THE COMMONER 
DISEASES 
THEIR CAUSES AND EFFECTS 
BY 
DR. LEONHARD JORES, 
O. O. PROFESSOR DER ALLGEMEINEN PATHOLOGIE UND PATHOLOGISCHEN ANATOMIE AN DER 
UNIVERSITAT MARBURG. 
AUTHORIZED ENGLISH TRANSLATION BY 
WILLIAM H. WOGLOM, M.D., 
ASSISTANT PROFESSOR IN COLUMBIA UNIVERSITY, ASSIGNED TO CANCER RESEARCH; ASSISTANT 
PATHOLOGIST TO ST. LUKE'S HOSPITAL, NEW YORK CITY. 
WITH 250 FIGURES IN THE TEXT 
PHILADELPHIA AND LONDON 
J. B. LIPPINCOTT COMPANY COPYRIGHT, IQI5 
BY J. B. LIPPINCOTT COMPANY 
Electrotyped and Printed by J. B. Lippincott Company 
The Washington Square Press, Philadelphia, U. S. A. AUTHOR'S PREFACE 
Although these lectures are published primarily as an 
aid to my pupils, I hope that they will commend themselves 
to the practitioner as well. 
The interests of both are best served, in my judgment, 
when there is added to the description of a lesion in any 
given organ an account of its sequelae and more usual com- 
plications, the post-mortem findings being combined in this 
way into a coherent whole. It has accordingly been found 
advisable to depart from the ordinary manner of presen- 
tation, which adheres strictly to the organ under discussion 
at the moment. 
While the task undertaken may seem at first sight easy 
of accomplishment, it is difficult, nevertheless, to confine 
within the limits of a single chapter the fluctuating and 
varied material appertaining to each subject. This method 
may not be invariably acceptable, therefore, to all, and yet 
I hope that the attempt to emphasize the connection between 
diseases of the various organs will be successful in a general 
way, at least. 
Starting with the assumption that the main character- 
istic of disease is disturbance of function, I have constantly 
endeavored to impress the relation of anatomical alteration 
to physiological derangement, for I am convinced that this 
manner of introducing the subject excels simple morpho- 
logical description, while at the same time it demonstrates 
the significance of pathological changes as the real basis 
of disease. 
Questions of pure morphology and of differential diag- 
nosis, on the contrary, have been scrupulously kept in the 
background, and matters relating to general pathology have 
been introduced only where they were necessary to supple- 
ment the description. 
III IV 
AUTHOR'S PREFACE 
Problems still unsettled have not been omitted, since it 
is part of the education of a physician to weigh and sift 
evidence, and to appreciate that progress can come only 
through the free interchange and discussion of conflicting 
opinions. 
The method of presentation here employed does not 
readily lend itself to the exposition of every branch of mor- 
bid anatomy, being particularly unsuitable in the case of 
local affections, and for this and other reasons I have not 
attempted a complete discussion of all phases of pathology 
in the present volume. Still, the more common and im- 
portant disorders will be found reviewed, and it is my inten- 
tion subsequently to add to the material already gathered. 
For the numerous illustrations of anatomical specimens 
which the purpose and scope of this book demand, I have 
relied chiefly upon photography. The photographs were 
taken under my direction by Fraulein Hedwig Jores, techni- 
cal assistant in my laboratory, who also prepared the fig- 
ures of histological preparations. The wash drawings and 
most of the water colors are the work of Fraulein Zenneck, 
of Bonn, while Figs. 22 and 79 were provided by Herr Thiel, 
of Cologne. 
The Author. 
Cologne. TRANSLATOR'S PREFACE 
The favorable recognition with which Professor Jores's 
book has been received in Germany, suggests that it be made 
available in an English translation. 
"While the author's text has been followed in the main, 
it seemed advisable in some cases to supplement his account; 
in most of these instances, the original paper under con- 
sideration at the time has been drawn upon for the necessary 
additions. A few minor eliminations have been made where 
such a course appeared to result in a more connected 
exposition. 
I 'wish to acknowledge here my indebtedness to Prof. 
Adam M. Miller, Prof. Karl M. Vogel, Dr. Clayton Sharp, 
and Prof. Frederick Tilney, for the help which they have so 
freely rendered in connection with their particular subjects. 
I am under especial obligation, moreover, to Prof. Francis 
Carter Wood, who has been so kind as to read the translation 
in manuscript and to offer many valuable suggestions. 
Wm. H. Woglom. 
New York City, July, 1914. 
V ABBREVIATIONS* 
A. d. Heilk Archiv der Heilkunde. 
A. d. Med. exp Archives de Medecine experimentale et d'anatomie patho- 
logique. 
A. d. Phys Archives de Physiologie normale et pathologique. 
A. f. E Archiv fiir Entwicklungsmechanik der Organismen. 
A. f. An. u. Phys Archiv fiir Anatomie und Physiologie. 
A. f. Derm Archiv fiir Dermatologie und Syphilis. 
A. f. kl. Chir Archiv fiir klinische Chirurgie. 
A. f. exp. P Archiv fiir experimentelle Pathologic und Pharmakologie. 
A. f. Gyn Archiv fiir Gyniikologie. 
A. f. Kind Archiv fiir Kinderheilkunde. 
A. f. Laryng Archiv fiir Laryngologie und Rhinologie. 
A. f. Ohr Archiv fiir Ohrenheilkunde. 
A. f. Oph Archiv fiir Ophthalmologie. 
A. f. Psych Archiv fiir Psychiatrie. 
Am. J. of M. Sc American Journal of the Medical Sciences. 
B. kl. d. Tub Beitrage zur Klinik der Tuberkulose. 
Berl. kl. W Berliner klinische Wochenschrift. 
Bibi, med Biblioteca medica. 
Bonner Ges Niederrheinische Gesellschaft fiir Natur- und Heilkunde 
in Bonn. 
B. z. kl. Chir Beitrage zur klinischen Chirurgie. 
C. f. B Centralblatt fiir Bakteriologie und Parasitenkunde. 
C. f. Chir Centralblatt fiir Chirurgie. 
C. f. H Centralblatt fiir Herzkrankheiten. 
C. f. d. m. W Centralblatt fiir die medizinischen Wissenschaften. 
C. f. Grenzg Centralblattfiir dieGrenzgebiete derMedizinund Chirurgie. 
C. f. i. M Centralblatt fiir innere Medizin. 
C. f. P Centralblatt fiir allgemeine Pathologic und pathologische 
Anatomie. 
Corr. f. Schw. A Correspondenzblatt fiir Schweizer Arzte. 
D. A. f. kl. M Deutsches Archiv fiir klinische Medizin. 
D. m. W Deutsche medizinische Wochenschrift. 
E. d. M. u. K Ergebnisse der Medizin und Kinderheilkunde. 
E. d. P Ergebnisse der allgemeinen Pathologic und pathologischen 
Anatomie der Menschen und der Tiere. 
F. d. M Fortschritte der Medizin. 
Festschr. f. Virchow. .Festschrift der Assistenten fiir Virchow. 
Fol. u Folia urologica. 
Frankf. Z. f. P Frankfurter Zeitschrift fiir Pathologic. 
G. f. Chir Verhandlungen der deutschen Gesellschaft fiir Chirurgie. 
G. f. Gyn Verhandlungen der deutschen Gesellschaft fiir Gynako- 
logie. 
* Based upon the abbreviations in Aschoff's Pathologische Anatomie 2d 
edition. 
VII VIII 
ABBREVIATIONS 
Gottinger Ges Nachrichten der Kgl. Gesellschaft der Wissenschaften zu 
Gottingen. Mathematisch-physikalische Klasse. 
H. d. path. Mikr Kolle-Wassermann, Handbuch der pathogenen Mikro- 
organismen. 
Johns H. H. Bull Johns Hopkins Hospital Bulletin. 
Johns H. H. Rep Johns Hopkins Hospital Reports. 
J. of Exp. M Journal of Experimental Medicine. 
J. of P Journal of Pathology and Bacteriology. 
Klin. Jahrb Klinisches Jahrbuch. 
Marburger Ges Sitzungsbericht der Gesellschaft zur Befbrderung der 
gesamten Naturwissenschaften zu Marburg. 
Med. KI Medizinische Klinik. 
Mitt. Grenzg Mitteilungen aus den Grenzgebieten der Medizin und 
Chirurgie. 
Mon. f. Derm Monatshefte ftir praktische Dermatologie. 
Mon. f. Geb Monatsschrift ftir Geburtshilfe und Gynakologie. 
Munch, m. W Miinchener medizinische Wochenschrift. 
Nothnagel Nothnagel's Handbuch der speziellen Pathologie und 
Therapie. 
Pfliiger Archivder gesamten Physiologiedes Menschen und der Tiere. 
P. G Verhandlungen der deutschen pathologischen Gesellschaft. 
Prag. W Prager medizinische Wochenschrift. 
Sachsische Ges Abhandlungen der mathematisch-physikalischen Klasse 
der Kgl. Sachsischen Gesellschaft der Wissenschaften. 
Tubingen P. I Arbeiten auf dem Gebiete der pathologischen Anatomie 
und Bakteriologie aus dem pathologischen Institut 
zu Tubingen, herausgegeben von Baumgarten. 
Volkmann Sammlung klinischer Vortrage. 
V. C. f. i. M Verhandlungen des Kongresses ftir innere Medizin. 
V. f. ger. Med Vierteljahrsschrift ftir gerichtliche Medizin und 6ffentlich.es 
Sanitatswesen. 
V. G. D. N Verhandlungen der Gesellschaft deutscher Naturforscher 
und Arzte. 
Virchow Virchow's Archiv ftir pathologische Anatomie und Physi- 
ologie. 
Wiener Akademie .. . . Sitzungsberichte der k. k. Akademie der Wissenschaften. 
Naturwissenschaftliche Abteilung. 
W. m. W Wiener medizinische Wochenschrift. 
Z. f. Chir Deutsche Zeitschrift ftir Chirurgie. 
Z. f. Geb Zeitschrift ftir Geburtshilfe und Gynakologie. 
Z. f. Heilk Zeitschrift fur Heilkunde. 
Z. f. Hyg Zeitschrift ftir Hygiene und Infektionskrankheiten. 
Z. f. k. M Zeitschrift ftir klinische Medizin. 
Z. f. Phys. Ch Hoppe-Seyler's Zeitschrift ftir physiologische Chemie. 
Z. f. Nerv Deutsche Zeitschrift ftir Nervenheilkunde. 
Z. f. Psych Allgemeine Zeitschrift ftir Psychiatrie. 
Z. f. Urol Zeitschrift ftir Urologie. 
Ziegler Beitrage zur pathologischen Anatomie und allgemeinen 
Pathologie. CONTENTS 
CHAPTER PAGE 
I. The Anemias 1 
II. Leukaemia 11 
III. Pseudoleukzemia or Lymphogranulomatosis; Tumor-like Af- 
fections of the Lymphatic and Haematopoietic Systems 21 
IV. Endocarditis 33 
V. Valvular Insufficiency; Idiopathic Cardiac Hypertrophy 42 
VI. Arteriosclerosis 56 
VIL Diseases of the Coronary Arteries; Cardiac Cicatrices; 
Pathology of the Atrioventricular Bundle .... 75 
VIII. Hemorrhage into the Brain and its Membranes; Internal 
Hemorrhagic Pachymeningitis; Thrombosis and Em- 
bolism in the Cerebral Arteries 87 
IX. Aneurisms of the Large Arteries; Wounds and Lacera- 
tions of the Heart and the Aorta 99 
X. Embolic Processes in the Lungs 114 
XI. Intestinal Infarction; Thrombosis of the Portal Vein; 
Pylephlebitis 122 
XII. Septicaemia and Pyaemia; Osteomyelitis; Puerperal Endo- 
metritis; Meningitis 128 
XIII. Lobar Pneumonia; Pulmonary Emphysema 143 
XIV. Diphtheria; Lobular Pneumonia; Scarlet Fever 156 
XV. Typhoid Fever; Dysentery 164 
XVI. Appendicitis 174 
XVII. Pulmonary Tuberculosis 185 
XVIII. Metastatic and Acute Generalized Miliary Tuberculosis 202 
XIX. Tuberculosis of the Genito-urinary System 218 
XX. Tuberculosis of the Bones and Joints; Amyloidosis . . . 230 
XXI. Syphilis 242 
XXII. Dementia Paralytica; Neurofibromatosis 254 
XXIII. Tumors of the Central Nervous System 263 
XXIV. Sarcoma of the Bones; Melanoma 272 
XXV. Mammary Carcinoma; Carcinoma of the Skin; Carcino- 
genesis 281 
XXVI. Primary Carcinoma of the Pleura and the Lung; Carci- 
noma of the (Esophagus and the Upper Respiratory 
Passages; Gangrene of the Lung 292 
IX X 
CONTENTS 
XXVII. Gastric Ulcer; Carcinoma of the Stomach and Intestine . 301 
XXVIII. Jaundice; Cholelithiasis and Cholecystitis; Carcinoma of 
the Gall-Bladder 316 
XXIX. Carcinoma of the Prostate; Osteoplastic Carcinosis; Pros- 
tatic Hypertrophy and its Consequences 326 
XXX. Carcinoma and Chorio-epithelioma of the Uterus .... 340 
XXXI. Atrophy and Cirrhosis of the Liver; Congestion and Re- 
generation, and Chronic Perihepatitis (Iced Liver) . 353 
XXXII. Pancreatitis; Necrosis of the Pancreas and Fat Necrosis; 
Diabetes 372 
XXXIII. Bright's Disease 383 
XXXIV. Rhachitis and Osteomalacia 399 ILLUSTRATIONS 
FIG. PAGE 
1. Fatty Degeneration of the Heart 1 
2. Fatty Degeneration of the Myocardium 2 
3. Iron-containing Pigment in the Liver Cells of a Case of Pernicious 
Anaemia 3 
4. Blood Picture in Pernicious Anaemia 4 
5. Atrophy of the Gastric Mucosa in Pernicious Anaemia 8 
6. Myeloid Tissue; Lymphoid Tissue 12 
7. Blood Picture in Myelogenous Leukaemia 13 
8. Blood Picture in Lymphatic Leukaemia 13 
9. Myeloid Transformation of the Splenic Pulp 15 
10. Leukaemic Infiltration of the Liver 16 
11. Lymphogranulomatosis 22 
12. Cut Surface of Porphyry Spleen in Lymphogranulomatosis 23 
13. Myeloma of the Humerus with Invasion of the Muscles 26 
14. Multiple Myelomata in the Calvarium ■ 27 
15. Myeloma 28 
16. Lymphosarcoma of the Anterior Mediastinum 30 
17. Lymphosarcoma 31 
18. Verrucous Endocarditis in the Mitral Valve 33 
19. Ulcerative Endocarditis in the Aortic Valve 34 
20. Rheumatic Myocarditis 37 
21. Anaemic Infarct in the Kidney 38 
22. Hemorrhagic Infarct in the Lung 39 
23. Fibrous Endocarditis of the Mitral 42 
24. Transverse Section Through the Base of the Heart in a Case of Mitral 
Stenosis 43 
25. Congestion of the Lung 47 
26. Congestion of the Liver 48 
27. Congestion and Atrophy of the Liver 49 
28. Healed Infarcts in the Kidney . 51 
29. Fibrous and Exudative Myocarditis 52 
30. Thrombi 53 
31. Moderate Degree of Arteriosclerosis in the Aorta 56 
32. Severe Arteriosclerosis in the Aorta 57 
33. Arteriosclerosis in the Cerebral Arteries 58 
34. Longitudinal Section Through the Aorta 60 
35. Arteriosclerosis in the Aorta; Early Stage 61 
36. Arteriosclerosis in the Aorta; Advanced Stage 62 
37. Atheromatosis in a Small Artery of the Brain 63 
38. Arteriosclerosis in the Aorta, Early Stage 64 
39. Adrenalin Sclerosis in the Aorta of a Rabbit 66 
40. Longitudinal Section of the Femoral Artery, Calcification of the Media 67 
41. Arteriosclerotic Iliac Arteries and Aorta 69 
XI XII 
ILLUSTRATIONS 
42. Cerebral Cysts 72 
43. Arteriosclerosis of the Pulmonary Artery 73 
44. Arteriosclerosis in the Coronary Arteries 75 
45. Openings of the Coronary Arteries Narrowed by Syphilitic Aortitis . 76 
46. Cardiac Infarct 77 
47. Yellow Necrosis and Cardiac Cicatrices 78 
48. Cardiac Aneurism 80 
49. Schema to Show the Position of the Sino-auricular and Atrioventricular 
Nodes 82 
50. Atrioventricular Bundle Passing Through the Annulus Fibrosus ... 83 
51. Atrioventricular Bundle After its Passage Through the Annulus 
Fibrosus 83 
52. Interruption of the Atrioventricular Bundle by a Cicatrix 85 
53. Spontaneous Hemorrhage in the Central Ganglia on the Right Side . 87 
54. Small Hemorrhages in the Central Ganglia 88 
55. Course of the Nerve-fibres in the Internal Capsule 89 
56. Apoplectic Scar in the Medulla and Cortex of the Left Temporal Lobe 90 
57. Isolated Aneurisms of Small Cerebral Arteries 91 
58. Aneurism of a Vertebral Artery 93 
59. Extradural Haematoma 94 
60. Fracture of the Vertex 95 
61. Aneurism of the Ascending Aorta, Perforating the Sternum; Anterior 
View 100 
62. Aneurism of the Ascending Aorta; Seen from the Side 101 
63. Aneurism of the Ascending Aorta; Sectioned 102 
64. Spontaneous Healing by Thrombosis of an Arteriosclerotic Aneurism 
in the Abdominal Aorta 103 
65. Aneurism of a Valsalvian Sinus and Multiple Aneurisms of the Ascend- 
ing Aorta 104 
66. Erosion of Vertebrae by the Pressure of an Aneurism 105 
67. Syphilitic Aortitis 106 
68. Spontaneous Rupture in the Ascending Aorta Ill 
69. Dissecting Aneurism of the Ascending Aorta 112 
70. Schema of the Circulation 115 
71. Fat Embolus in the Lung 116 
72. Embolism of the Pulmonary Arteries 117 
73. Schema of the Sinuses of the Dura Mater 120 
74. Schema of the Portal Vein and its Tributaries 124 
75. Multiple Metastatic Cerebral Abscesses 131 
76. Multiple Metastatic Abscesses in the Kidney 132 
77. Puerperal Septic Endometritis 135 
78. Schema of the Veins of the Female Genital Organs 136 
79. Suppurative Meningitis 139 
80. Gray Hepatization of the Upper Lobe 144 
81. Croupous Pneumonia 145 
82. Chronic Pneumonia, Especially Pronounced in the Lower Lobes . . . 147 
83. Chronic Pneumonia 148 
84. Horizontal Section Through Emphysematous Lungs Hardened in Situ 150 
85. Emphysema of the Lungs 151 ILLUSTRATIONS 
XIII 
86. Position of Ribs in the Emphysematous Thorax 153 
87. Lengthening of the Anteroposterior Diameter of the Thorax in Em- 
physema 154 
88. Pseudomembranous Inflammation of the Tonsils in Diphtheria . . . 156 
89. Lobular Pneumonia 158 
90. Necrotic Angina Following Scarlatina 161 
91. Acute Interstitial Nephritis in Scarlatina 162 
92. Portion of Small Intestine from a Case of Typhoid 164 
93. Lower End of the Ileum from a Case of Typhoid 165 
94. Typhoid Ulcers, the Bases of which have become Nearly Smooth . . 166 
95. Healed Typhoid Ulcers 166 
96. Necrosing Inflammation in the Mucosa of the Large Intestine . . . 171 
97. Dysenteric Ulcers in the Large Intestine 172 
98. Multiple Primary Infection, Beginning Inflammation in the Wall of 
Appendix 175 
99. Commencing Ulcerative Stage of Appendicitis 176 
100. Phlegmonous-ulcerative Appendicitis 179 
101. Appendicitis; Localization of the Process 179 
102. Phlegmonous-ulcerative Appendicitis; Localized at the Distal End . 180 
103. Appendicitis; Stage of Healing 182 
104. Tuberculous Peribronchitis 186 
105. Tuberculous Peribronchitis 187 
106. Pulmonary Tuberculosis with Extensive Cicatrization 188 
107. Pulmonary Tuberculosis; Apical Cavity and Caseous Broncho- 
pneumonia 190 
108 Pulmonary Tuberculosis; Caseous Pneumonia 191 
109. Pulmonary Tuberculosis; Cavities in Upper and Lower Lobes .... 192 
110. Tuberculous Ulceration in the Larynx and the Trachea 193 
111. Tuberculous Ulceration in the Larynx 194 
112. Tuberculous Ulceration in the Intestine, Mild Grade 196 
113. Tuberculous Ulceration in the Intestine, Severe Grade 196 
114. Fatty Liver, Moderate Grade 199 
115. Tuberculous Meningitis 202 
116. Multiple Tubercles in the Brain 203 
117. Lung of a Child with Metastatic Tuberculosis 204 
118. Cut Surface of a Spleen Studded with Tuberculous Foci 205 
119. Metastatic Tuberculosis of the Liver 206 
120. Section Through Caseous Bronchial and Tracheal Lymph-nodes . . 207 
121. Epithelioid Cell Tubercles in a Lymph-node 208 
122. Miliary Tuberculosis in the Lung 212 
123. Miliary Tuberculosis in the Lung 213 
124. Tubercle in the Pulmonary Vein 214 
125. Tuberculosis in the Thoracic Duct 215 
126. Advanced Stage of Renal Tuberculosis 218 
127. Tuberculosis in the Urinary Bladder 219 
128. Advanced Tuberculosis Affecting the Bladder, Left Kidney, and Ureter 223 
129. Almost Total Destruction of the Kidney by Tuberculosis 225 
130. Tuberculosis in the Testis 226 
131. Tuberculosis in the Tube 227 XIV 
ILLUSTRATIONS 
132. Tuberculosis in the Uterus 228 
133. Tuberculosis in the Vertebrae 230 
134. Tuberculosis in a Bone 231 
135. Tuberculosis in the Spinal Column 232 
136. Wedge-shaped Area of Tuberculous Necrosis ; 233 
137. Sago Spleen 235 
138. Amyloid Kidney 236 
139. Amyloid Degeneration of the Liver 237 
140. Amyloid Degeneration of Glomeruli in the Kidney 238 
141. Guttate Hyaline Degeneration of the Renal Epithelium 239 
142. Gumma in the Liver 242 
143. Gumma in the Testis 243 
144. Hepar Lobatum 244 
145. Adhesion of the Right Lung to a Gummatous Liver 245 
146. Syphilitic Scars and Defects in Pharynx and Larynx 246 
147. Syphilitic Scars in the Calvarium 247 
148. Gummatous Osteomyelitis and Areas of Necrosis in the Tibia .... 248 
149. Necrosis and Hyperostosis at the Lower End of the Humerus .... 249 
150. Syphilitic Endo- and Perivasculitis 250 
151. Syphilitic Osteochondritis 251 
152. Syphilitic Ossifying Periostitis, Humerus of a Child 252 
153. Congenital Syphilitic Interstitial Hepatitis 252 
154. Chronic Leptomeningitis and Atrophy of the Brain in Progressive Gen- 
eral Paralysis 255 
155. Leptomeningitis, Perivascular Cellular Infiltration, and Disappear- 
ance of Nerve-fibres in the Cortex in Progressive General Paralysis 256 
156. Multiple Fibromata in the Skin 259 
157. Nerve-free Portion of a Neurofibroma 259 
158. Nerves of the Cauda Equina, Containing Multiple Neurofibromata . . 260 
159. Bundle of Nerve-fibres Interrupted by a Fibrous Nodule 261 
160. Enlargement of the Right Hemisphere and Flattening of its Convolu- 
tions by a Central Tumor 263 
161. Frontal Section Through the Brain 264 
162. Glioma 265 
163. Sarcoma on the Inferior Aspect of the Right Frontal Lobe 266 
164. Fibroma of the Auditory Nerve, Occupying the Cerebello-pontine Angle 268 
165. Papilloma of the Fourth Ventricle 269 
166. Endothelioma of the Dura Mater 270 
167. Peripheral Sarcoma in the Lower End of the Femur 273 
168. Peripheral Sarcoma in a Long Bone 274 
169. Central Sarcoma in the Tibia 274 
170. Spindle-cell Sarcoma 275 
171. Giant-cell Sarcoma 275 
172. Round-cell Sarcoma 275 
173. Fibrosarcoma 275 
174. Chondrosarcoma 276 
175. Osteosarcoma 276 
176. Pigmented Mole 278 
177. Melanoma 279 ILLUSTRATIONS 
XV 
178. Metastatic Infiltrating Carcinoma of the Peritoneum and the Liver, 
Following Mammary Carcinoma 281 
179. Mammary Carcinoma 282 
180. Mammary Carcinoma 283 
181. Carcinoma of the Skin 284 
182. Schema of Growth in a Carcinoma of the Skin 286 
183. Primary Carcinoma of the Pleura 292 
184. Primary Carcinoma of the Pleura 293 
185. Primary Carcinoma of the Lung 294 
186. Primary Carcinoma of the Lung 295 
187. Carcinoma of the (Esophagus 296 
188. Squamous-cell Carcinoma of the (Esophagus 297 
189. Carcinoma of the (Esophagus 298 
190. Carcinoma of the (Esophagus Perforating into the Trachea 298 
191. Carcinoma of the Larynx 299 
192. Gastric Ulcer 301 
193. Gastric Ulcer Involving the Pancreas, with an Eroded Artery at its 
Base 306 
194. Carcinoma at the Fundus of the Stomach 308 
195. Adenocarcinoma of the Stomach 309 
196. Gelatinous Carcinoma of the Stomach 309 
197. Diffuse Carcinoma of the Stomach 310 
198. Ulcerating Carcinoma at the Cardiac Orifice 311 
199. Infiltrating Scirrhous Carcinoma of the Pylorus 312 
200. Carcinoma of the Large Intestine 313 
201. Metastatic Carcinomata in the Liver 314 
202. Impacted Gall-stone at the Mouth of the Common Bile-duct .... 317 
203. A, Cholesterin Calculus; B, Mixed Calculus 319 
204. Ground Surface of a Faceted Gall-stone 319 
205. Hydrops of the Gall-bladder, Stone in the Neck 320 
206. Chronic Cholecystitis 321 
207. Carcinoma of the Gall-bladder, Metastases from which have Caused 
Stenosis of the Common Duct 323 
208. Carcinoma of the Prostate 326 
209. Carcinoma of the Prostate 327 
210. Osteoplastic Carcinosis in the Pelvis 329 
211. Osteoplastic Carcinosis . 330 
212. Hypertrophy of the Prostate, with Dilatation and Hypertrophy of 
the Bladder 332 
213. Schema of a Longitudinal Section through the Neck of the Bladder and 
the Prostate 333 
214. Prostatic Hypertrophy 335 
215. Hydronephrosis 336 
216. Renal Calculus 337 
217. Pyelonephritic Abscesses in the Kidney of a Child 338 
218. Cancer of the Cervix 340 
219. Squamous-cell Carcinoma of the Uterus 341 
220. Carcinoma of the Body of the Uterus 342 
221. Adenocarcinoma of the Uterus 343 XVI 
ILLUSTRATIONS 
222. Lymph-channels and Lymph-nodes of the Uterus 344 
223. Extension of a Uterine Cancer to the Bladder 345 
224. Chorio-epithelioma of the Uterus 347 
225. Typical Chorio-epithelioma of the Uterus 34S 
226. Atypical Chorio-epithelioma of the Uterus 348 
227. Placental Polyp 349 
228. Hydatiform Mole 350 
229. Hydatiform Mole 351 
230. Acute Yellow Atrophy of the Liver 353 
231. Subacute Atrophy of the Liver 355 
232. Atrophic Cirrhosis of the Liver; External Surface 356 
233. Atrophic Cirrhosis of the Liver; Cut Surface 357 
234. Atrophic Cirrhosis of the Liver 358 
235. Varicose Dilatation of Veins in the (Esophagus and the Stomach . . 359 
236. Congestion, Atrophy, and Regeneration in the Liver 369 
237. Pancreatic Cirrhosis 376 
238. Island of Langerhans (normal) Surrounded by Secretory Parenchyma 377 
239. Hydropic and Hyaline Degeneration of an Island of Langerhans in 
Diabetes 378 
240. Glycogen in the Cells of Henle's Loop 381 
241. Cloudy Swelling and Fatty Degeneration in the Epithelium of the 
Convoluted Tubules 384 
242. Acute Glomerulonephritis 388 
243. Chronic Glomerulonephritis 389 
244. Chronic Glomerulonephritis 390 
245. Primary Contracted, or Red Granular Kidney 393 
246. Primary Contracted Kidney 394 
247. Primary Contracted Kidney 395 
248. Section Through the Lower Epiphysis of a Rhachitic Femur .... 399 
249. Disturbance of Endochondral Ossification in Rhachitis 400 
250. Deficient Calcification of Trabeculae in an Osteophyte from the Skull 402 THE COMMONER DISEASES 
CHAPTER I 
The Anaemias 
Pronounced anaemic conditions are easily recognizable 
at autopsy. The skin is extremely pale, post-mortem dis- 
colorations are few and indistinct, and while the total vol- 
ume of blood may not be diminished, all the organs are 
significant for their small content. Thus, for example, the 
vessels of the cerebral membranes are but partly full, while 
the brain itself shows on 
section only a few blood 
points. The outer sur- 
faces of the lungs are 
bluish gray, the cut sur- 
faces pale reddish gray, 
and the heart muscle is 
brownish or yellowish, or, 
in very severe cases, clay 
colored. In the parenchy- 
matous organs of the ab- 
domen, the ground color 
is a grayish yellow in- 
stead of the usual brown- 
ish red, and although cut 
surfaces of the spleen still 
preserve a brownish red 
tone, even in this organ the blood content is considerably 
diminished. 
These signs of anaemia may be discovered following a 
single severe hemorrhage, but impoverishment of the blood 
does not attain its extreme degree until the loss of erythro- 
cytes has gone on for an extended period, as it does in the 
Fig. 1.-Fatty degeneration of the heart. Mot- 
tled endocardium (natural aze). 
1 2 
THE ANEMIAS 
case of repeated hemorrhage, or after the prolonged action 
of toxins. Coincident with the development of severe anae- 
mia, multiple hemorrhages frequently occur in the mucous 
and serous membranes. 
In chronic anaemia, fatty degeneration of the cardiac 
muscle is almost invariably present. Small yellowish spots 
and stripes shimmer through the endocardium, giving the 
musculature a mottled appearance (Fig. 1). The lesion is 
generally most distinct in the 
papillary muscles of the left 
ventricle; then follow, in the 
order of their involvement, 
the papillary muscles on the 
right side, the walls of the 
left and right ventricles, and 
the trabeculae of the left and 
right auricles. Lazarus con- 
sidered that this order of in- 
volvement is of "noteworthy 
regularity. ' ' 
Microscopic examination 
shows that the muscle fibres 
are closely packed with tiny 
droplets of fat, which appear 
most distinctly after special 
staining methods, as may be 
seen by reference to Fig. 2. 
At first the droplets are arranged longitudinally in the 
sarcoplasm, and the structure of the fibres is still distin- 
guishable, but in more advanced stages the entire fibre 
appears to be replaced by fat. 
Fatty metamorphosis of the myocardium is encountered 
under many circumstances, being usually correlated with 
either local or general anemia of the muscle; it is conceivable 
that its association with this condition is the outcome of 
diminished oxidation in anaemic organs, although recent 
investigations (Kraus, Thiele and Nehring) have shown 
Fig. 2.-Fatty degeneration of the myo- 
cardium. Fat droplets stained red with 
Sudan III (greatly enlarged). HEMOSIDEROSIS 
3 
that the consumption of oxygen in anaemia not only is not 
lessened, but is actually augmented. Still, it is questionable 
whether this observation can annul the explanation given 
above, although Kraus has asserted that the hypothesis is 
untenable which ascribes to deficient oxidation the fatty 
degeneration associated with anaemia. 
The lesion under discussion affects other organs than the 
heart; but whether the fatty changes found in the intima of 
the arteries, or those microscopic deposits in the epithelium 
of the kidney, may be placed in the same category and 
brought into direct relation- 
ship with anaemia, appears 
doubtful, notwithstanding the 
fact that this is sometimes 
done. 
In many cases of anaemia 
there may be found intra- 
cellular granules of yellowish 
pigment, which assume a 
bluish color when the tissues 
are treated with a dilute acid 
and potassium ferrocyanide 
(Berlin blue reaction, Fig. 3). 
These are haemosiderin, an 
iron-containing pigment de- 
rived from the coloring matter of the blood. They are pres- 
ent in the kidney, the bone-marrow, the spleen, and the pan- 
creas, but are most abundant in the liver, and the amount 
contained in this organ may be sufficient to give it a yellowish 
red color which is so characteristic that the existence of 
haemo siderosis may be diagnosed even upon gross examina- 
tion. Thin slices of the affected tissue treated with ammo- 
nium sulphide soon assume a blackish color from the forma- 
tion of ferrous sulphide. 
Haemosiderosis is the result of an unusually widespread 
destruction of red blood cells, following which the pigment 
of the dead erythrocytes is taken up in the various organs, 
Fig. 3.-Iron-containing pigment in the 
liver cells of a case of pernicious anaemia, 
demonstrated by the Berlin-blue reaction 
(greatly enlarged). 4 
THE ANAEMIAS 
and when it is associated with anaemia of unknown cause, 
it may be concluded that the destruction of red blood cells 
stands in etiological relationship with the disorder. This 
is true, for instance, of those forms of progressive anaemia 
which are called pernicious, in the stricter sense of the term; 
a high grade of siderosis is regularly encountered in them, 
while it is absent in many secondary and aplastic anaemias. 
The behavior of the bone-marrow is of significance, for 
since Neumann's investigations (1868) it has been recog- 
nized as the site of elaboration for blood cells in the adult. 
The marrow in the long bones is not fatty, as it should be 
in adults, but lymphoid, like 
the marrow of childhood, 
and is grayish red in color; 
in pernicious anaemia, it 
has the appearance of rasp- 
berry jam, a condition indi- 
cating active regeneration 
on the part of its cells. Evi- 
dences of its regeneration 
can be obtained, also, from 
the blood, although this 
fluid is examined to better 
advantage during life; after 
death has occurred, the blood is clear and watery, the number 
of erythrocytes is greatly decreased, and clots are gelatinous. 
Smears from anaemic patients contain nucleated red cells 
(normoblasts) and polychromatic elements, the latter of 
which take up basic stains like methylene blue, for which the 
normal red cell has no affinity. Red blood corpuscles with 
basophilic granules also occur, which, like the polychromatic 
elements, are to be regarded as young cells. Together with 
these regeneration types there are found degeneration forms 
like the poecilocyte, a red blood-cell of irregular form, and 
the microcyte, an abnormally small erythrocyte. According 
to Ehrlich, the coexistence of numerous regeneration and 
degeneration forms is characteristic of all forms of anaemia 
Fie. 4.-Blood picture in pernicious ansemia 
(oil immersion), a, macrocytes; b, microcytes; 
c, megaloblast. THE MARROW OF ANAEMIA 
5 
except the aplastic variety, in which regeneration does not 
take place. 
Although blood formation in adults generally takes place 
through the normoblast, a nucleated erythrocyte (Fig. 6), 
the blood and marrow of many of the progressive anaemias, 
particularly the pernicious type, contain large, nucleated 
red blood corpuscles (megaloblasts) and large non-nucleated 
elements (megalocytes) with an abundant supply of haemo- 
globin (Fig. 4). The corpuscles last enumerated are regu- 
larly and easily demonstrable, but the megaloblast often 
requires prolonged search for its discovery. 
The bone-marrow in simple anaemia reveals areas of 
cellular hyperplasia corresponding to the increased fabri- 
cation of blood cells, and this condition is generally accom- 
panied by partial or complete disappearance of the fatty 
marrow. In the pernicious type of the disease there is asso- 
ciated with the nucleated red cells of the marrow a larger 
form, corresponding to the megaloblast, but it is of infre- 
quent occurrence. The marrow of pernicious anaemia con- 
tains in addition a great many neutrophile and eosinophile 
myelocytes; the lymphocyte content varies, but is often in- 
creased. Leucocytes are plentiful, those of the eosinophile 
class preponderating. The phagocytosis of erythrocytes 
by large cells has been described by Sternberg. 
The appearance of megaloblasts, which are not found in 
the adult organism under normal conditions, is, according 
to Ehrlich, to be viewed as a reversion to the embryonal 
type of blood formation, since the product is an immature 
cell. This view, however, is not generally accepted. 
Furthermore, Ehrlich believed that megaloblasts occur 
only in the clinical picture of pernicious anaemia described 
by Biermer, and that they are, therefore, characteristic of 
this disease, while in so-called secondary anaemia, regenera- 
tion is indistinguishable from the normal. But, since it has 
been proved that megaloblasts in small numbers do appear 
in various secondary anaemias, especially during that found 
in connection with Bothriocephalus, the conception of per- 6 
THE ANAEMIAS 
nicious anaemia as a sharply defined condition cannot be 
retained. The term is used by clinicians in various senses, 
and while some consider the clinical course of the disease 
and a type of blood regeneration associated with the produc- 
tion of megaloblasts as essential for the diagnosis, and so 
include cases of known etiology, others, on the contrary, 
count as pernicious anaemia in the strict sense of the word, 
only cases of unknown cause (Pappenheim, Grawitz). 
In addition to the bone-marrow, other organs participate 
in the blood formation, though to a slight extent only. The 
spleen, which is generally of normal size, or shows at the 
most a simple hyperplasia, may contain areas of myeloid 
tissue with erythroblasts and myelocytes-indeed, according 
to Meyer and Heineke, this is often the case in pernicious 
anaemia. And even though these areas be but small, as 
Sternberg has properly emphasized, they are still signifi- 
cant, since they permit an explanation of certain relations 
between pernicious anaemia and leukaemia, a point which will 
be discussed when the latter malady comes under considera- 
tion. Such areas may very rarely be found in the lymph- 
nodes also. The production of blood in the liver and spleen 
can be stimulated experimentally in animals rendered anae- 
mic by poisons which attack the blood (Domarus), although 
it takes place only when the intoxication is chronic, and the 
animals have had opportunity to recover repeatedly from 
the effects of the poison. Blumenthal and Morawitz found 
no myeloid transformation in the spleen after experimental 
post-hemorrhagic anaemia, but Stanci was able to produce it 
in this condition by making intraperitoneal injections of 
laked blood corpuscles, concluding from this fact, and from 
the behavior of experimental toxic anaemia, that stimulation 
to the genesis of extra-medullary blood-forming tissue orig- 
inates from disintegrated erythrocytes circulating in the 
blood. 
Intense as the regenerative efforts of the organism 
usually are, despite their irregular or abortive character, 
various clinicians, following the lead of Ehrlich, have de- ETIOLOGY 
7 
scribed progressive anaemias in which blood regeneration 
fails to appear. The marrow is fatty, and, like the blood, 
shows but few signs of regeneration. 
Some of the manifold causes underlying anaemia are 
demonstrable at autopsy, as in cases where the disorder 
follows repeated hemorrhages. Beyond a certain point, the 
body is no longer able to adjust the alterations resulting 
from frequent losses of blood; it may be assumed (Ehrlich) 
that the regenerative capacity of the blood-making organs 
becomes exhausted, and that a condition of chronic anaemia 
is thereby induced. Post-mortem examination often affords 
an explanation of the blood loss, and there may be discov- 
ered ulcerations of the digestive tract, or diseases of the 
uterus leading to hemorrhage, or even blood-sucking para- 
sites, especially Anchylostoma duodenale. Furthermore, 
anaemia may originate in a chronic infectious disease like 
syphilis or tuberculosis, or appear in connection with cir- 
rhosis of the liver. In Banti's disease, it often combines 
characteristically with the cirrhosis in the symptom complex. 
As for parasitic organisms, already suggested as an 
etiological factor, the presence of Bothriocephalus is of 
especial importance. That this parasite may be productive 
of severe anaemia is certain, and its relation to the disease 
is readily proved by the recovery of the patient after the 
worm has been dislodged. Still, anaemia does not make its 
appearance in every infected individual, and to explain how 
the parasite affects the blood is a difficult task. Direct with- 
drawal of blood is eliminated by the anatomy of this worm, 
so that either some influence upon the gastro-intestinal 
tract or the elaboration of a toxin must be assumed. 
Schauman and Tallquist were able to produce anaemia in 
dogs by feeding them with half-digested segments of tape- 
worm, or by injecting a saline extract of these parasites. 
According to Tallquist, the poison, which belongs among 
the lipoids, is an oleic acid cholesterin ester. 
In a number of cases of anaemia, carcinoma of the stom- 
ach is discovered, and is without doubt the cause of the 8 
THE ANAEMIAS 
blood condition, although its influence has not yet been satis- 
factorily explained. The interposition of nutritional dis- 
turbances has been suggested, while Lubarsch ascribed the 
anaemia in a case of his own to metastatic carcinomata in the 
bone-marrow. It is most probable, however, that haemolytic 
substances are elaborated by the tumor (Tallquist). 
It is of interest to observe that still other lesions of the 
stomach and intestine are associated with anaemia. Crypto- 
genetic pernicious anaemia is almost always accompanied by 
atrophy of the gastric mucous membrane (for bibliography, 
see Ehrlich and Lazarus), which appears strikingly smooth 
Fig. 5.-Atrophy of the gastric mucosa in pernicious aneemia (slightly enlarged), a, 
superficial epithelium; b, gastric crypts, reduced in number; c, gland-free area; d, attempts at re- 
generation on the part of the remaining glands; e, muscularis mucosae. 
and thin upon gross examination (Quincke). Microscopi- 
cally, the glandular layer is diminished in thickness, the 
number of glands is considerably reduced (Fig. 5) in severe 
cases, while the epithelium is undifferentiated and con- 
sists entirely of elements corresponding to the chief cells of 
the gastric glands. In the depths of the mucosa appears the 
glandular regeneration (Fig. 5) described by Herzberg, so 
that destruction and reformation both take place. In the 
interstitial connective tissue, which is increased in amount, 
there are found the characteristic hyaline corpuscles of 
Roussel, the genesis and significance of which are still 
uncertain (Lubarsch). GASTRIC LESIONS 
9 
The gastric lesion is considered by some authorities as 
inflammatory, by others as atrophic {atrophia gastro-intes- 
tinalis progressiva). The latter view, I believe, has more 
to commend it, by reason of the arguments which have been 
advanced by Herzberg. Certain authors have declared that 
the intestinal mucosa also is atrophic in cases of pernicious 
anaemia, although others (Faber and Bloch) have disputed 
this statement, attributing the condition to post-mortem 
changes. Further research is accordingly necessary before 
the presence of atrophy in the intestinal mucous membrane 
can be accepted. Degeneration of the plexuses of Auerbach 
and Meissner has also been described (Sasaki). 
Atrophy of the gastric mucous membrane was described 
more or less positively by earlier observers as the cause of 
pernicious anaemia., but at the present time such a relation- 
ship is not infrequently denied. Against referring the anae- 
mia to the condition of the mucosa there is opposed the fact 
that atrophy may occur alone. According to Schauman, 
achlorhydria or achylia is observed in a certain proportion 
of the cases of Bothriocephalus anaemia, but whether or not 
atrophy of the gastric mucous membrane underlies these 
symptoms also cannot be decisively stated, because the evi- 
dence is still insufficient. It may be, too, that the atrophic 
lesion does not precede cryptogenetic pernicious anaemia at 
all, but develops coincidently with it. In a case of early 
death from pernicious anaemia., Herzberg found evidences 
of beginning atrophy, though clinical examination had shown 
the secretory conditions to be still normal. The early 
appearance of the gastric lesion in pernicious anaemia, its 
absence in a majority of the cases of secondary anaemia, and 
the difficulty of explaining in what manner anaemia could 
produce atrophy of the gastric mucosa, combine to account 
for the position of those authorities who look upon gastric 
lesion and anaemia as coordinated processes, and ascribe 
them to the same intoxication. 
The work of several recent investigators (Tallquist and 
Faust, Berger and Tsuchiya) suggests that in cryptogenetic 10 
THE ANAEMIAS 
pernicious anaemia a haemolytic lipoid substance may appear 
in the digestive canal, and that it may originate in an in- 
flamed mucous membrane, but attempts to place this hy- 
pothesis upon an anatomical basis have so far miscarried 
(Herzberg, Schaepfler, Aschoff). 
Affections of the nervous system complicating pernicious 
anaemia, and first recognized by Lichtheim, are common 
enough. Degenerations of the posterior and lateral columns 
of the cord occur, originating, according to Nonne, in tiny 
areas of myelitis. The degenerations of the posterior col- 
umns are of variable extent, and are not identical with those 
of tabes. In the opinion of Minnich, a pupil of Lichtheim 
who has investigated thoroughly the spinal lesions accom- 
panying pernicious anaemia, there is a causal relationship 
between them and the latter disorder. They cannot be dis- 
missed as mere secondary phenomena, since they parallel 
neither the degree nor the duration of the anaemia; Minnich 
believed, however, that both could be referred to one common 
cause. CHAPTER II 
Leukaemia 
The term leukaemia was introduced by Virchow to de- 
note a condition in which the number of colorless cells in the 
blood is augmented. The increase is sometimes impressively 
shown at autopsy in the whitish appearance conferred upon 
the blood by its sedimented leucocytes (leukaemia-white 
blood). Estimation of the number of corpuscles during life 
shows that in many cases the proportion of white cells to 
red, which is normally about 1: 600, has risen to something 
like 1: 20, and even a greater increase may be observed. 
It is known from the work of Ehrlich, who separated the 
different classes of colorless cells, that various types of cor- 
puscles may undergo multiplication. In some instances the 
myelocyte (Fig. 6), an immature form which is found under 
normal conditions in the bone-marrow only, predominates in 
the blood; this cell is now generally regarded as the progeni- 
tor of the leucocyte of the normal circulating blood. Under 
other circumstances, the small lymphocyte (Fig. 6) is in- 
creased; though this element occurs normally in the circu- 
lation in moderate numbers, its usual habitats are the lymph- 
nodes and the lymphatic tissues. 
Thus the cells of either the myeloid (Fig. 6) or the 
lymphoid (Fig. 6) system may preponderate in the blood 
during leukaemia, and it is therefore customary to distin- 
guish a myelogenous and a lymphatic variety, although not 
solely according to the blood findings, as will be seen on 
subsequent pages. 
In myelogenous leukaemia, the blood contains (Fig. 7) 
an increased number of neutrophile myelocytes with a few 
from the eosinophile group (Fig. 7), and the mature poly- 
morphonuclear leucocytes are also augmented, as is the 
normally insignificant proportion of mast or basophile cells; 
the lymphocytes are multiplied to but a slight extent. 
11 12 
LEUKAEMIA 
lymphoblastic 
plasma-cell 
lymphocytic 
plasma-cell 
Lymphoid tissue. 
Lymphocyte 
Lymphoblast 
Lymphocyte 
Myelocyte with 
basophile 
granules 
Leucocyte with 
basophile 
granules 
Fig. 6.-Modified after Schridde. 
Myeloblast 
Myelocyte with 
neutrophile 
granules 
Leucocyte with 
neutrophile 
granules 
Myelocyte with 
eosinophile 
granules 
Leucocyte with 
eosinophile 
granules 
Myeloid tissue. 
Basophilic 
erythroblast 
Erythroblast 
containing 
haemoglobin 
Erythrocyte ERYTHROPOIESIS 
13 
Ill lymphatic leukaemia, on the contrary, the small 
lymphocytes predominate (Fig. 8), and, according to Naegeli 
and others, may constitute as much as 95-99 per cent, of all 
white cells present. 
Erythropoiesis is not entirely unaffected in leukaemia, 
for the red cell count is generally somewhat diminished, and 
normoblasts or degenerated cells (pcecilocytosis, polychro- 
matophilia) are occasionally encountered. The skin and 
Fig. 7.-Blood picture in myelogenous leu- 
kaemia (oil immersion). a, myelocytes; b, leu- 
cocytes; c, red blood cells. 
Fig. 8.-Blood picture in lymphatic leu- 
kaemia (oil immersion), a, lymphocytes; b, red 
blood cells. 
internal organs of those dead of leukaemia are generally 
anaemic, distinctly so in that variety which is believed to be 
a combination of leukaemia and pernicious anaemia, and is 
accordingly called leukanaemia (Leube, Pappenheim). How- 
ever, the elevation of this disorder to the dignity of a sepa- 
rate clinical entity is probably unjustifiable (Luce, Hirsch- 
feld). In favor of such a conception is the fact already men- 
tioned, that in pernicious anaemia and the anaemia produced 
by blood-poisons there takes place extra-myeloid prolifera- 
tion, proof that the blood-making organs may be driven to 
either haematopoietic or leukopoietic activity by the same 
stimulus. 14 
LEUKAEMIA 
The alterations in the blood during leukaemia corre- 
spond with analogous changes in the marrow, which, in the 
long bones, becomes grayish red and cellular; in the myelog- 
enous type, its color is yellowish gray, and in severe cases it 
may even assume the appearance of pus. 
Pronounced cellular hyperplasia occurs; in myelogenous 
leukaemia, this affects principally the cells of the myeloid 
system, and of these chiefly the neutrophile myelocytes, 
while in lymphatic leukaemia it is the lymphocytes which 
participate in the process. 
The findings in the bone-marrow indicate that prolifera- 
tion of myeloid or lymphoid tissue is part and parcel of 
leukaemia, an observation for which still more evidence will 
be adduced later on. Ehrlich connected myeloid tissue solely 
with the marrow, and hence employed the term myelogenous 
leukaemia; the lymphocyte he referred to the spleen and the 
lymph-nodes. This idea, however, could not be retained, 
for lymphatic leukaemias have been described in which only 
the bone-marrow was involved, without the spleen and the 
lymph-nodes sharing in the process (Walz, Pappenheim), 
while, on the other hand, it has become more and more prob- 
able that myeloid tissue can develop in other locations than 
the marrow. 
In myelogenous leukaemia, hypertrophy of the spleen is 
the most striking condition encountered at autopsy, for the 
organ occupies a large portion of the abdominal cavity and 
attains a weight of from four to six pounds. Upon cross 
section it shows a uniform grayish red pulp, although de- 
generative processes may be discovered in the form of 
large, whitish-yellow, firmer portions, corresponding to 
areas of the same color scattered over the surface of the 
organ and recognizable as necrosis. 
The splenic enlargement is not so prominent in lymphatic 
leukaemia, and the pulp of the organ is of a brownish-red 
color. On the contrary, there occurs in this disease a hyper- 
trophy of the lymph-nodes, which, in myelogenous leukaemia, 
are but slightly affected, if at all. The enlarged nodes form CELLULAR HYPERPLASIA 
15 
chain- or tumor-like swelling's, and their cut surface is 
grayish-red in color. 
Autopsy findings in the two types of leukaemia are, there- 
fore, fairly characteristic, apart from the histology of the 
blood and the marrow, and the two subdivisions created by 
Virchow (splenic and lymphatic) correspond, in the main, 
with the forms that are still distinguished to-day. 
The enlargement of the spleen and the lymph-nodes is 
essentially the outcome of cellular hyperplasia, and here 
the same elements are encountered that are met with in 
Fia. 9.-Myeloid transformation of the splenic pulp (oil immersion). 
the blood and the bone-marrow. In myelogenous leukaemia, 
a complete myeloid transformation of the splenic pulp makes 
its appearance (Fig. 9) ; it does not, however, begin in the 
follicles (Meyer and Heineke), which .remain unaffected 
until the encroaching myeloid tissue gradually destroys 
them by pressure. In later stages of the disorder, the con- 
nective tissue of the spleen undergoes hyperplastic pro- 
liferation. Similarly, myeloid tissue appears in the medul- 
lary cords and in the central sinus of the lymph-nodes, and 
here, too, the follicles retain their lymphatic character until 
they are destroyed. During lymphatic leukaemia, on the 16 
LEUKAEMIA 
contrary, myriads of small lymphocytes collect in the spleen 
and the lymph-nodes and obliterate their histological 
structure. 
Cellular infiltration of the liver is regularly present in 
leukaemia (Fig. 10), in consequence of which this organ may 
be enlarged; in severe cases of the myelogenous class, it is 
often yellowish-gray in color. The two cell varieties are 
distributed in different localities, the myeloid filling the 
capillaries (Fig. 10), while the lymphatic infiltrate the peri- 
portal connective tissue. 
Fig. 10.-Leukaemic infiltration of the liver (slightly enlarged). 
Leukaemic infiltrations are found in many other regions; 
they are less extensive in the myelogenous type of the dis- 
ease than in the lymphatic, where they occur, among other 
localities, in the kidney, the mucosa of the gastro-intestinal 
tract, the tonsil, the thymus, and the skin. 
The foregoing statements regarding lesions in the bone- 
marrow must now be supplemented by the remark that all 
the myeloid and lymphoid tissues in the body undergo pro- 
liferation, although it was originally believed that growth 
took place only in the case of the latter. There was no bar 
to assuming that lymphoid tissue can develop in any part 
of the body, since it is so widely distributed throughout the 
organism, particularly in the mucous membrane. On the UNITARY AND DUALISTIC HYPOTHESES 
17 
other hand, myeloid tissue was at first thought to exist only 
in the bone-marrow, whence its cells escape into the blood, 
and its presence in the organs (myeloid transformation) was 
accordingly explained by Ehrlich as a deposition of cor- 
puscles from the circulation, and described as metastasis, 
or colonization. The view is gaining ground, nevertheless, 
that in myeloid leukaemia also, areas of leukaemic infiltration 
arise in situ. Growth is said to be instituted from myeloid 
rests in the liver and spleen, where they represent a re- 
sumption of haematopoietic function such as properly be- 
longs to these organs during embryonic life. 
One ground for this view is the fact that heterotopic mye- 
loid tissue has been discovered in the absence of leukaemia, 
discovered, that is, under circumstances in which its pres- 
ence cannot very well be explained by deposition from the 
blood stream. Furthermore, cases of leukaemia have been 
described in which extra-medullary myeloid tissue was pres- 
ent, but where the bone-marrow took no part in the hyper- 
plasia, or underwent merely lymphadenoid overgrowth 
(Domarus, Rehn). 
Far from unessential to a clear explanation of leukaemia 
is the question whether cells of the myeloid and lymphoid 
systems are to be definitely distinguished, one from the 
other, or whether they may not be related, at least in the 
possession of a common ancestor. The former hypothesis 
is called dualistic, the latter unitary (for bibliography, see 
Domarus, Hirschfeld). The unitary hypothesis is upheld 
by Grawitz, Maximow, and Pappenheim; the dualistic, which 
Ehrlich founded, by Pinkus, Helly, Naegeli, Schridde, Wolff, 
and others. But these authors do not agree even among 
themselves. Thus, although Ehrlich designated the granu- 
lar myelocyte as the ancestor of the myeloid series, Naegeli, 
Schridde, and others assume that a large non-granular ele- 
ment, the myeloblast (Fig. 6), is the ancestor of the myelo- 
cyte. Here there enters the difficulty of distinguishing this 
non-granular ancestor of the myeloid family from the almost 
identical antecedent of the lymphoid series (Fig. 6). Ad- 
2 18 
LEUKAEMIA 
herents of the dualistic school have urged distinctions be- 
tween the two, the most fundamental, perhaps, being 
Schridde's discovery that Altmann's granules are demon- 
strable in cells of lymphoid derivation, although wanting in 
myeloblasts; the technic of the staining process, however, is 
complicated, and the method is not always successful. W. H. 
Schultze has recently shown that myeloid cells, but not 
lymphatic elements, contain an oxidase which may be dem- 
onstrated in microchemical reaction as blue granules. 
The confusion in our knowledge concerning the develop- 
ment of the white blood cell affects our conception of leu- 
kaemia. From the stand-point of the unitary hypothesis, it 
would be conceivable that the haematopoietic structures react 
with the production of either myeloid or lymphoid tissue, 
according to the variety or the severity of the stimulus, while 
according to the dualistic view, myelogenous and lymphatic 
leukaemias would be two sharply distinct conditions. Tran- 
sitions between the two types, cited by adherents of the 
unitary hypothesis in favor of their own view, are either 
denied by the dualists, or explained as apparently transi- 
tional only. It is probably correct to separate the two 
forms of leukaemia, especially because different types of cells 
are discovered in the organs, where they localize in different 
situations, so that, as Meyer and Heineke have said, the 
histojogical findings there, no less than the conditions exist- 
ing in the blood, divide leukaemia into two distinct forms. 
Particularly dependent upon the moot points just men- 
tioned is the interpretation to be placed upon a type of 
leukaemia not yet discussed, in which large, non-granular 
cells appear in the blood, while, at the same time they con- 
stitute the greater part of the hyperplastic process in the 
bone-marrow, the spleen, the lymph-nodes, and other organs. 
Findings of this sort concern chiefly those cases which ex- 
hibit an acute clinical course (acute leukaemia), in contradis- 
tinction to the chronic forms of leukaemia thus far described. 
From the unitary standpoint, these large-cell leukaemias 
would be included within one group, while the dualists would ETIOLOGY 
19 
distinguish a myeloblastic and a lymphatic variety. Ex- 
amples of both conceptions are to be encountered in the 
more recent literature, and myeloblastic leukaemia as an 
entity has received additional and valuable support since 
the introduction of the oxidase test by W. H. Schultze. 
The most prominent feature of the disease, which is rela- 
tively frequent, is hemorrhage into the skin and the mucous 
and serous membranes; there is little or no enlargement of 
the spleen and the lymph-nodes. 
Of the etiology of the various forms of leukaemia, nothing 
can be definitely stated. The haematopoietic organs and 
tissues are stimulated by some agency still unknown to 
the undue production of certain cell types, and these appear 
in the blood. Although the hyperplasia results in immature 
forms, it is not to be assumed that the body has lost the 
faculty of furnishing elements of the finished type, since 
patients with myeloid leukaemia, for example, not infre- 
quently die of lobar pneumonia, and it has been found that 
the inflammatory exudate contains, not myelocytes, but 
mature leucocytes, exactly as it does in non-leukaemic 
patients. 
Upholders of the deposition theory have compared mye- 
loid proliferation in the organs with metastases from 
malignant growths, and the attempt has been made (Banti, 
Ribbert) to explain leukaemia by including it among the 
tumors. This, however, I do not consider justifiable, for I 
believe, with Sternberg, that the myeloid metastases of 
leukaemia are distinguished from those of a malignant neo- 
plasm by the fact that they are composed, not of atypical 
tumor cells, but of typical elements from the bone-marrow, 
and again, by the fact that they never exhibit limitless 
growth. Nevertheless, Sternberg has sought to separate 
large-cell lymphatic leukaemia from the small-cell variety 
and to ascribe to it, under the name leucosarcomatosis, 
tumor-like characteristics. In the first place, he believed 
that these large cells were atypical, pathological elements, 
although he has not yet succeeded in demonstrating that 20 
LEUKAEMIA 
they are a special form distinguishable from the large 
lymphocyte. Secondly, he asserted that heterotopic pro- 
liferation can be demonstrated in lymphosarcomatosis 1 in 
the shape of macroscopic, or at least microscopic extensions 
into the capsule of the lymph-node. Still, similar heterotopic 
growth accompanies small cell lymphatic leukaemia (Fabian, 
Naegeli, Schatiloff), also, and Sternberg's leucosarcoma- 
tosis is now denied by the majority of investigators. 
That leukaemia is an infectious disease is the opinion of 
many observers, although all attempts to discover bacteria 
or other parasites (Lbwit) must be regarded as failures. 
And yet it resembles the infectious diseases in many ways, 
with which it is often combined, especially in the case of 
septic processes (Herz). Myelogenous leukaemia in particu- 
lar seems to be frequently associated with the infections, 
scarlet fever among them, but it must not be forgotten that 
these readily occur in leukaemic patients and that the infec- 
tion, therefore, may be secondary to the leukaemia. 
Leukaemia cannot be transferred from man to the lower 
animals, although Ellermann and Bang, who have been 
investigating a type which occurs spontaneously in fowls, 
have reported its transmission from one fowl to another. 
Since the disorder can be reproduced by both organ emul- 
sions and cell-free filtrates, these authors were inclined to 
consider fowl leukaemia as an infectious disease due to a 
filterable virus. 
1 Sternberg made the following distinction: Leucosarcomatosis is character- 
ized by atypical growth of the lymphatic tissues similar to that found in lym- 
phosarcomatosis, and by the appearance of mononuclear, non-granular, patho- 
logical cell forms in the blood. In lymphosarcomatosis, there is atypical growth 
of the lymphatic tissues without any alteration in the blood picture. CHAPTER III 
PSEUDOLEUKEMIA OR LYMPHOGRANULOMATOSIS ; TuMOR-LIKE 
Affections of the Lymphatic and Hemato- 
poietic Systems 
Pseudoleuk^mia is a term advanced by Cohnheim to 
include certain conditions which exhibit hyperplasia of the 
lymph-nodes and spleen in the absence of blood findings 
corresponding to those of leukaemia. Confusion rather than 
clarity, however, has been introduced into the conception 
of this group of diseases through the inclusion under this 
term by later observers of all cases presenting enlargement 
of the lymph-nodes in which the nature and etiology of the 
process are obscure. But since the labors of still more 
recent authorities have made it possible to subdivide pseudo- 
leukaemic affections into various classes, the demand has 
been general (E. Frankel, Sternberg) that the term pseudo- 
leukaemia be employed to designate only the enlargement 
of the spleen and the lymph-nodes due to a type of cellular 
hyperplasia analogous with that of lymphatic leukaemia. 
The distinction rests upon this, that in pseudoleukaemia 
new elements do not escape into the blood stream. As it is 
now known, however, that the essential process in leukaemia 
is hyperplasia of lymphoid or myeloid tissue, the attainment 
of the circulation by the cells in question appears to be a 
more or less accidental phenomenon due to a cause still 
unexplained, and clinical observation tends very strongly to 
support this view. 
Like leukaemia, pseudoleukaemia is not infrequently 
classified as lymphatic and myelogenous. Of these types, 
the lymphatic (Domarus) is the more common, while the 
myelogenous variety appears to be rare (E. Frankel) and, 
in practice, is difficult to separate from atypical leukaemia 
(Sternberg). But even lymphatic pseudoleukaemia, if the 
foregoing limitations be regarded, is no common disorder, 
21 22 
PSEUDOLE UKJ3MIA 
and if it has been more frequently diagnosed in the past, it 
is only because cases were included under this heading 
which, to-day, would be separated under the name 
Hodgkin's disease. 
LYMPHOGRANULOMATOSIS MALIGNA (HODGKIN^ DISEASE) 
This disorder has been described under a variety of 
names (lymphosarcoma, lymphadenoma., malignant lymph- 
oma, progressive hypertrophy of the lymph-nodes, Hodg- 
Fig. 11.-Lymphogranulomatosis (greatly enlarged), a, large cells. 
kin's disease, etc.). Sternberg was the first to show that 
among the pseudoleukaemias there occur cases with typical 
lesions in the spleen and the lymph-nodes; these contain 
masses of leucocytes, lymphocytes, and plasma-cells, as well 
as characteristic, large, polynuclear elements (Fig. 11) 
which are known as small giant-cells. These differ in mor- 
phology, however, from the giant-cells of tuberculosis,'and 
their nature and derivation are still uncertain. Among the 
leucocytes in these collections there is usually an especially 
large number of the eosinophile type, which in many cases MACROSCOPIC FINDINGS 
23 
are so abundant as to compose the whole cell mass, and even 
to infiltrate the remainder of the node. In earlier stages, 
lymphocytes and leucocytes appear alone without the 
characteristic giant-cells; later in the disease, the cellular 
elements, and particularly the small giant-cells, are enclosed 
by connective tissue (Fig. If). The histological changes 
just cited are interpreted as chronic inflammation with the 
formation of a characteristic granulation tissue. 
Before embarking upon a more minute description of the 
nature and etiology of this condition, it will be necessary to 
consider some of the macroscopic findings. The hyper- 
trophied lymph-nodes form large masses within which the 
Fig. 12.-Cut surface of porphyry spleen in lymphogranulomatosis (three-fifths natural size). 
individual nodes can be readily distinguished; the paren- 
chyma is of a pale yellow color and somewhat moist and 
transparent, so that its appearance has been likened to the 
raw flesh of fish. Regions may be found bearing the dull 
white color of caseation, and microscopic examination shows 
that these are necrotic. The spleen is almost always sown 
with yellowish, transparent areas which contain necrotic 
portions more often than do the lymph-nodes, and the irregu- 
lar inlaying of the dark red pulp with these areas of lympho- 
granulomatosis, which gives to it somewhat the appearance 
of porphyry (Fig. 12), is the characteristic finding in this 
disease (E. Frankel). Lesions may occur also in the mar- 
row of the long bones, in the liver, and, although not so fre- 
quently, in still other organs. 24 
PSEUD0LEUK2EMIA 
It is worthy of note that the cellular proliferation of 
lymphogranulomatosis often breaks through the capsule of 
the lymph-node and infiltrates the neighboring tissues. 
Jamasaki and Dietrich have recently described such cases, 
and there have even been reported patients suffering from 
this disease who seemed to have large mediastinal tumors 
(Weber and Ledingham, Chiari). It should not be con- 
cluded, however, that the disorder is a tumor-like process, 
for even though the foci seem to be distributed throughout 
the body in the manner of new growths, they are infectious, 
inflammatory lesions, and are, moreover, coordinated, and 
subordinate to a common cause, rather than metastases 
from one primary condition (Frankel). 
The lesions show a certain similarity to the caseous areas 
of tuberculosis, and indubitable evidence of a relation be- 
tween lymphogranulomatosis and that disease can be dis- 
covered in many cases. Thus, there may be found giant- 
cells of the Langhans type, or even perfect tubercles, and 
for this reason Sternberg formerly classed the process under 
tuberculosis, as 4'atypical tuberculosis of the lymphatic 
apparatus running the course of pseudoleukaemia," a desig- 
nation which he later admitted was too far-reaching. He 
continued, nevertheless, to emphasize the close connection 
between lymphogranulomatosis and tuberculosis, and many 
authors agree with him so far as to recognize that the 
coincidence of the two diseases cannot be merely a for- 
tuitous occurrence (Benda). Still, both the tubercle bacillus 
and histological signs of its presence are lacking in some 
cases, and inoculated guinea-pigs do not usually develop 
tuberculosis, according to the testimony of Aschoff and 
others, whom I am able to corroborate from my own experi- 
ence. The view is therefore justifiable that lymphogranulo- 
matosis occurs independently of tuberculosis, and that it is 
a separate infectious disease with an independent etiology. 
In this conflict of opinions, the discovery of Frankel and 
Much, that bacteria are demonstrable in lymphogranuloma- 
tosis under certain conditions, is of some importance. Much MYELOMA 
25 
had already described a phase of the tubercle bacillus in 
which it is not acid-fast, and can be stained by a modified 
Gram's method, appearing then as rows of tiny granules, 
and Frankel and Much, by the aid of Uhlenhuth and Xylan- 
der's antiformin method, found bodies in twelve out of thir- 
teen cases of lymphomatosis granulomatosa which could not 
be distinguished from these granules. It is true that they 
were but few in number, and that their demonstration was 
consequently difficult, since they are not always easily recog- 
nized, but these results have been confirmed by a number of 
other observers. The significance of the discovery is not 
readily to be estimated at present, though the granules are 
vouched for by their sponsors as the bacterial cause of 
lymphogranulomatosis. It may be that they actually are 
identical with the bodies found in tuberculosis, or that they 
represent a special phase of the virus of this disease-per- 
haps an attenuation. At any rate, Lichtenstein found 
lesions analogous to those of lymphogranulomatosis in ani- 
mals injected with tubercle bacilli of diminished virulence. 
There is, of course, always the possibility that the granules 
have nothing whatever to do with those of tuberculosis, and 
the problem can be settled only after more detailed study of 
the situation. 
The tumor-like diseases of the haematopoietic apparatus 
now to be described, must be separated from pseudoleukaemia 
and placed in a special category. 
MYELOMA 
First described by Rustitzky, this disorder is character- 
ized by the presence of multiple tumorous growths in the 
marrow. The bones frequently affected are the vertebrae, 
the ribs, the sternum, the calvarium, and the long bones of 
the extremities. Viewed from without, they show no change 
at all, or only some slight swelling, but grayish- or whitish- 
red masses exist in the marrow (Fig. 13); this, in the vicinity 
of the growths, may be either fatty, or grayish-red in color. 26 
PSEUDOLEUKJEMIA 
Fig. 13.-Myeloma of the humerus with invasion of the muscles; same case as Fig. 14 (one- 
half natural size). a, myeloma; b, unaltered bone; c, musculature of the upper arm; d, bone- 
marrow, transformed into myeloma. MYELOMA 
27 
The spongiosa is compromised, and the compact portion of 
the bone may be rarefied to such a degree that the masses 
show through on the outer surface (Fig. 14), while even 
resorption or fracture may take place, allowing the tumors 
to penetrate the neighboring tissues (Fig. 13). True meta- 
stasis, however, does not occur, and those cases with second- 
ary deposits in the internal organs (for bibliography, see 
Fig. 14.-Multiple myelomata in the calvarium; same case as Fig. 13 (two-fifths natural 
size). The lesions show through the inner surface as dark areas, which in the cadaver were dark 
red. Observe, also, the cut edge of the bone. 
Menne) either should be classed with the sarcomata, or the 
so-called metastases should be interpreted as extra-medul- 
lary proliferation of the haematoblastic or leucoblastic sys- 
tems (Lubarsch). Generally, there is no true primary 
tumor. 
Histologically, the growths consist principally of hyper- 
plastic marrow, and although various types of cells may com- 
pose them, the majority are made up of large, mononuclear, 28 
PSEUDOLE UREMIA 
non-granular elements (Fig. 15); a reddish color is lent 
to the growths when large numbers of erythrocytes are 
present. Myelocytes and small lymphocytes, though not 
entirely wanting, are but few, and cases in which the tumors 
consist almost entirely of myelocytes appear to be very rare, 
since only one has been reported (Sternberg). Ribbert 
described the cells in one instance, on account of the haemo- 
globin content of their protoplasm, as erythroblasts (ery- 
throblastoma), a n d 
most authors include 
a m o n g the myelo- 
mata growths com- 
posed of elements 
corresponding to the 
plasma-cell-plasma- 
cytoma (Hoffmann). 
The large, non- 
granular cells have 
here again been the 
ground of contro- 
versy, and there are 
not wanting authors 
(Scheele and Herx- 
heimer) who see in 
them the common an- 
cestor of the blood 
cell. It would then 
be possible to regard 
the myelomata as members of one single group, and to 
arrange as subtypes' all growths in which more differen- 
tiated elements have been discovered. Those who plead for 
the dualistic viewpoint believe that the cells of the myelo- 
mata are myelogenous in their nature, because, in accordance 
with the amount of protoplasm which they contain, and 
with still other criteria, they fall more readily with the 
myeloblasts than among the large lymphocytes; it is my 
opinion that the myeloma, is, in the great majority of cases, 
Fig. 15.-Myeloma; same case as Figs. 13 and 14 
(oil immersion). The tumor is made up of large, non- 
granular cells (myeloblasts). LYMPHOSARCOMATOSIS 
29 
myeloblastic in character. From the dualistic position, a 
lymphatic myeloma also would have to be distinguished. 
The process is accordingly not to be regarded as a neo- 
plasm in the strict sense of the word, but as a hyperplasia 
affecting the bone-marrow (Pappenheim, Lubarsch), which 
assumes tumor-like characteristics at certain points. Never- 
theless, lesions do occur in the marrow, which bear the stamp 
of the veritable tumor, as the investigations of Roman have 
shown. 
This disease is characterized by the presence of atypical 
growths in the lymphoblastic system. The process com- 
mences in a group of lymph-nodes or follicles and spreads 
to the neighboring nodes and follicles, but without ever be- 
coming so generalized as leukaemia or pseudoleukaemia. It 
does not remain limited to the lymphatic structures, how- 
ever, but invades and destroys the surrounding tissues, fre- 
quently extending beneath the mucous or serous surfaces; 
in this way the lower parts of the mucosa become fixed, and 
the whole wall of the affected organ is eventually stiffened 
by infiltration. True metastases are but seldom encoun- 
tered. In many cases a starting point-a sort of primary 
growth-can be determined, the cervical, mediastinal, retro- 
peritoneal, or mesenteric lymph-nodes sometimes forming 
tumors of considerable size. 
Lymphosarcoma of the anterior mediastinum is a fairly 
common and very characteristic condition. Upon the re- 
moval of the sternum there is discovered (Fig. 16) a large, 
whitish mass, displacing the lungs to one side. Above, the 
tumor does not usually overstep the level of the manubrium 
sterni, while below it often includes the pericardial sac, 
causing a thickening of this structure, sometimes in the form 
of nodules projecting from the inner surface. Not so fre- 
quently there is more widespread involvement, including 
not only the entire pericardial sac, but the epicardial fat as 
LYMPHOSAECOMATOSIS 30 
PSEUDOLEUKyEMIA 
well, which becomes so indurated that the occurrence of 
tumors beneath it would hardly be suspected. In such cases, 
microscopic examination shows penetration of this layer by 
the lymphocytic cells. Lymphosarcomatosis of the anterior 
mediastinum frequently affects the pleura, but a more exten- 
sive distribution than this does not generally take place. 
Fig. 16.-Lymphosarcoma of the anterior mediastinum, a, anterior border of the left lung; 
b, heart. 
When the disease originates in the bronchial lymph- 
nodes, the large vessels, the trachea, and the oesophagus may 
be compromised, the latter by infiltration of its walls, and 
even the lungs and bronchi may not be spared. Lympho- 
sarcomatosis in the retroperitoneal and mesenteric lymph- 
nodes affects omentum, mesentery, and intestine. 
The disorder may commence in the lymphatic tissues of 
the mucous membranes, and particularly in those belonging BLOOD FINDINGS 
31 
to the throat. The tonsils often attain a large size, and 
infiltration of the soft palate and the pharynx sometimes 
closes the laryngeal aperture; tumors from the nasopharynx 
may penetrate the skull. The disease may have its origin, 
also, in the mucous membrane of the tongue, the intestine, 
or, less commonly, the stomach. 
These tumors are composed of masses of lymphoid cells, 
usually somewhat larger than the small lymphocyte, which 
lie embedded in a ground tissue (Fig. 17). The stroma may 
retain in part the reticular structure proper to lymphoid tis- 
sue, or it may be irregular; it may be sparse, so that the 
cells preponderate, although a 
fibrous type ^ith fewer cells 
is recognized, and may, indeed, 
alternate with more cellular 
areas in the same tumor. In 
lymphosarcomatosis of the 
lymph-nodes, the architecture 
of these structures is de- 
stroyed, and the growth infil- 
trates the capsule or even the 
surrounding tissues. 
The blood findings are not 
yet absolutely defined. In cer- 
tain cases hyperleucocytosis is discovered, the cells being 
polymorphonuclear, in others, mononuclear and similar to 
those of lymphatic leukaemia, while in still others the blood 
picture is normal. 
The disease is distinguished from hypertrophy of the 
lymph-nodes, from pseudoleukaemia, and from lymphatic 
leukaemia, by infiltration of the neighboring tissues and by 
the fact that, even though it does advance from one region 
to another, its distribution is never so general as that of 
leukaemia. From the true tumors it is separated by its simul- 
taneous origin in a group of lymph-nodes and follicles, and 
by the fact that its spread is not metastatic in the usual sense 
of the word (Sternberg). 
Fig. 17. - Lymphosarcoma (greatly 
enlarged). 32 
PSEUDOLEUK^MIA 
CHLOROMA 
This extremely rare disease is characterized by the 
presence of tumor-like growths with a distinctly greenish 
color, consisting of large, non-granular cells, and localized 
principally in the periosteum and the bones (vertebrae, ribs 
and skull), although they sometimes occur in the soft parts. 
The blood picture is abnormal, corresponding to that of 
acute, large-cell leukaemia, and from the dualistic standpoint 
a lymphatic and a myelogenous chloroma are recognized. 
More rarely, granular elements (myelocytes) have been 
found (Sternberg, Saltykow). The earlier and widely 
accepted view that chloroma represents a variety of leu- 
kaemia, has to-day given way almost universally to the opin- 
ion that it is the product of atypical growth on the part of 
lymphoid, or, less frequently, myeloid tissue. The signifi- 
cance of the green color is not established; many observers 
consider that it is merely incidental, since it may be indis- 
tinct or even entirely lacking. It is not due to the presence 
of a pigment, and is generally explained as parenchymatous. CHAPTER IV 
Endocarditis 
This process runs its course principally in the endocar- 
dium covering the valves, extending but rarely to include 
that which lines the walls of the heart. In verrucous endo- 
Fig. 18. Verrucous endocarditis in the mitral valve; rheumatic endocarditis (three- 
fourths natural size), a, extension of the process to the wall of the left auricle; b, thrombus in 
the left auricle. 
carditis (Fig. 18), the leaflets of the valve are thickened, and 
sometimes adherent to one another, and their margins are 
bordered by grayish-red, warty vegetations. In the ulcera- 
tive type of the disease, there occur more or less extensive 
defects such as perforation, destruction of part or all of 
a valve (Fig. 19), detachment of chordae tendinae, etc. This 
form, also, is characterized by the occurrence of vegetations, 
3 
33 34 
ENDOCARDITIS 
which are frequently large (Fig. 19) and of a more polypoid 
type, and often conceal the valvular imperfection. 
Although two varieties are recognized, it should be borne 
in mind that the distinction can never be more than a rough 
means of classification, since cases which are etiologically 
related may nevertheless assume different anatomical types. 
Fig. 19.-Ulcerative endocarditis (mycotic) in the aortic valve (one-half natural size). 
a, polypoid vegetation on a semilunar valve; b, deep ulceration, extending from the point of 
attachment of the valve into the endocardium. 
It is much more correct to separate (Koniger) cases in which 
the process is caused by bacterial toxins (endocarditis bac- 
teriotoxica) from those in which it is produced by the bac- 
teria themselves (endocarditis mycotica). Such a classifi- 
cation coincides approximately with the division into endo- 
carditis verrucosa and ulcerosa, and even more closely with 
that of the clinicians, who recognize a benign and a malig- 
nant form. NECROSIS 
35 
Reverting now to the variety first mentioned (Fig. 18), 
the illustration shows an advanced degree of endocarditis 
bacteriotoxica. The milder forms and earlier stages accom- 
pany such infectious diseases as sepsis, pneumonia, or tuber- 
culosis, and it is here that the first delicate border of vege- 
tations is found on otherwise perfectly intact valves. The 
case from which the illustration was prepared gave a history 
of acute articular rheumatism, a disorder that is frequently 
followed by endocarditis of the bacteriotoxic type (endocar- 
ditis rheumatica). 
According to Koniger and others, the process is initiated 
by necrosis, which attacks the surface of the endocardium. 
Upon the roughened area there gather thrombotic deposits 
from the blood, while the connective tissue of the valve 
undergoes a reactive proliferation in the course of which 
the deposits are soon organized; hence, connective tissue can 
usually be discovered in vegetations which are large enough 
to be visible to the naked eye. Since necrosis is the primary 
lesion, the fibrinous deposits being laid down secondarily 
by the blood stream, endocarditis, strictly speaking, should 
not be looked upon as an inflammation, but as a degeneration. 
Bacteria are absent from the deposits and vegetations in 
this first type of endocarditis, or at the most exist in small 
numbers only in the more superficial parts of the valve 
(Koniger). 
Conditions are quite different in the second group, where 
the necrosis is more extensive from its very inception, and 
bacteria can always be found, even deep in the tissues 
(Koniger). The mycotic variety is generally ulcerative, 
and many cases of verrucous endocarditis prove to be 
mycotic upon careful examination. 
The chief etiological role is played by various strepto- 
cocci, the Staphylococcus aureus, and, less frequently, the 
pneumococcus and the gonococcus (for bibliography, see 
Koniger). It appears, too, that still other bacteria may 
occasionally be inculpated, as the meningococcus, the bacillus 
of influenza, and the Bacillus pyocyaneus. 36 
ENDOCARDITIS 
The question whether gonorrhoea ever causes malignant 
endocarditis, which Leyden was among the first to discuss, 
has been decided after much controversy by Lenhartz, who 
not only produced typical gonorrhoea by injecting cardiac 
thrombi, but isolated pure cultures of the gonococcus from 
endocardial vegetations. Endocarditis had already been 
induced in animals by injuring the valves and simultaneously 
injecting staphylococci into the blood stream (Wyssoko- 
witsch, Orth), while Ribbert attained the same end by inocu- 
lating staphylococci mixed with their potato medium in 
order that adherence of the organisms to the valves could 
occur with greater ease, and more recent investigations have 
shown that endocarditis can be produced by the introduction 
of still other varieties of bacteria. 
It will be readily appreciated from what has been already 
said, that mycotic endocarditis must be viewed as an infec- 
tious disease, and that it is closely related to the septic 
processes, among the consequences of which it is not seldom 
encountered. 
Before its relationship is discussed in more detail, how- 
ever, it will be advantageous to discuss the remaining 
changes which are associated with the lesion in question, 
first observing that it usually affects the valves on the left 
side of the heart, and that rheumatic endocarditis most 
frequently involves the mitral, while the mycotic type is 
generally localized at the aortic. Whether the chambers of 
the heart are enlarged, and their walls thickened, depends 
upon the amount of functional disturbance that has been 
caused; an advanced lesion, whether of the toxic or the 
mycotic variety, always adds to the work which this organ 
must perform, and hypertrophy and dilatation accordingly 
ensue. 
The myocardium is frequently attacked, and even with 
the naked eye there may often be seen dull, yellowish points 
due to emboli in branches of the coronary vessels. In myo- 
carditis rheumatica there occur characteristic nodular infil- 
trations, miliary or sub-miliary in size (Fig. 20), and com- RHEUMATIC NODULES 
37 
posed of large cells, the derivation of which is still uncertain 
(Aschoff). Aschoff has suggested a lymphoid origin, and 
Geipel, that they are connective-tissue elements. These 
nodules, which are localized about the vessels, are often 
necrotic in the centre, and Aschoff has asserted that they 
are specific for rheumatic infection. His belief is probably 
well founded, as their occurrence in this disease has been 
substantiated many times (Wachter, E. Frankel), while 
they are no.t found in non-rheumatic affections of the heart. 
Fig. 20.-Rheumatic myocarditis (greatly enlarged), a, large cells in a rheumatic nodule, which 
is surrounded by, b, lymphocytes, c, muscle fibres. 
These nodules are especially numerous and distinct follow- 
ing endocarditis in young subjects. 
Whether evidences of congestion will appear in the 
organs of those with endocarditis, depends upon the dura- 
tion of the disease and upon the influence which has been 
exerted on the activities of the heart. It is usually present 
in advanced cases. 
Infarcts in the various organs are very frequent accom- 
paniments of endocarditis, for the anatomical conditions are 
such that products of the disease readily attain the circula- 
tion, a process known as embolism. The emboli consist of 
vegetations or, more rarely, even portions of the valves 38 
ENDOCARDITIS 
themselves; they lodge most frequently in the spleen and the 
kidneys, occluding the arteries and producing yellowish, 
opaque areas (Fig. 21) projecting somewhat above the 
surface of the organ, sharply defined from the surrounding 
tissue, and, in the kidney, often bordered by a hyperaemic 
zone. These infarcts extend deeply into the organ in the 
form of a wedge, and vary from the size of a pea, or less (in 
the kidney), to really considerable proportions. When they 
Fig. 21.-Ansemic infarct in the kidney. 
are multiple, or of large size, they may involve the greater 
part of the organ. 
Following closure of the artery, coagulation necrosis 
(Weigert, Schmaus and Albrecht) appears, unless the vascu- 
lar arrangements favor establishment of a collateral circu- 
lation. Infarction occurs only in certain organs-beside the 
spleen and the kidney, which have been already mentioned, 
in the brain, the intestine, and the lung. The arteries of 
the spleen and the kidney belong to that type (terminal 
arteries of Cohnheim) in which there is no arterial anas- 
tomosis, and not even a sufficient capillary communication, EMBOLISM 
39 
between the end branches; hence no collateral circulation can 
be established, and necrosis readily follows. Emboli in the 
arteries of the brain are somewhat less commonly encoun- 
tered than in those of the spleen and the kidney, and true 
infarction is replaced by colliquative necrosis, which may or 
may not be accompanied by hemorrhage. Emboli in the 
arteries of the intestine are rare; they cause either simple, 
anaemic necrosis, or hemorrhagic infarction. In the lungs, 
Fig. 22 -Hemorrhagic infarct in the lung. 
on the other hand, infarcts are common; they are always 
hemorrhagic, and appear as reddish-black areas (Fig. 22), 
the color being due to infiltration with blood. They are 
firmer than the remainder of the pulmonary tissue, are 
widest at the surface of these organs, and average about the 
size of a walnut, although they may be large enough to 
include almost an entire lobe. Partial or complete necrosis 
supervenes sooner or later. 
That emboli in the arteries of the lung are followed by 
hemorrhagic infarcts, while these are infrequent in the 40 
ENDOCARDITIS 
spleen and still rarer in the kidney, is to be referred to the 
fact that collateral circulation in the affected area of the 
lung sets in late and remains incomplete, while at the same 
time the nutrition of the capillaries is disturbed, so that 
they allow the passage of erythrocytes. This permeability 
of the capillary wall may be a consequence of transitory 
anaemia, of some chemical action exerted by the embolus, of 
congestion, etc. 
Just what determines the tardy and imperfect capillary 
circulation is not yet clearly understood. Cohnheim assumed 
a back flow from the veins, but Litten discovered later that 
infarction takes place after the simultaneous ligation of 
both artery and vein. It is more probable, therefore, that 
suffusion of the affected region occurs either through a 
collateral capillary circulation (v. Recklinghausen), or by 
retrograde distention from the bronchial veins (Koster). 
The sources for emboli in the arteries of the lungs are 
not those concerned in the case of other organs. While in 
the latter instance, emboli pass from the left heart into the 
arteries of the general circulation (Fig. 70), the starting 
point of those in the lungs must be sought in the right heart 
or the venous system. Hence, pulmonary infarcts cannot 
be referred directly to endocardial vegetations, since these 
are found most frequently on the left side of the heart, but 
generally originate in secondary thrombi in the right heart; 
it not infrequently happens, however, that their source can- 
not be discovered at autopsy. It is justifiable to assume that 
certain of these hemorrhagic infarcts are the outcome of 
thrombosis of small arteries in the lung, consequent upon 
some local condition or upon small, non-obliterating emboli 
(Ribbert). 
It should be remembered that the serious disturbance 
of the pulmonary circulation which usually accompanies 
cardiac affections favors the occurrence of infarction, for 
in diseases where the lungs are not congested, embolism is 
not followed by infarction. Partly on the basis of this 
observation and partly upon other grounds, Grawitz doubted THE CONSEQUENCES OF EMBOLISM 
41 
the embolic origin of hemorrhagic pulmonary infarcts, incor- 
rectly, however, because the old teaching has been thor- 
oughly rehabilitated through recent investigations (Orth, 
Fujinami, Lubarsch). 
Thus, through the medium of embolism, manifold 
changes are brought about in many of the organs during 
the course of endocarditis. The significance of the process 
for the body as a whole, however, is various. Emboli in the 
spleen and the kidney produce fundamental disturbances of 
function in these situations only when the infarction is very 
extensive. According to Lbhlein, the hemorrhagic nephritis 
which occurs during ulcerative endocarditis is a result of 
embolism, as is suggested by the presence of tiny, homo- 
geneous nodules in the glomeruli. Pulmonary infarcts may 
not only produce clinically recognizable symptoms, but may 
be the basis of various diseases of the lungs and pleura, 
while to a still greater degree do emboli in the cerebral or 
mesenteric arteries dominate the clinical picture. 
In mycotic endocarditis, the infarcts often exhibit cen- 
tral suppuration because the emboli contain pus-forming 
bacteria; generally smaller than those which follow the de- 
position of bland emboli, these appear either in the form of 
abscesses or hemorrhages. Thus there becomes apparent 
at autopsy not only the distinction between toxic and mycotic 
endocarditis, but the relation of the latter to the septic dis- 
eases. Litten has emphasized this fact, and correctly, but 
it must be admitted that non-suppurative infarcts also may 
be found in mycotic endocarditis. Those examples showing 
multiple suppurative infarcts and abscesses with hemor- 
rhages into the skin, are certainly to be classed among the 
septicopyemic processes, and the wide distribution of the 
bacteria throughout the system is shown by the fact that 
they can be recovered from the blood. CHAPTER V 
Valvular Insufficiency ; Idiopathic Cardiac Hypertrophy 
Endocarditis may resolve' so completely that only a 
slight thickening of the valves persists, and the functional 
activity of the myocardium is not impaired; such an outcome 
Fia. 23.-Fibrous endocarditis of the mitral (one-half natural size). Leaflets thickened and 
adherent. Chorda: tendinee thickened. Large thrombus in the left auricle. 
I have seen in a few instances, and Amsler lias described 
several cases. Usually, however, the thickening and fusion 
of the valves disturbs cardiac function. The inflammatory 
process may subside, leaving valvular damage as its end 
product, or it may continue and undergo occasional exacer- 
bation (endocarditis chronica), during which fresh vegeta- 
tions are deposited upon the already distorted valves (endo- 
carditis recurrens). 
42 ENDOCARDITIS 
43 
The details regarding the manner in which the process 
may conclude are as follows: Upon endocarditis bacterio- 
toxica there supervene hyaline thickening of the valves, 
shrinkage, fusion of neighboring segments, thickening and 
shortening of the chordae tendinae (Fig. 23), induration, and 
sometimes even partial calcification of the papillary muscles. 
Fusion of the mitral segments (Fig. 24) confers upon the 
orifice a ring or a funnel shape (tubular stenosis), and the 
Fig. 24.-Transverse section through the base of the heart in a case of mitral stenosis (two- 
thirds natural size), a, right auricle; b, left auricle; c, thrombus in the left auricle; d, aortic 
opening; e, conus arteriosus and opening of the pulmonary artery. 
same condition may involve the aortic valve, although much 
less frequently; in other cases, the cusps of the latter valve 
become thickened and shrunken. Endocarditis mycotica 
may also undergo complete resolution, although this hap- 
pens more rarely than in the bacteriotoxic form. According 
to Koniger, the connective-tissue thickening in such cases is 
more irregular, and not infrequently calcified deposits re- 
main on the valves. 
Endocarditis, however, is not the only source of valvular 
defects. On the aortic valves, less often and less prom- 44 
VALVULAR INSUFFICIENCY 
inently on the mitral, there occur nodules of simple connec- 
tive tissue. The milder grades of this process are physio- 
logical (Veraguth and Nussbaum), but more extensive in- 
volvement is abnormal; this is almost always combined with 
considerable calcification, or even cartilaginous or osseous 
transformation. Some of these lesions appear to be identical 
with arteriosclerosis, although others originate independ- 
ently of this disease. The two forms of valvular sclerosis 
may be distinguished from one another in the aortic valve, 
by their localization (Monckeberg, Dewitzky). Syphilitic 
aortitis sometimes involves the aortic valve, leading to 
shrinkage and thickening. In Koch's case, one cusp had 
fused with a nodule in the aorta in such a manner as to 
produce the appearance and the result of a complete valvular 
defect. Tumors, or large, solitary, organized thrombi cause 
a disturbance (generally stenosis) in rare instances, if they 
project into or overlie an orifice, and freely movable thrombi 
(ball thrombi) are said to exert the action of a ball valve 
(Herz), although other observers (v. Recklinghausen, 
Lohlein) dispute this statement. 
To determine at autopsy whether the result of a valvular 
lesion has been insufficiency, or stenosis, or a combination 
of the two, is not easy in all cases, since the decision must 
be based solely upon the variety and degree of the departure 
from normal. Moreover, since closure of the cardiac orifices 
does not depend upon the valves alone, but to a very great 
degree upon the contractility of the muscular ring (Tiger- 
stedt, Koster, Krehl), it is possible for valvular insufficiency 
to exist during life and yet be undemonstrable at autopsy, 
a situation which frequently occurs in connection with the 
tricuspid. Thus, while it was formerly believed that the 
leaflets of the tricuspid valve cease to come into contact with 
one another when dilatation of the right heart takes place 
in consequence of an uncompensated lesion on the left side, 
greater importance is now ascribed to disturbances of mus- 
cular efficiency at the base of the heart and the auriculoven- 
tricular ring (Krehl). According to Magnus-Alsleben, the HYPERTROPHY AND DILATATION 
45 
relative insufficiency rests chiefly upon a common functional 
disturbance in the valvular and other musculature, par- 
ticularly that of the trabecular system. In the case of the 
mitral, too, patients may offer the clinical picture of insuffi- 
ciency, and present at autopsy a dilatation and hypertrophy 
corresponding exactly with that of mitral insufficiency, in 
spite of the fact that the leaflets of the valve are intact. In 
such instances, insufficiency on the part of the musculature 
of the auriculoventricular ring and the base of the ventricle 
may be a factor, since myocarditis can often be demonstrated 
in this region (Kelle). 
Hypertrophy and dilatation are regularly associated 
with valvular insufficiency, although they vary in their in- 
tensity and in the portion of the organ which they involve. 
In general, it can be said that both insufficiency and stenosis 
call for greater activity from that part of the heart lying 
up-stream from the damaged valves. In the case of stenosis, 
enough blood cannot pass through the narrowed orifice dur- 
ing diastole, and the deficiency can be overcome only through 
increased effort by that portion of the heart situated above 
the lesion; in insufficiency, blood is thrown with every sys- 
tole into the part lying above the damaged valve, augmenting 
the volume which this chamber must handle. But, in addi- 
tion to this, more work is thrown also upon regions below 
the lesion, since blood flows into them during diastole under 
higher pressure and in larger amounts. Hypertrophy fol- 
lows heightened activity, dilatation the accommodation of a 
larger volume of blood. 
If the hypertrophy of those portions of the heart directly 
concerned with the damaged valve is not sufficient to main- 
tain normal circulation, increased demand is made upon 
regions lying still further up the blood stream, and they 
in their turn undergo dilatation and hypertrophy. The 
auricles are never able to execute satisfactory compensation, 
and although they always show a thickening of their walls, 
in the course of which the endocardium becomes dense and 
whitish, the hypertrophy of the left auricle, for example, 46 
VALVULAR INSUFFICIENCY 
which is associated with mitral lesions, is not able to prevent 
the engorgement in this chamber from being transferred to 
the pulmonary circulation, and thus affecting the right heart. 
The latter hypertrophies in consequence, the conus arteri- 
osus, which becomes also somewhat dilated, being the portion 
first affected. Dilatation and hypertrophy of the right heart 
are regularly and characteristically associated with mitral 
lesions. In uncomplicated mitral stenosis, the left ventricle 
is neither hypertrophied nor dilated, although the left auricle 
and the right ventricle show both of these conditions; the 
left ventricle in the still unsectioned heart accordingly looks 
small in comparison with the enlarged right side of the 
organ, an appearance which has led to the erroneous diag- 
nosis of atrophy. 
The occurrence of atrophy of the left ventricle in mitral 
stenosis appeared to the older authors as well established, 
but the error was exposed by Lenhartz and his pupil Baum- 
bach, Oestreich confirming their views by observations upon 
the cadaver. 
In mitral insufficiency, on the other hand, in addition to 
the right ventricle and left auricle, the left ventricle is 
hypertrophied, although the greatest thickening in the walls 
of this chamber accompanies lesions of the aortic valves, 
especially incompetency. 
Still other variations in the distribution of hypertrophy 
and dilatation among the various chambers will occur if one 
valve be at the same time both insufficient and stenosed, or 
if several be involved. Augmentation of the hypertrophy 
may then result, or, on the contrary, the defects may counter- 
act one another. Thus, when aortic insufficiency or stenosis 
is combined with mitral stenosis, the hypertrophy of the left 
ventricle is much less than in the case of pure aortic lesions. 
After careful observation of the distribution of hyper- 
trophy and dilatation, it is often possible to infer what dis- 
turbance of function has been produced, and to supplement, 
in this way the conclusions drawn from conditions in the 
valves themselves. RESULTS OF HYPERTROPHY 
47 
The hypertrophied cardiac muscle is able to adjust the 
circulatory disturbances for a long time (compensation), 
but as the hearts of patients coming to autopsy are gener- 
ally in a state of broken compensation, evidences of insuffi- 
cient circulation are almost always demonstrable then, par- 
ticularly in the form of congestion in the various organs. 
Fig. 25.-Congestion of the lung (greatly enlarged), a, ectatic capillaries in the alveolar wall; 
b, desquamated alveolar epithelium, laden with blood pigment. 
The external surface of the lung exhibits a brownish 
hue, while the color of the cut surface is a dark red shading 
somewhat into brown, and the parenchyma seems tougher 
than normal and less disposed to retract, although there may 
be no diminution in the amount of air which it contains. 
The bronchial mucous membrane is generally reddened and 
the bronchi contain an abundant amount of grayish-yellow 
mucus (congestive catarrh),while red hepatization of rather 
extensive areas is not uncommon. That such organs are 48 
VALVULAR INSUFFICIENCY 
exposed to hemorrhagic infarction has already been sug- 
gested. The microscope shows (Fig. 25) congestion of the 
alveolar capillaries, which are tortuous and dilated, and the 
presence in the alveolar and bronchial secretion of cells 
(leucocytes and desquamated alveolar epithelium) contain- 
ing a yellow or yellowish-red pigment. 
The liver, also, frequently shows signs of congestion 
and, in fact, it is in this organ that the intensity and dura- 
tion of the condition find its characteristic expression (Fig. 
26). The congested areas 
appear as dark red 
patches and streaks, the 
tissue outside them being 
often of a yellow color 
from fatty infiltration; 
this condition is known as 
"nutmeg liver." In all 
cases where the conges- 
tion has persisted for 
some time, atrophy of the 
hepatic tissue supervenes; 
the cells compromised by 
the dilated capillaries di- 
minish in size until finally 
they are reduced to mere 
pigmented remnants (Fig. 27), and the shrinkage may be so 
extensive as to decrease the total volume of the organ. 
The spleen exhibits less characteristic signs of conges- 
tion. It is very firm and somewhat enlarged, although the 
increase in size is generally not great; its cut surface is 
of a deep reddish-black shade. 
The kidneys, too, are firm, and brownish-red in color; 
the glomeruli are hyperaemic, the capsular space contains 
albumin, and casts are found in the urinary tubules. I can- 
not accept the view that the congestion may, after long dura- 
tion, result in a contracted kidney (Schmaus and Horn). 
Congestion in the stomach and intestine is a frequent 
Fro. 26.-Congestion of the liver (natural size). LESIONS DUE TO CONGESTION 
49 
outcome of valvular disease. The mucous membrane is 
diffusely reddened, the condition sometimes affecting par- 
ticularly its folds in the small intestine, and it is at the same 
time profusely covered with mucus (congestive catarrh). 
Finally, in the list of lesions due to congestion there must 
be included oedema of the skin (particularly that of the lower 
extremities), lungs, cerebral membranes, etc>, and transu- 
dation into the serous cavities. 
Fig. 27.-Congestion and atrophy of the liver (slightly enlarged), a, central vein; b, areas 
of completely atrophic parenchyma; c, columns of atrophic cells; d, peripheral portions of the 
acini. 
Since all these manifestations of a general circulatory 
disturbance are referred to cardiac insufficiency, it may well 
be asked what anatomical changes can be demonstrated in 
the heart to explain the situation. Physiology teaches that 
this organ is able to fulfil its function independently of the 
central nervous system, but that its activity is governed in 
many ways, although not actually initiated, by certain nerves 
supplying it (vagus and accelerators). It possesses other 
nervous elements in its ganglion cells, but whether its auto- 
matic action originates from them (neurogenic hypothesis) 
4 50 
VALVULAR INSUFFICIENCY 
is so questionable that most physiologists, at any rate, now 
ascribe to the myocardium itself the capacity for spon- 
taneous contraction (myogenic hypothesis). The former 
hypothesis, moreover, receives no support from pathology, 
since no regular coincidence has been demonstrated between 
undoubted lesions in the ganglion cells and cardiac insuffi- 
ciency ; hence both clinician and pathologist unite in attribut- 
ing incompetency to changes in the heart muscle. 
Fatty degeneration of the myocardium was formerly con- 
sidered the anatomical basis for insufficiency in the heart 
with damaged valves, and the lesion exists not infrequently 
in such organs, although it is generally demonstrable only 
with the microscope. Krehl has shown, however, that it 
is generally not extensive enough to correspond with the 
clinical evidences of insufficiency, and has made the addi- 
tional point that widespread fatty degeneration may develop 
within a few days, while it must be assumed that incom- 
petency is of much longer duration. Furthermore, experi- 
ence has shown that fatty degeneration does not necessarily 
result in insufficiency (Hasenfeld and Fenyvessy, Linde- 
mann). On the other hand, Krehl found inflammatory foci 
consisting of small, round, and generally mononuclear cells, 
which were situated in the larger interstices of the myocar- 
dium or distributed among its fibrils, and was able to corre- 
late this myocarditis with the clinical signs of insufficiency, 
an observation which caused him to regard the lesion as 
probably responsible for the disturbance in cardiac func- 
tion. But it is not to be imagined that the myocarditis 
directly and mechanically disturbs the action of the heart; 
rather, the poison which results in this lesion, and which is 
generally of a toxic-infectious character, affects also the 
cardiac function. Aschoff, however, was unable to confirm 
the frequent and wide distribution of myocarditis in valvu- 
lar disease, and therefore denied this affection the signifi- 
cance assigned to it by Krehl. 
In hearts with damaged valves there are often discovered 
cardiac cicatrices, the larger of which are repaired infarcts, EMBOLISM 
51 
while the smaller frequently represent healed rheumatic 
nodules. The question whether these scars, which can exert 
at the most only a mechanical effect, are to be made answer- 
able for insufficiency, demands critical examination, and it 
can be answered in the affirmative only when the nodules 
are very large or very numerous. 
Thus many cases of valvular disease are associated with 
changes adequate to explain the incompetencv. but no ana- 
tomical condition which is entirely satis- 
factory, and applicable to every case, 
has yet been discovered. 
Returning once more to the findings 
in other organs, it may be mentioned that 
opportunity is afforded for embolism, 
although much less frequently than in 
the earlier stages of endocarditis. Prod- 
ucts of earlier infarction may often be 
found in the shape of scars, the origin 
of which is sometimes disclosed by the 
persistence of necrotic tissue. These 
nodules occur in the spleen and the brain, 
but far more frequently in the kidney, 
where they may produce numerous and deep retractions of 
the surface (Fig. 28); severe examples of this condition 
are sometimes called embolic contracted kidney. 
Fig. 28.-Healed infarcts 
in the kidney (three-fifths 
natural size), a, hilus. 
IDIOPATHIC CARDIAC HYPERTROPHY 
Hypertrophy and dilatation of the heart are not infre- 
quently encountered in the absence of valvular, arterial, or 
renal lesions. The condition is termed (Bollinger) idiopathic 
cardiac hypertrophy (Fig. 29), but this name others no etio- 
logical explanation, neither does it embrace a separate 
clinical entity, for it includes a series of unrelated disorders 
of unknown etiology. 
One group of these cases shows marked hypertrophy 
which is usually combined with dilatation. The myocardium 
is frequently of a cloudy yellow hue, and is sometimes the 52 
IDIOPATHIC CARDIAC HYPERTROPHY 
seat of cicatrices. Even where the unaided eye can discover 
no alteration, the microscope shows areas of fatty degenera- 
tion and others in which the muscle fibres have perished 
and the amount of connective tissue has been augmented, 
such lesions being often distributed throughout the entire 
musculature of the left ventricle. Recent myocarditis, also, 
may be discovered, in the form of localized or diffuse round- 
cell infiltration. 
Frequently there are found whitish thickenings of the 
endocardium, which have been improperly described as 
Fig. 29.-Fibrous and exudative myocarditis (slightly enlarged), a, small-cell (lympho- 
cytic) infiltration; b, myocardial fibres, separated by the proliferating interstitial tissue, and 
in part atrophic. 
chronic mural endocarditis; Baumler, however, has recently 
collected a series of these cases in which only a slight ten- 
dency of the myocarditis to involve the endocardium could be 
demonstrated. The pathogenesis of these simple white 
thickenings, which may be an unessential finding in other 
cardiac affections (valvular disease) and in old age, is not 
sufficiently understood (Nagayo), and they should not, there- 
fore, be brought into genetic relationship with idiopathic 
cardiac hypertrophy. 
More or less spherical thrombi may be found in the 
cavities of the heart, grayish-white, grayish-red, or dark red MYOCARDITIS 
53 
in color, and varying from the size of a pin's head to that of 
a walnut, or even larger; they are generally situated in the 
auricles or in the spaces between the trabecuhe in the ven- 
tricles (Fig. 30). They often show central softening, a whit- 
ish semi-fluid mass being released upon section (puriform 
softening), and may break spontaneously, pouring out their 
contents into the blood stream. 
Fig. 30.-Thrombi (a) between the trabecute of the right ventricle (one-half natural size). 
The presence of thrombi in the cardiac chambers suggests 
some such condition as retardation of the blood stream or 
localized lesions in the wall, and corresponding with the 
resulting embarrassment to cardiac function there are gener- 
ally found evidences of oedema, congestion, and infarction. 
The post-mortem findings in this group of cases indicate 
chiefly, therefore, a decrease in the heart's activity, and sug- 
gest that the anatomical basis of this insufficiency is usually 
to be sought in degenerative or inflammatory lesions of the 
myocardium. Disorders of the heart itself, myocarditis in 
particular, but pericarditis also, are the underlying con- 54 
IDIOPATHIC CARDIAC HYPERTROPHY 
ditions, the hypertrophy appearing as a consequence of the 
myocardial affection and probably in compensation for a 
damaged musculature unfit to perform its proper function. 
In a second class of cases, enlargement of the heart 
attains a grade so high that the organ has been described 
as bullock's heart (cor bovinum). The hypertrophy affects 
both sides but is more extreme in the left ventricle, dilatation 
is slight, or lacking, and the myocardium is brownish-red, in 
typical cases showing no change, even under the microscope. 
Congestion of the organs may be present, but is generally 
not very marked. It is typical of this group that the arterial 
system is involved, and the abdominal aorta contains numer- 
ous yellowish, slightly raised spots, which represent the 
degeneration of beginning arteriosclerosis. The medium- 
sized and smaller arteries present a similar appearance, 
and microscopic lesions can be discovered in the arteries of 
the kidney, the spleen, and other organs, but particularly 
in those of the heart itself. The slight lesions present in 
the kidney, such as destruction of the glomeruli, atrophy of 
the uriniferous tubules, and small foci of interstitial connec- 
tive-tissue overgrowth, I refer to arteriosclerosis of the 
smaller renal arteries, although Schmaus and Horn inter- 
pret them as a result of congestion. Since neither the arte- 
rial nor the renal lesions reach a degree sufficient to explain 
the hypertrophy, and since it is not probable that they are 
caused by the hypertrophy, no course remains open but to 
regard the cardiac enlargement and the arterial condition 
as coordinated products of a common cause; such an inter- 
pretation Bollinger found entirely applicable to the anatomi- 
cal findings in many cases of idiopathic hypertrophy. 
It can be concluded for the pathogenesis of this second 
group, therefore, that the injury does not affect the myocar- 
dium directly, but concerns the entire cardiovascular system, 
although the heart bears the brunt of the attack. A more 
exact explanation the autopsy table alone does not afford, 
but the hypothesis agrees well with many of the assumptions 
regarding the etiology of cardiac hypertrophy. Thus, Bol- ETIOLOGY OF IDIOPATHIC HYPERTROPHY 
55 
linger 1 ascribed the frequency in Munich of idiopathic car- 
diac hypertrophy to the plethora resulting from the con- 
sumption of large quantities of beer, and v. Recklinghausen 
had already stated that in cardiac hypertrophy without val- 
vular or gross arterial disease and without nephritis, there 
is an increase in the blood volume (plethora vera). When 
such cases come to autopsy, the impression is often very 
vivid that the blood volume is really augmented and that 
the vessels are dilated; still, there is no practicable method 
by which the amount of blood can be determined at post- 
mortem examination, and the question how frequently true 
plethora is present, if, indeed, it occur at all, is, in my opin- 
ion, debatable. At any rate, Bollinger's view has obtained 
wide acceptance, and it may actually be that the habitual 
imbibing of large quantities of beer will suffice to explain 
many cases of idiopathic hypertrophy of the heart. 
It is hardly necessary to emphasize the statement that 
the two divisions of idiopathic hypertrophy just described 
do not include all possible examples. Among other types, 
those cases merit a separate class where in the new-born 
and in children during the first years of life, cardiac enlarge- 
ment occurs without any cause being demonstrable at 
autopsy (Simmonds, Hedinger, Oberndorfer). Here again 
no indication of the cause can be discovered, and the investi- 
gator is once more driven to theoretical explanations. 
1 Bollinger's theory, it should be noted, included cases here placed in the first 
subdivision of idiopathic hypertrophy. CHAPTER VI 
Arteriosclerosis 
Arteriosclerotic changes in the vascular system are 
among the most frequent of all autopsy findings. Age is 
undoubtedly a factor in their production, but the earlier 
Fig. 31.-Moderate degree of arteriosclerosis in the aorta (three-fifths natural size), a, circum- 
scribed, smooth thickenings; b, thrombi; c, atheromatous ulcer, partly covered by thrombi. 
view, that the disease is solely one of later life, has long 
since been abandoned. Very advanced grades are extremely 
common in middle age, but signs of beginning damage to the 
vessels can be traced in the first few decennia, and even in 
childhood. 
56 ULCERATION AND CALCIFICATION 
57 
A highly arteriosclerotic aorta is thickened and dilated, 
and its inner surface is so uniformly irregular that hardly a 
normal spot can be found (Fig. 31), circumscribed nodules 
alternating with slightly yellowish flecks, and with flat 
calcareous patches. These placques may resemble gela- 
Fig. 32.-Severe arteriosclerosis in the aorta (two-thirds natural size), a, atheromatous ulcers; 
b, smaller ulcers overlying calcified areas; c, openings of vessels. 
till or cartilage by their uniform translucent whitish or 
yellowish appearance, but usually the pultaceous material 
which they contain shows through as a dull yellow mottling 
of the surface (atheroma). The intima is often defective 
(atheromatous ulcer, Fig. 32) over such lesions and over 58 
ARTERIOSCLEROSIS 
calcareous areas. Calcification may be so widespread as to 
convert the entire vessel into a stiff tube, although it is 
seldom so extensive in the aorta, with the exception, perhaps, 
of the portion just above the bifurcation (Fig. 41) ; the 
smaller arteries, however, show the transformation very 
frequently. These, and particularly the cerebral (Fig. 33), 
are often the seat of yellowish, circumscribed nodules like 
those just described in the aorta. Any artery may dilate and 
Fia. 33.-Arteriosclerosis in the cerebral arteries (natural size), a, right, b, left lateral ventricle; 
c, left, d, right frontallobe; e, left,/, right anterior cerebral artery. 
become tortuous in consequence when it is extensively in- 
volved, but this is more apt to occur in the case of the 
medium-sized and smaller vessels. 
To emphasize the dual nature of the arteriosclerotic 
process, its degeneration and its mural thickening, Marchand 
has proposed the term atherosclerosis. The thickening, 
which involves the inner coat, has been ascribed to inflamma- 
tory growth (endarteritis), but though proliferation does, 
as a matter of fact, belong among the processes which accom- 
pany inflammation, occurring where exudation continually ETIOLOGY 
59 
reappears, no exudative stage is demonstrable in arterio- 
sclerosis. Perivascular infiltration is sometimes seen in the 
adventitia (Fig. 37), and similar cellular deposits combined 
with connective tissue (mesarteritis) may appear in the 
media about areas of atheroma, that is, in the later stages of 
the disease, but, on the whole, undeniable evidence of inflam- 
mation is scarce, irregular, and, which is most significant, 
indistinct during the earlier stages of the disease. On these 
grounds, the inclusion of arteriosclerosis among the inflam- 
matory processes may be disputed (Marchand, Jores, and 
others). 
Further evidence can be adduced against the inflamma- 
tory hypothesis, in the fact that the intima becomes hyper- 
trophic not only over the nodular thickenings, but may 
undergo more general involvement (arteriosclerosis dif- 
fusa). If arteries thus affected be compared with the nor- 
mal, it will be found that some growth takes place in the 
inner coats of the aorta and other arteries in man, even 
under physiological conditions. 
After Langhans had recognized the intimal thickening 
of the aorta in advanced life, Thoma demonstrated in the 
intima of this and certain other vessels the development, 
from the first years of life onward, of a layer which he 
described as composed of connective tissue. He referred 
its origin to slowing of the blood stream in consequence 
of dilatation, and thought that it represented an attempt to 
equalize the increase in diameter by narrowing the calibre 
of the channel (compensatory endarteritis). 
The growing intimal layers contain beside the connective 
tissue, however, a layer formed by a characteristic hyper- 
plasia of elastic lamellae, the anlage and development of 
which also are to be recognized under physiological con- 
ditions (Jores, Westphalen, A. Aschoff). 
Inside the circular layer of muscle (media) in the aorta 
of the new-born, there occurs a longitudinal muscular coat 
bounded by two elastic membranes, which is extremely nar- 
row just after birth but becomes broader during the first 60 
ARTERIOSCLEROSIS 
few years of life. Inside this coat is found the hyperplastic- 
elastic layer of the intima, composed of interlacing elastic 
lamellae (Fig. 34), which are formed by the thickening and 
upheaval of fibres already present in the internal elastic 
lamina (Jores, Hallenberger). In the medium-sized and 
smaller arteries, those showing the muscular type of con- 
struction, the longitudinal musculo-elastic layer of the in- 
tima appears only where branches are given off (West- 
phalen, Jores), and the hyperplastic-elastic layer, which 
originates in a doubling 
or trebling of the elastic 
lamina, is chiefly limited 
to these localities. 
The phase of develop- 
ment thus far described 
has been called by Asch- 
off the first, or ascending 
period of vascular growth. 
Following its completion, the vessels remain for an uncer- 
tain and variable time in a state of equilibrium (Aschoff's 
second period), and this is succeeded by a third stage, in 
which the changes due to age begin to appear. With the 
advent of the last named, the connective tissue of the intima 
begins to increase, appearing between the lamellae of the 
hyperplastic-elastic layer and separating them from one 
another (Fig. 35), while inside of this it forms another coat, 
in which new elastic fibres may develop. 
The structures which arise during postembryonal vascu- 
lar growth are emphasized in the intima of arteriosclerotic 
patients. Sometimes there is an increase of the hyperplastic- 
elastic layer only, such as Friedemann has described for 
arteries of the contracted kidney (Fig. 247); such a process, 
although it cannot be called true arteriosclerosis, should not 
be separated so sharply as Friedemann and Aschoff have 
done, since it is always combined with this disease, particu- 
larly in the smaller arteries (Fig. 37), and can be demon- 
strated also in arteriosclerotic individuals in segments of 
Fig. 34.-Longitudinal section through the 
aorta of a two and one-half year old child (greatly 
enlarged), a, media; b, longitudinal muscular 
layer; c, hyperplastic-elastic layer of the intima. HYPERPLASTIC-ELASTIC LAYER 
61 
vessels that appear at first to have undergone no alteration. 
Hence, it can be said that arteriosclerosis almost always 
attacks vascular systems in which the hyperplastic-elastic 
layer is especially prominent. The development of this 
stratum can hardly be ascribed to the tension of growth, 
as Aschoff has suggested, because no such layer is found in 
animals, notwithstanding the fact that otherwise their arter- 
ies closely resemble those of man. I believe that the process 
Fig. 35.-Arteriosclerosis in the aorta; early stage (greatly enlarged), a, media; b, mus- 
culo-elastic longitudinal layer of the intima; c, hyperplastic-elastic layer of the intima, both 
involved by fatty degeneration. 
is not strictly physiological, but that the hyperplastic-elastic 
layer should be referred to tension resulting from increased 
strain on the vascular system. 
An explanation for arteriosclerosis has been sought for 
many years in mechanical and functional factors (Rokitan- 
sky, Virchow, Thoma, Marchand), and such increased strain 
as would follow the determination of abnormally large vol- 
umes of blood to certain organs or a rise in the blood- 
pressure, has been suggested by clinicians as productive of 
the disorder. These views are supported by the fact that 
hyperplasia occurs in certain mural layers at an early period 62 
ARTERIOSCLEROSIS 
in the disease, and as this process should be, and commonly 
is, regarded as a hypertrophy, it must have its basis in the 
strain incident to increased labor. The relation borne by the 
hyperplastic-elastic layer of the intima to arteriosclerosis 
offers, therefore, a histological demonstration that mechani- 
cal factors must contribute to that damage of which the 
end result is arteriosclerosis. 
Proliferation in the connective tissue of the intima can 
be described in general as a compensatory effort on the part 
of the vessel wall. This is the fundamental idea of Thoma, 
Fig. 36.-Arteriosclerosis in the aorta; advanced stage (slightly enlarged), a, media; b, 
musculo-elastic longitudinal layer of the intima; c, hyperplastic-elastic and connective-tissue 
layers of the intima, no longer separable; cl, atheroma. 
who demonstrated the invariable increase of connective tis- 
sue after amputation and ligation, and showed that in the 
neighborhood of the nodular thickenings of arteriosclerosis 
also, proliferation kept the lumen of the vessel approxi- 
mately circular. Whether these phenomena of adjustment, 
which Klotz was unable to confirm, are produced by slowing 
of the blood stream, as Thoma has suggested, or whether 
they follow a permanent diminution in the elasticity of the 
vessel wall, as Aschoff has said, is a question to winch, in 
my opinion, no categorical answer can be supplied. 
A discussion of the pathogenesis of arteriosclerosis 
would be incomplete without some further consideration of ATHEROMA 
63 
its degenerations. Atheroma involves the deeper parts of 
the nodular thickenings in the intima, including a portion of 
the connective-tissue layer, which here is generally very 
thick, but above all does it destroy the hyperplastic-elastic 
and the musculo-elastic laminae (Fig. 36). Thus the periph- 
ery of the lesion always extends at least as far outward as 
the media, and even this coat may contain lipoid substances. 
Fig. 37.-Atheromatosis in a small artery of the brain (slightly enlarged), a, lymphocytic 
infiltration of the adventitia; b, media; c, hyperplastic-elastic layer of the intima; d, area of 
degeneration (atheroma); e, connective-tissue thickening of the intima. 
Ill the smaller arteries, also, atheroma very distinctly occu- 
pies the hyperplastic-elastic stratum, being covered by a 
proliferate of connective tissue (Fig. 37). 
Beside nodular thickenings, the aorta contains a great 
number of degenerative lesions, chiefly in its longitudinal 
musculo-elastic and hyperplastic-elastic layers (Fig. 35), 
and the tiny yellow spots so often found in vessels showing 
no other evidences of arteriosclerosis (Fig. 38), have the 
same localization. These latter, Virchow distinguished from 64 
ARTERIOSCLEROSIS 
atheroma, as a primary fatty degeneration in the super- 
ficial cells of the intima, but since it is now known that they 
represent the first stage of arteriosclerosis (Jores), the 
distinction is no longer jus- 
tifiable. 
Atheromatous degener- 
ation is characterized by 
the appearance of lipoid 
materials, which after 
being stained with fat 
dyes, appear as granu- 
lar masses (Fig. 35) in 
the cells and ground 
substance of the intima, 
and even the elastic fibres 
early exhibit a sort of fat- 
ty transformation (Jores, 
Torhorst). These foci of 
degeneration are eventual- 
ly represented by a mass 
of detritus within which 
the single elements, in- 
cluding the elastic fibres, 
lie dead (Fig. 36). Most 
of the debris is doubly 
refracting (Kaiserling and 
Orgler), and consists main- 
ly of combinations of chole- 
s t e r i n and oleic acid 
(Aschoff). Windaus has recently shown by chemical means 
that in the atheromatous aorta the cholesterin ester content 
is augmented. 
While Virchow regarded atheroma as the expression of 
a parenchymatous inflammation, and Marchand has always 
emphasized the significance of degeneration for arterio- 
sclerosis, most recent observers have adopted the view that 
degeneration attacks the new-formed intimal connective tis- 
Fig. 38.-Arteriosclerosis in the aorta, early 
stage (three-fourths natural size). Yellowish, 
slightly elevated spots. FATTY DEGENERATION 
65 
sue secondarily, whether on account of strain and insufficient 
nutrition (Thoma), or the penetration of plasma from the 
blood stream into the interstices of the media (Ribbert). 
That hyaline degeneration is a secondary process and calcifi- 
cation a late phenomenon is undoubtedly true, and it cannot 
be denied that in certain instances fatty metamorphosis of 
the connective tissue is secondary. 
On the other hand, it is to be emphasized that the lesion 
last named must, in the main, be regarded from its very 
inception as an integral part of the arteriosclerotic complex, 
on account of its early supervention and its regular location 
in certain layers of the vessel wall. Early in arterioscle- 
rosis, moreover-that is to say, in the young-fatty de- 
generation often precedes the development of connective 
tissue, while the larger is the area of degeneration the 
greater is the fibrotic deposit overlying it. Nevertheless, 
it must be confessed that connective-tissue overgrowth un- 
doubtedly occurs in the smaller arteries in the absence of 
fatty degeneration (Aschoff and Hallenberger, Schmiedl). 
If the fatty changes are not a mere consequence of the 
intimal thickening, they must have an etiology of their own, 
though it remains still unknown. I have previously assumed 
that the functional overstrain to which the vascular system 
is subjected may lead eventually to degeneration of the 
hyperplastic layer, although it is true that attempts to prove 
this hypothesis in animals have not been satisfactory. By 
repeatedly suspending rabbits head downward, Klotz in- 
duced heightened blood-pressure in the cephalic half of the 
body with a consequent increase in the amount of work per- 
formed by the arteries concerned, and found that the elastic 
tissue had not only become hyperplastic, but that it contained 
areas of degeneration; Lubarsch, however, was unable to 
substantiate these findings. 
It is very probable that degenerative arterial lesions are 
produced in animals by the action of certain poisons. An 
account of the earlier experiments will be found in Salty- 
kow's article, and their description may be omitted here, 66 
ARTERIOSCLEROSIS 
since many of them were negative, while the positive results 
claimed for others will not bear the test of severe criticism. 
Josue was the first to produce arterial changes in rabbits 
by the intravenous inoculation of adrenalin, and his findings 
have been confirmed by Erb and a number of subsequent 
investigators (for bibliography, see Saltykow). After sev- 
eral injections of adrenalin, raised and sometimes umbili- 
cated patches occur in the media of the 
aorta (Fig. 39), the lesions representing 
a degeneration which affects principally the 
musculature. Calcification of the entire 
area soon sets in, and connective-tissue 
thickening may involve the intima at a later 
period, but its amount is insignificant and 
its appearance irregular. 
It is evident that adrenalin sclerosis 
differs in many essentials from arterio- 
sclerosis of the human subject, and Otto's 
attempts to correlate the two cannot be 
accepted. Nevertheless, this experimental 
lesion resembles the Monckeberg type, 
a form of arteriosclerosis in which the 
intima is not thickened, although the 
media contains areas of calcification 
(Fig. 40). This condition often affects the 
vessels of the extremities in association with the more com- 
mon arteriosclerosis, and it may well be assumed that it 
is not a separate disease, but rather a sub-class of the ordi- 
nary variety, and the product of local conditions. 
The study of experimental adrenalin sclerosis will with- 
out doubt do much to explain the vascular diseases of man. 
It is especially necessary to know, for example, whether the 
arterial lesions in rabbits are a result of the increased blood- 
pressure which follows the exhibition of adrenalin, or 
whether they are the outcome of some toxic action exerted 
by the drug upon the vessel wall. According to Erb, Kiilbs, 
Boveri, and others, the augmented blood-pressure alone does 
Fig. 39.-Adrenalin 
sclerosis in the aorta of a 
rabbit (natural size), a, 
areas of degeneration; b, 
aneurismal dilatation. EXPERIMENTAL ARTERIOSCLEROSIS 
67 
not suffice to explain the lesions, and it is evident that some 
toxic factor is in play; their position is strengthened by the 
fact that analogous, though less advanced, changes follow 
the introduction of many other materials. 
By inoculating staphylococci it is possible to obtain 
arterial lesions in the rabbit which approximate even more 
closely those of man (Saltykow). The aortic patches, which 
are more elevated, are the result of thickening and fatty 
degeneration of the intima, and Saltykow has recently re- 
ported that the elastic fibres, also, are implicated in the 
Fig. 40.-Longitudinal section of the femoral artery, calcification of the media (slightly 
enlarged), a, intima (hyperplastic-elastic layer); b, media; c, adventitia; e, f, areas of calcifi- 
cation. 
process. Although final judgment is not yet possible, it 
seems certain that these changes are much more closely re- 
lated to arteriosclerosis in man than are those produced 
by adrenalin. Their origin cannot be referred solely to the 
bacterial toxins, since, according to Saltykow, it is in great 
measure dependent upon a special diet of cow's milk. It is 
known that animal albumin alone will produce vascular dis- 
orders in the rabbit, for small lesions have been discovered 
in the intima after feeding with meat (Ignatowski) or calves' 
liver (Lubarsch). On the ground of such experiments, the 68 
ARTERIOSCLEROSIS 
latter author inclined to dispute the generally accepted 
hypothesis that arteriosclerosis in man is the result of 
heightened blood-pressure or other mechanical conditions, 
and to assume a toxic or an antitoxic etiology. In this, 
however, he has undoubtedly gone too far; the conditions in 
these experiments, where an animal diet was substituted for 
a vegetable, were equivocal, and the resulting alterations, 
although similar to arteriosclerosis in man, were not identi- 
cal. Without wishing to minimize in the least the value of 
animal experimentation, I must nevertheless ascribe to the 
findings in man chief importance in determining the 
pathogenesis of arteriosclerosis, and repeat that overstrain 
of the vascular system must be included among the factors 
responsible for this disease in the human subject. Of 
course it is not impossible that an unsuitable diet and the 
auto-intoxication resulting therefrom, might exert coinci- 
dent mechanical and toxic influences upon the vascular sys- 
tem, or that a similar effect could be produced under still 
other circumstances. Suggestive in this respect are the ex- 
periments of Starokadowsky and Ssobolew, who obtained 
in young rabbits lesions very similar to those of arterio- 
sclerosis in man, by causing degeneration and heightened 
blood-pressure at the same time. 
Saltykow has included infectious diseases among the 
injuries which may result in arteriosclerosis, but with this 
I cannot agree, since his position is supported neither by 
clinical observation nor by experiment. 
The results of arteriosclerosis are various; the arteries 
become dilated and less expansible or are transformed into 
stiff-walled and tortuous tubes (Fig. 41), and their func- 
tional activity is correspondingly affected. In early annular 
calcification, a narrowing of the vessel takes place, particu- 
larly in the case of the smaller arteries. Strasburger's ex- 
periments, which, as to method, may be accepted as the most 
reliable, show that even in the early stages of arteriosclerosis 
the vessel (aorta) is less expansible than normal arteries, 
although the degree of elasticity (return to its original con- THROMBOSIS AND EMBOLISM 
69 
dition) is approximately equal to that of the healthy aorta. 
Later, however, complete elasticity is forfeited. 
Arteriosclerosis favors the occurrence of thrombosis, 
particularly in the smaller arteries, where the condition 
Fig. 41.-Iliac arteries and lower part of the aorta, dilated and tortuous in consequence of 
advanced arteriosclerosis (one-half natural size). 
leads to stoppage of the vessel; in the aorta, where it is 
less common, thrombosis may be followed by embolism. 
It would be easy to imagine that diminished elasticity in 
the larger arteries, and particularly the increased resistance 
opposed by arteriosclerotic peripheral vessels, would throw 
more work upon the heart, and yet it is a matter of frequent 70 
ARTERIOSCLEROSIS 
observation that cardiac hypertrophy is not at all a con- 
stant event, and that it may be lacking even in the presence 
of advanced aortic disease. Hasenfeld has tried to explain 
the variable occurrence of hypertrophy by the distribution 
of the arterial lesions, suggesting that it is especially apt 
to accompany involvement of vessels lying in the splanchnic 
area, vessels which are said to be the most important regu- 
lators of the general arterial pressure. I can but agree with 
Marchand, who was not able to discover any constant rela- 
tion between cardiac hypertrophy and arteriosclerosis in the 
coeliac and the mesenteric arteries. It is true that the affec- 
tion is not at all rare in these vessels, and in one instance I 
found an atheromatous lesion about the size of a cherry pit 
in the latter, which had so nearly obliterated the lumen as to 
leave only a fissure. Such cases are exceptional, however, 
and usually the branches of the mesenteric artery are not 
greatly changed, even with pronounced cardiac hypertrophy. 
Arteriosclerosis is attended by malnutrition in the 
regions supplied by the affected vessels, and in this connec- 
tion it is interesting to observe the manner in which the dis- 
ease is distributed throughout the arterial tree. Rokitan- 
sky, and later Huchard, prepared a chart of its frequency 
in various regions, while extensive tables setting forth the 
frequency and intensity of the lesion in different locations 
have been published by pupils of Thoma. I consider such 
charts (they have been collected by Schrbtter) of little value 
because, prepared from various viewpoints, they come to 
no uniform conclusion. Guided by my own experience in the 
post-mortem room, I must emphasize the very frequent, if 
not invariable, participation of the peripheral arteries, for 
advanced cases in which the aorta is chiefly or solely attacked 
while the smaller arteries remain entirely free, are but 
rarely encountered. On the contrary, extensive involvement 
of the medium-sized and smaller vessels is often seen, in the 
presence of equally advanced or milder lesions in the aorta; 
in such cases, the abdominal portion is more affected than 
the thoracic. Among the vessels of medium size, the splenic, CONSEQUENCES OF ARTERIOSCLEROSIS 
71 
pancreatic, and iliac arteries are, as a rule, seriously 
damaged, the carotid and femoral suffering to a slight 
extent only. 
Albrecht, and later Oberndorf er, correlated the localiza- 
tion of arteriosclerosis with peculiarities in position and 
fixation; in other words, motility of the vessel appears to 
protect its wall from the more advanced grades of the lesion. 
The arteries of the extremities, including the radial, are 
often but little affected. The findings of palpation do not 
always correspond with the grade of the anatomical lesion 
according to Fischer and Schlayer, since what the examina- 
tion discloses is frequently a generalized thickening of the 
wall without degeneration (Hallenberger). The arteries 
supplying certain of the organs are often attacked, especially 
those of the brain, the heart, the kidney, the pancreas, and 
the spleen. The severity and distribution of the process 
vary; sometimes the very smallest branches are involved, a 
condition which is productive of considerable damage, par- 
ticularly in the case of the kidneys, the heart, and the brain. 
These organs may be affected in approximately equal de- 
gree, or one may suffer while the others escape; the dis- 
crepancy has been referred to a variable intensity of their 
functional activity. 
The disturbances which supervene in the organs as a 
consequence of arteriosclerosis may now be briefly sketched 
out; in so far as they are important findings at autopsy, 
they will receive adequate treatment in another place. The 
kidneys are smaller than normal, the capsule strips off with 
difficulty, and the outer surface is brownish-red and slightly 
granular; the cut surface is of a similar hue and the cortex 
practically unaltered. In certain areas there take place 
connective-tissue proliferation and destruction of the urinif- 
erous tubules, the glomeruli being hyaline and atrophic. 
The condition, which is called arteriosclerotic contracted 
kidney (Ziegler), or more appropriately, arteriosclerotic 
renal atrophy, is a consequence of arteriosclerotic degenera- 72 
ARTERIOSCLEROSIS 
tion in the afferent vessel. Ziegler described under the same 
name another type of contracted kidney, characterized by 
large, scar-like retractions of its surface, but I do not think 
that this variety can be referred, as a rule, solely to involve- 
ment of the vessels of the kidney. 
Arteriosclerosis of the coronary arteries may be in itself 
of grave pathological significance; it is sometimes respon- 
sible for the small yellow myocardial foci which subsequently 
become transformed into 
cardiac cicatrices. 
Affected cerebral ves- 
sels may rupture, causing 
apoplexy, or their involve- 
ment may so interfere 
with the blood supply as 
to result in small and 
often multiple points of 
softening, with which the 
entire brain is sometimes 
studded. In other cases 
there are found small, 
smooth-walled cysts con- 
taining a clear watery 
fluid (Fig. 42) and repre- 
senting the end result of 
earlier softening, and in 
still others, cysts from 
p r e v i ous hemorrhages. 
According to Alzheimer, the destruction consequent upon 
retarded circulation in the cerebral arteries may concern 
only the nervous elements, the glia showing signs of pro- 
liferation. The presence of such foci, which are frequently 
associated with softening and hemorrhage, results in 
arteriosclerotic atrophy of the brain; secondary atrophy 
often attacks the thalami, the deeper fibres of the hemis- 
pheres, and the pyramidal tracts. In contrast to paresis, 
normal areas can always be found. 
Fig. 42.-Cerebral cysts (natural size). ARTERIOSCLEROSIS IN PULMONARY ARTERY 
73 
The occurrence of arteriosclerosis in the pulmonary 
artery requires special mention. Here the disease assumes 
the form of slightly raised, yellow, mural lesions (Fig. 43) 
which, like those in the arteries belonging to the general 
circulation, consist of changes in the hyperplastic-elastic 
layer, lipoid degeneration, and connective-tissue prolifera- 
Fig. 43.-Arteriosclerosis of the pulmonary artery (natural size), a, pulmonary artery; b, pul- 
monary vein; c, lymph-nodes at the hilus of the lung, d, bronchi. 
tion (Torhorst, Ehlers). Large atheromatous areas do not 
occur, and calcification, which is rare, does not attain an 
advanced degree (W. Fischer). Higher grades of the dis- 
ease are marked by the presence of more numerous thicken- 
ings, generally distributed among the branches of the vessel, 
by stiffness of the wall, and microscopically, by connective- 
tissue proliferation (Bruning, Monckeberg). Arterioscle- 74 
ARTERIOSCLEROSIS 
rosis affects the pulmonary artery independently of sclerosis 
in the vessels of the general circulation; it very often 
attends mitral lesions, pulmonary emphysema, etc., or, in 
short, augmented blood-pressure in the pulmonary circula- 
tion and hypertrophy of the right ventricle. In some cases, 
where arteriosclerosis in the pulmonary artery has been 
very pronounced, and where no other cause for cardiac 
hypertrophy has been demonstrable, the arterial condition 
has been described as the primary lesion, and the hyper- 
trophy of the right heart as secondary (Romberg, Moncke- 
berg, Rossie). But since much more advanced sclerosis in 
the arteries of the general circulation is often followed by 
little or no change in the heart, I consider that this view is 
not well founded. CHAPTER VII 
Diseases of the Coronary Arteries; Cardiac Cicatrices; 
Pathology of the Atrioventricular Bundle 
As has already been stated, arteriosclerosis frequently 
involves the coronary arteries; in such a case, the branches 
Fig. 44.-Arteriosclerosis in the coronary arteries (natural size). 
coursing over the surface of the heart are tortuous and 
somewhat dilated, and yellowish thickenings project into 
75 76 
DISEASES OF CORONARY ARTERIES 
their lumina. Calcification is not at all uncommon, and 
may be so extensive that portions of the vessels are trans- 
formed into stiff and narrow channels (Fig. 44). These 
changes, if they are widely distributed, may interfere with 
the nutrition of the myocardium, and in this way be a cause 
of cardiac insufficiency. The orifices of both coronary 
arteries may be materially decreased, or even obliterated, 
Fig. 45.-Openings of the coronary arteries narrowed by syphilitic aortitis. The opening of the 
left coronary (a) is moderately, that of the right (b) greatly constricted. 
by sclerosis in the aorta (Fig. 45), though such a narrowing 
rarely follows ordinary arteriosclerosis; it is more com- 
monly an outcome of cicatricial, or syphilitic aortitis, a 
lesion usually localized in the ascending aorta and often 
combined with arteriosclerosis. Diminution of the coronary 
orifices is frequently found in patients who have suffered 
from angina pectoris, but ordinary arteriosclerosis in the 
coronaries is sometimes responsible for the attacks. INFARCTION 
77 
When the lumina of the coronary arteries are constricted, 
areas of disturbed nutrition ensue, in the form either of 
infarcts, or of yellow necroses due to localized anaemia.. 
Infarcts are usually distinguishable on the surface of the 
heart as dull patches often mottled with red (Fig. 46). 
Upon section they generally present a variegated appear- 
Fig. 46.-Cardiac infarct (one-half natural size), a, infarct; b, course of the artery supplying 
the infarcted area. 
ance, yellowish portions alternating irregularly with hemor- 
rhagic ; the latter, however, may be lacking, in which case the 
entire lesion will be of a dull yellowish hue (myomalacia). 
In foci that have existed for a long time, fibrous nodules 
replace the necrotic muscle (cardiac cicatrices). The cause 
of infarction is usually thrombotic closure of one of the 
larger branches, the thrombosis being generally referable 
to calcification; only rarely does embolism involve branches 78 
DISEASES OF CORONARY ARTERIES 
of the coronary arteries. Yellow necrosis appears on the 
cut surface of the myocardium as small areas which are 
often connected in such a way as to form a geographical 
design (Fig. 47). The musculature is partly necrotic and 
Fig. 47.-Yellow necrosis (paler areas, as at a) and cardiac cicatrices (white areas) in the wall 
of the left ventricle (three-fifths natural size). 
partly the seat of fatty degeneration, and by resorption and 
reactive inflammation these lesions also are transformed into 
cardiac cicatrices. Yellow necrosis has been ascribed to 
arteriosclerotic narrowing or closure of smaller branches 
of the coronary arteries, and such a view may be correct in ANASTOMOSIS: CORONARY ARTERIES 
79 
a general way; it is questionable, however, whether the 
cardiac cicatrices found in individuals with arteriosclerosis 
of the coronary arteries are always attributable to this 
lesion. At any rate, their situation does not always corre- 
spond with the distribution of the affected vessels (Fuji- 
nami, Strauch, v. Redwitz), and Thorel has suggested that 
the presence of some toxic factor may perhaps be required, 
in addition to the vascular lesion. 
Cardiac infarcts are hardly ever localized in conformity 
with the distribution of the affected vessel. The discrepancy 
was particularly noticeable in a case reported by Chiari, 
where the heart contained only small foci of necrosis in the 
right ventricle, in spite of an old thrombotic obliteration of 
the right coronary. Findings like this suggest anastomosis 
between the coronary arteries, and a connection has recently 
been demonstrated, in fact, by Jamin and Merkel and by 
Spalteholz. The existence of this anastomosis explains the 
variable result of closure of one of the larger coronary 
branches, as well as the observation that even when the main 
trunk is destroyed or tied off, the myocardium may remain 
intact (Pagenstecher, Thorel) and death may not occur. 
Cases like that of Oestreich, where one coronary was oblit- 
erated by a thrombus in the ascending aorta, and the other 
by an embolus from this thrombus, are rare. 
Experiments carried out upon animals agree with obser- 
vations upon the human subjects. Variable effects follow 
ligature or other experimental obliteration of the coronary 
branches, cardiac paralysis appearing sometimes, and not 
at others (for bibliography, see Thorel). Such investi- 
gations, and particularly the recent work of Hirsch, show 
beyond peradventure that closure of a coronary artery need 
not of necessity lead to suspension of the heart's activity. 
CARDIAC CICATRICES 
The effect of cardiac cicatrices upon the functional capa- 
city of the myocardium has been suggested on a preceding 
page, in connection with a description of the small scars 80 
CARDIAC CICATRICES 
accompanying valvular lesions. It must now be added that 
even such large cicatrices as follow infarction, yellow 
necrosis, and gummata, may be found in hearts which, dur- 
Fig. 48.-Cardiac aneurism (one-half natural size), a, wall of the left ventricle; b, thin, 
fibrous wall of the aneurism; c, thrombus lying in the aneurism; d, thickened endocardium 
above the aneurism. 
ing life, have shown no continuous evidence of insufficiency. 
This is to be explained by the fact that the effect of a cica- 
trix, strictly speaking, is the loss only of so much active 
musculature as has been supplanted by the scar, a loss which CARDIAC ANEURISM 
81 
can easily be made up by compensatory hypertrophy. The 
question arises, however, whether the situation of the cica- 
trices may not be of significance. They are often situated 
in the left ventricle, partly in the wall and partly in the 
anterior papillary muscle; their presence in the latter of 
these localities has been referred by Amenomija to the fact 
that the anterior papillary muscle on the left side is nour- 
ished by only one twig from the descending branch of the 
left coronary artery, while the others obtain their blood from 
both the right and left coronaries. Large cicatrices in the 
left ventricle are often situated near the apex, at the junc- 
tion of the septum with the anterior wall, and here the 
myocardium may be so attenuated as to bulge outward, pro- 
ducing a cardiac aneurism (Fig. 48). According to Strauch, 
these aneurisms most frequently occur in the region just 
described, and in two-thirds of the cases thrombi are encoun- 
tered on their inner walls (Fig. 48). They are often dis- 
covered in cases of sudden death from cardiac causes. 
Cardiac cicatrices may be of significance if they are so 
situated as to interrupt more or less completely the atrio- 
ventricular bundle. 
PATHOLOGY OF THE ATRIOVENTRICULAR BUNDLE 
Iii recent years, attention lias been directed toward cer- 
tain portions of the myocardium which exert a specific 
function, and investigation of the pathology of these regions 
is now well under way. His succeeded in demonstrating a 
muscular connection between auricle and ventricle, his re- 
searches making it seem probable that this structure is 
concerned in the transference of excitory stimuli from the 
auricles to the ventricles. Tawara continued his investi- 
gations. According to the observations of this latter author, 
the essential points of which have been repeatedly con- 
firmed (Fahr, Monckeberg), the atrioventricular bundle 
originates at the anterior edge of the coronary sinus (Fig. 
49), and soon becomes transformed into a muscle complex 
in which the fibres assume a reticular arrangement, forming 
6 82 
PATHOLOGY OF ATRIOVENTRICULAR BUNDLE 
a sort of node (atrioventricular node, Tawara's node). The 
position of this may be best seen in Fig. 49. Though not 
visible to the naked eye, it can be discovered with the micro- 
scope in the auricular septum, just above the fibrous plate 
which is interposed between the auricular and ventricular 
septa (annulus fibrosus). From the atrioventricular node, 
Fiq. 49.-Schema to show the position of the sino-auricular and atrioventricular nodes (after 
Koch). Red line between the vena cava and the auricle-sino-auricular node. Red spot above 
the point of attachment cf the tricuspid-atrioventricular node. The white line in the auricle 
divides the coronary sinus from tne rest of the cavity. 
the bundle passes through the annulus fibrosus (Fig. 50), 
dividing into two limbs (Fig. 51) when it reaches the ven- 
tricular septum; one of these runs on the left, the other on 
the right side of the septum. The left, lying just under the 
endocardium, divides into a large number of branches which 
go to the papillary muscles and other portions of the ven- 
tricle; these are analogous to Purkinje's fibres in the ungu- THE BUNDLE OF HIS 
83 
lates. The right limb soon penetrates the deeper muscu- 
lature of the septum, but further on in its course becomes 
again sub-endocardial in position, when it, too, divides into 
Purkinje fibres. 
The bundle of His must be an anatomically separate 
system, for the auricular portion is distinguished from the 
rest of the myocardium by the narrowness of its fibres, the 
less complete development of fibrillary substance, and the 
abundant sarcoplasm. The ramifications in the ventricles 
are of variable breadth; their sarcoplasm also exceeds the 
Fig. 50.-Atrioventricular bundle pass- 
ing through the annulus fibrosus (hand 
lens). S.a., auricular septum; S.v., ven- 
tricular septum; H.B., bundle of His. 
Fig. 51.-Antrioventricular bundle 
after its passage through the annulus 
fibrosus; division into two limbs (hand 
lens). S.a., auricular septum; S.v., 
ventricular septum; II.B., bundle of 
His; a, its right, b, its left limb. 
fibrilla? in amount, and is strewn with vacuoles. It is par- 
ticularly characteristic of these fibres that they contain 
glycogen (Aschoff). 
After the researches of His had established the proba- 
bility that the atrioventricular bundle represents the func- 
tional connection between auricles and ventricles, proof was 
brought by Hering that it transmits the contractile impulse. 
A second bundle has been discovered, which carries the 
stimulus from the superior vena cava to the right auricle. 
According to the physiologist, the first impulse to the heart's 
motion originates at the point where this vein enters the 84 
PATHOLOGY OF ATRIOVENTRICULAR BUNDLE 
auricle, and it was accordingly an interesting discovery 
when Wenckebach demonstrated a thin bundle of muscle in 
the outer posterior wall, running from the vena cava along 
the angle between vein and auricle. Koch, however, denied 
to Wenckebach's bundle the anatomical characteristics of 
a stimulus-conducting apparatus, and attributed transmis- 
sion of the contractile impulse to a muscle system described 
by Keith in the upper portion of the right auricle, the sino- 
auricular node (Fig. 49). Although it is in the neighbor- 
hood of this node that special stimuli arise, other areas in 
the right auricle are nevertheless automatically operative 
(Hering). 
Summing up the situation, it can be said (Hering) that, 
under normal conditions, the point of origin for cardiac 
activity (the birthplace of the primary nomotopic impulse) 
lies in the right auricle at the entrance of the superior vena 
cava, in the neighborhood of the sino-auricular node. A 
condition of ventricular automatism (heterotopic autom- 
atism) occurs, however, when the initiatory stimulus orig- 
inates with difficulty or not at all in the normal location, 
when the heterotopic impulse develops with greater rapidity, 
or when the conducting system is functionally or anatomi- 
cally disorganized at the point where the nomotopic impulse 
is conceived. 
It should be added that the specific muscular systems are 
in connection with nerves. In the neighborhood of the ter- 
minal portion of the superior vena cava, and particularly in 
the angle between vein and auricle, there lie numerous gan- 
glia, and Tawara, Wilson, and Engel (for bibliography, see 
Fahr, Engel) have shown that the atrioventricular bundle is 
interwoven and accompanied by nerve fibres. But for all 
that, convincing evidence can be adduced (Hering) to show 
that it is the muscular, rather than the nervous elements that 
conduct the cardiac impulse, since the pathologist has never 
succeeded in demonstrating any important lesion in the 
nervous apparatus. Thus, in the light of the most recent 
investigations, the myogenic theory appears to be the more HEART BLOCK 
85 
probable, and, indeed, it has received very material support 
through the discovery of the specific muscle systems. The 
role that these muscle groups really play in pathology 
becomes, therefore, a question of the greatest importance. I 
follow here in general Aschoff's lucid recapitulation of the 
subject (for bibliography, see also Heilhecker). 
Coordinative disturbances in the sequence of beats in 
the various chambers may be referred to the specific muscu- 
lar systems. In cases where the ventricular rhythm is inde- 
pendent of the auricular (total heart block, total interfer- 
Fig. 52.-Interruption of the atrioventricular bundle by a cicatrix (after Fahr). S.a., auric- 
ular septum; S.v., ventricular septum; a, right, b, left limb; c, sclerotic area in atrioventric- 
ular bundle. 
ence with the transmission of impulses), and where the dis- 
sociation has persisted for a time, some lesion has regularly 
been discovered in the atrioventricular bundle (Fig. 52); 
these have generally been gummata, cicatrices, or areas of 
calcification, situated in the main trunk. 
For incomplete heart block (dropped ventricular beat), 
the anatomical foundation is not so certain. Inflammatory 
changes involving the main stem of the bundle or its ramifi- 
cations have been found in some of these cases, but in others 
no alteration has been demonstrable; the latter are probably 
referable to some toxic damage exerted upon the muscular 
bundle, or to stimulation of the vagus. 86 
PATHOLOGY OF ATRIOVENTRICULAR BUNDLE 
Ill total auricular block (pulsus irregularis perpetuus), 
Schonberg and Hedinger both found inflammatory infil- 
tration of Wenckebach's bundle, while inflammatory and 
sclerotic changes have been demonstrated in the region of 
the sino-auricular node in connection with persistent 
arrhythmia (Freund, Koch). Aschoff has asserted that 
chronic pericarditis may affect the sino-auricular node, and 
I consider this very probable in the light of my own experi- 
ence. Furthermore, I have seen a case in which cicatricial 
thickening about the superior vena cava, originating in 
anthracotic lymph-nodes, appeared to have damaged the 
sino-auricular node. 
Monckeberg has referred myocardial insufficiency and 
sudden cardiac death to involvement of the atrioventricular 
bundle. He found that although this structure is highly 
independent of pathological conditions in the heart muscle, 
taking no part, for example, in atrophy or hypertrophy, it 
is subject to fatty degeneration, a lesion which he found 
frequently attending sudden death from cardiac causes. 
But according to Aschoff and Engel, fatty changes in 
Purkinje's fibres are physiological in advanced life, and 
their relation to cardiac death is inconstant. Monckeberg 
has nevertheless insisted that circumscribed lesions in the 
atrioventricular bundle do coincide with cardiac death, deny- 
ing the suggestion that the fatty changes are not pathologi- 
cal, at least in his own cases, and referring to the clinical 
observation that a condition is produced by interruption of 
conductivity, which, even though it be not immediately fatal, 
is nevertheless serious, and leads after a shorter or a longer 
period to cessation of the heart's activity. CHAPTEE VIII 
Hemorrhage into the Brain and its Membranes ; Internal 
Hemorrhagic Pachymeningitis ; Thrombosis and 
Embolism in the Cerebral Arteries 
One of the consequences of arteriosclerosis is spon- 
taneous hemorrhage into the brain. Viewed from without, 
the organ may present nothing abnormal, in rare instances 
Fig. 53.-Spontaneous hemorrhage in the central ganglia on the right side, with perforation 
into the ventricle (one-half natural size), a, hemorrhage; b, corpus striatum; c, optic 
thalamus. 
not even the evidences of pressure; in other cases, the inner 
membranes are suffused with blood over a considerable area 
of the cerebellum. This does not indicate that the hemor- 
rhage is superficial, but rather that blood from the ventricles 
87 88 
HEMORRHAGE INTO THE BRAIN 
has reached the cerebral membranes through an opening in 
the roof of the fourth ventricle (the foramen of Magendie) 
which connects this chamber with the subarachnoid space; 
if the lateral and middle ventricles be examined, blood will 
be found in them also. Fig. 53 shows a hemorrhage that has 
broken through into the ventricle; transverse sections made 
in this case to locate more exactly the situation of the clot 
Fig. 54.-Small hemorrhages in the central ganglia (one-half natural size), a, in lenticular 
nucleus; b, in optic thalamus; c, anterior, d, posterior segment of the internal capsule; e, cortex 
of the temporal lobe; f, island of Reil; g, posterior cornu of the left lateral ventricle. 
proved that the greater portion of the optic thalamus, part 
of the corpus striatum with the deeper lying nuclei, and 
some of the medullary substance in the left hemisphere had 
been destroyed. 
In the case of smaller lesions, their situation in the 
neighborhood of the optic thaMmi and the corpora striata 
can be even more readily made out (Fig. 54). The frequent SITES OF ELECTION 
89 
occurrence of hemorrhage in this region of the brain depends 
upon the fact that it is supplied from the largest branch of 
the internal carotid by vessels which are among the first to 
feel increased blood-pressure, and which are frequently 
affected by arteriosclerosis. Upon the frequent localization 
of the hemorrhage in the region indicated depends the fact 
that the internal capsule is so often destroyed, or at least 
injured. Motor and sensory nerve 
fibres from the cortex unite at the in- 
ternal capsule to run thence through 
the peduncle, the pons, and the medulla, 
to the spinal cord, and a comparison be- 
tween Figs. 54 and 55 will show how 
readily the interruption of important 
nerve tracts may be accomplished in 
this region. Reference to Fig. 55 will 
show that there is but a small space be- 
tween the central nuclei and the cortex 
of the island of Reil, and that neither 
Broca's convolution nor the cortex of the 
temporal lobe is far removed; hence, 
hemorrhages into the left side of the 
brain may endanger the speech centre. 
Additional sites of election for cerebral 
hemorrhage are the peduncle, the pons 
(paralysis of the respiratory centre), 
and, more rarely, the medullary sub- 
stance of the cerebrum and the cere- 
bellum. 
If life be prolonged for some time after hemorrhage has 
taken place, the fluid parts of the blood undergo resorption, 
and reactive growth of the surrounding glia and connective 
tissue sets in, through which the clot becomes encysted. The 
contents of the cyst are further transformed by gradual 
absorption of their coloring matter and the appearance of 
watery fluid, and the wall slowly assumes a yellowish hue 
from the presence of the remaining blood pigment. Shrink- 
Fig. 55.-Course of the 
nerve fibres in the internal 
capsule; schematic drawing 
to supplement Fig. 54. 90 
HEMORRHAGE INTO THE BRAIN 
age of the cyst and its replacement by a yellowish scar some- 
times takes place (Fig. 56). 
The basilar artery of the brain pictured in Fig. 53, and 
the smaller vessels at the convexity, were the seat of arterio- 
sclerosis, a lesion which is very frequently associated with 
spontaneous cerebral hemorrhage, as has previously been 
stated. In trying to account for this combination, earlier 
observers were not a little puzzled to explain how a lesion 
could produce thickening of the arterial wall and at the same 
Fig. 56.-Apoplectic scar in the medulla and cortex of the left temporal lobe; frontal 
section (three-fifths natural size;, a, dilated posterior cornu of the left lateral ventricle with 
cicatricial changes in its wall. 
time be responsible for rupture. The hypothesis proposed 
in 1868 by Charcot and Bouchard, who ascribed hemorrhage 
to the bursting of a miliary aneurism, was therefore received 
with widespread approval. Repeated investigation at first 
yielded little uniform information regarding the frequency, 
the character, or the origin of miliary aneurisms, but the 
situation has been recently clarified by Pick's new method 
of investigation (isolation of the smaller arteries about the 
hemorrhage by agitating the tissues in fluid). According 
to Pick and others (Eppinger, Ellis), some of the structures CAUSES OF HEMORRHAGE 
91 
to which bleeding has been referred are to be dismissed as 
false aneurisms, produced by distention of the perivascular 
lymph-spaces, and related in no way to the true aneurism. 
They are of traumatic origin, and those found in the neigh- 
borhood of cerebral hemorrhages are a result of this lesion 
rather than a cause (Unger). The larger hemorrhages, 
according to Pick, originate from aneurisms which are above 
miliary size and easily visible to the naked eye (Fig. 57), 
though they are sometimes due to the rupture of arterio- 
sclerotic vessels that are free from aneurism; the latter 
statement needs no explanation other than a reminder that 
the small arteries in the brain are often the seat of fatty 
degeneration in arteriosclerotic subjects (Marchand). 
Fig. 57.-Isolated aneurisms of small cerebral arteries (after Pick). 
While earlier authors referred some of the smaller 
aneurisms to degenerations other than arteriosclerosis, the 
experiments of Pick have shown that the larger ones are 
always an outcome of arteriosclerosis, which must therefore 
be acknowledged as an important factor in the pathogenesis 
of spontaneous cerebral hemorrhage. 
The relation between the two conditions is suggested 
by the frequency with which arteriosclerosis is discovered 
in the subjects of cerebral hemorrhage. Beside the arteries 
of the brain, the peripheral and larger vessels, as well as 
the aorta, are generally involved. Chronic nephritis is of 
frequent occurrence, particularly in the form of a more or 
less contracted granular kidney, and cardiac hypertrophy is 
then especially advanced, although seldom lacking even in 
the absence of renal lesions (Lowenfeld). This observation 92 
HEMORRHAGE INTO THE BRAIN 
explains the attitude of the clinicians, who see in heightened 
blood-pressure an important factor in the production of 
cerebral hemorrhage. 
It happens but rarely that the cause of apoplexy cannot 
be satisfactorily demonstrated at autopsy, for although the 
vessels at the base of the brain may not be arteriosclerotic, 
and the search for miliary aneurisms may miscarry, changes 
will be found at least in the remainder of the vascular 
system. 
Cerebral hemorrhage may be the result of causes other 
than those already reviewed, differing generally, however, 
in type and situation, as in the rare cases of cortical hemor- 
rhage attending sinus-thrombosis (Kaufmann). 
Traumatic hemorrhages, also, are chiefly confined to the 
cortex, and the meninges in the neighborhood of such lesions 
are accordingly always suffused with blood; removal of the 
inner membranes discloses foci of softening mottled with 
red, and extending a few millimetres into the cortex. Such 
lesions as these, which are apt to result from severe, local- 
ized trauma, sometimes occupy a portion of the cortex 
directly opposite the point at which the blow has been applied 
(centre coup), and are frequently more extensive in this 
location than in the immediate neighborhood of the injury; 
for example, if trauma has been received over the right 
frontal lobe, the lesions may be found in the left occipital 
region. Injury by centre coup is a result of sudden stop- 
page, by the unyielding bone on the opposite side of the 
skull, of the motion imparted to the cerebral mass. 
In many head injuries, hemorrhage takes place in the 
deeper lying structures of the brain, as when the displace- 
ment concentrates in a certain direction or against particu- 
larly resistant areas of the skull or the dura (Kocher). 
In their later stages, traumatic blood clots undergo the 
same transformation as the spontaneous. Cortical hemor- 
rhages sometimes leave only a yellowish stain and some 
slight cicatricial retraction of the cerebral surface, and COMMOTIO CEREBRI 
93 
shrinkage occurs in more extensive lesions, but cyst for- 
mation is rare. There is often a fusion between the involved 
portion of the cortex and the meninges. 
The shock accompanying head injuries may cause cere- 
bral damage even though the skull itself be not injured, and 
multiple capillary hemorrhages are often a result. This 
condition has been called commotio cerebri (concussion), 
but true concussion is not attended by hemorrhage. The. 
grave disturbance of cerebral function which follows concus- 
Fig. 58.-Aneurism of a vertebral artery (two-thirds natural size), a, ruptured, aneurism; b, 
right vertebral artery, of normal calibre. 
sion lias been referred to the presence of microscopic foci of 
degeneration, and the attempt has been made to support this 
hypothesis by experiments upon animals (Scagliosi, Bick- 
eles, Biidinger). Still, it is doubtful whether such changes 
represent the anatomical basis of commotio cerebri, since 
the symptoms point to a rapidly initiated and transitory 
paralysis of activity throughout the entire brain. Tilmann 
suggested as a cause the traction upon the boundary between 
gray and white matter which must necessarily follow sudden 
arrest of a blow or a fall, in consequence of the difference in 
their specific gravities. 94 
HEMORRHAGE INTO THE BRAIN 
Hemorrhages involving the meninges are also the result 
of either disease or traumatism. Small foci due to the 
hemorrhagic diathesis, infectious diseases, etc., may be dis- 
missed from consideration. Larger hemorrhages follow 
rupture of an aneurism in a basal artery (Fig. 58); in such 
cases a considerable area of the subarachnoid space is 
usually suffused, and the subdural space may contain fluid 
or clotted blood. The lesions which give rise to these hemor- 
Fig. 59.-Extradural hsematoma. 
rhages have no genetic connection, however, with the miliary 
or somewhat larger aneurisms previously described, and 
they are, in fact, much more apt to occur in the absence of 
arteriosclerosis. For some of them, no cause can be demon- 
strated, while others are embolic mycotic aneurisms in the 
sense of Ponfick and Eppinger-that is, the product of in- 
flammation and partial destruction of the vessel wall at the 
point of attachment of infectious emboli. Those of the 
latter group often accompany endocarditis (Simmonds). EXTRADURAL IDEM A TOMA 
95 
Traumatic hemorrhages may be purely intermeningeal, 
as in the case of injury to the pial veins, although they are 
usually localized elsewhere, a typical outcome of head in- 
juries being extradural haematoma (Fig. 59). The calvarium 
of the case illustrated was the seat of a linear fracture which 
started in the left parietal bone and extended toward the 
temporal and the base of the skull. Careful examination in 
such cases will usually disclose laceration of the middle 
meningeal artery and of that portion of the dura through 
Fig. 60.-Fracture of the vertex. 
which it courses, for it is this vessel which is generally the 
source of extradural bleeding. 
The fracture of the skull just described is only one ex- 
ample among many. Another is shown in Fig. 60; and 
although it would be impossible to consider all the varieties 
that may be encountered, fracture of the base, at least, 
merits description, since it often implicates the accessory 
sinuses. When the break is in the petrous portion of the 
temporal bone, the ethmoidal sinuses or the tympanic cavity 
are involved, a circumstance which explains the bleeding 96 
INTERNAL HEMORRHAGIC PACHYMENINGITIS 
from the nose or the ear which accompanies fracture at the 
base. 
Subdural hemorrhage, in which the blood lies between 
the dura and the pia, is to be distinguished from the extra- 
dural type just described. The blood is generally fresh, 
dark red, and only loosely clotted in cases which come to 
autopsy a short time after the injury, while later on it 
assumes a brownish hue from transformation of its coloring 
matter, and becomes partially organized, adhering to the 
inner surface of the dura as a membranous layer. Con- 
ditions like this are generally difficult to distinguish from 
internal hemorrhagic pachymeningitis, a spontaneous dis- 
ease which commences with the formation of a membrane on 
the inner dural surface, and leads secondarily to hemor- 
rhage. 
PACHYMENINGITIS CEREBRALIS INTERNA HEMORRHAGICA 
This disease is characterized by the deposition on the 
inner surface of the dura of a brownish, easily separable 
membrane, which sometimes shows evidences of fresh 
hemorrhage. In advanced cases, it consists of several 
layers, between which large blood-clots may be imprisoned 
(haematoma durae matris). Virchow referred the bleeding 
to newly-formed capillaries in an inflammatory membrane, 
and his authority was sufficient to cause general denial of 
the hypothesis that the membrane develops secondarily to 
the hemorrhage. Cases of the disease occurring in conse- 
quence of trauma were explained on the assumption that 
the hemorrhage merely furnished a stimulus to the develop- 
ment of pachymeningitis. 
In conjunction with my pupils, van Vleuten and Laurent, 
I have tried to reconcile the contradictory conceptions of this 
disease. According to our investigations, primary hemor- 
rhages, such as those following trauma, undergo organiza- 
tion and become closely adherent to the inner surface of the 
dura, resembling somewhat the membrane of pachymenin- 
gitis. A characteristic hyperplasia then involves the capil- ETIOLOGY 
97 
lary dural layer, producing a delicate external deposit com- 
posed of a network of large capillaries embedded in a fine 
and almost homogeneous connective-tissue stroma; this can 
be very easily separated from the dura. Although, in rare 
cases, such a membrane contains neither blood nor blood 
pigment (Jores, Laurent, Rossie), hemorrhage is the rule; 
as the resulting clots become organized, the differences be- 
tween traumatic cases and those of spontaneous origin 
gradually disappear, and a condition is produced which 
corresponds entirely with spontaneous hemorrhagic pachy- 
meningitis. 
In acute infectious diseases and in connection with the 
hemorrhagic diathesis, the inner surface of the dura mater 
often contains an exudative deposit; this is to be ascribed 
to a fibrinous-hemorrhagic inflammation of the dura, which 
terminates in thickening. The view of Ziegler and 
Melnikow-Raswedenkow, that it represents the first stage 
of pachymeningitis interna haeniorrhagica, is not only 
unproved but improbable as well. 
Spontaneous internal hemorrhagic pachymeningitis 
occurs in alcoholics, in connection with cerebral atrophy, in 
the neighborhood of dural tumors, etc. 
THROMBOSIS AND EMBOLISM IN THE CEREBRAL ARTERIES 
Returning- now to arteriosclerosis of the cerebral vessels, 
there remain to be described those cases in which thrombosis 
or embolism leads to closure of the lumen. The effect varies 
according to the vessel involved. Since the arteries at the 
base are in communication with one another through the 
circle of Willis, obstructions in this region can be compen- 
sated; except for this anastomosis, however, the arteries 
of the brain are end arteries, and their obliteration by throm- 
bosis or embolism is accordingly followed by necrosis. 
The middle cerebral artery is most frequently attacked. 
When stoppage occurs in its main stem it is the central 
ganglia, the internal capsule, and the adjacent parts of the 
medullary substance that suffer, the cortex being but little 
7 98 
THROMBOSIS AND EMBOLISM 
affected since the vessels which supply this area anastomose 
with neighboring arteries. Embolism and thrombosis of 
the anterior cerebral arteries are very rare. 
A focus of softening gradually becomes fluid toward the 
centre, and demarcated from the surrounding normal brain; 
it grows smaller by resorption, its contents become clearer, 
and the end product may be a cyst with watery contents. 
If the collateral circulation is insufficient, the lesion assumes 
a hemorrhagic color (red softening) which gradually be- 
comes yellow (yellow softening) through the transfor- 
mation of pigment and resorption. CHAPTER IX 
Aneurisms of the Large Arteries; Wounds and Lacera- 
tions of the Heart and the Aorta 
Figs. 61 and 62 reproduce a saccular aneurism of the 
ascending aorta, the latter showing the communication be- 
tween vessel and sac. This type is called asymmetrical 
to distinguish it from the symmetrical, in which the sac is 
uniformly distributed around the entire vessel. If there be 
no distinct pouch and dilatation involve a moderately long 
segment of the vessel, the aneurism is said to be cylindrical, 
or fusiform; there is no sharp distinction, however, between 
this condition and the slighter degree of enlargement which 
constitutes arteriectasis. The cirsoid aneurism, which is 
found most frequently in smaller arteries, is the product of 
dilatation of a considerable length of the vessel, which at the 
same time becomes tortuous. 
Saccular aneurisms, which are the most important, vary 
in size; in some cases, they are so small as to cause no dis- 
turbance of function, and constitute merely an incidental 
post-mortem finding (Fig. 65), while in others they attain 
the diameter of a man's head. Every aneurism becomes 
partially filled by laminated blood clots (thrombi), since 
abundant opportunity for their deposit is afforded both by 
alterations in the vessel wall and by retardation of the 
blood stream within the sac (Fig. 63). 
The thrombus may be so extensive as to fill the aneurism 
until the surface of the clot is level with the interior of the 
vessel wall (Fig. 64), and such an event may be described 
as spontaneous cure. Healing is sometimes effected in 
smaller arteries by total thrombotic closure of the vessel as 
far as its next branch; the aneurismal portion is thus elim- 
inated, and a collateral circulation is set up. 
It is more normal for an aneurism to increase gradually 
ANEURISMS 
99 100 
ANEURISMS OF LARGE ARTERIES 
in size in spite of partial thrombosis, on account of the pres- 
sure exerted by the blood stream, and the encroachment of 
the growing sac is so irresistible as to compress the neigh- 
boring soft parts and even to erode bone. The little saccular 
Fra. 61.-Aneurism of the ascending aorta, perforating the sternum; anterior view (one- 
half natural size), a, aneurismal sac; b, sternum; c, transverse section through the left 
clavicle. 
aneurisms which sometimes affect the sinuses of Valsalva 
may compromise the right auricle by pressure, or involve 
the superior vena cava so seriously as to produce constant 
and extreme cyanosis of the face, as in a case of my own CONSEQUENCES 
101 
(Fig. 65). Branches of the aorta, particularly the carotid 
and the subclavian arteries, are often diminished in calibre 
by aneurisms of the arch. 
Compression of the trachea, the large bronchi, or the 
oesophagus, is relatively frequent, and sometimes severe 
Fig. 62.-Aneurism of the ascending aorta; same case as Fig. 61, seen from the side (one- 
half natural size), a, passage from the ascending aorta into the aneurism; b, aneurismal sac, 
projecting beyond the sternum; c, transverse section of the third rib on the left side; d, trans- 
verse section through the left clavicle. 
enough to cause suffocation, while the lungs, particularly 
the left, may be seriously compromised. I have seen a large 
aneurism of the aortic arch with several secondary pouches, 
one of which had caused atrophy of the wall in the left 102 
ANEURISMS OF LARGE ARTERIES 
bronchus with total closure and consequent atelectasis, while 
another had perforated into the oesophagus. Pressure upon 
the left recurrent laryngeal nerve is not uncommon, since 
this encircles the arch of the aorta; the nerve on the right 
Fig. 63.-Aneurism of the ascending aorta; same case as Fig. 61, sectioned (one-half 
natural size), a, sharp boundary between vessel and aneurism; b, thin wall of connective 
tissue; c, thrombotic lining of the aneurismal sac; d, costal cartilage cut transversely. 
side, however, winds about the subclavian artery, and hence 
is but rarely involved. 
Large aneurisms of the ascending aorta produce pressure 
atrophy of the ribs, the sternum, or the subclavian artery, RUPTURE OF AN ANEURISM 
103 
and the sac may even penetrate the bony structures and 
project under the skin of the breast or the neck (Fig. 61). 
Aneurisms of the descending aorta usually erode the verte- 
brae; the intervertebral cartilages, however, are less affected 
and remain as projections between the hollows in the bones 
(Fig. 66). Pressure upon the intercostal nerves, with its 
attendant neuralgia, is 
a frequent consequence. 
Rupture of an aneu- 
rism generally occurs at 
a part of the wall that 
has become thinned out, 
or partially necrotic 
(v. Schrotter). Hemor- 
rhage rarely occurs ex- 
ternally, the blood gen- 
erally escaping into the 
pericardial sac (in the 
case of aneurisms of 
the ascending aorta), 
the trachea, the bron- 
chi, the oesophagus, the 
lungs, or the pleura. I 
have seen a case in 
which it was confined 
to the posterior medi- 
astinum, dilating this 
space and compressing 
the lungs, and Buberl 
has described rupture 
into the mediastinum 
and extension of the extravasate upward along the oesoph- 
agus to the base of the skull, with constriction of both 
pharynx and larynx. 
Perforation into the pulmonary artery or the superior 
vena cava is rare, and there is said to exist but one instance 
of rupture into the right auricle (v. Schrotter). 
Fig. 64.-Spontaneous healing by thrombosis of 
an arteriosclerotic aneurism in the abdominal aorta 
(one-half natural size), a, thrombus entirely filling 
the aneurism; b, coeliac axis; c, superior mesenteric 
artery; d, arteriosclerotic changes; e, bifurcation of 
the aorta. 104 
ANEURISMS OF LARGE ARTERIES 
The aorta usually contains other more or less pronounced 
lesions in addition to the aneurism, which are of importance 
on account of their etiological significance. Because aneu- 
risms are frequently associated with arteriosclerosis, it was 
at one time almost universally believed that they are a 
Fig. 65.-Aneurism of a valsalvian sinus and multiple aneurisms of the ascending aorta (one- 
half natural size), a, passage into the aneurism; syphilitic aortitis at b and other points. 
product of this disease. The hypothesis, however, was not 
entirely satisfactory, partly because aneurisms are not in- 
frequently found in the presence of a negligible degree of 
arteriosclerosis, but particularly because a great many 
advanced cases of arterial disease are unaccompanied by 
aneurism. MESARTERITIS 
105 
Koster and his pupil Krafft attached great importance in 
the pathogenesis of aneurism to inflammatory foci in the 
media (mesarteritis), which cause destruction of the muscu- 
lature and the elastic fibres. The same condition, however, 
was described by Helmstedter and Manchot as laceration of 
the medial elastic fibres; 
upon this interpreta- 
tion rests the view, sus- 
tained by Eppinger also, 
that aneurism follows 
the traumatic rupture of 
some constituent of the 
vessel wall, particularly 
the elastic fibres. 
The work of Doble, 
which has been so ably 
supported by Heller, has 
materially illumined the 
situation. This author 
described an aortic le- 
sion similar to arterio- 
sclerosis and often asso- 
ciated with it, but dis- 
tinctly separable, never- 
theless. It is character- 
ized by retraction of the 
inner surface of the ves- 
sel wall, which is some- 
times so extensive that 
the entire endothelial 
lining is corrugated (Figs. 45 and 65). The media is 
destroyed and replaced by connective tissue infiltrated 
with small round cells (Fig. 67), and arranged about 
the vasa vasorum, which show an advanced degree of 
arteriosclerosis. The muscularis in the neighborhood of 
such foci is disorganized, and a particularly prominent find- 
ing is destruction of the elastic lamellae, which have either 
Fig. 66.-Erosion of vertebra by the pressure of 
an aneurism (two-thirds natural size). On the 
right side of the illustration, portions of the ribs, 
covered by pleura. 106 
ANEURISMS OF LARGE ARTERIES 
totally disappeared or lie in fragments within the affected 
area (Fig. 67), terminating abruptly at the edges of the 
lesion as though they had been torn through. In advanced 
stages of the process, portions of the media sometimes dis- 
appear entirely. As Dohle and Heller found these changes 
in syphilitic subjects, they called the disease aortitis luetica. 
It was not immediately accepted on all sides as a separate 
Fig. 67.-Syphilitic aortitis (slightly enlarged), a, thickened intima; fa, media;c, adventitia; 
d, depression on the innersurtace of the vessel; e, connective tissue in the media, infiltrated with 
small cells (mesarteritis); f, remnants of elastic tissue and muscle in the mesarteritic areas. 
condition (see discussion of Straub's paper), but those 
authors who have devoted the greatest amount of thought to 
the problem (Benda, Heine, Chiari) have recently confirmed 
Dohle's observations. The lesion is due to the cicatrization 
of gummata (Benda) ; its earlier stages,in which gummatous 
infiltration of the aortic wall still persists, are rare and 
difficult to find, but they have been demonstrated by Benda, 
as well as by other earlier investigators. SYPHILITIC AORTITIS 
107 
This type of aortitis, the most frequent cause of aneu- 
rism, is localized by preference in the upper part of the 
vessel; it usually begins just above the valves, whence it 
spreads more or less toward the arch and the descending 
aorta, terminating at about the line of division between the 
thoracic and abdominal portions. Branches may be nar- 
rowed at the points where they issue from the main trunk, 
but the lesion shows no inclination to extend into them. 
Aneurisms are occasionally a product of other factors, 
such as arteriosclerosis or trauma. The more super- 
ficial arteries are, by their position, exposed to injuries 
of various sorts, which sometimes eventuate in aneurism; 
since the walls of the sac in such instances are composed 
chiefly of the surrounding connective tissue, these have been 
called false aneurisms to distinguish them from the spon- 
taneous variety, in which the pouch is said to consist at first 
of vessel wall. But Benda has pointed out that even in the 
true saccular aneurism, the pouch is not constituted simply 
by dilated wall, but is in part made up of a dissimilar tissue 
(the vascular callus of Manz) which, probably originating 
in the adventitia and the structures immediately external 
to it, bears at first the characteristics of young cicatricial 
tissue. The endothelium lining the aneurismal sac is, of 
course, a product of the vascular endothelium; not by the 
mere dilatation of this coat, however, does the interior of the 
pouch become clothed, but by its vigorous proliferation. 
The conception that a true arterial aneurism is purely the 
outcome of pathological stretching on the part of unaltered 
vascular tunics is therefore to be rejected, while, at the same 
time, the distinction between true and false aneurisms neces- 
sarily falls to the ground. Hence, an arterial aneurism is 
any cavity produced by mural changes, and at least tem- 
porarily in communication with the blood stream. 
According to Kallenberg and Heclinger, the walls of a 
traumatic aneurism are generally formed at first by the 
thrombus attending the injury, rather than from the connec- 
tive tissues about the vessel. 108 
ANEURISMS OF LARGE ARTERIES 
It is questionable whether the walls of large vessels, or 
single layers in them, can be torn by indirect violence and 
thus prepare the way for the development of an aneurism. 
A diseased aorta, to be sure, can be ruptured by indirect 
trauma, but though many authors have assumed that lacera- 
tion can be brought about in a normal arterial wall by the 
same factor, the hypothesis is not well supported by facts, 
and can apply only to exceptional cases. 
Certain aneurisms are called mycotic-embolic (Ponfick, 
Eppinger), because of the way in which they originate. 
According to the latter author, they follow destruction of 
the arterial coats in consequence of inflammatory processes 
which are set up by the lodgement of emboli containing 
microorganisms. 
Infectious inflammatory conditions like tuberculosis may 
cause an aneurism by destroying the vessel wall. This 
statement applies principally to the smaller arteries, the 
walls of which are sometimes involved by inflammation in 
contiguous structures (arrosion aneurism), as in the case 
of cavities of the lung, or ulcerative processes. 
It has long been believed that of all the processes ter- 
minating in aneurism the destruction of muscular and elas- 
tic elements is the most important, since the wall becomes so 
weakened as to bulge under the pressure to which it is 
subjected by the blood stream. It has been assumed, also, 
that the connective tissue which replaces contractile and 
elastic constituents is a weaker substance, unable to stand 
the strain of the circulation. To this hypothesis Benda has 
objected with perfect justice, that, as scar tissue is less 
expansible than the elastic elements, a cicatrized area 
should be more resistant to dilatation than the normal wall, 
and the fact that vascular injuries in animals are generally 
followed by the formation of a scar, but not by aneurism, 
is in perfect agreement with his view. Malkoff explained 
the absence of aneurism by the brief period during which 
the animals were under observation, but it may be replied 
that scar tissue at the suture-points in vessels transplanted ETIOLOGY 
109 
by Stich showed not the slightest dilatation, even after the 
lapse of a year. 
The experimental production of aneurism succeeds, 
however, if sudden and extensive damage be inflicted upon 
the more important mural layers, as in the experiments of 
Fabris, where widespread necrosis was produced by a caus- 
tic. B. Fischer attained the same end by introducing into 
the circulation substances which, like adrenalin and digalen, 
exert a toxic action upon the aortic wall and at the same 
time raise the blood-pressure. The aneurisms were found 
at points where the media had suffered such extensive and 
deep necrosis as to be entirely incapable of carrying out its 
function. 
In much the same way must those aneurisms develop in 
man which are based upon rapid inflammatory softening 
or traumatic destruction of the vascular wall, and it may 
well be inferred that some similar process is often respon- 
sible for large aneurisms in the aorta, now that the gum- 
matous stage of syphilitic aortitis has been demonstrated. 
There still remains, however, the problem of accounting for 
the fact that a considerable number of aortic aneurisms 
develop from mural cicatrices. It has been suggested by 
Benda that the rigidity of these scars causes them to be 
readily torn by the pressure of the blood, in consequence 
of which they become the basis of an aneurism; in this way 
he explained, also, the growth of connective tissue in the 
sac. It must be admitted that this hypothesis accords better 
than any other with the known facts, and that there does not 
exist a more satisfactory one with which to oppose it, 
although it can hardly be said to afford a final explanation 
for the development of an aneurism in association with 
cicatricial aortitis. 
Of other findings throughout the body in connection with 
aneurism, there is but little to be said. Embolism, as a result 
of thrombosis in the aneurismal sac, is rare. The heart may 
be unaffected, even in the presence of a large aneurism of 
the ascending aorta; in some cases, however, the left ven- 110 
WOUNDS AND LACERATIONS OF HEART 
tricle is hypertrophied (Marchand), and this is especially 
true of those in which syphilitic aortitis involves the aortic 
valves. Accordingly, cardiac hypertrophy more often 
accompanies cylindrical aneurisms in the first portion of the 
aorta than those of the sacculated type. 
Aneurisms of the pulmonary artery (Henschen) or its 
branches are generally cylindrical, and are nearly always 
a consequence of lues, in so far as they are not the product 
of other less frequent causes, or congenital in their origin 
(Henschen, Ploeger, Posselt). Thus, in Barth's case, which 
occurred in a syphilitic patient, there had taken place a 
fibrous degeneration of the media and adventitia which 
Barth compared with the lesions of syphilitic aortitis. 
WOUNDS AND LACERATIONS OF THE HEART AND THE AORTA 
Rupture of the aorta is usually due to severe trauma 
involving the thorax, but is sometimes produced by insignifi- 
cant pathological changes, as the following instance will 
show. 
A forty-five year old man, who had worked at his trade 
of stone mason in apparent good health, fell suddenly dead, 
and at autopsy 460 cubic centimetres of blood was found in 
the pericardial sac. In such a condition, which is called 
haematopericardium, or, less suitably, cardiac tamponade, 
the blood compresses both the venae cavae and the pulmonary 
veins, hindering and interrupting the return of blood to the 
heart, which therefore pumps itself empty (Rehn). The 
recent experimental work of Bode and Placzek has demon- 
strated that the excursion of the ventricles is diminished; 
if the pressure be removed, however, the heart's activity will 
be resumed, and herein lies the possibility of successful 
surgical intervention. 
The causes of haematopericardium are manifold. It is 
often an outcome of punctured or gunshot wounds of the 
heart, limited in rare instances to a coronary artery (B. 
Fischer), while additional etiological factors are perforation 
of an aneurism in a coronary artery, or spontaneous rupture 
of the heart. Rupture usually takes place at the site of an SPONTANEOUS RUPTURE OF AORTA 
111 
infarct, either recent or of sufficient age to have undergone 
softening (acute cardiac aneurism); it may be brought about 
also by gummatous myocarditis (Basett-Smith, Hueter), 
or by metastatic abscess. 
About a centimetre above the aortic valves in the case 
now under considera- 
tion, there was an 
oblique and somewhat 
irregular fissure about 
four centimetres in 
length, involving both 
intima and media, 
while the adventitia 
was elevated by a clot 
about one centimetre 
in diameter. Sponta- 
neous rupture of the 
aorta, another exam- 
ple of which is shown 
in Fig. 68, occurs al- 
most invariably at 
this site. 
Such tears usually 
occur in diseased ves- 
sels, although the le- 
sion is sometimes not 
especially striking 
upon gross examina- 
tion, as in the case 
now in question. In 
this instance, the per- 
ipheral arteries and 
the aorta were dilated, the enlargement of the latter vessel 
being especially pronounced in its ascending portion; its 
inner surface was smooth, on the whole, although areas of 
mild arteriosclerosis could be found, in which the degenera- 
tive stage preponderated. In regions corresponding to 
those where the intima was most noticeably damaged, the 
Fig. 68.-Spontaneous rupture in the ascending aorta 
(three-fifths natural size). All but a small portion of 
the heart muscle has been cut away. 112 
WOUNDS AND LACERATIONS OF HEART 
elastic lamellae of the media exhibited a few droplets of fat, 
and about the neighborhood of the laceration it contained 
a few microscopic tears. 
These findings correspond to those which have been 
described in other cases of aortic rupture (for bibliography, 
see Stern). Among recent authors, Bay has attributed 
Fig. 69.-Dissecting aneurism of the ascending aorta (after Busse). 
significance to the areas of calcification which he discovered 
in the immediate locality of tears, and has emphasized the 
importance of atrophic changes in the medial elastic tissue. 
None of the alterations just enumerated will completely 
explain laceration of the aorta, but the presence of such 
lesions can at least be accepted as evidence that the integrity 
and elasticity of the wall have been undermined. The appli- INTRAMURAL HAEMATOMA 
113 
cation of some such force as physical exertion or over- 
extension of the spinal column appears to be necessary; it 
seems hardly probable, however, that a normal aorta could 
be torn otherwise than by violent and direct trauma, and 
cases like that of Busse will hardly survive critical exam- 
ination. Cardiac hypertrophy appears to act as a predis- 
posing cause, by subjecting the aorta to greater pressure, 
and this is certainly true when it is combined with stenosis 
of the aortic arch. In such cases, the ascending aorta may 
be the seat of an aneurism (Sella). 
Lacerations of the aorta generally do not involve all the 
coats, and the blood penetrates between the various layers, 
giving rise to an intramural haematoma; the adventitia in 
particular is often elevated for a considerable distance. In 
the case under description, the blood clot extended down- 
ward to the commencement of the descending aorta and 
upward along the subclavian and carotid arteries for a short 
space, but it sometimes happens that the entire aorta is 
ensheathed down to, or even beyond, its bifurcation. 
Conditions in the vessel wall generally divide rupture 
into two stages, since the adventitia sometimes persists for 
a time after the other coats have been lacerated. When it 
does finally give way, the rent need not correspond to that 
in the inner and middle tunics either in size or in position, 
and as it does not tear at all in some cases, rupture of the 
aorta may be said occasionally to undergo spontaneous cure 
(E. Frankel, Lubenau, Camper). On the other hand, the 
hemorrhage separates only the intima, or this coat together 
with part of the media, and the blood contained between the 
mural layers may break through into the lumen further down 
the vessel (dissecting aneurism, Fig. 69). According to my 
own experience, at any rate, the intima in such cases is the 
seat of advanced degenerative arteriosclerotic changes, 
and this, or some similar condition, seems to favor detach- 
ment of the inner coat even without its being undermined 
by blood, since Babes and Mironescu found that the vessel 
wall beyond the limits of a dissecting aneurism separated 
into layers after the slightest handling (dissecting aortitis). 
8 CHAPTER X 
Embolic Processes in the Lungs 
A glance at a conventional schema of the circulation 
(Fig. 70) will suffice to show that emboli originating in the 
peripheral veins pass (excluding from consideration the 
portal circulation) into one of the venae cavae and are carried 
through the right heart, which usually opposes no hindrance 
to their passage, into the pulmonary artery. 
An exception to this rule is the rare paradoxical embolus, 
which reaches the general circulation through a patent fora- 
men ovale or a defect in the interventricular septum. 
The lungs, therefore, are seriously exposed to attack by 
emboli from the venous system, and examples of their vul- 
nerability are afforded not only by embolism in its more 
restricted sense, but by the occurrence in them of metas- 
tases from tumors or tuberculous lesions, by the deposition 
of placental cells in eclampsia, and by fat embolism. 
Fat embolism occurs after injury to a part of the body 
containing adipose tissue, and most frequently after frac- 
ture of a bone, contusion of the marrow being its most fre- 
quent cause in Ribbert's estimation; according to the same 
author, simple concussion may suffice. The lung is hyper- 
aemic and somewhat oedematous, and its capillaries contain 
fat (Fig. 71), sometimes in such large amount as to inter- 
fere with the circulation and cause death. Some of the 
fat may escape from the pulmonary circulation and reach 
the brain and kidneys. 
The lodgement of venous thrombi in the lung-pulmo- 
nary embolism in its more restricted sense-is a highly sig- 
nificant occurrence. Fig. 72 shows the process in its highest 
degree, the lumen of the pulmonary artery being almost 
entirely blocked by a clot which extends into and occludes 
both its right and left branches; sometimes the main trunk 
is free and only the right and left pulmonary arteries are 
114 EMBOLISM OF PULMONARY ARTERY 
115 
involved. Sudden death 
must necessarily be the out- 
come of such an interference 
with the flow of blood into 
the lungs, since all source 
of oxygen is immediately 
removed. 
It can sometimes be 
shown that embolism has 
taken place in two or more 
instalments, as when an 
occlusion is found in some 
of the smaller arteries 
within the lung in connec- 
tion with an entirely inde- 
pendent closure of the cor- 
responding pulmonary 
artery, or an old hemor- 
rhagic infarct with its em- 
bolus is discovered in one 
lung, and a fresh embolus 
of the pulmonary artery in 
the other. 
Closure of the right or 
left pulmonary artery is 
sometimes fatal when the 
lung on the opposite side is 
diseased. On the other hand, 
one of these vessels may be 
completely obliterated by 
an old, organized clot, and 
the corresponding lung still 
preserve its normal appear- 
ance, and even entire occlu- 
sion of the pulmonary artery itself may not be immedi- 
ately fatal (Hart). Preservation of the normal appearance 
of the lung in such cases Hart ascribed to the anastomosis 
Fig, 70.--Schema of the circulation. A, 
arteries of the lower, a, of the upper part of 
the body; LA, left, RA, right auricle; LV 
left, RV, right ventricle; PA, pulmonary 
artery; PV, pulmonary vein; Pf.A, portal 
vein; LV, hepatic vein; V.c ■ i., vena cava 
inferior; V. c. s., vena cava superior; K, capil- 
laries; KdJ, capillaries of the intestine; LbK, 
capillaries of the liver; LK, capillaries of the 
lungs. 116 
EMBOLIC PROCESSES IN THE LUNGS 
demonstrated by Kiittner between the bronchial and pul- 
monary arteries, whereby the former vessels are enabled to 
take over the function of the latter. Since part of the blood 
from the bronchial arteries may enter the pulmonary vein, 
according to Kiittner, although most of it flows through the 
bronchial veins into the azygos, Hart concluded that even 
functional substitution for the pulmonary arteries by the 
bronchials is a possibility. Naturally, if life is to be pre- 
served after total obliteration of the pulmonary artery, 
closure must occur slowly enough for the collateral circu- 
lation to become established, which can happen only when 
it results from an embolus enlarged 
by secondary thrombosis; in occlusion 
by pure embolism, obliteration of the 
vessel takes place too suddenly. 
In cases of stoppage of the pulmo- 
nary artery, it is usually easy to dem- 
onstrate that the plug lying in the ves- 
sel is a true embolus, since it can be 
distinguished from a post-mortem 
clot by its dry, inelastic nature; 
generally, too, it contains both red 
and gray portions. Furthermore, 
since emboli are casts of the vein 
in which they originate, they are of 
about the diameter of a lead pencil, and can occlude the 
much larger lumen of the pulmonary artery only by coiling 
and twisting into a mass (Fig. 72). They have no connec- 
tion with the wall of the artery, and easily drop out when the 
vessel is opened; finally, it is often possible to discover an 
area of fracture which affords evidence that they have been 
broken off from a thrombus. 
Pulmonary emboli are products of thrombosis in the 
veins of the peripheral circulation, coming generally from 
those of the lower half of the body and particularly from the 
femoral, the pelvic, or the inferior vena cava. Short veins 
produce emboli which are not sufficiently long to close en- 
Fig. 71.-Fat embolugin the 
lung (slightly enlarged). Fat 
stained black by fixation in 
osmic acid, a, alveolar wall; 
b, fat droplets in the capil- 
laries; c, fat in a larger vessel. THROMBOSIS 
117 
tirely the pulmonary artery, although in some instances, as 
in varices of the leg, the vesical and prostatic plexuses, the 
spermatic veins, or those of the parametrium, a vein may 
be the seat of a propagated thrombus which, upon reaching 
the larger venous trunk, becomes the source of a fatal 
embolus. 
Fig. 72.-Embolism of the pulmonary arteries (two-fifths natural size), a, embolus in 
right, b, in left pulmonary artery; c, arch of the aorta in cross-section; d, ascending aorta; e, 
inner surface of the pulmonary artery; /, right, g, left lung; h, heart; i, pericardium. 
In attempting to describe thrombosis, it is necessary to 
begin with a statement that the process cannot be directly 
compared with coagulation. The following paragraphs are 
based upon the investigations of Aschoff and his pupil 
Ferge, which have been of the greatest value in explaining 118 
EMBOLIC PROCESSES IN THE LUNGS 
the phenomena of thrombosis. The essential constituent of 
every autochthonous thrombus is a clear, colorless portion 
(white, or agglutination thrombus), which may exist alone; 
it bears surface markings indicative of its mesh-like skeleton 
of blood-platelets. Polymorphonuclear leucocytes range 
themselves along its trabeculae, but fresh thrombi contain 
no fibrin. When this white head-piece totally occludes the 
lumen of the vessel, there are added to it a red and white 
middle piece, and a red tail-piece (red, or coagulation throm- 
bus) which is often very extensive. Red thrombi are the 
result of coagulation induced by ferments set free upon 
the destruction of blood-platelets. The blood which con- 
tinues to flow for a time through the mesh of agglutinated 
platelets is gradually retarded, and its leucocytes accord- 
ingly reach the edge of the stream, where they adhere to 
the young thrombus; if movement become still slower, and 
finally cease, coagulation sets in. 
Since platelets can agglutinate in the blood only while 
it is circulating, the structure just described clearly distin- 
guishes a thrombus from a post-mortem clot. 
Slowing of the current is essential for the deposition of 
blood-platelets (Lubarsch, Ferge, Aschoff), and thrombi are 
accordingly formed where the way into the inferior vena 
cava is particularly difficult, or where eddies occur, as in the 
neighborhood of valves. The vulnerability of these regions 
is increased by such pathological conditions as changes in 
the chemical constitution of the blood, or in the agglutinative 
faculty of the platelets, but too little is known to permit any 
very definite statement to be made. An increase or decrease 
in the number of platelets may be influential, and, in the case 
of red thrombi, the amount of coagulating ferment contained 
in the blood. Changes in the vessel wall are not now consid- 
ered a very important etiological factor, since they do not 
occasion thrombosis in the absence of retardation of the 
circulation, as is shown by the relatively infrequent occur- 
rence of thrombi in the aorta of arteriosclerosis. 
As cardiac weakness is accompanied by an enfeebled cir- CAUSES OF THROMBOSIS 
119 
culation, it favors thrombosis (marasmic thrombi), usually 
in the femoral vein, while pressure by tumors or other patho- 
logical processes, or by mechanical agents like bandages, 
often slows the current sufficiently to cause thrombosis. 
Since the arterial current is not so easily retarded as the 
venous, thrombi occur in the arteries much less commonly 
than in the veins. 
The infectious diseases, such as wound infections, 
typhoid fever, and pneumonia, are an important and com- 
mon predisposing cause. The thrombi which accompany 
them may be confined to the inflammatory area, or occur in 
large veins remote from the seat of the infection; these dis- 
tant thrombi in important venous trunks may result from 
propagation of a thrombus already present in the infected 
area, or from extension of a thrombophlebitis, or they may 
develop spontaneously. According to Aschoff, those of inde- 
pendent origin are at first bland, becoming infected second- 
arily by bacteria imprisoned in them with the blood. It 
may be assumed that the infectious diseases initiate or 
strengthen the conditions necessary for thrombosis, and 
the same hypothesis will serve to explain those thrombi 
which sometimes supervene at a distance from an operation 
wound, and in the absence of infection; post-operative 
thrombosis is not necessarily a consequence of infection, 
as it was formerly believed to be. 
If the thrombotic source of an embolus be not large, only 
a medium-sized or small branch of the pulmonary artery 
suffers obliteration. Ribbert has expressed the opinion that 
plugs in the vessels of the lung are generally thrombi, rather 
than emboli, and that thrombosis does sometimes affect the 
branches of the pulmonary artery cannot be gainsaid; the 
question is, however, whether it takes place more frequently 
than embolism. Since stoppage of these vessels usually 
occurs in connection with thrombosis in the peripheral 
venous system (Lubarsch), and since the conditions for 
primary thrombosis in them are unfavorable, it seems more 
probable that their occlusion is brought about by small 120 
EMBOLIC PROCESSES IN THE LUNGS 
emboli which become enlarged by secondary thrombosis, a 
possibility that Ribbert did not neglect to suggest. 
Closure of the smaller arteries within the lung may take 
place without resulting infarction. If life be prolonged, the 
condition terminates in cicatricial obliteration, as in a case 
reported by Beneke, where nearly all the arteries of medium 
Fig. 73. -Schema of the sinuses of the dura mater and their relation to the petrous por- 
tion of the temporal bone (after Rauber-Kopsch). A, anterior fossa; B, middle fossa: C, 
posterior fossa; 1, cavernous sinus; 2, circular sinus (Ridley's sinus); 3, superior petrosal sinus; 
4, inferior petrosal sinus; 5, transverse, or basilar sinus; 6, lateral sinus at its transition into the 
sigmoid sinus; 7, torcular herophili; 8, occipital sinus; 9, marginal sinus; anterior to 8, and pos- 
terior to 5, communication with the spinal veins. 
calibre were effaced by white cicatrices which were without 
doubt the remains of organized emboli. Hemorrhagic in- 
farction generally occurs, as has already been stated during 
the discussion of endocarditis, when circulatory disturb- 
ances involve the lung, although there is an additional factor 
which favors its production-the deposition of a septic 
embolus. SINUS-THROMBOSIS 
121 
Small hemorrhagic infarcts are not infrequently found 
in the lung, each containing a yellow focus of thickish pus 
at its centre and originating, as a rule, in thrombosis of 
small veins in an inflammatory area. According to Aschoff, 
the thrombophlebitis which occurs in these veins is often 
secondary, existing thrombi becoming infected and trans- 
ferring the process to the vessel wall, as in the case of the 
puerperal uterus. On the other hand, infection may attack 
the wall from without (primary phlebitis), thrombosis be- 
ing then a secondary event, as in sinus-thrombosis. This 
very frequent source of small pulmonary emboli results from 
the extension of a purulent inflammation in the internal ear 
to the wall of the lateral sinus (Fig. 73), or from thrombo- 
phlebitis in the petrosal sinus or the upper part of the bulbus 
venae jugularis (Leutert). It is assumed by otologists 
(Korner) that sinus-thrombosis may be caused, also, by the 
absorption of infectious material from a mastoid abscess 
into the small veins of the bone (osteophlebitic pyaemia), 
although proof of their contention is lacking. 
Sinus-thrombosis which is not otogenic in origin affects 
chiefly the longitudinal sinus, and is generally the product 
of infectious processes in its neighborhood. 
Multiple infected infarcts lead to pyaemia, and death is 
usually determined by general infection. In the case of 
isolated lesions, however, life may be spared long enough 
for secondary conditions to ensue. Thus necrosis of the 
infarct may set in, terminating in gangrene of the lung from 
the presence of aspirated organisms, while pleuritis or 
empyema is sometimes a consequence. Hence empyema 
can sometimes be traced back by careful examination to past 
thrombosis in the peripheral veins. CHAPTER XI 
Intestinal Infarction; Thrombosis of the Portal Vein; 
Pylephlebitis 
A segment of small intestine and its corresponding 
mesentery, when both are the seat of hemorrhagic infarc- 
tion, are swollen and blnish-red in color. The most frequent 
cause of this disorder is embolism or thrombosis of the 
superior mesenteric artery or one of its principal branches, 
though it is sometimes brought about by closure of the 
mesenteric veins, and the changes which follow vascular 
obstruction are essentially similar in their etiology to anae- 
mic or hemorrhagic infarcts in other organs; the course of 
events in the intestine, however, cannot be arranged in a 
simple scheme. Both the arteries and the veins of the 
mesentery anastomose so freely that it is hard to under- 
stand how their closure can disorder the circulation; but 
though the mesenteric arteries are not end arteries in the 
anatomical sense, Litten has concluded that the superior 
mesenteric is functionally an end artery, since a collateral 
circulation appears in animals after its ligation only when 
the blood-pressure is unusually high. Faber referred 
hemorrhagic infarction to a regurgitant flow from the portal 
vein. 
The problem is made more difficult by the fact that anae- 
mic gangrene, instead of hemorrhagic infarction, is often 
an outcome of the closure of mesenteric vessels, the affected 
loop being then soft, with a dull surface, and of a pale dirty 
gray or grayish-yellow hue. Sprengel, who drew a sharp 
etiological distinction between these two conditions, ascribed 
anaemic gangrene to closure of both the arteries and veins 
of the affected intestinal segment. His pupil Niederstein 
recognized four separate lesions-hemorrhagic infarction, 
anaemic infarction, hemorrhagic gangrene, and anaemic gan- 
grene-and reported the production of all of them in 
122 THROMBOSIS OF MESENTERIC ARTERY 
123 
animals. Marek, however, was unable to agree with these 
results, and expressed the opinion that Niederstein's classi- 
fication could be supported neither from a pathogenetic nor 
an anatomical standpoint. Still other investigators (Bolog- 
nesi, Merkel, Josselin de Jong) have busied themselves 
with this problem, but the mechanism and outcome of 
circulatory disturbances in the domain of the mesenteric 
vessels remains a riddle in spite of their efforts. 
The length of intestine which is affected depends upon 
the area supplied by the occluded vessel. When large chan- 
nels are involved it may be very extensive, as in the case 
reported by Saxer, where the portal vein with all its tribu- 
taries and branches was thrombosed; in this instance the 
entire small intestine had undergone infarction. Oblitera- 
tion of the inferior mesenteric artery, which supplies the 
descending colon and the sigmoid flexure, does not usually 
cause infarction, because this vessel anastomoses freely with 
the superior mesenteric; in the few instances that have been 
reported (for bibliography see Merkel), the establishment 
of a collateral circulation had been interfered with by arte- 
rial disease or other circumstances. Merkel has described a 
case in which both mesenteric arteries were closed by 
thrombosis. 
The contents of an infarcted intestine are bloody, the 
wall cedematous and hemorrhagic, the mucous membrane 
reddish black and sometimes ulcerated, while the peritoneal 
surface is somewhat dull and covered with a delicate layer 
of fibrin; in the abdominal cavity there may be a small 
amount of blood-tinged fluid. These findings indicate plainly 
enough that the ultimate termination of intestinal infarction 
is necrosis and peritonitis, for even in the absence of per- 
foration the wall of the affected segment is permeable for 
bacteria. 
I once encountered an example of resolution, an outcome 
which may occasionally ensue if the occluded vessel again 
become patent. According to the clinical report, there had 
been a sudden intestinal hemorrhage many months pre- 124 
INTESTINAL INFARCTION 
viously, which was initiated by pain and severe general 
symptoms and which ceased entirely after the lapse of a few 
days; autopsy disclosed an organized parietal venous throm- 
bus. Bolognesi, also, has reported a case. 
Emboli of the superior mesenteric artery and its 
branches have their source in lesions of the heart or the great 
Fig. 74.-Schema of the portal vein and its tributaries (after Lenhartz). V.p., portal 
vein; V .1., splenic vein; V.j., jejunal vein; V.h., hemorrhoidal veins; V.m.i., inferior mesen- 
teric vein; V.c.d., vena colica dextra; V.c.s., vena colica sinistra. 
vessels, while those of the superior mesenteric vein and its 
tributaries are of variable etiology, accompanying the infec- 
tious diseases, for example, or inflammatory processes in 
the intestine. In a case recently seen, there was a thrombus 
in one of the tributaries of the superior mesenteric vein, and 
this was prolonged into the main trunk, although there it 
was parietal rather than obstructing. The portal vein (Fig. 
74) was entirely occluded by a thrombus which, since it was CAUSES OF PORTAL THROMBOSIS 
125 
grayish-brown in color and somewhat adherent to the wall, 
must have been the older of the two; the former, therefore, 
was one of those mesenteric thrombi so often secondary 
to portal thrombosis. 
THROMBOSIS OF THE PORTAL VEIN 
Naturally a reverse condition may be encountered, in 
which thrombosis of the portal vein is secondary to occlusion 
of some of its tributary vessels. Thus I have had pub- 
lished an instructive case of Loeb's, where it accompanied a 
thrombus in the splenic, which could be traced to infarction 
of the spleen from a chronic cardiac lesion. Lissauer has 
recorded three cases of secondary portal thrombosis follow- 
ing obliteration of the splenic vein, produced in one instance 
by a necrotic infarct in the spleen and in the others by 
chronic inflammation of the capsule of this organ. Similar 
examples may be found among those reported by Josselin de 
Jong. 
Portal thrombosis is due in some cases to pressure 
by tumors in the liver, the pancreas, the intestine, or the 
omentum, and it is very frequently caused by masses of 
carcinomatous or tuberculous lymph-nodes at the hilus of the 
liver. In a second group of cases, it is the product of circu- 
latory derangement in the liver; hence it sometimes accom- 
panies advanced cirrhosis. Although it used to be taught, 
conversely, that hepatic cirrhosis may be secondary to portal 
thrombosis, it is now believed that closure of the portal 
vein does not produce any very serious effect upon the liver. 
This organ usually shows no great change, and it is there- 
fore assumed that the hepatic artery is able to take over the 
function of the portal vein. Nevertheless, atrophy of the 
liver is not infrequently encountered in cases where throm- 
bosis of this vein has persisted for a long time. In a third 
and important group, where the condition is, to a certain 
extent, independent, as contrasted with the first two, in 
which it is often a mere complication setting in shortly 126 
THROMBOSIS OF THE PORTAL VEIN 
before death, the etiology of thrombosis is not easy to ascer- 
tain. Chief among the hypotheses that have been advanced 
is that which would ascribe it to mural changes in the portal 
vein. Borrmann has suggested that phlebosclerosis, a lesion 
analogous to arteriosclerosis, may be the primary cause, sus- 
taining this belief by his own investigations and his interpre- 
tation of the cases already reported, while Simmonds has 
recently adopted a similar attitude. Saxer has disputed the 
suggestion, however, on the ground that the anatomical data 
are insufficient, and it must be confessed that I agree with 
him; for if a sclerosis of the veins analogous to that which 
attacks the arteries exist at all, it never reaches an advanced 
stage, and it is well known that thrombi occur in connection 
with arteriosclerosis only after the vessel wall has under- 
gone considerable alteration. My own view coincides with 
that which Loeb has expressed-that the propagation of 
thrombi from tributaries of the portal vein into the main 
trunk of the vessel may be more frequent than is generally 
supposed, and that many cases of apparent spontaneous 
thrombosis of the portal vein may be thus explained. 
Attention has recently been directed to the influence of 
trauma. Thus Heller has reported a case of portal throm- 
bosis following about two years after an injury, and similar 
examples have been cited by Schmorl and Ponfick. 
Portal thrombosis of any considerable duration is accom- 
panied by such signs of a congested portal circulation as 
enlargement of the spleen, ascites, and a dilatation of col- 
lateral veins corresponding in general with that which ac- 
companies cirrhosis of the liver. 
Evidence of recovery from thrombosis of the portal vein 
is occasionally encountered at autopsy. The obliterated 
vessel is generally recognizable in microscopic sections only 
by its elastic fibres; the organized thrombus is canalized, 
and the small veins surrounding the portal in the hepato- 
duodenal ligament are so widely dilated as to give the tissue 
a cavernous structure (Heller, Loeb, Pick, Verse). Re- 
markable, although still inexplicable, is the fact that these PYLEPHLEBITIS 
127 
collateral channels do not exist in connection with hepatic 
cirrhosis (Pick). Since it is possible for other collateral 
vessels, particularly the cardial and the oesophageal veins, 
to undergo dilatation after the portal has been obliterated 
for a time, there can be no doubt that its closure may be 
entirely compensated. 
PYLEPHLEBITIS 
Thrombi in the portal vein sometimes suppurate and 
cause thrombophlebitis, and in severe cases the branches of 
this vessel are filled with pus for some distance into the liver 
(pylephlebitis). The underlying cause is always thrombo- 
phlebitis in a tributary of the portal vein, and this lesion, in 
its turn, is a result of inflammatory processes in the intes- 
tinal tract. The most important of these is appendicitis, 
although it should be remembered that both the appendicular 
lesion and the thrombophlebitis in smaller portal tributaries, 
may have undergone resolution by the time pylephlebitis 
is discovered at autopsy. 
Pylephlebitis is one of the manifold causes of multiple 
abscess of the liver, in which it almost invariably terminates. CHAPTER XII 
Septicaemia and Pyaemia; Osteomyelitis; Puerperal 
Endometritis ; Meningitis 
SEPTICAEMIA AND PYAEMIA 
The findings in the following case of septicaemia, where 
death followed nine days after the infliction of a contused 
wound, give a very good idea of the nature of this process. 
On the dorsal surface of the proximal phalanx of the ring 
finger there was a wound about four centimetres in length 
which contained within its depths a reddish-gray and rather 
thick fluid. The finger and the back of the hand were 
swollen, and a purulent fluid welled up from the subcu- 
taneous tissues after incision; this condition is known as 
phlegmon. The spleen was enlarged and congested, the 
left pleural cavity contained two or three hundred cubic 
centimetres of cloudy fluid, and the surface of the upper 
lobe of the left lung was covered with a fibrinous deposit. 
Through the inflamed pleura there showed a dull grayish- 
yellow area about as large as the palm of the hand, which, 
upon section, proved to be an area of pneumonia under- 
going purulent softening; this was the cause of the pleuritis. 
The relationship of these lesions in the lungs and pleura 
to the primary wound was demonstrated by bacteriological 
examination. Streptococci were recovered from the pneu- 
monic area, the pleural exudate, the pus from the wound, 
and the heart's blood, and this, in connection with the en- 
larged spleen, proved that septicaemia was the cause of 
death; the slight inflammation in the lung and the pleura 
would hardly suffice to explain the fatal issue. 
The work of Lenhartz and Simmonds has shown that 
bacteriological examination of the blood after death affords 
a thoroughly reliable indication of its antemortem bacterial 
content, unless decomposition be too far advanced. Micro- 
organisms can be even more readily demonstrated post- 
128 BACTEREMIA AND TOXINEMIA 
129 
mortem, because the decreased resistance of the body as 
the end approaches permits them to enter the blood in 
greater number, and, perhaps, to multiply there. 
The fact that pus-forming cocci can be recovered from 
the blood after death from septicaemia is the more valuable, 
since post-mortem examination often brings to light noth- 
ing but a primary wound, enlargement of the spleen, and 
parenchymatous degeneration in the heart and the kidneys. 
In some cases, the primary wound cannot be discovered 
on account of its minute size, or because it has already 
healed, and the diagnosis is made from splenic enlargement, 
multiple hemorrhages into the serous membranes, and the 
presence of pus-forming microorganisms in the blood. 
Leube called this condition cryptogenic septicaemia. 
Lymph-nodes in the neighborhood of the primary wound 
are not always able to hold back the infective virus, but it is 
not permissible to conclude, as Notzel has done, that they 
exert no protective action at all; Ribbert, indeed, has but 
recently reiterated their significance as filters. The regional 
lymph-nodes are usually enlarged in suppurative processes 
involving the skin, the subcutaneous tissue, or the muscles, 
but these structures do not afford absolute protection, and 
they may themselves succumb and break down into 
abscesses; in such cases the infection is apt to spread 
beyond them. 
The term septicaemia originally denoted absorption into 
the blood of the products of putrefaction, a condition which 
was believed to be related to the suppurative processes, but 
later it became customary to define septicaemia as a disease 
in which bacteria enter the blood and multiply there without 
producing metastatic lesions. At the present time, the 
term may be said to embrace two conditions-bacteraemia, 
in which organisms attain the blood stream and there pro- 
liferate, and toxinaemia, in which the symptoms are pro- 
duced by toxins circulating in the blood without the bac- 
teria themselves necessarily being present in it. Every 
bacteraemia in which pathogenic organisms are concerned 
9 130 
SEPTICAEMIA AND PYAEMIA 
is at the same time a toxinaemia (v. Kahlden), but a pure 
toxinaemia is not at all a rare condition, according to Len- 
liartz and Simmonds, who found that bacteria are not infre- 
quently absent from the blood in general infections like 
puerperal endometritis. 
The development of multiple suppurative foci through- 
out the body following the deposition of infected emboli or 
masses of bacteria, constitutes pyaemia. It cannot be 
sharply distinguished from septicaemia, because its under- 
lying cause is bacteraemia, and because it is almost invari- 
ably associated with toxinaemia. Still, it is almost always 
caused by staphylococci, while septicaemia, on the other 
hand, is usually a result of infection with streptococci. 
A good example of isolated abscess formation is fur- 
nished by suppurative encephalitis. Abscess of the brain 
may develop either by the extension of an inflammatory 
process in the adjoining tissues or by metastasis. The 
former type is sometimes referable to skull injuries, and 
very frequently to inflammation in the middle ear, while the 
metastatic variety (Fig. 75) has its origin most often in 
bronchiectasis, ulcerative bronchitis due to foreign bodies, 
or suppurative bronchial lymphadenitis. Although abscesses 
produced by the spread of a suppurative lesion lie in the 
immediate vicinity of their primary focus, those of the meta- 
static type have the most variable localization, being found 
in almost any part of the brain; the latter are sometimes 
multiple. 
The pus of a cerebral abscess is rather thick, and of a 
distinctly green hue. The surrounding tissue undergoes 
softening at first, but the lesion finally becomes walled off by 
reactive inflammation. 
Abscesses in the brain may be followed by suppurative 
meningitis; they may perforate into the ventricles, or 
determine a fatal issue by exerting pressure upon impor- 
tant centres. 
The case of pyaemia now to be described will illustrate 
generalized abscess formation. The lungs were punctuated GENERALIZED ABSCESS FORMATION 
131 
with innumerable small abscesses, most of which were en- 
closed by a smooth, yellowish wall, and at the points where 
these lesions approached the surface the pleura was cov- 
ered by a fibrinous exudate. A similar deposit overlay the 
greater portion of the heart, and the pericardial cavity con- 
tained a large amount of turbid fluid. The fibrinous exudate 
was particularly abundant at one point on the posterior 
Fig. 75.-Multiple metastatic cerebral abscesses (natural size). 132 
SEPTICEMIA AND PYEMIA 
aspect of the left ventricle, where there was discovered the 
myocardial abscess that had given rise to the pericarditis. 
It may be remarked in passing that, with the exception of 
the tuberculous variety, both fibrinous and suppurative peri- 
carditis are always secondary, resulting either from the 
extension of an adjacent inflammation, or as a result of 
metastasis. 
The kidneys contained a great many small suppurative 
foci, scattered over the surface and throughout the cortex, 
each surrounded by a red halo (Fig. 76). These renal 
abscesses, which are very 
common in pyaemia, are not 
all the product of embolism; 
some of them accompany the 
elimination of bacteria 
through the kidney. Accord- 
ing to Rolly, the excretion of 
microorganisms cannot be re- 
garded as a physiological at- 
tempt on the part of the kid- 
ney to relieve the blood of its 
infection, as Lubarsch has 
already explained, since the 
number eliminated in the 
urine is much too small in 
comparison with the number circulating in the blood. It 
is more probable that a small number of organisms escape 
incidentally during the filtration of fluid through the glomer- 
ular tufts, and, in Folly's opinion, it seems to make little 
difference whether the kidney be abnormal or not. Most 
observers, on the contrary, hold that only damaged capil- 
laries will permit the passage of bacteria, partly because 
these do not appear in the urine until several hours after 
their experimental injection into the blood stream, and 
partly because slight lesions of the renal parenchyma 
have usually been discoverable (for bibliography, see 
Jores). 
Fig. 76.- Multiple metastatic abscesses in the 
kidney (natural size). ACUTE SUPPURATIVE OSTEOMYELITIS 
133 
The cause of the pyaemia in the case now under con- 
sideration was osteomyelitis involving the left tibia. 
ACUTE SUPPURATIVE OSTEOMYELITIS 
This disease is an inflammation of the deeper regions of 
bone. The marrow is of a greenish-yellow color in conse- 
quence of purulent infiltration, but suppurative liquefaction 
generally involves only small areas. The process leads to 
circumscribed nutritional derangement when it extends, as 
it usually does, into the haversian canals; in such an event, 
more or less extensive areas of bone may be destroyed 
by suppurative periostitis. Rarefying ostitis (Schmidt) 
separates the sequestrum, as the necrotic fragment is called, 
and it becomes surrounded by a shell of bone (involucrum) 
produced in consequence of ossifying periostitis. As the 
involucrum is pierced by a number of apertures, pus is 
discharged into the surrounding tissues, involving them in 
the inflammation and gradually working its way toward 
the surface of the body, where it escapes through a fistulous 
opening. If large areas of periosteum have been destroyed, 
the involucrum will be incomplete; on the other hand, 
chronic productive ostitis may supervene, with eburnation 
and closure of the marrow cavity as its final outcome. 
It has been shown that the inoculation of staphylococci 
into the circulation of young rabbits and guinea-pigs is 
followed by the appearance of purulent foci in the bone- 
marrow ; generally, however, abscesses occur simultaneously 
throughout the rest of the body. A phlegmonous process 
will result if inflammation be promoted in the marrow before 
the bacteria are inoculated (Lexer), or if it be subjected to 
trauma (Ullmann); thus, the marrow must be made a point 
of least resistance. Osteomyelitis in man, according to 
Lexer, follows the settling of a large number of virulent 
organisms in the marrow or the development of colonies of 
staphylococci within the smallest vessels of the bone, com- 
bined, perhaps, with trauma. 134 
PUERPERAL ENDOMETRITIS 
The disease is most common between the eighth and 
seventeenth years of life, and attacks by preference the long 
bones. The epiphysis is less frequently involved than the 
diaphysis, though sometimes attacked secondarily by lesions 
in the latter situation. The joints are often affected, either 
by metastases or by extension, and some of the cases of 
serous arthritis seem to be due to the toxins of this disease. 
Rupture of a periostitic abscess may be productive of a 
widespread inflammatory process in the adjoining soft parts, 
and osteomyelitis in the ribs or the skull-bones may accord- 
ingly be a cause of suppurative pleuritis or meningitis 
respectively. 
By far the most frequent etiological agent of acute osteo- 
myelitis is the Staphylococcus pyogenes aureus, although 
the disorder may follow infection with the streptococcus, 
the pneumococcus, the gonococcus, the colon bacillus, the 
typhoid bacillus, or the bacillus of pneumonia. 
PUERPERAL ENDOMETRITIS 
This disease, which is often the outcome of infection 
with staphylococci or streptococci, is another frequent cause 
of septicaemia and pyaemia. The interior of the uterus, par- 
ticularly the placental site (Fig. 77), is covered with a 
grayish-yellow membrane, and there may be more or less 
extensive gangrene of the endometrium and the subjacent 
parts. Sometimes there are discovered cervical or vaginal 
lacerations, covered by a dirty deposit and surrounded by 
inflammatory infiltration. 
In septicaemia following endometritis, the genital tract 
may show no important alterations save those in the uterus; 
very often, however, the path taken by the infection can 
be traced outward from this organ. If it has travelled by 
the lymphatics, pus will be found in the lymph-channels of 
the parametrium (acute septic lymphangeitis); if, on the 
other hand, the infection has followed the veins, these vessels THROMBOPHLEBITIS 
135 
will contain grayish-red thrombi with suppurating areas 
(septic thrombophlebitis). 
Fig. 77.-Puerperal septic endometritis (one-half natural size). Membranous deposit on 
the inner surface of the enlarged uterus. Area of placental attachment at the fundus. Vaginal 
lacerations. 
Thrombophlebitis is due to secondary infection of 
physiological thrombi in the uterine veins at the placental 
site by streptococci, which enter from the interior surface 136 
PUERPERAL ENDOMETRITIS 
of the uterus (Duffeck), and the resulting infection of the 
vessel wall subsequently extends and produces further 
thrombosis (Aschoff). Thus the process extends, and it can 
often be followed from the veins of the parametrium into the 
ovarian veins (Fig. 78), one or both of which may be par- 
Fig. 78.-Schema of the veins of the female genital organs (after Lenhartz). R., kidney; 
V.c., vena cava; V.s.d., right ovarian vein; V.s.s., left ovarian vein; V .i., iliac vein; V.ft., 
hypogastric vein; U., uterus; T, tube; O., ovary; L.r., round ligament; P.u., uterine plexus. 
tially or completely occluded. Thrombophlebitis in the ves- 
sels mentioned, but particularly in the ovarian veins, is 
usually productive of a large number of emboli; hence, sup- 
purating infarcts are found in the lungs, and multiple 
abscesses in these and other organs. 
Puerperal lymphangeitis may give rise to pyaemia, or EMPHYSEMATOUS GANGRENE 
137 
lead to suppurative peritonitis through extension of the 
inflammation into the lymph-channels of the peritoneum. 
The latter condition may be caused, also, by progression of 
the uterine inflammation along the fallopian tube; in such 
cases the infection may attack the peritoneal cavity directly, 
or suppurative oophoritis may be interposed. In the latter 
event, the ovary will be the seat of an abscess which, even 
without perforating, may be the source of generalized 
peritonitis. 
Emphysematous gangrene, or gas-phlegmon, occupies an 
important place among the septicopyaemic processes. In a 
case recently encountered, the right arm was much swollen, 
the skin over all the rest of the body greatly distended, and 
the subcutaneous tissue, the blood, and all the organs con- 
tained gas bubbles (foamy organs). Shortly before the 
death of the patient a crepitating, emphysematous swelling 
appeared about the margin of the wound and extended 
rapidly up the arm. According to E. Frankel, the process 
is a special type of tissue softening caused by gas-forming 
bacteria, of which there are several varieties. The organism 
most frequently implicated is the anaerobic Bacillus aerog- 
enes capsulatus discovered by Welch and Nuttall in 1892. 
An organism which seems to be in all respects identical 
was described in 1893 by E. Frankel under the name Bacillus 
phlegmones emphysematosa. The association of inflam- 
matory phenomena with this infection has been denied by 
some authors (Lindenthal and Hitschmann) and affirmed 
by others (E. Frankel). 
SUPPURATIVE LEPTOMENINGITIS 
The occurrence of a serous inflammation in the men- 
inges, which is vouched for by clinicians (Bonninghaus), 
seems probable, although only a few instances have been 
discovered at autopsy (v. Hansemann). 
Patients suffering from an infectious disease sometimes 
exhibit symptoms similar to those of meningitis. While 138 
MENINGITIS 
the inner membranes in these cases of meningism may 
appear normal upon macroscopic examination, the micro- 
scope will nevertheless disclose the presence of small areas 
of inflammatory infiltration (Franz Schultze, Kirchheim 
and Schroder, Oseki) in some of them. In others, however, 
the findings are entirely negative (Stursberg, Kirchheim 
and Schroder), while in still others there exist microscopic 
areas of encephalitis (Schultze, Oseki). 
Suppurative leptomeningitis may result from extension 
of an adjacent inflammation, or occur by metastasis from 
purulent foci in other parts of the body, and it is usually 
generalized, although in the former event it may be some- 
what localized, at least in its earlier stages. The membranes 
of the spinal cord, also, may be attacked by inflammation in 
a neighboring structure. 
The ordinarily transparent meninges, particularly those 
over the cerebellum and the convexity of the cerebrum, are 
rendered opaque by the presence of a greenish-yellow in- 
flammatory exudate in the pia mater and between this and 
the arachnoid (Fig. 79). The products of inflammation 
collect especially over the sulci, in the spaces left between 
the two membranes as the pia dips down between the 
convolutions. 
According to Delafield and Prudden, suppurative menin- 
gitis is characterized by the accumulation of serum, fibrin, 
and a large amount of pus, along the walls of the blood- 
vessels and in the meshes of the pia mater. The quantity 
of exudate varies enormously; death sometimes occurs with 
so small an amount that the gross appearance of the mem- 
branes is quite normal, or at most moderately hyperaemic 
or cedematous, while in other cases the exudate is so abun- 
dant as to conceal the cerebral convolutions and most of the 
vessels of the pia, and even to form a sort of cast of the 
brain surface. The brain may be compressed and its convo- 
lutions flattened; its cortical regions may be merely oede- 
matous, or the seat of degenerative changes or punctate CEREBROSPINAL MENINGITIS 
139 
hemorrhages. Not infrequently the process extends to the 
ventricles, which then contain a turbid, purulent fluid. 
The direct cause of meningitis is the organism respon- 
sible for the disease which this lesion accompanies; it is 
generally a staphylococcus or a streptococcus. 
The epidemic cerebrospinal type is an important form 
of suppurative meningitis which appears to attack primarily 
Fig. "9.-Suppurative meningitis. 
the membranes of the cord and the brain. The spinal men- 
inges are very seriously involved and the cord is often 
covered by a greenish-yellow exudate; those of the brain, 
however, behave variously, participating sometimes but 
little in the process, while at others they suffer to an ad- 
vanced degree. Here the inflammation is hardly ever 
equally distributed; according to Busse, whose description 
I am now following, the occipital portion often remains 
entirely free, at least in its dorsal and lateral aspects, while 140 
MENINGITIS 
at the base the region of the sylvian fissure is but little in- 
volved ; the frontal and parietal areas, however, are gravely 
affected. The intensity of the process naturally depends 
upon the duration of the disease; at the height of the illness 
(from the fourth to the fifth day onward) the exudate over 
the parietal or the frontal region may be so massive as to 
cover the brain like a hood. 
The microscope shows a simple suppurative inflammation 
with but little inclination to follow the extensions of the 
pia mater into the cortex, the brain in general being thus 
spared. In the spinal cord, however, Liebermeister and 
Lebesanft discovered certain pathological changes which, 
though not characteristic in themselves, showed, neverthe- 
less, a typical distribution. The lesions varied with the 
duration of the disease, an observation which the authors 
thought would serve to explain the conflicting statements 
of other investigators. They found that during the first 
few days of the disease there occurs some slight degenera- 
tion in the marginal regions of the cord, and mild fatty 
metamorphosis in the medullary sheaths of the nerve-roots, 
both alterations being most distinct where the purulent exu- 
date is most abundant. These lesions gradually increase in 
severity, and in the course of from four to six weeks the 
posterior columns exhibit secondary degenerative changes 
in consequence of damage to the posterior nerve-roots; sec- 
ondary degeneration affects other regions of the cord as 
well, although not by any means so frequently. In this 
stage, too, degenerative lesions make their appearance in 
the ganglion-cells of the gray matter, especially in the 
anterior horn, but the anterior nerve-roots are not affected 
by secondary changes until a still later period of the disease. 
Other degenerations have been reported by Ludwig in 
cases with pronounced atrophy of the muscles, while Des- 
sauer and Lowenstein have recorded the occurrence of the 
hemorrhagic encephalitis described by Westenhbffer as an 
accompaniment of the later stages. 
Any form of exudative meningitis may involve the ven- INTERNAL HYDROCEPHALUS 
141 
tricles by extension along the velum interpositum. In sim- 
ple staphylococcus or streptococcus meningitis, the ven- 
tricular fluid is turbid and flocculent from the presence of 
pus, but in the epidemic type the ventricles are affected 
only to a slight extent in the earlier stages, and to many 
investigators have appeared to be quite free. Still, accord- 
ing to both Westenhbffer and Busse, careful examination 
will show some cloudiness of their contents or the admixture 
of a little pus. 
Internal hydrocephalus not infrequently marks the later 
stages of epidemic cerebrospinal meningitis, the lateral ven- 
tricles becoming dilated and filled with slightly turbid fluid. 
The vessels in their walls are widened, and in one of my 
cases this was so extreme as to impart to the whole inner 
surface a vivid red hue. 
Gbppert has referred hydrocephalus to isolation of the 
ventricles, although no organic obstruction could be discov- 
ered in a number of his cases. Collections of pus about the 
orifices in the fourth ventricle, especially the foramen of 
Magendie, are particularly apt to hinder the escape of fluid 
into the subarachnoid space. According to this author, pus 
collects from the third week onward in the cisterna magna, 
dilating this space and transforming its enclosing arachnoid 
into a thick membrane. 
The causal factor in epidemic cerebrospinal meningitis 
is the meningococcus of Weichselbaum {Diplococcus intra- 
cellularis meningitidis), which can be regularly demon- 
strated in the exudate. Westenhbffer, who tried to trace 
the route by which the organism enters the body and attains 
the nervous system, discovered an invariable redness and 
swelling of the pharyngeal tonsil; he therefore suggested 
that the cocci gain entrance during the course of an inflam- 
mation in this region, and pass to the brain by way of the 
lymph-channels. The organism has been isolated from the 
pharyngeal mucous membrane, it is true, but it may be 
found in healthy throats (Netter and others) as well; fur- 
thermore, catarrhal inflammations have been found involv- 142 
MENINGITIS 
ing other mucous surfaces, as those of the nose, the tym- 
panic cavity, the trachea, and the bronchi. These, however, 
Westenhoffer regarded as secondary. On the whole, it must 
be admitted that, probable though Westenhoffer's hypoth- 
esis may seem, it has not been definitely proved, and that the 
portal of entry may sometimes be located elsewhere. 
Westenhoffer found that the thymus, the faucial and 
pharyngeal tonsils, the bronchial and mesenteric lymph- 
nodes, and the follicles of the intestine are often swollen, and 
that the spleen in some cases is enlarged, congested, and 
softened. In these lesions he saw an expression of status 
lymphaticus, a constitutional anomaly which, he suggested, 
might predispose to infection by the meningococcus. 
Cerebrospinal meningitis is sometimes caused by the 
pneumococcus, and although a primary focus of infection 
by this organism can often be demonstrated, it not infre- 
quently happens that the manner in which it gained access 
to the body remains inexplicable. Grober assumed that it 
enters through the tonsil or through injuries to the skull, 
and reaches the brain by way of the lymphatics. 
It is a remarkable fact that, during epidemics of cerebro- 
spinal meningitis, the cases of cryptogenetic pneumococcus 
meningitis should increase in number, their occurrence 
assuming the characteristics of an epidemic. CHAPTER XIII 
Lobar Pneumonia; Pulmonary Emphysema 
Lobau pneumonia is an acute exudative inflammation 
involving one or both lungs or portions of them; its exudate 
consists largely of fibrin, and the diseas'e usually attacks 
entire lobes. The affected region is solidified, more volu- 
minous than normal, and contains depressions on its surface 
corresponding to the ribs; the surface is dull and covered 
with a slight fibrinous deposit, an expression of the pleurisy 
which regularly accompanies pneumonia. 
The cut surface is granular, uniformly firm, and grayish- 
red in hue at the height of the disease; since the color and 
consistency of the affected lung suggest the characteristics 
of the liver, this condition is described as red hepatization. 
The remainder of the organ is usually enlarged and 
occasionally somewhat firmer than normal in consequence 
of inflammatory oedema, setting free upon incision an abun- 
dant amount of frothy fluid; after this has run off, the dif- 
ference between the relaxed portion and that which has 
undergone hepatization appears with great distinctness. 
It can then be seen that the disease does not always attack 
whole lobes, but sometimes spares a portion; all of the 
affected area, however, is usually in the same stage, a much 
more important feature than the limitation to single lobes 
which has given it the name lobar pneumonia. Still, the 
existence of both recent and older areas of inflammation 
can sometimes be demonstrated, and if progressive advance 
of the process be a really striking characteristic, the term 
migratory pneumonia may be applied. 
Four stages are recognized in pneumonia-congestion, 
red hepatization, gray hepatization, and resolution. The 
anatomical findings so often advanced as characteristic of 
the first period are discovered more frequently in text- 
books than at the autopsy table. It lasts from a few hours 
143 144 
LOBAR PNEUMONIA 
to several days, and is succeeded by the second stage, 
already mentioned, which in turn gives way to gray hepat- 
ization (Fig. 80), and finally to resolution; during the last 
two stages the exudate disintegrates and is absorbed. 
Fig. 80.--Gray hepatization of the upper lobe (one-half natural size). 
The differences between these four stages depend upon 
the properties of the inflammatory exudate. In the first, the 
alveoli contain leucocytes, a little fibrin, and a large num- FOUR STAGES 
145 
ber of red blood cells, the last of which give to the sputum 
its hemorrhagic character. Later in the disease the ery- 
throcytes diminish, while the fibrin increases in amount to 
such an extent as to fill the alveoli (Fig. 81). At first the 
vessels in the alveolar walls are dilated, producing the dis- 
tinctive color of red hepatization, but with the advance of 
the disease the fibrinous exudate becomes so massive that 
Fig. 81.-Croupous pneumonia (moderately enlarged), a, alveolar walls; b, exudation in 
the alveoli. 
the alveolar walls grow anaemic from the pressure, and 
gray hepatization and resolution are initiated; according to 
Ribbert, thrombotic processes in these vessels contribute to 
the anaemia. During these stages the fibrin softens and 
disappears, leucocytes and exfoliated epithelium undergo 
degeneration, and the exudate is resorbed. 
Pneumonia is the product of bacterial toxins, the etiologi- 
cal agent being in most cases the Frankel-Weichselbaum 
diplococcus; this organism can be easily recognized in 
smears by its candle-flame outline, or can be isolated in 146 
LOBAR PNEUMONIA 
culture. In the rarer cases where the pneumo-bacillus of 
Friedlander is found, a characteristic mucoid secretion 
covers the cut surface of the lung. Still other bacteria, such 
as the bacillus of influenza, or the streptococcus, may cause 
lobar pneumonia in exceptional instances, but in the major- 
ity of cases these organisms produce the lobular type. 
According to Bezzola and Hibbert, the pneumococci are 
most numerous in the bronchioles, the alveolar passages and 
the central alveoli, and the authors therefore concluded that 
the process begins in the bronchioles and that the infective 
agent must accordingly be brought into the lung with the 
inspired air. The intense accumulation of leucocytes about 
large collections of organisms was compared to the manner 
in which these cells encircle the bacteria in other inflam- 
matory processes, and it was suggested that the leucocytes 
might hinder bacterial development not only through phago- 
cytosis, but by interfering with the supply of oxygen and 
other necessary materials. 
Only in rare instances is so much of the lung involved 
by pneumonia that death can be referred simply to the 
amount of parenchyma that has been rendered useless 
(Koschella); the fatal outcome is generally ascribed to 
heart failure, although in the majority of cases no ana- 
tomical proof to support this explanation can be discovered 
at autopsy, and myocarditis in particular is absent. Some- 
times, of course, there will be evidence of previous disease, 
especially coronary arteriosclerosis, but it is often neces- 
sary to accept the hypothesis of Romberg and his co- 
workers, who attribute death to toxic vasomotor paralysis. 
The remaining organs show no essential departure from 
the normal, except that the kidney is congested and its cor- 
tex slightly swollen; a certain amount of parenchymatous 
degeneration can almost always be discovered upon micro- 
scopic examination. 
Complications, which include simple and suppurative 
arthritis, are a result of the metastatic deposition of pneu- 
mococci. Suppurative meningitis is not so common, though COMPLICATIONS OF PNEUMONIA 
147 
Liebermeister has asserted that in twenty-five per cent, of 
the cases there is a distinct suppurative inflammation in the 
membranes of the spinal cord, even though their gross 
appearance be unchanged. 
Fig. 82.-Chronic pneumonia, especially pronounced in the lower lobes (one-half natural size). 
In endocarditis, which is a rare complication, the organ- 
isms have been demonstrated in the vegetations. From the 
blood, however, they are not regularly recoverable, to judge 
from the variable accounts of different investigators (for 
bibliography, see Jochmann). Since most of the cases in 
which they are found terminate fatally, Lenhartz concluded 148 
LOBAR PNEUMONIA 
that bacteraemia occurs during pneumonia only when the 
resistance of the blood has relaxed. 
Although the pneumonic exudate can be described in 
general as easy of absorption, its removal is occasionally 
retarded and sometimes fails altogether; in such cases the 
disease is of several weeks' duration. The organ is much 
firmer than the lung of acute pneumonia, while its cut sur- 
face is tougher, less granular, more uniformly smooth, and 
Fig. 83.-Chronic pneumonia (moderately enlarged), a, thickened alveolar walls; 
b, organizing exudate. 
generally dull grayish-white in color (Fig. 82), having often 
somewhat the appearance of flesh (carnification). The 
microscope may show remnants of fibrinous exudate; in 
other cases, this has almost entirely disappeared, leaving 
in its place a loose, cellular connective tissue (Fig. 83). 
Carnification is thus the outcome of organization of the 
exudate. Sometimes there occurs a thickening of the alve- 
olar walls with consequent encroachment upon the cavity; 
either process, however, eventuates finally in connective- 
tissue obliteration. CARNIFICATION 
149 
The new connective tissue has been referred to several 
regions of the lung, alveolar wall, interstitial tissue, and 
small bronchi having all been specified (for bibliography, 
see v. Kahlden); the variety of opinions finds an explana- 
tion in the fact that no one rule will apply to every case. 
Ribbert has shown that the bronchial wall is often a source 
of connective tissue; this is at first purely intrabronchial, 
but afterward grows into the alveoli, whence it spreads by 
way of the pores which have been shown to interrupt at 
various places the continuity of the alveolar wall (see p. 151). 
Hart, also, described the connective-tissue proliferation of 
chronic pneumonia as chiefly intrabronchial in the majority 
of cases. According to this author, there is a primary type 
of obliterating fibrous bronchitis which sets in without 
previous hepatization, and he was able to demonstrate 
transitions between it and the induration which follows 
pneumonia. 
Although it is impossible to explain with certainty why 
the pneumonic exudate should sometimes remain unab- 
sorbed, it is probable that destruction of the lymph-channels 
is of significance. This hypothesis would serve to elucidate 
the delayed resorption seen in connection with pleural 
adhesions (Marchand), as well as the fact that chronic 
pneumonia frequently appears in those who have previously 
had one or more acute attacks (Hart). 
PULMONARY EMPHYSEMA 
The air vesicles in the free borders and at the base of 
the lung in old people often undergo dilatation, and the 
affected regions assume a lighter hue by reason of a decrease 
in the amount of their pigment. In advanced cases, the 
lungs are distinctly enlarged, and fail to collapse when the 
pleural cavities are opened, while the dilatation of the air 
spaces is sometimes so extreme that these coalesce to form 
large cavities. As a rule the lung is not uniformly in- 
volved, the central and paravertebral regions usually 
remaining free (Fig. 84). These are the changes com- 
prised in the term emphysema, or, more accurately, sub- 150 
PULMONARY EMPHYSEMA 
Fig. 84.-Horizontal section through emphysematous lungs hardened in situ; from a preparation by Dr. Loeschcke (three-fourths 
natural size). In the right lung, which has been compromised by kyphoscoliosis, distribution of the emphysema is unequal, a, anterior 
free border, b, lateral portion of the left lung, with wide-meshed, emphysematous parenchyma; c, anterior free border, d, lateral portion 
of the right lung, not emphysematous; e, paravertebral portion of the left lung, not emphysematous; f, paravertebral portion of the right 
lung, emphysematous; g, transverse section of the aortic arch; h, transverse section of the descending aorta. 
stantive emphysema, since an interstitial and a vicarious 
are recognized, among other types. The present descrip- 
tion, however, applies principally to the substantive variety. ALVEOLAR STOMATA 
151 
Microscopic examination shows dilatation of the alveoli 
and rarefaction of their walls (Fig. 85), but there is no 
unanimity of opinion as to the way in which the latter 
process takes place. Certain authors (Sudsuki, Ribbert) 
have suggested that it is the result of dilatation of the pores 
described by both Kohn and Hauser as physiological com- 
munications between the alveoli. According to these 
authors, one or more stomata in the wall, each about the 
size of the nucleus of a connective-tissue cell, connect adjoin- 
ing alveoli. Eppinger, however, has pointed out that alve- 
Fig. 85.-Emphysema of the lungs (hand lens), a, dilated alveolar passages forming 
emphysematous vesicles. 
olar pores can be found neither in the lungs of newly-born 
children nor in the perfectly healthy adult lung, and he 
therefore regarded them as pathological. 
Besides the enlargement of alveoli, Ribbert has described 
dilatation of the alveolar passages and a gradual flattening 
of the septa which project into them, an observation that 
agrees entirely with my own experience. 
The elastic fibres are seriously involved in emphysema 
(Eppinger, Sudsuki, Tendeloo). They become separated 
from one another and undergo decrease in size, laceration, 
and degeneration; the smallest of them, however, are more 152 
PULMONARY EMPHYSEMA 
apt to be increased in number (Sudsuki, Tendeloo), and it 
may be assumed, with Orsos, that this signifies regeneration. 
The question is, whether the etiology of emphysema may 
profitably be sought in rarefaction of the alveolar wall, or 
whether this is merely the secondary product of another 
cause; the character of the lesion, at any rate, justifies the 
assumption that it is the outcome of mechanical factors. 
The alterations in the elastic fibres are in all probability 
the result of tension. Grawitz, it is true, attempted to 
explain the emphysematous change as inflammatory, but 
since his reasons were based upon a hypothesis of inflamma- 
tion which he alone supported, they necessarily fall with it. 
Tendeloo, a staunch adherent of the mechanical hypothesis, 
supported his belief in part by reference to the etiology of 
vicarious emphysema, a variety in which localized emphy- 
sematous patches occur about unexpanded portions of the 
lung in connection with tuberculosis, anthracosis, pleural 
adhesions, etc. Dilatation in such regions represents an 
attempt on the part of the lung to occupy vacant space, and 
since the condition is histologically similar to generalized 
emphysema, Tendeloo concluded that abnormal distention 
must be the cause of the latter also. 
Dilatation of the air spaces in the lung has been referred 
by some observers to recurrent or chronic respiratory dis- 
turbances, particularly such as would embarrass expiration. 
On the other hand, it has been suggested that the primary 
lesion is in the thorax, rather than in the lung itself. In 
severe emphysema, the chest cavity is enlarged, barrel- 
shaped, and rigid, and while this deformity was at one time 
regarded as secondary to the distention of the lungs, Freund 
has suggested, on the contrary, that it may be primary. He 
referred it to a degeneration of the costal cartilages, in the 
course of which they become lengthened, raising the thorax 
and fixing it in the position of inspiration. 
Loeschcke has accepted the view that a primary expan- 
sion of the chest cavity is responsible for emphysema, and 
that rigidity and dilatation of the thorax are the conse- UNDERLYING THORACIC DEFORMITY 
153 
quences of elongation of the costal cartilages. The lesions 
in the cartilages are not primary, however, but secondary 
to dorsal kyphosis. This is generally due to spondylarthritis 
deformans, a disease of elderly people in which, owing to 
pathological changes in the bones and joints of the spinal 
column, the vertebrae gradually sink under the combined 
weight of the head, shoulders, and arms (about 20 kilo- 
grams). The bending of the 
spine causes the ribs above the 
deformity to assume the posi- 
tion of inspiration, while those 
below it fall into that of expira- 
tion (Fig. 86) ; hence there 
takes place an expansion of the 
upper part of the thorax, and 
a contraction of the lower. In 
correspondence with Tendeloo's 
rule that localized dilatation 
of the thorax is followed by 
local overdistention of the lung, 
and localized contraction by 
local compression, the lungs of 
the kyphotic thorax are over- 
distended in their apical and 
parasternal regions, and con- 
tracted, perhaps even atelec- 
tactic, in their lower posterior 
portions. 
The distorted segment of the spine recedes so far from 
the sternum that the ribs and costal cartilages at the level of 
the deformity become lengthened; at the same time the 
affected ribs undergo lateral flattening, so that the normal 
circular outline of the thorax is replaced by an ellipse. 
Elongation of the cartilages, described by Freund as a 
primary lesion, thus proves to be the outcome of traction. 
Simultaneously with this increase in its anteroposterior 
diameter (Fig. 87), the thorax suffers another change, in 
Fig. 86.-Position of ribs in the em- 
physematous thorax (after Loeschcke). 
a, the sixth rib, which, in this case, 
marks the boundary between the upper 
ribs, raised to the position of inspiration, 
and the lower ribs, sunk to the position 
of expiration. 154 
PULMONARY EMPHYSEMA 
that its lower opening is increased in size through counter 
pressure exerted upon it by the abdominal contents as it 
settles down upon them. 
Although the thoracic changes vary somewhat with the 
location of the kyphosis, Loeschcke maintained that their 
general trend is similar in every case. Within certain limits 
the diaphragm is able to compensate for a rigid chest, but 
since it has no expiratory power it is unable to prevent 
the lungs from distending. 
Fig. 87.-Lengthening of the anteroposterior diameter of the thorax in emphysema (after 
Loeschcke). A, emphysematous, B, normal thorax. The position of the structures enclosed by 
dotted lines, W, spinal column, St., sternum, H., heart, was drawn from a sagittal section 
through the middle of each thorax, which was first hardened by the injection of formalin. 
Upon the sketch so made, were traced the outlines of sections through the lungs in the 
nipple-line. 
As for the significance of these findings for the clinician, 
it should be kept in mind that a slight degree of emphysema 
may exist without causing any symptoms, and secondly, that 
the spinal deformity may be concealed during life, as 
Loeschcke has said, by compensatory lordosis in other parts 
of the column. 
Of other findings there is little to be related. Bronchitis 
is a frequent accompaniment of advanced emphysema, prob- 
ably because a rigid thorax prevents the expectoration of HYPERTROPHY OF RIGHT VENTRICLE 
155 
mucus; the bronchi are therefore dilated and filled with yel- 
lowish-gray secretion, and their mucous membrane is 
injected, or, in some instances, pale in color. In severe cases, 
there is more or less hypertrophy of the right ventricle; 
this always attends interference with the capillary flow in 
the lungs, accompanying such conditions as anthracosis, 
certain forms of tuberculosis, and the pronounced thoracic 
deformity which is associated with severe kyphoscoliosis. 
In emphysema, it is the destruction of capillaries and per- 
haps, also, the deficient inspiratory activity of the lungs, 
(Hoffmann) that increases the labor of the heart. Diphtheria; Lobular Pneumonia; Scarlet Fever 
CHAPTER XIV 
In a typical case of diphtheria, the tonsils are greatly 
enlarged, and covered by a whitish-yellow membrane which 
is generally very adherent to the surface, while the mucosa 
of the soft palate and the 
pharynx, which is more or less 
livid in hue, bears a patchy de- 
posit of similar nature. The 
exudate becomes more exten- 
sive and continuous as the 
laryngeal entrance is ap- 
proached, and in advanced 
cases the inner surfaces of the 
larynx and the trachea are cov- 
ered without interruption (Fig. 
88). Below the glottis, the exu- 
date is not usually very adher- 
ent to the mucous membrane, 
and is apt to be readily de- 
tached in toto by the usual post- 
mortem manipulation. 
The inflammatory mem- 
brane is composed of fibrin, 
leucocytes, and bacteria, and 
where it adheres tightly to the 
mucous membrane it pene- 
trates the superficial layers, so 
that these undergo necrosis. 
To inflammations of this type 
Virchow applied the term diphtheritic, while that charac- 
terized by a simple non-adherent fibrinous membrane was 
termed croupous. Bacteriological studies have shown, how- 
ever, that this means of distinguishing diphtheria from 
Fig. 88.-Pseudomembranous inflamma- 
tion of the tonsils, pharynx, larynx, and tra- 
chea in diphtheria (one-half natural size). 
a, tonsils, and b, epiglottis, both covered by 
membranous deposit; c, reddened tracheal 
mucosa, freed of its membrane; d, mem- 
branous tracheal deposit, partly detached 
from the mucous membrane. 
156 DIPHTHERIA 
157 
croup is utterly unreliable, for in connection with the dis- 
ease which to-day is known as diphtheria, there may be 
found either a diphtheritic or a croupous membrane, and 
not infrequently both. To prevent confusion, therefore, in- 
flammations presenting the anatomical characteristics of a 
diphtheritic process are now called necrosing, and the terms 
diphtheria and diphtheritic are employed only in an etio- 
logical sense. 
The diagnosis is made by the discovery of the Bacillus 
diphtheria (Loftier) in the membrane, either by histological 
methods or, much more conveniently, by smears or cultures. 
This organism was formerly supposed to be restricted to 
the exudate, but more recent investigations have succeeded 
in proving that it reaches the blood stream and the internal 
organs. 
Uncomplicated cases of diphtheria show nothing beyond 
the throat condition except enlargement of the regional 
lymph-nodes and the spleen. The lesions in the lymph- 
nodes, which are characteristic, consist of cellular hyper- 
plasia, hyaline degeneration of the reticulum and the blood- 
vessels, fibrinous exudation, and areas of necrobiosis; they 
are distinct from those of suppurative adenitis (Oertel. 
Bulloch and Schmorl). 
LOBULAR PNEUMONIA 
Among the complications of diphtheria is occlusion of 
the air passages by the diphtheritic membrane; this is some- 
times a cause of death. If the exudate extend into the finer 
bronchi, bronchopneumonia is very apt to ensue, though it 
may set in, also, when the membrane does not extend so far 
downward; in the later stages of the disease, when the in- 
flammatory process in the upper air passages is subsiding, 
it sometimes constitutes the main post-mortem finding. 
The cut surface of the bronchopneumonic lung contains 
small, rather prominent, granular foci, corresponding to 
the pulmonary lobules (whence the name lobular pneu- 158 
LOBULAR PNEUMONIA 
monia); these lesions are distributed throughout smaller or 
larger portions of the organ, but involve particularly the 
lower lobe (Fig. 89). If they are very close together they 
produce the impression of hepatization, and the process is 
recognizable as lobular pneumonia only toward the periph- 
ery of the affected region, where the lesions are more 
Fig. 89.-Lobular pneumonia (three-fourths natural size). 
isolated. Microscopic examination shows that the alveoli 
are filled with an exudate consisting mainly of leucocytes 
and desquamated epithelial cells; fibrin is a rare and scanty 
component. 
Various degenerations may occur in the myocardium 
during the course of diphtheria, the most frequent of which 
is fatty metamorphosis. Ribbert has of late redirected 
attention to the waxy degeneration described by Bosenbach, DIPHTHERITIC MYOCARDITIS 
159 
a condition characterized by the appearance of homogeneous 
areas in the muscle-fibres; according to Ribbert, these are 
probably replaced by cardiac cicatrices after their absorp- 
tion. He was inclined to attribute to both waxy and fatty 
degeneration a pronounced effect upon the heart's action, 
particularly as he did not often discover any evidence of 
myocarditis. Lowenthal, on the other hand, has denied the 
frequent occurrence of waxy degeneration. Inflammatory 
infiltration of the myocardium (acute interstitial myocar- 
ditis), which is not at all rare, was first described by Hayem, 
but its thorough investigation and the explanation of its 
significance have been principally the work of Leyden and 
Romberg. Romberg found it in every case examined, and 
ascribed to it a greater importance in the production of heart 
failure than is possessed by the parenchymatous alterations. 
Leyden also referred to this lesion the heart failure of diph- 
theria. The different beliefs regarding the frequency and 
significance of the various myocardial affections depend 
in great measure upon the material chosen for investigation. 
When the heart is examined during all stages of diphtheria 
(Schemm), parenchymatous lesions are more apt to predom- 
inate than when observation is confined to cases in which 
death has been brought about by postdiphtheritic cardiac 
paralysis. This is shown particularly by the work of HolL 
wachs, who found such parenchymatous changes as fatty 
degeneration and vacuolization during the first week, while, 
from the ninth day onward, small-cell infiltration was of 
regular occurrence. The almost invariable presence of 
interstitial myocarditis accounts, in all probability, for 
sudden cardiac death in the latter stages of diphtheria, or 
after complete resolution of all inflammation in the upper 
air passages. 
Less commonly, diphtheritic myocarditis leads to dila- 
tation of the heart, slowing of the circulation, and throm- 
bosis (Deguy and Weil); in such cases, emboli have been 
discovered in the lungs and the brain (Escherich). 
For postdiphtheritic paralysis of the voluntary muscles, 160 
SCARLET FEVER 
no certain anatomical basis has yet been revealed. The 
condition has been ascribed by some authors to degenera- 
tive processes in the central and peripheral nervous systems, 
while Hochhaus has described a distinct inflammation in 
paralyzed muscles, limited chiefly to the connective tissue, 
and accompanied by slight interstitial inflammatory changes 
in the nerves. 
Parenchymatous nephritis is common, affecting the 
glomeruli less than the tubules, in contrast to that following 
scarlet fever. 
SCARLET FEVER 
Since death occasionally takes place during the first few 
days of an attack of scarlet fever, it must be assumed that 
the toxin of the disease may, in itself, be sufficient to ter- 
minate life (v. Jurgensen). The autopsy findings in these 
cases are negative. 
In later stages, the principal lesions are discovered in 
the upper respiratory passages. In severe cases, the ton- 
sils are involved by a necrosing inflammation (Fig. 90), 
which not infrequently includes the larynx and upper por- 
tion of the oesophagus; invasion of the lower end of the 
gullet is a less common occurrence. The presence of a 
membrane in scarlet fever was formerly ascribed to the 
coexistence of diphtheria, but it is now realized that the 
virus of scarlatina alone may produce such an exudate. 
The frequency with which an extensive necrosing inflam- 
mation occurs in connection with scarlet fever has been 
shown by the observations of Oppikofer. Among one hun- 
dred and twenty-eight cases he found sixty-six in which a 
membrane occupied the larynx, the trachea, or the oesopha- 
gus ; of these, the interior of the larynx was involved in 
twenty-six, in fourteen of which the process had progressed 
as far as the trachea, while in three it had invaded even the 
bronchi. In fifteen cases the pharynx and oesophagus were 
affected. 
Phlegmonous or gangrenous angina may be associated GANGRENOUS ANGINA 
161 
with scarlet fever. In the former, the tonsils are greatly 
enlarged and soft, and involved in a suppurative process. 
Gangrenous angina may succeed the phlegmonous type, or 
develop independently upon the basis of a necrosing in- 
flammation. The tonsils are large and mottled, their sur- 
Fig. 90.-Necrotic angina following scarlatina (two-thirds natural size), a, left, b, right 
tonsil, enlarged and necrotic; c, pseudomembranous deposit on the reddened pharyngeal 
mucosa; d, soft palate drawn upward, with its pseudomembranous covering; e, uvula. 
face is soft and shredded, and the casting off of gangrenous 
portions results in extensive ulceration. Either type may 
invade the lymph-nodes in the upper cervical region; these 
undergo at first a simple inflammatory hyperplasia, to which 
suppuration may be superadded. 
Streptococci can generally be recovered from the throat 
11 162 
SCARLET FEVER 
in scarlatina. They can be demonstrated m the blood (scar- 
latinal sepsis) in connection with suppurative adenitis, and 
sometimes even in the absence of lymph-node involvement. 
The post-mortem findings in scarlatinal sepsis include 
petechiae, swelling of the spleen, and parenchymatous 
degeneration in the heart, the kidney, and the liver; meta- 
static foci of suppuration in the internal organs are less 
common, and purulent arthritis is a rare complication. 
The relation between general sepsis and scarlet fever 
has prompted the suggestion that the latter disease may 
be a septic process due to the streptococcus; although the 
view cannot be contradicted 
so long as the actual cause 
of scarlatina remains un- 
known, it cannot be regarded 
as proved or as even proba- 
ble. Inclusions in the leu- 
cocytes of the blood and in 
other cells have recently 
been described by several 
observers (for bibliography, 
see Dbhle), but it is still too 
early to decide on their etio- 
logical significance. Bern- 
hardt has reported the pro- 
duction of a scarlatiniform 
disease in apes by inoculation of material from human 
patients. 
Nephritis is a very common accompaniment of scarlet 
fever. The kidneys are always involved to some slight ex- 
tent, at least, and show upon gross examination a little 
cloudiness of the parenchyma corresponding to fatty degen- 
eration in the uriniferous tubules. More important, how- 
ever, and more characteristic, is the presence of glomerulo- 
nephritis, which will be described later in detail; a special 
variety is sometimes encountered, in which the capillaries of 
the tufts are obliterated by thrombus-like masses (for bibli- 
Fig. 91.-Acute interstitial nephritisin scar- 
latina (slightly enlarged), a, glomerulus; b, 
uriniferous tubule; c, interstitial cellular infil- 
tration. ACUTE INTERSTITIAL NEPHRITIS 
163 
ography, see v. Kahlden). Acute interstitial nephritis some- 
times occurs (Friedlander) ; the kidneys are soft and very 
much enlarged, the cortex is wider than normal, its mark- 
ings are obliterated, and the whole parenchyma is of a spotty 
red hue. Microscopic examination shows that the lesion is 
essentially a proliferation and infiltration of the connective 
tissue (Fig. 91), glomeruli and tubules being separated by 
collections of small round cells. The process is thus an 
inflammation of the connective tissue, with no important 
change in the glomeruli and tubules, and, serious though it 
may appear upon gross examination, it does not disturb 
the parenchyma. 
According to Romberg, myocarditis is a frequent com- 
plication of scarlatina, though the process is never very 
far advanced; its relation to cardiac insufficiency is the same 
as in diphtheria. CHAPTER XV 
Typhoid Fever; Dysentery 
The principal changes in typhoid fever are localized 
in the solitary and agminated lymph-nodes of the intes- 
tine. Here there occurs 
a characteristic hyper- 
plasia (Fig. 92), which 
may be looked upon in 
general as the first stage 
of the disease, corre- 
sponding, as it usually 
does, with the end of the 
first week and the begin- 
ning of the second. The 
number of follicles in- 
volved varies within 
wide limits. The process 
is generally most intense 
in the neighborhood of 
the ileocaecal valve, and 
is limited, as a rule, to the 
small intestine and upper 
portion of the large; the 
large gut alone, however, 
may be attacked. The 
affected nodes ' are red- 
dish in color, rather 
softer than normal, and 
project more or less 
above the intestinal sur- 
face. 
Hyperplasia is succeeded by necrosis. On the surface 
of the swollen lymphatic structures there appear necrotic 
areas (Fig. 93), stained a yellowish or greenish hue by the 
Fig. 92.-Portion of small intestine from a case of 
typhoid, with swelling of Peyer's patches and the 
solitary follicles (one-half natural size). 
164 TYPHOID ULCERS 
165 
contents of the intestine. The sloughs loosen and are cast 
off toward the end of the third week, leaving ulcerated areas 
(Fig. 94); the periphery of the follicle is generally spared, 
and forms an enclosing wall about the depression. The floor 
of the ulcer gradually becomes clean and smooth, the inflam- 
Fig. 93.-Lower end of the ileum from a case of typhoid, with necrosis of the swollen patches; 
the necrotic portions are beginning to be cast off (three-fourths natural size). 
mation in its wall subsides, and cicatrization finally sets in 
(Fig. 95), substituting for the ulcer a thin, grayish, pig- 
mented scar, which finally disappears. It is characteristic 
of typhoid ulcers that the long axis corresponds to that of 
the intestine. The ulcerative process sometimes extends 166 
TYPHOID FEVER 
so deeply as to open a blood-vessel and lead to hemorrhage, 
which may be fatal; in other cases, the ulcer perforates the 
intestinal wall, with periton- 
itis as a consequence. Death 
is more apt to ensue during 
the periods of hyperplasia or 
commencing necrosis, and in 
Fig. 94.-Typhoid ulcers, the bases of which have 
become nearly smooth (two-thirds natural size). 
Fig. 95.-Healed typhoid ulcers (one-half 
natural size). 
so far as it is not a result of cardiac weakness it may then 
be attributed tq the severity of the typhoid toxin. Recur- 
rence of the intestinal lesions is often encountered at AUTOPSY FINDINGS 
167 
autopsy; that is to say, although the process as a whole is 
in the ulcerative stage, fresh tumefaction may be demon- 
strated, sometimes even in follicles that have already under- 
gone ulceration. The follicular lesions in children are 
generally superficial, and perforation does not usually occur. 
During the stage of hyperplasia, the mesenteric lymph- 
nodes are much enlarged and their cut surface is whitish- 
gray in color, the involvement corresponding in general to 
the distribution and severity of the process in the intestine; 
with the supervention of the ulcerative period, the swelling 
recedes. The lymph-nodes of the stomach and the trans- 
verse fissure of the liver may also be affected. The spleen 
invariably undergoes enlargement from hyperaemia and 
hyperplasia, as in other infectious diseases. 
Lymphatic enlargements occur in the liver in the form of 
the small, grayish-white collections of lymphoid cells dis- 
covered by Wagner in 1860. Not all cellular areas found in 
this organ, however, are the result of participation by the 
lymphatic system. On the contrary, most of them, accord- 
ing to M. B. Schmidt, represent localized areas of necrosis 
in the parenchyma. Typhoid bacilli have never yet been 
demonstrated in the latter lesion. 
After it had been shown that the walls of the gall-bladder 
might be the seat of inflammatory processes, Fiitterer 
demonstrated the presence in it of typhoid bacilli. Numer- 
ous subsequent investigations of the bile undertaken both 
at autopsy and at operation (for bibliography, see Chiari), 
have shown that the organisms are of regular occurrence 
in the gall-bladder, where they may cause no reaction 
(Hirsch, Frankel), a mild inflammation, or a more severe 
chronic process; in the presence of cholelithiasis, suppura- 
tive lesions sometimes set in. Although the possibility can- 
not be excluded that the gall-stones themselves may be a 
consequence of typhoid infection, they are more usually an 
incidental complication. Typhoid bacilli reach the gall- 
bladder by way of the liver, into which they are carried 
by the blood stream (Dorr, Blumenthal), but direct ascen- 168 
TYPHOID FEVER 
sion from the intestine seems to take place as well. Whether 
involvement of the gall-bladder be brought about by descend- 
ing or by ascending infection, however, the stagnation of bile 
is an important predisposing cause (Hirsch). Beside these 
two methods of infection there has been suggested a third- 
escape of the organisms into the gall-bladder from the capil- 
laries in its wall. 
The presence of typhoid bacilli in the gall-bladder is of 
the highest significance in respect of recurrence or transfer 
of the disease, since they may remain and multiply for a 
long period after recovery. An individual who harbors and 
excretes typhoid bacilli in this way is known as a typhoid 
carrier. 
According to post-mortem findings, the intestinal tract 
would seem to be the point at which the typhoid bacillus 
enters the body. The conception has nevertheless been 
entertained (Forster) that organisms taken in by the mouth 
immediately penetrate to the interior of the body and multi- 
ply there. At about the time when the disease first becomes 
manifest, they appear in the blood and are transported to 
the liver, whence they are carried into the gall-bladder with 
the bile and finally into the intestine, in which they multiply 
but little, or not at all. This view, however, is not supported 
by sufficient evidence (E. Frankel). 
Still more sweeping is the suggestion that typhoid fever 
is a general sepsis to which the intestinal lesions are second- 
ary (for bibliography, see Chiari), and this, too, must be 
considered unproved in most instances. Of course, the infec- 
tion is general in the sense that bacilli can be isolated from 
the blood, the spleen, the bone-marrow, etc. (Ebermaier and 
Quincke), but this general infection is secondary to the 
condition in the intestine. Nevertheless, typhoid septi- 
caemia, in the strict sense of the word, is not unknown, and 
there are, indeed, several groups of cases in which general 
infection occurs in the absence of any localized intestinal 
focus. The first includes those in which the enteric lesion 
is too insignificant to permit the diagnosis of typhoid to be COMPLICATIONS AND SEQUELAE 
169 
made, and those others in which the intestinal condition has 
run its course by the time the autopsy is undertaken (Chiari 
and Kraus, Weichardt, Neufeld); to the second group belong 
instances of infection of a foetus by the maternal blood (for 
bibliography, see Neufeld). The third group comprises 
auto-reinfection in typhoid carriers, in whom the dissem- 
ination of bacilli may take place either in consequence of 
some severe illness (Wood, Levy and Kayser, Busse, 
Kamm), or spontaneously; in the latter extremely rare 
event, the organs are unaltered, except for the spleen, which 
is enlarged, and typhoid bacilli can be demonstrated in the 
blood (Jores). 
The lesions produced by typhoid fever in regions of the 
body other than the intestine, as well as the complications 
and sequelae of the disease, still remain to be discussed. 
The muscles usually have the dry, brownish-red appear- 
ance of smoked beef. The rectus abdominis, the adductors 
of the thigh, and the muscles of the upper arm not infre- 
quently contain areas of waxy (Zenker's) degeneration. If 
the transformation be widespread, the muscle becomes pale 
and brittle, tearing readily, with the consequent appearance 
of hemorrhage. Complete regeneration is the rule, and only 
where rupture and hemorrhage have been extensive does 
there appear a scar (Kaufmann). 
As in other infectious diseases, the cardiac musculature 
may be the seat either of parenchymatous changes or of 
acute interstitial myocarditis. According to Romberg, the 
latter is a frequent accompaniment of typhoid fever, but 
Aschoff and Tawara have been unable to substantiate this 
statement. 
■Superficial erosions sometimes involve the posterior wall 
of the larynx, the vocal cords, or the epiglottis, and may 
terminate in extensive ulceration or even in perichondritis. 
With the inflammation of small bronchi which Curschmann 
regarded as "characteristic of typhoid fever" there is often 
associated a lobular pneumonia, while lobar pneumonia 
sometimes appears in consequence of infection with the 170 
DYSENTERY 
pneumococcus; this organism may exist alone, or in com- 
bination with the typhoid bacillus. The few instances in 
which only B. typhosus has been isolated (for bibliography, 
see Honl) require confirmation. 
Mild grades of parenchymatous nephritis are not rare, 
and according to M. B. Schmidt even an extensive necrosis 
of the renal epithelium is often encountered. 
Post-typhoid periostitis and arthritis, either of which 
may terminate in suppuration, have been but little investi- 
gated. 
Quincke was the first to demonstrate typhoid bacilli in 
the bone-marrow. As in other infectious processes, they 
occur principally in the red marrow of the vertebrae 
(Frankel), being demonstrable from the first week onward. 
The affected vertebrae are of normal macroscopic appear- 
ance, but the marrow contains microscopic areas character- 
ized by the collection of small mononuclear leucocytes and 
the presence of a dense network of delicate threads of fibrin, 
the meshes of which enclose necrotic cells. Frankel empha- 
sized the analogy between such foci and those described by 
Chiari in the marrow in connection with smallpox. Ordi- 
nary suppurative osteomyelitis occurs also, the outcome 
of mixed infection. 
The suppurative processes which sometimes attack the 
spleen, the muscles, the thyroid gland, and the liver, are due 
in part to mixed infection and in part to the typhoid bacillus 
alone. 
Evidence of the haemolytic poison secreted by the bacillus 
of typhoid fever is afforded by the increased deposition 
of haemosiderin in the spleen, the liver, or the lymph-nodes 
(M. B. Schmidt). 
DYSENTERY ( COLITIS ) 
Dysentery lias no uniform etiology, and it is very diffi- 
cult, or perhaps impossible, to classify it. One type is due 
to irritation by poisons (especially bichloride of mercury), AUTOPSY FINDINGS 
171 
or unsuitable foods, or accompanies coprostasis or the 
infectious diseases. This variety, however, cannot be dis- 
tinguished post-mortem from that about to be described. 
Infectious or epidemic dysentery begins with a catarrhal 
stage which is seldom observed uost-mortem unless there 
be opportunity for the 
examination of a large 
number of cases. This 
period of the disease is 
characterized by redness 
of the mucous membrane, 
involving the crests of 
its folds and due partly 
to injection and partly 
to ecchymosis; the mu- 
cosa may be somewhat 
loosened, oedematous, 
and covered with mucus. 
In the next stage, the 
mucous membrane un- 
dergoes necrosis, form- 
ing a branny deposit, 
which is later replaced 
by adherent sloughs 
(Fig. 96); the necrosis 
terminates in ulceration 
(Fig. 97). The ulcers 
are irregularly distrib- 
uted, yet are often 
arranged in three rows 
corresponding to the 
muscular bands in the 
wall of the gut, a localization which has been referred to 
the greater friction and irritation exerted upon these areas 
by the intestinal contents, as the bowel contracts. They 
have an irregular outline, a flat margin, and a smooth base, 
and may be so numerous as to coalesce and spare only small 
Fig. 96.-Necrosing inflammation in the mucosa of 
the large intestine (three-fourths natural size). 172 
DYSENTERY 
islands of mucous membrane; if they heal, they are replaced 
by superficial scars. 
The bacilli responsible for epidemic dysentery, of which 
the most important are the Shiga-Kruse and the Flexner 
types, can be found in the contents of the intestine, but 
Fig. 97.-Dysenteric ulcers in the large intestine (three-fourths natural size). 
whether they appear also in the wall of the gut and the 
lymph-nodes, is uncertain. It has not been possible so far 
to gain any concrete idea regarding the relation of the 
organism to the anatomical changes in the gut; thus, it is 
not known, as v. Baumgarten has pointed out, whether the 
organisms infect the mucous membrane directly, after the AMCEBIC DYSENTERY 
173 
manner of the diphtheria bacillus, or even whether they are 
the sole bacterial cause of the necrosis and ulceration. 
The post-mortem findings in amoebic dysentery, which 
is endemic in tropical countries, are somewhat different. 
Here there are found more isolated and irregular ulcers, 
with undermined margins; the process starts from the sub- 
mucosa (Councilmann and Lafleur), which is often soft and 
necrotic while still covered by mucous membrane (Kruse 
and Pasquale). The amoebae can be demonstrated in the 
ulcers and elsewhere in the intestinal wall. Among several 
varieties, Entamoeba histolytica and Entamoeba tetragena 
are the most important, but it is still a disputed question 
whether these organisms are the sole cause of the disease, 
whether they act in combination with bacteria, or whether 
they coexist merely as parasites. Tanaka, who investigated 
dysentery in Formosa, suggested that it is caused by a 
species of bacteria still undiscovered, and that the resulting 
ulcers merely offer a favorable soil for the growth of amoebae. 
Hara, however, was able to produce typical amoebic dysen- 
tery in cats by feeding them with infected human feces, and 
concluded, therefore, that there could be no doubt regarding 
the pathogenicity of the amoeba which he had discovered. 
Abscess of the liver is the most important of the affec- 
tions secondary to dysentery; it is associated principally 
with the amoebic type, but even though the suppurative foci 
contain amoebae, it is probable that bacilli are an important 
factor in their production (Kruse and Pasquale). CHAPTER XVI 
Appendicitis 
In discussing inflammation of the vermiform appendix, 
1 shall follow, in a general way, the writings of Riedel, 
Kretz, Oberndorfer, Ribbert, Sprengel, and particularly 
Aschoff. 
According to Aschoff, the various forms of acute appen- 
dicitis are not separate types, but represent so many stages 
of one process, which commences in the mucous membrane 
of the appendix. The mucosa is traversed by longitudinal 
and circular furrows which readily harbor microorganisms, 
and it is in the deepest of these that the lesions of the pri- 
mary infection are especially apt to be found (Fig. 98). The 
earliest change is the collection underneath the epithelium 
of an extraordinarily large number of neutrophile leucocytes 
and a few eosinophile leucocytes and lymphocytes, with the 
disappearance of that portion of epithelium immediately 
overlying the infiltrated area. The resulting epithelial de- 
fect is soon occupied by a plug of fibrin and leucocytes. 
The process extends rapidly by way of the lymphatics, the 
area of leucocytic infiltration broadening as the serosa is 
approached, and accordingly assuming the form of a wedge, 
with its base lying on the serosa and its apex at the infected 
furrow. The shape might suggest a hematogenous origin, 
were it not that, according to the vascular arrangement de- 
scribed by Kelly, the wedge in such a case would have to 
occupy a reverse position, with its base against the mucosa. 
The arrangement of the lymph-channels (Kelly), however, 
readily explains the wedge-like configuration of the inflam- 
matory area. 
Bacteria can be found at this stage only in the fibrin 
plug, where they are almost exclusively intracellular. Since 
they are never demonstrable in the deeper layers of the wall, 
even though the leucocytic infiltration reach as far as the 
174 PHLEGMONOUS STAGE 
175 
serosa, extension of the lesion must be referred to the 
absorption of toxic substances by the lymph-channels. 
When, as almost invariably happens, there are several 
primary lesions, the second, or phlegmonous, stage (the 
Fig. 98.-Multiple primary infection with beginning phlegmonous inflammation in the 
wall of the appendix (after Aschoff), a, lacuna with defective epithelium; 6, inflammatory 
cellular infiltration; c, lymph-follicle. 
catarrhal appendicitis of earlier authors) follows almost 
immediately; this is the stage in which are found nearly all 
appendices removed within about twelve hours after the 
onset of the attack. It is characterized, according to Aschoff, 176 
APPENDICITIS 
by confluence of the infiltrated areas, and in accordance 
with the wedge-like form of these lesions, the serosa and 
outer muscular layers become the seat of a more or less con- 
tinuous zone of leucocytic infiltration, while toward the 
lumen of the appendix the process becomes progressively 
Fig. 99.-Commencing ulcerative (ulcerative-phlegmonous) stage of appendicitis (after 
Aschoff). On the left, a miliary perforation threatens. 
less extensive, involving in the mucosa only the regions 
about the ends of the furrows; except for the defects already 
mentioned, the epithelium therefore appears intact. The 
older the lesion, the larger is the proportion of eosinophile 
to neutrophile leucocytes. 
Even in this stage it is not possible to discover bacteria 
in the outer mural layers, a fact which suggests that both the ULCERATIVE STAGE 
177 
appendicitis and its accompanying localized peritonitis are 
essentially of a toxic, non-bacterial nature. 
Although the inflammation very frequently resolves at 
this time, it goes on in some cases to the production of an 
abscess, and if the slight changes at the bottom of the fur- 
rows recede there will be found a mural abscess in the pres- 
ence of an apparently normal mucous membrane. The per- 
forations which occur during this stage from the rupture 
of an abscess are of microscopic size; in a few fortunate 
instances they communicate with the lumen of the appendix, 
but more often they open upon its external surface. In the 
latter event, peritonitis ensues, unless the preceding inflam- 
mation in and about the appendix has walled it off from the 
general peritoneal cavity. In a few rare instances, the 
submucosa undergoes suppurative softening throughout 
part or all of its circumference, the mucosa and the lym- 
phatic layer of the submucosa then becoming separated from 
the outer layers of the wall, and forming in some cases a 
complete sequestrum. 
The phlegmonous stage, though it may resolve, often pro- 
gresses to the ulcerative (Fig. 99) by gradual enlargement 
of the epithelial defects, and the appendix finally becomes 
lined with ulcers which are separated from one another 
solely by the tips of the folds in the mucosa, the only region 
where the epithelium escapes destruction. The purulent 
softening is almost always accompanied by an exudation of 
fibrin, and this process results in the production of a mem- 
branous deposit resembling that of diphtheria; the fibrin 
content of the exudate is increased by frequent hemorrhages. 
Beside suppurative liquefaction, there are concerned in the 
production of ulcers certain necrotic alterations caused by 
the toxins of various bacteria; the organisms at fault may 
be any of those found in the gastro-intestinal tract. In the 
opinion of Aschoff, ulcerative appendicitis is never primary, 
with the exception of the rare instances in which it is the 
product of some mechanical cause. 178 
APPENDICITIS 
Even the ulcerative stage may resolve, though it often 
goes on to perforation. In contrast to those of the phleg- 
monous stage, its perforations are generally macroscopic. 
A second complication is necrosis or gangrene of the wall, 
for which there are required not only bacteriotoxic in- 
fluences, but circulatory disturbances dependent upon 
lesions in the vessels of the meso-appendix. Perforations 
which attend necrotic processes in the appendix are usually 
of large size. 
The macroscopic appearance of the appendix is not 
greatly altered at first; according to Sprengel, there is little 
to be recognized except stiffening, and some swelling and 
injection of the mucous membrane. In the phlegmonous and 
ulcerative stages, however, the gross changes, which are sub- 
ject to wide variation, are much more pronounced. Part 
or all of the appendix is often thickened (Fig. 100), a puru- 
lent exudate just under the surface may show through with 
a greenish-yellow color, or soft, yellowish-green or partially 
hemorrhagic areas of gangrene may be present, the hemor- 
rhagic discoloration sometimes including the whole appen- 
dix ; a gangrenous tip not infrequently undergoes dilatation. 
It can often be shown that the inflammatory lesion has 
set in just behind an angulation, a fact affording consider- 
able support to the view that stagnation is an important 
factor in the production of this disease; the fact that the 
proximal region often remains unaffected for a long time 
has been referred to by Aschoff as a valid proof that the 
infection does not come from the caecum. In its later stages, 
the inflammation at the tip of the appendix begins to spread 
through the various coats, particularly the subserous, and, 
passing the angulation, finally attacks the proximal portion. 
Although an important influence was formerly ascribed 
to fecal concretions, the hypothesis that they produce ulcer- 
ation mechanically is now discredited (Sprengel, Aschoff), 
while the view that their rich bacterial content is a source 
of danger also lacks sufficient foundation (Aschoff). It is FECAL CONCRETIONS 
179 
now known that these masses, which consist of feces and 
mucus (Ribbert), with the admixture of epithelium, leuco- 
cytes, and bacteria (Brunn), may occupy the appendix with- 
out exciting any inflammatory condition at all (Sprengel, 
Aschoff); still, even though they be not the sole cause of 
appendicitis, it is agreed by all that they not only favor the 
occurrence of this disease, but render its course more seri- 
Fig. 100.-Phlegmonous-ulcera- 
tive appendicitis. The appendix 
is bent, its distal portion dilated, 
and its surface covered with fibrin. 
The arrow indicates a perforation. 
Fig. 101. - Appendicitis; 
localization of the process 
above and below a fecal con- 
cretion, a. The mucous mem- 
brane in the proximal part 
of the appendix is normal, b. 
ous. They act chiefly by causing the contents of the appen- 
dix to collect behind and, to a certain extent also, ahead 
of them. They lie, as a rule, in regions that are free from 
inflammation, and the lesion is usually in the distal end of 
the appendix or, occasionally, in front of the concretion 
(Figs. 101 and 102). Perforation does not take place in 
the region where a fecal concretion is situated, except when 
extensive necrosis of the wall has occurred in consequence 
of changes in the vessels of the meso-appendix. Foreign 180 
APPENDICITIS 
bodies, to which so much importance was formerly attrib- 
uted, are but rarely a cause of appendicitis. 
Stagnation of the contents of the appendix is followed by 
an increase in their bacterial content, and this by infection 
of the wall. The colon bacillus and the pyogenic cocci are 
both under suspicion, but it is still an open question which 
of the two has the greater pathogenetic significance; 
although the former is more frequently encountered, most 
authors look upon the latter as the chief cause. 
Fig. 102.-Phlegmonous-ulcerative appendicitis, localized at the distal end behind a fecal con- 
cretion. A portion of the greater omentum is adherent to the appendix. 
To the view already offered regarding the mode of infec- 
tion is opposed a hypothesis which regards appendicitis 
as a metastatic lesion, intimating some relation between it 
and angina. The large amount of lymphoid tissue contained 
in the appendix does, indeed, suggest that this structure 
may serve as a protective organ for the intestinal tract in 
the same way that the tonsils guard the pharynx (Klemm), 
and the production of appendicitis by experimental infection 
of the blood has been reported, but according to Ghon and 
Nambu, the procedure is neither certain nor convincing. 
Kretz, who sought to adduce anatomical proof regarding EXPERIMENTAL APPENDICITIS 
181 
the connection between appendicitis and angina, empha- 
sized the frequent coexistence of the two diseases. He de- 
nied that appendicitis commences in the manner described 
by Aschoff, maintaining, on the contrary, that it originates 
in the lymphatic apparatus, and he described emboli of cocci 
in the follicles, accompanied by hemorrhages, which he inter- 
preted as an inflammatory reaction. Aschoff has properly 
objected, however, that no true inflammatory process was 
demonstrated, that the hemorrhage was probably traumatic, 
and that Kretz had not succeeded in tracing the development 
of appendicitis from the lesion described as the primary 
stage. It cannot be denied, of course, that the deposition 
of pyogenic bacteria in the wall of the appendix by the 
blood stream may be a cause of appendicitis, but such an 
etiology must be exceptional. 
Experimental investigations in animals have thus far 
done but little to explain the pathogenesis of this disease. 
The most suggestive are those recently published by Heile, 
who succeeded in producing a condition analogous to appen- 
dicitis in man by ligating the caecum in dogs. The procedure 
was only successful, however, when this cavity contained 
fecal masses; in the absence of these, neither suppuration 
nor necrosis ensued. Experiments like this confirm the 
significance of stagnation and the pregnant words of 
Aschoff: "No stagnation, no appendicitis." 
Acute appendicitis may resolve in any of its phases. 
In the primary stage of infection, complete restitution will 
follow, but the phlegmonous and ulcerative stages heal by 
granulation and cicatrization, and the signs of inflammation 
persist for a long time; extensive deformity of the appen- 
dix, and even obliteration of its lumen (Fig. 103), is a not 
uncommon outcome. 
The existence of primary chronic appendicitis, in the 
form of granulating wounds in the mucous membrane, has 
been denied by Aschoff, who referred these lesions to a pre- 
ceding acute process in which healing had been delayed. 182 
APPENDICITIS 
Both Riedel and Oberndorfer, on the contrary, have argued 
in favor of chronic appendicitis, although they held differ- 
ent views regarding it. Still, the observations of Aschoff 
conducted as they were upon material free from post-mortem 
changes, are remarkably accurate (see Aschoff's contro- 
Fig. 103.-Appendicitis; stage of healing, with obliteration of the lumen (hand lens), a, 
obliterated lumen; b, submucosa with inflammatory cellular infiltration; c, point of attachment 
of the meso-appendix. 
versy with Oberndorf er), and Oberndorf er later retracted 
voluntarily the greater portion of his argument. 
Obliteration of the lumen of the appendix, a common 
finding at autopsy, was formerly believed to be a physio- 
logical process in some instances, but it is now realized 
that this invariably represents the end stage of appendicitis. PERITONITIS 
183 
The most important sequel of appendicitis is suppura- 
tive peritonitis, which does not differ anatomically from 
that due to other causes. In the acute stage, while the 
amount of exudate is still small, the intestine is dilated 
and its coils are matted together by delicate threads of 
fibrin. Where loops are adherent, the serosa is greatly in- 
jected and the remainder of the peritoneum, both visceral 
and parietal, is somewhat reddish and lustreless. The abdo- 
men and the pelvis contain more or less free fluid, which may 
be slightly turbid, or consist almost entirely of pus; in 
cases of the latter type, the amount is apt to be abundant, 
and the peritoneal injection is not very pronounced. Surgi- 
cal experience shows that the exudate in the earlier stages 
of appendicitis may be serous instead of fibropurulent; such 
an exudate is of toxic origin. 
Appendicitis and its accompanying peritonitis are often 
confined to the ileocsecal region, and isolated by adhesions 
from the rest of the abdominal cavity. In some of these 
cases, the pus finally escapes into the general peritoneal 
cavity, while in others it follows an extraperitoneal route, 
burrowing into the retroperitoneal tissue of the inguinal 
region; from this situation it may extend to the thigh and 
the external genitalia by way of the inguinal or the femoral 
canal, or spread over the abdomen. Extraperitoneal exten- 
sion upward behind the caecum to the kidney is common, 
and in rare instances the exudate may even invade the 
tissues of the back, or reach the pelvis (see Winkler for 
details of the various routes which the pus may traverse). 
Special conditions must be present if the suppurative 
process is to spread beyond the confines of the peritoneum, 
for even the most fulminant inflammation never breaks 
through of itself; the determining factor is the position of 
the appendix. Thus, a path into the extraperitoneal tissues 
will be furnished when a necrotic appendix is adherent to 
the peritoneum, or when a suppurative focus perforates into 
the meso-appendix; the retrocascal abscess is found in those 184 
APPENDICITIS 
cases where the appendix is drawn upward behind the 
caecum. 
As the inflammation often invades organs to which the 
appendix has become adherent, perforation into the caecum 
is not at all infrequent. If the appendix reach well down 
into the pelvis, the tubes and ovaries may be invaded, either 
directly, or by way of the blood- or lymph-channels; there 
follows, then, an acute suppurative lesion, or else a more 
chronic process resulting in adhesions. Conversely, inflam- 
matory conditions in the pelvic organs sometimes attack 
the appendix, and it is often impossible to decide which 
is primary. Perforation into the urinary bladder, the ure- 
ter, or the gall-bladder is rare (for bibliography, see 
Tanaka). CHAPTER XVII 
PULM'ONARY TUBERCULOSIS 
This disease, in spite of the manifold variations which 
it exhibits, is easily and surely recognizable from the exten- 
sive destruction of lung tissue and the presence of its char- 
acteristic lesion, the tubercle. 
The miliary tubercle (Figs. 105 and 121), so called be- 
cause it corresponds in size with a millet seed, is just visible 
to the naked eye; lesions which exceed this size are produced 
by the conglomeration of smaller ones. A young tubercle is 
grayish and translucent, but as it increases in size its centre 
becomes dull, opaque, and yellowish, from the supervention 
of coagulation necrosis, or caseation, as the lesion is called, 
on account of the macroscopic appearance of affected areas. 
A tubercle develops in the following manner. 
Lodgement of the bacillus in the tissues is followed by 
the appearance of lymphocytes, epithelioid cells, giant-cells, 
and fibrin, the proportion between these constituents vary- 
ing in different cases; some tubercles are made up exclu- 
sively of epithelioid cells (Fig. 121). The epithelioid cell, 
a large polymorphous element with a clear nucleus, is de- 
rived from connective tissue (v. Baumgarten, Pertik), 
according to the majority of investigators, rather than 
from the cells of the blood. A giant-cell is a large element 
with an oval or roundish contour and bearing a number of 
peripheral or polar nuclei (Langhans type). It is still a 
question for discussion whether this cell is the product of 
repeated nuclear division within a cytoplasm which does 
not undergo concomitant fission, or whether it results from 
the coalescence of a number of elements; I incline toward the 
former hypothesis. Tn any case, it is probably a derivative 
of the epithelioid cell. 
Epithelioid and giant-cells together make up a central 
area, which is surrounded by a zone of lymphocytes. The 
185 186 
PULMONARY TUBERCULOSIS 
proliferative changes induced by the tubercle bacillus grad- 
ually obliterate the blood-vessels and, as no new ones are 
formed, the tubercle, particularly toward its centre, is de- 
Fig. 104.-Tuberculous peribronchitis (two-thirds natural size). 
prived of blood. Partly by reason of this circumstance 
and partly on account of the presence of deleterious products 
elaborated by the bacillus itself, the central area undergoes TUBERCULOUS PERIBRONCHITIS 
187 
regressive changes (coagulation necrosis), and accordingly 
loses its affinity for stains. 
Because of their multiplicity, the conditions to which 
the tubercle bacillus gives rise in the lung have been classi- 
fied in a variety of ways. Two main types, however, stand 
out with a certain degree of distinctness-tuberculous peri- 
bronchitis, in which proliferative changes predominate, and 
tuberculous bronchopneumonia, which is principally an 
exudative lesion. 
Fig. 105.-Tuberculous peribronchitis (slightly enlarged), a, tubercles; b, confluent tubercles; 
c, caseation in the centre of a tubercle; d, giant-cell. 
In the former (Fig. 104), tubercles develop in the inter- 
stitial connective tissue about the bronchi. Some of these 
lesions eventually suffer caseation while others, in conse- 
quence of a vigorous proliferative tendency in and about 
them, undergo cicatrization. The resulting scars are stained 
gray or black by the presence of carbon particles, and a 
peribronchitic area, therefore, not infrequently appears as 
a black spot, with an areola of younger lesions about its 
periphery. The tendency toward cicatrization is sometimes 
so strong as to produce scars several centimetres in diame- 188 
PULMONARY TUBERCULOSIS 
ter, which may give rise by coalescence to large, irregular 
areas of fibrosis (Fig. 106). In this manner tuberculosis 
Fig. 106.-Pulmonary tuberculosis with extensive cicatrization (two-thirds natural size), a, 
connective tissue, studded with tuberculous nodules; b, old cavity with caseous contents. 
undergoes spontaneous cure, the eruption of fresh tubercles 
at the margin of the lesion slackening and finally ceasing 
altogether, cavities becoming contracted and encapsulated CICATRIZATION 
189 
while, in the meantime, their contents undergo calcification; 
nevertheless, bacilli enclosed within these calcified lesions 
are still virulent, as can be shown by inoculating them into 
guinea-pigs. The granulation tissue lining a healed cavity 
becomes gradually transformed into a firm, smooth layer 
of fibrous tissue, and in some cases epithelium grows in from 
a communicating bronchus and clothes the wall (v. Hanse- 
mann). The wide distribution of tuberculosis, and the fre- 
quency with which recovery takes place, may be appreciated 
from the investigations of Nageli, Burckhard, Lubarsch, 
Hart, and others, who found healed foci in from 90 to 97 
per cent, of all individuals coming to autopsy. Even exten- 
sive lesions may recover, although a favorable outcome in 
these cases is rather rare (Hauser, B. Fischer). 
Cicatrization, although a conservative process, some- 
times results in the development of cavities. Thus, fibrous 
tissue in the vicinity of a bronchus may lead to bronchi- 
ectasis and the wall of the dilated segment may be attacked 
by bacilli from lesions elsewhere in the lung. The bronchi- 
ectatic origin of smaller cavities can often be demonstrated, 
but in larger ones the process is too far advanced. These 
latter (Fig. 107) may be sufficiently large to include an 
entire lobe, and so complicated that the extent of their 
ramification often remains unsuspected until the lung has 
been incised in several directions. Their walls are covered 
in some places with a fibrinosuppurative exudate, while in 
others they are the seat of caseation or ulceration; a char- 
acteristic feature is the presence of festoons of tissue, 
which represent the remains of more resistant portions of 
the lung, and not infrequently contain blood-vessels. The 
vessels, therefore, seem longest able to resist destruction, 
but they finally suffer arrosion, and haemoptysis occurs in 
consequence unless thrombosis has taken place in the mean- 
time. 
In cases coming to autopsy shortly after a hemorrhage, 
the cavity is full of blood; as a rule, it is not difficult to 190 
PULMONARY TUBERCULOSIS 
discover the affected vessel, and frequently it can be shown 
that an arrosion aneurism has been responsible for the 
rupture. If several days have elapsed, areas of lobular 
pneumonia can usually be demonstrated in the lower por- 
Fig. 107.-Pulmonary tuberculosis; apical cavity and caseous bronchopneumonia (one- 
half natural size), a, cavity; b and c, areas of caseous pneumonia at the base of the upper lobe; 
d, surface of lung between upper and lower lobes, covered with fibrin. 
tion of the lung, their dark red color stamping them as 
products of the aspiration of blood. 
Not only by causing hemorrhage, however, do cavities 
influence the course of tuberculosis. Their pus contains, 
in addition to the tubercle bacillus, pyogenic and other TUBERCULOUS BRONCHOPNEUMONIA 
191 
organisms of all sorts, the toxins of which are absorbed by 
the body; furthermore, this highly infectious material is 
readily carried by aspiration into the lower portions of the 
Fig. 108.-Pulmonary tuberculosis; caseous pneumonia (one-half natural size), a, upper 
lobe; b, upper part of the lower lobe, both studded with areas of caseous pneumonia; c, base of 
the lung, containing pneumonic areas that show no caseation, or only the earlier stage of this 
condition; d, old cavity at the apex. 
lungs, where it sets up fresh lesions, often in the form of 
bronchopneumonia (Fig. 107). 
In tuberculous bronchopneumonia, which is essentially 
an exudative process, as has already been said, an exudate 
consisting principally of cells, like that of lobar pneumonia, 192 
PULMONARY TUBERCULOSIS 
involves small groups of alveoli throughout the lung; exten- 
sive patches with a caseous exudate are known as cheesy 
pneumonia (Fig. 108). These appear as isolated, rosette- 
shaped, dull yellow, granular nodules, projecting somewhat 
Fig. 109.-Pulmonary tuberculosis, with cavities in both upper and lower lobes and pleural 
thickening (one-half natural size), a, thickened pleura; b, basal surface of the lung, covered 
with fibrin. 
above the cut surface; the fusion of such lesions gives rise 
to large areas of more regular outline, which may be so 
extensive as to include an entire lobe. In the case illustrated 
by the figure, the disease had overrun both lungs in the form 
of confluent, caseous patches of lobular pneumonia, without PRODUCTIVE AND EXUDATIVE TUBERCULOSIS 
193 
giving rise to the nodules ordinarily associated with tuber- 
culosis. 
A productive type of tuberculosis was distinguished 
from an exudative by the earlier investigators of the dis- 
ease, and although the 
discovery of the specific 
organism proved that 
both are the outcome of 
a com m o n etiological 
agent, not a few observ- 
ers, and Orth in par- 
ticular, have continued 
to distinguish the two 
forms anatomically, and 
to assume that prolifer- 
ation and exudation, 
combined though they 
generally are, may take 
place separately. A pure 
caseous hepatization may 
therefore involve the 
lung in the absence of 
tubercles or diffuse thick- 
ening of the alveolar 
septa, while, on the other 
hand, a tubercle some- 
times contains no exu- 
date. In v. Baumgar- 
ten's opinion, on the con- 
trary, proliferation and 
exudation are invariably 
associated. Investigating tuberculosis experimentally in- 
duced in rabbits, he found that the smaller the number of 
bacilli and the lower their virulence, the more distinct were 
the proliferative features and the less salient the exudative, 
while conversely, the greater the number of organisms and 
the higher their virulence, the more prominent was exu- 
13 
Fig. 110.-Tuberculous ulceration in the larynx 
and the trachea (one-half natural size). 194 
PULMONARY TUBERCULOSIS 
dation; since there was always some evidence of prolifer- 
ation, however, the two processes were to be regarded as 
inseparable. No pulmonary lesion which would represent 
anatomically a pure fibrinous pneumonia with secondary 
caseation had been reproduced in animals experimentally 
infected with the tubercle bacillus. 
Cheesy pneumonia is accompanied by the destruction 
of lung tissue, and the necrotic material, easily reaching a 
Fig. 111.-Tuberculous ulceration in the larynx (one-half natural size), a, superficial ulcera- 
tion on the right vocal cord; b, deeper ulceration on the inner surface of the epiglottis. 
bronchus, is evacuated; in this way, also, do cavities arise. 
Where areas of bronchopneumonia or caseous pneumonia 
are present, it may be inferred that the course of the 
disease has been rapid, particularly when the latter lesion 
is extensively distributed (phthisis florida). 
Unaffected regions of the lung may be either normal or 
oedematous; the portions surrounding tuberculous areas 
sometimes have a gelatinous character (gelatinous pneu- TUBERCULOUS PLEURITIS AND LARYNGITIS 
195 
monia), due to the collection of epithelial cells and a serous 
or serofibrinous exudate within the alveoli. 
In the presence of cavities, bronchitis makes its appear- 
ance; the mucous membrane of the bronchi is then injected, 
and covered with an abundant, grayish-yellow, more or less 
fluid secretion. Secondary involvement of the bronchi by 
tuberculosis has already been described in connection with 
the discussion of cavities; primary lesions are rare 
(Hedin ger). 
A lung which is less widely affected than its fellow gen- 
erally undergoes compensatory hypertrophy, if that on the 
opposite side be extensively diseased. 
The pleura is nearly always implicated, its lesions, which 
are various, including tubercles and serous or serofibrinous 
processes. Suppurative pleurisy (empyema) generally re- 
sults from the extension of a cavity to the surface, or from 
the breaking down of a superficial area of caseation, while 
perforation of a cavity into the pleural sac gives rise to 
pyopneumothorax. The end results of pleurisy are a com- 
mon finding at autopsy; the lung is partially or totally 
attached to the chest wall by adhesions which may be deli- 
cate but are usually thick and very firm; in the latter in- 
stance, the pleura frequently undergoes dense fibrous thick- 
ening (Fig. 109), and encloses caseous or calcified foci. 
The bronchial and often the tracheal lymph-nodes are 
swollen in pulmonary tuberculosis, and their cut surface 
shows grayish points which are easily recognized as 
tubercles. 
Calcification sometimes takes place in such nodes, but 
caseation is rare, except during childhood. 
Tuberculous laryngitis is characterized by flat, lenticular 
ulcers which are sometimes continued into the trachea 
(Fig. 110), or by deeper ulceration involving the vocal cords 
or the arytenoid cartilages (Fig. 111). It is not of uniform 
occurrence, and in many consumptives the mucous mem- 
brane of larynx and trachea remains perfectly intact. 196 
PULMONARY TUBERCULOSIS 
The intestine is almost always attacked, and at least a 
few isolated ulcers will be found in connection with any 
fairly advanced pulmonary lesion; according to Albrecht, 
it is invariably affected if cavities of any size exist in the 
Fig. 112.-Tuberculous ulceration 
in the intestine, mild grade (three-fifths 
natural size). 
Fig. 113.-Tuberculous ulceration in the intestine, 
severe grade (two-thirds natural size), a, ulcers; b, 
folds of mucosa. 
lung. From slight participation there exist all degrees of 
involvement up to widespread destruction of the mucosa 
in both the small and the large gut. The tuberculous ulcer 
of the bowel (Figs. 112 and 113) is characterized by its 
roundish or ovoid form and the position of its long axis, 
which generally lies transverse to that of the gut. The TUBERCULOUS ENTERITIS 
197 
margin is raised and the base is often smooth, being fre- 
quently strewn with grayish or yellowish tubercles; in 
advanced cases, the ulcer reaches as far as the serosa. 
These lesions originate as tubercles in the solitary or 
agminate lymph-follicles, where caseation results in small 
ulcers which gradually enlarge by the eruption and breaking- 
down of fresh tubercles in their margin and floor. As the 
disease is prone to spread along the lymph-channels, the 
presence of ulcers can be recognized at a glance as soon as 
the abdomen is opened, by the groups or chains of tubercles 
upon the external surface of the gut. Perforation is com- 
paratively uncommon, though tuberculous ulcers ordinarily 
show no tendency toward cicatrization. It is worthy of 
note that the mesenteric lymph-nodes are not often attacked 
during the course of secondary tubercular enteritis; they 
may be somewhat swollen, but they rarely contain tubercles 
or undergo caseation. 
The origin of tuberculous laryngitis is to be referred 
principally to infection by the sputum, though a few cases 
develop independently of pulmonary lesions, by the deposi- 
tion of bacilli from the blood- or lymph-streams; this latter 
statement concerns particularly that variety of laryngitis 
characterized by papillary outgrowths. Tuberculous enter- 
itis is a consequence of the ingestion of sputum containing 
tubercle bacilli, and severe involvement is sometimes dis- 
covered in connection with insignificant apical lesions; in 
such cases, the disease pursues the course of a general infec- 
tion (Passler). That it may occur primarily also, cannot 
be denied, but in adults this is a most unusual occurrence 
(B. Fischer). 
B. Fischer and his pupils have demonstrated that, in 
patients with tuberculous enteritis, the contents of the 
thoracic duct and blood taken from the portal vein contain 
tubercle bacilli; the organisms are not found in these situa- 
tions, however, in consumptive individuals with no involve- 
ment of the intestine. Tuberculous lesions in the bowel, 
therefore, flood the body with bacilli which, though they 198 
PULMONARY TUBERCULOSIS 
may exert some immunizing influence upon the organism, 
as Fischer has suggested, may, on the other hand, give rise 
to additional metastatic lesions in the lungs. 
Secondary processes in the larynx and intestine furnish 
one example of the many ways in which tuberculosis may 
spread; in both instances the infection is ectogenous, being 
secondary only because the bacilli happen to be deposited 
from a lesion already present. 
A second method of dissemination is carriage of the 
bacilli to distant organs by the blood- or lymph-streams. 
It is now known that in the middle or later stages of tuber- 
culosis the organisms are very frequently recoverable from 
the blood, and that they regularly enter the thoracic duct 
during tuberculous enteritis. In spite of this, haematog- 
enous metastasis is an uncommon event, which does not 
occur until late in the disease, a fact which is probably to 
be explained by the presence of an immunity acquired by 
the body toward its own bacilli (Romer). 
By animal inoculation, Liebermeister demonstrated the 
presence of bacilli in the organs of those dead of tuber- 
culosis, even when there was no lesion present except chronic 
inflammation, and his findings serve well to introduce the 
statement that certain conditions appear during the course 
of pulmonary tuberculosis which are due, not to the bacilli, 
but to their toxins. Here belong those affections of the 
skin known as tuberculides, as well as simple inflammatory 
lesions of the kidney (Heyn), but it is doubtful whether the 
parenchymatous nephritis of tuberculosis (for bibliography, 
see W. Fischer), the atrophy and hyperplasia of the liver 
(Jores), or the phlebitis obliterans (Liebermeister), have 
any direct relation to the virus of the disease. 
During the course of pulmonary tuberculosis there occur 
in the various organs changes which have no immediate 
connection with this disorder, among them fatty metamor- 
phosis in the liver. In this condition, a certain degree of 
which is very commonly encountered, some metabolic dis- 
turbance affects the hepatic cells in such a way as to permit CARDIAC ATROPHY AND HYPERTROPHY 
199 
the accumulation of fat within them. They become greatly 
enlarged by droplets of variable and often considerable 
size, and since these are frequently deposited first in the 
cells at the periphery of the lobule, the marginal portions of 
these divisions appear on the cut surface of the liver during 
the earlier stages of the process as yellowish lines (Fig. 
114). In advanced cases, the entire organ is enlarged and 
doughy and its cut surface is of a uniform yellowish hue; 
fat remains on the knife with which it has been laid open. 
Helly has described the wide variations shown in the dis- 
tribution of the fat, both within the 
lobules and within the cells them- 
selves, attributing them to pecul- 
iarities in the blood supply. 
The general emaciation in tu- 
berculosis is usually extreme, and 
the muscles pale and poorly devel- 
oped ; in accord with this latter 
finding the heart is small, and its 
musculature of a brownish color 
from the deposition of pigment 
granules about the nuclei of the 
shrunken fibres (brown atrophy) 
While emphasis was formerly laid 
upon the atrophic heart of tuber- 
culosis (Rokitansky, Beneke, and others), a poorly developed 
myocardium can no longer be regarded as necessarily corre- 
lated with feeble action, since a small heart may be perfectly 
able to meet the functional demands imposed upon it. Thus, 
the work of W. Muller has shown that the size of the heart 
bears a certain relation to the body mass, or, as Hirsch has 
more accurately expressed it, to the volume of the skeletal 
musculature. 
It has frequently been asserted that the right ventricle 
hypertrophies during the course of pulmonary tuberculosis, 
and it is perfectly true that extensive cicatricial contraction 
of the lung may be followed by an obvious cardiac enlarge- 
Fig. 114.-Fatty liver, moderate 
grade (natural size). 200 
PULMONARY TUBERCULOSIS 
ment. Nevertheless, the effect exerted upon the heart by 
the usual combination of tubercles, slight cicatrization, and 
cavity formation, is not distinct, and is certainly not sig- 
nificant ; its occurrence, indeed, has even been denied, 
though such an attitude is probably unwarrantable. Only 
a determination of the relative weight of the heart after 
Muller's method can decide this question, and this, so far 
as I know, has never been carried out. 
A mild grade of verrucous endocarditis is a common 
accompaniment of pulmonary tuberculosis, but the etiologi- 
cal importance of the tubercle bacillus is problematical, 
though the organism can often be demonstrated in small 
numbers (for bibliography, see Koniger). It is permissible 
to speak of true tuberculous endocarditis, of course, only 
when tubercles can be discovered in the vegetations, and 
such cases are rare. Indeed, Koniger has asserted that the 
endocarditis is invariably a product of secondary infection, 
denying the power of the tubercle bacillus to produce such 
a lesion, and referring the occurrence of this organism 
in the absence of histological evidences of tuberculosis to 
simple deposition from the blood-stream. 
There are several conditions which may serve to explain 
the vulnerability of the lungs, and particularly of their 
upper portions. For example, the statement that aeration 
is incompletely performed at the apices is supported by 
Birch-Hirschfeld, who found that the bronchus running to 
the apex ascends so abruptly as to cause an interruption 
to the respiratory air current. Again, it has been assumed 
by many authors that blood circulates but sluggishly in the 
upper extremity of the lung (for bibliography, see Hart). 
Furthermore, an individual belonging to a tuberculous 
family may have a flattened thorax, an anomaly which is 
often associated with a decrease in its transverse, and a 
simultaneous increase in its long dimension (Rokitansky). 
Another thoracic malformation in young persons of tuber- 
culous stock was described in 1859 by Freund, who discov- 
ered that the first rib on one or both sides is often so short- THORAX PHTHISICUS 
201 
ened as to reduce the thoracic aperture; ossifying periostitis 
encloses the cartilage in a sheath of bone, and rigidity of 
the thorax is a common outcome. These observations have 
been confirmed and extended by the careful work of Hart, 
according to whom the thoracic aperture is not only reduced 
in size, but altered in shape. Since the deformity, beside 
being congenital, as Freund assumed, may be the result of 
scoliosis affecting the cervical and upper thoracic verte- 
braq Hart and Harras have distinguished a primary (con- 
genital) and a secondary (acquired) type. According to 
Hart, who has investigated it in the most thorough manner, 
the deformity known as thorax phthisicus is a secondary 
product of the anomaly just described and he would reserve 
the term, accordingly, for such cases as show the typical 
narrowing and deformity of the upper opening, not apply- 
ing it to the flat thorax with no abnormality of its aperture. 
The malformation which Freund described is attended 
by pressure upon the lung, and a groove is imprinted by the 
intruding first rib. According to Schmorl, the compression 
so produced brings about the retention of secretions and 
favors invasion by the tubercle bacillus. 
To anomalies of the thoracic aperture, which are exceed- 
ingly common, Hart ascribed great significance. They pro- 
mote the development of apical tuberculosis, no matter 
whether the bacilli reach the lung by way of the air passages, 
the blood-stream, or the lymph-channels; other types of 
ossification in the first costal cartilage, including that of 
advanced life, may act in the same way. Finally, both 
v. Hansemann and Hart have made the interesting obser- 
vation that tuberculosis attacking a lung which is compro- 
mised by some such thoracic deformity as kyphoscoliosis, is 
apt to be localized in the compressed portion rather than at 
the apex. 
Hart is entirely justified in maintaining that the mal- 
formation which he and Freund investigated results in "a 
mechanical predisposition of the apex toward tuberculosis," 
the significance of which can hardly be underrated. CHAPTER XVIII 
Metastatic and Acute Generalized Miliary Tuberculosis 
In tuberculous meningitis, the membranes in the region 
of the brain stem and the sylvian fissure have a gelatinous, 
Fig. 115.-Tuberculous meningitis (natural size). 
dull, gray or yellowish appearance; upon close examina- 
tion the pia is found to be studded with tubercles (Fig. 
115), which, except in a few cases, are so small that they can 
202 TUBERCULOUS MENINGITIS 
203 
just be discerned by the naked eye. Microscopic examina- 
tion shows that the meninges are infiltrated by leucocytes, 
lymphocytes, and plasma cells (Wolff), and that the 
arrangement of the tubercles is very often periarterial 
(periarteritis tuberculosa) ; the inner layers of the vessels 
are sometimes invaded, and may undergo caseation (Hek- 
toen; for bibliography, see Askanazy). It is the base of 
the brain that is earliest and most frequently affected, 
although small, isolated foci are sometimes found on its 
convex surface. The disease does not ordinarily attack the 
Fig. 116.-Multiple tubercles (a) in the brain (two-thirds natural size). 
cerebral cortex, which, however, is sometimes the seat of 
softened hemorrhagic areas (hemorrhagic encephalitis) in 
the neighborhood of the meningeal lesions; according to 
Askanazy, these are a consequence of thrombosis in small 
veins involved by tuberculous phlebitis, and are accordingly 
to be regarded, not as inflammatory, in the strict sense of 
the word, but as due to hemorrhage and softening. 
The ventricles of the brain are dilated, containing an 
increased amount of clear, watery fluid (inflammatory 
hydrocephalus), and over their ependyma are scattered fine 
granulations, some of which are tubercles (Ophuls) ; in 204 
METASTATIC TUBERCULOSIS 
many cases the ependyma, and even the brain substance 
itself, is softened. 
The so-called solitary tubercle is frequently encountered 
in the brain, either with or without tuberculous meningitis. 
This is a caseous lesion (Fig. 116) about the size of a walnut, 
Fig. 117.-Lung of a child with metastatic tuberculosis (three-fourths natural size). A 
little above the middle of the picture can be seen the enlarged and caseous lymph-nodes of the 
hilus. 
or occasionally much larger, surrounded by a narrow zone 
of granulation tissue containing microscopic tubercles; it 
may be found in any region of the brain or, more rarely, in 
the spinal cord. It is sometimes multiple. 
Both tuberculous meningitis and the solitary tubercle 
are more common in childhood, and both are secondary PORTAL OF ENTRY 
205 
diseases resulting by metastasis from a primary infection 
which, in children, is nearly always to be sought in caseous 
bronchial and tracheal lymph-nodes. Seldom, however, are 
they the sole secondary lesions, for it is usual to find evi- 
dences of tuberculosis in the lungs and many of the other 
organs. In some instances of tuberculous adenitis, the 
Fig. 118.-Cut surface of a spleen studded with metastatic, caseous, tuberculous foci 
(two-thirds natural size). 
metastatic process is limited almost entirely to the lungs, 
while in others it is distributed throughout the thorax and 
the abdomen, the brain meanwhile remaining free. 
The lungs in children with metastatic tuberculosis offer 
a familiar picture. They are thickly and uniformly beset 
with tubercles (Fig. 117), many of which are visible even 
from the pleural aspect (Fig. 120), while on the cut surface 
they are innumerable; these foci may be either small and 
grayish or larger and yellowish, and even the smallest of 206 
METASTATIC TUBERCULOSIS 
them are sometimes surrounded by groups of daughter tu- 
bercles or by an area of caseous pneumonia. The differences 
in size are usually slight, whence it may be inferred that 
if the lesions are not of simultaneous development, they 
have at least originated within a short period of time; this, 
taken in conjunction with the fact that they are uniformly 
Fig. 119.-Tuberculosis of the liver; from a case of metastatic tuberculosis in a child 
(two-thirds natural size). 
distributed throughout the lungs, suggests that the bacilli 
must have reached the lungs by way of the blood-stream. 
Tubercles may be discovered in the kidneys, although in 
smaller number, in the spleen (Fig. 118), the liver (Fig. 
119), and, rarely, in the myocardium. 
As has already been said, the starting point for these 
manifold secondary foci in children is generally tuberculous TUBERCULOUS LYMPHADENITIS 
207 
lymphadenitis which, beside the tracheal and bronchial 
groups (Fig. 120), may affect the subpleural lymphatic tis- 
sue, the tracheal, supraclavicular, cervical, or mesenteric 
nodes (tabes mesenterica). In the microscopic picture of 
advanced lymphadenitis the predominant feature is casea- 
tion, but in the earlier phases only young tubercles are 
present; these possess, 
in the main, the charac- 
teristics of those al- 
ready described for the 
lung. 
Tuberculous affec- 
tions of the lymph- 
nocles are important in 
their relation to ques- 
tions regarding the pri- 
mary site of infection, 
since it is usually the 
nodes contiguous to the 
point of attack which 
are first involved, the 
tubercle bacillus pene- 
trating the m u c o u s 
membrane in young sub- 
jects without leaving 
any trace of its passage. 
Hence, it should be rela- 
tively easy to trace the 
route of infection by 
means of the resulting 
lymphadenitis. 
Although transfer of tuberculosis through the placenta 
is possible (Birch-Hirschfeld), and tubercular disease of 
the placenta is a frequent lesion in consumptive women 
(Schmorl), the experience of paediatrists who have em- 
ployed the tuberculin tests suggests that tuberculosis, even 
in the youngest of infants, is usually an acquired, rather 
Fig. 120.-Section through caseous bronchial and 
tracheal lymph-nodes, from a case of metastatic 
tuberculosis in a child; the portion of lung remain- 
ing in the preparation contains metastatic tubercles 
(one-half natural size), a, caseous lymph-nodes; b, 
bronchus; c, upper lobe, seen from the surface; d, cut 
surface of lower lobe. 208 
METASTATIC TUBERCULOSIS 
than a congenital, disease. Furthermore, it may be inferred 
-always assuming that one is dealing with regional lymph- 
adenitis-that, corresponding to the greater frequency 
with which the bronchial lymph-nodes are involved, the 
lungs in children are attacked more commonly than the 
gastro-intestinal tract. Since Behring has suggested that 
infection during early life takes place almost invariably 
by way of the intestine, it is of interest to see how frequently 
primary anatomical tubercular enteritis is encountered; 
according to Heller, it is found in 21 per cent, of cases, 
Fig. 121.-Epithelioid cell tubercles in a lymph-node (slightly enlarged), a, epithelioid cells; 
b, giant-cells. 
while other authors (for bibliography, see Beitzke) give 
somewhat different figures. On the whole, it can be said 
that it is much more common than was formerly supposed, 
yet not by any means so frequent as Behring's hypothesis 
demands. 
The view has been advanced that lymph-nodes at a dis- 
tance from the portal of entry may be involved by extension 
of the tubercular process along the lymph-channels, and in 
particular has it been proposed that the tracheal and bron- 
chial nodes may become infected from the cervical group; HEMATOGENOUS PULMONARY TUBERCULOSIS 
209 
the theory which would ascribe tuberculosis to infection 
through the tonsil is founded in part upon this view. 
Against this conception stands the observation of Beitzke, 
that communication between the cervical and bronchial 
lymph-nodes is not of regular occurrence, or, if it be present, 
is so slight as hardly to explain frequent extension of the 
infection from one to the other. Moreover, the assumption 
that there is a direct lymphatic path between the cervical 
nodes and the apex of the pleural cavity has been proved 
fallacious, and a lymphatic route from the mesenteric nodes 
to the lungs, while not an impossibility, does not seem at all 
probable (Most). 
On the contrary, there is but little doubt that bacilli 
may reach the lungs by passing from the lymph-stream into 
the blood. Evidence for the truth of this statement is to be 
gathered from many animal experiments, such as those 
of Orth and Rabinowitsch, where tubercle bacilli intro- 
duced into the rectum were discovered after a few days in 
the lymph-nodes, the blood, and the lungs, and it can be 
confidently asserted on the basis of still earlier work by both 
Orth and v. Baumgarten, that a disease analogous to pul- 
monary tuberculosis in man follows haematogenous infection 
in animals, as after the introduction of large numbers of 
bacilli into the uninjured urinary bladder (v. Baumgarten). 
The etiology of haematogenous pulmonary tuberculosis 
in the human subject has been variously explained. Ribbert 
has assumed that the bacilli enter the blood-vessels of the 
lung from another part of the body, usually from the bron- 
chial lymph-nodes, after which they settle partly in the 
perivascular lymphatic tissue and partly in the alveoli and 
alveolar passages. The hypothesis of Behring has already 
been mentioned, according to which every case of pulmonary 
tuberculosis may be referred to primary infection through 
the intestinal tract during infancy, the bacilli finally causing 
tuberculous disease of the lungs after a sojourn of years in 
the lymph-nodes (latent stage). The hypothesis is faulty, 
however, in that it exaggerates the frequency of infection 210 
METASTATIC TUBERCULOSIS 
by way of the intestine, which it represents as the sole cause 
of pulmonary phthisis. It was formerly open to serious 
doubt, too, whether tubercle bacilli were able to remain 
latent in the body for very long, and v. Behring had no proof 
that they could; nevertheless, more recent experiments sug- 
gest that they do, Bartel, in particular, having shown that 
after experimental infection there develops first a "lymph- 
oid stage," upon which may supervene a manifest tuber- 
culosis. In the lymphoid stage, the lymph-nodes are swollen 
and hyperplastic, and it is possible to demonstrate the 
bacilli in them, although this can be done only infrequently 
and with difficulty. According to this author, tuberculosis 
may develop secondarily from this first stage, and produce 
the impression of a primary lesion, but the real primary 
infection, which initiates the lymphoid stage, is always 
lymphogenic. 
In Bartel's opinion, it is possible for evidences of im- 
munity to appear even during the first stage, and for rein- 
fection to take place later, a significant inference, since 
changes in the relations between the body and its infecting 
bacilli may supervene during the course of the disease and 
alter the action of the organisms. Certain writers have 
gone so far, indeed, as to propose dividing tuberculosis 
into stages analogous with those of syphilis (Hamburger), 
and to explain thereby the differing manifestations of the 
former disorder in children and adults. 
Finally, it has been suggested by v. Behring and mem- 
bers of his school, that pulmonary tuberculosis is actually 
an indication of immunity. Koch had found that guinea- 
pigs which survive an injection of tubercle bacilli react less 
severely to inoculation with these organisms than do normal 
ones, showing, therefore, a certain degree of immunity. 
Romer, supplementing the investigations of v. Behring, 
Orth, and others, showed that immune guinea-pigs develop 
chronic pulmonary tuberculosis with cavity formation upon 
re-inoculation with large doses of tubercle bacilli, although 
these produce in normal animals an acute, generalized, and AEROGENOUS INFECTION 
211 
rapidly fatal process. The majority of individuals are 
somewhat resistant to tuberculosis, in consequence of infec- 
tion during early life, and if it be possible to transfer the 
above findings to man, the subsequent appearance of pul- 
monary tuberculosis with cavity formation would be to some 
extent-absurd as the statement may seem-an evidence of 
immunity. 
According to Kretz, the conditions governing the de- 
velopment of pulmonary lesions depend upon the varying 
relations between the infected organism and the bacilli 
which it harbors. 
Interesting though these speculations may be, I cannot 
regard them as assured. Still, so much is certain, that 
whereas the simple assumption of infection by inhalation 
once seemed to explain adequately the development of pul- 
monary tuberculosis, the problem is now known to be in- 
finitely more complex. The fact that this disease may be 
engrafted upon latent or manifest tuberculous lymphade- 
nitis can hardly be taken as a warrant for denying categori- 
cally the occurence of direct aerogenous infection of the 
lung; indeed, it has been found possible to evoke a condition 
in guinea-pigs which is entirely parallel with pulmonary 
tuberculosis in man, by causing the inhalation of small 
numbers of bacilli (Fliigge, Findel). And since direct aerog- 
enous infection is the type which best explains the ordinary 
post-mortem findings in the human subject, as Albrecht 
maintained, it must be regarded, even yet, as the most 
probable method. 
This is a special type of metastatic tuberculosis which is 
characterized by the uniform minuteness of its lesions, the 
cut surfaces of affected organs looking as though they had 
been strewn with sand (Fig. 122). 
Where the disease remains confined to the lungs, a pri- 
mary lesion can be demonstrated elsewhere in the body; 
for example, I have seen these organs involved by them- 
ACUTE GENERALIZED MILIARY TUBERCULOSIS 212 
GENERALIZED MILIARY TUBERCULOSIS 
selves alone in consequence of caseous osteomyelitis in the 
vertebrae, or tuberculosis of the uterus. Tn such instances 
the tubercles are frequently of somewhat larger size, though 
Fig. 122.-Miliary tuberculosis in the lung (one-half natural size), a, areas of primary tuber- 
culosis. The remainder of the cut surface is sprinkled with very small nodules. 
still recognizable as metastatic by their uniform distribu- 
tion. A transitional type, rather rare in adults, and charac- 
terized by the presence of miliary lesions in the lungs and DISTRIBUTION 
213 
a few metastatic deposits in other locations, leads to that 
in which all the organs, including the lungs, are studded 
with miliary foci (generalized miliary tuberculosis). Tu- 
bercles are particularly abundant and visible even to the 
naked eye in the kidney, the spleen, and the liver; tubercular 
meningitis frequently co-exists, but may, on the other hand, 
be absent. 
In a typical case, the tubercles are small and of approxi- 
mately the same size, a fact which suggests that they are of 
Fig. 123.-Miliary tuberculosis in the lung (slightly enlarged), a, tubercles, with b, caseous 
centres; c, unchanged alveoli. 
recent, almost simultaneous, origin, and the inference is 
strengthened by their isolation and the absence of any con- 
siderable reaction in the surrounding tissues (Fig. 123). 
The abundance of the tubercular eruption indicates infec- 
tion by a multitude of organisms, and its universal distribu- 
tion can be explained only by postulating a saturation of 
the blood with bacilli, either sudden, or completed within a 
relatively short period. 
Weigert must be credited as the first to recognize this. 
From anatomical conditions alone, and at a time when the 214 
GENERALIZED MILIARY TUBERCULOSIS 
bacillus of tuberculosis was still undiscovered, he formu- 
lated his conception of the pathogenesis of miliary tuber- 
culosis and intimated the way in which the blood is over- 
whelmed by the tuberculous virus. In the veins, especially 
those of the lung, he discovered large ulcerated tubercles, 
the contents of which, therefore, had direct access to the 
circulating blood. Such lesions (Fig. 124) appear in the 
form of yellowish, largely caseous projections into the lu- 
Fig. 124.-Tubercle ia the pulmonary vein (natural size), a, pulmonary vein, opened; 
6, tubercle; c, pulmonary artery. 
men of the vessel, about the size of a bean, or even larger; 
they are sometimes polypoid. Certain cases of miliary 
tuberculosis, Weigert referred to tuberculosis of the tho- 
racic duct, discovered by Sir Astley Cooper, and later, inde- 
pendently, by Ponfick. More or less of the duct becomes 
thickened and caseous (Fig. 125), or, as in other cases, 
small multiple tubercles are found in a wall of approxi- 
mately normal thickness; the latter of these lesions, as well 
as the former, probably gives rise to generalized miliary 
tuberculosis, although here the question has not been 
definitely settled. Finally, it has been demonstrated by TUBERCULOUS ENDANGEITIS 
215 
more recent research that foci affecting the heart or the 
arteries are occasionally responsible for the dissemination 
of tuberculosis throughout the body. 
Though Weigert referred lesions in the veins to invasion 
of the vessel wall by a tuberculous process in the neighbor- 
ing tissues, and especially by caseous lymphadenitis, it is 
possible that they represent metastases from some distant 
lesion, a few bacilli reaching the circulation and attacking 
the intima. The latter method of infection, at first assumed 
for duct tuberculosis, was afterward recognized as 
responsible for tuberculous affections of the aortic 
wall, and Benda has but recently expressed his be- 
lief that the greater proportion of venous tuber- 
cles originate in the same way, i.e., as tuberculous 
endangeitis. 
Naturally, the vascular lesions must possess 
certain characteristics if they are to be regarded 
as a cause of generalized tuberculosis; in particu- 
lar must they permit the escape of a large num- 
ber of bacilli into the blood. This a characteristic 
tubercle of the intima will generally do, since it 
is usually caseous, and contains a large number of 
bacilli; when several tubercles exist, as is not sel- 
dom the case, there is the greater chance that gen- 
eralized miliary tuberculosis will be the ultimate outcome. 
Ribbert has asserted that a sudden invasion by myriads 
of bacilli is not absolutely necessary for the occurrence of 
generalized tuberculosis; the disease may ensue when, even 
in the absence of any special vascular lesion, a small number 
of organisms reach the blood-stream and, under favorable 
conditions, multiply there. His view is contradicted, how- 
ever, by the observation that the blood of tubercular pa- 
tients often contains a few bacilli, though such individuals 
do not necessarily develop generalized tuberculosis. The 
tubercle bacillus, moreover, is not ordinarily an inhabitant 
of the blood, or, at least, it is not able to multiply there so 
extensively as an organism like the anthrax bacillus. But 
Fig. 125.- 
Tuberculosis 
in the thorac- 
ic duct (nat- 
ural size). 216 
GENERALIZED MILIARY TUBERCULOSIS 
the pathogenic significance of vascular tuberculosis is em- 
phasized above all by the fact that no such lesion has yet 
been discovered without its accompanying generalized 
tuberculosis, and by the complementary fact that the per- 
centage of cases of generalized tuberculosis in which the 
point where the bacilli entered the circulation cannot be 
detected, is relatively small. Still, it requires skill and ex- 
perience to demonstrate these lesions in the vessels, and it is 
necessary to conduct the autopsy with this particular end in 
view; hence, while Weigert found a vascular focus in but 
about 50 per cent, of his cases of generalized miliary tuber- 
culosis, more recent observers (Schmorl, Lubarsch, Benda) 
place the percentage as high as 95. 
It must be emphasized, however, that such a great pro- 
portion as this will not be revealed unless the metastatic 
tuberculosis of childhood (which was formerly classified as 
miliary tuberculosis), and transitional forms between this 
and the acute generalized miliary type, be left out of the 
reckoning. Undoubtedly, acute generalized miliary tuber- 
culosis combined with vascular foci does occur during the 
earlier years of life, but in the case of metastatic tubercu- 
losis the vessels are not often invaded; hence, it can be 
asserted that, in the latter instance, the sudden entrance 
of large numbers of bacilli into the blood is not a patho- 
genetic requirement, and it is accordingly justifiable to 
separate metastatic from acute generalized miliary tuber- 
culosis, although an anatomical distinction, made solely 
upon the nature of the tubercles, is frequently difficult. 
Benda, who favored this restriction in the conception 
of acute generalized miliary tuberculosis, said that in every 
case of this type which he examined, he found foci in the 
vessels or the thoracic duct. He suggested, moreover, that 
the clinical phenomena of miliary tuberculosis, in so far as 
they are not consequences of the disproportionate involve- 
ment of single structures (lungs, meninges), can depend 
neither upon the presence of tubercles nor upon the total 
mass of tuberculous tissue and bacilli which they represent, BACTERIEMIA AND TOXINJEMIA 
217 
since in the chronic type of the disease the amount of tuber- 
culous tissue may be just as great, or perhaps even greater. 
The general features of the febrile movement and the intoxi- 
cation can be very satisfactorily explained, however, by an 
intermittent sowing of the blood-stream with bacilli and 
their toxins, such as would take place from tubercles in the 
blood-vessels; he therefore regarded the vascular focus as 
the most significant lesion in acute generalized miliary 
tuberculosis, and relegated the disseminated tubercles to 
the position of a secondary process. 
Tuberculous endangeitis and tuberculosis of the thoracic 
duct are secondary lesions, as has already been stated, 
representing, therefore, a connecting link between some 
primary lesion and the terminal generalized infection. The 
primary focus is not infrequently concealed or compara- 
tively insignificant. Pulmonary tuberculosis is rarely the 
starting point for a generalized process; this has its source 
much more often in lymphadenitis involving the bronchial, 
mediastinal, mesenteric, or lumbar nodes, or in tuberculous 
disease of the bones, particularly caseous ostitis. 
According to Simmonds, miliary tuberculosis is 
often engrafted upon lesions of the male genital organs, 
especially those of the prostate and the seminal vesicles, 
although any very apparent communication between such 
foci and the vascular system is only exceptionally demon- 
strable. It is the belief of this author that the increased 
congestion attendant upon sexual intercourse is responsible 
for the dissemination of bacilli. Tuberculosis in the genital 
tract of the female, also, may become generalized, a process 
in the uterus resulting first in abortion and subsequently, 
after the blood-channels have been thus exposed, in acute 
generalized miliary tuberculosis (for bibliography, see 
Weil). CHAPTER XIX 
Tuberculosis of the Genito-urinary System 
Tuberculosis of the kidney appears under various 
forms, of which metastatic miliary foci have already been 
discussed, while the large, solitary, caseous nodule is so 
infrequent that it need but be mentioned. The most com- 
mon type is the caseous, ulcerative, or massive, or phthisis 
Fig. 126.-Advanced stage of renal tuberculosis (two-thirds natural size), a, caseous ulcers 
connecting with the renal pelvis; b, caseous areas in the cortex. 
renalis (Fig. 126). Great cavities with a caseous lining and 
thick, purulent contents, are distributed throughout the 
affected organ, and in advanced cases most of the paren- 
chyma is destroyed. Those parts of the cortex which have 
escaped obliteration are of a pale yellowish-gray color, and 
218 ULCERATIVE TUBERCULOSIS OF KIDNEY 
219 
contain tubercles or large caseous areas, the preliminary 
stages of cavity formation. 
Cavities sooner or later communicate with the renal 
pelvis, which they infect with their discharge, and from the 
pelvis the process often travels down the ureter to the blad- 
der. The pelvis and the ureter undergo dilatation, and their 
mucosa, together with that of the bladder, shows the pres- 
ence of tubercles and areas of caseation (Figs. 127 and 128). 
When ulcerative tuberculosis of the kidney is contrasted 
with the miliary type, which is the product of metastasis by 
Fig. 127.-Tuberculosis in the urinary bladder (two-thirds natural size), a, caseous areas in 
the mucosa; b, probe in the right, and c, in the left ureter. 
way of the blood-stream, the temptation is great to regard 
it as a primary lesion. The tubercle bacillus, however, 
enters the body through this organ rarely, if ever, and a 
primary focus can almost always be discovered elsewhere, 
although it may be much less extensive than the renal lesion. 
Primary tuberculosis of the urinary tract has been de- 
scribed, it is true (for bibliography, see Simon), but the 
cases do not seem sufficiently convincing to prove that the 
kidney may be the point of first attack. Since primary renal 
tuberculosis, in the strict sense of the word, probably does 
not occur, it is necessary to seek some other feasible ex- 
planation. 220 
TUBERCULOSIS OF GENITO-URINARY SYSTEM 
The lymphatic system can be disregarded as it is prob- 
ably without significance, although v. Frisch has suggested 
that the bacilli may traverse this route from the bladder to 
the kidney. Wildbolz, however, was not able to produce 
renal tuberculosis in animals by introducing infectious 
material into the wall of the ureter, except when the lesions 
perforated into the lumen. 
From the situation of renal tubercles with regard to 
the uriniferous tubules, Orth concluded that some of them 
result from the excretion of bacilli (elimination tubercu- 
losis), but this circumstance, while of scientific interest, has 
no practical significance for ulcerative tuberculosis. 
There remain for consideration, then, haematogenous 
and urogenetic infection, the latter implying upward pro- 
gression of the disease along the urinary passages to the 
kidney. The simultaneous involvement of pelvis and ureter 
seems to argue in favor of urogenetic infection, though the 
bladder is not often attacked, and the frequency with which 
tuberculous processes in the kidney are associated with 
lesions of the generative organs has been interpreted in the 
same way. A critical examination of the post-mortem find- 
ings, however, suggests that renal and genital tuberculosis 
are at least co-ordinate lesions, or even that the latter may 
be the secondary condition (Steinthal and others). The 
observations of the surgeon, too, are instructive, and those 
of J. Israel are especially valuable. The investigation of 
operative material, in which the earlier phases of the dis- 
ease can be studied to best advantage, have shown that 
renal tuberculosis is more often unilateral than would be 
anticipated from the account of the pathologist, for whom 
only the advanced stages are generally available. 
But even under the most favorable conditions the inter- 
pretation of anatomical findings is fraught with difficulty, 
hence the experiments of v. Baumgarten and Kramer are 
significant. In a series of experiments upon rabbits, these 
investigators found that infection of the bladder or the 
urethra with bacilli of the bovine type was followed by MODE OF INFECTION 
221 
tuberculosis of the prostate; the kidney, the ureter, the vas 
deferens, and the testis, on the contrary, were never 
attacked, even when a rapidly progressing and metastasiz- 
ing process had run on for a year. Infection of the testis 
or the epididymis, however, was invariably succeeded by 
lesions of the vas deferens and the prostate, v. Baumgarten 
concluded, accordingly, that the tubercle bacillus, in con- 
trast to other pathogenic organisms, was unable to make its 
way against a stream of blood, lymph, or secretion, and that 
tuberculosis of the urinary tract, although able to advance 
from the kidney to the renal pelvis, ureter, and bladder, 
could not travel in the reverse direction. 
There are anatomical characteristics of renal tuber- 
culosis which harmonize well with this hypothesis. The site 
of predilection for tuberculous cystitis, for example, is at 
the mouth of the ureter corresponding to the diseased kid- 
ney, as Kramer has pointed out, while, furthermore, the 
upper portion of the ureter is often affected without involve- 
ment of the lower, although the opposite condition is never 
encountered. Moreover, according to this writer, if tuber- 
culosis in the male ascended from the genital organs to the 
kidney, the disease should occur simultaneously in both 
locations more commonly than it does in the female, where 
transmission from one tract to the other cannot take place 
so readily. This, however, is not the case, as a critical 
examination of the statistics will show. 
Thus, the post-mortem findings agree, on the whole, with 
v. Baumgarten's hypothesis, the experimental basis for 
which has been broadened by the work of a number of other 
investigators (for bibliography, see Wildbolz). 
Nevertheless, the exaggerated emphasis laid upon it has 
invited a certain amount of contradiction to which I can 
but subscribe; it is unwarrantable to deny totally the occur- 
rence of ascending infection. First, the disease may easily 
obstruct the flow of urine, and ascent of other infectious 
process under these circumstances is not only consistent 
with v. Baumgarten's hypothesis, but has actually been 222 
TUBERCULOSIS OF GENITO-URINARY SYSTEM 
demonstrated by Kappis, who produced tuberculosis of the 
kidney by tying off a ureter with suture material contam- 
inated with bovine bacilli. Secondly, recent experiments of 
Wildbolz have shown that the ascent of organisms from the 
bladder to the pelvis and parenchyma of the kidney is 
possible under certain conditions, even in the absence of 
stasis. He succeeded in infecting the kidney by introducing 
tubercle bacilli through a fine catheter into the uretal open- 
ing, and, which is more significant for human pathology, 
in infecting the kidney from the bladder when he induced 
this organ to contract by distending it. These latter experi- 
ments he based upon the investigations of Zemblinoff, and 
of Lewin and Goldschmidt, according to which mechanical 
stimulation of the distended bladder in rabbits produces 
energetic contraction with an antiperistaltic wave which 
sweeps the vesical contents in the direction of the kidneys. 
It is true that the renal lesions were accompanied by foci 
in other organs, but any objection that they were due to 
hamatogenic infection, rather than to ascent of the organ- 
isms along the ureter, was met by the inoculation of bacilli 
of the human type; after the introduction of these, which are 
less virulent for the rabbit than are bovine organisms, the 
kidney alone was attacked. Finally, when the experiment 
was varied in another way, one ureter being tied off after 
infection of the bladder, it was found that the kidney corre- 
sponding to the ligated ureter remained free from infection. 
Even though the results of these experiments be appli- 
cable to human pathology, the fact remains that ascending 
tuberculosis is not common, as Wildbolz himself maintained. 
Here again anatomical data are of value. Eckehorn con- 
cluded from the examination of a series of extirpated kid- 
neys that only one of the renal lesions, as a rule, is of 
luematogenic origin, and that the others are derived from 
this one, the papilke, especially exposed to damage as they 
are by their contact with the infected urine in the pelvis, 
being first affected, and their lesions gradually invading 
the rest of the kidney. In support of the occurrence of this ADVANCED TUBERCULOSIS 
223 
Fig. 12S.-Advanced tuberculosis affecting the bladder and the left kidney and ureter; 
less advanced lesions in the right kidney (one-half natural size), a, dilated pelvis with caseous 
wall; b, caseous pyramids; c, large caseous area in the parenchyma; d, intact pelvis; e, linear 
abscesses with caseous margins. 224 
TUBERCULOSIS OF GENITO-URINARY SYSTEM 
ascending infection, I would call attention to the streaky 
abscesses which can be found in the medulla of the organ 
in suitable cases (Fig. 128); these, which are entirely analo- 
gous to the lesions of suppurative pyelonephritis, can be 
interpreted in no other way. Their occurrence, so far as I 
am aware, has been described only by Pels-Leusden, and 
their significance is still but little realized. 
Another problem is, whether one kidney ever suffers 
urogenetic infection from a lesion in the organ of the oppo- 
site side. Kramer denied the possibility, but it is not at all 
necessary, as he seemed to think, that an ascending infec- 
tion shall proceed by continuity, and I have found the 
typical medullary foci in the second, early in its involve- 
ment, sometimes when its pelvis and ureter were still en- 
tirely free (Fig. 128). I do not wish to say more, however, 
than that urogenetic infection of one kidney from the other 
may come to pass; how frequently this takes place cannot 
yet be estimated. Still, when it is remembered that renal 
tuberculosis is generally unilateral at first, although at 
autopsy both kidneys are usually found involved and one 
more seriously than the other, it seems as though urogenetic 
infection of the second kidney must be fairly frequent. 
Renal tuberculosis may lead to perinephritic abscess, 
according to Israel, even while the surface of the capsule is 
still intact, the disease apparently spreading by way of the 
lymph-channels. In the experience of this author, fungoid 
perinephritis and caseous nodules in the fatty capsule of 
the kidney are both uncommon. 
The opinion is rather widely held among surgeons that 
small foci of renal tuberculosis often heal spontaneously, 
and that some of the cicatrices so often encountered in the 
kidney may originate in this way. Even in the case of 
advanced and widespread cavity formation, the process 
may come to a standstill and exhibit undeniable evidences 
of healing. The cavities then contain a white, chalky mate- 
rial exactly like that found in obsolete lesions in the lung, 
and are enclosed by a smooth, thick wall of hyaline con- SEQUELAE 
225 
nective tissue (Fig. 129). Remnants of the parenchyma still 
persist in greater or less amount, but signs of active tuber- 
culous inflammation have been lacking in those few cases 
which I have had the opportunity to examine. The renal 
pelvis is shrunken or destroyed, the hilus contains a mass 
of fat, and a portion of the ureter is usually much dilated 
Fig. 129.-Almost total destruction of the kidney by tuberculosis (two-thirds natural size). 
and filled with white, chalky material, the remainder being 
obliterated or stenotic. This obliteration of the ureter is 
generally referred to the destruction of the kidney. 
In advanced tuberculosis of the reproductive system 
in the male, all the organs are generally implicated. The 
testes undergo an enlargement which involves especially 
the epididymis; they may contain cheesy areas, but the 
epididymis is more seriously affected, undergoing complete 
caseation (Fig. 130). Investigation of the earlier stages of 226 
TUBERCULOSIS OF GENITO-URINARY SYSTEM 
the process in organs removed by operation shows that the 
process generally begins in the epididymis and attacks the 
testis secondarily. 
The presence of foci in both the seminiferous tubules 
and the interstitial tissue has raised the question of their 
site of origin. Two types of lesion have been described by 
v. Baumgarten and Kramer 
-the intracanalicular and 
the interstitial, the former 
of which is the more com- 
mon. As the disease pro- 
gresses, however, the dis- 
tinctive characteristics of 
its earlier stages gradually 
disappear, and the two 
varieties can no longer be 
distinguished. 
In advanced cases of 
genital tuberculosis, the vas deferens is often thickened and 
its inner surface entirely caseous, an appearance presented 
also by the seminal vesicles when they are attacked. Tuber- 
culosis of the prostate is a very common lesion; according 
to Koch, this organ is affected alone with relative frequency. 
In females, the fallopian tube is thickened and tortuous 
(Fig. 131), and contains a cheesy or creamy pus when its 
abdominal end is closed; it is often adherent to the sur- 
rounding structures (Fig. 132). 
In the uterus, which is rarely involved alone, the 
mucosa generally undergoes total caseation (Fig. 132), and 
the disease may later involve the musculature. Although 
the lesions are usually limited to the body of the organ, 
the cervix is sometimes attacked by tuberculosis, which 
may assume the papillary form. The vagina may be the 
seat of tuberculous ulcers (Fig. 132). Tuberculosis of 
the ovary is a very rare condition. 
v. Baumgarten's hypothesis applies to the advance of 
tuberculosis along the genital tract also; the disease pro- 
Fig. 130.-Tuberculosis in the testis (two- 
thirds natural size), a, caseous epididymis; b, 
testis. PROGRESSION OF THE DISEASE 
227 
gresses with the secretory stream unless abnormal. con- 
ditions favor another route. Thus v. Baumgarten and 
Kramer produced lesions in the vas deferens and the pros- 
tate of rabbits by infecting the testis, but not by introducing 
bacilli into the urinary passages, and in corresponding 
experiments by v. Baumgarten, infection of one horn of the 
uterus was followed by descending tuberculosis which in- 
vaded the portio vaginalis and the upper part of the vagina, 
Fig. 131.-Tuberculosis in the tube (two-thirds natural size), a, body of the uterus; b, proxi- 
mal portion of the left tube; c, peripheral portion, laid open; wall almost entirely caseous. 
while the opposite horn was spared. On the other hand, 
experimental lesions in the upper part of the vagina re- 
mained localized there. Hence, the route traversed by the 
semen or the ovum indicates the direction in which the 
disease will advance, and tuberculosis of the genital tract 
in either sex is independent of foci in the urinary organs. 
It has been suggested that anomalous lesions occur in 
the female reproductive system, which are similar to those 
probable examples in the urinary tract (Jung). Repeating 
the investigations of v. Baumgarten, this author demon- 
strated invasion against the stream, and sought, with Engel- 
horn, to prove that inanimate material (carmine granules) 228 
TUBERCULOSIS OF GENITO-URINARY SYSTEM 
may be carried from vagina to uterus during the antiperi- 
staltic movements associated with the sexual orgasm. 
Genital tuberculosis, like that affecting the kidney, is 
not usually a primary lesion. It is possible, of course, for 
Fig. 132.-Tuberculosis in the uterus; adhesive perimetritis; with tuberculous ulceration 
in the vagina (two-thirds natural size), a, caseous uterine mucosa; b, caseous areas in the 
perimetritic adhesions. 
bacilli to be introduced into the reproductive system of 
the female from without, and cases of primary, ectogenic 
tuberculosis have been recorded (Kaufmann, Simmonds), TUBERCULOUS PERITONITIS 
229 
but even in women the disease is almost always secondary. 
Dissemination may take place either by way of the blood- 
stream or in consequence of elimination. The latter method 
has been demonstrated for the seminal vesicles and the 
fallopian tubes by Simmonds, who discovered a few exam- 
ples of very early involvement of these structures, in which 
the lumen was filled with puriform fluid containing myriads 
of tubercle bacilli, the wall being still unchanged. He 
assumed that the organisms were excreted upon the mucous 
membrane, where they first produce catarrhal inflammation 
and afterward tubercular infection, and believed that tuber- 
culosis of the reproductive organs often begins in this way. 
Since it is known that small, inert, foreign bodies, such 
as particles of stain, may be carried from the peritoneal 
cavity into the tubes, it seems reasonable enough to infer 
that tubercle bacilli can traverse this route. Nevertheless, 
v. Baumgarten was unable to produce tuberculosis of the 
genital tract in animals by infecting the peritoneal cavity. 
He ascribed this failure to the early appearance of degener- 
ative changes and pathological exudates in the peritoneum, 
which not only disturbed the normal current toward the 
mouths of the tubes, but eventually obliterated the openings. 
Notwithstanding the negative outcome of these experi- 
ments, cases occur in man where the post-mortem findings 
suggest an extension of the tubercular process from the 
peritoneum into the tube. Conversely, tuberculosis of the 
tubes not infrequently attacks the peritoneum. 
Tuberculous peritonitis, however, may follow the ex- 
tension of foci in other locations, or be part and parcel of 
a tuberculosis involving the serous membranes, or repre- 
sent an independent process. 
In the earlier stages of the disease, the peritoneum is 
studded with fine granules and a serous exudate may be 
present, while later, yellow, caseous, conglomerate tubercles 
are found. In advanced cases, the coils of intestine are 
often matted together or adherent to the abdominal wall, 
and the adhesions sometimes enclose foci of caseation. CHAPTER XX 
Tuberculosis of the Bones and Joints; Amyloidosis 
The parosteal abscesses associated with tuberculosis of 
the vertebrae (Fig. 133) contain a whitish pus, in which no 
Fig. 133.-Tuberculosis in the vertebrae; periosteal abscess (two-thirds natural size), 
a, shreds of periosteum; b, defects in the intervertebral discs; c, more extensive lesion in a 
vertebra. 
organisms except the tubercle bacillus can be demonstrated 
unless the lesion communicate with the surface of the body 
(Garre). They generally develop along the side of the 
230 HYPOSTATIC ABSCESS 
231 
spinal column from tuberculous foci in the vertebrae, their 
purulent contents accumulating slowly and with but slight 
inflammatory reaction in the surrounding tissues (cold 
abscesses). It is these lesions which form the starting 
point for the common hypostatic abscess, in which the pus 
burrows by gravity between muscles and fasciae and along 
the sheaths of vessels and nerves, usually following the 
iliopsoas muscle and sometimes extending under Poupart's 
ligament into the thigh. 
Fig. 134.-Tuberculosis in a bone (slightly enlarged), a, trabeculae; b, space due to shrink- 
age during fixation; c, tuberculous granulation tissue; d, tubercle containing giant-cells. 
The surfaces of the vertebrae are roughened and soft 
(tuberculous caries), and more or less extensive cavities 
may be present. The tuberculous granulation tissue that 
develops in the marrow (Fig. 134) brings about necrosis of 
the surrounding trabeculae, or itself undergoes caseation 
and suppurative softening (Fig. 135). This caseous ostitis 
is often productive of the most serious results; whole verte- 
brae are sometimes destroyed, and the spinal column col- 
lapses in consequence (kyphosis, or Pott's curvature, Fig. 
135). If the patient recover, the detritus is eventually 232 
TUBERCULOSIS OF BONES AND JOINTS 
absorbed, neighboring vertebras become united, and healing 
occurs after the lapse of months or years through the for- 
mation of granulation tissue which finally ossifies and sub- 
stitutes for the lost vertebrae a uniform bony mass. The 
deformity produced by tuberculous disease of the spine 
need not necessarily encroach upon the spinal canal. 
Tuberculous foci in the vertebrae may be peripheral, or 
may occupy the central or the epiphyseal portions. These 
Fig. 135.-Tuberculosis in the spinal column; destruction of a vertebra and compression 
of the cord (three-fifths natural size). Sagittal section through the spine, a, caseous abscesses 
in the posterior, and b, in tne anterior wall of the spinal canal; c, spinal cord compressed. 
three different sites of origin have been sharply distin- 
guished by Wullstein, who referred the variation to the 
distribution of blood-vessels within the bone. 
Where the disease affects the epiphyseal portion, the 
intervertebral discs are bathed in pus and soon become 
necrotic (Fig. 135); the process sometimes spreads pos- 
teriorly, producing an abscess at the periphery of the 
vertebra which bulges into the spinal canal and compresses 
the cord (Fig. 135). SPINA VENTOSA 
233 
Tuberculosis of other parts ot the skeletal system, also, 
may appear as a periosteal and parosteal abscess, which 
sometimes communicates with the surface of the body by a 
fistulous tract. Sometimes, particularly in the case of the 
ribs, the periosteum is the first point in the bone to be 
attacked, and tuberculous lesions in the bone itself, espe- 
cially caries, follow in consequence. In tuberculous osteo- 
myelitis, on the other hand, the process involves the central 
regions of the bone, where 
it is often enclosed by a 
shell of dense osseous tis- 
sue due to a reactive osteo- 
sclerotic process; in other 
cases, the whole area be- 
comes necrotic and is cast 
off as a caseous sequestrum. 
A special type of tuber- 
culous sequestrum is repre- 
sented by those wedge- 
shaped lesions (Fig. 136) 
which are found most fre- 
quently at the extremities 
of the long bones. They 
are of moderate size, as a 
rule, sharply defined, and 
yellow or yellowish-gray in 
color; they may separate 
without suppuration. Their 
shape suggests that they 
originate from emboli, and 
while no direct proof of 
such an assumption can be 
adduced, W. Muller has 
produced wedge-shaped sequestra in the epiphysis of the 
tibia in goats, by injecting tuberculous material into the 
nutrient artery. 
Spina ventosa, so called because of the inflated appear- 
Fio. 136.-Wedge-shaped area of tuberculous 
necrosis (a) in the upper part of the femur (two- 
thirds natural size). 234 
TUBERCULOSIS OF BOXES AND JOINTS 
ance of the affected bone, attacks the phalanges of the hand 
and less commonly those of the foot, in young persons; the 
lesion may be multiple. Its essential features are pro- 
gressive destruction of the central portions of the bone, and 
elaboration by the periosteum of a surrounding shell of new 
osseous tissue. 
The perforation of a tuberculous lesion into an articu- 
lation results in arthritis. Seropurulent or purulent fluid 
accumulates within the joint and the articular cartilage may 
be stripped off, sometimes ulcerating out. 
Primary tuberculous arthritis may commence with the 
formation of tuberculous granulation tissue, which often 
undergoes proliferation (arthritis fungosa) rather than 
caseation. The joint contains a cloudy, serohemorrhagic 
or serofibrinous fluid, and, in chronic cases, roundish carti- 
laginous or fibrous masses (rice bodies), which may be 
either free or attached to the synovial membrane. Although 
these were formerly described as simple fibrin clots, it is 
more probable that they consist of proliferative products 
(Goldmann and others). They are found also in non- 
tuberculous articular processes. 
A second variety of primary tuberculous arthritis is sup- 
purative from the first, eroding the cartilage and attacking 
the bone. Like the secondary type, it is apt to deform or 
destroy the articular surface, and the reactive ostitis and 
ossifying periostitis which are superadded not infrequently 
result in ankylosis. The inflammation often extends to the 
muscles and connective tissues about the joint (tumor 
albus), or pus may break through the capsule; the peri- 
articular abscess so produced is apt to empty its contents 
at the surface of the body by a fistulous tract. 
Tuberculosis of the bones and joints is nearly always 
secondary to some lesion elsewhere in the body, as both 
post-mortem experience and experimental investigation 
show. It is probable, however, at least in rabbits, that 
trauma is an important factor. Thus Krause, who dis- TUBERCULOUS ARTHRITIS 
235 
torted the joints or fractured the bones in guinea-pigs and 
rabbits with generalized tuberculosis, found that synovial 
tuberculosis appeared in almost every instance, while in a 
few of the animals, large foci were found in the epiphyses 
also. Several investigators (Cornil and Babes, Arloing, 
Courmont and Dor) who have carried out analogous experi- 
ments with attenuated material have been able to elicit 
tubercular arthritis in this way, even in the absence of 
generalized infection. 
Conversely, tuberculous lesions in the bones and joints 
may re-infect the body, as has been already suggested in the 
discussion of generalized miliary tuberculosis. 
amyloidosis 
The long continued suppuration so characteristic of 
tuberculosis of the bones and joints is the most frequent 
Fig. 137.-Sago spleen (natural size). 
source of generalized amyloid degeneration. Certain of 
the organs, namely the spleen, the lymph-nodes, the liver, 
the kidneys, and the intestine, are affected first, most fre- 
quently, and most seriously. 
In the spleen, the degeneration falls into two types. 
In the first (sago spleen), only the follicles are affected, 
appearing upon the cut surface as clear, somewhat elevated 
granules (Fig. 137), resembling boiled sago; these areas 
turn a distinct mahogany brown upon the application of 236 
AMYLOIDOSIS 
a solution of iodine and potassium iodide. In the second 
type, in which the degeneration is uniformly distributed, 
the spleen is firm and its cut surface has a uniform waxy 
appearance (waxy spleen). The iodine test gives a diffuse 
brown stain. 
When the liver is seriously affected its large size, its 
firmness, and its translucent, pale, brownish-red or yellow- 
ish-gray color are very striking. Treatment with iodine 
produces a design of delicate brown lines and small spots. 
Fig. 138.-Amyloid kidney; extensive degeneration of the parenchyma (natural size). The 
amyloid substance is not visible. 
Mild degrees of amyloid degeneration in this organ are not 
recognizable by the naked eye. 
An affected kidney is greatly altered in appearance. It 
is enlarged, and its surface is smooth and of a somewhat 
translucent, grayish-yellow hue. Examination of the cut 
surface (Fig. 138) shows that the cortex is wider than nor- 
mal, very translucent, and grayish-yellow in color, while 
the entire organ often exhibits a prominent yellowish mot- 
tling. The brownish-red pyramids stand out distinctly 
against the cortex, and amyloid glomeruli become visible 
after treatment with iodine as brown points just large 
enough to be detected upon gross examination. 
An adequate conception of the process can be obtained SAGO SPLEEN 
237 
only in histological preparations. In a sago spleen, the 
degeneration is confined to the arteries, the capillaries, and 
the reticulum of the follicles. The follicles are entirely, or 
almost entirely, changed into homogeneous masses of amy- 
loid material which, in their fresh condition, are glassy 
clear; the reticulum about the degenerated areas is in part 
destroyed, while some of its remaining fibres are themselves 
transformed into amyloid. The walls of the arteries which 
Fig. 139.-Amyloid degeneration of the liver (moderately enlarged). 
pierce the follicles are attacked at an early period of the 
disease. In the waxy spleen, there are streaks of amyloid 
which correspond to degenerated veins in the pulp, and the 
reticulum between them is likewise involved. 
In the liver, also, the degeneration affects the capil- 
laries, and the amyloid material is accordingly found in the 
form of tiny streaks and rings (Fig. 139), between which 
lie the atrophic cells of the parenchyma; the walls of the 
arteries are transformed at an early period. In regions 
where the parenchymatous atrophy is extreme, there re- 238 
AMYLOIDOSIS 
main eventually only blood-vessels, amyloid material, and 
remnants of liver cells. In cases where the degeneration is 
limited to the arteries, the parenchyma escapes destruction. 
In the kidney, the disease is localized chiefly in the 
glomeruli, where it attacks at first only isolated loops. 
Finally, however, it alters the whole vascular tuft (Fig. 
140), and, in addition, the walls of small arteries. In the 
capillaries which surround the uriniferous tubules, the amy- 
loid material appears late, and in small amount. 
Although the parenchyma may be spared (Raubitschek), 
it is more often seriously affected. The cells lining the 
tubules are swollen, and their cytoplasm is granular, often 
containing great drops of a hyaline material (guttate 
hyaline degeneration, Fig. 141). By many authors (Land- 
steiner, Pfister), this le- 
sion is included among the 
advanced grades of cloudy 
swelling, but it is more 
properly regarded as a 
special type of degenera- 
tion. It is almost con- 
stantly met with in the 
amyloid kidney (Sar- 
razin), though rarely en- 
countered in association 
with other renal affec- 
tions. Fatty metamor- 
phosis of the tubular 
epithelium, formerly described as a common accompani- 
ment of amyloid degeneration, is not often present, accord- 
ing to Raubitschek, whose opinion I can corroborate. Homo- 
geneous casts of albumin, or more or less granular amor- 
phous masses, may be discovered in the tubules; the latter 
occur also in the intracapsular space. In the later stages of 
amyloid disease, glomeruli and portions of the tubules dis- 
appear and an overgrowth of connective tissue sets in, 
which may be extensive enough to result in a true contracted 
Fig. 140.-Amyloid degeneration of glomeruli in 
the kidney (slightly enlarged). DISTRIBUTION 
239 
kidney; in short, there may be in play beside amyloid degen- 
eration, phenomena similar to those of Bright's disease. 
Moreover, the characteristic gross appearance of the 
affected organ (Fig. 
138), which without 
doubt has often been 
responsible for the diag- 
nosis of large white kid- 
ney, is a result of the 
degeneration a c c o m - 
panying amyloidosis. 
That the excretion 
of albumin and the epi- 
thelial degeneration are 
results of the amyloid 
transformation of glomeruli and blood-vessels, is rendered 
very probable by the constancy of their association with 
this lesion. On the other hand, the view has been expressed 
(Lubarsch) that amyloidosis may be a product of chronic 
renal disease, though I have never seen a case that would 
bear such an interpretation. 
Other organs beside those already discussed may be 
affected, and the vascular system in particular is apt to 
suffer. The aorta, the larger arteries and veins, and the 
myocardium contain microscopic deposits, and while it is 
often said that the smaller veins escape, they may neverthe- 
less be involved (M. B. Schmidt), though less constantly 
than the small arteries. The intestinal mucosa and the 
adrenal are often the seat of microscopic lesions, but the 
cutis, the dura mater, and the fasciae-the connective tissues 
of special function, in brief-remain free (Schmidt). 
Amyloid turns dark brown upon treatment with iodine, 
and light blue upon the further addition of sulphuric acid. 
Its reaction toward iodine thus resembles that of starch, 
and Virchow, who discovered this fact, chose the name amy- 
loid. Violet aniline dyes stain the amyloid substance red 
and the remainder of the section blue (Figs. 139 and 140). 
Fig. 141.-Guttate hyaline degeneration of the renal 
epithelium (moderately enlarged). 240 
AMYLOIDOSIS 
It lias been known for a long time that amyloid contains 
an albumin, and this knowledge was materially supple- 
mented when Krakow discovered that the albumin is com- 
bined with chondroitin-sulphuric acid, a substance nor- 
mally present in cartilage and elastic tissue. The charac- 
teristic staining reactions are evidently due to the latter 
constituent, since they become progressively less distinct 
as it gradually disappears, although the optical and mor- 
phological characteristics of amyloid, which depend upon 
its albuminous component, are preserved. Further evi- 
dence exists in the observation that the staining reactions 
of old amyloid are feeble and incomplete. 
The manner in which amyloid is distributed throughout 
the tissues has led to the assumption that it is deposited 
there through the agency of the blood-stream, in which, 
however, it is not previously elaborated. In support of this 
transudation hypothesis there has been adduced the fre- 
quent involvement of the capillaries, and the observation 
that the stroma of many of the organs (kidney, thyroid, 
pancreas) is affected only in combination with capillary 
amyloidosis; the lymph-nodes, spleen, and intestinal villi, 
are exceptions to this rule, and their reticular fibres may 
be attacked when the capillaries themselves are unaltered 
(Schmidt). The transudation hypothesis alone does not 
suffice to explain the predisposition of the vascular system, 
since acording to Schmidt, amyloid degeneration in larger 
arteries attacks both media and adventitia by preference. 
Amyloid usually lies in the tissue spaces (Wichmann), 
and connective-tissue fibres and parenchymal cells are only 
exceptionally involved. Any injury to the parenchyma, 
therefore, is secondary. 
In Schmidt's opinion, the formation of amyloid may be 
referred to a fermentative coagulation, which leads to a 
deposition of this substance in the tissue spaces or lymph- 
vessels from fluids already present in these situations. 
Albumin, chondroitin-sulphuric acid, and ferment are thus 
the three essential factors. The ferment is produced in ETIOLOGY 
241 
the spleen, according to Davidsohn, who found that amyloi- 
dosis does not appear in animals ordinarily disposed to it, 
if this organ be removed. 
Amyloid degeneration is associated with long continued 
suppuration or tissue destruction, its most common cause 
being chronic tuberculosis. Other etiological factors are 
syphilis and ulcerating, malignant growths (both of which 
may be accompanied by amyloidosis even in the absence of 
suppuration and tissue destruction), chronic suppuration 
following staphylococcus or streptococcus infection, and 
certain metabolic diseases, particularly gout (Schmidt). 
Occasionally, no cause can be detected at autopsy. In such 
cases, Schmidt refers the lesion to a past disease, such as 
typhoid, since amyloid remains unabsorbed for a long time. 
Amyloidosis has been observed in animals with chronic 
suppurative inflammations, and after the injection of dead 
microorganisms or turpentine and other chemical sub- 
stances (Czerny, Lubarsch, Nowack). The degeneration 
appears in a relatively short time after inoculation with 
staphylococcus pyogenes aureus, but even this promising 
method sometimes fails. Amyloid produced experimentally 
in animals is more pultaceous than that of the human sub- 
ject; both are no doubt identical, their variations depend- 
ing upon differences between human and animal albumin. 
It is evident from what has been said that amyloid 
degeneration is a consequence of intoxication, principally 
with the bacterial poisons. 
Localized amyloidosis must be distinguished etiologi- 
cally from the generalized type. It attacks structures 
which, like cartilage and elastic tissue, contain chondroitin- 
sulphuric acid, often appearing in tumor-like masses at the 
base of the tongue, in the larynx, or in the trachea. Transi- 
tional cases between localized and generalized amyloidosis 
have been described (Edens, Heuter), and some authors 
(Edens, Oskar Meyer) have concluded that the two varie- 
ties are not so sharply separable as has been supposed. 
Their view, however, seems hardly justifiable. CHAPTER XXI 
Syphilis 
Gummata of the liver occur with relative frequency m 
syphilitic subjects. These lesions vary in their dimensions 
from the size of a cherry-pit to that of a hen's egg, and 
may be even larger. Some are of a uniform yellow hue, 
while in others a yellowish centre is surrounded by a zone 
Fig. 142.-Gumma in the liver (slightly enlarged). 
of grayish-white connective tissue which radiates into the 
surrounding parenchyma. 
The architecture of a hepatic gumma is characteristic. 
The lesion consists of a necrotic area (Fig. 142) surrounded 
by a dense zone of granulation or fibrous tissue; in rare 
instances, giant-cells may be present. 
Gummata, which are included among the granulomata, 
develop in almost any region of the body during the tertiary 
stage of lues as nodules varying in size from microscopic 
dimensions to the diameter of a large apple; their granu- 
lation tissue may undergo either necrosis or cicatrization. 
242 GUMMATA OF LIVER 
243 
They are very common in the cutis, where they ulcerate 
after reaching the surface; in this location, however, they 
are an object of clinical, rather than of anatomical interest. 
In the testicle (Fig. 143), they appear as yellow, caseous 
masses which may simulate very closely the lesions of tuber- 
culosis. They are found, furthermore, in the muscles (Stock- 
mann), including the myocardium, and also in the brain. 
After the necrotic portion of a gumma has been absorbed, 
cicatrization sets in; the liver in particular is apt to be 
extensively scarred, and 
as gummata are often 
multiple, a lobulated ap- 
pearance is sometimes 
conferred upon it (hepar 
lobatum, Fig. 144). Syph- 
ilitic processes in the 
liver occasionally result 
in adhesions between this 
organ and the diaphragm 
(Fig. 145) ; in two of my 
cases necrosis and cica- 
trization extended into 
the midriff, causing sup- 
purative pleuritis, and in 
another destroying the 
tissues of the lung itself. 
Syphilis in the adult will not be taken up systematically 
in this chapter because some of its lesions are described in 
other places. Suffice it to say that most of the organs show 
not only the characteristic luetic inflammation, but an inter- 
stitial process as well. Thus, in the liver, interstitial hepa- 
titis accompanies the gummata and their resultant scars; 
interstitial myocarditis is often of syphilitic origin, par- 
ticularly in children, while in the testicle there is very often 
present, in addition to the gumma, a fibrous orchitis which 
can usually be attributed to luetic infection. 
Fig. 143.-Gumma in the testis (natural size), a, 
testis; b, epididymis; c, gumma. 244 
SYPHILIS 
A few syphilitic affections merit more detailed descrip- 
tion. In Fig. 146 the mucous membrane of the pharynx is 
shown, scarred and constricted near the base of the tongue 
by a fibrous band from which cicatricial strands run to the 
epiglottis. In the lower portion of the pharynx, on both 
sides, there are several thickenings, and the epiglottis and 
the aryepiglottic ligament contain extensive defects. The 
pharyngeal stenosis in this case had produced considerable 
Fig. 144.-Hepar lobatum (two-fifths natural size). 
compensatory hypertrophy of the muscles about the isthmus 
of the fauces. 
The death of the individual in whom these defects were 
discovered was brought about by a combination of pulmo- 
nary emphysema, diffuse bronchiectasis, and lobular pneu- 
monia. The process last named was a deglutition pneumonia, 
referable to the disturbances in respiration and the intake 
of food produced by the pharyngeal constriction. 
Extensive defects are caused in the larynx by syphilitic 
ulceration. Deep ulcers associated with perichondritis may 
interfere with the nutrition of the cartilage and result in 
serious deformities on account of the resulting necrosis, GUMMATOUS LIVER 
245 
Fig. 145.-Adhesion of the right lung to a gummatous liver (one-half natural size), a, 
gumma in the upper part of the liver; b, diaphragm; c, scars in the lung, probably of syphilitic 
origin. 246 
SYPHILIS 
while the larger bronchi sometimes undergo stenosis as a 
result of gummatous infiltration and cicatrization. 
Ulceration and even total destruction of the soft palate 
may be a consequence of syphilis; in the hard palate, 
the lesion in the mucosa readily invades the bones, causing 
Fig. 146.-Syphilitic scars and defects in pharynx and larynx; stenosis of the pharynx 
(three-fourths natural size), a, tonsil; 6, constricting scar in the pharynx; c, hypertrophic 
pharyngeal musculature; d, epiglottis with scars and adhesions. 
periostitis and ostitis gummosa with necrosis and perfora- 
tion as a final outcome. Such a process is especially apt to 
attack the superior maxilla, the nasal bones, and the vomer. 
In the nose, it usually commences with localized or diffuse 
gummatous infiltration of the mucous membrane, and the 
bones are involved secondarily; more rarely, the bones are GUMMATOUS OSTEOPERIOSTITIS 
247 
primarily attacked. The necrosis and its accompanying 
septic infection lead to the formation of a sequestrum and 
are accordingly a cause of grave deformity, the well-known 
saddle-nose being produced in this way. 
The skeletal system is a favorite site for syphilis 
although advanced lesions are not often seen, owing to 
modern therapy. When the bones are invaded, the skull is 
apt to be seriously involved, becoming the seat of irregular 
Fig. 147.-Syphilitic scars in the calvarium (two-fifths natural size). 
ulcers with dense, osseous margins, to be finally replaced 
by deep scars surrounded by sclerotic bone (Fig. 147). 
According to M. B. Schmidt, these ulcers are a result of 
gummatous osteoperiostitis, during the course of which por- 
tions of bone become necrotic and are cast off. The occur- 
rence of necrosis is favored by secondary infection of the 
marrow and its consequent nutritional disturbance. The 
process is similar in the long bones, which are sometimes 
extensively involved by gummatous osteomyelitis (Figs. 
148 and 149); if the disease be situated in the vicinity of a 248 
SYPHILIS 
joint, arthritis may be a consequence. That gummata can 
develop deep within a bone, and even in its marrow cavity, 
has been proved by the researches of Chiari, according to 
whom these deep-lying lesions are more common than is 
ordinarily suspected. 
Ossifying ostitis appears about syphilitic foci in the long 
bones also, often leading to cicatrization and cure, while 
Fig. 148.-Gummatous osteomyelitis and areas of necrosis in the tibia (one-half natural size). 
A, cut surface; outer surface; a, areas of caseous necrosis. 
ossifying periostitis frequently produces more or less dif- 
fuse thickening near the seat of the lesion (Fig. 149). 
There is another and independent variety of syphilitic 
ossifying periostitis and ostitis which affects principally the 
tibia or the clavicle, where it results in the appearance of 
hyperostoses and exostoses. 
Tertiary syphilis is often productive of gummatous 
meningitis and arteritis, or of gummata in the brain itself. 
The first of these conditions is characterized by the presence SECONDARY STAGE 
249 
of more or less circumscribed macroscopic areas of yellow- 
ish-gray infiltration, principally about the sylvian fissure; 
in these the arteries lie embedded. Such lesions occasionally 
contain nodules resembling tubercles (Durck, Beitzke). 
Microscopic examination shows that the pia is infiltrated 
with innumerable small round cells, which have a charac- 
teristic tendency to surround the blood-vessels (Fig. 150). 
The media may be infiltrated also, though less extensively, 
and the intima is the seat of connective-tissue overgrowth 
(Fig. 150) which is usually of an advanced degree (endar- 
teritis syphilitica). These vascular changes, which were 
first described by Heubner, 
are sometimes discovered in 
the absence of gummatous 
meningitis. 
A certain percentage of 
the cases of acquired syphilis 
show enlargement of the 
spleen. In the primary and 
secondary stages this may be 
referred to the infection, as 
in other parasitic diseases; 
in the tertiary, however, it is 
usually due to hyperplasia of 
the stroma. 
In contrast to tertiary 
syphilis, the lesions of the 
secondary stage, such as 
transient periosteal swellings 
and skin eruptions, are not 
often encountered at post- 
mortem examination. 
The induration at the edge 
and floor of the primary lesion is due to proliferation of the 
connective-tissue elements and dense infiltration with small 
round cells; in the deeper portions of the chancre the latter 
is distinctly perivascular. The smaller vessels, parti cu- 
Fig. 149.-Necrosis and hyperostosis at 
the lower end of the humerus (two-thirds 
natural size), a, area of necrosis with a 
sequestrum at its base. 250 
SYPHILIS 
larly the veins, are the seat of obliterating endangeitis. 
Cicatrization finally occurs, preceded in most cases by ulcer- 
ation. Since the disease advances by way of the lymph- 
channels, the regional nodes soon become enlarged; here 
the process is not essentially different from that which 
accompanies non-specific inflammation. 
Fig. 150.-Syphilitic endo- and perivasculitis (slightly enlarged), a, gummatous infiltra- 
tion in the periphery of a vein; b, periarteritis; c, syphilitic endarteritis (connective-tissue thick- 
ening and small cell infiltration); d, internal elastic membrane. 
The Spirochceta pallida, discovered by Schaudinn and 
Hoffmann, can be found regularly in the secretions from 
primary and secondary ulcers. It is a delicate, corkscrew- 
like organism, in which the spirals are uniform and close-set. 
Its isolation in culture (Noguchi) has been achieved so 
recently that the organism has not yet been thoroughly 
investigated, but its etiological importance may be taken for 
granted from its frequent presence in syphilis and its CONGENITAL SYPHILIS 
251 
absence in other diseases, the enormous number of obser- 
vations that have been made rendering it almost certain 
that this organism is the cause of lues. 
CONGENITAL SYPHILIS 
The Spiroch(Eta pallida can often be demonstrated in 
the organs of children with congenital syphilis even though 
the tissues exhibit none of the anatomical changes ordinarily 
associated with the disease. The 
organism is found in large numbers 
principally in the liver, the spleen, the 
lungs, and the adrenal, lying generally 
outside the cells, although it may be 
intracellular (Gierke). 
The anatomical changes of con- 
genital syphilis are analogous to 
those of the acquired disease only in 
the case of syphilis congenita tarda, 
and here but in part, a certain degree 
of individuality being conferred upon them by the predom- 
inance of connective-tissue overgrowth, no less than by the 
fact that the organs which they attack are still in course of 
development. 
Since the skin lesions of congenital syphilis are not 
recognizable in the cadaver, it may be said that the most 
common post-mortem finding is osteochondritis, first de- 
scribed by Wegner in 1870. It is recognized by the broad, 
jagged appearance of the fine yellow line which normally 
borders the ossification zone of the diaphysis (Fig. 151). 
The area of calcification, which in normal intracartilaginous 
ossification is represented by a narrow rim at the lowest 
portion of the cartilage, is widened, and the development of 
medullary tissue at the ossification line is increased (M. B. 
Schmidt), so that nothing remains at the lower part of the 
cartilage but the calcified walls of its cavities. This region, 
therefore, becomes brittle, and the epiphysis sometimes sep- 
Fig. 151.-Syphilitic osteo- 
chondritis (one-half natural 
size). 252 
SYPHILIS 
arates; Separation may be brought about, also, in the later 
stages of the disease, by the development of granulation 
tissue between the epiphysis and the diaphysis (Schmidt). 
Osteochondritis has no great 
clinical significance, for it ex- 
ists only during the first few 
Fig. 152.-Syphilitic ossifying periostitis, 
humerus of a child (two-thirds natural size). 
a, periostitic growth; b, outline of old bone; 
c, marrow cavity; d, infraction. 
Fig. 153.-Congenital syphilitic interstitial hepatitis 
(slightly enlarged). 
months of life and eventually undergoes recovery. On the 
other hand, it is valuable to the pathologist as an infallible 
indication of congenital lues, since it occurs almost con- 
stantly in this disease and is readily demonstrable in the 
long bones, even in the presence of advanced decomposition. 
Less commonly, congenital syphilis is responsible for a 
periostitis ossificans, which is so active that it entirely 
ensheaths the old bone (Fig. 152). Necrosis analogous to 
that of acquired syphilis has been described, as well as gum- 
matous periostitis, and gummatous ostitis and osteomyelitis 
with caries sicca (Pommer). 
According to Hochsinger, there occur in the earlier stages 
of congenital lues a series of other changes in the skeletal 
system, such as disturbances of growth and inflammatory 
hyperplasias and degenerations; into the details of these, 
however, it is impossible to enter now. VISCERAL LESIONS 
253 
Of the visceral lesions, only the most important can be 
mentioned here (see Hochsinger, Herxheimer). Those re- 
gions of the liver which are attacked by the disorder are of 
a yellowish, translucent appearance, and somewhat firmer 
than normal; the alteration may be either diffusely distrib- 
uted or localized in irregular areas which alternate with 
normal reddish-brown portions, giving to the organ in the 
latter case somewhat the appearance of flint. Microscopic 
examination shows proliferation of the interstitial tissue, 
which widely separates the strands of cells from one an- 
other and causes them to undergo necrosis (Fig. 153). Vas- 
cular changes, also, are said to affect the liver, and Hoch- 
singer has described a small cell infiltration of the periportal 
connective tissue in which the macroscopic appearance of 
the organ is unaltered. 
The lung sometimes shows connective-tissue overgrowth 
combined with extensive desquamation of the alveolar epi- 
thelium (Heller). Remnants of fetal lung may be discerned 
in the new connective tissue (Hochsinger). The lesion 
affects large areas and even entire lobes, which become firm 
and a little enlarged, and assume a whitish color (white 
pneumonia). 
It may be stated in conclusion that hyperplasia of the 
spleen is a frequent accompaniment of congenital syphilis. CHAPTER XXII 
Dementia Paraeytica ; Neurofibromatosis 
Progressive general paralysis is associated with chronic 
leptomeningitis (Fig. 154), which generally attacks the 
membranes overlying the anterior regions of the brain. 
When these are stripped away, particularly in the frontal 
region, small particles of cortex generally adhere to them, 
a phenomenon which was formerly considered highly char- 
acteristic of general paralysis and which, of late, has been 
too much depreciated. According to Wernicke and Alz- 
heimer, the adherence of brain substance is in part an accom- 
paniment of commencing post-mortem decomposition; at 
least, it is more marked in brains that are no longer quite 
fresh. Klippel distinguished between the purely superficial 
lacerations following the removal of a delicate pia, and a 
deeper variety extending, into the medullary substance and 
produced by stripping off thickened meninges. In the first 
instance, neurogliar outgrowths into the pia are torn; in 
the second, it is thickened vascular sheaths (Alzheimer). 
The cerebral convolutions are atrophic, especially in 
the frontal and occipital lobes; the parietal is often less 
affected. More rarely, the process is localized (Fig. 154). 
Though cerebral atrophy is by no means an invariable 
accompaniment of paralytic dementia, since it is absent in 
the earlier stages and in acute cases, when it does occur it 
may reduce the size and weight of the brain to a point seen 
in no other disease. The figures of Ilberg show that the 
cerebral hemispheres (chiefly the frontal lobes) are most 
frequently attacked, the brain-stem less often, and the cere- 
bellum least commonly of all. As a rule the optic thalamus 
suffers. 
The skull is thickened, and pachymeningitis interna 
hemorrhagica is present as in other atrophies, involving 
both the convexity and the base. 
254 HISTOLOGICAL FINDINGS 
255 
The amount of subdural fluid is augmented (external 
hydrocephalus). As the amount of fluid in the ventricle is 
increased, these cavities are somewhat dilated, and the lin- 
ing membrane (ependyma) of the fourth in particular 
assumes a finely granular appearance. 
Fig. 154.--Chronic leptomeningitis and atrophy of the brain in progressive general paraly- 
sis (one-half natural size). The anterior portions of the meninges are whitish and opaque. The 
atrophic areas are represented by depressions in the frontal and parietal lobes. 
Although no one of these macroscopic changes is charac- 
teristic of progressive general paralysis, it is the general 
opinion that the co-existence of several renders the diagnosis 
highly probable. 
Microscopic examination affords additional and still 
more valuable evidence. The pia always shows inflamma- 256 
DEMENTIA PARALYTICA 
tory infiltration (Fig. 155), while the brain contains peri- 
vascular collections which are made up chiefly of plasma 
cells, with a few lymphocytes and mast cells. 
The plasma cell, 
upon the presence of 
which in general pa- 
ralysis Nissl laid such 
great stress, was first 
described by Unna. It 
is characterized by a 
relatively large cell- 
body with an intense 
affinity for basophile 
dyes, and an excentric 
nucleus with radially 
arranged chromatin; 
near the nucleus, the 
protoplasm is often 
somewhat clearer 
(Fig. 6). A spirited 
controversy has been 
waged for a long time 
over the origin of these 
elements, but at pres- 
ent it seems most prob- 
able that they are de- 
rived from the lympho- 
cyte. 
Plasma-cells are 
found in almost all in- 
flammatory infiltrates, 
in not a few of which, 
like lupus of the skin 
or gonorrhoeal salpin- 
gitis, they are so 
numerous as to predominate over all the other elements. 
Accordingly, they are not characteristic of dementia para- 
Fig. 155.-Leptomeningitis, perivascular cellular 
infiltration, and disappearance of nerve-fibres in the 
cortex in progressive general paralj^sis (slightly en- 
larged). a, medulla; b, cortex; c, pia mater. CHANGES IN GANGLION-CELLS 
257 
lytica, although as they regularly occur in this disease in 
large numbers (Nissl, Alzheimer) and widely distributed 
(Behr), Nissl was justified in his assertion that their pres- 
ence is an essential for the anatomical diagnosis. 
Changes in the ganglion-cells can be demonstrated with 
Nissl's stain. They are not characteristic of paralytic 
dementia, however, and may be found in other conditions. 
In advanced cases, the number of these elements is consider- 
ably diminished. 
An important and early sign is the disappearance of 
medullated fibres from the cortex (Fig. 155), commencing 
in the second and third ganglion-cell layers of Meynert and 
extending gradually downward on the one hand, and toward 
the tangential fibre-layer on the other. In some cases, the 
destructive process selects the fibres about the blood- 
vessels (Oskar Fischer). 
In the cortical and medullary regions, the fibres and cells 
of the glia are always considerably increased, especially in 
the neighborhood of the vessels. Though this is partly in 
compensation for the loss of nervous elements, there is little 
doubt that some independent proliferation takes place also. 
Nissl has described an elongated cell which may be regarded 
as an important factor in the anatomical diagnosis by reason 
of its very frequent presence. This element, in his opinion, 
is of mesodermal origin, though no cogent proof for this can 
be advanced. 
Discussing the nature of progressive general paralysis, 
Alzheimer contended that the disease cannot be wholly 
explained as an inflammation emanating from the blood- 
vessels, and assumed a destruction of nervous tissue occur- 
ring independently of the vascular condition; the essential 
feature of the disorder would thus be the destruction of 
parenchyma. Nissl described two separate processes-in- 
flammatory and regressive; Obersteiner, primary damage 
to the nervous tissue in the presence of a characteristic 
inflammatory lesion. 
17 258 
DEMENTIA PARALYTICA 
Alterations in the spinal cord are almost invariably 
associated, the most common of which is degeneration in 
the posterior columns; hence the term taboparalysis. Other 
regions, also, may be involved, particularly the pyramidal 
tracts. These changes are in part secondary to such cere- 
bral lesions as result from the arteriosclerosis which often 
affects the vessels of the brain in connection with paralytic 
dementia. 
In most cases, aortitis can be demonstrated, usually in 
the ascending aorta alone, and Straub showed that this con- 
dition, formerly regarded as ordinary atheromatosis, is 
identical with the aortitis luetica of Doble. Since still other 
syphilitic changes are usually disclosed, and the Wasser- 
mann reaction is almost invariably positive, it is evident 
that luetic infection plays an important part in the causa- 
tion of dementia paralytica; indeed, the disease may be 
referred to syphilis very frequently, and, in the opinion of 
many psychiatrists (see Plant), invariably. Additional evi- 
dence in favor of this view is to be found in the recent work 
of Noguchi, who has succeeded in demonstrating the spiro- 
chaete in the brain in association with progressive paralysis. 
The extreme emaciation which invariably characterizes 
the later stages of paralytic dementia depends partly upon 
general nutritional causes, though it is partly, also, the 
expression of a marasmus which has no direct relation to 
the intake of food. The trophic and vasomotor disturbances 
accompanying the disease favor the supervention of decu- 
bitus, a lesion that is sometimes followed by multiple pyamiic 
abscesses. In some cases death is due to bronchopneumonia, 
while in others it is brought about by cystitis, pyelitis, and 
pyelonephritis, consequences of a nervous derangement of 
the vesical function. MULTIPLE FIBROMATA 
259 
NE UROFIBROMATOSIS 
Disregarding the rare multiple lipomata, no condition 
but multiple fibromata of the skin could produce the effect 
pictured in Fig. 156. These 
growths are composed of in- 
terlacing bands of a moder- 
ately cellular adult connec- 
tive tissue (Fig. 157), and 
are thus simple tumors of 
the first group in our cate- 
gory (see page 260). 
It is almost superfluous 
to say that, since the time of 
Virchow, only those lesions 
which owe their presence to 
tissue proliferation are reck- 
oned among the true tumors, 
regeneration, hypertrophy, or inflammation being, of 
course, excluded. 
Fig. 156.-Multiple fibromata in the skin. 
Fig. 157.-Nerve-free portion of a neurofibroma (greatly enlarged), a, longitudinally and b, 
obliquely cut fibrous bands. 
Fibromata are of slow growth, in accordance with their 
derivation from finished connective tissue, and neither 260 
NEUROFIBROMATOSIS 
invade the surrounding structures nor lead to metastasis. 
Lacking the chief characteristics of malignancy, therefore, 
they are classed with the benign tumors. 
CLASSIFICATION OF TUMORS 
I. Mature tumors of the connective tissues, the muscles, 
the nervous tissues, and the vessels: 
Fibroma, lipoma, chondroma, octeoma, glioma, 
myoma, neuroma, angioma. 
Fig. 158.-Nerves of the cauda equina, containing multiple neurofibromata (two-thirds 
natural size). 
II. Immature tumors of tire connective tissues, the muscles, 
the nervous tissues, and the vessels: 
Sarcoma 
(a) Lower grades of maturation: Spindle-cell sar- 
coma, giant-cell sarcoma, round-cell sarcoma. 
Alveolar sarcoma. CLASSIFICATION OF TUMORS 
261 
(5) Higher grades of maturation: Fibrosarcoma, 
chondrosarcoma, osteosarcoma, myosarcoma, 
gliosarcoma. Angiosarcoma, endothelioma. 
III. Epithelial tumors retaining the type of superficial or 
glandular epithelium: 
Papilloma. Adenoma. 
IV. Atypical epithelial tumors: 
Carcinoma. 
V. Mixed tumors and teratomata. 
The fibromata now under discussion are of special inter- 
est because of their connection with the nerves. They may 
occupy the finer nerves, or larger ones like the great sciatic 
or the tibial, and are very common in the cauda equina 
Fig. 159.-Bundle of nerve-fibres interrupted by a fibrous nodule (hand lens). 
(Fig. 158) ; they have been found in the sympathetic also. 
In a case described by Peusquens, nearly all the cranial 
nerves were involved in their foramina at the base of the 
skull. 
It was v. Recklinghausen who discovered the relation 
between the nerves and multiple fibromata of the skin, and 
the coexistence of these growths with neural tumors 
(v. Recklinghausen's disease). He traced the neoplasms to 
the connective tissue of the nerves, particularly the endo- 
neurium, and applied to them the term neurofibroma. 
In passing through the tumors or coursing around them, 
the nerves suffer no serious amount of degeneration; hence 
their function is not disturbed. 262 
NEUROFIBROMATOSIS 
Other growths are of fairly common occurrence in 
v. Recklinghausen's disease, but I shall not stop to mention 
all that have been described and brought into connection 
with it (see Adrian). In some instances, they are undoubt- 
edly adventitious complications. A few conditions, however, 
such as gliomata of the cord, tumors of the spinal and cere- 
bral membranes, and hyperplasia of the adrenal (Kawash- 
ima), may be genetically related to multiple neurofibroma- 
tosis. It has been suggested that these form one group with 
the neurofibromata, in so far as all affect the supporting 
and investing tissues of the nervous system, and it is prob- 
ably true that all have one common cause in some congenital 
predisposition. According to Verocay, the neurofibromata 
differ from ordinary connective tissue "in the presence of 
characteristic nucleated bands, and fine pale fibrillae 
arranged in bundles;" in other words, they are composed, 
not of connective tissue, but of a "specific, neurogenic 
tissue." His conception would readily explain the associa- 
tion of glioma with multiple fibromatosis, since the whole 
process would then represent a systemic disease referable 
to some early disturbance in the embryonal development of 
those specific elements in the nervous system which give rise 
to ganglia, glia, and nerve-cells (neurogliocytes of Held). CHAPTER XXIII 
Tumors of the Central Nervous System 
The presence of a neoplasm in the brain, when the growth 
does not appear upon the surface, is often shown by the 
enlargement of a hemisphere (Fig. 160). 
Fig. 160.-Enlargement of the right hemisphere and flattening of its convolutions by a central 
tumor (one-half natural size). 
The most common brain tumor is the glioma (Figs. 160 
and 161), the structure of which reproduces that of the 
normal supporting substance, the neuroglia (Fig. 162). 
Neither the properties of the cytoplasm nor the relation of 
cells to fibrils can be made out, however, without the aid 
of special staining methods, and even in the normal glia 
263 264 
TUMORS OF THE CENTRAL NERVOUS SYSTEM 
these questions are not easy to answer. Thus, while Wei- 
gert described the neurogliar fibres as entirely extracellular 
structures bearing the characteristics of an intercellular 
substance, the histologists of our own time, and Held in 
particular, believe that they are not entirely independent. 
They run from cell to cell, surrounded throughout part of 
their course, at least, by cytoplasmic projections which 
communicate with one another, forming a sort of syncytium. 
Fig. 161.-Frontal section through the brain reproduced in Fig. 160 (two-thirds natural size). 
a, glioma in the right hemisphere. 
Ill correspondence with the structure of the tissue in 
which it arises, the glioma contains nuclei, fibres, and a 
protoplasmic reticulum (Stumpf). According to this author, 
the component last named forms the ground-work of the 
tumor, enclosing both the fibres and the nuclei. Some of 
the nuclei are free, others surrounded by a darkly staining 
cell-body which varies in shape; in certain cells it is a more 
or less narrow, circular rim, while in others it is oval in 
outline. The differences, however, are often due to the plane 
of the section. A few cells throw out a number of processes, GLIOMA 
265 
which gradually lose themselves in the ground-substance or 
anastomose with projections from other cells; these are the 
astrocytes, described by Stroebe and others. 
The very cellular glioma is known as gliosarcoma, glio- 
blastic sarcoma, or glioma sarcomatodes. Its growth is 
rapid but only to a slight degree infiltrative, and the advance 
of the tumor is very apt to be checked by the inner mem- 
branes. This growth must not be confused with the small 
cell sarcoma of connective-tissue origin; the latter destroys 
the neuroglia (Stumpf). 
The transition between a glioma and the neighboring 
brain tissue, from which it departs but little either in color 
or consistency, is so gradual 
that it is often very difficult to 
define the boundaries of the 
tumor with the naked eye (Fig. 
161); this applies especially to 
the cellular variety, since the 
fibrous type is very often per- 
fectly demarcated. 
There are tumors (diffuse 
gliomata) which it is utterly im- 
possible to delimit. They are 
recognized only by enlargement 
of the affected portion of the brain, which may amount to 
an entire hemisphere or even more. 
The gradual transition between a glioma and the sur- 
rounding structures is responsible for the assumption that 
this tumor grows by inciting the neuroglia at its margin to 
tumorous proliferation, a type of growth that has been 
described as infective. According to the investigations of 
Stumpf, however, the glioma obeys the general law of tumor 
growth, increasing in size only through the multiplication 
of its own cells. Landau has suggested that diffuse glio- 
mata develop from innumerable foci (multicentric growth). 
The hemorrhage and softening to which gliomata are 
predisposed result in the production of cysts, which some- 
Fig. 162.-Glioma (greatly enlarged). 266 
TUMORS OF THE CENTRAL NERVOUS SYSTEM 
times attain the size of an apple. They may lie either within 
the tumor or just beyond it. 
Another type of cyst is lined by a row of cells. These 
have been referred to elements snared off from the ventricles 
or the medullary tube (Stroebe), a hypothesis which, in con- 
junction with the more frequent incidence of gliomata in 
Fig. 163.-Sarcoma on the inferior aspect of the right frontal lobe (two-fifths natural size). 
childhood, suggests that these tumors develop from em- 
bryonal rests. 
Cysts occur, also, in connection with gliomata of the 
spinal cord, producing a condition simulating syringo- 
myelia ; still, it is hardly justifiable to regard true syringo- 
myelia as a tumor, since the proliferation of neuroglia about 
the cavities is without doubt merely reactive. 
Cysts are frequently discovered in combination with 
other brain tumors, either within the growth or outside it, SARCOMA 
267 
and these often attain a large size. Here again it may be 
assumed that tumor and cyst both depend upon one common 
developmental anomaly. 
Sarcomata are of frequent occurrence in the brain (Fig. 
163), of which they may attack any portion. They are 
usually spindle-cell or fibrosarcomata, and originate in the 
membranes or in the connective tissue of the blood-vessels. 
The more common neoplasms of the central nervous 
system having been reviewed, it remains to discuss the con- 
sequences of a brain tumor. The intracranial pressure is 
increased, the cerebral convolutions are flattened (Fig. 160), 
and in many cases the internal table contains a number of 
shallow, atrophic depressions due to rarefying ostitis. The 
dura is generally tightly stretched and the pacchionian 
granulations so prominent as to cause deep pitting of the 
inner table; these structures may even perforate the bone 
and project upon the outer surface of the skull under the 
periosteum. The pacchionian granulations are villous 
processes of the arachnoid communicating with the sub- 
arachnoid space, which project into venous cavities of the 
dura connecting with the longitudinal sinus and transfer 
the cerebrospinal fluid to the circulation. Their enlarge- 
ment is due to congestion. As soon as all the available room 
within the cranial cavity has been occupied, pressure is 
exerted upon the contents of the skull. The brain itself 
yields but little; space is gained, however, by some slight 
displacement of the medulla and the cerebellum into the 
vertebral canal, and additional room by compression of the 
cerebrospinal fluid and the venous blood. The former 
escapes at first into the spinal canal and the veins, but its 
passage is soon rendered difficult by the congestion which 
follows the constantly rising intracranial pressure; finally, 
the veins and capillaries are emptied of their contents and 
anaemia supervenes (Kocher). 
Though the phenomena attending intracranial pressure 
have been investigated principally in the lower animals, it 268 
TUMORS OF THE CENTRAL NERVOUS SYSTEM 
is known that, in man as well, the amount of blood contained 
in the compressed brain is small. 
Internal hydrocephalus accompanies many cerebral 
tumors, especially those involving the corpora quadrigemina 
or the cerebellum, when they prevent communication be- 
tween the ventricles or produce venous engorgement by 
pressure upon the vena magna Galeni. 
Sharply circumscribed neoplasms generally compress 
the adjoining cerebral tissues, causing anaemia or softening; 
Fig. 164.-Fibroma of the auditory nerve, occupying the cerebello-pontine angle. Compres- 
sion of pons and medulla (after Henschen). 
death occurs if the process involve a vital area like the 
respiratory centre. 
The consequences of compression vary so according to 
the situation of the tumor that a concrete description is 
difficult; the following, however, may be offered. 
Tumors of the parietal lobe often injure the motor areas 
in the cortex, or, if situated more deeply, the internal cap- 
sule. This important region may be damaged, for example, 
by the sudden enlargement of a tumor in consequence of 
hemorrhage into it, with results comparable to those of CEREBELLAR TUMORS 
269 
apoplexy. Growths in the left frontal and temporal lobes 
frequently compromise the speech-centre, while those about 
the pulvinar, the optic thalamus, the corpora quadrigemina, 
and the occipital lobe, may interfere with vision. Neoplasms 
in the cerebellum and in the cerebello-pontine angle (which 
lies between the cerebellum, on the one hand, and the pons 
varolii and medulla on the other), compress both pons and 
medulla (Fig. 164). 
Fig. 1G5.-Papilloma of the fourth ventricle (after Vonwiller). 
Tumors of this angle include fibromata or fibrosarcomata 
of the meninges, and papillomata (Fig. 165) developing 
from the epithelium of the choroid plexus in the fourth ven- 
tricle, which approaches the surface at the flocculus. These 
growths sometimes invade the ventricle. Papillomata may, 
however, arise primarily within the fourth ventricle, some- 
times, also, from its ependyma (Vonwiller). In the lateral 
ventricles, they originate in the choroid plexus. Other 
tumors found in the cerebello-pontine angle are those which 
develop at the base of the skull and involve this region 270 
TUMORS OF THE CENTRAL NERVOUS SYSTEM 
secondarily, particularly fibroid growths of the auditory 
nerve (Fig. 164). According to Henschen, these originate 
from the embryonal connective tissue between the branches 
of the nerve at the bottom of the internal auditory meatus, 
a tissue which retains its undifferentiated condition after 
that at the exits of all the other cranial nerves has matured. 
This statement explains the observation that fibroid neo- 
plasms affect the auditory much more commonly than any 
of the other nerves at the base of the skull. 
There is a neoplasm found at the base, in the immediate 
neighborhood of the infundibulum and the chiasm, loosely 
connected with the brain, and often cystic; it may attain 
the size of an egg. Its 
cells, which are arranged 
in bands, resemble squa- 
mous epithelium in which 
keratinization is scanty 
and incomplete, or even 
absent, and its stroma is 
generally the seat of mu- 
cous or hyaline degener- 
ation. Tumors of this 
type have been described 
as endotheliomata or 
cylindromata, but in the opinion of Erdheim, they originate 
from remnants of the hypophyseal duct. 
Neoplasms of the hypophysis itself produce atrophy in 
the neighboring bony structures, distend the dura mater, 
and threaten the nerves of vision or those supplying the 
muscles of the eye. 
For the sake of completeness it should be added that 
such new growths of the cranial cavity as originate in tissues 
other than the brain and its inner membranes, or as pene- 
trate it from without, exert the same effects as tumors of the 
brain itself. Beside fibromata of the cranial nerves, already 
mentioned, this class includes endotheliomata of the dura 
mater, which are frequently localized at the convex surface. 
Fig. 166.-Endothelioma of the dura mater (great- 
ly enlarged). PSAMMOMA 
271 
This neoplasm consists of bands and concentric masses of 
small and rather elongated cells (Fig. 166), which some- 
times undergo hyaline transformation and calcification. 
When these changes are extensive, they produce the macro- 
scopic appearance of sand grains, and this type of endo- 
thelioma is accordingly known as psammoma. 
The most common neoplasms in the spinal cord are 
tumors of its membranes, such as fibromata, fibrosarcomata, 
endotheliomata, or neurofibromata of the nerve roots, all 
of which generally exert distinct compression on the cord. 
Among new growths of the cord itself, glioma is the most 
important. CHAPTER XXIV 
The periosteal, or more accurately, peripheral sarcoma 
(Figs. 167 and 168) so often referred to the periosteum, de- 
velops in the opinion of Ribbert, from the periphery of the 
bone itself (spongiosa). In its growth, it invades this tis- 
sue and intrudes between it and the periosteum, which be- 
comes stripped off in consequence. Like all tumors 
(Ribbert), it grows by the multiplication of its own cells, 
never inciting the adjacent periosteal elements to malignant 
proliferation. 
The central, or myelogenic variety (Fig. 169), appears 
as a soft grayish-red mass which dilates and fills the marrow 
cavity, thinning out or destroying the surrounding bone. 
These tumors are sometimes enclosed in a more or less 
complete bony shell produced by an ossifying periostitis. 
The microscopic structure of the growth shown in Fig. 
167, a perfect example of spindle-cell sarcoma, is repro- 
duced in Fig. 170. Bands of spindle-cells run in various 
directions, and the plane of the section therefore cuts them 
longitudinally, obliquely, or transversely; usually they fol- 
low the vessels, which constitute the only supporting frame- 
work in this group of neoplasms. 
The spindle-shaped cells are fibroblasts, though they 
usually contain more protoplasm than do those of finished 
connective tissue, and correspond in a general way with 
those found in the embryo, or during regeneration. Since 
they elaborate no fibrillary ground substance, or, at the 
most, a minimal amount only, the tissues composing the 
tumor can never attain perfect maturation; hence, a sar- 
coma may be defined as a new growth made up of unfinished 
connective tissue (classification, p. 260). According to Borst, 
sarcomata which, like those of spindle-cell type, consist 
solely of cells, occupy the lowest plane among the tissues. 
Sarcoma of the Bones ; Melanoma 
272 GIANT-CELL BONE SARCOMA 
273 
The giant-cell bone sarcoma (Fig. 171), a member of the 
spindle-cell group, is generally central. It differs from 
the growth just described in the presence of a great num- 
Fig. 167.-Peripheral sarcoma in the lower end of the femur (one-half natural size). 
her of large multinuclear elements which, in their form and 
in the arrangement of their nuclei, simulate the giant-cells 
of the bone-marrow whence they are derived. Some giant- 274 
SARCOMA OF THE BONES 
cell sarcomata, however, belong among the round- or the 
mixed-cell sarcomata. 
The giant-cell sarcoma is frequently encountered in the 
jaw, in the form of a roundish tumor intruding between the 
teeth (epulis); here it shows little or no tendency to metas- 
Fig. 168.-Peripheral sarcoma in a long 
bone (two-thirds natural size). 
Fig. 169.-Central sarcoma in the tibia 
(three-fifths natural size). 
tasize, or to recur after removal. In some cases, an epulis 
is purely fibrous, or contains newly-formed bone. 
The group of low-grade tumors now under discussion 
includes, also, the round-cell sarcoma (Fig. 172), a neo- 
plasm composed of small round-cells and a very scanty con- 
nective-tissue stroma carrying the blood-vessels. 
A higher class, of frequent occurrence in bone, repre- OSTEOSARCOMATA 
275 
sents a type in which differentiation has been carried fur- 
ther forward and includes the fibrosarcoma (Fig. 173), the 
chondrosarcoma (Fig. 174), and the osteosarcoma (Fig. 
Fig. 170.-Spindle-cell sarcoma 
(greatly enlarged), a, spindle-cells 
cut transversely. 
Fig. 171.-Giant-cell sarcoma (slightly enlarged). 
Fig. 172.-Round-cell sarcoma (great- 
ly enlarged). 
Fig. 173. - Fibrosarcoma 
(moderately enlarged). 
The osteosarcomata, neoplasms which tend more or less 
to produce bone (Fig. 175), are particularly common. In 
some, the tumor cells lie among homogeneous trabeculae 
of uncalcified tissue (osteoid sarcoma), while others contain 276 
SARCOMA OF THE BONES 
true bone evolved by the calcification of their osteoid ground 
substance. 
This second division embraces those bone sarcomata in 
which groups of tumor cells are enclosed by an extensive 
and wide-meshed connective-tissue stroma, the whole struc- 
ture imitating so faithfully that of the epithelial tumors 
that such growths were formerly described as primary bone 
carcinomata. Further investigation having shown, how- 
ever, that an epithelial tumor can develop only from epi- 
thelial cells, it became necessary to remove these neoplasms 
Fig. 174.--Chondrosarcoma (greatly enlarged) 
Fig. 175.--Osteosarcoma (slightly enlarged). 
a. osteoid substance; b, tumor-cells. 
from among the carcinomata, and they are regarded to-day 
as endotheliomata, developing from the endothelium of the 
blood- or the lymph-vessels. 
The sarcomata are counted among the malignant new 
growths, since they exhibit that tendency to infiltrate and 
to metastasize, which is the anatomical expression of malig- 
nancy. Infiltration procures the advance of a neoplasm 
by the destruction of opposing tissues, metastasis its dis- 
semination to regions remote from the primary tumor 
through the transfer of its cells to a new location by the 
blood- or lymph-stream, and their subsequent multiplication 
there. Since the penetration of malignant tissue into a GENERAL SARCOMATOSIS 
277 
lymph-channel or a blood-vessel is responsible for tumor- 
cell emboli, the cause of metastasis, in the last analysis, is 
infiltrative growth. 
The various bone sarcomata are not equally malignant. 
Many of them, like the giant-cell tumor of the jaw, may be 
described as almost benign, while those involving the long 
bones do not usually metastasize until they have attained 
a large size. When metastasis does occur, it generally takes 
place by way of the blood-stream, and the lungs, therefore, 
are especially apt to contain secondary tumors. 
MELANOMA ( MELANOBLASTOMA) 
These neoplasms appear in the skin as small, prominent, 
dark brown or black verruciform nodules. They almost in- 
variably recur and metastasize, and secondary deposits may 
be found in the skin and the internal organs even in associa- 
tion with small growths; the condition is so widespread in 
some cases as to merit the term general sarcomatosis. 
Melanomata usually develop from pigmented moles, and 
a short description of the nsevus will therefore help to ex- 
plain their structure. This is a congenital, brownish, 
slightly raised spot in the skin, generally small, often ver- 
ruciform (naevus verrucosus), and sometimes covered with 
hair (naevus pilosus). It consists of masses of rather large 
cells (Fig. 176), which lie directly underneath the epider- 
mis and extend more or less deeply into the cutis, according 
to the size of the naevus; these cells contain greater or 
smaller quantities of melanin, a brownish pigment analo- 
gous to the physiological coloring matter of the skin. 
In the connective tissue surrounding the cell groups, and 
within these themselves, there are found spindle- or star- 
shaped elements enclosing pigment granules, and similar, 
therefore, to the chromatophores of the cutis. 
The melanoma is an atypical naevus (Fig. 177). Its cells 
are large and similar to those of epithelium, an arrangement 278 
MELANOMA 
in nests being still recognizable and even distinct in many 
places; in other regions, however, this pattern is replaced 
by a simple, sarcoma-like architecture. The amount of 
pigmentation is variable, both in the cells of the tumor 
themselves and in those resembling the chromatophores, 
and areas are often found which are entirely devoid of any 
pigment whatsoever. 
Fig. 176.-Pigmented mole (greatly enlarged), a, nestg of nrevus cells; b, chromatophores in 
the connective tissue. 
The place to be occupied by the melanomata depends 
upon questions to which no satisfactory reply has yet been 
returned; depends, that is, upon the origin of the naevus cells 
and the formation of pigment. The naevus cells were re- 
ferred by v. Recklinghausen to the endothelium of the lymph- 
vessels, and while his view obtained these tumors were in- 
cluded among the sarcomata, the resulting name "melano- 
sarcoma" being even now widely employed. An opposing NATURE OF THE MELANOMA 
279 
view, that the naevus cells are epithelial structures and that 
tumors composed of them should be called melanocarcino- 
mata, has been advocated by Unna. For a considerable 
period it met with little favor, but later investigation, and 
particularly the work of Wieting and Hamdi, and of Favere, 
has contributed materially to- 
ward its support. Ribbert de- 
scribed the roundish elements 
of the naevus as immature 
forms of the branched chro- 
mato pho re melanoblast). 
thus viewing the pigmented 
tumors as derivatives of the 
pigment-forming element, as 
the term melanoma implies. 
This conception it is possible 
to endorse, without sharing 
Hibbert's view regarding the 
nature of the naevus cell. 
It is not yet known which 
element elaborates the chief physiological pigment. Accord- 
ing to Ehrmann's hypothesis, the pigmented spindle- or 
star-shaped chromatophores elaborate the coloring matter 
and transfer it to the epithelial cells, which are unable to 
prepare it. I am inclined, however, to accept the view that 
the epithelial cells are themselves invested with the power 
of pigment formation, a hypothesis which has been sup- 
ported and rendered probable by the investigations of 
Wieting and Hamdi, Meirowski, Favere, and Keibich. A 
distinction is thus drawn between the epithelial cells which 
manufacture pigment (melanoblasts), and the branched 
connective-tissue elements (chromatophores), which take it 
up and transport it. In accordance with their epithelial 
origin, the large round cells of the naevus and the melanoma 
would then be analogous to the melanoblast. 
Melanomata of the retina are generally included with 
those of the skin (Ribbert), and for many reasons properly, 
Fig. 177.-Melanoma (greatly enlarged). 
a, round cells containing pigment; b, 
branching cells, intensely pigmented. 280 
MELANOMA 
although the two varieties are not histologically identical. 
There is a sarcoma-like tumor containing but little pig- 
ment, which occurs in the choroid, and which Schieck has 
included among the melanomata. Such a classification may 
be suitable for many of the choroid neoplasms, but Schieck 
has gone too far in transferring nearly all the sarcomata of 
this region, even the unpigmented, into the melanoma group. 
According to the epithelial hypothesis, it would have to 
be assumed that the physiological coloring matter of the 
choroid originates in the retinal epithelium and reaches the 
choroid by emigration, but so far as I am aware, melano- 
mata of the eye have not yet been investigated from this 
standpoint. CHAPTER XXV 
Mammary Carcinoma; Carcinoma of the Skin; Carcino- 
genesis 
Metastatic carcinomata differ widely in their distribu- 
tion, even when the mother tumors are similar. 
Fig. 178.-Metastatic infiltrating carcinoma of the peritoneum and the liver, following 
mammary carcinoma, a, liver; b, stomach; c, transverse colon; d, coils of small intestine; 
e, sigmoid flexure; f, caecum; g, peritoneal cavity, which was full of fluid. 
In the case of mammary cancer, the liver, which is a site 
of predilection for metastatic carcinoma (Fig. 201), con- 
tains a few nodules; if many be present, they are apt to be 
small. 
281 282 
MAMMARY CARCINOMA 
A common situation for secondary deposits is the skele- 
tal system, where the metastases are sometimes responsible 
for the production of new bone (osteoplastic carcinoma). 
The pleura is almost always involved. That this may 
occur purely by metastasis seems probable, but it takes 
place, also, in consequence of the progressive growth of 
the tumor through the thoracic wall, and invasion of the 
lymph-channels. 
Carcinosis of the peritoneum, which is not at all a rare 
consequence of mammary cancer, often occurs in the form 
of isolated nodules on the outer surface of the intestine; 
these may invade the wall as far as the mucous membrane, 
Fig. 179.-Mammary carcinoma, a, tumor; b, fat; c, pectoral muscle, containing metastatic 
nodules, d. 
or encircle the gut. In the latter instance, they frequently 
result in stenosis. The process, however, may be more dif- 
fuse (Fig. 178); the peritoneum is then thickened and 
shrunken, and the coils of intestine are gathered into a solid 
mass. 
In the breast itself, the nipple may be retracted, a sign 
upon which the clinician is apt to lay some emphasis; on 
the cut surface of the organ (Fig. 179), the tumor can be 
seen radiating into the adjacent fat. In more advanced 
cases, the neoplasm extends from the surface of the breast 
into the pectoral muscle, and small skin metastases often 
surround the nipple. The later stages are marked by ulcer- 
ation. HISTOLOGY 
283 
Histologically, cancer of the breast (Fig. 180) is an 
excellent example of the carcinoma group. Its essential 
characteristic is the presence of masses or bands of epi- 
thelial cells enclosed within a connective-tissue stroma, upon 
which they depend for nutrition; the two tissues are sharply 
separate at all times. Wax models constructed from serial 
sections show that all the cell groups are connected and that 
a carcinoma therefore represents an intricate system of 
branching processes (Petersen). 
Fig. 180.-Mammary carcinoma (slightly enlarged). 
The consistency of the tumor depends upon the relative 
amounts of parenchyma and stroma. Where the epithelial 
portion preponderates, the growth is soft (medullary car- 
cinoma, carcinoma molle), while those in which the stroma 
exceeds the parenchyma in amount are characterized by 
their firmness (scirrhous carcinoma). In some cases, the 
stroma is infiltrated by small round-cells like those associ- 
ated with chronic inflammation. 
Tumors of the class to which mammary carcinoma be- 
longs, develop from glandular epithelium, as contrasted 
with those of a second group, which originate from super- 
ficial epithelium. 284 
CARCINOMA OF THE SKIN 
The parenchyma of the ordinary skin carcinoma (Fig. 
181) preserves so faithfully the characteristics of stratified 
epithelium that a basal-cell, a prickle-cell, and a horny layer 
are often distinguishable within the alveoli. The keratin- 
ized cells of the layer last named assume a concentric 
laminated arrangement toward the centre, giving rise to 
epithelial or cancroid pearls. 
Certain carcinomata of the skin are devoid of keratiniza- 
tion. They are generally made up of small and often spindle- 
CARCINOMA OF THE SKIN 
Fig. 181.-Carcinoma of the skin (slightly enlarged), a, epithelial pearl. 
shaped elements, the nuclei of which lie so close together 
that the cell groups are very dark in stained preparations. 
The parenchyma is therefore clearly distinguishable from 
surface epithelium, with which its cells come into connec- 
tion only secondarily. A glandular structure is sometimes 
encountered (Krompecher). 
These growths, which are not very malignant, were for- 
merly grouped with the endotheliomata (Borst), but their 
epithelial nature is now perfectly apparent; it is only their 
source that remains still unexplained. Krompecher has ex- 
pressed the view that they are derived from the basal layer 
of the skin (basal-cell carcinoma), and Borrmann, that they GROWTH ENERGY 
285 
arise from epithelial rests congenitally deposited in the 
corium (corium carcinoma), while Ribbert has assumed 
their genetic connection with the surface epithelium. 
Carcinomata of the skin appear clinically either as shal- 
low ulcers which undermine and destroy the integument, or 
as nodular or warty outgrowths which eventually ulcerate. 
Cancer of the skin has served for a long time as a means 
for investigating the development of carcinomata in gen- 
eral, and it was in connection with this type of growth that 
Thiersch and Waldeyer founded their hypothesis referring 
the origin of carcinoma solely to the epithelial tissues. 
The epithelium just beyond a young carcinoma often 
produces the impression of invasive growth, as though it 
had undergone cancerous transformation. Ribbert has 
shown, however, that this appearance is due to a coalescence 
between the normal epithelium and that of the carcinoma, 
as it spreads through the corium (Fig. 182). According to 
this author, a tumor grows only by the multiplication of its 
own cells, never inciting the adjoining structures to malig- 
nant proliferation. Thus the incipient neoplasm would be 
limited to a very small area, though, according to Petersen, 
a carcinoma of the skin may originate from several such 
foci (multicentric origin). 
Once a carcinoma has developed, it is able to invade 
any tissue in its path by reason of the vigorous prolifera- 
tive power of its cells. This characteristic is common to all 
the malignant tumors, and is of greater importance in 
microscopic diagnosis than is histological structure. 
How great the growth energy of a malignant neoplasm 
may be, has become apparent in the investigation of mouse 
tumors. Spontaneous carcinomata of the white mouse are 
transferable to other individuals of the same species, and 
some have been propagated through more than a hundred 
generations without losing any of their capacity for pro- 
THE GENESIS OF CARCINOMA 286 
CARCINOGENESIS 
liferation. While the normal growth of the body finally 
reaches a stage of equilibrium, after which no more occurs 
than is necessary to compensate for wear, the growth of a 
tumor is boundless. Furthermore, the new tissue produced 
by physiological growth or regeneration has its proper 
place in the economy of the body, whereas a malignant 
Fig. 182.--Schema of growth in a carcinoma of the skin (after Ribbert). I, small carci- 
noma with three branches, surrounded by very cellular connective tissue; T, sebaceous gland; 
II, hair-follicle. II, destruction of the skin overlying the carcinoma, and lateral growth of the 
tumor along the lower border of the epidermis to surround T and II. Ill, the carcinoma has 
become still larger, and has ulcerated. All but a remnant of T and H has been destroyed. 
neoplasm is to a certain extent independent of the organism, 
and behaves somewhat after the manner of a parasite 
(Ribbert). ETIOLOGY OF CARCINOMA 
287 
How do the cells of a malignant tumor attain this power 
of limitless, destructive growth? The question cannot be 
answered. Many hypotheses have been advanced which, 
however, cannot be fully discussed here, great though their 
interest may be for the special investigator. 
It was formerly believed that mechanical or chemical 
stimuli, especially those of long duration, would initiate 
malignant growth, and the fact that carcinoma is most apt 
to occur in regions exposed to mechanical insult (the lip in 
pipe-smokers, the scrotum in chimney-sweeps) seemed to 
justify this assumption, as did the occurrence of cancer 
upon the ground of chronic inflammation or ulceration 
(lupus, gastric ulcer, X-ray dermatitis). The question has 
been emphasized anew by the discussion of a precarcino- 
matous stage (Orth), which is said to prepare the ground 
for the development of carcinoma by inducing certain trans- 
formations in the tissues. The character of this interven- 
tion, however, is still a mystery, though it can be asserted, 
at any rate, that neither mechanical nor chemical influences 
are concerned. 
It has been maintained by a number of investigators that 
cancer is an infectious disease, and a great deal of time and 
energy have been expended in the search for its causative 
agent. But most of the structures described as protozoa 
have proved to be either artefacts or products of degenera- 
tion in the cell or its nucleus, while in those cases where 
actual parasites have been found, no etiological relationship 
to the tumor has been demonstrable. 
The pathologist has always viewed the parasitic theory 
with suspicion, because malignant tumors do not correspond 
with the infectious diseases in their behavior. They are 
transferable from mouse to mouse, it is true, but this fact 
holds not the slightest support for contagion; on the con- 
trary, the growth of a tumor in a new host is a perfect 
example of transplantation, and it conforms to all the laws 
which hold for the engrafting of normal tissue. Secondly, 
the metastatic extension of a malignant neoplasm has no 288 
CARCINOGENESIS 
analogy among the infectious diseases. There, metastases 
are produced entirely by the tissues in which the circulat- 
ing causal agent is arrested, while in the case of malignant 
growths the tumor cells themselves multiply in the new loca- 
tion to which they have been transported. Therefore, a 
secondary infectious lesion resembles the tissue in which 
it develops, while a metastatic tumor invariably reproduces 
the architecture of the primary growth, hepatic metastases 
from an oesophageal carcinoma, for example, being com- 
posed, not of liver cell, but of squamous epithelium 
from the oesophagus. In both transplanted and metastatic 
tumors, the sole portion contributed by the new locality is 
the connective-tissue stroma; hence, transplantation may be 
described as artificial metastasis. Finally, no known para- 
site has the power to release proliferative activity. None of 
those so far investigated exerts any effect but cell injury, 
apparent instances of lawless growth such as the tumor- 
like protuberances of plants being the product of reactive 
processes in the neighboring tissues. Summing up, then, it 
may be said that critical examination leaves no parallel 
between the new growths and the infectious diseases. 
The question whether growth can be inaugurated by 
stimulus may be regarded, on the whole, as still debatable. 
Virchow assumed the existence of a formative stimulus, but 
Weigert concluded that stimulus could only injure, and 
that proliferation was a mere secondary event which repre- 
sented an attempt to fill out the resultant defects. Ribbert, 
an active disciple of this latter view, has been especially 
energetic in denying the participation of stimulus in tumor 
genesis. In so far as he has rejected the possibility that 
new proliferative impulses can be introduced into the organ- 
ism, his attitude will meet with perfect agreement, but there 
is no necessity to refute the idea that certain stimuli may be 
able to release a growth tendency already in existence 
(v. Hansemann); in fact, the more recent knowledge of 
chemical correlation within the organism suggests many 
possibilities in this direction. In any case, the cessation COHNHEIM'S HYPOTHESIS 
289 
of inhibitory forces assumed by Weigert and Ribbert is 
actually a stimulus to proliferation, negative though it be. 
According to Ribbert, epithelial growth is encouraged 
by inflammatory changes in the connective tissue, the escape 
of epithelium from its normal physiological restraint being 
the ultimate cause of cancerous proliferation. He has thus 
extended Cohnheim's hypothesis, which ascribed the de- 
velopment of neoplasms to misplaced or redundant embry- 
onic rests, and explained unlimited growth by assuming that 
these remnants retained their inherent embryonal capacity 
for multiplication. Originally referred by Ribbert to single 
mechanical factors, the emancipation of epithelium appears 
in the later forms of his hypothesis to be a process more 
complicated and, at the same time, more vague and prob- 
lematical. 
The mere mechanical displacement of a tissue is not in 
itself, however, productive of a tumor, as experience proves, 
and the majority of chronic inflammations do not terminate 
in malignant growth. Ribbert's contention that all carci- 
nomata have their origin in small cell infiltration of the 
connective tissue has not successfully withstood the criti- 
cism to which it has been subjected (Borst) and it may be 
said, on the whole, that his views have not been generally 
approved. The majority of authors attribute the limitless 
proliferation of the cancer cell to the possession of some 
special faculty (Hauser, Marchand, Borst), though of the 
manner in which this property is assumed by the normal 
element, nothing is known. That the condition should be 
congenital (Borst) seems improbable; it is more reasonable 
to suppose that the cancer cell acquires its characteristics 
gradually, and gives rise finally to a new race of cells 
(Hauser). 
The deviation of the carcinoma cell from the normal 
epithelial element is biological. Only insignificant morpho- 
logical alterations are recognizable, which may be referred 
in a general way to loss of differentiation (v. Hansemann, 
Borst); v. Hansemann has applied the term anaplasia to 290 
CARCINOGENESIS 
this morphological departure from the normal. The con- 
dition is in part a consequence of malignant growth and 
has no bearing upon etiology. 
The study of transplantable tumors of the mouse and 
rat, begun by Hanau and by Jensen, and extended by Borrel, 
Bashford and Murray, and Ehrlich and Apolant, has yielded 
the most valuable results, though no light has yet been cast 
upon the origin of malignant growths. It has been shown 
that the majority of carcinomata of the mouse are trans- 
ferable to other mice, and that the percentage of successful 
results generally rises during the course of progressive 
transplantation. The histological structure of the primary 
tumor is preserved during propagation. 
A few growths have been described with a parenchyma 
capable of transforming the stroma into a sarcoma, which 
is transplantable, and which soon overgrows the epithelial 
portions (Ehrlich, Apolant, Haaland). 
It has been shown, furthermore (Clowes and Baeslack), 
that mice in which a transplanted tumor has been absorbed, 
or those which have been inoculated with normal mouse 
tissue (Bashford and Murray, Schone), become immune to 
transplantation, since they fail to furnish the stroma neces- 
sary for the support of a graft (Russell). As the absorption 
of one variety of neoplasm will protect against other types 
also, immunity to transplantation is in no sense specific, 
and is thereby sharply distinguishable from that evolved 
against the bacterial poisons. 
Attempts to produce a primary carcinoma by the trans- 
plantation of embryonal tissues, the introduction of para- 
sites, the production of chronic inflammation, or by treat- 
ment with various chemical agents, have all failed, though 
B. Fischer achieved suggestive results by injecting oily 
solutions of fat stains (Sudan III, Scharlach R) into the 
skin of the ear in rabbits. Considerable proliferation of 
the surface epithelium and the hair follicles can be induced 
in this way, and the microscopic appearance of the resulting 
lesion is very similar to that of squamous-cell carcinoma; EXPERIMENTAL PROLIFERATION 
291 
but as the condition neither persists nor exhibits any ten- 
dency toward infiltrative growth, it cannot be called malig- 
nant. Similar changes follow the injection of indol and 
skatol, materials elaborated by the body itself (Stoeber and 
Wacker). 
In what manner these materials cause proliferation has 
not been fully explained; according to Wacker and 
Schmincke, their action is in some way connected with a 
power to dissolve lipoids. Reinke succeeded in producing 
atypical growth in salamander larvae by treatment with 
ether, another solvent of lipoids, and Askanazy found that 
the growth energy of embryonal rat tissue is much increased 
by the same agent. 
The artificial production of a malignant growth is one of 
the most important goals imaginable, since not until this has 
been accomplished is there any hope that tumor genesis will 
be explained (Orth). CHAPTER XXVI 
Primary Carcinoma of the Pleura and the Lung; Car- 
cinoma of the CEsophagus and the Upper Respira- 
tory Passages; Gangrene of the Lung 
The pleural cavity generally contains a large quantity 
of clear yellow fluid, which displaces the heart and com- 
presses the lung. In some cases, the exudate is hemor- 
Fig. 183.-Primary carcinoma (endothelial cancer) of the pleura (one-half natural size), 
a, section through the left lung and b, the thickened pleura; c, base of the lung with thickened 
pleura; d, parietal pleura studded with tumors. 
292 ENDOTHELIOMA 
293 
rhagic; turbidity is generally due to infection during 
paracentesis. The greatly thickened pleura may be fairly 
smooth, or covered with tumor nodules (Fig. 183), and its 
cut surface has the white marrowy appearance associated 
with neoplastic tissues. 
Characteristic examples of pleural carcinoma are com- 
posed of large elements, rich in protoplasm and arranged 
in masses and bands like those of a carcinoma; still more 
typical are the clefts or 
gland-like spaces with their 
lining of tumor cells (Fig. 
184). 
It is not easy to classify 
these tumors. At a time 
when the superficial cellu- 
lar layer of the pleura was 
believed to be of endothelial 
origin, it was difficult to 
correlate their carcinoma- 
tous structure with their de- 
velopment at a site sup- 
posedly devoid of epithe- 
lium, and Wagner there- 
fore instituted a new group, 
endothelial cancer, for 
which the name endothelioma was later substituted. If it 
could be proved that they arise from the pleural lymph- 
channels, the latter term would be perfectly satisfactory, 
but cogent reasons have been advanced for referring them 
to the mesothelium (Benda) and since this is an epithelial 
derivative, many authors now classify these neoplasms as 
carcinomata (Benda, Ribbert). 
They depart from the ordinary carcinoma, nevertheless, 
in several particulars. With but little tendency to overstep 
the boundaries of the pleura, they rarely invade the chest 
wall, hence the thickened costal pleura can always be 
readily stripped away at autopsy. Furthermore, metas- 
Fig. 184.-Primary carcinoma (endothelial can- 
cer) of the pleura (greatly enlarged). 294 
PRIMARY CARCINOMA OF PLEURA AND LUNG 
tasis is an uncommon event; if it take place at all, the sec- 
ondary nodules are apt to be situated in the lung of the 
affected side. Finally, these growths do not produce any 
great degree of cachexia. 
Fig. 185.-Primary carcinoma of the lung (one-half natural size). 
Other primary tumors of the pleura are uncommon. The 
list includes sarcomata (Gutmann), chondromyxosarcomata 
(Busse), and fibromata (Schmidt), and I have seen a fibro- 
sarcoma with many purely fibrous areas, which metastasized 
in the pleura of the opposite side and in the epicardium. 
The rare primary carcinoma of the lung (Fig. 185) may 
be solid throughout, or necrotic toward the centre. They COMPLICATIONS AND SEQUELAE 
295 
frequently occupy the hilus, and as they develop from the 
bronchial mucous membrane (Langhans) are sometimes 
found still confined to, or penetrated by, a bronchus. It has 
been possible to demonstrate their origin in a few cases from 
the wall of a tuberculous cavity (for bibliography, see 
Schwalbe). 
In a few instances, the growth has been referred to the 
alveolar epithelium (for bibliography, see Piissler), 
although, according to this author, such an origin cannot be 
actually proved. 
Fig. 186.-Primary carcinoma of the lung (slightly enlarged). The cell-nests resemble 
bronchial epithelium. 
Those which spring from the bronchial mucosa are adeno- 
carcinomata, and generally recall the bronchial epithelium 
(Fig. 186), although growths with indifferent, and even 
squamous epithelium, have been described. 
Carcinomata of the lung frequently involve the pleura, 
sometimes setting up in addition an exudative pleuritis; 
metastasis in other organs, particularly the brain, is not 
uncommon, and Piissler has recorded the occurrence of pneu- 
monia and pulmonary gangrene from the aspiration of 
necrotic tumor tissue. 296 
CARCINOMA OF THE (ESOPHAGUS 
Pulmonary carcinomata may produce stenosis of the 
bronchi and the trachege, either by infiltration and projection 
into the lumen, or by 
pressure from without; 
by the latter means 
they sometimes com- 
promise the arteries 
and veins of the lung. 
According to Passler, 
involvement of the peri- 
cardial sac with conse- 
quent pericarditis, is an 
infrequent complication. 
CARCINOMA OF THE (ESO- 
PHAGUS AND THE UPPER 
AIR PASSAGES 
The most common 
oesophageal carcinoma 
is situated opposite the 
bifurcation of the tra- 
chea, and involves a 
length of from three to 
seven centimetres, en- 
circling the canal and 
thickening and c o n - 
trading the adjacent 
wall (Fig. 187); such 
growths are generally 
o f the squamous-cell 
variety, and not infre- 
quently contain epithe- 
lial pearls (Fig. 188). 
The abundant stroma 
and scanty parenchyma of many of these tumors explain 
their characteristic firmness and their tendency to constrict 
Fig. 187.-Carcinoma of the oesophagus (one-half nat- 
ural size), a, carcinoma; b, cardiac orifice. METASTASIS AND INFILTRATION 
297 
the gullet even while they are still-small; the stenosis may 
eventually reach a point where the lumen is reduced to the 
diameter of a lead pencil. A second and less common type, 
in which the parenchyma is less highly differentiated, is 
softer and more cellular. 
Other sites of predilection for carcinoma are the transi- 
tion between pharynx and oesophagus, and the lower end 
of the oesophagus (Fig. 189). Here they are larger, nodular, 
and soft, and, like the much rarer sarcoma (Rieke; for 
bibliography, see Hacker), generally cause no obstruction, 
on account of their elasticity. 
The ordinary constricting cancer of the gullet does not 
metastasize widely, and generally involves only the lymph- 
Fig. 188.-Squamous-cell carcinoma of the oesophagus (slightly enlarged). 
nodes of the posterior mediastinum; the softer tumors are 
more apt to give rise to secondary growths, which are some- 
times found in other portions of the oesophagus itself. 
The common variety often infiltrate adjoining struc- 
tures, and, corresponding to their usual location opposite 
the tracheal bifurcation, most commonly attack the trachea 
and large bronchi; the resulting growths sometimes ulcerate 
and give rise to communications between the respiratory 
and digestive tracts. It is not at all rare, however, for 
perforation to be caused by purulent mediastinitis, which 
develops in the region of the tumor and subsequently in- 298 
CARCINOMA OF THE (ESOPHAGUS 
Fig. 189.-Large carcinoma of the oesophagus only 
slightly ulcerated (one-half natural size). 
Fig. 190.-Carcinoma of the oesophagus perforating 
into the trachea (one-half natural size), a, point of per- 
foration; b, tracheal lymph-node; c, trachea, pushed 
to one side; d, transverse section of the arch of the aorta. 
vades trachea and bronchi. The ulcerating growth may in- 
duce gangrene in the adjacent portion of a lung, or, more 
rarely, penetrate the pleura or the pericardium, and even the COMPLICATIONS AND SEQUELAE 
299 
aorta may be perforated by suppurative inflammation in 
this vicinity. In such cases, the intima contains a small 
fissure, surrounded by an area in which the vessel wall is 
somewhat thinned out; under the break there appears a 
small suppurating cavity, and beneath this, the carcinoma. 
Perforation of the aorta 
is followed by fatal hem- 
orrhage into the oesopha- 
gus, and at autopsy the 
stomach is generally found 
distended with blood. 
Soft tumors situated in 
the upper portion of the 
oesophagus are less apt 
to perforate this canal, 
although I have seen a 
very necrotic, soft carci- 
noma communicating with 
a gangrenous upper lobe 
in the right lung. 
Cancerous obstruction 
of the oesophagus inter- 
feres seriously with nutri- 
tion, and general emacia- 
tion is therefore a promi- 
ent symptom. Areas of 
lobular pneumonia are 
often present in the lower 
lobes, produced either by 
the aspiration of necrotic 
tumor fragments which 
have escaped into the air 
passages, or of solid or liquid food in consequence of the 
oesophageal constriction; the latter is the more common 
cause. 
Primary cancer of the pharynx is not common, and 
growths in this region are generally extensions from the 
Fig. 191.-Carcinoma of the larynx (one-half 
natural size). 300 
GANGRENE OF THE LUNG 
tongue or the upper part of the oesophagus. Carcinomata 
of the tongue, which belong to the squamous-cell type, 
generally appear first at the margin as small ulcerating 
nodules; in their subsequent growth they invade the organ 
so extensively as sometimes to destroy the greater part of 
it. In the larynx, squamous-cell carcinomata occur prin- 
cipally on the vocal cords; they originate in small papillary 
excrescences (Fig. 191), and are often papilliform. 
GANGRENE OF THE LUNG 
As aspiration pneumonia is frequently followed by pul- 
monary gangrene, the latter condition is relatively frequent 
in connection with carcinomata in the upper regions of the 
digestive and respiratory tracts. If the lesion be a recent 
one it appears in the form of a mushy, discolored area with 
a very foul odor; the pleura overlying the more superficial 
foci is generally covered with a layer of fibrin. Liquefac- 
tion sets in later, the surrounding normal lung meanwhile 
undergoing an inflammatory reaction which walls off the 
lesion, and the final result is a cavity containing a purulent 
fetid mass, and lined by a pyogenic membrane. 
Pulmonary gangrene may be found, also, in connection 
with pneumonia, infarction, the aspiration of large foreign 
bodies, etc.; occasionally there exists no demonstrable 
cause. CHAPTER XXVII 
Gastric Ulcer ; Carcinoma of the Stomach and Intestine 
Disregarding the rare tuberculous, and the still more 
uncommon syphilitic ulceration, gastric ulcers (Fig. 192) 
Fig. 192.-Gastric ulcer (one-half natural size). . a, oesophagus. 
are round or ovoid in outline (ulcus rotunduni ventriculi) ; 
they may be as large as the palm of the hand, though the 
diameter does not generally much exceed one and a half 
centimetres. The margin is characteristically sharp and 
301 302 
GASTRIC ULCER 
smooth, and the floor clean; in many cases they invade the 
layers of the stomach wall progressively, assuming the form 
of a funnel with terraced sides. In fresh erosions, the floor 
consists wholly or in part of a narrow necrotic zone, beyond 
which there lies a thin layer of young connective tissue, the 
product of reactive inflammation. 
The situation of the gastric ulcer suggests some connec- 
tion with the digestive activity of the gastric juice (ulcus 
pepticum), since the lesion occurs only in the presence of 
this fluid, that is, in the stomach and the beginning of the 
duodenum. 
It is self-evident that the gastric juice can attack ne- 
crotic cells, but entirely another question whether it is able 
to digest living tissue also, or whether it is in any other way 
responsible for the progressive tendency of the ulcer, a 
characteristic which contains within itself the main problem 
of pathogenesis, as Cohnheim and all recent investigators 
have indicated. 
There was at one time (J. Hunter) an inclination to 
deny that living tissues can be digested, but some doubt was 
cast upon this view by a famous experiment of Claude 
Bernard: the thigh of a living frog, after its introduction 
through a fistula into a dog's stomach, was digested down 
to the bone, though the frog remained alive. Still, the out- 
come of this test was largely due to the hydrochloric acid of 
the gastric juice, which in itself is capable of corroding the 
tissues, as Bernard discovered. Its significance has been 
demonstrated more recently by Matthes, who found that 
digestive mixtures where hydrochloric acid is replaced by 
non-corrosive acids have no effect upon living cells, and 
concluded that the enzymes which digest albumin are power- 
less in the face of living, undamaged tissue, and therefore 
precluded from attacking the body in which they arise. 
Nevertheless, a pseudo-vital autodigestion is possible, when, 
under circumstances which still remain to be more definitely 
fixed, living material is first killed by the hydrochloric acid 
of the gastric juice. EXPERIMENTAL ULCER 
303 
Such experiments as these account for the generally 
accepted view (Matthes, Riegel, and others) that digestion 
of the gastric mucosa is preceded by partial necrosis, and 
that extension of the lesion is particularly favored by per- 
sistence or recurrence of the factor responsible for the pri- 
mary damage. Furthermore, it may be assumed that if 
the gastric juico contain more than its normal quantity of 
hydrochloric acid, as it frequently does in the presence of 
gastric ulcer, it will be in a position to kill and then to digest 
the living tissue on the floor of the lesion. 
Certain additional factors must be present to facilitate 
the action of the gastric juice, since defects in the mucosa 
produced experimentally in animals by caustics, mechanical 
injuries, etc., heal in a short time (Korte, Cohnheim, Griffin! 
and Vassale, Matthes), and violence done to the human 
stomach by the passage of sounds or during operation, is 
not apt to be followed by ulceration. This, perhaps, may 
be so because the hydrochloric acid content of the gastric 
juice has not been abnormally high at the time of injury, a 
suggestion which gathers strength from the fact that 
Matthes delayed the healing of wounds in the mucous mem- 
brane by raising artificially the proportion of this acid. 
The discovery (Griffini and Vassale, Matthes, and others) 
that the stomach wall in dogs contracts powerfully about an 
experimental defect in the mucosa in such a way as to 
protect it with mucous membrane, might suggest that ulcer- 
ation is a result of diminished contractility, were it not that 
experiments seeking to prevent the mucosa from covering a 
wound either have been entirely negative (Matthes), or, at 
the most, have resulted merely in delayed healing (Adolph 
Schmidt). Still, some connection between ulceration and 
motility might be safely inferred, even in the absence of 
experimental proof. The hypothesis would explain the pref- 
erence shown by the disease for such regions as the pylorus, 
or the lesser curvature, with its fewer folds of mucous mem- 
brane. Aschoff has described a number of physiological 304 
GASTRIC ULCER 
constrictions where the mucous membrane is in contact with 
the gastric juice for an unusually long interval, but it seems 
more probable that it is rather the normal contractions, 
demonstrable by the X-ray and described by my pupil 
Beckey, which afford the opportunity for prolonged ex- 
posure; ulceration involves the areas which project during 
contraction. Ulcers occur, however, in localities where no 
relation to contraction is evident, as at symmetrical points 
on both sides of the lesser curvature, or in the first portion 
of the duodenum. 
The primary impulse toward the development of a gas- 
tric ulcer apparently originates in various ways. Hauser 
has described an instance preceded by infarction and ne- 
crosis, and embolism, disturbances of the venous circula- 
tion, and aneurism or arteriosclerosis in the gastric vessels 
have all been suggested as antecedent conditions. Never- 
theless, it seems improbable that any of these should 
be more than an occasional cause; infarction and necrosis 
are too rare, while neither experimental embolism (Cl. 
Bernard, Cohnheim, Pannum) nor the ligation of arteries 
(for bibliography, see Litthauer) has been regularly fol- 
lowed by lesions parallel with the gastric ulcer of man. 
Payr, to be sure, caused progressive perforating ulcers in 
animals by injecting alcohol, hot saline solution, or formalin 
into the wall of the stomach, but the damage produced was 
so great that his results possess but little significance for 
human pathology. 
Virchow suggested that gastric ulcers originate in hemor- 
rhagic erosions (the stigmata of Beneke), and his view has 
obtained wide acceptance, though, as Langerhans has indi- 
cated, such lesions cannot be regarded as the sole cause. 
These small, multiple, and fairly common defects, which de- 
velop after a hemorrhage, as their reddish or blackish color 
shows, have been referred to the digestion of areas of 
mucosa rendered necrotic by the bleeding; according to 
Beneke, however, necrosis is the primary condition, the 
hemorrhage, which is sometimes absent, being secondary. ETIOLOGY 
305 
Beneke and Kobayashi have attributed the stigmata to 
spastic ischaemia from the stimulation of certain nerves, 
and it is an interesting fact that nervous influences do seem 
to play some part in the development of gastric ulcer. Thus 
division and stimulation of the vagus or extirpation of the 
coeliac ganglion gives rise in rabbits to ulcers simulating 
those of man in both morphology and clinical course (for 
bibliography, see Zironi, and Lieblein and Hilgenreiner). 
The relation, however, is probably indirect, ulceration being 
a result of the hyperacidity or the pyloric contraction fol- 
lowing stimulation of the nerves. Rossie has expressed the 
view that gastric ulcer may be secondary to other disorders 
through the intervention of the vagus; a series of diseases, 
or, particularly, operations about the abdomen, the head 
and neck, the hip-joint, or more rarely the extremities, may 
be the source of vagus stimulation and this, in turn, of hemor- 
rhagic erosion and anaemic necrosis of the gastric mucosa, 
in the sense of Beneke. 
Anaemia is undoubtedly a factor in the development of 
ulcer of the stomach, as is shown by the occurrence of this 
disease in anaemic and chlorotic individuals. In animals, too, 
the experimental anaemia produced by such blood poisons as 
lead, or phenylhydrazine and its derivatives, is followed by 
hemorrhagic erosions and ulcers (Heinz, Jores). 
Substances exerting a deleterious action upon the mucosa 
of the stomach may also be a cause of ulceration, and both 
v. Baumgarten and Sternberg have been able to reproduce 
this lesion by the administration of alcohol. 
That ulcer of the stomach should be of an infectious 
nature, as Neumann and Nauwerk have maintained, seems 
hardly probable. 
The invasive tendency of a gastric ulcer brings serious 
consequences in its train. Arteries may be eroded (Fig. 
193) even by the smallest of lesions, or the ulcer may per- 
forate, causing fatal peritonitis if the contents of the gastro- 
intestinal tract escape into the abdominal cavity. In the 
presence of adhesions, an encapsulated abscess is the out- 
20 306 
GASTRIC ULCER 
come. Ulcerated areas often become adherent to the liver, 
the pancreas (Fig. 193), or less commonly, to the spleen, and 
large vessels like the renal vein (Merkel) may be opened. 
Necrosis of the pancreas has been described (for bibliog- 
raphy, see Fritsch), and adhesions to the diaphragm, while 
Pick has reported perforation into the pleura or pericar- 
dium. 
Fig. 193.-Gastric ulcer involving the pancreas, with an eroded artery at its base (one-half 
natural size), a, eroded artery; b, pancreatic tissue on the floor of the ulcer. 
On the other hand, the complete healing of a small ulcer 
is possible; larger ones become indurated at the margin 
through the supervention of chronic inflammatory connec- 
tive-tissue proliferation (ulcus callosum). Cicatrization and 
its consequent contraction result in such deformities as 
stenosis of the oesophagus or hour-glass stomach. CARCINOMA OF THE FUNDUS 
307 
It has been known for a long time that carcinoma may 
develop at the edge of an ordinary round ulcer, and Payr and 
Kiittner have described its occurrence in the indurated 
lesion; but since carcinomata themselves may ulcerate it is 
not always easy to decide which was the primary condition. 
Hauser, however, has described certain criteria which may 
be of value. 
CARCINOMA OF THE STOMACH AND INTESTINE 
The anatomical conditions associated with carcinoma of 
the stomach are very variable, partly because of differences 
in the localization of the tumor and partly on account of 
the variety of histological types. Though it is customary to 
classify these growths according to histological structure, 
we shall, on the contrary, group them according to their 
situation, for the sake of convenience. The first division 
includes those at the fundus (Fig. 194); they generally de- 
velop from the lesser curvature, and are sometimes as large 
as the palm of the hand, or even larger. Small neoplasms in 
which ulceration is not very far advanced appear here as 
thick, raised plaques about the size of a silver dollar; in 
cases where ulceration has progressed further, the necrotic 
central area is surrounded by a raised margin (Fig. 198). 
Histologically, these tumors generally belong to the 
adenocarcinomata (Fig. 195), that is, to a class of growths 
in which the proliferating epithelium retains the glandular 
arrangement. The attempt at gland-formation, however, is 
abortive, and the resulting structures differ from a normal 
gland in both their form and their epithelial lining; the lat- 
ter not infrequently has several layers, in which the single 
cells may present variations from the normal type. Classi- 
fied according to their cells, these tumors are cylindrical 
cell carcinomata. 
Adenocarcinomata of the stomach develop from the 
glands of the mucous membrane (Hauser), originating some- 
times in benign adenopapillomata. Inflammation or ulcera- 
tion is also believed to favor their inception, and indeed, in 308 
CARCINOMA OF STOMACH AND INTESTINE 
the opinion of Ribbert, they are invariably preceded by some 
pathological condition of the mucosa. 
Carcinomata of the fundus are not infrequently gelat- 
Fig. 194.-Carcinoma at the fundus of the stomach (one-half natural size). 
inous, and this degeneration is often so widespread that the 
condition becomes apparent upon gross examination. The 
stroma is still recognizable (Fig. 196), but of the epithelial GELATINOUS CARCINOMA 
309 
masses which should fill its alveoli there are left only a few 
remnants, the remainder of these spaces being filled by 
Fig. 195.-Adenocarcinoma of the stomach (slightly enlarged). 
Fig. 196.-Gelatinous carcinoma of the stomach (moderately enlarged), a, cylindrical 
epithelium. 
mucus. It is to be noted, therefore, that the cells of a car- 
cinoma are able to retain the function possessed by their 
mother tissue. 310 
CARCINOMA OF STOMACH AND INTESTINE 
Reverting now to the classification of gastric carcinoma, 
tumors of the second group, which also occur at the fundus, 
are characterized by their tendency to extend as flat infil- 
trative growths. When they spread along the submucosa 
they produce a thickening of the mucous membrane, which 
may be circumscribed, as in the case of carcinomata develop- 
ing from ulcers, or involve diffusely the entire wall of the 
Fig. 197.--Diffuse carcinoma of the stomach (three-flfths natural size), a, cardiac orifice; 6, pylo- 
rus; c, thickened musculature of the stomach; d, lesser omentum invaded by the tumor. 
stomach. In the latter case, the size of the organ is dimin- 
ished by the thickening and contraction of the walls (Fig. 
197). The neoplasms of this group are usually composed 
of small cell groups, which invade the submucosa and the 
muscularis. 
The third class includes tumors of the ostia. Those of 
the cardia (Fig. 198) usually resemble ulcerative carcino- PYLORIC CARCINOMA 
311 
mata at the fundus; infiltrating growths which encircle and 
narrow the aperture are more rare. 
Cancers of the pylorus, which are relatively common, 
Fig. 198.-Ulcerating carcinoma at the cardiac orifice. Metastases elsewhere in the mucosa 
(one-half natural size), a, oesophagus; b, ulcerating carcinoma; c, metastases. 
surround the pars pylorica for some considerable distance, 
and, according to Beckey, frequently involve that region 
known as the pyloric canal. Here, as at the fundus, car- 312 
CARCINOMA OF STOMACH AND INTESTINE 
cinomata may appear either in the form of ulcerating 
tumors, or of diffuse thickenings under the mucous mem- 
brane. 
The tumor itself may be insignificant enough for the 
condition to resemble simple stenosis; in such instances, the 
epithelial elements are sparse, of inconsiderable size, and 
arranged in small groups (Fig. 199) which are surrounded 
by an inflammatory reaction so dense as almost to obscure 
the carcinomatous nature of the lesion. Such cases un- 
doubtedly have been interpreted in the past as non-malig- 
nant hypertrophy and stenosis, but a number of investi- 
Fig. 199.-Infiltrating scirrhous carcinoma of the pylorus (greatly enlarged). 
gators now maintain that benign stenosis of the pylorus does 
not exist, with the exception of the congenital form (for bibli- 
ography, see Krompecher); with this attitude my own views 
coincide entirely, notwithstanding Krompecher's recently 
published series of cases of sclerostenosis. Pyloric stenosis, 
when not due to carcinoma, is in all probability caused by 
contraction of the pyloric canal (Beckey); this is often ex- 
treme in the cadaver, particularly where the musculature is 
highly developed. 
Carcinomata of the intestine attack almost exclusively 
the large gut, especially the caecum, the flexures, and the 
rectum. They encircle the wall and usually ulcerate exten- INTESTINAL CARCINOMA 
313 
sively (Fig. 200), almost invariably resulting in contraction 
and stenosis. Adenocarcinomata, which in this location, 
also, develop sometimes from papillary adenomata, re- 
semble those of the stomach in every particular. 
Beside adenocarcinoma, an- 
other and much rarer tumor 
is found in the large intestine, 
particularly about the caecum; 
it does not originate in the mu- 
cous membrane, but seems to 
develop in the deeper layers of 
the wall, and its indifferent epi- 
thelium is arranged in solid 
alveoli instead of on the glan- 
dular plan. 
Constricting neoplasms of 
the stomach and intestine cause 
dilatation of the canal immedi- 
ately above them, and the mus- 
culature of the distended por- 
tion is often distinctly hyper- 
trophic. 
Cancers of the gastro-intes- 
tinal tract always metastasize 
ultimately, though the occur- 
rence varies in time with the 
different types; secondary de- 
posits are particularly abun- 
dant in connection with ulcerat- 
ing adenocarcinomata. Those 
involving the stomach attack the lymph-nodes in the omen- 
tum or anterior to the spinal column, while tumors of the 
large intestine generally invade the lumbar or pelvic nodes. 
The liver is particularly exposed to metastatic invasion 
(Fig. 201) on account of its intimate lymphatic and vascular 
connection with the gastro-intestinal tract, and generally 
contains a number of large secondary growths, except in 
Fig. 200.-Carcinoma of the large intestine 
(one-half natural size). 314 
CARCINOMA OF STOMACH AND INTESTINE 
Fig. 201.--Metastatic carcinomata in the liver (one-half natural size). 
the case of scirrhous carcinomata of the pylorus; these, with 
their scanty parenchyma, clo not metastasize freely. Metas- 
tases are more rarely encountered in other organs. METASTASIS AND INFILTRATION 
315 
After a carcinoma of the stomach has reached the 
serosa, it invades the lymph-channels and extends as a fiat 
hard tumor, frequently infiltrating the omentum. Here the 
fat disappears, and the proliferating connective tissue which 
forms the stroma of the growth contracts until the omentum 
has been transformed into a firm nodular mass. Metastases 
in the mesentery at its attachment to the intestine appear 
as whitish tumors which invade the serous coat, producing 
stenosis, or infiltrate the wall. Cancer of the stomach may 
be followed by general peritoneal carcinosis. The tumor 
occasionally perforates, leading to peritonitis unless rup- 
ture take place into the intestine. 
Rectal cancers of long duration sometimes invade the 
pelvic connective tissue, more rarely, the vagina or the 
bladder. CHAPTER XXVIII 
Jaundice; Cholelithiasis and Cholecystitis; Cabcinoma 
of the Gall-Bladder 
In a typical case of jaundice, the liver is stained dark 
green, the skin and the mucous and serous membranes more 
or less yellow. The condition is a result of some obstruction 
to the flow of bile, and its cause is always demonstrable at 
autopsy if the discoloration be extreme; in the milder cases, 
however, it is sometimes impossible to find any obstacle. 
The milder instances, where no obstruction can be found, 
were formerly distinguished as haematogenous jaundice, 
since it was assumed that the bile-pigments are elaborated 
in the blood, and were contrasted with hepatogenous jaun- 
dice, resulting from an obstructed biliary flow. It was 
shown by Stern, and by Minkowsky and Naunyn, however, 
that bile-pigments are produced nowhere but in the liver, 
and that without this organ there can be no icterus; hence, 
jaundice in the absence of demonstrable obstruction may be 
explained by the assumption (Minkowsky) that the liver, 
like so many other glands, possesses both an internal (glyco- 
gen formation and urea) and an external secretion (bile), 
and that, in the case of damage to its cells, bile reaches the 
body fluids over the path ordinarily taken by the products 
of internal secretion. Furthermore, Nauwerk, and later 
Szubinsky, showed that the liver-cells, in addition to their 
intracellular bile-capillaries, have a second capillary system, 
which communicates with the blood-capillaries. In view of 
this observation, jaundice seems to be more than anything 
else the result of abnormal function on the part of the liver- 
cells, and there is accordingly no such radical difference be- 
tween its appearance after mechanical obstruction and after 
any other cause as the old distinction between haemato- 
genous and hepatogenous jaundice demanded. 
316 JAUNDICE 
317 
In the icteric liver, the bile-capillaries are dilated and 
often filled with hyaline coagulation products, while the 
cells themselves take up the greenish-yellow bile-pigment. 
According to Eppinger, fissures can be recognized in the 
dilated ends of the bile-capillaries, and he was inclined to 
Fig. 202.-Impacted gall-stone at the mouth of the common bile-duct (two-thirds natural 
size), a, duodenal mucosa; b, duodenal papilla with an impacted stone; c, common duct, greatly 
dilated above the stone; d, entrance of the cystic duct. 
consider the masses within these channels (biliary thrombi) 
as the cause of obstruction, in cases where no other obstacles 
can be demonstrated. Thus, in his belief, every jaundice is 
an obstructive jaundice. 318 
CHOLELITHIASIS AND CHOLECYSTITIS 
G-all-stones are a common source of interference with 
the escape of bile (Fig. 202). Impaction is followed by 
dilatation of that part of the duct lying above the obstruc- 
tion, and by a retardation of the biliary flow which favors 
the ascent of bacteria from the intestine. The colon bacillus 
is particularly apt to invade the biliary passages under 
these circumstances, where it gives rise to cholangeitis. The 
milder grades of the process are not apparent upon gross 
examination, but a more advanced degree is characterized 
by the presence of multiple hepatic abscesses. 
Biliary calculi originate in the gall-bladder. The dif- 
ferent varieties and their conditions of origin have been 
recently investigated anew by Aschoff and Bacmeister, 
whose researches have modified the older work of Naunyn 
in many important particulars. 
The cholesterin stone is apt to occur singly. When pure, 
it is whitish or yellowish in color and almost transparent, 
with a smooth or slightly irregular surface (mulberry 
stone); grinding will demonstrate its radial, crystalline 
structure (Fig. 203). It consists of pure cholesterin, which 
is deposited as crystals about a nucleus of some such organic 
material as mucus or epithelium; the amount of calcium 
is negligible. This type of calculus is formed during obstruc- 
tion of the biliary flow without co-existing inflammation. 
Inflammatory processes in the gall-bladder alter the 
composition of the bile. The amount of calcium is increased, 
and calcium salts are accordingly precipitated; mixed stones 
are produced by the addition of cholesterin and calcium, 
or of pigment and calcium, to pre-existing cholesterin calculi 
(Aschoff). In the mixed stone, a stratified zone encloses a 
radial nucleus (Fig. 203), a structure which Naunyn referred 
to transformation. 
The more intense is an acute inflammatory condition, the 
more likelihood is there that the accompanying gall-stones 
will be multiple, and the more certain are they to contain 
CHOLELITHIASIS AND CHOLECYSTITIS PURE AND MIXED CALCULI 
319 
a larger proportion of bilirubin and calcium, since chole- 
sterin is characteristic of those associated with little or no 
inflammation, as has already been said. Hence, great 
variety is possible-cholesterin-calcium, cholesterin-pig- 
ment-calcium, bilirubin-calcium, etc. The preponderance 
of cholesterin and calcium 
confers a chalky appear- 
ance, the presence of bili- 
rubin and calcium a 
brownish or blackish 
color, while pure bilirubin- 
calcium stones appear as 
small, soft, blackish cal- 
culi, or crumbly masses. 
Facets, which are very 
common (Fig. 204), occur 
when adjacent nuclei lie 
so close as to hinder dep- 
osition at their points of contact, or when portions of stones 
are removed by attrition. 
A cholesterin stone often becomes impacted at the neck 
of the gall-bladder (Fig. 205). Since the consequent stag- 
nation and infection favor the deposi- 
tion of additional calculi, such a stone 
often bears a cap of cholesterin, bili- 
rubin, and calcium on the end toward 
the gall-bladder (see the upper end of 
the calculus reproduced in Fig. 203), 
while the presence of a number of 
mixed calculi in that organ itself is 
not at all uncommon. 
The mere presence of stones in the 
gall-bladder favors the development of inflammation, and 
with the lapse of time the process becomes more severe. 
According to Aschoff, the primary phase of this condition 
is phlegmonous infiltration of the submucous layers, com- 
mencing in Luschka's ducts. These are diverticula from 
A B 
Fig. 203.-A, cholesterin calculus; B, mixed 
calculus (natural size). The ground surface is 
shown in both cases. 
Fig. 204.-Ground surface of 
a faceted gall-stone (natural 
size). 320 
CHOLELITHIASIS AND CHOLECYSTITIS 
the mucous membrane, which are clothed with epithelium 
and extend into the muscular coat or even beyond it into 
the outlying connective-tissue layer. The primary attack 
may subside, leaving the fibrous and serous coats thickened. 
Mild cholecystitis with simultaneous closure of the cys- 
tic duct by a calculus results in distention of the gall-bladder 
by a serous fluid (hydrops vesicte felleae, Fig. 205). This 
condition, formerly ascribed to obstruction, has been re- 
ferred by Aschoff to long-continued inflammatory exudation. 
The wall, which is not very greatly altered at first, may 
later undergo thickening in consequence of chronic inflam- 
mation. 
Recurrent attacks of acute cholecystitis are followed by 
a chronic condition in which phlegmonous and ulcerative 
processes predominate, leading to destruction of the epi- 
thelial ridges and to even deeper defects; advanced cases are 
characterized by intramural abscesses in Luschka's ducts, 
necrosis, ulceration, and perforation. The healing of these 
Fig. 205.-Hydrops of the gall-bladder, stone in the neck (one-half natural size). CHRONIC CHOLECYSTITIS 
321 
extensive lesions is accompanied by the greatest thickening 
of the fibrous and subserous coats (Fig. 206), and stones 
or fragments of cholesterin may be found in the scars, which 
are sometimes so massive as partially or entirely to oblit- 
erate the cavity of the gall-bladder. As recovery progresses, 
there appear such adaptive and regenerative phenomena 
as replacement of lost epithelial folds, proliferation of 
Luschka's ducts, development of a secreting epithelium, and 
the formation of mucous glands and lymph-nodes. 
Fig. 206.-Chronic cholecystitis (one-third natural size). Thickening of the wall of tha 
gall-bladder and destruction of mucous membrane. Stone in lower part of the gall-bladder. 
The liver is slightly cirrhotic. 
Obstructive jaundice is often a consequence of carcino- 
mata in or about the biliary passages, which may be com- 
pressed from without by tumors in the pancreas or duode- 
num, or by metastatic growths in the lymph-nodes at the 
transverse fissure; on the other hand, the common duct may 
be narrowed by primary or secondary carcinomata within 
its walls. 
Primary tumors, which are not at all common (for 
CARCINOMA OF THE GALL-BLADDER 322 
CARCINOMA OF THE GALL-BLADDER 
bibliography, see Konjetzny), occur at the junction of the 
cystic and hepatic ducts, but principally at the point of en- 
trance of the common duct into the duodenum (papilla 
Vateri), where they form either papillary or infiltrating 
growths. 
Secondary carcinomata are usually metastases from 
tumors in the gall-bladder; they infiltrate the wall of the 
duct and cause stenosis long before they have attained any 
great size (Fig. 207). 
Carcinomata of the gall-bladder (Fig. 207) appear in 
their earlier stages as circumscribed thickenings, generally 
at the fundus, though they may be situated at the neck. In 
advanced cases, the entire wall is transformed into a nodular 
ulcerating mass. 
Carcinomata of the gall-bladder are almost invariably 
associated with calculi; according to Siegert's figures, stones 
are present in 95 per cent, of the cases. This fact may be 
explained either by assuming that the calculi develop in 
consequence of the tumor, or that the mechanical irritation 
exerted by the gall-stones is responsible for the presence 
of the malignant growth. Many observers (Marchand, 
Siegert) prefer the latter hypothesis, which has in its favor 
the frequent co-existence of the two diseases, the rarity of 
calculi in connection with secondary cancer of the gall- 
bladder (Siegert), and the inference that carcinoma in this 
location is more common in women than in men because 
biliary calculi occur with greater frequency in the female 
sex. 
In spite of these arguments, however, the relation of 
biliary calculi to cancer of the gall-bladder is but problem- 
atical, as Aschoff and Bacmeister have recently emphasized, 
pointing out that only in the case of cholesterin stones can 
it be assumed that the calculus antedates the cancer. Choles- 
terin-calcium and bilirubin-calcium stones, the presence of 
which presupposes cholecystitis, are more probably second- 
ary to the malignant growth. RELATION OF BILIARY CALCULI TO CANCEL 
323 
Fig. 207.-Carcinoma of the gall-bladder, metastases from which have caused stenosis 
of the common duct (two-thirds natural size), a, tumor; b, upper, c, lower boundary of an area 
of carcinomatous infiltration in the common duct; d, opening of the common duct into the 
duodenum; e, duodenal mucosa; f, hepatic duct dividing into its intrahepatic branches; g, liver. 324 
CARCINOMA OF THE GALL-BLADDER 
Cancers of the gall-bladder are generally adenocarcino- 
mata, composed of small groups of cubical epithelium in 
which the glandular arrangement is often indistinct. Squa- 
mous-cell carcinoma also occurs in this situation, and it 
is of particular interest that it may be combined with cylin- 
drical-cell cancer. Gelatinous carcinomata are rare 
(Treutlein). 
The squamous epithelium might be attributed to em- 
bryonal rests, though such an explanation is hardly appli- 
cable to the gall-bladder (Herxheimer). On the other hand, 
there is a manifest tendency to refer the appearance of 
squamous carcinoma in this location-it occurs in the uterus 
as well-to metaplasia. 
Though in Virchow's time metaplasia, or the transfor- 
mation of one variety of tissue into another, was widely 
assumed, the hypothesis is viewed to-day with great sus- 
picion, since it is now recognized that cells can give rise 
only to similar elements after once having achieved a cer- 
tain degree of differentiation (law of the specificity of cells 
and tissues). Hence it is believed at the present day that, 
under pathological conditions, metaplasia can occur only 
between types of tissue that are closely related. The direct 
conversion of old cells probably does not occur; rather, the 
new form is assumed by younger elements, so that meta- 
plasia is always associated with neoplasia (Lubarsch). Ac- 
cording to Schridde, cells are able either to revert to an 
earlier stage of differentiation or to retain a partial dif- 
ferentiation characteristic of some stage of embryonal life; 
in either case, further development progresses in an abnor- 
mal direction. This conception may be conveniently applied 
to explain the occurrence of squamous epithelium in carcino- 
mata of the gall-bladder, since it might then be inferred that 
some of the cylindrical elements of the tumor had returned 
to a partially undifferentiated state, and that their descend- 
ants subsequently assumed the garb of squamous epithelium. 
Cancers of the gall-bladder almost always metastasize INFILTRATION AND METASTASIS 
325 
widely in the liver. This organ may be strewn with multi- 
ple nodules, or a large growth may be produced by direct 
invasion of the malignant process; carcinomata situated at 
the fundus and in that part of the wall nearest the liver 
are especially apt to extend in the latter way. 
A carcinomatous gall-bladder is usually adherent to the 
adjoining structures; the tumor may advance along the 
adhesions and attack the transverse colon, the duodenum, 
or more rarely, the stomach, sometimes producing communi- 
cations between these cavities and the gall-bladder. CHAPTER XXIX 
Carcinoma of the Prostate ; Osteoplastic Carcinosis ; 
Prostatic Hypertrophy and Its Consequences 
A carcinomatous prostate is moderately enlarged, as a 
rule, though occasionally the size of the organ is diminished, 
Fig. 208.-Carcinoma of the prostate (two-thirds natural size), a, nodules of tumor at 
the neck of the bladder; b, reddened areas in the vesical mucous membrane; c, lateral lobe of 
the prostate, not carcinomatous; d, colliculus seminalis; e, urethra. 
as lias been shown by the investigations of Kaufmann, from 
whose work I shall draw very largely in the following para- 
326 VARIETIES OF PROSTATIC CARCINOMA 
327 
graphs. The surface of the gland is smooth, or more rarely, 
nodular, and ulceration does not usually take place. 
Adenocarcinoma is to be distinguished from simple en- 
largement by its departure from the normal histological 
structure and by its invasive growth, but the distinction is 
rendered difficult by the fact that malignant growths may 
develop in a hypertrophied prostate. 
Fig. 209.-Carcinoma of the prostate (slightly enlarged). 
Solid carcinomata (Fig. 209) also occur, usually com- 
posed of small cells; the parenchyma is often abundant and 
the stroma scanty in amount. There is no very sharp boun- 
dary between this growth and the adenocarcinoma, however, 
and the two may be found in combination. Scirrhous car- 
cinomata are rare. 
Carcinoma of the prostate not infrequently attacks the 
fundus of the bladder (Fig. 208) in the form of a diffuse in- 
filtration which may spread to other portions of the wall. 328 
OSTEOPLASTIC CARCINOSIS 
Damage is but rarely inflicted upon either the urethral 
orifice or the entrance of the ureters, hence the evidences 
of retention are slight and of irregular occurrence. In a few 
cases, the infiltrated bladder wall has perforated, giving 
rise to peritonitis (Engelhardt). 
The seminal vesicles are often invaded, the urethra but 
rarely; since the malignant process seldom breaks through 
the muscular zone surrounding the prostate, extension to 
the pelvic connective tissue is uncommon; thus, though the 
tumor may project into the rectum, the walls of this passage 
are usually spared. Adjacent lymph-nodes are not impli- 
cated with such readiness as by other varieties of car- 
cinoma. According to Kaufmann's figures, those situated 
in the true pelvis and along the large vessels are most often 
involved; the inguinal group, also, is sometimes invaded, 
although these are not literally regional. 
OSTEOPLASTIC CARCINOSIS 
Prostatic carcinoma shows a special tendency to metas- 
tasize in the skeletal system (Fig. 210), where its second- 
ary tumors often induce a vigorous growth of bone 
(v. Recklinghausen); osteoclastic phenomena, however, may 
make their appearance at the same time. 
The osteoplastic carcinosis accompanying cancer of the 
prostate affects most commonly the pelvis, the vertebrae, 
and the femur, while that associated with mammary car- 
cinoma attacks the skull, the sternum, the vertebrae, and the 
pelvis, in this order of frequency. According to Kaufmann, 
the site of predilection in the femur is the upper portion 
of the marrow-cavity; in the pelvis, it is the ileum that is 
most often invaded (Fig. 210); in the skull, the parietal 
and frontal bones; in the ribs, the anterior portion and the 
angle, while in the sternum the process is diffuse. 
The trabeculae of the sclerotic bone are close together 
and often thickened, and the fibrous marrow, infiltrated here 
and there with round cells, contains carcinomatous deposits VULNERABILITY OF SKELETAL SYSTEM 
329 
(Fig. 211). The formation of new bone was referred by 
v. Recklinghausen to fibrous ostitis. According to this hy- 
pothesis, the fibrous marrow is transformed directly, and 
in the absence of osteoblasts, into an osteoid tissue which 
is subsequently converted into true bone by calcification. 
Erbslbh, however, has described the presence of osteoblasts, 
which, as Kaufmann has emphasized, are often difficult to 
distinguish from cancer-cells. 
According to both v. Recklinghausen and Erbslbh, the 
vulnerability of the skeletal system is to be ascribed to the 
Fig. 210.-Osteoplastic carcinosis in the pelvis. 
ease with which emboli of cancer-cells can be retained in the 
capillaries of the marrow, particularly when the blood 
supply has been diminished by contraction of the nutrient 
artery. Since a decrease in the calibre of this vessel may 
be brought about by mechanical factors, those portions of 
the skeleton which, like the vertebrae, are most exposed to 
stimulus, are more often invaded than others. Neusser has 
referred the appearance of bone metastases in connection 
with certain varieties of carcinoma to some relationship 
between the skeletal system and the other organs, an ex- 
planation that has been accepted by Paltauf and Bamberger. 
Vaguely expressed though the conception may be, it may 330 
OSTEOPLASTIC CARCINOSIS 
nevertheless represent a step in the right direction, since 
secondary deposits are probably guided by chemical factors 
in their choice of a location, as Askanazy has indicated. 
At any rate, Schmorl is undoubtedly correct in his assertion 
that the occurrence of bone metastases cannot be referred 
exclusively to the mechanical deposition of tumor emboli, 
but must depend upon the existence in bone, as such, of 
conditions favorable to their development. Thus, he was 
able to show that metastasis might take place also in ossified 
Fig. 211.-Osteoplastic carcinosis (slightly enlarged), a, bone trabecula; b, bone-marrow; 
c, nests of carcinoma cells. 
laryngeal cartilages, while the rest of the body remained 
free from secondary growths. 
Osteoplastic metastasis, though most often secondary 
to prostatic carcinoma, occurs in association with carcino- 
mata of the mamma, of the thyroid, and in exceptional cases, 
with carcinomata in other organs. Not all metastatic car- 
cinomata in the skeletal system, however, release osteoplas- 
tic activity; on the contrary, many exert a destructive 
effect through rarefying ostitis (osteoclastic carcinoma). 
Why some of them should stimulate the formation of new 
osseous tissue it is impossible to explain, though it can ETIOLOGY 
331 
be said, at least, that this property seems to be connected 
neither with the histology nor the size of the primary 
tumor, for it may be so small as to escape observation until 
attention is directed to the prostate by the presence of 
secondary growths in the bones. 
v. Recklinghausen ascribed the new formation of bone 
to the venous hyperaemia which follows cancerous oblitera- 
tion of efferent blood-vessels; Askanazy, to minute areas 
of necrosis. According to Schmorl, however, neither hy- 
pothesis is adequate; congestion or obliteration of the veins 
takes place in osteoclastic carcinoma also, and conversely, 
the very smallest metastases, though incapable of producing 
congestion, nevertheless exert an osteoplastic action. In 
the second place, osteoplastic tendencies are evident in sec- 
ondary growths that contain no necrotic areas. He has 
therefore assumed that the cancer-cell stimulates bone- 
forming elements in much the same way that the parenchyma 
of a scirrhous carcinoma exerts a desmoplastic influence 
upon the surrounding fibrous connective tissue, the presence 
of new bone depending upon the rapidity with which the 
metastases grow, as only in the case of a slowly proliferat- 
ing nodule would there be sufficient time for its production. 
In contrast to the frequency of bone metastases from 
carcinoma of the prostate is the rarity of secondary growths 
in other organs; leaving out of account the lymph-nodes, it 
is both lungs and pleura which are most commonly attacked. 
A complication of prostatic carcinoma is compression of 
the cord by metastatic tumors in the vertebral column. 
PROSTATIC HYPERTROPHY AND ITS CONSEQUENCES 
The entire prostate is frequently hypertrophic, though 
the median or both lateral lobes may be involved alone; of 
the latter, that on one side is sometimes more extensivly 
affected than its fellow. Enlargement of the prostate dis- 
torts the urethra, lengthening its prostatic portion, and in- 
creasing the curvature of the membranous by elevating the 
neck of the bladder (Socin and Burckhardt, Reerink). Hy- 332 
PROSTATIC HYPERTROPHY 
pertrophied lateral lobes compress the urethra, but the 
greatest disturbance in urination follows enlargement of the 
Fig. 212.-Hypertrophy of the prostate, with dilatation and hypertrophy of the bladder 
(two-thirds natural size), a, greatly enlarged middle lobe; b, moderately enlarged lateral lobes; 
c, urethra; d, hypertrophic vesical musculature; e, prominent rugie. 
median, which then projects into the bladder at the urethral 
orifice (Fig. 212) as a spherical or grooved tumor about the 
size of a cherry or a walnut. Lying in this position, the THE NORMAL PROSTATE 
333 
hypertrophied lobe is capable of narrowing or closing the 
urethral orifice, in all probability playing the part of a valve 
as the contents of the bladder press it against the opening. 
Mercier has described a true muscular valve at the 
urethral orifice, but this condition must be very rare in the 
absence of prostatic hypertrophy, though the possibility of 
its occurrence cannot be denied (Hirt). Many of the earlier 
examples, however, are undoubtedly referable to thickening 
Fig. 213.-Schema of a longitudinal section through the neck of the bladder and the pros- 
tate (after Ciechanowski). A, normal; B, in prostatic hypertrophy, a, lateral lobe; b, posterior 
commissure (pars intermedia); c, portion of the middle lobe developed from accessory glands 
at the neck of the bladder; d, sphincter of the bladder; e, internal urethral orifice;/, vas deferens; 
g, seminal vesicle; h, urethra. 
of the sphincter, or to a hypertrophy of the middle lobe char- 
acterized by the predominance of muscular tissue. 
To comprehend the derangement of vesical function 
brought about by a hypertrophied prostate, it is necessary 
to understand the anatomical relations between the gland 
and the sphincter of the bladder. This muscle, which is 
continuous with the muscular fibres of the prostate, readily 
suffers invasion by the proliferating glandular tissue, even 
when enlargement involves the lateral lobes; in the case of 
the median, however, the situation is even more character- 
istic. The normal prostate consists of two lateral lobes, 334 
PROSTATIC HYPERTROPHY 
joined behind the urethra by a glandular portion (pos- 
terior commissure, portio intermedia, Fig. 213), and in front 
of the urethra by a poorly developed anterior commissure. 
The so-called middle lobe is a purely pathological structure; 
it does not develop solely from the posterior commissure, as 
was at one time believed, but principally from accessory 
glands which exist in small number beneath the mucous 
membrane of the urethra even under normal conditions 
(Jores). The sphincter muscle (Fig. 213) accordingly lies 
behind the middle lobe (Dittel, Jores, Ciechanowski). The 
posterior commissure, which also undergoes enlargement, 
unites with the glands anterior to the sphincter at the neck 
of the bladder, and the muscle is pushed still further upward 
and backward (Fig. 213), becoming so invaded by glandular 
tissue as the process continues that it can no longer be identi- 
fied. Insufficiency, the inevitable result of this infiltration, 
is added to the mechanical obstruction described above. 
Prostatic hypertrophy is the outcome of adenomatous 
growth; in other words, an enlarged gland is a true tumor. 
Microscopic examination shows the presence of greatly 
dilated glands (Fig. 214) which correspond with the normal 
type both in form and in the nature of their epithelial ele- 
ments ; the lumina contain desquamated cells, amyloid bod- 
ies, and sometimes a few leucocytes. Areas may be found 
in which muscular tissue predominates, and in which only 
a few glands or, according to earlier accounts, none at all, 
are discoverable; these myomata, as they have been called, 
appear to the naked eye in the form of nodules about the 
size of a lentil. Since Virchow's day, the form of prostatic 
enlargement in which they preponderate has been contrasted 
with the glandular variety under the term myomatous hy- 
pertrophy, but there is not much difference in the two types. 
Hypertrophy of the prostate is regarded by Ciechanowski 
as an inflammatory process, on account of the cellular infil- 
tration to be found here and there throughout the affected 
organ; this inflammatory lesion is said to obliterate the 
excretory ducts and to result in dilatation of the glands; ETIOLOGY 
335 
his hypothesis, which would thus refer hypertrophy to en- 
largement of the glands rather than to proliferation, has re- 
ceived from Rotschild the support withheld by Wichmann, 
Runge, Jores, Tsunoda, and others. In Wichmann's opin- 
ion, the inflammatory processes accompanying prostatic 
hypertrophy are too insignificant in amount and too irregu- 
lar in appearance, and according to Tietze, it is hardly pos- 
Fig. 214.-Prostatic hypertrophy (slightly enlarged). 
sible to explain the formation of a middle lobe in any way 
other than through glandular proliferation, even though 
the positive histological demonstration of multiplying 
glands has not been successful. 
These discussions have an important bearing upon eti- 
ology. Ciechanowski naturally ascribed enlargement to in- 
flammatory conditions in the prostate and the urethra, an 
assumption which the histology of the disease does not 336 
PROSTATIC HYPERTROPHY 
sustain. It seems much more probable that the condition 
is a tumorous process and therefore of unknown etiology, 
and this view coincides with clinical experience. 
The attempt has been made in France (Gyon-Louvais) 
to refer the entire symptom-complex of prostatic hyper- 
trophy (prostatism) to a sclerosis analogous with that which 
attacks the vascular system. Such an attitude agrees well 
with the conception of arteriosclerosis prevailing in France, 
but the view has not survived the criticism levelled at it 
from the German standpoint (Casper, Ciechanowski). 
Hypertrophy of the prostate is always complicated by 
certain changes which are referable to obstructed flow, or 
ascending infection, or to a combination of the two. These 
are in no sense characteristic, however, since they may 
accompany a number of other conditions such as carcinoma 
or tuberculosis of the pros- 
tate, various diseases of the 
bladder, compression of the 
ureters, calculi in the renal 
pelvis, affections of the 
urethra, or finally, nervous 
disturbances of urination. 
Interference with the es- 
cape of urine is first felt by 
the bladder (Fig. 212), 
which undergoes dilatation 
and hypertrophy. Between 
its muscular elements, on 
the inner surface, divertic- 
ula are occasionally found. 
If stagnation reach beyond the bladder it distends the 
ureters, the renal pelves (hydronephrosis), and particu- 
larly the calyces (Figs. 215 and 223). The papillae are flat- 
tened, the parenchyma is atrophic, and in advanced cases 
the kidney is replaced by a large cyst, in which the papillae 
are represented by fan-like septai and the parenchyma by 
microscopic remnants in the wall. 
Fig. 215.-Hydronephrosis (one-half natural 
size). HYDRONEPHROSIS 
337 
According to Orth and Ponfick, the atrophy associated 
with hydronephrosis affects first the uriniferous tubules, 
sparing the glomeruli for a time; the interstitial connective 
tissue undergoes proliferation. 
The higher grades of atrophy are attained only by unilat- 
eral lesions commencing in early life. A frequent cause of 
unilateral hydronephrosis is oblique insertion of the ureter 
into the pelvis, an anomaly which produces, in a way, the 
effect of a valve, since the ureter is intermittently com- 
Fig. 216.-Renal calculus, a, dilated renal pelvis; 6, dilated calyces; c, atrophic cortex; 
d, calculus; e, its projections into the calyces. 
pressed as the pelvis fills; other causes are congenital steno- 
sis or atresia of a ureter, or its compression by a tumor. 
Calculi situated in the pelvis of the kidney constitute still 
another, many obscure cases of hydronephrosis being due 
to past nephrolithiasis (Ponfick). Sand and gravel in the 
pelvis are capable of producing transient obstruction; true 
stones (Fig. 216) are generally armed with prolongations 
which extend into the dilated calyces. They are usually 
composed of phosphates, oxalates, uric acid, or urates. 338 
PROSTATIC HYPERTROPHY 
The stagnant urine of hydronephrosis often contains 
pus (pyelitis, pyonephrosis), since infection is generally a 
result of obstruction. Stagnation, however, is not a prime 
requisite for infection, since inflammatory processes ascend 
from the bladder to the kidneys in its absence, and indeed, 
this mode of infection (urogenetic) is the rule with processes 
due to the pyogenic bacteria. 
The mucosa of an inflamed bladder generally shows 
no gross changes, ex- 
cept that the edges of 
its folds are reddened. 
In more severe cases, 
which are but rarely 
encountered, the mu- 
cous membrane is of a 
dark red hue and cov- 
ered by a tightly ad- 
h e r e n t, branny, or 
sloughing membrane, 
which may be limited 
to the top of the ruga» 
or diffusely spread 
over large areas. In- 
flammation of the mu- 
cosa of the ureters and 
the pelvis is character- 
ized by slight injec- 
tion, though in severe 
pyonephrosis the mu- 
cosa is of a brighter 
red color, thickened, 
and s t u cl cl e cl with 
hemorrhages. 
When an ascending 
inflammation involves the kidney, streaky abscesses (Fig. 
217) appear in the medulla and the cortex (suppurative 
pyelonephritis), showing through in groups on the external 
Fig. 217.-Pyelonephritic abscesses in the kidney 
of a child (two-thirds natural size). A, outer surface; 
B, cut surface. SUPPURATIVE PYELONEPHRITIS 
339 
surface of the organ. The markings on the cut surface are 
obliterated and a linear reddening occurs; the medullary- 
area is of a particularly vivid red hue. The tips of the 
papillae, or even whole pyramids, may suffer necrosis, prob- 
ably from the action of bacterial toxins, and necrotic por- 
tions may break away and be passed with the urine; in one 
such case, I found a necrotic pyramid wedged in the ureter. 
The capsule of the kidney is at first little affected, but in 
later stages it undergoes an inflammatory, and often indura- 
tive thickening. Superficial abscesses sometimes rupture, 
and give rise to peri- and paranephritic abscesses, although 
such an event is comparatively rare. 
The presence of linear abscesses in the medullary zone 
during the earlier stages of suppurative pyelonephritis 
shows that the organisms ascend the collecting tubules. 
Though any of the pyogenic bacteria may be responsible, it 
is the colon bacillus which most frequently causes suppura- 
tive lesions in the kidney (Albarran, Schmidt and Aschoff). 
Pyelonephritic affections analogous with those of man have 
been produced in animals by inoculating cultures of this 
organism into the ureter above a ligature. CHAPTER XXX 
Carcinoma and Chorio-epithelioma of the Uterus 
Carcinoma of the cervix (Fig. 218) ultimately invades 
both the vaginal vault and the corpus uteri as a rule. Even 
when the mucosa of the body is not attacked, it may undergo 
certain alterations; its glands and connective tissue become 
hyperplastic, and multiplication of the epithelial layers com- 
bined with squamous transformation has been recorded 
(Kraus). In their earlier stages, it is not difficult macro- 
scopically to distinguish 
cancers of the vaginal 
from those of the supra- 
vaginal portion, but later 
in the disease such a 
separation is no longer 
possible. 
Carcinomata of the 
portio vaginalis (Fig. 219) 
develop from the squa- 
mous epithelium which 
clothes it. In rare in- 
stances, cylindrical-cell 
cancers occur, originat- 
ing in erosions, but they 
seldom preserve a truly 
glandular architecture. A 
carcinoma in this region may commence as an ulcer, or as 
an infiltrating or a papillary growth; the second and third 
types ulcerate sooner or later. 
Cancers of the supravaginal portion may be composed 
either of flat or of cylindrical cells. They may be infiltrative 
or circumscribed and, like those described in the preceding 
paragraph, tend to destroy the cervix by ulceration. 
Fig. 218.-Cancer of the cervix (three-fifths 
natural size), a, extension to the fundus. 
340 CARCINOMA OF THE UTERINE BODY 
341 
A third form affects the body of the uterus (Fig. 220). 
In its earlier stages, it appears as a somewhat irregular 
circumscribed thickening of the mucous membrane, but at 
a later period the entire mucosa is involved. As the growth 
invades the uterine wall its superficial portions become 
necrotic, and the interior of the organ is eventually trans- 
formed into a large, irregular, ulcerated cavity. 
Carcinoma of the body, which belongs to the cylin- 
drical-cell group, may be alveolar, though it is more fre- 
Fig. 219.-Squamous-cell carcinoma of the uterus (slightly enlarged), a, tumor alveolus; 
b. cervical gland. 
quently adenomatous. The glands in adenocarcinomata 
still retain their general similarity to those of the normal 
mucosa, but they lie much more closely together and assume 
a dilated and irregular form (Fig. 221). The epithelium, 
of which there are sometimes several layers, may fuse with 
that of neighboring glands, or show an inclination to fill 
up the lumen, which, however, rarely becomes entirely 
obliterated. 
Epithelial irregularities such as these constitute the first 
evidence of malignancy, and penetration of the uterine wall 342 
CARCINOMA OF THE UTERUS 
clinches the diagnosis, though an invasive tendency is but 
poorly marked in early carcinomata of the corpus uteri. 
In a certain type of carcinoma, which may involve either 
cervix or body and is known among gynaecologists as ade- 
noma malignum, the glandular pattern is particularly dis- 
tinct; it has been said, too, that the epithelium is regular, 
and arranged in one layer only. Kaufmann has shown, 
Fig. 220.-Carcinoma of the body of the uterus (three-fifths natural size), a, carcinoma; 
b, right ovary; c, left tube. 
nevertheless, that many of the glands are not only poly- 
morphous but possess more than one epithelial layer, and 
since transitions can be demonstrated between these neo- 
plasms and those of alveolar structure, adenoma malignum 
should be included among the adenocarcinomata. 
Areas of squamous epithelium, which are not infre- 
quently discovered in cylindrical-cell cancers of the uterine CARCINOMA OF THE CERVIX 
343 
body (for bibliography, see Hitschmann), may be referred 
to metaplasia, as in the case of the gall-bladder (p. 324). 
Cancer of the cervix invades the parametric lymph- 
channels with great frequency, where its extension can be 
discovered microscopically some time before the appearance 
of palpable infiltration (Seelig) ; eventually it attacks the 
connective tissues of the pelvis. Metastases in the lymph- 
Podes are of early occurrence. The first group to be in- 
volved is the hypogastric (Fig. 222), which lies in the angle 
between the external and internal iliac arteries and along 
Fig. 221.-Adenocarcinoma of the uterus (slightly enlarged). 
the external iliac vein (Peiser), and is in direct connection 
with the cervix; from these nodes, channels run to the ex- 
ternal iliac and inferior lumbar. The cervix is also in com- 
munication with one or two sacral lymph-nodes which, in 
their turn, connect with still others of the sacral, and with 
the inferior lumbar group. The lymph-vessels draining the 
body of the uterus traverse the broad ligament and finally 
reach the lumbar nodes. 
According to Schauta, the lymph-nodes are attacked in 
the following order: hypogastric, iliac and sacral, lumbar, 344 
CARCINOMA OF THE UTERUS 
coeliac, and inguinal. In its final stages, however, cancer 
of the cervix may metastasize much more widely, and even 
the nodes lying upon the vertebral column may not be spared, 
nor those of the thorax and the anterior mediastinum (for 
bibliography, see Offergeld). I have seen a case in which 
Fig. 222.-Lymph-channels and lymph-nodes of the uterus (after Peiser). 1, uterus, 
drawn sharply forward; 2, broad ligament; 3, uterine artery; 4, obturator artery; 5, obturator 
nerve; 6, bladder; 7, ureter; I, lymphatic vessels from the cervix, running in the broad ligament 
to the hypogastric glands, Hi Hi Hs; II, lymphatic vessels from the cervix running in the sacro- 
uterine ligament to the sacral nodes, Si Ls; Ji Ji Ja, external iliac nodes, communicating with 
the hypogastric nodes; Li-L-„ inferior lumbar nodes. 
the lymph-nodes of the anterior mediastinum were large 
enough to simulate clinically a primary mediastinal tumor. 
Carcinoma of the body of the uterus shows less tendency 
to metastasize; it does not extend to the parametrium until 
the cervix has been involved, though secondary growths in 
the genital tract below the tumor are not at all rare. 
Uterine carcinomata, and particularly those of the cer- UTERINE CANCER 
345 
Fig. 223.-Extension of a uterine cancer to the bladder (two-fifths natural size), a, tumor 
projecting under the vesical mucosa; b, tumor projecting near the opening of the left ureter; 
ureter no longer patent; c, probe in right ureter; d, dilated left ureter; e, right ureter, laid open; 
f, pelvis of left kidney greatly dilated; commencing atrophy of the kidney; u, right pelvis slightly 
dilated. 346 
CHORIO-EPITHELIOMA OF THE UTERUS 
vix, are very apt to invade the bladder about the trigonum 
in their later stages (Fig. 223). The figure illustrates, 
also, dilatation of the ureters and hydronephrosis, due to 
compression and carcinomatous infiltration. A similar 
condition may attend secondary processes confined to the 
parametrium alone, the part of the ureter most endangered 
being that just above the anterior aspect of the vaginal 
vault. 
Carcinoma of the uterus rarely extends to the rectum. 
On the contrary, it often attacks the peritoneum, appearing 
in Douglas's cul-de-sac as nodular masses which, however, 
seldom cause generalized carcinosis, probably because death 
takes place too soon. Perforation, with its consequent 
peritonitis, is an occasional complication. 
Uterine carcinoma metastasizes by way of the blood- 
stream only in its most advanced stages. Secondary growths 
may be found in the lungs, the liver, the kidneys, and rela- 
tively early in the brain (Offergeld). According to this 
author, metastasis in the adrenals, the thyroid, the bones, 
the spleen, or the skin is a very uncommon circumstance. 
Chorio-epithelioma (Fig. 224) occurs in the uterus after 
pregnancy under a variety of forms, and gives rise to wide- 
spread metastases. In the brain, these appear as dark 
red nodules about the size of a cherry and so loosely con- 
nected with the cerebral substance that they can be shelled 
out with the greatest ease. The lungs are often strewn with 
hemorrhagic and necrotic tumors bearing a general resem- 
blance to thrombi, and there is hardly an organ in which 
secondary growths may not be discovered. It is especially 
worthy of notice that a metastatic tumor not infrequently 
appears in the vagina at an early period, an event which 
often serves to render the diagnosis more certain. 
The chorio-epithelioma was described as a decidual 
sarcoma (Sanger) until Marchand demonstrated its deriva- 
tion from the chorion. 
CHORIO-EPITHELIOMA THE CHORION 
347 
This structure bears two layers of epithelium, both of 
which are now regarded as fetal structures of ectodermal 
origin. The inner (Langhans' layer), which lies in apposi- 
tion with the connective-tissue stroma, consists of separate 
cells with clear cytoplasm; it commences to disappear with 
the termination of the first half of pregnancy. 
Fig. 224.-Chorio-epithelioma of the uterus (one-half natural size). 
The outer (chorionic syncytium) is a homogeneous mass 
of protoplasm studded with nuclei. 
Both layers are represented in the common and typical 
form of chorio-epithelioma (Fig. 225); an atypical variety, 
however, according to Marchand, is composed of syncytium 
alone (Fig. 226). 
Fig. 226 shows clearly the infiltrative growth so highly 348 
CHORIO-EPITHELIOMA OF THE UTERUS 
characteristic of the chorio-epitheliomata. Their tendency 
to invade the blood-vessels, a quality which they retain 
from the normal chorion, explains at once their frequent 
and extensive metastasis and the fact that they contain large 
Fig. 225.-Typical chorio-epithelioma of the uterus (greatly enlarged), a, syncytium; 
b, Langhans' cells. 
Fig. 226.-Atypical chorio-epithelioma of the uterus (moderately enlarged). 
amounts of blood, though possessing no vascular supply of 
their own. 
The chief requisite for the origin of a chorio-epithelioma 
is pregnancy, either normal or abnormal (extra-uterine 
pregnancy, abortion, hydatiform mole). The tumor least HYDATIFORM MOLE 
349 
often follows normal gestation, for placental remnants in 
the uterus are not usually a source of malignant growth; 
occasionally, however, these give rise to placental polypi 
which may be mistaken for the neoplasm now under dis- 
cussion. A polyp (Fig. 227) is composed of chorionic villi, 
most of which lack epithelium; its stroma is often necrotic. 
Hemorrhage adds to the volume of the mass and increases 
the resemblance to chorio-epithelioma. 
In the majority of 
cases, and perhaps in- 
v ar i ably (Veit and 
others), chorio-epithe- 
lioma originates in a hy- 
datiform mole; accord- 
ing to the statistics of 
Risel, it followed this 
condition in 36-41 per 
cent, of the cases, abor- 
tion in 31-33 per cent, 
and normal pregnancy 
in 22-28 per cent. Even 
though not every hy- 
datiform mole be succeeded by chorio-epithelioma, it is evi- 
dent, at least, that some very close relationship exists 
between the two. 
The conception is strengthened by the fact that hydati- 
form mole is itself a disease of the chorion. Affected villi 
are transformed into a mass of gelatinous, pedunculated 
vesicles (Fig. 228), the cedematous condition of their 
stroma (Fig. 229) suggesting that the condition is due to 
circulatory disturbances (Gottschalk). Marchand, on the 
contrary, has emphasized the significance attending certain 
evidences of growth to be discerned in the epithelium cover- 
ing the villi. In the experience of other investigators, how- 
ever, this proliferative activity is not invariably present, and 
it seems probable that it may be largely a characteristic of 
those moles that have already become malignant-for there 
Fig. 227.-Placental polyp (slightly enlarged), a, 
chorionic villi; b, necrotic chorionic villi. 350 
CHORIO-EPITHELIOMA OF THE UTERUS 
is a type in which, the villi persistently invade the uterine 
blood-vessels. Thus Salowij and Kryszkowski have re- 
ported a singular case in which a hydatiform mole not only 
infiltrated the entire uterus, but produced metastatic occlu- 
sion of the right ovarian vein with secondary nodules in 
the lungs. Evidently all transitions may be found between 
benign and malignant moles, and between the latter and 
chorio-epithelioma. 
The growth of lutein cells in the ovary has been recorded 
Fig. 228.-Hydatiform mole. 
ill connection with both hydatiform mole and chorio-epithe- 
lioma, partly as a cyst lining, and partly as solid cell groups 
(for bibliography, see Risel), but whether their prolifera- 
tion bears any etiological relationship to the hydatiform 
mole is questionable. Those who assert that it does (see 
Pick), base their assumption on the hypothesis that lutein 
secretion regulates the embedding of the ovum in the uterus. 
More recent authorities (Danger, Gottschalk, Risel), how- 
ever, are inclined to deny any connection between the growth 
of lutein cells and the development of a mole. ECTOPIC CHORIO-EPITHELIOMA 
351 
Chorio-epitheliomata may be found also in the uterine 
Wall or the fallopian tube. In some instances a primary 
growth is actually lacking, nothing but metastatic deposits 
being discoverable (ectopic chorio-epithelioma). Thus 
Schmorl has described a case in which the tumor occupied 
the vagina, while Pick reported coincidently a similar ex- 
ample with a hydatiform mole in the uterus. In a series 
of analogous instances, the metastatic tumor was situated 
in the vagina, or, more rarely, in an internal organ. 
Fig. 229.-Hydatiform mole (slightly enlarged), a, proliferating chorionic epithelium; 
b, cedematous stroma of a villus. 
Ectopic chorio-epitheliomata have been explained as 
metastases from a primary tumor previously existing in the 
placenta (Schmorl), while Marchand has pointed out that 
they may develop from transported fragments of chorionic 
epithelium that do not take on malignant growth until after 
reaching the site at which they have been deposited. 
Not all chorio-epitheliomata are malignant, for spon- 
taneous recovery ensues in some undoubtedly authentic 
cases. 352 
CHORIO-EPITHELIOMA OF THE UTERUS 
Ill conclusion, it may be added that chorio-epithelio- 
matous tissue is occasionally discovered in tumors. In a 
metastasizing teratoma of the testis, Schlagenhauf er dis- 
covered structures which corresponded both macroscopically 
and microscopically with chorio-epithelioma in the female, 
and several similar instances have been recorded since then. 
He referred in his explanation to the hypothesis of Mar- 
chand and Bonnet, according to which a teratoma develops 
from isolated blastomeres, or from a fertilized polar body 
situated among the blastomeres. Structures such as these, 
equivalents of the ovum, could of course give origin to a 
chorio-epithelioma (Schlagenhaufer, Marchand). 
More difficult to explain, however, are those tumors re- 
sembling chorio-epitheliomata which occur in the generative 
glands or in other regions of the body, in the absence of 
teratoid tissue. Such growths are probably, in part, tera- 
tomata in which the chorio-epitheliomatous portions have 
developed so vigorously as to suppress the remainder of the 
neoplasm, although, on the other hand, chorio-epithelio- 
matous, and particularly syncytial structures, may be dis- 
covered in tumors that cannot be described as teratoid. It 
is very doubtful whether these are analogous with fetal ecto- 
derm; much more probable is it that they represent some 
other variety of syncytium. Sternberg has described the 
syncytium-like tissue in his cases as abnormal capillary 
anlages, suggesting that the examples reported by other 
authors can be so explained as well; even the chorio-epithe- 
liomatous portions of teratomata represent, in his opinion, 
endotheliomatous or peritheliomatous pseudosyncytial 
structures. Extreme though this view may be, one may 
safely preserve an attitude of critical doubt toward the ap- 
parently chorio-epitheliomatous portions of non-teratoid 
tumors. CHAPTER XXXI 
Atrophy and Cirrhosis of the Liver; Congestion and Re- 
generation, and Chronic Perihepatitis (Iced Liver) 
Acute yellow atrophy of the liver is generally fatal, 
only a few cases of recovery having been recorded. The 
organ is diminished in size, flabby, friable, and of a yellowish 
color, which is sometimes mottled with reddish-yellow areas. 
On the cut surface the markings are obliterated, and a thin 
Fig. 230.-Acute yellow atrophy of the liver (slightly enlarged). 
crust of leucin and tyrosin crystals is deposited if the speci- 
men be allowed to lie for a time undisturbed (Kaufmann). 
The remaining organs contain nothing of importance. 
Microscopic examination shows that the parenchyma 
is destroyed and absorbed (Fig. 230), leaving only the con- 
nective tissue and the capillaries. When death is postponed, 
as it is in rare instances, the organ is firmer, and the red 
atrophic portions more sharply demarcated from the yellow, 
353 354 
ATROPHY AND CIRRHOSIS OF THE LIVER 
iii which the cells still retain their outline though already 
attacked by degeneration. Signs of regeneration now be- 
come evident in the atrophic parts of the organ; bile-capil- 
laries appear, and rows of new liver-cells begin to develop 
from bile-capillaries and that portion of the parenchyma 
which has been spared (Meder, Marchand, Strobe). The 
yellow areas contain large well-formed hepatic cells suggest- 
ing regeneration or compensatory hypertrophy. 
If the course of the disease be still more delayed, regener- 
ation may become so prominent a feature as to produce 
great nodules of new parenchyma (nodular hyperplasia; 
Marchand, Strobe). 
The connective tissue in the non-hyperplastic portions 
sometimes undergoes a proliferation like that of cirrhosis, 
conferring thereby an entirely new aspect upon the disease, 
which now has nothing in common with acute yellow atrophy 
except an origin presumtively similar. There can be but 
little doubt, however, that a number of disorders appear 
in the guise of nodular hypertrophy or the end stages of 
yellow atrophy, which are neither pathogenetically nor etio- 
logically similar, and which have not yet all been separated 
and identified. 
This group includes phosphorus poisoning which, in 
acute cases, produces hepatic changes much like those asso- 
ciated with acute yellow atrophy. Furthermore, when it is 
not immediately fatal, or when its course is subacute by 
reason of the absorption of small amounts of the drug, its 
lesions resemble the end stages of acute yellow atrophy and 
nodular hyperplasia (Paltauf), except that in yellow 
atrophy the liver cells are more apt to be destroyed by 
necrosis, while in phosphorus poisoning they undergo fatty 
metamorphosis. In phosphorus poisoning, too, regenerative 
changes are more vigorous in the later stages (Paltauf), 
and, finally, a more generalized and distinct fatty degenera- 
tion affects the other organs. 
There is no proof that an acute period has actually pre- 
ceded every condition which at autopsy resembles nodular SUBACUTE ATROPHY OF THE LIVER 
355 
Fig. 231.-Subacute atrophy of the liver (one-half natural size), a, dark red, atrophic areas; b, unchanged parenchyma. 356 
ATROPHY AND CIRRHOSIS OF THE LIVER 
hyperplasia or the later phases of acute yellow atrophy; 
in fact, such atrophies sometimes develop insidiously. This 
Marchand has proved in the case of nodular hyperplasia, 
and I have reported an example (Fig. 231) resembling the 
later stages of acute atrophy, though according to its clini- 
cal and anatomical characteristics it had to be interpreted 
as a subacute condition running a progressive course up 
to the moment of death. The injurious noxa in such cases 
exerts its atrophic effect upon the kidney (Jores, Schmorl) 
and the lung (Klopstock) also. 
Fig. 232.-Atrophic cirrhosis of the liver; external surface (one-half natural size). 
The most common type of cirrhosis is the atrophic 
(Laennec's cirrhosis). The liver is small, nodular (Fig. 
232), and more or less yellow in hue, and the cut surface 
(Fig. 233) exhibits a characteristic design, in which small 
circular islands of yellowish parenchyma are surrounded by 
firm grayish-red connective tissue. The liver cells often 
suffer an advanced grade of fatty infiltration. 
The organ thus undergoes an enormous increase of con- 
nective tissue (Fig. 234) and a simultaneous destruction of 
parenchyma, lesions which account for its diminished vol- 
ume. The presence of chronic inflammatory processes in the REGENERATION OF PARENCHYMA 
357 
connective tissue is suggested by a round cell infiltration 
which is often extensively distributed. In other regions, the 
stroma may be less cellular, firmer, and more contracted. 
The islands of parenchyma are new-formed liver tissue, 
not simply areas of parenchyma which have escaped destruc- 
tion as was at one time supposed. Kretz has shown that 
they have not the acinous structure characteristic of the nor- 
mal organ, but that the central vein is often entirely lacking 
and the capillary arrangement reticular instead of radial. 
Fig. 233.-Atrophic cirrhosis of the liver; cut surface (one-half natural size). 
That these atypical lobules are the outcome of regeneration 
may be inferred, furthermore, from the fact that the central 
vein is often eccentric, a situation which must be referred 
to the destruction and renewal of parenchyma, since such 
lobules show no signs of compression. Finally, the liver is 
noted for its regenerative capacity (Ponfick). 
Regeneration is evident, again, in the formation of new 
bile-ducts, which appear in the connective tissue as minute 
canals (Fig. 234) lined by rows of cells. Though their 
lumina are too small to be seen in histological sections, any 
doubt regarding their nature is removed by the observation 358 
ATROPHY AND CIRRHOSIS OF THE LIVER 
that they can be injected through the hepatic duct 
(Ackermann), while there is but little difficulty in making 
out their anatomical connection with the islets of paren- 
chyma. It is not known whether these new ducts are off- 
shoots of pre-existing ones (Ackermann and others), or 
whether they develop by metaplasia from surviving liver- 
cells (Kiener and Kelsch), but I consider the latter alter- 
native more probable. 
Fig. 234.-Atrophic cirrhosis of the liver (slightly enlarged), a, connective tissue; b, islands of 
liver cells; c, newly formed bile-ducts. 
The formation of islets of liver tissue by regeneration is 
characteristic of cirrhosis, but the proliferation of bile-ducts 
is a feature of several other hepatic disorders, particularly 
those associated with destruction of the parenchyma. 
Since both bile-ducts and parenchyma are regenerated 
during the course of atrophic cirrhosis, it seems reasonable 
to infer that the activity of the liver would remain for a long 
time undisturbed by the cirrhosis, so far, at least, as the 
secretion of bile is concerned, and, as a matter of fact, the 
occurrence of jaundice is not a common event. The slight 
icterus which occasionally appears is of the obstructive ASCITES 
359 
type, as Eppinger lias demonstrated, and probably due to 
the compression of precapillary bile-ducts. 
The increasing connective tissue does interfere, how- 
ever, with the portal circulation, probably as follows. The 
capillaries of the portal vein undoubtedly undergo a diminu- 
tion in number, the multitude of those in the new connective 
tissue belonging chiefly to the hepatic artery, since they can 
be readily injected from this vessel, but only with the 
Fig. 235.-Varicose dilatation of veins in the oesophagus and the stomach (natural size). 
greatest difficulty from the portal vein (Ackermann). The 
hepatic artery becomes dilated, and the greater influx of 
arterial blood raises the capillary pressure and embarrasses 
the exit of portal blood from the liver, while an additional 
obstruction is opposed by the inadequacy of the circulation 
within the distorted acini (Kretz). This interference with 
the portal circulation frequently results in ascites and the 
abdomen may contain several litres of clear yellow fluid. 360 
ATROPHY AND CIRRHOSIS OF THE LIVER 
The obstruction is compensated, although incompletely, 
by the formation of an extrahepatic collateral circulation, 
in which the veins of the stomach and lower part of the 
oesophagus (Fig. 235) usually participate, becoming dilated 
and tortuous, or even varicose. The portal blood in such 
cases flows through the coronary vein of the stomach and 
the superior oesophageal, intercostal, and azygos (or hemia- 
zygos) veins, into the superior vena cava. Saxer has de- 
scribed an instance in which anastomosis had taken place 
between a large varix in the stomach wall, and the greatly 
dilated left suprarenal vein. 
Varices of the stomach and lower part of the oesophagus 
give rise not infrequently to fatal hemorrhage. The rup- 
tured vein can usually be demonstrated at autopsy, in con- 
tradistinction to a type of intestinal hemorrhage associated 
with cirrhosis, for which no anatomical cause is discoverable 
and which is, therefore, explained as parenchymatous. Ac- 
cording to Saxer, however, this variety also is due to the per- 
foration of a vessel, though the defect may be so minute as to 
escape the most practised eye. 
Although it is the gastric and oesophageal veins which 
most often participate in the formation of a collateral circu- 
lation, other routes may be opened (see reviews of this 
subject by Thomas and by Saxer). Thus, the veins of the 
hepatic capsule and the diaphragm frequently undergo dila- 
tation, and, in rare instances, those about the umbilicus 
(caput medusas). 
While the establishment of a collateral circulation un- 
doubtedly hinders the supervention of ascites, this fact alone 
does not explain the absence of an abdominal transudate 
in many cases of cirrhosis, or its late appearance or actual 
recession in others, nor does it account for the lack of any 
relationship between the amount of fluid and the extent of 
the connective-tissue proliferation in the liver, on the one 
hand, and the development of a collateral circulation on 
the other. 
Many authors (Talma, Klopstock, and others) have sug- SPLENIC ENLARGEMENT 
361 
gested that, in some cases at least, the ascites is due to in- 
flammation of the peritoneum, rather than to circulatory 
disturbances, but no proof has been adduced in favor of 
this view. It is true that chronic peritoneal thickening may 
be associated with long continued ascites, to which, however, 
it is in all likelihood secondary. The variable conduct of 
ascites in cirrhosis of the liver certainly demands more thor- 
ough investigation, although the fact must not be overlooked 
that irregularities are manifest in the etiological relations 
between congestion and oedema under other circumstances 
also, as after destruction or ligation of veins in the extremi- 
ties. The view has accordingly been advanced (Lubarsch) 
that, in addition to congestion, "other factors must be pres- 
ent if the obliteration of a vein is to be followed by oedema. ' ' 
The spleen of a cirrhotic patient is almost always en- 
larged to two or three times its normal size, a condition 
which was for a long time attributed to the portal obstruc- 
tion. But the enlargement, which is due to hyperplasia of 
the splenic pulp and, in later stages, to proliferation of the 
connective tissue, occurs even in the absence of such evi- 
dences of congestion as ascites or dilatation of the veins and, 
furthermore, the spleen of cirrhosis is not anatomically 
identical with that of congestion, being generally larger 
than the spleen of cardiac disease, and neither so firm nor so 
hyperaemic (Ostreich). Hence, the splenic enlargement 
accompanying cirrhosis of the liver cannot be ascribed solely 
to congestion, and it is customary to refer the lesions in the 
two organs to one common cause. 
Grawitz and Hartwig have suggested that the spleen 
undergoes enlargement in compensation for the destruction 
of liver tissue, but the relation between the two conditions 
is probably more complex, as would be intimated by the fact 
that the blood is sometimes involved during the course of 
cirrhosis. Red marrow is regularly encountered in the 
long bones, and the liver and spleen often contain iron pig- 
ment (siderosis), an evidence of the destruction of erythro- 
cytes, as was shown in the first chapter. To conclude from 362 
ATROPHY AND CIRRHOSIS OF THE LIVER 
such findings as these, however, that the underlying cause 
of hepatic cirrhosis is to be sought in some alteration of 
the blood (Bleichrdder, Lintarew), is to assume too much. 
It is much more likely that here, again, the two lesions 
represent coordinate effects of one common etiological 
factor (Simmonds). 
Banti has defined a clinical condition characterized by 
splenic enlargement and anaemia, to which is subsequently 
added cirrhosis of the liver (Banti's disease, splenomegaly 
with hepatic cirrhosis). In the earlier stages of the disease, 
the spleen is said to show engorgement and hyperplasia, 
neither of which is particularly characteristic, while at a 
later period the connective-tissue fibres of the reticulum be- 
comes thickened (fibroadenia). In proof of the view that 
the splenic lesion is responsible for the hepatic cirrhosis, 
it was stated that recovery follows extirpation of the spleen. 
Although not a few clinicians regard Banti's disease as an 
independent condition, the pathologist is apt to adopt a 
more cautious attitude, since this disorder appears to em- 
brace several others (Marchand) and because, moreover, 
the too scanty anatomical investigations of its earlier stages 
are not always quite so convincing as might be desired, as 
in the case reported by Umber. Of the later stages, it must 
be said that in spite of Banti's more recent studies, they 
cannot be separated anatomically from ordinary cirrhosis 
of the liver. On the whole, therefore, no adequate anatomi- 
cal basis has yet been found permitting Banti's disease to 
be distinguished from hepatic cirrhosis, on the one hand, 
and from anaemia merely coincident with splenomegaly, on 
the other. 
In hypertrophic cirrhosis (Todd, Hanot), as contrasted 
with the atrophic variety, the liver is enlarged and its sur- 
face is smooth, or only slightly uneven. In consequence of 
the jaundice constantly associated with this disease the 
organ assumes a yellow or greenish color. 
The new connective tissue has a somewhat different 
arrangement from that which characterizes the atrophic BILIARY CIRRHOSIS 
363 
form, surrounding small groups or rows of liver cells and 
being thus intralobular rather than perilobular; the isolation 
of islands of parenchyma so typical of atrophic cirrhosis is 
rare. Furthermore, there is no great destruction of liver 
tissue, and it is said that the parenchyma may even be hyper- 
trophic (Hanot and Schuchmann). There seems to be no 
impediment to the portal circulation, and both ascites and 
dilatation of the veins are accordingly absent. Splenic 
hypertrophy, however, is an invariable accompaniment. 
Beside the two forms of cirrhosis thus far considered, 
there is distinguished a third or biliary type, which super- 
venes after long-continued gall-duct obstruction, and in 
which the connective-tissue overgrowth is said to be initiated 
at the periphery of the bile-ducts. According to Janowski, 
the liver is at first enlarged, smooth, and firm, although later 
it becomes atrophic from contraction of the fibrous tissue. 
Jaundice is, of course, a feature, but portal congestion, 
ascites, and splenic enlargement are all lacking. 
Biliary cirrhosis has been the object of extensive experi- 
mental investigation. Necrosis and connective-tissue pro- 
liferation in the liver have been described after ligation of 
the gall-ducts (Charcot and Gombault, Simmonds), although 
the growth of interstitial tissue cannot be regarded as 
definitely proved, since the animals survive operation for a 
few days only (Steinhaus). In man, also, the development 
of the disease has been attributed to necrosis following the 
rupture of bile-capillaries (Janowski), and subsequent in- 
flammatory proliferation of the connective tissue. 
The three types of cirrhosis which have been now re- 
viewed are not so sharply separable that any given case can 
be immediately assigned a position in one certain group. 
On the contrary, deviations and transitions are very numer- 
ous; jaundice may accompany atrophic cirrhosis, or ascites 
be absent, and the volume of the liver and the size and num- 
ber of nodules on its surface are all subject to variation. 
The surface may be only slightly nodular, or even smooth; 
in such cases the liver is exceptionally firm, the fibrous tissue 364 
ATROPHY AND CIRRHOSIS OF THE LIVER 
more diffusely distributed, the islands of regenerating 
parenchyma are incompletely formed, and ascites and 
icterus lacking. 
The pure hypertrophic cirrhosis of Hanot seems to be 
rare (Kretz), notwithstanding the large variety of cases 
that have been described as such in the literature. 
There exists an inclination to view hepatic cirrhosis, 
from the anatomical standpoint, as a single process, in spite 
of its protean character, but whether this be justifiable 
cannot be decided until its etiology is more clearly under- 
stood. For the present it is necessary, in my opinion, to 
recognize several types, in order that our survey of the mani- 
fold lesions may be facilitated and a way prepared for 
further investigation. 
As for the pathogenesis of cirrhosis, the connective- 
tissue proliferation was formerly referred to chronic pro- 
ductive inflammation, and the compression and final death 
of the parenchyma to contraction of the newly-formed 
fibrous tissue. The opposite view, advanced many years 
ago by Ackermann but neglected until its adoption by 
Kretz, regards destruction of the parenchyma as the pri- 
mary lesion, and connective-tissue overgrowth as a second- 
ary reactive process with reparative tendencies. 
The assumption that the liver cells are destroyed by 
the contracting fibrous tissue has little or no histological 
support, since all signs of pressure and congestion are want- 
ing in the parenchymal islets (Kretz). The allegation of a 
preliminary stage of hypertrophy in which the fibrous tissue 
has not yet contracted is unsupported by fact. 
According to Kretz, the changes found in connection with 
the healing of subacute degenerative lesions of the liver are 
the key to the situation, the islets of regenerating paren- 
chyma being comparable to the nodules of cirrhosis and 
the new connective tissue analogous with its interstitial 
fibrous strands. Cirrhosis is to be viewed, therefore, as a 
chronic, recurring, degenerative process to which regenera- 
tion is added as long as the liver is capable of renewing itself, ETIOLOGY 
365 
and to which the proliferation of connective tissue is sec- 
ondary. Cognizance must be taken, also, of those experi- 
ments in which the liver-cells have been damaged with 
various toxic substances. Such are the investigations of 
Wegner, who, by poisoning animals with phosphorus, pro- 
duced hepatic changes similar to those characterizing cir- 
rhosis in man, as well as those in which arsenic, chloroform, 
bacterial toxins, and even hepatoxic sera have been em- 
ployed (for bibliography, see van Heukelom, Fischler, 
Joannovics). Fischler, who tested the function of the liver 
after the organ had been damaged by phosphorus and sub- 
sequently by ethyl and amyl alcohol, concluded that con- 
nective-tissue proliferation does not set in until hepatic 
function has been disturbed. 
It must be confessed that the end stages of hepatic 
atrophy and the experimental lesions just mentioned both 
show certain variations from cirrhosis. Whereas the 
parenchymatous destruction and connective-tissue prolifer- 
ation of cirrhosis are so intimately combined that atrophy 
and degeneration cannot be recognized, extensive parenchy- 
matous destruction may be encountered in hepatic atrophy 
in the absence of any connective-tissue growth (Marchand, 
Jores). Experimental proliferation takes place about 
branches of the portal vein and at the periphery of the 
acini, and is therefore not so irregularly distributed as in 
man, while regeneration of the parenchyma, in the sense of 
Kretz, does not usually occur, though it has been reproduced 
recently by Joannovics. 
Notwithstanding these objections, the view that the 
parenchymal destruction of hepatic cirrhosis in man is refer- 
able directly to the injurious noxa, is pretty well estab- 
lished. Still, I do not believe that the connective-tissue pro- 
liferation is to be regarded as a mere replacement fibrosis; 
it is more probable, as van Heukelom has suggested, that 
the deleterious agent which destroys the parenchyma exerts 
a simultaneous action upon the connective tissue, whereby 
an inflammatory proliferation is induced. 366 
ATROPHY AND CIRRHOSIS OF THE LIVER 
Cirrhosis of the liver has been ascribed to a number of 
injurious agents, most frequently to alcohol, and cirrhotic 
patients do, indeed, often admit the consumption of large 
amounts; the fact is, however, that not every alcoholic de- 
velops cirrhosis, as Orth has said in his text-book. A con- 
siderable percentage escape (v. Hansemann, Klopstock, 
Fahr), while every pathologist knows that alc'ohol can be 
definitely excluded in many cases; this substance, moreover, 
has not been so frequently successful in animal experiments 
as have others. And yet, notwithstanding all this, 
Klopstock's conclusion that alcohol only creates a tendency 
toward the development of cirrhosis, is too far-reaching. 
It has been suggested that cirrhosis is caused by toxic 
materials brought from the gastro-intestinal tract by the 
portal vein, and some support for this hypothesis seemed to 
be offered by the experiments of Boix, who found consider- 
able connective-tissue overgrowth in the livers of rabbits 
after the introduction of lower fatty acids; his results, how- 
ever, could not be obtained with any regularity by other 
observers, van Heukelom has suggested that even the posi- 
tive results which follow poisoning with phosphorus, alcohol, 
etc., need not of necessity be ascribed to a direct action 
upon the liver-cells, since it is possible that these substances 
exert their effect indirectly by inducing some important 
change in the digestive canal. 
It has been known for a long time that cirrhosis of the 
liver may attend syphilis, and this disease, in addition to 
alcohol, must be reckoned with in the rather rare hepatic 
cirrhosis of children (Marchand). (For bibliography, see 
Schichthorst.) 
The production of cirrhosis by other infectious diseases 
I do not regard as entirely proved, although in association 
with tuberculosis (Jores) and typhoid (Hubschmann), 
atrophy and regeneration sometimes appear in the liver, 
where they may, perhaps, bear some relation to the develop- 
ment of cirrhosis. 
Tuberculosis and cirrhosis frequently occur together, COMPLICATIONS 
367 
and Stoerk lias observed the combination in animals with 
experimental tuberculous lesions. Following the appear- 
ance of tubercles in the liver of the guinea-pig there came a 
second stage, in which specific tuberculous products vanished 
and a fibrous interstitial tissue was substituted; the surface 
of the organ was not nodular, however, and the process did 
not resemble genuine Laennec's cirrhosis. Still, Stoerk be- 
lieved it to be parallel with other types of cirrhosis in man, 
for which, therefore, it would be allowable to assume a tuber- 
culous etiology, and in this view he has received not a little 
support; Isaac, among others, has recorded the coincidence 
of tuberculosis and hypertrophic cirrhosis in the human sub- 
ject, which he has explained in accordance with Stoerk's 
conception. In my own opinion, however, Stoerk's findings 
are not transferable to man. 
I cannot subscribe, either, to Klopstock's attempt to 
bring tuberculous peritonitis into etiological relationship 
with cirrhosis. It is true that this disease is found with 
striking frequency in connection with cirrhosis, usually in 
its exudative form, although ascites may be absent, but its 
occurrence is probably to be explained by reactivation of 
the tubercle bacilli in old lesions (W. Fischer), and their 
growth in the favorable soil offered by the peritoneum and 
its exudate (Quincke). The tubercular process would there- 
fore be a complication of the cirrhosis, and this explanation 
may be equally true in some of the other instances where 
these two diseases coexist. 
Proliferation of the connective tissue in the pancreas 
often accompanies cirrhosis of the liver. In "bronzed dia- 
betes," hepatic cirrhosis and siderosis are combined with 
pancreatic cirrhosis (diabetes; for casuistics and bibliog- 
raphy, see Simmonds). According to Poggenpohl, the 
changes in the two organs do not run a parallel course as 
regards their intensity, and the dependence of either lesion 
upon the other is therefore doubtful. Both he and 
Simmonds were inclined to regard them as independent 
processes, due, possibly, to enterogenous causes. An ex- 368 
HEPATIC CONGESTION AND REGENERATION 
planation is given, perhaps, by the investigations of Gilbert 
and Chabrol, who found that ligation of the portal vein in 
animals is followed by the growth of interstitial tissue in 
the pancreas. 
Naunyn has assumed the almost constant presence of 
cholangeitis in hepatic cirrhosis, but no histological support 
is to be found for this hypothesis. 
Parenchymatous nephritis and arteriosclerosis are com- 
mon accompaniments of hepatic cirrhosis, and thrombosis 
of the portal vein may occur secondarily. The peritoneum 
may undergo chronic inflammatory thickening which results 
in contraction of the mesentery; suppurative peritonitis 
that was not referable to paracentesis has been recorded. 
Cancer sometimes develops in a cirrhotic liver. The ob- 
servation is of interest because primary carcinoma of this 
organ is rare, but above all because carcinoma originates in 
other regions also, such as the skin, after regeneration has 
been in progress for a long time. 
HEPATIC CONGESTION AND REGENERATION ( PSEUDOCIRRHOSIS, 
CARDIAC CIRRHOSIS) ; CHRONIC PERIHEPATITIS (iCED LIVER) 
Long-continued congestion is one of the conditions said 
to be responsible for cirrhosis, and the French have included 
in a special category (cirrhose cardiaque) those cases where 
connective-tissue proliferation supervenes in the congested 
liver. 
There is no doubt that congestion produces after a time 
a condition resembling that of the cirrhotic organ. The liver 
is fairly small, of a dark brownish-red color, and finely nodu- 
lar, although the characteristic last named is not so prom- 
inent as in cirrhosis. On the cut surface, too, an insular 
arrangement of the parenchyma can be discerned, but the 
islands are small and not clearly delimited from the sur- 
rounding tissue, which differs from them only in its darker 
red hue. 
These islands are composed of large regenerating liver- CARDIAC CIRRHOSIS 
369 
cells (Fig. 236). However, it is only the elements immedi- 
ately surrounding branches of the portal vein, those which 
always escape the atrophy of congestion, that take part in 
this process, and even they have not the power of complete 
renewal so characteristic of cirrhosis (Eisenmenger). The 
rest of the parenchyma lies atrophic among its dilated 
capillaries. 
The condition therefore represents regeneration, or bet- 
ter still, hyperplasia of the parenchyma combined with the 
atrophy of congestion (Saltykow, Eisenmenger). That 
Fig. 236.-Congestion, atrophy, and regeneration in the liver (slightly enlarged). 
connective-tissue overgrowth should set in under such cir- 
cumstances has been often assumed (Pick, Beneke), but ac- 
cording to my own experience this is not the rule. When 
it does, in exceptional instances, the amount of fibrous tissue 
is insignificant and the distribution at variance with that 
typical of cirrhosis. Thus so far as the term cardiac cir- 
rhosis is employed at all, it should be used only to denote 
this combination of congestion and regeneration as Eisen- 
menger has proposed. 
Ascites is sometimes associated with congestion of the 
liver, even though there be no increase in the amount of 370 
HEPATIC CONGESTION AND REGENERATION 
connective tissue. To this condition Pick has applied the 
term pericarditic pseudocirrhosis of the liver, because the 
congestion is frequently a result of chronic adhesive peri- 
carditis. According to my own experience, the heart is at 
the same time dilated and hypertrophied, and as still other 
cardiac lesions may underlie pseudocirrhosis, this disorder 
is to be regarded in the main as a complication of heart 
disease, especially since the enlarged spleen also shows the 
characteristic features of congestion. 
The ascites can hardly be referred directly to the hepatic 
changes; at least, it is difficult to see how these could produce 
any circulatory embarrassment. 
In chronic perihepatitis, first described by Curschmann, 
the surface of the liver is white, as though covered with icing. 
According to clinical authorities, the organ is enlarged in 
the earlier stages of the disease, but in the later stages, 
post-mortem examination discloses a small liver with 
rounded margins. The capsule of the spleen is also white 
and thickened, and the parietal peritoneum sometimes under- 
goes a similar alteration. 
The cut surface of the liver, pale brown in color, lacks 
its characteristic markings. Though the organ is in a gen- 
eral way free from fibrous tissue, its capsule and the adjoin- 
ing periportal connective tissue undergo some thickening. 
Chronic perihepatitis is accompanied by ascites, peri- 
carditis, and pleuritis. The ascites can hardly be referred 
to obstruction of the portal circulation, although Cursch- 
mann assumed that the thickened capsule exerts general 
compression, and it is probably due to the chronic inflam- 
mation in the hepatic capsule or the peritoneum. The 
accompanying pericarditis and pleuritis are related to the 
hepatic condition in so far as they represent an extension 
of the process to other serous membranes (polyserositis). 
This statement immediately raises the questions: Where 
does the inflammatory condition originate, and in what man- 
ner does it progress? It is instructive to learn that the 
right pleura alone is frequently attacked (Siegert), since the CHRONIC PERIHEPATITIS 
371 
observation suggests extension from the liver. Siegert has 
pointed out that some of the lymph-channels leaving the 
surface of this organ collect into a trunk which traverses 
the falciform ligament, pierces the diaphragm, comes into 
contact with the right pleura, and finally reaches the neigh- 
borhood of the pericardium. The assumption that a chronic 
inflammation may follow this route cannot be rejected, 
though any one of the three regions which it touches might 
be regarded as the starting point of the process; most inves- 
tigators, however, hold that the disease commences in the 
liver. On the other hand, the belief that one common noxa 
attacks the serous membranes simultaneously is not without 
its advocates (Heidemann); viewed from the latter stand- 
point, the condition has been called polyserositis. Not a few 
authors refer it to tuberculosis, but though this disease does 
undoubtedly attack several serous membranes at the same 
time, the fact cannot be applied in the explanation of chronic 
perihepatitis, which is rather the consequence of a noxa still 
unknown. CHAPTER XXXII 
Pancreatitis ; Necrosis of the Pancreas and Fat Necrosis ; 
Diabetes 
Suppurative pancreatitis appears most frequently as a 
solitary focus of pus, more rarely in the form of multiple 
abscesses (Oser). In the majority of cases the infecting 
organisms reach the gland by way of its duct, their invasion 
usually occurring in consequence of the presence of calculi. 
The inflammation is often localized at the tail of the 
pancreas, whence it extends into the neighboring tissues, 
most commonly in the direction of the spleen; involvement 
of the retroperitoneal tissue at the root of the mesentery, 
however, is not at all infrequent, and I have seen the process 
spread from the head of the pancreas, under the duodenum, 
to the liver. That general peritonitis may be a consequence 
of pancreatitis it seems scarcely necessary to mention. 
In necrosis of the pancreas, often incorrectly described 
as pancreatitis, the organ is increased in size, mottled with 
dull, yellow areas, and often contains punctate or larger 
hemorrhages (pancreatic apoplexy). Microscopic examina- 
tion shows that the process is essentially a necrosis to which 
inflammatory changes, in so far as they occur, are secondary. 
The disease is generally accompanied by necrosis of the 
adipose tissue. In and about the interstitial fat of the gland 
there are found whitish opaque spots which are often sur- 
rounded by a halo of hemorrhage, and the necrosis is not 
infrequently of such wide distribution as to involve the 
omentum and all the retroperitoneal and mesenteric fat. 
The confluence of these foci in advanced cases gives rise to 
large areas of softening which contain an opaque, brownish 
fluid, together with shreds of friable, dark green, necrotic 
fat, and the pancreas may even become entirely isolated from 
NECROSIS OF THE PANCREAS, AND FAT NECROSIS 
372 NECROSIS OF PANCREAS AND FAT NECROSIS 
373 
the surrounding structures (Frankel). Such an abscess may 
perforate into the abdominal cavity, or in rare instances, 
evacuate its contents including the necrotic pancreas 
(Frankel, Chiari) into the gastro-intestinal canal. 
Areas of fat necrosis, first described by Balser in 1882, 
contain opaque, irregular, and often scaly masses corre- 
sponding in size to the fat cells; these are due, as Langerhans 
showed, to the combination of calcium with fatty acids. 
When the calcium has been dissolved, the altered fat can 
be made out, about the calcified areas. According to 
Langerhans, the process commences with a breaking down 
of intracellular fat; after the absorption of fluid materials, 
the solid fatty acids remaining enter into combination with 
calcium. 
Our ideas regarding the etiology of fat necrosis are 
gradually becoming clearer. While an excessive growth of 
fat-cells (Balser), or marasmus (Chiari) and similar con- 
ditions, were at first suggested as causative factors, 
Langerhans suspected, and afterward proved, that the lesion 
is produced by the pancreatic juice. This fluid, as his ex- 
periments and those of Hildebrand, Jung, Dettmer, Korte, 
and others (for bibliography, see Chiari, Hess) have shown, 
attacks the pancreas and subsequently the neighboring 
structures. The dependence of fat necrosis upon necrosis 
of the pancreas had long been assumed, Chiari having been 
particularly active in elaborating and establishing this 
hypothesis, but the connection is regarded to-day as proved. 
Fat necrosis is not due, however, to the action of trypsin, 
as was formerly supposed, but to steapsin. 
The injection of fat into the pancreatic duct in animals 
causes a disease analogous to necrosis of the pancreas in 
man (Hess), soaps formed in the gall-ducts being the in- 
jurious factor, and Hess has also been able to reproduce 
the disease by allowing fat-containing duodenal contents to 
reach the gland. Again, the injection of bile into its duct 
causes necrosis of the pancreas (Opie), while ligation of the 
duct will lead to necrosis if all the excretory passages (there 374 
DIABETES 
are several in the dog) be closed at the height of digestion. 
According to Polya, bacteria are of insignificance in so far 
as they, in association with bile, can activate the secretion 
of the gland. 
Experiments such as these suggest that fat necrosis in 
man may follow interference with the flow of pancreatic 
juice, either by pancreatic calculi or by gall-stones in the 
common duct, or that it may be a consequence of the escape 
into the pancreatic duct of bile, or of duodenal contents 
mixed with bile or fat. Trauma has been advanced in ex- 
planation of certain cases (Simmonds, Seiburg), while 
Chiari has referred the disease to endarteritis obliterans 
(arteriosclerosis), which is common in the pancreatic 
artery; in a case of my own there was found arteriosclerosis 
with thrombosis in a branch of this vessel. 
Once the pancreas has been involved by necrosis, the 
attacking ferment invades the surrounding structures, 
partly by direct imbibition and partly, it is assumed, by 
way of the lymph-channels and blood-vessels. 
Fat necrosis is rapidly fatal in most instances, death 
being due to a general intoxication (Guleke). This was at 
one time ascribed to trypsin, though according to Hess it 
is to be attributed to soaps which result from the reaction 
between ferment and fat. Bergmann and Guleke, however, 
have disputed this hypothesis, maintaining that the pan- 
creatic secretion and the autolyzed gland itself are respon- 
sible for the intoxication. 
DIABETES 
The relation of diabetes to anatomical changes in the 
pancreas has been shown by experiment, and experimental 
data still form the basis of this hypothesis. It is known, how- 
ever, that other organs probably have something to do with 
the regulation of sugar metabolism. According to Claude 
Bernard's famous experiment, puncture of an area in the 
middle of the floor of the fourth ventricle is immediately fol- EXPERIMENTAL DIABETES 
375 
lowed by the appearance of sugar in the urine; still, patho- 
logical conditions in this region operate only rarely as a 
cause of diabetes in man. The diabetes which can be in- 
duced in animals by the administration of phloridzin is of 
the renal type, since hyperglycaemia does not appear if the 
ureters be tied off or the kidneys extirpated. These organs, 
therefore, either become abnormally permeable to sugar, 
or split off sugar from the phloridzin (Naunyn). There is 
no anatomical evidence for the existence of renal diabetes 
in man, and the same may be said of the hepatic type, but the 
pancreas, on the contrary, frequently, and in v. Hanse- 
mann's opinion invariably, contains certain lesions in asso- 
ciation with clinically true diabetes. 
Bouchardat (for a historical sketch, see Sauerbeck), 
the earliest believer in the relation of pancreatic changes 
to diabetes, undertook extirpation of the gland in animals, 
but his experiments miscarried on account of the technical 
difficulties involved. Not until 1889 did v. Mehring and 
Minkowski succeed in proving that complete removal of the 
pancreas in dogs is followed by the appearance of sugar in 
the urine, an anomaly which they ascribed to the removal 
of an internal secretion. 
The question now arises, whether the pancreatic alter- 
ations found in diabetic subjects are sufficient to interfere 
with the inner secretion of the gland and, in consequence, 
to produce diabetes. Neither carcinoma of the pancreas nor 
suppurative pancreatitis is followed by diabetes, as a rule. 
It may be inferred that enough parenchyma is spared to 
continue the secretory function, though v. Hansemann has 
described total replacement of the pancreas by carcinoma 
without the appearance of sugar in the urine; these cases 
he has explained by the assumption that the tumor cells 
retain the power to elaborate the internal secretion. 
In some diabetics the pancreas is atrophic; it may 
undergo simple diminution in size and weight, retaining 
its normal macroscopic appearance, or its parenchyma may 
be replaced by fat (lipomatosis). In the not inconsiderable 376 
DIABETES 
number of instances in which the organ looks normal to the 
naked eye, the microscope will show various lesions. 
Sometimes there is an increase in the amount of connec- 
tive tissue and a destruction of parenchyma (Fig. 237); 
this alteration was described by v. Hansemann as granular 
atrophy. From this condition Herxheimer subsequently 
differentiated pancreatic cirrhosis, in which there is added 
to the connective-tissue overgrowth a proliferation of ducts 
analogous to the new formation of bile-ducts in cirrhosis of 
the liver. Both granular atrophy and cirrhosis generally 
Fig. 237.-Pancreatic cirrhosis (slightly enlarged), a, glandular parenchyma; b, island of 
Langerhans; c, artery. 
occur in elderly individuals; in younger diabetics, on the 
other hand, it is the islands of Langerhans that are apt to 
be involved. 
These (Fig. 238) are small, round or oval bodies, some- 
what similar in form and size to the glomeruli of the kidney, 
and composed of cells distinguishable from the rest of the 
pancreas by their clearer protoplasm. At one time attrib- 
uted to the connective tissue, they are now universally 
recognized as epithelial structures. They are traversed by 
a rich capillary network and separated sharply from the 
remaining parenchyma by connective tissue, although, per- 
haps, not throughout their entire circumference. Their HISTOLOGICAL FINDINGS 
377 
number is subject to variation, and they are not uniformly 
distributed throughout the gland, but are more numerous 
at the tail than toward the head. 
The microscopic changes affecting these cell islets in 
connection with diabetes have been the object of extensive 
investigation (Opie, Sauerbeck, Weichselbaum and his pupil 
Herxheimer). According to Weichselbaum, one of the 
lesions is hydropic degeneration; some time after a pigment 
which stains a brownish-red with eosin has made its appear- 
ance in their protoplasm, the cells undergo liquefaction, or 
Fig. 238.-Island of Langerhans (normal) surrounded by secretory parenchyma (greatly 
enlarged). 
become smaller and assume the appearance of lymphocytes 
(Fig. 239). In older subjects, investment and penetration 
of the islands by connective tissue is generally combined 
with granular atrophy, and these changes are usually asso- 
ciated with arteriosclerosis in the smaller vessels, to which 
they seem to be etiologically related (Weichselbaum). 
Advanced hyaline degeneration of the islands of Langerhans 
is sometimes encountered (Weichselbaum). 
In a considerable percentage of diabetics, the number 
of islands is decreased. The diminution may be apparent 
simple inspection, or only appreciable by certain methods 
of enumeration (Opie, Sauerbeck, Weichselbaum, Heiberg). 378 
DIABETES 
The discovery that the islands of Langerhans may be 
the seat of pathological changes without the secretory paren- 
chyma being affected, led to the assumption that these struc- 
tures are organs of internal secretion, and that their lesions 
represent the essential cause of pancreatic diabetes, but this 
hypothesis, supported and elaborated by Opie, Sauerbeck, 
and Weichselbaum and his pupils, has not been accorded 
universal recognition, its chief opponent being v. Hanse- 
mann. 
Fig. 239.-Hydropic and hyaline degeneration of an island of Langerhans in diabetes (greatly 
enlarged), a, totally hyaline area; b, remaining cells, resembling lymphocytes. 
Its adherents rest their case upon the regular occurrence 
of insular changes in diabetes and the absence of extensive 
involvement of the islands of Langerhans in other diseases, 
v. Hansemann, however, has denied the uniform occurrence 
of alterations in these structures, and has asserted recently, 
moreover, that parenchymatous changes may exist without 
any lesion in the islands themselves. According to other 
opponents of the insular hypothesis, the islets possess 
neither anatomical nor physiological independence, and it 
is useless to attempt to prove by enumeration that some are ISLANDS OF LANGERHANS 
379 
destroyed in diabetes, since their number fluctuates so widely 
under normal conditions; furthermore, it is said that secre- 
tory parenchyma may be transformed into islands, and 
also, that these structures regenerate, even during the course 
of diabetes. On the other hand, Weichselbaum, basing his 
position on the investigations of his pupil Kyrle, has denied 
the variable nature of the islands of Langerhans and has 
pointed out that regeneration, which takes place from the 
ducts rather than from the gland proper, proves the im- 
portance of insular changes in the causation of the disease, 
since it indicates preceding destruction. The fact that re- 
newal falls short of this destruction would argue, finally, 
not against, but for the significance of insular lesions. 
Saltykow has suggested that if the islands of Langerhans 
had no specific function, they would not be so constantly 
replaced under pathological conditions, and additional evi- 
dence of their independence has been adduced in the obser- 
vation that they are often spared after the parenchyma has 
degenerated, particularly in acute pancreatitis, cirrhosis, 
and carcinoma of the pancreas, or closure of its duct by 
concretions. While this statement may not obtain in every 
instance, it can be confidently asserted, nevertheless, that the 
islets are undoubtedly more resistant than the parenchyma 
toward certain processes; thus, ligation of the pancreatic 
duct in animals, though followed by alterations in the 
parenchyma, does not affect the islands of Langerhans. 
The fact that sugar does not make its appearance in the 
urine under these conditions is one of the most valuable 
supports of the insular hypothesis, v. Hansemann, it is 
true, has objected that islets are more numerous in non- 
secreting glands than when digestion is in progress, and 
has referred this persistence after ligation to secretory 
inhibition. 
As will be appreciated from the foregoing paragraph, it 
is difficult, if not impossible, to come to any decision regard- 
ing the significance of the islands of Langerhans and their 
relation to diabetes; consequently, observers are not lack- 380 
DIABETES 
ing who pursue the middle course, and refer diabetes to 
pathological conditions in both islands and parenchyma 
(Herxheimer). 
The deposition of glycogen throughout the body during 
diabetes is a matter of some interest. Under normal con- 
ditions, this substance, which is easily demonstrable with 
Best's stain, is less abundant in the organs of the adult than 
in those of the foetus; some tissues are always free, others 
possess a variable amount, while still others invariably con- 
tain it (Lubarsch, Gierke, Klestadt). Glycogen appears 
under the microscope as small globules or somewhat larger 
masses, situated in the nucleus as well as in the cytoplasm, 
as recent investigation shows. 
The kidney of a normal individual contains no glycogen, 
or, at the most, shows occasionally a few isolated droplets 
(Lubarsch), but in diabetes, the cells of Henle's loops con- 
tain large amounts (Fig. 240). Ehrlich, one of the first to 
investigate this fact, referred the presence of glycogen to 
the reabsorption which, according to Ludwig's hypothesis, 
takes place in Henle's loop, and his inference is supported 
by Loeschcke's observation that glycogen can be found in 
the glomerular capsule and the lumina of the uriniferous 
tubules also. It may be assumed either that it is excreted 
as such by the glomeruli (Loeschcke), or that it is syn- 
thesized from the sugar of the blood as this passes through 
the glomerular epithelium (Fahr). 
The earlier belief that experimental pancreatic diabetes 
(Fichera) and diabetes of the human subject (Ehrlich) are 
characterized by diminution of the glycogen content in other 
organs, has been overthrown by an improved technic. Gly- 
cogen occurs in abundance, not only where it is normally 
present, but in regions which contain little or none under 
ordinary circumstances, and may be demonstrated, for ex- 
ample, in the lymphatic sheaths of the cerebral capillaries 
(Best), in the optic nerve and the retina (Best), and in the 
hypophysis (Neubert). The liver generally has a large GLYCOGEN AND FAT 
381 
amount and here, as in the kidney, it is apt to be situated in 
the nuclei (Klestadt). 
Still, the occurrence of visible glycogen has little to teach 
concerning the pathology of diabetes, since this material 
is deposited in connection with other diseases as well (in- 
flammatory conditions, circulatory disturbances, and 
tumors). It may be said in a general way that the appear- 
Fig. 240.-Glycogen in the cells of Henle's loop (slightly enlarged). 
ance of glycogen in a cell represents a phase of metabolism 
which has become morphologically fixed (Gierke), but since 
it may indicate either increased accumulation or diminished 
dispersion it is difficult to determine just what the presence 
of this substance implies in any given case. 
The cells of the diabetic kidney almost always contain 
fat, and a diffuse fatty condition is not uncommon 382 
DIABETES 
(Fichtner). In the opinion of v. Hansemann, certain fatty 
lesions in this organ, including those associated with 
diabetes, are to be regarded as infiltration rather than 
degeneration. Leaving out of account the fact that earlier 
distinctions between the various fatty lesions can no longer 
be retained, the presence of fat in the kidney of diabetes is 
in all probability another token of the metabolic disturb- 
ances which accompany this disease (W. Fischer). Accord- 
ing to Gierke, there is some close connection between the 
deposition of fat and of glycogen, and they frequently co- 
exist in the same cell. 
The relation of carbohydrate to fat metabolism also de- 
termines the occurrence of lipaemia in diabetes, this disease 
being, in fact, its most frequent underlying cause. The 
serum is milky, and in severe cases may even resemble thick 
cream (B. Fischer); fat droplets may be demonstrated in 
it microscopically, but since they are as fine as dust they 
can be recognized with certainty only by the aid of the 
highest magnification. In Fischer's case, where fatty 
lesions involved almost ail the organs of the body, the blood 
contained 18.129 per cent, of fat (ether extract), cholesterin 
and salts were increased, and water and albuminous sub- 
stances diminished. 
Regarding the nature of lipaemia there exists no clear 
conception (for bibliography, see Fischer). Assuming that 
food fat is split up in the blood and its cleavage products 
absorbed and resynthesized by the body cells, Fischer would 
refer lipaemia to a decrease or absence of the lipolytic power 
of the serum, a condition which may even result in reversal 
of fat synthesis; it was suggested by this author that lipo- 
lytic activity might be inhibited by the acids present in 
diabetes. 
The remaining lesions of diabetes offer nothing charac- 
teristic, and in young persons particularly, who die in coma, 
the findings are apt to be entirely negative. Beside evi- 
dences of some intercurrent disease, most older individuals 
exhibit arteriosclerosis, the lesion responsible for diabetic 
gangrene. CHAPTER XXXIII 
Bright's Disease 
(parenchymatous nephritis ; acute and chronic glomerulo- 
nephritis ; SECONDARY CONTRACTED KIDNEY ; THE PRIMARY 
CONTRACTED kidney and its relation to diseases 
of the vascular system) 
There is a group of renal disorders in which the members 
possess a certain similarity in spite of the difference in their 
lesions, being characterized by varying combinations of 
degenerative and inflammatory changes which affect both 
kidneys diffusely, and by the appearance of albumin in the 
urine. It would be a difficult task to define the process per- 
fectly, since pathologists are not entirely agreed concerning 
it, and the definition just given, therefore, is not to be re- 
garded as complete. For want of a better name I have 
included this group of disorders under the term Bright's 
disease, and shall give my own views a somewhat prom- 
inent position in the discussion which is to follow. 
Parenchymatous nephritis is characterized by degenera- 
tion of the epithelium lining the uriniferous tubules, with 
little or no involvement of the glomeruli. It follows the in- 
fectious diseases, particularly during childhood, or any of 
the various intoxications. 
The kidney is slightly enlarged, the cortex somewhat 
broad, and the normal translucence of the cut surface is a 
little dulled. 
In unfixed specimens (Fig. 241), the epithelial elements 
appear swollen and granular and the presence of fat can 
usually be demonstrated, since the cloudy swelling which 
involves them readily leads to fatty degeneration. The 
globules of fat generally collect at the base of the cell, re- 
placing the cytoplasm entirely if the process be far advanced, 
and affected cells eventually perish. When the lesion is 
383 384 
BRIGHT'S DISEASE 
extensive the fat is recognizable macroscopically as dull, 
yellowish areas. 
Although the distribution of fatty degeneration has been 
extensively investigated (Ribbert, Prym, W. Fischer), no 
exact conclusion can yet be drawn regarding the effect of 
this lesion upon renal function; in Bright's disease, it is not 
uniformly distributed throughout the organ, or even 
throughout any given tubule. There can be but little doubt 
that fatty changes in convoluted tubules of the first order 
Fig. 241.-Cloudy swelling and fatty degeneration in the epithelium of the convoluted tubules 
(greatly enlarged). 
are of significance; according to Ribbert, the arched tubules 
and those of the second order are often attacked, though in 
this situation the condition is not always pathological (W. 
Fischer). 
The kidney of parenchymatous nephritis shows such 
signs of the excretion of albumin as the presence of a granu- 
lar deposit in the intracapsular spaces or the lumina of the 
convoluted tubules, and the tubules, including those of the 
straight variety, may contain hyaline casts. 
As a general rule there is no cellular infiltration of the 
connective tissue, though small areas may be so affected. PARENCHYMATOUS NEPHRITIS 
385 
Under parenchymatous nephritis I include cases with 
other degenerative conditions, such as guttate hyaline de- 
generation, abnormal granulation (Ffister), and coagula- 
tion necrosis. The term acute parenchymatous nephritis 
was originally applied to the renal lesion now under dis- 
cussion because Virchow regarded cloudy swelling as an 
expression of inflammation, and the name is still widely 
employed. It is customary at the present time, however, to 
group cloudy swelling among the degenerations (Albrecht, 
Lukjanow), though the attempt has been made to sustain 
the conception of a parenchymatous inflammation. Thus 
Aschoff has asserted that epithelium does react to inflam- 
matory stimuli, while others have suggested that parenchy- 
matous changes are associated from the first with every 
inflammation, even though the etiological relations between 
the two conditions do not readily lend themselves to analysis. 
I incline, nevertheless, to agree with those who, like Ribbert, 
wish to see the degenerations separated from the inflamma- 
tions. Still, the term parenchymatous nephritis may be 
retained for lack of a better one, in the same way that mye- 
litis and many other appellations have been preserved, in 
spite of the fact that they no longer accurately express our 
ideas. 
It was sought for a time to uphold the inflammatory 
nature of parenchymatous nephritis by a hypothesis which 
interpreted the excreted albumin as an inflammatory exu- 
date. Casts do, in fact, exhibit to some degree the staining 
reactions characteristic of fibrin (Ernst), yet it is doubtful 
whether they are actually fibrinous (Lubarsch). On the con- 
trary, it is almost certain that some of them are composed 
of degenerated epithelium (Burmeister), while others result 
from the coagulation of albuminous urine (Ribbert). 
The significance of fatty degeneration deserves at least 
a few words. Virchow's view, that the presence of fat 
globules in a cell is referable to a breaking down of its 
cytoplasm, in contrast to fatty infiltration, where they are 386 
BRIGHT'S DISEASE 
absorbed with nutrient fluids, is now untenable, since it has 
been shown that the droplets in so-called fatty degeneration 
also enter the cell from without. Both Lebedeff and 
Rosenfeld have demonstrated that the fat in hepatic lesions 
in dogs poisoned with phosphorus or phloridzin must be 
derived from the fat depots. It is possible, however, par- 
ticularly in human pathology, that the fat normally present 
in the cytoplasm becomes visible in fatty degeneration 
(Kraus). At any rate, the appearance of fat droplets is, in 
itself, not a sign of necrobiosis, since it may be merely the 
expression of some metabolic disturbance. 
But the earlier conceptions of fatty degeneration have 
undergone still further modification. Kaiserling and Orgler 
have proved that some of the droplets present in fatty de- 
generation, and a majority of those found in the kidney, 
are doubly refractive (anisotropic) under the polarizing 
microscope. This property does not belong to the fats them- 
selves, but to certain substances (myelin, protagon) found 
in the brain and other tissues. It has been discovered re- 
cently that these anistropic bodies,or lipoids,as they are also 
called (see Aschoff), are cholesterin esters; this has been 
proved not only by chemical analysis but by the observation 
that artificially prepared cholesterin ester either pure or 
mixed with fats, fatty acids, or cholesterin, assumes the form 
of doubly refractive globules (Adami and Aschoff). Hence, 
according to Aschoff (Kawamura), the appearance of doubly 
refractive droplets in a cell is to be regarded as a modifi- 
cation of fatty metamorphosis, and two varieties of this 
degeneration may therefore be distinguished-a glycerin 
ester or fat, and a cholesterin ester or lipoid type. 
The pathological significance of fatty degeneration of 
the kidney has been questioned by Rosenfeld, who could find 
no correspondence between the amount of fat in histological 
sections and the fat content of the organ as determined by 
chemical means. A large quantity could be demonstrated 
in kidneys where none could be detected in sections, and con- 
versely, kidneys which exhibited under the microscope an ACUTE AND CHRONIC GLOMERULONEPHRITIS 
387 
advanced degree of degeneration showed an actual decrease 
in their fat content when they were subjected to chemical 
analysis. Dietrich, on the other hand, employing different 
methods, did not encounter such contradictory results in the 
morphological and the chemical determination of fat, and in 
spite of Rosenfeld's observations the microscopic demon- 
stration of fat is of value. Ribbert has pointed out that 
variations in the distribution of fat are not appreciable by 
chemical means, and that even though such methods show 
no increase of the total amount of fat in a degenerated organ, 
they cannot controvert the microscopic evidence that certain 
cell groups contain more fat than others. 
It is highly probable that parenchymatous nephritis gen- 
erally undergoes complete recovery, since lost renal epi- 
thelium can be replaced by the regeneration of remaining 
cells. The process may be followed particularly well in ani- 
mals with degenerative lesions of the tubular epithelium 
caused by such poisons as mercuric chloride and salts of 
chromium and uranium (Thorel). 
Long-continued poisoning results in a cicatricial con- 
dition which has been described, perhaps too hastily, as con- 
tracted kidney. No one has ever succeeded, however, in 
evolving a progressive renal disorder exactly analogous with 
the chronic form of Bright's disease. 
ACUTE AND CHRONIC GLOMERULONEPHRITIS 
The gross appearance of a kidney involved by acute 
glomerulonephritis resembles that described for the paren- 
chymatous type. The etiology of the lesion is similar, also, 
and it is particularly apt to follow scarlet fever. The sole 
evidence of participation by the vascular tufts is often an 
augmentation in the number of their nuclei depending upon 
multiplication of both endothelial and epithelial elements. 
In more advanced cases, a crescentic mass of desquamated 
cells occupies the capsular space (Fig. 242). 
These changes are described as inflammatory because 
they are accompanied by proliferative processes in the con- 388 
BRIGHT'S DISEASE 
nective tissue, and because the stroma contains areas of 
small cell infiltration, frequently localized about the 
glomeruli. 
When a hemorrhagic exudate is present (hemorrhagic 
nephritis), the surface of the organ is mottled with dull red 
spots, and the microscope shows the presence of blood in 
the capsular spaces and the uriniferous tubules. 
Fig. 242.-Acute glomerulonephritis (greatly enlarged), a, desquamated epithelium in the 
capsular space; b, increased number of nuclei in the glomerular tufts. 
Glomerulonephritis is dignified as a separate class, first, 
because it might be expected that lesions of the vascular tufts 
would be followed by disturbances of function different from 
those accompanying changes in the tubules. Schlayer and 
Hedinger, for example, found that the function of either the 
glandular or the vascular apparatus in animals could be 
disturbed, according to the poison administered. It may be, 
however, that the distinction is more functional than ana- CHRONIC GLOMERULONEPHRITIS 
389 
tomical (Takayasu), and that it is not immediately trans- 
ferable to nephritis in the human subject. 
A second reason may be found, nevertheless, in the fact 
that glomerulonephritis does not undergo such complete re- 
covery as does the parenchymatous type. Cases character- 
ized by desquamation of the glomerular cells generally pur- 
sue a subacute course, and some of them progress to chronic 
nephritis. Advanced changes are to be found in the glom- 
Fig. 243.-Chronic glomerulonephritis (greatly enlarged), a, b, hyaline areas. 
eruli after the disease has persisted for several months 
(Lbhlein); their vascular tufts become adherent in places 
to the capsule, while portions of the loops contain but few 
nuclei, a condition indicating partial destruction of the 
glomerulus (Fig. 243). A chronic form of glomerular 
nephritis is accordingly recognized, and this always in- 
volves nearly all the malpighian bodies to a greater or less 
extent. 
The lesions in the remainder of the parenchyma which 390 
BRIGHT'S DISEASE 
accompany these chronic glomerular changes contribute 
other characteristic features. To the naked eye, the organ 
always appears greatly altered, being generally enlarged and 
smooth. The cortical markings vary; clear areas containing 
blood (Fig. 244) may alternate with dull anaemic portions 
(large mottled kidney), while in other cases the chronic 
glomerular lesions produce the large white kidney. It should 
be emphasized in this connection, however, that the type of 
nephritis can never be determined solely from the macro- 
scopic appearance of the organ. 
The kidney of chronic glomerulonephritis always shows 
degenerative changes in the tubular epithelium, particularly 
fatty metamorphosis. In advanced conditions, the lipoid 
material may be found in phagocytes throughout the inter- 
stitial tissues (Stoerk). 
(Edema usually accompanies this type of renal dis- 
order, and the condition 
known as chronic parenchy- 
matous nephritis or chronic 
nephritis with hydrops (Fr. 
Muller) is identical with 
chronic glomerulonephritis 
in the majority of instances 
(Lbhlein). 
The connective tissue al- 
most invariably undergoes 
proliferation, and since this 
fibrosis was at one time uni- 
versally regarded as inflammatory it was customary to 
distinguish a parenchymatous and an interstitial type of 
nephritis. Weigert showed, however, that chronic paren- 
chymatous lesions are nearly always associated with inter- 
stitial growth, interpreting connective-tissue proliferation 
as an attempt to fill in the defects caused by the destruction 
of parenchyma (replacement fibrosis), and I have not the 
slightest doubt that the interstitial proliferation of chronic 
Bright's disease may be chiefly attributed to such a process. 
Fig. 244.-Chronic glomerulonephritis 
(natural size). SECONDARY CONTRACTED KIDNEY 
391 
The earlier phases of destruction in the vascular tufts, which 
are entirely independent of any connective-tissue over- 
growth, have been already described (Fig. 243); if these 
lesions progress still further the glomerulus is totally de- 
stroyed, and replaced by a homogeneous mass containing but 
few nuclei and surrounded by a thickened capsule. As the' 
disease continues, more and more uriniferous tubules are 
destroyed, partly by degeneration of their epithelium but 
partly, also, on account of the loss of glomeruli, as will be 
seen later. 
Though it be thus inferred that fibrosis is a secondary 
process, such an assumption does not exclude the possibility 
that proliferative processes may be strengthened by the in- 
flammatory lesions which betray their existence in areas of 
small cell infiltration throughout the stroma. 
SECONDARY CONTRACTED KIDNEY 
Extensive parenchymatous destruction and connective- 
tissue overgrowth produce the secondary contracted kidney, 
the development of which from acute nephritis has been 
observed clinically in many instances. Since Lbhlein has 
shown that the organ in this condition resembles that of 
chronic glomerulonephritis, the secondary contracted kidney 
may be defined as the end stage of this disorder. 
The secondary contracted kidney is often greatly reduced 
in size. It is generally of a grayish white color (Aufrecht), 
and either uniformity and finely nodular, or covered with 
larger, irregular, grayish-yellow protuberances. The histo- 
logical changes already discussed are enhanced, and the 
tubules, the cells of which become enlarged, undergo compen- 
satory dilatation. The more prominent nodules on the sur- 
face of the organ are usually composed of parenchyma that 
has undergone compensatory enlargement in this manner. 
With acute and chronic glomerulonephritis and the sec- 
ondary contracted kidney is associated cardiac hypertrophy, 
a condition which Bright recognized as etiologically related 
to the renal lesions. Even the more acute forms of nephritis 392 
BRIGHT'S DISEASE 
may be accompanied by enlargement of the heart, if their 
duration be not too brief, and the chronic type is almost cer- 
tain to be accompanied by considerable hypertrophy, though 
in a few cases the enlargement is but slight. Such an ad- 
vanced renal disorder as secondary contraction may be en- 
countered in the absence of cardiac hypertrophy (Jores), 
but the condition is so rare that its occurrence has been 
doubted (Volhard, Lohlein). 
As a rule, arteriosclerosis does not involve the arteries 
of the secondary contracted kidney. Fahr has suggested, 
however, that these vessels may be attacked secondarily 
after the disease has persisted for a long time, a circum- 
stance which Heineke has recorded in the case of the large 
arteries throughout the body. 
THE PRIMARY CONTRACTED KIDNEY AND ITS RELATION TO DISEASES 
OF THE VASCULAR SYSTEM 
This most common type of contracted kidney, the red 
granular, or genuine contracted kidney, differs in many 
essentials from that described in the preceding paragraphs. 
The organ is greatly reduced in size, brownish-red in color, 
the surface is everywhere finely granular (Fig. 245), and 
the cortex narrow. No cloudy areas obscure the lustre of the 
cut surface. 
Bands or wedge-shaped areas of fibrous tissue (Fig. 
246) enclosing atrophic tubules and obliterated glomeruli 
alternate with active parenchyma. There is little or no 
degeneration to be observed in the epithelial cells lining the 
uriniferous tubules. 
Those glomeruli which are situated amid proliferating 
connective tissue are small, hyaline, almost destitute of 
nuclei, and surrounded by a thickened capsule; in other 
words, they have suffered total destruction. Throughout 
the rest of the kidney, however, the glomeruli are normal, or, 
at the most, contain a little albumin in the intracapsular 
space. Since stages intermediate between these two ex- 
tremes are but rarely encountered, it would seem that the PRIMARY CONTRACTED KIDNEY 
393 
glomerular destruction is abrupt rather than gradual; where 
they do occur, the loops exhibit partial or, more commonly, 
complete fatty metamorphosis. 
The walls of the arteries in a primary contracted kidney 
are always affected. The hyperplastic-elastic layer becomes 
thickened and the intima of the smallest arteries undergoes 
fatty degeneration (Fig. 247); thus the vessels are involved 
by changes which are in part hypertrophic and in part 
arteriosclerotic. 
Friedemann, the first to describe hyperplasia of the elas- 
Fig. 245.-Primary contracted, or red granular kidney (natural size). 
tic lamellae in small arteries of the contracted kidney, as- 
cribed it to the high blood-pressure of nephritic patients. 
For my part, I believe it should be referred to arteriosclero- 
sis, since it is of regular occurrence only in those vascular 
systems which are the seat of this disease, and again, since 
it is not constantly associated with the contracted kidney 
(Both). Degenerative lesions in the arterioles, which re- 
cent investigation (Prym, Jores) has shown to be widely 
distributed throughout the primary contracted kidney, are 
undoubtedly phases of arteriosclerosis. 
The vascular changes associated with the primary con- 394 
BRIGHT'S DISEASE 
tracted kidney have been recognized for a long time. Gull 
and Sutton described them as " arteriocapillary fibrosis," 
German authors as endarteritis obliterans, a condition which 
was not always sharply distinguished from arteritis defor- 
mans (arteriosclerosis). 
Recent investigation, moreover, has substantiated the 
observation of Gull and Sutton that the smaller vessels are 
involved throughout the entire body; arteriosclerosis is 
usually demonstrable in the arterioles of the brain, the 
spleen, the pancreas, and the heart, more rarely in those 
of the stomach, the intestine, the liver, the retina (Kriick- 
mann), and the skin, while those of the skeletal muscles 
Fig. 246.-Primary contracted kidney (slightly enlarged), a, area of interstitial growth, 
with atrophy of the parenchyma; b, glomeruli, totally destroyed; c, surviving tubules showing 
compensatory hypertrophy. 
do not participate in the process at all (Jores, Fahr). 
The disease is generally appreciable, also, in the medium- 
sized arteries of the affected organs, even upon gross ex- 
amination, and involves the larger arteries as well, al- 
though here it is often so insignificant that the aorta and 
the larger vessels seem almost intact. 
Arteriosclerosis is regarded by the majority of observers 
as a consequence of the increased blood-pressure attending 
nephritis, and that this view is valid in some instances can- 
not be denied. In most cases, however, the reverse is true: ARTERIOSCLEROSIS 
395 
vascular lesions are the chief factor in the production of a 
contracted kidney (Jores, Fahr, Gaskell, Ophuls). It is 
easily apparent that extensive arteriosclerosis in the arter- 
ioles must be followed by nutritional disturbances in the 
parenchyma, the glomeruli appearing to be especially en- 
dangered when the vasa afferentia are involved; once they 
have succumbed, the corresponding tubules become atrophic 
Fig. 247.-Primary contracted kidney (slightly enlarged), a, artery with thickened 
hyperplastic-elastic layer; b, arterioles with fatty degeneration of their thickened intima; c, 
glomerulus, with fatty degeneration of its capillary loops; d, glomerulus with a greatly thick- 
ened capsule; e, increased amount of interstitial connective tissue. 
from disuse (Thoma, Ponfick) and finally disappear. Fur- 
thermore, lesions which are exactly similar, although less 
advanced, to be sure, attack the kidney in connection with 
generalized arteriosclerosis, as has already been seen, and 
their dependence upon the vascular changes has been recog- 
nized (Ziegler). 
But, however this may be, it is not yet entirely clear 
whether every contracted kidney associated with lesions in 396 
BRIGHT'S DISEASE 
the arterioles can be referred solely to arteriosclerosis. 
Cases come under observation from time to time which do 
not correspond wholly with the primary contracted kidney, 
either macroscopically or microscopically. In these, the 
dilated tubules contain casts in abundance, the epithelium is 
the seat of fatty degeneration, and the fibrous tissue is 
irregularly distributed. In my opinion, however, vascular 
disease exerts an important influence upon both the develop- 
ment and the course of this chronic renal lesion also. Fahr 
discovered desquamation of the capsular epithelium in these 
kidneys, an evidence of glomerulonephritis, and as Volhard 
had described a clinical form of contracted kidney which he 
referred to the concomitant action of inflammation and 
arteriosclerosis (combined type), so Fahr saw in his own 
findings an anatomical basis for the existence of a "com- 
bined type. ' ' Such an interpretation appears to advance in 
some degree our knowledge of chronic diseases of the kidney, 
even though it may not represent a final solution of the 
problem. 
As the reader must have inferred already, much remains 
to be accomplished. The renal conditions that have been 
discussed are only types, after all, and cases in which the 
development of the disease cannot be traced, as well as 
atypical forms, are manifold. The one thing that stands out 
clearly is this, that it is glomerulonephritis on the one hand, 
and arteriosclerosis in the small vessels of the kidney on the 
other, that indicate the position from which the pathogenesis 
and course of chronic Bright's disease may be most advan- 
tageously investigated. 
Among the changes found throughout the remainder of 
the body in connection with the primary contracted kidney 
are such consequences of arteriosclerosis as cerebral hemor- 
rhage, which is of frequent occurrence, and necrosis of the 
myocardium, which supervenes only rarely and as a result 
of extensive disease in the coronary arteries. 
Pronounced cardiac hypertrophy is associated with the 
primary contracted kidney, affecting chiefly the left ven- CARDIAC HYPERTROPHY 
397 
tricle, and many hypotheses have been advanced to explain 
its occurrence, no one of which, however, dominates the rest 
(see Thorel, Passler). That the heart should be directly 
stimulated to increased activity will hardly be believed to- 
day, and it is much more probable that an augmentation of 
the resistance opposed by the peripheral vessels throws an 
increased amount of work upon the cardiac musculature. 
The obstruction was referred for a time directly to the renal 
capillaries, but all such hypotheses may be regarded as 
overthrown (Senator). There is a great deal of evidence, 
however, to suggest that the resistance is offered in the 
peripheral arteries, perhaps through frequent or persistent 
contraction of the smaller ones, and that this results in 
heightened blood-pressure and eventually in cardiac hyper- 
trophy. This view, of course, would account only for the 
enlargement of the left ventricle; involvement of the right 
chamber which, according to Hasenfeld, is always present, 
probably takes place in compensation for the insufficiency 
of the left (Passler). 
The mechanism that raises the blood-pressure is probably 
activated by materials which collect in the blood in conse- 
quence of disturbances in the secretion of urine. It has been 
suggested, also, that large amounts of adrenalin attain the 
circulation, some authors having maintained that hyper- 
trophy of the medulla of the suprarenal body (Schur and 
Wiesel), or of the chromaffin substance (Nowicki), or an in- 
creased adrenalin content of the suprarenal gland (.Schur 
and Wiesel, Goldzieher), can be demonstrated in those dead 
of nephritis. Since others (Aschoff, Oberndorfer) have been 
unable to substantiate these observations, neither constant 
and uniform adrenal hypertrophy (Thomas) nor an in- 
creased amount of adrenalin in the suprarenal bodies (Ingier 
and Schmorl) can be said to be associated with chronic 
nephritis. 
For some reason still unknown, the cardiac hypertrophy 
connected with the primary contracted kidney is more ad- 
vanced than that associated with any other form of Bright's 398 
BRIGHT'S DISEASE 
disease. Investigating this question, I found that the de- 
gree of cardiac hypertrophy can depend neither upon the 
variety nor the severity of the renal lesion; furthermore, the 
enlargement is present while the changes in the kidney are 
still insignificant. I therefore consider it possible, nay, even 
probable, that in the case of the primary contracted kidney 
the heightened blood-pressure is not produced, or at least 
not solely produced, by the condition of the kidney, but 
rather by extrarenal causes. This being true, a primarily 
heightened blood-pressure would have to be regarded as the 
basic condition responsible for both the cardiac and the 
renal lesion (Frank), or, as I have expressed it, it would 
have to be assumed that the noxa which causes the contracted 
kidney induces, from the first, an augmentation in the blood- 
pressure. CHAPTER XXXIV 
Rhachitis and Osteomalacia 
One of the principal signs of rhachitis is a swelling of the 
ribs at the costochondral junction (rhachitic rosary), and of 
the extremities of the long bones, the intensity of the lesion 
in any given location depending upon the rapidity with 
which physiological bone formation goes on at that site. 
Active centres of growth are attacked at an earlier period, 
or, if involvement affect all portions of the skeletal system 
simultaneously, suffer more seriously, than those possessed 
of less proliferative energy. 
The region of endochondral ossification is widened (Fig. 
248), while between the white 
(resting) cartilage and the point 
of commencing ossification the 
zone of proliferating cartilage is 
recognizable as a broad, trans- 
lucent area, irregularly demar- 
cated from the bone. The dia- 
physis, particularly in the neigh- 
borhood of the cartilage, is 
softer than normal, more richly 
supplied with blood, and fre- 
quently more compact. 
In histological preparations, 
a widening of the proliferating cartilage is again the most 
prominent feature (Fig. 249). The columns of cartilage 
cells are longer and broader than normal, and the zone of 
preparatory calcification present at their diaphyseal ends 
under ordinary circumstances, is usually lacking; it may 
be demonstrable in the earlier stages of the disease, though 
it does not form a continuous line. In healthy bone, a sys- 
tem of parallel blood-vessels from the medullary cavity pene- 
trates and breaks up these rows of cartilage cells, each vessel 
Fig. 248.-Section through the lower 
epiphysis of a rhachitic femur (two-thirds 
natural size), a, zone of proliferating 
cartilage; b, osteoid tissue; c, centre of 
ossification. 
399 400 
RHACHITIS AND OSTEOMALACIA 
Fig. 249.-Disturbance of endochondral ossification in rhachitis (slightly enlarged), a, 
zone of resting cartilage; b, zone of proliferating cartilage; c, bone with deficient calcification; 
d, vessels; e, islands of growing cartilage within the ossification zone;/, trabeculae made up en- 
tirely of osteoid tissue; y, trabeculae with central calcification and osteoid margins. HISTOLOGICAL FINDINGS 
401 
attacking one column, but in rhachitis the invasion takes 
place with the greatest irregularity; the vessels push more 
deeply and in greater number through imperfections in the 
calcification zone, and each erodes a group of cell columns 
instead of one, while other portions of the cartilage remain 
undisturbed. Thus the boundary line between bone and 
cartilage becomes irregular. 
The widening of the zone of proliferating cartilage is 
caused, not by its excessive growth, but by its delayed con- 
version into bone (Heubner, Schmorl), as the latter author 
has proved by the persistence of the cartilage canals. These 
are channels carrying blood-vessels from the perichondrium, 
which penetrate the cartilage and end blindly toward its 
central portion. Under normal conditions, one after another 
fuses with the medullary cavity as the line of ossification 
sweeps by, but in rhachitis they remain, in consequence of 
the delayed replacement of the cartilage by bone. In severe 
cases, several persisting canals, arranged one above the 
other, confer upon the cartilage a characteristic terraced 
structure, an appearance capable of no interpretation save 
that the cartilage does not undergo dissolution. 
The marrow is abundantly supplied with large blood- 
vessels, and its fibrous constituent (the endosteum, according 
to Ziegler) is augmented at the expense of its cellular 
portion. 
Rhachitis is characterized, furthermore, by the overpro- 
duction of osteoid tissue, but the newly-formed trabeculae 
do not undergo calcification except toward the centre (Figs. 
249, 250), and in very severe cases many of them contain no 
lime at all (Fig. 249). 
As for the etiology of rhachitis, Kassowitz emphasized 
the importance to be placed upon the hyperaemia of bone- 
forming tissues. To this condition, which he regarded as 
inflammatory, he ascribed all the other lesions of the disease, 
and deficient calcification in particular. More recent inves- 
tigators have been reluctant to accept his hypothesis, and 
especially loath to refer the hyperaemia to inflammation. 402 
RHACHITIS AND OSTEOMALACIA 
Ill the opinion of Ziegler, the disordered endochondral 
ossification of rickets is due to an abnormal proliferation 
of the endosteum and the periosteum in the subchondral re- 
gions, and the disturbances of calcification in the cartilage 
and newly-formed osteoid tissue are the consequence, not of 
a deficient supply of lime, but of this overgrowth, which is 
the essential lesion of the disease. Oehme, however, con- 
sidered that Ziegler's hypothesis is controverted by the in- 
constant appearance and 
irregular distribution of 
the fibrocellular tissue 
which he had described. 
The imperfect de- 
struction of cartilage and 
the consequent irregu- 
larities in enchondral 
ossification have been at- 
tributed by Schmorl to 
deficiency or absence of 
the preparatory calcifi- 
cation zone, a conception 
harmonizing with that 
hypothesis which regards 
a failure in the deposi- 
tion of lime salts as the 
essential feature of rha- 
chitis. He and Stoeltzner have embraced Pommer's view, 
that the chief anatomical feature of rhachitis is the produc- 
tion of an abnormally large amount of osteoid tissue. When 
this springs from the periosteum it results in the production 
of soft, hypersemic masses (Fig. 250) on the external surface 
of the bone (rhachitic osteophytes); these are frequently 
found over the frontal and parietal eminences. 
When finished bone is absorbed in rhachitic individuals, 
it is replaced by osteoid tissue, a fact which explains the 
extreme and rapid softening of areas of bone like that which 
frequently takes place in the occipital region (craniotabes). 
Fig. 250.-Deficient calcification of trabeculre in 
an osteophyte from the skull (slightly enlarged). 
a, osteoid trabeculae; b, central calcification in the 
trabeculae; c, medullary spaces. ETIOLOGY 
403 
It is a disputed question whether bone is more extensively 
absorbed in rhachitic subjects; Kassowitz has asserted that 
it is, but Pommer, Schmorl, and others, have maintained that 
absorption does not overstep the normal bounds, and that 
the softening in the skeletal system is amply explained by 
the substitution of a tissue with little or no lime (osteoid) 
for the absorbed bone. Only rarely, and in cases of long 
duration, does absorption exceed deposition (Stoeltzner). 
According to M. B. Schmidt, however, as cited by Kaufmann, 
there occur cases of "rhachitis with osteomalacia," which 
should be distinguished from common rhachitis (with the 
proliferation of lime-free tissue) under the term severe 
rhachitis (with the proliferation of lime-free tissue and 
halisteresis); as v. Recklinghausen showed, these are charac- 
terized by active decalcification of both old and new bone. 
The lack of rigidity in rhachitic bones renders them liable 
to bend in accordance with muscular traction or other 
mechanical demands, and the resulting deformities are 
perpetuated after the recession of the disease, which takes 
place very slowly. Normal lengthening of the lower ex- 
tremities is sometimes seriously affected, with dwarfism 
as a consequence. 
Lesions may be demonstrated in the bones of young ani- 
mals kept on a diet deficient in lime, which, however, are not 
regarded by most investigators as identical with those of 
rickets. They consist of osteoporosis, with periosteal thick- 
ening at points subjected to muscular traction; the osteo- 
porosis is brought about by increased resorption (Stoeltz- 
ner) in the presence of normal apposition. When stron- 
tium phosphate is administered in combination with a diet 
poor in lime, changes very similar to those of rhachitis are 
produced (Stoeltzner, Oehme), since this drug, according 
to Stoeltzner, excites the osteoplastic tissues to greater 
activity. 
Dibbelt asserted that the alterations produced by a diet 
containing insufficient lime differ only quantitatively from 404 
RHACHITIS AND OSTEOMALACIA 
those of rhachitis, bearing otherwise ah the anatomical and 
chemical characteristics of that disease, and concluded that 
the cause of rickets is to be sought in some abnormality of 
lime metabolism. 
The etiology of rhachitis is still a mystery. Infection 
can hardly enter into the question, even though Morpurgo 
has recorded softening of the bones in rats after infection 
with a diplococcus. Improper nourishment and unfavorable 
environment probably exert an influence, and Stoeltzner has 
suggested some disturbance of suprarenal secretion. How- 
ever, the appearance of this gland in rhachitic subjects offers 
no support to such an assumption (Jovane and Carlo Pace). 
The following changes are frequently found at autopsy, 
beside those already described in the skeletal system: Dilata- 
tion of the ventricles in the brain (internal hydrocephalus), 
a firm and hypertrophic condition of this organ, lobular 
pneumonia, fatty infiltration of the liver, and, very fre- 
quently, enlargement of the lymph-nodes, particularly those 
of the mesenteric group. There is little or no enlargement 
of the spleen, or, if the size be increased, it is doubtful 
whether this can be attributed directly to the rhachitis 
(Stark). Severe rickets may be combined with anaemia 
infantum pseudoleukaemia (infantile pseudoleukaemia, 
splenic anaemia of children). Aschenheim and Benjamin 
have referred this latter disorder to the rhachitis, since the 
findings in the marrow are essentially the same in both dis- 
eases-lymphoid transformation and a large number of 
erythroblasts. 
The presence of characteristic lesions in the muscles 
(rhachitic myopathy) has been both asserted (Bing) and 
denied (Martins). 
Rickets usually appears between the ages of six months 
and seven years, but may occur at any time up to the period 
when growth ceases (rhachitis tarda) ; the identity of late 
rickets with the more usual type has been histologically 
established (Schmorl, Looser). OSTEOMALACIA 
405 
Softening of the bones in adults was formerly described 
as an independent disease, and separated from rhachitis 
under the terms osteomalacia, or senile osteoporosis. It 
was maintained that rickets is characterized by the new for- 
mation of osteoid tissue, osteomalacia, on the contrary, by 
the disappearance of lime salts from finished bone. But in 
the light of our more recent knowledge of halisteresis such a 
view can be no longer entertained, and the two diseases must 
be regarded as anatomically identical; v. Recklinghausen, 
indeed, included in one group with the diseases just men- 
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Senator, Z. f. kl. M., 72, 1911.-Hasenfeld, D. A. f. kl. M., 59, 1897.-Schur 
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P. G., 9, 1905. 405. v. Recklinghausen, 1. c., 403. INDEX 
Abscess, cold, 231 
hypostatic, 231 
Achlorhydria in anaemia, 9 
Achylia in anaemia, 9 
Acute yellow atrophy, 353 
Adenocarcinoma of the intestine, 313 
of the lung, 295 
of the prostate, 327 
of the stomach, 307 
Adenoma malignum, 342 
of the prostate, 334 
Adrenal, amyloidosis of, 239 
hypertrophy of, in nephritis, 397 
Spirochaeta pallida in, 251 
Altmann's granules, 18 
Amyloidosis, 235 
Anaemia, aplastic, 5 
in Banti's disease, 362 
and Bothriocephalus, 5, 7, 9 
and carcinoma, 7 
causes of, 1,7 
cryptogenetic, 9 
experimental, 6 
and gastric ulcer, 305 
infantum pseudoleukaemia, 404 
and leukaemia, 13 
pernicious, 5 
regeneration in, 4 
secondary, 5 
splenic, of children, 404 
Anaplasia, 289 
Anasarca, 49, 53, 361, 390 
Aneurism, 99 
arrosion, 108, 190 
cardiac, 81 
cerebral, 90, 94 
miliary, 90 
mycotic-embolic, 108 
Angina pectoris, 76 
in scarlet fever, 160 
Aorta, amyloidosis of, 239 
arteriosclerosis of, 57 
of new-born, 59 
wounds of, 110 
Aortic insufficiency, 46 
GjfpnncjiQ 4-K 
Aortitis, syphilitic, 44, 76, 105, 258 
tuberculous, 215 
Apoplexy, 72 
in nephritis, 396 
pancreatic, 372 
Appendicitis, acute, 174 
chronic, 181 
Arrhythmia, 86 
Arteries, amyloidosis of, 237, 239, 240 
development of, 59 
syphilis of, 44, 76, 105, 248, 258 
tuberculosis of, 215 
Arteriocapillary fibrosis, 394 
Arteriosclerosis, 56 
in cardiac hypertrophy, 54 
causes of, 58 
consequences of, 68 
and diabetes, 377, 382 
diffusa, 59 
distribution of, 70 
experimental, 65 
and fat necrosis, 374 
and hepatic cirrhosis, 368 
Monckeberg type, 66 
and nephritis, 392 
and paralytic dementia, 258 
Arthritis, fungosa, 234 
serous, 134 
syphilitic, 248 
tuberculous, 234 
Ascites, 49, 359, 363, 364, 369, 370 
Astrocyte, 265 
Atheroma, 57, 63, 64, 73 
Atherosclerosis, 58 
Atrioventricular bundle, 81 
Atrophy, acute yellow, 353 
Auditory nerve, fibroma of, 269 
Auriculoventricular ring, insufficiency 
of, 44, 45 
Bacillus aerogenes capsulatus, 137 
carriers, 168 
diphtheriae, 157 
phlegmones emphysematosae, 137 
Bacteria, elimination through kidney, 
132 
in endocarditis, 35 
Bactersemia, 129 
Ball thrombus, 44 
Banti's disease, 7, 362 
Berlin blue reaction, 3 
Bile ducts, regeneration of, 357 
Bile pigments, in gall-stones, 318 
production of, 316 
Biliary cirrhosis, 363 
Bladder, dilatation of, 336 
hypertrophy of, 336 
inflammation of, 338 
secondary carcinoma of, 327, 346 
tuberculosis of, 219, 221 
Blood, in anaemia, 4 
in chloroma, 32 
417 418 
INDEX 
Blood, fat in, 382 
formation, in the adult, 5 
in the embryo, 5, 17 
in the liver and spleen, 6 
in hepatic cirrhosis, 361 
in leukaemia, 11 
in lymphosarcomatosis, 31 
pressure in nephritis, 394, 397 
in pseudoleukaemia, 21 
tubercle bacilli in, 197, 198, 209, 
213, 220, 222, 229 
Bone, rhachitic lesions in, 399 
sarcoma of, 272 
secondary tumors of, 282, 328 
syphilis of, 247, 251 
tuberculosis of, 230 
Bone-marrow, in anaemia, 4 
in hepatic cirrhosis, 361 
in Hodgkin's disease, 23 
in leukaemia, 14, 17 
lymphoid, 4 
in myeloma, 25 
regeneration of, 4, 5 
in rhachitis, 401, 404 
secondary carcinoma of, 8 
typhoid bacillus in, 170 
Bothriocephalus anaemia, 5, 7, 9 
Brain, abscess of, 130 
anaemia of, 267, 268 
aneurisms in, 90, 94 
atrophy of, 254 
compression of, 267 
concussion of, 93 
cysts in, 266 
gumma of, 243, 248 
hemorrhage into, 87, 268, 396 
infarction of, 39 
softening of, 254 
solitary tubercle of, 204 
thrombosis and embolism in, 97 
tumors of, 263 
Bright's disease, 239, 383 
Bronchi, carcinoma of, 295 
syphilitic, stenosis of, 246 
Bronchitis, in emphysema, 154 
obliterating fibrous, 149 
tuberculous, 195 
in typhoid fever, 169 
Bronchopneumonia, 157 
tuberculous, 187, 191, 194 
Bronzed diabetes, 367 
Bullock's heart, 54 
Bundle, atrioventricular, 81 
of His, 81 
of Wenckebach, 84 
Calcification, of arteries, 57, 73, 76 
of cardiac valves, 43, 44 
of lymph-nodes, 195 
of papillary muscles, 43 
Calculus, renal, 337 
Cancer, see Carcinoma. 
Capillaries, amyloidosis of, 237 
Carcinogenesis, 285 
Carcinoma, and anaemia, 7 
basal-cell, 284 
of the bronchi, 295 
corium, 285 
epithelial, 284 
etiology of, 287 
of the gall-bladder, 321 
in gastric ulcer, 307 
gelatinous, 308, 324 
genesis of, 285 
glandular, 283 
growth of, 285 
and hepatic cirrhosis, 368 
and inflammation, 289, 290, 307 
of the intestine, 312 
of the lungs and pleura, 292 
of the mamma, 281 
medullary, 283 
mole, 283 
in the mouse, 285, 287, 290 
of the oesophagus, 296 
osteoplastic, 282 
of the prostate, 326 
of the rectum, 315 
and regeneration, 368 
scirrhous, 283 
squamous-cell, 284, 324, 342 
of the stomach and intestine, 307 
and tuberculosis, 295 
of the uterus, 340 
Carcinosis, peritoneal, 282, 315, 346 
osteoplastic, 328 
Cardia, carcinoma of, 310 
Cardiac cicatrices, 50, 52, 72, 78, 79, 
159 
cirrhosis, 368 
tamponade, 110 
Carnification, 148 
Cartilage, amyloidosis of, 241 
Caries, syphilitic, 252 
tuberculous, 231 
Catarrh, congestive, 47 
Central nervous system, tumors of, 263 
Cerebello-pontine angle, tumors of, 269 
Cervix, carcinoma of, 340 
tuberculosis of, 226 
Chancre, 249 
Children, cardiac hypertrophy in, 55 
splenic anaemia of, 404 
Chloroma, 32 
Cholangeitis, 318 
Cholecystitis, 318 
Cholelithiasis, 167, 318, 322 
Cholesterin calculi, 318 
Chondromyxosarcoma of pleura, 294 
Chondrosarcoma, 275 INDEX 
419 
Chorio-epithelioma, 346 
Choroid, tumors of, 280 
Chromatophore, 277 
Cicatrices, cardiac, 50, 52,72,78,79,159 
Cirrhosis, atrophic, 356 
biliary, 363 
cardiac, 368 
Hanot's, 362 
hepatic, 356 
and anaemia, 7 
and diabetes, 367 
hypertrophic, 362 
Laennec's, 356 
pancreatic, 367, 376 
Cirrhose Cardiaque, 368 
Cloudy swelling, 383 
Cohnheim's hypothesis, 289 
Colitis, 170 
Commotio cerebri, 93 
Concussion of the brain, 93 
Congestion and oedema, 49, 361 
Contracted kidney, 48, 51, 60, 71, 238, 
387, 391, 392 
Contractile impulse, 83 
Contrecoup, 92 
Cor bovinum, 54 
Coronary arteries, diseases of, 75 
Corpuscles of Roussel, 8 
Craniotabes, 402 
Cylindroma, 270 
Cystitis, in prostatic hypertrophy, 338 
tuberculous, 219, 221 
Degeneration, amyloid, 235 
fatty, 50, 52, 64, 158, 382, 383, 384, 
385 
guttate hyaline, 238, 385 
and inflammation, 385 
waxy, 158 
Zenker's, 169 
Dementia paralytica, 254 
Diabetes, 374 
and cirrhosis, 367 
hepatic, 375 
phloridzin, 375 
renal, 375 
Dilatation of heart, 36, 45 
Diphtheria, 156 
Diplococcus intracellularis menin- 
gitidis, 141 
Dropsy, see Anasarca, (Edema, and 
Ascites. 
Dualistic hypothesis, 17, 32 
Dura mater, endothelioma of, 270 
Dysentery, amoebic, 173 
infectious, 171 
Embolism, in arteriosclerosis, 69 
of cerebral arteries, 97 
of coronary arteries, 77 
Embolism, in endocarditis, 37, 51 
fat, 114 
of mesenteric arteries, 124 
pulmonary, 40, 114 
Embolus, paradoxical, 114 
Embryonic rests, 289 
Emphysema, pulmonary, 149 
Empyema, 195 
Encephalitis, hemorrhagic, 203 
suppurative, 130 
End arteries, 38 
Endangeitis, syphilitic, 250 
tuberculous, 214 
Endarteritis, 58 
compensatory, 59 
syphilitic, 249 
Endocarditis, 33, 42, 147 
bacteriotoxica, 34, 35 
chronic, 42 
chronic mural, 52 
gonorrhoeal, 36 
malignant, 34, 35 
mycotica, 34, 35 
recurrent, 42 
rheumatic, 36 
tuberculous, 200 
ulcerative, 33, 35 
verrucous, 33, 35, 200 
Endometritis, puerperal, 134 
Endothelial cancer, 293 
Endothelioma, 270, 276, 284, 293 
Enteritis, tuberculous, 196, 208 
Epithelioid cell, 185 
Epithelium, experimental proliferation 
of, 290 
Epulis, 274 
Erosions, hemorrhagic, 304 
Erythroblastoma, 28 
Fallopian tube, chorio-epithelioma of, 
351 
tuberculosis of, 226, 229 
Fat, in blood, 382 
embolism, 114 
necrosis, 372 
Fatty degeneration, 50, 52, 158, 382, 
383, 384, 385 
of the intima, 64 
of the kidney, 238, 382, 383, 
384, 385, 390 
of the liver, 198, 354, 386 
of the myocardium, 2, 50, 52 
infiltration, 382, 385, 404 
Fibroma, 259 
of auditory nerve, 269 
of meninges, 269 
of pleura, 294 
of spinal cord, 271 
Fibrosarcoma, 275 
of meninges, 269 420 
INDEX 
Fibrosarcoma, of pleura, 294 
of spinal cord, 271 
Foamy organs, 137 
Fowls, leukaemia in, 20 
Frankel-Weichselbaum diplococcus, 145 
Friedlander pneumobacillus, 146 
Gall-bladder, carcinoma of, 321 
hydrops of, 320 
inflammation of, 318 
typhoid bacilli in, 167 
Gall-stones, 167, 318, 322 
Gangrene, diabetic, 382 
emphysematous, 137 
of the intestine, 122 
of the lung, 298, 300 
Gas phlegmon, 137 
Gelatinous carcinoma, 308, 324 
Genito-urinary tuberculosis, 217, 218 
Giant-cell, in Hodgkin's disease, 22, 24 
sarcoma, 273 
in tuberculosis, 185 
Glioma, 262, 263, 271 
Gliosarcoma, 265 
Glomerulonephritis, 162, 387, 391 
Glycogen, in the bundle of His, 83 
in diabetes, 380 
Gout and amyloidosis, 241 
Granular atrophy of the pancreas, 376 
kidney, 392 
Gumma, structure of, 242 
Haematogenous jaundice, 316 
Haematoma, extradural, 95 
subdural, 96 
Haematopericardium, 110 
Haematopoiesis, 13, 17, 19 
Haemoptysis, 189 
Haemosiderosis, 3, 361 
Halisteresis, 405 
Hanot's cirrhosis, 362 
Heart, aneurism of, 81 
block, 85 
contractile impulse of, 83 
dilatation of, 36, 45 
hypertrophy of, 36, 45, 51, 69, 74, 
155, 199, 370, 391, 396 
nervous control of, 49 
nodes of, 82 
physiology of, 49, 81 
relative size of, 199 
wounds of, 110 
Hemorrhage, cerebral, 87, 268, 396 
extradural, 95 
gastric and oesophageal, 360 
parenchymatous intestinal, 360 
subdural, 96 
Hemorrhagic nephritis, 41, 388 
Hepar lobatum, 243 
Hepatic diabetes, 375 
Hepatitis, interstitial, 243, 356 
Hepatization, 47, 143 
Hepatogenous jaundice, 316 
His, bundle of, 81 
Hodgkin's disease, 22 
Hour-glass stomach, 306 
Hydatiform mole, 349 
Hydrocephalus, external, 255 
internal, 141, 203, 268, 404 
Hydronephrosis, 336 
Hydrops vesicae felleae, 320 
Hyperplastic-elastic layer of intima, 60, 
393 
Hypertrophic cirrhosis of the liver, 362 
Hypertrophy, of the adrenal, 397 
of the heart, 36, 45, 51, 69, 74, 155, 
199, 370, 391, 396 
of the lung, 195 
of the prostate, 327, 331 
Hypophysis, tumors of, 270 
Iced liver, 370 
Icterus, 316, 358, 362, 363, 364 
Idiopathic cardiac hypertrophy, 51 
Immunity, to tuberculosis, 198, 210 
to tumor implantation, 290 
Infantile pseudoleukaemia, 404 
Infants, cardiac hypertrophy in, 55 
Infarction, 37, 48 
Infectious diseases, nephritisin, 383,387 
Infiltration, fatty, 382, 385, 404 
leukaemic, 16 
Inflammation, croupous, 156 
and degeneration, 385 
diphtheritic, 156 
and malignant growths, 289, 290, 
307 
necrosing, 157 
Insufficiency, myocardial, 53, 86, 146 
valvular, 44 
Intestine, amyloidosis of, 239, 240 
carcinoma of, 312 
congestion of, 48 
gangrene of, 122 
infarction of, 39, 122 
necrosis of, 39 
tuberculosis of, 196, 208 
typhoid ulceration of, 164 
Intima, in arteriosclerosis, 62 
fatty degeneration of, 64 
hyperplastic-elastic layer of, 60, 61, 
62, 393 
Islands of Langerhans, 376 
Jaundice, see Icterus. 
Joints, syphilis of, 248 
tuberculosis of, 234 
Keith, node of, 84 
Kidney, abscess of, 132, 338 
amyloidosis of, 236, 238, 240 INDEX 
421 
Kidney, in arteriosclerosis, 54, 71, 392 
atrophy of, 336, 356 
calculi in, 337 
congestion of, 48, 54 
contracted, 48, 51, 60, 71, 238. 387, 
391, 392 
in diabetes, 380, 381 
diseases of, 383 
elimination of bacteria through, 
132 
embolic contracted, 51 
fatty degeneration of, 238, 382, 
383, 384, 385, 390 
glycogen in, 380 
infarction of, 38 
large mottled, 390 
large white, 239, 390 
in scarlet fever, 162 
tuberculosis of, 206, 213, 218 
Kyphoscoliosis, 201 
Kyphosis, 153, 231 
Laennec's cirrhosis, 356 
Langerhans, islands of, 376 
Larynx, amyloidosis of, 241 
carcinoma of, 300 
syphilis of, 244 
tuberculosis of, 195 
Leptomeningitis, 137, 254 
Leucin in acute yellow atrophy, 353 
Leukaemia, 11 
acute, 18 
in fowls, 20 
lymphatic, 11, 13, 15, 18 
myelogenous, 11, 14, 15, 18 
and pernicious anaemia, 6 
splenic, 15 
Leukaemia, 13 
Leukaemic infiltration, 16 
Leukopoiesis, 13 
Lipaemia, in diabetes, 382 
Lipoids, in fatty degeneration, 386 
and proliferation, 291 
Liver, abscess of, 127, 173, 318 
acute yellow atrophy of, 353 
amyloidosis of, 236, 237 
atrophy of, 198, 353 
cirrhosis of, 356 
congestion of, 48, 368 
fatty degeneration of, 198, 354, 386 
infiltration, 404 
glycogen in, 380 
hyperplasia of, 198 
leukaemic infiltration of, 16 
nodular hyperplasia of, 354 
pseudocirrhosis of, 370 
regeneration in, 354, 357, 368 
secondary tumors in, 281, 313 
syphilis of, 242, 243, 253 
tuberculosis of, 206, 213 
Lung, abscess of, 131 
atrophy of, 356 
carcinoma of, 294 
congestion of, 47 
embolism of, 40, 114 
gangrene of, 298, 300 
hepatization of, 47 
infarction of, 39, 48 
Spirochaeta pallida in, 251 
syphilis of, 253 
tuberculosis of, 185, 205, 211 
Lutein cells, growth of, 350 
Lymphadenitis, syphilitic, 250 
tuberculous, 195, 197, 205, 207, 
208, 215, 217 
Lymphadenoma, 22 
Lymphangeitis, acute septic, 134 
Lymph-nodes, amyloidosis of, 240 
calcification of, 195 
in diphtheria, 157 
in Hodgkin's disease, 22 
in leukaemia, 14, 19 
myeloid tissue in, 6, 15 
progressive hypertrophy of, 22 
protective faculty of, 129 
in pseudoleukaemia, 21 
in rhachitis, 404 
tuberculosis of, 195, 197, 205, 207, 
208, 215, 217 
Lymphogranulomatosis, 22 
Lymphoid tissue, in leukaemia, 11,16, 21 
production of, 18 
relation to myeloid, 17 
Lymphoma, malignant, 22 
Lymphosarcoma, 22 
Lymphosarcomatosis, 20, 29 
Malignancy, 276 
Mamma, carcinoma of, 281 
Marrow, see Bone-marrow. 
Mediastinitis, 297 
Melanin, 277 
Mel anoblast, 279 
Melanoblastoma, 277 
Melanocarcinoma, 279 
Melanoma, 277 
Melanosarcoma, 278 
Meninges, hemorrhage into, 94 
tumors of, 269 
Meningism, 138 
Meningitis, epidemic cerebrospinal, 139 
suppurative, 130 
syphilitic, 248 
tuberculous, 202, 213 
Mesarteritis, 59 
Metaplasia, 324, 343, 358 
Metastasis, 276, 288 
Mitral insufficiency, 45, 46 
stenosis, 46 
Mole, pigmented, 277 422 
INDEX 
Mouse, tumors of, 285, 287, 290 
Munich heart, 55 
Muscles, gumma of, 243 
Myeloid tissue, in leukaemia, 11, 14, 15, 
16, 17, 21 
in lymph-nodes, 6, 15 
production of, 18 
relation to lymphoid, 17 
in spleen, 6 
Myeloma, 25 
Myocarditis, at auriculoventricular 
ring, 45 
in diphtheria, 158 
in idiopathic cardiac hypertrophy, 
52, 53 
rheumatic, 36 
in scarlet fever, 163 
in syphilis, 243 
in typhoid, 169 
in valvular disease, 36, 50 
Myocardium, abscess of, 132 
brown atrophy of, 199 
fatty degeneration of, 50, 52, 158 
gumma of, 243 
infarction of, 77, 79 
necrosis of, 77, 396 
tuberculosis of, 206 
Myogenic hypothesis, 50, 84 
Myomalacia, 77 
Myopathy, rhachitic, 404 
Naevus, 277 
Necrosis, endocardial, 35 
fat, 372 
intestinal, 39 
myocardial, 77, 396 
pancreatic, 306, 372 
Neoplasm, see Tumors, Carcinoma, 
and Sarcoma. 
Nephritis, 383 
experimental, 388 
hemorrhagic, 41, 388 
and hepatic cirrhosis, 368 
interstitial, 163, 390 
parenchvmatous, 160, 170, 198, 
383, 390 
scarlatinal, 162, 387 
Nephrolithiasis, 337 
Nerves, fibroma of, 261 
Neurofibromatosis, 259 
Neurogenic hypothesis, 49, 84 
Neuroglia, structure of, 263 
Neurogliocyte, 262 
New-born, cardiac enlargement in, 55 
Node, atrioventricular, 82 
Keith's, 84 
sino-auricular, 84 
Tawara's, 82 
Nodular hyperplasia of the liver, 354 
Nose, saddle-back, 247 
Nutmeg liver, 48 
CEdema and congestion, 49,361 
in idiopathic cardiac hypertrophy, 
53 
in nephritis, 390 
(Esophagus, carcinoma of, 296 
varices of, 360 
Orchitis, syphilitic, 243 
Ossification, disturbances of, 399 
Osteochondritis, 251 
Osteoid sarcoma, 275 
Osteomalacia, 405 
Osteomyelitis, suppurative, 133 
syphilitic, 247, 252 
tuberculous, 212, 233 
Osteoplastic carcinosis, 328 
Osteoporosis, 405 
Osteosarcoma, 275 
Ostitis, syphilitic, 247, 252 
tuberculous, 231 
Ovary, abscess of, 137 
tuberculosis of, 226 
Pachymeningitis interna hemorrhagica, 
96,' 254 
Palate, syphilis of, 246 
Pancreas, abscess of, 372 
amyloidosis of, 240 
apoplexy of, 372 
atrophy of, 375 
cirrhosis of, 367, 376 
necrosis of, 306, 372 
Pancreatitis, suppurative, 372 
Papilloma of the fourth ventricle, 269 
Paralysis, postdiphtheritic, 159 
progressive general, 254 
Paresis, 72, 254 
Periarteritis, tuberculous, 203 
Peribronchitis, tuberculous, 187 
Pericarditis, chronic, 53, 86, 370 
suppurative, 131 
Perihepatitis, chronic, 370 
Periostitis, syphilitic, 248, 252 
tuberculous, 233 
Periostium, sarcoma of, 272 
Peritoneum, carcinosis of, 282, 315 
Peritonitis, suppurative, 137,183,368,372 
tuberculous, 229, 367 
Pharynx, carcinoma of, 299 
syphilis of, 244 
Phlebitis, obliterans, 198 
tuberculous, 214 
Phlebosclerosis, 126 
Phloridzin diabetes, 375 
poisoning, 386 
Phosphorus poisoning, 354, 386 
Phthisis florida, 194 
renalis, 218 INDEX 
423 
Placenta, tuberculosis of, 207 
Plants, "tumors" of, 288 
Plasma cell, 256 
Plasmacytoma, 28 
Plethora, 55 
Pleura, tumors of, 282, 292, 295 
Pleurisy, 195, 295, 370 
Pneumonia, aspiration, 299, 300 
cheesy, 192, 194 
chronic, 148 
gelatinous, 194 
lobar, 143, 169 
lobular, 157, 169, 299, 404 
tuberculous, 187, 191 
white, 253 
Polyp, uterine, 349 
Polyserositis, 370, 371 
Porphyry spleen, 23 
Portal circulation in cirrhosis, 359, 363 
vein, thrombosis of, 125, 368 
Pott's disease, 230 
Precancerous stage, 287 
Primary contracted kidney, 392 
Prostate, adenoma of, 334 
carcinoma of, 326 
hypertrophy of, 327, 331 
normal anatomy of, 333 
tuberculosis of, 217, 226 
Prostatism, 336 
Psammoma, 271 
Pseudocirrhosis, hepatic, 368 
Pseudoleukaemia, 21 
infantile, 404 
Pulmonary artery, arteriosclerosis of, 
73 
embolism of, 114 
thrombosis of, 119 
vein, tuberculosis of, 214 
Pulsus irregularis perpetuus, 86 
Pyaemia, 130 
Pyelitis, 338 
Pyelonephritis, 338 
Pylephlebitis, 127 
Pylorus, carcinoma of, 311 
stenosis of, 312 
Pyonephrosis, 338 
Pyopneumothorax, 195 
Rectum, carcinoma of, 315 
Regeneration, of the bile-ducts, 357 
of the blood, 4, 13 
of the bone-marrow, 4 
and carcinoma, 368 
of the liver, 354, 357, 368 
Retina, melanoma of, 279 
Rhachitis, 399 
Rheumatic endocarditis, 36 
myocarditis, 36 
nodules, 36, 51 
Rickets, see Rhachitis. 
Rosary, rhachitic, 399 
Roussel, corpuscles of, 8 
Saddle-nose, 247 
Sago spleen, 235 
Salpingitis, gonorrhoeal, 256 
tuberculous, 226, 229 
Sarcoma, of bone, 272 
of brain, 267 
giant-cell, 273 
glioblastic, 265 
in mouse carcinoma, 290 
osteoid, 275 
periosteal, 272 
of pleura, 294 
round-cell, 274 
spindle-cell, 272 
Scarlet fever, 160 
nephritis in, 162, 387 
Scoliosis, 201 
Secondary contracted kidney, 391 
Seminal vesicles, secondary carcinoma 
of, 328 
tuberculosis of, 217 
Septicaemia, 128 
puerperal, 134 
typhoid, 168 
Siderosis, 3, 361 
Sinus-thrombosis, 121 
Skin, carcinoma of, 284 
Skull, fracture of, 95 
Softening of the brain, 254 
Spina ventosa, 233 
Spinal cord, tumors of, 271 
Spirochaeta pallida, 250, 251, 258 
Spleen, amyloidosis of, 235, 240 
congestion of, 48, 370 
infarction of, 38 
myeloid tissue in, 15 
porphyry, 23 
relation to amyloidosis, 241 
sago, 235 
Spirochaeta pallida in, 251 
tuberculosis of, 206, 213 
waxy, 236 
Splenic anaemia of children, 404 
Splenomegaly, 14, 21, 249, 253, 261, 
362, 363 
Spondylarthritis deformans, 153 
Stigmata, gastric, 304 
Stomach, carcinoma of, 307 
congestion of, 48 
ulcer of, 301 
Syphilis, 7, 241, 242, 258, 366 
acquired, 242 
congenital, 251 
secondary, 249 
tertiary, 242 
Syringomyelia, 266 424 
INDEX 
Taboparalysis, 258 
Tamponade, cardiac, 110 
Teratoma, 352 
Testis, chorio-epithelioma of, 352 
syphilis of, 243 
tuberculosis of, 225 
Thoracic duct, tuberculosis of, 214, 216, 
217 
Thorax, emphysematous, 152 
phthisicus, 200 
Thrombophlebitis, 119, 135 
Thrombosis, 116, 117 
in aneurisms, 99 
in arteriosclerosis, 69, 118 
of cerebral arteries, 97 
coronary, 77, 79 
etiology of, 117 
in idiopathic cardiac hypertrophy, 
52 
portal, 125, 368 
pulmonary, 119 
Thrombus, ball, 44 
Thyroid, amyloidosis of, 240 
Tongue, amyloidosis of, 241 
carcinoma of, 300 
Tonsils, in diphtheria, 156 
in scarlet fever, 160 
Toxinaemia, 129 
Trachea, amyloidosis of, 241 
secondary carcinoma of, 297 
Tricuspid insufficiency, 44 
Tubercle bacillus, in the blood, 197, 
198, 209, 213, 220, 222, 229 
entrance of, 207 
in Hodgkin's disease, 24 
lesions produced, 185 
in the lymph-stream, 198, 208, 
210, 220 
virulence of, 193 
Tubercle, miliary, 185 
solitary, 204 
Tuberculosis, acute miliary, 211 
aerogenous, 211 
and anaemia, 7 
and carcinoma, 295 
exudative, 193 
febrile movement in, 217 
genito-urinary, 217, 218 
haematogenous, 197, 198, 209, 213, 
220, 222, 229 
and hepatic cirrhosis, 366 
and Hodgkin's disease, 24 
immunity to, 198, 210 
inspiration, 211 
latent stage of, 209 
lymphogenic, 198, 208, 210, 220 
lymphoid stage of, 210 
metastatic, 202 
and perihepatitis, 371 
productive, 193 
Tuberculosis, pulmonary, 185 
etiology of, 200, 209 
urogenetic, 220 
urogenital, 218 
Tubular stenosis, 43 
Tumor albus, 234 
Tumor-like affections of the lymphatic 
and haematopoietic systems, 21 
Tumors, of the brain, 263 
of the cardiac valves, 44 
of the central nervous system, 263 
chorio-epitheliomatous tissue in, 
352 
classification of, 260 
etiology of, 287 
growth of, 285 
of the hypophysis, 270 
and inflammation, 290 
and irritation, 287, 290 
of the mouse, 285, 287, 290 
of the nerves, 261 
and parasites, 287, 290 
of plants, 288 
of the spinal cord, 271 
transplantation of, 285, 287, 290 
Typhoid bacilli in the gall-bladder, 167 
carriers, 168 
fever, 164 
and amyloidosis, 241 
and hepatic cirrhosis, 366 
septicaemia, 168 
Tyrosin in acute yellow atrophy, 353 
Ulcer, gastric, 301 
Ulcus callosum, 306 
Unitary hypothesis, 17, 28 
Ureter, tuberculosis of, 219 
Urogenital tuberculosis, 218 
Uterus, carcinoma of, 340 
chorio-epithelioma of, 346 
polyp of, 349 
tuberculosis of, 212, 217, 226 
Vagina, tuberculosis of, 226 
Valves, lesions of, 33, 42 
Vascular system, amyloidosis of, 237, 
239 
diseases of, 56 
in nephritis, 392 
Veins, amyloidosis of, 237, 239 
sclerosis of, 126 
tuberculosis of, 214 
Vertebrae, tuberculosis of, 230 
Vocal cords, carcinoma of, 300 
Waxy spleen, 236 
Weichselbaum, meningococcus of, 141 
Wenckebach, bundle of, 84 
Zenker's degeneration, 169 MAH 1 8 1915