemorrhage may oceur from tlie new I dood -vessels* Histologic 
examination of the gnmnles in the pns shows the niiero-organisms 
in the form of interlaeing threads. Bixlies resenihling spores have 
oceas i on a 1 1 y bei^ n d e. ;e r i [>e< 1 . 

The organism has not as yet l»e4'n definitely ekussified. It is 
certainly allie*! with the aetinomyees, hut proljably not identieal. 
It has been euhivated npon varions media, partieularly infusions 
of hay and the like^ rendered slightly aeid in reaction. It forms 
Fm:dl nodnlar ajid hard growths, whieh become rose-red in color 
%vhen tfiey eling to the sides of the t*'st-tyi)e near tlie snriiiee of 
the liquid, i»r hrownish when they sink to the bottom. Upm 
agar isolated grayish or later rose-reil ehtstei's are formed. In- 
oculation-experiments have thus far met with little suceeaa. 
Lfx'al reaction has been so prodneed, Imt not a definite disease. 
Several invesligators iiave rea<'liet! the eonehision that there are 
two or more kinds (*f miero-organisms that have an etiologic 
relation to cases of Madura-foot. It has in particnlar l)een sug- 
gested that the white and black varieties of the disease have a 
distinct liaeteriotogy. These views need further confirtnation. 

Otlier Streptothrices and Cladothrices, — Several other less importunt 
foraii* »^f tkcK' p;riiups luivt; been di\^eribed, lis, fur eXEiinple, the variety of 
Cladothrix found hy Epiviii^er in ahseer.?4 (*tthe limiii, imd the t^t re ptoth rices 
diHCovered hy Flexaer and by Biiehhfdtz in psendotnbtTeiilnsiK nf the Inng. 
Tattle ha* colleclt'd Ivvelv*^ eii-^es i^t' ^^treptothricosis tn>ni llie literjiture in 
all of whieh the or^aiii>tn wa.s pre.scnt in saeli libundance antJ eharsieterislie 
distrihution as tu ^eeiii fif <lelinlte etioht^ie importance. Thesie orgauiisniH 
have not as yet reeoivi-d definite clossitieatioii. In thij* ennncTtifin it J8 
interesting to note that thti tahercle haeiUus under ci-rtain conditi^ma 
assumes forms wuf^ge^^tiii^ a rlorte reliition.ship with the streptothrices^ nnd 
that a baeilhH ha?i heen ff)und u]inu Ui,iy and varioiiH vegetiibles, and in the 
feces* of animal"*, that cauf*ed iitypieal tnbercle?* whc^ii injeetc^d into an in nils 
in pure culture. 


Definition.— 'Relapsing feviT, or typhns reenrrens, is an infee- 
tioiifi and euntaij;ions disease, prohably eaus*'*! Uy a speeitie organ- 
hu\ which i> fuund in the blood. 

Etiology, — The Spiroeluetn < )l»crmeieri is a spiral organism, 
in length several times the width of the retl etFrpnsele {16 to 40/i/) 
It is found in the fresh blood, and presents active movenxents due 


to rotation and probably flagella (Fi^. 103). Recently it has been 
claimed by Schaiidinn that this and other spirochaetes belong to 
the g£OWi^ o( flagellaies (animal parasites) and are closely related 
to the trypanosomea. Novy's investigations appear to have com- 
pletely disproved this view. The organism stains well with ordi- 
nary anilin dyes. The relation of this spirillum to the disease can 
hardly be questioned, as it is invariably present and appears in 
the blood during the paroxysms of fever and disappears in the 
intervals, thus showing its relatiou to the symptoms of the disease. 

The organism has not as yet been cul- 

qqO^O ^ tivated, but by inoculation with blood 

O ^w/ Oo ^ number of investigators have trans- 

/>\^ ferred the disease to monkeys and 

OcsJiX J/^ human beings. 

^O ^j • Pathologic Anatomy. — The 

o spleen becomes greatly enlarged ; it 

.f^r^^""^ ->^00:sC^^^ frequently presents a variegated ap- 

r\^ r\^ Q pearance on section, due to areas of 

€jq^^O C^q' anemic infarction and necrosis or fatty 

O degeneration alternating with deeply 

Fig. 103.— SpIrochsBta Obermelcri p.x«,-o«fnr1 nnrtmne 
in the blood (von Jaksch). COngCfeieU porilOUS. 

Pathologic Physiology. — The 

peculiar feature of relapsing fever and the one that has given it 
its name is the recurring i>an>xysms of fever. The cause of this 
periodicity is as yet unknown, though it is likely that the develop- 
ment of the spirochseta is such as to determine the relapses. 


Definition. — Influenza is an infectious disease occurring in 
widespread epidemics and caused by a si)ecific bacillus. 

Ktiology. — The Bacillus influenzae was discovered by Pfeif- 
fer and Canon in 1892. The bacilli are extremely small and 
usually occur singly, though they are occasionally united by the 
ends, forming short chains. They may be stained with the ordi- 
nary anilin dyes, esj^ecially with carbol-fuchsin, but are decolorized 
by Gram's metluMl. The ends of the bacillus are somewhat swol- 
len and usually stain rather more deeply than the shaft. This 
gives the orgsmism somewhat the appearance of a diplococcus or 
dumb-b(»ll-shaped bacillus. It is not motile. The first generation 
of the l)a(;illi will grow only in the presence of hemoglobin and 
arc therefore cultivated upon glycerin agiir, the surface of which 
has been smeared with rabbit or human blood, forming minute 
drop-like colonies, seen with ditiiculty witli the naked eye, but 
clearly with the aid of a lens. The colonies do not coalesce. The 
appeanuice of the growth is somewhat like that of condensed 
moisture on the surface of the culture-medium. Later generations 
of bacilli may be cultivated on agar or in bouillon. 



The bacilli ooeur abuudaiitly in the sputum of the disca8<^, 
decreasing in quantity as the ease advances. Wlien pundoiit 
expeetonition ceases the Imeilliis disiippoars entirely. Not rarely 
the orgaiiisnis are readily recf^^nized in the sputum hy simple 
staiuiiip^ methods, A ctTtain diiignosis is not possible iu this way 
and even in cultures oth^T <u*ganisnis (see below) liave a puzzling 
resemblance. In fitted cases it Ijas been found iu abuiulauce in 
the tissues of the bmg, parlicularly iu eases iu which complieatiug 
pneumonia has existed. It dot-s not occur in nther diseases. 
Animal experimentation has thus far been uusatislhctory, tbougli 
the organism hns ]>ruvi'd patlu>gruie fur rabbits and monkeys. 
The symptimis art- suggi stive of human influfns'a but entirety con- 
clusive results have never been obtaini-d. Tlic specific cliaracter 
of the i^rganism is tlu^rcfore infcrrt^d ratlicr thim denuiustrated. 

Pathologic Anatomy *^Thf ►re are no speeitie h sions iu tins 
disease. The organ isuis ]U'ovoke iufeusi^ catarrhal process* -s and 
doubtless at times pueumuuia. In some cases th<' jun umtaiia of 
grip is caused i>y mixed or secondary infection. luflamnjatory 
lesmns and hemorrlmgic infiltrations iu the niend>rancs of the 
brain and just beutatli the membrjues havt^ been otjserved. 

Pathologic Physiology, — Very little is kn*>wu regarding 
the mode uf activity of tlie bacteria* The eoustitutinual symp- 
toms suggest toxemia, but the u:ttnre of the puisnu is nbscnre. 
The immunity from the tlisease must be exceedingly ghort, as 
reeurring uttacks aiKl relapses may be frequent and sueeecil one 
another nipidly. It has been found tliut thr iriHuenm bacillus 
may remain in the brourhial tubes, espfei;dly in tuberculous cases, 
tor moiitljs or years. From tiuie to time renewed acute infect iuu 
takes phice. Certain coujpli exit ions and setpu Is, siuli iis inHamiua- 
tions of the serous surtacrs and juuritis, iudirate geueralizrd infec- 
tion and intoxieixtiou. The tu'guuism dues not seem ti; thrive or 
multiply in the bliKHl. It has Ijccn found in otitis media and 
other ccHulititins \vin\4i suggest a metastatic deposit. In gt tu ml, 
however, intftieuza seems to be a local iufectiou with trtueral tttx- 
emJa litit rarely general iufi'ctinu. 

Organisms resembling the influenza bacillus. — A very similar 
organism callcHl tlie psc udtHinfluenza bacillus has been described. 
It is somtnvliat larger an<l tends to ffU^m long filauu'uts. 

The Koch - 1 1 Wks bar Hh ^s* o f e]u d e m i c co n j u n c t i N i t i s d i t! e m i n 
its manner nf growth antl in the fiict tljat luriH>g!ol>iu is not nec- 
essary^ in the nu'dia. It is uou-|mtl»ugent<* in nuimals. 

Au organism described as tht^ cause of whoopiiig c^ugh is alscv 
closely related. Its position is still imcertaiu. 





Definition.— The biiboiiic plague, or pest, is an irifectioUB 
disease due to a peculiar bacillus. 

Etiology. — The baeillus of bubonic plague was discovered 
bv Yersin in 1894. In blood drawn from a iiuncture of the 
skin and in pus from the aifeettd glands, nuiy be found small 
bacilli somewhat rei^embling the infloenza-baellfus. These organ- 
isms may be stained readily, and often more deeply at the 
poles than in the center (Fig. 104). This gives them an ajipear- 


Flu* lui.— BucilliLikr iii buUiui€ |hLjLgu«i (YeimioL). 

ance resembling tlxat of the diplococci, and in specimeuB from the 
bloixl or tissneB there is an indtstinet eapsule. The organism is 
mther oval in shape but club-yhape^d f >rms are frequent and in 
cultures long chains are met \vitli. The bacillus is feebly motile; 
recently it is e!aime<l that Hagella have been detected. Pure cul- 
tures have been obtained upon various media, l^jron glyeerin- 
a^nr moist, roundeil, whitish or bluish- white colonies are formed. 
Portions of such eo Ionics removed for eje ami nation show the 
bacilli ranged in chains. 

Pathogenicity. — The baeillii8 has Ijcen found pathogenic for 
miee. nil.H, guitiea-i)igs, and rabbits, and the symptoms produced 
by [>nre cndtures are the same as those induce*! I>y inoeutating 
uniujalh with hhwid wt jMjrtions of tissue from iliseased persons. 
Thr lyjn|j|ijitie glands may be swollen and petechial hemorrhage 
may oeeiir an in the human disease. 

OtitHbution. — In the human lieing suffering from bidmnic 
[ilaguc iht^ Ijueilli are found in tlie local lesions of 1 he lymphatic 
glandrt, lh»* bul»tM*3s ; and also in the blooil and various organs. 
Rats arjd mir-e and flies frequently die during epidemics, and 
dc»ubtlef«H helfi U\ Miread the tlisease by infecting the soil and dust 
aliout tlwelling?s. Versin showed that flies die of the disease, and 
flucceeded in obtaining the bacillus from their dead bodies. The 



bacilli require nioigture, absence of strong light, and a low tem- 
perature lor their gmwth anrj Diultiplieatioii. They do not flour- 
ish in water, but thrive in milk, butter^ and cheese, and these 
food-stuff*! may spread the ec^ntagion. The pneumonic form is 
usually caused by inhalation of dust that has not dried sufficiently 
long to destroy the bacteria, but is not neeessarily due to inhala- 
tion of the ^erms in all cases. 

Inm'uiation iu man is most frequently caused by injuries of 
the skin» sui*li as scratch-marks, etc* Infection may, however, 
occur through tlie hings. 

Pathologric Anatomy, — The organism |>mdiices swellings 
and suppuniti^JU of lympliah'e glands, particularly those of the 
groin J and s^^eondarily lesions td' internal organs. Tlie lymphatic 
glands swell qui<'kly, become tender and congested^ and tlien 
soften, forming a rather thick pus. This is sometimes somewhat 
bhxKl-tinged. Petechial hemorrhages and lilood-stained effusions 
into the scpjus cavities may occur. Petechiie of the skin are apt 
to develo]> as a result of slight traumatisms. Thus the bite of an 
insect, instead of prmincing its usual results, may cause distinct 
ecehyraoses in persons suffering from tlie disease. A form of 
bronchopneumonia occurs in a consitleraldc proportion of cases. 
This mav be quite independent of glandular enlargements exter- 
nally. In these the priniar^^ infection may be caused by the 
inhalation of dust. A *' septicemic form ■ * is charaeteriKed by 
general infection with generalized involvement of the lymphatic 
glands, but without distinct l>uboes. 

Pathologic Physioloiry.— It seems that the distribution of 
the bacillus in the hloo<l, as well us toxic substances, contributes 
to the general disturbanee of health. By euceessive inoculation 
immunity has been produced, and antitoxic sera have thus been 
obtidned. The senim has been used in man with consideralde 
success as a [>rotective and al&r.t a curative agent. It often fails 
in advanced cases. 

Haffkine has used his method of inoculation as in cbolem and 
obtained encouraging results. 


This condition occurs in new-born infants and in older children 
or adults who have become weakened by disease. The organism 
called C/tdiam alfjiraus is a budding fungus, though some believe 
it a form of mould. If some of the milk deposits on the mu- 
cous membrane of the mouth which characterize the disease be 
removed and examined mierosco pi cully, mycelia-th reads and 
conidia are observed. Ttie organism may he cultivated upon 
gelatin plates, in the fonu of whitish colonies on the surface, or 
granules with radiating processes in the depth of the medium. 


On potato and on bread it forms a white coating. The organism 
is present in the air and in various articles of food, so that infec- 
tion readily takes place. 


The Leptothrix buccalis is a normal inhabitant of the mouth, 
and occasionally produces a pathologic lesion of clinical interest 
The organism probably belongs to the group of pleomorphic bac- 
teria, though its exact position is not determined. It consists of 
fine threads, of wavy or spiral character, composed of rod-like 
segments. Occasionally, spore-like bodies are found at the free 
ends of the filaments. The organism sometimes penetrates and 
multiplies in the crypts of the pharynx, causing a chalk-like 
nodule or deposit. Secondary inflammation may be occasioned. 
(See also Diseases of the Pharynx.) 



Definition. — Syphilis is a specific contagious disease of man, 
of uncertain etiology. The disease has never been observed in 
any of the lower animals. 

Btiology. — The attempts to find a specific cause of this dis- 
ease have not as yet met with definite success. The organism 
which until very recently had the best claim to recognition is that 
observed by Lustgarten. This resembles the tubercle-bacillus 
very closfely. It is 3 to 7 /i long, and often somewhat curved and 
swollen at the ends. It stains with difficulty, and a complicated 
method was suggested by the discoverer. The bacilli are found 
in the diseased areas in small numbers, lying within the cells and 
partly between them. It has also been claimed that they occur in 
the blood. The organism has never been isolated or cultivated 
upon artificial media. Furthermore, it is difficult to distinguish 
this supposed specific germ from other bacilli, notably the smegma- 
bacillus, by the staining-niethods suggested. 

Repeated attempts to inoculate animals with material from 
syphilitic sores, with syphilitic blood, etc., have, until recently, 
failed. The results obtained in certain monkeys have been only 

In 1905 Sehaudinn discovered an organism in syphilitic lesions 
which he named Spirochccta ])all!cJa, Later during the same year 
and with the co-operation of Hoffman he was able to demonstrate 
the organism in every case of uncomplicated syphilitic disease 
examined by him. The spirochieta is described by Sehaudinn (see 
Fig. 105) as an extremely delicate, actively motile, faintly refractile 



spiral » long, thread-like organism, tapering at both extremities and 
terminating in pointed ends. It propels itselfj during life, by rotat- 
ing around its longitudinal axis, lir^t in one direction and then iu 
anotlier. In the resting states undulating movements may be 
observed passing along tlie length of the organism, suggestive of 
an undulating membmne. In addition, bending, twisting, twin- 
ing and whipping movements of the whole body may be noticed. 
Tiie organism varies from 4 fi to 14 ft in lengthy ranges iu thick- 
ness from a size too minute fur measurement to tl25 /t m the 
largest specimens. The spirals range from to 14 in number j 
they are regular, narrow and deep, corkscrew-like and appear 
constantly so, no matter whether the specimen be derived from 
initial lesions, papules, lymphatic glands, spleen, et€,, or from the 

from a sijeeiui^. 

.^Ttnth miule by Dr. IL E, iMfemon 
.1 by lir. U, Fox. 

8clero«ies of apes. By means of lY(>ffler8 metbo<l of staining flagella 
a long delicate fiagellum has been noted at each end of the organ - 
ism: in some specinifos two flagella at cnie end were seen, giving 
the appearance of an attem|)t at lougitudiual tlivision. Novy 
could find no evidence, whatever, of lougittidinal division. Schau- 
dinn has failed to discover any signs of an nndulating membrane or a 
nucleus in tlie stain^^d specimens, though the latter has been 
reported by Weehseluianu and Lo?wenthal iu specimens examined 
with the aid of nn ultramieroscope. 

The Spiroehfeta |rallida has been fuund in the initial lesions, the 
secondary papules, the enlarged lymphatic glands, the mucous 
patehes, etc., but not thus far in the lesions of tht^ tertiary stage 
nor in patients undergoing active treatment. 

Many of the most eonscrvative anthorities accept this as the 
probable cause of syphilis. At present there is some difficulty 
in distinguishing positively between the Spiroohieta fnillida and 
some common non-pathogenic lorms* Tix> much weight camiot 


therefore be given to the discovery of spiral organisms unless the 
investigator has had considerable experience. 

Schaudinn has recently maintained that the spirochetes are ani- 
mal organisms belonging to the group of flagellates and has pro- 
posed the name Tt-eponema paUidum, The researches of Novy 
seem to be conclusive that this i§ not the case. He could find no 
evidence of an undulating membrane, nucleus, or longitudinal 
division, and on the contrary only the transverse fission charac- 
teristic of bacteria. 

Whatever the nature of the organism, it is quite certain that 
the disease is definitely infective. In the great majority of cases 
infection occurs by direct inoculation in sexual intercourse. It 
may, however, be conveyed in many other ways. Physicians are 
sometimes infected in performing surgical o{>erations or in exam- 
ining syphilitic cases ; persons have frequently been inoculated in 
the process of tattooing or vaccination when saliva or vaccine- 
lymph from diseased indiWduals was employeil. Infection may 
be caused by kissing, or indirectly l)v the use of drinking-vessels 
which have been employed l)y tlie diseaseil. The new-lx>m may 
be syphilitic in consequence of disease of the father or mother ; and 
healthy wet-nurses may be infected by syphilitic nurslings. In 
addition to the specific cause, surn)unding conditions and individ- 
ual susceptibility doubtless play a part. During the Middle Ages 
this disease at times and in certain places almost attaineil the char- 
acter of a universal scourge. Its manifestations were severe, its 
course rapid, and in ever\- sense its nature was malignant. Cases 
of this description are exceedingly rare at the present day. 

Pathologic Anatomy. — The patholoiri^' course* of this dis- 
ease may be divide<l into three stages : the initial stage^ the secojid- 
arjf staf/Cy and the tertianj staff*. The disease may al)ort at any 
stage, hilt such an occurrence is rare. Not infrequently, especially 
in women, the first and even the second stage as well may be 

Chancre. — In the initial stage there is forme<l at the jx^int of 
inoculation a primary- lesion. comm<»nly ternuH.1 chancre. This 
may make its appearance first as a S4nuewluit nxl and inflamed 
j)apule, or as a vesicle which ruptures and thus pnxluces an ero- 
sion. When it In^gins as a papule the surface S4X>n Ixvomes enxleil, 
and thus a superficial ulceration is estal>lisluHl. The (Kvuliar feat- 
ure of this lesion, to which Hunter calkil |)articular attention, is 
its hanlness or induration, and it is by this foatun^ largely tliat it 
is distinguished from the soft chaucrt* or chancroid. The initial 
or primary lesion may remain indolent or as a small erosion for a 
long time, or it may soon cicatrize and leave a more or less definite 
scar. The chancre occurs upon the glans i)enis or prepuce, or 
within the urethra of the male ; and in the vagina, urethra, or upon 
the cervix uteri and external genitalia of the female. Extrageni- 



fal eliaiifTt'8 may be observed in the reetum or aiius» oii the lipg 
or tongue, tonsils or pharynx, the tinger.s, or other parts. 

Secondary Leaions.— At the enil of a \'aria}>le |>eri(xl (if time 
after the eruption of the initial sore seeoiidary manitestationi? of 
the disease make tlietr appearance. The liri>t among these, as a 
rnle, are swelling and induration of the ncighlMU*iug: lympliatic 
glands (^yphUffk bHbo). loiter the snix^rfieial lymjvh-glaiids of 
the entire body beeome swollen and, like those* in the neif:!;libor' 
hood of the legion, indnnitc*(L At the same time eruptions n|»c>n 
the skin and mucous membranes make their appearanee. The 
inter\*al between the primary and the secondary manifestations ii=i 
variable. Sometimes it is but a lew weeks (three or fmir), at tether 
tinit*s it may be several months. The manifi'stntions of the sec- 
ondary sta^re nmy hv^'m with fever ai>d const itutinnal sym(*toins, 
suggesting sudden and reeent infeetion, and at the sami* time 
changes in the blotxl {rapid reduction of red cor|HiscIes, UKnlerate 
leukL*cytos[s) make tlieir appcamnee. Among the iesion^ of the 
skiv various forms of jiapnlr^s, macides, and scaly eruptions are 
most fretpieut and eharacteristic. Tlie lesions are usually sym- 
metrically arrangeil on the two sides of the body and cause but 
little irritation. The color of the skin is freqiieutly said t<» l>e 
somewhat coppery. On the mucous nieiuliranes and neigiil>oring 
skin the most eharacteristic lesion of this stage is the eonduioma 
laiunij or mucous paieh. Tliis appears as a somewhat elevated 
patch with supertieial erosion or idee rat inn. Tlie surface has a ne- 
crotic appearance, and may i^e co\ereiI with more or less secretion. 

Tertiary Lesions. — ^Thesc may take the ft)rm of ordinary in- 
Hammatory ehaiiges of the nuieous membmne.s or of otiier parts, 
with a j>ronounced tendency to fibrous-tissue overgro^vth and 
thickening, or of definite nodules — the syphilitic tpimmaUt, or 
»^phUomfihu Aniou.i^ the *litt'iisc syphilitic changes ui the tertiari^ 
Btiige may he raid^cd atheromat<»us thickening of tlje ijuima of the 
bhKKl-vessels, certain eliang(s in the liver, spleen, kiibieys, am! 
heart-muscle^ and doubtless also similar alterations in the nervous 

The localized lesions of the tertiary stage — the gnmmata — are 
most frerpieut in the iHines (tibia, sternum, and skull) ; and in the 
internal cprgtms, such a,s the liver, lungs, kidneys, heart, and brain. 

The gumma pres(_iits itsi'lf as a nodular mass, varying in size 
from small tul>crch^like fonuatinus (miliary gummata) to tumors 
the rize of an orange, or larger (Fig. 106). It is hard^ and has 
frequently an elastic character, which has suggested the name 
gummy tumor or gumma. On section the substance is frerpiently 
found to be gelatinous or uuicoid in ap]ieanince : but there is 
nearly always eousideralde induration, either peripheml, in the 
form of a capsular enclosure, or striate, in the form of" bands 
extending from tlie center to the periphery and into the sur- 
rounding tissue. Occasionally gunuuata soften ver}' rapidly and 



become converted more or less completely ioto pun form eollectioo!!. 
When 8ituak*<l in the mueons membranes or adjacent to the sur- 
faces of the body, suppurative, fatty or necrotic ^^ftening may 
lead to the formation of superficial ulcerations, The.*ie may re- 
main indolent, or may j^dually become cicatriatc*!. Sometimes a 
gummatous lesion disappears entirely by absorption without leav- 
ing a trace of its existence. 

Histology* — In syphilitic processes of all kinds and in all of 
the stages there is a tendency lo accumulation of round cells and 
proliferation of connective-tissue cells, the processes being first 
manifest around the smaller blood-vessels, but subsequently ex- 
tending: to other parts of the tissue. The waits of the blood- 
vessels themselves are frequently Lnvol\*ed, and thickening of the 
inner or of all the coats may be observed. Complete destruction of 
the vascular channels is not rartly the consequence. Some authors 
lo<.ate the earliest changes in the small veins and lymphatics. In the 

Fi*». 10S.^Onnjiuiitji of the llvtr, 

subsequent course of the disease there is a tendency to the forma- 
tion of distinct cicatricial connective tissue* giving rise to intluratiKi 
scars or diffuse sclen^sis ; and a less pn^noimced ti-ndency to the 
(K_*currence of tlt'jyrpnerations, mucoiil and tatty, ctiusing areas of 
(lege n erati v e sf > ft en i n g* 

Tlie Chancre.^ — Tlie initial lesion first; presents small areas of 
niund-cell infiltration in the deeper layers of the skin or mucous 
memViranc, and as a rule in the neigh borhcwxl of the b I o<id- vessels. 
The connective tissue at the same time underg*x»s prolifcmtive 
change, antl spindle-sluifx-d cells t»r irregular embryonal connec- 
tive-tissue cells are found mingled with the round lymphoid celLs, 
or surrounding the foci of the latter* Giant-cells are nirely 
present ♦ Thickening of the blocKl- vessels may be oliserved in 
the later stages or frtmi the very first. The tissue-elements of 



the ekin and of the siihoutaneoiis tissue are usually separated by 
iiifiltratiiig lujukl, and tlie latter may loosen the tissiues of the 
surfiiee iinri oauise cxioliatiou of the Fuperfieinl qvitUrniis, and thus 
lead to tlie develo|mient ui' the prnnary vt\siele or the erosion so 
coramonly seen. The induration of the ehanere h probahly the 
result €vf the selerosts of the vessels and the general conneetive- 
tissue hyperplasia, as well as in part due to the tense infiltration 
of serous liquid. 

The Mucous Patch.— The condyloma latum in very mmilar in 
strueture to the initial le.^iou. There ii^, tirst» round-eel I iutittrti- 
tion of the deeper layers of the nineous menil>rnue, with serous 
exudation and erosion of the surfaee, Tjuter, there is a tendency 
to conneelive-tis.^ue hyperplasia, thcjug-h this is less marked than 
in the ease of the ehanere. 

The Tertiary Lesions, — The j^umnia is composed in large part 
of round cells derived from the blood-vessels and prolifei-ated 
coDDeetive-tissue t*ells having a spindle-shape or various irreg- 
ular forms. Epithelioid eelk are less abundant^ and giant-cells, 

iiu. ID^, — CiuMicDAtoiis me[li^go-CIlcepllB1itl^ i/^rkiii j 

though occurring at times* are usually few in number. Plasma 
cells may be abundant in syphilitic lesions, and mast^cells occur 
in small nnmbcrs. The IdorRl-vessels are nearly always nujre or 
less affected, the intinui lieing thickened and tiie adventitia being 
also involved to a variable extent. Periarterial changes are very 
conspicuous. There is some new formation of IiIockI- vessels, the 
lesion in this n^speet ditfrring frfmi the nodi da r lesion of tuliereu- 
losis ( Fig» lt)7). Secondary changes are abunst alwavs seen in 
gummata of consitlemble dimensions. Among these may be recog- 
nized a gradual necrotic transformatitm of the cells in the center 


of the lesioD, with distinct fatty degeneration or myxomatous 
change. The degenerated tissue may be infiltrated by leukocytes 
in a state of fair preservation. 

In the diffuse tertiary lesions of syphilis the tissues of the 
affected organ are indurated, the connective tissue showing more 
or less pronounced hyperplasia. These processes cannot he cer- 
tainly distinguished by their microscopic or general features from 
sclerosis due to other causes unless there are associated miliary or 
massive gummata. 

Pathologic Physiology. — Syphilis is one of the most per- 
sistent of the infectious diseases, and occasions widespread changes 
that are doubtless toxic in character. The nature of the toxic 
principles, however, is entirely unknown. In the tertiar>' stage 
pronounced anemia (cachexia) is frequent ; and in the secondary 
stage rapid chloro-anemia with leukocytosis is quite common. 

Congenital Syphilis. 

Syphilitic lesions may be found in the new-bom, or may 
develop some time after birth. Not rarely they occur in the new- 
bom fetus, and cause its premature death. Frequently there is 
maceration of the fetus prior to expulsion. Among the lesions 
observed, sclerotic changes in the lungs, liver, spleen, jiancreas, 
and other organs are conspicuous ; and a certain condition of the 
bones is quite characteristic. The latter consists of a hyperplasia 
of connective tissue and fatty degeneration at the junction of the 

epipnyses of the long bones with the 
snafts. Various superficial lesions of 
the skin in the form of vesicles or 
bullse, fissure, and the like may be 
FiG.i08.-Hutchin8on'8teTth. obscrved. The blood may present 

considerable excess in the number 
of leukocytes. An almost distinctive condition of second denti- 
tion is that known as Hutchinson's teeth. This consists of a 
notched indentation of the cutting surface of the upper central 
incisors. In addition, the teeth are often wedge-shaped and peg- 
like (Fig. 108). All cases of inherited syphilis do not present this 
condition, and it occasionally occurs in non-syphilitic children. 


Definition. — The soft chancre or chancroid is an infectious 
venereal sore appearing upon the external genitalia. The bacil- 
lus of Ducrey may be the specific organism. 

'SiWoXogy. — The soft chancre occurs almost exclusively upon 
the genital organs or the surrounding parts. It is always caused 
by direct contagion. 

The bacillus of Ducrey and Unna is a rod-shaped organism 



about lv8 /I ill length and 0.5 /i in tbicknGss, iiml appears somewlmt 
cQinpressed in the middle, so tiiat it hn^ a Hgnru-of-H shape. The 
ends are raiinded and the organisms often occur in ehains, or later 
in the disease in pairs as a diplobacillus. 

The demonstratian of the haeillus in the pns is comparatively 
easy. The .specimen is stained witli alkaline solutions of niethyl- 
ene-blue and quickly decolorized with ^veak acetio-aeid solntion. 
It raay be well stained with carbol-fuelisin, aleoliol being nsed to 
decolorize* In the tissues the demonstration is more diffieult* 

Growth is most luxuriant in a medinm of fresh blood and 
bouillon, but unmixed liuman blocMJ is the best medium for obtain- 
ing cultures from a soiiree open to contamination, the fresh bh)od 
apparently inhibiting to a certain extent the growth of extraneous 
organisms. Cultures on ordinary media have thus far been unsuc- 

The bacillus is fonml in the pus of the mA\ chancre, as well as 
in the deeper parts, lying between the cells and fre(picntly witliin 
the leukocytes. It has also been discovered tn the pus and walls 
of ulcerating bnboes, but is genenilly absent in the pus of nn- 
opeued buboes. 

Mired Infection. — Various other organisms have been found 
associated with the bacillus, inclntling streptocncci, staphylococci, 
tlit^ gonocnecos, and bacilli nf nncertain nature. 

Pathologic Anatomy- — Tiic soft chancre is an ulcer of 
variable characten Usually it is a simple nicer, with suppurating 
base and edges, not 4I iff e ring from n leers due to other causes. 
Sometimes the ulceration seems more maiignant and takes on a 
phagedenic or seT|>igjnous character (sec Uh'cration). Tlie neigh- 
boring lymphatic glands arc nsually enlarged and sometimes 
undergo supjmrative softening (bubo). 

Pathologic Physiology. — Little is known of the existence 
of special tt»xic Ijovlies in this disease. It is believed, however, 
by some that toxins are produced by the bacilli, and that these are 
capable of producing secondary lesions (bul*o) without the presence 
of tlie bacilli themselves. 


BefiBition* — Yellow fever, or typhus icteroides, is now recog- 
nized as infectious autl tmnsmissible through the bite of a certain 
form of mosquito, the Slcf/omififf Juseia. The specific organism 
lias not been iileu titled. 

Etiology, ^ — The Baciii*u^ icieroiden^ discovered iu 1897 by 
Sanarelli, seems, iu the light of the recent work of Reed, to be a 
secondary invader, an<l n<U the cause of yellow fever. It is not 

f>resi'nt in all cases. This is a small bacillus, from 2 to 4 ft in 
engtii, with rounded extremities. It is frequtmtly united iu pairs, 


and is actively motile, the motility being due to from four to ei^ht 
lateral flagella. The organism is pleomorphous. It is readily 
stained by the ordinary anilin dyes, but is decolorized by Gram's 
method. Reed regards it as a near relation of the hog-cholera 

Cultivation. — Sanarelli succeeded in obtaining cultures upon 
the ordinary media, but the growth on the surface of agar is most 
distinctive. When incubated for twelve hours at 37° C. (98.6° F.) 
and then allowed to develop further at lower temperatures there 
will be found, first, semitrausparent rounded colonies, and, later, 
enlargement of these with the formation of a thick white border, 
giving the appearance of a drop of sealing-w^ax. The character- 
istic growth is thus obtained in twenty-four hours. 

Distribntion. — Sanarelli found the bacillus in the various organs 
as well as in the blood. He succeeded in obtaining cultures in 58 
per cent, of the cases studied. Failure in a large proportion of 
cases he attributed to the small number of bacilli present. 

Pathogenicity. — The pathogenic rdle of this organism is not 
proven. The discoverer succeeded in producing in animals lesions 
and symptoms very analogous to those of the human disease. The 
dog responded most satisfactorily. Injected into the veins of a dog 
there is active cmesis, tlien hemorrhages throughout the body, and 
finally extensive fatty degeneration of the liver and kidneys. In 
one case extreme jaundice developed. Blood-serum of patients 
suffering with yellow fever causes agglutination of the bacillus of 
Sanarelli, according to some observers, but Reed states that such 
agglutination is practically Manting, while hog-cholera serum 
causes more marked agglutination. 

Other Micro-organimuM, — Previous to Sanarelli's work a great 
variety of orgjinisnis had been described. Among others a bacil- 
lus by Richardson, a micrococcus by Finlay and Delgado, a 
bacillus by (Jibier, and other orgjmisnis by Freire and Carmona 
and by StiTiiberg. None of these orgjinisins appears to have im- 
portance*, or to be i\w sjune as that discovered by Sanarelli. The 
orgimisms isolated by Ilavelberg about the sjime time as Sanarelli's 
a|)iM'jir to be of no iin|M)rtance. 

The Hole of Motifjultoo*, — Recent exjx^riments of Reed, Car- 
roll, and Agnunont<' have elemonstrated the inijH)rtance of mos- 
quitoes art agents in the transmission of the dis(»ase. It has been 
(Icfinitcly proved by Reed and his asso<*iates tliat a special form of 
mosfjuito, the Sfrf/fnnffif/f(iMri(tf(t, carries the contagion from one per- 
son to another. The germ must pass a certain incubation period 
in the body of the m(H(jnitc>, as the bite of the latter is not found 
to cjuis(» infe(;tion until after an interval of twelve days or more 
from the time it has fed on the yellow-fever patient. A bite at 
an earlier period after i'ontaniination did not confer immunity 
against a rtubw(|Uent attack of the disease. Experiments were con- 



ducted directly in non-immimc volunteers, and the transmi^silviiity 
of the dist^asc was positively proved. The iucidiiition period of the 
disease^ the time elapsing from th<' time of tlie mos(|uito'.s bite up to 
thi' first deHuite symjitoms, varied from ft>rtyHine hours to five days 
and (?eveutL"i'n liuuns. jMo.^tjuitue^ that had fed on yellow-fever 
paticmts were ciipalilf of trausniittiug t!ie disease for many days after 
their reception of ihr iufceted hlood. The resnlts of the practical 
nteasures of cpiarantine instituted at Havana in accordance with 
Keed*s work — tlestruction of alt nios(|nitoes and careful exclusion of 
mosquitoes fnuu tlie patients, with entirt* disrcgtinl ot* clothing, bed- 
ding, etc, — show that the disease is not directly contagious. Nou- 
imnrune nurses attend yellow-fever patients with impmdty. The 
mosquito alone seems the carrier of contagion* Tlie ilisease can 
also be transmitted ex|KU'i]ucntally hy suhcntaneons iujections of 
blood taken from ]iutients in the tint and second days of tlie dis- 
ease^ which proves the presence of the juirasite iu the l»h>od at 
least in the earlier stages iA* tlie disease. Tlie passage of tlie |iara- 
eite through an intermediary host is therefore not essential, In 
this respeet yellow fever resembles malaria. 

Pathologic Anatomy. — The Icsiruis of this disease are 
nuiiuly those of the inierua! org:*us — liver and kiihieys. In tlic 
liver extensive fatty degt neration h^ads t^> some swelling and light 
color of the organ, and on seetiiUi tliere may be mottied appear- 
ance due to the a kern at ion of healthy and fatty areas. In tlu; 
kidneys degenerative changes of the pa rend ly ma aud extravasation 
of bf*M>d are associated in varying pn>portions. The aj>[>eaninee 
may be that of an acute hemnrrliagic nephritis, or more particn- 
larly that of degenerative nephritis. Hemorriiages iu the nmeons 
and sfsruus surfaees are frequent, particularly extrava.sation of the 
mucosii of the stomach. 

Pathologic Physiology* — The organism of yellow fever 
probably prmluces abtmdant tuxiu. Smiarelli has claimed that 
antitoxic serum is obtainable from immuni;eed animals. 


Measles, or rnbeola, is an jufectirms aud contagious disease in 
all proliabitity due to souic nd<vro-org:tuisru, A uuniber of mitTo- 
organisnis have been discovered. Several observers (Canon and 
Pielicke, Czajkewski) have foiuid a bacillus somewhat resemldiug 
that of influenza ; <ithei> have hiimd bacilli rcsendiling the psendt»- 
diphtlieria ba(*ilhi>-, but the liacteriology is still unsettled, ]>oelde 
di^seril)ed a protozoan orgmusm uf^cnrring iu the bloml, Hektoen 
lias inoculated he.'althy persons with the blood from cases of measles 
and lias denionstrated the trjiiismissibility. 

Mild catarrhal inflamniatious of the faneial, nasal, and con- 
junctival meuibnines and of the l>rouchial mucosa are customary 



lesions. With these conditions is asscKiiatetl some oongestive ujul 
iiiflammjitorv tnlarij^ement of tlie re^notial lyniphatit' g:iands. In 
severe frascs pseu<h>iiiembninon8 inii;unniatiuiis uf the thruat are 
sonn'tiiMcs met witl^, aiul 1>ronehotmeiiiiiunia ami pareneliv matons 
nepliritis are iKrasional compiieatiinis* TJie eni()tioiJ at* tht* skin 
is tlie visible evidenee of a nnn^lemtt^ dermal am! t-nhdennal in- 
flammation, Foeal neerojaes of the liver have been dea-rilieih 
Many of the lesions are doubtless caiiHcd by ^eondary infections. 


Scarlet fever, or scarlatina, is an infections and contagious 
disease probably due to a niicro-org-anisni. A variety uf organ- 
isms Imve been discovered in cases of H?arlet fever, but none as 
yet hii^ proved to be Bpecifie. Among other bacteria the pyo* 
genie mieroeocei ( streptococci) have been regarded as etiologic 
agents. This, liowever, is by no means established. Protozoan 
organisms liave also been descril>ed (Doehle), Mallory has recently 
desiTibed under the Jiame uf Cyela^teriun searlatiiiale structures 
which present the apjiearance of proto/xm* These will be discussed 
under the liead of Aninud Parasites. 

Lesions of the inueons nicnxbranes and glands similar to those 
of measles, but usually more intense, are generjilly ju^esent. 8ujv 
punitiun of the glands of the neck is a possible termimition, and 
severe inflammations of the throat, middle ear, larynx, arid trachea, 
Avith endoeanlitis iir jiericarditis, are much nuire frcipient tlmn in 
measles. Many of these complicating eomlitions are caused by 
secondary infection with tlie Streptococcus })yogenes. Dijihtheria 
(as t*ontnisted with streptococcic lesions of the thn>at presenting a 
similar appearance) is not rare as a complication. Pareuchy* 
ma tons nephritis is a lesion of great clinical interest, while local 
necroses of various organs are observed in fatal cases. 


The bacteriology of mumps is uncertain. Charrin and Capitan 
isiilated a numljcr of organisms, mainly mieroeocei and motile 
iiaeilli. A number of other authors subsequently ol>tained simi- 
larly indeiiuite results. Laveran and C'atrin in 1893 found a 

The pathology of mumps is that of an acute inHammation of 
the pnroti^l or submaxillary gland. This rarely terminates in 
Buppuration or on recovery in induration of the gland. 


Wollstein has found bacilli differing slightly from those of 
»enza iu practically all cases of wdiooping-eough examiued in 


the early stages. Tlie stvriiin from cases of whooping-eoiigh agglu- 
tinates this bacillus in dihitious up to 1 : 200 and does not agglu- 
tinate intiuenza bai'ilH. 

A short baeilhw was di.seoveivd in the expertoratiou of jiertu?^- 
sis by Afanassiew iu 1887, He iiijrcted cidtures t>f this iiit<i tl»e 
tracliea and lungjs of dogs, and fonutl that the uniiiuds Ijeeanie ill 
and Jied^ after presenting convulsive eoiigh with bronchitis similar 
to that of whooping-eoiigh. Wendt ennfirnied these results; but 
Ritfer found a dipioeoecus in his easels, antt (_ olui and Neumann 
found small eocet, often arrungud \\s di|dtK'ocei or more rarulv as 
short chains. Czjijilewski and Hensi-l ilosrrilie a bacillus resem- 
bling the xerosis bacillus, and l)elieve tliat the oi-gauisms of 
Cohn and Xenmanu were identical with theirs. Others have dis- 
covered organisms similar to the ordinary pyogenic niicrcKNwci ; 
and some have described jn'oto/i>a in the blood. 

The lesions of a persistent bronchitis are ji resent, but are ni>t 
eharaeteristic. r)eci<led relative excess of lymphocytes is a valu- 
able diagnostic peculiarity of the blood. 


The etiology and other features will be discussed in the section 
on Animal Parasites. 


A number of raieri>-organisms have been discovered in this 
disease, hicluding strepto-baeilli (Hlava), small trranular bodies 
growing to thrc^aild ike organisms (Thoi not and Calmette; Lewa- 
scheff ), diplococei (Dubief liuiI Brfdil), Lewasehetf' has more 
recently concluded from a study of 158 cases that tlie microcoeei 
of Duldef and Bridd, whicli have also been descrilxnl by others, 
are the itnp<»rtant agents, and proposes the name Mierocoecm 

The lesions of typhus fever suggest an intense infection and 
intoxication. The blood is often dark -colored and rapidly put ri- 
fles. Various orgtins sucli as the liver, kidneys ami beai*t sliow 
pronounced f-Ioudy swellint,^ or fatty degeneration of tlie cells. 
The spleen is notably enlarged, often fpute soft an<l may present 
infarctions due to tbrombus formation. 

Inflammations of the mucous membranes, especially bronchitis, 
pliaryngitis and laryngitis, are common and pneumonia is a fre- 
tjuent result, 


Etiology. — We have every reason to believe that rahie:^ is due to a 
upeciiie germ. In 1903 Neg^ri described ao orgranism which bus received 
considerable reco^Dition a?* the probable !>ipecific cause of the di.seajie. The 
** Negri bodies " tave been found iu tbe large nerve cells of the central 


nervous system, especially in the cornua Ammonis, in various animals and 
human beings affected with rabies. They are absent in other conditions. 
In early stages of the disease the bodies are sparsely present and are exceed- 
ingly minute structureless spherules lying in the protoplasm of the nerve 
cells. Later the bodies increase in numoer and size and contain one or 
more darkly staining granules. Stained by the Nocht-Romanowsky method 
the bodies are robin-egg blue, the granules darker in color. The investi- 
gations thus far published seem to establish as probable that these bodies 
are protozoa, that they are of extreme diagnostic importance on account of 
their absence in all other conditions than rabies and their easy demon- 
stration, and that they are the specific cause of the 

Virus, — In rabic animals the virus is found principally in the saliva and 
in the central nervous system. It is occasionally known to pass into other 
organs, such as the lacrimal gland and the pancreas. It is never found in 
the blood or in the liver, spleen, kidney, or the muscle- tissues. The con- 
tents of the stomach may contain it, owing to the swallowing of the saliva. 
It affects principally the central nervous system, and is found in the most 
concentrated form in the medulla oblongata. The virus may be present in 
the saliva for at least three days before the animal shows any symptoms of 
madness, and it may be present eight days before any symptoms appear. 
It may be present in the central nervous system two days before the appear- 
ance of any symptoms. The symptoms do not show themselves until the 
poison or virus has remained in the nervous tissue long enough to produce 
structural and functional change. After it is introduced into the body it 
undoubtedly " multiplies itself" during the period of incubation. It is a 
" solid body," as it may be removed from the saliva by filtration through 
porcelain. The virus penetrates to the nervous system by following the 
nerve- trunks from the site of injury to the spinal cord. * This has been 
proved by comparison of portions of the cord and of the nerves at varying 
periods after inoculation. The virus is destroyed by drying and by the 
action of light. 

The loss of virulence by drying is gradual and regular ; hence this is 
taken advantage of for the production of ** vaccine." The virus is com- 
pletely destroyed at a temperature of 50® C. (122® F.) in one hour. It 
remains uninjured by exposure to extremes of cold — 10° or 20® below zero. 

The Danger from Bites. — The richer the nerve-supplv, the greater the 
danger, and punctured wounds are more dangerous than lacerated wounds. 
The wolf, the cat, and the dog, in the order named, are the most dangerous 

Perixxl of Incubation. — Man, forty days ; rats, fourteen to twenty-eight 
days; dogs, twenty-one to forty days. Other animals vary from fourteen 
to fifty-six days. 

The Season.— ^lore frequent during the period from April to September 
than any other part of the year. 

Preventive Inoculation. — Pasteur devised a method of treatment which 
consists essentially in successive inoculations with emulsions of spinal cords 
of increasing virulence. The virulence of the matcJial used for the first 
inoculations is decreased by drying the cords for varying periods and the 
injections are begun with the older cords and continui?d with increasingly 
virulent material. 

Pseudohydrophobia or Lyssophobia.— This is simply a condition of 
fright, and tlie patients invariably recover. 

Pathology. — Gross Appearances in Organs. — There is no gross lesion 
that can be considered specific of the disease. The cadavers are apt to be 
emaciated and to become putrid rapidly. The blood is usually dark and 
thick. The brain and the membranes may be congested, and may even 
show slight hemorrhages. The gastro- intestinal tract and the respiratory 
tract may be congested and also show slight hemorrhages. Perhaps tho 



_^__ji^ fcant feature h the prci^eiice f>f foreign bodies, surh as wood, straw. 
SflrT^S^ in the stoniach. This condition i» fouad iu about DO per cent, of 
all aiMn. 

Microscopic Appearance. -^There is nothing diHtinctive outside of tlie 
nervous e^yslem. Chiinges are found in the ganglia of the cerebrospinal and 
sympiithetie systems, and are especially marked in the plexifurin ganglion 
of the j)rieum<i«j^iiHtrie nerve and in the Gasserian ganglion. Normally, 
these ganglia are eoniposied of supporting tissue holding in it^ nieshen the 
nerve-cells. These nerve-eel Ib are surrounded hy an endothelial layer and 
capsule. The rabic vinii* brings aV>out an abundant multiplication of the 
celb lining ihi^ capsule, leading finally to the deJiiruetion of the normal 
ganglion, and leaving in its place a collection of nmnd-cells. All ganglion 
cells are not ni ark edly changed ; some are slightly or not at all clianged; 
others are entirely de-'?troyed* These changes are particularly marked in 
the dog, leKH so in man, and «till less so in the rabbit. The ganglion of the 
pneuniogastric nerve h the one generally chosen for examination^ and it 
fthould he removed immediately alter death and placed in absolnte alcohol 
or in formalin solution. i 


The Badllua proteiis vuli^nru and its several sub- varieties occur in decom- 
posing animal matter and iti it^sociation with necrotic and gangrenous pro- 
cesses in the living body. The organism ia a small, motile bacillus, occur* 
ing in pairs and leas often in ciiain formations. It is abundantly sup- 
plied with llagella. 

Cultivation and Demonstration.— The organism grows very well at 
ordinary temperatures, and forms characteristic growths on gelatin plates. 
At first yellowish colonies with outgrowths are formed ; the gelatin lique- 
fies, and the outgrowths move about in a tortuous manner and oecome sepa- 
Tated from the original growtlu Peculiar figures are formed, and the term 
Bneilliui fi^uram hva lieen applied. The cultures have a putrid odor. The 
oreani^^m is readily stained with ordinary solutions like carbol-fuehsin. 

Pathogenicity.— Injected intravenouftly in animals, hemorrhagic vomit- 
ing and diarrhea result. In man the bacillua haa been found associated 

with pblegnionouri inflammations, gangrenckus processes, cystitis, pyelitis, 
and in infectious icterus (Weil's disease). 


W The Ijeninrrlmsfit^ diseust's ennstittite a group r>f affections of 

I probably quit*^ divergent cdiararter\ whieh, however, are similar 
I in pn^eotiiig: hetiiorrhiJifos m atn! f'rutji the mueoii>; nienibrnne?^. in 
ft the skin, serotis surfaces, and in the deeper tissues or organs. 
■ The general causes of hemorrhage nuist be eonsiden'd in eon- 

" Tieetion Avitli these diseases. Among the causes capable of pro- 
diictng hemorrhages stich as iK'eur iu the heniorriiagie diseases are 
mecbantpfti rmifJition^, as iitlicronia or other diseases of the walU 
of the lih Hjd- vessels ; /or/r coj^f////oii>*, such as poisoning l»y the 
venom nf nnijiials and hy various hto(Kl-|)i)isons, and proimldy 
obseiu'e poisons j>rodueed in the course of anemic or other dis- 
eases ; iufectioiis contiifiom^ such as occur in hemorrhagic variola, 
pearlatina, etc. ; and ?>^Troiw crrndtttoiiit, as are ilhistratcd in the 
hemorrhages following injuries to the l>raiu arid those aeeonipany- 
ing certain states of eerebral excitation. 



Clinically the hemorrhagic diseases or purpuras may be classi- 
fies! ai$ primary and secandaryy the former occurring without any 
definite preceding disease ; the latter being symptomatic of various 
disorders. Among the primary there are: (1) infectious formSy 
including, with more or less probability, purpura, scurvy, and 
various forms of cryptogenetic sepsis ; (2) toxic formsy as those due 
to drugs and venom of animals ; (3) mechanical formSy as hemo- 
philia. Among the secondary purpuras are : (1) infectious formSy 
as scarlatina, variola, and the like ; (2) mechanical formSy as those 
due to cardiac and arterial diseases, or embolism ; (3) toxic formSy 
as those resulting from intestinal auto-intoxications, jaundice, 

Eernicious anemia, etc. ; and (4) nervous formsy as those due to 
ysteria, diseases of the brain, etc. 
The infectious purpuras interest us particularly in the present 
place. Various micro-organisms have been found in diflTerent 
forms of hemorrhagic disease. Kolb described a bacillus patho- 
genic for animals, which occurred in five cases of hemorrhagic 
Curpura. Babes and Oprescu isolated a bacillus from one case of 
eraorrhagic septicemia, and others have found various micrococci, 
especially the streptococcus. It is not unlikely that many of the 
micro-organisms may assume a peculiar virulence and acquire the 
{X)wer to produce hemorrhages under certain circumstances. 

The plague bacillus and the Bacillus icteroides or hog-cholera 
bacillus are closely allied in their pathogenicity to the group of 
organisms here under consideration. 

Some recent investigations seem to indicate that scurvy is a 
toxemia due to i)oisons generated in preserved meat-foods as a 
result of autolysis. In scurvy, however, several micro-organisms 
have been describcKl, but the one* whicli has the best claim for 
consideration is that discovered by Ribes, a delicate bacillus 
iKvurriii^ in the gums. Streptococci were found in association 
with it. Some Japanese investigators have recently claimed to 
have discovered a six^cific bacillus in tlie blood and viscera, 
agglutiiiable to the serum of scorbutic patients. Present indica- 
tions, however, do not very strongly substantiate the probability 
of a bacterial cause for this disease. 


Definition. — Acute articular rheumatism is probably an in- 
fectious condition ; the nature of the infectious agent, however, is 

Etiology. — ^The manifestations of rheumatism agree very well 
with those of infectious diseases, and some of the lesions frequently 
^complicating the disease, such as endocarditis, are invariably in- 
fective. The relationship between tonsillitis and rheumatism has 
been explained by some as that between primary and secondary dis- 



orJen It is supposoil tlmt the infectious agents effect an entrance 
into the budy throii^li the toiisik, oausin*i priraan^ tonsillitis and 
secoiitiary general inleetion, with looatization in the joint.^. In 
other cases it has been hehl that the organisms enter through 
al>rasious of the skin or in other way^. 

Gottniann, one of the first to maintain the infeetipus origin ^ 
describecl a StanhvloctK-eus nvoetenes flavus diseovered in one of 

this cases. Siddi fonnd an i»rg;inism whieh he elassifird as Staphylo- 
coecus pyogenes eitrens. He enmieiated the theory tijat rheuma- 
tism represents a fnrni of stapliy!oec»ceie infection, the organisms, 
however, being of a low |tTitide i\i virulence. They are not found 
abundantly in tlie exurlations in the joints, as they remain fixed in 
the synnvia! tissues. Hence, they are difficult of discovery. 
Other organisms, including various forms of bat^illi, liave been 

I/4'ydeii and others have described a streptncnccus, and it lias 
been shown that this orgjiuism is capable of producing arthritis, 
etidocarditis, and in pericarditis in experimental animals, A eon- 

, fiiderable jumiber of n-cent investigators have isolated a micro- 
coccus or strept<K"occus tVrvm cases ttf rheuumti^io and have suc- 
ceeded in producing joint lesions, endocarditis and pericarditis in 
animals inoculated with it. (Jtliers, liowever, have jiroduced 
similar lesions with streptococci from other sources. 

Achalmc described a bacillus wdiich he and others found in 
a numljcr of cases of acute articiUnr rheumatism. It is a 
large bacillus rest nibling that t»f anthrax ; sometimes it is motile ; 
it stains well with anilin <lyes and with (iramV stain; may liave 
a capsule ; and fi»rnis jiolar spores mucli hirgcr than the baciUus. 
This organism is obligate-anacrol>ic, growing l>cst in liquid media, 
in whicli it forms smal! bubbles of g-as. The organism is closely 
allied to or identical with Welcirs Bacillus aerogencs, Thioroloix 
claims to have produced tyjiical symptoms in the rahlut ; and the 
inocu hit ion -experiments i>f others have given suggestive results. 
This bacillus was obtained from tlie blood in a number of cases; 
and from the [XTicardital Huid and blood in a state of purity in one 
case. The organisms liave been fount] in sections of the heart- 
nuiscle and valves. 

The tact that i»nc (organism <tr anr»tlier produces iuflamniatury 

'lesions in the joints, emhtetmlium, fir perieanlium of animals when 
iujccteti intravenouslv docs not prove a specific relation of the 
organism to rheumatism. Doubtless various organisms are capable 
of prcKlticing such lesions anil it is not iruprohaljle that the clinical 
disease rheumatism may include a variety of infections, 

[For the iKiihologic anatomy of rheumatism, see Diseases of 
the Joints,] 



Sjnumyms. — Meditemnean Fever ; Gibraltar Fever ; Febris 


Defini^ioil. — ^Thb disease has been described as a form of 
irregular fever occarring along the Mediterranean coastSw It 
has been r^rarded as an aberrant form of typhoid fever, bat is 
certainly independent. 

Btiology. — The micro-organism discovers! by Bmce, and 
designated Microooccns melitensis, is by many K^nleil as the 
specific caase. This is an oval microeoccas about \ a in diameter, 
occurring «ingly or in pairs, and in cultures as short chains. It 
has no motility of its own. It may be stained with «»rdinary solu- 
tious of anil in dyes, but not by Gram's method. It occurs abun- 
dantly in the spleen, but not in the blood. Pure cultures have 
been obtained, and inoculation in monkeys has seemed to give 
positive results. ^lalta fever is not contagious. The micro- 
organisms seem to enter the body through the respiratory or the 
intestinal tract. 

Pathologic Anatomy. — The mucoas membrane of the small 
intestine is red and the solitary follicles and Peyers patches are 
sometimes swollen. The mucosa of the large intestine is generally 
dark red and presents small round or larger irregular ulcerations, 
from which intestinal hemorrhages occur. In some cases lesions 
of the ileum resemblincf those of typhoid fever have been de- 
8cril>ed ; but it is doubtful if the cases in which these occurred 
were Malta fover, and not typhoid. 1 he spleen is enlarged and 

Pathologic Physiology. — Malta fever is characterised by 
irregular febrile movements. The cause of this im^ularity and 
the nature of the toxic substance generated in the tlisease are un- 
known, liecently a serum-reaction, like that of Widal for typhoid 
fever, has lx*en obtained with the serum and cultures of Malta 


I>efinition. — This disease is an infection due to undetermined 
causes. It occurs in tropical and sul)tn>pical countries, and is 
characterized by muscular weakness, general izt»fl muscle-pains, 
<lropsy, and cardiac failure. The essential lesions seem to be 
deg(»nenition and inflammation of the j)eripheral nerves. 

Htiology. — Beri-beri occurs among young persons and usually 
affects numbers of i)eo])le. It is most frequent along ocean coasts 
and gr(»at rivers, and is most prevalent during damp seasons of 
the year. It does not seem to oe contagious. Dietary conditions 
appear to be imi)ortant as a predisiK>sing factor. 


Various micro-organisms Jiavf lu'cn described, including a 
number of l>ae!lli imd iiiicroi'<x'€ij as will as organism Rresenaliliiig 
the malarial lu^rimtdZija. One observer (Tavlor) was alile to 
prmluce the disease iji aniniaLs by the injeetidu of blood from a 
diseased jiersou. 

Pathologic Anatomy* — Among the lesions observed are 
pmiotate bem<»rriia<i:es in the serous j^n r faces ; parenchymatous aud 
iatty degeuemtioii of the liciirt-musele ; eukirgement of tlie bver 
ami spireiv. iJe^euenHioii and inflaninintion of tlie peripheral 
nerves are constant and important euuditioiis. 




Class ification.^^diAflS I MfzojtfHkt (Saretwlina), forms resembling the 
amiebii, aint characterized espeetally by the presence of pseudiipiRlH. 
I Clxss II. i'7<'/i/e^/fl^t (Mjisti^ophonU, protozoa^ characterized by the 
' preseDce of one or aiore long Iji^b-hke ilagella, used for progression or ac- 
quiremtat of food. 

Class III. Spomzoa^ forais* living as parsuiitea i n the tissues of other ani- 
..maL^ receiving their fo*»d only by osmosia. Reproduction by meana of en- 
Icysted tfporet?. 

Class I V . fn/nmna (Ciliata), cell-body of fixed sbapc with cilifie ; living 
free in water or as panisites. 

Class V. Smiona, cell -body provided with Buctorial tubes. Usually 
ectoparasites in water aniaials and plants 


DesCTiption* — Tins orgjinism, first accurately described by 
Lofech, i^ iui ameboid bfaly fnjm 20 to 30 fi m tUamcter, eonsisting 
of a elear protoplasmic refractive outer portion and a finely or 
coarsely gramdar prot4»[>lasm witlnn (Fig, lOf*), It frequently 
Bhow*^ vaeuole.s aufl sometimes a nueleus. It piTsent^ aetive ame- 
linhl movements when studied on a warm stage uf the luieroseope ; 
and fretjuently contains foreign bodiejs, sueli as bacteria, pigment- 
part ieles, and portions of blood-eorpuseles or other cells. 

In the movements of the organism pscudoptwlia arc projected 
from some part of the periphorv* These at first draw upon the 
clear periphenil zmie, but after their formation the grannloplasm 
flow8 mto the projected pseudopods. When in nnfavoraI>e sur- 
roundings the organisms uudergoes a form of change called the 
encyMed fflafe. In fids the btMly becomes spherical, and the wall 
is eventually stift'and firm and usually presents a donble contour. 
The division into a clear and a granular protoplasm is lost, the 
organism being uniformly graiudar. 

* Bmun (Die tierisckt'n Pimihiten des Menschen) 1903* 



Distribution and Pathogenesis.— The organism in ques- 
tion has been found abundantly in the stools of patients suffering 
from dysentery. It is readily detected in the necrotic particles or 
the mucus of the stools, and has also been found in the tissues of 
the bowel- wall adjacent to the dysenteric ulcers and abundantly in 
the liver-abscesses secondary to dysentery. 

Fig. 109.— Amoeba coll in intestinal mucus, with blood-corpuscles and bacteria (L8sch). 

The pathogenic importance of this organism cannot be positively 
established until cultures are obtainable. Thus far, attempts to 
secure pure cultures have failed. Ver}' recently (Musgrove and 
Clegg) amoebae have been cultivated in cultures of bacteria. The 
injection of mucous containing the amoeba into the rectum of 
cats and other animals has occasionally produced typical dys- 
entery, but this does not prove the mthogenicity of the amoeba. 
The regularity of the occurrence of the organism in certain forms 
of dysentery and its relations to the lesions are the strongest evi- 
dences in favor of its pathogenic rdle, 


This smaller amoeba (10 to 20 /i in diameter), also differing from 
the Amoeba dysenterise in having a less greenish color, less distinct 
ectoplasm and endoplasm, less distinct pseudopodia, in the usual 
absence of vacuoles, the almost invariable presence of a nucleus 
and well defined nuclear membrane, and in rarely ingesting red 
corpuscles, has been found in the feces of from 50 per cent, to 70 
per cent, of healthy persons in various localities. Possibly under 
certain conditions the amoeba may become patiiogenic ; usually it 
has been found in persons entirely well. 



Several otber amcebge of tester inijmrtaiice have l>een discovered. 
Among these are the Amrehtf nrhtfdi^, i\mn4 \u the urine in (*a!=;es 
of cystitis, ami ^ev^^ll forms met with in the nM»uth, e^peeially 
about the tet^tli. An amoeboid organ i^fni of uncertain patliogenie 
signiiicauee has been discovered in the abdunniial Hnid of eases of 
aecites. It has been nametl Leifdetmr f/nrnntpara. It has a pul- 
sating vaeiiole and niielcns and multiplies by budding or division. 


This organi?^m is a pear-shaped ixHly m ith a j-harp anterior ex- 
tremity providtHl witli a delicate short ciliun*. The broader jios- 
terior end i» proviiled with a long, tail-like tiagellum. A larger 
aoil a smaller variety have been described iFig. 110). The former 

Fio. 110— C'^rcooKuiaa hominis : o, larger, b. stEiftner variety (DavaloeK 

is the variety usually fijund, and is from 10 to 12 /i in length. A 
minute oval aperture has been found at the anterior extremity* 

M'<iffmficfiti€r. — The orj^^anism has been discovered in great num- 
bers in various diarrheal conditions, especially in eholera. It ba.s 
however been found in the stools of IVom 10 to 25 [)er cent, oj 
healthy persons in tropical countries antl is not known to ha%'e 
tlefinite patliogenie powers. It is not impruhal)le that the organ- 
ism is in reality a form of triehomonas. 

Other eloselv allied cereomonades have been found in the urine 
(BoiJo nriuarius; Cercomonas uriiiarius), 


A single observation of this organism was made by May. The 
body of the |iarasite was not quite the size of a red corpuscle j 
rather granular and glistening and slightly greenish. It was 
spiodle-shape^b the anterior end more blunt tlian the ^Ktsterior. 
Jour cilia were found attached to this end, and upon one side of 
the organism was seen an tmdnlating membrane. In the same 
case smaller bodies, less deveh>pc*d and probably younger para- 
sites, were discovered. The patient suffered from ciircinoma of 
the stomach and chronic diarrhea. 



This omnusm is pear-shaped ; from 10 to 15 ;£ in length 
and 7 /i in breadth (Fig. 111). The anterior end is blunt; the 
posterior end is prolonged into a sharp, tail-like projecticHL 

Fm. lllwTrichomoiuw intestinalifl (Zanker). 

The body is granular and contains one or two bodies resembling 
vacuoles. Near the anterior end at one side may be seen a row 
of ten or twelve cilia, which give the organism active motility. It 
has also ameboid movements. 

Significance, — This organism has been found in cases of diar- 
rhea, but its significance is doubtful. 


This form is rather smaller than the last, with an attenuated 
caudal end and a more blunt anterior portion, provided with three 
or four flagella ; there is a lateral unclulating membrane with six 
or seven short cilia. 

Hignificance. — The organism has been found in cases of vagini- 
tis due to various causes, but also in the vagina in the absence of 
evident disease. 


Stcrnlwrg has found several forms in the mouth, and especially 
about the teeth. These have been termed Trichomonas fiagellata. 
Tric^ioinonas caudata, and Trichomonas elongata. A trichomonas 
closely rolat<»(l to T. vaginalis has been found in gangrene of the 
lung and in putrid bronchitis. 


This orgiinism in its active state is irregularly pear-shaped, and 
presents at its broad end a cup-shaped depression situated obliquely 
at one side (Fig. 112). On the anterior edge of the depression are 
attached two long cilia, and at one point of the posterior lip are 
two pairs of cilia. In the base of the depression are seen two 
vesicular structures ^nuclei) united by a band. The protoplasm 
is finely granular and is surrounded by a delicate capsule. When 


free the organism U capable of rather rapid motion, but in the in- 
tej^tine it is attat^hptl to the epithelial cells by its ciip-shsipeJ 
depression. The urpmism exists in this fr>rm in the duodenum 
and jejunum. In the t'<ih>n or other iintavc^rahle sitnationi? it 
forms oval eueystinl brtdies ^showing the nuclei and eilia within. 

Fig. 112.— L&tnbliii liiiefitltiaUK from the inteBttnes of a mouu (Grjual &nd BchewiakofT ). 

Sigmfionnee. — T^auiblia is a frecjut^nt parasite of t lie monse, but 
has heeu found in x\iv intestines of other animals^ and oeeasioaally 
ill man, It has been found rspeeialiy in eljronie diarrlieal oou- 
ditious, and at times appears iu tlu^ stools in immense numbers. 
Nu flefiuite lesions have l>een found, and the pathogenicity of the 
genu is uncertain. 


Several varieties of trypanoscmie have been recognized in 
animals, notably in horsi^s and csittle. Among these, T. Eranm 
(Steel) has been tlujnd in the itisease **snrra^' in liorses and mule?? 
in India and Hurniah ; the T. Bmeei (Plimrner and Bradfiird) ha?^ 
been found iu " na^ana " a ^liseasc of horses and rattle in ( 'cntral 
Africa ; a tbrm jimlialily iclcntieal witli T, Brnca has l>een found 
in *' mal ile C iideras,*' a (list'ase similar to surra and uatrana in 
Central South Africa and Brazil ; 7", equiperthim (I)oflein) or 
T, roiiffefi (Laveran) in the disease of horses known as **douriue^' 
in Algeria and other countries. A comparatively harmless variety 
(T* Lewisi, Kent) oecurs in a large proportion of wild rats. It 
has been the ft>rra on whifh many of the studies of trypanosomes 
have b^en made, A few other forms have been recognized. 

The trypanosoma was discovered in the blood of a human patient 

aao * 


hy Duttoo. Tlie curlier reported csfei of Kqyrien mie apea to 
fione doobC The patieiil, mn Eoglttluiiaa, lad been mloog^ the 
Gatmbia Rirer, and his sjinpiOfBui weie wmA tbe same as diose 
mel with in animals from tbe .^ame panntie nrrasion. Grettt 
wa^stiiig and weakoese^ especial] v in the 1^ ; iiRgvlar l ebpfiiag 
fever ; edema, eqtecially about the erea; injeetioii of tbe skin ana 

^eonjuDctivse; enbrngemeDt and leodemesB of tbe spleen, and 
'^ f^aent pulse and re^piraticNis^ vere tbe principal sTmptonis. 

'Cast*.lkiii announcetl in 1902 hi^ di<co%*eiy that tbe sleeping 
fever of the African negro is caused by a varietr of trrpanoeoaiew 
The name Trmanotoma Gambimm (Dotton) has been pn>- 
posed for the parasite of man. 

Tm, 113.— Tiyp«no»«>niji Qanihienae^ (is frmn the blood, (2) from sero-AQgQlAolest 
ttuM, (1) form •biiwinir nrntii'led pu»terior eittreniitj and gTBaoUr protoplJiKm. M> dlridin^ 
form. X about 29100. (LAvermo and Hetnit). 

The trvpaoosome h a mioiite, womi-Uke Ixidy, difficult to see in 
th*f fresh blf>od with a raagnification of 300 diameters. One end 
of the parasite is drawn out into a flagelluni ; the other end is 
hluntly conical. An undulating raemhrane is attached along the 
IkhIv, which is short and thick and irranidar Near the {xisterior 
cml Is found a n*fractilc sj»ot (vacuole). The j>arasite moves by 
nn^arn of tln' Hagellum, anterior end in front, hut it may move back- 
wiinh fifpnxhiction occurs by longitudinal fission. The organism 
n-arlily dies in fresh preparations. In the stained preparation it was 
founJ 18 /i to 25 /I in Jength and from 2 ft to 2.S // in width. 

Xovy and MeNeal stjre»:»ed(Hl in cultivating trypanosomcs in ar- 
tificial mc<lia cfimpnsi'd nf fine* part of nutrient agar anil two parts 
of frcsti dciihriiiatcd or lakcd rabbit or rat blood. The oi^Disms 
retain their vinilenco in cultures for long periods of time. 

The trypanortome of man has been found pathogenic for certain 
monkeys and for dogs, cat.s and rats. 

Trnniminsum of (he DiscaMe.-^The tnmsmission of the parasite 
is effected by various blood sucking flie:j. The T. Gambiense is 


conveyed by the Glossuin palpfttk; T. Briicei mainly by the tsetse 
fly, Glm»in(t ruofHi'tfms ; T. Ltnvisi by flt-as. 

Tfie orgiinisoi may exist in the bloud in man for a long time 
witlumt eaiL-^iiig symptoms. I^atcr itetitiis tlie rereltrospinal fluid 
ami then caHse,s the ehametenstio mani testa tion.s. As a nile there 
is first irregular fever, later pains and swelling of the extreniities, 
and fuiaily emna. 

Tlie le>ions discovered at autopsy eonsist *»f «'erein'ospiiuil men- 
ingeal eongestiiin witli increased fluid and enlargement <tf the 
spleen and liver, 

Immnnization of animals has lieen aeeom])lislitMl by repeated 
inoiidations and immune fii}rd of deeirled poten<y have been pro- 


Tlie orgimisnis which are now reeogai^ced as the eause of mala- 
ria belong to the protozoan group. Most untbors regard them 
assporozoa» snljorder liemosporidia. The organism is found in die 
blood and the vascular channels of the various organs, deriving 
its nourishment, fur the most part^ directly from the blood-eor- 

Malaria has been regarded as a water-borne and as an air- 
borne disease* Xo proofs have been olitained for either view. 
Direct contagion docs not occur^ but it has lieen shown that the 
bhxHl is iixfci'tiikus when intro^luced into tlie circulation of a 
healthy person. The tlrinking i»f the blood does not give rise to 
the disease. 1 *ertain external conditions are favorable or necessary 
to tlie development of the disease. These external conditions are 
moist, marshy soil, atmospheric humidity, nnd high temperature. 
Tlie disea-^e occurs in the lowlands or bottomlands, and very rarely 
in high and dry ground. Extensive excavations und the like may 
cause the apix^arance of the disease or increase it, and, on the other 
hand, suitafde drainage may cause its diminution or disap[>eanince. 
The relation of all these conditions to malaria is explaim'd l>y the 
demonstration of the part played by mosquitoes in the transmission 
of the contagion. 

Three distinct sjietvies have been identifie<l : the organism of 
tertian fever (Pirtmnojhfm virftx)^ that of quartan fever (Phmno- 
dium mafaria) and that of esti\'<>autnmnal te\cr {Piffsinndium 

i/iyjEcox), Each of these has a double lifi? cycle, one within the human 
lost, the other in the body of the mosfjuito. In the human cir- 
culation, spleen or elsewhere asexual reproduction of the parasite 
occurs until it has exliauste^l its repnHluctive power or antagonis- 
tic biKlies have destroyed it; while in tlie mosquito sexual repro- 
duction occurs l>y conjugation. 

Plasmodium vivax. The cyck' of development in the blood of 
man begins with a small hyaline spherule about 2 /i in diumet^r 


which is attached to or within a red corpuscle. Soon piement 
particles appear within the parasite being derived from altered 
hemoglobin (melanin). The pigment particles are more or less 
actively motile due to currents in the protoplasm. Later the 
body increases in size and the corpuscle in which it is contained 
becomes paler. Finally the sphere increases to perhaps twice the 
size of a normal corpuscle. In all stages amoeboid changes in the 
shape of the organism may be observed. In the spleen and to a 
less extent in the circulating blood division of the parasite may be 
observed about the time of the expected paroxysm of the disease. 
The pigment collects in the center and the organism forms a 
rosette and then divides into 15 or 20 rounded segments or 
merozoites. These escape from the destroyed red corpuscle and 
are then ready to attack a new corpuscle and begin the same cycle. 

In the earlier stages the hyaline body appears as a light area 
on an otherwise normal red corpuscle, somewhat later its rounded 
shape suggests a ring and the term ring-bodies is given. This is 
conspicuous in preparations stained with a chromatin stain such 
by the Nocht-Romanowsky method. The body of the parasite is 
blue and at one point in the periphery may be seen red chromatin 
matter, thus suggesting a signet ring. Before segmentation the 
chromatin collects in the center and eventually divides, a portion 
being found in each of the merozoites. The cycle of develop- 
ment of this form occupies about 48 hours. 

In long standing infections sexual forms, gametocytes, are found. 
Of these the microgametocyte (male sexual form) is a large, poorly 
staining form with filaments of chromatin in the center in an 
achromatic area surrounded by the pigment. The macrogameto- 
cyte is a large extra corpuscular deeply-staining body with chro- 
matin near the periphery. 

Pla.wiodium malaricv. The organism of ijuartan fever differs 
from the tertian in that it is less pigmented and the j)igment is 
usually coarser. The segmentation is more regular, forming a 
wheel-like figure with nine to twelve segments which form the 
spherules or merozoites. The segmentation occurs only in the cir- 
culating blood and the cycle occupies 72 hours. The corpuscle 
containing the organism does not enlarge nor grow pale as in 
the case of the tertian form. 

Plamiodium prcecox. The organism of estivo-autumnal fever 
and also of tropical or malignant forms, is smaller than the others, 
occupying only a third of the red corpuscle. Segmentation occurs 
in 48 hours and takes j)lace mainly in the sj)loen, hone- marrow, 
liver, and capillaries of the brain. There is less pigment than in 
other forms but the particles are coarse. The segments are from 
seven to ten in number. 

Gametocytes are a conspicuous feature in the later stages of 
this type of infection. At first they are oval bodies, later 















\ /^ 







Variou.-* forms of malarial parasites (Thayer and Hewetson): Fijjs. 1 to 10, in- 
clusive, ttrtiaii orKaiiinms; Fips. 11 to 17, inclusive, quartan organisms; Figs. 18 to 
27, inclusive, estivo-autumnal organisms. 

Via. 1. — Young hyaline form ; 2, hyaline form with beginning pigmentation ; 
.'5, piginente<i form : 4, full-grown pigmented form ; 5, (», 7, 8, segmenting forms ; 9, 
extracellular pigmented form; 10, flagellate form. 

Via. 11. — Young hyaline form; 12, l.'J, pigmented forms; 14, fully-developed 
pigmented form ; 15, 16, segmenting foruis : 17, flagellate form. 

FiGK. 18, 19, 20. — Ring-like and cross-like hyaline forms; 21, 22, pigmented 
forms; 23, 24, segmenting forms ; 23, 2(J, 27, crescents. 


they hf?€unie crescents with centrally placed pigment sur- 
rounding tlie ehrornatiu. In bhiod kept nuder observation the 
chromatin of some ut' the cre.soents ]>rf*jeets as ilagella after 
the crescent hus changed to a sphcrieiil form (flagellate f<irni). 
The gametiK'vtcs arc siguiii(*ant af long standing iideetion. 
The gamct»H\vtes do not form wlien the infection h recent 
and the asexual cycle of development is active. Ijater they 
represent the same process of sexual dificrciuiatiou that regularly 
ijceurs in the mosquito (see below)* The llagelk of the flngelltite 
form (in the bh>otl of birds) liave been seen to break away from 
the corpuM'h; fnjiu uiiit'li they were derived and enter other, 
spherical, bodies. The flngelhi n^piv.sent llie male element, the 
pplierieal l)o<lies the female. 

Tlie Relations of the Mosquito to Malaria. — It lias been posi- 
tively demcinstrated tltal wlieii ccrtnin mnsrpiitoes (of the geuus 
Afiopheit\s) are allowed to i'wd npou malarial patients and later 
upon normal individuals,, the latttr aetpure the tlisease. Also, it 
has l)een shown that susceptilde pers<ius nvM' live in tlic most 
malarious district*^ witliuut aeipiiring the disease, provided they 
are careful ly screened from mos<juitoes. Some of tlje earlier in- 
vestigtitious in this direction failed k'cause speeinu^ns of Cuitx and 
other gen uses (not Anophefes) were used. Th(» .ittnphrh's ciavi^rr 
or qitaiit'imarnitttd and others ui* tiiis geuus alone seem capable of 
conveying tht^ diseuse. When the n)t)squito takes tlie lilood (d' the 
malarial patient into its stomach (midintestine), Hagellate forms 
(micrfjgametoeytcs) are developed, and the tiagella (nucrogametes), 
each containing some part of the nuclear substance oi' the parent 
cell, are discharget!, and, moving toward <»ther of ihe jianisites which 
do not form flagcHa (macroga metes), lerttHze tiiese by penetrating 
die body of the kitten The fertilized parasites then invade the 
intestinal walls, entering between the epithelia^ and lodge in the 
surrounding tissues, where they segment and develop a distinct 
capsule. The cystic structures so formed (ootysts) eontain nnnier- 
ous minute rods or s|>orozm*its tliat liavc resulted fn>m tlie seg- 
mentation of the panisite. The CHJcysts pmject into the efelom- 
cavity of the mosquito and eventually rupture into this, whence 
the sfxjrozooits, discharged into it, are carried to diticrent parts 
of the body and eventually lo the salivary glands. fn>m which 
they are introchieeil into any person subsefpieutly stung by the 
insect. In this manner tlie e.\traeorj>orcal cycle of development 
of the organism is completed and the periR-tuation nf tlie disease 
provided for. 

The recognition (jf the relation of the mosquito to malaria ex- 
plains certain hitherto obscure facts regarding the conditions that 
favor the development of the disease, Tiiis knowledge has also 
led to the iutroductiou of sanitary measures that have proved 
extremely use fob 

Pathologic Anatomy. — The most important fact in malarial 


infrrtion is the (U'striU'tinii that it oreui^ion.^ in the IJrM^tl, Rnjnd 
ant-niia with libei*ation of the hem*>g"h>hin (lit'nujjflohiiiemia) :ind 
tlie nppeamnt'e of j^niuular pij^mieiu in tin* hlood are anioug rho 
rei:*ult.<. The pifxmerit iicriimuhitis in the spleen^ liver, bone- 
marn>w, and in other situation m. Extreme disorganiziition of the 
bloofl may occasion henioglol>innria and widespread pigmenta- 
tion. Conj^estive enhirgement of the spleen, and, after long-con* 
tinned attacks, cirrhoiio ehanj2:es in that organ, may be observed. 
Thrombi of the capitlaries and arterioles are not rare, and to 
these, in part at least, are due tlie focal necroses observed in the 
liver and el >e where. 

Pathologic Physiology, — The curiously paroxysmal seiz- 
ures of nialaria are probably the n\«ult of tlit* lil)eration of toxic 
snbstnnces at the time of segmentation of the hematozoon. The 
I>eriodicity ilepends upon tlie duration of the cycle of develop- 
ment of the orpmism. A single group of tertian oi^anisms 
cause a tertian fever (a pamxysm every other day). Infection 
with two groups of tertian organisms, maturing on alternate 
daysj ]>roduee6 a quotidian fever (a paroxy-m every day). One 
group of (luartan organisms causes quartan fever (a paroxysm 
every third day); these groups (maturing on successive days) 
cause quotidian fever. 

Texas Fever of Cattle*— This dijisease h of interest in connect i*m with 
malaria becimse of the relationship of the parasitie cause. The oriranism 
h a small, actively anitelioid body which occuoies the red blood -corpuscles. 
Frequenlly it occurs in pairs in the corjmsrlcs, and the name Pirmoma 
bujeuilnum wa>i given to it on t!ii^ aceouriL Texas tVver is* t liaracterized by 
acute fever and tmiuently by hemi|flobinuria. The spleen is enlarged, and 
hemorrhages are obscrveil in viiri<>iiH fjrgaoH of the body. When the blotMi 
of a diseased animal is iiijeeted into a healthy one, the latter acmiircs the 
disea^^e. Transmission has been traced to the cattle tiek i Ijtoih» bnvu)^ 
The arother tick, after it.s detachment from the inferte<l animal on which 
it huf? fed, tninsmits the iafectioiLs agent to its hirva^ through the ova. The 
young ticks then convey the in feet ion to healthy cattle. 

Sporozoa im Birds and Cold-blooded Aninials.^Many blood parasites 
have been studied in birds^ reptiles, atid other cold-blooded animals. In 
birds two species ffipffutpt'oftfin Dnnakwektjl ami HnlUrhliitin Ihnmlnt^h^ 
have beea cloMely studiea, thus throwing much light on the life biHtory of the 
malarial organisms, 

Leishman-DonOTan BodieB. In certain ciu*t^ of severe malaria-like 
fever and >ptenomegaly of the tropics (known as <lum-duni fever or kala- 
ftzar) Leislujian and later Dr>novan described hodiej* of cirenlar s^hape, 2^ 
to 4w in diameter, containing a double nucleus, one largt' and staining 
feebly ai* compared with the smaller. Opinions difler as to the nature of 
these bodies but they are probably piroplaHmala. iJonovan and others hav- 
ing observed intra-corpuseutar forms in the circulating blood. 

These para.sitcs are found in the large endothelial cells of the spleen and 

There is great enlargement of the spleen, fever, emaciation, bleeding 
from the mucous membranes and edema, 

Wright and others have shown the presence of r>rffanisnia very similar 
to» if not identical with, the Leishman-Donovan bodies in the tissues of 
Oriental Sore. The identity of the two forms has not been established, and 


if Uiey are the same species, the benign character of Oriental Sore woiild, 
aceording to Mansion, indicate that the organism is* one of reduced viru- 


Description, — The c<:>ccidia are small bodies from 30 to 40/i 
ill k'lifrtii inul fnini 15 to 20 ft m width, hiiviiig a itelieato outer 
CiXiting, find within this a toiigh^ diJiilile-contouivd capsule. The 
bodv is filled with granular material, whieh i^ not rarely a^j^re- 
g:ated ill the center* Outside the liody s|X)rulatioii takes place. 
The gmiiular protoplasm divides into fi»ur rounded capsulatcd 
spores, eaeh containing a granular resting body lying in the con- 
cavity between two sickle-shaped druigliter-spores. Sometimes 
endogenous sporulation is said to occur, the pa ra^iite simply break- 
ing up into a large number of sickle-shapc^d bodies. Tlie terra 
pHorospei-mio', is applied to the rounded spores found in the coc- 
cidiutu (Fig* 114)^ 

OccTirrence and Pathogenesis* — ^The coccidiiim is a fre- 

Fia* IH,— Coccidiumovlforme, Bbowlug melbod of reproducLton. 

quent par:! site of rabbits and certain other animals* It leads to 
the ion nation of yelkiwish nrMlules in the liver. It is an iutni- 
celluiar [tamsitc, tirst invading the (*ells of the bdiary passages 
and afterwanl the surrounding hepatic cells as well (Fig. 115), 
Less frequently it oeeurs in the intestinal tract, giving rise to 
nodular thickenings or ulcerations. 

The parasite escapes from the bcKly in the stools ami then un- 
derg4.)es sporulation. Other animals are probably infcctcil by 
ingestion of the spores or spornlating cmnndia. Occasional ly the 
disease decimates rabbits or guinea-pigs kept in confinement. The 
animals fjeeome languid, lose their appetite, emaeiate^ and have 
fever. Later they sutler from convulsions, stupor, or coma, and 
die in this condition. 

A few cases of ctRH'idial disease of the liver have been observed 
in man. The lesions present themselvc^s as cystic nodules spring- 
ing fntni the bih*-ducts, or less c*onnnonly as a ditluse involvement 
of the liver with cirrhosis and eausing jaimdice. Coccidial lesions 
of the intestines have also been discovered in man, and less com- 
monly invasion of tlie heart, of the kitlneys, and other parts. 

The close assoi-iation of the organism with the lesions, and the 



number of or^nisnis discovered in tlie tif^siies^ ji^s^dy the belief 
that it is tlie ^{►eeifir fiiuj^e of tli€ lesions. 

The eoccidiuiii of the iiUestinal tmrt is ji;:i"iiendiy smaller mid 
tlie 8|>orulatioD more rapid tlian that of theliepatif form. It was 
therefore suppose*! by Leiickart to be a special variety, and has 

Fio, 115-— CV'iM'Mia iii tlie wjill of ihu bilo'<1iH't. TJu- cut shi^ws fn thfrt-ntcr nctivcpro* 
lifemtion of iliv wall of thu iluct, nviiU iiunicruu.-. (ivold loci iiJiti iniisst.Hi iu Uie tlsfrue^ 

been called Coevkliuin prrforfDus or Coretdhan hominh, ilore 
reeenlly this ha.s l>eoij regarded as identical with the orditiary 

Coccidiimi bigemiimiii, Htiles. — Tbi^! variety has been found in dogs, 
cuts, ]H)ie-csiLH ana nisiii. Tlie ev^t divideti iiUti two parts uiid theu forms 
four spores. 

Eimeria homijlis. — Eimeri a is characterized hy the forumtiun iu eaeh 
adult parasiLe ^if a .^inp:le spore contaiuiri*: an indetiulte uumWr of 
»pnrozoite». The Eimtria ftomini^ waw discovereil in the purulent exudate 
of a t-ase of pUnirisy. Tlie Bpores ivere of hurge tiize und eiintaiued from ten 
to twenty spornznites. a€Couipauied by a [krotopla-^iuie reuiuaut. The exaet 
origin of the organii^ma iu this case was not determineiL ;?ouie\vlmt s*imilar 
ortraniHins were found hy Virchow in a tumor of the liver, and by Severi in 
the lung. 


The sarcogporidia, also railed Hainey\s and Mieseher's tubes, are met 
with in a nuniherof mauimalf^. The or^:ani8ni i* eonipoi^ed of a protophy*- 
mic mass eovered with a ca|tHule, and forming at the sta^eof maturity a 
larp:e nnrnber of sickle-shaped or faleiforni spontzojtes. The orjranism$ 
usually ofcur in nui^sfcles, either within or l>etween the nuisele bundles, and 
are, therefore, elonprated or tubular in shape. Iu conneetive tlssnew the 
ortranisni may be rounded and »r>metimea prows to the size of asutall chem% 
Several varieties have beea described, aod a few observations have been 
made iu man. 

at the 



Bakatidiom or Paramecin m coli is a njtinded body from 
0.07 to (XI mm, m length atid slightly k\ss in breadth (Fig. 
116). It is surroimded by a eimt of eiliu el^l^ely set. 
is an oral aperture at one end aud an annl opening 
other The &iil>staiiee of tlie parasite is gnumlar, 
and eon tai II s a n u e 1 e us and t w o ct * ti t m et i 1 e v ae u u 1 e:^ 
bej^ides variiiiis foreign matters. Ene vested form.s 
with a tidekened eap^nh* have l>een de!seril)ed, 

Skjnifii^anir.^Tlw hog is tlie natural liost 
of this parasit4i. Man is probably infeeteii 
through drinking-water or eon tarn iua ted tood- 
atufls. It is ftitind ])articularly in the nortliern 
countries of Eiin^pe, and oeeurs in eaws **f 
diarrhea, pnneipally involvin^j: the large int*'s- 
tine, Chronie catarrhal uirtafiiiaation an<l dysen- 
teric lesions have lieen described. The organ- 
ism is probably irritating, but whether pathogenic or not is 

Fig. Ho. — B*lttti- 
ticiiuracon (Mdlai- 

JialantUlitm minutum. This ^pecien resembles tlie Balatidium coli, but 
is smaller (40 u long), liaf* a more prominent moutb, and but one vacuole. 
It has been fouail in iis-soeifttioii witli Stronfjyhide^j Anki^hsfomtij and Amcelm. 
Ita 8igni^can€e i!^ uucertaia. 


Definition.— MoUnseu 10, or Epithelioma Oaitagiosum» is an 
mtretious tlisease of the skin marked l)y the ap[>earanee of white 
and pink papules* 

Etiology. — The cause of this disease is, no doulit, a micro- 
organism of some sort. Its contagiousness is evidenced by the 
occurrence of epidemics in houses or asylums, by the occnirrenee 
of accidental innenlations, and by direct experiments. The Incn- 
bat ion-period seems to lie a long one — ^sometimes extending to 
several months. The lesions have l)een foTind to contain small 
b<Mlies whose resend^lanee to eoccidia was long ag*> jiointed out 
by Vireliow. It is uncertain whetlier these are really parasites or 
epithelial degenerations. Some authors are jK^itivc reg-arding the 
parasitic nature of the IxMlies ; withers are equally convinced of 
their nnn[>arasitie eharacti'r. 

Appearances. — The tlisease oe4'nrs as single or, moiie fre- 
quently, multiple psqudes, at Hrst quite small, but later beermiing 
nodules of considerable size. Jii tlie larger a central ileprcssion or 
uml>ilientiun is 8een, and on pressnre cheesy matter may be ex- 
pressed from this. After reaching about 3 or 4 mm, in diameter 
they rt^main stationary, i»r undergo softening and supjinnition. In 
exceptional ciis^'s the tumor mav reach the size of a small orange, 



Seats. — This disease occurs on the face, nevk, chest, genitals^ 
or r^ometinies scjit:tere<l over the wliole ImkIv, sparing only the 
palms anil sole^?. The lenioos have oecasifjnally heeii found on 
the m neons memb ra iiea. 

Structure. — MiLToseopieally the I e.^ ions of this disease are 
fonnd to consist of epithelial prolifenitioni^ haviiij^ a somewhat 
acinous arrangement, a hair-folliele occupying the center of t*aeh 
group of cells, Tlie interior of the nrKlnk\s is fiHed with soft, 
eheesy matter which may l>e expressi'd. The epithelial cells ait; 
arranged in scvend layers, tlie upper being normal cells with hu^e 
nuclei, the dcej>cr layers showing hcside the noelens small drop- 
lets, or roumled spherules, the so-called moifmeum-boiUeK These 
bodies grow in size, and may be so large ns to fill the cell, pushing 
the protoplasm and nucleus to one sid<_'. In this process the cell- 
wall and pr(>to|dasm beeinBe horny, and practically the entire 
body consists <tf thr enlarged niolluscum-eorpuscle. Certain 
granulations and mt»re or less definite segmentations within these 
bodies have been described as spondating conditions. The nature 
of these bodies is ver\" doul>tfu! ; they may be coceidia, gregarin- 
id«e, or ameboid bodies ; but they may also, as some contend^ be 
the resultia of epithelial degeneratious. 


A number of liacteria have been ilescribcd from time to time 
in these diseases, and various micrococci in particular have been 
found in the pustules, but none of these ctin be considered as 
specific. Several bacilli, one form resembling the diphtheria 
bacillus J have been recently described. 

In 18S7, Pfeitter and van der Ixeff indepemdently dcseribed a 
jirotozoan parasite of tlii^ orfler s]>orozoa, '^vliich ofcnrs in the cells 
of the rete. This organism was found in %'ariola as well as in vac- 
cinia. Pfeiffer, (Tuarnieri, and other investigators iound that by 
inoeulation of the cornea of mbbitis large nund>ers c>f the supposed 
parasite's make their apjK'anince in the epitlielial cells. These organ- 
isms are rounded bodies lying in the protoplasm of the cells, some- 
times singly, sometimes in groups of two or three. Slow ameboid 
movenients are visible and the organisms present one or more 
nuclei. Spure-fonnatron has been observed by several investiga- 
tors, (luarnieri suggested the name O/fwi/fM^ rariofc^ sett v(SCCin€F. 

Councilman, Magrath, and Brinckerhoff in lf)03 confirmed the 
findings of Gtiaruieri is 1892 and of Wasielewski some years later 
as to cell iuclusious in lesions of vaecinia and variola* They look 
upon them as living organisms antl the probable etiological factor 
of vaccinia and variola. The organisms arc first seen as small 
structureless bodies from 1 n to 4// in diameter and lying in vac- 
uoles in the protoplasm of the celh They enlarge, become retic- 
ulated and finally segment to form small round bodies about one 


micron in diameter. This constitutes what is known as the eyto- 
phisiiiic eyoU\ 

The nucleus of the eell up to this time having shown little 
change is now iuvmleti hy one or more uf the intract'lhilar bndie.s 
resulting tVom the segmeutatiou. These in size, take on 
a vacuolated structure and linally break up into a number of 
small ring- like betdies or spores. This intranuclear body is 
regarded as a more advanced ffu*ni of the intraeel hilar body and 
is pussil)ly the true infecting material of variola, 

Tlie t-ytuplasmic eyele is fouud in vaeeiuia and in vaiiola, the 
intranuelrar cycle only in variohi. These hivestigators, there- 
fore, regard it as prol>able that in small [xix the complete develo|>- 
naent ot the parasite through two cycles takes place and that in 
vaccinia the primary cycle only. These organisms are foiuid iu 
the epithelial cells of the lesions of vaccinia and variola and iu 
the endothelial cells of the capillaries and lymph 8pace8 beneath 
tlie epithelium. 

The formation of the exanthem may be due to the infected 
endothelial cells of the capillanes or lym]>h S|>iiees being carried 
to the skin capillaries by the Idnod current. No differential 
methml of staining has as yet been uffered. The nature and the 
signilicance of tiiese suppose*! organisms have not yet been posi- 
tively determined. Some authorities as Ewing look nj)on them 
as products of cellHlegenemtion. 

Secondary infections witli various micrococci or itther <frgan- 
isms are common in small-pox and vacri nation, and may play an 
important part in pnstulation, and in tlif nuuv definite complica- 
tions, such as septicemia, pneumonia, hemorrhagic septicemia, ery- 
sipelas, and the like. 

Councilman, (Amer. Medicine, Oct. 21, 1906) in discussing 
the relations of variola vera, vaccinia, and variola inocnlata^ show^s 
first of all that vaccinia diflers from small-pox iu three ways: 
first, the perifKl of incubation is shorter, being five days in man 
and three days in calves, while that of variola is twelve days. 
Second, in vaccinia the general eruption is absent. Third, for 
the development (»f vaccinia, the virus must be placed in contact 
with a susceptible epithelial surtace, and cannot he carried by the air. 

In his studies of 52 autO]isifs, carefid study was nuule to deter- 
mine the existence of a primary variolons pustule from which the 
general infection might have urcurred. None was found nor are 
there any symptoms of sufh a primary lesion. Never tlieless a 
simplepox, in the hmgs for instance, might t^^casi on no distinc- 
tive signs. He believes that tlic iufectii»u passes through the air 
and enters the system tlirongli the lungs. 

Regtirding immunity conferred Ity vaccination, he states that 
all the evidence goes to show that it is dne to germicidal power 
of the bhxMl serum which enables the serum to destroy the virus 
of vaccinia and small-pox. 




Tlie Ptinlogy of cliickeii^iHix Is even less definitely deterniinecl 
than that of sm{ill-i)ux. Pieitler diseovered tlie same organism 
doserihed hy him in vaceinin and variola. Raeteria of one srnrt or 
another have been occasionallv iomid. 

Future uivestigatioiis decide whether 


Certain invest i^itors have diseuvered Ijodiej^i having some of 
the appearances of ]>rotozoa in measles, scarlet fever, ]H'rnii'ioii8 
anemia, leukemia, sarcomata of varions sorts, and in a nnnd>er \>i 
other diseases. These observations, hi>wever, do nol merit turtlier 
discussion in tins place 
they liave heen aeciirale or mrt 

Mallf>ry (Journ. Mt^h Res.j Jan/04.)foruid in the skin of four 
cases of scarlet tever, dying in the early stages of the iliseasi:, cer- 
tain bodies which in tiieir morphology suggest tliat they may be 
various stages in the developmental cycle of a protozcKin. They 
were found once in small numbers in the ejiitlcrnds of the tongue, 
Tliey were not present in the skin of six eases tlying in the early 
stages of tile tliscase, nor in a luimljcr exauiin*'cl iji the desqua* 
mative stage. They occur in an<l between the ejiitheba! cells of 
tiie epidermis, and free in the su|Kn'ficial lymph vessels and spaces 
of the corium. They vary from 2 ti to 7 ft in diameter and stain 
delieiUely but sharply with nu^tliylene blue. The various formic 
including definite r<»settes with nutuerons segments suggest an 
analngv to the scries seen in the asexual development (schizngr)iiy) 
of the malarial ]»ar:isites. 

Tlierc are in addition to tlicsc forms larger coarsely reticulated 
forms which may represent stagt*s iit sporogony or degeneratians 
of the other forms. 

The name CijdaMnion scarlaiinak has been ])roposeil by Mal- 
lory for this organism. 


General Biology,— The life-history of the different forms 
of tape- worms is much the same, TIkt have two states of exist- 
encCj the larval^ which is genemlly found in one species of ani- 
mals (the intermediary host), and the adult ntah'^ usually occurring 
in another sjHnaes (the host). It is supposed that in tlie case of 
one or two tape-worms an intermediary lH»st is unnecessary, but 
this is doubtfuL Tlie adult worm, or tajie-worm, occupies the 
intestinal tract of njan or tlie lower {vertebrate) animals. It con- 
sists of a headf by which the worm fastens itself to the mucous 


surface ; and aft^r tlie head, a neck of greater or less size and 
lenorth, and a liody t-onsistin^ of .^pparate /iftL^ or progioiiUh^, 
The latter represent eoniplete organisms, c'cmtaining^a eomplicated 
genital a]>panitiis, hermaplirnditie in natnre, which prndnees nu- 
merous ^'^^^^ Thei'ggs an* partly disci larged from tlit* sctrmeufs in 


FiQ. 117.— Segm I'll ts of a) Tit^nlA saititiata. i2) BothriocephAliu Liitui, and U^) Tamia sciUum, 
showing urriiMiEeinent ijf uterus. 

the intestinal tract tlirough a fpnihil jfon\ hut especially eseape 
into tire outer world whtii the npe segments are sejmrated fnmi 
the body of t lie worni^ are discharged from tlie bowel, and snhsc- 
quently rupture and scatter the contained ova (Fig. 117). The cf/r/ 
ttr fivum encloses an immature larval organism, which, when 
received into a suitalile interniediary liost, penetrates the walls of 
the stomarh or intestine ajid finds its wny to the museles or organs, 
where ii iniheds itself an<l fornis the well-known //^fr^s/fv* (see Figs. 
117 and 118), These are seen with the naked eye as small cyst- 
likf^ Ixxlies lying het\v(*en the mnscle-Hl>eTs. They contain a neolex 
or head, like tliat of the ndult-worrn, inverted into a sac Hlled with 
clear, watery licjuid. When the measles or iufsficerci occur in hol- 
low cavities, i^ueh as ilv^ vcntrieles of the hndn, they may r<^ach 
eonsidenible size. They differ somewhat in diflerent forms of 
tape-worm, an will he descriljed in eoixneetioji w4th the individual 
species. When flesh infested with larval tape-worms is eaten by 
man or «ome snitalde aninud, the cysts are dissolved and the scolex 
fa^stens itself upon the mucous niend>nine of tlu' intestine. The 
IhmIv of the worm is then slow^ly or nipidly iormed. 

Man is the host of tape- worm b of adult or of larval type; most 




FiQ, ll&k.— Eggs" of various worms found in the 
alhueutBry carut) of man: a» A&carls himbri* 
coldi's ; II, r Oxyuris ventiiculHrfs: t), TrJchix^e- 
phahi§ trinbiuru!^: £, Arikylosiomiim Oii'HK'tmlo: 
y, Fiist'jrrlii ln'jj.ttti(!a: o, PitT'iro'llum Intir-eatiJiu ; 
Jl/lVii la sodium; uTieniafagiuata ; n, UibothrlO' 

frcH^upody the fornier. In one tnise, the Ta?niu ecliinoe*>eciis, only the 
lar\;tl worm uccnrf? in the human bmly,in th*^ foriimf liyiliitiil ry^^t,s, 

Patliologic Physiology » 
— Adult taiJt-woruis may 
oxist in the intestines of 
nnin with nut can si n^^ clis- 
t u riiances < it' any ki iid. Fre- 
fjnently, hmvever, diges- 
tive Jistnrlmi)oet§ and pain 
and various reMex niani- 
i es t a I i o n s ii ri ^e * The se n j ay 
he eau^ed hy tlie action of 
tlie worm as a simple for- 
eign btxly, or may result 
from poisonons agents gen- 
erattnl l>y tlie worm in its 
normal life, or as a con- 
sequence of death and de- 
generation of the segments. 
Wlien there are many 
worms ( as i n 1 1 le case of Hy- 
vu'iifjrjtis nana)^ the 4li-S- 
turhunces of digestion may he hirgt-ly mceltanieal ; under similar 
circumstances, ur wlieu a single wcirm' hcc(*mes ecMled and forms a 
mass, intestinal obstruction miiy be iR'casioned, In the ease of 
I)thfiikriorvphaiH8 /a^^i^ poisonous sulistanee.s are undoubtedly pro- 
duced, and to these must be ascribed the severe forms of anemia 
eansixl by this worm. Other tape-wnrms rarely occasion anemia, 
and never the jwrnicions Ty|H' jnst reterred to. 


This iunn, ^onu'times called the pork 
tape-worm, iiccnrs in the adult state in 
man as a worm two or three nictei's in 
length ; and in the Irog or nirely in man 
in its larval condition. The head is 
abtitit the s^ize of u pin-head and very 
<lark. Anterinrly it has an rostellnin 
armed with a double row of fn^m 
twenty-two to thirty-two hfjoklets. At 
the sides of the head arc fuur suckers 
(Fig. 119). Attached to the liead is a 
neck of thread-like appearance, which 
terminates at onee in the tairly develo)>ed 
segments <»f the anterior part uf the 
Inwly. The segments at ftrst aiT broad 
and short, but become longer in jn'optrtion to tlie breadth towaixl 
the jKisterior end. The sexually mattire segments are fonud at 

Fie. 119.— Head of Taeina Rolium 
(Mo«ler and Feiper). 


the MutMle ami the posteriur eml tit" the wonii. They contaui a 
uterus consisting af a nunlian tithe and six to twelve lateral 
branches (Fig. 117), The genital pure is found at one f^ide of the 
isegnieiit, irregularly alternating ill succ€\'^sive proglottides. The 
egg^f whieh may be squeezed from tlie segments or obtained free iu 
the feces, are eillier oval or spherieal, from 0.030 to 0,035 mm. 
in diameter, un<l of a ])eripheml striated zone and a eeutral 
gran u la r j jortion , showi ng i ndi st i net ly six 1 i nei^- represen t i ng lio< >k- 
lets (Fig. nil). Groups of segments maybe discharged from time 
to time, but this is not frequent ; the discharge of single segments 
is less frequent. The proglottides have independent movement, 
and may sonu-times lie seen to move about upon the bed-elothes. 

Tlie cyst iee reus stage which gives rise to the Taenia solium 
lives nornudly in the intmmuscular ctmneetive-tissue and other 
orgtms of the doniestic pig, but it is known to exist also in a few 
otlier mammals as well as iu man. 

The I^arval State in Man.^ — When the ova are taken into 
the stomach the shell is digested and the embryo with its six 
booklets h set free. This jienet rates the wall of the stomacli or 
intestine, and in some uneertjun manner reaches the muscles or 
organs, where it effects a hjdgement. The Iiookleis are discanied 
and a little cyst containing clear liquid is formed, and at one prjint 
may be found a Imd-like projection into the sac. This develops 
a scolex or hea<l, which eventually In-t^omes identical with tlie head 
of the fully formed worm. The cyst may be surrounded l>y a 
wall of reactive couuectivc tissue. The dunition of tliis process 
of formation of the ei/aticereuJi varies somewliat {five to ten or 
twelve weeks). The size of t!ic cysts in 
the muscles varies fi'f>m nnnnte points to 
t ha t o f a pea . I n t h e \' e 3 1 1 ri c 1 e s o f t h e b ra i n 
the cyslieerci may be as large as a small 
cherrv. Occasionally t^omprmnd or rffve- 
inose cyi^ilirn^i are met with. 

Among the seats of special interest are 
the brain, the muscles, especially the per* 
iphemi mus<"b's, tongue, and heart-muscle, 
and the siibciitau<'Ous tissues. 

The Adult Worm in Man. — ^When 
measlefl meat (hog, occasionally tliat of 
deer, sheep, and other animals) is eaten in 
insufficiently cunkml form by man the cajv 
sules r^f the cysticerci (Fig, 120) are dis- Zli 
84>lved, the scolex attaches itself to the 
mucous membrane of the small intestine, and the worm is devel- 
opd. l^snally there is Init one worm; occasionally several occur 
in the ^ame ease. The worm may remain in the intestine for 
years, despite rei>eated efl'orts to dislodge it. In other cases it is 

Fig l20.~Mi.'iif!ltid p*«Tlc ; two- 
thirds tlie imtunil siz^i (Illicit- 



ti poll tan en u sly fliscliar^retl. Reverse jK^ristalsis may rair^'o portions 
to l>e carried to the stoiiiarli, wlieiice tliey may be <lispharij<Al by 
vomiting. lu i?ome ciii^ei? tlie iithilt worm ami the larval form ha%'e 
been fount! in the s*ime iiKlividual (man). This i.s explaineil by 
tlie assumpf ion that the efi^gs liave readied the stumaeli, where tlie 
hirvie have been t^et at liberty to penetrate the wall of the .stoniaeh 
and thur^ reaeli the tissues of the body. 

Geographical Bistribution,— Tlie Trenia solium in an ex- 
cecHlin^ly mre parasite in America. It seems to be more common 
in certain parts of Europe. 


This form* sometimes cidled the beef tape-worra> is theeommon 
tai>e-worm of man. It is larger than the ])reeeding forra^ being 
from four to eight meters in length, though it may reach a length 
of :]5 meters. The head \s large (2 mm. broad), culvoitlal, and 
prtivided with four suckers. There is an abortive rostellum, but 
im booklets (Fi^* 121). The neck is rather long and j^lender and 

FlO. 12l."Hemi of Tfuijia sagtnaUl 

FlQ. 122,- Cy^tlPfm* TronK^ sagl- 

tlie segments rapidly become broader than long, luit in tlie posterior 
half I ►f the worm, where the sexually mature prnghittides are found, 
the segments are longer than hroail. The uterus is ft^rmed like 
that of the Taenia solium, but the lateral bnincbes are more 
nnimeroi«s (twenty t<» thirty, and often dichotomously branched) 
(Fig, 117). The i^gfi^ are rather mure oval and larger than those 
Ld' Taenia solium, but ntherwise eh»sely resemble the latter. 

The larval form, ur eystieeri^us, tK'cnrs in the ox and some- 
times in the giraffe. The measles ai*e found in the muscles, liver, 
hiogs, and i^casionally in otiier organs (Fig. 122)* 


The adult fontl oeeurs t>nly id man, and fwcupies the small 
iiiU'wtino, Tlir |trf5senee of tlm worm *It>es not hvem to octtisinii 
any defiiiite (Tisease uf the illtestint^s, ext^qit iii rare eases, when ii 
iiimiUer are foimd present iu a eoiliMl mass, nr win n mm \V(*nu is 
similarly r*»ilefl. This may eiyi>c iiitestiiuil uhstrac titai^ anrl pos- 
sibly in execpttrmal instant rs rupture ni' the hovvel* 

The symptoms ascribed to tiipe- worms are Miine <»f them clnul>t- 
less reflex ; but it is noteworthy that they are often absent until 
the (Kitient 4lis( overs sej[j;ments in the stools. (Further reier- 
enee to ptsi^ible patliologie results is made in the discujisiou t>f 
DilHithrincejjhalus latus.) It is an exeeed- 
in^i^ly eiiinmnn parasite in eertaiii countries 
(Afrieiiaml the East), but is more or less com- 
monly fouufi in ail parts of the world. 


Til is form, Munetitjies ealle<l the dirrfrf 
t(tjK-i('onn, in its adult state is 1 — ^1.5 cm. in 
length (may reaeli 2.5 em.) (Fig. 123 and 
124J. It has a rounded bead, witli a rnstel- 
lum that may be protruded or retmeted and 
that bearr^ a single circle of t\venty-tw<» to 
thirfy h«>oklets. The nuiture segments of the 
p<»sterior end f>f the w*u m have a yelhnv eohm 

rhe irenitiil pnre i^ nn (lie 

Fame side in all the seg- 

me n t,s. The eggs are o \' a 1 

in shape, whitish and 

trans)varent ; they are 

from ilOM (o (KOoO mm. 

long and U.0:i2 to 0.042 

mm. broad. 

Tlie intermediary boat 

FiG.l^,^H)menoWj.i. «** ^'^^^ *'*^™ 1=^ "^'^ cer- 
natiH nlHml uulural siZ4> tiUnlv kuoWU, hut IS SUD- 
(Mr«krau(l Peiper). 'i i ^- */- 

posed to be some lorn^ ot 
insf^t orj^nail. In the rat the larval form 
0€«:^urs in tiie intestinal walls at the base of the ^'^o. I2i.-Hymennievii 

.ii. . 1 i» .* - -1 1-11 uauft.much cnimrijediMuB- 

Vllll in the torm «it a evsticerctad, whieb later ler and Pel pen. 

iliseharges its contained embryo into the intes- 
tine, where it matures. The same secpienee may c*ccnr in man. 
The adult parasite alone tK^eurs in man. Tlu^ head attaches itself 
deeply in the tn neons membrane of the iKAvel, and may cause eon- 
side ralde local ilisturbance. There are usnally several or many 
worms associated ; sometimes there may be several thousands. 






This form (probably identical with Taenia flavopunctata) is from 
20 to 60 cm. in length ; the head is elongated and verges gradu- 
ally into the neck. The suckers are small, but there is neither 
rostellum nor booklets. The segments are marked by a yellowish 
spot which represents the male genital organs. It has been found 
only six times in human beings, five of the six occurring in chil- 
dren. The intermediate host is a species of small moth {Asopia 
farinalis). It has also been found in several other small insects. 




FIG. 125.— Dip- 
ylidium Cani- 
niim (M osier 
and Pelper). 


This form is identical with the worm formerly 
known as Taenia elliptica. It is a common parasite 
of dogs and cats. The length is from 15 to 30 cm. ; 
the head is provided with a rostellum bearing sixty 
booklets ranged in four rows ; the rostellum may be 
protruded or retracted. At the junction of the seg- 
ments there is a considerable contraction of the dia- 
meter of the worm, giving the body a markedly 
linked character (Fig. 125). The mature segments 
have a reddish-brown color from the presence of the 
eggs. Each proglottide has a double sexual appara- 
tus with a genital pore at each side. The interme- 
diary host is probably the louse of the dog and 
occasionally the flea. The adult worm usually occurs 
in numbers in the intestinal tract, and in some cases 
seems to produce inflammatory disturbances. 


This form is from 25 to 30 cm. in length ; the head is marked 
bv four large suckers and a rostellum bearing about ninety 


The Taenia echinococcus in its adult form occurs in the upper part 
of the intestine of the dog, less commonly of the wolf and jackal, the 
larval condition occurring in man and in some of the lower animals. 
The mature worm is about 2.5 or 5 mm. in length, and consists 
of four segments (Fig. 126). The head, which constitutes the 
first, is provided with four suckers and a rostellum bearing two 
to four dozen booklets in a double row. The second segment is 
about the breadth of the head, but somewhat shorter. The third is 
considerably larger ; and the fourth is the largest of all, consti- 
tuting about one-half or two-thirds of the entire worm. The 
uterus consists of a median portion with few a lateral branches. 


The eggs are oval, from 0.030 to 0,036 mm, iii diameter, and the 
shell is rather thinner tliaii in the eggs of other tape- worms. 

Tliese eggs ilepostted usually in water, or on 
vegetaijles, or ronvi'Vfd hy tactile eLOomuiiicatiun 
from tlie boiiy of tlie tk»gj iwv reeeived into the 
mouth of man, and several of the lower animals and 
a few birds. From the stomach or intestine the em* 
brj'o liberateil by solution of the egg capsule l)ores 
its way int^> the vascular system by which ii nmy 
be ciinveye<l to any jiart of tlie boily of its lioht, 

EchinococctlS Cysts, — Wheii the eggs reach 
tlie stomach or nmre probably the intestine of tnun 
the embryo is fitted and penetrates the mneons 
membrane. It is carried by the blood or lym- 
phatic stream to the liver or other org;ms wliere 
it dev^clops an eeluHocofeuJi e\fd (Fig- 1-7), of which 
there may be several varieties. The wall of the cyst 
is composed of two layers, an tniter cnticnlar and 
an imier part^nehymatous, grauidocellnlar layer 
is snrrnimdcd l>y an adventitons capsule of fibrous looking 
tissue derived from the organ of tlie liost. Within tlie cyst 
is a clear, limpid, sometimes amljer-colorcd fluid, having a 

\'ii*, 126,— Tff-nia 
crhint>ctjt:cus; tjn- 
liirj?ci! t-Moslcruud 

The whole 

Fill- 127,— Bchliioewifuii-cystof the liver (fnun n spccimeii In the Myst^um of Ihe PhUa- 

rlelpHiid lluApittil. 

specific gravity of from 1009 to 1015, of neutral er alkaline re- 
action, and containing no albumin or only traces lint a eunsiderable 
tpiantity of chloride of sodinnj. Hook lets are usually present and 
are of considerable diagnostic value. Sugar is sonn-tinies fonnd 
in tlie fluid. Such a cyst may increase in size hot with no altera- 
tion in its general structure thus forming an Acrphaheifiii (Lijennec). 
This form is ibund in some of the lower animals and in cattle 
where it may attain the size of an apple or an orange. 

In other eases large nnm tiers of small Inillow '" brood capsules'' 
are formed within the internal sjiaee, in which the order of layers 



¥m. 1^.— Fonnatioii of 
" brond rapeules ' \i\Mn\ 
Ihe |:H(r«iich>'mBiouii lnyiT 

IS just tlie rt'verse to what it is in tho purfiit cy^t^ that is, they are 
lined inside by a thin eiitiele and have tfie pnreiiehyinatons layer 
Oil their external surface. From the ** brui)d capsules/^ thescuHcea 
or eehiiiiieoeeus heads devehip as exteruiil p)*iitrusiuns, at tlie distal 
end ut" whieli the suckers and luxjklets of tlie s<'ulex are formed 
(Fig. 128)* 8t>nie ehuni that the setdiees may develop ilireetly 
from the eyst wall withont the medium of the 
brood capsules. To this form is given the 
term EehhtotoccHs rdennontm or i'>ft//«t>- 
rocff(x fieol i t' } pari CUM ^ It oeenrs ehiefly in 
donn'sticated animals. 

Ill man and only rarely in cattle the mother 
cyst may develop '* daughter cysts/* which, 
thontrh smaller than the pa i-ent, resemble it in 
the strnetnrc of their walls, which are eovere«I 
externally by a stmtilied enticle and internally by the |nireiiehy- 
mutoiis layer. They arise from snndl detached ]i(»rtions of the 
pareutOiymatous layer in the sti'ata <»f thc^ cuticle rd" tljc mother 
eyst ; they may Ind^e inwardly or outwardly and may st-panitje 
themselves entirely from tlie mother cyst. The ** * laughter cysts" 
may remain sterile or may pro<luce broml capsules and scolices or 
otiier cysts ( 'Errand -tlauirhter cysts"). To this eyst the term 
h'ehiHocoerus hominiA or KcliiitttctH^Hs ttffnripttriruft is applied. 

There is another form oi" echinococt us oc^-nninir in n)an as well 
as in animals and tenne*! J'Jrhlnoeoci'm muftlforuiaris (Fig. 129). It 
varies from the size nf a list to a chihrs head, presents a collection 
of cysts from 0.1 mm to o mnu in diannter and is indteddeci in a 
connective tissue stroma. Kin-li eyst is covered with stratified 
enticle^ an<l accord inir to the size contains either solid c<*l hilar i-on- 
tents or a cavity lincfl with a piu'cnehyn nitons layer, Tlie flnid in 
this cavity may be transparent or opjn[nedue to the presence of fat 
gloi>nlcs, bile jngment if the cyst be in the liver, hematoidin and 
fat crystals. Tlie cysts are usually sterile thoUfrb scolices may be 
present in some, In man the centre of the pa ni site dishiteirrates, 
leavintr ii larj^e cavity tilled with a bnnvu or greenisli fluid con- 
taining shreds of the wall, eidcareous biulies, ^nmll cysts, scolices 
and hmiklets, fat, hemattiidin, nnirgstrin, cliolesterin and concre- 
tions of lime. Nothing positive is known as to the development 
nf this form» that is, whether it springs from ti single oncosphere or 
from a nnmber of* oneos]ilieres, or whether its r^on formation is 
brought al>out by pecnliarities in its snrronndings. 

Echinr»c(M!eus cysts may continue to grow until they liave reached 
huge dimensions withont undergoing any secondary changes. In 
other cases the pinisite may die and the growth may cease, 
or active proliferation of the tissues around the cyst may lead in 
early destruction. In still other eases snppnnitive change occurs 
in the cyst or its wall. In all eases when the cyst reaches a cer- 
tain sisse the tissues amund jinMluee a connective-tissue cajisnle of 

AaXIMal pahasites and diseases caused by them. 349 

greater or less diickness. When the {mrasite dies inspissation of 
the liquitl t>ecui*s, tim\ h may evoiituully disappear ar he coq verted 
into a thiek wliitish tnaterial ; the eyst-walis ami the coriueetive- 

tissue capside at the same time shrivel and j present peeuliar eon- 
centrie hiim"llati<nis tlviit are very eliaraeteristie, Eveiitiially eal- 
eiiieiititju of tJir wall <)f the eyst antl to a eertaui extent of its 
eontt»nLs takes place. 

Seats. — Erhiniieoeeus eysts are m*jst fretpieat in the liver. 
They nlm iH-enr in the lungs, kidiuys, spleen, and onientum, an<l 
less fre<]ueutly in tlie l>raiu or other parts of the nervous system. 
Tlie {xithohigie etieets are |)rodLi(*ed hyrlireet ineelianieal pressure. 

The geographical distribution is extrusive, hut tlie dis- 
ease is eomnmn only iii restriete<l loealities, espeeiaUy in northern 
countries (north ni' l^nni]R', lee land). 


The Dibothriocephalus latus is the largest tape- worm of man, 
reaeliiog the length of from 2 to 9 m. or more. The liead is tiat- 
tened and cluh-shaped and presents tw*) gro<Jve- 
like suckers at its sides (Fig. 130). The neck is 
thin anil gradually increases in diameter. The 
ripe segments are (^uatlrate, aud are tlistiuguished 
by a rosette- 1 ike forruatiou of the uterus^ wliicli 
is plai idy visihlc in the center of each proglottid 
(Fig. 117). The genital pore is upon the flat sur- 
face of the segment and always up in the same 
si<le of the worm. The eggs are oval in shape 
and enclosed in a shell presenting a hinged liil at 
one j^Mjle. The intermeiiiary h*ist is some form 
of fish, most frequently the pike. The eggs first 
undergo a certiiin amount of development in water, 
the embryo becoming free and floatiug about, or being projwlled 
by a ciliated outer covering, ami then entering the digestive 
tract of fish. Transmission of the parasite to its lumian htjst is 
believed to he confined to tlie eating of the flesh of infected fish 
imperfectly dalted or cooked. 

ria. i:ki— Ueii*3 
and neekuf lHKK»lb- 
riocepbaiua latus 


The geographical distribution is comparatively restricted. 
It is frequent in certain northern countries, as in Sweden, and in 
parts of central Europe, especially in Switzerland. It is only 
occasionally met with in America in immigrants. 


This variety is much smaller than the last, the maximum being 
from 1 to 1.25 (jl. The head is short, broad, and heart-shaped, 
and the suckers are placed upon the flat surface. The uterine 
structure differs from that of Dibothriocephalus latus in being 
narrower and more elongated, and also in having lateral branches. 
The body of the worm contains granular calcareous matter. This 
parasite is found commonly in the seal, the walrus and the dog in 
Greenland and Iceland, occasionally in man also. No doubt its 
larva lives in fishes. 


This variety occurs only in the larval form in man, nothing 
being known of the characters of the adult worm. It has been 
found in the region of the loins, in the urinary passages, and in the 
tissues about the eyes. The head of the worm is distinguished by 
a papilla-like projection. 


This parasite measures up to 10 m. in length. The scolex is 
unknown. On the ventral surface are two grooves in which lie 
the genital pores. The ova are brownish, oval, measuring 0.063 
mm. in length and 0.048 mm. in width. It has been observed 
twice in Japanese. 


The Ascaris lunibricoides, or ordinary round-worm, is one of the 
most freijuent intestinal parasites. The male may n^ach a length 
of 25 cm. and a thickness of 2 to 4 mm. ; the female is longer, up 
to 40 cm., and thicker, up to 5 or 6 mm. The body of the worm 
is brownish or sometimes pinkish in color, and presents parallel 
ridges or rings somewhat like those of the earth-worm. The head 
is provided with three rounded prominences or lips, between which 
the month is placed (Fig. 131). The male shows two chitinous 
spicules at the cloaca. The eggs of the worm are produced in 
peat numbers ; they are elliptical, measuring 0.05 to 0.07 mm. in 
length, and 0.04 to 0.05 in l)readth and are covered with a tough 
shell, surrounding which is a clear material in an irregular mass. 




The contents of the e;i^s consist of a granular material, sometimes 
showing the linear outlines of an embryo. 

The ascariii devt'loj>s in man from shallowing of the eggs in 
infesietl tlrin king- water or foixL The parasites may be present 
singly or in numbers. They woupy the 
small intestine, but frequently tuigrate^ 
entering the gall-cluets, ttie stomauli, the 
esophagiLs, and even the larynx or nasal 

Patholoi^c Physiology, — Ascarides 
may give rise to violent symptoms hy uh- 
strnction of various passage* ways, and when 
in numbers or united in masses even intes- 
tinal obstruction may be caused. It is 
probable that asea rides produce irritating 
secretions, as it has been observed that 
ctinsiderable dermatitis sometimes arises 
in persons handling them. Occasionally 
abscess-cavities ctrntoining lumbricoids are 
found in connection with ulcerations and 
perforation of the intestines. These ab- 
scesses were liclieved hy older authors to be 
caused by the worms ; at the present time 
it is more generally held that the worms 
play no important part, their presence 
being flue only lo their coincidence in the 


This fiirm, wdiieh is eommon in eats 
and dogs, is rarely met with in man. It 
is much smaller than the ordinary round- 
worm, the male reaching a length\>f 45 or ^jj^' ^1^^:;;^?::"^ mZ'c; 
60 mm., and the leuKile 120 to VM mm tft^S^^^\^^X: 
The head js distmguished by two lateral 
wing-like projections composed of chitiuous materiah 


This form has been observeil but once, and the female alone 
was found. 


The oxyuris, seat-worm, or pin-worm, is one <pf the commonest 
pai*asites of man. The male is 2,5 to 5 mm. in length : the female, 
10 to 12 mm, (Fig, 132). The posterior end of the male is blunt 
and curved u|>on itself; in the female it is elongated. The eggs 
of the oxynris, which are produced in great numbers, are oval or 



elliptical and al>Hyt 0.05 nini. l«>iiu. Tlu' endcvn is visible witliin 
as a lobulateil boily. The para^site i^ developed direetlv ihmx the 
eggs* When thesr are swallowed the outer coating is dissolved 
in the stoniaeh nil J the embrvos escape^ to reach their full de- 
velopinenl in the small intestine. The impregnation oeeni^ in 
tbe small intestine and witliin a sliort time alter the swallowing 
of the e^gs. After inipreguatitm and ripeuin*; the female para- 
sites move toward the reetuin and may be dix-hartri'fb ^>r may 
leave by their own movements. The life 
of the worm is siiort, but there is always 
the ])Ossihility of reinleetimi. 

Oxyiiris is espeeiuUy etmimou in eluld- 
hood. It is prohalde that the worms 
sometimes eanse inHammatory trouliles. 
In cases in which theyaeenmnlate in num- 
bers a form of verminous diarrhea may he 
j)n>4kiced. In female children vanrinitis 
Irequently results fi*om tlie migration 
of the parasites into the vagina. 

Yi<y. ll"2.— Oxyiirti VAjnnJcu- 
larb lU feumle , 0, male iMtts- 
l«r ttwl eeipcr). 


The Tri(*hinella spiralis oeetirs !n its larval form in the muscles 
or organs of man and in the Inwer animals ; in the adnlt form it is 
found in the intestines uf nian ur animals. 

The adnlt male is aijuni L5 nun. in length and 0.04 mm, in 
thickness. At the posterior end there is a rc*tractite cloaca Hanked 
by two projections. The female is 2 to 4 inm. in length and iKOf] 
mm. in thickness. The eggs are provided with a very thin shell, 
and the cniln'yc>s esra|K^ from this within the litems. They are 
j^riKluced in iiuniense numbers. The young emliryiis fViiiu<l in the 
intestinal tract are Irom 0.1 t^^ O.lti nun. in length, tlie anterior 

end being thicker than the posterior. 
In part they escape^ with tire feces and 
die ; the greater part penetrate the in- 
testinal wall and art^ carried to variuus 
parts of the system, iMu bedding them- 
stdves especially in the nniscles, where 
they unnergo further changes. Here 
tlie organism (*oils itself and becomes 
surrtunnled with a cajjsnie, which is at 
first transjiareut, but may subse<|iiently 
nndergn ealcan oils change antl become 
opaque (Fig. ll^ll). 

Tricliiuelhcarc acquired by man by 
eating inipn>perly C(X>ked ham. The ca|)snh^saiv digested and the 
larval Irichinellfie set Iree. In the small intestine thev reach their 

Fio.133.— Tri*^hlrien(i-ciit«»iilewith 
tts connec'tivt'-U*sut' coverinj? : «, 
early sUise; 6* cnlclfled (Leuclciin). 


maturity in abuut three tJays ; here impregnation takes place^ after 
whirl I tlio ma Irs *Ue, wliile the females either bore more or less 
deeply into the villi, or, hv way of the glands of Lieberkiihn, 
penetrate the mnrons me mh nine, and so rt-aeh the lymj>hatic 
spaees where they dep<jsit their young. These are disseminated 
tfirougliout the hody hy their own migrations or by means of the 
ly m I ) h a ti d h 1 ih id -st rea m h. 

The tavorite seat is tlie striated musele-tissne, and they lie 
within the mnsele-bnndles t!iems*'lve>i or less frequently between 
them. Tlun' reach their destination in ten days alter the jn'imary 
invasion, but snbseciUent erops are deposited as the yonng eontinne 
to mature in tlie intestines. In two or three weeks they l>egin to 
berome eneysled in the nmscles, where they remain alive, eapahle 
of develo[)niej)t for naniy years. 

When the embryos are liberated in the stomaeh and intestines 
they oeeasion violent g-astm- intestinal irritation, with vomiting, 
diarrhea, and often more or less prononneed eul!ai>se. Jn their 
later migration the worms set up intense nniseular pains of rheu- 
matoid eharaeter, with e<lematons swelling and fever, 

Triehiniasis is e<jnnntai in all jiarts of the worhh but has been 
la rge 1 y red u w'd In* g rea t e i* * 'a re in t h e et h >k i n g of |>or k . 


The Ankylostonmni dmidenale, or Doehmins duodenalis, is a 
cylindrieal worm, the female being from 12 t*i IM nun. in length ; 
the male, from 8 to 10 nmi. The head is rounded, and is armed 

b a 

Fte^ 134.— Aukyiostomtim rtuodenale : a, mule, natnml size : h, fetnnle, natural sUe ; r. mate 
liuicnlf)<^<^ ' ^'. fenmk mairnirieci : f , head, grtiitely iniigtiiftt d ; /. egicrs (von Jukscb). 

with six sharp, liook-like teeth. The iemale is usually of a brown- 
ish or reddish color, due to the absorption of coloring-matter from the 




blood. The eggs are easily distinguished^ bring elliptical -shaped, 
fmm 0.056 to 0.003 mm, in lengtii and 0.036 iu 0.04 mm. in 
tliiekuoss. The shell is st'|ximteil iVom the coiitenLs, and the latter 
have a gnimdar apj>earaniTj Jire brownish, and in a ^tate uf seg- 
mentation. Tlie eggs nmy a[)pear in the stools in great numbers. 
If now they meet witlj the proper ctmditions chief of whicli are 
a warm elimatc anil damp earth, they hatch ont and the active 
embryo is set free. It mpidly acquires organs of digeation and 
after casting its skin seveml times and undergoing other evolution- 
ary changes is ready to re-enter a linman host. Loos has proved 
quite conclusively that, white the organism may nirely enter tlte 
human alimenUiry canal by the month, the prohuijle method of 
entrance is far more com plicated. 

After completing its exogenous phase of developni(*nt, a 
suitable opportiniity offering, the little worm |x*nct rates the skin 
generally of the feet an<l legs i>f the coolies or others working in, 
or passing through the contaminated earth in which the anky- 
lostome ova had Jjeen |>reviously de|K>sited. The embryo enters 
the skin through some f<jlliele and thence jmsses into a bh>yd- 
vesstd and so is carrietl iinally to the lungs. Here it leaves the 
blood- vessels and undergoing further changes to enable it to resist 
the gastric jiitec, enters an air vesicle, jmssc^s to a bronchus and 
so by w^ay of the trachea^ (esophagus, and stoniacli iinally arriving 
at the small intestine. Sexual cluiracters are now assumed and 
reproduction commences, the ova falling into the contents of the 
gnt and so passed out in the stools. 

The adult worm tnay be present in small or large numbers, 
and is usually rather firmly attached to the mnccms membrane^ 
Changes in the latter, however, are not pnmouneed. 

The raetfiwl of entrance of the ankylostome to its human liost 
throws important light cm the condition known as " coolie itch " 
or "gi'<^^i'**l itch ■■ wliieh often is a forerunner of the intense 
anemia and other symptoms tif the condition known as Ankylos- 
tomiasis ; *'ct)olie itch" is a sort of papuhnpustular dermatitis 
generally attacking the feet and legs, anil at times other surfaces 
as welt of the coolie laborers on plantations. It is probably 
caused by the passage of the ankylostorae erabryos tlrrough the 
skin, Ankylotsomiasis or uncinariasis is characterized by severe 
and intense anemia, abflominal discomfort or pain, general wast- 
ing often followed Ijv {leatli. This pirasite was also found in many 
C4tses of Egyjitian chlorosis, and was the canse of the intetise 
anemias (|R^rnicious anemia) of the laborers engaged in building 
the St. Got t hard tunnel. 


This parasite is shorter and more slender than Ankylmiomum 
duodenakf the male being 6 mm. to 9 mm. long and the female 


8 mm. to 15 mm, long. There are also minute differences in tlie 

head and body though tlie general struetui*e of the twtj parasites 
i^ die same. Thr ova are Jargt-r tlian Lho,se of the A. tiHotientih'f 
being 0,0t>8 mm. in h^ugth and UJI^jH lum. iij lirLadth, otherwise 
they are similar. This ibrm has Ijufu found esjKH'ially in tropical 
an<l suhtropiail Amerira aiul in the West Imliau islands. The 
condititnis produced by tlie Auieriean hook-wurm are sinular to 
those caused by the old world ibnu but are probal>ly less intense. 


This parasite t>eeurs in two genei"atii.ins or types : thi* parasit- 
leaK in wnieh the iudividual i»f female habitus re])reseut> l*otli sexen 
and reprodni-es by purthenogenusis ; und the free living generatiniiy 
in whieh tlie two sexes are represented by different individuals. 
The parasitieal generation (Anf/Hli/ufa uih^sfinafifi) lives in tlie 
upjM'r intestinal tract b(*ring deeply into the nuieous membrane 
and fretjuently into the epithelinni of Iiiel>erkuhn*s glands both 
for nourishment and ovi position. This form is 2.2 mm, in length 
and 0.034 nun. in breadth ; tl*e month is surrounded by four lips, 
the cesophugns is almost cyliiidrieal and a cjnarter t!ie hiigth of the 
entire bmly ; the eggs measure 0,050 mm. to 0.058 nun, in length, 
and 0,030 mm. to 0X)34 nm». in breadth* The v^y^s develop in the 
intestinal wall and the rhabditiforrn kr%ie, whieh measure 0.2 mm. 
in length, reaeh the lumen of the intestine and grow to double or 
three tinie^si that size until they are passed out wilh the feces. With 
the proper temjieratnre (2(Jto35^ C. ) tbt-y devilo|i in ab*kut thirty 
houi*s into the free living generation ( Anguillnla stereoralis). This 
form is sexually dilfe rent iated ; its body is smtupthaud eylindrieat, 
with pointed tail end. The mouth has fonr distinct lips ; the 
crsophaguH is sliort with a double (rhal>ditis-lifce) dikition ; there 
are three small erirved spicules at the liase of the tail. In the males 
the posterior end is rolled up, in tlie females it is straight and 
pointcsL The males measure 0.7 mm. in h'ogth and 0X>3o nun. 
in breadth. The females measure 1 nun. in lengtli and 0.05 mm, 
in hreadth. The ova are thin shelbnl, yellowish, and measure 
0.07 mm. in length and 0.045 mnu in Ijreadth. The eDd>ryo as 
it emerges from the fg^ often within the nterus measures 0.22 
mm. in lengtli an*l resembles the parent form. After growing to 
about 0.5i> mm, in length it moults and then takes on the ebar- 
aeteristies of the jiarasitic form (Strongyloid or Filariform larvie). 
In the Euro|>ean strcmgyloides the free living generation is absent. 
This may also be true* in the strongyloides of tropical origin where 
external conditions are unfavorable to the development of the 
rhaMitis form. 

There are, as has been mentioned, two methods of repro* 
dn<'tion ; that by direct transfr*rmation of the rliabditiform larvm 
into tilariform and then into a<lnlts, and the indireetj through the 



interniediate geueratioi\. By this arrangement the parasite may 
reproduce directly if extcvrnal caruHtious are iiiifavorablt^, and 
indirectly when oimditiuns arc favorable. The latter method seenif? 
to be more eunnnon in I lie tropics than in colder countrre!*. The 
adalt form alone is parasitic in the true sense; the other form 
representing only a stage for the perpetuation of the ,s]>e€i€*s. 
Unlike the aidcylostonic, v^^s of strongyloides are rarely found 
in the st4iolri excepting after purgation. Infection i>robahly occurs 
through tiiiutcd water and fiMjd, but recently experiments have 
bc^en carried ont to show that tlu* embryo muy jjenetrate through 
the skin and thus gain access to the bofly. 

Strongyloides is coninion in tropical countries, and was first 
discovered iu cases of Cochin China diarrbt^a. It is probably 
capal>le of ea using intestinal irritation, and seems rarely present 
in healthy pcrsLai>, bat its pathogenicity is still uncertain. It has 
recently been discovered in the United States. 


The anterior portion of this parasite is thin and thread-like, 
while the posterior portion is tbicker. The lengtb of the worm is 
from 4 to "> em., tbe male being somewliat the smaller. The 
thicker ]>art of the male is curled ni>on itself and blunt at the 
end, while that ^tf the female is straight and nion* ]vointed. The 

Fio. 185-— TriehoccphttluB trichiurui ; naturftl ilao (HeUcr), 

eggs are %^ery characteristie, being brownish iu color, eo%^ered with 
a thick capsule^ and having at either pole a button-like projection 
(Fig. 118). The egg is 0.050 mm. Iot)»054 mm. in length and 
0.02^ mm. in brea^lth. 

The parasile, commonly known as the '* \vhi[>-worm," occupies 
tlie ceciun in man, fteeasionally the verm i form appendix, and some- 
times the small intestine. It is one of the most common intesti- 
nal parasites in this country and appears to he well distributed 
over the entire surface of the globe, being particularly frerjiient in 
children in Syriii and Egypt. It does not, as a rnk% prLHluce 
serious disturlmnce, but may cause intestinal or reflex nervous 
symptoms. Recently it has been claimed that the parasite? cause?* 
considerable disturbance by abstmcting bhwd. 



The Filaria or Jhaeujicniua Jhtlitiefiah i>j a round-worm in- 
fostJiig the siibciitjuieous tis?iue and the skin. The iHule ha.s nut 
l>een recognized with eertiiinty, thougli two recent observers have 
found a sjnaller, degenerated antl imrtly ciileilied form in assficia- 
tion witii the feniiile Hlaria. TJie female isometimes reaeliej* a 
length of 50 to 80 cm.; it ia yellowisli in coh.>r and exceedingly 
elastic; tlje anterior extremity is roundif^h, the posterior terminat- 
ing in a spine. In geiiei-al a[>iM*anince it resembles a string of 
catgut* The body of the worm contains a highly develojjed 
uterus, which practically fills the cavity of tlie W(inn» the intesti- 
nal tulte being crowded tt> one side. The uterus is fonnd to con- 
tain innnmerable small ivmbryos ; these escape wlien the parasite 
is rufvtured. 

The process or place of impregnaiiou is unknown. W hen 
ovulation, however, is complettHl the parasite moves down to the 
leg or ff>ot (>f her ho^t, whence she will lie better aide to deposit 
her young in w;iter, whieli is alisolutely necessary icir their develop- 
nK'iit. Here she drills a small Imle in the dernuu but eh"es not 
penetrate the epidermis. Over this a small Idister ur l>Hlla formiJ 
which soiai rujitures, disehising the small ojiening in the center of 
a sup<?rficial erosion. When the host now enters the water a ]ior- 
tir>n of the uterine tnbe is forced out through the month of the 
worm by the contraction i*f the ninsculo-eutaneous integun\ent and 
ruptures, setting iVee myriiids of the embry** worms. This is 
repeatetl at intervals until the entire nlerus is expelled and par- 
turition is completed. This takes, as a rule, two to three weeks. 
The worm now dies, and is expelled or pulled out bit by hit or 
entire w^ith or withrmt suppnratitm. Forcible attempts at removal 
of the worm from the tissues may result in its niprure. tbns setting 
free milhons of embryos in tlie tis.snes wht^sc^ presence, associated 
with suppuration, which risnally follows, results in a condition of 
consideraljle danger to the patient. It is, therei'ore, better to wait 
until parturition isconipleted before attempting removal ofthc worm. 

The embryos having been deposited in the water take np their 
aljode in the intern»ediarv- host, the body cavities of a species of 
Cyclops. They enter by penetrating the delicate nicndirane that 
unites the phites of tlie ectoskeletou of tlie erustaceaiK Tlie life 
histor)^ from here on is a blank. It has been thought that after 
projXT develo])ment the parasite m swallowed in drinking water 
while still in the Imdy <tf the crnstacean, or it may be after it has 
escaped from this intermediary. Or it may obtain entrance to its 
human host by Imring its way tliriiugh the skin. 

The organism occurs very alinnduutly in tropical countries of 
the old world, notaldy Arabia, along tlie ct«ist ofthc Caspian Sea, 
in Abyssinia, and tjuinea. The parasite is sometimes called the 
Guinea- wonn. 



Several varieties of filariae have been found in the blood and 
are included under this generic term. The discovery of the 
organism, or rather of the embryos, was made by Wucherer, in a 
case of hematuria. 

The embryos of FUaria Bancrofti or F. sanguinis hominis 
appear in the blood, urine, the lymph, and the tissues as thread- 
like structures, varying in size in tlie different varieties. The 
ordinary form has a thickness of about the diameter of a red cor- 
puscle, and is as much as 0.13 to 0.30 mm. in length. It consists 
of a transparent sheath, almost completely filled with the embryo, 
the ends, however, projecting a little beyond the organism, in a 
sac-like fashion (Fig. 136). The embryo is actively motile, 
squirming, thrashing, or curling and uncurling itself rapidly, and 
thus producing more or less agitation of the corpuscles or solid 
bodies in its vicinity. 

The number of the embryos found in the blood varies greatly ; 
in many cases a search through several cover-glass preparations 
may be necessary to detect a single one. Usually they are more 
abundant. A feature of importance is that they occur only during 
the night, unless the patient reverses the usual conditions and rests 
during the day. 

The adult worms occupy the lymphatic channels, the male and 
female being found together. The male is colorless and measures 
about 40 mm. in length and 0.1 ram. in thickness. The cephalic 
extreraiiy is a little thickened, the posterior extremity is bent and 
rounded but not spiral. The female is brownish, 76-80 mm. in 
length and 0.2-0.3 mm. in thickness. Both extremities are 
rounded. Almost the entire body is occupied by the two uterine 
tubes in which may be seen the ova and already developed larval 
filarise. These enter the circulation and are discharged in various 
ways, especially in the urine. The common tropical mosquito 
{Oalex fatigam) has been found to act as the intermediary host in 
which the embryo reaches its fuller development. The embryo 
filariae are taken into the midgut of the mosquito together with a 
certain amount of blood at a time when thefilarite are found in the 
peripheral circulation. Here in the thickened j)lasma the embryos 
are able by their active movements to break through their sheath. 
Now by means of a short delicate spine and a circle of hooked 
lips at the head end, the organism bores its way to the thoracic 
muscles of the mosquito. Here in the course of one to three weeks 
it goes through a series of changes and increasing considerably 
in size. It now works its way to the head of the mosquito, 
and finally passes down into the labium or sheath of the proboscis, 
where it awaits the opportunity to enter a human host when the 
mosquito next feeds on man. It then fiuds its way into the lym- 
phatic trunks where the sexes come together and the youngare born. 


FilariasiS i^ partiealarly coninion in the warmer el i mates, hut 
is occasiomilly met with in tlii^ country, especial ly in tlie Southern 
Stat^. Otie nf its most frequent ibrniK is ehanieterized el in teal ly 
by hemaiochyluria. The embryos in these eai^ej^ may l>e iouo^I in 


i-]u, i::.ri. — i^iiarm cmLryo. sUive ni ihe tulood {t V. Henry). 

the l>lood and also in the chyhuns urine. Pat lio logically no gross 
ehaoges may lie fmmtl, but there; may be in uther cases evident 
distentir^n of the lymphatit^ channels ami bloiMl-vessels of the 
pelvis of the kidneys, ureters, nr bkidder ; and the emlirvos may 
\h* found hi the substance of the kiflneys or Jii the walls of the 
hlrMHl-vessels. Another Ibrm of tilariasis is t'Icph(ttiiia,^i^. In 
these cases there is ohstnietion of the lymphatic vessels in con- 
sequence of the pn^senee of the parasites, of thrnmlii» or td inflam- 
matory lesions and us a it\sult of these conditiims tlilatation of the 
periplieral lymphatic vessels occurs. Tlie skin may be riipture*l 
and chvlous liouid niav exude. The embn^os mav be found in 
this on micros<^<>]ui' exannuatiou. 

Varieties.^Mausoa has desenbed tln-ee varieties of embryonal 
filuria^ — die tjrigimil tonn, or Fdann noetnnta ; a second varietv, 
in wliicli the embiyns are found at any time, night or day; ealli^l 
Juht/ift pcfHtanH chai^aelcrizcfl nUo by its small hii^e (t>/2 mm, in 
length), grt^at motiHty and absence of :i slieath ; tluit he believes is 
the cauhc of certaiji skin diseases {Craw-(_Vaw) of Africa ; the 
adult worm is unknown. The third form is die FUarm (Uitrna^ 
whii'h a|»|M*ars lu the blooil imly diu'ing tlie dav. The last is 

f>n>bably the embryo of Fiiun'ti ioa, a ft>rm iM-cnrriiig in the eye, 
ying under the etiujunctiva. It is found in Africa and trt epical 
Amt rir:a, Mansou believes tliat the nuingrove fly is the itilernie- 
diary liottt. 


The Fiiaria leniiti was fuuud in the lens in a case of eataraet. 
The Fihtria labiffUs was discovered in a pustule an the lip nf a 
si ut lent in Naples ; the Fikiriu fttmthifi^ orij^ was found liy I^idy 
ir» the month of a eliiid ; and Fi/oria in-ififonnu was found in the 
urine of a jmtient by the same observer. The Filarki hnmitia: 
IB the common fiiaria of the dog^ and has been found in man. 


The FUaria ozzardi was found in the blood of Caribs of British 
Guiana. The FUaria loa is confined to Western Africa. The 
FUaria bronchialis was found in the bronchial lymphatic glands in 
a case of phthisis, and has also been found in the trachea and 
bronchi. The FUaria Demarquayi and F, Magalhcesi are forms 
whose identity has not been sufficiently established. FUaria con- 
junctivoRj F, lyinphatica, and F. Romanorum-orientalis are others 
that have been aescribed. 


This is a large round-worm, the body being marked by distinct, 
transverse, parallel rings. The male may be from 7 to 10 cm. in 
length, the female from 31 to 50 cm. There is a retractile rostel- 
lum, with six rows of booklets, at the anterior end, each row com- 
posed of eight spicules. The parasite occupies the small intestine of 
the hog, and has been found occasionally in man. The intermediate 
host seems to be the grub of the cockchafer and the June-bug. 

Other varieties of echinorrhynchus have been described, but 
are not well-determined si^ecies. 


The female of this species may reach a length of 1 m. ; the 
male is but one-third this size. The anterior end of the worm 
is retracted, and the mouth surrounded by six papillse. The 
posterior end is expanded, and provided with a spicule projecting 
from the cloaca. The color of tne worm is brownish or blood-red. 
The parasite is found in the pelvis of the kidneys, ureters, and 
bladder of dogs, horses, cattle, and other animals, and rarely in 
man. Among its results are enlargement of the |)elvis of the 
kidney and atrophy of the kidney-substance. 


This parasite was found in the lungs of a child. It resembles 
the strongyhis met with in the lungs of sheep and other animals. 


This organism has been described by Loos as being found in 
the intestines at autopsy of natives of the Egyptian lowlands. 


Tlie fluke- worms are usually flattened organisms, somewhat 
tongue-shajKid and provided with powTrfnl suckers and occasion- 
ally with booklets. The intestinal canal begins in the oral 


orifice anteriorly, but m cloKcdat the posterior extremity. Repro- 
duet inn may Uikv place directly ur by the formatiim ot' iin inter- 
me<liate urt^anisni wliieb is pamsitie to eeriuiu lower lUHmals. In 
tlii^ jitage tliey are aetively motile, swimming about in water, and 
are known as the cereariie. 


The Faseiola he[Kitira, (ir livi'r-flnke, is from 15 to 35 mm, in 
length and 6 to 20 mm. in breadth; it is jMnntr^l at either end, and 
anteritirly is provided with two suckers* 
one at the head and one upon tlie ventral 
surtaee, s*iniew liat posterior in the first 
(Fig. 137). The genital jmre lies l)etween 
the two truckers. The eggs are oval in 
shafw, 0.14 to 0.1 5 mm. in length, and pro- 
vided wnth a lid at one pole. 

The adnh organism neenpies tbe bibarv 
duets and is a fre*pujnt pa m site of sheep. 
It is oecasionally met with in numj usually 
oeenrring in e<msi<lerable numbers. It 
gives rise to ifimt ruction of tbe biliary 
jmssages a nd eonsecj uen t e n la rgeme n t , e< m- 
gestion, and later deg<*ueration of tbe liver. The galbduets above 
tbe ]KMnt i^f obstructitui have sometimes bcf'n found eonsi*lend)ly 
dilated m' eystie. C'linieally ascites an*l jiuindiee have been found, 
with gastro-intestitjal symptfun^ and faseiola-eggs in the stools. 

Flu. 137 —Fasclola Uf iMUica 
tW(Klhir(i« tbe rmtunil sixc 


This form measures from 8 to 10 mnh in length and 2 to 2.5 
mm. in breadth. The two suckers are far ajiart, and tbe genital 
pore lies between tliem (Fig. 138). Tlie 
eggs are OJH tnO.U;") mm. in length and 0.03 
mm. in breadth. 

This parasite is frequently ass»ieiated with 
the last, and weupies the biliary passiiges id' 
sheep and cattle. It is oeeasionally met 
with in other animals and in man. 


This form varies in size with the degree 
of eontraction but \8 usually 8 to 11 unn. 
in length and 1.5 to 2 mm, in breadth, 
are far apart, and the genital pore is just in 

Tic \:^.—T>wfovfvUnm 
laru.ieiitiim ; twi^thirtls tht- 
natiiml (>ize (. Mueller and 

The two «-uekers 
front of tlio ventral 


sucker. The eggs are oval, operculated, measuring 0.03 mm. 
in length and U.Ol mm. in oreadth, and contain a ciliated 
embryo when deposited. This jmrasite inhabits the gall bladder 
and bile ducts of the domestic cat in particular, but is also found 
in the dog, fox and man. It has l>een observed in France, 
Germany, Russia, Holland, Italy and Japan. 


This parasite resembles the 0. felineus in shape and color. 
The length is 10 to 14 mm., the breadth 2.4 to 3.9 mm. The 
eggs are oval witli a sharply defined oix»rculum at the ])ointed pole, 
they measure 0.030 mm. in length and 0.017 nnn. in breadth. 
This parasite inhabits the bile duct^ and gall bladder of domestic 
dogs and cats as well as of human subjects. It is found frequently 
in Japan, also in China and India. 


This organism, sometimes called Bilharzia, cxjcurs in sexually 
distinct forms, the male and female, however, occurring together. 
The male is 12 to 14 mm. in length and 1 mm. thick, and the 
body back of the large ventral sucker is somewhat flattened and 
curved ventralward to form a groove, in which the female is 
attached (Fig. 139). The latter is 16 to 1« mm. long, and 0.13 mm. 
thick. The eggs are 0.1 35 to 0.180 nmi. long and 0.055 to 0.060 
mm. l)roa(l, not operculate<l, and having a spine at one end or at 
the side of one encl. The adult parasite occupies the ])ortal vein 
and the veins of the spleen, mesentery, and the plexuses of the 

Fio. 139.— vSrhistosoraum hematobium, with e^gs (von Jaksch). 

bladder and rectum. The eggs of the organism may be found in 
any of the organs, notably in the liver, in the intestinal walls, 
and in the mucous membranes of the urinary passages. They 
probably occupy the vascular system ordinarily, but cause rupture 
of the walls of the vessels and thus escape into the tissues. 

The pathologic changes caused by this parasite and included in 
the term Bilharziasis are more strikingly seen in the ureters and 
bladder in acute cases. Hyj>eremic spots or small hemorrhages 
may be seen in the mucous membrane, and the surface is covered 
with blood-stained mucus containing the ege:s. In cases of longei 
standing roughness of the mucous membranes and usually small 


ecohymotic elevati«jns or outgrowths, Hitggesting pa|jillomata, ai'e 
observed (Fig. 140). iSectifni tlinnigli the«e shows that they cou* 
Bist of prulifemted cells witli enlarged 
bloml-vcs^^Ls, from which the adult wunu 
may be removed. The tissues siirruuinl- 
iiig the vessels may eoiituin eggs in euc*r- 
luous uiinibers. The mueous nie nil) rune 
is frequeiuly eoveretl witli a ealcareous 
deposit c<tmpiHed td^ urate aiul oxalate 
of sodium, and the exerescenoe,*? luay he 
converted into ciileified jMdyps. Among 
the final result.s may he cieatrieiid strict- 
ures of the ureter, jnelitis, and distension 
of the pelvis of the kidney , with nti'<ifihy 
of the kidney-suhstauce. Hi in i hi r patht*- 
logic processes may he found in t!ie rec- 
tum. When the portal vein is txTupiefl, 
the eggs of the Bilharzia may beahunilant 
in the liver-substance. Sehistns(»mura 
hematohiura is u parasite occurring with 
enormous frequency in Xorthcrn Africa 
and neighboring (countries. It is compara- 
tively rare in other parts of the world. 

Fig. UO.^PApnUry thicken^ 
liig of thti mucouH mcmbnuie 
Lit Um bludder. i*h«>vvHig schJfi- 
t<>si'iimini-4>uKs in situ (MosKt 
am] IViperi- 


Sp jai>onictnn c»r S. cattoi has recently 
been discovered in Kiisicrn Asia and Japan. Tins ]varasite 
inhabits the arterial side of tlic portal system. It is somewhat 
smaller than X henmlobium^ and the male is distinguished by his 
uon-tubcreuhited integument, Tiie ovum has no spine, is regu- 
larly oval, [lerfectly smootli, and with a nnieh tliinner shell. It 
rese ni I > I cs c 1 ( >se 1 y the o \ u n i of A n !v y h )s t o n » n m il % n k Ic n a I c . ' f h ey 
are deposited in the niucusa and stihrnucosa of tlic large an<l small 
intestine, cs{»eeially the former. Vvmw In^re tliey escape with the 
feces. No more is known of the life liistory froni tliis jjoint than 
is the «ise with theN. hematobium. It causes a peculiar kind of 
chronic enteritis and anenxiaj associated with enlargement of the 
spleen and liver, terminating in a fatal cachexia. Cat^s are sus- 
cjeptible to this parasite as well as man. 


This org:inism is Irom H to 10 nini. in length and from 5 to 6 
mm, in breadth. The eggs are hmwuishi and iroin 0.08 to 0.1 
mm, in length. The worm occurs in the lungs, oecupyiug exca- 
vated spaces, usually near the periphery of the organ. These cav- 
ities contain redtlish or quite hemorrhagic mucopurulent liquid 


and abundant eegs. The cavities are in communication with the 
bronchi, and clinically the disease is marked by cough and 
hemorrhagic expectoration or even repeated hemoptysis. The 
parasites themselves are rarely coughed up. The small tumors or 
burrows have also been found in the scrotum, liver and brain. 
In the brain they may give rise to grave nervous symptoms often 
simulating those of intra-cranial tumor. This parasite occurs very 
frequently in Japan, China and Corea. 


Among other forms of fluke- worms of less importance are Faeio- 
lopsis buskij met with a few times in the intestine; Cotylogonimus 
lielerophyes ; Didoma ophthcdmobiuin, found in the lens of the 
eye ; Opidhorchis novercGy occurring in the liver ; and the Mono- 
sioma lentis, occurring in the eye. The Ga^trodiscus hominis 
occurs in the intestinal tract. Tavo forms, the Hexathyridium 
venarum and Hexathyridium pinguicola, are possibly forms of 
encapsulated Fasciola hepatica. 


Two forms of leeches are of some pathologic importance. The 
Hirudo Ceylonica is a form occurring with great frequency in 
Ceylon and other islands and in parts of South America. It is 
found in vegetation, and attaches itself to the skin of the legs and 
to other parts of man by means of a sucker and its short teeth. 
It may give rise to painfid ulcerations when removed. The 
JRrudo vorax is met with in parts of Europe and Africa. It gains 
access to the mucous membranes of the mouth, larynx, trachea, or 
nasal chambers, and leads to inflammatory troubles. It is not able 
to effect a lodgement upon the skin. 


A number of parasites belonging to the groups Arachnoidea 
and Insecta are met with in man. Most of these, however, are 

Surely external parasites, and are fully described in works upon 
iseases of the skin. There are two forms, however, that merit 
brief description here : the Linguatula Rldnaria, ihn larval form 
of Pentastonimum tsenioidcs ; and the larvse of various flies, the 
presence of which in the gastro-intestinal tract and other parts of 
the body is termed myicms, 


This parasite is occasionally found in the liver and rarely in 
the spleen, intestinal walls, lungs, and kidneys of man. It is dis- 
covered in small nodular lesions, which consist of the more or less 
degenerated parasite lying in a cheesy or semicalcified material. 


surrouiuled by a fibroiiH or calcareous capsule. The panisite is 
fnjiu 4 to T) miiK in length and 1.5 uiui. iu breadth ; has a rather 
rounded biwly, whlcli is eucireled I»y parallel rm^n armed with 
spicules; and is provided with two pair8 of stout ehittnous h(»ok- 
lets, one pair lying on either side of the nioutli. Tlic adnlt fonn, 
LlnffHtduia rhimindy re.senjbles itH larva in structure, but is ecm- 
siderablv larger, the male being from IfJ to 18 mm. long, the 
female from HO to 100 mm. This form h>dgc,s in tlie nasal cavities 
and frontal sinuses of the dog and other animals, and produces 
eggs etnitaining the embryos, which tsseape with tlie nasjd secivtioii 
and eventually gain access to the alimentary tract of other animal?* 
or of man» 


This speeies has lieen iliseovered in man in a few eases, and 
only iu Us larval form. It diffei>» from Linf/uafaiff rhltiana m 
being larger (in to 14 mm. in length), and having a smoi>lh snr- 
iace. It has Ijeen found in the peritoneal eavity, intestines, liver, 
and lungs. 


A number of flies, of the onlers Efttridjt% Musca, Lueilia, and 
8areopliag:i, may deposit tlieir eggs in woirnds or in eavilies nf the 
hotly to wliieh they gain aeeess, sneh as tlie nasal ur jiharyiigenl 
chanil»ers ami the eomrminieating jKisstiges* The eggs so dejw>sited 
are hatched, and tlic larval insects may be retained and may occa- 
sioii intense irritation. Sometimes the larva* are found in the 
gastro-intestinal tract, the eggs having been swaliowetl with ftxHl. 
Immense numbers may be disebsirgrd fnnn tlie intestines, and in 
some eases the larva^ seem to oeeasiou intestinal irritation. The 
term mi/ia^k is given to tiie invasion of these htrval insects. 





The blood is m liquid tissue con^iosed of corpuscles or cells 
nod a fluid intercellulsr sinhstance. The celL< are of three kinds : 
the red corpuscles, or eryihroeytts ; the white corpuscles, or leuko-- 
eylt^ ; ami the blood-plaqtus, or hematoblaM^ The fluid element 
of the blood, the Hqucnr wtt^gumUy or plafma. is an albuminous and 
saline liquid of a slightlv >'aryine composition. The blood as a 
whole L* refl in color, rather viscid, and alkaline in reaction. The 
total quantity is about one-thirteenth of the body-weight. 

The erythrocytes, or red corpuscles, are biconcave disks 
avetaging 7 /t in diameter and having a yellowish or amber color. 
They anr quite uniform in size and regularly rounded. Histo- 
logically thfry are composed essentially of an albuminous substance 
containing hemoglobin embedded in a delicate stroma. The hemo- 
gloliin in the important element, and constitutes about 95 per cent, 
by weijrht of the c-orpuscles. In early fetal life most of the red 
f:ffrimr^'U'^ arr- nuch'ated, but the nucleateil forms later decrease in 
numlKT and an- comparatively <canty at the time of birth. 
Within the firht few months of post-fetal life all of them dis- 
apjK'ar, and in subsequent years nucleated corpuscles are present 
only in ca«eh of di«ease. 

There are alxiut o,rXK),000 corpuscles in the cubic millimeter 
of the blrK^l of normal individuals. The figures var^- slightly at 
different time?* in the same individual, and numy influences con- 
tribute U) the ])roduction of more lasting changes in number (see 
|>age 385). The volume of the red corpuscles in the blood is 
de[)f'ndent u]K>n the number of corpuscles and upon their size. 
(>b.«er\'ers have reached varjing results in studying the volume, 
but it may l>e placed at between 40 and 50 j)er cent, of the total 
bulk of the blofxl. 

The leukoc3rtes, or white corpuscles, are rounded or 
spherical IxKlieH presenting a more or less granular appearance in 




the fresh state. They vary In ^ize from the diameter of the red 
corpuscles to seveml tiiiiei^ the mz^ of the latter. The leukoeytes 
are identieal with the lyriiph-eorpiiscles. They are of 8c*veral more 
or less distinet varieties ; the classilication, however, \^ exeeediiigly 
diffieiilt, as transitional forms are ahiindant* The classification 
most frequently adopted is that of Ehrlich aud of his pupils, and 
while it is not entirely satisfactory, it has one advantage over 
others, viz., that of simplicity. Ehrlich distinguishes (Fig. 141) : 

^^ ^ 

Fio. HL— Various forma of blotKl-corrniniplfts : a. tyui^-hopyte; b, lyniphocy-te Approacb- 
Jligf; c. l«rpe iBonotiucllejir; (i, transitional; r, |rt4ynKirfthuiniekar ntutrophile ; /^ p*>ly- 
morpfriomiek^ftr ernsinfiptille; <?, bnikeii «o«Inoi»hilc;; ft, rieulropbilic iiiyLifuytoi i, eodlno 
phlloua myelocyte; j; twuiopliiie, maat-cell,' i, red corptJSfie»; i, iiuclcaU^d rud corpueclex. 

1. Small mononnclear leukocytes, or Isrmptiocytes. These are 

smaller, ahout the same size as, or slightly larf^L^r tlian the red 
corpuscles ; are spherical, and «H»ntaiu a relatively large nucleus, 
the protoplasm ofteu forming a sea reel v vif^ihle hantl around the 
nucleus. The latter is rich iti chroniatiu ami stains deeply. Sonit*- 
times cells considerahly larger than tlie typical lymphocyte may 
resemble them in other respects, and it may lie ilifficult to deter- 
mine whether these are lymphocytes or lar^c mononuelt^ar cells 
(Fig. 141, //). The protoplasm of lymphocytes normally eon- 
tains no s^ramdar matter when stained hy the ordinary methods. 
Det^p staining with nietlivh'ne-hlue with the ai<l of heat docs, how- 
ever, frequently lead to the detection of a slightly granular char- 
acter in the protoplusm. The lymphocytes constitute *20 to 25 per 
cent, of the normal leukocytes. 

2. Large mononuclear leukocytes. These forms arc larger than 
the lymphocytes, being from two to three times tlu^ diatoetcr <»f 
the red cells. They are often oval in ontline, and the nnrlcus is 
poorer in chromatin than that of the lymphocyte, so that it appears 
comparatively pale in the stained bloml. The protoplasm is 
usually free of granules, hut it may show fine and very pale gran- 


ules when stained with intense basic stains like methylene-blue. 
This granular condition is probably due to staining of the reticulum 
of the protoplasm. 

3. Transitional lenkocsrtes. These are similar to the last, but 
differ in that the nucleus is often a little indented. It is very 
often impossible to determine satisfactorily whether a certain cell 
is a large mononuclear or a transitional form, and the two may be 
considered as practically the same. The protoplasm, as a rule, 
contains no granules, but neutrophilic granules (see page 369) 
have occasionally been detected. The large mononuclear and 
transitional forms together make up 4 to 8 per cent, of the normal 

4. Polymorphonaclear lenkocytes ; polsmudear lenkocytes ; nen- 
trophiles. These are the most numerous forms. They are some- 
what smaller than the large mononuclear elements, and are dis- 
tinguished by a polymorphous nucleus which is richer in chroma- 
tin than that of the large mononuclear form, though i)erhaps less 
rich than that of the lymphocyte. The nuclei are elongated, and 
variously curved or distorted so as to resemble the letters S, U, 
V, Z, etc., and in some cases they are wreath-shaped. Frequently 
parts of the nucleus are so thin that they are scarcely visible, or 
actually become broken, and the term polynuclear was therefore 
applied. This name is, however, less appropriate than the term 
polymorphonuclear. 'The amount of chromatin in the nucleus 
varies greatly, and the size of the nucleus is correspondingly 
variable. The protoplasm usually contains fine granules, which 
are closely set and almost completely fill the cell. These granules 
have a strong affinity for neutral mixtures of anilin or other stains, 
and have therefore been called the neutrophilic granules (see page 
369). The polymorphonuclear neutrophiles constitute 60 to 70 
per cent, of the normal leukocytes. 

A small proportion of the poly moq)honucl ear leukocytes of the 
blood contain eosinophile grannies. These cells are usually larger 
than the neutrophilic forms, and the nucleus is more nearly like 
that of the typical transitional leukocyte. 

5. Myelocytes. These are large cells identical with the large 
granular cells of the bone-marrow. They are often three or 
four times the size of the red cornuscles, and are distinguished 
by a large, pale, oval nucleus generally placed dose to one side of the 
cell. The pr()toj)lasm usually contains neutrophilic granules, but 
occasionally contains eosinophilic granules. The nucleus is fre- 
quently somewhat irregularly outlined, and not rarely suffers de- 
generative change. Smaller cells, resembling the typical myelo- 
cyte in the diameter of the nucleus and protoplasm, are sometimes 
observed, and are difficult to classify. Myehx'vtes occur in ex- 
ceedingly small numbers, if at all, in normal blood. They are 
abundant in certain formsof leukemia, and also occur in pernicious 
anemia and various infectious and svstemic diseases. 



The *' stJiniilation forms" of Turok are probably closely related 
to myelcMzytes, though they differ m having no granules. The 
nucleus is ovoid and the protophism mUier deeply s^taiuing, Tlie 
ftppearance of the cell suggests a fusion of the gninules of a mye- 
locyte into a homogcneons baud surrounding the nucleus. 

The following varieties of leukoc>i:es are distinguished by their 
granulations, rather than by their gross morpholfigy. They will 
be again referred to nnde*r the discussion of granulations, but have 
such <listinctive ehamcters that they are enumerated here just as 
they are usually included in differential counts. 

(J. EosinopMles, These are slightly larger than the polvmor- 
phonuclear neutrophiies, their nuclei are polymorphous, though 
Dot so much divided and not so basic in staining aflinity as the 
Duelei of the nentrophile. The protoplasm contains large granules 
which stain inten.sely with acid stains. They constitute 1 to 4 per 
cent, of the leukocytes of the normal b!of)d. 

7. Basopliiles. These ar<' polymorphonuclear cells the nucleus 
of which stains deeply with basic stains. Tin* protoplasm con- 
tains irregular sized granules of intense basic affinity. About 
0.5 percent, of the leukocytes of the normal blood are of this type. 
Granules. The granules of llie leukocytes are classitied aci word- 
ing to their behavior with the anil in stains. We may distinguish 
four im|3«jrtant type^ of granules {Figs. 141 and 142): 

L a-gramiles, eosinophile granules, or DX^rplule granules. Tliese 
are coarse gran ides giving the appcamnce in the unstained blood 
of minute fat-droplets; they arc Idghly refractivCj and liave been 
shown to be comfKised of ulbuniinons mate rial* Tliey are dis- 
tinguished by their strong affinity for acid stains/ aud in [larttcular 
for eosin. This circumstiince has given rise to the name e*isino- 
pliile and oxypliile (Fig. 148). 

The eosinophile granules in the normal blood fwcur only in 
[Xjly morplionuclear lou koey tes, 

2. ^-granules; mast-celi granules. These are intensely baso- 
philie, caarse gmnnles, cK'curnng in mononuclear cells. The mast- 
cell is identical with Waldt yer's |>lasnia-eell of the tissues. It Is 
present in suimII proportions in the rK*rmal Ido<Kl (Fig. 142). 

3. <?-graiiules arc fine bte^philic granules rxieurri ng in the 
Ivmphocytes or large mononuclear cells (Fig. 142). 

4. e-granules; neutrophilic granules. These are the most abun- 
dant and the most important of all the forms. They occur as 

* The term ncid stnin is here uae<! in a »ense somowhat *lifferent from that of 
the chemisl. A Btain in which the aciiluloua part nf the compotind carries the 
coloring-principle is known a^ an acid stain* while oiu^ in which the basic ele- 
ment ifl the staininp:-pr!ndple is called hnBio, For example: picrste of ain- 
mrmiiim ia an acid stjiin tn-cause the picric urid is the staining-element. Mixt* 
nre» of certain acid with basic stains may he prepareil so that tissue-elflmentii 
having a strong acid alHiiity will select the a«'id Ktain, thoiu? having & basic affinity 
the basic stain, while other elements without such apecial affinity rcr^ive a mixed 
or neutral stain. It h prokd>ly more c*jrrect to regard the neutrophilemiiturea 
■0 weakly oxyphile. 
24 ' 



fine gn&naLilioiis filling up the protoplasm of the polymorphous 
oelk, and diey are occasionally present in transitional leukocytes. 
They are dktingni^hed by their affinity for the neutral mixtures 
of Ehrlich (Fig. 148). It must be recx>gnized, however, that these 
granules are in rtjality faintly oxv-philic, receiving the aeid s»tainSy 
fsuch as eosin or acid fuchsin, mure readily than oasic stains. In 
a few instances 1 have found them distinctly basophilic. 

The Tialure of the grunuloi of the blood is ?>till obscure. They 
are undoubtedly connected in some way with the specific function 
of the leukocytes, but whether they are specific cellular secretions 
(Ehrlich) or essential anatomical structures (Altmann) is unknown. 



*v o 





Tva. 1421— Leu kocyies, showing various fbrtni or emnulaiionB ; a. Neiuaer's bMoptdlle. 

rrinuclejir ^ninule* ; h, large mononuclear cetl* with igmnul^s ; c, mastccU f^ranules: 
baaophllic l> niptiucytes* A-gratiiUes ; the JiUin in h, c, und d was a mixture of eosln and 
llflmatuxylm, the cover-glMfi being kept in the stain several tioun at 37^ C« (S6.G° F.), 

The chemical compositioii of tlie leukocytes is of considerable 
importance, Init is diffieolt to <l(*terniiiK^ inm\ the iniiw.ssiliility of 
olibiiiiin^ large numbers free from otiier elements. It is known, 
however, that tliese cells contain among other bodies leukonuclein, 
histon, lecithin, and cliolesterin. They also eon tain more or less 
abundnntly glycop:eii and fats ; and sidiiie constituents including 
potassium salts in partictdan Tiie teukonuclein is a combination 
of the phosphorus^containing niieleinie acid and an albumin. It 
is presrf'Ut in the nuclei of nu(dcate<l red corpuscles and in other 
nucbvi, but espet^ially iix those of the leukocytes. It is more or 
less intimately e<uubined witli histon, a body rescndjiiug the albu- 

The number of leukocytes iu the normal blood varies consider- 
ably. The average number, however, is probably between 6000 



and 8000, Alterations in the number under various circumstances 
will be discussed below. 

ProportiQiis of the Different Forms. — Tlie relative proportions 
("differential count '^) of the different leukocytes are determined 
by counting large numbers anc! calculating the percentage pro]K>r- 
tiou of each form. Approxiniatidy t lie re are 20 to 30 per cent, 
lymphocytes, *iO to 70 per cent, {xilyniorphonuelcar tbrnis (ueu- 
trophiles and eosinophiles), 4 l« 8 per cent, transitional and large 
mononuclear. About 1 to 3 per cent, td' all the leukocytes coq- 
tain eosinopliile granules, and occasionally a larger pniportion is 
met with in normal hhitxl. About 0.5 j>er cent, of the normal 
leukocytes arc basophilic. 

Blood-plaqttes. — These are small disks somewhat resem- 
bling tlie red corpuj^cle.s, though smaller and without the eharac- 
teristie bieoneavity of the latter. They rarely exceed 3 /i in 
diameter, and are often much less. They are viscid, and tend to 
adhere to the other corpuscles or to become agglntinated in clusters. 
The total number has been estimatc<l at from 150,<K>0 to 50t>,()00 

Eer eul>ic millimeter. The tenn hematoblast was applied by 
tavern in the belief that the plaques are the progenitors of the 
red corpuscles, liec^nt iuvestig;itions make it seem probable that 
the plaques are formed by fragmentations of the red corpuscles. 
Some authors claim that tht*y are nucleated. It is clear that dif- 
ferent structures have been destTibcd as plaques. 

The plasma of the blood is an albnmiuous liquid containing 
serum -album in and serum-globulin and various saline compounds. 
The relative pro[>ortion of seTum-glolmlin to scrum-albumin is as 
1 to 1 or 1:^. Of the saline constituents sodium salts are most 
important, the phosphates, carbonates, sulpluites, and chlorids 
being most abundant. Various other nitrogenous and non-nitro- 
genous substaners are presient in small prop<jrtions. Reference 
will be made to some of these below. 


The process of blood-formation is still obscure in some particu- 
lars. In early fetal liie blooiUxirpnscles are undoubted ty formed 
in the mesoldastic columns in which the blotKl-vessels are devel- 
oped. At a later stage the liver is active in their production. 
Subsequently the spleen and the bone-marmw scom to assume the 
principal rSie. According to Neumann an*I liizzozero, the red 
corpuscles are developed from nucleated hemoglobin-rontaining 
ce lis of the I >one-m a r ro w , w h i c li lose t h t • i r nuclei I )y a p nw ess of 
grndnal disintegratiriu, Otiicrs have held that tlie nuclei are ex- 
truded from the nucleated eelL According to these views, all of 
the red corpuscles are derived from nucleated red cells, or ertfth- 
rMa^iM, Other observers, however, liolil that the red corjniscles 
and leukocytes originate from a common pareut-cell free i'rom 



hemoglobin. This parent-ciell gives rise to two series of dc 
ante; one series contain] Dg hemc»gIobin and leading to the formation 
of red eoq^uscles, while the other series is free from pigment and 
formj* the leukocytes. The principal place of formation of the 
red rorpui5<:»le% during adult life J^eeras to be the bone-marrow, but 
the spleen and the lymphatic tisgues probably also play a P&it. 
French writers, followiug Hayem, hold that the progenitor of the 
red coq>u5cle is the blood-plaque» This view, however, is not 
sustained by sufficient evidence. 

The leukocytes undoubtedly originate in the lymphoid collec- 
tions of the lx>ne-raarrDW, the lymph-glands, and spleen. Accord- i 
ing to some autliorities, they all originate in one mother^cell, the' 
different types \mng derived one from the other. This view, 
however, is combat^^d by many investigators who claim to have 
proved the separate origin of the different types Irom distinct 
parent cells. The latter position is gaining ground, but still lacka 


The size of the red corpuscles varies in diseases of different 
kinds. The term anisoctfimis has \wqi\ suggested for this irregu- 
larity. There may be dwarf corposeles, 2 to 4 or 5 // iu diameter 
(microci/t^s) ; or, on tlie t>tlier liaud, giant-cells {ineffalocifUitU from 
9 to 15 ti nr even 20 /i in diameter. The small forms frequently 


Fio. na.— Blood from a cue of pernicious Anemia t a, megnlocftes; h. mlcroeyt«B{ c,po|> 
kllocytci ; cf« oucleatiHl erythrocytes; t, ncinnal enrthrocjteH ; / leukocTtes. 

have a sphericat shape rather than the disk-like form of the nor- 
mal corpuscle, and may be deeply pignieiitod. The large corpus- 
cles are often irregular in shape, and are prone in he paler and 
more btisie than normal corpuscles, and usually appear without 
the concavity of the iionoal cell (Fig* 143). Some observers have 
found that the average size of the red eorpuscle is greater in certain 



diseases than in health. This is probably the result of hydropic 

The shape of the corpuscles often suffers great change, and 

many forms of irregularity may be observed. The term poikUoci^- 
tosis is applied to this condition (Fig. 143), Some of the poikilo- 
cytes may be exceetlingly small and may present active movements. 
These have been termeil pseudobacilli by Hay em. These clianges 
of form in red corpuscles are regarded by many authorities to be 
the result of degenerative changes in the protoplasm with conse- 
quent ameboid movement which occasions irregular projections. 
The small forms are doubtless in mmiy cases the result of frag- 
mentation. EhrlJch used the term schistocyte to indicate this fact 
Dilst-corptiBCles. — MuUer recently described certain small 
spherical bodies somewhat resembling the leukocytic granules, but 
lying free in the plasma and often actively motile. These he 
termed kernokouife^ or dust-corpuscles. They occur in normal bl(X>d 
as well as in that of various diseases. A number of theories have 
been ytU't'ed regai'diiig tlie tiature of these bodies. Honie authors 
rfgarit them as extruded ieukoeytic granules ; otliers as portions 
of protoplasm of the leukocytes. My own belief is that they are 
fragments of red corpuscles^ similar to those that may be producetl 
by heating fresh bh^od under a cover-gluss to destruetive tempera- 
tures. Under these circumstances small, bud -like ]>rocesses are 
formed on the periphery of thv red corpuscles, and some of these 
may break off :md float free in the plasma. 

Visible ameboid movemeiits may sometimes be observe*! 
under the microseupe, especially in severe anemias, such as per- 
nicious anemia- 
Nucleated red corpuscles, or erythrablasts, occur in the 
severe anemias as in tlie fetal blncKL Ttiev are more freoueiit in 
the severest cases, and in particular in the anemias of children. 
Some are exceedingly small {microbkisiH}^ some about the size of 
the normal red corpustde {fionnobkist^\ aud some large and irregu- 
lar (m/yafoWox^/r). The stained nueleusof the normoblast is darker 
and more compact than that of the megaloblastj and is often near the 
p*_' ri p he ry o f t h e cc II or a ]>pu re u 1 1 y [)a r 1 1 y ex t r u d ed . The smaller 
ibrms appear first and in the more moderate anemias; oeeasioually 
they ociiur in great numbers or crops from time to time (hfomi- 
ctiaes). Degenerations of nucleated red corpuseles may occur, and 
very frequently an^ seen in the circulating erythroblast. The 
usual forms are karyolysis— solution of the chromatin ; karyor- 
rhexis — fragmentation of the nueleus; and pyknosls— clumping or 
condensation of the nuclear structure, (iranular degenei'atioUj 
vaeuolatiou, and nuclear atrophy also occur, 

Karyokliietic figures are mx^asionally seon in the nuclei of 
eryth rob lasts, in pernicious<iuemiaJn lenkemiaj in dibothrioeephalus 
anemia, and in certain anemias of children. 



Shadow corpuscles arc red corpuscles that have lost their 
color aloufst eonipletoly and an* scarcely visible. They may be 
obm^rverl ill severe anemias, and especially in cases of intoxication 

with blood*poi«ons. 

Ring Bodies. ^Cabot, by means of Wright's niodifieaticm of 
Leishniarrs >?tain» has ilemunstrated in the red eel Is of anemic bloo*l 
tlie presetiee of ring b(j<lies wlneli he is inelinetl to Ijelieve repre- 
sent the remains of a previnii^ly rxisting nucleus. 

They were found in three ease.s of pernicious anemia, three of 
lead poisoning, and one of lymphatic leukemia, in all uf which nor- 
moblasts were also ftmnd. 

The rini(s appear to be made up of a series of grannies in sr)me 
cells, ill some others of a continuous line. They usnally stain red, 
though blue is not unconimon. 

FolyclironiEtOpllilia., — ^The n<>rmal red eorpusele [las a s}>e- 
cial affinity for aeitl stains. In iltseased com lit ions it may develop 
an affinity for basic stains, and when colored witl* mixtures of acid 
and basic stains may present tints eumljiuing all the stains employed. 
Thus in staining with eosin and hematoxylin the degenerated cor- 
pnsi'les may present a purplish or violet color, instead of a pink. 

Vacuoiation and pigmentatiott of the red corpuscles are 
rare forms of degeneration. The pigmentation is due to separa- 
tion of tile hemoglobin in the fiirm of irregular granules. 

Basic degeneratioil is a form of degeneration in which 
minnte or mther ct^arse granules that stain with certain basic stains 
are found in the substance of the red corpuscles. The uumber of 
granules in the cell may be small or large ; the cell may bo other- 
wise little altered ; it may be polychromatophilic. The con- 
dition has been found in various diseases, such as leukemia, 
perniciijus anemia, and malaria, l>ut is most frequent in lead- 

Alterations of Isotonieity.— All tbrms of cells have cer- 
tain osmotic relations, in eonsequence of which they retain their 
constituent elements in the presence ijf surrounding liquids of 
certain kinds. If the osmotic relations vary or tlie surronndiug 
liquids are altered, the constituents of the cell may be extruded* 
In the case of bkMxl-torpus*jIes distilled water rapidly abstracts 
the hemoglobin and other substances, but saline solutions of cer- 
tain strengths do not so afteet the corpuscle, Tlie exait strength 
of a certain sidine solution may be determined which will preserve 
the corpuscle, and this is knuwn as the isotonic strength of the 
cori>uscle expressed in percentage-terms of the saline used. De- 
generated corpuscles more readily yield their constituents, and the 
isotonic saline solution is therefore of higher percentage. In 
normal blood the isotonic! ty of the red cor|JUscle is general ly 0,46 
to 0.48 per cent. NaCl ; that is, solutions of eoinmon salt of this 
strength do not affect the red corpuscles. In anemic diseases the 
isotonic solutions may be from 0,5 to 0.6 per cent. 




Very frequently degenerations of the nuclei of the leukocj'tee 
are observed in the form of fragmentations or karj^olytic change. 
Attention has recently been called (Neiisser) to the presence of 
basophilic granuIcH iiboiit the nucleus in certain forms of disease, 
such as lenkeniia, gout, and litheraia In its widest sense. These 
grannies are supposed to be significant of disintegration of the 
nuclei in the process of uric-acid formation. Their nature and 
significance, however, are unsettled. Occasionally vacuolization 
and fatty degeneration of leukocytes are observetl, and sometimes^ 
aa in infectious fevers and in suppuration, glycogen may be found 
in abnormal quantities. In cover-glass preparations the leuko- 
cytes are s^raetimes found broken or fragment^l, or fenestrated, 
basket-like, palc'Staining forms are seen. The latter doubtless 
occur to some extent in the circulating blood and are frequently 
spoken of as ** leuki»cytic ahadows/' 

/of/opA//fViv— This term is ajvplied to a condition of the blood 
in whieli there are fonnd in the leukocytes or the plasma granules 
that stain with iodin like glycogen. The term " glycngcnie reac- 
tion*^ was formerly applietl, though recently some question has 
arisen as to the glycogenic nature of the granules in question. 
The leukocytes involved in this form of granulation are chiefly 
the polymoqvhonuclcar. Basojdiilic leukocytes may l>e afFectetl, 
but never the eosinopliiles* The intracellular material is found 
in the form of small granules of regular shape and size, which 
stain a yellowi^h-red or brown color with iodin. Less commonly 
the leukocytes may be diffusely stained, the granules being wanting 
or so small as to be indistingnishablc as granules. The cxtra- 
corpuseular granules are found in more advanceil cases. They 
resemble the intnicorpuscular granules in aj>pearance. 

The signifieance of ioilophilia has ntvt l>eeu positively deter- 
minerl. The <THiilition is fiund in association with leidiocytosis 
or less commonly iu the absence *if leukocytosis, but it bears no 
quantitative relation to the degree of leukocytosis. It has been 
found in vari^ius forms of toxemia, in grave anemias due to loss 
of blooil or to other causes^ in fevers, and in various other con- 

The blood-film, without previous fixation, is etained with iodin 
and iodid of potash in a gum-arabic solution. 


Various disorders of the plasma have been studied. These are 
raaialy of a chemical sort, and consist of the presence of abnormal 
substances or of normal constituents in excessive quantity. Urea 


ift pr^a^m in large quaothies in somecases of nephritisand omnia, 
and ddcT antborhies believed the srmptonis of memia due to the 
presence of this sobstance. This view is no loi«r held. Uric 
acid occurs in small quantities in health ; but in large quantities 
in some cases of gout, fenkemia, in some forms of lenkocytosisy and 
other disorders of the blood. The xanthin bases mav be present 
in considerable quantities in die same cases. Gljoogen or grape- 
sugar is found in excessive quantities in diabetes and, according to 
hotne observations, in cases of carcinoma. Levuloee and other 
carijohvdrates are rare constitueots of the plasma. Fatty acids 
mav be present in leukemia, diabetes, acute vellow atrophv of the 
livfrr, aini some other diseases. The quantity of sodium in the 
pla«ma increases in anemic diseases. 

Certain changes occur in the plasma or gerum in anemic dis- 
eases, as a result of which the globulicidal character is increased. 
The nature of these changes Is obscure. The presence of toxic 
substances the result of b^terial action is referred to in the dis- 
cossion of bacteria. 

/i^7ip€r((miedy of fA^ Mrum is a term indicating that t^^ 
the plasma or serum is such that the blood may be somewhat diluted 
without destruction of the corpuscles. By graduated dilutions the 
degree of hypertonicity may be estimated, «md is found less in cer- 
tain diseases than in health (see Isotonicitv of the Red Corpuscles). 

HyperinoM and hypinasU are terms designating increased and 
decreased capability for fibrin-formation. The former is met with 
at times in chlorosis, leukemia, or other anemic affections, and in 
certain infectious diseases. The latter is notably present in leu- 
kemia, p^'micious anemia, and some cases of hemolysis. There 
has lK'^;n much theorizing in regard to these conditions, but very 
little knowledge of practical importance has been acquired. 


Plethora is the name applied by the older writers to a condition 
in which the total quantity of blood was supposed to be excessive. 
It is now re<!C)gnized that plethora is much less frequent and per- 
manent than was formerly believed. Several vaneties were de- 

Plethora vera was the name given to the condition in which 
the quantity of the blood was supposed to be increased without 
change in its quality. Persons supposed to have this condition 
are cJes^^ribed as robust, with high color and vigorous circulation. 
They are generally individuals living in luxury. The terra " fuU- 
blo<Kied " is still applied, but it is recognizee! that the fulness of 
the HU|K;rficial vessels is the result of peculiarities of the circulation 
rath(;r than of increase in the quantity of blood. 

Plethora apocoptica is the term given to conditions in 
which there is local increase in the blood. 



Plethora hydremica is a condition in wlneh the total cjtiao- 
tity of the blood is increased by dilution, This was regarded as 
frequent in cases of eachexiaj after hemorrliages, etc. 

Experimental evidence might be referred to to substantiate the 
view that plethora in the strict sense does not often occur as a 
lasting condition, Terajxirary plethora is produced by the drink- 
ing of large quantities of liquid, but the excretory organs sooa 
dispose of this excess. 


Oligemia is a temi indicating reduction in the quantity of blood. 
This is met with temporarily after hemorrhage, but very soon 
serous liquid from the tissties enters the blood-vessels and restores 
the original quantity. At tlie time of the hemorrhage the quantity 
may be immediately reduced to a very great degree witho