qbeedie citaelt : Raaeapiiats : : cece = - CRF PA aa tae et SS vivre hts area ea cane Nees NG ans Sore ‘4 oi nik hate) eae aes ests es State 2% .ao Sos me atatatg eq dsgeo4 Eggs Rees Rieti geariteetit a a Saeed aay see tet Sag sasg Ka cee Sete : ayers eal 4] Pa feagesaae Rea Bares eee sa ataeaiaatiaier ey Reet COST HtRDRetReeespepnoeesy Ege select a4y pata sseu ees eheg ted se epthisactaa aye yacey tae tesge rere ge eae Peake eee Nt \<, as no ¥ $4 UZ pasaas ty 3s, iidiieoseniist aus (A Rar eater Weeds trou SHG aat as oF Reinet raieete este OI aS senate 3, Bxtg Pesonastesse sec seater sees teae ange sere ey Sea IRN a Maange Seen ay ae Sesh aes rapists ene Sag erk yee cartes eet bebepreabetayeheret at Gai sarae oH ise eae. preroep uuMagnsanens cu ghennrt "Dal MA Se ys Prat hees Oates Seis monet i ae sae ees nate as a i Sree Seton ¥, ie 4 Q sacs HS siaheseie Sea testa WELD GaSe MR PERE PEELS, ox a ead iM ae Paoisneiaiciiaieis apie eee att ahaha ‘ eornaty a Perera ttre eos Seo su et MyDS Brie seein ne Bs i cS ieseke ai see Be thetets tesed ties Rares rbsewea Deobetahoeetenvee esitieesey esas fe Stopetebeeh AQ Se5e sate peeae taser setae sie Patt ere een ee eae phen aes ASSES ere eee eet ere) Cy pieteieiee tedan gt etic prprnepresyt: pia tena tessa wis 3 Cie ateleteaeeie tes cet) nied * ena aa ie = ote es nae ated ne BR is Ay aaa eta rea o a Maas Sta ed | ig peninrneticd ase tk yx bert es Se yee aS 5 5C eS Beseseriererisg? aaiitstet nas sd eesasasases gaa Mielec oats Ch eee ee Masai seesaiasias eee etait PAA ADS Ee ro Aa Rear pete eta eee Ta ye is aS SASS: SP arersreroceepe Rt oat a Ria tasass ataseateheyties Gaited, isteie c nS ey o rick beeen eae Bane ¢ = KS u 4 Siero seh snreseas dae tere maecisteriea at Se anes - Vet a eeetee cS eet Pat aes tia ey on me io rScs ey A a ty S naa ae aed eea saa cod ee ~ en men nti he eset esahtts Me ee tat teeth eae; toto te re oa Paes aR se ‘ oe — te a Cae ae tyes coc Crea anetet aes St oe ot ae or ton Dearie ernie tok og iy iitase ra ie 5 aerated nats ecarecsrss seltaiedie o cee eek coneeadsees ei ase fos 3 aay rots yeah: Sania ote PS Ay aa Nee a Taha sah paisa fat aoe a aa iterates pana ae ator eda pee Cte et kk ate) > aa att ea taatutae tae tet tania tia ier eerere tia feataaaaietseat ta Nese aa5e5 eighdochisiete eats. pee ye Lertese 1d a Sp Sats Sg Sea ea yg aS eget, Aeiicn tae ictesy iets oaanes coger ude stata tata “4 ts iasge party ate cto a sasese eianris Radek tdid donned st rt aa ahaa hein tains aaa, fea aad a egg ear thst ee see tte ye sada oe ed ahaa aS heh ha Sas de ot at ot ee toe mMatatettets Sajna Sates tite§ f 17 4 ‘at at etek ater kad on aoe ak akan aa aoe be ne Mekripaieonets thane Saha aa aaa ax ocuaea eet Oke ata veces Kea es, one oa mee hein arm eae Gn iy PORSCHE rere renege Ce Sse leiasaieae the ba toenail Sie ey We Pegs ies We pe peor star est on bee NA aS os 3 See ed ee Stes Sess ated eden inset igagi re ccaca tears eohet shad aeee eel ete ed oa 1d odd Haare aed aang et oe baSeseS SeSaha Sa Sed ety esate Se safe Cpe Leer oo we 5 rare Ware ee ieee aes. wy td Sesh, EPs ae Baie oa fetejetesciat) Brobetet ores é See eee er ete eater ee FASS aad sa Sat ga ae toed Sasa Ta Ae ane b bebhecetbretecpeoL ator sracbosteter heed peeesty etal ater tyr ye ate aarp Seon c on kat okt one eee sonar) 2 Sa eserss relents etter prereee pe ptars Ga er Spibircetebt at Skaterster tip etpiotp ersten reter ear aee ye oeresesay “ hehehe tt oc ested erat ret ere easere one tatsa oes t sees a brats eoatass 2 eorertreea raat eet ereraes Seles raesel eats caesarean sane aea katate os epivereaots Dphad tbeteheketpteeateh been shen aPce ue pe atses No Hah Rsapenies epaoanea ects Sehetge) OE a i) beMIeS raat anes fe ate tetete’ ete kedetadeds Cees Cory etee esate ‘| nate ese peseeees Peete peers e ee! aot seaeae gt atnts tesa aod aod tas tie PP ees saia%s Sleiaticfes Aa eto eS te hee ceo toetens (etetite setae sig Tobeutshortre-ptabebeteratet ees saecracaoeoteeonse etait ae eieetsess Means oct yas ¢ a4 S Sea Seta ea Sea Coe 2 Srieietes 2 ey SSE yee Mea (or SG there cba pees a eet oe onaes ieease® ae Cony Sc i) ra eae) *, cos Pl ae x - Fi Yat Sep Ee Sees Sree suceen a a ne vote sSebe CORNELL UNIVERSITY. THE Roswell P. Flower Library THE GIFT OF ROSWELL P. FLOWER FOR THE USE OF THE N. Y. STATE VETERINARY COLLEGE 1897 8349-1 my MANUAL OF PATHOLOGY INCLUDING BACTERIOLOGY, THE TECHNIC OF POSTMORTEMS, AND METHODS OF PATHOLOGIC RESEARCH BY o W. M. LATE COPLIN, M.D. PROFESSOR OF PATHOLOGY AND BACTERIOLOGY, JEFFERSON MEDICAL COLLEGE, PHILADELPHIA}; PATHOLOGIST TO JEFFERSON MEDICAL COLLEGE HOSPITAL AND TO THE PHILADELPHIA (BLOCKLEY) HOSPITAL; BACTERIOLOGIST TO THE PENNSYLVANIA STATE BOARD OF HEALTH THIRD EDITION, REVISED AND ENLARGED With Three undred and Thirty Mllustrations and Seven Colored Plates MANY OF WHICH ARE ORIGINAL PHILADELPHIA P. BLAKISTON’'S SON*@& CoO, IOI2 WALNUT STREET 1900 Nolb 4 COPYRIGHT, I900, By P, BLAKISTON’s Son & Co. RB ltl C 7B IG oo es WM. F. FELL & CO., ELECTROTYPERS AND PRINTERS, 1220-24 SANSOM STREET, PHILADELPHIA. TO W. W. KEEN, M.D. PROFESSOR OF THE PRINCIPLES OF SURGERY AND CLINICAL SURGERY IN THE JEFFERSON MEDICAL COLLEGE, AS A TOKEN OF RESPECT AND GRATITUDE THIS VOLUME IS DEDICATED BY THE AUTHOR. PREFACE TO THIRD EDITION. In presenting to the profession and students of medicine the third edition of this work the author wishes gratefully to acknowledge the cordial reception that was accorded the last edition. Although over twice the size of the first edition, the second was exhausted in nearly the same length of time; it appeared late in the autumn of 1897 and was exhausted in the following year. The pressure of other duties rendered it impossible for the author to give the work the revision that seemed necessary, and therefore it has been out of print for nearly two years. During that time the author has occupied his spare moments in revising, rewriting, and rearranging the subject-matter. A number of the old illustrations have been replaced by new, and many original drawings have been added. The author's conviction that properly prepared figures are of the utmost importance in elucidating the subject under considera- tion remains unchanged ; in accord with this view the number of illustrations has been increased from two hundred and sixty- eight to three hundred and thirty; practically all those added are original. For the first time, a few colored plates are intro- duced. The chapter on postmortems has been revised, and new methods have been introduced in the chapters on technic. Bac- teriologic technic has been placed in a chapter by itself, and the technic of blood examination has been transferred to the chapter on the blood, with which it properly belongs. Special technic has been added throughout the book ; whenever it was necessary to adopt any special means for demonstrating a reaction or for satisfactorily staining morbid products, the method has been v vi PREFACE TO THIRD EDITION. given with the consideration of the materials to be treated. New chapters have been added, including the following: The thymus body, ductless glands, muscles, bones and joints, and the ner- vous system. These, added to the very much lengthened chap- ters originally present, have increased the size of the volume by a little over one-third. The chapter on diseases of the nervous system has been written by Dr. H. F. Harris, Associate Professor of Pathology in the Jefferson Medical College, whose experience as a clinical teacher of diseases of the nervous system and work as an investigator have fitted him for the consideration of the subject with which the chapter deals. The author has been placed under many obligations to Dr. Harris for his supervision of the additional drawings, many of which have been made under his direct superintendence. The author is also greatly indebted to Dr. Randle C. Rosen- berger for aid in the compilation of stain reactions and biologic peculiarities of the bacteria, as well as for arranging the index of parts land II. Dr. Frederick J. Kalteyer has aided by kindly loaning specimens for illustrations. The table on the blood occupying pages 448 and 449 is largely the product of his energy. Mr. Duncan L. Despard has assisted in the preparation of the index. The reproduction of the new illustrations, both in black and white and in colors, has been trusted entirely to the publishers, to whom the author is under many obligations for the careful execution of this most difficult task. In conclusion the author wishes to state that the object of the book has not been changed, and that the present edition, although greatly enlarged, remains exactly what the author intended the previous edition to be: namely, “ not a treatise or book of reference, but, as its title indicates, a manual that the author hopes may be useful in the laboratory and postmortem room and in clinical diagnosis by the aid of the microscope.” PREFACE TO SECOND EDITION. During the winter of 1894 and 1895, Messrs. P. Blakiston, Son & Co. published, in serial form, abstracts of the writer’s lectures, entitled “ Lectures on Pathology.’ At the close of the college session the fasciculi were bound, and the resulting volume placed on the market. Very much to the surprise of the publishers, as well as of the writer, the edition lasted less than nine months. It was exhausted at a time when the teach- ing of the college year precluded the revision which the matter so much needed. During the past six months the entire book has been revised, the larger part having been entirely rewritten. The first edition contained 250 pages and 51 illustrations ; the present volume, in the face of every effort to condense without sacrificing accuracy, has reached 638 pages and contains 268 illustrations. The most difficult problem has been to keep the volume from assuming undesired dimensions, and, now that the work is completed, the writer wishes to say, parenthetically, that a volume of twice the size could have been produced with prob- ably less labor. Being practically a new book, there are, no doubt, typographic and grammatic errors. The writer acknowl- edges in advance his appreciation of any communication calling his attention to such lapses. In the publication of the original fasciculi the writer was favored by the aid of Professor Kyle and Dr. Bevan. Professor Kyle wrote the fasciculus on “Tumors,” and Dr. Bevan the article on “ Bacteriology.’ In the revision of the work both articles have been somewhat enlarged, but the thoroughness of the original has not demanded any extensive revision. There have been made some additions and a rearrangement of subjects, in order to secure greater conformity with the remainder of the vu viii PREFACE TO SECOND EDITION. book. In the original, acknowledgment of the assistance was given with the fasciculi ; it is now incorporated here. Practically, all the added illustrations appear for the first time in a work on pathology in the English language. The source is credited with each cut. Of the original illustrations it is not the author’s province to speak. They have been prepared in the writer’s laboratory from specimens and slides of which the clinical and pathologic histology were fully known. In this connection the writer wishes to acknowledge the invaluable assistance of Professor H. F. Harris, who personally superin- tended the execution of most of the original drawings. Miss E, G. Harding, artist, has, with great patience, made the original drawings, often redrawing an illustration a number of times before submitting it for approval. To Drs. R. C. Rosenberger and W. P. Read the author wishes to acknowledge valuable aid in proof-reading and other detail work in the completion of the volume. Instead of the usual method of inserting a table of illustra- tions, arranging the figures in the same order as they appear in the pages, an alphabetic list, by subjects, is inserted, for the arrangement of which I am indebted to Mr. L. H. Prince. In conclusion, the writer wishes to submit the volume, not as a treatise or book of reference, but, as its title indicates, as a manual that he hopes may be useful in the laboratory, post- mortem room, and in clinical diagnosis by the aid of the micro- scope. To attain as fully as possible the last-named aim, the chapters on the microscopic examination of tissues, blood, and urine have been most fully illustrated. Thanking the profession for its kindly reception of the previous edition, this volume is respectfully submitted for consideration. TABLE OF CONTENTS. PART I,—TECHNIC, CHAPTER I. PosTMORTEM EXAMINATIONS,. . 2 2... ee Description of Instruments Needed, ER ee ade 2 11. Long, Thin, Brain Knife, © Gam Gabe acess BE Mon aati be! ae Gee em Gacy Ge Sy ge. 0B 12. Enterotome, .. .- ty Saran eho ce as ss Pate Rig wists Gee! sae Mca “eB it Pee phe kk cae wba ee eS eee Ce S Be 14. Dissecting Forceps, . - - - ee ee ptt tt ttt 37 15. Malletor Hammer, .. - . - ee ee tt 37 16. Heavy Line Indicating Course Taken enby Saw-cut in So- called Undertaker’ s Method,. .. . fel He es, ion. 3°39) 17. Circumferential Saw- ‘cut, 39 18. Wedge- ee Calvaria Removed byt the Line of ‘Saw- cut Recommended, 40 19. Chisels, . . - ; : 41 20. Myelotome, soe ee 42 21. Scalpel with Blade Shaped Somewhat Like a , Bistoury, . es -. 42 22. Double Saw for Sawing through the Laminz of Both Sides at Once, .. 44 xili LIST OF ILLUSTRATIONS. . Bone-cutting Forceps, .. . . Postmortem Needles, . BAK . Metallic Table for Fixation and Paraffin Infiltration, ee . Block for Mounting Tissues Infiltrated with Paraffin, . . Properly Trimmed Block, fe 2 . Method of Applying Paper to Block, . Block Showing Tissues in Position, é . Mounted Tissue Ready for Sectioning, a . Naple’s Paraffin Bath for Infiltrating Tissues in n Paraffin, . Forceps Convenient for Handling es Blocks of Tissues, and Sections, . . Laboratory Microtome, : ewe oa Chk . Small Microscopic Scissors,. . . 1... 2... s. . Ryder Microtome,. . . Ranvier’s Microtome (Lusty ated from Gould’s Dictionar: )5 . Minot Microtome,. .. .. . Ss ise "soe Haste! 4 Be RS Ne as . Drying Oven, . . ra « Needles and Brush Suitable for Handling Sections, 8 . Dish for Removing Paraffin and Corrosive Sublimate and for Dehydrating, Dropping Bottle with Barnes’ Dropper, Which Closes the Mouth of the Bottle Like a Rubber Stopper,. . . . 2-1 7 ee ee eee . Proper Size Labels for Labeling Microscopic Slides, . . . Microscope Suitable for General Pathologic and Bactericlogic Work, . Moist Chamber for Potato Culture, . . - a . Instrument for Cutting Plugs of Potato for Potato Cultures, ‘ . Agate-ware Water-bath (Farina Kettle), gs 8 . Agate-ware Funnel for Filtering Hot Fluids, 3 . Test-tube Basket, Made of Tinned Metal, for Holding Test- tubes, | . Double Wall Hot-air Sterilizer, for Sterilizing Test-tubes, Glassware, and Other Laboratory Appliances and Instruments, . . Diagram of Interior of Hot air Sterilizer (Copiin and Bevan), . Apparatus for Filling Culture Containers, . ‘ - Arnold’s Steam Sterilizer for Sterilizing Culture Media, etc., . Arnold’s Steam Sterilizer, Boston Board of Health Form, . Autoclave, or Digestor, Used for Sterilizing by Steam Under Pressure, é . Blake Bottle Used for Bottle Plates os and Bevan), . gd @ Dish: Devised: by Petry, 09.94.05. . ca aa is ny 8 Sey we BS ae we . Platinum Inoculating Needles Mounted in Glass Rods,.. . . - Method of Holding Tubes, Cotton, and Platinum Wire while Inoculating Solid Media (Koch’s Method, Mod? ified from Woodhead), . Method of Holding Tubes, Cotton, and Platinum Wire e while Tnoculating Liquid Media, . Apparatus for Counting Colonies, . Hesse’s Aeroscope, and 63. ‘Two Forms of Stewart's s Cover-glass F “orceps, . Kalteyer’s Cover-glass Forceps, ‘ . Novy’s Apparatus for Anaerobic Cultivation in Plates and Test- tubes, : . Sternberg’s Anaerobic Culture-tube, I et . Wright’s Method for Anaerobic Cultivation in n Liquid Media, e3 . Drop-culture Slide, . . eee . Small Incubator Sufficiently Large for Individual Work, Wie, toate lh «2. Ge . Apparatus for Holding a Mouse or Rat for Inoculation (Devised by Dr. Lydia Rabinowitsch and Dr. Voges), . - Koch’s Syringe for Hypodermic, Intraperitoneal, and Other Injection Methods for Inoculating Animals, i Spatula Used for Searing the Surfaces of Organs Before e Making Incisions into Their Interiors for oe Culture Material, . Sternberg’s Flask, . Kitasato’s Filter, 100 IOI 105 107 108 109 IIlI Ill LIST OF ILLUSTRATIONS. XV FIG. PAGE 75. Bacillus Typhi cee 8 By hl gD see Tg 76. A Positive Reaction, . ose Bod igh Sam, 114 77. A Pseudo-reaction, Ears anise tee 115 7 Water Centrifuges 2: d eoiis ek owe a ee ne 119 79. Conic Glass Suitable for the Sedimentation of Urine (Coplin and Bevan),. 120 80. Centrifuge with Hematocrit Attachment, . . 120 81. Phantom and Distorted Red Blood-cells Found in Urine, Most Commonly That of Renal Hematuria (Zandois), 2. 2... 123 82. Blood-cells in the Urine (Gould), . . . 123 83. Blood-cells in the Urine, Lymph- -corpuscles, Leukocytes or Pus. cells, and Crystals of Triple Phosphate (LandOIs), ig 8 oe ee eee a ere} 84. Pus-cells in Urine (Gould), . . lala 223 85. Epithelium from the ree, Part of the © Urinary Apparatus, Mostly fromthe Bladder, 2 3-2 a0s-y 24 Ae ek Re 123 86; ‘Renal. Epithelmim, 2 sj a3 bee Geb ea 123 87. Seminal Elements, Some of Which May be Found in Urine, gS ey eo Teg 88. Illustrating the Formation of Casts pene), fg ik ee Pa TOR 89. Epithelial Casts (Zandois),. . Bae Ee Be oe oe ee go. Blood-cells and Blood-cast (Landois, e 6.9 oe Se ee a se eed le 125 gi. Tube Casts (Zandois), . . . Sieben SS Ue ap ae anh Ae ve NES 92. Granular Casts (Zando’s), 2. 2 125 93. Urinary Casts (Zandois),. . . i) 5) Go 25 94. Crystals of Uric Acid; Bacteria, Molds, and Yeasts ts (Lanois) ho ae oe CEZS, 95. Some Forms of Uric Acid (Lanois), a ee es ek kk Se we . 126 g6. Acid Ammonium Urate, .. 2... 0... ee 126 97. Hippuric Acid. Four-sided Prisms with Two or Four Beveled eee (Gould), .. 126 98. Some Deposits in Acid Fermentation of the Urine (Landvis), a were te (ao HT 99. Some Deposits from Ammoniacal Urine, . . teh oe) SEP? Ioo. Whetstone and Irregular Crystals’of Uric Acid (Landis), . the & BP AERT 1o1. Ammonium Urate. ‘+ Hedgehog’’ Crystals (Gould),. . . 2... . 127 102. Stellate and Feathery Crystals of Triple Phosphate (7ysoz),. . . . . . 128 103. Forms of Crystals of the Ammoniomagnesium Phosphate ( Zysoz), ... . 128 104. Ammoniomagnesium Phosphate (Triple Phosphate) Saou ) seh of 28 105. Magnesium Phosphate (Gould), . . Sg @ « 128 106. Amorphous Granules of Calcium Carbonate (Gould i dress ais epee ee oe NS 107. Oxalate of Lime, . . 129 108. Amorphous Granules, Wedge- shaped Crystals, Some Arranged i in Roses, of Calcium Phosphate (Gozl?),. . 129 109. Dumb-bell and Octahedral Crystals ‘of Calcium ‘Oxalate ( Gould is : 129 110. Calcium Sulphate; Elongated Transparent Needles or Tablets ‘(Gould ) 129 111. Crystals of Cystin and Oxalate of Labi Bp ig Bs 129 112. Leucin and Tyrosin,. ... . SR eee 2 ewe & & eos TBO 113. Leucin and Tyrosin,. . . . ) ee ee ee ee ee 130 rrq, Cystin (Gould), a ee ee a Re ee ae ae “ZO 115. Cholesterin (Landots), . 6 6 0 ee ee ee ee ee 130 116; Indipo (Gould), 2 2 ee see SR Ee ee we ep ZO 117. Squamous Epithelium,. . . . ooh Bi ws She en bare, wa ee, oe Gee EBT 118. Curschmann’s Spirals (Schmaus) i, pl ee a ee ew ee a eS Be 119. Charcot-Leyden Crystals (Zandots), . . 6 ip a tg a ee ye, BB 120. Propagation by Fission (Colin and Bevan), ; ey me ey ew 147 121. From Culture of Bacillus Deo es and Bevan), od ye ie oe AB 122. Bacillus Butyricus, .. . hus see doge ee AS 123. Bacillus Acidi Lactici, . . . . : : : sore es 152 124. Actinomyces (Ray Fungus). From Bovine " Actinomycosis (Coplin and Bevan), . . ee ee ee ee ee 160 125. Favus from a Mouse (Coplin and Bevan), ae Re Bg ke eS ws. 163 126. Microsporon Furfur (Coplin and Bevan), i Pe eee Boh ow 163 127. Saccharomycetes Cerevisice (Coplin and Bevan), . ica welge A ee ee ee TOK Xvi FIG. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160, 161. 162. 163. 164. 165. 166. 167. 168, ~ 169. 170, 171. 172. iy: 174. 175. 176. 177. LIST OF ILLUSTRATIONS, Saccharomycetes Albicans (Thrush Fungus) (Copiin and Bevan), é Diagram Illustrating the Nomenclature of Schizomycetes Based en Their Morphology (after Schenk), tonne Diplococcus of Gonorrhea, Gonococcus (Coplin and Bevan), Diagram of the Diplococcus of Pneumonia, Illustrating Relation of. Cap: . sule to the Contained Germ (Coflin and Bevan), Micrococcus (Staphylococcus) Pyogenes Aureus ia and Bewn), Streptococcus of Erysipelas (Copii and eee é ua Bacillus Gedematis Maligni, ‘ Bacillus Anthracis (Coplin and Bevan), : Bacillus of Symptomatic Anthrax oes and i Bevan), ; Bacillus of Rhinoscleroma, . Bacillus Mallei (Copliz and Bevan), : Bacillus Tuberculosis (vom Jaksch), 5 ra Diagram Illustrating the Forms of Bacillus ‘Tetani (Coplin and Bevan), ‘ Bacillus Typhosus, Showing Flagella ( Gould )» ote . Bacillus Typhosus (Coplin and Bevan), ‘ Bacillus of Influenza, . . Bacillus of Leprosy (Coplin and Bevan), Bacillus Syphilidis (Lzstgarten), : Spirillum Tyrogenum (von Jaksch), : Spirillum of Cholera (Copflin and Bevan), Spirillum of Asiatic Cholera (von Jaksch), . . Spirillum of Relapsing Fever (Spirochzeta Obermeieri) (Coplin and Bevan), Coccidium Oviforme from the Human Liver (after Leuckart.— Gould), Distoma Hepaticum, Bilharzia Hzematobia, Male and Female, the Latter in the Canalis Gynz- cophorus of the Former (after Leuckart. —Gould ), soy ly 48 Ascaris Lumbricoides and Eggs (Copiin and Bevan), . Oxyuris Vermicularis (Coplin and Bevan), ena te Trichina Spiralis (after Leuchkart), . . Cephalic Extremity of Dochmius Duodenalis, Profile and Front View (after Leuckart. roamed. ‘ ‘ ee. i Men se te ape Filaria Embryo, : Tzenia Saginata (Gould), ‘ Cephalic End of Tzenia Saginata, . . Head of Tzenia Solium. On the Right, Egg of Tenia Solium (Gould), Cysticercus Cellulosze. Completion of Head Formation Me Leuckart. —Coplin and Bevan), . . Bothriocephalus Latus (after ‘Leuckart.— Gould i : ; Free- ae Embryo of the Bothriocephalus Latus (after ‘Leuckart, _ Gould), . . Club-shaped Head of the - Bothriocephalus 1 Latus 5 (after Leuckart.— Gould ), , , e Tenia Flavopunctata, ; ey i Tzenia Echinococcus (after Leuchart. _Coplin and Bevan), : Hydatid Cyst, Showing Daughter Cysts, yk es Echinococcus. A ae of Scolices, Echinococcus, ‘ Echinococcus- hooklets, Acarus Scabiei and Portion of Epidermis Showing the. Burrows with Con- tained Eggs (after Leuckart.— Gould), . Pediculus Pubis, Illustrating Different Forms of the Malarial ‘Organisms with Their Stages of Development (Tyson’s ‘* Practice of commas. aii Fatty Infiltration of the Liver, Pseudohypertrophic Muscular "Paralysis (Fliitterer), Liver Cells Showing Fatty Infiltration (Schmaus), Amyloid Liver (Semidiagrammatic) (Aindfleisch), PAGE 165 166 167 168 170 172 175 176 176 178 179 180 182 183 183 185 188 189 190 1g IgI 192 193 196 196 197 197 ; . 198 199 200 202 202 203 203 204 204 204 205 205 206 207 207 208 209 211 213 226 227 227 228 _ LIST OF ILLUSTRATIONS. XVil FIG. 178. Section of Lung Showing Infiltration of the Connective Tissues of the sie Alveolar Wall by Coal-dust (Anthracosis) (/eimdfleisch), . . 2... 232 179. Section of a Lung Showing Chalicosis (Schmaus), . . o 23 180. pen aera! of the Epithelial Lining of the Kidney Tubule © (lit COREU Vas: ae se 242 181. Granular Degeneration of a Muscle- fiber (Schmaus), og be ee ¥ os a 182. Cloudy Swelling of the Liver Cells (Schmaus), 1... 6... 0, . 242 183. Fatty Degeneration of the Liver Cells (Schmaus), Seg wee eg 243 184. Confluence of Two Tubercles. Section of Lung, . . 253 185. Section through a Part of a Vein with Its Contained Onganizing Thrombus (Schmaus), — . 271 186. Transverse Section ‘of a Thrombosed Blood- vessel in Which Organization and Canalization of the Thrombus Are in Progress,. . . . . . . 273 187. Leukocytes of a Aas pee 646 2s nee Se ee ee e285 188. Pus-cells, . . Sas ah de Get Ke eb Boe Soe Bae So Se 280 189. Lymphoid Cells, aan 287 190. Karyokinetic Figures Observed in the Epithelium of the Mouth | Cavity of of _ a Salamander (Sféh4r) . . 297 191. Cellular Elements of Granulation Tissue (Schmaus), pw aoa Goes apa? 290) 192. Granulation Tissue (Schmaus), . 6. 6 6 ee ee ee ee ee 300 193. Formation of Capillaries (Zandozs), . . it & 2 BOT 194. Section through the Border of a Healing Wound (Rindfleisch), og) ate B02) 195. Papilloma (Gould), . . oe 4 « 312 196. Papilloma with Tendency toward Villous Formation (Schmaus), o& dot BEB 197. Adenoma of the Cervix Uteri,. . . . . --- e+ Se aye de BUG 198. Glioma (Gould), . . Se mniy- gt Cty GPSS, Rape one ee A » « BIZ 199. Squamous ‘Epithelioma (Gould hig Pudte eit, @ ee) by Be be oe ae ee B22 200. Section of a Squamous Epithelioma (Rinfetsch), tte tah weg BO AE a aie R22 201. Cylindric-cell Cancer of the Stomach, . . Bad? Swe Oey te, asee . 324 202. Section of Carcinoma of the Liver, . . Bk ee a ee Ge, BBG 203. Cylindric-cell Epithelioma of the Cervix Uteri, =e 326 204. Part of Cutaneous Surface of Right Mamma, the Seat of a "Centrally Placed, Primary Scirrhous Carcinoma and of a ee Nodule, . . 329 205. Granular Carcinoma of the Liver, . . - - - 2. +: - ©. sibs ee Ae BBO! 206. Encephaloid Carcinoma (Gould), . . 332 207. Glandular Carcinoma in Which the Stroma Has Been Converted into i Mucoid Tissue (Gozld), . cals ee aed Mth aie Ge Seale te ae ey BBS 208. Colloid Cancer (Rindfeiseh), . 5 Bg hE tg be he eR ey BSB 209 and 210. Diffuse Lipoma of the Neck. _ (Illustrations lent the author by Dr. J. Shelton Horsley). . 6. ee 2 ete tt 834 ati. Lipoma (Gould), 6 ee 335 212. Chondroma (Gould), © 6 1 0 ee 336 213. Soft Fibroma, . 338 214. Section (Longitudinal) “of the ‘Uterus ‘Showing Uniform. | Myomatous E En- largement, . . ane 340 215. Liomyoma (Gould), . s wok 48 8g Be Soe Bae Oey & Bale 216. Cavernous Hemangioma (Gould), « ee ee eae ee . 343 217. Myxoma, . ee ee ee ee ee 218. Round-cell Sarcoma (Rindfleisch), « SRW ak ae GE ae Sh RLS, 4 219. Round-cell Sarcoma ( Gowld), - hob 2b ee a 30349 220. Round-cell Sarcoma y a Lymphatic Gland I (Gould I ie oho ee abe wese ode we eB BAO, 221. Spindle-cell Sarcoma ena koe Re Sh gov ae ua a od “ae BGO: 222. Giant-cell Sarcoma, be oe ee TA So Si ph ak Lt ee “a ep aa SE 223. Alveolar Sarcoma ( Gould), Bs sina Ao i SBedon Mae eC ee RR See et cae 352 224. Melanotic Sarcoma Springing from the Subcutaneous or 1 Possibly f from the Periosteal Connective Tissues,. - - 6 ee ete es 353 225. Alveolar Melanotic Sarcoma eee bsg. ae ee Ree eee Bw, BS 5853 226. Endothelioma (Gould), . pho ty getty eae, Bie ek a a Re a Se BOA XViii FIG. 227, 228, 229. 230. 231. 232. 233. 234. 235. 236. 237: 238. 239. 240. 241. 242. 243. 244. 245. 246. 247. 248. 249. 250. 251. 252. 253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 266. 267. 268. 269. 270. 271. LIST OF ILLUSTRATIONS. piaes of the Structure of a Tubercle ; a Purely Theoretic Idea, mas Demonstrated (Gomi? ), 3 Acute Disseminated Tuberculosis of the Lung (Schmaus), Gower’s Hemoglobinometer, Improved Form, . Von Fleischl’s Hemoglobinometer, . i 38 Oliver’s Hemoglobinometer, Dare’s Hemoglobinometer, : Dare’s Hemoglobinometer, . . . . . - 1 ee ee ee ee Thoma-Zeiss Hemocytometer, . . Capillary Mixing Tube of the Thoma-Zeiss Apparatus (von Jaksch), Counting Chamber of the Thoma-Zeiss ee saan: Hematocrit Tube... . se aoe oth “a ; Rotating Frame of the Hematocrit, BS cancer chia (in, Be cae Beghas Seal eee A Method of Filling the Centrifuge Tube, ‘ Diagrammatic Representation of Various Forms and Sizes of Red Cells, Types of Red Blood-cells ; also Houkonyles eet Poikilocytes, ; Crenated Red Blood- corpuscles (L andois), Diagrammatic Representation of ees Hodgkin’s Disease, Heart Showing Villons Pericarditis ; Ascending and Transverse Portion of Arch of Aorta Showing Aneurysm, with Contained Clot, and cael into Pulmonary Artery and Pericardium, ‘ Vertical Section through an Inflamed Serous Membrane after the Forma- tion of the Fibrinous Exudate (Schmaus), Acute Tubercular Peficarditis, Vertical Section of Inflammatory Exudate (Schmaus), : by inte pastas ea Fatty Degeneration of the Heart, Chronic Myocarditis (Schwaus), . . Aortic Orifice Laid Open, Showing the Valve Leaflets, “Acute Endocarditis (Redrawn from Schmaus), : Acute Endocarditis of the Mitral Valve, Section | at Line "of Contact (Rindfleisch), . Narrowed Mitral Orifice Showing Results of Adhesions with Considerable Fibroid Thickening (Button-hole Mitral), Bae Adjacent Aortic Cusps, Showing a Small Vegetation Developing Just Below the Point of an Old Adhesion, . ‘ Adherent and Thickened Valve Leaflets (Rindpisch), a Obliterative Endarteritis, s ae Symmetric Aneurysm of the Abdominal Aorta, ‘ Varicose Veins of the Leg (Gouwla), Section of the Lung, Pneumoconiosis (Rindfleisch), Section of Lung Showing Chalicosis (Schmaus), . . Granular Degeneration (Cloudy Swelling) of the Liver ‘Cells (Schmaus) Fatty Degeneration of the Liver Cells (Schmaus), é Granular Degeneration of the Kidney eee (Cloudy Swelling) (Schmaus), Z a e Section of Wall of Bronchus, Chronic Bronchitis, ‘ 34 Vertical Section through the Pseudomembrane and Part of the Wall of the Larynx in Pseudomembranous Laryngitis (Schmaus), Fibrinous Cast from the Bronchi, Case of Croupous Pneumonia (Schmaus), Vertical Section of Mucous Membrane, Showing Diphtheric or Gangrenous Inflammation, from a Case of Dysentery (Schmaus), Margin of Tubercular Ulcer of the Intestine, . We shes ai ho Eas Tubercular Ulcer of the Mucous Membrane of the Trachea. Vertical Sec- tion of the Tracheal Wall (Schmaus), ; Bayes ees Perichondritis with Laryngeal Ulceration, . Tracheal and Partial ee Stenosis F ollowing Cieatrization OF a Gumma,...... beget ser =e oe PAGE 368 370 402 403 405 409 410 415 416 416 418 419 419 423 423 424 424 428 466 477 480 484 494 498 505 506 507 509 510 516 521 524 533 534 536 536 536 540 542 544 546 549 557 558 560 FIG. 272. 273. 274. 275. 276. 277. 278. 279. 280. 281. 282. 283. 284. 285. 286, 287. 288. 289. 290. 2g1. 292. 293. 294. 295. 296. 297. 208. 299. 300. 301. 302. 303. 304. 305. 300. 307. 308. 3009. 310. 3IL. 312. 313. 314. 315. 316. 317. LIST OF ILLUSTRATIONS. . Chronic Caseous Bronchitis, Tuberculous Bronchitis, Caseous Softening of the Bronchial Wall, with ene of the Peribronchial oe Peri- bronchitis Chronica’ (Schmaus), ; ak : Pulmonary Emphysema (Fiiitlerer), . sda Three Alveoli Filled with Fibrinous Exudate. " Croupous Pneumonia, Stage of Hepatization (Schmaus), : Croupous Pneumonia. Single Air Vesicle in 1 the Second ‘Stage, * with Slightly Contracted Exudate, Two Alveoli and a Part of a Third from Lung i in Catarrhal Pneumonia, 2 Tubercular Pneumonia (Schmaus), . , Tuberculosis of the Lung, . . : Wall of a Tuberculous Cavity (Schmaus), RC we ae a ee ee ee Longitudinal Section of the Kidney ( Zysoz, after Henle), eS tun fans ele aa Diagram of Blood eemelye to page ee a eel toh $a ho ds Gal Solitary Kidney, 5 ee TIS te 1 4s. Horseshoe. Kidnéy, . aos ke eke ee Re ee a SY Persistent Fetal Kidney Due to "Anastomoses ‘between the Renal ae and Vein, .. Cloudy Swelling of the Epithelium Lining a Kidney Tubule (Fliitterer), : Chronic Parenchymatous Nephritis, PB Bw ee pee, on te eh (Safa 1 : Kidney Showing Chronic Interstitial Nephritis, iin Sy baer ed & Kidney Showing Advanced Chronic Interstitial Nephritis, Kidney, Chronic Interstitial Nephritis, Tuberculous Pyelonephritis; Chronic ‘Ascending Tuberculosis of the Kidney, . BP Ag Gh YS eS Congenital Cystic Disease of the Kidney, ae ee ee ee ee Kidney, Congenital Cystic Disease ; Laid Open,. . ... . Congenital Cystic Disease of the Kidney, de sts WD Uo hth sees SA Congenital Cystic Disease of the Kidney,. ©. ........ Congenital Cystic Disease of the oe Part of Wall of a Larger ia Loss of Tissue Due to Noma, . . Bee get ee. VAs den ay eS ep Section from Right Parotid, Bgl G8 Section of the Left Parotid under a ‘Very Low Power, | e ye doe Intussusception at Ileocecal Valve, Intussusception Diagram Intended to Show the Relation of the ‘Several Parts in Figure 299, . . Typhoid Ulcer during the Early Part of Third Week of the Disease, Section through a Typhoid Ulcer, End of Second Week of the Disease (Schmaus), Section of the Intestinal Wall at the pesiah ‘of ‘a Typhoid | Ulcer, t, Beginning of Third Week of the Disease, . Tubercular Ulcer (Schmaus), . . ee ee ee = Fatty Infiltration of the Liver (Rinafleisch), . SNyap GP thecnate ap! aaa ena Liver, Amyloid Infiltration (Rinafleisch), din inp ky rape tree Beginning Cirrhosis of the Liver (Rindfleisch), Superior Aspect of Liver, Showing Unusual Degree of Cirrhosis with *« Hob-nailed’’ Surface, . . ‘ ‘ Atrophic Cirrhosis of the Liver, Advanced (Schmaus), 2 ako dytg Under-surface of Liver Showing Results of Congenital Syphilis, Oke Syphilitic Cirrhosis of the Liver (Schmaus), . . : Part of Left Lobe of Liver, Showing Primary Cylindric- cell Carcinoma, s Pancreas Showing Increase of Fibrous Tissue. Chronic Interstitial Pan- creatitis ae oe ee ne ee ee Section Taken from the Gastrocnemius Muscles of a Child ‘Suffering from Pseudohypertrophic Muscular Paralysis, . snag de Be Bes eas Progressive Muscular Dystrophy, Erb Type, . . Section of Bone-marrow of Rabbit, Showing the Delicate Connective- tissue Reticulum Containing the Different Elements of the Marrow See Elements of Human Bone-marrow (S/éhr), es XIX PAGE 562 573 583 584 592 597 600 602 608 609 610 611 612 616 621 624 625° 627 631 632 633 634 635 636 641 644 656 657 659 660 661 662 669 670 675 676 677 679 680 681 688 699 700 706 7°7 XX FIG. 318. 319. 320. 321. 322. 323: 324. 325. 326. 327. 328. 329. 330. LIST OF ILLUSTRATIONS. Acromegaly, . . ; Osteophytes on the Popliteal Aspect of the Lower End of the Femur, : OSteomyelitis Involving the Tibia and, to a Limited Extent, the Lower End of the Femur,. . . Exterior of Femur, Showing Result of Chronic Osteitis Associated with Chronic Productive Periostitis, dy Pcseg Femur. Longitudinal Section of Bone Shown i in ‘Figure 321, : Fracture of the Femur, Showing Overlapping of the Fragments with Rota- tory Displacement of the Lower BEeeisnh and ee Union in This Position, . . 6 Poe ee Se oh Re aay 8 rae Ten-day-old Fracture ( Schmaus), Spina Bifida, Section of Cerebral Cortex and Meninges’ from a 1 Case of Suppurative Meningitis, . . . ae Section of Human Brain, Including Wall of | Cerebral Abscess, Spinal Cord, Showing Posterior Sclerosis, 2 Nerve. Acute Interstitial Neuritis, Longitudinal Section of Musculospiral Nerve Removed from a Man who Died as a Result of Alcoholic Multiple Neuritis, Se Scobie for ta "753 PAGE 713 714 719 723 723 728 729 760 776 788 791 792 INTRODUCTION. Pathology bears the same relation to a proper study of dis- ease that physiology does to a knowledge of those complicated phenomena the sum total of which is called life. Physiology deals with the normal processes,—the functions of organs and tissues in health,—while pathology is a study of the causes and manifestations accompanying disease. Physiology is the science of normal life; pathology is the science of abnormal life—dis- ease. It has been said, and quite truly, that pathology is mor- bid physiology—the physiology of disease. The two subjects demand associated study, as from a knowledge of one is ac- quired more or less information bearing either directly or indirectly upon the other. A detailed study of the intricate problems of morbid processes, and of the relations of tissue change to alteration of function, and a thorough acquaintance with the normal, render at once apparent the intimate associ- ation of pathology and physiology. Throughout the study of pathology it is to be remembered that the changes contemplated are but perversions of the normal. Disease, with its alterations in structure and function, is not an entity from without, not an importation whose existence within the body is passive, but all morbid processes, while they may arise from causes acting from without,—causes having an existence as a part of the outside world properly so called,—are them- selves essentially but perversions of normal vital activity. The same cells, or their progenitors, active in a morbid process, were the essential elements in the normal life of some tissue of the body. As the result of altered conditions the cellular activity has been perverted, and the new line of cell life is but a change in the manifestations of cellular activity—not a new, nor foreign, nor extraneous life carried on within the affected tissues. The apparent exception to this, in the growth of animal and vegetable parasites within the tissues, is not really an exception ; so long as the life of the normal cells is not in any way disturbed, disease does not result ; as soon, however, as the foreign elements inter- fere with the usual course of events, those cells performing cer- II 12 INTRODUCTION. tain functions in a manner recognized as normal for the species under observation assume a new role, and manifest their activity along a line foreign to their usual course. It therefore becomes evident that the diseased tissue is the result of changes in the normal, and that the cellular elements present are but modified forms of normal cells. In order properly to appreciate the sig- nificance of tissue alterations a careful investigation into the causes of disease becomes an absolute necessity ; with advance in the study of etiology it has become possible to comprehend many diseases and fully to understand phenomena previously inexplicable. The study of the active process associated with disease and its results implies the investigation of gross alterations,—the morbid anatomy ; and, what is truly included as a part of the anatomy, the changes in the finer structure of the tissues—the morbid histology. That the study of these two divisions of the subject may have important bearing on practical medicine it is necessary to observe the relation maintained between both gross and microscopic lesions and the function of the diseased organ; this constitutes a study of morbid physiology, the perversion of the normal, due to, or associated with, the lesions, either gross or microscopic, themselves the active phenomena of disease ; and, lastly, the pathologist must be familiar with the results following the subsidence of morbid processes. The methods of study must of necessity vary with the mor- bid process under consideration. When any of the lower animals are susceptible to the disease under investigation, for evident reasons the experimental method offers many advantages. Being able to vary the conditions. under which disease is induced in an animal, to kill the animal at any period in the development of the morbid process, and more fully to control external condi- tions, make this method in many instances of the greatest value. Like all methods for studying disease, experimentation is open to certain objections ; it is not possible in all cases fully to interpret the results, or they may not be applicable, on the whole, to man. While such important objections to the method often hold true, the author does not recall a single instance in which, after prolonged effort, it has not been possible to learn something, and in a number of diseases the method under con- sideration has afforded full and entirely satisfactory explanation of phenomena previously obscure or absolutely unappreciated. In many diseases all that is known has been tediously worked out by this form of research. Again, many diseases to which man is liable can not be induced in animals, and in such cases INTRODUCTION. 13 the method fails. It has been urged that the end attained does not justify the suffering induced in the animal experimented upon. Such an objection need not be answered here, since those who hold it can not know of the advances made by the experi- mental methods of study, or are not in that condition of mental receptivity necessary to appreciate scientific truths. The results attained by the investigation of disease in lower animals have probably done more to alleviate suffering in them than in man. Comparative pathology—the study and comparison of morbid processes in the lower animals and in man—also affords ample opportunity to obtain information as to the causes of, and altera- tions in, disease. In all pathologic study, to attain the best results the statistical method must be used to a certain extent. The collection of a large number of cases, with a careful analysis of recorded data, can but yield valuable conclusions. The constancy of associated lesions—as, for example, the association of certain nervous and nutritive phenomena with removal or disease of the thyroid gland—often indicates a path for investigation that may termi- nate in a happy solution of some obscure problem. The study of diseased organs or tissues postmortem or after removal from the body need hardly be mentioned as a most fruitful source of knowledge concerning morbid processes. In addition to the above methods, it can not be an error thor- oughly to study morbid processes during life. Therein lies the strength of the science. The symptoms of a disease are but expressions of the lesions—the morbid physiology induced by chemic, mechanical, or structural alterations. From symptoms it is possible in many cases to infer the character of the tissue changes, or, by studying the alterations in the normal chemistry and structure, the symptoms may be explained. He is far at sea who believes that the study of pathology begins and ends with the postmortem. PART |. TECHNIC. PART I.—TECHNIC. CHAPTER I. POSTMORTEM EXAMINATIONS. I. INSTRUMENTS NEEDED. A postmortem may be made with a very few instruments ; those supplied in an ordinary dissecting case may suffice for the examination unless the central nervous system is to be removed, in which case a saw will be found necessary. Scarcity of in- struments is rarely a justifiable excuse for failure to avail one’s self of an opportunity to hold a postmortem. A most thorough examination may be made with a knife such as is ordinarily ‘used by butchers, a saw, and a carpenter’s hammer and chisel. The following list of instruments and appliances may be pro- cured by those contemplating the making of postmortems, the extent of their purchase being largely a matter of taste and money available. The instruments marked by an asterisk are consid- ered indispensable, the others being conveniences to facilitate or lessen the work of making postmortems : * One Virchow postmortem knife. * Two strong scalpels. * Two small scalpels ; one probe-pointed. One costotome, or, when this can not be obtained, a cartilage knife or a saw may be substituted. * At least two dissecting forceps: one with corrugated blades and one with rat-toothed blades. A number of such instru- ments will be found useful. * One pair of scissors: one blade sharp and one probe-pointed. One enterotome, or, when this is not available, a small cork or piece of wood may be pushed over the tip of the sharper pointed blade of the ordinary scissors. Two long probes: one should have an eye and one should be quite slender ; the latter is convenient for tracing ducts. An instrument to be commended is a combined grooved director and 2 q7 18 TECHNIC, probe. For the examination of sinuses and whenever it can be employed, there is no instrument that can be used to better advantage than the trained finger. * One saw with a well-bellied cutting-edge. * One grooved director. * Two large postmortem needles. * Two spools of flaxed thread: one white, one black. * One mallet; the rawhide mallet has the advantage of making but little noise when used on the chisel. The steel hammer ordinarily supplied with postmortem cases has a blunt hook on the handle, which is useful for removing the calvaria, and occasionally for other purposes. The objectionable noise made by pounding on a metallic chisel may be overcome, at least partly, by covering the chisel with a folded towel. Fic. t.—COMPLETE POSTMORTEM CASE. It is convenient to have a leather covering for the case. One chisel. Of the various forms of chisels recommended, the lower one in figure 19 will be found most useful. Some of the forms of hatchet-chisel, however, will be occasionally used. A brass or German-silver ruler, graduated in inches and in cen- timeters, will be found useful. Such a ruler should be at least twenty centimeters in length, and the graduation throughout should be in tenths; a finer graduation on instruments of this kind can rarely be read at the postmortem table. As a result of attempts to reduce the number of instruments contained in the postmortem case, the writer has had the long, thin-bladed brain knife, shown in figure 11, graduated along its back. As the instrument is useful for incising organs, it makes the gradua- tion convenient and always at hand. POSTMORTEM EXAMINATIONS, 19g A double rachiotome is a very useful instrument, but is not, however, convenient for carrying around to private postmortems. A strong bone forceps will occasionally be needed, Aleasures of Capacity.—Small graduates measuring from o.1 c.c. to 50 c.c. will be found useful. Larger measures should be at hand. Any agateware or tin vessel (the former is preferable) may be standardized by a smaller graduate, and being very much less fragile and less expensive, is therefore to be preferred. A syringe for sucking up fluid from the bottom of cavities not easily accessible is a convenience. In well-appointed hospitals, morgues, etc., a room is usually set apart for postmortems. This room should be well lighted and capable of thorough ventilation. The floor should be of impermeable concrete, the walls tiled or built of enameled brick, or, in the absence of these, covered by lusterless white enamel paint. A capacious postmortem table should be so placed in the room as to be well lighted and accessible on all sides. The size of the table is often a matter of individual preference. The table preferred by the writer is three feet wide, six feet long, substantially constructed, zinc or slate covered, the covering slightly raised at the edges of the table, and the top gently sloping toward a large grate-covered drain in the center. This drain, thoroughly trapped, may be directly connected with the sewage system, and may be so attached to the ventilation system as to secure a strong downward draft, thus drawing downward all odors which would otherwise rise and permeate the room. For convenience in measurements a centimeter and inch scale may be ruled upon the edge of the table. Although never to be used when it can be avoided, an abundance of artificial light should be at command. The best artificial light for the postmortem room is afforded by Welsbach burners with porcelain reflector and shade; thirty-two candle- power incandescent lamps with thoroughly frosted globes are the next best substitute for natural light. All forms of artificial light so modify the color of organs as often to afford misleading pictures to the uninitiated. Water-supply—Suspended just above the autopsy table and coming down to within an inch or so of the table should be a rubber hose connected with proper metallic fixtures, so arranged as to afford a mixing device, by means of which hot and cold water can be mixed and delivered through the rubber tube at any temperature that may be desired. By permitting the rubber tube to project practically to the table the end can be kept in a pan, thus affording a small reservoir of constantly clean water. The 20 TECHNIC, flexible rubber hose. affords facilities for washing the table and keeping the instruments and appliances in use clean. A capacious sink in some part of the room is desirable ; into this should drain a slate dripping-slab sixty centimeters wide and two meters long. Two scales should be at command—one for weighing from a fraction of a gram to ten or twenty grams, the other for heavier masses. Although rarely at hand, a scale for weighing bodies is desirable. Scales for weighing organs and tissues should have large brass pans that can be readily cleaned. A head block twelve inches long and six inches square, with a notched depression near the center for receiving the neck, will be found useful in supporting the head, and similar blocks may be used for arching the body during the examination of the spine and the removal of the cord. Heavy boards, fifty by sixty centimeters, will be found ser- viceable for the support of organs during section. A vise will be occasionally needed. Of the various forms of head holders in the market, the writer has never felt that any was better than the hand. Every well-equipped postmortem room has a book for record- ing the data obtained at postmortems. This book is usually made up of printed’sheets, having a heading arranged according to some definite form which has been adopted by the pathologist. Such headings are useful in making it reasonably certain that no matter who makes the postmortem, the customary routine will be followed. The volume should not contain a very large number of pages, certainly not over four or five hundred, as a large number would make it too bulky for convenient handling ; nor should the sheets be too large. The book to which the writer is accustomed has a page forty centimeters long by twenty-eight centimeters wide, and has printed on each alternate page the form given in the foot-note on page 21. At the time the book is printed it is well to have two or three hundred sheets left unbound, so that at postmortems made outside the institution it will not be necessary to carry the book. II. PRELIMINARY DATA. Before beginning the postmortem it is desirable to know and record the name ; age; residence, or, in hospital cases, the ward and bed; sex ; color; date and hour of death; date and hour of postmortem ; methods of preservation if any have been used ; the clinic diagnosis ; the name and residence of the physician, if POSTMORTEM EXAMINATIONS. 21 any, who last attended the case, and, if possible, his presence should be had at the postmortem. In medicolegal cases the body should be identified. If the time at which death took place is not known, it may be approxi- mated by the postmortem evidences. Ill. THE POSTMORTEM. In order that the record of a postmortem may be perfect, it is absolutely necessary to follow a definite method in each case. If circumstances demand a variation from this routine method, the reason for varying should constitute a part of the record. The following presents nothing original, and is the method adopted by the writer: ° (A) The Date and Hour of the Postmortem. (B) External Examination of the Body. (a) Is the body dead? The following observations should be made and recorded as a part of the postmortem notes, as they FORM OF APPROVED POSTMORTEM BLANK. [NAME oF INSTITUTION. ] POSTMORTEM. Ward... Register No... .-seeececeeeeeee Name, Age, and Sex of Patient... ieee COLOY cece esses esesneeteneeees Physician or Surgeon... | Residence «.......ccccccccccesessseesseseeeeeetseneennesenes Resident Physiciam.........-00: secs | Birthplace sae Gee eccntnrerecenepaess Date and Hour of Death.........000c Date and Hour of Postmortem............ Clinical Pathologic Diagnosis. Diagnosis. When possible, it is desirable that the following order of examination and recording the postmortem shall be followed: I. External examination: Evidence of injury. General nutrition. Ante- or postmortem marks, etc. Il, Internal examination. : 1. Abdominal Wall. 8. Thymus; Thyroid. 14. Pancreas. 2. Peritoneum. g. Spleen. ‘ 15. Intestines. 3. Pleuree. to. Adrenals and Kidneys. 16. Esophagus. 4. Pericardium. ur. Bladder and Internal 17. Vena Cava and Aorta. 5- Heart. and External Genitals. 18. Head. 6. Lungs. 12. Stomach and Duodenum. 19. Spinal Cord. 7. Larynx; Trachea; Bronchi. 13. Liver. 20. Miscellaneous. 22 TECHNIC, cover not only the signs of death, but constitute a part.of the evidence of diseased conditions: (1) Examine for evidence of respiration and circulation. (2) Look for opacity of the cornea, loss of sensibility in the conjunctiva, pupillary reaction, which may, in doubtful cases, be tested by atropin or eserin ; if the eyes are sunken, with wrinkled tunics, the evidence is clear. (3) Pallor of the body may or may not be present, and while valu- able as a sign of death, it may be found in the living during swooning, the algid state of ague, collapse, etc. (4) Cooling of the body to the temperature of the surrounding medium (a/gor mortis) occurs in from fifteen to twenty-four hours. The bodies of children and old and lean bodies cool quite rapidly, while bodies of fat, young, and middle-aged individuals retain the heat much longer. The bodies of persons dying from suffocation, electricity, tetanus, and yellow fever very slowly yield their heat. (5) Cada- weric rigidity, or rigor mortis, occurs at a varying interval after death. It may become manifest but a few minutes after death, or it may be delayed eighteen or twenty hours ; usually, it develops simultaneously with the loss of body heat. The duration of rigor mortis is extremely variable, lasting in some instances but a few moments ; in other cases, hours, days, or even weeks. (6) Cadaveric lividity (the cadaveric blotches called vores mortis) and suggillation are terms applied to the livid or violet-colored discoloration which is seen usually several hours after death. It becomes apparent in the most dependent portion of the body, and is the result of blood gravitating into the capillaries. (7) Futrefaction is an indubitable sign of death. The time at which it Lecomes manifest varies greatly, and is dependent upon the condition of the body, the surrounding media, and the cause of death. (8) Experimentally, we may infer that the body before us is dead by injecting ammonia water under the skin; in death such a procedure leaves no mark, but in simulated death it occasions a dark spot. A dead body can not be blistered. (0) General Considerations—The amount of adipose tissue, the muscular development, and the nutrition of the body should be carefully noted, and the record completed or verified as the internal examination proceeds. In case the body has not been identified an elaborate description should be made for the pur- pose of further identification: the height, weight, measurement of chest, limbs, hands, and feet, color of eyes and hair, and of the latter some should be preserved. A careful survey of the mouth as to dental peculiarities, absence of teeth, filled or irreg- ular teeth, or, better, a dental impression taken in wax or plaster. If false teeth are present, they should be removed as POSTMORTEM EXAMINATIONS, 23 possible aids to future identification. Abnormalities, malforma- tions, marks of any kind, should be noted, and, when possible, a photograph should be obtained. Such data may, with perfect propriety, constitute a part of any postmortem record ; indeed, they are desirable although rarely incorporated in the protocol. Except in the cases mentioned they might have little value in any given postmortem, but in the compilation of important data based of necessity on a large number of cases—ze. g., the size and weight or organs as compared with the height and weight of the individual—such records would become invaluable. (c) Evidence of Violence or Disease.—LEcchymoses should be carefully described as to size, shape, and position. This form of discoloration may be distinguished from suggi/lation in that it does not disappear on pressure, and if an incision be made into it, bloody fluid will escape, or a clot may be discovered in the subcutaneous tissue. All abrasions, eruptions, bed-sores, ulcers, cicatrices, wounds, edema, pigmentations in the skin and mucous membranes must be accurately described, and their positions carefully recorded. Fractures and dislocations must be closely observed, and their character and the parts involved noted. The external orifices of the body should be examined, and their condition and contents noted—e. g., mouth and nose for foreign bodies, evidences of corrosive poisoning, etc. ; in the female, the breasts, abdomen, and external genitals should be examined for evidences of disease, violence, or physiologic processes, such as menstruation, recent delivery, or evidences of past gestation, as shown by the mamme, abdomen (linea alba), or external genitals; in the male look for evidence of malformation of the sexual organs or venereal disease, also seminal stains. Examine the anus for fissures, inflammation, fistula, morbid growths, cica- trices, etc. Examine the hernial outlets for evidences of rupture. If the body is that of an infant, examine the fontanels and sutures, and note the various diameters of the skull. Measure the body and examine the umbilical cord. In the male the scrotum should be examined to determine if the testicles have descended ; note, also, the presence or absence of vernix caseosa. Carefully examine the epiphyses, and especially that of the lower extremity of the femur. ~ (C) Internal Examination of the Body. Ss gded ; The large Virchow knife is used for most of the incisions ; it is grasped firmly in the hand by the thumb, middle, ring-, and little fingers, while the index-finger rests upon, or at the side of, the blade. Cuts are made with a drawing movement, the shoulder- and elbow-joints acting as centers, the wrist and 24 TECHNIC, fingers rigid. Pushing the knife through a tissue or organ, as one would a chisel, is to be avoided, and equally, objectionable are sawing and hacking. In ordinary dissection a scalpel is held like a pen, motion being at the joints of the fingers and wrist—a process entirely too tiresome and slow for postmortem work except when very delicate dissections are to be made. The body rests firmly upon the back, and the operator, if right-handed, stands upon the right of the cadaver. To expose the abdominal and thoracic cavities, an incision should be carried from the lower border of the thyroid cartilage, or from the inter- clavicular notch, to the symphysis pubis, making a sharp semi- circular turn to the left at the umbilicus in order to avoid injury to the remains of fetal organs at that point. The point in the neck at which to begin the incision will be determined by circum- stances over which the operator quite frequently has no control. If he can select the starting-point of his incision, he will ordi- narily begin just under the chin, or may even make a Y-shaped Fic. 2.—MOopDIFIED VIRCHOW POSTMORTEM KNIFE. Twenty-four centimeters long, of which 9.5 cm. is cutting-edge. cut extending to the angle of the jaw on either side ; this permits a most careful examination of the floor of the mouth, pharynx, larynx, and adjacent structures. So extensive a mutilation is rarely demanded ; in most instances the loosened skin can be retracted upward in such a manner as to permit the removal of the tongue when the vertical incision does not rise above the level of the thyroid cartilage. Still, as before stated, circum- stances will more commonly settle this point than any arbitrary rule. Over the abdomen, the first incision should pass through the skin and subcutaneous tissue; then carefully cut through the abdominal wall immediately below the ensiform cartilage ; insert two fingers of the left hand, drawing the abdominal wall upward ; continue the incision, the fingers being used as a guide to the knife. A most excellent rule, never to be forgotten by the beginner, is to always keep the point of the knife in view, or, if this is not possible, it should be guarded. If the novice makes it a rule never to cut anything until he has determined what it is and what are its relations, using touch possibly more than sight POSTMORTEM EXAMINATIONS, 25 to determine these facts, he will often be astonished at the dex- terity which he quickly acquires and the rapidity with which his senses become trained to recognize the tissues before him. Note Fig. 3.—THE STERNUM, CosTAL CARTILAGES, AND ARTICULATION OF THE CLAVICLE, AS EXPOSED AFTER IURNING BACK THE SOFT PartTs.—(Modtfied from Virchow.) On the left is shown the line of in¢isions made through the cartilages from below upward, if acostotome is used; from above downward, if a knife or saw is employed; and also the incision necessary for disarticulating the clavicle. When it is not desirable to disarticn- late the clavicle, the manubrium is separated from the gladiolus at point A, the incision being made from behiud. the amount and color of the subcutaneous fat in the abdominal wall, its consistency, and the presence or absence of edema. Examine the muscles for pallor, hyaline spots, degenerative 26 TECHNIC. changes (such as occur in typhoid fever), and small white ovoid bodies, encysted trichine. Dissect the tissue from the chest- walls as far back as the junction of the costal cartilages with the ribs ; then make strong traction on the abdominal walls to break up the rigor mortis. After breaking up the rigor mortis the muscles can be further incised, and examined for evidences of bruises, inflammation, and suppuration, and suspicious portions removed for microscopic study. ABDOMINAL Cavity.—First note the relative position and color of the liver, stomach, and intestines ; and also the relations of the viscera to the costal and ensiform cartilages. The exami- nation of the cavity is not of the organs individually, but of their relation to one another and to the walls ; also examine the serous membrane—the peritoneum. A careful search should be made for adhesions and other evidences of inflammation, recent or old, Fic. 4.—COosSTOTOME. and for thickening and opacity of the serous membrane. The amount and character of any fluid in the cavity must be noted, and, if in excess or abnormal in character, the source or cause of the morbid condition must be sought. The color of the liver should be observed before those changes incident to the oxidation of the blood occur. Search carefully for perforations of the bowel, stomach, bladder, or gall-bladder, whenever the fluid in the cavity is abnormal. Note accurately the position of the dia- phragm: ordinarily, on the right side it ascends as high as the fourth rib or interspace ; and on the left, to the fifth rib. Remove any fluid present in the cavity before going to the thorax, as fluids in the abdominal cavity would flow into the thoracic cavity and thereby complicate the examination. Tuoracic Cavity.—With a heavy knife, or costotome (or, in the absence of the latter, when the cartilages are calcareous, a POSTMORTEM EXAMINATIONS, 27 saw may be used), sever the costal cartilages close to the ribs, care being exercised not to injure the tissues beneath. If the costotome is used, the blade inserted beneath the cartilage should be made to hug that structure closely; if a knife or saw .takes the place of the costotome, the incision through the carti- lages should begin above and before one cartilage is completely severed, the blade or shank of the instrument should be made to rest on the next cartilage, thus preventing sudden thrusts which may wound underlying structures. When the last cartilage is reached, it should be gently raised by the unoccupied hand, at the same time depressing the underlying structure, thereby avoiding the danger of wounding the latter. Divide the attachment of the diaphragm, raise the sternum, and dissect off the attached tissue, taking care to direct the edge of the knife toward the bone in order to avoid injury to the peri- cardium or other intrathoracic tissues, Cut the ligaments which bind the clavicle to the sternum, divide the sternal attachment Fic. 5.—Saw. A large firm handle is wanted, with good pistol grip. of the sternocleidomastoid muscle, and pull the breastplate to one side. In a cadaver in which the section of the thorax has been made as just directed, the shoulders, having lost the support of the clavicle through their sternal attachment, col- lapse together, making the chest appear very much distorted. To avoid this, in cases where the body is to be viewed, it is sug- gested that the manubrium and gladiolus be disjointed, which may be accomplished by drawing the edge of the knife across the under surface of the articulation of the manubrium and gladiolus (see Fig. 3, p. 25) and raising the lower segment of the sternum. Examine the pleure for evidences of inflammation, either remote or recent; note presence or absence of fluid, also its quantity and character, as in the peritoneum. Fluid in each pleura should be removed, so as to prevent its flowing into the pericardium ; or, in case the pericardium contains much fluid and any escape into the pleura, its quantity may be accurately esti- mated.. The fluid in each cavity should be measured, and the 28 TECHNIC. quantity made a part of the record. Adhesions should be looked for and described. The pericardium should now be opened by an incision extending from base to apex in a line parallel to the long axis of the heart. In opening the pericardium the writer has seen the heart injured so often that he desires to insert a. Fic. 6.—HEART SHOWING THE LINES FOR INCISIONS IN THE PRELIMINARY EXAMINATION AND FINAL SECTION, FULLY ExPOSING THE VALVES.—(A/ter Virchow.) A, Pulmonary artery. 2. Aorta. C. Rightauricle. The incision 47 to Vis that advised by Virchow. ‘The one preferred by the writer is from X to /, for the preliminary opening of the right ventricle. The preliminary opening of the right auricle is made at C. The preliminary opening of the left auricle is made at D. The preliminary opening of the left ventricle is made at Fto&. Afterthe heart is removed, the incision made at Cis carried out through the vena cava; the incision from X to J is carried through the pulmonary artery between the letters 17 and A, and below is carried around by Hto J. The in- cision AZ to Mis not made. The incision F to Z, in the left ventricle, is carried around behind the pulmonary artery, 4, and comes out in the aorta at Z. From the lower portion, at &, the incision is carried upward to about where the letter G is shown; this permits the flap to be turned back so that the mitral valve may be examined ; the incision made may then be carried through the mitral orifice. word of caution and give a little more detailed method for pre- venting this accident. The pericardium is picked up in a fold either by the index- and fore-finger of the left hand or by the use of ‘“‘rat-toothed’”’ forceps; by gentle traction this fold of thé pericardium can be raised to a distance of 2.5 cm. The back POSTMORTEM EXAMINATIONS. 29 of the knife is now placed against the heart and the fold, made as previously directed, is transfixed and the opening completed by cutting from within outward. A similar incision has been long recommended by surgeons while operating upon hernia when wounding of underlying tissue may be attended by calamitous consequences, and if applied to the pericardium with but slight precaution, wounding of the heart may be entirely avoided. From this incision, which is two or three centimeters in length, the Fic. 7.—HEART SHOWING THE INTERIOR OF THE RIGHT VENTRICLE AND PULMONARY ARTERY.—( After Virchow.) If the incision J/ to J, figure 6, be made as advised by the writer, the papillary muscle (4) will be carried over with the ventricular wall (2), thereby better exposing the auriculo- ventricular orifice. incision in the long axis of the heart, as previously directed, may be readily made. Incisions at right angles to the long incision are rarely, if ever, demanded ; the writer does not recall an in- stance in which he has needed a larger incision than that afforded by the opening extending from the apex to the great vessels. Examine the layers of the pericardium for evidences of inflam- mation, and look carefully for adhesions, particularly about the great blood-vessels. Measure the pericardial fluid and note its character. The heart should now be examined. Note the con- 30 TECHNIC. dition of contraction or relaxation of the heart’s wall ; open the heart zz situ; raise the organ by its apex, pass the fingers of the left hand under the organ, and so grasp it that the thumb and first finger will close the auriculoventricular orifice of the right side, and then make an incision into the auricle between the vene cave. Examine and note character of contents ; without relaxing the grasp on the auriculoventricular orifice, Fic. 8.—HEART WITH THE LEFT VENTRICLE LAID OPEN, SHOWING THE AORTIC CUSPS AND THE VENTRICULAR ASPECT OF THE MITRAL VALVE.—(A/ter Virchow.) The letters have the same significance as in figure 6. open the right ventricle by an incision in line with the pulmonary artery and close to the ventricular septum; insert the index- finger of the right hand and examine the contents. The left heart is opened by grasping it as in opening the right. The auricle is incised near the appendix and immediately above the auriculoventricular septum, and its contents are noted. The left ventricle is opened by an incision almost parallel to the opening POSTMORTEM EXAMINATIONS. 31 made in the right ventricle, but on the opposite side of the sep- tum, and the incision is directed toward the aorta. The presence or absence of blood or clots in the left ventricle must be care- fully noted. Examine the great vessels as to abnormality, aneurysm, or other disease discernible externally. In the new- born it may be advisable at this time to trace the pulmonary artery and aorta, demonstrating the relation of one to the other, and the condition of the ductus arteriosus. Remove the heart, dividing the great vessels from below upward, severing the aorta last. Test the valves as to competency, being sure to wash out all clots before making the test. Measure the valvular orifices. Enlarge the incisions already made so as to be able to examine Fic. 9.—ScIssors. Those shown in the upper cut will be most useful, particularly if the blade shown in the cut as having the sharper point be slightly probe-pointed. the endocardium in detail. Carry the incision in the right auri- cle out through the two cave; prolong the incision in the right ventricle through the pulmonary artery and the incision in the left ventricle through the aorta. The left auricle is opened by continuing the incision already made into the pulmonary vein. Note any vegetations on the valves, thickenings or opacity of the endocardium; examine closely the condition of the foramen ovale. State the general appearance of the cardiac muscle. _ Examine coronary arteries by passing a director into each in turn, and, with knife or scissors, opening the artery as far as possible. Probe-pointed scissors may be used to advantage, and if the probe-pointed blade is small, the arteries may be opened even to their smaller branches. Weigh the heart. 32 TECHNIC. Both lungs may be. removed at once. Adhesions must be carefully broken up; this can usually be accomplished by the fingers alone ; occasionally, however, the knife or scissors (pref- erably the latter) will be necessary. If the organs are adherent to the diaphragm, it is best to detach the latter from the ribs and remove it with the lung; often only a patch will require removal, at other times the entire diaphragmatic pleura may be adherent. Incise the great vessels as they pass out of the thorax ; cut through the trachea, being careful not to injure the esopha- gus. Gentle protracted traction will strip the organs from the tissue behind, bringing forward with the pericardium the aorta, which must be severed at the diaphragm. If it is desired to leave the aorta, this can easily be done by separating it from the pericardial attachments before delivering the lungs. When removed singly, the left lung is removed first. Note the gen- eral appearance, color, and condition of the lung. The incisions made in the lung should be conspicuous by reason of their length, and the longer, other things being equal, the better. To FIG. 10.—GROOVED DIRECTOR. Useful for opening arteries, tracing sinuses, ducts, etc. accomplish this, it is best to use a long section knife, which should be exceptionally sharp, making an incision from apex to base, extending through all the lobes in a line corresponding, as nearly as possible, to the axillary aspect of the organ. Lay open and dissect down the bronchi, and carefully examine their condition, a sharp lookout being maintained for the presence of foreign bodies. Note the appearance of the peribronchial glands. Weigh each lung separately. Examine larynx, trachea, bronchi, and thymus and thyroid glands. The examination of these structures is usually best accomplished after their removal ex masse, together with the contents of the floor of the mouth and the pharyngeal wall. If the primary incision was carried to the chin, but little difficulty will attend the removal of these organs; on the other hand, if they must be removed subcutaneously, considerable difficulty will be encountered. The skin must be carefully dissected from the underlying tissues, and a long-bladed knife passed from below upward, entering the floor of the mouth as far anteriorly as possible, making an incision laterally on both sides along the POSTMORTEM EXAMINATIONS, 33 rami of the lower jaw. The mouth is then opened widely, and the incision carried backward and upward, detaching the soft palate from the hard palate, and at the same time freeing the tonsils. The removal of this mass is accomplished by pulling the esoph- agus and larynx downward, pushing a long-bladed knife up behind the esophagus, and severing posteriorly and laterally the pharyngeal wall as high as possible. After removal the esoph- agus may be dissected from the larynx, and examined later, with or after the stomach, or it may be at once severed near the diaphragmatic opening, a ligature being applied to prevent the escape of the stomach-contents. If removed with the adjacent structures, it is opened on the posterior aspect, the larynx and trachea being opened anteriorly. The incisions should be made through the longest diameters of the thymus and thyroid glands, as most of the lesions in these structures will be more important from a histologic standpoint than from their gross anatomy. ABDOMINAL VISCERA.—The sf/cex is now removed. This is accomplished by gently lifting the organ out of its normal bed, pulling it forward, and severing the blood-vessels close to the hilum. As a result of past peritoneal inflammation, diaphrag- matic pleurisy, or inflammation of some adjacent viscus or tissue, as the colon or perirenal structures, the spleen may be anchored by firm adhesions of its capsule to adjacent structures. Under such circumstances it is best to dissect the organ out with very great care, as protracted or violent traction may cause rupture of the organ; and if it be softened as a result of infectious dis- eases or other cause, the entire splenic pulp may be forced through a comparatively small opening in the capsule of the organ. Its general appearance described, make one long incision through the back of the organ down to the hilum. Note color and consistency of parenchyma, prominence of the Malpighian bodies, and stroma. Weigh the organ. The Kidneys.—Ascertain whether both are in their normal positions, if possible. The left suprarenal body and left kidney are next examined. As a rule, the adrenal and corresponding kidney may be removed together. This can readily be done simply by tearing the peritoneum along the upper and _ posterior border of the kidney and gently dissecting with the fingers the connective tissue which holds the adrenal in place. Raise the kidney from its normal position, note condition of blood-vessels and incise them ; examine ureter and sever it. With very little effort the ureter may be traced downward to the bladder. This should be done before severing the kidney, as later it may be 3 34 TECHNIC. quite impossible to demonstrate that the canal contained no obstruction. The perirenal fat should be carefully removed from the kidney and the surface of its capsule accurately described before incising it. Hold the kidney in the left hand, with the pelvis directed toward the palm, and with one sweep of a sharp knife incise, from the cortex to the pelvis, in the long axis of the organ. On section, note consistency, color, the relative propor-’ tion of cortex and pyramid (normal cortex equals one-half the pyramid) ; the condition of capsule, whether thickened, tense or flaccid, or adherent to cortex ; also note appearance of stripped surface of cortex, whether smooth or rough, etc. Examine pelvis of kidney, and weigh the organ. The same process is repeated upon the opposite side. Examine Jladder and internal genitals. The technic of this examination depends largely upon the conditions present. When the examination of the upper urinary tract (kidney and ureter) has led to any suspicion of disease, it is best not to detach the kidney from the ureter or ureter from the bladder until the 1 9 10 HW 12 13 4 15 ft gg TT my ay my Wr Be wa 8 7 8 6 Fic. 11.—Lonc, THIN, BRAIN KNIFE, OF VALUE FOR INCISING ORGANS. Originally designed for brain dissection, but at present used for incising kidney, liver, spleen, tumors, etc. As shown in the illustration, the instrument should not havea cutting-edge measuring less than sixteen centimeters. The graduation along the back of the knife affords a convenient measure. On the other side the graduation is in inches. examination has been completed. The examination of the pelvic viscera can usually be best accomplished after evisceration of the pelvis. It is best, however, to open the bladder and examine its contents before eviscerating, and in the female, when there is any question of criminal abortion, a thorough examination should be made by finger and speculum, using no cutting or probe- pointed instrument of any kind until wounds have been excluded as far as it is possible to do so before the examination is com- pleted. Evisceration of the pelvis is best accomplished by an incision anteriorly, under the pubic arch, hugging the true pelvis posteriorly, and removing the rectum with the other contents of the pelvis. The testicle may be removed without any external incision in the scrotum by simply dissecting the skin anteriorly from the pubes and pulling the testicle by the spermatic cord gently up into the wound, from which it may be removed, if necessary dissecting the cord around to the seminal vesicles. The penis may be simply retracted through the floor of the pelvis, and removed with the prostate and bladder. POSTMORTEM EXAMINATIONS, 35 The removal of these organs without the full consent of the deceased’s family should never be made, as the excision of the genital organs is always looked upon as having been done merely to gratify morbid curiosity, and exactly why it is always discovered seems very hard to determine ; the fact remains that the uninitiated have been severely censured for the removal of the external genital organs, even in cases where it was perfectly justified by the findings and where it was necessary to exclude other possibilities. The rectum should be dissected from the posterior wall of the bladder in order to expose the prostate and seminal vesicles. In the female, as this is not necessary, the rectum is opened on its posterior aspect, the vagina laterally, and the urethra and blad- der anteriorly, thus permitting all the parts to be restored to their normal relation with each other. The opening on the lat- Fic. 12.—ENTEROTOME. Useful for opening stomach, duodenum, intestines, etc. Not uncommonly the blunt-pointed lower blade is so made that it forms a tooth, like the barb on a fishthook, and when intro- duced, can not be withdrawn. Never purchase such a hook-pointed enterotome. eral aspect of the vagina is carried anteriorly at the upper end and continued through the cervix and body of the uterus in the anterior wall. If urine be present in the bladder, its character and quantity should be noted, and it should be preserved for future examination. The left semilunar ganglion is examined, and any firmness or inflammatory signs noted. The ganglion should be preserved for microscopic examination. The corresponding organ of the right side is next in order of examination. The Stomach and Duodenum.—tIn cases where poisoning is suspected, ligatures are tied at the cardiac extremity of the stomach and the upper end of the duodenum, and the organ removed ; in order that the contents may be carefully examined, the stomach, without opening, should be placed ina clean jar and sent to the chemist. In case it is decided to open the duo- denum and stomach 2x sifu, as is best when the question of poison- 36 TECHNIC. ing does not enter into the case, make an incision along the anterior surface of the duodenum and greater curvature of the stomach. Examine contents, condition,and appearance of mucous membrane. Foreign bodies are frequently met with in the stomach. Deter- mine if the bile-duct is patulous by pressing upon the gall-bladder and watching for the escape of bile. In case this simple procedure does not reveal the presence of the ampulla and demonstrate that the cystic and common ducts are patulous they should be carefully dissected out. This can not be done after the removal of either the duodenum or liver ; as it is important in many, if not all, cases to assure one’s self of the condition of the hepatic, cystic, and com- mon ducts, and as cutting through either of them may render later demonstration unsatisfactory or even quite impossible, they should, therefore, be dissected out zz stfu. Open the ductus communis choledochus, examine mucous membrane, and con- tinue the incision upward into the gall-bladder and hepatic duct. The portal vein, hepatic vein, and vena cava may be opened before the removal of the liver ; or, as the first two must be severed during the removal of the liver, they may be examined at that time. Fic. 13.—PROBES. These should be at least fifteen or twenty centimeters long. One should be very slender. The condition of their contents and appearances of their walls must be noted. The /2ver may now be detached from the diaphragm, or, if it is adherent to that structure, the two may be removed together ; when the lung, liver, and diaphragm are fused by adhesions at their points of contact, and when there may be any suspicion of a suppurative lesion burrowing in either direction, it may be best to let the lung remain zz sztu until the proper time for the removal of the liver, when the three structures may be removed together ; neither the lung nor the liver should be sacrificed, but only that part of the diaphragm immediately involved need be removed with the attached viscera. The shape and color of the liver and any deformities of the lobes should be noticed, the anterior margin examined, and its condition recorded. The inci- sion made to disclose the interior of the liver should be a long, sweeping cut, on the superior aspect of the organ, extending through the longest axis, including both right and left lobes and sufficiently deep to permit the folding of the two parts without tear- ing the narrow band of tissue which holds them together on the in- POSTMORTEM EXAMINATIONS. 37 ferior surface of the organ. On section, the firmness or resistance should be noted; also the color, whether uniform or mottled, and whether or not bile staining be present. Weigh the organ. The pancreas may now be removed, and any peculiarity or change carefully noted. The esophagus should next be examined, and the dutestines removed. The latter should be carefully opened, and the con- HTM rm, [ia Fic. 14.—DISSECTING FORCEPS. One of these should be toothed. These will be needed in the finer dissections, as in tracing the hepatic duct, portal vein, and receptaculum chyli. tents examined as the incision is gradually extended. After the incision made by the enterotome has been concluded the mucous surface should be gently washed by a slowly flowing stream of water, and examined for inflammation, ulcers, cicatrices, perfora- tions, constrictions, etc. It is probably best to open the intes- tines before washing them out, in order to more accurately determine their contents, examine for animal parasites, locate Fic. 15.—MALLET OR HAMMER. foreign bodies, etc., but cleanliness and convenience often lead to an unwise reversal of the proper order. In cases of suspected poisoning the intestines should be sent, unopened and in a clean jar, to the chemist. The thoracic duct should now be traced, and the receptaculum chyli examined ; also the mesenteric and retroperitoneal glands. The aorta and its branches may now be examined in detail. 38 TECHNIC. Tue Heap.—Insert the scalpel, with its back toward the skull, just behind one ear, and carry an incision across the ver- tex, cutting from within outward. If the knife is not too sharp, the hair may be parted and thrown backward and forward as the hand and knife are withdrawn. The incision should be far enough back to be invisible from the front when closed. The scalp is reflected forward and backward from this incision as low as the superciliary ridge in front and the occipital protuber- ance behind. In many cases great care must be used to avoid a tear at or around the ear, as tension is produced by pulling the anterior and posterior scalp-flaps down; to avoid this unsightly tear, Fic. 16.—HEAvy LINE INDICATING COURSE TAKEN By SAW-CUT IN SO-CALLED UNDERTAKER’S METHOD. It is possible that the base line as drawn in this illustration is too low; however, this is im- material, as the method is under all circumstances to be avoided. which may run down in front of the ear, insert the knife under the skin, in the incision already made, just behind the ear, and dissect the skin free from the deeper structures behind and in front of the ear. The scalp-flaps, as already described, do not include the temporal fascia or muscle, which is now cut through and reflected in the line of the contemplated saw-cut. Sawing is greatly facilitated.by having all soft tissue free of the line of the contemplated cut, as the soft parts clog the teeth of the saw. When the skull-cap is replaced, the fascia and the muscles may be sewed together, thereby securing the bone in place—a matter of great importance in private postmortems when the body is to be exposed at a funeral or to friends. POSTMORTEM EXAMINATIONS, 39 Inspect the skull for evidence of injury or disease. In open- ing the skull there are three methods of procedure—one should never be used when it can be avoided, one may be used in a few cases, and one is applicable in the vast majority of instances : (1) The “undertaker’s cut” consists in sawing across the fore- head just back of the hair line, from one temporal fossa to the other, and carrying a second saw-cut around the posterior base, parallel with the base line, joining the anterior cut in each temple. This method does not permit of satisfactory removal of the brain. (2) The second method should always be used in medicolegal cases, and whenever the question of fracture may arise. It does not demand the use of a chisel, and affords Fic, 17.—CIRCUMFERENTIAL SAW-CUT, TO BE PREFERRED IN ALL MEDICOLEGAL CASES. The exact location of the line will vary slightly, depending upon the conformation of the skull. It is usually about as indicated above. abundant opportunity for examining the skull’s interior, A circumferential line is drawn around the base of the skull, on a level with the superciliary ridge in front and the occipital pro- tuberance posteriorly, and the skull sawed through at this line. (3) The third method, and the one most commonly employed, consists of a V-shaped incision ; as viewed laterally, the anterior arm of the V is parallel with the base of the skull, on a level with the superciliary ridge, and extends backward as far as % of an inch behind the external auditory meatus. The other arm of the incision passes obliquely across the vertex just back of the incision already made in the scalp. It may be necessary to break out the angles of the saw-cut with a chisel ; care must 40 TECHNIC. be used not to mutilate the ear in making the saw-cut. The adjustment and retention of the calvaria in place may be further aided by making the posterior saw-cut also V-shaped. The angular junction of the two lines which form the V are directed upward, something like the occipitoparietal suture. To repeat : This makes two V-shaped saw-cuts as follows : Viewed laterally, the anterior arm of the first V is parallel with the base line, and extends from the superciliary ridge to just behind and above the. external auditory meatus, the posterior arm of this V being sub- divided into the two arms of a second V, which, as viewed from behind, is upside down. The advantage of this incision lies in Fic. 18.—WEDGE-SHAPED CALVARIA REMOVED BY THE LINE OF SAW-CUT RECOMMENDED. (See Text ) If the posterior cut isso made, from the tight and left sides, that the point just above the figure 7 will be the apex of a triangle, two sides of which are formed by posterolateral saw-cuts, there will be no difficulty in retaining the wedge-shaped calvaria in place. the easily adjusted calvaria, the wedge-shaped cap being readily replaced and secured in position, so that no external evidence of the postmortem will be visible when the scalp is returned to place and sutured. Inspect the interior of the calvaria for evidence of injury or disease, noting its thickness and the condition of the diploe and of the external and internal tables. The dura may be removed, or, rather, reflected back, by incising it along the lower saw-cut and detaching the falx cerebri from the crista galli. When, as in the very young, it may be necessary to remove the dura with the calvaria, it will only be necessary to incise the dura along POSTMORTEM EXAMINATIONS. 4I the line of the saw-cut, and to sever the falx anteriorly and pos- teriorly before making any attempt to raise the calvaria. Inspect the surface of the brain for superficial injuries or dis- ease, but make no incision into it, It may here be necessary to note the relation of brain landmarks to the skull, fixed points of the latter being selected for the comparison. The brain is next to be removed, beginning in front by care- fully raising it from the base, being sure to raise the olfactory bulbs with the hemispheres ; still cautiously elevating the hemi- spheres, sever the nerves as they pass out of the skull, those in front first, and then in order as they appear. When the ten- torium is reached, detach it from the temporal bone and follow, the base, severing the nerves as they find exit from the posterior Th —— | FIG. 19.—CHISELS. If only one is to be purchased, the lowest one will be of most use. fossa ; lastly, pass a long, slender-bladed knife along the basilar process of the occipital bone, and down into the spinal canal, cutting the cord as low as possible. In order to section the cord as nearly transversely as possible and to avoid the oblique incision made in the manner just directed, some operators pre- fer the use of a myelotome. After section of the cord the entire brain can be easily removed. Complete the examination of the interior of the skull, noting the condition of the bone, blood- vessels, sinuses, etc., dissecting the dura from the base to facilitate the examination of the bone. Before detaching the dura the contained sinuses should be slit up and examined for evidences of thrombi, septic processes, etc. The posterior part of the orbit and the eyeball may be examined by chiseling the roof; in the 42 TECHNIC. same way examine the frontal, sphenoid, mastoid, and ethmoid sinuses and the internal ear. The drain should be, in most instances, hardened before dis- section ; if this can not be done, immediate examination may be made as follows : Make a careful examination of the meninges, and note the color, consistency, etc., of the external surfaces, includ- ing the base; the consistency is best determined by gently pal- pating the entire cortex. Examine the blood-vessels at the base, FIG. 20.—MYELOTOME. Used for separating the brain from the spinal cord. The advantage claimed for this instru- ment is the facility with which the cord may be cut transversely, thereby avoiding the objectionable oblique incision which is usually secured when the ordinary knife is used for the same purpose. tracing them into the brain-tissue. An incision is made on each side, just over the corpus callosum, into the lateral ventricles, and continued backward and forward, that they may be care- fully inspected ; the amount and character of the fluid present are noted, The lateral ventricles are joined by an incision through the fornix, reflecting the corpus callosum backward, exposing the tissues beneath. Search for hemorrhages, areas of softening, tumors, inflammation, abscesses, etc. Lateral Fic. 21.—SCALPEL WITH BLADE SHAPED SOMEWHAT LIKE A BISTOURY. Useful in removing the brain and spinal cord, The aneurysm needle and tenaculum shown are useful at times, but are not essential. incisions are now made in the cortex from the ventricle outward, so as to note the condition of the cerebral substance; the incisions should be parallel, not over one centimeter apart, and the membranes should not be cut through, as they will retain the cut parts in position. The brain is then turned over, and the tissue of the base examined by transverse incisions through the medulla, cerebellum, etc., examining for such changes as pre- viously noted. Weigh the brain. POSTMORTEM EXAMINATIONS, 43 While occasionally much information can be obtained by the gross examination of.a freshly removed brain, improvements in histologic technic have made the microscopic examination of greater importance. In order to obtain valuable information from this method, it is necessary to secure sections which permit of the rebuilding of the organ, so that the connection between different parts may be traced. This implies the use of some serial method similar to that employed in embryologic work. The size of the human brain precludes satisfactory serial sections of the entire mass, and as the serial sections are for the purpose of demonstrating histologic lesions in paths or bundles, each case will become to a certain extent a law unto itself. For the study of the neuroglia immediate fixation in special fluids is necessary (see section on Nervous System), and for the demon- stration of different lesions a different technic may be required. The Pitres-Nothnagel Method—The lateral ventricles are opened as described ; the pons and cerebellum are severed by sec- tion of the peduncles; the cerebrum is divided’ by a vertical section (longitudinal) through the median line—the third ven- tricle; each half of the cerebrum is then incised from above downward, transversely to its long axis and as nearly as may be parallel with the fissure of Rolando: (1) Five centimeters in front of fissure of Rolando ; (2) through posterior margin of the frontal convolutions ; (3) through ascending frontal convolution ; (4) through ascending parietal convolution ; (5) three centimeters posterior to fissure of Rolando; (6) one centimeter in front of parieto-occipital sulcus. The fixation of each of these sections completed, serial sec- tions are made from each area. While much more tedious and requiring greater care, this method permits of reconstruction and the adaption of parts so as to follow fillets, or paths, with a pre- cision not possible by the cruder methods. For demonstrating the condition of the blood-vessels at the sacrifice of everything else, the brain may be gently washed away and the blood-vessels floated out in a basin of water. Tue SpinAL Corp.—The body is turned upon the abdomen, and blocks are so arranged as to arch the vertebral column. An incision is then made through the skin, over the spinous processes, extending from the occiput to the sacrum, and the muscles, fascize, etc., detached from the vertebra so as to expose the laminz on both sides. These are then sawed through, the saw being held parallel with the spinous processes, and the saw-cut made near where the laminz join the pedicles. These are sawed through from the second vertebra to the sacrum and removed, 44 . TECHNIC. the chisel or bone-cutting forceps being used as aids if necessary. Inspect the meninges and remove these with the cord, carefully detaching, with a sharp knife, the nerve-roots as they pass out of the canal. The lower end of the cord, with its membranes, is first detached, and the removal continued from below upward. During the removal of the cord, whatever traction may be neces- sary should be made on the meninges only, and traction on, or crushing of, the cord should be carefully avoided. Lay open the meninges and examine the cord by making transverse incisions a centimeter apart. The examination of the joszts and dones of the skeleton may have preceded the visceral examination, but ordinarily it is deferred until that has been completed. Sometimes it is desir- able to obtain bone-marrow without fracturing or otherwise Fic. 22.—DouBLE SAW FOR SAWING THROUGH THE LAMIN®= OF BoTH SIDES AT ONCE. It saves time and labor, but equally good work can be done without it. severing the continuity of the bone. This is best accomplished by two saw-cuts parallel, one or two centimeters apart; and extending a little over half-way through the bone; by means of a chisel this block of bone is split out, bringing with it the marrow. A block of wood may be slipped into the space occu- pied by the piece of bone removed, and, where this fits tightly, bringing the tissues together over it will usually prevent the occurrence of a fracture during the ordinary handling of the body. The removal of the salivary glands is not often demanded. The sublingual and submaxillary glands may ordinarily be removed by the method already described when considering the larynx and pharynx. A portion of the parotid gland can some- times be removed by dissecting the skin down from the tem- poral region anteriorly, and below the incision already advised for exposing the skull. POSTMORTEM EXAMINATIONS, 45 In order to make a bacteriologic examination, it will be necessary to have on hand a Bunsen burner, alcohol lamp, or other means of sterilizing the instruments used. Cover-glasses, cover-glass forceps, platinum wire, various culture media, and labels will be needed. In order to secure material not contami- nated by accident, it will be necessary to enter all cavities through an aseptic field. The disinfection of the area is best accomplished by heat. In order to secure inoculations from the peritoneum, it will be necessary, as soon as the wound in the abdominal wall approaches the cavity, to sear the surface with a hot scalpel, or, what is better, a spatula; this must be done thoroughly ; through this seared surface, with instruments kept sterile by frequent passage through the flame, the wound is cau- tiously extended until the cavity is reached. At once cover- glass spreads and inoculations are made. Ina like manner the pleura may be opened through an intercostal space. Inocula- tions from the interior of the pericardium are best obtained by FIG, 23.—BONE-CUTTING ForRCEPs. These are not absolutely essential, but will be convenient. They should be long—not less than fifteen centimeters. cautiously searing the fold raised as already directed (p. 28), and puncturing with a hot knife or scissors. To secure blood from the heart, a part of the surface is sterilized by searing with a hot iron, or one of the great vessels may be similarly treated and opened, using for this purpose a hot knife or scissors. A plati- num loop may then be thrust into the cavity, and inoculations and spreads made in the usual manner. In considering organs a definite field or plan should be adopted. Of course, this will be quite often varied, but it has the advantage of occupying no more time than any other method, and assures a systematic record which makes all postmortems comparable. The following is advised, although each worker will probably acquire a routine of his own: (1) Malposition, and, if out of place, is the malposition congenital or acquired, and what influence has it had on the position or function of other organs: ¢. g., a misplaced right kidney may press upon the 46 TECHNIC. duodenum or bile-duct or upon both. After removal it is too late to determine such facts, which may be of the highest impor- tance in explaining symptoms. (2) Malformations. (3) Make measurements of the organ and weigh it; as the organ can be weighed only after removal, and as the removal severs its con- nection with the body, note must be made of color, consistency, density, and shape,—the latter being outlined when the measure- ments are made,—and a full description of its external appearance must be given; at the time of severing its attachments the /w//- ness of the blood-vessels, the presence or absence of edema, and, if it possesses a duct, the condition and contents of that struc- ture, must all be recorded. Whatever observations are to be made with regard to the ducts of organs must be completed before severing their connections. These studies enable one, to a cer- tain extent, to record the presence or absence of the following points, Fic. 24.—POSTMORTEM NEEDLES. which come next in order: (4) These should be sight to.Hfeensentt Atrophy, including hypoplasia or heavy. aplasia. (5) Aypertrophy, including hyperplasia. (6) Infiltration. (7) Degeneration. (8) Inflammations, including acute 7fections. (9) Lesions of systems: (a) vascular ; (b) lymphatic ; (c) ner- vous. (10) Chronic infections, (11) Tumors. (12) Parasites. If the steps indicated be followed, but little will be overlooked. As soon as an organ is incised pieces should be removed and fixed for microscopic study; the records may be completed after the microscopic examination is finished. PRESERVATION OF TISSUES. For preserving gross specimens alcohol is most commonly used. The tissue is washed in running water for a few hours to remove adhering blood, and is then placed in fifty per cent. alco- hol; at the end of from two to four weeks the alcohol should be replaced by sixty per cent. alcohol, in which the tissue may be preserved indefinitely. If a snowy whiteness is desired, a mix- ture of glycerin one part, water three parts, and alcohol five parts will be found useful for the final preservative. Specimens that have been preserved in glycerin mixtures are of little value for microscopic purposes, as they can be frozen, embedded, or infil- trated only with the greatest care, and usually with unsatisfactory results. Of late, formalin * has come into great demand for the * Formalin is a proprietary article; a forty per cent. aqueous solution of formal- POSTMORTEM EXAMINATIONS. 47 hardening and preservation of tissues. A ten per cent. solution in water will be found convenient, or the following when more time is available: The specimen to be preserved is lightly washed in water only, to remove adhering blood. It is then placed for ninety-six hours in— Formalin, . , BH ae ie BHOveLC: Nitrate of potassium, eH é Io gm. Acetate of potassium, . ie Na wa ae i ew 30 gm. Water, é I liter. Wash thoroughly in water and place in eighty per cent. alco- hol for twenty-four hours, and permanently preserve in a mixture composed of acetate of potassium one part, alcohol sixteen parts, and glycerin two parts. This mixture preserves the color fairly well, and after a time the specimen can be handled without injury to the hands. The following solution may be substituted for the final pre- serving mixture containing alcohol: - Acetate of potassium, . & waoae fing 200 gm. Glycerin, .. YG i Wh 400 c.c. Water, . ee . wk ia « 2000 c.c. Fixation is accomplished in the formalin solution and is followed by placing the tissue in eighty per cent. alcohol for twenty-four hours, then in ninety-five per cent. alcohol for twenty- four hours, and by final preservation in the mixture of acetate of potassium, glycerin, and water. Exposure to the light for any great length of time causes the colors to fade. After con- siderable fading partial restoration may be brought about by immersion in amylic alcohol. ; Organs or specimens not too large (one kilo) can be preserved in formalin vapor by placing the material to be preserved ona bed of cotton in an air-tight jar, previously moistening the cotton with pure formalin, and for the first few days keeping the speci- men covered by filter-paper moistened with formalin. For hardening brain-tissue, formalin has largely superseded Miiller’s fluid * for the gross specimen, and for certain purposes affords a satisfactory fixation for histologic research. Miller's fluid darkens the tissues, and thus alters their macroscopic appearance. Small cysts, such as those of the echinococcus, are best pre- served in a ten per cent. solution of chloral in water. dehyd gas, dissolved in water. The original formalin was expensive, but equally efficient solutions, under other names,—as formalose, formo/,—can be obtained now at a price making preservation by this method cheaper than with alcohol. * For formula of Miiller’s fluid see next section, p. 49. CHAPTER II. HISTOLOGIC METHODS.* Morbid Histology.—Z¢chnic.—Sections of the fresh tissue may be cut either free-hand or by means of Valentine’s knife, which consists of two parallel knife-blades of the utmost sharp- ness, separated from each other by a small aperture just as wide as the section is to be thick. Both methods are unsatisfactory, and are rarely used. Fresh tissue may be cut by freezing, as will be directed later. Since the publication of the first edi- tion of this book, extended experience has convinced me of the necessity of thoroughly fixing all tissues before attempting to section them. By &c/déng or fixing is meant the destruction of all metabolic processes and the securing of the tissue perma- nently in just such a condition as it presented during life, retain- ing the cell pictures as perfectly as possible. The following methods are advised : (a) Chromo-aceto-osmic acid mixture (Flemming’s solution). For this solution keep on hand the following stock solutions, and make up for use as wanted, in the proportion given : Quantity needed to make Stock solutions to be kept on hand. up Flemming's solution. lie een. agueOne solution of chromic acid, . . . . 25 volumes. I s¢ «© osmic CE eae ee LO oe IL “e ee oe “cc acetic oe A . Io “ee Waterce kegs ee wie ee GS ee All the water used in making the stock solutions or the final mixture must be distilled, and all containers should be chem- ically clean and dust free. Fixation of small pieces will be complete in from one-half to *In the present edition of this book there have been inserted, whenever their im- portance seemed to demand it, such technical directions as may be necessary for the demonstration of special reactions or methods. When searching for directions bear- ing on some point, the student is advised to consult the index. No attempt can be made in such a work as this to go into the subject of histologic technic with elaborate detail. A few methods can be taught, it is believed, thoroughly; but for further detail as to special methods the student had best familiarize himself with that best of all books for the worker with the microscope, ‘‘ The Microtomist’s Vade-mecum,’* by Arthur Bolles Lee. 48 HISTOLOGIC METHODS. 49 two hours, although a longer time may do no injury. A period beyond a few hours, however, is likely to make the tissues brittle. After fixing, wash thoroughly in water. This is best accomp- lished by washing in flowing water for at least six hours. Pro- ceed to embed at once or preserve in seventy per cent. alcohol until needed. (6) Platino-aceto-osmic mixture (Hermann). Like the fore- going, it is best freshly prepared : Quantity needed to Stock solutions to be kept on hand. make up above solution. I per cent. aqueous solution of platinic chlorid, . 15 volumes. a ae ee on osmic acid, 2 & Glacial acetic acid, . : T volume. This solution is used as already directed for Flemming’s solu- tion, and should be followed by the same careful washing. Tissue so prepared may be treated as already directed for tissue prepared in Flemming’s solution. (c) The most useful fixing agent for general use is corrosive sublimate. The solution keeps well and fixes thoroughly, although for pure cell study the foregoing solutions are probably better. The solution is prepared by dissolving 125 gm. of corro- sive sublimate ina liter of 0.5 per cent. solution of sodium chlorid in water. The solution of the corrosive sublimate being effected in the boiling salt solution, on cooling crystals of corrosive subli- mate are thrown down, but are again taken up as the solution is used over. Small pieces of tissue fix in this solution in from one-half to two hours. The used solution is filtered back into the stock solution, and the tissue washed in water or, what is better, seventy per cent. alcohol. A little experience soon enables one to infer when the stock solution has become ex- hausted. By reason of its convenience, keeping qualities, cheap- ness, and the simplicity of the technic, it is most used. In fixing by any of the above methods, the tissue should be in small pieces, not larger than 0.5 to 1 cm. cube. The quan- tity of the fluid used should be abundant, and exceed several times the volume of the tissue to be fixed. For the preparation of tissue containing nerves, or the central nervous system, nothing has been more generally used than bichromate of potassium. It is used in two to five per cent. aqueous solutions, Miiller’s fluid, or Erlicki’s solution : Miller's Fluid. Erlicki’s Solution. Bichromate of potassium, . 2 parts. Bichromate of potassium, . 2.5 parts. Sulphate of sodium, I part. Sulphate of copper, 1.0 part. Water, : . 100 parts. Water, d 100.0 parts. 4 50 TECHNIC. The latter hardens much more rapidly ; a spinal cord may be hardened in two weeks by this mixture, while by Miiller’s fluid as many months would be necessary. As the penetration of neither of the above is rapid, nerve tissue placed in them should be freely incised to aid penetration, a spinal cord being cut trans- versely every centimeter. As soon as the fluid becomes dark or cloudy it should be changed, and the quantity should always be several times the bulk of the tissue. After hardening is com- pleted, the tissue should be thoroughly washed in water before transferring to alcohol. The foregoing bichromate solutions have been largely sup- planted by two more recent acquisitions : Lenker’s Fluid. Bichromate of potassium, 2.5 parts. Sulphate of sodium, I part. Corrosive sublimate, 5 parts. Water, enough tomake. . 95 ae Glacial acetic acid, to be added just ‘before using, 5 “s Fix small blocks of tissue, 0.5 centimeter in thickness, for from one hour to twenty-four hours; wash in running water for: twelve hours and preserve in eighty per cent. alcohol. Orth’s Fhidd. Miiller’s fluid, . . 100 parts. Formaldehyd ‘(forty per cent. solution), Io‘ The fluid should be-freshly prepared from the two stock solu- tions. The material should be small pieces—cubes from 0.5 to 1 cm. Fixation will ordinarily be complete in from two to four days ; the material should then be washed in running water for from six to twelve hours and preserved in eighty per cent. alcohol. Alcohol is sometimes used as a fixative. To be efficient it must be as nearly ‘absolute as possible. Weaker solutions give rise to easily recognized and quite characteristic artifacts. For the demonstration of bacteria in tissue, fixation by alcohol is permissible ; it has, however, no advantages over corrosive sub- limate, even for this purpose, and is always associated with a very grave disadvantage, in that one desiring to study the nuclei may find that the fixative has not properly preserved them. Alcohol is largely used as a dehydrating agent and for the preservation of tissues during the interval between fixation and the final steps in the embedding process. It is the ideal agent for neither purpose, but for the present it seems to be the best that we possess. HISTOLOGIC METHODS. 51 SECTION CUTTING. INFILTRATION METHODS. 1. Paraffin.—After fixing and washing as already directed, the tissue to be infiltrated is dehydrated by passing through alco- hols of increasing strength—seventy per cent., twenty-four hours ; eighty per cent., twenty-four hours; ninety per cent., twenty- four hours ; absolute, twenty-four hours. As alcohol does not ' mix with paraffin, it must be displaced by some agent that will dissolve paraffin. For this purpose numerous reagents have been used, such as chloroform, turpentine, xylol, toluol, benzol, cedar oil, and many allied bodies. Many of these alter the tissues ; probably all of them do slightly, but the least objection- able is cedar oil. From absolute alcohol the tissue is carried into the clearing agent, preferably cedar oil, and, to make the FIG. 25. Flat-iron-shaped copper table, which may be used for paraffin infiltration as well as for the fixation of blood films. Ifa Bunsen burner be placed under the tip of the sharpest corner, to the right of the single leg, and the strip be heated to a constant temperature, so that the extreme end from the burner may be cold, any degree of temperature between the cooler part and that part over the burner, which is practically red-hot, may be obtained. As shown in the cut, asmall paraffin dish is placed over a spot where the paraffin is kept barely melted. change gradual, the cedar oil is diluted with an equal part of absolute alcohol ; after twenty-four hours’ treatment in this mix- ture the tissue is transferred to pure cedar oil for twenty-four hours, and then to paraffin, which in summer has a melting- point of 50° C., in winter of 45° C. The paraffin must be kept as near the melting-point as possible by means of a paraffin oven and a thermoregulator. After twenty-four hours the tissue is transferred to fresh paraffin at the same temperature, in which it is kept from twelve to twenty-four hours. The gentle heat, continu- ously applied, displaces the cedar oil and permits the paraffin to infiltrate the interstices of the tissues. A wooden block—about a two-centimeter cube—has one end warmed over a Bunsen burner and dipped in the melted paraffin. It is then wrapped with a strip of paper four centimeters wide, so that the paper projecting from the end of the block that has been warmed and .coated with 52 TECHNIC, paraffin forms a well as deep as the tissue to be mounted. The block of tissue is then placed in position at the bottom of the well, arranged to cut to the best advantage, and melted paraffin 30mm. 22mm. Fic. 26. FIG. 27. Block of hard wood or of rubber fiber as Same block as figure 26, with corners properly usually received in the laboratory. trimmed to receive paraffin or celloidin for embedding. Fic. 28. Method of applying paper to block. is poured in until the well is filled. This is allowed to cool and the paper is then removed. The paraffin is now gray, appears granular, and is said to be in the crystalline form; if put ina warm place,—care being taken that it is not warm enough to HISTOLOGIC METHODS. 53 melt the paraffin,—it soon becomes transparent, or, it is said, the paraffin becomes amorphous or hyaline. The block is now ready to cut. It is trimmed down nearly to the tissue, each side being cut so as to present a surface square to the knife, the general aspect of the block being that of a truncated pyramid. The paraffin trimmed off is remelted, and may be used many times. The block is clamped in the holder of the microtome so that the cutting-edge of the knife strikes squarely against the block along its whole length ; the knife is so arranged that it cuts like a chisel, and not with a drawing motion. To get the best sections, the paraffin must be of the A A \ SN A A foe trro--ne if 1 kK—-P-1 4, 8 ! asd RS x Ro Ne ad x Pas nai eee T me a ret ia eM c Fic. 29. FIG. 30. Paper (A, A, A, A) properly wrapped around block (C), with block of tissue (B) to be em- bedded, ready for pouring ee in and completing the cast. After the cast cools see text) the paper is removed and the paraffin is trimmed, as shown in figure 30, care- red avoiding the block of tissue, which should be thoroughly covered by the paraffin at all points. proper temperature, as this determines the density ; in summer the block may have to be cooled by ice ; in winter it may require warming. The most important factor in paraffin infiltration is thorough dehydration and clearing. Absolute or approximately absolute dehydration is necessary in order to secure penetration of the clearing agent—cedar oil, xylol, or whatever it may be. If the pieces of tissue are small, the stages of the process may be shortened. ‘Tissue kept too long in strong alcohol or in the clearing agent or paraffin (warm) not infrequently becomes brittle. The occurrence of this condition should lead the worker to shorten the stages sufficiently to overcome the difficulty. When 54. TECHNIC. osmic acid methods have been used for the purpose of determin- ing the presence of fat, the clearing agent and paraffin may, under some conditions, partly remove the fat. In osmic acid preparations, when the fat is to be retained, celloidin infiltration is to be preferred. iy i Ht Wie Fic. 31.—NAPLE’sS PARAFFIN BATH FOR INFILTRATING TISSUES IN PARAFFIN. The apparatus consists essentially of a series of receptacles for holding the melted paraffin, with a surrounding water-bath retained at an even temperature by a thermoregulator. FIG. 32.—FoRCEPS CONVENIENT FOR HANDLING COVER-GLASSES, BLOCKS OF TISSUES, AND SECTIONS. It will be seen that the foregoing process requires days, and to . overcome this objection Reeves has recommended the following : (1) Fixin saturated alcoholic solution of corrosive sublimate for one hour. By this method fixation and dehydration go on together; (2) absolute alcohol, one hour; (3) xylol, one i i Fic, 33-—LABORATORY MICROTOME, Can be used, as shown in the cut, for celloidin sections; an attachment for freezing may be substituted for the clamp shown in the illustration immediately below the knife. For paraffin blocks the knife must be turned with its cutting-edge at a right angle to the plane of the knife-carrier. 55 56 TECHNIC. hour. As xylol has a very low volatilizing point, it quickly evaporates in the paraffin bath, and permits the rapid penetration of the paraffin ; it is kept one hour in the first paraffin and one hour in the second, when it is cast. In order to prevent the crystallization of the paraffin the cast is plunged into ice-water as soon as its surface has cooled sufficiently to form a thin film ; the cooling may be facilitated by holding the block out of the window in winter or by gently blowing upon it in summer. The cast is now trimmed and cut. Of course, the pieces of tissue to be prepared in this way must be very small,—not over 0.5 cm. cube,—and the results can not be considered as comparable to the slower method already described. Mounting Paraffin Sections—If the sections be properly cut and the infiltration has been satisfactory, they will adhere in chains or ribbons as they come away, or each section may be removed from the knife as rapidly as cut, using a short sable Fic. 34.—SMALL Microscopic Scissors. Suitable for trimming sections and labels and for other microscopic work. brush for the purpose. To insure thin sections, the knife must be of the utmost sharpness. Before the sections are cut it is best to prepare the slips to receive them. The slips or slides are thoroughly cleansed with alcohol and dried, using toilet- paper or a soft cloth for that purpose, Place on the center of the slide a very small quantity—less than a drop—of Mayer's albumin, and with a perfectly clean finger wipe it off. This leaves an almost imperceptible layer of the albumin. On this place a few drops of water,—enough to float the section just clear of the albumin,—and place the section on the water ; gently warm the slide, being careful not to melt the paraffin; as the section becomes warm it will straighten out, all folds and wrinkles disappearing. Now carefully pour off the excess of water, and the section falls upon the layer of albumin, to which it adheres. Mayer's albumin is composed of egg-albumen (white of egg) and glycerin, of each 100 c.c., to which one gram of salicylate of sodium has been added to aid the glycerin in preserving the HISTOLOGIC METHODS. 57 albumin ; after thoroughly mixing, the mass is filtered through paper—a process requiring weeks. The albumin fixes the section to the slide, so that it may be taken through the subsequent Fic. 35.—RYDER MICROTOME. Expressly adapted for paraffin sections and for cutting in series; can not be used for frozen a Can be used for celloidin if the chloroform method of hardening has been adopted. Fic. 36.—RANVIER’S MICROTOME, Blocks of tissue infiltrated with celloidin or paraffin may be cut in sections free-hand with an ordinary razor; better results may be obtained by even so simple a microtome as the above (Ranvier’s microtome), or very much better results by the Ryder, Minot, or Bausch and Lomb instruments.—(Jd/ustration from Gould's Dictionary.) processes without the least trouble. After the section has been drained of the water upon which it was floated to facilitate 58. TECHNIC. straightening out, it is placed in a drying oven to get rid of any remaining water. In ordinary work where no great haste is demanded the slide may be placed in some warm place, protected from the dust, until perfectly dry. After drying, which may require from four to twenty-four hours, the slide is gently warmed until the paraffin just melts, and no more; it is then thrust into ordinary a i On Fic. 37—MINoT MICROTOME, » - Two sizes of the instrument are made: the illustration is of the smaller size. The corrug- ated metal plate just above the knife is intended to receive the block of tissue which is cemented on by the use of melted paraffin. The writer has found this extremely difficult and tedious, and has devised a clamp which replaces the complicated orienting attach- ments shown in the cut, and grasps the block shown in figure 30, without the necessity of cementing the tissue to the microtome. kerosene, or, what is slightly better but much more expensive, xylol; either of these quickly removes the paraffin, usually re- quiring about fifteen minutes; wipe off the excess of xylol, rinse the slide in alcohol, and place the slide in that liquid until the xylol is removed. From the alcohol the section is stained as will be directed later. If the tissue was fixed in corrosive HISTOLOGIC METHODS. 59 sublimate, this must be removed by treating the section with tincture of iodin, in which it is immersed for fifteen minutes ; it is then washed with a few drops of alcohol and placed in a jar of alcohol, from which it is removed for staining when desired. 2 2. Celloidin Infiltration.—Celloidin is a proprietary product first used in wet plates for photography, and is nothing more than a nonexplosive gun-cotton. As used, it is dissolved in equal ' Fic. 38.—DRYING OVEN. A, Three tubes for admitting air to interior. At Dare three similar exit tubes. 2B. Shelves upon which slides are placed at the student’s desk, from which, after labeling each slide and placing under the slides a piece of paper with his name and desk number, he places the tray in the oven. C. Thermometer. Z£. Thermoregulator. /. Water-gage. Cock for emptying the water space. The temperature of the oven should never reach the melting-point of the paraffin, and had best be between 37° C. and 40°C. parts of alcohol and ether, thus making a collodion that, so far as the author can observe, has ‘no advantage over a good collodion made from gun-cotton. The alcohol used for this purpose should be absolute ; the solution will be facilitated by placing the celloidin in a tightly stoppered bottle—a citrate of magnesia bottle is to be recommended—and pouring on the absolute alcohol, which should be allowed to remain in contact with the celloidin for twenty-four hours, when an equal volume of ether should be added. By this method solution will be complete and no time will be lost. As ordinarily used, two solutions are needed— 60 TECHNIC. one a thick, syrupy solution, and a second thin solution made by diluting the thick solution with an equal quantity of alcohol and ether. The tissue to be infiltrated is fixed and dehydrated as already described for paraffin ; it is then placed for twenty- four hours in a mixture of equal parts of alcohol and ether. From this the tissue is transferred to the thin solution of cel- loidin. The best results are obtained by leaving the mass for infiltration several days in this solution, when it is placed for an equal length of time in the thick solution. A block is then soaked in alcohol and ether for one or two hours or longer, and one end is coated with celloidin and wrapped in paper, as already directed for paraffin. Into the well the infiltrated piece of tissue is placed, arranged as desired for cutting, and the thick celloidin solution is poured over it; the mass, which is now said Fic. 39. NEEDLES AND BRUSH SUITABLE FOR HANDLING SECTIONS. to be cast, is placed under a lightly fitting bell-jar or cover until the celloidin begins to set, when it is thrown into eighty per cent. alcohol for hardening. At the end of twenty-four hours it will be found sufficiently hard for cutting, but it may be kept in- definitely in the alcohol and cut when desired. Unlike paraffin, celloidin must be cut with the microtome knife at an angle to the block,—that is, with a drawing motion,—and, while the paraffin was cut with a perfectly dry knife, the celloidin must be cut with a knife kept flooded with eighty per cent. alcohol. Each section is removed from the knife as cut and is transferred to eighty per cent. alcohol, in which it may be preserved until wanted for use. The great advantage claimed for celloidin is that, unlike paraffin, it need not be dissolved out before the section is stained. Stains such as carmin and hematoxylin may be used, the celloidin holding the sections together during the manipula- tions incident to staining. ¢ HISTOLOGIC METHODS. 61 Guson’s Method.—A satisfactory method of celloidin infiltra- tion is that devised by Gilson, in which, after dehydration and treating with the alcohol and ether mixture, the tissue is placed in a test-tube containing several centimeters of thin celloidin solution ; after a few days in the thin celloidin, the test-tube is immersed in a water- or paraffin bath at about 42° C., at which temperature the solvents (alcohol and ether) rapidly evaporate, thereby hastening penetration and increasing the density of the infiltrating mass. When the solution has evaporated to about one-third its original bulk, it is turned out and cast as in the slow process. The hardening of the block is greatly facilitated and the results are improved by hardening in chloro- A-GROUND SURFACE. RRA Sa SSW WS yy) CROSS-SECTION ATB SHOWING SLIDES IN POSITION. LID WITH EDGE GROUN. 70 HIT fi, e Fic. 40.—DISH FOR REMOVING PARAFFIN AND CORROSIVE SUBLIMATE AND FOR DEHY- DRATING. s May also be used for staining, and for the same purposes as the Stender dish. After the sections are cemented on the slide the slides are placed back to back and slipped down in the groove, as shown at B at the bottom of the dish. If the slides are thin, the dish will hold ten at one time. form. The process is applicable to blocks that have been infil- trated either by the slow or by the rapid method. As soon as possible after the cast is made the mass is placed in a desiccator or sieve dish, or in a bottle containing a teaspoonful of chloroform and having a tightly fitting stopper. A support is arrfiged above the chloroform, on which the block to be hardened is placed, and the vessel is then tightly closed. From two to twelve hours will be sufficient for the hardening, after which the block is placed in a mixture of cedar oil two parts and chloroform one part ; more cedar oil is added from time to time until nearly pure cedar oil is attained. The sections are cut dry, 62 TECHNIC. as in the paraffin method. The block may be preserved indefin- itely in the cedar oil.* After cutting, the sections are washed in alcohol in order to remove the cedar oil, and may then be stained. Sections obtained by the celloidin embedding and infiltration process may be secured to the slide by ether vapor or by a very thin layer of celloidin. The best method is to float the section on to the slide, blotting it carefully with bibulous paper, and, from a bottle containing a small quantity of ether, to pour the vapor of the ether upon the section. This will sufficiently soften the celloidin to make it adhere to the slide during the rest of the manipulations. It is to be remembered that celloidin sec- tions must be kept moist throughout the entire course of their preparation. Drying them is, asa rule, injurious, if not destructive. 3- Congelation Method.—Fresh tissue may be frozen and sectioned, but the best method is that of Hamilton: (1) Harden ; (2) wash out the hardening fluid; (3) place in sugar solution for from two to twenty-four hours; this solution is composed of two ounces of sugar dissolved in one fluidounce of water ; after removing from the syrup, wash lightly in water and (4) place in mucilage for two hours. The tissue may now be put on the drum of the freezing microtome, frozen, and cut. Remove sec- tions from the knife with a soft brush, and wash them thoroughly in water to remove the gum and sugar; the staining is proceeded with as for other sections. Remarks onthe Foregoing Processes.—For small pieces of tissue the paraffin method is best ; thinner sections can be cut, and the method of cementing them on the slide makes the hand- ling most convenient. For large blocks, such as an eye, and for tissues from the brain, spinal cord, or larger nerve-trunks, celloidin is to be preferred. After using the freezing method to a very large extent for about ten years, the author is thoroughly con- vinced that it is not to be relied, upon. The ice crystals that form in freshly frozen tissue break up the cells and give results that may mislead the most experienced investigator. The distor- tion of structure incident to the use of congelation masses, their macerating properties, and the difficulty in removing the infil- trate, have led me to give them up entirely for laboratory work ; only the crudest kind of pathologic work can be performed by * Since the publication of the last edition of this manual the writer has known of considerable difficulty by reason of the softening of the celloidin when preserved in cedar oil. The cause of this unfortunate complication was not at first discovered. It would appear that the success of the method depends upon the quality of the cedar oil. Mayer has recently informed Harris that cedar oil prepared by Schimmel did not in the least soften the celloidin, HISTOLOGIC METHODS. 63 the freezing and congelation methods at present at our disposal, and the results are always open to criticism. ‘ STAINING AND MOUNTING. General Remarks.—As a rule, it is best for the student to work with one stain until he is familiar with it ; and before com- bining two or more stains it is best for him to familiarize himself with the action of each stain when used alone. The student should remember that there are two principles involved in staining: (1) When a stain shows unusual selectivity in certain bodies, such as cell nuclei, it is allowed to act only long enough to color the desired bodies ; its action is then stopped and the preparation of the mount continued. (2) The stain is per- mitted to act until everything that will receive the color is stained, and then some agent is applied that differentiates cer- tain elements by removing the stain from other structures. Thus, acid alcohol is used to differentiate in carmin staining, and water after hematoxylin. Alcohol or water, either of which may be used with or without acidulation, are also used to differentiate with the anilin dyes. The objection to examining sections un- stained is that no one structure is prominent; and if everything in the section be uniformly colored, nothing is gained by the staining. For this reason differentiation is more or less applica- ble to all stains. After differentiation, or in some instances simultaneously with this process, dehydration is necessary in order to proceed with the next step—clearing the section. The process of clearing is necessary in order to examine the section by transmitted light. Clearing also makes the application of a permanent medium, such as xylol balsam, possible. The clearing agents mentioned in the preceding and following pages are not all applicable under all circumstances. The best clearing agents are cedar oil, creasote, xylol, and possibly one or two other agents having more or less special uses. , Carmin and Hematoxylin.—The two stains most frequently used in laboratory work are carmin and hematoxylin. Strongly alkaline stains, such as lithium carmin, are no longer to be com- mended; the same is true of bulk staining. The carmin most useful in the laboratory is Grenacher’s alcoholic borax-carmin : Alcoholic Borax-carmin. Carmin (best No. 40), s : : . 3 parts. Borax, ‘ 4“ Mix and pulverize thoroughly in a mortar, and add Ioo parts of water; boil for half an hour; add an equal bulk of seventy per cent. alcohol ; set aside for one week, and then filter. 64 TECHNIC. To stain, add enough of the stain to the section on the slide abundantly to cover it, and allow it to act for from five to ten minutes or longer. Drain off the excess of stain, wipe around the section with paper or soft cloth, and apply acid alcohol. Acid Alcohol. Hydrochloric acid, : I part. ‘Water, 29 parts. Alcohol, ‘i 7o .«€ The section, as soon as the acid alcohol is applied, turns trom a purplish-red to a light crimson, and becomes more nearly transparent ; it is then washed in strong alcohol, the excess wiped from around the section, and the latter is covered with creasote. The alcohol dehydrates and removes the acid, which is the differentiating agent, and the creasote renders the section clear for examination by transmitted light. As soon as the sec- tion is clear remove the excess of creasote, apply a drop of balsam, and cover with a thoroughly cleansed cover-glass ; label the section. It will now keep indefinitely. One of the best carmin stains is Mayer's carmalum. This is made by dissolving 1 gm. of carminic acid and 10 gm. of alum in 200 c.c. of distilled water, using heat if necessary. In order to preserve the solution add 0.1 per cent. of salicylic acid, or 0.5 per cent. of salicylate of sodium. The solution is clarified by decanting or, better, by filtration. The great advantage of this solution lies in the fact that it is almost impossible to overstain with it, and by careful washing and differentiation practically all intermediate degrees of staining can be obtained. It may be differentiated in acid alcohol, as already directed for borax-car- min, or, if the alcohol used for the subsequent dehydration be strongly tinted by the addition of picric acid, the combined action of the two stains (the carmin being a nuclear stain and the picric acid a protoplasmic stain) will afford one of the best general stains found in the laboratory. Picric acid may be used in the same way with borax-carmin, but the result is not so satis- factory. Hematoxylin Staining.—One of the best forms of this stain is Delafield’s, made as follows: Dissolve 4 gm. of hematoxylin crystals in 25 c.c. of strong alcohol; add this solution to 400 c.c. of a cold, filtered, saturated aqueous solution of ammonia alum ; expose to light and air for several days. Filter and add: Glycerin, . ee aS od - » 100 cc. Methylic alcohol, . . . . ‘ - Iooc.ec. HISTOLOGIC METHODS. 65 Allowed to stand in the light, with the bottle loosely corked, this mixture turns dark purple, almost black ; it should then be filtered and kept in tightly stoppered bottles. For use it should be much diluted ; the amount of dilution must be determined for each lot, varying with the degree of oxidation and with the age of the stain. If made with distilled water, and provided that all vessels and containers are kept chemically clean, this stain will keep for years. To use it, the sections on the slide, prepared as already directed, are covered with the diluted stain for from five to fifteen minutes, washed with water, dehydrated in alcohol, cleared with creasote, and mounted in balsam as directed in the last steps for carmin, except that differentiation is secured by the use of water, and not by acid alcohol. A better stain is secured Fic.. 41.—DROPPING-BOTTIE WITH BARNES’ FIG, 42.—PROPER SIZE LABELS FOR LABEL- DroprpER, WHICH CLOSES THE MOUTH OF ING MICROSCOPIC SLIDES. THE BOTTLE LIKE A RUBBER STOPPER. These bottles are usually of one ounce capacity, and are convenient for holding stains and staining reagents. by taking enough distilled water in a bottle or staining dish to immerse the slide on end; to this add enough of the hema- toxylin to just a little more than color the water ; the sections cemented on the slide are left in this overnight (or even for twenty-four hours), washed in water, and treated as previously directed. Hematoxylin not only stains the nucleus, but affords a light tint to the protoplasm as well. This latter, however, can be better secured by using eosin. After the section is stained in hematoxylin and washed in water, the excess of the water is removed and the section is treatéd for a moment in an alcoholic solution of eosin (0.5 per cent.), followed by alcohol and crea- sote, and is then mounted in balsam. The nuclei are stained purple by the hematoxylin and the cell protoplasm pinkish by 5 66 TECHNIC. the eosin. This makes a very fair contrast stain, and brings out some pathologic bodies not shown by the hematoxylin. In addition, it shows red blood-corpuscles to the very best advan- tage, being a specific stain for hemoglobin. Preric acid may be used with hematoxylin to advantage, particularly if the sections are a little thick or if they are overstained in the hematoxylin. After washing the hematoxylin stain thoroughly in distilled water, the subsequent dehydration is accomplished by the use of alcohol containing a trace of picric acid. The nuclear stains obtained by this method are sharp, and the yellowish proto- plasmic tints are beautifully transparent. Anilin Dyes.—In addition to the use of these agents for staining bacteria, they have become important and useful adju- vants in certain microchemic reactions, which will be referred to under special headings throughout the book; and also for general stains. For practical purposes the anilin dyes may be divided into two groups: z. Basic group, in which the staining property is due to the base present in the compound. 2.,Acid group, in which the staining property is due to the acid principle. The basic colors are, as a rule, sharp nuclear stains, while the acid dyes stain, more or less diffusely, the protoplasm in the cell. As a rule, the dyes are used as concentrated solutions (1) in water ; (2) in five per cent. carbolized water; (3) in thirty to sixty per cent. alcohol, preferably about fifty per cent. Under some conditions the dyes seem to act best if the solutions are rendered faintly alkaline; or at other times, faintly acid. The alkalinity is usually secured by the addition of a very small quantity of carbonate of potassium, and the acidity by an extremely dilute solution of acetic, formic, or hydrochloric acid. The basic anilin dyes commonly used are safranin, fuchsin, methylene-blue, thionin, gentian-violet, toluidin-blue, etc. The acid stains mostly used are eosin, orange G, acid fuchsin, etc. The following formulas and methods are introduced as ex- amples, and after the student has familiarized himself with the technic given, he may apply the knowledge so obtained to stain- ing with other and similar anilin dyes.* * One of the great difficulties with anilin dyes is the inconstancy of their composi- tion and the unreliability of many samples placed on sale. For this reason it is recommended that in purchasing the anilin dye the student should always specify the make of Griibler. HISTOLOGIC METHODS, 67 Safranin is a most excellent nuclear stain. The following formulas are to be recommended : Saturated solution of safranin in water, heated to 75° C.; after thorough saturation, filter ; stain from two to five minutes to twenty-four hours, depending upon the tissue, length of fixation, etc. ; wash in water, differentiate and dehydrate simultaneously in alcohol, clear in xylol, and mount in xylol balsam. A mixture compared of one part of the above solution of safranin and one part of a saturated alcoholic solution of alcohol-soluble safranin makes a satisfactory stain, and may be used in the same way. Methyl-violet.—One or two per cent. solution in water. Stain from two to five minutes or longer, and treat in the same manner as already given for safranin. Methylene-blue.— Unna’s alkaline methylene-blue solution :* Methylene-blue, . ae I part. Carbonate of potassium, * Litt Water, . 100 parts, The stain should be diluted to one-tenth its strength when required for use. Stain from half an hour to several hours, rinse in water, differentiate and dehydrate in alcohol, clear in xylol, and mount in xylol balsam. Toluidin-blue.—Make a one per cent. solution of the stain in a five per cent. solution of carbolic acid in water; stain from five to ten minutes to twenty-four hours, differentiate and dehy- drate in alcohol, clear with cedar oil, and mount in xylol balsam. Ziehl’s Carbolfuchsin.—Rub up 1 gm. of powdered fuchsin with 10 c.c. of alcohol in a glass mortar; dissolve 5 gm. of crystalline carbolic acid in 100 c.c. of distilled water ; mix the two solutions and the stain is ready for use. The stain may be prepared by the addition of 10 c.c. of a saturated alcoholic solu- tion of fuchsin to 90 c.c. of a five per cent. aqueous solution of carbolic acid. Stain sections two to five minutes to several hours ; differentiate and dehydrate in alcohol, clear in clove oil or xylol, and mount in xylol balsam. As a rule, sharpness of nuclear stain is obtained by overstain- ing, followed by careful aiferentiation, which must be stopped at a certain time; the best results are obtainable after repeated experiments and many failures. Alcohol as a differentiating * This stain resembles, when diluted, Léffler’s alkaline methylene-blue, the formula of which is as follows: Saturated alcoholic solution of methylene-blue, Le 30 c.c. Potassium hydrate (0.01 per cent. aqueous solution), . 100 c.c. May be used for staining tissues, but is more useful in bacteriologic staining. 68 TECHNIC. agent does not give the best results, nor is the differentiation in alkaline or faintly acidulated water ideal. Two of the most satisfactory differentiating agents with which the writer is familiar are glycerin-ether and styrone. The glycerin-ether mixture (Unna) is obtained from Gribler, and should be diluted at least one-half for use. Sections are stained rather deeply in Unna’s alkaline methylene-blue solution or Unna’s polychrome methylene-blue or in carbol-toluidin-blue, rinsed in water, and covered with the diluted glycerin-ether mixture. At first the dye comes out in clouds; later, differen- tiation progresses more slowly. The exact point at which to arrest the differentiation can be learned by experience only. In order to arrest the action of the glycerin-ether the excess is poured off, the section washed in alcohol, cleared in cedar oil, and mounted in balsam. Styrone is a solid, camphor-like body at a low temperature ; at the ordinary room-temperature it assumes a syrupy con- sistence. It is a differentiating agent that also acts as a clear- ing agent and is superior to other differentiating agents in that the tissues may be watched under the microscope, without a cover-glass, during the process of differentiation. In order to apply it, the section, stained as already advised for glycerin- ether, is hastily washed in water, followed by alcohol, and the styrone is at once applied. The styrone first applied becomes cloudy, deeply dyed, and is poured off; fresh styrone is added, and the slide is placed on the stage of the microscope. As soon as the differentiation has become satisfactory the styrone is washed off with cedar oil, the application of the latter agent being con- tinued until all differentiation has ceased ; the cedar oil is then re- moved and xylol balsam and cover-glass are applied. In clearing sections stained by basic anilin dyes, disaster commonly follows the application of creasote. Xylol is considerably better, but the best results are obtained by the use of cedar oil, which acts slowly and must be given time; gentle warming hastens the clearing, but is rarely necessary if the dehydration has been complete. Eosin may be used with either of the nuclear stains previously given. It is particularly useful with the toluidin-blue. Eosin, either as a saturated solution in water of the form soluble in that medium, or saturated solution of eosin in alcohol, using the form soluble in that agent, may be used as contrast stains before or after the toluidin-blue or methylene-blue; as both of these agents are discharged by eosin solutions, it is possibly better to stain first with eosin, rinse in water, and apply the nuclear stain HISTOLOGIC METHODS. 69 afterward. If the eosin be used after the nuclear stain, it should not be allowed to act too long, otherwise the nuclear stain may be discharged. As eosin acts as a differentiating agent, when used after the nuclear stain, care and experience are necessary~ ~ to secure the best results. After the use of eosin, dehydration in alcohol and clearing in cedar oil are recommended. For the use of eosin as a contrast stain with hematoxylin, see page 65. For the use of picric acid for the same purpose and with carmin, see pages 64 and 66. THE MICROSCOPE, A Desirable Laboratory Microscope.—Figure 43 illustrates a stand useful in a pathologic laboratory. The horseshoe base gives solidity by its long arms and great weight. To this base is attached the upright, which supports the superstructure ; the stand should be handled by this piece entirely, never grasping the parts above in moving the microscope, as such a procedure is likely to injure the adjustments. At the upper termination of the upright is the joint for inclining the microscope for conveni- ence in working. Running to the front from this joint is the stage upon which the slide is placed for examination ; clips are shown for retaining the slide in position. Beneath the stage are the substage mountings, consisting of diaphragms for lessening the light, condensers for increasing the rays’ jntensity, and a mirror for reflecting the light upward through the optic axis of the instrument. These parts are adjustable by lateral movement, by rack, pinion, and screw motion. Behind the inclination joint, and above the stage, what is known as the upright arm rises ; at its upper part is placed the fine adjustment, worked by a milled thumb-screw. Passing off in front of this upright arm is the horizontal arm, to which is attached the coarse adjustment by rack and pinion moved by the milled heads shown at both sides. The tube carrying the optic parts is attached to the horizontal arm by the rack and pinion coarse adjustment. The tube is so made that it may be drawn out to a standard length. At the upper end of the tube is the eye-piece ; at the lower end, the objec- ‘tive. ‘In the laboratory instrument, when, for any reason, an oil- immersion objective may not be desired, two objectives (a % of an inch and a ¥ or + of an inch) are mounted ona double nose- piece, by means of which either objective may be brought into use. In bacteriologic examinations in which an oil-immersion lens is indispensable, three objectives are mounted on a triple nose-piece, as shown in the cut. (Fig. 43.) In nearly all cases y 79 TECHNIC. : | il il sl FIG. 43.—MICROSCOPE SUITABLE FOR GENERAL PATHOLOGIC AND BACTERIOLOGIC WORK. As shown here, it is fitted with three objectives, a 3 of an inch, 3 of an inch, and y, of an inch mounted on a triple nose-piece. For bacteriologic work the ,; of an inch oil-immersion objective is necessary, but for normal and pathologic histology only the 3 of an inch and 3 of an inch will be needed. The stand here figured is also fitted with an Abbe condenser, iris diaphragm, and blue-glass. (For method of using and for description of parts, see pages 69 and 71.) HISTOLOGIC METHODS. 71 the examination should deg7z with the lower power, followed, if necessary, by the higher power. To Use the Microscope.—The instrument is placed in front and slightly to one side—usually the right side—of the observer, and tilted at the joint so as to afford a comfortable position for observation without craning the neck or stooping the shoulders. By daylight, northern light or light from white clouds is prefer- able ; if the window is exposed to the direct rays of the sun, a piece of thin tissue-paper is pasted over the glass, or the glass may be frosted or painted ; direct sunlight should never be used except for photomicrography. If an artificial light is to be used, the microscope is placed about thirty centimeters from the light, and to one side, so that neither the heat nor the direct rays from the light will be thrown in the face or eyes of the observer. The best artificial light is afforded by the Welsbach burner or a thirty-two candle-power incandescent burner with a thoroughly frosted globe. While for convenience in general work the stand is tilted, when examining mounts of liquids, urine, hanging-drop culture, etc., the stand must be upright so that the stage is’ per- fectly level. Place the slide on the stage and loosely secure it by the clips ; so adjust the mirror as to illuminate the center of the field; without placing the eye to the eye-piece, rack the objective down until it almost touches the slide ; then look into the instrument and perfect the illumination by adjusting the mirror again, if necessary; slowly focus upward by the coarse adjustment until a satisfactory focus is obtained ; in moving the slide about, the fine adjustment will be all that will be necessary. Never focus downward until you have mastered the method just given ; careless, or even at times the most careful, downward focusing will crush the slide or the lens by passing over the true focus and jabbing the objective into the slide. Before removing the slide, always rack the objective upward until it is at least % of an inch from the slide. To use the ;,-inch oil-immersion objective: First, wei a lower power, find and accurately center some object in the field upon which to focus; rack the tube upward until the objective is four or five centimeters from the slide ; rotate the nose-piece so that the j1,-inch objective drops into the optic axis of the instrument. Place the stand erect so as to make the stage level. Place on the cover-glass a drop of cedar oil, at such a point that when the objective is racked down it will touch the drop of cedar oil at its center. The objective is now racked down into the cedar oil ; looking into the instrument, adjust the light so that the field is well illuminated, the light uniformly 72 TECHNIC. distributed, but not too brilliant or glaring; this, if present, should be overcome by closing the iris diaphragm until a soft, even illumination is obtained. Now, with the fine adjustment, slowly focus upward but one or two turns of the milled head; the object should come into view. If it is indistinct or hazy, try readjusting the iris diaphragm or the light, or the Abbe con- denser may be moved downward or upward until the desired effect is secured. In examining stained specimens of bacteria the iris diaphragm is kept open ; for unstained specimens it is choked down, admitting but little light. The successful study of any specimen is largely dependent upon securing perfect adjustment of all the parts of the microscope, and particularly the illumina- tion. In case the field fails to clear up after careful adjustment of the instrument, examine the lenses to see that they are not dirty. CHAPTER IIL. BACTERIOLOGIC TECHNIC. In order satisfactorily to study microorganisms we must be able to secure, and if possible to maintain, pure cultures, a term to be explained later. The soil upon which bacteria are grown is called a culture medium. The soils, or culture media, are classed under two heads—the natural and the artificial; of each of these we have two kinds, the fwd and the sold. Natural Culture Media.—//uzd: Blood-serum, milk, urine, aqua coca, hydrocele fluid, eggs or egg-albumen, etc. Solid: Blood-serum, eggs, potatoes and other “tubers, and fruits. Blood-serum is the most valuable of all natural culture media, and may be used either in the fluid or in the solid state. The serum may be obtained from any of the lower animals, though that of the calf or ox is to be preferred. The blood is collected in clean jars at the time of slaughtering; a gallon fruit or museum jar answers the purpose. If the blood is passed directly from an artery into a sterilized jar, it will remain sterile. The freshly drawn blood is allowed to coagulate in the sterile receiver ; it is then removed to the laboratory. A sterile glass rod is passed around the outside of the clot, between the clot and the jar, in order to detach the fibrin from the jar and to per- mit the clot to contract. The jar is then placed on ice. In from twelve to twenty-four hours the clot will have separated, and the serum may be siphoned off with a sterile siphon. If it is clear, it may at once be placed in tubes ; if there be much suspended coloring-matter,—red blood-cells,—it may be set in the ice- ‘box for sedimentation, after which the clear supernatant fluid may be poured into the culture containers. If this operation be conducted with proper care, the serum will not require steriliza- tion, and may be used in its fluid state. In order to avoid infec- tion the greatest care must be taken in every stage of prepara- tion. Containers, pipets, instruments, hands, etc., must be sterilized with the greatest care and maintained in an aseptic condition. It is hardly necessary to say that such extreme care can rarely be taken, so that the Councilman-Mallory method (given below) has practically superseded this more tedious pro- 7 74 TECHNIC, cess. If, however, a solid medium is wanted, the serum is sterilized and “ set’’ by heating. In order to sterilize blood-serum it must be heated one hour _ each day for four days; as high temperatures cause coagulation of the albumin, the heat had best not exceed 65° C. If it is desired to use it as a solid medium, the conversion from a liquid to a solid medium is accomplished by gradually raising the tem- perature until coagulation is just sufficient to render the serum solid ; at this stage it is slightly opalescent, of a yellowish straw color, and easily penetrated by a needle. The temperature necessary for solidification rarely exceeds 70° C. Councilman and Mallory avoid the foregoing tedious process in the follow- ing manner : Blood is collected in a clean jar; it is permitted to coagulate and the fibrin is detached, as already directed. The more or less clear serum is then siphoned off. The small amount of blood present does not interfere with the subsequent handling or with the use of the medium for culture purposes. Previously sterilized test-tubes, prepared as directed under Culture Con- tainers (p. 80), are at once charged with the fresh serum. The tubes are placed in a slanting position in a dry-air sterilizer, the temperature of which is raised to 80° or go° C. The heating must be gradual, and must not exceed the temperature given. As soon as solidification is complete the serum is transferred to a steam sterilizer (the tubes being placed on end), and is ster- ilized at 100° C. for thirty minutes each day for three successive days. Loffler’s blood-serum mixture contains : Bouillon containing one per cent. ereseres I part. Blood-serum, 3 parts. The two are mixed, placed in the tubes, and sterilized as directed for blood-serum. The medium is especially useful for the bacillus diphtheriz, but may be used for almost any organism, and is, taken all in all, one of the best all-round media found in the laboratory. The advantages offered by the Councilman- Mallory method may be utilized in the preparation of this medium. The formula and preparation of bouillon are given with artificial culture media (p. 76). Milk is a very useful culture medium. It may be alkaline, neutral, or acid; with the addition of an indicator it is used for testing the reaction of growing cultures. Test-tubes charged with the desired quantity of skimmed milk (all the fat should be removed) are thoroughly sterilized by exposure to steam. Cer- BACTERIOLOGIC TECHNIC. 75 tain bacteria may be identified by their peculiar action upon milk. Thus, some organisms induce coagulation of the casein, while others peptonize it ; some develop an alkaline reaction, others an acid reaction. While they are useful, the employment of urine, aqua coca, and hydrocele fluid is not general. Boiled potato affords a splendid culture medium for the growth of many bacteria. Potato used as a culture medium is first thoroughly washed in water to remove dirt; it is then washed in a I : 1000 solution of corrosive sublimate, followed by sterilized water for ten or fifteen minutes to remove the mercury. The potato is then cut into- slices. With an apple-corer pieces of the proper size are cut from the slices, slipped into sterilized test-tubes, and a small quantity of distilled water is added to prevent rapid drying after steriliza- tion. Instead of using an Fic. 44.—MoIsT CHAMBER FOR PoTATO CUL- TURE. To use this dish, or any similar chamber, for potato cultures, the dish is sterilized ina hot-air sterilizer and allowed to cool. In the bottom is placed a blotter, moistened apple-corer, the potato may be cut into a long, pyramidal piece resembling a gigantic exclamation point. The small end of the pyramid should be long, and should project downward into the water at the bottom of the tube, thus preventing desiccation of the upper part of the piece, upon which the culture will be made. The pieces are now with ai :1000 solution of corrosive sub- limate. The potato is cleaned as described in the text, and is sterilized whole; a thin knife, such as is shown on page 34, is also sterilized; the worker thoroughly disin- fects his hands and takes the sterile potato in the left hand and the sterile knife in the right hand; the potato is then incised in its longest diameter, and, without separat- ing the two halves, an assistant raises the upper half of the dish by the knob while the potato is quickly placed on the sterile blotter, the two halves being separated so that the freshly incised surface of each half is turned upward; the lid is now quickly replaced. If no growth occurs on the potato in three or four days, it may be considered sterile, and may be inoculated. ready to be sterilized, which may be accomplished by placing them in an autoclave for from twenty to twenty-five minutes ; or, by fractional sterilization, for an hour a day, for from three to five days, in a steam sterilizer. They are now ready for inoculation. Sterilized eggs are occasionally used for the cultivation of anaerobic bacteria. The eggs are thoroughly sterilized at a low temperature, as already directed for blood-serum, a point in the shell is carefully penetrated with a sterile borer, the egg is inocu- lated, and the puncture is then sealed with wax. Occasionally, sterilization may not be necessary ; but without it incubation can not well be applied, as the chick develops too rapidly. After inoculation the egg may be dipped in hot paraffin, which, on cooling, forms an air-tight covering. 76 TECHNIC. Artificial Culture Media.—/vmd: Inorganic solutions, or- ganic mixtures, bouillon, and vegetable and animal infusions. Solid: Bouillon, milk, etc., solidified by the addition of gelatin, agar-agar, or gelatin and agar-agar. To cultivate certain bac- teria,—the tubercle bacillus, for instance,—it may be necessary to add glycerin to the medium. , The most useful artificial culture media are infusions of beef and mutton containing a small quantity of peptone. Most of the bacteria develop quite readily in such media. The stock culture medium is Koch’s alkaline-beef-peptone bouillon. For ease Fic. 45.—INSTRUMENT FOR CUTTING PLUGS OF POTATO FOR POTATO CULTURES. The cut plugs are washed in water and pushed down into test-tubes into which the potato segment fits closely. Enough water is added to come just up to the lower end of the plug. The tubes are then sterilized as directed in the text. and rapidity of preparation the following is recommended: Take an ordinary farina boiler (agate-ware is best), and fill the out- side kettle with sufficient water to well inclose the inside can; into the latter put one liter of water, which had best be distilled ; with a diamond or file mark on the side of the can the height of the fluid. Marks made on the side of the can are often difficult to find or to differentiate from other scratches, particularly when the can is more or less filled with steam and boiling fluids. An equally efficient and a somewhat simpler method is to take a glass rod and mark upon it the depth of the BACTERIOLOGIC TECHNIC. a7. fluid, subsequently maintaining the same depth by the addition of water. Obtain 0.5 of a kilogram of finely chopped lean beef from which the fat has been carefully removed; add this to the water, a little at a time, stirring constantly so as to make sure that every piece of the meat is well pene- trated. The original directions required that this mixture macerate for twelve hours before proceeding with the next step. We do not now, commonly, find this necessary, although some workers apparently always macerate for the twelve or twenty-four hours, as originally advised. Whether we macerate or not, the next step is to add the peptone and salt. Take ten grams of Witte’s dried beef-peptone and five grams of salt (sodium chlorid), and mix them thoroughly in a mortar or tea- cup; add just enough water to rub the mixed powders into a thin paste, which is now added to the meat-and-water mixture in the farina kettle and thoroughly stirred into the mass. The water in the outside kettle is now brought , to a boil, during which time the mixture in the inside kettle has been frequently stirred. As soon as the albumin begins to coagulate the stirring is stopped, and when it is fairly advanced, after fifteen or Fic. 46.—AcATE-WARE WATER-BATH : , "y: at (FARINA KETTLE). twenty minutes boiling the inside Used in making culture media, and kettle is removed from its sur- convenient for many purposes , i about the laboratory; the capacity rounding water-bath and its con- should be about 1000 ¢.¢. for inside oller. . tents brought to a boil over the flame, care being taken that it does not boil over. The meat and coagulated albumin will collect into a rather dense mass, which should be broken up, so that the interior may be fully penetrated by the boiling fluid in order to extract the salts contained in the meat. After thirty minutes’ boiling the mass is removed from the flame and strained through flannel. The water lost by evaporation must be made up by pouring enough cold water over the meat in the strainer to bring the filtrate to one liter. If any fat is seen over the surface of the fluid, as much as possible is removed with a spoon or by gently touching it with paper or a clean cloth. The filtrate will usually be clear, and, if not, it must be filtered. Tested with an indicator, this fluid will be found acid, and must be made neutral or faintly alkaline. This is best done by adding, drop by drop, a ten per cent. solution of 78 TECHNIC, caustic soda (sodium hydroxid). The best indicator is a phenol- phthalein solution, made by dissolving one gram of phenol- phthalein in 1000 c.c. of fifty per cent. alcohol. A watch-glass containing about one centimeter of this solution is placed con- veniently, and into this a drop of the bouillon is mixed, a different watch-glass being used for each drop; as soon as alkalinity is reached, the indicator turns a bright rose-color, which, while dis- tinct, should be faint. _ Litmus paper may be used instead of the foregoing, but is less delicate, although for all ordinary purposes it is sufficiently accurate. With the disappearance of acidity the bouillon becomes faintly cloudy, the salts and albumins, insoluble in an alkaline fluid, precipitating. To complete the formation of this precipitate the fluid is thoroughly boiled for at least thirty minutes, and then filtered. It is advisable, when a perfectly clear fluid is absolutely essential, to cool the medium, filter, reboil, and again filter ; this is rarely done, and is useless except that it assures the medium remaining clear ; after each boiling, and before finally filling the culture vessels, the alkalinity of the fluid must be tested, for, in some inexplicable manner, a fluid previously known to have been neutral, Fic. 47—Acate-ware oF even alkaline, may become acid. When Funnet For Fit- finished, the resulting fluid is known as neu- FLuIps. tral-, alkaline-, or acid-beef-peptone bouillon, oe ae paps the first word of the name always indicating tne erettrstss op the reaction. When intended for the cultiva- culture media. tion of tubercle bacilli, glycerol (glycerin) is added (the amount commonly employed is six per cent.)—60 gm. of the glycerol, which must be weighed and not measured, to 100cc.c. of the bouillon. It is now known as alkaline-glycerin-beef-peptone bouillon. Instead of the 0.5 of a kilogram of beef used in the above, two grams of meat extract (Liebig’s or Armour’s) may be substi- tuted. The preparation is practically the same, except, of course, the flannel filter is not needed, and, as the meat salts are exceed- ingly difficult to remove, filtering while hot, and again when cold, may have to be frequently repeated to secure a perfectly clear fluid. Media prepared with an extract are not so satis- factory as those made from the beef direct. Streptococci grow indifferently or not at all upon media prepared from beef extract. When it is desired to render the foregoing solid, gelatin or agar, or both combined, may be used. BACTERIOLOGIC TECHNIC. 79 Beef-peptone-gelatin.—To 1000 c.c. of cold bouillon add 100 gm. of gelatin (‘‘ gold-leaf,” in sheets), torn or cut into frag- ments ; macerate for fifteen or twenty minutes, until the gelatin swells up and becomes flaccid; it is then easily dissolved by gently heating in a water-bath; by the time it has reached a temperature that will not scald the fingers the gelatin will be dissolved. It is now removed from the water-bath and cooled until the fingers can be comfortably held in it for some time— about 50° C. or lower. When the gelatin is thoroughly dis- solved, the fluid will require realkalinization ; as gelatin is con- stantly acid, the previously alkaline bouillon is rendered acid. The alkalinization must be most carefully done, otherwise the gelatin may fail to solidify when finished. Again, one must be sure that all the gelatin is dissolved before alkalinization or, later, the reaction may be found acid. It must be but fazud/y alkaline. If by accident the fluid be made too alkaline, a few drops of dilute acetic acid will correct the error. When the reaction is found to be satisfactory, the white and finely broken shell of one egg is thoroughly mixed in with the gelatin ; this is heated to the boiling-point in a water-bath, followed by boiling over the naked flame (which is best distributed by wire gauze) for at least half an hour; the water lost by evaporation is made up, and enough of the mixture filtered to half fill a good-sized test-tube ; this is boiled repeatedly for several minutes, to see that all the albumin is coagulated, the reaction as desired, and that the gelatin remains clear ; if so, the remainder is filtered and filled into test- tubes. When properly made, gelatin is the clearest solid medium at present attainable. It is liquid at temperatures above 22° C., and can not, for this reason, be incubated. As some bacteria liquefy gelatin and others do not, it constitutes a test culture medium of the greatest value. Beef-peptone-agar.—Agar-agar is a gelatinoid substance derived from a Japanese seaweed. It is used for making culture media solid in the following manner: To 1000 c.c. of bouillon add ten grams of the agar threads cut into fragments not over two centimeters in length; place at once to boil over the naked flame, stirring frequently to prevent burning and the threads adhering to the bottom of the pan. It usually requires about an hour to secure perfect solution, without which filtration is impos- sible. Longer boiling does no harm, the quantity of the medium being maintained by adding, from time to time, enough water to compensate for that lost by evaporation. When fully dissolved, it is filtered. As it filters with much more difficulty than gela- tin, and as the same precautions are necessary, I have deferred 80 TECHNIC. the description until now. An efficient, heaVy, preferably already folded filter (machine-folded filters are by far the best) is care- fully opened and adjusted in the funnel; then, with the greatest care; thoroughly moistened with boiling water; a moment is allowed for the contraction of the filter, which always takes place ; it is then again moistened with boiling water, the excess poured off, and the agar or gelatin poured down a glass rod on to the side of the filter—vot into the center and never rapidly, as either will probably break the filter. In the case of agar it is best to have it boiling and add but 250 c.c. or less to the filter at one time, keeping the remainder hot in the water-bath and heating to boiling just before pouring into the filter. Gelatin can not be boiled very long or it may fail to gelatinize; with agar this danger is not present. Gelatin burns to the pan unless carefully watched ; agar may do so, but less fre- quently. Gelatin should always be cleared by an egg; agar may be, but does not require it. Agar solidifies at about 42° C., and melts only at near the boiling-point ; it is not so clear as gelatin, but, as it can be incubated, has many advantages. It remains solid when prepared with glycerin bouillon, which gelatin does not always do. i Urine agar, which is particularly use- Fic. 48—Test-tuse Basxer, ful for the cultivation of the gonococcus, Mabe or Tinnep MeTAL, is made by using urine instead of bouil- FOR HOLDING TEST-TUBES. is 7 : These baskets should be 128 lon. The urine is neutralized or ren- ee MID Bae We BS ened faintly alkaline, or it may be used in its acid condition. One per cent. of peptone and o.5 per cent. of salt may be added, although this is not ordinarily necessary. After filtration, preliminary boiling, and filtration while hot and again when cold, the agar is added, dissolved, and filtered as already directed. Culture Containers.—Cultures may be made in bottles, flasks, or test-tubes; the last two are the most used. If per- fectly new, a thorough rinsing in clean water will suffice; if the tubes have contained cultures, or have in them cultures either growing or dead, they should be placed in the sterilizer for a couple of hours, with the cotton plugs in place ; remove from steri- lizer, take out the plugs, pour out the contents of the tubes, and boil one hour in a two per cent. solution of washing soda; wash with test-tube brush and rinse in several changes of clean water ; rinse in a one per cent. solution of hydrochloric acid; carry BACTERIOLOGIC TECHNIC. 81 through several changes of water, and set up to dry with bottom upward. When dry, plug with cotton; for this purpose we use ordinary cotton batting, clean and free from the cotton hulls. Absorbent cotton possesses no advantages. A more or less square or octagonal disc of cotton, about ten centimeters in diam- eter, has its corners folded into the center so as to make a plug twice as long as the diameter of the tube or the neck of the flask. The plug should fit so tightly that the tube or flask can be lifted safely Fic. 49.—DoOUBLE-wALL Hovt-AIR STERILIZER, Fic. 50.—DIAGRAM OF INTERIOR FOR STERILIZING TEST-TUBES, GLASSWARE, OF HoT-AIR STERILIZER.— AND OTHER LABORATORY APPLIANCES AND (Coplin and Bevan.) INSTRUMENTS. The construction must be such that a jacket of hot air sur- rounds the inside chamber, by the cotton plug, which should and thereby assures an 5 equal distribution of heat enter the mouth to a distance equal to the interior. to twice the diameter of the tube or the neck of the bottle or flask, and should project at least one centimeter. The test-tubes used for cultures should be of the best Bohe- mian glass, with a lumen of 13 mm. to 15 mm., and 130 mm. to 1so mm. in length. The flasks should be of the Erlenmeyer form, with a capacity of 100 c.c. Larger sizes, 250 c.c. to 1000 c.c., will be needed for storing media. After clearing and plugging, the tubes and flasks are put in the hot-air sterilizer for twenty minutes at 130° C. In the ab- 6 82 TECHNIC. sence of a hot-air sterilizer any cooking oven may be used, leav- ing the tubes in the oven until the cotton just begins to brown, a temperature which approximates 140° C. The tubes are now ready to receive the medium. An ordinary percolator or funnel has a rubber tube ten centimeters long, connected to the tubula- ture at the bottom by means of a perforated cork and a short glass tube ; at the lower end of the rubber tube a second glass tube is connected so that it projects about ten centimeters be- low the rubber tube; the latter is then collapsed by means of a thumb pinch- cock (Mohr’s spring pinch-cock) applied A to the rubber tubing between the ends y of the two glass tubes. The liquefied medium is poured into the percolator ; the test-tubes are then arranged in the baskets at the side of the percolator. A test-tube or flask is grasped by the left hand, preferably by the thumb and index- finger ; the cotton is rotated and loosened by means of the thumb and index-finger of the right hand, and removed by grasp- ing the projecting tip between the ring- and little fingers of the right hand; the tube is now carefully slipped over the filling tube from the percolator, care being taken that no fluid comes in contact with that portion of the tube into which the cotton plug 7s to go ; relax the pinch-cock Fis. st. and admit to the test-tube or flask the Apparatis to be attached te desired quantity: close the pinch-cock, the lower end of a funnel, as shown in the cut, for 19 OF 2 - 2 OMilling testtaben, remove the tube, using the same care to The outside glass tube avoid wetting the mouth of the tube, and prevents the medium that q Hine onthe iasiaseihs reinsert the cotton plug. This is _re- withthe mouth ofthetest- peated until the desired number of tubes tube Supng soc? or flasks are Allied, If any of the medium spring pinch-cock. remains, it may be run into a flask, ster- ilized as will be directed later, and pre- served for future use. The amount of medium placed in each tube varies with the medium and the purpose for which it is intended. For some experiments a measured quantity will be needed, but for ordinary purposes the tube should be about half filled with bouillon or gelatin, and with agar to a depth equal to a little more than twice the diameter of the tube. Flasks | MENT Ze SONS i PHYLA. BACTERIOLOGIC TECHNIC. 8 3 should never be more than half full when intended for culture, and often very much less will be sufficient. Sterilization.—The Arnold steam sterilizer or the autoclave is used. If the former is used, fractional sterilization is best, keeping filled tubes in the steam chamber, at 100° C., thirty minutes a day for three successive days ; in the intervals between sterilizations they are kept at room-temperature. The object of this is to destroy all organisms in the adult or fully developed stage. It is known that spores are not destroyed by a tempera- ture of 100° C. unless it be very long applied; any spores that escape the heat on the first day have time to develop by the second day, or, to assure their being caught, a third steriliza- tion is resorted to. Experience teaches that this is usually suffi- cient ; however, the tubes should be watched for three or four days, and if any of them show a growth, the process should be repeated for all. By means of the autoclave a temperature of 130° C. is ob- tained in the steam chamber, which, in from twenty to thirty minutes, destroys both fully. developéd bacteria and _ their spores ; it is of great convenience for bouillon, agar, potatoes, milk, and many other culture media, but can not be used for blood- serum or gelatin. The latter Fic. 52.—ARNoLp’s STEAM STERILIZER ; ss FOR STERILIZING CULTURE MEDIA, usually fails to gelatinize after ETC. being subjected to the high temperature ; indeed, gelatin must always be sterilized with the greatest care, as prolonged exposure, even to the temperature of 100° C., should be avoided. Potatoes require prolonged ex- posure to high temperature, as they usually contain earth organ- isms difficult to destroy. In order to increase the surface area of media containing agar or blood-serum, the tubes, while the medium is in a liquid state, are inclined with the mouth just high enough to prevent the agar flowing up to the cotton ; when “ set,” they may be stood on end, as other tubes. STERILIZING CHAMBER 84 TECHNIC, To Prevent Stored Media from Drying.—For this purpose the writer has tried rubber caps, rubber tissue, oiled paper, cork and rubber stoppers, and the paraffin method, none of which seems fully satisfactory. One of the best methods is to trim the cotton even with the top of the tube, and push it down 0.5 cm. below the tube-lip ; take a coin of proper size to just drop inside of the lip of the tube ; heat the lip of the tube and the body of the tube as far down as the cotton extends, until the cotton is slightly browned, and at the same time heat the coin; drop the coin upon the tube, and, while still warm, seal it to the tube at FIG. 53.—ARNOLD’S STEAM STERILIZER, BOSTON BOARD OF HEALTH ForRM. This is the most convenient and the best sterilizer for general laboratory purposes, the margin, using for this purpose a good quality of stationer’s sealing-wax. This process is tedious, and is most useful for tubes containing cultures that require long incubation, such as the tubercle bacillus. A much more useful plan, and one almost as efficient, consists in pushing the cotton down, heating the mouth of the tube and inclosed cotton, and placing over the end a disc of quite thick tin-foil, which is evenly folded over the lip of the test-tube. For this purpose commercial tin-foil, which contains a relatively large proportion of lead, may be used, as it is much cheaper than chemically pure tin. Such a cap is easily BACTERIOLOGIC TECHNIC. 85 removed and replaced. It offers all the advantages of rubber, and can, if sufficiently heavy, be readily sterilized. Dunham’ s Peptone Solution.—Rub up in a mortar five grams of salt and ten grams of peptone, with enough water to make a paste ; finally, dilute to 1000 c.c., boil, and filter. Asa rule, the filtrate is neutral or alkaline - in either case, after sterilizing as already described for bouillon, it is ready for use. For plating it is always best to have on hand a number of tubes of gelatin and agar, each tube two-thirds full. iL fii Name ‘ao FIG. 54.—AUTOCLAVE, OR DIGESTOR, USED FOR STERILIZING BY STEAM UNDER PRESSURE. The lid is held in place by three winged nuts, which are thrown down to the side in order to raise the lid. The solid copper chamber on the inside has placed in it two liters of water, and the material to be sterilized is placed upon the tray with perforated bottom shown at the side of the cut; this is then placed inside of the autoclave, and the lid is closed down and secured by the winged nuts; the gas is now lighted and the heat applied until steam escapes from the small cock at’ the left, which is then closed. The pressure within the apparatus now rises until the safety-valve, which may be set at any pressure, blows off. Sterilization by this means may be secured, at temperatures ranging from 100°C. to 140°C., in from twenty to forty minutes. Pure Cultures.—A pure culture is one containing the pro- geny of a single germ; for example, a pure culture of the tubercle bacillus must contain no other germ. When two kinds of bacteria are growing together, the culture is said to be a maxed culture. Under nearly all conditions various organisms are found together, and in order to separate them we must resort to plating. The object to be attained is the separation of each germ, in order to enable it to grow into a colony by itself; so 86 TECHNIC. that, if the original mixture contained three kinds of bacteria, we may obtain three kinds of colonies, and from these obtain cultures which have but the one variety—that is, a pure culture of each. Bottle Plates.—Any strong, clear, flat-sided bottle will do. The capacity should be about 500 c.c.; clean, plug with cotton, and sterilize in hot-air sterilizer ; charge with gelatin or agar, usually about twenty cubic centimeters. Sterilize as already directed for culture media, and set the bottle aside until wanted for plating; to prevent drying of the medium, the cotton may be pushed downward in the neck so as to admit a short rubber stopper, or the neck and lip may be covered with tin-foil as already directed. As a rule, the bottle will be used within one month, areas during which time it should not become dry. tre, Usep ror When ready for use, at least three bottles will ere be needed. Liquefy the medium in the ster- ilizer or water-bath ; cool to 50° C. or below, inoculate the first bottle with a small loopful of the mixed cul- ture or suspected material, as pus or blood, stopper the bottle with the cotton plug, and shake, to thoroughly mix ; inoculate the second bottle by carrying a loopful from the first to the sec- ond, replace the plug, and shake ; and in the same manner inocu- late a third bottle from the second, and shake as before. Lay the three bottles on the flat side; the medium will spread out and cover the side of the bottle ; label the three bottles a, 4, and ¢, the first being a. Petri Dish Plates.—Three or more test-tubes containing sterile agar-agar or gelatin, filled to within an inch or so of the cotton, as already directed, are placed in a water-bath or a sterilizer and the contained medium liquefied ; while this is in progress an equal number of Petri dishes are steril- ized in the hot-air chamber and allowed to cool. The liquefied medium is cooled to aS TECTIA oe Fic. 56.—DisH DeEvIsED under 50° C. A tube is inoculated with By Psne e i Used almost exclusively for the material to be plated, as directed for plating; the, most con bottles; from the first tube a second is hon Gao oe inoculated, and from the second a third, and so on, each tube having the medium thoroughly mixed by using the inoculating needle as a stirrer. Remove the cotton from the first tube and pass the lip of the tube through the BACTERIOLOGIC TECHNIC. 87 flame ; raise the lid of a sterile Petri dish just enough to get the mouth of the tube under it, and quickly pour the contents of the tube into the dish, which is then gently tilted from side to side, allowing the medium to flow over the bottom and cover it fully. A second dish receives in the same way the contents of the second tube, and so on, through as many tubes as may be desired. The plates are labeled as directed for the bottles. Esmarch’s Tube Plates.—Three or more tubes of sterile agar or gelatin, each tube not containing more than two or three cubic centimeters of the medium, are liquefied and inoculated as directed for the Petri dish method. A block of ice, with a flat or nearly flat upper surface, has a channel made in it by laying a test-tube of the same size as those to be used, filled with hot water and corked, upon the top of the ice, the corked end pro- jecting beyond the edge of the ice ; this tube is rolled over and Fic. 57.—PLATINUM INOCULATING NEEDLES MOUNTED IN GLass Robs. Showing the shape of the ends as may be found useful for: a, stab cultures and stroke cul- tures; 5 and c, stroke cultures and smear cultures. over in the same spot until a channel is so made as to half bury the tube, the bottom end being a little lower than the corked end. Into this channel one of the infected tubes is laid so that the medium flows up to within two centimeters of the cotton but does not touch it; the tube is then rolled, at first slowly, then more quickly, until, within the first minute, it is spun rapidly ; the medium is in this way congealed over the entire inside of the tube nearly up to the cotton; if the latter comes in contact with the medium, it prevents easy removal of the plug by making it stick to the side of the tube. Each tube is treated in the same way, after which it is labeled as directed for other plates. When set, the tubes are placed on end. With gelatin this can be quickly done; with agar, however, the tube must be kept ina nearly horizontal position for several hours, generally overnight, otherwise the agar may slip down. After the plates are made by either of the foregoing methods « 88 TECHNIC. we have to await the growth of the colonies ; agar may be incu- bated. At the end of a varying period the colonies appear as Fic. 58.—METHOD OF HOLDING TUBES, COTTON, AND PLATINUM WIRE WHILE INOCULAT- ING SOLID MEpDIA.—(Kuch’s method, modified from Woodhead.) The tubes c and d are grasped _as shown in the illustration. The cotton from d is removed with the thumb and index-finger of the right hand, and held between the ring-finger and little finger of the left hand, at 4; that portion of the cotton which was within the tube is not touched by the fingers, but is directed upward. In the same way the cotton is now removed from the tube c and grasped by the ring-finger and middle finger, as at a, the same precautions being used as described for the other tube. The lipsof the tube are now passed quickly through the flame of a Bunsen burner, to remove any adhering dust, and the platinum wire and the glass rod are sterilized in the flame, the rod being heated'toa greater distance than it is expected to enter the tube. Supposing that d is the tube from which it is desired to remove the culture, and c is to receive it: the platinum wire, while still warm, is thrust into the culture medium to one side of the growth to cool the needle; the growth is then touched by the needle, thus infecting the needle, which is quickly with- drawn and the tube ¢ inoculated; immediately upon the withdrawal of the inoculating needle the cotton stoppers are placed in their respective tubes, and the needle ts at once sterilized and set aside. Never lay down an infected needle! The tube inoculated is labeled, dated, etc., and set aside for observation. All this can be done quickly, and the beginner should practise the manipulation on tubes of media which are not infected ; if they become infected during the process, his technic is faulty, and should be perfected before working with pure cultures. distinct dots in and on the culture medium. In plate a@ they will commonly be too close together to be distinct ; plates 4 and ¢ BACTERIOLOGIC TECHNIC. 89 will bebetter. Selecting a colony which is alone, transplant this into a test-tube in the following manner : Take the platinum needle and heat its entire length to redness, at the same time heating all of the attached glass rod that is likely to go into the test-tube, bottle, or dish. If the colony to be removed is within a bottle or test-tube, it will be best to bend Fic. 59.—METHOD OF HOLDING TUBES, COTTON, AND PLATINUM WIRE WHILE INOCULAT- ING Liquip MEDIA. The steps and the lettering are the same as in previous figure. The right hand should not be over the tubes, as it appears in this illustration, but the tubes in the left hand should be so inclined that there will be but little danger of anything dropping into them. the tip of the inoculating wire like the letter L; immediately after sterilizing the needle, holding it like a pen in the right hand, take the bottle and test-tube or both test-tubes in the left hand ; remove the plugs from the tubes or bottles by grasping the pro- jecting cotton of both tubes between the middle finger and ring- finger and the ring-finger and little finger of the right hand; pass the lip of the bottle or tube through the flame to burn off go TECHNIC. any adhering dust ; pass the needle into the bottle or tube, and lightly touch the colony from which it is desired to obtain a cul- ture ; this will infect the needle; quickly withdraw the needle and pass it into the tube upon which it is desired to inoculate the growth. The inoculation made may be: (a) a streak or stroke culture, in which case the needle is drawn from below upward in a straight line over the slanting surface of an agar or blood- serum tube; (4) a smear culture, made by gently rubbing the infected wire over the surface of the medium; or (c) a stab culture, made by a straight needle-thrust, from above down- ward, through the medium. Stroke and smear cultures are the most used on all solid media except gelatin, in which stab cultures are best. In transplanting from a Petri dish culture, the lid is raised barely enough to introduce the previously ster- ilized needle, which is then touched upon the colony, removed, and applied to the culture tube as previously directed. The platinum needle used in bacteriologic work consists of a platinum wire, from one millimeter to two millimeters in thick- ness and from five centimeters to eight centimeters in length, fused into the end of a glass rod about five millimeters in thick- ness and from fourteen centimeters to eighteen centimeters long. The rod is used asa holder or handle for the loop. The latter is variously curved, looped, or may be used straight, as for stab cultures. (See Fig. 57.) Bacteriologic Examination of Water and Other Fluids.* —Sterilize a container in the hot-air sterilizer, and collect the water for examination. As bacteria multiply very rapidly, the examination should be madeas soon as possible after collection ; after a few hours’ standing, particularly if the weather be warm, the results obtained will be without value as to quantity of bacteria. Prepare a dozen Petri dishes and a corresponding number of tubes for plating. Sterilize two burets so graduated as to accur- ately measure 0.02 to I c.c. Thoroughly agitate the water in order to diffuse the bacteria equally throughout the spécimen, and fill a sterile buret with the sample under examination. The test-tubes of media, gelatin, or agar having been fully liquefied, are cooled to 45° C. in a water-bath ; to each of two of the tubes is added 0.02 c.c. of * Bacteriologic examinations of water and air are introduced here as being good examples of the practical application of improved plating methods, and in order that the student may familiarize himself with the technic of preparing plates and securing pure growths therefrom. BACTERIOLOGIC TECHNIC. gl the infected water ; to another pair of tubes 0.05 c.c. of water is added ; to another, 0.075 c.c.; to another, 0.1 c.c.; to another, 0.§ c.c.; and to another, 1.0c.c. The tubes are thoroughly shaken, immediately poured in the usual way, and set aside for the colonies to develop. If agar has been used, the plates 2 ae < geititinn: (WLE ; te A SAY Fic. 60.—APPARATUS FOR COUNTING COLONIES. Petri dishes are placed upon the ruled circle, and the colonies counted as directed in the text. An ordinary slate may be ruled as in the above figure and used for the same purpose. may be incubated. As soon as the colonies develop they are counted. A Petri dish counting apparatus may be used, ora slate upon which has been ruled a diagram like that shown in figure 60. All the colonies in the plate may be counted or the number determined in one, two, or more of the wedge-shaped areas oO o 92 TECHNIC. bounded by the radii and the arc, and the resulting number found for one wedge-shaped area multiplied by the total number of divisions—sixteen. The number of colonies found in the whole plate represents the number of bacteria in the water used for the plate. For example: Several areas counted give an average of twenty colonies to each area; there are sixteen areas: 20 X 16 = 320, the total number of colonies in the plate; assuming Fic. 61.—HESSE’s AEROSCOPE. This consists of a hollow cylinder of glass, a, sixty centimeters in length, four centimeters in diameter, plugged with cotton at both ends, sterilized, and charged with a layer of culture, much as the Esmarch plates. The two ends are covered by caoutchouc, one of the rubber caps having a hole to admit a glass tube by which the tube a is connected with the gravity flask 6, which is further connected to the flask c. The flask 6 is filled with water. When ready for use, the rubber cap and the cotton plug at d are removed, the flask & is tilted so that the contained water flows into the flask c, thereby aspirating as much air into the tube @ as water is allowed to flow from the upper to the lower flask. The tube a is now plugged and set aside for colonies to develop. These can be counted and transplanted as in other plate methods. Petri has improved the foregoing by sub- stituting for the tube a a short tube packed with sand and sterilized, aspirating air through it, and then mixing the sand with gelatin and pouring into plates. Sedgwick and Tucker use sterilized granulated sugar instead of the sand. The sugar and sand methods give the best results. that the quantity of water used in making the plate was 0.1 c.c., then one cubic centi- meter will contain ten times 320 or 3200 bacteria. If dif- ferent quantities of water are used, the result, reduced to the unit,—say, one cubic centimeter,—should be ap- proximately the same, one series being a control for another. In the examination of sew- age and of other materials exceedingly rich in bacteria the large number of organ- isms present in even the smallest, most easily meas- ured quantity may be too great for the satisfactory counting of the colonies after their development on plates. To avoid this difficulty, the material to be examined is diluted with an equal quan- tity of sterile water; should this not be sufficient, further dilutions may be made. In the final calculation the dilution must be taken into considera- tion. The foregoing test determines the number of bacteria in the sample. If it is desired to find what germs are present in the water, to make the test complete, the colonies are transplanted and studied as already directed when considering pure cultures. (See table illustrating the method of recording principal charac- teristics of an organism, p. 116.) Bacteriologic Examination of Air.—The principle upon which BACTERIOLOGIC TECHNIC. 93 the examination is conducted is to depend either upon sedimen- tation upon a sterile surface, as a Petri dish containing media,— a very unsatisfactory method,—or to secure the bacteria in a sterile filter by aspirating through it a known volume of air. Figure 61, with the attached legend, will explain the methods used. Staining Bacteria.—Staining bacteria greatly facilitates the study of their morphologic characteristics. For this purpose the anilin dyes are almost exclusively used. The anilin stains commonly used in the laboratory are fuchsin, gentian-violet, methyl-blue, and a few others; they are all ap- plied in practically the same manner. For stock, it is best to keep the dye as a saturated alcoholic solution. For staining, however, alcoholic solutions are of little value, as they do not seem to Fics. 62 AND 63.—TWo FoRMS OF STEWART’S COVER-GLASS FORCEPS. Method of holding cover-glass and applying the stain. Convenient for blood work, and abso- lutely necessary for bacteriologic work; useful also in sputum examination, etc. The lower instrument shows a cover-glass with stain in position. If the cover-glass be grasped with the film or spread side toward the side of the forceps that has the circular bend in- tended to fit the thumb, shown at A, there will be no danger of losing trace of the side con- taining the spread, as this side of the forceps is practically always upward. possess the penetration of watery solutions. The usual strength of solution is two per cent. of the dye dissolved in water ; as the dyes are disagreeable to handle, the solutions are commonly prepared by taking a test-tube, from thirteen to fifteen milli- meters in diameter, filling it about two-thirds full of distilled water, and adding the saturated alcoholic solution of the dye, drop by drop, until the water is so colored that, by ordinary diffuse light, one can barely see through it. This is then poured into a bottle adapted with a Barnes dropper. (See cut of appro- priate stain bottle, p. 65.) The solution so prepared is about 1.7 per cent., and may be used whenever a one or two per cent. solution of the dye is recommended. The addition of carbolic acid to aqueous solutions of some anilin dyes seems to increase 94 TECHNIC. their staining power and keeping properties. For this reason, instead of using plain distilled water, as previously recommended, many workers use a five per cent. aqueous solution of chemically pure carbolic acid. It is of the greatest importance that the carbolic acid should be chemically pure, as many of the samples of commercial carbolic acid contain contaminants and extraneous chemic bodies that are injurious to the anilin dyes. One of the most useful stains is the Koch-Ehrlich anilin-water solution. This should be freshly prepared each time it is wanted, asit willnot keep. Take, in a test-tube, about twenty cubic centi- meters of distilled water ; add anilin oil, drop by drop, shaking thoroughly until no more of the anilin is dissolved, the drops floating on and in the water, which may become milk-like as the result of emulsification of the oil; filter until clear: usually one filtration will be enough, but occasionally two or three will be required. Formula for stain : Saturated solution of anilin oil in distilled water, . 100 parts. Saturated alcoholic solution of gentian-violet, methyl- violet, or fuchsin, . ... ..... ; Ir“ Alcohol, . 1... .. i 5 ro.“ As it is not desired to stain laboratory utensils any more than can be avoided, it has been found that practically the same results as those secured by measuring can be obtained by drop- ping the solutions: 100 drops of the anilin water, 21 drops of the alcoholic solution of the dye, and 20 drops of alcohol. Liffter’s Alkaline Methyl-blue Solution : Saturated alcoholic solution of methyl-blue, .. . 3 parts. Aqueous solution of caustic potash (1 : 10,000), tog Zichl’s Carbolfuchsin.—For formula, see page 67. This is probably the most useful bacterial stain yet introduced. . To Stain Bacteria —Thoroughly cleanse a cover, dry, and polish it; grasp it with a cover-glass forceps and pass it through the flame a number of times to burn off any bacteria or other organic material that may be on it; avoid heating too much, as the cover may warp or crack. Spread on this, with a previously well-sterilized platinum loop or needle, a thin film of the mate- rial; permit it to dry wzthout using any artificial heat. Mt is then “fixed” by passing through the flame, as follows: Stand about thirty centimeters from the flame and carry the cover-glass through a circle, the diameter of which is represented by the dis- tance between the flame and the worker ; pass it through the flame three times. Stain from two to ten minutes; wash thoroughly BACTERIOLOGIC TECHNIC. 95 in water, dry, and mount with. the film side downward. Films must be thoroughly dried before mounting ; evaporation of the water accomplishes the same result as the application of alcohol in sections—dehydration ; the use of a clearing agent, such as creasote or cedar oil, is usually unnecessary, as the residual oil present in the balsam will clear satisfactorily, provided the film is dry. The presence of either alcohol or water in the film when mounted on balsam leads to more or less clouding, owing to the emulsification of the residual oil in the balsam. Temporary mounts are often made, thereby avoiding the use of reagents so disagreeable and sticky as damar or balsam. If the examination is to be made with a dry mount, the film is turned over, with the spread side downward, into a drop of water, the excess of which is removed to prevent the cover-glass from floating. When an oil-immersion lens is to be applied, the FIG. 64.—KALTEYER’S COVER-GLASS FORCEPS. This instrument may be used exactly as the forceps shown in figures 62 and 63; in addition, it may be used as in the illustration. The danger of forgetting which side of the cover is coated is less than with any other type of forceps. most satisfactory temporary mounts are made in the same oil as used for immersing the objective. The thoroughly dried film receives in its center a droplet of the oil, and is then inverted on the slide; a droplet of oil is placed on its upper surface, and the examination is proceeded with in the usual manner. For method of focusing immersion objective, see page 71. Spreads may be made directly on the slide, followed by fixation, staining, etc. Such spreads may be examined without a cover-glass—a method commonly in vogue, but one with which the writer is not in sympathy. Weigert's Method for Sections of Tissue Contaimng Bacteria. —Place sections for from six to eighteen hours in a one per cent. aqueous solution of any of the basic anilin dyes ; after re- moval from the stain, wash in one-half saturated solution of potassium carbonate, then in distilled water, next in sixty per 96 TECHNIC, cent. alcohol, and finally dehydrate in absolute alcohol. Clear in oil of cloves, xylol, or cedar oil, and mount in xylol bal- sam. Heating the stain or using a stronger solution will hasten the staining process, though it may not be so satisfactory. In case the particular basic dye used gives an unsatisfactory result another should be tried, using the same formula and method. Gram’s method may be used either for cover-glass films, pre- pared in the usual way, or for sections. Stain in the Koch- Ehrlich solution, made with gentian-violet (see p. 94), from two to five minutes, in most cases; to twelve or twenty-four hours in others; rinse for a moment in water, and apply Gram’s solu- tion. Grams Lodin-iodo-potassic Solution : Todin, . . . ‘ A - I part. Potassium iodid, 2 parts. Distilled water, 4 joo In films, after one or two minutes, the iodin solution is washed off with water, followed by alcohol. From time to time the cover may be mounted in water and examined with a 4-inch or 4-inch objective, and as soon as the excess of dye and precipi- tate has been fully removed, it may be dried and mounted in xylol balsam. As soon as the section becomes a dark brown, wash in sixty per cent. alcohol, dehydrate in absolute alcohol, continuing the latter as long as any perceptible amount of color is discharged, clear in oil of cloves or cedar oil in which a small amount of color may be discharged, pass through one or two changes of xylol, and mount in xylol balsam. After washing in sixty per cent. alcohol, sections may be contrast stained with carmin or hematoxylin, or with a one per cent. aqueous solution of vesu- vin or Bismarck brown. Netsser’s method of spore staining consists in preparing the cover-glass as before, floating it upon the Koch-Ehrlich solution (made with gentian-violet) in a watch-glass, and heating to near the boiling-point for an hour. The film is next washed in water and decolorized by a solution composed of twenty-five parts of hydrochloric acid and seventy-five parts alcohol. This removes the stain from the bacilli, but if not allowed to act too long, leaves the spores stained. The preparation is next stained with methylene-blue, washed in water, dried, and mounted. Flagella Staining.—Loffler’s method requires two fluids, the first being a mordant, the second the stain. First solution con- sists of : BACTERIOLOGIC TECHNIC. 97 Aqueous solution of tannin (20 gm. tannin to 80 c.c. water), 3 é erie 2d) ALOP GLC, Aqueous solution of ferrous sulphate, saturated in the cold,. . . : : : to 4 » SEC Saturated alcoholic solution of fuchsin, I cc. The coloring solution is composed of saturated solution of fuchsin in anilin water, to which are added a few drops of caustic soda (1: 1000) until opalescence commences. The mordant is applied to the cover-glass film, heating slowly over the flame for one minute. It is not necessary for the liquid to boil. Wash in distilled water and then in alcohol. Stain by placing on the film a drop of the alkaline staining solution, heating again gently for one minute; wash in distilled water, dry in air, and mount. Different species of bacteria require an acid or alkaline reac- tion to the mordant, and for this purpose two solutions are necessary : (1) Caustic soda, one per cent. aqueous ; (2) an aque- ous dilution of sulphuric acid, of which one cubic centimeter will: just neutralize one cubic centimeter of the alkaline solution. For spirillum of cholera, one-half to one drop of the acid solu- tion to sixteen cubic centimeters of the mordant ; for bacillus typhosus, two cubic centimeters of the alkali to sixteen cubic centimeters of the mordant, and so on; the number of drops of either solution can be determined only by experiment upon the organism in question. The bacillus pyocyaneus and many varie- ties of the spirillum require an acid reaction, while the bacillus typhosus, bacillus subtilis, bacillus of malignant edema, and bacillus of symptomatic anthrax require an alkaline reaction, Pitfield has recommended the following stain for flagella, using but one solution for. mordant and stain : (A) Saturated aqueous solution of alum, . 10 c.c. Saturated alcoholic solution of gentian-violet, Ic.c. (B) Tannic acid, : : I gm. Distilled water, s « Toe. These are made separately, filtered; and mixed. The resulting mixture—stain and mordant combined—is applied and heated gently almost to boiling-point, washed in water, dried, and mounted. McCrorie’s flagella stain is a one-fluid stain having the follow- ing composition : Night blue, saturated alcoholic solution, Io c.c. Tannic acid, 10 per cent. aqueous solution, 10 c.c. Alum, 10 per cent. aqueous solution, . IO c.c. 98 TECHNIC. Spreads are made from cultures eighteen to twenty-four hours old; the film is dried and fixed as usual. The stain is applied for two minutes cold and then warmed until a faint haze of steam is given off. Wash thoroughly in water, dry, and mount in balsam. Of the many stains for flagella that have been advised, this seems to yield the best results. Microscopic Examination of Stained and Unstained Mounts.—In tissues stained by any of the methods given, the location, under a low power,—+-inch objective,—of bacteria can often be inferred by agminated areas of the stain known to stain such organisms. Having located such an area, a higher power may be used. Always begin the examination with a low power. (For description of microscope and method of using same, see pp. 69 to 71.) Gas Formation.—The development of gas may well be investigated in connection with our study of yeasts. Thus, if a saccharometer charged with a sterile culture fluid containing glucose be inoculated with the saccharomyces cerevisiz, gas will collect in the measuring-tube, showing its production by the growth of the yeast. In addition to the production of gas, it can be shown that the fluid contains other substances ; simul- taneously with the gas production alcohol is elaborated. The equation is written as follows : GLUCOSE ALCOHOL + CarRBON DIoxID. C,H,,O, = 2C,H,O + 2C0O, The study of gas formation is conducted for other organisms after the same method as described for the yeasts ; while saccha- rine fluids are mostly used for this study, other media have also been found available. Gelatin or agar shake cultures are sometimes used to detect gas formation. Either medium is liquefied, cooled to below 50° C., and inoculated while liquid; it is then thoroughly agitated and allowed to solidify. The growth of organisms producing gas will be evident by the appearance of small bub- bles throughout the medium. The test is, at times, facilitated by using a medium containing glucose, in which case the reaction may be identical with that previously described ; in many cases it is, however, a much more complex problem. Anaerobic Cultures.—WNovy’s Apparatus (Fig. 65).—Petri plates, Esmarch plates, or culture tubes are placed inside, the dome, 4, is put in position and secured by the vise-like clamps, JD, D,; the glass stopper is turned, as shown in the cut. The tubulature not having the L-shaped extension down- BACTERIOLOGIC TECHNIC. 99 ward is connected with the hydrogen generator, and a con- stant stream of gas is carried through the apparatus for some hours. As soon as the air is displaced, the stopper, C, is turned one-fourth of a turn, thus cutting off the connection between the tubulatures on the side of the neck and the inside of the appa- ratus. If carbon dioxid is used instead of hydrogen, it is admitted through the tubulature that communicates with the in- " ‘ lt \ ! | ia | Fic. 65.—Novy’s APPARATUS FOR ANAEROBIC CULTIVATION OF PLATES AND TEST-TUBES. The apparatus consists of the following parts: A, the base, a solid glass cylinder having a capacity of about one liter and ground at its upper edge with a flange to make an air-tight joint with B, the dome, the two being clamped together by the vise-like clamps, D, D, the joint being more per- fectly assured by rubber bands. The top of the dome, B, arches into a neck like that of a bottle, and is closed by C, which is an ordinary ground-glass stopper ground into the mouth of the neck, to the dome 2. Through the side of the glass stopper, C, are two openings, so arranged that when Cis turned as shown in the cut the open- ings permit gas to pass into the interior of the apparatus through either of the tubula- tures shown at the side of the neck. On the inside of the stopper an L-shaped tube is fused, so that anv gas carried into the apparatus through that tubulature passes below the level of the opposite tubulature. Ss SF mR E (S55 Fic. 66.—STERNBERG’S ANAEROBIC CUL- TURE TUBE. The tube is an ordinary culture tube of rather large size. The culture medium, e, is inoculated, the cotton plug, d, while at the top of the tube, is cut even with the glass and held in the flame until thoroughly browned, fully to steri- lize it, and is then pushed down into the tube with a sterile glass rod. A cork, c, with two perforations, through which pass the L-shaped tubes, a, is fitted to the mouth of the test-tube and sealed with wax at 6. Hydrogen gas is now passed through the apparatus for an hour or so, depending upon the size of the tube, until all the air is dis- placed ; the entrance and exit tubes are then sealed at a’ a’ by fusing the glass. The advantage of this simple method is that any tube can be used with any of the common media in use in the labora- tory. side through the L-shaped piece. The author has fancied that the exclusion of air, when using hydrogen, was facilitated by attach- ing to the L-shaped piece a soft-rubber tube extending to the bottom of the apparatus ; as air is much heavier than hydrogen, this device causes the gas admitted through the opposite tubula- ture to displace the air more rapidly. The method devised by 100 TECHNIC. Sternberg is explained in the legend beneath figure 66. A more recent appliance for excluding the air without the use of hydro- gen or carbon dioxid is that devised by Wright. Its form and method of application are indicated in figure 67. Fic. 67.—WRIGHT’S METHOD FOR ANAEROBIC CULTIVATION IN LIQUID MEDIA. a. Spindle-shaped glass tube, at the lower end of which is attached a short piece of rubber tubing (lower B). c. Rubber tubing connecting upper end of A with lower end of pb. D. Glass tube stoppered with cotton at upper B, and continued upward by the rubber tube §. For use, the apparatus is prepared as shown on the left, sterilized by steam, and may be kept in stock. Before inoculation the medium in the tube is boiled to drive off absorbed gas, cooled, and inoculated. Suction is applied to the rubber tube E£, draw- ing the contained fluid upward to point indicated in drawing on the right; the tube is then thrust downward, kinking the rubber tube c, and in a similar manner closing the rubber tube at the lower end of a. It is claimed that this apparatus affords a ready gassed of securing, at the same time, both aerobic and ana eine cultures in the one tube, Hanging-drop Cultures for the Demonstration of Motility. —lIf a drop of liquid culture be placed on a slide and covered in the usual manner, examination with a high power will usually demonstrate the motility of an organism. This crude method is not accurate, as heat currents always occur in fluids under a cover-glass, and may mislead the observer. For demonstrating motility the drop-culture slide is used. This consists of a thick slide of the same dimensions as the ordinary microscope slide, BACTERIOLOGIC TECHNIC. IOI with a concavity ground in its center. A clean cover-glass is grasped in the forceps and is passed through the gas-flame to sterilize it. The concave slide is prepared in the same way, allowed to cool, and around the concavity is painted a thin line of any nonvolatile oil—ordinary sperm oil, vaselin, or, when the slide is to be incubated, paraffin or oleum theobroma liquefied by gentle heat. A droplet of the culture in bouillon or Dun- ham’'s solution is placed in the center of the cover-glass, which is then inverted over the hollow slide, care being taken that the droplet is very small,—not larger than a small pinhead, so that it will not sway from side to side,—and that it does not come in contact with the slide at any point. With the stage of the microscope perfectly horizontal, the droplet is carefully focused upon. The moving bacteria can be easily seen, provided the illu- mination is satisfactory ; the iris diaphragm should be closed to admit but little light, otherwise the field will be so flooded with light that the small, colorless bodies—the bacteria—may escape detection. It is often advisable to center the drop with a low power—say, a %-inch or %-inch objective—before attempting Fic. 68.—DROP-CULTURE SLIDE. (75 X 25 mm., of polished plate glass, with a cavity 18 mm. in diameter.) to focus with a high power. If the organism is growing on a solid medium, a small part of the culture is mixed with the bouillon or Dunham’s solution on a sterile cover, and the hang- ing drop is prepared from the mixture. The “ hanging-drop culture ’’—as such the foregoing is known —may be incubated and kept under observation for a long time if care is used to avoid infection during its preparation and to exclude bacteria by a perfect oil seal. By observation in the in- cubator, bacteria can be seen dividing, yeasts watched while forming and throwing off buds, and other observations made. (See Widal’s test, p. 112.) During the growth of many bacteria, bodies are elaborated that change the reaction of the culture medium. This test is applied by adding an indicator to the fluid, or other medium, and ob- serving whether the color of the indicator changes. The two indi- cators most commonly used are litmus and phenolphthalein ; the former is kept in stock as a tincture, and the latter as a 0.1 per cent. solution of the salt in fifty per cent. alcohol. To apply the test, a number of tubes of culture media—milk, bouillon, or, what is best of all, Dunham’s solution—are prepared ; although 102 TECHNIC, much less suitable, solid culture media, such as gelatin, agar or potato, may be used. In bulk, some of the medium— enough to fill several test-tubes of the size intended for use—has added to it enough of the indicator to show, faintly but clearly, the reaction’; one part of the medium should be but faintly acid, very dilute acetic acid being used to acidify; another portion should be rendered faintly alkaline by the use of one per cent. caus- tic potash, while a third is neutral. With great care sterile media may be sensitized without subsequent sterilization ; as a rule, however, after sensitizing it will be necessary to resterilize the test medium. The same quantity should be in each tube. A number of tubes belonging to each series are inoculated with the germ in question, and several are left as test or control reserves. In the course of a few days, often in less than twenty-four hours, it will be observed that the reaction of the two series is changing. If the germ produces an alkaline reaction, the neutral series evinces the change first, followed by the acid series becoming less markedly acid and, in some instances, eventually manifesting a clearly defined alkaline reaction. The alkaline series may show a slight intensification of the alkaline reaction or may not change at all. The control tubes should remain constant. If the organism produces an acid, the reaction just given will be reversed. Rosolic acid is also used as an indicator ; the stock solution is prepared by adding 0.5 gm. of the acid to 100 c.c. of eighty per cent. alcohol. Its use is the same as the foregoing ; it pales when acid, intensifies its rose-color when alkaline. Indol.—Among the chemic tests applied for the identification of bacteria is that for indol. Several tubes are charged with seven cubic centimeters of Dunham’s solution, sterilized, and three or four inoculated with the germ under investigation, and twice the number reserved for controls. After twenty-four hours add to one of the controls ten drops of chemically pure sulphuric acid, and to another one cubic centimeter of a sodium nitrite solution, freshly prepared, and made by dissolving one gram of chemically pure sodium nitrite in 10,000 c.c. of ammonia-free water. To the second tube also add ten drops of sulphuric acid. Both tubes should be watched for fifteen or twenty minutes ; no color should develop, as they contained no indol. To one of the inoculated tubes add the sulphuric acid, and if in from ten to twenty minutes no reaction occurs, add the sodium nitrite solu- tion, as previously directed ; if indol be present, a distinct rose- color appears. Occasionally the rose-color may appear without the addition of the sodium nitrite, in which case the organism BACTERIOLOGIC TECHNIC. 103 has produced not only indol, but also a ‘reducing agent, com- monly a salt of nitrous acid. Thermic Disinfection.—Each organism thrives best at a certain temperature, known as its optzmuz temperature. WVaria- tions above or below the most favorable degree of heat influence the growth of the germ in question. The lowest temperature at which growth takes place is called the meximum temperature ; the highest, the maximum temperature. The three thermal points are rarely the same for any two organisms, and hence constitute important tests in the identification of a germ under investigation. The cherma! death-point is that degree of heat destroying the life of a germ; a knowledge of the point at which the organism is destroyed also aids in the differentiation of bacteria. The thermal death-point is not constant for the same microbe under all conditions, varying, in some cases, with the age of the organism, the presence or absence of moisture, etc. Again, moist heat is usually destructive to bacteria at a lower temperature than dry heat ; and moist heat under pressure (superheated steam) more penetrating and more rapidly fatal than dry heat at the same temperature. ' In order to determine the thermal death-point of a given organism all the foregoing factors must be borne in mind, as well as the length of time of exposure. The latter also varies with the conditions under which the test is made. A tempera- ture of 70° C., moist or dry, and continued for one or two hours, may be, to a given organism, as certainly fatal as 100” C. with an exposure of ten minutes. The thermal death-point in the presence of moist heat is commonly determined by exposure of bouillon cultures, infected material, or dried threads—prepared as described under Chemic Disinfection (see below)—to different temperatures and for different lengths of time in the steam steri- lizer (Fig. 52, p. 83) or in the autoclave (Fig. 54, p. 85). In making the test with dry heat the hot-air sterilizer (Fig. 49, p. 81) is used, and previously dried infected materials, espe- cially dried threads, make the best test-objects. After exposure of the infected material to the heat, inoculations are made upon suitable culture media, and the tubes are incubated and kept under observation a sufficient time for the development of any unde- stroyed germs. The thermal death-point of an organism may be determined even before its successful cultivation. Such an ex- periment is permissible only when we can not successfully culti- vate the germ. In order to make the test we must be able to infect an animal. Material that is known to contain the organism in question is subjected to heat, and, after definite exposures, is 104 TECHNIC, inoculated into susceptible animals. If disinfection has been complete, the inoculated animals escape. A source of error lies in the well-known fact that the pathogenicity of an organism may be lowered without of necessity destroying its viability ; if, how- ever, the experiment has rendered the germ no longer capable of inducing disease, its infectivity is removed, and therefore dis- infection, in the theoretic sense, has been secured. Theoretically, there should be two death-points—a maximum and a minimum; but experience has satisfactorily proved that there is at present available no temperature sufficiently low to act as a disinfectant upon which it is possible to rely. Reduc- tion below zero commonly determines only a stage of inactivity that ends with return of the organism to conditions again com- patible with growth. Chemic Disinfection.—In addition to the influence of thermic changes on bacteria, it is necessary to study the effect of disin- fectants belonging to the chemic group. The relation of other physical agents than heat may also be studied: ¢. g., drying, light, and electricity. In studying disinfectants, solutions are to be used almost exclusively ; insoluble disinfectants are of more than doubtful value. Again, a culture medium must be used that does not alter the chemical in question. Thus, if, in the study of corrosive sublimate, a culture medium rich in albumin or strongly alkaline be used, the mercurial is instantly decom- posed when it comes in contact with the culture medium, and, it may be, before it has had time to act upon the bacteria. Having found the desired culture medium, the next point to determine is the exact point at which the body under investigation ceases to be antiseptic: that is, inhibits the growth without of necessity destroying the life of the bacteria. For this purpose a series of tubes of culture media are prepared containing the antiseptic in varying quantities. These are best prepared, if possible, by taking 50 or 100 tubes of the medium it is desired to use, steri- lized in the usual way: To ten of these enough of the agent is added to make the strength ten per cent.; to another ten, enough to make the strength five per cent. ; to another ten, four per cent. ; and so on, covering various percentages. All these tubes are inoculated with the germ that it is pro- posed to use for the test. A series will be found beyond which the agent is in such dilution as not to interfere with the growth and above which the dilution may be antiseptic without of neces- sity destroying the germ—inhibits growth but does not disinfect. The strength at which disinfection—that is, destruction of repro- ductive power—occurs may be approximately inferred by dilut- BACTERIOLOGIC TECHNIC. 105 ing with the same sterile culture medium the tubes in which no growth has evinced itself, so that the proportion of the disinfect- ant in the dilution shall be less than that already found to not inhibit growth. After this dilution the bacteria that have not been destroyed develop, showing in what strength disinfection has been complete. This has, however, taken so much time— probably days—that doubt may still exist as to the rapidity with which the agent in question acts ; and as the time required by a given solution to destroy viability is important, we must determine the rapidity of action and the strength necessary to use to be practically available. For this purpose a number of methods have been suggested, all of which are open to certain sources of error. To a number of cultures in a liquid medium the agent in question is added, so as to make the percentage such as has been found in the previ- ous test to be destructive ; the added solution is thoroughly mixed with the culture, from which inoculations are made at intervals of minutes for as long as an hour. The re- moval must be made into tubes containing sufficient of the medium to dilute the mate- rial carried over beyond the strength already shown to have an inhibitory action, SO Fic. 69.— SMALL INCUBATOR SUFFICIENTLY that any undestroyed bacteria LarGe FoR INDIVIDUAL Work. may be free to develop. The source of error by this method lies in the clumping of the germs in the original tube ; if grouped in clumps, the agent may not have penetrated the clumps. Penetration is a most im- portant point, for without this power a disinfectant is of little practical value; as, in all purposes for which germicides are used, a certain degree of penetration is necessary, this apparant objection is not without its good side. To get rid of the clumps, cultures are made in a medium containing fine quartz sand ; this is shaken up in the culture and the culture filtered through glass wool and the filtrate used for the test. Tubes containing the sand may have mixed with them growing cultures containing no 106 TECHNIC. sand. Again, threads of silk from two centimeters to six centi- meters in length may be placed in tubes of liquid culture media, the tubes sterilized as usual, and, when sterile, infected with the germ that it is intended to use for the test. When the culture is well grown, it is shaken, the threads are withdrawn, and may be used as test bodies to disinfect; they may be first dried in sterile dishes or they may be used moist. A source of error lies in the quantity of the disinfectant that the thread may convey into the tube into which it is transplanted after treatment with the disinfectant. In some cases this may be partly avoided by washing the thread in sterile water or in some solution, or by exposing it to a vapor, which, by chemic action, converts the dis- infectant into an insoluble or inactive compound. Thus, threads which have been in corrosive sublimate solutions may be ex- posed to ammonium sulphid vapor, the solution converting the mercurial into an insoluble and inactive sulphid. It will be noted that one of the essential elements is to make the transplantation, after treating the thread or culture with the disinfectant, into such a quantity of new noninfected medium as to assure a dilution beyond the inhibiting point, which may be due to any of the antiseptic carried over on the thread or on the platinum loop. Thus, if a thread has been exposed to a solu- tion of an agent,—say, in the strength of 1: 100,—and the inhibiting action is present in a solution having a strength of I : 1000, it will be necessary to carry the thread into a medium having a minimum bulk, in order to be safe, of at least 100 times the quantity carried over on the thread, in order to assure such dilution as not to preclude the disinfectant preventing growth of any undestroyed organism. In testing gases, threads, cultures, and other infected materials are exposed in a closed chamber, such as a bell-jar, to the gas, either pure or with a known dilution of air. _ Inaddition to the foregoing system of tests, so-called practical tests are made. A known quantity of pus, blood, sputum, or feces is mixed with a known quantity of the disinfectant, and cultures are made at intervals of from two to five minutes. Varying strengths of the disinfectant are used with exposure for different lengths of time; in this way purely laboratory experiments are controlled by what are considered practical methods. Again, animals may be inoculated with cultures or threads that have been exposed to disinfectants. In the latter case it is to be remembered that in rare instances the pathogenicity may be reduced without the germ being destroyed. To study the pathogenesis of an organism. inoculation of BACTERIOLOGIC TECHNIC. 107 animals is necessary. The animals most used are rabbits, guinea-pigs, rats, and mice. The absolute requisite to success is careful asepsis at every stage of the process, and during the post- mortem if the animal dies. If the disease or a disease is pro- duced, and it is desired to obtain cultures, they must be secured with the same strict attention to detail. All instruments used in the various stages of inoculation, examination during life, or postmortem, should be sterilized by heat: preferably dry, although moist heat may be used. Chemic disinfection must be regarded with suspicion, although syringes may be sterilized in a five per cent. solution of carbolic acid allowed to act for one or, better, two hours, during which time the solution should be kept warm. Pure formalin may be used on instruments. No matter what chemic body is used, it must be thoroughly removed by washing in sterile water before pro- ceeding with the operation. The hands of the operator and of Fic. 70.—APPARATUS FOR HOLDING A MOUSE OR RAT FOR INOCULATION. (Devised by Dr. Lydia Rabinowitsch and Dr. Voges.) The inoculation is usually made just over the root of the tail. the assistants, and the table upon which the operation is to be conducted, should be washed with soap and water as hot as can be tolerated, followed by alcohol, ether, and finally corrosive sublimate solution (1 part of the salt dissolved in 1000 parts of normal salt solution), which should be allowed to act several minutes, followed by thorough washing in sterile water. Of the many methods for inoculating an animal, the following will be found useful : r. Subcutaneous inoculation is the one most frequently used. The site of the contemplated operation is shaved, washed with soap and water, water, alcohol, ether, alcohol, and corrosive sublimate solution (1 : 1000), and the last removed by thorough washing with sterile water. Between the scapula and near the tail are the most convenient sites for inoculation, but any point where the tissues are lax will answer the purpose. The skin is stretched and made tense, an incision or pocket is 108 TECHNIC. made in the tissues about five millimeters to ten millimeters in length and correspondingly deep under the skin ; into the pocket so made a loop of the growing organism or suspected material is introduced, after which a layer of sterile cotton is laid over the wound and a thick coating of collodion applied; in a few min- utes this will dry ; the animal is then liberated and kept with an uninoculated animal known as the control. Subcutaneous in- jection of bacteria, suspended in sterile water or bouillon, may be resorted to as directed for intraperitoneal inoculation. 2. Lutraperitoneal injections are made by preparing the animal as before. A syringe graduated in cubic centimeters is neces- sary for this method. The skin of the abdominal wall—the site of the operation—is prepared as previously explained, grasped by an attendant, and raised as a fold, into which the needle is introduced and forced onward into the peritoneum, then partly Fic. 71.—KocuH’s SYRINGE FOR HYPODERMIC, INTRAPERITONEAL, AND OTHER INJECTION ETHODS FOR INOCULATING ANIMALS; THE CAPACITY SHOULD BE AsouT Two Cusic CENTIMETERS. A withdrawn to make sure it is free in the peritoneal cavity. The syringe is now attached, a given quantity of bouillon culture is introduced, and the wound is sealed as before. 3. Intravenous inoculation is made directly into the vein; the most convenient veins are those of the rabbit’s ear. The over- lying skin is prepared as already directed, and an incision is made down upon, but not into, the vein; when the vein is thoroughly exposed, the needle of the hypodermic syringe is thrust into the vein in the line of the blood-current, and the contents of the syringe are slowly injected. Great care must be used to see that no air enters the vein, and that no clumps or other solid material that might cause embolism are thrown into the blood. 4. Inoculation into the Anterior Chamber of the Eye.-—Anes- thetize the cornea by cocain, wash with sterile water, perforate the cornea at the scleral margin with a hypodermic needle, through which the material is injected; the quantity should be BACTERIOLOGIC TECHNIC. 109g very small—scarcely a half drop; otherwise a disturbing tension is created that greatly modifies the result of the operation. 5. Tissue Implantation—Sometimes a small piece of patho- logic tissue is used for inoculating (as in glanders and tubercu- losis). The implantation may be made into the subcutaneous tissues or serous cavities. In the first instance a pocket is pre- pared as already directed for subcutaneous inoculation, into which the block of tissue (which should not be larger than from two to five millimeters cube—the smaller the better) is implanted, the wound sealed, if necessary, sutured, and covered as already directed. For transplantation into a serous cavity, the peri- toneum is usually selected. Under the strictest asepsis the cavity is opened, the tissue dropped in, and the opening closed. In some instances, in order to assure vascularization, a tip of the omentum is brought out, the block of tissue rolled in the serous membrane, and the roll secured by a stitch. The foregoing methods demand the use of a piece of tissue of macroscopic pro- portions, and leave a wound through which accidental infection ctl Fic. 72.—SPATULA USED FOR SEARING THE SURFACES OF ORGANS BEFORE MAKING INCI- SIONS INTO THEIR INTERIORS FOR OBTAINING CULTURE MATERIAL. may occur. In many instances the difficulties just indicated may be evaded by rubbing up the material in a sterile glass mortar with a small quantity of sterilized water. Unless there is an unusual amount of connective tissue, the maceration may be sufficient to permit of injection through a comparatively large hypodermic needle. When there is reason to believe that the water may act deleteriously, some other menstruum, such as normal salt solution or blood-serum, may be used. After-treatment of the Animal.—Medication of all kinds should be avoided; overcome the immediate shock by the gentlest handling of the animal, abundance of fresh air,and warmth. It should be treated exactly as a control (an uninoculated animal of the same species), but, as a rule, should be in a cage or inclos- ure by itself; otherwise the control may injure the inoculated animal. The Postmortem.—If the animal dies, the body should at once be washed with soap and water and with water and alcohol, and immersed in I : 1000 corrosive sublimate solution, followed by washing with sterile water. A postmortem is made under strict IIO TECHNIC. asepsis. As soon as the heart is exposed, a spot on the surface of the right auricle is seared by heating a spatula and laying it down on the surface of the organ; this thoroughly disinfects the surface. Thrust a sterile inoculating needle into the auricle, and move it through the blood backward and forward until a drop emerges along the side of the needle, when it is withdrawn and a tube of medium inoculated, which may be at once poured into a plate. (See Plate Methods.) This operation is repeated for each cavity of the heart and for all important organs of the body. Pieces of tissue are hardened, either in absolute alcohol or corrosive sublimate, and prepared for sections in the usual manner. (See Killing and Fixing of Tissues, p. 48; also Stain- ing of Bacteria, p. 93.) Method of Preparing Toxins and Antitoxins.—The preparation of the diphtheria antitoxin is as follows : As the bacilli develop their toxins most rapidly in the pres- ence of a moist current of air, a flat-bottomed vessel with two lateral tubes is charged with bouillon containing two per cent. of peptone. After thorough sterilization, inoculate with fresh viru- lent cultures of the diphtheria bacillus. Incubate at 37° C. until development begins, and then force through the lateral tubes a current of moist air.* A sufficient quantity of toxin will be developed in from three to four weeks. Filter through a Pasteur-Chamberlain filter, preserve in well-stoppered bottles, and keep in a dark place. In doses of 0.1 c.c. this filtrate should kill a guinea-pig weighing 500 grams in from forty- eight to sixty hours. For the purpose of immunizing animals, this fluid is in many cases too strong for the first injections, and should be diluted with one-fourth its volume of Gram’s solution. Roux and Vaillard have determined that the toxin is much less dangerous when combined with iodin. A medium-sized rabbit should receive an injection of 0.5 c.c. The injection is repeated in a few days, and thus continued for several weeks. With each successive injection the proportion of Gram’s solution should be diminished, and the dose slightly increased until the pure toxin is reached. After injection of the toxin the animal not infre- quently manifests a slight rise in temperature, with accelerated pulse, and sometimes an evident malaise. A second injection should not be given until all symptoms of the previous injection have disappeared. The amount of toxin is gradually increased until the animal bears without inconvenience a dose equal to 100 * The aeration of the flask is no longer practised, experience having shown that it is not demanded. BACTERIOLOGIC TECHNIC. III minimum fatal doses. If during this time a loss in body-weight becomes manifest, the injections should be discontinued, or there may be induced a fatal cachexia. Dogs, sheep, goats, horses, and cows may by this procedure be rendered immune. The milk of immune animals may offer an important source of the antitoxin. The horse is easily im- munized, and will supply large quantities of the antidiphtheric serum. Horses bear propor- tionately large doses better than other animals, and but a transient fever will succeed a dose of from two to five cubic centimeters of a strong toxin. Fic. 73.— STERNBERG’S FLASK, USED FOR COLLECTING FLUIDS, WATER, ETC., AND FOR HOLDING CULTURES IN LIQUID CUL- TURE MEDIA. ; Before using, it is sterilized in the hot-air oven. To fill, the point is broken off and FiG. 74.—KITASATO’S FILTER. The material to be filtered is placed in the upper bulb, which is connected with the central bougie of unglazed porcelain. The point of connection between the receiving chamber and the filter bougie is covered the bulb is heated, thus expelling some of the contained air; the point is then thrust into the fluid, and, as the bulb cools, the fluid rises into it ; when the desired quan- tity is drawn into the bulb, the point is sealed in a gas-flame Certain brands of antitoxin are now dispensed in bulbs simi- lar to the one here illustrated. by a rubber cork, which fits very tightly into the neck of the flask. Through the lateral arm of the flask, extending out to the right, the air is exhausted from the interior. In this way filtration, ordinarily slow, may be accelerated by air pressure. The filter is mostly used for separating germs from their toxins. Antitoxin is obtained from the animal by bleeding under the strictest conditions of asepsis, receiving the blood through a cannula into a sterile jar, flask, or other container, as already directed for the preparation of blood-serum for culture purposes. The obtained serum may be preserved by the addition of tricre- sol, thymol, carbolic acid, camphor, etc. It should be sterile, and if care has been taken to exclude contamination during the various stages in its preparation, the addition of a preservative will be unnecessary. 112 TECHNIC. In order to estimate the strength of an antitoxin, we must first know the minimum fatal dose of a toxin. This information is obtained by selecting a number of guinea-pigs, each of which weighs 250 gm., and by injecting subcutaneously different quan- tities of the toxin under investigation. The minimum fatal dose is that which kills a guinea-pig weighing 250 gm. on the fourth or fifth day. In order to exclude possible error, arising from unusual susceptibility or insusceptibility of the animal, a number of injections should be made and a fairly uniform result finally attained. The strength of the antitoxin present in the serum, obtained as previously described, is expressed in zimmunity units. An immunity unit is ten times the quantity of antitoxin necessary to protect a guinea-pig weighing 250 gm. from ten times the minimum fatal dose of toxin. In order to determine the strength of a given serum we proceed as follows: A number of test doses of the toxin are prepared, each con- taining ten times the minimum fatal dose. To each test dose is added a measured quantity of the serum in question. To one dose is added 0.01 c.c. of the serum ; to another, 0.05 c.c. of the serum; to another, 0.1 c.c. of the serum; to another, 0.5 c.c. ; and to still another, I c.c.,andso on. The mixtures are now injected into guinea-pigs and the results observed. Protection implies that no swelling, rise in temperature, or evident disturb- ances of nutrition follows this administration. The mixture con- taining the smallest amount of serum and yielding this result contains 0.1 of an immunity unit. Assuming that the quantity of serum present in the test dose that yielded the foregoing result was 0.1 c.c., then I c.c. of such serum contains an im- munity unit of the antitoxin. Antitoxin, as placed upon the market, is labeled as containing a certain number of immunity units, and the measured quantity of serum necessarily varies, as the number of units obtained are rarely exactly the same in two animals. For the treatment of disease the antitoxin is administered sub- cutaneously. Widal’s Test for the Diagnosis of Typhoid Fever.*— Culture Employed —The culture used in the Widal test should be * This description of the method was abstracted by Dr. J. C. Da Costa, assist- ant in clinical microscopy, Jefferson Medical College, from his article in the ** New York Medical Record,’’ August 21, 1897, in which he reports an examination of over 100 cases, and also an analysis of the literature on the subject up to the date of publication. I am also indebted to Dr. Da Costa and to the publishers of the journal for permission to use the accompanying illustrations. More recent im- provements in technic have been added. BACTERIOLOGIC TECHNIC. 113 taken from an agar growth that has been allowed to develop at ordinary room-temperature for at least twenty days. From this. agar culture inoculations are made into tubes containing neutral beef bouillon, and these tubes, after incubation at 37.5° C. for from eighteen to twenty-four hours, are used in the test. Instead of making bouillon growths, emulsions in sterile distilled water may be used with good results by thoroughly mixing a bit of a recent agar growth with about 2.5 c.c. of sterile water in a test-tube until a uniform cloudiness appears. The precautions previously indicated must be followed to avoid certain false or pseudo-reactions, which sometimes occur when normal blood or blood from individuals suffering from diseases other than enteric fever is added to a virulent culture of the typhoid bacillus. Method of Conducting the Test—The blood is obtained by puncture of a finger, and three separate drops are allowed to fall upon the surface of a perfectly clean glass slide that has been passed through a flame and cooled just beforeuse. The glasses are permitted to dry, and are then placed in a box to await examination at a convenient time. To one of the blood-drops a large drop of sterile distilled water is added to effect a solution of the dried blood ; and while this is going on, the other preparations for the test are being made, by cleaning and sterilizing by the flame two cover-glasses and a “concave slide,’’ to be used for the microscopic examina- tion of the specimen. On one of the cover-glasses six drops of the typhoid bouillon are now placed, and to this is added a large drop taken with a platinum loop from the summit of the blood solution, and the whole is thoroughly mixed together. From this mixture of blood solution and typhoid bouillon a minute quantity is now placed with a platinum needle upon the center of the second cover-glass, which is immediately inverted over a hollow-cell slide, sealed with either vaselin or cedar oil, and examined under the micro- scope with a ¥%-inch dry objective. (See Hanging-drop Cul- tore, p. 61.) . Instead of the glass slide previously recommended for receiv- ing the blood, a small piece of highly glazed paper may be sub- stituted. Whether using the glass slide cover-glass, foil, or paper, the blood as received at the laboratory is dry, and the difficulty that at once confronts the investigator is to restore this to its original volume. It does not seem probable that accurate restoration is ever possible, and for this reason the dry method must always be liable to error, depending upon our total inability 8 114 TECHNIC. accurately to determine the dilution that is being used. The majority of observers are in favor of a 1 : 20 dilution, and for this purpose the writer is not familiar with any method that pos- sesses advantages over that devised by Cabot. A drop of blood is placed in a tube or other container, and at once there are added, using the same pipet, nine drops of sterile water. This fluid is taken to the laboratory and one drop mixed with one drop of a bouillon culture of the typhoid bacillus, giv- ing as nearly as can be obtained a dilution of 1: 20. If not unnecessarily agitated, the corpuscular elements will lie mostly at the bottom, and the supernatant fluid may be, ina short time, clear. When the mixture has not cleared, sedimentation may be hastened by the use of the centrifuge. FIG. 75.—BACILLUS TyPHI ABDOMINALIS. Fic. 76.—A PosiTIVE REACTION. Hanging-drop culture, prepared as directed saa clumps of motionless bacilli separated on page to1. The bacilli are actively y open spaces. The few bacteria out- motile throughout the field. side the clumps are devoid of motility. Appearance of the Reaction.—lf the reaction is positive, the observer will see large clumps of motionless, agglutinated bacilli, which appear as irregularly shaped islands, separated by open spaces containing, perhaps, a few isolated bacteria, whose power of propulsion is either decidedly inhibited or entirely lost. If the reaction be negative, the bacilli will appear as actively motile rods, darting across the field in every direction, and showing no tendency to form into masses, although occasionally small clumps of the microorganisms may be noted. In negative reactions, however, clump formation never progresses to any marked degree, and motility persists, regardless of the time during which the specimen is watched. If any doubt exists as to the nature of a reaction, a “control”’ slide should be pre- BACTERIOLOGIC TECHNIC. IIS pared with normal blood and typhoid bouillon, for purposes of comparison. (See Figs. 76, 77, 78.) The time required for the completion of a reaction varies, but in a general way it may be said that typhoid blood will cause definite clumping and loss of motility of the typhoid bacilli within thirty minutes in the great majority of instances. In some cases a much longer time will be necessary before a cor- rect interpretation of the test can be arrived at. A reaction may Fic. 77.—A PSEUDO-REACTION. A few small clumps of bacilli having impaired motility. Persistent motility of the bacteria in other parts of the field occurs. not be classed as positive unless both clump formation and loss of motility coexist, and those reactions in which etther of the phe- nomena are wanting may not be called typical in any sense. Systematic Records.—In order to render comparable studies made by different investigators, as well as for comparison of the characteristics of different bacteria, it becomes necessary to select some definite order of study and a method by which accurate records may be kept. The method which follows presents nothing original, and is that in use in the laboratories under the author’s supervision. The entire blank, as well as the outline drawings of culture tubes (4, ¢, d, ¢, table on p. 116), are sup- plied to the student, and on these blanks he draws in black, or better in color, the cultural peculiarities of the microorganism under investigation. For noting the changes observed in the culture from day to day the drawings made each day are kept, and the entire series clamped or gummed together for filing. The table not only affords a satisfactory means for recording the characteristics of an organism, but also indicates what data should be worked out, and the usual sequence in which the results attained are recorded. 116 TECHNIC. TABLE ILLUSTRATING METHOD OF RECORDING THE PRINCIPAL CHARACTERISTICS OF AN ORGANISM. (A) Where found. (B) Morphology. («) Form, (4) size, (¢) arrangement. (C) Stains. Reaction to Gram’s method of staining. as (1) Flagellate. AP] Motility { e Nor femelle (E) Method of reproduction. (F) Products of growth: (a) Acids, (4) alkalies, (c) odor, (¢) color, (e) gases, (f) enzyme, (g) indol, (2) toxin, (7) other chemicobiologic reaction or product. (G) Characters of growth on: (a) Plates. ca MAKE DRAWING. CC CC Kod et (5) BouILLon. (c) GELATIN. (d) AGaR. (e) BLoop- (7) SPECIAL SERUM. MEDIUM. BACTERIOLOGIC TECHNIC. 117 . . f (1) Facultative. (H) (a) Aerobic, (4) anaerobic { (2) Obligate. (I) Reaction of medium best adapted toits growth. Reaction of cultures in milk. (J) (a) Optimum temperature, (4) thermal death-point { (3) Dey nek (K) Influence of antiseptics and disinfectants. (L) Pathogenesis. (M) Immunity, method of securing, duration, blood characteristics in and influ- ence of blood-serum of immune animal on the organism. (N) Remarks: Peculiarities not embraced in foregoing form. CHAPTER IV. MICROSCOPIC EXAMINATION OF URINE. Collection of Sample-—The amount of urine necessary for the examination will-depend somewhat upon the object of the exami- nation and upon the condition of the urine. In most instances at least eight ounces should be submitted to the examiner. It is best that it be collected in a perfectly clean bottle and delivered at once. When bacteriologic examination is desired, the con- tainer should have been disinfected, as already directed on page 80. When an examination is to be made for tubercle bacilli, or, indeed, in any bacteriologic examination, it is desirable to have all parts of the external genital organs that are likely to come in contact with the urine cleansed, or, what is even better, the urine may be drawn with a thoroughly cleansed catheter. Smegma bacilli are so abundant in the external genital organs of the female that it is best to use extra precautions, and, if possible, to remove the urine by means of a glass catheter that has been sterilized in a hot-air oven at a sufficiently high temperature to carbonize any bacteria that may be upon or within it. As soon as received, the urine should be sedimented. This may be accomplished by permitting it to stand in a conic glass, such as is shown in figure 79. A better and more convenient means for securing sedimentation is by the centrifuge. Of the various forms of centrifuge, those in which the power is supplied by the hand or turbine are to be preferred. Method of Conducting the Examination.—As soon as the sediment has been secured by either of the methods previously indicated, a sterile pipet, closed by the finger at the upper end, is cautiously introduced through the supernatant fluid into the sedi- ment, the finger is cautiously drawn to one side, permitting a few drops of sediment to enter. The finger is then held tightly over the pipet, which is at once withdrawn from the urine. The fluid on the outside of the pipet is then removed with a cloth or paper, and, holding the pipet perpendicularly, a small drop is placed on the slide and a cover-glass applied. Drain off excess of fluid with blotting-paper, and examine with % of an inch and 4 or ¥% of an inch objectives. 118 MICROSCOPIC EXAMINATION OF URINE. IIlg Preservation of the urine may be aided by adding a crystal of thymol, camphor, or menthol. If it be desired to preserve the sediment, this is best accomplished by carefully decanting the supernatant fluid and adding an equal quantity of a saturated aqueous solution of potassium acetate, allowing this to remain forty-eight hours, again decanting, and adding fresh acetate solu- tion. After repeating this three times, no difficulty will be found in preserving casts, blood, epithelium, etc., present in the sedi- A = TH LTT) | | FiG. 78.—WATER CENTRIFUGE. The number of revolutions depends on the water pressure and on the size of the supply pipe. A pipe at least % of an inch should be used, and the larger the better. The ordinary city pressure is about 25 pounds; with %-inch pipe this will give 1200 revolutions a minute ; 30 pounds will give 1400; 35 pounds, 1500. By enlarging the supply pipe the speed rapidly increases. A thousand revolutions a minute are sufficient for urine sedimentation. Tubes A and B hold one ounce each. : ment. Casts may be preserved indefinitely in chloral, provided they have been washed according to the methods just indi- cated. The chloral solution should have a strength of about twenty grains to the ounce of water, and should exceed in volume one hundred times the volume of the sediment to be preserved. ORGANIZED SEDIMENT (Cellular Constituents)—Red Blood- corpuscles—When these corpuscles occur in large numbers and y 120 TECHNIC. in good condition without being intimately blended with the urine, they are usually from the bladder or urethra ; but when they do not form a red sediment after many hours’ standing, and have lost their coloring-matter and appear as pale yellow, washed-out rings (phantom corpuscles of Traube), espe- cially if associated with blood- casts, the hemorrhage has probably occurred in the sub- stance of the kidney, renal pelvis, or ureters. Fic. 79.—Conic GLass SUITABLE FOR THE SEDIMENTATION OF URINE. — (Coplin and Bevan.) In position is shown a candle-wick filter for securing urinary sediment. The filter consists of aglass tube so bent that the longer arm is outside and opens below the level of the bottom of the conic glass. Through the bent glass tube are drawn a few strands of candle-wick to fill the tube rather tightly. By capillarity the urine rises in the bent tube and eventually flows over ; inso doing it deposits all the sedi- ment on that end of the candle-wick whichis at the bottom of the glass. This is gently brushed over a number of slides, cover-glasses are applied, and the slides examined at once. os —_— > fT if | (— |BAUSCH&LOMB OPTI CO. ROCHESTER NV ° HAEMATOKRIT URINE Fic. 80.—CENTRIFUGE WITH HEMATOCRIT ATTACHMENT. The attachment for sedimenting liquids such as urine is shown in position for use. This may be lifted off and the hematocrit at- tachment shown in the upper part of the figure substituted in the place of sedi- menting attachment shown in position. There are two gears, one for sedimenting blood, knownas the high gear, and which gives 10,000 to 14,000 revolutions a minute; the lower gear, for sedimenting urine, giving from 2500 to 4000 revolutions a minute. The crank is easily transferred from one gear to the other. ° FPus.—Urine containing pus in any quantity is always turbid when voided, and shows decided reaction for albumin if the quantity of pus be at all large. Pus-corpuscles are nearly twice the size of red blood-corpuscles, and appear as pale, circular, granular discs with several nuclei, and are practically identical with mucus corpuscles, white blood-corpuscles, and lymph- cells. MICROSCOPIC EXAMINATION OF URINE, I21 They may show ameboid movements when examined in the fresh state, but, as seen in urinary sediment, their protoplasm is coagulated into coarse granules. Epithelium.—{ Make drawings of different forms. ) Squamous epithelium. Transition epithelium. Epithelium from bladder. Urinary Casts. I. Those consisting of cells, II. Those that consist of the products of cellular change. III. Hyaline casts. Examine with 14-inch or 4-inch objective and make drawings of— Blood-casts, Lpithehal casts, Granular casts, Waxy casts, Fatty casts, flyaline casts, Pus-casts, Bacterial casts, Cylindroids, false casts, composed of urates or crystals, Casts from seminal tubes. Spermatozoa are thread-like bodies, 50 y long, provided with a head and a long, tapering, tail-like extremity. Their constant deposit indicates spermatorrhea. They are easily identified in urinary sediment, or may be stained as follows : Spread a thin layer of the sediment on a clean cover-glass; dry without heat; stain in carbolfuchsin for two seconds; wash in water ; dry, and mount in balsam. Nonpathogenic Fungi: Molds, or large segmented rods. Yeast plants (saccharomyces urine and other yeasts) are arranged in bead-like forms with budding cells attached. Bacteria of decomposition. Pathogenic Fungi.—7ubercle Bacilli.—In all cases of puru- lent urine accompanied by anemia, wasting, and evening rise in temperature, the urinary sediment should be examined for tuber- cle bacilli. Purulent deposits of tuberculous urine should be treated the same as sputum in searching for tubercle bacilli. The centrifuge aids materially in this examination. Experience shows that residual urine drawn with a catheter after the patient has appar- 122 TECHNIC. ently voided all the contents of the bladder is more likely to con- tain tubercle bacilli than the tidal urine.* (For method of demonstration see Tubercle Bacilli.) Gonococcus (Neisser).—Minute, roll-shaped diplococcus found in urine containing gonorrheal pus. (For method of staining and description see article on Bacteriology.) Distoma Hematobium.—The eggs of this parasite, about 125 yu in length, are oval or flask-shaped, and are found accompanied by blood-cells and pus. Filaria Sanguinis Hominis——The embryos are occasionally found in chyluria. (See Animal Parasites.) UnorGANIZED SEDIMENT (Crystalline and Amorphous). Sediment of Acid Urine.—(Examine and draw the various crystals.) Uric acid (whetstone crystals). Oxalate of lime (envelop crystals). flippuric acid. Urate of soda. Tyrosin and leucin. Soaps of lime and magnesium. Amorphous deposits. Urates. Brown and yellow concretions. Sediment from Alkaline Urine. Triple phosphates (coffin-lid crystals). Urates of Ammonium (hedgehog crystals). Indigo. Cholesterin. Amorphous deposits. Phosphate of lime. Carbonate of lime. * Bryson, American Association of Genito-urinary Surgeons, May 6, 1897. MICROSCOPIC EXAMINATION OF URINE. ILLUSTRATIONS OF VARIOUS URINARY SEDIMENTS.* Fic. 81.—PHANTOM AND DISTORTED RED BLOoOD-CELLS FOUND IN URINE, Most COMMONLY THAT OF RENAL HEMATURIA. —(Landots.) am 8 O.™, ® "Gog *» oO » s oO G00 € o> * c og ¢ eS Go oO % 6,° @9@ 22,68 @ ve, “3 @ Ba 9G a % — Cag? aga ges Sacre sage igs ado @ Fic. 82.—BLOOD-CELLS IN THE URINE.—( Gould.) The cells that appear almost normal could not have been subjected to the ac- tion of the urine but for a short time. q) ey Fic. 85.—EPITHELIUM FROM THE CONDUCTING PART OF THE URINARY APPARATUS, MOSTLY FROM THE BLAD- DER. Note in the upper left-hand part of the figure the cells that resemble renal epithe- lium. Fic. 84.— PUS-CELLS IN URINE.—( Gould.) Many are irregular or frag- ment forms. Fic. 83.—BLOOD-CELLS IN THE URINE, LyMPH-CORPUSCLES, LEUKOCYTES OR PUS-CELLS, AND CRYSTALS OF _ TRIPLE PHOSPHATE. XX 350 diameters. —(Landots.) Fic. 86.—RENAL EPITHE- LIUM, The four cells below and to the left are fatty. This form of epithelium will be found on casts and free in the urine. It will be noted, however, that it so closely resembles epithe- lium from one layer of the conducting apparatus that the diagnosis of free renal epithelium may be open to criticism. See figure 85, epithelium from the bladder. * Experience has convinced the writer that the best way to learn to recognize the various urinary sediments is to take as good an illustration, or series of illustrations, as can be secured, and work at the microscope with the illustrations at hand until able to recognize all the ordinary forms. 124 TECHNIC, Fic. 87.—SEMINAL ELEMENTS, SOME OF WHICH May BE Founp IN URINE. a,a. Spermatozoa. 6. Seminal cells. c. Epithelium. d, d. Seminal granules. Io agri thTEN a ead spa eE ES ot ee ot —_ Soh = Fic. 88.— ILLUSTRATING THE FORMATION Fic. 89.—EPITHELIAL CAsTs.—(Landozis.) oF CAsts.—( Rindfleisch.) a. Hyaline cast in place. If it comes away bringing nothing with it, it will remaina hyaline cast. If it brings epithelium, it will bean epithelial cast ; ifthe epithelium is granular, it will bea granular cast; if fatty, a fatty cast. c. Granular cast. The two casts in the lower corner, and to the left, are hyaline ; the remaining casts are largely hyaline, but bear a few epithelial cells. A. Epithelial cast, the lower end of which is coarsely granular. B. Epithelial cast in which the epithelial cells, though themselves granular, have not broken up. MICROSCOPIC EXAMINATION OF URINE. 125 Fic. 90.— BLoop- CELLS AND y FIG. 91. FIG, 92 —GRANULAR Casts. — (Lan- BLOOD-CAST.— Hyaline cast. B. Hya- dois.) ; line cast with a few at- A. Granular casts in which the gran- (Landois.) tached leukocytes. C. ules are fine and the dissolution of Hyaline cast with at- the epithelial cells is complete. &. tached epithelium, truly Granular casts in which the gran- an epithelial cast.— ules are coarse and the outlines of (Landois.) the epithelial cells at points faintly distinguishable. FIG. 93. . Cast made up almost purely of leu- kocytes. &. Casts composed of acid sodic urate; crystalline casts. Yeast.—(Landozis.) —(Landots.) FIG. 94. a, a, 6, ¢. Crystals of uric acid. d, g. Zooglea masses of cocci and bacilli. e. Mold. f. 126 TECHNIC. Fic. 95.—SOME ForRMS OF URIC AciD. 1. Rhombic crystals. 2. Whetstone forms. 3,3. Quadrate forms. 4, 4, 5. Irregular forms. 6, 8. Groupings into roset forms. 7, 9. Bundle forms, precipitated by adding hydro- chloric acid to the urine, The crystals may be pigmented or lightly colored brownish- yellow; the pigment is presumed to be uroerythrin, alsocalled urochrome.—(Landozis.) Fic. 96.—Actp AMMONIUM URATE. F1G. 97.—H1Ppuric AcID. FOUR-SIDED PRISMS. WITH Two oR Four BEVELED EDGES.— ( Gould.) MICROSCOPIC EXAMINATION OF URINE. 127 FIG. 98.—SOME DEposITS IN ACID FERMENTATION OF THE URINE.—(Lavdozts.) u. Bacteria. 64. Amorphous sodic urate. c. Uric acid. d@. Calcium oxalate. \ FIG. 99.—SOME DEPOSITS FROM AMMONIACAL URINE (ALKALINE FERMENTATION). a. Acid ammonium urate. 4. Ammoniomagnesium phosphate. c. Bacteria. a ae °° % % OK % oe oe ee 2» Fic. 100. — WHETSTONE AND IRREGULAR Fic. 101. — AMMONIUM URATE. ‘‘ HEDGE CRYSTALS OF Uric AciID.—( Gould.) HOG” CRYSTALS.—(Goz/d.) 128 Fic. 104. — AMMONIOMAGNE- SIUM PHOSPHATE (TRIPLE PHOSPHATE).—( Gould.) Triangular prisms with beveled edges; “coffin-lid ” crystals. TECHNIC, 20. 2 ao" Fic. 105.—MAGNESIUM PHOS- PHATE.—( Gould.) Elongated rhombic tablets, which may be fused together in variously formed masses. Fic. 106.—AMORPHOUS GRANULES OF CAL- c1uM CARBONATE.— ( Gould.) MICROSCOPIC EXAMINATION OF URINE, 129 Fic. 108.—AMORPHOUS FIG. 109.—DUMB-BELL AND OCTA- Fic. 110.—CALCIUM SUL- GRANULES, WEDGE- HEDRAL CRYSTALS OF CALCIUM PHATE; ELONGATED SHAPEDCRYSTALS, SOME OXALATE.—( Gould.) TRANSPARENT NEEDLES ARRANGED IN Ros- OR TABLETS.—( Gould.) ETS OF CALCIUM PHOSPHATE.—( Gould.) FIG. 111. uw. Crystals of cystin. 4. Crystals of oxalate of lime. c. Hour-glass forms of 3. 9 130 TECHNIC. FIG. 112. a. Leucin balls. 6, 5. Tyrosin sheaves. Fic. 113.—LEUCIN AND TyYROSIN, FIG. 114.—CYSTIN, SIX-SIDED PLATES, OFTEN A, A. Leucin; yellowish, highly refracting SUPERIMPOSED.—( Gould.) spheres, with radiating lines. B,B. Ty- rosin, needles and sheaf. FIG. 115.—CHOLESTERIN.—(Landots.) Fic. 116.—INDIGO.—( Gould.) Amorphous granules, fine needles, and crys- tals of a blue color. CHAPTER V. TECHNIC OF SPUTUM EXAMINATION. Collecting the Specimen.—Great care should be exercised in obtaining the sputum for examination. Avoid the collection of sputum immediately after eating, as, under such circumstances, it contains particles of the food, which unnecessarily complicate the examination. The first sputum raised in the morning is to be preferred. An effort should be made to instruct the patient to avoid collecting mucus brought from the nose and pharynx. The amount of sputum to be obtained will, of course, vary with circumstances : while a very small amount may be examined and give satisfactory results, five or ten cubic centimeters or more should be obtained when possible. Have the patient expectorate directly into a small stone cup or sterilized salt-mouth bottle ; as soon as a sufficient quantity of sputum has been collected, the container should be at once sealed with adhesive plaster or tightly corked, and labeled. When ready for examination, the sputum should be poured upon a piece of ordinary window glass with the under side painted black, or a Petri dish placed over a blackened surface. Upon this black surface the small, white, opaque portions, which are best for examination, can be readily seen, removed by forceps or platinum hook, and placed in the center of a glass slide. A cover-glass is laid on the specimen, and slight pressure made to obtain a uniform layer. White blood-corpuscles are found in all sputum. ; Bie, Sp Sava nous Red Blood-corpuscles—Their presence in open found in sputum small numbers is not significant. In pneu- and in urine. In the 7 7 former it is from the monia they occur as pale, discoid bodies, and miu AF pens in hemoptysis the sputum may consist almost _ from the vagina. entirely of red corpuscles. Epithelium.—Squamous, from the mouth. Ciliated, usually from the trachea and bronchi. Alveolar, from the alveoli of the lungs. Elastic Fibers.—When these fibers display an alveolar arrange- 131 132 TECHNIC, ment, they have been derived from the pulmonary alveoli, and indicate a destruction of lung tissue. They occur in tuberculosis and bronchiectasis, and occasion- ally in pulmonary abscess and pneumonia. The slide of sputum is prepared in the usual way, and examined with a 4-inch objec- tive. The elastic fibers exhibit a double contour, are dark colored, Fic, 118.—CURSCHMANN’S SPIRALS.—(Schmaus.) wu. X 80 diameters. 54. X 300 diameters. slightly curved, and vary much in length and breadth. They can be most readily collected for demonstration by rapid sedi- mentation in a centrifuge. Curschmann’s spirals are found in sputum of asthmatic pa- tients, and appear as thick white bodies having a twisted tubular form. When examined with a low power, they show a central, TECHNIC OF SPUTUM EXAMINATION. 133 highly refracting, twisting thread, around which is a meshwork of delicate fibers. They require no stain. Fibrinous casts are tree-like casts of the terminal bronchial tubes, found in bronchitis and pneumonia, and composed of fibrin or mucin containing entangled cellular elements. (See Fibrinous Inflammations of Mucous Membranes.) Charcot-Leyden Crystals—These crystals are colorless, havea Fic. 119.—CHARCOT-LEYDEN CRYSTALS.—(Landois.) pointed octahedral form, and are found chiefly in the semi-solid, grayish-yellow pellets discharged during an asthmatic attack. Tubercle Bacillus.—(For technic of examination see article on Bacteriology.) Bacillus of leprosy occasionally occurs in sputum. (For technic of examination see article on Bacteriology.) Pneumobacillus, Pneumococcus (Friedlander, Frankel).—(For technic of demonstration see article on Bacteriology.) PART Il. GENERAL PATHOLOGY. 135 PART IIl.—GENERAL PATHOLOGY. CHAPTER I. General pathology comprehends those variations in struc- ture and function that may attack any organ. It is the study of morbid processes independent of their location, while special pathology is the study of diseases of organs independent of the same disease occurring elsewhere than in the organ under con- sideration. By development, pathologically, we mean the growth of tissues into organs—the proliferation or production by arrange- ment or otherwise of a tissue not identical with that from which the original cells arose ; thus, in the development of the fetus, certain cells give rise to different organs—the alimentary canal, including the pancreas and the liver, arises from cellular ele- ments that are identical. These organs are not produced by mere growth, but are dependent upon the process of develop- ment. Growth is the increase in size of an organ by proliferation of its normal cellular units; theoretically, with a single liver lobule a whole liver could be produced by the mere process of growth. Our knowledge of the normal is obtained by studying healthy individuals or organs not manifesting disease, and considering as normal that condition which is commonest. Any deviation from the normal must come under one of three heads —malpost- tion, malformation, or disease. 1. Malposition is the misplacement of an organ from that position in which it is most commonly found, or any alteration of its relation to other organs. The heart may be rotated on its axis and not occupy the normal relation to the surrounding tissue, and still the heart may be in place; so that malposition implies either that the organ is not in place, or that, being in place, its parts do not bear their normal relation to surrounding structures themselves normally placed. 137 138 GENERAL PATHOLOGY. Malpositions may be congenital or they may be acquired. Congenital forms are by no means always permanent, although they usually are. The acquired forms are less likely to be so, although, if they persist, such changes may occur as to render them incapable of resuming normal positions and relations. Hernia may be congenital or acquired, and in either case may become perma- nent through adhesions, inflammation, etc. The heart may be pushed to the right side by a left-sided hydrothorax, and return to its normal position with the subsidence of its causative lesion. If the heart be transposed with other viscera during intra-uterine life, the position assumed becomes permanent, although the organ may be in nowise diseased. 2. Malformation is a deviation in structure or in develop- ment from that which is most commonly found. A malformed organ may not be a diseased organ, so that malformation, like malposition, is not of necessity disease; as to whether it was brought about by previous disease or not is a question that can not always be determined; so that a malformation may be the result of maldevelopment,—congenital malformation,— or it may be acquired as the result of disease; in the same way acquired malpositions may occur. °o "Sy Maximum, 38° C. Minimum, 25° C. Gonococcus.— (Cop- aR a , lin and Bevan.) X 800 Aerobiosis.— Aerobic. diameters. Reproduction.—Binary division. Pathogenesis.—Produces gonorrheal inflammation when inocu- lated upon mucous membranes ; has been found in the joints in gonorrheal rheumatism and in the heart-valve in ulcerative endo- carditis secondary to gonorrhea. Demonstration.—Make spread of the discharge on cover-slip ; dry and fix. Stain with saturated alcoholic solution of methylene-blue for from five to fifteen minutes; wash with water, and then stain with saturated alcoholic solution of eosin for the same length of time. Wash in water, dry, and mount. The nucleus of pus- corpuscles, as well as the gonococci, will be stained blue, while the protoplasm of pus-cells is stained pink with eosin. Does not stain by Gram’s method. Trachomcoccus or micrococcus of trachoma (Sattler, 1885). Place Found.—Conjunctiva, follicles, and inclosed follicles of trachoma. Variety of Coccus.—Roll-shaped diplococcus. 168 GENERAL PATHOLOGY. Motility —Nonmotile. Growth.—May be cultivated upon gelatin, agar, blood-serum, and potato. Formsa shining, light gray film along the stab, or small globular colonies develop along the streak. Does not liquefy gelatin. Temperature.—Optimum, 36° C. Acrobiosis.—Acrobic. Reproduction.—Binary division. Pathogenesis.—Pathogenic only in man. Inoculation in the conjunctiva followed by the development of typical trachoma. Stains with gentian-violet, methylene-blue, and carbolfuchsin ; also other anilin dyes. Stain from five to ten minutes ; wash in water, dry in air, and mount. Stains also by Gram’s method. Diplococcus Pneumonia (A. Frankel, 1884). Place Found.—In the sputum of those suffering from croupous pneumonia, severe cases of empyema, and occasionally in the exudate of cerebrospinal meningitis. Variety of Coccus.—Diplococcus, lance-shaped. Usually asso- ciated in pairs, end to end. Five or six may be arranged in the form of a short chain. In the exudates oP from the body they are found in capsules, ; which disappear when cultivated upon arti- ficial media. @ Go a) Motility.—Nonmotile. Growth—Develops slowly and with dif- Fig. 131—Dracram oF ficulty upon, and does not liquefy, gelatin. preumonta, Ittus- Usually forms small discrete colonies with TRATING RELATION OF Carsute To THE Con- Sharply defined edges and of a whitish TAINED GERM.— (Cof- : toe : linand Bevan.) color. Upon agar delicate, shining, semi- transparent colonies, which are almost in- visible. Upon blood-serum a delicate, transparent, moist film. Nonliquefying. Temperature—Optimum, 35° C. Maximum, 42° C. Mini- mum, 24° C. o \ come manifest in from twenty-four to twenty- . Fic. 136.—BACILLUS OF eight hours. The color and general appearance SYMPTOMATIC are much the same as shown in plates. Con- Gee Bevan) 3a siderable gas, having an acid, penetrating odor, PPHeS is developed. The gelatin is liquefied. Temperature —Optimum, 37° to 40° C. Minimum, 13° C Maximum, 70° C. Aerobtosis.—Strict anaerobe, Reproduction.—Spores and fission. BACTERIA AS CAUSES OF DISEASE. 177 Pathogenesis—The specific cause of symptomatic anthrax (black-leg or quarter evil); known to the French as ‘“charbon symptomatique,’”’ and to the Germans as ‘“ Rauschbrand..:’ Guinea-pigs very susceptible. Cattle, sheep, and goats sus- ceptible. Cats, dogs, pigs, rabbits, pigeons, chickens, and ducks immune. Stains with the usual anilin dyes, but only partly by Gram’s method, requiring prolonged staining and not bearing differentia- tion well. (For spore staining see p. 96. Bacillus Pneumoniz (Friedlander; Friedlander’s pneumo- coccus, or, more correctly, pneumobacillus). Place Found.—In lungs affected with croupous pneumonia. Form and Arrangement.—Oval and short, thick rods. The oval organisms are often in pairs, with their ends in juxtaposi- tion. When obtained from the lungs, usually incased in cap- sules, which are lost during cultivation. Motility —Nonmotile. Growth.—Grows well upon gelatin, agar, blood-serum, and potato. On gelatin and agar in about twenty-four hours a slight grayish growth becomes visible along the inoculation streak, which later widens and produces the nail-head appear- ance on the surface. The gelatin becomes brownish, but is not liquefied. In a few days the growth takes on a peculiar glaze. Gas is formed. Temperature.—Optimum, 37° C. Minimum, 14° C. Maxi- mum, 40° C. Thermal death-point, 56° C. Aerobiosis.—Aerobe. Reproduction.—Fission. Spore formation doubtful. Pathogenesis —May occasion a croupous inflammation in man. Mice, guinea-pigs, and dogs susceptible. Stains with the usual anilin dyes, but not by Gram’s method. Friedlander's direction for staining the capsule (spreads, prop- erly fixed, or sections): (1) Stain in the following solution for twenty-four hours ° Saturated alcoholic solution of gentian-violet, 50 parts. Distilled water, : arae Peace 100 “* Acetic acid, . 3 7 i 2% Io‘ (2) wash one or two minutes in one per cent. aqueous solution of acetic acid; (3) dehydrate in alcohol ; (4) clear in cedar oil ; (5) mount in xylol balsam. Bacillus Pyogenes Feetidus (Passet). Place Found.—In fetid suppurative processes. Form and Arrangement.—Short rods with rounded ends, I2 178 GENERAL PATHOLOGY. singly and in short chains. Length, 1.45 y, and approximately 0.5 # in breadth. Motility —Motile. Growth.—Grows profusely upon gelatin, agar, blood-serum, potato, and bouillon. In twenty-four hours a light gray streak becomes visible along the line of inoculation, whence it spreads over the surface of the culture medium. Gradually the growth assumes a brown hue, becomes thicker, opaque, and shining. Produces an exceedingly malodorous gas. Gelatin not liquefied. Growth very rapid. Temperature.—Optimum, 30° to 37° C. Aerobtosis.—Aerobe. Reproduction.—Spores and fission. Pathogenesis —Pyogenic. Rapidly fatal to mice and guinea- pigs. Stains with usual anilin dyes and by Gram’s method. Bacillus Pyocyaneus (Gessard). Place Found.—In green pus. Form and Arrangement.—Short, delicate rods, 1.5 # in length and 0.5 y in breadth. Motility. —Motile. Growth.—Grows upon gelatin, agar, potatoes, and milk. On solid media a transparent film develops over the surface in about twenty-four hours. Later, it becomes a light gray or greenish color. The medium gradually becomes fluorescent. Gelatin is liquefied. Growth rapid. Temperature —Optimum, 26° to 37° C. Aerobiosis.—Aerobe. Reproduction.—Fission. Pathogenesis.—Pyogenic, producing green pus; it is also capa- ble of producing septicemia. As a result of abundant growth in the intestine, particularly of children, it is believed that it produces a special form of in- Say toxication. Fatal to guinea-pigs. Stains with usual anilin dyes and by Gram’s we method. wW Bacillus of Rhinoscleroma (von Frisch). Place Found.—Tissue from the nose of per- Fic, 137 Spacttus OF son suffering from rhinoscleroma. X 1400 diameters. Form and Arrangement.—Short rods with rounded ends and oval elements. Found singly, in pairs, and in short chains. Commonly about 1.5 yu long and 0.5 » broad. Motility.—Nonmotile. ¢ t BACTERIA AS CAUSES OF DISEASE. 179 Growth,—Grows upon gelatin, agar, blood-serum, and potato. In tube culture growth becomes visible in from twelve to twenty- four hours: first, as a milk-white film along the inoculation streak ; later, spreads over surface of culture medium. Does not liquefy gelatin. Grows rapidly. Lemperature.—Optimum, 36° to 38° C. Aerobtosis.—Facultative anaerobe. Reproduction.—Fission. Spore formation doubtful. Pathogenesis.—Specific cause of rhinoscleroma. Injected sub- cutaneously in mice, guinea-pigs, and rabbits, produces inflam- mation, suppuration, and death. Stains with usual anilin dyes and by Gram’s method. Bacillus Mallei (Loffler and Schultz). Place Found.—In the nasal secretions and the nodules of glanders and farcy. Form and Arrangement.—Rods 2 p to 5 # long and 0.5 pz to 1.4 # broad. Motihty.—Motile. Growth.—Grows well on all the common culture media, but especially so upon glycerin-agar. Develops as a pale, white, moist, transparent film along the track of inoculation. Frequently such cultures show ry transverse striations. Does not liquefy gela- Se tin. Old cultures on potato show a peculiar "4 inf . ¥ Le . ” reddish-brown (chocolate or ‘ café-au-lait ) Geecieoeuwrcene color, with discoloration on the surface of the MALLEL.— (Cop- - lin and Bevan.) X mediurn. 800 diameters. Temperature.—Optimum, 37° C. On gly- cerin-agar grows at room-temperature. Maximum, 42° C. Minimum, 25° C. Thermal death-point, 85° C. Aerobiosis.—Facultative anaerobe. Reproduction.—Fission and spore formation. Pathogenesis —Specific cause of glanders. Man, horses, rab- bits, guinea-pigs, and field-mice susceptible. Stains —Requires prolonged staining with the usual anilin dyes and bears washing poorly; is not stained by Gram’s method. Usually stains irregularly. Demonstration —Place a small piece of infected tissue or a minute quantity of the culture in the peritoneal cavity of a male guinea-pig. Within from twenty-four to forty-eight hours tes- ticular swelling will appear, which may be followed by abscess ormation ; later, the animal may develop inflammation of the nasal mucosa; swelling of the joints and characteristic nodules may be found in the viscera. The swelling of the testicle is 180 GENERAL PATHOLOGY. sufficient for preliminary diagnosis. The diagnosis of glanders may be made by the use of mallein, which is prepared in the same way as tuberculin. (See Tuberculin. ) In healthy animals mallein induces no fever and but slight local disturbance, which quickly subsides. In the glandered animal it produces a ‘sudden rise of temperature (1.5° to 2.5° C.), notable prostration, and a local swelling, which does not subside for a week or more. Bacillus Tuberculosis (Koch). Place Found.—In tubercular products and processes. Form and Arrangement.—Rods slightly curved or bent, ends rounded. Length, 1.5 » to 3.5 4; breadth, 0.25 yp. Motihty.—Nonmotile. Growth.—May be cultivated upon blood-serum and glycerin- agar. Upon blood-serum small, transparent, light gray colonies first develop along the inoculation streak. Later, they become FIG, 139.—BaAcILLus TuBERCULOSIS.—(Von Jaksch.) XX 800 diameters. confluent, forming a grayish-white growth. Upon glycerin-agar small white colonies first develop ; then, after a few days, coal- escing, they form a uniform yellowish-white layer, which is wrinkled or scale-like—the so-called ‘ bread-crumb” appear- ance. The growth develops very slowly, requiring from two to three weeks to make its appearance on blood-serum, and from one to two weeks on glycerin-agar. Temperature.—Optimum, 37.5° C. Minimum, 30° C. Maxi- mum, 42°C. Aerobiosis.—Aerobe. Reproduction,—Fission. Spore formation probable, though involved in doubt. Stain.—Requires prolonged staining, but bears differentiation well. Stains with the usual anilin dyes and by Gram’s method. (See demonstratign below. Demonstration (sputum). —Search is made for yellowish, opaque, BACTERIA AS CAUSES OF DISEASE. 181 round particles, and, when found, a spread is made on a thin cover-glass by means of a platinum needle. The film of sputum thus obtained is allowed to dry in air or is held high over a flame until dry. To coagulate the albumin and to fix the specimen, it is passed through a flame three times. It is then covered with carbolfuchsin solution and heated for three minutes over an alco- hol lamp or some distance above a Bunsen burner, not allowing the stain to boil or to become dry. Wash in water and apply a few drops of acid methylene-blue (Gabbett’s counterstain) for three minutes, or until all red color has disappeared. Wash in water and mount in water, or dry and mount in balsam, and ex- amine with a 4-inch objective, followed by 34-inch oil-immersion lens. The tuber cle bacilli appear as short red rods, while the ground, cellular elements and other bacteria are stained blue. When a hurried diagnosis is not required, the cover-glass spread may lie in carbolfuchsin for twelve hours, without heating, and be counterstained as just described. Specimens prepared in this way retain their color much longer, and when the organisms are not found by the rapid method, the slow stain should be tried. Gabbett’s Acid Methylene-blue (counterstain) : Methylene-blue, . . 2 parts. Twenty-five per cent. aqueous “solution of sulphuric acid, By ee aE - . Too * Ziehl-Neelsen Method for Staining Tubercle Bacih in Tissues.— Stain the section for fifteen minutes in carbolfuchsin, which should be heated ; decolorize in a twenty-five per cent. aqueous solution of nitric or sulphuric acid; wash in sixty per cent. alcohol ; for contrast, stain with methylene-blue; wash and dehydrate with alcohol. Clear with oil of cloves and mount in balsam. The tubercle bacilli will be stained red, and the tissues blue. For the demonstration of the tubercle bacillus in the urine the specimen should be treated as already described on page 118. The sediment so obtained is spread upon cover-glasses, and treated as previously described for sputum. A large number of covers snould be examined, as the number of organisms present is often small. The smegma bacillus is less resistant to acids and is decolorized by prolonged washing in absolute alcohol ; in films differentiation from the tubercle bacillus is difficult. Inoculations on animals may be necessary, and, even after inoc- ulation tuberculoid nodules may be produced that can be differ- entiated from true tubercles only with difficulty. Animals suffering with pseudotuberculosis do not react to tuberculin, and cultures obtained from the tuberculoid nodules 182 GENERAL PATHOLOGY. differ materially from the growths produced by the tubercle bacillus. The demonstration of the tubercle bacillus in milk, butter, etc., is attended with the same difficulties noted when considering urine. Bacillus Tuberculosis Gallinarum (Bacillus of Avian Tuberculosis ).—The bacillus of bird tuberculosis stains like the ordinary tubercle bacillus, but grows more readily at a lower temperature on the same media. It may be readily cul- tivated at a temperature of 43% C. The growth is moist and soft, not dry and crumbly. Dogs can not be infected, while comparatively large doses of the bovine organism may render them tuberculous. Recently it has been claimed that the bacil- lus of bovine tuberculosis may be converted into the bacillus of avian tuberculosis by placing bouillon growths of the organism in sterile collodion capsules and permitting these to remain for a variable length of time, usually months, in the abdominal cavity of a fowl. Cultures made from capsules so treated can not be differentiated from the bacillus of avian tuberculosis. The bacillus of fish tuberculosis grows at a comparatively low temperature, 23° to 25° C., and not at 39° C. Tuberculin.—The diagnosis of tuberculosis in animals is usually made by the injection of tuberculin, which produces, in tuberculous animals, rapid elevation of temperature lasting a few hours ; this temperature reaction is associated with the formation of an inflammatory zone around the tuberculous areas. Tuber- culin is prepared by growing the tubercle bacillus in large flasks containing glycerin bouillon for about six weeks, or until an abun- dant, thick, folded pellicle forms on the surface of the medium. The culture is then steamed for one hour, ° \ ay filtered through a Pasteur filter, and, if necessary, concentrated by evaporation \ ne over a water-bath. The dose depends # upon the toxicity of the preparation and of] a F fo is determined by experiment upon ani- | mals. No reaction should occur in non- Fic. 140.—D1aGram Itius- tuberculous animals. TRATING THE FORMS OF BACILLUS | TETANI.— Bacillus Tetani (Nicolaier, Kitasato). oplin an evan. a 2 a. Spool shape. 2, Chain ‘ Place Found.—Earth. In the discharge orm. c¢. Clubbed bacilli, i Whi eee ae tom wounds of persons having tetanus. d. Club without spore. e. Form and Arrangement. — Straight, Spindle form with spore a a incenter. f.Freespores. Slender rods with rounded ends ; irregu- lar and involution forms occur. Motility—Motile, except when spore bearing. Growth.—Grows upon blood-serum, agar, gelatin, and bouil- BACTERIA AS CAUSES OF DISEASE. 183 lon. The most favorable medium is nutrient gelatin having a slight alkaline reaction and containing one per cent. of grape- sugar. The growth becomes visible at the end of three or four days. In gelatin stick cultures, colonies first make their appear- ance along the puncture below the surface. They usually coal- esce, and form a branching or radiate growth. Gelatin is lique- fied ; a small amount of gas is generated. Does not form acid. Temperature —Optimum, 36° to 38° C. Minimum, 14° C. Maximum, about 42° C. Thermal death-point of spores, 100° C. Aerobiosis.—Anaerobe and, after long cultivation, facultative aerobe. Reproduction.—Fission and spore formation. Pathogenesis.—The specific cause of tetanus. Man and many of the lower animals susceptible, especially guinea-pigs and rabbits. Stains with usual anilin dyes and by Gram’s method. (Stain for spores as described upon p. 96.) Demonstration.—Make anaerobic cultures ; after full develop- ment subject cultures to steam (80° C.) for one hour ; this treat- ment usually destroys the associated bacteria. The presence of “ drumstick”’ organisms in cultures is quite significant. Bacillus Typhosus (Eberth, Gaffky). Place Found.—Spleen and intestines of typhoid cadavers, feces, urine, and water. Form and Arrangement.—Straight rods with rounded ends, 1 # to 3 win length, 0.5 # to 0.8 win breadth. Found singly, in irregular groups, and in cultures, forming long filaments. Fic. 141.—BAcILLuS TyPHOSUS, SHOWING Fic. 142.—BACILLUS TypHosus.—( Coplin FLAGELLA.—(Gould.) X 1200 diameters. and Bevan.) X 800 diameters. Motility —Motile. Numerous lateral flagella. Growth.—Grows upon gelatin, potato gelatin, agar, potato, milk, and blood-serum. Upon agar the growth is quite rapid. It first becomes visible along the line of inoculation as a grayish- white, semitransparent film. Later on it takes a yellow or brownish cast. The growth on acid potato is significant ; at first it is invisible, but imparts to the potato a moist, shining appear- 184 GENERAL PATHOLOGY. ance by the development of a perfectly transparent film. The typhoid bacillus is nonliquefying. Temperature.—Optimum, 36° to 38° C. Will grow at room- temperature. Thermal death-point, 60° C. Aerobiosis.—Aerobe, facultative anaerobe. Reproduction.—Fission. Pathogenesis.—Specific cause of typhoid fever. Stains with usual anilin dyes, but not by Gram’s method. One of the most difficult differentiations that a bacteriologist may be called upon to make is between the bacillus typhosus and the bacillus colicommunis. The following is a modified and extended form of a table from Pearmain and Moor, presenting the points of difference between the bacillus typhosus and the bacillus coli communis : MEDIA AND TESTS. BACILLUS TYPHOSUS. BAcILLusS CoL1 COMMUNIS. Gelatin plates. The colonies on the surface form large grayish-white expan- sions with irregular edges, and after a time become somewhat yellowish- brown. The deep colonies are darker, with regular edges. Under a low power the colonies exhibit a characteristic woven structure. The gelatin is not liquefied. The colonies are round and oval, with smooth-rimmed mar- gins. The surface colonies form dirty-white expansions _ that, on magnification, exhibit a fur- rowed appearance. The col- onies later become dirty yellow- ish-brown in color. The gelatin is not liquefied. Gelatin culture, streak Produces a grayish-white ex- pansion with irregular edges. The growth has a tendency to keep to the inoculation streak, and often has a bluish iridescence. Dirty yellowish- white expan- sion, which spreads all over the surface of the medium, and often has a bluish iridescence when viewed by transmitted light. Gelatin shake \ culture. Agar streak culture. Potatoes. Broth. Beis broth : 7000). Milk. { | } No gas bubbles. Grayish-white expansion, which covers the surface of the medium. Generally a faint grayish-white growth; the growth varies, how- ever, on different potatoes. Turns faintly acid. No coagu- lation takes place. Rendered turbid, and gives no indol reaction. No growth. Copious formation, Dirty yellowish-white expan- sion, which spreads over the surface of the medium. Shmy yellowish growth. Curdled after one to three days. Rendered turbid, and gives a well-marked indol reaction after from twenty-four to forty-eight hours. Growth. BACTERIA AS CAUSES OF DISEASE. 185 MEDIA AND TESTS. BacILLus TypHosus, BAcILLUS CoLI CoMMUNIS. Elsner’s differ- entiating me- dium, * Growth rarely apparent under | forty-eight hours. Colonies small, finely granu- lar, shining, looking not unlike droplets of water. Growth in twenty-four hours. Colonies large, coarsely gran- ular, brownish, and growing more rapidly. Widal reaction. Positive reaction with blood- serum from a typhoid patient or an animal immunized against ty- phoid bacillus. No reaction in either case. Melted gelatin, in incubator. Uniform clouding. Flakes or flocculi throughout the tube. Indol. None produced. Present in bouillon cultures. Neutral-redagar. ¢ No fluorescence. Fluorescence may be present. Reaction not constant. Thermal death- point. 56°C. 60° C, Pyogenesis. Not pyogenic. Pyogenic. Bacillus of Influenza (Pfeiffer, Canon). Place Found.—In bronchial secretion and nasal mucus, and, although less commonly, in the blood of persons suffering from influenza. Form and Arrangement.— Small rods, 0.5 # to 0.8 w in length, and 0.2 # in breadth. Motility —Nonmotile. Growth.—Grows only on special media and requires frequent transplantation. (See demonstration.) Temperature.—Optimum, 36° to 38° C. Does not grow below 28° C. Thermal death-point, 60° C. Fic. 143.—BACILLUS OF INFLUENZA. X 1000 diameters. * Elsner’s differentiating medium : Selected potato, thoroughly cleaned, . Water, - 0.5 gm. 1.0 liter. Boil thoroughly, mashing the potato in order that the salts may be extracted and a part of the starch dissolved. Sufficient gelatin is added to render the medium solid: usually ten percent.; after solution, sodium hydroxid is added until the reaction is but Saintly acid, using litmus as the indicator; clarify, filter, and prepare as usual. To this medium one per cent. of iodid of potassium is added. The plates are made in the usual way. Original article, ‘‘ Zeitschr. f. Hyg.,’’ Bd. xxL, 1. ¢ To apply test, add four drops of concentrated aqueous solution of neutral red to 10 c.c. of liquefied agar and 0.5 c.c. of twenty-four-hour bouillon culture of bacillus typhosus. 186 GENERAL PATHOLOGY. Aerobiosis.—Aerobe. Reproduction.—Fission. Spore formation not observed. Pathogenesis.—Specific cause of influenza. Men, apes, and rabbits very susceptible. Stains with ordinary anilin dyes, but not by Gram’s method. Demonstration.—Smear the surface of agar slants or agar in Petri dishes with fresh sterile blood; inoculate surface with blood of influenza patient or nasal or bronchial mucus, which may be diluted with sterile water. The essential requisite to growth is blood, not blood-serum ; and any similar organism growing on usual media may be excluded. The developed colonies are small (they may require a lens for demonstration), moist, dew-like drops, which do not coalesce. Bacillus Pestis (Bacillus of Bubonic Plague). Place Found.—The organism is most abundant in the affected lymph-nodes, which, in advanced cases, are crowded with bacilli. It is also present in the spleen and is occasionally found in the blood of patients suffering from the disease. The stools also contain the organism. form and Arrangement.—Small spindle-shaped bacilli (2.3 » by 1.7 #4), arranged in sharply and repeatedly bent chains ; also long and short forms, with intermediate stages, and sometimes with rounded ends. In the glands polar staining sometimes creates an appearance resembling diplococci. Motility —Varies as to motility, but possesses flagella. Growth.—On agar forms moist, white growth; on potato, scanty growth. In bouillon the growth should not be disturbed, but placed on a perfectly steady shelf; twenty-four to forty- eight hours after inoculation flakes appear underneath the surface, forming small islands of growth (Haffkine). Produces indol. Does not liquefy gelatin and may show a tree-like growth resembling the anthrax bacillus. Does not coagulate milk. The best medium is an alkaline solution of peptone containing one or two per cent. gelatin. It causes acid formation. Temperature.—Optimum, 37° C. Thermal death-point, 76° C. for thirty minutes, or a much more brief exposure to 100° C. Aerobiosis—Aerobe and facultative anaerobe. Reproduction.—By fission. Pathogenesis.—Pathogenic in man, small laboratory animals, as rats, guinea-pigs, and rabbits ; pigeons are exempt. Stains with usual anilin dyes, but not by Gram’s method. Demonstration.—A drop of serum obtained by hypodermic puncture from one of the swollen lymphatic glands will usually show the organisms in abundance. In addition to the differen- BACTERIA AS CAUSES OF DISEASE. 187 tiating points already given, an inoculation made on agar contain- ing three per cent. of salt, and incubated at a temperature of 37° C., develops involution forms resembling yeasts. As this devel- opment takes place within twenty-four hours, it constitutes an important test. The ease with which rats may be infected and the characteristic glandular involvement of the lymph-nodes could be utilized to advantage. Bacillus Lacunatis (Morax-Axenfeld). Place Found.—Found in the diplobacillary conjunctivitis of man. form and Arrangement.—Rods about 2 » in lengthand 1 p in width, arranged in pairs placed end to end, and sometimes in short chains of from four to six elements. In cultures the or- ganism is pleomorphic, growing as short diplobacilli that can not be differentiated from diplococci, and also in chains such as pre- viously described. By the end of one week of cultivation many involution forms occur. Motility —The organism is nonmotile, and flagella have not been demonstrated. Growth.—When first removed from the eye, it can be success- fully grown only on serum or in media containing serum, and at a temperature approaching 37° C. In streak cultures on serum tubes a moist, shining growth occurs along the line of inocula- tion. The solidified serum is gradually liquefied, forming a fur- row, which at first extends in depth only, but later widens. Smear cultures develop as individual colonies, which pit the serum. After cultivation through a series of serum tubes the organism may, in some instances, be grown upon agar, where it then forms “translucent, discrete colonies, like dewdrops.”* In bouillon containing one-third serum a turbidity quickly develops, which is not lessened by the occurrence of a grayish- white precipitate on the sides and bottom of the tube. The organism requires frequent transplantation. Temperature.—Optimum temperature, 37° C.; does not grow below 30° C. or above 40° C. Thermal death-point, 56° C. Aerobiosis.—The organism is an obligate aerobe, and dies as a result of absence of oxygen. Reproduction.—By fission. Spore formation has not been demonstrated. Stain.—Stains slowly but clearly with the usual dyes. Stains best with an aqueous solution of Bleu de Roux. The reaction * For careful study of this organism see paper by J. W. Eyre, M. S., M. D., in the ‘* Journal of Pathology and Bacteriology,’’ vol. v1, No. 1, May, 1899. 188 GENERAL PATHOLOGY. of Gram’s method is peculiar, partial discoloration taking place ; the staining is never characteristically that of Gram’s method. This peculiarity is to be utilized in identifying the organism. Pathogenesis —Is not pathogenic in lower animals; on the human conjunctiva Morax, Axenfeld, and Eyre have produced characteristic inflammation of the conjunctiva. Demonstration.—Cover-glass smears are stained in the usual way and by Gram’s method ; the organism may be identified by points already mentioned. BACILLI NOT CULTIVATED OUTSIDE THE BODY. Bacillus Lepre. Place Found.—In leprous lesions. Form and Arrangement.—Rods resembling the tubercle bacil- lus. Usually, they are from 4 4 to 6 win length and 0.6 yw in breadth. Mothty.—Nonmotile. Growth.—Bordoni-Uffreduzzi has obtained growths of what he believes to be the lepra bacillus upon blood-serum containing peptone and glycerin. The India Leprosy Commission claims to have obtained cultures of the lepra bacillus upon blister-serum. As the organism culti- 4 cS 6 ye vated by Bordoni-Uffreduzzi greatly differs \ ye é from the lepra bacillus in leprous lesions in \ ( both size and shape, its specific character ie. aaseacnees oe Maybe doubted. Carasquilla, Spronck, FP ay ee and Campana also claim to have successfully diameters. © cultivated the bacillus lepre. From their ater pacmaiy’“@ — descriptions it would appear that the organ- Slightlycurvedforms. isms cultivated are dissimilar, and hence the claim of successful cultivation should await confirmatory demonstration before being fully accepted. The possibility, or, indeed, the probability, of successful cultivation must be admitted. Reproduction.—Fission, and possibly spore formation. Pathogenesis,—Specific cause of leprosy in man. Stains with usual anilin dyes and by Gram’s method. Like the tubercle bacillus, the bacillus leprz stains with difficulty, but, once stained, retains the stain, so that, as in tuberculosis, the differentiation from other organisms is largely effected by bleach- ing one stain out, as carbolfuchsin, and after-staining with a second stain, as methylene- blue, the bacillus of leprosy ; retaining the first stain and associated bacteria the other. BACTERIA AS CAUSES OF DISEASE. 189 Demonstration.—Bacillus leprae resembles the tubercle bacillus in many particulars, but may be differentiated by the absence of pathogenicity in lower animals and inability to cultivate it. Bacillus of Syphilis (Lustgarten). Flace Found.—Syphilitic secretions and lesions. form and Arrangement.—Straight and curved rods, 3 to 7 pt in length, and closely resembling the tubercle bacillus. Their outlines are irregular and their ends bulging. Reproduction.—Fission. Spore formation probable. d eat Pathogenesis.—Claimed by Lustgarten to La be the specific cause of syphilis. Fic. 145.— BACILLUS Growth.—Has not been successfully cul- oo ae tivated. Stain.—Tissues are stained as follows (Lustgarten’s method) : (1) Anilin-water gentian-violet (p. 94), twenty to twenty-four hours ;. (2) wash in alcohol, two or three minutes ; (3) aqueous solution potassium permanganate (1.5 per cent.), ten seconds ; (4) very dilute aqueous solution of sulphuric acid, two seconds ; (5) aqua destillata. Repeat the last three procedures until the section is colorless. Wash in alcohol, clear in oil of cloves, and mount. SPIRILLA CULTIVATED OUTSIDE THE BODY. Spirillum Proteus, Spirillum of Finkler-Prior. Place Found.—Intestinal canal and dejecta from patients with cholera nostras. form and Arrangement.—Curved rods from 0.6 p# to 2.5 # in length, 0.5 4 to 0.6 # in breadth; resembles the spirillum of Asiatic cholera, but the “commas” are longer and thicker and not so uniform in diameter, the central portion being thicker than the pointed ends. The spiral filaments are not numerous, and are usually short. Motility.—Motile ; possesses a single flagellum at one end. Growth.—Grows on agar, gelatin, blood-serum, potato, and bouillon. On agar a moist, thick, slimy layer is quickly devel- oped. On gelatin plates, at the end of twenty-four hours, small, white, punctiform colonies are seen, which cause a rapid lique- faction of the gelatin. In gelatin stick cultures the liquefaction progresses rapidly, at the end of forty-eight hours assuming the shape of an old stocking, and rapidly progressing to complete liquefaction. On blood-serum the growth is rapid, and causes liquefaction of the medium. On potato it produces a slimy, 190 GENERAL PATHOLOGY. grayish-yellow, glistening layer. _Coagulates milk. Does not {orm indol. Temperature.—Ordinary room-temperature. Aerobiosis.—Aerobe and facultative anaerobe. Reproduction.—By fission. F Pathogenesis.—Pathogenic for guinea-pigs when injected into the stomach by Koch’s method. Is not the specific cause of cholera nostras. Sfazus with usual anilin dyes. Spirillum Tyrogenum (Deneke). Place Found.—Old cheese. Form and Arrangement.—Curved rods and long, spiral fila- ments resembling spirilla of Asiatic cholera. The diameter of the commas is uniform throughout. The turns in the spiral filaments are longer and closer together, and the diameter of the curved segments is less than that of the cholera spirillum. Motility —Motile, possessing a single flagellum. Growth.—On agar, gelatin, potato, and bouillon. On agar thin, yellowish layer forms along the inoculation streak. On gela- tin plates small, yellow, puncti- form colonies are developed Fic. 146.—SPIRILLUM Tyrocenum.—(von that have a sharp outline, but Barend: Sera ete when liquefaction commences, the sharp outline disappears. In gelatin stick cultures liquefaction occurs along the whole line of puncture, the spirilla sink to the bottom as a coiled mass, while a thin, yellowish layer forms upon the surface. On potato a yellow layer is usually developed. Temperature.—Ordinary room-temperature. Aerobiosis.—Aerobe and facultative anaerobe. Reproduction.—By fission. Pathogenesis.—Pathogenic for guinea-pigs when injected into the stomach by Koch’s method.* Stains with usual anilin dyes. Spirillum of Asiatic Cholera (Comma Bacillus) (Koch). Place Found.—In the intestinal canal and feces in cholera. Form and Arrangement.—Short, comma-like elements ; also U and S forms and long, spiral filaments. VON LOE Ah Havre * The stomach is rendered alkaline by carbonate of potassium before the introduc- tion of the organism. BACTERIA AS CAUSES OF DISEASE. IgI Motility.—Motile. Commonly possesses a single terminal flagellum. Growth.—Grows upon gelatin, agar, blood-serum (which it liquefies), potato, and bouillon. The growth on gelatin is most characteristic. In gelatin plates the surface at first presents an appearance resembling that produced by sprinkling the medium nS with delicate glass splinters, an appearance $5 that is lost with beginning liquefaction. G5? The gelatin plate should be kept at 22° C.; in about twenty-four hours liquefaction be- mie Feat eo tee comes evident, and usually progresses so, po amtanagt ie that in a few days the entire plate is lique- the formation of come fied. Under the microscope the beginning fan ene an colonies are granular with irregular borders, pe eee and white or yellowish-white in color. In stab cultures the growth begins at the surface and proceeds along the line of puncture. Liquefaction begins at the surface and accompanies the growth along the course of the needle- track. The area of liquefaction presents a funnel-like appear- ance, and an_ air-bubble is ETE MAT RM ey WIM ately usually observed in the broad, WTO RalCo se LSS FAN WSS S 31S WIEN x UWA WON: x BoA RN SEI CECT expanding portion of the fun- MIELE AD Bebccany nel. Milk is not coagulated. of ks Vyas ee Temperature.—Optimum, 37° C. Minimum, 14° C. Maxi- mum, 42° C, Thermal death- point, 55° C. Aerobiosis.—Aerobe, faculta- we CF Wig Z4 fe IP palin eae ONG Wie Aires DO yg SUI tive anaerobe. Fic. 148.—SPIRILLUM OF ASIATIC CHOLERA. Reproduction.—Fission and —(von Jaksch.) X .0o diameters. spore formation (?) (arthro- spores). Pathogenesis. —Specific cause of Asiatic cholerain man. Asiatic cholera has been experimentally produced in guinea-pigs with this spirillum. Stains with usual anilin dyes, but not by Gram’s method. SPIRILLUM NOT CULTIVATED OUTSIDE THE BODY. Spirillum of Relapsing Fever (Obermeier). Place Found.—In the blood of relapsing fever patients during the fever paroxysms. Form and Arrangement.—Delicate, flexible, spiral, or wave-like 192 GENERAL PATHOLOGY. filaments, with pointed ends. Their length is from 16 y to 60 p, and their breadth about 0.1 4. The number of complete spirals in one organism may be from ten to fifteen. Motility —Very actively motile. Reproduction.—Fission. Pathogenesis.—Specific cause in man of relapsing fever. Monkeys are susceptible. Stains with usual anilin dyes, but not by Gram’s method. Demonstration.—The organisms are present in the blood in large numbers during the crisis. They are less abundant just before the occurrence of the crisis, and after it is past they disappear rapidly. They are not present in the peripheral circu- lation during the nonfebrile period. In order to demonstrate the presence of the organism in the blood, the finger or lobe of the ear is properly cleansed, disinfected, and pricked by a needle. (See Technic of Blood Sg Examination, chap. 1, part m1.) A drop of ce blood is received on a slightly warmed slide mA : : wri and a cover-glass is at once applied. As OY soon as the blood flows near the margin of the cover-glass a ring of oil or vaselin Fic. 149—Sririttum Should be painted around the cover-glass in CE nLAPSING FEVER order to prevent too rapid drying during the Meany Segeediane progress of the examination. As the organ- eters. ism possessed a transverse diameter approx- imately that of the cholera spirillum, it will be necessary to conduct the examination with high powers. The presence of spirilla is indicated by the agitation of the cor- puscular elements. At first the spirals may be too active to be readily focused upon, but in a short time they become sufficiently quiet to permit examination. Just before and during the crisis the number of spirilla may approach one organism for every twenty erythrocytes. After the disappearance from the peripheral cir- culation Metschnikoff has succeeded in demonstrating them in the splenic pulp. In moist films or in suspension in normal salt solution the motility may be evident for twelve hours or longer. The organism is evidently destroyed by a comparatively low temperature, a fact which has been taken to indicate the absence of spores. Dry films, prepared as described in the chapter on The Blood, may be stained as already directed for other bacteria. (See p- 93.) ANIMAL PARASITES. 193 ANIMAL PARASITES. Sporozoa, psorosperms (gregarinidia), are animal para- sites belonging to the protozoa. Coccidia are oval, ege- shaped organisms, the smallest measuring from 2.5 pL to 4 # in diameter, while the largest, fully developed cell may attain a long diameter of from 26 » to 28. The trans- verse diameter of the ovoid is usually a little more than half its length. During the development of the morbid pro- cesses with which coccidia are commonly associated the parasite is usually found within the epithelial cell. In the earlier stage of development the epithelial cell (for example, the tall, cylin- dric, epithelial cell of the bile-duct) remains zz stu ; later, it is thrown off and lies free in the cavity. During the intracellular development of the organism a vesicular structure resembling a nucleus is seen near the center of the parasite; by some this is believed to be the nucleus. There is a sugges- tion of a cuticular membrane. After rupture, the epithelial cell disappears by disintegration, and the contents of the cuticular membrane, or pseudo- capsule of the parasite, contracts into a spherule. The later stages of de- velopment are usually not observed < Js A ; Fic. 150.—CocciDIUM OVIFORME in the morbid processes with which So ae Home Lee = the organism is associated, but occur id ftenLevenart.- Gould.) as : A. X 200diameters. B,C. X 800 when the coccidia are exposed to a diameters. suitable temperature with a sufficient quantity of moisture. Under such conditions the spheric mass previously mentioned splits up into psorosperms, or spores, each sphere producing four of the new bodies. The spores, or psoro- sperms, or sporules, acquire a membranous envelop, inside of which the sporule assumes a form suggestive of a rod bent as a crescent—the so-called sickle-shaped sporule. Here the process of evolution is again arrested. Introduction into a suitable host is followed by the digestion of the cuticular membrane surrounding the sporule, after which the young parasite enters the epithelial cell of the intestine, bile-duct, or other structure, where the cycle of development is completed as already indicated. The demonstra- tion of the coccidium perforans as a distinct member of the group does not seem to be complete, so that the majority of observers are inclined to regard it as but one form of the coccidium oviforme. 13 194 GENERAL PATHOLOGY. In the lower animals a number of diseases are produced by members of this group; coccidial disease of the liver in rabbits affords an opportunity to study the coccidium oviforme, to which the disease is due. A similar cystic lesion occurs in the liver of man, the cysts containing coccidia. Qccasionally, the coccidial masses resemble tubercles, solid, fibrous, or caseous areas. While most common in the liver, the spleen, kidney, and ureter may be involved. Molluscum contagiosum, also known as contagious epithe- lioma, is a disease occurring in the skin, and showing, as its name indicates, a certain contagious element. It sometimes spreads from nurse to infant; families may show infection, and occasionally epidemics occur in hospital wards. The mollus- cum nodule rises rather abruptly from the skin, and may, in rare cases, be pedunculated ; it rarely reaches a transverse diameter of five millimeters, although it may be much larger. The surface is usually flat, or it may be slightly umbilicated, and, in most instances, contains a hair, more or less centrally placed. The center of the nodule contains caseous material, which can usually be readily expressed. The number of nodules varies: sometimes they are abundant, and in other instances compara- tively few are seen. They may occur anywhere on the cutaneous surface, but are more frequent on the back, face, and neck, and around the genital orifices and the anus. Properly fixed and stained sections show marked proliferation of the rete Malpighii, with degenerative changes resembling casea- tion. The smaller coccidial bodies are situated in the third or fourth row of epithelial cells, counting from the corium outward. They are first noted within the epithelial cells ; later, by enlarge- ment, they displace the nucleus and eventually become more conspicuous than the epithelial cell. That they are the specific cause of the disease is questioned. Their constant presence, however, and the fact that no other satisfactory explanation of the morbid process has been forthcoming, have led many observ- ers to regard them as the etiologic factor. The alleged coccidial origin of carcinoma will be referred to when considering the etiology of tumors. Cercomonas intestinalis, length 10 4 to 12 4, pear-shaped, with two terminal filaments, one of which is rigid, the other motile, by the action of which the parasite moves. In addition to the terminal filaments there are three tentacles on each side. The parasite is found in the stools during life and in the intestine postmortem. A diseased condition of the intestinal mucosa ANIMAL PARASITES. 195 seems necessary before this parasite will thrive in the intestine ; but when once present, it induces diarrhea. Closely resembling the preceding is the trichomonas intes- tinalis, which differs in having a disc anteriorly supplied with cilia. The ¢vchomonas vaginalis resembles the foregoing ; it is, however, smaller. Amebz belong to the rhizopodia. A number of forms have been described, the most important of which seems to be the amoeba coli, associated with dysentery and hepatic abscess. As seen in stools, amebe are oval in outline, 12 to 35 yw in diame- ter ; while living and in the fresh state, motile. The nucleus, when present, is round or ovoid ; the perinuclear protoplasm is granular, and often contains vacuoles and included blood-cells, pus-cells, bacteria, and granules. It would appear that prolifera- tion by direct division is possible, Harris having observed the process. Amebe have been found in the stools from dysentery, in the intestinal wall, in hepatic abscess secondary to dysentery, in the pus from abscess of the lower jaw, and in the urine in inflam- mation of the bladder. Demonstration.—A satisfactory demonstration of the parasite, particularly in the hands of the novice, demands that he should see it send out pseudopodia : he should observe active movement. In order to do this, it is necessary to have the material reasonably fresh. In the case of feces, admixture with urine is to be avoided. A drop of the suspected material is placed upon a slide and a cover-glass applied. The slide may be gently warmed, or the microscope may be kept in a reasonably warm place, under which conditions movement will be more active. Fresh speci- mens may be best stained by mixing with the suspected material, placed upon a slide, a drop of a watery solution of toluidin-blue. This reagent acts as a fixative and at the same time stains the amebe intensely and rapidly. Pieces of tissue are best fixed in corrosive sublimate, embedded in paraffin, and the sections stained in eosin, followed by toluidin-blue for twenty or thirty minutes ; wash and differentiate in alcohol, clear in cedar oil or xylol, mount in balsam.* Flukes.—Certain forms of these are common in sheep. In man they infest the alimentary canal, or wander into ducts or canals emptying into it. The liver flukes: distoma lanceolatum is 7 to 1omm. in length, 1.85 to 2.25 mm. wide ; the distoma hepati- * See remarks on the use of anilin dyes, p. 66; also toluidin-blue, p. 67; eosin with toluidin-blue, and differentiation of anilin dyes, pp. 67 and 68, 196 GENERAL PATHOLOGY. cum, 15 to 32 mm. in length, 8 to 20 mm. wide ; the distoma crassum, 5 cm. in length; and the forms apparently so abun- dant in Japan, the distoma endemicum and distoma pernicio- sum, infest the duodenum and jejunum or invade the bile pas- sages, producing cholangitis, jaundice, hepatic enlargement, and sometimes ascites. The irritation is not uncommonly associated with bacterial infection, which eventually proves fatal. A form of hematuria—endemic hematuria of Egypt—is due to the blood fluke, bilharzia heematobia (distoma hema- tobium). The female is from 15 to 20 mm. in length and 0.1 to 0.2 mm. in diameter, and inhabits the portal vein and the veins of the spleen, mesentery, kidney, and bladder. The eggs are oval, possessing a spicule, which may be located at one end Fic. 151.—DIsTOMA HEPATICUM. Fic. 152 —BILHARZIA HA:MATOBIA, MALE AND FEMALE, THE LATTER IN THE CAN- ALIS GYNECOPHORUS OF THE FORMER. —(After Leuckart.— Gould.) or at the side. They measure 0.12 mm. by 0.04 mm., and may be found in the liver, intestine, mesentery, and vascular plexus of the bladder, rectum, etc. Inflammations occur in the ureter and bladder, and also in the rectum ; the inflammatory exudates contain ova, and ova may also be found in the submucosa of the area involved. Ulcerations sometimes develop, followed by cicatrization, which may induce stricture or other deformity. There may be marked interference with nutrition, and, in addi- tion to the blood in the urine, chyluria may occur. Distoma ringeri, distoma pulmonale, or bronchial fluke, is the cause of the parasitic hemoptysis endemic in China and Japan. The parasite is ovoid, 8 mm. to 10 mm. long, 3 mm. to 6 mm. wide. The eggs are yellowish, thin-shelled, and from 0.08 mm. to 0.1 mm. long, by 0.05 mm. broad. The parasite ANIMAL PARASITES. 197 inhabits small cavities situated at the periphery of the lung and communicating with the bronchi. It has been found in the lungs of tigers. The sputum resembles that of tuberculosis, and the associated hemoptysis further complicates the diagnosis ; finding the eggs, or occasionally the parasite, readily clears up the diagnosis. Ascarides, or Round Worms.—tThe ascaris lumbricoidcs is a yellowish or yellowish-brown worm, varying in length: the female measures about 15 cm. to 30 cm.; the male, 9 cm. to 20cm. The wortn is striated transversely with four longitudinal bands. Round worms are most common in children, occupying the upper portion of the small intestine, from which they may wander into the bile-ducts, stomach, esophagus, nose, Eustachian tube, and larynx. The num- ber in any case varies ; rarely are they present in large num- bers. The ova are ellipsoid, 0.06 mm. in their longest di- ameter, with a dense envelop- ing membrane. FIG. 153.-—ASCARIS LUMBRICOIDES AND FIG. 154.—OXYURIS VERMICULARIS.—( Cop- Eaos.—( Coplin and Bevan.) lin and Bevan.) a. Female. 6. Male. Oxyuris vermicularis, ¢hreadworm or pinworim, inhabits the colon and rectum, occasionally in the female invading the vulva and vagina. The female parasite is from 8 mm. to 12 mm., and the male 3 mm. to 6 mm. in length. Eggs are 0.05 mm. long by 0.025 mm. thick, and possess a thin shell, which offers some protection to the contained embryo when subjected to the influ- \ 198 GENERAL PATHOLOGY. ence of drying. The parasite wanders from the anus and pro- vokes violent itching, which not uncommonly leads to the indi- vidual injuring the surrounding parts by active scratching, even lacerating the skin, thereby favoring bacterial infection and sub- sequent inflammatory disturbances. Trichina Spiralis.—Infection by this parasite occurs by in- gesting trichinous flesh. In the muscle the parasite, in the form of its embryo, will be seen as a coiled-up worm 0.05 mm. in length, surrounded by a capsule that at first is translucent, later becom- ing opaque, and eventually calcareous. If meat containing the embryo be eaten, the capsule is digested in the stomach, the em- bryo liberated, and its final development into the adult worm com- pleted in the small intestine. The fully developed female trichina measures 3 mm. to 5 mm., the male about half as much. The embryos liberated in the intestine wander into the mucosa, pene- trate the wall of the intestine, and become widely disseminated throughout the organism. The destination of the worm seems to be in the muscles; here it coils up, and is surrounded by a capsule partly produced by the reaction of the surrounding tissue. The changes that this capsule undergoes have already been noted. TZ7ichiniasis is the term applied to the symptoms and lesions observed at the time of dissemination of the embryo. It is estimated that from 1000 to 2000 embryos may be hatched by a single female trichina. The dissemination of these by the FIG. 155.—TRICHINA SPIRALIS. — (After route previously indicated may e ESTED Oo ... be associated with fever, mus- u. Encapsulated. 6. Same with calcific 7 capsule. cular pains, more or less edema, and even paralysis. A small percentage of the cases terminate fatally. A recent and important contribution to the diagnosis of trichiniasis is the discovery of the enormous increase of the eosinophile cells in the blood. Demonstration.—This may be accomplished by teasing the suspected muscle as follows: Clean a slide thoroughly and breathe upon its surface, thereby slightly moistening it; upon the moistened surface lay a fragment of the muscle to be examined ; with needles tear the fragment to pieces; * add a * This procedure is technically known as ‘‘ teasing’ the specimen. ANIMAL PARASITES. 199 drop of glycerin and a cover-glass; examine with a 14-inch or %-inch objective. In order to make the specimen permanent, wash out the glycerin with water, dehydrate with alcohol, clear in creasote or oil of cloves, apply balsam, and cover. The frag- ment of muscle may be obtained. by incision, using cocain as a local anesthetic, or it may be removed by a punch or harpoon. Anchylostoma duodenale, strongylus, or dochmius duode- nalis is associated with certain forms of anemia and Egyptian chlorosis. The male is about 8 mm. in length, with a distinct bursal enlargement at the tail end. The female is much the larger, measuring, not uncommonly, 18 mm. By a series of tooth-like hooks with which the mouth is provided the parasite attaches itself to the mucous membrane of the duodenum. Inflammation of the intestinal mucosa results, and, in some cases, this may assume a hemorrhagic form; profound anemia is one of the most con- stant associated phenomena. The profound disturbances of 5 ‘ 7 nutrition that mark the severe ""“mibs DuopeNatis, PROFILE AND-PRONT + oe View.—( After Leuckart.—Gould.) cases of anchylostomiasis are brought about .partly by the loss of blood induced through the wounding of the duodenum, partly by the associated inflammatory processes, which: may not be marked, and possibly, to a certain extent, by the absorption of metabolic products elaborated by the parasite. Infection occurs by drinking polluted water. In Egypt, Italy, Russia, and the South American States the inhabitants not uncommonly suffer, but in North America but little is known of the parasite. The recognition of the condition during life is often effected by finding the ova in the stools. The ova are about 0.05 mm. in diameter, egg-shaped, with a thin enveloping membrane. Filaria.—In the lower animals filaria are not uncommon, but in man only a few forms of the parasite have been identified with disease. The filaria sanguinis hominis, so constantly asso- ciated with chyluria, hematochyluria, lymph-scrotum, and a con- dition resembling elephantiasis, is probably the most important. The male is small, and is rarely found. The female is a thread- like worm, 4 cm. in length, and 0.25 cm. in diameter; the head is club-like ; about one millimeter behind the head is the opening of the vagina, which terminates in a bifid uterus, extending back- 200 GENERAL PATHOLOGY. ward almost the entire length of the parasite, and crowded with embryos in all stages of development. An alimentary canal runs the entire length of the parasite. The worm inhabits the lymphatics, into which it pours an enormous number of embryos. These are nearly 0.25 mm. in length, 7 # in thickness, about the diameter ofa red blood-cell, thus permitting their transfer from point to point in the circulation, to which they gain ingress through the lymphatics. Their presence in the peripheral blood is peculiar, in that it is cyclic, appearing only in the night or during sleeping-hours. In most cases they can not be found in the day, but in individuals who sleep during the day the parasites can then be found. Manson expresses the opinion that the nocturnal appearance of the parasite is due to the fact that it adapts its habits to those of the mosquito, which Fi. 157.—FILARIA EMBRYO.—( From F. P. Henry’s case.) The two embryos shown above were drawn from %-inch objective; the lower from %-inch objective. Red blood-cells are introduced for comparison. he regards as an intermediary host. At the autopsy of a sui- cide, at 8.30 a. M., the filaria were found in the vessels of the lung and myocardium, and but few in the liver, spleen, or kid- ney. If, at the appropriate time, a drop of blood be drawn and examined in the fresh condition, but little difficulty will be found in detecting the embryo parasite: the movements are rapid, and the enveloping membrane or shell is delicate, transparent, and so elastic that it in nowise impedes the movements of the embryo. The presence of the parasite is not suspected until blocking of some of the lymph-channels gives rise to one of the conditions previously mentioned. The parasite is often abundantly present in the blood of the inhabitants of the tropics and subtropics. The filaria medinensis, dracunculus medinensis, or guinea-worm, of which only the female is known, is about 60 ANIMAL PARASITES. 201 cm. to 90 cm. in length and 2 mm. in diameter, and is usually solitary, although not always so. The parasites—probably both male and female—enter with the food; only the female develops. It penetrates the mucosa and eventually reaches the subcutane- ous tissues, in which it completes its development. Harrington does not believe in the entrance of the parasite through the alimentary canal. He believes that it is introduced either in some embryonic form, as by the mosquito, or that in some other way it gains access to the subcutaneous tissues directly from without. In no other way can he explain the fact that over “seventy-five per cent. of the lesions occur in the lower extremi- ties, and the greater number below the knee. During the period in which the parasite is developing in the subcutaneous tissues it may be distinctly palpable ; finally suppuration ensues and the worm is cast off, with innumerable ova, which enter water, where, in the cyclops (?), further development occurs. The parasite has been observed in a patient, a native, and always a resident, of Philadelphia, but it is rare in this country. The suppurative and inflammatory lesions that follow the deposit of the parasite, and that continue during its discharge, form the anatomic basis of the morbid condition called dracontiasis. Among the other filaria occasionally observed in man are: jilaria bronchialis, found in the bronchi; flaria loa (3 cm.), found in the conjunctiva ; filaria hominis oris, in the mouth ; etc. Our knowledge of the evolution of filaria outside of the body is Still incomplete. Exactly what animal constitutes the inter- mediary host, if such a host is necessary, has not been conclu- sively established. The present tendency is to believe that some member of the mosquito family may act as intermediary host, either depositing the altered parasite in drinking-water or directly inoculating in a way analogous to that observed in malaria. Trichocephalus dispar, or whip-worm ; the female measures about five centimeters; the male is shorter. The anterior two- thirds of the body is thread-like; the remainder is conic, and in the male is rolled like a spring. The eggs are oval, 0.05 mm. long, with thick shell, which, at each end, possesses a knob-like protuberance. The parasite inhabits the colon, particularly the cecum, and may invade the small intestine and the vermiform appendix. Tapeworms, or Cestodes.—Of these, four only are of suffi- cient interest to merit description : 1. Tzenia mediocanellata or saginata, or beef tapeworm. The head is quadrate, 1.5 mm. to 2.25 mm., surmounted by four suckers arranged in a quadrangular outline, in the center of 202 GENERAL PATHOLOGY. which is a fifth rudimentary sucker or flattened groove ; the head is void of hooklets, hence the worm is known as the “un- armed tapeworm.” The head is attached to a slender neck, varying in length and terminating in the first link, proglottis, zooid, or segment—terms used synonymously. The segments when fully developed are between 8 mm. and 10 mm. broad and about 18 mm. long, and thicker than the proglottides of the tenia solium; like all tapeworms, each segment is hermaphro- ditic. The genital pores are placed laterally; the uterus shows dichotomous branching more characteristically than the tenia solium; the number of branches varies, but is ap- proximately about fifteen; the Fic. 158.—T4NIA SAGINATA.—(Gould.) FIG. 159.—CEPHALIC END OF TENIA SAGINATA. A. Retracted head. B. Extended head. segments are commonly thrown off spontaneously, while the tenia solium rarely sheds a single proglottis. The length of the worm varies greatly; the number of segments may exceed 1000, and the entire worm may measure between four meters and ten meters. The ova constantly appear in the stools, and the segments show the uterus distended with them. Each ovum is 0.03 mm. in its long axis, is ovoid, or egg-shaped, with a striated outer membrane and a thick shell. The eggs and segments thrown off in the feces are ingested by the ox ; the larva or juvenile parasite is liberated, and reaches the muscles, ANIMAL PARASITES, 203 for the most part, although it has been observed in the heart, lungs, and liver. At the point of deposit there develops a cyst, varying in size from 2 mm. to 2 cm. in diameter, whitish in color, and oval in outline. In this is the larval worm; the cyst wall is of connective tissue. In this stage the parasite is known as cysticercus saginata, Beef rarely contains many such cysts, and their small size not uncommonly causes them to be overlooked. Beef containing the cysts is said to show “measles.” It is not known that man suffers from cysticercus saginata. 2. Tzenia solium, also known as the pork tapeworm, soli- tary tapeworm, and armed tapeworm. The name tenia solium, or solitary tapeworm, is not appropriate, as the pork tapeworm is more commonly multiple than the beef tapeworm ; Fic. 160.—HEAD OF TANIA SOLIUM. ON Fic. 161 —CYSTICERCUS CELLULOS©. Com- THE RIGHT, EGG oF TANIA SOLIUM.— PLETION OF HEAD FORMATION.—(A/ter (Gould.) Leuckart. — Coplin and Bevan.) X12 diameters. indeed, Leidy regarded the latter as rarely multiple. The adult parasite is a soft, white, band-like worm, rarely over four meters in length. The head is round, 0.5 mm. to I mm. in diameter ; there are four discoid or cup-like suckers and a centrally placed papilla, proboscis, snout, or rostellum, surmounted by two rows of hooklets, each row having from twelve to fourteen hooklets ; the hooklets of the inner row are the larger. The neck is very thin, about 2.5 cm. in length, terminating in the gradually developing segment. The segments are from 10 mm. to 12mm. long, and from 6 to 8 mm. broad. The proglottides differ in this respect from those of the beef tapeworm ; the segments nearer the head may be much broader than long. The uterus is broader, coarser, and the median tube larger, with fewer branches—six to ten, but little over half the number commonly séen in the beef tapeworm. The eggs are about the same size as those of the beef tapeworm, 0.03 mm., but more spheroid. 204 GENERAL PATHOLOGY. The scolex, larval, juvenile, or cysticercus form of the tzenia solium has long been known, but Kiichenmeister, by feed- ing experiments, demonstrated that the so-called cysticercus cellulose is but the larval form of the tenia solium. The larve are most frequently developed in the hog, gaining ingress as already described when considering the similar stage in the beef tapeworm. The habits of the hog, however, render measles much more common in that animal than in the ox. Either by the accidental contamination of the hands and subsequent ingestion Fic. 163.—FREF-SWIMMING EMBRYO OF THE BoTHRIOCEPHALUS LatTus.— (After Leuckart.—Gould.) Fic. 164.—C1-UB-SHAPED HEAD OF THE BOTH- RIOCEPHALUS LatTus.—(A/ter Leuckart. —Gould.) Fic. 162.— BOTHRIOCEPHALUS LATUS.— A. Seen from the edge. B. Seen from flat (After Leuckart.— Gould.) surface. of the ova, or possibly by regurgitation during vomiting, occasion- ally the ova reach the human stomach ; as in the beef larva in the ox, the liberated larve of the solium in man may become widely disseminated. Cysticercosis in the insane is usually the result of coprophagy. When the parasite lodges, a cyst follows, and whether in man or the hog, a ‘‘ measle”’ results. The cyst formed is much larger, as a rule, than in the ox, and may attain the size of 20 mm., the beef measle rarely exceeding 7 mm. While the beef measle is unknown in man, this form is not infrequent. ANIMAL PARASITES. 205 The method of invasion is probably the same from both cysticerci ; both the embryos, when liberated in the stomach, have six hook- lets, arranged in pairs, by which they tear and propel their pas- sage through the wall of the stomach or intestine. 3. Teenia lata, broad tapeworm, or, more correctly named, as it belongs to another genus, bothriocephalus latus. The head is clavate, rather elongated, has a long elliptic sucker on each side, measures about 1.5 mm. long by I mm. wide, and is without either rostellum or hooklets. The fully developed joints are from two to four times as broad as long; the breadth of the link may reach 1.8 cm. The genital aperture is always on the one side, the ventral aspect, and is central. The eggs are brownish, oval, 0.07 mm. in length, and the shell is fur- nished with a lid or operculum, Fic. 165.—T4NIA FLAVOPUNCTATA. Fic. 166.—T@nia Ecutnococcus.— (After Leuckart.—Coplin and Bevan.) a, Adult parasite. 54. Head of echinococcus veterinorum. On the left, a detached hooklet, as seen in fluid from cyst. through which the embryo escapes after some months in water. Braun has observed scolices, believed to be of the bothrioceph- alus, in pike and trout, and by feeding the fish to dogs has led to the development of the tapeworm in the dog. The fully devel- oped worm is said to be the longest of tapeworms. 4. Teenia flavopunctata is a short tapeworm, not exceeding 40 cm. in length. The segments vary in length from 0.2 mm. at the neck to 0.5 mm. when fully developed, and in breadth from 0.6 mm. to 2.5 mm. at the same points. A peculiarity of the segments is the alternation of fertile with sterile segments, the former so laden with eggs as to obscure its interior and being 206 GENERAL PATHOLOGY. much larger than the nonova-bearing links. The eggs are spheroid, brownish in color, with a diameter of 0.07. mm. Nothing is known of the larval stage of the parasite. Tzenia Echinococcus, or Dog Tapeworm.—The sexually mature worm inhabits the intestine of the dog and wolf. It is an insignificant parasite in appearance when compared with the larger forms, rarely attaining a length of five millimeters. When fully developed, there are five segments; the anterior is slender and is continuous with the head; the following segment is the Fic. 167.—HYDATID Cyst, SHOWING DAUGHTER Cysts. In the lower part of the figure is a whitish mass containing parts of the walls of ruptured daughter cysts. The thick wall of the mother cyst 1s well shown. (Removed by Dr. H R. Loux from the liver of a man aged twenty-seven years. The illustration is two-thirds the natural size. Weight,197 gm. The patient recovered.) shortest, and the last, the longest. Often more than half of the length of the parasite is in the last segment; from time to time the large link is thrown off, so that it is not uncommon to find but the three proglottides. The parasite is short lived, and is prob- ably the least prolific of the tapeworms ; this is compensated for by the proliferative power of the parasite in the juvenile or larval stage. The anterior segment, or scolex, is surmounted by four suctorial discs, anterior to which, between the quadrately placed sucking discs, is the rostellum, with its hooklets, numbering from thirty to forty. The adult parasite is not found in man. The ANIMAL PARASITES. 207 ova thrown off by the parasite, entering the alimentary canal of man and some lower animals, hatch the embryo, which, wander- ing into the tissues of an organ, develops into a cyst—the encysted parasite. These cysts occur in three forms : 1. Echinococcus scolicipariens, echinococcus granulo- sus, or echinococcus veterinorum, is a bladder-like cyst, vary- ing in size, often 5 cm. to 15 cm., or even 20 cm.,, in diameter. The wall of the cyst is formed of two layers, as a rule, easily distinguished from adjacent structures and from each other. The outer layer is supplied by the invaded organ, and is called the cuticular membrane, the tissue of which shows distinct lami- nation ; the inner layer, which is finely granular, constitutes the Fic. 168.—Ecui1nococcus. A GRouP OF Fic. 169.—ECHINOCOCCUS. 9 : SCOLicEs.— (Frum Dr. Loux Ss Eases Scolex: uw, pedicle of attachment to endo- see Fig. 167. )4-in. obj. ; I-iu. oc.) cyst. Just above are shown the some- what disarranged hooklets.— (From Dr. Loux’s case, see Fig. 167. \-in. obj.; 34-in. oc.) granular or parenchyma layer. When the cyst has attained a diameter of 2 cm. to 10 cm., the development of brood capsules begins. These will be found attached to the granular layer, first as dot-like bodies, later as distinct cysts, in which many young parasites occur; hence they are spoken of as brood cysts. The heads or scolices projecting into the cyst are about 0.3 mm. long, have developed four suckers, and a rostellum with attached hooklets ; the interior shows a vascular system and sometimes granular, chalk-like bodies within; at times a parasite may be found with the scolex invaginated into the posterior part of the body, as though retracted. 2. Echinococcus hydatidosus, echinococcus altricipariens, or echinococcus hominis, is characterized by the development 208 GENERAL PATHOLOGY. of daughter cysts, probably from degeneration of the brood cap- sules already described. From the daughter cysts another gen- eration of parasites may develop, forming still another series of cysts. The number of daughter cysts may be enormous: as given by Thoma, 1000. 3. Echinococcus multilocularis bears little resemblance to the forms just mentioned; the cysts never attain any great size, but occur in enormous numbers. The liver is the common site of this form, which is very rare in the other organs. Earlier observers regarded the growth as an alve- olar, colloid tumor. The cysts rarely attain nN 6 by \ a diameter of over one centimeter, are spheric or ovoid, the wall formed by a Ad @ Va dense connective-tissue membrane, which, under the microscope, may contain still Fic. 170.-Ecuixococcus- smaller alveoli; the alveoli are filled with HOOKLETS —(from Dr. s = A Loux's case, see Fig. a more or less gelatinoid or colloid mate- 167. K-in-objtinec-) rial containing a few of the histologic ele- ments of the scolex. Often only on pro- longed examination can these be demonstrated. The cysts may communicate with one another. Stte.—Echinococci may occur almost anywhere, but over forty-five per cent. of the cysts are found in the liver. (See Parasitic Cysts.) Demonstration.—The diagnosis of echinococcus-cyst is com- monly based upon the finding of the hooklets or scolices. The presence of a fluid with a comparatively low specific gravity, and nonalbuminous or containing but a minute trace of albumin, should always be looked upon as indicating an echinococcus-col- lection. When the fluid is clear and contains but a small quan- tity of suspended material, sedimentation should be permitted to take place, and the sediment may be further brought together by the centrifuge, if necessary. A small quantity of the sediment is placed on a slide in the same manner as already directed for urine ; examination made by the 14-inch objective will usually show the hooklets quite plainly. Occasionally, coccidial cysts, and possibly cysts arising from other causes, contain sickle- shaped bodies, which may mislead the inexperienced. The hook- lets of the echinococcus have on the concave side a knob, or pro- tuberance, or hump, which never has been successfully imitated by anything with which the author is familiar. The brood cap- sules and contained scolices can rarely be demonstrated in the fluid drawn from such cysts by tapping. If, however, the cyst wall be accessible, gentle scraping will usually detach the cap- ANIMAL PARASITES. 209 sules; some of which may escape rupturing. These are best shown on the slide under comparatively low magnification— I-inch or ¥%-inch objective. (See Figs. 168 and 169.) Occasionally, the cyst may be inspissated as a result of the death of the contained parasites. Under such circumstances the contents may be cheesy, resembling the caseous collections of tuberculosis and syphilis. The demonstration of the hook- lets in this material becomes somewhat more difficult. A con- siderable quantity of the suspected material should be washed in alcohol, the alcohol drained off, and the washing repeated ; _ this may be followed by washing in ether to remove any fat, and, finally, the remaining sediment may be removed to the slide and examined as already directed. If these directions are care- fully followed, the hooklets can usually be found; some- times, however, prolonged search will be necessary. | FIG, 171. A. Acarus scabiei. B. Portion of epidermis, showing the burrows with their contained eggs. —(After Leuckart.—Gould.) Acarus scabiei (arachnida), the parasite that causes scabies or itch, is known as the itch-mite or sarcoptes hominis. The female is nearly double the size of the male, and can often be picked out of the furrows found in the skin in cases of itch. The parasite is from 2 mm. to 5 mm. in length, and over one-half as broad. It possesses four pairs of legs, two pairs anteriorly and two posteriorly. From each of the foremost pair of the anterior legs extend delicate processes, supplied at the distal end with dis- coid terminations for attaching themselves to surfaces ; in the male these addenda are on the hindermost pair. The other legs end ‘ in bristles. The posterior border has a number of bristle-like hairs; similar hairs are seen on the rounded head of the mite. The parasite burrows into the epidermis, in which it forms 14 210 GENERAL PATHOLOGY. cavernous systems attended with inflammation of the adjacent mucous layer. In the cuticular caverns the female deposits her eggs, which hatch into young mites. These burrow, shed their external coatings, and repeat the process of reproduction of kind. , Leptus autumnalis, or harvest-nute (larva of trombidz), is a red-colored parasite deposited upon the skin from grass, bushes, and certain cereals; it induces inflammation by its bite or by boring into the epidermis. Pentastoma denticulatum is the juvenile form of the pentas- toma tenioides. The mature female is 50 mm. to 125 mm. in length and 6 mm. to 10 mm. broad ; the male is much smaller— 15 mm. to 25 mm. long and 2 mm. to 5 mm. in breadth. The larva is between 3 mm. and 5 mm. in length, andis from I mm. to 2 mm. wide—an egg-shaped mass occasionally found in the viscera. The mature worm is found in the frontal, nasal, and maxillary sinuses of some of the domestic animals. The demodex, or acarus folliculorum hominis, inhabits the ducts of sebaceous glands and occasionally the hair follicles. It is broad just back of the head, from which point it tapers down to a blunt hinder extremity ; at the broadest part are four short, thick legs. The length of the parasite varies greatly,—between 0.5 mm. and 1 mm.,—and the insect is usually about.one-tenth as broad at the widest point. Ixodes ricinus, or wood-tick, inhabits decaying wood in dry places (dry rot of timber), from which it attaches itself to dogs, and occasionally to man. The head is black or brownish, and supplied with a boring disc, which penetrates the skin, and through which the parasite sucks blood. Pediculus capitis, pediculus ordinarius, /ead-louse, or com- mon louse, inhabits the hairy scalp. The adult parasite is about 2 mm. to 3 mm. in length, and, pathologically, is an epizoon, securing nourishment by attacks upon the skin. The irritation produced by the bites is sometimes followed by inflammation, which may be eczematous in character. The eggs are oval, with slightly flattened ends, attached'to the hair by a chitinous cement, which also covers them. An egg hatches out in from seven to ten days. Pediculus vestimenti, pediculus corporis humanus, clothes- louse or body-louse, inhabits the clothing, in which it deposits its eggs. The fully developed parasite is considerably larger than the head-louse. From the clothing the parasite makes in- cursions to the skin, from which it obtains nourishment, The bites induce changes similar to those of the head-louse. ANIMAL PARASITES. 2II Pediculus pubis, pediculus inguinalis, phthirius pubis or inguinalis, or crab-louse, infests the hairy pubis, axilla, and, rarely, the beard and eyebrows. The parasite is smaller than either the head- or body-louse. Its habits are practically the same as those of the head-louse. Cimex lectularia, cimex hirun- dinis, or Jdedbug, dwells in beds, floors, and cracks of woodwork, from which it invades the skin, the bites producing slight inflammatory lesions. * The adult parasite is 3 mm. to 6 mm. in length; the eggs are laid between Fic. 172.Pepicutus Pusis. the months of April and October, and require eleven weeks to hatch and develop the mature parasite. Pulex irritans, pulex hominis, or aman flea; the pulex serraticeps, pulex felis, pulex canis, or dog flea. The two parasites closely resemble each other, and by some are held to be identical. They infest the hair of the dog and cat, from these animals wandering to man. Closely related to these is the sand- jiea, pulex minimus cutem penetrans, or pulex penetrans, an excessively annoying parasite, smaller than either of the fore- going, and found in the sandy areas of the tropics and sub- tropics. The mosquito and certain forms of the gvat belong to a sub- division of the parasitic genera known as the culex. The caudex ciliatus, or large mosquito; the culex equinus, or horse mosquito ; the culex damnosus, or common mosquito of the lowlands of the Eastern States, and the ca#lex pipiens of Europe, are the most important members of the culex group. The local lesions induced by these parasites, while not wholly unimportant, are now considered of more importance than formerly. It is held by Manson and others that these parasites are intermediate hosts for the smaller parasites, the larva of the filaria, and that certain mosquitos inoculate man with the parasite of malaria. Maggots, occasionally seen in dead tissues, and, before the antiseptic methods of to-day, one of the parasites found in wounds, are the larval form of certain flies. The eggs deposited on the wound surface, dressings, etc., hatched, the resulting juvenile parasite being known as a maggot. Hematozoon, or hematomonas malariz, also known as the plasmodium malariz. During the period in which the temper- ature of the malarial patient is rising and approaching the chill 212 GENERAL PATHOLOGY. stage, and in many cases quite independent of the paroxysm, if a drop of blood be prepared for examination as directed (see Tech- nic of Blood Examination, chap. 1, part 11), the parasite will commonly be readily found. Presuming that the examination be begun at the period when the chill is in progress or impend- ing, in the tertian intermittent form of malaria: The parasite is now in the sporulation stage, a period in the cycle of its develop- ment when not of easy demonstration. A magnification of about 1000 diameters (;,-inch oil immersion) will be found convenient, but not absolutely necessary, as the discoverer of the parasite, Laveran, commended a magnification of 600 diameters (%-inch or ¥-inch objective, with a good eyepiece). Carefully focusing ° ona part of the field in which the red blood-cells are thinly spread, the slide is slowly moved, a close watch being kept for pale bodies in the corpuscles or for pale corpuscles, in which the parasite is to be looked for. At times a red cell will be found, with a mulberry-like mass occupying the greater part of the cell ; the cell is likely to be deformed, ovoid in outline, with loss of evident biconcavity. (See Fig. 173, 4,, 4g, Ag, Ay.) A little later the red blood-cell breaks up and the sporulating plasmodium is freed in the blood. Its recognition in this stage is most difficult ; the somewhat irregular hyaline bodies are not readily recognizable until they again attach themselves to a red blood-cell. Shortly after the paroxysm red blood-cells appear with the so-called epicorpuscular forms, the hyaline ameboid bodies usually eccentrically placed, almost never round, but irregular, with out-branching, pseudopod-like arms, and, if the slide is warm or the observation made in a warm room, the hyaline body changes its shape and position. It is owing to this ameba-like motion that we can most readily detect its presence. The so-called vacuoles or hydropic spots occasionally seen in the blood may mislead the inexperienced and unwary; the knowledge of their possible presence should prevent such an error, As soon as the parasite becomes fully intracorpuscu- lar and advances in its growth, there appears agmination of the red blood-cell coloring-matter apparently into the parasite, which, therewith, assumes the pigment stage; now it is most easily recognized ; it occupies a variable extent of the blood-cell, and has within it the moving granules of pigment; if the cell be cooled or in the least dried, pigment motion ceases, and the quiet pigment closely resembles extraneous material that micro- scopists roughly designate as dirt. The freshly drawn blood with the moving pigment within the parasite, and the latter again within the red cell, offer no excuse for failure in identification, ‘te « ) 800 +e ww a “ey 4 ul ee #3 Fic. 173.—ILLUSTRATING DIFFERENT FORMS OF THE MALARIAL ORGANISMS WITH THEIR STAGES OF DEVELOPMENT.—( 7yson's “' Practice of Medicine.”’) Aj, Ao, Ag, Ay. Sporulation stage. B, Bo. Sporules separating. 41, do, A3, Ag, Fi, and Bo. Stages in the so-called rosette form of the parasite. (Cj, C2. Free sporules. 1, De. Epi- corpuscular forms. Nonpigmented, or hyaline, ameboid bodies. £1, Ay, £3, £4. Intra- corpuscular forms, with varying amounts of pigment. /), #. The large extracorpuscular body. G), Go. The flagellateforms. A, >, Hs, Ay, H3, Hy. The parasite of estivo-autumnal malaria. A;, Crescent showing remains of red blood-cell in the concavity. A», Hy, As, and H;. Ovoid and discoid or ring forms of the parasite. A. Flagellated organism. 213 ~ 214 GENERAL PATHOLOGY. (See Fig. 173, Dy, Dy, Fy, 2, £3, and Ay, partly diagram- matic representations of the nonpigmented and pigmented para- sites.) The number of parasites in any specimen of blood varies, but in a fairly marked case one should expect at least one to every two or three fields, but a more extended search may be necessary. As the development of the parasite progresses, faint lines radiate from the center toward the periphery, near which each pair of marginal markings are joined by a short arc; near the outer extremity of each of these wedge-shaped masses we see a small granular body, possibly the nucleus. The clumps of these wedge-shaped masses around a common center give the parasite a rosette shape. This rosette may or may not be sur- rounded by a visible rim of the remaining red corpuscle. This is the mulberry-like form, which is the sporulating stage, ready to free the spores, at which time the malarial paroxysm usually occurs. The freed sporules are not recognizable in the peripheral blood, but probably are liberated in the large viscera, in which they attach themselves to the red corpuscles and again appear in the peripheral circulation. The differentiation between the tertian and quartan parasites is based upon certain differences in the morphology at various stages in their development : TERTIAN PARASITE. QUARTAN PARASITE. Size, . | About that of red blood-cell. | Smaller. Pigment, es Fine, light, active. Coarse, dark, less active than tertian. Red blood-corpuscle, . . | Swells and fades in color. | Shrinks around the parasite and deepens in color. Sporulation segments, . . | Fifteen to twenty or more. | Usually not over ten, at times fewer. Cycle, Completed every other day. | Completed every third day. The parasite of irregular malarial fever—the estzvo-autumnal type—is less regular, so far as we can ascertain, in the cycle of its development, but presents certain characteristics by which its identification is assured. In the earlier stages it may escape notice, as it is not abundant in the peripheral circulation. The small hyaline bodies are few, very small, ring-like or crescentic, with scant pigmentation ; the red cell containing the parasite is com- ANIMAL PARASITES. 215 monly much shrunken, the hemoglobin, with but little granulation, surrounding the parasite, leaving the outlying segment of the red blood-cell but faintly, if at all, colored. The parasite in this stage is small, rarely occupying as much as one-fourth of the cell. The later stage of the cycle occurs in the viscera. Later there appears the crescentic form, upon the recognition of which the diagnosis so largely depends. (Fig. 173, H,, Ay.) Crescents are not seen until the fever persists several days. They are assumed to develop from the hyaline form, which gradually enlarges, loses its motility, and becomes crescentic, with agmination of its pigment granules near its center. Cres- cents occur in freshly drawn blood, and, when observed under suitable conditions, may be seen to assume elliptic, ovoid, and round forms (Fig. 173, 73, 74, /7;); when the round form is attained, the pigment granules become actively motile, which may be a step toward sporulation. Extracorpuscular and flagellate forms of the malarial para- site are seen as changes not presumed to occur in the circulating peripheral blood. The former are believed to be the same as the intracorpuscular bodies liberated from the blood-cell by post- mortem changes, and not observed until some moments after the blood is drawn. At times, particularly if the blood drawn be kept in a moist chamber and warmed to near the normal blood- heat, there appears a series of phenomena, by close attention to which flagella may be demonstrated. First, around or near a malarial parasite may be seen a group of red corpuscles in active motion, as though being lashed about; by careful focusing we may make out a filmy, almost imperceptible, whip-like process, attached to the malarial parasite and in active motion; it may show a few pigment granules along its length, and possibly at its end a slight bulbous enlargement, in which there may be pig- ment. (Fig. 173, G1, G,, and H,.) Occasionally a flagellum may become detached and show active motility, progressing among the corpuscles through several fields. The foregoing brief description applies to the fresh slide of blood. When, for any reason, staining is found necessary, the methods advised in the section on the blood may be utilized. (See The Blood, chap. 1, part 11.) _ Many views have been maintained as to the route by which the malaria organism finds access to the blood. It has been held that introduction into the circulation occurs through air, water, food, etc. At present the trend of scientific opinion is toward the view that infection occurs through the bites of certain insects. It is now generally conceded that the most important 216 GENERAL PATHOLOGY. infecting parasites are the anopheles maculipennis and the culex pipiens.* The mosquito takes in the malaria organism with the blood, and within the body or glands of the mosquito it is not improbable that certain changes take place in the malaria para- site ; in other words, the mosquito acts as an intermediary host, within which the malaria parasite undergoes alterations in form, and possibly in some of its essential powers of infection. Sporule forms of the parasite have been found in the venomosalivary gland, and as the lancet of the mosquito is anointed by the secre- tion from this gland, it becomes possible to understand how infection may be brought about. *Koch, ‘* Deutsch. med. Woch.,’’? Sept. 14, 1899. CHAPTER II. HYPERTROPHY, HYPERPLASIA, METAPLASIA, HETERO- PLASIA, ATROPHY, HYPOPLASIA, AGENESIS OR APLASIA. Hypertrophy may be defined as increased functional power having a tendency to persist, and that is beyond the normal for a given tissue under its existing conditions ; thus, a heart weigh- ing twelve ounces may be normal for the adult, but would be hypertrophic in a child. Hypertrophy is not simply increased size: e¢. g., the amyloid liver may weigh six kilos and be func- tionally inactive. The foregoing definition also excludes tumors, which perform no function. Hypertrophy is usually associated with abnormal size and weight, but the reverse is not necessarily true. Many clinicians and pathologists teach that hypertrophy is essentially a structural alteration; in other words, that it is simply an increase in al]l the elements entering into the forma- tion of an organ or tissue, each element retaining. its normal relation to the associated structures. It is to be granted that this is true, but a definition, or even the idea of hypertrophy, based simply upon this fact alone, must of necessity be erroneous. Occasionally, one finds a tumor of the mammary gland that structurally can not be differentiated from the normal gland. The glandular elements are exactly like those normally present, but the mass is surrounded by a capsule and is sharply differen- tiated from the normal gland. The normal gland being called upon for the manifestation of its associated functions, will hyper- trophy, while the tumor mass may or may not show any such enlargement. It certainly produces no milk, nor are its false ducts and imitative acini connected with the normal structures. It is a new growth—something situated in the mammary gland, but having no more connection with the functions of that struc- ture than if it were located elsewhere in the economy. The continued power to do more work than normal implies, and is nearly always associated with, an increase of the tissue perform- ing the function; but this does not alter the fact that the essen- tial feature of hypertrophy is power to accomplish more work than the normal organ. Hypertrophy must be differentiated from 217 218 GENERAL PATHOLOGY. the so-called reserve force of organs; thus, the heart, during a period of intense excitement, may perform effectually two or three times the work that is normal for it, and still the organ may not be hypertrophied. The condition, however, does not persist ; it is temporary. Causes of Hypertrophy.—Increased work with supplied nutri- tion are the causes most active in extra-uterine life. Examples of increased work with supplied nutrition, followed by hyper- trophy, are abundant. The most familiar instance, and the one most often cited, is the hypertrophy of the heart that occurs as a result of alterations of the valves or orifices, thereby increasing the force demanded of the diseased organ. Thus, a narrowed aorta or aortic orifice may demand twice the normal force to propel the blood through the abnormal obstruction. As an admirable example of increased functional power, the properly trained athlete may be cited. Evidence is not wanting to show that, under careful and continuous training, nearly all the tissues of the body may take on additional activity. These, however, fail to account for certain enormous overgrowths of organs or tissues that occasionally occur. Thus, general or partial giant growth may arise without any apparent extra demand for work, although, of course, the extra nutrition is supplied. This phe- nomenon (giant growth) has been said to arise from congenital impulse—an expression that only moves our ignorance of the actual cause back to a period in which we know less of the functions of organs. Since we have come to appreciate the fact that many organs perform functions of nutrition, secretion, heat production, etc., it is to be conceived that some extraordinary call has been made upon them, the nature of which we can not in the present state of our knowledge estimate; this extra call may constitute the demand for additional tissue, and hence hy- pertrophy. There can be no apparent reason for an enormous hypertrophy of the facial and long bones, as is sometimes seen ; but there must be some reason for the change, and whether this be attributed to changes in innervation or to unusual demand for some functional activity that we can not estimate (such as blood- making by the marrow) remains to be further studied. The two conditions—supplied nutrition and conversion of the added nutrition—are necessary ; if work be increased without sufficient nutrition, wasting occurs ; on the other hand, nutrition may be abundant and, without work, the tissue may waste; as an ex- ample of the latter, we have the wasting of the muscles of the arm when splinted for the treatment of fracture—the nutrition may be just as abundant as when the organ is uninjured. PHYSIOLOGIC HYPERTROPHY. 219 Hypertrophy is sometimes said to be true or false; the latter is not possible. The term false hypertrophy, or pseudohypertro- phy, is applied to large organs in which the increase in size is not attributable to increased functional power or to increase of the elements in the normal proportions, but rather to increase in size due to the invasion of the tissues by a new element, overgrowth of some existing tissue, or some similar condition. The enlarge- ment of the liver, associated with amyloid disease, fatty infiltra- tion, or red atrophy, may be taken as types of so-called pseudo- hypertrophy. The term is a poor one, and should not be used. Hypertrophy is said to be simple and numerical; by the former is meant an increase in the size of the cells, and by the latter, an increase in the number of cells. Kolliker has observed that the unstriped muscle-fiber of the uterus, at the end of ges- tation, is eleven times the length and four times the width of the normal fiber of the nonpregnant organ. Hare and Coplin, in their studies of the influence of digitalis on the cardiac muscle, note a marked increase in the transverse measurement of the fiber, an observation-supported by Tangl, who found that in the ordinary form of hypertrophy of the heart there was an increase in the size of the muscle-fibers, which increase bore a definite relation to the increased weight of the organ. It is probable that in most instances of hypertrophy there is an increase in the number of cells as well as an increase in the size of the existing elements, both old and new; it is not probable, however, that both enlargement and increased number of cells are equally marked in all cases. Physiologic hypertrophy differs from other forms of hyper- trophy in that it anticipates the increased work that may be de- manded of the tissue. In a certain sense all forms of hyper- trophy are physiologic ; hypertrophy is not a disease; but the condition referred to as physiologic hypertrophy is typified in the enlargement of the mammary glands and the increase in muscu- lar power of the uterus in anticipation of lactation and labor. Unlike all other forms of hypertrophy, this condition apparently arises independently of existing increased work; as far as our knowledge goes, it anticipates such work. Hypertrophy is said to be compensatory when one organ performs the work of another ; thus, if one kidney be diseased, the opposite organ may undergo hypertrophy ; if one lobe of the liver be destroyed by disease, the remaining lobes may increase in size. The term compensatory hypertrophy is also used by clinicians in another sense: ec. g., if the orifice of the aorta has been narrowed, thereby demanding more cardiac force, and if the 220 GENERAL PATHOLOGY. heart hypertrophies to meet the new condition, it compensates from the abnormal obstruction, and the hypertrophy is said to be compensatory. Once such hypertrophy develops, and later con- ditions lead to its failure, it is said that the compensation has failed; a like expression is not uncommonly used to indicate a preliminary failure. Compensatory hypertrophy develops with more certainty in the young, while in extreme age the tissues commonly fail to respond to demands made for additional work. When a tooth has been extracted, the opposing tooth becomes longer, as the result of diminished wear, and possibly of lessened resistance. This is sometimes referred to as a form of hyper- trophy. Limitations of Hypertrophy.—If the occurrence of hyper- trophy depended entirely upon the demand for work, there is no reason for its failure to progress indefinitely. Experience, how- ever, shows that a point is always reached, sooner or later, when compensation fails, and work demanded beyond this point leads , to wasting. As previously remarked, the older the individual, the earlier this occurs—a fact that suggests that the blood-vessels are responsible, to a certain extent, for the arrest of the process. It is observed in athletes that if a man has thoroughly trained early in life, he remains competent to train into ‘“ condition” throughout the major part of his days. Early in life the blood- vessels are more capable of increasing their carrying capacity than in later years—a fact very well known of the arteries ; besides, the conditions favoring hypertrophy are more marked in intrauterine life and become less powerful with advancing years. It has been shown that antenatal hypertrophy of the kidney is associated with the formation of new glomeruli and tubules, while postnatal hypertrophy evinces itself only by an increase in the size of the glomeruli and possibly in the length of the tubules. Theoretically, once an organ begins to hypertrophy there is no reason for arrest of the process, provided the conditions per- sist ; but a stage is eventually reached when the blood supply is no longer competent, the arteries being inadequate or unable to transmit the demanded additional blood. When this stage is reached, not only is hypertrophy arrested, but if the demand for increased work be continued, wasting occurs; clinicians recog- nize, in the treatment of heart diseases, that, even with well-estab- lished hypertrophy and good nutrition, a stage is reached in which the best results are attained by diminishing the work to be done rather than by lashing an already overworked organ and hoping for continued hypertrophy. Hyperplasia is an increase in the connective tissue of an METAPLASIA—-HETEROPLASIA——-ATROPHY. 221 organ, either associated with or independent of increase of the elements upon which the functional activity of the organ de- pends. If there be an increase of the functionally active cells of the organ, the increase in connective tissue must be in excess of that which is normally present, in order to be a hyperplasia. The term hyperplasia is also applied to disproportionate increase in any element of an organ. Thus, a new growth of bile-ducts is spoken of as hyperplasia ; newly developed gland-cells, or an excess of one constituent of an organ without corresponding growth of the other elements, is spoken of as hyperplasia. Metaplasia is the direct transformation of a tissue into a dissimilar tissue. This is only possible of tissues of the same type. Different forms of epithelium may change, one into an- other, or one connective tissue may be converted into another, as cartilage into bone, or fibrous or loose connective tissue into fat. Transposition of type is not possible; epithelium never becomes connective tissue, nor is connective tissue ever converted into epithelium. An ulcerative process in the trachea, after cicatriza~ tion, is covered by flat epithelium from the genetic layers of ad- jacent columnar epithelium, the procéss constituting a form of metaplasia. In order that it may be a pure metaplasia there must be no intervention of embryonic tissue. Theoretically, such a thing is possible ; but whether a cylindric cell is ever actually con- verted into a squamous cell, without the intervention of what is essentially an embryonic cell, seems somewhat doubtful. Heteroplasia implies the production of a tissue in some struc- ture when such a tissue, which may be perfectly normal elsewhere, is not a normal constituent of the organ in question. The de- velopment of cartilage or bone in certain glandular structures, such as the parotid, ovary, or testicle, constitutes a heteroplasia. The best type of heteroplastic tissue is a tumor of the typical series. It will be observed that heteroplasia usually implies a change analogous to metaplasia. Thus, in the instances given the bone or cartilage found in the gland must have arisen from connective-tissue elements normally present, and, hence, prob- ably a part of the normal gland. In such elements the prolifer- ative change terminating in the formation of cartilage or bone implies metaplastic power. Atrophy is the reverse of hypertrophy, and hence is dimin- ished functional power, which has a tendency to persist or to in- crease, and which is associated with structural alterations in the tissue involved. It is not merely diminished size or weight, as, in the condition known as red atrophy of the liver, the organ may be much increased in size. Atrophy is not an arrest of de- 222 GENERAL PATHOLOGY. velopment. Atrophy occurs in developed tissue, although the arrest in development may be followed by atrophy of that tissue that has already developed. Causes.—Atrophy may be physiologic : ¢. g., the atrophy of the thymus gland shortly after birth, atrophy of the uterus after labor, atrophy of the sexual organs after the menopause. Atrophy may be caused by pressure, as the pressure atrophies of the liver. Asa result of pressure from a belt or a corset, a deep fissure may be produced in the liver tissue. Again, atrophy of the hepatic structures may follow pressure brought about in other ways: for example, in red atrophy of the liver the blood dammed back, as a result of obstruction to its onward flow in the heart or lungs, gradually distends the hepatic capil- laries, thereby making pressure upon the surrounding cells, which, in turn, is followed by atrophy. (See Red Atrophy of the Liver.) In the chronic indurative processes taking place in the liver the newly formed fibrous tissue, by contraction, presses upon the hepatic lobule and gives rise to atrophy. (See Atro- phic Cirrhosis of the Liver.) Atrophy due to pressure is further shown in the absorption of tissues as a result of the constant pressure of an enlarging aneurysm. JDzsuse of a tissue will lead to its gradual atrophy. Atrophy from disuse may be dependent upon lessened nutrition, as it is well known that the inactive tissues may be poorly nourished. This is the type of atrophy that leads in generations to the disappearance of tissues and organs no longer used. The wasting incident to the fix- ation of a limb in the treatment of fracture is in part due to its disuse, and also, in many cases, the pressure of dressings. /zan- ?tion or faulty nutrition, whether general or local, will give rise to atrophy ; as examples of general atrophy due to inanition we have the progressive muscular wasting that occurs in consump- tion, in the cachexia of malignant tumors, and in profound blood dyscrasias. In the atrophies due to faulty nutrition the cellular elements having the most work to do usually suffer most. That this is not always the case, however, is shown by the extréme muscular wasting that occurs in pulmonary tuberculosis, and by the fact that the kidney and liver may not, at the same time, show any perceptible lessening in weight or in functional power. The lessened nutrition, upon which inanition atrophy depends, must not be too suddenly applied, nor must the starvation of the tissue be extreme ; as a result of either of these conditions the tissue may undergo necrosis rather than atrophy. The induction of local atrophy by a local starvation has been utilized in treat- ATROPHY. 223 ment ; rapidly growing, inoperable tumors have had their growth successfully limited—for the time being, at least—by ligation of the arteries supplying them with nutrition. Certain atrophies are spoken of as trophic : e. g., atrophy asso- ciated with disease of the anterior cornu of the spinal cord ; uni- lateral neuropathic atrophy of the face. It is presumed that certain elements in the central nervous system preside over nutri- tion, and that disease or injury of these elements will bring about nutritive changes in the tissues over which they preside ; thus, destruction of the motor cells in the cord is associated with wasting of the muscles with which the cells are connected. It is evident, of course, that here we have to deal with a complex process ; in addition to the so-called trophic influence of the cells we have the wasting incident to disuse of the muscles involved. Lhflammatory processes may lead to atrophy by pressure and by interference with the nutrition. It is believed by some that cer- tain substances in the general circulation may manifest a selective activity upon given tissues, thereby leading to their atrophy and absorption. Exactly how this change is brought about it is quite impossible to say, but there can be no doubt that examples apparently coming under this head occur. Atrophy of the thyroid gland during the administration of iodin and atrophy of the extensor muscles of the forearm in chronic lead-poisoning may be cited as examples of atrophic processes apparently depending upon bodies introduced into the circulation by internal administration. In the cells and tissues involved in atrophy there is general shrinking of the diseased structures; the cells become granular and not uncommonly pigmented; it is reasonable to suppose that in this granular or fatty condition absorption of the cells is readily possible; certainly, functional activity is enormously diminished, if not, in advanced cases, suspended. This association of structural change with absorption and dis- appearance of cells has led to the name degeneration atrophy. It is probable that all atrophies are associated with some degen- erative phenomena in the cells; by no other means can we ex- plain the disappearance of structure. It is held, however, that atrophy is possible without appreciable cell change ; such a condi- tion has been termed simple atrophy. Again, the term simple atrophy is used to indicate a diminution in the size of the cells, while numerical atrophy implies a reduction in the number of cells. It is possible that in nearly all atrophic processes reduc- tion both in size and number occurs. When the atrophic phe- nomena are due to the inability of the cell to assimilate supplied 224 GENERAL PATHOLOGY. nutrition, the lesion is said to be an active atrophy; when the fault lies in deficient nutrition, it is called passive. The same causes acting upon different tissues may give rise to atrophy in some and not in others. Again, two tissues, apparently similarly placed with regard to nutrition, may show different degrees of atrophy, although the indications are that the cause acts equally upon the twoelements; thus, the connective tissue of glands atrophies slowly, while the parenchymatous structure may show a far more marked atrophic change. Hypoplasia differs from atrophy in that development has been arrested either before or after birth; it is not the wasting of tissue, but the failure to reach the normal development. The process may involve the whole body, or it may be restricted to one or more organs or parts of organs, or to the organs belong- ing toa single system ; as, for example, hypoplasia of the genital apparatus. Dwarfs are examples of hypoplasia. When the process is not universal, but is restricted to one side of the body or of an organ, as the brain (microcephalus), it is known as asymmetric hypoplasia. The cause may lie in incomplete development, or partial occlusion, of the blood supply to the tissues involved. This not rarely proves to be the case where syphilitic endarteritis has lessened the blood supply to an organ or a part of an organ; an example of the first is sometimes seen in the kidney, and of the latter, in the liver. The environment of organs may lead to hypoplasia, as when bands of inflammatory tissue restrict their growth, or failure in the development of the skull limits the increase in the size of the brain. Agenesia, agenesis, or aplasia should be restricted to mean entire failure of development: that there has been no effort at the production of an organ or tissue. This is seen in the kidney at times, and is usually due to obliterative disease of the renal artery. The term is also applied to the disappearance of partly developed organs. It may be used to indicate the failure of a given structure of an organ to develop. As an example of the latter, occasionally the fibrous tissue of an organ develops with- out any corresponding development of the parenchyma, in which case there is said to be agenesis of the parenchyma. CHAPTER III. INFILTRATION AND DEGENERATION. (A) INFILTRATION. ” Infiltration is the “filtering in,” or deposition in organs, or the addition to organs, of elements not normally present, or an excess in quantity of a material that is normally present. It will be observed that the term “infiltration” is here applied toa material and not to a tissue, although one must confess that the difference is not striking. If tissues are included as infiltrating bodies, then a tumor invading an organ would be an infiltration ; such is not the meaning of the term in the sense here used. The materials studied in the infiltrations are chemic bodies, rather than bodies with definite histologic structure. Thus, fat, lime salts, the various pigments, glycogen, and even amyloid mate- rial, are bodies with definite chemic composition, and not compos- ite mixtures of many agents, as are the tissues. It is true that amyloid material has a rather characteristic histologic structure and stain reaction; so have many crystals, but this does not make them tissues, in the common acceptation of the term. In- filtrations are (1) fatty ; (2) amyloid or albuminoid or, possibly more correctly, lardaceous ; (3) pigmentary; (4) calcareous ; (5) glycogenic. 1. Fatty infiltration consists in the addition of fat to an organ in which fat is not normally present, or the addition of a large amount of fat in an organ that normally contains less. Under certain conditions the deposit of fat may properly be con- sidered as physiologic. This same deposit, however, carried to excess, may interfere with the nutrition and function of the tissues involved or of adjacent tissues, and when this stage is reached, the process becomes essentially pathologic. As evidence of the physiologic deposit of fat one need but cite the fat normally present in the hepatic cell, which is apparently necessary for the proper functions of that structure. A certain amount of fat is normally present in the subcutaneous tissue, in the orbit, in the perirenal tissues, and elsewhere. Physiologically, the fat de- posited in the areas named may perform a number of functions : the first, and probably the most important, function is the 15 225 226 GENERAL PATHOLOGY. storage of reserve food that may be called upon when the usual source of nutrition for any reason becomes inadequate. - The fat in the orbit as well as that around the kidney acts as a cushion, offering to the adjacent organ a certain amount of protection from injury. Causes.—Increased nutrition ; decreased work ; slowed circu- lation ; reduced or faulty oxidation. In the increased nutrition fat is stored in the cells, being in excess of the quantity that the cells can utilize for existing demands. If the functional activity of the cell be reduced by lessened demand, and the normal amount of blood is sent to the cell, the nutrition is in excess, and fatty infiltration may result. Moderate slowing of the circulation gives rise to fatty infiltration ; thus, slowing of the circulation Fic. 174.—FATTY INFILTRATION OF THE LIVER. (Semidiagrammatic.) V,V. Hepatic vein. LP oz. Portal vein. A. Hepatic artery. G. Bile-duct. The Vv globular cells loaded with fat are seen in the periphery of each lobule.—( Rindfleisch.) partly accounts for the fat infiltrated into the connective tissue of the omentum and mesentery in cirrhosis of the liver, and also for the fatty infiltration that occurs in the liver lobules in cirrhosis. The infiltration of fat occasionally seen in the liver in tubercu- losis, and associated with marked emaciation, and the infiltration seen in the subcutaneous tissues in chlorosis, where the blood findings would certainly indicate that nutrition is not in an ideal condition, are taken to be examples of fatty infiltration depending upon faulty oxidation. The origin of the stored fat has been a matter of much discussion. It is now generally conceded that it may arise from a number of sources. ‘In the fatty deposits of hypernutrition it is usually held that it represents the fats and sugars in the food, and, to a limited extent, the albuminoids. In INFILTRATION AND DEGENERATION. 227 deposits from other sources it is not improbable that the albu- minoids are more important as sources of the fat than the usual food-products to which it is attributed. Sites. — The cells normally containing fat as one of their essential constituents are first to show excessive deposit of the material when changed condi- tions lead to infiltration. In the liver, particularly in the periph- eral zone of the liver lobule; in the general subcutaneous tis- sues, with the exception of the lax areolar tissues of the scro- tum, eyelids, lips, ale of the nose and ears ; in the connective tissue between the muscle-fibers (pseudohypertrophic muscular paralysis); in the subserous *'°coiSn Paratysis; Fatty INSILTRA structures ; and in other connec- TION: OF MUSCUR = Uiislercr:) tive tissues. A more or less circumscribed collection of fat constitutes a neoplasm known as a lipoma. The general infiltration of fat into an organ—such, for example, as the heart—is referred to as lipomatosis of the organ involved. When the infiltration of fat is extensive, con- stituting what might be termed a universal lipomatosis, the con- dition is commonly spoken of as obesity or adiposity. Microscopically, the fat is taken up by the connective-tissue cell ; the nucleus is crowded to one side, the fat existing in the cell as a single large fat-globule; in the liver tissue the fat is taken directly into the liver cell. The nuclei of the infiltrated cells are not diseased, but merely show crowding to one side. In the muscles the fat is infiltrated between, and not into, the muscle-fibers, a condition easily, Ge oe eae mone differentiating fatty infiltration from fatty SHowinc FattvInru- degeneration. It is not intended to imply TRATION. X 250 diam- f , eters.—(Schmaus.) that fatty infiltration is always essentially a simple process; not uncommonly it is combined with an associated fatty degeneration, the two conditions being so intermingled as to lead many observers to hold that they are essentially similar. There can be no doubt Muscle-fibers. Infiltrated fat. 228 GENERAL PATHOLOGY. that fatty infiltration can exist independent of fatty degeneration, and that the reverse is equally possible. As the degenerative lesion is the graver, the infiltration is less important in the mixed lesion. 2. Amyloid or albuminoid infiltration, also known as albu- minoid disease, lardaceous infiltration, waxy or bacony in- filtration. Of the many names applied to this condition, the term lardaceous offers certain advantages and has the official sanction of the Royal College of Physicians ; to avoid the confu- sion incident to our ignorance in regard to the ultimate char- acter of the processes it is deemed most wise to avoid calling it either an infiltration or a degeneration, and for the present to ae Pron? ea SAE INES eee esoSe Gees OOS FIG. 177.—AMYLOID Liver. (Semidiagrammatic.) A. Branch of hepatic artery with amyloid walls. G,G. Bile-ducts. £,f. Portal veins. v,v. Hepatic veins. The colorless area occupying the intermediate zone of the liver lobules is, for the most part, lardacein.—( Rindfleisch. refer to it as lardaceous change or lardaceous disease. Amyloid material, or, more properly, lardacein, is found during health in the prostate gland, and has been observed in the pia mater. Causes.—Amyloid material probably represents an altered pro- teid normally present in the blood—possibly fibrin, or, more correctly, the proteid body or bodies whose end is in fibrin. It can be made artificially by suspending the spinal cord in alcohol for a few months. The artificial product so made responds to the chemic tests for lardacein, and can not be differentiated from the natural material. If fresh blood be whipped, and the fibrin so obtained washed and treated with a 1 : 2000 solution of hydro-: chloric acid, the mass becomes gelatinous, clear, and pultaceous, INFILTRATION AND DEGENERATION. 229 and answers all the stains for amyloid material. As amyloid in- filtration commonly occurs in connection with long-standing sup- puration in which the alkaline salts are drained in excess, and as the product resembles a dealkalinized fibrin, it was supposed that the morbid process naturally arose as a result of the removal of alkaline salts from the blood; this is not borne out, however, by the fact that lardaceous disease occurs in malaria and syphilis, very often unassociated with suppuration. Tuberculosis is often the cause (50 per cent. of the cases), especially bone and lung tuberculosis ; anything that greatly reduces the general nutrition favors its development. By some, lardaceous disease is regarded as a degeneration. In a sense this is true ; in the blood the alteration is of the nature of a degeneration ; the material itself is a degeneration product, as, probably, is melanin. As deposited in organs, it represents an additional element—an infiltration; and as the degenerative process is restricted to the origin of amyloid material, the term infiltration is applied to the deposit in organs and tissues. There is not adequate proof that, where found, it results from a degenerative change in the tissues at hand: ¢. g., it is not prob- able that the amyloid liver weighing 7 kilos is the result of a degenerative change in an organ normally weighing 2.5 kilos. Wherever found, lardacein presents evidence of being an added product ; but as to the method by which the addition is accom- plished, we know but little. It may be that primarily there is a deposit of some. body that later is converted into lardacein. Attempts at the artificial production of amyloid infiltration by the injection of bacteria or of bacterial products into animals have not yielded uniformly successful or satisfactory results. Krawkow’s experiments were unsatisfactory, in that the artificial lesions did not resemble, with any detail, the disease as seen in man. Later experiments by Davidsohn seem to have been more successful. The artificial production of amyloid disease must be considered, for the present at least, as being in the experi- mental stage. Sites.—The process usually begins in the blood-vessels, deposi- tion taking place in the intima and between the intima and adven- titia, displacing, or, to a certain extent, replacing, the muscular coat. The deposit occurs almost exclusively in the arteriole, but may be seen around the capillaries, and occasionally in the larger blood-vessels. The organs most commonly involved are the liver, the spleen, the kidneys, the blood-vessels of the mucous membranes,—more particularly those of the intestines, —and the lymph-glands. ,Of 118 cases of lardaceous disease. 230 GENERAL PATHOLOGY. observed by Dickinson, the reaction was present in the kidney in 95; in the spleen in 76-; in the liver in 65; in the intestines in 35; in the stomach and suprarenals, each g ; in the lymphatic glands in 5 ; in the pancreas, thyroid, esophagus, testis, and en- docardium, each 1. ' Morbid Anatomy.—The organ is large, heavy, and pale, the paleness being due to the infiltrated material and to the anemia ; the borders of the organ are rounded ; it is tough in texture ; decomposition takes place very slowly ; the organ possesses a specific gravity very much higher than the narmal. In the spleen the Malpighian bodies are largely involved, and usually show as small translucent grains, resembling boiled sago, and hence the name ‘“sago-spleen.”” (For description of morbid anatomy of lardaceous disease of the liver, spleen, kidney, etc., see chapters on those organs in part III.) , Chemic Tests and Reactions of Amyloid Material—Amyloid material is but slightly digested by pepsin, and only when pre- sented in a finely divided state. It is soluble in ammonia and in strong hydrochloric acid, but is not dissolved by dilute mineral acids or by acetic acid, or in saline solution or in water. The iodin reaction, which is usually applied for the detection of amyloid material, is obtained as follows: A watery solution of iodin, such as Gram’s solution (p. 96), is applied to the cut surface of the suspected organ, first carefully removing any blood that may be present. The amyloid material is stained a mahogany-brown, (see Plate I), while the normal tissue takes on a canary-yellow color. If asmall piece of tissue be stained with iodin, as pre- viously directed, and afterward treated with a five to ten per cent. aqueous solution of sulphuric acid, the lardaceous material will redden and eventually turn blue. Occasionally, this reaction can not be obtained, the sulphuric acid but deepening the brown- ish hue already given by the iodin. The fact that amyloid material does not always respond in exactly the same manner has led to the belief that we are dealing with a number of bodies so closely allied that, with the means at present at our command, differentiation is impossible. For the histologic demonstration of lardacein the material should be fixed in absolute alcohol, the sections stained in Gram’s solution, washed in water, and mounted in glycerin or glycerin jelly. Unfortunately, permanent mounts quickly lose the characteristic color. Sections may be, without previous staining, dehydrated in a mixture composed of one part of tincture of iodin and three parts -of absolute alcohol, cleared, and mounted in oleum origani cretici. A number of anilin dyes Puate I. Cut surface of spleen, showing lardaceous change. The wedge-shaped area shows the iodine reaction. (Atlas of Pathology, Sydenham Society.) ; INFILTRATION AND DEGENERATION. 231 afford reasonably characteristic stains for amyloid material. Sec- tions are stained in a one per cent. solution of methyl-violet for five minutes, washed lightly in one per cent. aqueous solution of acetic acid, followed by water to remove the excess of the acid, and mounted in glycerin or glycerin jelly. The tissues by this method are stained blue and the amyloid material a reddish- violet. Iodin-green may be applied in the same manner, although a longer time in the stain is usually demanded ; with this reagent the tissue stains green, the lardacein, reddish-violet. Birch-Hirschfeld recommends a combination of gentian-violet and Bismarck brown. Sections are first stained five minutes in a two per cent. alcoholic solution of Bismarck brown, washed in alcohol followed by water, and this in turn by a two per cent. aqueous solution of gentian-violet for ten minutes; they are differentiated in one per cent. aqueous solution of acetic acid, washed in water, and mounted in glycerin or glycerin jelly, or, best, in levulose. The tissue is stained brown by this method and the amyloid material red. Harris recommends the follow- ing method: Fix material in alcohol, stain sections three to twenty-four hours in carbol-toluidin-blue, rinse with water, and mordant for one or two seconds with a two per cent. solution of ferrocyanid of potassium, wash in water, and differentiate in acid alcohol. Dehydrate, clear in cedar oil, mount in balsam. Lar- dacein is stained red ; other elements, varying shades of blue ; the slightly reddened fibrous tissue is easily identified. In addition to the specific stains previously indicated, satisfactory exhibition of the amyloid areas is afforded by any good hematoxylin stain, followed by eosin and mounted in the usual manner. Sections so prepared keep well and exhibit both the normal and abnormal structures to advantage. : 3. Pigmentary infiltration, also known as pigmentation, consists in the introduction into the tissues or cells of pigment granules. These pigment granules may arise from two sources : (2) They may be imported into the body, and are therefore extraneous pigments, or (4) they may arise as the result of changes in elements normally present in the body—autochthon- ous pigments. Another form of pigmentation, known as pseudomelanosis, has been described; it is essentially due to- hydrogen sulphid coming in contact with the iron present in the tissues postmortem. It is usually seen on the under surface of the liver, and occasionally on the intestines; sometimes the spleen shows it. One knowing of its possible presence post- mortem is not likely to be mistaken, or fail to recognize the condition when it is present. 232 GENERAL PATHOLOGY. (a) External or Introduced Pigments.—These are well illus- trated in pneumoconiosis. (See Diseases of the Mucous Mem- branes in part ur.) In this type are included solid pigments arising from external sources, such as hard coal in miners, iron in laborers in iron manufactories, and, in stone-cutters, particles of sand. Any of these insoluble pigments can secure access to the tissue through a wound, in which they are probably retained by the action of phagocytes. A form of, this pigmentation, as it occurs in wounds, is seen in tattooing, also in the small grains of powder that may be thrust into the skin in powder explosions. In pneumoconiosis the foreign material enters by way of the air-passages, and may consist of any solid body that is capable of dissemination in a sufficiently finely divided state to permit FIG. 178.—SECTION OF LUNG SHOWING INFILTRATION OF THE CONNECTIVE TISSUE OF THE ALVEOLAR WALL BY COAL-DUST (ANTHRACOSIS).—(Rindfletsch.) its inhalation. When the solid material is hard coal, the condi- tion is spoken of as anthracosis; when the material contains iron, the condition is known as siderosis ; when composed of sand or of fragments of stone, as in stone-cutters, it is called lithosis or chalicosis. Once the pigment passes through the protecting membrane,—either skin or mucous membrane,— it reaches the lymphatic spaces, and may pass on to the lymph- glands, or even further, and may eventually reach the circula- tion. A lymph-gland may break into a blood-vessel, and the solid pigment may be carried everywhere by the circulation. Weigert asserts that this is a method by which any extraneous pigment reaches other viscera than the lung: ¢. ¢., the liver and spleen. : INFILTRATION AND DEGENERATION. 233 Other extraneous pigments do not enter the body as pigments, but are converted into pigments by the action of the body-juices. Silver may be taken as a type of these pigments entering the circulation and coming to the surface of the body as an albumi- nate. It is deposited in the skin by the action of light as metal- lic silver, the resulting condition being known as argyria. (0) Pigments Derived from Elements Normally Present in the Body.—Pigmentation is a normal process in the skin of the negro, and in the iris, etc. Pigments derived from the blood—so-called ee pr ut > O Gee ewe KO Be FRRERS FIG. 179.—SECTION OF A LUNG SHOWING CHALICOSIS. P. Pleura. 6. Nearly normal air vesicles; some are slightly emphysematous. a. Mass of in- filtrated material with dense fibrous capsule and situated in the pleura. a’. Similar mass in the lung tissue; other masses are shown. £; Blood-vessel around a branch of which is forming an area of infiltration. z. Thickened fibroid, interlobular septum.—(Schmaus.) X 30 diameters. hematogenous pigments—are the results of changes in the normal hemoglobin during life. In health the hemoglobin is not yielded to any of the tissues with which it comes in contact; in certain conditions, however, the blood coloring-matter may be altered, as in hemoglobinemia, or the hemoglobin may pass off with some of the excretions, as in hemoglobinuria. During life the two blood pigments resulting from changes in the hemoglobin are hema- toidin and hemosiderin ; the latter differs in many respects from the former: the principal difference is that hemosiderin contains iron. A pigment very closely allied to the foregoing is mc/anin ; 234 GENERAL PATHOLOGY. with hemosiderin, melanin forms the chief pigment of malaria. Melanin is a normal pigment in the skin of the negro and around the nipple in the white ; it is also seen in tumors, where the con- dition is known as melanosis, or the tumor is said to be melan- otic ; it may be produced by the cellular activity of the part, and it may follow hemorrhage. In Addison’s disease melanin is de- posited in the skin of certain parts of the body ; in malaria melanin may be found in the large glandular viscera, such as the liver and spleen. When any of the hematogenous pigments are deposited in organs, the tissue affected is said to show hemochromatosis, a name given to the condition by von Recklinghausen. Hemo- chromatosis is seen in the liver, spleen, lymph-glands, bone- marrow, lungs, and kidneys, and, in very rare instances, in the mucosa of the intestine. Jaundice.—A form of pigmentation in which the pigment is derived from blood coloring-matter, but which, at the same time, would not occur without the intervention of another process in metabolism, is jaundice... While it is true that certain blood pig- ments, including hematoidin, are chemically identical with bilirubin, and that the latter is abundantly formed when there is rapid hemol- ysis, still, there is not sufficient reason for believing that this pro- duction is ever sufficient to give rise to jaundice. Bile pigment is produced in the liver, and by reabsorption enters the circulating blood, and is the agent that produces the discoloration of the various tissues so markedly influenced in jaundice. The pearly white of the conjunctiva is usually first to manifest the discolor- ation ; afterward we see all of the tissues more or less discolored. Commonly, the brain and spinal cord escape pigmentation. It is said that the gastric and pancreatic secretions do not show the yellowish tinge. With regard to the sources of the pigment cir- culating in the blood two views have long been in force, these leading to the recognition of two forms of jaundice, one hepatog- enous and the other hematogenous. Hepatogenous jaundice is presumed to depend upon the pro- duction of bile pigment in the usual way, and its absorption by the blood as a result of retention within the biliary channels. This retention may depend upon swelling of the mucous mem- brane of the duct, biliary calculi, tumors within or without the duct and pressing upon it, inflammatory adhesions, kinks, pressure by a misplaced viscus, such as the right kidney, parasites in the bile-duct, etc. The resorption of bile as a result of such obvious obstructions as those just considered deserves no special comment. There are forms of jaundice, however, that are not obstructive in INFILTRATION AND DEGENERATION. 235 the sense previously indicated. It is alleged that jaundice may depend upon the overproduction of bile (polycholia) ; the abnormal bile may be viscid, slow-flowing, and hence offer opportunities for resorption, or, entering the intestine in large quantities, it may be taken up by the portal circulation and returned to the liver, which may not be equal to the continued removal of the pigment from the blood, which, escaping the hepatic cells, passes onward into the general circulation. Hematogenous jaundice is seen in connection with various morbid processes in which blood destruction constitutes an im- portant element. Itis the erythrocytolysis of yellow fever, pyemia, pernicious malarial fever, and allied diseases that causes the form of jaundice in question. The jaundice associated with venom- poisoning, phosphorus-poisoning, etc., belongs with this group. The fortunate possession of an agent (toluylenediamin) destroying the blood and bringing about this form of jaundice has enabled in- vestigators to study the changes that accompany the condition. It has been shown that destruction of the blood-cells leads to the production of a bile whose viscosity prevents rapid flow through the biliary capillaries, and hence permits regurgitation, or at least increases biliary pressure to an extent compatible with resorption. At the same time there is more or less catarrhal swelling of the mucosa of the biliary passages, which further impedes the flow. The jaundice is then truly obstructive, and not actually of hematog- enous origin, although the initial step in the process was prob- ably the erythrocytolysis. Experimental studies of the jaundice produced by phosphorus and arseniureted hydrogen offer con- clusive evidence that the production is due to the same conditions as toluylenediamin jaundice. Further, it has been shown that if the liver is removed and poisoning by some of the before-men- tioned agents brought about, blood pigments appear in the urine, though bile pigments are not found. Jaundice i is not properly considered with the infiltrations of bie ment: it is more truly the diffusion of a soluble pigment. Its action, however, on many cells closely resembles that of insoluble pigments. There is a form of pigment known as hemofuchsin, seen in the heart muscle, and occasionally in unstriped muscle, having been noted mostly in the muscular layer of the jejunum. The chemic characteristic of hemofuchsin is that it does not contain iron, and, therefore, resembles hematoidin ; its color is of the brightest red, and the granules are finer than hematoidin. Its source has not been definitely determined. A pigment closely allied to hematoidin is Zein, which is the 236 GENERAL PATHOLOGY. coloring-matter of the yolk of the egg, and is found in the corpus luteum. There are a few pigments that do not enter the body as such, but are developed in the body from elements not normally pres- ent; as an example of these we have the pigmentation follow- ing the administration of silver, argyria, to which reference has already been made. Bacterial Pigmentation.—Certain pigments produced by bacterial growth occur in suppuration. The bacillus pyocyaneus is the organism most commonly producing pigment in pus, or even catarrhal discharges from such mucous surfaces as the nose, uterus, and, rarely, the bowels. Occasionally, the cells whose particular function it may be to elaborate given pigment fail to doso. Such failures often become as conspicuous and as easily recognizable as the overproduction of pigment under other circumstances. The albino is an exam- ple of congenital absence of pigment production, particularly in the skin, the hair, the irides, and the choroid coats of the eyes. A minor degree of failure in pigment formation is seen in the condition spoken of as leukoderma, in which whitish areas appear upon askin otherwise normal. Occasional instances of this peculiar disorder have been observed in the colored race, the skin at times showing areas of snowy whiteness, which strongly contrast with the surrounding normal areas. No satisfactory explanation of this condition is at present forthcoming. The failure in the production of blood pigment seen in certain blood diseases, probably deserves a separate classification. Demonstration of Pigment in Tissues.—With the usual processes of fixation most pigments can be readily recognized within and between the cellular elements of the areas involved, but their identification is a more difficult task. The chemic and micro- chemic reactions of the various pigments are but poorly under- stood. In addition to the differentiating points previously indi- cated, the most important demonstration is that of iron. As before stated, hemosiderin contains iron; there are probably a number of pigments included under the name of hemosiderin merely from the fact that iron is present. The demonstration of the iron is usually accomplished as follows: Tissues that have been fixed in absolute alcohol are sectioned in the usual manner. Sections are treated for from one to two hours in a one per cent. aqueous solution of the ferrocyanid of potassium, and mounted in glycerin containing 0.5 per cent. hydrochloric acid. The pigment containing iron, not in the so-called concealed or masked form, will show the bright blue reaction. In order to secure the reac- INFILTRATION AND DEGENERATION. 237 tion with both ferric and ferrous salts it may be necessary to use a mixture of ferrocyanid and ferricyanid of potassium, each 0.5 to I gm. to 100 c.c. of water. 4. Calcareous infiltration or calcification consists in the deposition in the tissues of salts of lime and magnesium ; the lime salts are the phosphate, carbonate, chlorid, and fluorid ; the mag- nesium salt is a phosphate. The term petrification or petrifaction has been applied to deposits composed purely of magnesium and other than lime salts, while the term calcification has been restricted to lime salts. That so sharp a differentiation is advisable or even possible is, in the opinion of the writer, doubtful. Causes—Calcification is practically never a primary process ; most frequently it is-secondary to some destructive change in the cellular elements of the area involved : ¢. g., local changes in nutri- tion, coagulation of albumin, slowing of the circulation, inflam- mation, and chronic infections. It may be said, in a general way, that calcification is an evidence of age, and that the more marked the calcification, the older the particular tissue involved must be. Calcification is one of nature’s methods of limiting infection, as is shown by the calcareous masses that collect around tubercular areas and in actinomycotic masses and in the fungus itself. The ultimate cause of the deposit of lime salts may be said to be unknown. The fact that it is more or less constantly associated with tissue death, or senescence, would indicate that disorganiza- tion or dissolution of proteid bodies favors the deposit ; for this reason it has been held that the tissue elements in process of disorganization enter into chemic combination and retain within them the earthy salts, which, under normal conditions, escape or remain in solution. Morbid Anatomy.—The lime salts may form distinct concre- tions, as in tubercular abscesses and tubercular glands, or they may be diffused between or into the cellular elements of a tissue : e. g., the cartilages of the ribs. This latter process is analogous to ossification observed in bone; calcification differs from ossifi- cation in that the former does not have any distinct histologic structure. Seats.— Healed-in”’ infectious processes, or where attempts at “healing in” have been made ; it also occurs in the cartilages : ¢. g., those of the ribs ; it is frequently present in cicatricial tissues, particularly in those connected with the periosteum ; it is seen in certain tumors,—e. g., psammoma of the brain,—in thrombi, and in areas that have undergone hyaline, fatty, and possibly other degenerative and necrotic processes. The salts may be deposited 238 GENERAL PATHOLOGY. both within and between the cells. Deposit within the cells is met with in the ganglion cells of senescence, but elsewhere the process is most commonly between the cells: that is, in the in- tercellular substance. Calcification following attempts at repair is seen secondary to inflammation of serous membranes, notably of the pleura and pericardium. It occurs as a sequence of inflamma- tory and degenerative processes in the blood-vessels, particularly the arteries, and is also seen around the cardiac orifices and in the older sclerotic areas in valve leaflets. One of the remarkable instances of calcific deposit is that occasionally seen in the dead fetus of a ruptured ectopic gestation. In the course of years a fetus remaining in the abdominal cavity may be extensively infil- trated with lime salts, thereby producing a body spoken of as a lithopedion. Calcification of the placenta is occasionally ob- served. The demonstration of calcific deposits does not commonly re- quire any other aid than the gross examination. The deposits are usually sufficiently well marked to be readily recognized by palpation, and may be further shown,by the occurrence of frac- ture on bending—a test particularly applicable to blood-vessels and valve leaflets. In sections the calcific deposit is not uncom- monly first discovered by the nicking of the microtome knife. When the deposit is scanty, the fine granules or grosser collec- tions may be readily recognized under the microscope. The strong affinity of the salts for hematoxylin also constitutes an im- portant test. The application of a five per cent. aqueous solu- tion of hydrochloric or nitric acid leads to their disappearance, the carbonates effervescing as a result of the liberation of the carbon dioxid. The demonstration of lime salts may be further made by the addition of sulphuric acid, which leads to the forma- tion of gypsum (sulphate of lime), which may be recognized as needle-like crystals. (See Fig. 110, p. 129.) Uric Acid Deposits.—With gout is associated the abundant deposit of uric acid and its salts, particularly in connection with the joints, although the kidneys, skin, and fibrous tissues of the body are also likely to be involved. Wherever the deposit takes place there is usually a surrounding area of local necrosis, or at least marked degenerative changes. The cause of the deposits has not been definitely determined. We do not even know whether it is defective excretion, overproduction, or faulty oxida- tion. The deposition is frequently associated with local pain and inflammation. The statement commonly made that the deposits consist of sodium urate is not strictly true, as Roberts has satis- factorily demonstrated that they are composed of sodium biurate, INFILTRATION AND DEGENERATION. 239 probably precipitated i in the tissues involved from thé quadriurate circulating in the blood. The uratic deposit in the cortex of the kidney is irregularly distributed, while in the medullary portion it follows the course of the straight vessels. The tophi in the cartilaginous external ear (the helix), the deposits in the eyelids, around the tendons, in the fibrous textures of the palms of the hands and plantar tissues are composed of inflammatory, nec- rotic, and hyaline elements containing a varying amount of sodium biurate. 5. Glycogen Infiltration.—Glycogen, like fat, is a normal constituent of liver tissue, arising from the metabolism of grape- sugar by the extraction of a molecule of water: GRAPE-SUGAR. WATER. GLYCOGEN. C,H20, — HO = C,H )O5 That it can also be produced from albumins there seems no reasonable doubt; but the uncertain composition of the proteid bodies makes the chemic change of albumin into glycogen an unsolved problem in physiologic chemistry. While produced normally in the organism, it is in diabetes that we see its most remarkable generation. When we have solved the pathology of diabetes, the production of glycogen, and particularly its tissue infiltrations, may become apparent. It has a rather remarkable resemblance to amyloid material, and still, that it is not the same, can be easily established. It reacts with an aqueous solution of iodin very much as amyloid material, but does not give the blue with iodin and sulphuric acid; if treated with ptyalin or amylop- sin, it quickly loses its iodin reaction ; while amyloid is insoluble in water, glycogen is freely soluble. Glycogen is converted postmortem into grape-sugar. The extraction of glycogen from the liver is accomplished by dissolving it in an alkali and precipi- tating by alcohol. It is a white powder, freely soluble in water, giving the solution an opalescent tint. Demonstration.—To demonstrate glycogen in the tissues, use anhydrous alcohol for fixation, infiltrate with celloidin, and harden in cedar oil and chloroform. (P. 61.) For staining, Barfurth advises a glycerin solution of iodin, and Ehrlich a syrupy solution of iodin in gum acacia. By either of these solutions it stains br own, like amyloid, but is differentiated by the insolubility of the last- named body. Fixation in absolute alcohol lessens its solubility but does not render it insoluble. It does not give the blue reaction with iodin and sulphuric acid, as lardacein may do. As an infiltration, glycogen is found in the liver, epithelial cells of Henle’s loops, in leukocytes and pus-cells, in tumors (particu- 240 GENERAL PATHOLOGY. larly carcinoma and adenoma of the testicle), in sarcoma of bone, and, rarely, in similar tumors in other situations. It is present in the leukocytes in diabetes, and it is claimed that the diagnosis of diabetes can be made, before sugar appears in the urine, by the glycogen reaction of the white cells. Morbid Anatomy.—Organs showing glycogenic infiltration resemble amyloid organs with the following exceptions: The specific gravity is low; there is not the bacony density ; anemia and brittleness are less marked; the organs never attain the size sometimes seen in amyloid disease; and the difference given above in the chemic stain reaction. Cholesterin Infiltration.—There is much doubt as to this being an infiltration; in degenerative processes cholesterin is likely to be found, but gives no macroscopic evidence of its pres- ence. Under the microscope it may be recognized as thin, rhom- bic plates with not very regular edges, and quite commonly a small square out of one corner, appearing as though it had been cleanly cut out. (See Fig. 115, p. 130.) In addition to the degen- erative processes already mentioned, cholesterin is found in the contents of cysts, and sometimes in inflammatory exudates and in atheromatous areas. Hydropic Infiltration.—In edema the tissues involved are bathed in the fluid that distends the lymph-spaces, and the cells of the area may take up a varying amount of this fluid. By some this is considered an infiltration, and is spoken of as drop- sical or hydropic infiltration. It is practically always associated with more or less degenerative change in the cells, and it has, therefore, seemed to the writer best to consider it with the degen- erations. (See Edema.) (B) DEGENERATION. Degeneration implies that the cellular elements of an organ are undergoing or have undergone such changes, both chemic and structural, as to preclude their proper maintenance of func- tion ; degeneration differs from infiltration in that infiltration is something carried to the organ or cell and deposited, or some- thing manufactured by the cell and retained, while degeneration implies that the cell, including its chemic and physical elements, has undergone important nutritive changes, which may be entirely independent of any extraneous material brought to the organ involved. Infiltration may lead to degeneration, and degenera- tions may be accompanied by infiltrations; the processes are, however, distinct. Notwithstanding the entity of each, an infil- INFILTRATION AND DEGENERATION. 241 tration may be associated with a degeneration, the two processes apparently going on side by side, thus affording an obscure pic- ture of both. In such complex processes, however, the degen- eration is likely to be the lesion that is most detrimental, and while it may have been preceded by the infiltration, or the infil- tration may have arisen after the inception of the degeneration, still, the degenerative lesion will constitute the important patho- logic phenomenon. Degenerations are also known as metamor- phoses; occasionally a degeneration is spoken of as a necrobi- osis; this term is not, however, correct, as the latter condition implies molecular death, and an organ may be degenerated or a cell may be degenerated and may not as yet be dead, although ultimately the cell may perish. The degenerations are paren- chymatous, fatty, hydropic, colloid, mucoid, and hyaline. 1. Parenchymatous degeneration, also known as cloudy swelling, granular degeneration, and parenchymatous meta- morphosis, consists of a precipitate, within the cell protoplasm, of what seems to be albumin, or other cell proteid, in a finely granular form. The nucleus of the cell is obscured, or even hid- den, by minute granules, and, late in the process, may be de- stroyed ; the perinuclear protoplasm contains an abundant granu- lar precipitate; the cell outlines are indistinct, and the entire body may be disintegrated. It is probable that the process, if continued, terminates in a fatty degeneration, and that the granular bodies seen are eventually converted into oil. The cell may again be cleared up by the use of dilute acetic acid or a strong alkali. The nucleus will again become visible, although the granular bodies may merely agminate and not disappear. Causes.—High temperature ; poisoning by carbonic, phosphoric, and arsenious acids, and by the salts of mercury, copper, antimony, etc. ; intense or long-continued hyperemia, vascular stasis, and edema ; inflamed mucous membranes usually show it to a high degree ; a similar process is seen in inflammation of muscle: e.g., acute myocarditis ; in acute yellow atrophy of the liver many of the cells will be found granular and many of them fatty to a high degree ; any malnutrition may simulate the condition, and many poorly nourished gland-cells, particularly in atrophic pro- cesses, show the change. Bacteria and their products, as well as other organic poisons,—the latter due to faulty metabolism or deficient excretion, or to combinations of both processes,—venoms, etc.,are also causes. Morbid Anatomy.—The organ is swollen, increased in size, cloudy or opaque on its surface, appearing cooked, softer than normal, and, when the process is simple, there is evidence of 16 242 GENERAL PATHOLOGY. anemia, but, as commonly seen, there is an increased amount of blood in the part: ¢. g., the cloudy swelling seen in the kidney may be the initial stage of inflammation, and the organ, under such circumstances, will be distinctly hyperemic. Termination.—If the cause be early withdrawn, it is probable that recovery of the cell may occur ; if the cause continue to act, fatty degeneration ensues, the cells are destroyed, and new cel- lular elements must be produced by the undestroyed tissue ele- ments or the connective tissues. Demonstration.—The alterations previously described in the gross organ usually enable one readily to recognize the condition. The examination of fresh cells obtained by scraping the surface of the tissue involved may offer confirmatory evidence, to be consid- ered with the gross appearance. Too much confidence, however, Fic. 180.—CLouDy SWELL- Fic. 181.—GRANULAR_DE- Fic. 182.—CLoupy SWELL- ING OF THE EPITHE- GENERATION OF A MUus- ING OF THE LIVER LIAL LINING OF THE CLE-FIBER, LAST STAGE, CELLS. 250 diame- KIDNEY TUBULE.— NEARLY FATTY.— ters.—(Schmaus.) ( Flitterer.) (Schmaus.) can not be placed in the examination of detached cells. In such cells the granules clear up or agminate when treated with a one per cent. aqueous solution of acetic acid. They are not soluble in alcohol, ether, chloroform, or other agents that dissolve fat, nor are they blackened by osmic acid. Pieces of the organ under obser- vation should be fixed in an osmic acid solution (see pp. 48 and 49), infiltrated with celloidin (paraffin is not applicable), and sectioned in the usual manner. The granules are not blackened by this process. ‘Tissue fixed in corrosive sublimate or in Zenker’s fluid (see pp. 49 and 50), sectioned, and stained with hematoxylin and eosin will commonly show the alterations to advantage. The intensity with which the granules take the acid anilin dyes is always to be remarked. 2. Fatty Degeneration.—This probably represents but a later stage of the preceding. In the cells, at this stage of the process, INFILTRATION AND DEGENERATION. 243 the granular bodies, before noted, are converted into minute oil drops ; the nucleus is destroyed and can not be made to reap- pear; the cell is shrunken and not swollen; its outlines are apt to appear irregular, or evident cell dissolution may be manifest. The oil drops usually do not run together as in fatty infiltration. The compound granule cells in brain softening represent a type of fatty degenerated cells. The cellular debris is usually manifest. Causes.—(1) The causes already given for cloudy swelling ; (2) anemia; (3) some of the forms of necrosis are accompanied by fatty degeneration: c. g., caseation. Total or circumscribed fatty degeneration usually results from embolism, infection, or the noxious influence of bacterial toxins and allied agents. Morbid Anatomy.—As soon as the removal of fat by absorption begins, the organ diminishes in size, becomes soft, almost pulta- ceous, feels oily, and greases the knife with which it is cut. The organ is paler than normal, yellow in color, markedly anemic, and may show interstitial or parenchymatous hemorrhage due to the degenerative processes involv- ing the capillaries. The color of the or- gan may not be uniform, but mottled, as a result of the process being more active or more marked or at a later stage at some points. The color is also influenced by the Fic. 183—FATTY DEGEN- amount of blood in the organ and by the ERATION OF THE LIVER CELLS. XX 250 diame- presence or absence of hemorrhage or of ters.—(Schmaus.) associated pigment. The conversion of the proteid matter into fat leads to a reduction in the specific grav- ity. The parenchymatous cells show the alteration earlier and in a more characteristic manner than the connective-tissue elements, which may escape. When the process is focal and marked, and in certain tissues,—as, for example, the central nervous system,— the softening may go on to complete liquefaction. (See Soften- ing of the Brain.) Sites.—Epithelial surfaces and glandular viscera, muscles, nerves, and blood-vessels ; occasionally observed in the brain, and there constitutes a variety of softening. In certain localities the process is apparently physiologic : for example, the production of fat by the breaking down of the central cells of the acini in the mammary gland leading to the formation of milk, and the fatty change seen in the uterus after labor. (See Fatty Degenera- tion of the Heart, Blood-vessels, Liver, etc., part 11.) Demonstration.—The highly refractive oil globules can usually be recognized under the microscope. In fresh tissues they are 244 GENERAL PATHOLOGY. not cleared up by acetic acid ; they are blackened by osmic acid ; the black or brownish-black granules produced by treating fat with osmic acid are not soluble in alcohol during the subsequent dehydration, but may undergo solution during the process of clearing for paraffin infiltration, and particularly during the treatment by fat solvents, such as chloroform, turpentine, xylol, etc. For the demonstration in sections fixation in alcohol is not applicable. Tissues should be fixed in one of the osmic acid solutions (see pp. 48 and 49), dehydrated, infiltrated with celloidin, and sectioned. The fat. globules will be blackened by this method. Blocks of tissue may be fixed in Miiller’s fluid (see p. 49) or in Orth’s fluid (see p. 50) or in a ten per cent. solution of formaldehyd for a week or ten days. The tissue is then trans- ferred to Marchi’s fluid, which consists of : Miiller’s fluid, . 2... 2 2. = . 2 parts. One per cent. aqueous solution of osmic acid, I part. The tissue is permitted to remain in this solution for a week or ten days. For successful treatment the blocks of tissue should be very small—not over two to five millimeters in thickness. Embedding in celloidin is permissible. After cutting, the sec- tions are cleared in cedar oil and mounted in balsam without staining. The fat globules will be black or brownish-black. When desired, sections may be stained in the usual manner, which will permit an examination of the nuclei and of the asso- ciated structures to advantage. Paraffin infiltration does not yield so satisfactory or trustworthy results as celloidin, as the preliminary clearing agents are liable to extract a part of the fat. 3. Hydropic degeneration (cellular dropsy, cellular vacuo- lization) is practically an intracellular edema. The affected cells are very much larger than normal, and contain many so-called vacuoles, usually in the perinuclear protoplasm, although the nucleus may be involved. The evident cell damage is less than in parenchymatous degeneration, but may be most marked when the two processes are associated, as is not uncommonly the case. Causes.—Edema, inflammation, infectious processes, and de- generative lesions in general when affecting the large ganglion cells of the central nervous system. Sites —Epithelial surfaces, particularly the mucous membranes, glandular viscera in inflammation and edema, edema of the mus- cular tissues in which many fibers are swollen and, on transverse section, show extensive central vacuolation. The morbid anat- omy is practically that of edema, but hydropic degeneration is often present when no gross lesion is manifest. INFILTRATION AND DEGENERATION. 245 Demonstration —No specific method has as yet been devised for the demonstration of this process. Rapid and powerful fixa- tives are demanded in order to prevent the cell from emptying itself of the fluids, before fixation is completed. Probably the best results are obtained by fixing small pieces of the tissue in corrosive sublimate (see p. 49), followed by hematoxylin and eosin staining. 4. Colloid degeneration is a process by which cellular proto- plasm is converted into a homogeneous, gelatinous, structureless mass. The exact cause of this change is not known; it occurs in connection with epithelial cells, to which it is practically restricted. Itis, therefore, a common phenomenon in glandular structures where exit is prevented by occlusion of the duct; it is seen in the kidney and in ovarian cysts ; it occurs in goiter and in cancerous masses. The constancy with which it is found in the thyroid gland has led many observers to believe that it is a normal constituent of that organ, and, when greatly increased in amount, the condition is spoken of as colloid goiter. The exact chemic nature of the material has not been definitely settled ; it is not precipitated by alcohol or acetic acid, it is insoluble in water, and is not rendered opaque by chromic acid. Macroscopically, the material is gelatinous, stringy or ropy, and is usually colorless, but may be slightly bluish or yellow. Microscopically, it will occasionally be observed to be arranged in concentric masses. It does not stain well with the anilin dyes, but stains with carmin. Colloid degeneration of muscle has been described by Zenker, and is closely allied to the hyaline degeneration, which he also describes. Colloid material is found in some cancers, particularly in those of the alimentary canal ; it is also found in cysts pos- sessing an epithelial wall. Colloid transformation occurs in the cerebral vessels, where, according to Mallory, it is particu- larly subject to subsequent calcareous change. (For demon- stration and differentiation from amyloid, mucoid, and hyaline material see paragraph following Hyaline Degeneration.) 5. Myxomatous degeneration, also known as mucoid de- generation or myxomatous metamorphosis. Myxomatous material is normally found in Wharton’s jelly and in the vitreous humor. The process terminates in the formation of a semifluid, hyaline body containing a varying quantity of mucin. A further study of mucin has led to the recognition of the fact that what was originally considered to be a chemic entity is now found to occur under a number of conditions and in more than one form. In epithelial structures the mucin exists in the mucus elaborated 246 GENERAL PATHOLOGY. within certain of the cells, which assume, as a result of the accumu- lation in their interior, a goblet form, and hence are called godlet cells. The free end of the cell opens and the accumulated con- tents flow out, the cell returns to its normal shape and resumes the manufacture of mucus. In other instances the cell is actually shed, undergoes dissolution, and liberates the elaborated product. During inflammatory processes in epithelial surfaces the quantity of mucus thrown off is increased. The production of mucoid material is not, however, restricted to the epithelial tissue, but is intimately associated with the connective tissues, and arises from the transformation of the cell, or, more fre- quently, and probably more truly, of the intercellular substance into a jelly-like material containing mucin. Chemically, the material seems to be made up of complex albuminous com- pounds in which mucin is abundantly present. The affected area is gelatinous and trembling, almost perfectly clear, and colorless. Microscopically, mucoid material is quite homogeneous, and not uncommonly contains large multipolar cells with long, branching filaments. These form a reticulum, which supports the gelatinous material and maintains its conformation ; it is not arranged in concentric masses, like colloid material. Mucoid material is precipitated by alcohol and acetic acid, and is best fixed by corrosive sublimate. It will absorb considerable water, which causes it to swell; it does not, however, undergo solution. It is dissolved by neutral salt solutions and by alkalies, even in comparatively weak solutions. (For further remarks on demon- stration see paragraph following Hyaline Degeneration.) Sites.—As before indicated, ucotd degeneration occurs in both connective and epithelial tissues; it is present in certain’ con- nective-tissue tumors, most commonly in myxoma and lipoma, occasionally in sarcoma or chondroma, and rarely in carcinoma. 6. Hyaline degeneration, also known as vitreous or glassy degeneration or hyaline metamorphosis. The exact nature of the material produced, and the method by which it is elabo- rated, have not been worked out ; the body seems closely related to colloid material, but is firmer, more fragile, and arises in a dif- ferent class of tissues ; it is most commonly found in the lymph- atic glands and blood-vessels and capillaries, around which it may form a distinct mantle ; it is occasionally observed just out- side the intima of the blood-vessels and around the capillaries, thus closely resembling amyloid material. It does not, however, give the amyloid reaction. Hyaline material is occasionally observed in the brain, in the stroma of epithelial tumors, and in the INFILTRATION AND DEGENERATION. 247 dendritic filaments of papilloma of the bladder and other mucous surfaces. The degenerative change observed in the muscles in typhoid fever, particularly in the abdominal recti and the muscles of the upper portion of the thigh, has been variously placed. By some it is regarded as a special degenerative change restricted to muscle; by others it is grouped with the hyaline degenera- tions ; while still others regard the change as a form of coagula- tion necrosis. Amyloid, colloid, mucoid, and hyaline materials are closely allied bodies. Thoma, von Recklinghausen, and Graham regard each as representing but different stages in the evolution of the same body. Lardacein apparently presents sufficiently distinct reactions to entitle it to be considered alone. That the remain- ing conditions are separable by methods at present at our dis- posal seems doubtful. Differentiation by stain reaction—the only method at present available—is not fully characteristic or always satisfactory. Hyaline and colloid materials seem to select acid stains, while mucoid is commonly best stained by basic dyes. Pianese differentiates these materials by fixing small pieces of tissue (2 mm. thick) in a mixture composed of 15 c.c. of a I per cent. aqueous solution of chlorid of platinum and sodium; 5 c.c. of a 0.25 per cent. aqueous solution of chromic acid ; § c.c. of a 2 per cent. aqueous solution of osmic acid; and one drop of chemically pure formic acid. After thirty-six hours’ fixation the tissues are washed in flowing water and transferred to eighty per cent. alcohol. Sections are stained for half an hour in the following solution : Martius yellow, a fale Bi: sap tens 0.01 gm. Acid fuchsin, 5 ‘ : o.I gm. Malachite green, . : ¥M : ; 0.5 gm. Distilled water, . .. . : . 150 «ac Alcohol (96 per cent.), . . ‘ 50 ce After staining, wash in absolute alcohol, treat with xylol, and mount in xylol balsam. By this method mucin is stained sky- blue ; hyaline, brick-red ; colloid, bright green. CHAPTER IV. NECROSIS. Necrosis is the local death of a part, as distinguished from somatic death. When necrosis of tissue results from trauma applied directly to the tissue, it is known as direct necrosis ; when the change is dependent upon causes applied through the circulation, innervation, or degenerative processes, it is called indirect necrosis. Causes.—Anything that destroys the vitality: ¢. g., burns, scalds, and chemic destruction or injury sufficient to interfere with nutrition. The influence of trauma need but be mentioned, as the extensive laceration of the cells, with the associated disturbances of circulation, both hemic and lymphatic, makes cellular death inevitable. The action of poisons in the production of necroses is not always so apparent. There can be no doubt that of the many poisonous agents possessing the power of producing necro- sis their activity is, to a certain extent, selective, some acting upon one kind of tissue and others upon dissimilar structures. Of the many poisons endowed with the property now under con- sideration, certain of them are inorganic, such as mercury, phos- phorus, copper, arsenic, etc.; others are organized poisons, which may be again subdivided into at least three groups: (1) Vegetable poisons (from the higher forms of vegetable life many bodies might be mentioned: ¢. g., oil of mustard, abrin, ricin, etc.), bac- teria, and bacterial poisons, such as the toxin of the bacillus diph- theriz ; (2) poisons belonging to the animal kingdom, such as those elaborated by poisonous reptiles ; (3) certain poisons pro- duced by the tissues themselves. As an example of the noxious influence of the last group, it is but necessary to refer to the extensive hepatic necroses that occur in uremia, and in that par- ticular form of intoxication known aseclampsia. The association of inflammation with necrosis may be either primary or second- ary: that is to say, necrotic processes may give rise to or may be followed by inflammation ; on the other hand, inflammation is always associated with a varying degree of necrosis. Obstruc- tion to the circulation—arrest of the arterial influx, capillary flow, or of the venous exit—may cause necrosis ; lymphatic ob- struction may have practically the same effect ; capillary stasis, 248 NECROSIS. 249 thrombosis, or rhexis is usually followed by necrosis of the tissues involved. As nutrition is, in part, governed by the trophic nerves, it is held that certain necrotic changes result from lesions of these nerves or the central nervous system acting through them. Such necrotic processes are known as neuropathic necroses. The cause of any given necrotic process may have been com- plex, more than one element, and in some instances many ele- ments, entering into its formation. In the weak and debilitated, after fevers, in malignant diseases, and, in certain instances, fol- lowing profound shock, necrotic changes are induced by injuries and other causes that, in the physically strong, would give rise to but little or even no alteration in tissue. As examples of necrosis arising in part through such influences, marasmic and senile necroses may be mentioned. Results —The tissue involved may undergo (1) regeneration or the nearest approach thereto, repair ; (2) absorption, more or less complete ; (3) retention in some form or another; or (4) it may be discharged. The possibility of associated or subsequent in- flammation is not to be forgotten. I. Regeneration and Repair—tin some instances the necrosed elements are thrown off or absorbed, and adjacent cells or em- bryonic constituents of the tissues involved may produce new tissue structurally and physiologically identical with that lost, in which case the lost structures are said to be regenerated. More frequently, absorption of the liquefied elements occurs, and repair proceeds to the formation of cicatricial tissue, which remains as a scar marking the point of the original lesion. 2. Absorption is only possible when the liquefaction can be complete and when bacteria do not gain access ; such absorption is typified in bruises in which the extruded blood-cells are, in time, completely removed. 3. Retention—The entire mass may be retained, or partial absorption and reparative changes may leave but a part; thus, if an infarct cut off the blood supply in a branch of the renal artery, the area involved—say, a part of a pyramid—dies ; after certain degenerative processes, leukocytes and fixed connective-tissue cells wander in and convert the mass into embryonic tissue, from which granulation tissue is evolved and eventually cicatricial tissue (or- ganization). Only a part of the involved tissue may be retained, and this may be much altered: ¢. g., in the blood cyst, or hema- toma, a fibrous capsule may be formed surrounding the escaped blood. Some of the fluid contents may be removed by the ab- sorbents, and the remaining solid material, consisting of the clot 250 GENERAL PATHOLOGY. and cellular elements, becomes permanent, or degenerative changes may convert the mass into a cyst. 4. Discharge-—The necrotic mass may be thrown off, as in gangrene, or it may be slowly disintegrated, as in suppuration, ulceration, and caries. Forms of Necrosis.—Liquefaction necrosis, coagulation necrosis, fat necrosis, cheesy necrosis, sphacelation ez masse, or gangrene. 1. Liquefaction or colliquative necrosis arises as the result of infection, particularly by pyogenic organisms and irritants that are not sufficiently active to produce coagulation necrosis. It differs from coagulation necrosis in the absence of coagulation ; there is the same infiltration of the tissues with fluid, but coagu- lation does not occur. Pus production resulting from infection represents a type of liquefaction necrosis, in that bacterial products liquefy the intercellular substance that holds the embryonic cells, and thus convert the area involved into a liquid. Liquefaction necrosis is sometimes seen to follow coagulation necrosis, and coagulation of previously liquefied areas is occasionally observed. Morbid Anatomy.—The gross appearance depends largely upon the tissue involved, and, to a certain extent, upon the cause. The increased amount of fluid in the part may make it softer than nor- mal—indeed, it may fluctuate ; in other situations the associated increased tension gives rise to apparent induration, which disap- pears on incision or puncture permitting the escape of some of the fluid. In the absence of coloring-matter and blood pigment or its derivatives, the color is lighter than the normal. Concur- rent fatty degeneration leads to the presence of minute oil drops, —an emulsion,—which may give the softened area a greasy ap- pearance. Histologically, the structural elements pass through hydropic, fatty, and other degenerative processes, and, finally, may no longer contain a single normal constituent. Absorption, retention in part or as a whole, and discharge are possible termi- nations ; repair, more or less complete, occasionally occurs, but regeneration is extremely rare, if even possible. Site—F luid exudate in burns, vesicles, etc.; softening in central nervous system; secondary liquefaction of coagulated exudates, as in croupous pneumonia, and of blood-clots and thrombi. 2. Coagulation necrosis occurs as the result of infection ; as a result of embolism or capillary plugging ; in areas of interstitial hemorrhage and in blood-clots, the mass undergoes coagulation necrosis. The tissues are matted together with fibrin, which entangles whatever cellular elements may be present. When occurring in superficial structures, as on or in the mucosa in diphtheria, the fibrin found may be hyaline or homogeneous, fib- NECROSIS. 251 rillar, and in some instances granular. The view at one time held that fibrin of the blood was essential to the process, is now admitted to be incorrect, as lymph containing fibrinogen may induce the change. Zenker’s degeneration of muscle is, by some, held to be a form of coagulation necrosis. As an example of coagulation necrosis following infection may be mentioned its occurrence in diphtheria, tuberculosis, typhoid fever, and allied conditions. It does not seem that bacteria at the point of necrosis are necessary, but that the process may be engendered by the activity of bacterial products; that it is due to the chemic agents is shown by the intravascular injection of aérin or ricon, which is ‘ followed by coagulation necrosis in various organs. After the tissues are matted together by fibrin, fragmentation of the nuclei and more or less complete dissolution of the cells occur. In active inflammatory processes, or in the tissues immediately adja- cent, coagulation necrosis is nearly always present. It not un- commonly precedes caseation, and may be present in the neigh- borhood of caseous areas. Morbid Anatomy.—Early in the process the tissues become very much firmer than normal; not uncommonly the area can be recognized by palpation, even when situated some distance beneath the surface. Upon incision the freshly cut surface may resemble the opaque, glassy appearance of cloudy swelling. Later, softening not uncommonly occurs, which may progress to liquefaction. In the absence of blood or of blood coloring-mat- ter or its derivatives, the area is lighter than normal. Histolog- ically, the cell outlines soon disappear and the normal microchemic reactions are altered. The nuclei at first stain very faintly with the basic dyes, but later not at all, and just before complete dis- solution of the cell its entire structure may take only the acid dye. Occasionally, however, even late in the process, fragments of nuclear chromatin may be irregularly disseminated through the area, and may show as irregular granules taking the basic dye in the midst of a fine granular mass that selects the acid stain. By suitable methods the presence of fibrin can be shown at some stage in the development of the process. For the purpose of demonstrating the presence of this body Weigert’s fibrin stain is recommended. Sections of alcohol- hardened tissue are fastened to the slide by an approved method. The subsequent staining is conducted as follows : Anilin gentian-violet solution (see p. 94), two to ten minutes ; rinse in normal salt solution ; * apply solution of lugol (iodin, 4 * Sodium chlorid, 0.75 per cent. in water. 252. GENERAL PATHOLOGY. parts ; iodid of potassium, 6 parts; water, 100 parts); rinse in water; blot with filter-paper; differentiate in a mixture composed of anilin 2 parts, xylol 1 part; complete differentiation in xylol, which should be applied and removed at least three times ; when the section becomes fully cleared, mount in balsam. Dehydration and differentiation with alcohol are not permissible. Termination.—Discharge may occur as in pseudomembranous formation. (See Pseudomembranous Inflammation of Mucous Membranes.) Liquefaction, absorption, retention, and suppura- tion not uncommonly occur. More or less absorption, followed by repair, is not infrequent. As in liquefaction necrosis, regen- eration of the destroyed tissue is rare. On the surface of the mucous membranes, however, the destroyed cellular elements are not infrequently regenerated. Site.-—Wherever embolism may occur, and in all forms of cap- illary stasis ; it occurs on epithelial surfaces and in glands made up largely of epithelium, such as the liver; the same condition has been observed in the connective tissues, muscles, and fat. 3. Fat Necrosis.—Whether this deserves a distinct position among the necroses is not fully determined. It is most constantly associated with hemorrhagic pancreatitis, in which condition it oc- curs in the pancreas, peripancreatic fat, and in the fat of the abdom- inal wall. It has been found in other conditions, and with no dis- coverable lesion of the pancreas. The areas of fat necrosis vary in size from one or two millimeters to five centimeters, are usually spheroid or ovoid in outline, are white, and resemble, in a way, disseminated neoplasms or tubercles. In time they may be infil- trated by lime salts; this infiltration is further explained if we accept the statement of Langerhans that the necrotic areas con- sist of a combination of the fatty acids with lime salts. Some- times areas are softened, but later, asa result of the calcific matter present, they may be gritty. The exact cause of the process is unknown. The presence of steapsin, the fat ferment of the pan- creas, has led to the belief that the presence of this body is the determining factor. Some hold that the process depends upon bacteria or bacterial products, while others believe that it is brought about by trophic influences. Recent clinical and experi- mental evidence would seem to indicate that the change in the fat was brought about through the activity of the pancreatic ferment. 4. Cheesy necrosis, or caseation, frequently begins as a coagulation or liquefaction necrosis, followed by a fatty degene- ration of the cellular elements and the conversion of the mass into a liquid or semifluid material resembling cheese. The fluid is NECROSIS. 253 taken up by the lymphatics, in some cases giving rise to dry case- ation, such as is seen in old tubercular abscesses in which the fluid has been absorbed, leaving nothing but the cellular detritus. Caseation is not always dependent upon the removal of the fluids and the retention of the cellular detritus, as is shown by the fact that many caseous areas undergo no diminution in size at any period in their evolution. This is partly explained by the occur- rence of cell migration into the necrotic area, the newly arriving Fic. 184.—CONFLUENCE OF TWo TUBERCLES. SECTION OF LUNG. Hardened in corrosive sublimate, infiltrated with paraffin, stained with hematoxylin and eosin, and mounted in balsam. The mass has originated in the vesicular wall, parts of which can be seen at a, a, a, running off to surround adjacent air vesicles; 6 and c have been two distinct tubercles, which are now beginning to show caseation. Around the caseous area is a zone of lymphoid cells in which, at d, is a solitary giant cell. Such eccentrically placed giant cells are not infrequent. The vesicular walls, which leave the tubercle mass at a, a, a, show considerable thickening (%-inch objective, 44-inch ocular). cells themselves undergoing necrosis and their solid constituents remaining. The entrance of cells and fluids, as well as the ab- sorption of the latter, account for the nodules retaining approxi- mately their original size. In addition to the detritus arising from disintegration of the normal elements present and the necrotic cells, caseous nodules may contain bacteria. The or- ' 254 GENERAL PATHOLOGY. ganism most frequently present is the tubercle bacillus, which may be at times demonstrated in caseous nodules that are evidently old. Recently formed caseous areas are not uncom- monly surrounded by a zone of inflammation. Older nodules may, from causes not well understood, show recrudescence of the original process. Causes.—The process arises almost exclusively in connection with tuberculosis, but is occasionally seen in other chronic infec- tions; in some instances small nontubercular abscesses may caseate. Caseation is sometimes seen in serous cavities: ¢. &., pericardium or pleura. Rarely, the retention of mucoid materials, as in the Fallopian tubes, may be followed by inspissation and caseation. Results —Once the caseous mass is thoroughly encapsulated, it becomes permanent; the capsule is likely to become calcareous, and lime salts may be infiltrated into the cheesy material, con- verting it into a stone-like structure. The condition can not be properly said to be a cure, but only a quiescent stage, likely at any time to be followed by recrudescence of the original exciting cause. 5. Sphacelation en masse, or Gangrene.—This process is also known as mortification. A surgical term, xecrosis, is applied to death of bone ez masse. Gangrene or mottification is the death of any tissue, followed by putrefaction, while attached to the living body. Varieties —(a) Motst gangrenc, which is further divided into (2) circumscribed and (2) spreading ; (6) dry gangrene ; (c) hospital gangrene. (2) Moist gangrene may arise from disturbance of the blood supply—arrest of arterial influx, capillary flow, or venous exit. Gangrene may result from edema ; when due to injury, it is known as traumatic gangrene ; when caused by inflammation, it is called wnflammatory gangrene. The inflammatory processes arresting capillary circulation, coagulation necrosis occurs, followed by gangrene. The cutting-off of the blood supply may result from occlusion of the artery by an embolus or thrombus, or a similar obstruction of a vein. Continuous pressure upon an area by progressive lessening of the blood supply leads to softening, and is followed by infection giving rise to gangrene. Destruction of tissue vitality by injury, whether traumatic, chemic, or thermic, leads to gangrene if putrefaction occur. Gangrene in all its forms represents death of the tissue in- volved, plus infection. Without infection mummification, or dry- ing without putrefaction, would occur. Such a condition is rarely, NECROSIS. 255 if ever, seen. The odor of dry gangrene is significant of infection. In spreading gangrene a violent infection occurs, spreading by the lymphatics, and with such rapidity as to preclude arrest by the resources of the tissues involved. The infectious processes asso- ciated with gangrene are not fully understood. There is, how- ever, a form of spreading gangrene—malignant edema, due to a bacillus—that has been thoroughly studied. (See Bacillus of Malignant Edema, p. 175.) Noma, or cancrum oris, is a gangrenous process that attacks the mucosa of the mouth, lips, and adjacent structures. (See Diseases of the Alimentary Canal, part 11.) A similar if not identical process has been observed in the external genitals, particularly in the female. In a number of these cases the diph- theria bacillus has been found. Symmetric gangrene—Raynaud’s disease, or digitu mortui —is a form of gangrene assumed to be due to arteriovascular spasm. It most commonly involves the same fingers on both hands, and is associated with or preceded by nervous or neuralgic phenomena that indicate its association with the nerves—sensory and, probably, trophic. Morbid Anatomy of Gangrene.—The tissues involved become soft, pulp-like, with liquefaction of the fat and cellular elements ; as this proceeds blebs form upon the surface and discoloration occurs—reddish-purple, then black, with varying shades of green. Putrefactive bacteria gain ingress and give rise to the chemic phenomena of putrefaction. Gases may be produced, and these, infiltrating the gangrenous tissue, give rise to gangrenous emphy- sema,; the blood pigment breaks down and discolors the fluids, which may be extruded through the skin. The gases of putre- faction give rise to the horribly fetid odor at times present. Where the gangrenous mass joins the living tissue, a line of de- marcation occurs; this line represents the point at which the tissue is viable, and where tissue death and the processes of in- fection are arrested, although the chemic agents engendered below this point may be absorbed. At this line of demarcation embryonic tissue, followed by granulation tissue, develops ; these, progressing from the surface, separate the dead from the living tissues; in the soft parts this progresses with considerable rapidity, while in bone the process is much slower. In the dead tissue putrefaction proceeds exactly as it would if the tissue were separate from the body; advanced fatty changes occur in the cells, which eventually liquefy. The gases produced are com- pounds of hydrogen, sulphur, ammonium, etc. During the destructive metabolism of tissue, induced and car- 2 50 GENERAL PATHOLOGY. ried on by bacteria, in addition to the products already mentioned are certain chemic bodies always the essential result of microbic growth—ptomains. These, for the most part, are highly diffusible, and are rapidly absorbed by the living tissues, and, entering the circulation, give rise to the systemic symptoms of gangrene. As well known clinically, we can understand, pathologically, how the intensity of the symptoms depends upon the amount of poison generated in the gangrenous focus, the rapidity of its absorption, and the resistance of the patient. In spreading gangrene the infection promises to be rapidly fatal by its quick spread and the extreme activity of the noxious agents absorbed ; hence, the surgeon lays great stress upon the necessity of immediate removal of the invading element. The urgency of the case is augmented by the fact that no line of demarcation occurs. In circumscribed gangrene the bacteria present may not be able to invade the adjacent normal tissues possessing their usual degree of resistance. In spreading gangrene, however, the evidence would seem to indicate that the tissue resistance must be reduced or that the bacteria possess the power of infiltrating and destroying tissue not previously injured. By some, spread- ing gangrene is believed to be an infection of the lymph-spaces, along which the bacteria travel, elaborating their poisons, which, in turn, destroy the adjacent tissue. (2) Dry gangrene differs from the preceding in that the less juicy nature of the tissues involved resists infection and shows a more marked tendency to mummification. It commonly results from atheroma or obliterative changes in the blood-vessels to the part. The skin being unbroken, there is little tendency toward infection and consequent putrefaction. It is associated occasionally with diabetes and other adynamic states in elderly people having the vascular lesions already noted. It is spoken of as senile gangrene and as diabetic gangrene under the conditions just named. (c) Hospital gangrene is now.a historic disease, modern anti- sepsis having led to its disappearance. It probably represented an infection the exact nature of which we can only surmise. CHAPTER V. CIRCULATORY DISTURBANCES, Anemia.—The term anemia is used to designate certain changes in the blood in which its functional activity is lessened ; but, as here considered, reference is made to the local anemia dependent upon changes in the circulatory apparatus, and not, essentially, upon changes in the blood itself; it is, therefore, an ischemia. Causes—(1) Faulty distribution of the blood, as in shock, when the blood tends to accumulate in the larger veins, particu- larly the splanchnic veins. (2) A very much weakened circula- tion, whether due to shock, disease, or the influence of poisons, may be too feeble to force the blood through the capillary sys- tem, particularly in the skin and brain; hence, cerebral anemia and cutaneous anemia may arise. (3) Diseases of the blood- vessels, such as atheroma ; obliterating inflammation of an ar- tery will lead to lessened blood supply in the distribution of that vessel. (4) Pressure. (5) Occlusion of an artery, whether com- plete or partial, as by ligature, pressure of a tumor, thrombosis, or embolism. (6) Spasm of the blood-vessel, due to contraction of its muscle fibers, either dependent upon or independent of the innervation. (7) An abnormal perivascular pressure in the area involved may lessen the possible ingress of blood. This in- creased perivascular pressure may arise in a number of ways. Organizing cicatricial tissue may, by its contraction, so increase the pressure normally exerted upon the capillaries that the blood flow may be greatly diminished or even obliterated in some, if not all, of the capillaries of the area involved. Morbid Anatomy.—tThe area is pale and bloodless, and the tem- perature is likely to be lower than normal, or, when the general body-temperature is above the normal, the anemic area will show a less marked elevation; there may be some edema, and, as will be seen later, the stagnation of regurgitation may be evident. Liffect.—If the ischemia be temporary, there will be but slight interference with function ; if the process be slowly developed, a gradual lessening of function will occur, and the area may undergo degenerative, necrotic, or atrophic changes; the same result may follow a slight anemia that persists. If the local 17 257 258 GENERAL PATHOLOGY. anemia be suddenly developed, and the blood supply is insufficient to maintain nutrition, death of the part may ensue; such a con- dition may follow ligation of the main artery of a limb. Local anemia lessens the functional activity of the tissues involved, diminishes their reparative power and resistance to infection, and if the flow be greatly reduced or abolished, even for a short time, degenerative changes take place in the capillary walls which in- crease their permeability and favor the formation of exudates, and sometimes capillary hemorrhages, upon the reentrance of blood or the reestablishment of the circulation, or after the occurrence of satisfactory collateral anastomosis. If the cutting-off of the blood supply occur in an artery sup- plied by a branch that communicates indirectly with the area in- volved, and the circulation be turned through the branch to sup- ply nourishment in the indirect route indicated, such a process is spoken of as collateral anastomosis. With the occlusion of an artery the blood-pressure beyond the obstruction gradually les- sens until a point is reached when it is less than the pressure in the veins. Backward distention may now occur, so that an area that at one time.showed marked ischemia now becomes an area distended by venous blood. This constitutes stagnation or regurgitation, and probably ends in infarction. (See Embolism.) Ischemia is sometimes said to be collateral or compensatory when it results from the accumulation of blood elsewhere. Hyperemia (“ Active Hyperemia” or “ Active Congestion”’ of Some Authors).—This condition is dependent upon an increased arterial influx, a distention’of the capillaries by arterial blood, and hence called arterial hyperemia, in contradistinction to a condition, to be considered later, in which the blood present is essentially venous. Causes—(1) Physiologic, as the hyperemia of the mucous membranes during digestion or of the uterine mucosa during menstruation. (2) In inflammation hyperemia constitutes the first stage, and usually persists during the activity of the pro- cesses. (3) Increased arterial pressure or tension; ordinarily, it is probable that the greater quantity of the blood is in the venous system, but when there is increased cardiac activity, the arterial and arteriocapillary systems become surcharged ; examples of this are seen in the flushed face of active exercise and in the apoplexy that follows violent exertion. (4) Meuroparalytic, as when the stimulus to the vasoconstrictors is withdrawn. (5) Neurotonic, as when there is hyperactivity of the vasodilators. (6) Local anemia is, at times, quickly followed by a more or less marked arterial hyperemia. Thus, prolonged pressure is CIRCULATORY DISTURBANCES, 259 not uncommonly followed by active hyperemia of the area. A similar hyperemia is seen to follow the removal of Esmarch’s bandage, applied for the purpose of preventing hemorrhage during the progress of operations. The local anemia produced by cold is frequently followed by an arterial hyperemia. (7) A sudden stroke applied to the skin is quickly followed by the occurrence of a local hyperemia, probably depending upon a temporary par- alysis of the vasoconstrictors. (8) Certain chemic bodies also induce hyperemia: e. g., mustard, chloroform, cantharides, etc. These probably act by inducing inflammation,—in other words, as irritants,—and the result should therefore be considered with inflammatory hyperemia. Hyperemia is said to be compensatory and collateral when the blood is forced into one area by reason of its inability to enter another, or as the result of anemia else- where; such a condition is observed in the increased amount of blood sent to one lung when the other is solid or compressed. Morbid Anatomy.—During life redness, increased cellular activ- ity, and usually a slightly elevated temperature are manifest ; swelling, discomfort, and, perhaps, pain may accompany the condi- tion ; if the process is physiologic, the functional activity is usually | increased; in pathologic hyperemia inflammation is likely to occur. Persistent physiologic hyperemia may lead to hypertrophy ; simi- lar pathologic hyperemia may cause some of the degenerative processes already described. Postmortem, the evidence of hyper- emia may be wanting, as the result of the emptying of the arteriole and capillary. Microscopically, however, there will usually be found capillary rhexis, and, if the process has persisted, degenera- tive or inflammatory changes may have ensued. Plethora, also known as polyemia and repletio, implies an abnormal fullness of the entire vascular apparatus. Several forms have been described, dependent upon the material that is increased in the blood, whether it be an increase in the water, in the albu- minous compounds, or in the corpuscular elements, Thoma speaks of a plethora vera, in which the blood present is normal ; hydremic plethora, as dependent upon an additional quantity of water; again, when the plethora seems to involve the entire vascular system, it is said to be general plethora; a localized form is described that is analogous to congestion, but is sometimes spoken of as vascular plethora. An overdistention of the lymph-spaces is spoken of as lymphatic plethora, a condi- tion closely allied to edema. (See also chapter on the Blood, pt. 11.) Hemorrhage.—The escape of all the constituents of the blood constitutes what is ordinarily spoken of asa hemorrhage. Hem- otrhages are said to be arterial, venous, capillary, or mixed, 260 GENERAL PATHOLOGY. depending upon the vessel or vessels from which the bleeding occurs. Hemorrhages as a result of solution in the continuity of the blood-vessels are spoken of as hemorrhages per rhexin. The hemorrhages that arise as a result of trauma are properly to be classified with this group. The injury to the vessel may not be sufficient to permit the escape of blood at once, but later degen- erative or inflammatory change may cause the vessel to give way. Increased arterial tension is also said to be a cause of hemor- rhage. It is probable, however, that the normal blood-vessel, whether it be artery, capillary, or vein, not previously injured or diseased, never ruptures as the result of a simple rise in the blood-pressure. Developing blood-vessels may form exceptions to this rule. Whena hemorrhage occurs from a blood-vessel (cap- illary or vein) without manifest solution in the continuity of its wall, the condition is spoken of as hemorrhage per diapedesin. Such hemorrhage is seen to occur as a result of venous obstruc- tion. The increased permeability of the blood-vessels is largely induced through interference with their nutrition, as after persist- ent local anemia, or as a result of injury, mechanical or thermic, as well as chemic; including under the last-named the destruc- tive influences manifested upon the vascular endothelium by the poisons of many bacteria. As illustrating the influences of bacteria and bacterial poisons in the production of capillary hemorrhage, the cutaneous, mucous, and submucous hemorrhages of septicemia, cholera, yellow fever, and allied diseases may be cited. There is a growing belief that rheumatism may be a bacterial disease, and, if so, the capillary hemorrhages present in the disease called purpura rheumatica may be of infectious origin. The extensive ecchymoses that occur in phosphorus-poisoning are probably brought about by alterations in the blood and by degenerative changes in the capillary walls. A similar explanation is probably operative with regard to the capillary hemorrhages induced by the poison of venomous reptiles. In addition to the morbid conditions just considered,—in which it would appear that the occurrence of hemorrhage was dependent upon an acquired alteration in the blood or blood-vessel, or in both, and hence called an acquired hemorrhagic diathesis,—we occasionally find individuals possessing an extraordinary tendency toward the occurrence of severe hemorrhage resulting from the most trivial cause, which tendency seems to have been trans- mitted from ancestors who manifested the same peculiarity. Such a condition is called zxhertted hemorrhagic diathests, or hemophilia. Hemophilia, or bleeding diathesis, is transmitted commonly from the mother ; as a rule, the male children manifest the disease but CIRCULATORY DISTURBANCES. 261 do not transmit it. The female children, on the other hand, usu- ally show no manifestation of the habit, but transmit it to their children. No satisfactory explanation has been offered for this congenital hemorrhagic diathesis, although cases undoubtedly occur in which the hemorrhages are arrested by the application of agents favoring the coagulation of the blood. When inflammatory, suppurative, infectious, or ulcerative pro- cesses approach the blood-vessel from without and destroy its walls, the consequent hemorrhage is spoken of as hemorrhage by diabrodosis, or hemorrhage per diabrosin. Such hemorrhages occur from blood-vessels in the cavities due to pulmonary tubercu- losis and occasionally as a result of suppurative processes around the large vascular trunks of the neck. The influence of the nervous system in the production of hem- orrhage is but little understood. It may act indirectly through the vasomotor system, raising the arterial tension and increasing the pressure in diseased blood-vessels that are already taxed to withstand the normal blood-pressure, and hence, under the in- creased pressure, give way. Such action of the nervous system fails to explain hemorrhage from the stomach and intestines in diseases of the crura cerebri, and the occasional instances of vica- rious menstruation manifested by hemorrhages from the nose, mouth, lungs, etc. The hemorrhages of hysteria would seem to be properly classed with this group. Small areas of hemorrhage with sharply defined margins, at first red, then purplish, and eventually purplish-black, are known as petechia. Purpuric hemorrhages manifest themselves by numerous petechiz situated in the submucous or subcutaneous structures; they are also occasionally observed under serous membranes. An ecchymosis is a submucous or subcutaneous hemorrhage, commonly due to injury, but also arising from other causes. Extensive infiltration of the connective tissues by blood is spoken of as hemorrhagic infiltration, or bloody suffusion, or suggillation. When blood collects so as to form a distinct tumor, it is called a hematoma, Hemorrhages from various cavities and surfaces have received special names, depending upon their location or on the phenomena to which they give rise : hemorrhage from the nose is called efzs- taxis ; hemorrhage from the lungs, dronchopulmonary hemorrhage, or hemoptysis; excessive menstrual flow is mcnorrhagia, and uterine hemorrhage occurring independently of the menstrual flow, metrorrhagia ; hemorrhage from the bowels, exterorrhagia ; hemorrhage of the urinary organs, kematuria ; hemorrhage into joints, hemarthron or hemarthros ; hemorrhage into the brain, 262 GENERAL PATHOLOGY. cerebral apoplexy, or hematencephalon ; blood in the pleural cavity, hemathorax ; a collection of blood in the pelvic peritoneum or in the tunica vaginalis testis is spoken of as a hematocele ; hemor- rhage into the central canal of the spinal cord, hematomyela ; hemorrhage into the pericardium, hemopericardium ; hemorrhage into the peritoneum, /emoperitoneum ; and so on. The effects of hemorrhage may be local or constitutional. The local changes to be considered are only those that arise in con- nection with accumulations of blood that remain in contact with the living tissues. Blood coming in contact with the digestive juices is more or less modified by their action. In the stomach it forms a brown or brownish-black, grumous substance, resembling coffee-ground ; hence the term “ coffee-ground vomit,” used to designate the vomiting of more or less altered blood. Within the intestinal canal the alteration is more marked when hemor- rhages have occurred sufficiently high to permit prolonged con- tact with the intestinal juices. The blood of rectal hemorrhage may escape with but little alteration. In hemorrhages arising in the upper intestine the blood is usually converted into a tarry substance. Blood thrown out into the serous cavities may be absorbed. The fate of hemorrhages into the connective tissues is largely dependent upon the amount of blood extravasated and upon the damage to which the tissue has been subjected. In small hemor- rhages the blood rapidly breaks down, the red corpuscles yield their hemoglobin and undergo fragmentation, and eventually solution, the resulting products being carried away by the lymphatics. The display of color that occurs in bruised areas or areas of local hemorrhage is dependent upon alterations in the hemoglobin. Distinct collections of blood (hematomata), if still communicating with an artery, may remain as false aneurysms. (See Aneurysms.) The small amount of infiltration at the periphery of the tumor is replaced by cicatricial tissue, which, with the condensed structures, forms a false wall; this false wall may limit the hemic tumor or may gradually yield and eventually rupture. Similar collections, not communicating with an artery, usually, in time, undergo complete absorption ; sometimes, how- ever, they are walled off by a newly formed connective-tissue membrane, which may become calcareous ; in time, this may con- tract and eventually leave nothing but an area of induration. Small residual collections of unabsorbed blood may undergo cal- careous change. The systemic phenomena induced by hemorrhage are dependent upon the amount of blood lost and upon the rapidity with which CIRCULATORY DISTURBANCES. 263 it escapes. A considerable quantity of blood may be lost by a slowly oozing hemorrhage without giving rise to any conspicuous symptom. A much smaller quantity, however, suddenly ejected by an artery, may induce a rapidly fatal issue. In severe hemorrhage the blood-pressure begins to fall coincident with the blood loss. This fall in blood-pressure lessens the amount of blood that will escape (in the same length of time under higher blood-pressure the loss would be greater), and favors the occurrence of coagu- lation, at the same time permitting contraction of the blood- vessel. The sudden drop in blood-pressure, with the associated faulty distribution of the blood, give rise to cerebral anemia, which, if the fall be marked or long continued, may terminate fatally. Under lower blood-pressure a clot not uncommonly forms in the wounded vessel, and with the complete arrest of hemorrhage the volume of blood is made up as soon as possible by removal from the lymph-spaces of the available fluid in the body, gradually restoring the circulatory volume and paving the way to complete regeneration of the blood. (See Blood.) Congestion.—Congestion is also known as venous hyperemia or venous congestion, passive hyperemia or passive congestion. This condition is due to faulty exit of the blood, and to its accu- mulation in the veins and capillary system of the area involved. In contrast to hyperemia, in which there is an increased amount of arterial blood, in congestion there is an increased amount of venous blood. Causes.—Any condition that prevents free venous exit, and that at the same time does not limit arterial ingress ; pressure, and con- stricting bands that compress the easily collapsed veins and not the more rigid arteries ; diseases of the veins, such as inflamma- tion and thrombosis ; tumors, and pressure from surrounding or adjacent organs or structures; in a feeble circulation congestion is favored by gravity, as in the congested extremities of individuals suffering from valvular heart-disease ; this congestion, dependent upon feebleness of the circulation, is illustrated in the hypostatic congestion of the lungs that accompanies typhoid fever and other adynamic states; here the congestion is favored by gravity, as already noted. Arrest of arterial flow may lead indirectly to con- gestion depending upon the regurgitation of blood from veins in which a more or less constant pressure is maintained ; such vas- cular distention, at first manifested in the larger veins, but sooner or later reaching the venules and capillaries, is termed the con- gestion of regurgitation. Morbid Anatomy.—This is largely dependent upon the duration of the process and its magnitude. During life the area involved is 264 GENERAL PATHOLOGY. edematous, swollen, bluish, with a temperature usually lower than normal. The cause of the swelling will be further considered when dealing with edema. The gradual reduction in circulatory activity gives rise to overdistention of the capillaries of the area involved, degenerative changes in their walls, diapedesis, and corpuscular plugging. The distention of the capillaries by plugs in which the cellular elements may no longer be recognized (stasis) is fre- quently seen. Asa result of the breaking down of these quies- cent red blood-cells, both within and without the blood-vessels, a certain amount of pigmentation may be present, particularly where the process has been long continued. Prior to complete stagnation and dissolution of the cellular elements restoration of the circulation is possible. The process is likely to terminate in degenerative, atrophic, or necrotic changes in the tissues involved ; this is due to the fact that nutrition in any given area is as dependent upon the removal of the products of cell life as it is upon the supply of pabulum. If the area involved be large, and the process be sufficiently marked, coagulation necrosis, followed by gangrene, may occur. Such extensive necrotic processes are, of necessity, preceded by stasis. Congestion is likely to persist postmortem and to be evident, thereby differing from hyperemia. The form of congestion that develops after the cessation of circu- lation, known as suggi/lation, must be differentiated from conges- tion that develops during life. Postmortem suggillation is not usually accompanied by edema, and does not show the nutritive changes that accompany antemortem venous stasis. (See p. 22.) Stasis.—When, as the result of the slowing of the circulation, the obstruction of gravity, inflammation, or of injury, the blood stops circulating in the capillaries of an area, the condition is spoken of as stasis. It is a very common sequence of congestion, occasionally occurs in hyperemia, and is a more or less constant phenomenon in inflammation. The extent of stasis in inflamma- tory processes is dependent upon the activity of the inflammation and upon the recuperative powers of the circulation. The viru- lence of the infection is no doubt also a determining factor. In addition to the causes just mentioned, stasis occasionally arises as a result of tension occluding the blood-vessels to or from an area, and may also be caused by inspissation: as, for example, from prolonged exposure of serous surfaces, notably the peritoneum. The corpuscular changes terminate in dissolution, fragmentation of the cells, and not infrequently necrosis of the capillary walls ; the necrotic change may also involve the perivascular structures. Edema implies abnormal or excessive transudation of the fluid portion of the blood into, or its abnormal retention in, the lymph- CIRCULATORY DISTURBANCES. 265 spaces. As the large serous cavities are generally conceded to be lymph-spaces, the accumulation of serum such as is seen in the ascites that may accompany cirrhosis of the liver belongs truly to the edematous condition. Causes.—The pathology of edema is intimately associated with the normal process of lymph formation. When physiologists satisfactorily determine the origin of lymph, we will be better able to appreciate the overdistention of the lymph-spaces seen in edema. It is probable that the cause of edema is never a single factor, usually depending upon a combination of conditions, among which may be considered alterations in the blood, in the blood-pressure, and in the capillary wall, and interferences with the normal flow of lymph. To these may possibly be added decreased perivascular pressure, and possibly chemic and struc- tural changes in the tissues ; that the nervous system may exert a certain causative influence can not be overlooked, but what the factor is or the manner of its action can not be so accurately determined. Some are inclined to believe that mere changes in the blood will not produce edema until sufficient time has elapsed for the blood changes to give rise, either directly or indirectly, to changes in the vessel walls. The changes in the vessel walls consist, for the most part, of alterations in the endothelium of the capillaries. The endothelium may become granular, cloudy, or even partially exfoliated. With such alterations in the endothe- lium, enlargement of the stomata occurs, or even separation of the endothelial plates along their line of juncture. It is probable that in all forms of edema that arise from increased blood-pressure some change in the endothelium is an essential part of the process. When there is an obstruction to the onward flow of the blood, such as may occur from ligation or occlusion of the principal veins, or when there is backing of the blood, which increases the pressure in the capillaries and leads to such degenerative changes in the endothelium as to permit extravasation of the serum, edema occurs. Similarly, venous congestion, due to inability of the heart to propel the venous blood, may induce the same lesion. That edema produced by obstruction to the onward flow of the blood is directly due to the increased intracapillary pressure can not be said to be definitely demonstrated. It is probable that it arises, in part at least, as a result of associated degenerative changes in the endothelium, increasing the permeability of the vascular wall and permitting the occurrence of serous transuda- tion. The fact that the blood-vessels in an edematous area may show no recognizable structural lesion has led to the belief that edema may, under certain circumstances, be dependent upon an 266 GENERAL PATHOLOGY. increased secretory action of these cells, presuming, of course, that the normal lymph is produced by a process of secretion and not simply by transudation. The presence of certain materials in the circulation undoubtedly favors the occurrence of edema. For the most part these are toxic substances, of which certain bacterial poisons may be taken as examples. It is not improba- ble that they increase the diffusibility of the serum and at the same time injure the endothelial cells. The edemas that occur in the last stages of tuberculosis and in various cachexie associated with lowered nutrition, are probably dependent upon the faulty nourishment of the vascular endothelium as well as upon altera- tions in the blood, and in not a few of these the presence of toxic materials in the circulating fluids can not be positively excluded as adjuvant factors. The influence of tissue tension in the occur- rence of edema must not be overlooked. With vascular changes practically the same, edema must, of necessity, occur with more rapidity in lax tissues, such as the eyelid and scrotum, than in tissues of greater density, such as periosteum and bone. Nor- mally, the nutrition of the tissues is maintained, in part at least, by serum passing out from the vessels into the perivascular struct- ures (primitive lymph-spaces) ; the cells abstract from this fluid the elements necessary for their nutrition, and yield to it excre- mentitious products, after which it is removed from the tissues by the lymph-stream. It will be seen that any obstruction to the onward flow of the lymph, such as may result from pressure upon the lymph-duct, may give rise to an accumulative edema in the area drained without the necessity of presupposing any degenera- tive change in the blood-vessels of the part. A form of edema known as edema ex vacuo is said to occur when brain-tissue or tissue from the spinal cord disappears by any process, and the resulting cavity, or loss of tissue, or shrink- ing of the organ, must be filled in. ‘Edema is often named for the cause that gives rise to the lesion in the blood-vessel or blood primarily. Such edema may be known as éoxic, infectious, cachectic, traumatic, ischemic, inflamma- tory, thermal, or, in some cases (as when the dilatation of the blood-vessels is dependent upon errors or lesions in innervation), the condition may be spoken of as trophic edema or neuropathic edema. Morbid Anatomy.—Edematous tissue is usually pale, pits on pressure, and, as a result of the deficient circulation of the blood, is lower in temperature than the normal. On incising, serum escapes, and the watery condition of the tissue can be readily seen. By reason of the deficient circulation, the resist- CIRCULATORY DISTURBANCES. 267 ance of such tissue is lowered, and this renders it extremely sus- ceptible to infectious and necrotic processes. Not uncommonly the edematous tissue shows well-marked and advanced degener- ative changes. (See Hydropic Degeneration, p. 244.) Edema fluids, spoken of as ¢ransudates, differ materially from inflamma- tory accumulations, called exudates. Edema fluids possess a low specific gravity, are poor in cells, and contain a relatively small proportion of albumin. A specific gravity of 1016 to 1020 is not uncommon in inflammatory exudates, while dropsical collec- tions rarely attain a specific gravity of 1010, usually falling below —1006 to 1008. Transudates are commonly clear; exudates are turbid and usually rich in leukocytes. Different names have been given to the accumulations of drop- sical fluids, based upon the location, cause, or admixture with other fluids. When the edema is more or less general, the term hydrops universalis is applied; edema of the connective tissues, particularly of subcutaneous connective tissues, is called anasarca ; dropsy of the peritoneum is spoken of as hydroperito- neum or ascites; dropsy of the pleura, as Aydrothorax, which condition may be unilateral or bilateral ; dropsy of the pericar- dium, as hydropericardium ; fluid accumulation in joints, as dropsy of the joints or hydrops articult ; etc. The origin of edematous collections is sometimes indicated by the name: as, for example, renal dropsy, cardiac dropsy, congestive dropsy, angiosclerotic edema (edema associated with sclerotic changes in the blood- vessels). Reference has already been made to toxic and infec- tious edema and other forms of edema. THROMBOSIS. A thrombus is a more or less uniformly solid or a semi- solid body, formed during life in the heart or blood-vessels, and resulting from causes that lead to the agmination, agglutination, or coagulation of one or more elements present in the blood. The older definition—an antemortem intravascular clot—did not take into consideration the agmination and agglutination of platelets and leukocytes. Most thrombi, however, are nothing more than fibrinous coagula, relatively rich in leukocytes and platelets. The term thrombosis is applied to the process ter- minating in the formation of a thrombus. It is also somewhat loosely used to cover the associated conditions. In most instances there is little difficulty in differentiating thrombi from postmortem clots. Coagula formed after death have certain points that are highly characteristic ; they are usu- 268 GENERAL PATHOLOGY. ally smooth on the surface, and show no attachment to the ves- sels in which they lie, although they may be entangled: as, for example, in the muscular columns or the tendinous cords in the heart. This absence of attachment is highly important, even when a thrombus has been dislodged from its point of attach- ment; the point from which the thrombus has been detached will usually be easily recognized as a roughened area upon the blood-vessel or heart wall, a cardiac orifice or valve leaflet. In many instances a point can be found on the thrombus that shows evidence of past attachment. The postmortem clot has a moist, glistening surface, is usually red in color; some part of it always shows the redness due to red blood-cells, and an im- portant differentiation, for which we are indebted to Cohnheim, is that in the thrombus there is little difficulty in longitudinal splitting. The thrombus usually hasa frayed-out end. A post- mortem -clot does not show the changes that may be seen pro- ceeding ina thrombus. (See p. 271.) Occasionally, where coagulation of the blood postmortem goes on very slowly, sufficient time elapses for the red blood-cells to settle to the most dependent portion, giving rise to a clot the upper layers of which are colorless and jelly-like, while the lower portion shows a deeper color than usual by reason of its contain- ing more red blood-cells. Very often, when life is almost extinct (agonal period), the very slow rate at which the blood is flowing may favor the oc- currence of thrombi, which, later, become continuous with post- mortem clots, coagulation going on around the thrombus after. death. While not restricted to the right side of the heart and the pulmonary artery, such clots frequently occur in that location. Red thrombi contain blood coloring-matter usually in the entangled red blood-cells ; these are the thrombi that form in stagnant or practically quiescent blood. White thrombi are thrombi consisting of fibrin with a varying number of leukocytes and blood platelets, and are formed in flowing blood. Thrombi may be mixed—the so-called gray thrombi, in which the gradual slowing of the blood has led to a slight deposition of the red blood-cells with the fibrin. As a result of ribbed, “ frayed- out,” or irregular thrombus-formation, longitudinal cavities are sometimes formed in which the more or less quiescent blood pro- ceeds to clotting, and enters into the formation of the completed thrombus. This condition gives rise to thrombi that may be, in a sense, mixed, certain parts of the thrombi being distinctly red, other parts gray, and still other areas red and jelly-like, closely CIRCULATORY DISTURBANCES. 269 resembling the thrombi formed in quiescent blood. When the thrombus is made up of layers, such as occur in the cavity of an aneurysm, the thrombus is said to be stratified. Whena throm- bus remains where it originated, and arises independent of other thrombi, it is called a primary thrombus. The term propagated thrombus is applied to a thrombus that extends some distance from the point at which it originated ; such thrombi are extremely likely to show different ages at different points, and may extend to an indefinite length. A thrombus developing from an embolus, or a thrombus that arises secondary to an ex- isting thrombus, is known as a secondary thrombus. When a thrombus leads to occlusion of the blood-vessel in which it lies, it is said to be an obstructing thrombus. When it permits the blood to flow one way and occludes a current flowing in the opposite direction, it is termed a valve thrombus. When the thrombus lines the wall of the cavity,—e. g., an aneurysm.or a blood-vessel,—it is said to be a parietal or a mural thrombus. When a thrombus extends around a blood-vessel, it is said to be annular. When a thrombus has formed with a distinct canal, it is spoken of as a channeled or canalized thrombus. The “ball thrombus’ is not attached, although evidence of recent attachment may be present either on the thrombus or on the vascular or cardiac wall; a point of separation from a fragment, still attached, may often be recognized. Ball thrombi are most frequently found in the dilated left auricle in cases of mitral stenosis. Polypoid or pedunculated thrombi, so-called cardiac polypi, are most frequently seen in the left auricle ; the point of attachment is usually the margin of the fossa ovalis or its imme- diate vicinity. The pedicle, and not uncommonly a larger part of the thrombus, may show advanced organization. The struc- ture of such partly organized polypi may resemble fibrous or myxomatous tissue, and hence they have been termed /bro- matous and myxomatous polypi respectively. An endothelial covering is sometimes demonstrable, and calcareous infiltration may be in progress or even in an advanced stage. The most important division of thrombi is into simple or bland and infected or infective, the former meaning aseptic thrombi, containing no bacteria, the second meaning thrombi containing bacteria, hence infected thrombi. A further division of infected thrombi has been proposed. It is suggested that the term septic thrombi be applied to those containing organisms of suppuration, and the term putrid thrombi to those that contain bacteria of decomposition. The fact that the bacteria of decom- position may be present alone or associated with the organisms 270 GENERAL PATHOLOGY. of suppuration deprives such a division of much of its theoretic value. Thrombi are sometimes called arterial or venous, and, under the latter, a separate form is named, dependent upon its loca- tion in a distinct venous system—portal thrombi. Causes.—The essential exciting cause of a thrombus is that process terminating in coagulation of the blood. Other causes are : (1) Any body within the circulation, not covered by endothe- lium, will lead to attachment of the third corpuscle and to the subsequent formation of a clot or thrombus ; (2) roughening of the vascular wall, as observed in atheroma ; (3) slowing of the circulation, such as occurs in partial occlusion of a blood-vessel, or in complete occlusion, as represented by ligation. It is main- tained, and probably justly, that a blood-vessel may be ligated and its lumen occluded without the intervention of a clot. This implies great care in applying a ligature, so that it does not injure the endothelium. When a blood-vessel is ligated in its continu- ity, two thrombi are usually formed: one on the cardiac side, known as the proximal thrombus, and a second in the blood- vessel, beyond the point of ligation, known as the distal throm- bus. It is probable that complete or partial obstruction gives rise to changes in the endothelium of the vessel wall, and this favors the mural lodgment of leukocytes and third corpuscles, and hence of a thrombus. As will be noted later, the formation of a thrombus is not essential to the obliteration of a blood-vessel in which the circulation has ceased. Indeed, it is held by some authors that thrombosis interferes with the obliterative endarter- itis that normally leads to the disappearance of a blood-vessel. (4) Any alteration in the vessel wall that injures the endothelium favors the development of a thrombus. (5) Chemic changes in the blood also favor the development of thrombi; examples of these are seen in diphtheria and in adynamic conditions with very much slowed and enfeebled circulation. Such thrombi are called marasmic thrombi. (6) Hyperinosis, such as develops in pregnancy, is nature’s method of anticipating: hemorrhage, the increased amount of fibrin favoring the arrest of bleeding by the development of thrombi. Hyperinosis is not of itself an exciting cause of thrombosis, as many conditions are asso- ciated with an increase in the amount of fibrin-forming elements in the blood without any marked tendency toward the occurrence of thrombosis. (7) Chemic changes leading to a thrombus may be produced in the blood by the injection of certain agents: ¢. g., ether. (8) Where a tumor infiltrates or comes in contact with a blood-vessel, a thrombus is likely to form. (9) A primary CIRCULATORY DISTURBANCES. 271 thrombus favors the development of secondary thrombi. (10) Mycoses of the blood favor the development of thrombi. (11) Embolism favors thrombus-formation. Changes That a Thrombus May Undergo.—These changes are dependent upon whether the thrombus is simple or infective. ~~? Ord Sim oeetsias. be ae eer Fic. 185——SECTION THROUGH A PART OF A VEIN WITH ITS CONTAINED ORGANIZING THRoMBUS.—(Schmaus.) W. Wall of vein. a. Adventitia. m. Media. 72. Intima. lV. Blood-vessel in the wall of the vein. 7. Thrombus, now largely composed of granulation tissue. c,c,c. Young blood- vessels; those near the intima are larger and more fully developed than those extending into the thrombus, the latter being younger. In infective thrombi the only changes that are likely to occur are those constantly associated with infection : namely, “guefaction, softening, or breaking down; rarely, in infected thrombi, dis- lodgment may occur. The changes to be considered in semple thrombi seldom occur in the infected thrombi, with the exception 272 GENERAL PATHOLOGY. of softening. The fragments of an infected thrombus become infected emboli, and lead to the dissemination of the infective material and to its deposition in other parts of the organism ; besides this, infected thrombi are constantly throwing into the circulation bacteria or the products of bacterial life, this condition constituting what is known as septicemia or mycosis of the blood. When the infected material contains pyogenic organisms, the emboli, lodging, give rise to abscesses ; such abscesses are spoken of as pyemic or metastatic, and the disease is known as pyewia. Before the elucidation of the subject of blood-poisoning, afforded by our knowledge of bacteria and infectious processes, it was pre- sumed that metastatic abscesses resulted from the presence of pus in the blood; hence the name pyemia. We now know that the condition is due not of necessity to the presence of formed pus, but to that of agents capable of inducing suppurative processes. The following changes may occur in thrombi: I, Dislodgment.—Vhis occurs but rarely. The cases that the writer has observed have been from large tumors of the uterus, where a thrombus has formed in one of the massive sinuses of such a tumor, and, becoming dislodged, has reached the lung and blocked the larger vessels to that organ, leading to almost instant death. Dislodgment of a thrombus is favored by any sudden increase in the rapidity of the circulation, particularly when the accelerated current is brought directly in contact with the thrombus ; manipulation of the affected part, or even com- paratively slight muscular movement in the affected limb, when an extremity is involved, may give rise to dislodgment. 2. Decolorization.—Decolorization is possible only in the red thrombus, and is due to the gradual absorption of the coloring- matter by the circulating blood, which flows over, around, or through it. 3. Re-solution.—lt is difficult, if not quite impossible, to demon- strate the occurrence of this process ; but there can be no doubt that the simple, noninfected thrombus, due to temporary con- _ ditions, may be dissolved or may undergo solution upon the re- moval of the cause.” 4. Softening —This is not so common in the simple as in the infected thrombus, and is usually due to conditions of develop- ment, to the location and size of the thrombus, and to blood changes that militate against the process of organization. Wien this change occurs without infection, it is termed sewple softening when bacteria are present, septic or infective softening. When softening and breaking down occur, the fragments, reaching the eretlatcns form simple or infective emboli, depending on whether CIRCULATORY DISTURBANCES. 273 the thrombus contained viable organisms or not; more com- monly, instead of softening, there is really a condition of Srag- mentation, in which merely the end of a thrombus is broken off. 5. Organization.—This process is possible only in the absence of infection. It may occur in infected thrombi after the subsidence of infection, although upon this point there must remain much doubt. The conversion of the thrombus into connective tissue is effected largely through the activity of the endothelial cells of the intima. Before the beginning of organization considerable con- traction is usually brought about by removal of the fluids present in the thrombus, and possibly by a certain amount of liquefaction and absorption. Where the thrombus becomes continuous with Fic. 186.—TRANSVERSE SECTION OF A THROMBOSED BLOOD-VESSEL IN WHICH ORGANIZA- TION AND CANALIZATION OF THE THROMBUS ARE IN PROGRESS. a. Newly formed connective tissue of the thrombus. 6. Tunica media. c. Tunica intima. d. Young cell infiltrate of the thrombus. A similar infiltrate of the coats of the vessel is shownat/, 7. e,e. Remainder of the not yet organized thrombus. . Developing canals. the intima, the endothelium gradually extends .over its surface. From this endothelial covering processes of young connective- tissue cells extend downward into the thrombus, forming capil- laries. A similar proliferation of the endothelium beneath the thrombus also takes place, and young blood-vessels from the adjacent nutrient vessels are pushed forward into the proliferate. During the extension of this embryonic tissue formation further absorption and shrinkage of the thrombus occur. Gradually the new connective tissue replaces the thrombus, and organization of the cicatricial tissue is completed as usual. (See Process of Re- pair.) The activity of the leukocytes in this process is no longer conceded to be important. With the presence of infection large numbers of leukocytes may be found. They are not, however, 18 274 GENERAL PATHOLOGY. regarded as essential elements in the production of the embryonic tissue through which organization is eventually completed. The influence of the organized body upon the blood-vessel will be, of course, dependent upon the extent and location of the thrombus and upon the completeness with which it occludes the vascular lumen. The influence of the subsequent cicatricial contraction is shown by the deformity that it induces, and is particularly marked in the organized thrombi that constitute the vegetations on the valve leaflets in endocarditis. (See Results of Endocarditis.) 6. Calcification —When a thrombus forms in a slowed circula- tion,—e. g., of a dilated vein,—and is attached to the vein or lodged in the sinus of the valve, infiltration by lime salts not uncommonly occurs, and produces the so-called phlebohths, or “vein stones’’; arterioliths and stone-like concretions attached to the cardiac walls or orifices are produced in a similar manner ; infiltration of lime salts is also likely to occur in a thrombus that is organizing or that has organized. Modifications of some of the foregoing conditions are occasion- ally considered as separate processes; thus, a large thrombus may exhibit a ceztral softening, and postmortem or during an operation—e. g., on aneurysm—a thrombus may be found in which liquefaction necrosis has occurred, converting the center of the thrombus into a reddish or yellowish fluid; this was at one time spoken of as cystic degeneration of a thrombus. An attached thrombus may remain more or less quiescent for a con- siderable length of time, or the changes that it may undergo may be so poorly marked as to be scarcely recognizable. Results of Thrombosis.—These are largely dependent upon the character, location, and cause of the thrombus and upon the changes that the thrombus itself has undergone ; the results due to such changes will suggest themselves : ¢. g., an organizing or obstructing thrombus may more or less occlude the blood-vessel ; the evidence of such occlusion will be dependent upon whether the blood-vessel is the main trunk to a limb or one of the less. important branches ; again, if the thrombus form slowly, the col- lateral circulation may sustain the nutrition to the limb or part. The alterations produced in the blood-vessel are dependent upon the changes that the thrombus undergoes; these also suggest themselves or have been indicated. CIRCULATORY DISTURBANCES. 275 EMBOLISM. An embolus is any body transported by the circulating blood, and capable, by reason of its physical characteristics, of obstruct- ing the flow of blood in any part of the vascular system. As Park states, the essential element is transportation or carriage of some solid or semisolid body in the circulation. Oil and air, while not solid bodies, may be impacted within the capillaries, and hence may constitute emboli. The transportation and lodg- ment of emboli and in part, at least, the resulting changes con- stitute the process of embolism. Emboli are usually too large to pass the capillaries. They may be composed of : (1) Thrombi detached or in fragments. (2) Fragments of the cardiac valves or endocardial vegetations ; the latter truly thrombi. (3) Calca- reous plaques. (4) Fragments of morbid growths torn from tumor masses that have penetrated a vessel wall. (5) Purely extraneous bodies, such as bubbles of air, pieces of bone, or oil globules that may have gained ingress as a result of fracture or injury to bone; extensive laceration of adipose tissue may also give rise to oil embolism. The writer had an opportunity to observe a death from fat embolism following excision of the mamma for carcinoma; the patient was an unusually obese woman, fifty years of age. As a result of trauma, not only fat but fragments of tissue may enter the circulation; laceration of hepatic tissues may result in the displacement of fragments that, later, may be recognized in pulmonary infarcts. (6) Certain parasites, such as the echinococcus, filaria, etc., are transported by the circulating blood. Thrombi or emboli are sometimes spoken of as (1) arterial, (2) venous, or (3) capillary ; multiple ; miliary ; traumatic; neo- plastic, arising from tumors; specific and nonspecific; simple and malignant: these terms explain themselves. Occasionally, an embolus arising in the venous system passes directly from the right to the left side of the heart, through a defect in the septum between the auricles or ventricles, in which case it is spoken of as a paradoxic or crossed embolus. In very rare instances, as a result of sudden alterations in the blood- pressure affecting only one area, emboli may float backward in the venous stream, producing what is known as recurrent em- bolism, or they are called retrograde emboli. This was, at one time, assumed to explain certain abscesses of the liver, which are now known to be due to emboli arising in the portal system. The most important classification of emboli is the division into 276 GENERAL PATHOLOGY. simple and infective, the terms having the same meaning as already given when considering thrombi. Changes Induced by an Embolus.—An embolus floats along in the blood stream until it reaches the bifurcation of a blood-vessel either branch of which is too small to transmit the mass, or until it enters a vessel the progressive narrowing of which soon leads to its impaction; it obstructs or arrests the stream, and com- monly leads to the formation of a thrombus ; the blood supply transmitted by the occluded vessel is arrested, and the area beyond suffers from the altered circulatory conditions. The changes that take place in the affected area vary in degree, and are greatly influenced by a number of factors, among which may be mentioned the character and size of the embolus, the func- tional importance of the tissue involved, the presence or absence of an abundant collateral circulation, and the possibility of sec- ondary infection or of a primary infection in a simple necrotic area. With regard to the character and size of the embolus, it may be said that, as a rule, massive emboli, such as dislodged thrombi of considerable size, are likely to obstruct the circulation of an area that may be sufficiently large at once to induce alarm- ing symptoms or immediately fatal results. Thus, emboli of con- siderable size thrust into the pulmonary artery may lead to almost instantaneous death. For the production of this result it is not necessary that the circulatory arrest be dependent upon the occlusion of a large trunk; the scattering of a considerable number of small emboli (an embolic shower) brings about exactly the same result. The shape of an embolus may be such as only partly to obstruct a blood-vessel, and therefore not at once to cut off nutrition to the area beyond. Soft emboli plug vessels more completely than the more solid ones, which do not so readily mold themselves to the vessel lumen. The functional importance of the tissue involved scarcely merits more than mere mention. Thus, it will be evident that a small embolus involving cutaneous, subcutaneous, or allied structures may induce so little change as to escape detection, while an em- bolus of the same size involving either the coronary artery or a cerebral area presiding over functions of great importance might, in either case, cause immediate death. The suddenness with which symptoms manifest themselves is also, to a certain extent, dependent upon the importance of the tissue involved. The pos- sibility of at once establishing sufficient collateral circulation to supply nutrition to the area determines, to a large extent, the character of the subsequent changes. With the sudden stoppage of circulation the distal portion of the artery empties itself of blood, CIRCULATORY DISTURBANCES. 277 and an area of ischemia is thereby induced. The sudden and persistent diminution in the intracapillary pressure favors the influx of blood from adjacent capillaries whose contained blood is, as a matter of course, directed in the line of least resistance. Coincident with the changes just mentioned dilatation of anasto- mosing or collateral arteries occurs, increasing the amount of blood traveling through those vessels. When the anastomosis between the artery involved and the arteries whose circulation still remains intact is sufficiently free, there is quickly formed a circulation adequate to maintain the nutrition in the previously ischemic area. With the establishment of sufficient collateral circulation the nutrition and function of the area may be resumed, while the changes that take place in the lodged embolus may be practically those already considered when discussing the changes to which a thrombus is liable. In the absence of a sufficient circulation in the area, degener- ative or necrotic processes occur. In the brain, in the spleen, and, to a cértain extent, in the kidney, there is not, beyond a given point, a liberal anastomosis between the blood-vessels of adjacent areas. Such blood-vessels are said to be zerminal; this implies that the tree-like branches given off by one vascular stem do not communicate with similar branches of adjacent vessels. The plugging of such vessels is followed by death (necrosis) of the area involved, which is now called an infarct. When the area remains ischemic (anemic or white infarct), the uncomplicated necrotic process presents the changes already described when considering coagulation necrosis. The area is wedge-shaped on section—truly cone-shaped, with the apex of the cone corre- sponding to the point of embolic obstruction and the base directed toward the surface of the organ. This typical cone shape is greatly modified by the presence of even a moderate degree of anastomosis at the periphery, and in large infarcts, or when multiple infarcts join, it may not be present. The consist- ence of the tissue is dependent upon the amount of coagulable ma- terial present. When the necrotic area has been infiltrated with lymph from the adjacent tissue, the swelling and increased density may be conspicuous. If the area be very large, the center may undergo fatty degeneration and may soften, converting it into a cyst; when liquefaction necrosis has followed the coagulative processes, the fluid may be absorbed and cicatrization may ensue. When the area is smaller, repair not uncommonly takes place. Proliferation of the connective-tissue elements occurs, resulting in-the production of embryonic tissue and finally in cicatrization ; into this lime salts may be infiltrated. 278 GENERAL PATHOLOGY. During the progress of the necrotic processes the resistance of the tissue to infection is greatly reduced, and not infrequently an infarct, resulting from a simple embolus, may develop suppuration. If the necrosis is so situated as to offer favorable opportunities .for infection, the chances of its occurrence are greatly increased. The foregoing description applies to the anemic infarct and to the process spoken of as anemic infarction. In some instances, after a varying period of anemia the capillaries of an ischemic area become overdistended with blood, admitted through adjacent communicating capillaries, or, possibly, by venous regurgitation ; from the congested capillaries extravasation of blood into the connective tissue occurs, and, in addition to the coagulation necrosis in progress in the cellular elements of the area, a further fibrinous matting together results from the associated hemor- rhagic infiltration. The resulting change constitutes a hemor- rhagic infarct,.and the process terminating in its formation is known as hemorrhagic infarction. The shape of the area is not altered by the occurrence of hemorrhagic infiltration. The swelling, however, is more marked; the color is dark red, at times almost black ; and the density is greatly increased by the presence of the coagulated blood. The subsequent changes are the same as those occurring in areas of anemic infarction. It has been held that an anemic or white infarct is but a later stage of the hemorrhagic form and that it is dependent upon the removal of the blood coloring-matter from the latter. It is possible that such a change occurs, and that the results of the two processes may be the same ; but certain infarcts are appar- ently anemic from the beginning, and others are hemorrhagic early in their development. The changes revealed by the histologic examination of the necrotic tissue will not be the same in different stages of the process. They are practically those already mentioned when considering coagulation necrosis. (See p. 250. In emboli containing bacteria (infective emboli), and in those containing the specific cellular elements of tumors (neoplastic emboli), arrest is followed by the development of the morbid process whose etiologic factor they transmit. If the embolus contains pyogenic organisms, an abscess is engendered ; by reason of the constant presence of these abscesses in pyemia, they have long been known as pyemic abscesses. By reason of the fact that such abscesses change their location, they’ were called metastatic abscesses. Emboli containing tubercle bacilli in- duce tuberculosis at their point of lodgment. It is probable that the amedic abscesses seen in the liver arise as the result CIRCULATORY DISTURBANCES. . 279 of emboli brought from the intestinal lesion. A tumor in- filtrating the wall of a blood-vessel, particularly a vein, may have swept into the circulation small fragments that projected into the blood stream, and these, in turn, arrested in the distant capillary, may resume their growth and give rise to a secondary tumor nodule, or metastatic growth. From the infected, parasitic, and neoplastic emboli secondary thrombi may form, from which, again, emboli may be broken off to continue the process of dis- semination. CHAPTER VI. INFLAMMATION AND REPAIR, INFLAMMATION. Probably the most acceptable definition of inflammation is that given by Park, which is, as he states, a modification of Sutton’s : “Inflammation is an expression of the effort made by a given organism to rid itself of or to render inert noxious irritants arising from within or introduced from without.’ It is probable that inflammation represents the process of repair plus infection or the removal of dead tissue, a relationship to be further brought out when considering the causes of inflammation. Etiology.—As just indicated, inflammation is ordinarily pro- duced by irritation or injury. The forms that these factors may assume are manifold, and any attempt to enumerate the various etiologic elements leading to inflammatory manifestations would lead far beyond the contemplated scope of the present article. The surgical tendency to consider inflammation as always the result of infection can scarcely be considered justifiable. After all, infection acts only by destroying the cells or irritating them by the noxious products of bacteria. It is true that bacteria are the most frequent irritants, and that a large percentage of the in- flammatory processes arises as a result of bacterial activity. Bacteria or their products destroy or irritate the cells, and mani- fest a peculiar action upon the fixed and migratory cells of the economy, thereby inducing inflammatory processes more or less constant for each particular species of organism. The activity of the inflammatory processes induced by bacteria depends upon one or two factors: (1) the pathogenic power of the germ in question ; (2) the degree of susceptibility of the tissues. As an example of the first condition it will be noted that if the two ears of a rabbit be inoculated with the anthrax bacillus or with the streptococcus pyogenes, using germs that are somewhat attenu- ated in one ear, anda more virulent organism for the other, there will be a decided difference in the local reaction as mani- fested in the two organs. Many experiments conducted along this line have led to conclusive proof that the pathogenicity determines to a large degree the activity of the ensuing inflam- 280 INFLAMMATION AND REPAIR. 281 matory process. The importance of the second factor in the production of inflammation is equally well established. The sus- ceptibility of the tissues may be augmented by reduced vitality ; associated irritation, by the absence of immunity, either inherited or acquired, and by circulatory disturbances, or certain perver- sions of the nervous system. The susceptibility of the animal to a given infection undoubtedly varies at different times—a fact well shown by the occurrence of severe inflammatory processes after most trifling injuries, which, under other conditions, appar- ently give rise to little disturbance. Injury to the tissue, whether it be mechanical, chemic, or thermal, is followed by the occurrence of the phenomena of in- flammation ; the extent of the inflammatory process may be de- pendent upon a number of associated factors. As just indicated, infection truly represents a chemic injury to the tissue, the noxious irritant being the specific product of the infecting organism. Inflammation may be induced by the injection of bacterial products without the presence of bacteria. Here we are dealing with chemic bodies alone. As further evidence of the phlogistic power possessed by chemic bodies may be cited the inflammation induced by the subcutaneous introduction of calomel, turpen- tine, croton oil, and similar irritants. That such inflammations are not purely of experimental production is established by their occurrence after the use of powerful antiseptics in too concen- trated a form. There can be no doubt that the abundant use of mercurial solutions in wounds—a frequent procedure in early antiseptic surgery—led to necrosis of a large number of cells and to the occurrence of a certain degree of inflammation. Recog- nizing this, surgeons have adopted asepsis whenever possible. Even in infected areas abundant flushing with sterile fluids has been found to be attended with less local reaction than the use of even mild antiseptics. Ina comparatively frequent fornt of conjunctival inflammation in the new-born, evidently the cause has not been the microorganism usually present (gonococcus), but the vigorous use of agents directed toward its destruction. In this instance and in the instances previously given the inflam- mation arises as the result of cell destruction brought about by agents directed toward the prevention of infection or toward the removal of existing organisms. The destruction of tissue and the production of exudates by chemic agents is further illus- trated by the tissue reactions resulting from the application of so-called counterirritants, such as mustard, cantharides, turpen- tine, and chloroform, all of which induce an inflammatory -tesponse. Wounds of all kinds involve destruction of a varying 282 GENERAL PATHOLOGY. number of cells and injury to others. The wound made by the sharpest instrument is walled by a microscopic layer of lacerated cells. The more extensive the wound, the greater the number of cellular elements involved ; and, of course, injuries made by dull, tearing, vulnerating bodies contain more lacerated cells than wounds of like extent made by sharp, clean-cutting instruments. It will be observed that the whole list of inflammatory causes embraces at every turn the destruction of cells. The destroyed cells at once become irritants and induce inflammation in the ad- jacent viable tissues. The simple aseptic inflammatory reactions differ from the septic, in that the latter contain destructive agents that are constantly increasing, and, hence, the inflammatory pro~- cesses seen in wounds made under aseptic conditions are but trifling as compared with the extensive inflammations following destruction of tissue associated with the introduction of infective agents that themselves further extend the cell necrosis and actively antagonize the process of repair. For this reason the surgeon has been led to regard repair as dissociated from inflammation, and to say that aseptic wounds heal without inflammatory phenomena. The pathologist must, however, recognize that all tissue injuries are attended by a certain amount of cell destruction, and that the effort made by the tissues to rid themselves of the dead elements constitutes, in a certain way, a part of the reparative effort. Still, with this admission before us we are to remember that the essential phenomena of inflammation and the essential phenomena of repair are, to a certain extent, dissimilar. Inflammation is attended by cell necrosis and degen- eration ; and repair by cell ‘proliferation and regeneration. The possible admixture of the two processes can not be gainsaid. Of course, the same cellular elements at a given point are not evincing both processes, but one may be in close proximity to the other. The periphery of an inflammatory area nearly always shows, in the absence of rapid extension, a marginal zone of reparative effort. Were the effort at repair to remain quiescent until inflammation had terminated, repair would prob- ably become an impossibility. Morbid Anatomy.—The lesions to be studied in inflammation are: (1) The changes in the blood-vessels ; (2) intravascular changes, or those occurring in the vessel contents; and (3) changes in the perivascular tissues. Changes in the Blood-vessels—These can be well studied in any vascular, transparent membrane, such as the tongue, mesén- tery, or web of the hind foot of a frog or the mesentery of any warm-blooded animal. If such transparent tissues be so ar- 7 INFLAMMATION AND REPAIR. 283 ranged as to permit of their examination under the microscope, the following changes will be noted : At the beginning of the examination the normal capillary pre- sents itself as a transparent tubule, within which can be seen the circulating blood. As a rule, the application of an irritant is not necessary ; exposure to the air, with the asso- ciated trauma incident to the arrangement of the tissue, will usually bring about the modifications to be observed. In other instances, as in the web of a frog’s foot, it may be necessary to snip off with the scissors a thin layer of the epithelial covering, carefully avoiding any wound to the underlying blood- vessels. The blood-vessels at once contract, and at the same time the current is markedly accelerated; within the first hour after the injury the brief period of contraction is fol- lowed by beginning dilatation. At first the dilatation is regu- lar ; it then becomes varicose, and, in more marked cases, saccu- lar projections of the capillary wall may be observed. Capillaries at first not recognizable, or at least not transmitting blood, dilate and become more or less distended. A similar dilatation of the arterioles, and particularly of the venules, is also to be noted. The changes so far observed are probably due to increased capillary tension and to the influence of the noxious agents directly upon the vessel wall. The rise in capillary ten- sion is probably brought about by relaxation of the arterioles through which the blood supply to the part is admitted. The increased amount of blood present in the area is evident to the unaided eye. It is not possible at this stage to recognize any structural alterations in the cells that compose the capillary wall, nor are we able to see any enlargement of the capillary stomata, or any separation of the endothelial plates. A study of properly fixed preparations usually shows that the endothelial cells are swollen, and, when the process has lasted for any length of time, there is not uncommonly evidence of degeneration or prolifera- tion, depending upon the activity of the noxious agent. Changes in the Blood and Blood-current ; Intravascular Changes. —Before the manifestation of inflammatory phenomena the stream within the capillary will be noted to be composed of two parts : (a) An axial stream, composed of the corpuscular elements of the blood, and therefore spoken of as the corpuscular stream ; (6) a circumferential or parietal stream, composed of blood-plasma, and hence called the plasmatic stream. During the period of acceleration—a period that corresponds to the contraction and beginning dilatation of the capillaries—these two clearly differen- tiated divisions of the capillary contents are easily recognized. 284 GENERAL PATHOLOGY. With further dilatation and beginning slowing of the current the axial stream widens and the plasmatic stream grows correspond- ingly thinner. Within the first hour or so the narrowing of the plasmatic stream becomes marked, and instead of remaining clear, it contains a progressively increasing number of leukocytes.* At first these leukocytes roll along the vessel wall ; later, they become attached at some point and hang off into the slowing stream as pear-shaped bodies, the small end of the pear corresponding to the point of attachment. The margination of the leukocytes is conspicuous in the small veins, but the size of even the larger dilated capillaries does not render the demonstration easy. As the dilatation of the blood-vessel becomes more marked there is poured out into the perivascular tissues a fluid derived from blood- plasma ; this fluid constitutes the liquid exudate. Along with this certain of the leukocytes, as the result of their ameboid movement, pass through the vessel wall and reach the perivascular tissues. During the dilatation of the blood-vessel the blood-current becomes slower and slower, and shows only a slight pro- gression with each heart-beat, and eventually oscillates in the capillary lumen; finally, this oscillation is arrested, and stasis or stagnation occurs. Before this final stage the differentiation into the axial and peripheral streams has disappeared, and the cellular contents of the vessel occupy the entire lumen. With the occur- rence of stasis the red corpuscles at points arrange themselves in columns composed of cells piled upon one another (rouleaux). Migration of the leukocytes continues, and many of these cells present in the stagnant blood migrate toward the periphery and eventually reach the perivascular tissues. In properly fixed speci- mens the leukocytes can be seen in various stages of diapedesis. At first a pseudopod is projected through the capillary wall, appearing on the exterior as a small, roundish, knob-like pro- tuberance. The extravascular portion of the cell increases in size by the protoplasm of the cell flowing through the narrowed portion into the extravascular projection. Finally, the nucleus passes through, and apparently the solution in the continuity of the vessel wall disappears. (See Fig. 187.) After the migration of the leukocytes and the lessening of the intracapillary tension by the pouring-out of the exudate, resumption of circulation may be at times observed. To a certain extent the character of the irritant determines the * Before attempting to follow the various steps of diapedesis and the functions of the leukocytes in inflammatory and reparative processes, the student is advised to familiarize himself with the table describing and differentiating the leukocytes. (See chap. I, of part III.) INFLAMMATION AND REPAIR. 285 form of leukocyte most abundant in the exudate. In many of the infections, and particularly in pyogenic infection, the finely granular oxyphile cell (polymorphonuclear leukocyte or micro- phagocyte) is abundant. In other inflammatory conditions the hyaline cell (macrophagocyte) is most abundant. Exactly what factors determine the occurrence of one or the other of these cells has not been definitely ascertained. It would seem, however, that in the more acute, and particularly in the suppurative, inflammatory conditions, as already stated, the microphagocyte is abundantly present ; in the more chronic lesions, with less active irritants, the macrophagocyte is in excess. It is not possible to affirm, however, with any degree of definiteness, in the present stage of our knowledge, exactly what conditions determine the presence of one or the other of these phagocytes. As to the causes leading to the occurrence of migration and bal oye re “6 . =i i f My = S&S CRE? t, r . 3A 5 6 8 40 Minute Fic. 187.—LEUKOCYTES OF a FroG.—(Stéhr.) X 560 diameters. Extending out from the side of the leukocyte will be seen a number of projections, called : pseudopods. In the diapedesis or, migration of the leukocyte through a blood-vessel wall _ in inflammation these pseudopods are first thrust through the wall, the cytoplasm of the leukocyte flowing through into the pseudopod, carrying with it the nucleus, thereby de- jivering the cell upon the outer side of a blood-vessel wall. to the development of the exudate, two views have been held. It was long maintained: that it was purely a physical process ; the increased vascular tension, with the associated alterations in the capillary wall, led to the escape of part of the fluid contents of the vessel. By this theory the vessel wall was presumed to be passive. Later investigations have seemed to establish an entirely different opinion. Under the older view it was believed that the fluid normally present in the lymph-spaces of the various tissues was filtered through the vessel wall as a result of the intravascular tension. Later observers hold that the endothelium of the capillary secretes this fluid, and that instead of being a transudate, as originally thought, it is purely a secretory product of the endothelium. Admitting the correctness of this view, the material that we have been considering as an exudate must now be considered, at least in part, a secretion. The technical 286 GENERAL PATHOLOGY. difficulties that surround efforts to demonstrate the correctness of either theory have been so great that neither is at present deemed fully acceptable. The theory that the migration of the leuko- cytes is dependent upon increased vascular tension can not, of course, be maintained, as wandering cells already present in the tissues adjacent to an inflammatory area show migration toward the center in spite of the fact that such migration must be in the direction of the point of greatest pressure. Changes in the Perivascular Tissue.—In the perivascular tis- sues two distinct classes of elements must be considered: (1) Changes occurring in the elements normally present; (2) changes that follow in the fluids and cells coming from within es m = oe 6 7 @e a : & Z fo a aa eo (BH) Dg 2 a S SZ = 2. e5 a) ~ Qe Sa 2) ~~ 6) € —S a 3 ‘ : Bin “@ e 2D By QB. Xr oD: ° a Se 6 oo =“ F — Fic. 188. Pus-cells under high magnification from center of one of the infiltrated areas in a section of the cerebral cortex and meninges from a case of suppurative meningitis. Section stained with toluidin-blue.* (Zeiss y,-inch oil immersion; Queen oc. B.) the vessels. It ‘has been stated, and apparently correctly, that changes occurring in the normal perivascular structures are essentially the same as those seen: in tissues that are nor- mally nonvascular. As a type of such tissue, the cornea may be studied. The corneal tissue is abundantly supplied with lymph-channels, but contains absolutely no blood-vessels. The lymph circulating through the corneal lymph-spaces is derived from the capillary circulation surrounding the organ. Destruction of a small, superficially placed central area of the cornea by means of chemic irritants, or the removal of a thin _ * The microscopic drawing made from this section will be found in the chapter on Diseases of the Nervous System, under the head of Suppurative Meningitis. INFLAMMATION AND REPAIR. 2 87 superficial layer is followed by opacity at the point of injury, extending as a zone of haziness for some distance beyond. The preliminary degenerative changes in the corneal corpuscles are quickly followed by reparative efforts. Leukocytes surround and eventually infiltrate the area, while the undestroyed connec- tive-tissue cells (corneal corpuscles) begin to show evidence of proliferation. The proliferative changes manifested in the cor- neal corpuscles are evidently the initial steps in the process of repair. The leukocytes present in the area could not have arisen as a result of increased pressure directed toward the point of injury, but must be present as the result of some other factor. This leads us to discuss causes inducing the evident migration of leukocytes toward the area of injury. De Bary observed that certain @ : = a (eS) plasmodia moved toward the nu- @) @) & a tritive material placed in their vicin- 9 ~ @ Q@ © ®& ity, and a further study showed @) @ ~ . Oe @ that at least three classes of sub- go 2 ®@) eo” © stances could be recognized: (1 e © “—“@°9 © Substances toward which the plas- @ @) oe ® © @ modia moved ; (2) substances that @ © @) © Tee did not seem to influence the or- 7 @ 5) @ @ ganism ; (3) substances from which ve the organism receded. This prop- Fic. 189. erty of cellular attraction and te- RF Ecos menace pulsion is called chemotaxis, or Section stained with toluidin-blue. (Zeiss ¢y-inch oil immersion ; Queen chemiotaxis. When the cell is oc. B.) evidently drawn toward the body, the condition is called positive chemotaxis ; when repelled, nega- tive chemotaxis. Positive chemotaxis is admitted. Negative chemotaxis interests us but little ; the existence of such a condi- tion has been doubted, although experimental evidence would indicate its occasional occurrence. Experiments are not wanting to show that leukocytes travel toward certain infecting bodies, and that dead tissue is apparently attacked by these cells. The ultimate explanation of chemotaxis is still wanting ; we do not know whether it is a chemic affinity or a phenomenon allied to diffusion in simpler bodies, or whether it is an essential charac- teristic of certain cells not dependent on known chemic and physical explanations applicable under what seem to be similar circumstances. The cells influenced by positive chemotaxis arrive at the area of irritation from two directions: from the blood-vessels 288 GENERAL PATHOLOGY. come the polymorphonuclear leukocytes in large numbers, while from the adjacent connective-tissue spaces come the large hya- line cells and eosinophiles. Eventually, the field of observation becomes so clouded by the cellular elements present that con- tinued study of the previously transparent tissue is no longer possible. Whether all the leukocytes present in the area came from the sources just indicated or whether some of them are the result of proliferation has not been definitely determined. It is reasonable to conclude, from data at hand, that a certain number of the leukocytes result from proliferation of migrated cells. That this number is large, or that proliferation constitutes an important process in the production of the large number of cells present, seems doubtful. The changes that take place in the fixed cells of the tissue involved, as well as the alterations that the invading cells may undergo, are dependent upon a number of conditions. If the irritant be active,—as, for example, the poison of virulent bacteria, —many of the cells are at once destroyed. When the patho- genicity of the irritant is less marked, degenerative changes may be more conspicuous than actual cell death. The characteristics of these degenerative changes will vary in different tissues, and are more marked in organs whose cellular constituents are largely of epithelial origin. In the liver and kidney the degenerative phenomena that attend inflammation may be more conspicuous than the exudate. In such epithelial structures cloudy swelling, fatty degeneration, and hydropic distention of the cells with nuclear fragmentation may be conspicuous. In the connective tissues mucoid and hyaline transformation may be present. The amount of degenerative change and the associated cellular dis- integration are also dependent upon the intensity of the irritant ; such degenerations are most marked in the various infections of which the pyogenic constitutes a typical example. The fluid exudate now present in the perivascular tissues varies in quantity and composition. The quantity is depen- dent upon the character of the irritant as well as upon the tissue involved. The more richly vascular the area, as a rule, the greater the amount of the exudate. Loose connective tissues, such as the eyelid, scrotum, and labia, show marked accumu- lation of exudative fluids. The same is commonly true of serous membranes, and, to a lesser degree, of the subcutaneous and sub- mucous connective tissues. The fluid differs in chemic composi- tion from the fluid in edema ; its specific gravity is higher (edema, about 1.010, rarely over 1.015; inflammatory exudate, 1.020 to 1.025); it is highly albuminous, not uncommonly containing INFLAMMATION AND REPAIR. 289 five times the quantity of proteids present in edema fluids; it is rich in fibrin. When bacteria are present, the fluid usually con- tains. peptone, which, in old suppurative processes or when the lesion is extensive, may enter the general circulation and may be excreted in sufficient quantity to be recognizable in the urine. For evident reasons the inflammatory exudate is rich in cells, an abundance of which may render the fluid quite opaque. The leukocytes brought into the area by any of the processes indicated at once attack the infecting organism,—if bacteria be the cause of the inflammation,—or proceed to remove the dead tissue when the inflammatory process is associated with, or has arisen secondary to, cellular destruction. The phagocytes active in this process have been mentioned. As already stated, when considering phagocytosis in its connection with immunity, it is not improbable that certain phagocytes liberate antitoxic or bactericidal bodies that exert a certain amount of influence in subduing infection. (See Phagolysis, p. 156.) The fluid portion of the exudate relieves the intravascular ten- sion by its escape, dilutes the irritant present in the tissues, carries with it antitoxic and bactericidal properties, and possibly in some instances affords increased nutrition (?) to the cells of the area. The fibrin-forming bodies contained within the exudate reaching the perivascular tissues form fibrin, which acts not uncommonly as a limiting body, retarding the dissemination of bacteria and lessen- ing the rapidity with which the toxic bodies present are diffused into the surrounding tissues. Its function in the repair of wounds will be considered later. Terminations of the Inflammatory Process —These are largely dependent upon the activity and persistence of the cause, as well as upon the susceptibility of the tissue, including under this term the activity of the protective agencies whose tendency is always directed toward the arrest of irritant action. When the etiologic factor is readily overcome, or is quickly withdrawn, restitution to the normal may be brought about without leaving any evi- dence of a past inflammation. In the early stages of the inflam- matory process the withdrawal of the cause will be quickly fol- lowed by absorption of the exudate and the reestablishment of the circulation. The exudate passes off by the lymphatics or is taken up by the veins, and the few extruded leukocytes reenter the circulation, either directly, through the blood-vessels, or in- directly, through the lymphatics, eventually leaving no recog- nizable tissue alteration. As the inflammatory process continues, so favorable a termination becomes less and less possible, until finally the tissue alterations are such that a return to the normal 19 290 GENERAL PATHOLOGY. is no longer to be expected. Under such circumstances the occurrence of repair is the best that can be expected; and the longer such repair is delayed, the less effectual it is likely to be. The most important factor in the prevention of repair is infection ; and the more active this infection, the more grave the tissue alterations will be, and the less perfect the subsequent repair. Suppuration.—The organisms most active in the production of suppuration are the staphylococci and streptococci—pyogenic cocci. While the foregoing are the usual bacteria active in sup- purative processes, it is not to be forgotten that many other organisms share this pus-producing power. Thus, the bacillus coli communis, bacillus pyogenes fcetidus, bacillus typhosus, gonococcus, micrococcus cereus flavus, micrococcus cereus albus, pneumococcus, the fungus of actinomycosis, bacillus pyocyaneus, bacillus anthracis, and other organisms, occasionally manifest pyogenic activity. In most instances suppuration is due to a mixed infection. Commonly, at least two organisms are present, and in many instances a number may be associated. A series of unpublished investigations conducted by Lockett in the writer’s laboratory showed that of one hundred consecutive suppurative processes, a single infection was the exception. These obser- vations are corroborative of many similar studies made by other observers. Abscess.—lIn infection by pyogenic organisms the continued action of the irritant (a necessary sequence of bacterial prolifer- ation and of the continued production of toxins) prolongs the period of exudation and necrosis and increases the quantity of the exudate, which is particularly rich in phagocytic cells, the most abundant of which is the finely granular oxyphile cell. The bac- terial products lead to degenerative changes in the fixed tissue elements, associated with liquefaction of the intercellular sub- stance, converting the area so affected into a mass of cellular detritus in which the cell longest retaining its morphologic characteristics—the finely granular oxyphile cell, now the pus- corpuscle—is most abundant. The fluid’ resulting from these changes is called pus. Pus is a creamy fluid possessing a faint, sweetish odor; its specific gravity ranges between 1.020 and 1.035, with a mean of about 1.032. Essentially, pus is com- posed of two elements—the fluid and cellular portions. The fluid constituent is called the “guor puris ; it represents the fluid portion of the exudate, to which has been added the fluid result- ing from the liquefaction of the intercellular substance and, pos- sibly, from the dissolution of a number of the tissue elements, and, it may be, of some of the cells. It is comparatively rich in INFLAMMATION AND REPAIR. 291 albumoses, to which the absence of coagulability has been attrib- uted. It also contains leucin and tyrosin. The pus-cell is richly granular, usually polynuclear or polymorphonuclear, and for a brief period following its removal from the body may show well- marked ameboid movements ; in its present form it can not be differentiated from the polymorphonuclear or finely granular oxyphile cell, which earlier reached the inflammatory field from the blood-vessel. With regard to the hyaline or mononuclear cell, occasionally present in pus, our information is less satisfac- tory ; the tendency at present is to regard these cells as invaders from the adjacent connective-tissue spaces—in other words, they are believed to be celomic wandering cells. In the production of the abscess liquefaction first takes place at the center of irritant action, from which, as we pass outward, toward the sur- rounding uninvolved tissue, all intermediate stages of the inflam- matory process may be recognized. The wall of the abscess is, therefore, composed of the normal tissues of the part, showing various degrees of inflammatory infiltration, degeneration, and necrosis. The zone lying nearest to the pus is composed of necrotic tissue rich in leukocytes. Surrounding this will usu- ally be seen a zone containing the exudative fluids and numer- ous white blood-cells. There is usually present more or less fibrin entangled among the fixed connective-tissue cells, the latter not uncommonly showing proliferative changes. In this zone efforts at repair and at the prevention of dissemination may be evident. Externally, this zone gradually fades into the normal tissue, and internally it is continuous with the necrotic zone to which reference has already been made. If let alone, the abscess tends to travel along the path of least resistance ; as the infective agents tend to extend in all directions, but are met by the protective forces of the tissues, the path of least resistance must be through those tissues where the protec- tive agencies are least active. The vascularity of the part, and hence the richness in leukocytes, usually results in the extension of the abscess toward the surface, through which it eventually ruptures and discharges its contents. Relieved of this tension, the direction of the fluid exudate is now strongly toward the abscess cavity. This results in the flushing out of the surround- ing lymph-spaces, and favors the action of the protective forces —the phagocytes, antitoxic and bactericidal bodies present in the inflammatory area. When the infective organisms are destroyed or rendered inert, the liquefaction and formation of pus cease ; after incision and evacuation the walls of the abscess collapse, and reparative efforts become ascendant. 292 GENERAL PATHOLOGY. Ulceration.—The younger Gross often spoke of an abscess as a subcutaneous ulcer, and in the present state of our knowl- edge many ulcers could, with propriety, be called superficial or, more correctly, exposed abscesses. Where suppurative pro- cesses are so situated that a wall is formed on but one side,—in other words, are exposed,—the floor of the ulcer is structurally quite like the wall of an abscess. This applies, of course, only to ulcers in which infection is active. Exposed or denuded sub- cutaneous tissues where the removal of the overlying structures has been brought about under strict aseptic precautions bear little resemblance to the formative stage of an abscess. When, however, the ulcer has resulted from infective processes, giving rise to necrosis of the overlying structures, the early stages of ulcer formation are practically identical with those seen in the wall of a developing abscess. The pus formed by such ulcers finds ready egress, and the protective powers of the underlying tissues usually limit and arrest the spread of the ulcerative lesion. Occasionally, however, ulcers show continued necrosis, gradually extending in one or more directions, thereby indicating the inefficiency of the protective powers in the adjacent tissues. The fact that such ulcers appear to extend in one or more direc- tions, as though something were eating away the tissues, led to their being called phagedentc. In addition to abscess formation and ulceration, there are allied forms of infection in which the anatomic peculiarities of the tissues involved, or the absence of resistance, or the intensely toxic power of the infection, give rise to changes resembling abscess formation, but by no means identical. Closely allied to abscess formation is the occurrence of suppurative lesions of the serous membranes. Here the collection of pus takes place in the serous cavity, and is not usually referred to as an abscess. (For the description of suppurative inflammation of serous mem- branes, see Disease of Serous Membranes, part 11.) Suppura- tive processes leading to the accumulation of pus in cavities lined by epithelium occur. As in serous cavities, these are not usually referred to as abscesses ; thus, purulent accumulations in the pelvis of the kidney are spoken of as ‘‘ pyonephroses,” and in the Fallopian tube purulent distention is called ‘ pyosal- pinx.”’ At times the extension of infection proceeds with such rapid- ity that a distinct accumulation of pus may not be evident. Thus, in inflammation of the cellular tissues, and in inflammation of the lymph-vessels (angioleucitis) due to virulent infection or to greatly reduced resistance on the part of the individual, the INFLAMMATION AND REPAIR, 293 inflammatory process may extend with remarkable rapidity, and may even terminate fatally before the occurrence of any recogniz- able purulent collection, Sometimes along the paths of such rapidly spreading infections a variable quantity of macroscopic- ally recognizable pus may be developed. Such a condition is sometimes referred to as diffuse suppuration, suppuration of the cellular tissues, purulent infiltration, and, without any apparent reason, is sometimes called purulent suffusion. The occurrence of gangrene asa result of infection has already been considered. (See Spreading Gangrene.) The terms acute, subacute, and chronic, as applied to inflamma- tory processes, are used to indicate, to a certain extent, the period of time, or duration, as well as the activity of the inflam- mation, and, under certain circumstances, its location and sequels. That form of chronic inflammation in which the process extends over a long period of time and is associated with the formation of fibrous tissue in excess is sometimes referred to as productive inflammation. The changes that take place in the interstitial tis- sue of the kidney in chronic interstitial nephritis may be taken as a type of this form of inflammation. (See Chronic Interstitial Nephritis, chapter on Diseases of the Urinary Organs, part 1.) The view that all tissue changes associated with an increase in fibrous tissue are to be regarded essentially as manifestations of productive inflammation is no longer strongly urged. Thus, in degenerations that involve parts of the glandular viscera the disappearance of the essential normal elements may be fol- lowed by the development of fibrous tissue. This is sometimes spoken of as ‘ substitutive fibrosis,’ and by some is not con- sidered to be an evidence of past or existing inflammation. Such increase in fibrous tissue is spoken of as ‘ noninflammatory hy- perplasia,” thereby differentiating it from the increase in fibrous tis- sue that is clearly consecutive to inflammation and constitutes the terminal tissue changes in many inflammatory processes. When considering the pathology of organs, further reference will be made to chronic inflammatory processes and substitutive fibroses. (See Interstitial Pneumonia and Cirrhosis of the Liver, part 111.) Inflammatory processes not associated with infection are sometimes spoken of as simple or common. To speak of such processes as common in the sense that they are frequent is probably an error, as most inflammations are due to infec- tion. Inflammations due to some particular organism, or even when the organism is not known, as in chancroid, are called specific. While not restricted to syphilis, the term specific infec- 2904 GENERAL PATHOLOGY. tion is most frequently applied to syphilitic lesions. When the essentially secreting or actually functionating cells of the organ are involved, the inflammation is spoken of as parenchymatous ; when the interstitial tissue (connective tissue) is the principal seat of the lesion, the inflammation is called zutersitial. By reason of the intimate physiologic and structural relation of the connective tissues of organs with the essential functionating cells it does not seem probable that an inflammation could ever be strictly parenchymatous or strictly interstitial. That one or the other tissue may be apparently more involved justifies, to a certain extent, this nomenclature. Suppurative, pyogenic, puru- lent, or phlegmonous inflammations have already been consid- ered. Such inflammations are appropriately called septic, in contradistinction to the inflammatory conditions in which bac- teria have no part—aseptic inflammations. When considering inflammations of the mucous membranes, reference will be made to catarrhal, pseudomembranous, fibrinous, croupous, diphtheric, gangrenous, suppurative, and hemorrhagic inflammations of those structures. (See Diseases of the Mucous Membranes, part 111.) Dry, moist, serous, serofibrinous, fibrinous, plastic, adhesive, exudative, and other inflammatory processes affecting serous membranes will be considered with diseases of those structures. (See Diseases of Serous Membranes, part 1.) It will not be amiss, at this point, briefly to discuss the cardinal symptoms of inflammation and to indicate the relation that exists between these usually recognizable changes and the morbid pro- cesses to which they owe their presence. The more or less active inflammatory conditions, and even certain inflammations characterized by sluggishness, possess one or more of the so- called cardinal symptoms: namely, heat, pain, discoloration, swelling, and disordered function. Morbid Physiology of Inhammation.—z. Aeat—Practi- cally, the recognizable rise of temperature is dependent upon the increased amount of blood distributed in the area, which, coming from internal organs, possesses a temperature higher than the blood present in the superficial circulation under normal condi- tions. Theoretically, the following features are also active ; it is not probable, however, that their influence is of practical im- port : (a) the increased cellular metamorphosis ; (6) the increased oxidation that is going on in the area involved ; (c) the friction of the increased blood-currents and the impact of stasis may also increase the temperature. 2. Fain is due to pressure or to stretching of the nerves by the swelling, and to the irritant action of the inflammatory exudates INFLAMMATION AND REPAIR. 295 upon the nerve filaments. At this point it is well to note that pain may be beneficent in inflammation, in that it secures rest of the part, thereby leading the patient to favor the progress of ep processes. Discoloration is dependent upon (a) the increased amount of eer in the area ; (0) the proliferation of the cellular elements ; and (c) the character of the inflammatory exudate ; thus, the i in- creased amount of blood may give rise to redness, which becomes scarlet, brownish, or bluish, passing through the different shades to black. In nonvascular exudates the structure may be white instead of red; this is shown in the cornea, where occurs the ground-glass appearance, due to the inflammatory products, there being no red blood-corpuscles in the cornea. Redness, when present, is represented by the injection of the adjacent conjunctiva. The exudate in inflammations of serous membranes renders the surface white, unless the inflammatory processes be hemorrhagic. 4. Swelling is due to (a) the increased amount of blood in the part; (0) the proliferation of the cells; (c) the exudate in the perivascular tissue. As already stated when considering the de- velopment of the exudate, swelling may manifest beneficial ten- dencies. (See p. 289.) Under certain circumstances it becomes dangerous ; thus, if the swelling be great, the capillary circulation may be obstructed, and, as a result of faulty nutrition and of the activity of the inflammatory process, degenerative changes, necro- sis, and even gangrene may occur. This unfortunate termination is sometimes observed in inflammation of the subcutaneous tissues (cellulitis, angioleucitis), where the extensive swelling cuts off nutrition to the overlying structures and gangrene ensues. In- flammation of the juxta-epiphyseal disc may lead to thrombosis of the capillaries supplying the epiphysis, followed by necrosis of that structure. It is not necessary to multiply examples, although reference should be made to the corneal sloughing that .takes place as a result of intense swelling of the surrounding con- junctiva, cutting off ingress and egress of lymph from the avascular, transparent membrane. 5. Disordered function is due to (a) alteration in the tissue cells present, both the essential functionating cells and the interstitial elements ; (0) the mechanical interference with function resulting from the exudates ; and (c) the fact that the exudates prevent the activity of the innervation upon which the function of all tissue so largely depends. Systemic Phenomena of Inflammation.—These are largely embraced in the term fever, and are due to the absorption of the 296 GENERAL PATHOLOGY. inflammatory materials from the seat of the morbid process. The character of the fever and the severity of its manifestation are dependent upon the activity of the agents absorbed. In the simple aseptic fluids taken up by the lymphatics from an ordi- nary sterile wound, such as is typified in a broken bone, the manifestations are slight and temporary. When the materials absorbed contain the products of bacterial life, marked alteration in the tissue elements elsewhere in the body may occur. Degen- erative processes arise in the viscera independent of the presence of bacteria. The disturbances of glandular activity are repre- sented in the diminished secretions and excretions. The epithe- lial surfaces show, under the influence of bacterial agents, a de- cided tendency to undergo degenerative processes; this is most marked the more severe the infection, so that in the gangrenous and specific inflammations—for example, those of diphtheria— coagulation necroses in the large glandular viscera are not uncommon. The nervous phenomena that accompany inflam- mation are probably due to the direct action on the nerve sub- stance of the poison under consideration, or to the influence of the poison upon the capillaries distributed in the nerve tissues, giving rise to inflammatory or degenerative processes in those structures. Exactly what causes the condition called fever will be discussed later. REPAIR. Cell Reproduction.—As a part of the processes of repair (repair modified by infection, regeneration, inflammation so called, hyperplasia, certain forms of hypertrophy, etc.), prolifica- tion, proliferation, or reproduction of cells must be studied. There are two methods by which cells are reproduced: (1) Direct division, or amuitosis ; (2) indirect division, also known as karyokinesis, Raryomitosis, and, quite commonly, a more con- venient term, as 72foSts. 1. Amitotic Division.—In this form of segmentation the cell shows a constriction that involves both the cell protoplasm and the nucleus. This constriction is followed’ by a separation of the two portions, the nucleus first dividing and passing to the two ends of the protoplasm, which gradually separates, giving rise to two cells; during the process there is no manifest sys- tematic change in the chromatin of the nucleus, as is seen in the next form. 2. Mitosis.—As a rule, the cell divides only into two parts ; this is not, however, constant, as occasionally three cells may be developed simultaneously from one cell (J. Arnold). The steps INFLAMMATION AND REPAIR. 297 of mitosis may be approximately stated as follows: In the rest- ing nucleus the chromatin increases and groups itself as a skein, which later becomes thinner (smother skein). During this process the nuclear membrane disappears, and, if the cell possessed a nucleolus, this is lost sight of. Immediately following this—prob- ably in progress at the same time—there are soon developed, apparently from the achromatin, delicate lines that pass off toward the two poles of the cell, giving the central portion of the cell an arrangement shaped like a spindle, and hence the name nuclear spindle. The chromatin now divides transversely to this Close skein (viewed from the side). Looseskein (viewed Mother stars Polar field. from above: z.e., (viewed from from the pole). the side). Polar ra- diation. Spindle. Mother star Daughter stars. a (viewed from (Beginning.) | (Completion.) above). Division of the protoplasm. Fic. 190.—KARYOKINETIC FIGURES OBSERVED IN THE EPITHELIUM OF THE MOUTH CAVITY OF A SALAMANDER.—(Stéhr.) X 560 diameters. The picture in the upper right-hand corner is from a section through a dividing e g of siredon pisciformis. The centrosomata, also the first stages of the development of the spindle, can not be seen by this magnification. nuclear spindle, and passes, one half in each direction, toward the points of the spindle. The mass of the chromatin at each end of what was the spindle now constitutes what are spoken of as the daughter stars. During the arrangement of the chromatin as daughter stars an hour-glass-like contraction of the protoplasm of the cell appears, formed by an annular narrowing gradually developed around the center of the cell. At first the daughter stars situated in the two poles of the cell are joined by delicate striation, which probably represents the remains of the achromatin formerly constituting the nuclear spindle ; these lines disappear, 298 GENERAL PATHOLOGY. the two masses of chromatin show now no connection, and the hour-glass contraction is completed, separating the cell into two parts, in each of which parts there is a daughter skein, which now rearranges itself as a resting nucleus, around which a new nuclear membrane may appear. Lavdowsky has described another form of cell division that he calls dizzston by force. It appears in this form: two portions of the protoplasm of the cell move in opposite directions, appar- ently pulling themselves apart. Thoma has described and illus- trated this process as occurring in the white blood-cells of the frog when stimulated by electricity. Inflammation is repair plus the removal of dead tissue or infec- tion. When there is no dead tissue to remove, or when this is in a minimum, and when there is no infection, injury to tissue is followed immediately by the process of repair. As studied by the surgeon, healing is said to take place in the following ways : 1. Union by First Intention.—Thus, if the surfaces of a recent wound be brought immediately in contact and retained, the fol- lowing phenomena occur: Liquor sanguinis is poured out, im- mediately followed by its coagulation, forming a fibrinous cement —the so-called inflammatory lymph—that binds the two sides of the wound together. Into this leukocytes wander from the adjacent blood-vessels, and, by means of their phagocytic action, they proceed to the removal of the dead tissue. Proliferation of the fixed connective-tissue cells rapidly ensues, leading to the formation of embryonic tissue. It is now generally conceded that embryonic tissue is largely the product of the fixed connective- tissue cells. It can not, however, be established, beyond the possibility of doubt, that the migrated leukocytes have nothing to do with its formation. Particularly is this true when we con- sider that many of the cellular elements present can not be distinguished, either morphologically or tinctorially, from the hyaline leukocyte. Many of the cellular elements present in such tissue show active mitosis, and eventually lead to the for- mation of fibrous, cicatricial, or scar tissue. By reason of what appears to be the specific function of such cells they are called Jibroblasts. Exactly how fibrous tissue is formed by or from the fibroblasts is not fully determined. It is held by some that the fibrous tissue is laid down by the fibroblasts, partly as a secre- tion, ina manner similar to the laying down of cartilage and bone by chondroblasts and osteoblasts respectively. By others it is held that a part of the fibroblast becomes actually transformed into the new fibrillated elements. Among the other cellular ele- INFLAMMATION AND REPAIR. 299 ments of doubtful origin and often observed in reparative pro- cesses are giant-cells. The origin, structure, and function of giant-cells have been the source of much controversy since their description by Johannes Miiller in 1838. They probably arise in one of two ways: (1) Nuclear division without associated protoplasmic segmentation ; (2) confluence of the protoplasm of cells, resulting in the formation of a type of giant-cell resemb- ling that caused by the massing of other cells, called plasmodia. The number of nuclei present in the giant-cell varies; as many as eighty have been observed in a single cell. The researches of Heidenhain, Koch, Metschnikoff, Soudakewitsch, Faber, and FIG. 191.—CELLULAR ELEMENTS OF GRANULATION TISSUE.—(Schmaus.) 500 diameters. u,u. Spindle-forming, ene and round cells. 64. Mother star. c. Daughter star. d. Skein stage. ¢. Round or lymphoid cells. ”,/ Polymorphonuclear leukocytes. others seem to establish the inclusion and phagocytic power of giant-cells. In order to maintain the nutrition of the developing tissue blood-vessels are necessary. While in the embryo other forms of capillary development are recognized, the only form admittedly present in reparative processes is development by budding. From the walls of the nearest capillaries there extend conic projections into the developing tissue. These projecting buds, after passing some distance from their point of origin, unite with other buds, thus forming loops, through which the circulation is established. 300 GENERAL PATHOLOGY. The tissue previously known as embryonic tissue is now granu- lation tissue. When seen, for example, in the floor of an ulcer, each loop or group of loops forms a minute elevation called a granule; hence the name granulation tissue. It is possible that capillaries formed in this way may later develop thicker walls, and may ultimately become arteries or veins. Around the newly formed capillaries the development of fibrous tissue con- tinues. At first the cicatrix-scar is red, or at least pinkish, the heightened color being due to the richness of its blood supply. FIG. 192.—GRANULATION TISSUE. LATER STAGE IN ORGANIZATION THAN FIGURE 191.— (Schmaus.) XX 250 diameters. u. Round or lymphoid cells. 6. Fibroblasts. c. Spider cells, multipolar cells. d. Space from which cellular elements have dropped out; possible primitive lymph-spaces. e. Point where the evolution of fibrous connective tissue is most advanced. 7, Leukocytes.with several nuclei. Through this area will be seen young capillaries, branched and bud- ding ; the same are shown below the blood-vessel indicated by the upper g. g,g. Blood- vessels. A, Matrix of intercellular substance forming fibrillated tissue. Later, contraction of the interlacing fibrous tissue occurs, dimin- ishing, by pressure, the number and carrying capacity of the newly formed vessels, the tissue eventually becoming white. The tendency of developing fibrous tissue to contract gives rise to structural and functional disturbances in organs whose nutrition it so profoundly influences. The evidence of such contraction is clear in diseases of certain viscera, such as the liver in chronic interstitial hepatitis, and the kidney in chronic interstitial nephritis. INFLAMMATION AND REPAIR. 301 There is sometimes described a form of repair that closely re- sembles union by first intention—repair upon a framework or scaffold. To illustrate how this may occur, let us suppose that there is a large “ dead space,” such as would result from chiseling a cavity in bone; into this dead space blood oozes and coagu- lates. The coagulated fibrin forms a scaffold, upon which young blood-vessels and embryonic and granulation tissue advance from the sides and eventually complete the process of repair. Materials other than blood have been used for the scaffold ; sponge, chips of bone, cartilage, ivory fragments, and allied sub- stances that can be readily antisepticized may be used. 2. Healing by second intention is said to occur in wounds the edges of which can not be brought together, and in which the scaffolding process, already referred to, is not available. The FIG. 193. The formation of capillaries in embryonic tissue. A, A,X. Endothelial plates with proto- plasmic projections, a,a, which later become capillaries. Other communicating branches are shown. A part of the vascular loop contains red blood-cells, 7,~.—(Landozs.) ordinary recent traumatic ulcer is an illustration of this process. Suppose that considerable skin surface is removed, and that a raw surface is presented for healing: Within a few hours a layer of coagulated fibrin and partly inspissated serum will be seen upon its surface. Dead elements are attacked by the phagocytes and are removed, and proliferation of the connective-tissue cells and leukocytes proceeds to the formation of embryonic tissue. Young capillaries spring out from the adjacent vessels and convert the embryonic tissue into granulation tissue. By continuous prolif- eration of the cellular elements, with pushing up of the capillaries, the cavity is gradually filled, and when this new tissue reaches the surface, covering over by epithelium occurs. The epithelial regeneration is secured through the activity of the epithelial cells near the edge; these proliferate, and by ex- 302 GENERAL PATHOLOGY. tension from the periphery, in favorable cases, gradually cover the granulating surface. Epithelium may be ingrafted upon the embryonic tissue, and new centers of epithelial regeneration may be thus established. Another form of healing that is truly repair by second in- tention is sometimes referred to as healing by third intention. This is illustrated when two granulating surfaces are brought to- gether; the two adhere, blood-vessels pass from one to the °S ANG) SAO a 0. >I 5 58882 FIG. 194.—SECTION THROUGH THE BORDER OF A HEALING Wounp (Diagrammatic).— (Rindfletsch.) X 300 diameters. w. Surface of ulcer. 6. Granulation tissue composed of embryonic tissue with the capillary loops developed from the vessels below. c. Later stage in the development of the granu- lation into spindle-cell elements; young cicatricial tissue that is older at d. ¢,/, g&. The epithelium spreading over the surface of the healing area. other, and cicatrization occurs, exactly as already described. The final cicatrization and obliteration of an abscess cavity is se- cured in this manner. After the evacuation of the pus and the destruction of the bacteria the collapsed walls, coming in con- tact, unite. It was once considered that union under a scab represented another form of healing, but it is now recognized that granulation and skinning over by epithelium, as already INFLAMMATION AND REPAIR. 303 described, occur. It is not, therefore, a distinct process, but merely a form or combination of some of the foregoing. A close examination of the forms of repair as just given will show a distinct resemblance of each to all the others; the dif- ference, so striking clinically, is far less marked when we come to investigate the essential changes through which each must pass. In all there is the same preparation for repair, usually effected through the activity of phagocytes. Following or accompany- ing this, proliferation of preexisting elements and probably certain leukocytes lead to the development of fibroblasts, through the presence of which final cicatrization is brought about. Even the epithelial regeneration is not essentially anything out of the common, as wherever the skin has been wounded, whether the line of injury is microscopic or the surface involved large, prolif- eration and extension from the margin must be the only normal method of covering the young connective tissue. Regeneration.—Repair may occur without regeneration. Thus, muscle may be repaired by fibrous tissue, the scar joining the severed ends of the muscle. It does not seem, however, that new muscle is produced. With regard to nerve and bone, this is different ; repair terminates in regeneration, and new tissue may be produced that is identical with the original tissue. Regeneration occurs in but few tissues ; nerve and bone are the best examples. Repair seems possible in almost any tissue, but such repaired tissue may be, in part at least, functionally inactive, because regeneration has not been complete. Thus, a large cica- trix upon the skin does not contain sweat-glands or hair follicles, and, while it protects the subcutaneous tissues, it performs none of the special functions of the skin. Destroyed kidney tissue may be followed by repair, but apparently not by regeneration. Many authorities regard regeneration and repair as essentially identical processes ; thus, when repair terminates in the forma- tion of fibrous tissue, they say it is regeneration of the fibrous tissue. No one doubts the regeneration of fibrous tissue, but when a large area of the skin or a considerable volume of an organ is converted into fibrous tissue, with the total disappearance of every other structure but the fibrous tissue, it certainly is not correct to say that the organ is regenerated, and the enormous in- crease in fibrous tissue amounts to something more than the mere regeneration of that element. Repair, as described here, is synonymous with regeneration of the fibrous tissue described by other writers. Regeneration, as already defined, implies the pro- duction of new elements structurally and functionally allied to, if not identical with, the destroyed tissue that they replace. CHAPTER VII. TUMORS. The word tumor, which means szedling, has been variously applied in medical literature. Some writers evidently include among the tumors cellular collections clearly of inflammatory origin; to such aggregations of cells is given the name inflam- matory tumors, granulation tumors, etc. The tendency at present is to exclude all such masses and restrict the term tumor to—(1) neoplasms ; (2) cysts. NEOPLASMS. A neoplasm is a pathologic new growth that has a tendency to persist or to increase independently of the structure in which it lies, and that is functionally inactive. A tumor, therefore, differs from an zuflammatory enlargement by its tendency to per- sist and to enlarge, while inflammatory new formations tend to disappear or to reproduce the tissue of their matrix. Besides, inflammation has marked clinical phenomena, and not infrequently an assignable exciting cause. A hypertrophy differs from a tumor in the fact that it is the result of increased physiologic demands or of a local nutritive change, and that it tends to subside after the withdrawal of the exciting cause. Also, as a rule, hypertrophy does not destroy the natural contour of a part, while a tumor does. Hypertrophy is associated with increased functional power. General Considerations.—For purposes of clinical descrip- tion and pathologic study certain terms are used in connec- tion with tumors with which the student should be familiar. In studying tumors for either diagnostic or pathologic pur- poses there should always be a definite routine in the method of examination, as has already been insisted upon when considering postmortems. The following order is commended : (1) Describe the tumor ; (2) its relation to surrounding tissue and organs ; (3) the history of the tumor; (4) the history of the patient. In purely clinical studies it is common to begin with the history of the patient, and the foregoing order may be reversed without affecting its usefulness. 34 TUMORS. 305 1. In describing the tumor the following points may be of aid in diagnosis, and ought to be developed in the history: (a) Its siteation, superficial or deep, on epithelial or connective- tissue surfaces, or within a structure composed of one or both tissues ; this includes the organ involved. (6) The conforma- “zon of the tumor : Is it globular, flat, bossed, pendulous, pedun- culated, pyriform, conic, excrescent, polypoid, dendritic, ses- sile, cauliflower, tuberous, lobulated, fungoid, etc. ? (c) The size ofa tumor may be approximately estimated before the tumor is removed from the body. After removal accurate measuré- ments should be made and the mass should be weighed. (d) .Vumber : Is the tumor single—that is, solitary—or is it multiple ? If multiple, was it so from the beginning, or was one tumor fol- lowed by a succession of others? Are all the tumors apparently alike, having the same conformation, consistency, and similar location? (e) Consistence: Some tumors are so soft that they fluctuate; others are semisolid, gelatinoid, solid, hard, or even eburnated. (f) Color: This includes the color of the overlying structures. The tissue covering a tumor may be normal or in- flamed ; it may contain tortuous veins; it may be edematous, or even pigmented; it may be so vascular that the color is of a blood tint, either pink or red, or, in some instances, cyanotic. (g) The mobility of the tumor: Is the tumor movable in the tissue that surrounds it? Is it movable only with the organ involved, or has the tumor, as well as the organ involved, be- come attached to adjacent tissue? () Scusibility: Is the tumor painful, tender, sensitive to changes in temperature or to other atmospheric conditions? Is the pain or tenderness constant, remittent, or intermittent ? 2. The zufluence of the tumor, if any, upon surrounding struc- tures: Are they involved, inflamed, edematous, sensitive, or anesthetic ? 3. The /ustory of the growth: How long has the tumor per- sisted? Is it growing rapidly or slowly? Has its growth been constant or intermittent? Is its growth influenced by any of the functions of the body? (For example, some tumors in women enlarge during menstruation.) What pathologic proc- esses, if any, is the tumor undergoing ? Is there evidence of in- flammation, gangrene, cyst formation, suppuration, infiltration, or of degenerative processes ? 4. Flistory of the patient—Age.: Some tumors appear in the young, others are more frequent in middle life, and some occur in the old. Sex. Some tumors are more frequent in the male ; others, in the female. Carcinoma of the male breast occurs in 20 306 GENERAL PATHOLOGY. about one per cent. of all cases of mammary cancer. Social condition: Married or single. Occupation: Certain tumors have long been recognized as frequently associated with given occupa- tions: ¢. g., chimney-sweep’s cancer. adits: Some tumors are dependent, apparently,—to a certain extent, at least,—upon given habits: ¢. g., smokers’ cancer. Heredity: There is reason to believe that in some tumors inheritance may play a part. Has the general nutrition of the patient been influenced in any way? and is the influence purely mechanical, such as may result from the weight of the tumor, or is it attributable to the position? Have ulceration or infectious processes modified general nutri- tion? In the absence of any other explanation, it may be in- ferred that the tumor itself has been prejudicial to the patient’s health. Previous history of the organ or tissue tnvolved: Is there a history of injury or inflammation, such as might occur in the breast during lactation? Has there been any previous disease of the gland or structure involved, such as eczema ? Causes.—It is not improbable that different tumors arise as a result of the action of various causes. As, however, we know very little concerning the exact cause of any particular tumor, certain general considerations are permissible. The older theo- ries, attributing the occurrence of tumors to alterations in the humors of the body, particularly of the blood, and similar hypotheses, may be at once discarded. The following hypothe- ses are deserving of consideration : I. The Inclusion Theory of Cohnhetm.—vThis theory is based upon the supposition that, during embryonic development and the specialization of the cells entering into the formation of or- gans and adult tissues, more embryonic elements are produced than are necessary, and that these cellular elements become quiescent in the tissues, where they may remain, constituting embryonic ‘‘rests” or ‘‘remnants,’’ from which, later, tumor formation takes place. Such embryonic rests or remnants would be exceedingly likely to occur where developmental processes are complex, as, for example, where different forms of epithelium join. Such points of tumor election undoubtedly occur, as is shown by the development of cancer at the various orifices of the body and at points of epithelial transition, such as the lip, cervix uteri, etc. This theory also explains to advantage the occurrence of chondroid tumors in or from bone, and of mela- notic sarcomata from quiescent pigmented cells in moles, and affords a most acceptable explanation for the development of dermoid cysts. The theory, however, is wanting in several TUMORS. 307 ways. In the first place, admitting the occurrence of these remnants, it would appear that a further etiologic factor is neces- sary-in order to stimulate them to renewed activity. Anothér objection is afforded by the fact that many localities in which complex developmental processes occur, such as the heart and the nervous system, are singularly free from tumors, and that when they do occur in such tissues, they are not commonly situ- ated at points at which the complexity of development is most marked. Epithelial rests are sometimes demonstrable, and yet no tumor formation occurs. The occurrence of tumors as the result of trauma (to be considered later) is not fully consistent with this theory. 2. Injury and inflammation appear to be, in a certain percent- age of tumors, important etiologic factors. Persistent or long- continued irritation seems to favor the development of tumors belonging to the epithelial group. As examples of such tumors the following may be mentioned: Carcinoma of the scrotum in chimney-sweeps ; epithelioma of the arm in workers with par- affin and tar ; smokers’ cancer of the lip or tongue and cancer of the tongue apparently due to injury by a carious tooth ; and epithelioma originating in the margins of chronic ulcerative processes. Among the nonmalignant epithelial tumors the - development of which may appear to be favored by injury or irri- tation may be cited the papillomatous masses that occur, appar- ently as the result of irritation due to the accumulations of irri- tating discharges, particularly around the anus and external gen- ital organs, when the parts are not kept properly cleansed. Sar- coma following fracture or injury of bone, and fibroneuromata of the severed ends of nerves after amputation, may be men- tioned as connective-tissue tumors offering strong support to this theory. The occurrence of tumors at points particularly liable to injury is another argument in its favor. Numerous objections have been made to the acceptance of this theory. In about eighty-five per cent. of the cases no history of injury can be obtained. On the other hand, the frequency with which injuries are received is not at all in proportion to the total number of tumors occurring. Parts particularly subject to injury, such as the hands and feet, are not commonly affected, and the nipple, which is frequently injured, is rarely the seat of a tumor. 3. Parasitic Influence.—The germ theory has been invoked to explain the formation of tumors, particularly the malignant tumors, in which metastases are conspicuous. By some the essential parasitic body is believed to be an animal parasite 308 GENERAL PATHOLOGY. belonging to the protozoa and resembling, if not identical with, the coccidia already described. (See p. 193.) Others believe that the infecting body is a vegetable organism belonging to the blastomycetes. In further support of the parasitic origin of tumors the demonstrable autoinoculability of cancer is adduced. Thus, it has been shown that cancer of one labium may attack the point of contact upon the opposite labium; cancer of the cervix may attack the contiguous vaginal vault; and cancer reaching the peritoneal surface may show a similar inoculability. It may be said at this point that such inoculability may be an evidence of grafting, just as epithelial cells may be grafted from place to place without of necessity invoking the intervention of any parasite. A similar explanation is offered with regard to the grafting of cancer from one animal to another. The inoculation of tumors believed to be sarcomata, and occurring on the geni- talia of dogs, is believed by some to be an evidence of the inocu- lability of sarcomata. Others maintain that the tumor in ques- tion is not a sarcoma, but that it belongs to that group of inflammatory embryonic cellular collections not easily differen- ‘tiated from round-cell sarcoma. 4. Parasitism of Cells.—It is not impossible that normal cellu- lar elements may take on a certain parasite-like property that, in the presence of reduced resistance afforded by other elements, permits of their extension beyond normal limits. Thus, in cancer cellular elements that we believe to be of epithelial origin are found abundantly infiltrating connective tissues. Normally, epi- thelium does not so extend, nor, in most instances, even when introduced experimentally, does it acquire any such property. Should further experiment show that conditions may arise under which epithelium can acquire or manifest the faculty of intracon- nective-tissue growth, without the intervention of any other factor, we may assume that the manifestation of this parasite-like character leads to the development of cancer. The foregoing brief consideration of the most plausible reasons advanced to explain neoplastic growths indicates our ignorance of the essential etiologic factor in tumor formation. There are, however, certain predisposing elements worthy of consideration. Some of the conditions previously considered may be active only inthis way. Trauma and inflammation may predispose to tumor formation, just as they predispose to infection, and long-continued irritation or prolonged ulceration may act only as predisposing elements. With regard to age, it may be said, in a general way, that physiologic activity favors the development of sarcoma, while senescence, or physiologic decline, predisposes to the TUMORS. 309 occurrence of cancer (Da Costa). The influence of inheritance can not be entirely ignored, although it is probably slight. Neoplasms are subject to two general laws: 1. Muller's Law.— The tissue that forms the tumor has its type in a tissue of the organism, either adult or embryonic. By this is meant that, no matter what the cellular elements of a tumor may be, such elements occur as normal structures in the adult tissues or in the tissues of the embryo at some period of its development. 2. Virchow’s Law.—T7he cellular elements of a tumor are de- rived. from the preexisting cells of the organism. Virchow adds that they are derived from the cells of the connective tissue—a view not to be fully accepted. By the acceptance of these two laws we arrive at the fact that tumors spring from structures once normal, and represent, when fully developed, tissues that were normal; in other words, tumors are not importations into our bodies, but, like all other morbid processes, are perversions of normal cellular activity. Tumors, in a general way, obey the laws that regulate normal tissue, yet to some extent they live independently of the surround- ing tissue. They usually possess their own circulation, and dis- seminate and proliferate at the expense of the adjacent tissue. While the patient may show every evidence of failing nutrition, and the adult and fully formed tissues of the body are undergoing progressive wasting, the tumor cells may not lessen in the least the rapidity of their growth. Tumors are ‘said to enlarge or to extend either by (a) inter- stitial growth or by (/) dissemination. By the former is meant that the growth within the tumor is uniform; that it increases in size by proliferation of its cells, without any dis- lodgment except that incident to one cell pushing another during the process of multiplication. Such tumors are likely to form capsules, the capsule developing either as a part of the tumor cells or by condensation of the surrounding tissue. The simple nonmalignant tumors may have capsules formed in either of the two ways indicated, but the malignant tumors are less likely to have anything like a capsule, by reason of the fact that they grow largely by dissemination. (2) Growth by dissemination is said to be—(1) growth by infiltration; (2) growth by metastasis. 1. Local dissemination or infiltration is an extension of the tumor into the surrounding tissue; this usually occurs by the entrance of the tumor cells into the lymph-spaces. Tumors growing by infiltration have no sharply defined border, and are, therefore, without any capsule, thus rendering the surgeon 310 GENERAL PATHOLOGY. unable to determine definitely how far from the neoplasm it is necessary to keep in order to remove all of the tumor tissue. 2. Metastasis.—When, as just indicated, the tumor cells infiltrate the primitive lymph-spaces, it will be seen how easy it is for such infiltrated cells to be caught in the lymph stream and carried to the glands into which the lymphatics of the area involved empty; such extension is most common in cancers, although it may occur in sarcoma, and is known as metastasis by the lymph stream. Metastasis by the Blood.——In certain tumors, particularly in sarcomata, the walls of the blood-vessels are poorly formed— indeed, nothing structurally comparable to the normal wall may be demonstrable; the blood traversing such tumors passes through what may be called sluiceways, the walls of which are not uncommonly formed entirely of tumor cells. These cells may drop off into the blood stream and be carried along as em- boli (neoplastic emboli), reproducing the tumor wherever they lodge. Again, a tumor may infiltrate the wall of the blood- vessel and project into its interior, and small fragments, break- ing off, may be carried to distant parts. The walls of the veins being thinner than those of the arteries, infiltration is ren- dered easier, and the circulatory conditions make the conse- quences more disastrous. Neoplastic emboli formed by penetra- tion of the femoral artery can be carried only to the structures of that limb; if, however, the emboli be thrown into the femoral vein, their next point of lodgment would probably be the lung. Pigmentation occurring in tumors may be due to hemorrhage within the tumor and to the breaking down of blood color- ing-matter, or it may be due to the fact that the tumor produces a pigment, such as is seen in the chloroma, melanotic sarcoma, and a few other tumors. It may also be due to the development of certain bacteria, particularly if the tumor be ulcerated. Classification.—Clinically, tumors are said to be (2) benign or (6) malignant. By the former is meant that the tumor of itself does not necessarily involve danger to life, while the latter implies that, if let alone, the tumor will eventually prove fatal. A tumor ordinarily innocent or benign may destroy life simply by its location: for example, a fibrous tumor growing on the in- side of the skull. This, however, does not justify our placing fibrous tumors with the malignant neoplasms, as the fact that it proves fatal, in the particular instance cited, is what Park has termed ‘“‘ malignancy by accident of location.” At one time it was quite the custom for clinicians to classify tumors according to some symptom or peculiarity of shape. TUMORS. 311 As examples of this, we have scirrhus, for hard, and encephaloid, for soft; again, bleeding tumors, when fungoid, all came under the one head, “fungus hzmatoides.” No fully satisfactory classification of tumors can be made at present; when we be- come familiar with their etiology, it is probable that more may be accomplished. The extension of our knowledge as to the minute structure of tumors has led to a classification based upon their morbid histology and histogenesis. Classification Based on Histogenesis.—Granting the cor- rectness of the law of Miller, a tentative classification is possible, based upon the resemblance of tumors to the normal tissues, either adult or embryonic. All tissues spring from one of two types: (z) Epithelium; (2) connective tissue. Trac- ing these back to the blastodermic layers, they are developed as follows : (7) £pithelium, from the epiblastic and hypoblastic layers (or outer and inner layers) of the blastoderm. (2) Connective tis- sue, from the mesoblast (or middle layer) of the blastoderm. All neoplasms spring from one of these two types, each type of tissue having two varieties : (1) Epithelium: (a) Adult or typical ; (0) embryonic or atyp- ical, (2) Connective tissue: (a) Adit or typical ; (6) embry- onic or atypical. By adult or typical tumors is meant those having their type in the adult body ; clinically, these are dengan. Embryonic or atypical tumors are composed of cellular ele- ments resembling those found in the embryo at some stage of its development ; clinically, such tumors are malignant. EPITHELIAL TUMORS. ADULT EPITHELIAL TUMORS. I. Papilloma.—These growths are formed from cutaneous and mucous papillae, and consist of a fibrous stroma, or stem, con- taining blood-vessels and lymphatics, and possessing an epithe- lial investment. The epithelium is of the kind normal in that particular situation. The histologic structure of a papilloma is the same as that of the ordinary papilla, and consists of a basis of connective tissue, richly cellular, from which: project toward the surface numerous papillary processes, each process support- ing blood-vessels that end in a capillary loop, the whole being enveloped in a covering of epithelium. The papille vary in length: in the ordinary wart they are 312 GENERAL PATHOLOGY. short; in the wous papilloma they appear as long, delicate fibrils, giving off secondary and tertiary shoots. On the skin the epithelial covering is thick, hard, and stratified, and actually binds the papille into a solid mass; on mucous membranes the slender vascular processes are covered with very delicate and easily lacerated epithelium. Site.—Papilloma may appear anywhere on the skin or mucous membrane; as a rule, they grow from, and closely imitate, pre- existing papilla. They rarely occur where no papille exist ; in such rare cases they spring directly from the subepithelial connective tissue—this is the case in the stomach and larynx. Clinical Characteristics. — Clinically, warts are benign, or innocent. They may occur at any age; may be single or multiple; may disappear without any operative interference: this is especially true of multiple warts. When occurring on mucous -surfaces, they are highly Fic. 195.—PAPILLOMA.— vascular, and, owing to their thin epi- Goulds) thelial covering, cause much trouble, and even death, by bleeding.. This is especially true in the bladder and in the urethral orifice. In the young, warts are occasionally transformed into sarcomata ; in advanced life warts and warty surfaces (ichthyosis linguz) may be converted into cancer. Varieties —(z) Skin warts ; (2) villous warts ; (3) intracystic warts. 1. Skin Warts.—(See Fig. 195.) Skin warts are overgrown papillz, and on section the epithelium will be found to pass from one papilla to another in an unbroken line without invading the fibrous framework. They vary in size, and may become mottled with black pigment (melanotic). Cutaneous warts may be sin- gle or multiple, and may disappear in one area and appear in another, thus leading the laity to believe them migratory. Ordi- narily, the cutaneous papilloma appears as a hard, abruptly ele- vated mass, apparently of epithelium, presenting an irregular or ‘“warty” surface, usually divided by deep fissures. -On section, the relation between the stroma and the epithelium may be seen even with the naked eye. 2. Villous Warts.—These commonly spring from the mucous membrane, usually of the bladder, and occasionally of the renal pelvis ; the condition is termed wllous disease. The general ap- “ pearance of the long, branching, feathery tufts resembles that of TUMORS. 313 the delicate chorionic villi; structurally, the villi consist of a connective-tissue core traversed by delicate blood-vessels, the whole being surmounted by epithelium. They may be single or multiple, sessile or pedunculated. The tearing off of small villi may occasion hemorrhage, which, with frequent recurrence, gives rise to profound anemia. The size of the villous mass often bears fo relation to the severity of the hemorrhage; the writer has examined, at autopsy, a fatal case in which the papilloma- tous mass was not larger than a grain of wheat. The detach- ment of the villi is usually brought about by their being forced, during the last stage of urination, into the urethra, where fimbriz are caught ; distention of the bladder pulls upon the incarcerated FG. 196.—PAPILLOMA WITH TENDENCY TOWARD VILLOUS FORMATION.—(Schmaus.) «. Connective-tissue basis containing numerous blood-vessels. 5, 6. Epithelial covering. villi, breaking them off, and thereby inducing hemorrhage. Car- cinomatous transformation of vesical papilloma occurs. 3. Intracystic Warts.—These may occur within almost any cyst cavity lined by epithelium, more especially those cysts formed in glands: ¢. g., mammary cysts, thyroid cysts. In cysts formed in the mammary gland, particularly in those cysts arising during the growth of fibrous tumors of the breast, the wall may be formed by a papillomatous outgrowth. Tumors composed of papilloma- tous masses in the interior of dilated galactophorous ducts or mammary acini are spoken of as zntracanalicular papillomata. Sometimes the cyst is said to be papillomatous. In many in- stances it may be quite impossible to determine whether the cyst _ 314 GENERAL PATHOLOGY, preceded the papillary growth or whether the reverse was the case. Examination of a number of such cysts usually shows that the papillomatous growth is evidently a secondary process. Occasionally, the cyst may be distended with the papillary masses, the fluid, probably present at some time, having entirely disap- peared. Cysts containing such papillomatous masses are some- times seen in the liver. The villous outgrowth resembles that of villous papilloma, and the epithelial covering is usually the same as that of the cyst wall; it may be cylindric, tall or flat, and even ciliated. The size of such masses varies within wide limits, and the fact that their presence is at times unsuspected would lead one to regard them as sources of no danger. Occa- sionally, however, scirrhus of the breast follows or is associated with such masses. II. Adenoma.—An adenoma is a tumor constructed upon the type of a gland. Adenomata are of slow growth, and are be- lieved to have their origin in some quiescent, congenitally dis- placed rudiment; their ducts do not communicate with the normal gland nor do their acini elaborate a secretion ; they are, as a rule, completely encapsulated, thus distinguishing them from localized hypertrophies. Clinically, they are benign. The sec- ondary changes to which they are liable are fatty degeneration of the epithelium, dilatation of the saccules and tubules into cysts, and mucoid softening. As adenomata contain both connective- tissue cells and epithelial cells, transformation into sarcoma and into carcinoma is possible; the former is more frequent in the young, and the latter in the aged. Sife.—They may develop in any glandular structure or in any tissue containing glandular structure. The chief species of ade- noma are: Mammary, sebaceous, thyroid, prostatic, parotid, hepatic, renal, ovarian, testicular, gastric, Fallopian, and uterine. Varieties.—(1) dcinous ; (2) tubular. 1. Acinous Adenoma.—This variety consists of numerous saccules or acini lined with small epithelial cells, which are often two or three layers deep. The acini communicate with one another and are grouped together, being separated by a connec- tive-tissue matrix-in which are situated the blood-vessels. The connective tissue or fibrous stroma varies in amount. Adenoma of the breast is generally seen in young girls at about the age of puberty. The tumor is usually bossed or lobulated, irregular in conformation, and encapsulated. Acinous adenoma is rare, but two cases having come under the author’s observation among the hundreds of tumors sent to the laboratory. Fibromata showing more or less glandular structure are not uncommon, TUMORS. 315 and are called fibroadenomata. It is often quite impossible to determine whether the gland structure present is newly formed or merely the incarcerated normal breast tissue. 2. Tubular Adenoma.—This variety is very common in mucous membranes possessing tubular glands. Tubular adeno- mata are usually soft, slightly translucent, and somewhat vascu- lar. The tubes are lined with cylindric-cell epithelium. .On section, when cut transversely, the tubes appear as circles, with a FIG. 197,—ADENOMA OF THE CERVIX UTERI.—(From a specimen sent to the author by Dr. £. Q. Thornton.) The gross specimen was a strawberry-like, pear-shaped mass, 2.5 cm. in length, and attached bya edicle to the anterior lip of the cervix uteri just at the marginof the os. The tissue was fixed in corrosive sublimate, infiltrated with paraffin, stained with hematoxylin and eosin, and mounted in balsam. Drawn from 14-inch obj., %-inch oc. The irregularly formed gland tubules, lined by tall cylindric epithelium, are well shown. central lumen and a border of regular cylindric epithelial cells. When cut longitudinally, they often show lateral buds, or even bifurcations, terminating, at one end, in the mucous membrane, where they open, at the other end in blind sacs extending to varying depths ; the tubes may be so closely packed together as to show but little fibrous stroma; the cylindric cells lining the tubes are usually two or three times as long as normal. This 316 GENERAL PATHOLOGY. variety of adenoma is prone to undergo malignant transforma- tion, many of the cancers of the rectum and uterus arising from this tumor. Rectal adenomata are most frequently seen in children, although they may occur at any age. They are strawberry- like or raspberry-like tumors, rarely over one or two centimeters - in diameter, although the author has had the opportunity to examine such a tumor that was six centimeters in its longest diameter. Most observers have found them multiple; this has not been the author’s experience. The glandular structure imi- tated is the gland of Lieberkithn. The tendency to transfor- mation into carcinoma (cylindric-cell epithelioma) is remarkable ; the author has never known a tubular adenoma to persist for any great length of time and escape the change. The same is true of a very similar tumor—adenoma of the cervix uteri. The great difficulty found in differentiating, histologically, between this tumor and cylindric-cell cancer will be referred to when consider- ing the cancer. III. Neuroma.*—A zeuroma is a tumor consisting almost entirely of nerve tissue; pure neuromata are among the rarest of new growths. The term “false neuroma” has been applied to many growths found in connection with nerves ; under this head should be classed the fibrous, myxomatous, and gummatous tumors found on, in, or around nerves. The plexiform neuroma is composed of a series of nodules along the course of a nerve or in a nerve plexus; at one time this was thought to be a true neuroma ; at present it is believed that the new tissue is essentially fibrous, and hence the tumor belongs among the false neuromata or, properly, among the fibromata of nerves. The small multiple fibromata or neuromata of superficial nerves are usually heredi- tary. The amputation neuromata—which consist usually of fibrous tissue, but which may contain partially regenerated nerve- fibers—form bulbous masses at the cut end of nerves in stumps after amputation, and are intimately connected with the cica- tricial tissue of the stump; they are usually painful. Varieties of Neuroma.—Many tumors found in connection with the nervous system have been shown, with the later improved methods, to contain a quantity of nervous tissue insufficient to justify their special consideration as neoplasms composed of that * The exact oncologic position of neoplasms arising from the central nervous system is still a matter not fully determined. Recent researches bearing upon the embryology and histology of the nervous system indicate that neuromata and gliomata may be, for the present, considered with neoplasms of epithelial origin. TUMORS. 317 structure. In theory all true neuromata could be classed under one of three heads: (1) Tumors composed of or containing ganglion cells—ganglionic neuromata ; (2) tumors made up or composed largely of newly developed medullated fibers—zszye- linic neuromata ; (3) tumors composed of or containing evidently _newly formed nonmedullated nerve-fibers—amyelinic neuromata. IV. Glioma (Gluey Tumor, Virchow).—The sustentacular tis- sue of the nervous system, according to recent observations, is a derivative of the ectoderm, and, therefore, tumors arising from or composed of such elements should be classified with the neo- plasms of epithelial origin. Gliomata are tumors apparently derived from the sustaining tissue of the central nervous system, —the neuroglia,—and are composed of glia cells more or less closely imitating the normal elements. As the glia cell differs at various stages in its development, the adult cell scarcely more than resembling its embryologic ancestor, so differ the cellular elements that enter into the formation of gliomata. In some in- stances the tumor is made up of cells showing a relatively small number of fibers, comparatively large in ‘ size ; other tumors are particularly rich in fibers. With regard to the size of the cell, it may be small, large, or even approaching the size of a giant-cell. Again, tumors occur that appear to be appropriately classed with the gliomata, and in which the cells more closely Oy a, @ resemble ependyma cells. For this class je Paes of tumors Flexner has proposed the AAPA name ependyma-cell glioma. Gliomata F16- 198.—Gtioma.—(Gould.) are sometimes found containing cellular elements indistinguishable from the cells found in small round- cell sarcoma, and, unfortunately, to such tumors the name gliosarcoma has been given. Tumors of this type are most frequent in the eye, apparently originating from the retina. That some of them are true sarcomata is indicated by their occurrence in the young (children from two to six years), by their extension in continuous structures, such as the optic nerve, and by the involvement of the contiguous tissues; not uncommonly they produce fungoid masses, which project from the orbit; they recur after removal. Gliomata of the brain do not involve the membranes; sarcomata do. Glioma contains, in nearly all instances, medullated nerve-fibers ; sarcoma rarely. (For the stain and differentiation of glia elements see article on Central Nervous System, in part II.) 3 18 GENERAL PATHOLOGY. Gliomata appear as more or less circumscribed or slightly dif- fuse tumors of the central nervous system. As already indi- cated, their consistency is largely dependent upon the character of the cellular elements that enter into their formation. Occa- sionally, the tumor may be so soft that it can be handled only with difficulty; in other instances it is firm, and even elastic. The color is dependent upon the amount of blood present and upon the presence or absence of hemorrhage or of degenerative change. Areas of softening or even of cyst formation are occasionally present. Sometimes these cysts show an epithelial lining, the cells of which resemble those forming the wall of the central canal. Commonly, but a single tumor is present ; in rare instances, however, the tumor may be primarily multiple, and in still other cases tumors evidently of different ages may be found. In a pure glioma metastasis apparently does not occur. When rapid growth and metastasis are present, the tumor is probably a sarcoma. Site.-—Brain and cord ; optic nerve and retina; olfactory lobe. EMBRYONIC EPITHELIAL TUMORS. Carcinomata, or cancers, are embryonic or atypical neo- plasms that do not have their type in adult epithelial structures, but revert to the embryo for their prototype. They always develop from the efithelial cell, which cell becomes abnormal in form and, if growing in glands, fills up the lumen of the gland’s tubule, acinus, etc., penetrating the basement or limiting mem- brane, and infiltrating the lymph-spaces of the connective tissue. Carcinomata are composed, for the most part, of epithelial cells growing out of place. ffistology.—In carcinoma two essential elements must be de- scribed: (1) the epithelial cells, (2) the stroma, which bounds the space in which the epithelial cells le, the space being known as the alveolus. Cells —The cells are characterized by every diversity of out- line; they may be round, oval, squamous, fusiform, cylindric, or caudate, and with prominent nuclei and nucleoli. The nuclei may be single or multiple, but are always large and prominent. The variation in form of the cell is due to the pressure to which it is subjected within the alveolus and to the shape of the cell from which the cancer arose. The cells are loosely nested in the alveoli, and do not attach themselves to the fibrous stroma. fibrous Stroma.—The amount of fibrous stroma varies: it consists of distinctly fibrillated tissue, arranged so as to form the TUMORS: 319 alveoli, The alveoli communicate with one another and form a continuous cavernous system, within which the epithelial cells are found. The character of the stroma depends largely on the rate of growth. If rapid, it will contain some round and spindle-shaped cells ; if the growth has been slow, or has ceased altogether, the tissue will contain few or no recent or round cells, and will be more dense and fibrous in character. The latter is the most common condition in scirrhus, the former in encephaloid cancer. The stroma not uncommonly contains a varying number of un- striped muscle-cells, or other histologic elements of the tissue in which the carcinoma is developing. The stroma of uterine can- cer is particularly rich in involuntary muscle-fibers, and cancer involving bone may show more or less osseous structure within the stroma. Situated in this stroma are the blood-vessels, which are limited to the stroma, and do not pass into the alveoli or communicate with epithelial masses; they have distinct walls that are not infrequently thickened. The lymphatics communi- cate freely with the alveoli, which fact accounts for the frequency of infection of lymphatic glands. It is through these channels that carcinoma spreads. The alveoli were originally lymph-spaces, and therefore communicated directly with the primitive lymphatic ducts draining the area. This communication is not interfered with by the growth of the cancer, but is probably facilitated by the distention of the primitive lymph-spaces by the epithelial cells. As already indicated, the epithelium may readily pass onward, entering the primitive lymphatic ducts, and later the larger ducts, and eventually the gland or gland chain lying between the carcinomatous area and the lymphatic duct that empties into the vein. The extension of cancer along the course of nerves—as, for example, the inferior dental nerve—or along vascular trunks is probably due to the presence of lymph paths that follow the course of the vessel or nerve sheath. By some authors, however, it is considered as a distinct form or method of cancerous extension. Clinical Characteristics.—As a rule, carcinoma occurs after the age of thirty-five. Over fifty per cent. of all cancerous growths develop after the forty-fifth year. The age of the patient is not so important as the evident age of the structures involved. Thus, the author has seen a well-formed scirrhus of the breast in a patient of twenty-two. The mamma involved, as well as its fellow of the opposite side, showed distinct atrophic changes. The diseased mamma was removed, the tumor did not return, and the patient passed the menopause at thirty. Such instances, 320 GENERAL PATHOLOGY. while apparently exceptions to the rule that cancer occurs in middle life, are only apparent and not true exceptions. Such individuals are aging prematurely, and in the diagnosis of cancer such factors must be taken into consideration. The growth is usually primarily single. Generally, the tumor is hard. The so-called soft cancers are those that have undergone some sec- ondary change, as fatty or colloid, or are made up of epithelium in excess, as the encephaloid. Cancers tend to infiltrate adjacent connective tissues. There is usually a central tumor mass, from which processes radiate into the surrounding tissue. The bor- der of the tumor is not sharply defined ; the typical connective- tissue and epithelial-tissue tumors, on the other hand, are likely to have well-defined margins, and, in most instances, can be enucleated from the tissues in which they lie. Carcinoma has no capsule and can not be enucleated. Secondary carcinoma is usually multiple, has a more sharply defined or circumscribed border, and, while it projects into the neighboring tissues, does not tend to infiltrate them with the same rapidity as did the primary tumor; as a rule, the mass is much softer. These characteristics are probably due to the recent and rapid growth of the neoplasm. Secondary Changes.—The most important are certain forms of degenerative change, among which is fatty degeneration. This depends somewhat on the rate of the growth; the more rapid the growth, the more rapidly this change takes place ; hence it is usually most marked in encephaloid cancer. Colloid degenera- tion of the alveolar contents and myxomatous degeneration of the connective-tissue stroma are occasionally observed. These pro- cesses are particularly marked in carcinomata involving the stomach. Pigmentation, or melanosis (melanotic cancer), is rare. Calcific deposit, or even true bone formation, may occur ; they are, however, quite infrequent. The cysts occasionally formed in cancer arise as the result of liquefaction necrosis or of degen- erative changes in the cellular elements, or, probably, in most instances, are dependent upon the presence of cysts prior to the carcinomatous development. The contents of such cysts may be fluid, mucoid, or colloid material, and, in rare instances, they may contain more or less blood; the extravasated blood may undergo degenerative and necrotic changes, leaving little of the normal constituents to be recognized, except the altered brown- ish pigment. Small areas of hemorrhage into the stroma are not so infrequent, and when ulcerative processes have exposed the surfaces, or when associated necrosis and infection are present,—as in cancers of the uterus and stomach, and oc- TUMORS. 321 casionally in cancer of the mammary gland,—hemorrhage may be severe and even fatal. The size of the cancer often bears no relation to the amount of hemorrhage, the latter being appar- ently dependent upon the size of the vessels involved, and pos- sibly, to a less degree, upon the activity of the infective processes. Various infections occur in carcinomatous tissue. After solu- tion in the continuity of the superficial covering, infection may be marked, and the systemic phenomena of sepsis may interfere with the general nutrition, sometimes demanding operative pro- cedures in cancers the extent of which precludes the possibility of complete removal. The associated infections are usually pyogenic. Numbers of saprophytic organisms may be present. Tuberculous processes, for example, in the esophagus or larynx may become carcinomatous, or an ulcerating carcinoma may become tuberculous. Tuberculosis and associated cancer of the skin have been observed, and lesions apparently primarily syphi- litic, have become cancerous. Evidences of gumma formation in cancer are less frequent, if ever present. Distinct abscess formation is infrequent. Necrotic processes, and even extensive gangrene, may at times be observed. Szte.—The presence of epithelium being the essential requisite, any surface, tissue, or organ containing this element may become carcinomatous. To a certain extent the various forms of epithe- lium seem to influence the occurrence of different varieties of cancer. The cause of this influence will. become more evident as we proceed with the consideration of the forms of carcinoma. Varieties —(1) Epithelial carcinoma ; (11) glandular carcinoma. The term epithelioma is used in a broad sense by some writers as referring to all carcinomata. It is here applied to those varieties of carcinoma that usually spring from epithelial surfaces, and is often spoken of as superficial cancer. I. Epithelioma assumes three types: (7) Sguamous; (2) cylindric-cell ; ( 3) tubulated. 1. Squamous Epithelioma.—This variety always grows from surfaces covered by squamous epithelium, either cutaneous or mucous; its epithelial elements closely resemble squamous epithelium ; the distortion in shape of the cell is due to the pressure to which it is subjected during its growth. The cells penetrate from the surface epithelium into the lymph-spaces of the connective tissue, and follow those channels that intercom- municate. Occasionally, single isolated epithelial cells may be recognized in the connective tissue of.the growth. Transverse sections of the epithelial masses show typical nesting of cells— the so-called concentric globes or epithelial nests. When these 2I 322 GENERAL PATHOLOGY. nests undergo hardening,—a change incident to age and to attempted desquamation,—they are spoken of as ‘‘ pearts,’”’ hence the term pearl epithelioma. These yellowish spherules, composed of cornified or keratinized epithelium, are commonly microscopic bodies situated within the alveolar contents, and showing a marked affinity for acid dyes, notably for the picric acid stains. In rare instances they may be large enough to be seen with the naked eye. The author possesses one specimen of this kind. The diagnostic importance of such bodies (they were at one time held to be pathognomonic) is lessened by their occurrence in other conditions associated with in- flammation of the skin; they are occasionally seen at the margins of ulcerative pro- cesses that evidently are -not cancers, and are prone to occur at the edges of the granulating tissue around in- Fic. 199. —SQUAMOUS EPITHELIOMA. — Fic. 200.—SECTION OF A SQUAMOUS EPITHE- (Gould.) LIOMA.—(Rindfleisch.) X 500 diameters. a. The down-growing epithelium if which are two cell nests or pearls. 6,4. The stroma, in which, at c, a few lymphoid cells are to be seen. growing nails and in onychitis. The fibrous stroma may show some inflammatory infiltration, particularly if the ulceration inci- dent to softening and infection has occurred. It shows little of the alveolar arrangement that characterizes some of the other varieties of carcinoma. The ulceration, which occasionally oc- curs early, may not be due to inflammatory or infective processes, as is usually the case, but to fatty degeneration of the cells. The growth usually begins as a small nodule, situated in the connective tissue just under the epithelial layer, with which it is continuous ; the skin is not movable over the indurated mass. Not uncommonly the spot of induration may appear to be TUMORS. 323 in the epithelial layer. As a rule, the overlying epithelium is pushed upward, giving rise to moderate elevation; this indu- rated elevation may show slight umbilication, due to fatty changes, absorption, and shrinking in its interior, before super- ficial exfoliation or ulceration occurs. When fully developed, the cancerous surface presents an irregular, ulcerated, warty appearance, exuding from its surface at times a clear, or slightly tinged, or, it may be, an irritating, ichorous fluid. The ulcera- tion occurs in the center, surrounded by an indurated area, be- yond which may be firm and distinct nodules. There is often a distinct tendency toward scabbing, particularly when situated on the general cutaneous surface, the lip, and at other mucocutaneous junctions. The scab remains attached for a varying length of time, and then falls off or is removed by the patient; after its removal the underlying cancer, just described, is seen to be slightly larger than before the scab formed. This gradual increase in the size of the cancer, observable after each exfoliation of the scab, is often of diagnostic importance, as is the gradual extension of induration in the tissue beneath. The area of recognizable in- duration is not the limit of the tumor—a fact always to be borne in mind during its removal. On section, the tumor is firm, and the fibrous stroma may show as white glistening bands. Asa rule, there is no hemorrhage; there are few blood-vessels near the surface. The process develops slowly, and glandular involve- ment may not occur for years, although in rare instances it has been observed within the first year. Site-—Squamous epithelioma usually occurs at the junction of the skin and the mucous membrane, or where two kinds of epithelium join. It is frequently found on the lower lip, nose, penis, scrotum, vulva, anus, and tongue; less commonly on the gums, palate, tonsils, larynx, pharynx, esophagus, bladder, os uteri, and general cutaneous surface ; rarely on the hands and feet. 2. Cylindric-cell Epithelioma (Adenoid Cancer, Columnar- cell Epithelioma, Malignant Adenoma).—This variety of cancer is characterized by irregular or tubular cavities, paved with one or more layers of cylindric cells, and separated by a stroma, which may be fibrous, embryonic, or mucoid. In structure it is said to occupy an intermediate position between the simple adenoma and true cancer. The cylindric cells are similar to those that cover certain mucous or glandular cavities, and are always implanted more or less perpendicularly to the wall. The epithelial ele- ments are similar to those of the mucous membrane from which they grow, but differ microscopically from the arrangement in the normal mucosa in the absence of a basement membrane (mem- 324 GENERAL PATHOLOGY. brana propria). The slower the growth, the more nearly typical is the attempted gland formation; in rapid growths and recur- rences the cells are small and the lumina imperfect. Cylindric-cell carcinomata are soft, and are often of a gelatinous consistence. On section, they present a soft, watery appearance. The rate of growth varies in different cases, and often within wide Fic. 201.—CYLINDRIC-CELL CANCER OF THE STOMACH. Tissue fixed in corrosive sublimate, infiltrated with paraffin, stained with hematoxylin and eosin, and mounted in balsam. A. Drawn from \%-inch obj., %-inch oc. &. Drawn from %-inch obj., %4-inch oc. The upper and right-hand quadrant of the circle shows the fully developed cancerous tissue. The lower portion, just above the letter &, shows the begin- ning production of the gland-like tubules and the extension of the cancerous tissue into the gastric wall. At C,and also in other parts of the field, the stroma resembles myxo- matous tissue. limits ; it may be rapid or slow—frequently rapid. Glandular involvement, or metastasis, usually occurs early and progresses rapidly. In cylindric-cell cancer of that portion of the alimen- tary canal drained by the portal vein metastasis to the liver is common. Uterine and other forms of pelvic cancer may be simi- larly disseminated. TUMORS. 325 Age.—Cylindric-cell epithelioma, as a rule, occurs earlier than any other variety of epithelioma. Site.—Rectum (rectal carcinoma may occur very early in life), stomach, uterus, ovary, gall-bladder, liver and biliary passages, and respiratory tract ; cylindric-cell cancer may occur in any por- tion of the intestine. oo bg OSI RLY ae Sap KGL fees ee @e 2 eS Qe ~ 7S FIG. 202.—SECTION OF CARCINOMA OF THE LIVER. Tissue fixed in corrosive sublimate, infiltrated with paraffin, stained with toluidin-blue and eosin, and mounted in balsam. Drawn from Y-inch obj., %-inch oc. A,A,A. The liver tissue adjacent to the tumor. The rest of the field consists of three complete alveoli, and parts of five other alveoli. Two of the complete alveoli occupy the central portion of the drawing, while the third alveolus (ec tealy complete) is in the extreme upper portion. The parts of alveoli are indicated by the letters &,B,B,B, B. About one centimeter inward, and to the left of the second B from above, a small area of hemorrhage is to be noticed. A similar but smaller area of hemorrhage is seen just below the lower alve- olus. The section was taken from a primary cancer of the liver, which showed, in some areas, a structure closely resembling the cylindric-cell cancer; in other areas the absence of any intra-alveolar arrangement of the cells leads to an encephaloid appearance. It will be noticed that in the alveoli shown there is not the characteristic cylindric arrange- ment of the cells to be seen in figure 201._ At some points, however, there is seen _a dis- tinct attempt at such an arrangement. The absence of any capsule, or of any effort at capsule formation, between the tumor and the adjacent liver-tissue is well shown. An illustration showing the gross appearance of this tumor is to be found in the chapter on the Liver, part 111. As secondary growths, this variety of cancer occurs in the lymphatic glands, liver, lungs, and kidney, and in bone. The secondary nodules possess the same characteristics as the pri- mary growth. The most common forms of degenerative change are mucoid and colloid. 3 26 GENERAL PATHOLOGY. As already remarked, cylindric-cell cancer resembles very closely the tubular adenoma. (See p. 315.) The very close resemblance of the two varieties of tumor has led observers to regard them as possibly identical; the structural difficulty has been concealed by associating with it the clinical phenomena ; Fic. 203.—CYLINDRIC-CELL EPITHELIOMA OF THE CERVIX UTERI. The cervix and most of the body of the uterus have been destroyed by the necrotic process, The grooved director, shown in position, passes through a perforation into Douglas’ pouch. The ovary shown on the left is much enlarged, and is apparently invaded at its point of attachment to the uterus behind. The vaginal vault and the posterior bladder wall have been destroyed. thus, we find in the German literature constant reference to simple adenoma and to malignant adenoma, meaning by the former the tubulated adenoma, and by the latter the cylindric-cell cancer at present under consideration. It is evident, clinically, that the two tumors are not identical. The small, strawberry-like polyp TUMORS. 327 of the rectum, in children, never recurs after removal, and of the many specimens of simple adenoma of the cervix uteri that the author has seen, nene has recurred if removed early in life. In tracing the cases of clearly marked cylindric-cell cancer not a single instance has occurred in which recurrence did not take place in the course of time. Sometimes the newly formed tubules are surrounded by a distinct membrana propria; such a tumor must evidently be a simple adenoma. In the typical tubules of the cylindric-cell cancer no basement membrane is ever demon- strable; in the caricer there is a more lawless, purposeless, irregular distribution of the gland-like epithelial cells, and usually a sufficiently prolonged search will show areas so clearly cancer- ous that the diagnosis can not be doubted. That the simple adenoma may be converted into the cancerous tumor there can be no doubt. Admitting this possibility, we must concede that intermediate structural gradations occur, and that occasionally tumors are found in which, from the examination of a single slide, it is quite impossible to state definitely whether they are simple or malignant. Recognizing that adenoma of this kind is likely to become, without any apparent reason, malignant adenoma, it seems to the author that the method of treatment of such cases is at once simplified—the dangerous character of all doubtful growths of this kind should be admitted, and, in the absence of positive knowledge'‘to the contrary, they should be treated as cancer. 3. Tubulated Epithelioma (also variously known as Rodent Ulcer, Tubular Epithehoma, Noli me tangere, Lupus Excdens, Herpes Exedens, etc.).—This form of epithelioma is composed of irregular pavement epithelium arranged in plugs or cylinders that anastomose with one another and are embedded in a stroma consisting of connective tissue—embryonic, mucoid, or, more commonly, dense and fibrous. When mucoid, it is more likely to undergo further degeneration and to become cystic. The epithelial nests and pearls seen in the squamous epithelioma are absent. In some instances the histologic arrangement resembles scirrhus. With regard to the gross appearance and development of this tumor, descriptions have been given that evidently include true lupus (cutaneous tuberculosis). The resemblance is often striking, and a microscopic examination is, in most instances, necessary to differentiate between the two conditions. Tubulated epithelioma occurs in the aged; it appears on the mucous surfaces earlier in life than on the cutaneous surfaces. The majority of cases coming under the author’s observation have begun on the lower 32 8 GENERAL PATHOLOGY. eyelid. Ulceration appears early, but progresses very slowly, and the process may remain stationary for months, or even for years. The edges of the ulcer are usually elevated, irregular, and indu- rated. The degree of induration depends largely upon the duration of the process. In old, slowly extending ulceration the induration is more marked than in rapidly progressing lesions. Instances are not infrequent in which partial healing of the ulceration has taken place, and in which, after a variable period of quiescence, extension has been resumed. Sometimes, without any discernible cause, the growth suddenly assumes remarkable activity, and in a comparatively short time shows extensive in- volvement of adjacent tissues. The author recalls a case in which a tumor developed on the lower eyelid asa small ulceration, ovoid in outline, and, after three years, its diameter did not exceed 0.5 cm. It was excised and its cancerous nature was satisfactorily determined by microscopic examination. Within a year a small recurrent lesion appeared at the site of excision, which, in five years, showed but little tendency toward extension. The tumor then began active growth, and inside of two months had involved the entire lower eyelid and part of the cheek, and had almost en- tirely destroyed the eye. Excision was again attempted, but seemed to exert but little influence on the rapidity with which the cancer extended. Glandular involvement is more uncertain in these cases than in any other variety of cancer; in some instances the spread is rapid ; in others, slow; in some cases it does not appear at all. When upon the mucous surfaces or upon the eyelid, the growth is frequently rapid. Site.—The most frequent location is on the face, tongue, gen- eral cutaneous surface, intestine, uterus, and ovary. When oc- curring in the skin, the mass is believed to develop from the sweat-glands, or, possibly, from the hair sheaths. II. Glandular Carcinoma.— Varieties —(z) Scirrhus; (2) en- cephaloid carcinoma. 1. Scirrhus (Acéxous Cancer, Chronic Cancer,-Hard Cancer, Fibrous Carcinoma).—This variety of carcinoma is characterized by the amount and density of its stroma and by its irregular growth. The tumor occurs as a hard, firm mass, varying in appearance according to its location. In the breast, which is its usual site, it forms a hard, rounded or irregular mass, which soon becomes firmly attached to the subcutaneous tissue, and eventually to the skin. By the contraction of the fibrous stroma it causes retraction of the nipple and puckering or dimpling of the skin—* bacon-rind” skin. (See Fig. 204.) TUMORS. 329 On section, it presents a grayish-white glistening appearance, dotted with yellow patches of fatty tissue. The fibrous bands and fatty areas are more marked toward the center of the tumor. Toward the periphery it is more vascular and less fibrous ; it is nonencapsulated. On microscopic section, the tissue is com- posed of two structures, connective tissue and epithelial cells, the connective tissue or stroma being arranged so as to form a series of rounded or irregular spaces (alveoli) in which the epithelial cells are nested. The blood-vessel walls are thickened and fibrous. Microscopic section from the central part of the tumor will show the connective tissue more dense and fibrous and the FIG. 204.—PART OF CUTANEOUS SURFACE OF RIGHT MAMMA, THE SEAT OF A CENTRALLY PLACED, PRIMARY SCIRRHOUS CARCINOMA AND OF A SECONDARY NODULE. Just to the left of the letter 4 is the nipple, showing the retraction or umbilication, with puckering or dimpling of the skin of the surrounding areola. The ‘‘ bacon-rind””’ appear- _ ance is even more marked just to the left of B. To the right of C is a secondary nodule, firmly attached to the skin, which is drawn in around the neoplasm; the surface of the neds shows the stretched skin, which at the five pale ovoid or irregular areas is greatly thinned. alveoli much smaller, with the epithelial cells small and atro- phied, or possibly degenerated. With the increase in the fibrous stroma there is increased contraction, causing irregularities of the surface ; when occurring in the breast, this contraction gives rise to retraction of the nipple—umbilication. During the development of the morbid process contraction of the fibrous tissue may be more rapid than epithelial proliferation, and the organ involved—for example, the breast—may actually diminish in size with progressive induration ; when this contrac- tion is marked, the tumor is said to be atrophic or “ withering.” 330 GENERAL PATHOLOGY. (See Atrophic Scirrhus.) Another diagnostic point depending upon the contraction of the fibrous tissue is the “ cupping ” of the center of the mass when divided by an equatorial incision ; this is not always present, but can usually be demonstrated. If the neoplasm be cut in halves by a clean, smooth incision, the central part of the cut surface of each half will retract, thereby Fic. 205.—GLANDULAR CARCINOMA OF THE LIVER (SCIRRHUS). Tissue fixed in corrosive sublimate, infiltrated with paraffin, stained with hematoxylin and eosin, and mounted in balsam. Drawn from %-inch obj., %-inch oc. A,A,A,A,A. Con- nective-tissue stroma. 8,8,8,B.2. Epithelial cells occupying, but not filling, the alveoli. Communication between the alveoli is well shown, as practically all the large alveoli communicate. Just below Cis shown a small alveolus containing two epithelial cells, and a little to the right is a similar alveolus. A number of efforts were made to demonstrate that the clear space surrounding the epithelial cells was occupied by some material that would not stain by the method used in the section from which this drawing was made. All efforts to secure such demonstration were futile. It is probable that the space is produced by the contraction of the epithelial cells during the process of fixation or hardening, or that the spaces shown are filled during life with some fluid not coagu- lable by the fixing method used. depressing that part of the incised surface below the surround- ing margin—the depressed area constituting the so-called “cup.” Glandular involvement usually takes place within the first year. Degenerative Changes.—The forms of degeneration that are likely to occur are fatty, colloid, mucoid, and hyaline, and, TUMORS. 331 rarely, caseous necrosis. Melanotic, or pigmentary, and calca- reous infiltrations occur. , Stte—Most common in breast, uterus, stomach (pylorus), esophagus, rectum, and kidney; rare in ovary, testes, and prostate. Atrophic Scirrhus.—When the production of fibrous tissue predominates, and the epithelium proliferates but slowly, the re- sulting tumor contracts much more rapidly than it grows. The epithelial cells are therefore pressed upon, and often disappear from many areas. This form of scirrhus is a breast tumor, and, once developed, it is generally found that the gland and tumor progressively diminish in size. The malignancy is low, and if the fibrous tissue development persists in its excess, the patient rarely succumbs. The writer had a case under observation, a woman seventy-two years of age, who had refused an operation nearly twenty years previously. The entire breast of one side, and the overlying and adjacent skin, showed puckering and con- traction; the breast of the other side was also invaded, but ulceration had not taken place over either gland. Glandular involvement may be long delayed, or, in a few cases, may not occur. In the case just mentioned there was very slight involvement in the last few years only. The patient died at seventy-four, of erysipelas. Microscopically, such tumors are mostly fibrous stroma, with few alveoli ; the contained epithelial cells are advancedly atrophied or degenerated, or both. 2. Encephaloid Carcinoma (Medullary Carcinoma, Soft Can- cer, Acute Cancer).—This rare variety of carcinoma is a soft, rapidly growing, brain-like tumor, in which the fibrous stroma is more nearly embryonic, not uncommonly myxomatous, and very scanty; the alveoli are large, and are filled with large, rapidly growing epithelial cells. The tumor appears as a soft, at times almost fluctuating, nodular mass, which tends to ulcer- ate and to bleed (fungus hematoides). There is early involve- ment of the skin (“bacon rind’’), soon followed by superficial necrosis and ulceration. As a rule, encephaloid carcinoma occurs earlier in life than scirrhus, and has been reported in the young. It may occur as a ptimary or secondary growth. The growth is exceedingly rapid, and glandular involvement takes place early—within the first six months. There is no retraction of the nipple when occurring in the breast, and the rapidity of growth produces a more clearly circumscribed mass than scir- rhus ; it is, however, more rapidly fatal. Site, —Primarily, most common in mammary gland and in 332 GENERAL PATHOLOGY. testes; may occur as a secondary growth following scirrhus, particularly when the latter involves the internal organs. En- cephaloid cancer is much less common than scirrhus. Colloid or gelatiniform carcinoma is a form of cancer in which degenerative changes take place in the protoplasm of the epithelial cells of the alveoli or in the connective-tissue stroma. The typical colloid cancer belongs to the glandular group, although a similar change is sometimes observed in the cylindric- cell epithelioma, particularly of the liver. The two conditions are, however, by no means identical, and are therefore easily differentiated. Gelatinous transformation of glandular carcino- mata occurs frequently in cancer of the intestinal canal, particu- larly of the stomach, and less frequently in cancers of the mam- mary gland, testes, and ovaries. Gelatinous areas are sometimes FIG. 206.—ENCEPHALOID CARCINOMA (SOFT Fic. 207.—GLANDULAR CARCINOMA _ IN CANCER).—( Gould.) WHICH THE STROMA Has BEEN Con- A, A. Stroma made up of developing con- VERTED INTO MUCOID TISSUE.—( Gould.) nective tissue. At the upper 4 the stroma Note the stellate cells, so closely resembling is almost myxomatous. #&. Epithelial those seen in myxoma. cells occupying an alveolus; three other alveoli are shown. found that no longer contain any of the structural elements by which we identify carcinomatous processes. In the younger parts of the tumor, however, advancing transformation may usu- ally be recognized ; a varying number of epithelial cells may be found, centrally placed in the alveolus, and surrounded by con- centric lamella of gelatinous material. The tumors are soft and trembling, glassy, and at points semitransparent. In the mam- mary gland metastasis may be delayed; in the stomach rapid extension to the peritoneal surface, and more or less diffuse car- cinomatosis of the serous surface, may be rapidly developed. (For the chemistry of colloid and mucoid changes see p. 245.) Mucoid Carcinoma.—wWhen the substance that distends the alveoli is more viscid in character, it is believed to be a mucoid TUMORS. 333 degeneration of the intercellular substance, rather than a colloid change commencing in the cell. It is the transformation of the albuminoid constituents of the tissue into mac’z. Until our methods of differentiation become more accurate, and until we know more of the evolution of mucoid and colloid carcinomata, it would probably be best to consider them both under the -head of gelatinous or gelatiniform cancer. Fic. 208.—CoLLoip CANCER.—(Rindfletsch.) X 300 diameters. The stroma has been but little involved, while the intra-alveolar structure has been converted almost entirely into gelatiniform material. Melanotic carcinoma is, in the writer's experience, a very rare tumor. It is believed that the pigment-forming cells of epi- thelial origin are present in certain forms of cancer, and that melanosis in such tumors is due to the activity of these cells. Melanotic cancers are usually malignant to a high degree, mani- festing a tendency to metastasis early ; the secondary nodules are pigmented. CONNECTIVE-TISSUE TUMORS. ADULT CONNECTIVE-TISSUE TUMORS. I. Lipoma.— Varieties.—(z) Simple ; (2) fibrous. A lipoma or fatty tumor is a localized, more or less circum- scribed, new formation of fat. Lipomata are usually lobulated, soft, doughy, pseudofluctuating, and inelastic. As to shape, they are ovoid, spheric, or flat, commonly sessile, rarely pedunculated. If encapsulated, the capsule is exceedingly thin ; nonencapsulated fatty tumors are sometimes spoken of as diffuse lipomata, the margins being often not clearly defined. Lipomata are rarely 334 GENERAL PATHOLOGY. multiple ; instances, however, occur in which a large number may be present. The author recalls a case in which the presence of lipomata of the axilla, groin, and neck led to the diagnosis of Hodgkin’s disease. The diagnosis in this case was made more difficult by the presence of calcareous infiltration and true bone formation in the interior of the tumors, rendering them more dense and causing a striking resemblance to multiple lymphade- nomata. Multiple lipomata are said to occur in families; not infrequently the inherited tendency is transmitted through several generations. An interesting phenomenon observed in fatty tumors FIG. 209. Fic, 210. DiFFUSE LIPOMA OF THE NECK. Case reported by Dr. J. Shelton Horsley in the ‘‘ Philadelphia Medical Journal,” July 8, 1899 (reproduced by permission). is “ gravity wandering” ; this feature may be present in tumors developing in the subcutaneous tissues and possessing slight at- tachment to the surrounding structures. Fatty tumors develop- ing on the upper portion of the chest-wall, near the axilla, or on the back, may, in the course of time, descend to the level of the pelvic brim, and lipomata of the thigh may wander as far as the knee. The distance traveled and the rapidity of movement are, of course, influenced by the amount of attachment and by ana- tomic relations. TUMORS. 335 Microscopically, fatty tumors consist of cells containing fat and of a variable quantity of connective-tissue stroma. The cells are like those of adipose tissue, though usually larger. The blood-vessels are distributed in the fibrous stroma. If the fibrous tissue is in excess, the neoplasm is called a fibrolipoma, or fibro- fatty tumor. The fibrous fatty tumor, or fibrolipoma, differs from the simple lipoma only in the amount of fibrous tissue that it contains. In the fibrolipoma this is abundant; there is no cap- sule, and, if the tumor be grasped at its base and the skin made tense, dimpling of the cutaneous covering occurs, owing to the fibrous bands that traverse the tumor pulling the skin in at their points of attachment. Lipomata containing myxomatous tissue are called myxo- - Lipomata. Clinically, \ipomata are benign tumors of slow growth and of variable size. The zzjfiltrations and degenerations that — Fic. 211.—Liroma.—(Gouid.) they may undergo are calcareous infil. The glohivar tarrete the cell tration and mucoid degeneration, ossi- margin are well shown. fication, ulceration, and cystic degenera- tion ; secondary inflammatory and necrotic changes also occur. Szte.—Connective tissue ; subcutaneous tissue of trunk, espe- cially of back and abdominal walls; intermuscular septa; sub- synovial and subserous tissues ; rare in stomach and intestines and in internal organs. II. Chondroma (Luchondroma, Enchondrosis, Chondroid Ex- ostosis)—Chondromata are masses of new tissue, composed of hyaline, elastic, or white fibrocartilage. Chondromata de- veloping from preexisting cartilage, such as the cartilages of the larynx and trachea and the costal cartilages, may assume a polypoid shape, and are not uncommonly multiple, and are spoken of as ecchondromata. Developing from bone or in tissue not normally containing this element, the cartilaginous tumors are called exchondromata. The term chondroid exostosis is applied to a cartilaginous tumor growing from bone; such a tumor may appear as a periosteal, subperiosteal, or medullary growth. Car- tilaginous tumors are usually rounded, smooth, tuberous, or lobulated tumors of very dense consistence ; they often appear to be encapsulated, owing to the compression of the surrounding tissues; not uncommonly, however, they have a well-marked capsule. The cut surface presents a pearly, bluish-pink appear- ance, identical with fresh cartilage. As a rule, cartilaginous 336 GENERAL PATHOLOGY. tumors are nonvascular ; but if vascularization occurs, it is at the center or through the fibrous septa. Tumors composed of car- tilage are most frequent in the young, and are rare after puberty. Microscopically, they resemble true cartilage tissue ; the inter- cellular substance may be hyaline, faintly or distinctly fibrous, or, in rare instances, mucoid. They are not, as a rule, composed of dense cartilaginous tissue, but of islands of cartilage surrounded by fibrous septa. The cartilage matrix is hyaline, except at its junction with the fibrous stroma, where it is usually more or less fibrous. Within the matrix are the lacunz containing the cartilage cells; these resemble the nor- mal cartilage, and are either rounded or oval in shape. The lacune of the matrix are occasionally branched, so as to cause the appearance of a series of stellate spaces, with cartilage cells lying in their Fic. 212. —CHONDROMA.— centers. rca Lnfiltrations and Degenerations.—Fatty, calcareous, mucoid (most common), and- cystic ; ossification may occur, especially when the tumor springs from the junction of the epiphysis and shaft of a long bone. Site—Bones ; as bones are developed largely out of cartilage, it may be supposed that remnants of the embryonic cartilage are left over, and that they afterward develop into tumors. Chon- dromata occur most frequently on the metacarpal bones and phalanges of the hands; not so frequently on the corresponding bones of the foot. They are not infrequent on the femur and bones of the pelvis, in the last-named situation not uncommonly attain- ing the largest size ; they also occur on the ribs and scapule, rarely on the face and skull, sheaths of tendons, and bronchial cartilages. Chondromata are infrequent in the soft parts, but have been observed in the testicles, ovaries, mammez, and sali- vary glands. Chondroid and osteoid masses occasionally develop from the inner table of the skull and from points of junction of the cranial bones that normally coalesce. III. Osteoma.—A tumor-like mass of bone developed with- out the occurrence of inflammation or incident to the process of repair ; usually occurring at the point of junction between a bone and its cartilage. Osteomata are classified, according to their position, as (1) exostoses, or those growing from the exterior of a bone, and (2) enostoses, or those growing from the interior of abone. According to their structure they are divided into (1) eburnated ; (2) compact; (3) cancellous or spongy. TUMORS. aay 1. Eburnated Osteoma.—These occur most frequently on the inner table of the skull, and are not uncommonly syph- ilitic. They are extremely hard, symmetric, and usually multi- ple. On section, the dense bony structure is found to be com- posed of lamelle, which are arranged parallel with the surface of the tumor. In the lamelle there are no blood-vessels and no Haversian canals, but canaliculi similar to those found in the cementum of the teeth; these run toward the surface. 2. Compact Osteoma.—This variety is composed of ordinary compact bone, similar to that found in the outer layer of the long bones. The growth is nodular, usually beneath or in the perios- teum, and is commonly met with in the long bones. On section, it is found to differ from the eburnated osteoma, in that the vessels and Haversian canals run at right angles to the long axis of the bone. The tumor possesses a periosteal fibrous covering, with a layer of small round cells (osteoblasts), and with young bone formation in progress beneath. Regular Haversian systems may be clearly defined. 2 3. Cancellous or Spongy Osteoma.—lIn this variety the trabecule are very thin and are not numerous ; the medulla is em- bryonic in character, and often appears as a gelatinous mass. In rare cases it is distinctly fibroid. The whole tumor is essentially like the spongy tissue of which the ends of long bones and the bodies of shorter ones are composed. Clinical Characteristics.—Osteomata are benign tumors of slow growth, usually arrested with advancing age, and rarely attaining a large size. They are often hereditary and multiple, in which case they usually occur in early life. Osseous growths that exhibit malignant characteristics are osteosarcomata, or sarcomata that have undergone partial ossification or extensive calcareous infil- tration. Secondary Changes.—Osteoma may become inflamed, may be- come carious, or may undergo zecrosis. Rarely an osteoma may be transformed into a sarcoma. Site-—Most common in connection with bone,.periosteum, me- dulla, or cartilage ; may occur in the soft parts of the body, in the brain substance, in the dura mater and pia mater, in the pleura, diaphragm, and pericardium, in the skin, in the choroid coat of the eye, in the air-passages, around or in glands, in nerve-centers, and in tendons. IV. Fibroma (fibroid, Desmoid, Steatoma, Lnoma).—Fibro- mata are tumors composed of wavy bundles of fibrous tissue. Simple Fibroma.—This variety is typified by the paznful sub- cutaneous tubercle, which consists of a tubercle about the size of a 22 33 8 GENERAL PATHOLOGY. coffee-bean in the subcutaneous cellular substance. It is of firm consistence, and is apparently quite circumscribed, being situated loosely in the cellular tissue immediately under the integument. From the extreme pain produced by these small nodules, many have imagined that they must contain nerve-fibers ; careful re- search, however, has in all cases failed to demonstrate their existence. They occur more frequently in the female than in the male. Lg Mei: YYYGMY) « JE M1 t LALA FY, pe FIG. 213.—SOFT FIBROMA. By some authorities fibromata are said to be hard or soft, the density being dependent upon the degree of development. The hard or dense fibroma (fibroma durum) is of the type of dense fibrous tissue, while the soft fibroma (fibroma molle) is composed of a younger cell growth, and contains fewer fibers and more cel- lular elements. The hard fibroma is firm, usually lobulated, and encapsulated. The soft fibroma is much less dense, and in tex- TUMORS. 339 ture resembles the lipoma ; it may be lobulated and encapsulated. The density of the fibroma, upon which the foregoing subdivision is based, may be dependent upon factors other than the develop- mental stage of the fibrous element. Myxomatous transformation of the intracellular substance (wzyxofibroma) and edema produce soft, often semifluctuating fibrous masses. In addition to the fibrous tissue, other connective-tissue elements may be present ; when such elements are sufficiently abundant, the condition is indicated in the following manner: For fatty tissue, /pormatous foroma, or fibroma lipomatodes ; for bony tissue, ossifying fibroma, or fibroma ossificum ; a fibroma rich in capillaries is called angio- fibroma or telangiectatic fibroma, or fibroma telangiectaticum. Molluscum Fibrosum (Synonyms: /7brocellular Tumor, Dermatolysis, Pachydermatocele).—This variety of fibroma occurs in a rather extraordinary condition, in which the chief feature is an overgrowth, apparently not inflammatory, of the fibrous struc- ture of the skin and subcutaneous tissues. The new growth may affect a small area, such as the scalp, or it may involve a large extent of skin on the trunk or extremities, or both, causing it to hang in pendulous folds. Sometimes the tumors form as separate nodules scattered over the skin. Microscopically, the tissue is composed of fibrous bundles with intervening branched cells, the processes of which clasp the bundles. In the dense fibrous bands there are few cells. The cells are, in many in- stances, almost embryonic in appearance, and the tissue is par- ticularly rich in nuclei. Merken has recently studied fibroma molluscum, and concludes that it depends upon some congenital factor closely allied to that operative in the production of nevus. Keloid (Cheloid, Kelis)—This is a rare variety of fibroma. It takes the form of tuberous, sausage-like, or discoid growths seated in the corium beneath the papillary layer. Varieties.—(1) True or spontaneous keloid ; (2) cicatricial keloid. 1. True Keloid.—This consists of a fibrous growth in the corium, covered with a papillary layer ; the papilla and epidermis are intact. It is most common in the negro. It consists of bun- dles of coarse fibers, and in the early stage contains numerous spindle cells. 2. Cicatricial Keloid.—This variety grows in the substance of a scar, and differs from the true keloid in that it is not covered by the papillary layer. In other respects it resembles the true keloid. Site-—Fibromata originate in connective tissue, cutis, or sub- cutaneous tissue, from submucous or subserous tissue, from fascia, periosteum, neurilemma, or the connective tissue of organs (uterus, 340 GENERAL PATHOLOGY. ovaries, testicles, mammary gland, and labium majus). Clinically, they are benign tumors of slow growth, and, with the exception of keloid, do not tend to recur after removal. Degeneration.—Serous infiltration (as in molluscum fibrosum), mucoid degeneration, fatty degeneration (especially in the simple fibroma of syphilitic origin), calcification (fibroma petrificum) ; suppuration and ulceration also occur. FIG. 214.— SECTION (LONGITUDINAL) OF THE UTERUS SHOWING UNIFORM MyYoMATOUS ENLARGEMENT. At A is a small subserous myoma beginning to forma pedicle. The small depressions shown on the incised surfaces are sections of sinuses, some of which contained thrombi.—( From a specimen in the museum of the Jefferson Medical College. The drawing is one-fourth natural size; the artist has slightly exaggerated the transverse diameter of the uterine cavity. Weight of specimen, 5760 gm.) V. Myoma.—tThe myomata are tumors composed of muscle- tissue. Two forms of the myoma are recognized, depending upon the kind of muscle that the tumor attempts to simulate. A tumor composed of nonstriated muscle-fiber is called a “omyoma, or myoma levicellulare ; a tumor containing a varying amount of striped muscle-fiber has been described, and is called rhabdomy- ona, or myoma striocellulare. TUMORS. 341 1. Liomyoma.—These tumors occur most frequently in the uterus, and not uncommonly contain more fibrous tissue than similar tumors occurring elsewhere. Liomyomata also occur in the prostate, esophagus, stomach, and intestines. As a rule, this variety of tumor arises only in situations containing unstriped muscle-fiber. The tumors vary in size. Myomata of the intes- tinal wall are usually small; myomata of the uterus may attain the size of a fetal head, or, in rare instances, they may be larger ; a number of instances have been reported in which the tumor weighed over one hundred pounds. Severanu removed a uterine myoma weighing 195 pounds.* Myomata may be sizgle or mitl- tiple. Multiple myomata, as when a number of tumors occupy the same organ, give rise to a tuberous, bossed, lobulated, or irregular surface. Myomata in the intestinal wall may project from the serous surface as distinct, pedunculated tumors. The same condition is possible in the uterus. Uterine myomata are said to Yj be sudserous when situated immedi- ately beneath the peritoneum, szd- mucous when located immediately (| under the mucous membrane, zz/er- stitial, or intramural, when more or less centrally placed in the uterine wall. Most authorities agree that all uterine myomata begin as interstitial, | f or intramural, growths. As a result Fic. 215.—Liomvoma.—(Gould.) . The rod-shaped nuclei are shown of the contractile power of the normal A dee fedinel soto ce ne uterine muscle, as well as of the pres- pseudobundles at the margin, and in transverse section in the sure brought to bear upon the tumor center, of the illustration. by its continuous enlargement, it is forced along the line of least resistance, which must be toward the serous or mucous covering. A submucous myoma may be- come a pedunculated polyp, the length of the pedicle varying in different cases. Sometimes the pedicle may be sufficiently long for the polyp to project from the os uteri, or even from the vulvar orifice. Similarly formed subserous polypi occur. Asa result of twisting or kinking of the pedicle the blood supply to the polyp proper may be arrested, and extensive necrosis, or even gangrene, may occur. Wherever a myoma occurs it may be distinctly circumscribed, surrounded by fibrous capsule, or an ill-defined irregular mass in the midst of the muscle-tissue. * Williams, ‘* Lancet,’’ Sept. 23, 1899. 342 GENERAL PATHOLOGY. Microscopically, liomyomata are made up of elongated spindle- cells, with rod-shaped nuclei, more or less distinctly grouped into fasciculi of various sizes; the connective tissue varies in quantity. The irregularly arranged muscle elements pass in all directions through the tumor. The few blood-vessels present are found in the connective tissue. Occasionally, liomyomata are telangiectatic. Such richness in blood-vessels, however, is rare. More frequently a tumor contains comparatively large, irregular sinuses, which, in the larger tumors, may attain a trans- verse diameter of from 1 to 1.5 cm., and possess a_ tortuous length of from 5 to 10cm. Suchirregularly formed cavities may contain thrombi. (See p. 272.) Secondary Changes.—Of these, the most frequent are calcare- ous infiltration (so-called ‘‘womb-stone’’) and fatty and myxo- matous degenerations. Inflammation (due to injury), abscess formation, ulceration, and other necrotic processes occur. Clin- ically, the liomyomata are benign tumors, but sarcomatous trans- formation is occasionally seen. 2. Rhabdomyoma.—This variety of myoma, made up of, or containing, striped muscle-fiber, is exceedingly rare, and is usually congenital. It is not improbable that tumors of this class are met with only as a result of the higher evolution of sarcoma- tous tissue (zyosarcoma), in which the imperfectly developed muscle remains, for the most part, in an embryonic stage. The muscle-fibers present in rhabdomyoma are irregularly formed, and are often more or less spindle-shaped or club-shaped. As already stated, the tumor is in most instances congenital, and is usually found in the kidney, heart, or uterus. VI. Angiomata are tumors formed of, or following, the type of vessels—either blood-vessels or lymph-vessels. The term angioma has been applied to tumors composed of blood-vessels, and has that significance when used alone. For the purpose of description it is purposed to divide the angiomata into hem- angioma and lymphangioma. (A) Hemangiomata are tumors consisting of blood-vessels bound together by a small amount of connective tissue. Some of these may be composed of newly formed blood-vessels, while others consist of more or less altered preexisting vessels. The pure hemangiomata are composed of tissue entirely of new for- mation, but, by many, the tumors formed by alteration in pre- existing vessels are included under this name. Varieties.—(1) Simple ; (2) cavernous ; (3) plexiform. 1. Simple Hemangioma (.S¢mple Nevus, Telangicctoma, Birth- mark, Mother's Mark, Angioma Ti elangicctoides).—This is the most TUMORS. 343 common variety, and affects the skin and subcutaneous tissues. Simple hemangiomata are flat, slightly elevated, sessile tumors of a violet or dark-red color, rarely bright red or pink ; they are most frequently located upon the face, around the orbit, or on the neck, are usually congenital, and after birth may increase in size. On section, the vessels are found to be thin-walled (dilated, fusi- form, cylindric, sacculated, or spheric), and to be embedded in a fibrous or cellulo-adipose matrix. There are usually two or more large vessels that establish a communication between the nevus and an adjacent artery or vein. Sife.-—Skin of the face, scalp, neck, and back. May occur on the labia, lips, tongue, and conjunctiva ; rarely on the limbs. The varieties of simple hemangioma are: (z) Mevus flammeus (straw- berry mark). These marks are of a bright-red color. (2) Mevus zunosus. These are of a dark-red or port-wine color, and are known as port-wine marks. 2. Cavernous Hemangioma.—This variety differs from simple hemangioma in that the vessels are less tubular. The tumor is composed of a series of irregular cavities formed by thin, fibrous septa. On section, these cavities appear as irregular sinuses separated by a nucle- ated fibrous network of spindle-cell tis- sue. Many of the walls are incomplete, which fact shows the communication of the spaces. The cavity walls are lined with endothelium. Cavernous heman- giomata are spoken of as erectile tuinors, owing to their resemblance to the erectile tissues, such as the corpus cavernosum g of the penis. They are rarely congeni- F16. 216.—Cavernous Hem- Ae ANGIOMA.—( Gould.) tal, and may develop from preexisting 4,4. Caverns that were filled simple hemangioma. Usually they occur the upper one at By B. 7 1 -, 7 e rous walls of the early in life, and are rare in old age. ae ae When this form of tumor occurs in the skin and forms a livid, raised, and uneven patch, it is referred to as a nevus prominens. Sitze.—Common in the skin and subcutaneous tissue, and occa- sionally in the liver; may occur in the kidney, spleen, uterus, intestines, bladder, voluntary muscle, bone, mamma, tongue, larynx, subperitoneal tissue—in fact, in almost any vascular tissue. 3. Plexiform Hemangioma (Racemose Aneurysm, Aneurysin by Anastomosis, Cirsoid Ancurysm).—Properly, this is not a neo- plasm, but a pathologic alteration of the vessel. The vessels 344 GENERAL PATHOLOGY. become dilated and convoluted ; the dilated vessels press on the intervening tissue and cause atrophy. The vessel-walls are usually thickened. The tumor may be congenital or acquired. When occurring in the most superficial vessels, it is by some called a nevus vasculosus. Plexiform angioma has been observed to follow injury. Site.—Scalp (frontal and temporal region), extremities, labia pudendi, and spermatic cord. (8) Lymphangioma is a tumor made up of dilated lymph- vessels. Rarely, the dilated vessels may form distinct caverns or sacs—the cavernous lymphangioma. More commonly, the masses are of dilated vessels, and hence are analogous to the telangiectatic hemangioma already described. The tracts are the lymph-vessels, and not blood-vessels. Stte-—Lymphangioma occurs most frequently in the tongue or lip, constituting macroglossia and macrocheilia respectively. In both these localities it is not uncommonly associated with what appears to bea proliferative change in the unstriped muscle present. A special form of lymphangioma occurs in the lym- phatics carrying chyle (chylous vessels, lacteals), and is called a chylangionta. VII. Lymphoma, or tumor of the lymph-gland, covers a multitude of conditions, many of which are in no sense tumors. Thus, the glandular enlargements of tubercle, syphilis, etc., are known as tubercular or syphilitic lymphomata. To the same _group belong the inflammatory lymphomata that accompany many infections : ¢. g., chancroidal lymphoma, suppurative lymph- omata of various kinds, and the glandular enlargements found in the cervical glands in various throat affections, such as diphtheria and scarlet fever, not any of which are tumors. Lymphosarcoma is a sarcoma of the lymph-gland, and differs but little from other forms of sarcoma except in such histologic peculiarity as must arise from the site. The lymphatic en- largement that accompanies leukemia is probably an infectious process, with hypertrophy and hyperplasia of the cells and stroma of the lymph-gland, or is a form of sarcoma attacking the lymph-glands : the latter view may be considered as most popu- lar at present. Such a condition is noted in Hodgkin’s disease, when the hypertrophied glands are known as lymphadenomata. (See Diseases of the Lymph-glands, part 111.) VIII. Myxoma.—tThis form of tumor is composed of mucous tissue, which is not, strictly speaking, an adult structure ; it is, at least, the lowest grade of adult connective tissue. The tissue is identical with that surrounding the vessels of the TUMORS. 345 umbilical cord (Wharton’s jelly), and resembles the vitreous humor. The tumor always contains a certain amount of fibrous stroma, and resembles an edematous fibroma. In fetal life myx- omatous tumors are met with in those subcutaneous tissues from which fatty tissue is later developed. Macroscopically, the tissue appears as a homogeneous, structureless, gelatinous mass. The majority of the cells present are angular and stellate, with long anastomosing prolongations ; others are indistinct (owing to the refractory nature of the intercellular substance), oval, spheric, or fusiform in shape. The blood-vessels are readily located, but are few in number. Frequently, between the cells fine elastic fibers can be demonstrated. Clinically, myxoma is a peculiar, soft, gelatinous tumor, grayish or reddish- white in color, and on section yields a gelatinoid, whitish, albuminous, or muci- laginous material Myxomata usually occur after middle life, are of moderately slow growth, may be single or multiple Fic. 217.—Myxoma. (commonly multiple), vary in size (rarely large), and not uncommonly recur after removal. This return may not be a true recurrence, but may be due to imperfect re- moval, after which the remaining myxomatous elements develop. Myxomata may be pedunculated or sessile ; rarely, the mass is lobulated. Primarily, they are benign tumors. Secondary Changes—-Hemorrhage (capillary), if extensive, may form blood cyst; fatty degeneration; they may become in- flamed, ulcerated, or necrotic. Site. —Connective tissue ; most common in subcutaneous and subserous fat ; submucous (nares, uterus) and intermuscular tis- sues ; rare from periosteum and medulla of bone, connective tissue of organs, and perineurium. Myxomata occasionally spring from the placenta (one form of wterine hydatids, probably incorrectly so called). EMBRYONIC CONNECTIVE-TISSUE TUMORS. Sarcoma. Rouna-cell (small and large). Spindle-cell (small and large). Giant-cell (myeloid). Mixed-cell, Alveolar. wos Varieties ; Qo ys 346 GENERAL PATHOLOGY. The sarcomata are tumors composed of embryonic connective tissue in which the cellular constituents predominate over the inter- cellular substance. The embryonic cells tend to infiltrate the surrounding tissues, as a result of which sarcomata are rarely, if ever, encapsulated. If a capsule surrounds the growth, it may result from condensation of adjacent tissues, or it may be a part of the tumor; in either case it is sure to be infiltrated by the tumor cells. | Histology.—All sarcomata consist of embryonic connective- tissue cells embedded in a peculiar intercellular substance, which intercellular substance varies in amount and character. Asa rule, the sarcomata contain very little true fibrous tissue, the whole mass being composed of embryonic cells; the cells are uninucleated or multinucleated, and rarely possess a limiting membrane ; the shape, size, and arrangement of the cells determine the variety of the tumor. The intercellular substance, which is usually small in amount, is closely connected with the cells, as in all connective tissues. The consistence of the tumor depends upon the character of the cell and intercellular substance, and upon the presence or absence of a fibrous stroma. The blood-vessels are very numerous, and are usually in direct con- tact with the cells, or they may be separated from them by a layer of thin fibrillated tissue. The vessels frequently lack dis- tinct walls, the wall being composed of densely packed embryonic cells. These cells may become detached, and may be carried along in the current; hence, sarcoma spreads by the blooa- vessels. Owing to the thinness of its walls, hemorrhage, with extravasation of the blood, takes place; when this occurs, the tissue becomes pigmented, and the tumor is known as melanottc ; or this extravasated blood may become encysted (blood cyst). As will be seen later, melanosis may arise from other causes. As a rule, the edge of the tumor is not clearly defined, there being no line of demarcation between the tumor and adjacent structures. When the tumor is of slow growth, an apparent capsule may be formed of the surrounding connective tissue, due to condensation. Clinical Characteristics —As a rule, sarcomata occur most fre- quently in early and middle life, but may occur at any age, and are among the most malignant of tumors. They are character- ized by their tendency to extend locally, to infiltrate surrounding structure, to recur after removal, and to give rise to metastasis. They may be localized, and at first sharply circumscribed ; but are liable to become rapidly disseminated, both by local infil- tration and metastasis. Secondary growths occur most fre- TUMORS. 347 quently in the lung. Sarcomata may disseminate much more rapidly than carcinomata. The round-cell and large spindle-cell variety are of rapid growth and are very malignant. The small spindle-cell variety is much firmer, of slower growth, and less malignant. When occurring in bone, if subperiosteal, they are more malignant than when located in the center of the bone. The following are the chief signs of malignancy in any tumor, be it sarcoma or carcinoma. They are inserted here by reason of their special applicability to the sarcomata : Z. Size of the Cell—As a rule, it may be said that the smaller the cells of a tumor, the more malignant will it probably be. Thus, the small round-cell sarcoma is a more malignant tumor than that composed of giant-cells, and the small epithelial cells of a scirrhous cancer of the mamma give rise to a more malignant growth than the large, flat epithelial cells of the skin, as seen in the squamous epithelioma. 2. The Number of the Cells.—If a tumor be purely cellular, the likelihood of its recurrence is great. 3. Activity of the Cells—One of the chief diagnostic features of a malignant tumor is the tendency of its nuclei and cells to divide ; if on section a large number of the cells show mitosis in some stage of progress, the prognosis is unfavorable, recurrence being almost a certainty. 4g. Shape of the Cell.—aA small, round cell, like a lymph cor- puscle, will be more readily transported by a blood-vessel or lym- phatic than one that is long and tapering; hence the former will have a greater tendency than the latter to reproduce the tumor in neighboring parts. The round-cell sarcoma forms sec- ondary tumors in neighboring organs, infiltrates blood-vessels, and evinces metastasis with greater readiness than one of the spindle-cell type. The foregoing applies not only to local infil- tration, but also to distal metastases. The large, irregular cells of the squamous epithelioma will be less likely to reach distant parts through the blood-vessels or lymph-vessels than the small, round, plastic cells of a sarcoma. 5. The Manner in Which the Cells Are Held Together.—So far as regards the sarcomata, at least, the more loosely the cells are held together, the greater is the tendency of the tumor to recur. This is equivalent to saying that the more fluid the intercellular sub- stance, the more malignant the tumor. Fluidity of the intercel- lular substance implies that the neoplastic cells are loosely held together; this lack of cohesion between the elements of the tumor permits of the ready dislodgment of one or more cells, or 348 GENERAL PATHOLOGY. masses of cells, and hence favors displacement of the tumor ele- ments into the lymphatics and blood-vessels. The fluidity of the intercellular substance may be partly judged by the consistency of the tumor; a soft, almost fluctuating tumor, has but little firmness in the intercellular substance. Such soft, pseudofluc- tuating tumors are not infrequent among the sarcomata. The author has known of one or more instances in which the surgeon has cut into a sarcoma under the impression that he was dealing with a cyst or a cold abscess. Indeed, the cellular elements of some of the small, round-cell sarcomata are so loosely attached that a needle—for example, an exploring needle—passed into the tumor may not infrequently be moved about from place to place, the operator not being able to detect the presence of any solid constituent within the mass. 6. Absence of Any Tendency to Complete Their Developiment.— Of all signs of malignancy, this, in the case of sarcoma, is perhaps the most unequivocal. The cells do not complete the formation of connective tissue that normally they were destined to generate. Instead of their energy being occupied in the metabolism neces- sary to secrete the matrix peculiar to each, it is wholly expended in causing the cell to reproduce itself. At certain stages in the process of repair the proliferated cellular elements may con- stitute a mass of embryonic tissue which, if we take into consid- eration only the character of the cells, can not be differentiated from sarcomata possessing similar cellular elements. In the tissue elaborated during reparative processes we nearly always see the cellular elements in one or more parts progressing to their proper histologic end—cicatricial tissue, osseous tissue, etc. In some sarcomata an effort in this direction may be apparent. It is, however, never fully successful. 7. Tendency of the Cells to Spread into Neighboring Interfibril- lar Spaces—In examining a tumor, the tissues round about it should be carefully investigated, with a view to noticing whether the cells of the tumor have invaded adjacent structures. If so, such a tumor is dangerous, and should be excised with a wide margin. A single cell left in the surrounding parts will repro- duce the tumor. Cancer of the mamma shows more tendency to penetrate the surrounding stroma of the gland than perhaps any other tumor. Itis also one of the most malignant of tumors (Hamilton). 1. Round-cell Sarcoma (Excephaloid or Medullary Sarcoma). —This is a rather infrequent form of sarcoma, and consists of round cells with very little intercellular substance. The cells contain large, easily stained nuclei. Blood-vessels are abun- TUMORS. 349 dant, and appear as channels or sluiceways passing directly between the cells ; there are no lymphatics present. The cells rapidly infiltrate the surrounding tissues ; the tumor tends to recur FIG. 218.—ROUND-CELL SARCOMA.—(Rindfleisch.) X 300 diameters. a,a. Blood-vessels without distinctly formed walls. 4, 4. Points where the round cells have partly fallen out, sfowing the slight basis of reticular tissue. after removal, and gives rise to secondary deposits. The variety known as large round-cell sarcoma differs from the small round- cell variety in that the cells are larger and more irregular in size ; they may be mononuclear or polynuclear. The round-cell sar- Fic. 219. — ROUND-CELL SARCOMA. — FIG. 220.— ROUND-CELL SARCOMA OF A Lym- (Gould.) PHATIC GLAND.—( Gould.) The cells have dropped out at places, showing the remainder of the intercellular trabecule. coma may occur in any tissue and at any age, even in the fetus 2 utero. It is a soft, rapidly growing tumor, which, when on the surface, ulcerates early, and usually proves fatal in a few months. 350 GENERAL PATHOLOGY. 2. Spindle-cell Sarcoma (Recurrent fibroid (Paget) ; /vbro- plastic Tumor (Lebert) ; fibrosarcoma ; Oat-cell Sarcoma ; (Fascic- ulated Sarcoma).—The spindle-cell sarcomata are the most common. They are firm in texture, and on section are transiu- cent, and grayish or yellowish-white in Neutral potassium oxalate, . a doe ee Na | OF Distilled water, ye 4 300.0 C.Cc. The anilin dyes contained in the foregoing solutions stain the leukocytes, and thereby facilitate their enumeration. Differential Counting.—Dried and fixed films are stained by Ehrlich’s stain, and are mounted as already directed. Then the leukocytes are counted by traversing, in straight lines, more or less of the stained field, carefully avoiding going over the same point twice, and counting at least 1000 leukocytes. A mechan- ical stage greatly facilitates the count. Ona piece of paper by the side of the microscope are arranged columns, at the top of which are written the forms of leukocytes; after counting the required number, the columns are added up and the percentage of each form present is calculated. Differential counting of diseased red cells is sometimes resorted to, and may be done in the same manner. Hematocrit.—This instrument (see Fig. 80, p. 120) readily enables one to estimate the volume of the red corpuscles. It con- sists of: I. Two glass tubes, 50 mm. long, with a lumen of 0.5 mm., and graduated into 100 parts. (Fig. 237.) Fic. 237,—HEMATOCRIT TuBE. (Twice natural size.) The tube as illustrated has been filled with blood and rotated, as directed in the text, until the erythrocytes have collected at one end, occupying 45 degrees (or graduation-marks). This, multiplied by 100,000, gives 4,500,000o—the number of erythrocytes to the cubic milli- meter of blood. 2. A metallic frame (Fig. 238), in which the glass tubes are fastened—on the outer side by a metallic cup in the frame, and at the proximal extremity by a spring, which is attached toa hollow metal cylinder, which projects downward from the center of the frame, and by means of which the frame can be made to rotate on a vertical axis. The cups receiving the ends of the glass tubes contain rubber washers that also act as cushions. 3. A vertical support, which can be made to rotate. A speed of at least 10,000 rotations a minute is necessary. 4. A metallic box, to be fastened to a table, and containing the machinery by which the vertical support is made to rotate. THE BLOOD. 419 To Use the Hematocrit —One of the graduated tubes, previously well cleaned, is attached by means of a short piece of pure rub- ber tubing to a medicine-dropper. The bulb of the dropper is gently compressed, and the end of the graduated tube is presented to the escaping blood ; the compressed bulb of the pipet is slowly FIG. 238.—ROTATING FRAME OF THE HEMATOCRIT. The tube on the right is in position; the tube on the left shows the graduation and the direc- tion which the smaller end should take when in position. The entire metal frame is to be placed on the vertical support, as described in the legend of figure 80, page 120. released, thereby sucking the blood into the capillary tube. As soon as the tube is full, the end in the drop of blood is pressed against the patient’s thumb, without withdrawal from the drop, and the rubber tube and the medicine-dropper are removed. Figure 240 and the legend explain the usual method by which Fic. 239.—A METHOD OF FILLING THE CENTRIFUGE TUBE. A. The hand of the patient. The thumb has been punctured and is firmly supported by the left hand of the operator, as shown at B. C. The right hand of the operator, holding the capillary tube, to which is attached a rubber tube, D. To the latter suction is applied, thereby drawing the blood up into the capillary tube. By some workers this method is preferred to that recommended in the text. the tube is filled. If but one tube is to be filled, the other should be in place in the rotating frame of the instrument, to act asa counterpoise to the charged tube. As soon as the latter is filled, it is placed in position in. the frame, which is at once rotated at the rate of 10,000 revolutions a minute for two minutes. The 420 SPECIAL PATHOLOGY. red blood-corpuscles collect in the distal extremity of the tube, the leukocytes in the center, and the liquor sanguinis in the proximal portion. Find the number of degrees the red cells occupy, and, as each degree has been found to represent ap- proximately 100,000 cells to the cubic millimeter, the addition of five ciphers gives the number of red cells to the cubic millimeter. Thus, if the red cells occupy fifty graduations on the scale, there are 5,000,000 red cells to the cubic millimeter. (See Fig. 237.) It is apparent that the result is in volume of red cells, and not the number that must be obtained by a calculation that does not take into consideration the size of the cells. When the red cells are larger than normal, the greater volume would give a misleading result. The reverse is equally true. GENERAL PATHOLOGY, COMPOSITION, AND STRUCTURE OF THE BLOOD. The circulating normal blood consists of a fluid portion (the liquor sanguinis) in which are suspended the solid elements—the blood-corpuscles or blood-cells. The liquor sanguinis is proba- bly identical—or practically so, at least—with the circulating medium outside the blood-vessels in the primitive lymph-spaces, and which passes to the lymph-glands and is returned to the cir- culation. As a part of the blood, the liquor sanguinis is more than a mere vehicle for the transportation of the solid elements, and with its complex chemistry is the essential food-carrying body to the tissue at large. Itis composed of the elements out of which serum and fibrin may be formed; and while this separation, so far as the plasma is concerned, is largely a death change, still, evidence is not wanting to show that fibrin formation, may be an essential element in the protection of the organism and in repair. Thus, the distinct wall of fibrin that forms around infected areas or covers an infected serous surface, such as a pleura, and through which osmosis and the absorption of bacterial products are reduced to a minimum, acts not only as a scaffold upon which embryonic tissue, and eventually granulation tissue, can build the framework which is to repair the injured part, but also as a pro- phylactic, limiting membrane, through which infection travels only with the greatest difficulty. Again, of all the structures pro- duced within the body, fibrin offers the greatest resistance to many of the injurious incidents to which the tissues are liable ; the constant pressure of the circulating blood, as in an aneurysm, may lead to atrophy and to the disappearance of bone, unless conditions arise that determine the intervention of a wall of THE BLOOD. 421 fibrin, through which, not uncommonly, we may hope for a cure. The exact factors that enter into the chemistry of fibrin forma- tion are not known ; although the third corpuscle would seem to bear some causative relation to the process, the character and extent of such influence remain one of the unsolved problems of physiologic chemistry. An excess of fibrin, or, more truly, of fibrin-forming elements, constitutes hyperinosis—a condition present in pregnancy, and occasionally in chlorosis and other forms of anemia. Hypino- sis, or reduction in the fibrin-forming elements, is sometimes ob- served in leukemia and pernicious anemia. In addition to the influences modifying the amount of fibrin, there are marked dif- - ferences in the rapidity with which it is formed. As a rule, intravascular coagulation begins shortly after death. To this, however, there are notable exceptions. The author recalls a case of pernicious anemia in which, at the postmortem, made twelve hours after death, the blood had not coagulated. After removal from the cardiac cavities a quantity collected in a jar for later study developed a satisfactory coagulum. The blood is less coagulable in hemophilia, in which disease its coagulability may be, in some cases, increased by the administration of calcium salts, while in other cases the local application or the internal ad- ministration of these agents fails to influence the condition. Lessened coagulability is present in the blood after death from poisoning by carbonic acid or by carbon monoxid and in some cases of asphyxia. Snake-venom and bacterial products lessen the coagulability of the blood. Hydremia is a condition in which the blood contains an excess of water. After a hemorrhage the volume of blood is made up by the abstraction of fluid from the tissues at large, and consequently there is a more or less temporary hydremia. When it is reasonable to believe that there is an increased amount of blood, and that the increased quantity is due to the addi- tion of water or saline solutions, as after the injection of a large quantity of normal salt solution, the condition is called hydremic plethora. Under ordinary conditions hydremia quickly disap- pears, as a result of the excretion of water by the emunctories, particularly the kidneys. Anhydremia is the reverse of hydremia. The lessened amount of water present in the blood usually résults from its rapid extraction, although it is conceivable that a diminished supply would induce the same condition. The concentration is usually brought about by the discharge of fluid by the skin, intes- tine, or kidney. As the principal constituent so removed is 422 SPECIAL PATHOLOGY. water, it is this element that is reduced. As a rule, anhydremia, like hydremia, is temporary. In the former condition the tissues quickly supply the requisite amount of fluid. In a number of morbid conditions the blood plasma contains abnormal bodies or normal constituents in abnormal quantities. A small quantity of fat is present in normal blood ; occasionally, however, as in alcoholism, diabetes, and a few other conditions, it may be markedly increased, producing a condition called lipemia. The fat may be recognized in the freshly drawn blood as small, highly refractile granules, which not uncommonly mani- fest active movement. The examination is conducted as already directed. (See p. 397.) Dry spreads fixed in osmic acid (pp. 48 and 49) will show the blackened fat droplets. (See also Demon- stration of Fat, p. 243.) The serum obtained by the centrifuge may contain enough fat to render it turbid. The small quantity of glucose normally present in the blood is markedly increased in diabetes, in which disease it may be present to the extent of 0.7 per cent. instead of the normal, 0.117 per cent. An in- creased amount of sugar in the blood is called glycemia. In leukemia, in pneumonia, in some forms of anemia, and at times in Bright’s disease there is an increase of uric acid, or, more properly, of uric acid salts, in the blood. In gout the increase in urates (uratemia) is most marked. The presence of bile pigments in the blood (cholemia) is the essential phenomenon of jaundice (p. 234). Clinicians recognize a form of intoxication which has long been termed uremia. At one time this was presumed to be due to the presence of an excess of urea in the blood. Later investigations have shown, however, that no quantity of urea, however large, introduced into the circu- lation reproduces the clinical picture of the uremia. Blood plasma also contains certain globucidal bodies destructive to red blood- cells of other animals. The bactericidal and antitoxic bodies in the blood have already been considered. (See pp. 155 to 159.) Recent investigations, both experimental and clinical, seem to indicate that a study of the freezing-point of the blood may be of value in certain cases. Normal blood freezes at about 0.56° to 0.58° (C.), below the freezing-point of distilled water. Agents causing renal irritation or necrosis, such as cantharides, and morbid conditions associated with renal insufficiency, may lower the freezing-point to 0.6° or 0.7° (C.). The removal of the kidney similarly influences the freezing-point. The so-called solid constituents of the blood are the corpuscles : the red, or erythrocyte; the white, or leukocyte; and the third corpuscle—blood-platelet, or hematoblast. THE BLOOD. 423 The red blood-cell, or erythrocyte, of man is a smooth, highly elastic, biconcave disc, which does not possess a nucleus. From seventy to eighty per cent. of the erythrocytes possess an average diameter of 7.5 ww. Of the remaining twenty per cent. about half are slightly larger, and the remaining cells slightly smaller, than the average given. In the normal blood, cells smaller than usual are probably more frequent than the larger cells. The smaller cells usually meas- ure between 6 yw and 7 yp, al- though cells measuring less than 4 » (dwarf cells) may occasion- ally be observed. The larger cells are more conspicuous in infancy, and are rarely seen after adolescence. In a number of morbid processes abnormal form and size constitute important alterations. In certain anemias many of the cells are small (microcytes); the condition is called microcytosis, or micro- cythemia. In some instances a varying number of the erythro- O ae Dos : Q e ye ee pee, oO -S— b “Oe a a é FIG. 240. — DIAGRAMMATIC REPRESENTA- TION OF VARIOUS FORMS AND SIZES oF RED CELLS.—(From a case of per- nictous anemia reported by Dr. J. C. DaCosta, Jr.) . Erythrocyte (introduced to give an approximate idea of the size of other cells). 6, 6. Microcyte. c. Megalo- blast. ad, d. Macrocyte (larger macro- cytes are also outlined, some of which are poikilocytes). ¢,¢,e¢,é@,¢,e,é@. Poi- kilocytes ; other poikilocytes are also shown. J. Finely granular oxyphile (polymorphonuclear) leukocyte. The granules are not shown, but the ex- treme irregularity of the nucleus is indicated. cytes possess diameters of 8 “org #, or are even larger ; an occa- sional cell may attain a diameter of 15 w. Such cells are called Fic. 241.—TYPEs OF RED BLOoD- CELLS; ALSO LEUKOCYTES, AS AT a.—(Landois.) macrocytes, or megalocytes, and the condition is known of as macrocyto- sis, or macrocythemia. Microcytes are not uncommonly spheric, and in macrocytes the biconcavity is often inconspicuous or absent. Microcyto- sis and macrocytosis are frequently associated. The small hemal element described by Eichhorst is really an irregularly staining microcyte from 2.54 to 44 in diameter. It differs from the usual microcyte in the in- tensity with which it stains. As a result of disease, erythrocytes may change their form, 424 SPECIAL PATHOLOGY. becoming ovoid, pyriform, knobbed, bobbin-shaped, etc. Cells showing such abnormality in form are called poikilocytes, or schistocytes ; the condition is called poikilocytosis. Microcytes and macrocytes, as well as the nucleated forms to be considered later, not uncommonly show more or less irregularity in shape, and may be properly considered as poikilocytes. It is possible, by error in technic, to produce a distor- tion of the erythrocytes, which may mis- lead the uninitiated. If, in making the cover-glass spreads, as already directed, Fic. 242—Porxtrocytes. the two cover-glasses (p. 398) be left in contact too long, the act of separation may stretch the erythrocytes so that one diameter will be greater than another, a condition frequently observed in poikilocytosis. A careful study of such a field will show that the cellular dis- tortion leads to an elongation of all the affected cells in one direction, a condition never observed in true poikilocytosis. Crenation is an appearance closely resembling poikilocytosis, but develops after the blood has been drawn. Crenated cells are irregular, and show knobbed projections from their surfaces associated with more or less shrinking of the protoplasm; by some it is believed that crenation is the extravascular analogue of intravascular poikilocytosis. Early in fetal life the nucleated red blood-cells normally present at that period begin to disappear, and at birth, or shortly after, are no longer present in the normal blood. In certain morbid conditions, how- ever, they form conspicuous hemal elements. It is usually held that at some stage in its evolution the red blood-corpuscle possesses a nucleus, which disappears before the cell is Fic. 243.—CRENATED RED assumes the function of a hemal cell. Ex- BLOOD - CORPUSCLES. — actly how this dis f th 1 eee y isappearance of the nucleus Often seen in improperly i i xe ood slides, in is accomplished has not been accurately Hh cecwe ide d determined. According to some observers, after prolonged study 7 ‘ 3 under the microscope, the nucleus disappears by extrusion, while in urine, etc. others think it is removed by a process of absorption or of disintegration. The nucleated cells seen in the blood are of different sizes, justifying to a certain extent the divi- sion into three kinds. Normoblasts are nucleated red cells the diameter of which is approximately that of the normal erythrocyte. The size of the nucleus varies, and it is usually eccentric in location. It is rich THE BLOOD. 425 in chromatin, stains with intensity by the usual nuclear stains, and not uncommonly shows a fine, intranuclear net. Occasion- ally, the nucleus will be found partly outside of the protoplasm— a condition that suggests its extrusion. Sometimes, in prop- erly fixed preparations evidences of mitosis may be present, or the cell may contain two or even three nuclei; these may ap- pear distinct and separate, while in other cells connecting bands of chromatin may be recognized. The perinuclear protoplasm contains more or less hemoglobin, and hence stains with the acid anilin dyes. The outline of the cell is commonly uneven, so that a varying percentage of these cells may be properly called nucle- ated poikilocytes, or poikiloblasts. The microblast is a small nucleated form, smaller than the normal red blood-cell; both nucleus and protoplasm are dimin- ished in quantity, although occasionally microcytes may be found possessing a nucleus as large as the nucleus of the normoblast. Intranuclear changes are infrequent. The perinuclear protoplasm is not uncommonly shredded, and the cell is regarded by most observers as a degenerated necrobiotic or fragmenting form of the normoblast. Megaloblasts, or macroblasts (also called gigamtoblasts), are abnormally large red cells possessing nuclei ; the diameter of such cells usually exceeds 10 y, and may attain 16 w. The nucleus is relatively large, but stains with less intensity than the nucleus of the normoblast. The perinuclear protoplasm is usually rich in hemoglobin. The cell not uncommonly shows degenerative changes, as indicated by the unevenness in staining and by the occurrence of vacuoles in its interior. Frequently such cells are irregular in conformation, and may be properly called poikiloblasts. The demonstration that unusually large red blood-cells (megalo- cytes or megaloblasts) may contain more hemoglobin than cor- puscles normal in size possibly explains the fact that in certain diseases in which these cells are comparatively abundant the color- index may be high. (See Pernicious Anemia.) In addition to abnormality in size and shape, certain necrotic alterations are sometimes present in the red blood-cells. By some, poikilocytosis is regarded as an evidence of necrotic change, and the endoglobular alterations about to be described are not uncommonly associated with, or terminate in, the produc- tion of poikilocytes. The central normally pale area of the cor- puscle may increase in pallor, and may eventually lose all its coloring-matter; the periphery at the same time may show deepening of color. Sometimes hyaline or vacuolated spots ap- pear in the periphery of the cell, or the cell becomes ovoid in 426 SPECIAL PATHOLOGY. profile with a vacuole at one or both ends. A number of these changes, associated with solution of the hemoglobin and other soluble parts of the cell, have been grouped by Arnold under the name erythrocytolysis, or plasmolysis. Crenation, which ordinarily is not developed for some time after the blood is drawn, may be present immediately after shedding. The knob- like projections seen on crenated cells may break off (plasmor- rhexis) and float free in the blood. The numberof red blood-cells normally present is approximately 5,000,000 in man and from 4,000,000 to 4,500,000 in woman to each cubic millimeter of blood. Blood containing more corpuscles than normal is said to show polycythemia; a reduction in the number of erythrocytes is called oligocythemia. Within the first twenty-four hours following birth a maximum of from 6,000,000 to 6,500,000 may be reached. The number is reduced by hemorrhage and by various anemias, which will be considered later. The number is reduced by prolonged exertion, and men- struation usually induces a slight decrease. The most marked diminution in number is seen in pernicious anemia, in which the oligocythemia may be extreme. Counts as low as 500,000 are not infrequent, and a minimum of 143,000 has been recorded. Aside from the physiologic increase in the number already noted as present for a brief period after birth, little is known of the etiologic factors active in the production of corpuscular plethora, or polycythemia. Impeded circulation, or even the influence of gravity, may slightly increase the number of corpus- cles present in a given area. In cyanosis and in cardiac lesions associated with peripheral stasis relatively high counts are not infrequent. The polycythemia observed in the cyanosis of congenital heart disease may be extraordinary, as in the case reported by Baunholtzer—g,447,000 erythrocytes, 160 per cent. of hemoglobin. Asa result of the loss of fluid from the vascular system,—as by serous diarrhea, profuse sweating, excessive vom- iting, etc..—the temporary concentration of the blood increases the number of corpuscles present ina given quantity. The condition is, as a rule, temporary under such circumstances. An interest- ing form of polycythemia is that which develops during residence in high altitudes. As a rule, the maximum polycythemia result- ing from this cause does not manifest itself for a month or more, but not infrequently within twenty-four hours after the ascent a notable increase in the number of red blood-cells may be observed. Solly records an instance in which a day’s excur- sion was attended by an increase of 600,000 red cells. The total rise in the number of red cells may reach from twenty THE BLOOD. 427 to fifty per cent., not infrequently exceeding the latter. The erythrocruorin does not keep pace with the increase in red blood- cells, although the percentage of hemoglobin is usually aug- mented. Whether the polycythemia is due to an inspissation of the blood, to increased peripheral distribution, to more active blood production, or to the lengthened life of the red blood-cells has' not been. satisfactorily determined. The facts that the red corpuscles increase more rapidly than the hemoglobin, that there is an increase in the average diameters of the red blood-cells, and that the normoblast nuclei are found free in the blood, all favor the view of increased production of cells. The polycythemias of phosphorus-poisoning and carbon-monoxid-poisoning have not received any fully satisfactory explanation. Structurally, the red blood-cell appears to be composed of two elements—a delicate reticulum or stroma, but partly soluble in water, inclosing spaces within which lies an albuminous soluble portion of the cell, which contains the hemoglobin. This part is freely soluble in water. Hemoglobin, or erythrocruorin, is the soluble pigment to which the color of the blood is due. It is a complex proteid, readily decomposable into a number of so- called reduction products. Some of these have been consid- ered with pigments. (See Pigmentary Infiltration, p. 233.) The amount of hemoglobin present in the blood varies within certain limits. It may be said that, approximately, 100 gm. of blood contain about 14 gm. of hemoglobin. It will be recalled that in considering the methods of estimating the quantity of hemoglo- bin the results are commonly given in percentages of the normal. It will, therefore, be apparent that when a hemometer or hemoglo- binometer records 100 per cent., the quantity indicated is 14 gm. in 100 gm. of blood. Hemoglobin combines with oxygen to form oxyhemoglobin, which, when carried to the tissues, yields its oxygen, the hemoglobin remaining as reduced hemoglobin. With CO it forms a more stable compound, called carbon-monoxid- hemoglobin. The carbon monoxid compound is not readily dis- sociated, and hence in poisoning by carbon monoxid the oxygen- carrying power of the blood is held in abeyance as a result of the inability of the oxygen to displace the more firmly combined gas. Methemoglobin, hematoidin, hemin, and other pigments derived from the blood have. been considered with pigments where they possess any pathologic significance, and for further consideration the reader is referred to text-books on physiology. As the amount of hemoglobin present in the corpuscles largely influences their specific gravity, the latter has been utilized as a method of determining the percentage of hemoglobin present. (See p. 412:) 428 SPECIAL PATHOLOGY. When the quantity of hemoglobin falls below the normal, the condition is called oligochromemia. Hemoglobin is dimin- ished in all anemias, and not uncommonly its diminution is in direct proportion to the reduction in the number of red blood- cells; in other instances the corpuscular richness in hemoglobin may be greatly reduced without any marked reduction in the number of red blood-cells. These alterations in the quantity of hemoglobin present will be considered with more detail when dealing with individual forms of anemia. Leukocytes.—The white cells of the blood, unlike the red, are found in a number of forms, the relationship of one form to another not having been clearly established. Unlike the red blood-cells, the leukocytes are nucleated, and normally con- tain no hemoglobin. The proportion of leukocytes to red blood-cells varies widely in health, the va- riation depending upon the temporary rise and fall in the number of leukocytes, irrespective of coincident changes in the number of erythro- cytes. All authors rec- ognize these fluctuations in the number of leuko- cytes, but all are fairly agreed that the relative. proportion of leukocytes to red blood-cells is 1 FIiG. 244.—DIAGRAMMATIC REPRESENTATION OF LEUKOCYTES. of the former to 500 or a,b. Lymphocytes. c. Hyalinecell. The cell outlines are not so sharpas indicated. d,d,d,d,d. Finely 600 of the latter. The granular oxyphile (polymorphonuclear) leuko- yarious forms of leuko- cytes. e. Myelocytes. f. Coarsely granular oxyphile (eosinophile) leukocytes.—(From spleno- cytes exist in the blood medullary leukemia ; drawn by Dr. J. C. DaCosta ri . Jr.) See Fig. 188, p. 286; Fig. 189, p. 287. * in fairly constant pro- portions. The different forms, the general descriptions, and the percentages present in the normal blood will be found in the accompanying table. (See pp. 430 and 431.) In addition to the groupings there given, several of which possess only historic interest, we must recognize that certain cells are essentially hemal and that others are essentially celomic, although each not uncommonly invades the other's territory. The normal number of leukocytes in a cubic millimeter of blood approximates from 6000 to gooo. THE BLOOD. 429 In many conditions a reduction in the number of leukocytes (hypoleukocytosis, leukopenia, or leukocytopenia) occurs. Such reduction in the number of leukocytes is seen at times in protracted febrile processes, unassociated with pyogenic infection, in typhoid fever occasionally, rarely in pneumonia, and at times in tuberculosis. Blum * believes that the leukopenia seen in typhoid fever, influenza, and certain cases of tuberculosis is due to involvement of the lymphoid tissues of the alimentary canal, and particularly in the intestine. Sometimes in pernicious anemia a marked fall in the number of leukocytes occurs. This phe- nomenon is not a constant feature of any disease. The leuko- cytes are reduced by starvation, and preliminary to leuko- cytosis—particularly to that form called inflammatory—a tem- porary leukopenia is sometimes present. In marked cases of hypoleukocytosis the number of leukocytes may be 600 or even less to the cubic millimeter of blood. The essential cause of this condition is not known. It is held by some that there is a faulty production of leukocytes; by others, that there is an increased destruction—leukolysis. It is not improbable that both factors are operative. Faulty distribution may have some- thing to do with absence of leukocytes from the peripheral circu- lation, the normal distribution being altered as a result of leuko- cytic accumulation in the large viscera, particularly the lung. In addition to the reduction in number, leukocytes not uncom- monly show evidence of extensive karyolysis. One of the most marked karyolytic changes is that seen in the finely granular oxyphile cell in pyogenic processes. The pus-cell, with its many irregularities in protoplasm and nucleus, is a finely granular oxy- phile cell showing the results of karyolytic change brought about by the activity of the bacterial toxins. In pronounced anemia, or in other conditions associated with blood destruction, the leukocytes may contain fragments of red blood-cells and particles of pigment derived from various sources; such cells are called melaniferous leukocytes. Abnormality in color, reaction, position, size, and distribution of leukocytic granules is not uncommonly present ; such variations are probably evidences of degenerative change. Leukocytosis.—As already indicated, a wide variation in the number of leukocytes is compatible with health. Efforts to draw absolutely exact limits beyond which the normal fluctuations do not go have been, for the most part, illusive. If we adopt a com- paratively low standard, such as 8000 or 9000, or even 10,000, * «Wiener klin. Woch.,’’ April 13, 1899. VARIETIES OF Wuarton | Max KanTHACK PERCENTAGE PRESENT Jones. | SCHULTZE. METSCHNI- EHRLICH. AND Haven. in NormMaL 1846. | 1865, BORE Harpy. | Boop. | | | Small | 7, ho- Lympho- | Small round ate. ee Small o. type. 15 to 30, Non- cell I, | Leuco- | granular i) foo NG Lympho- J ____ cytes of ar nucleated | , cyte the first cells. ! | lanes Macro- | Large Hyaline vanety: Large wane roun t Ld, type. . | | cell I1, |PBaBocyte | ar ae tah Granule Cells with Cells neutrophile Finely cells finely finely Micro- in man,ampho- | granucar | Leucocytes of the 60 to 72 granular. granular | phagocyte. | phile in some of oxyphile second variety. protoplasm. the lower animals. cecls. ‘ Ci Z; Granule Cells with eranulay Rarely over two per cells coarsely Eosino- Leucocytes with oxyphile or Leucocytes of the | cent.; in childhood coarsely granular phlles. a granules. acidophile third variety. may reach 11 to 14 granular, jProtoplasm: Cells. per cent. nook Coarsely Rarelyifever presentin ers granular. normal blood, present %. Fiasrzelien i basophile in celomic fluids and ; cells. connective tissues. Granule Cells with Finely cells finely finely Basophile cells granular Rarely e. ds .25 granular. granular with 6 granules. basophile rely exceeds .25. protoplasm. cells. 430 Myelocytes. Marrow cells. (‘Markzellen’’ of German writers). 4 Hypertrophied white cells, “yf; Not present; found in bone marrow (red) and present in blood in leukemia. * After Adami’s table (Albutt’s «Sys. Med.,”” vol. 1, p. 79); LEUKOCYTES.* Size. FurRTHER DeEscRIPTION AND REMARKS. 5 to rr pw, usually about the size of a normal red blood cell, 7-5 Be Deeply staining, relatively large nucleus occupying most of the cell. Faint ring of non-granular protoplasm, Contains, rarely, basophilic granules, Neither ameboid nor pha- gocytic. The larger of these cells cannot be differentiated from the hyaline cell. Lobula- tion or polymorphism of the nucleus rarely present. Irtom5p. 7.5 tor. Faintly staining, relatively large, round, oval, notched or reniform nucleus, slightly larger than above. Broader ring of hyaline, faintly pinkish, grayish or light blue, non- granular protoplasm, Actively ameboid and phagocytic. Nucleus sometimes surrounded by faint rim of hyaline protoplasm, outside of which basophilic granules may be present. (This reaction best brought out by eosin and methylene blue). This cell is also known as the polymorphonuclear leucocyte or polymorphonuclear neu- trophile. It is sometimes called the polynuclear leucocyte. Irregularly staining nucleus; the nucleus is irregular, lobulated, reniform and not uncommonly like the figure 3, 5 or 7, or it may resemble the letters, zor u. The nucleus may be apparently divided into three, five or even six parts, commonly connected by “‘ underground” bands of chromatin; ina- bility to demonstrate connection between the different parts of the nucleus led to the supposition that the cell was multi- or polynucleated. Irregularity in the contour of the nucleus is probably due to its being dried and fixed while stiil manifesting ameboid activ- ity. The nucleus is rich in chromatin bands which may form a recognizable network in its interior, Protoplasm finely granular. The granules believed to be neutrophile are now regarded as faintly oxyphile or acidophile. The granules are commonly recognized over as wellasaround the nucleus. The cell is actively motile and phagocytic. Mitotic and amitotic division of the cells is sometimes demonstrable. These cells are sometimes re- garded as the adult leucocytes of the blood. They are the most important if not the only pus cell. Sometimes cells are seen in the blood partaking of the characteristics of both the mononuclear and faintly oxyphile types ; such cells are sometimes spoken of as transi- tional leucocytes,* * The writer is not kindly inclined toward the use of the word “ transtional.’’ The only excuse for its use is the fact that in enumerating leucocytes we occasionally come across cells which cannot be definitely placed. Reference has been made to this when considering the lymphocytes and hyaline cells between which we believe we recognize intermediate forms. Sufficient care in staining and careful tocusing will usually, although not always, enable one to differentiate between these types. Usually smaller than the preceding type. Diameter ranges between 7and ro pw. Nucleus possessing many of the characteristics of the preceding variety, Rarely cen- trally placed. Chromatin network less conspicuous, often not recognizable ; cells not un- commonly clearly polynuclear without recognizable connecting or ‘* underground”’ chro, matin bands between the different nuclei. Horseshoe-shaped and reniform nuclei frequent- Cell protoplasm not easily identified, with the exception of the granules, which are conspic- uous even in the unstained cells. Granules large, clearly defined, highly retractile, usually discrete, but may be so abundant that differentiation is not easy. Take acid stains in tensely. Stain reddish-brown with Ehrlich’s stain. Actively ameboid, not usually believed to be phagocytic. Granules or matrix may contain bactericidal substances. Relatively large; may exceed 20 mw. Faintly staining, round or oval, structureless nucleus. Protoplasm usually difficult to demonstrate, may appear irregularly notched at the margin, granules slightly refractile in unstained specimens, large and abundant; stain deeply (purplish blue) with methylene blue or with the dahlia formula. Rarely attains size of the finely granular oxyphile cell, usually much smaller. Finely granular and coarsely granular cells are described by some writers as ‘‘mastzellen.’”’ Nucleus round or irregularly indented. Stains faintly, usually with less intensity than the granules, but of the same color. Granules like preceding variety, but very fine. Usually rz to 18 sw; average about 15 pw. Pale, uniformly staining, eccentrically placed, ovoidal or round nucleus, resembling the hyaline cell. Protoplasm varies in quantity. The granules present in the protoplasm are usually not to be differentiated from the granules of the finely granular oxyphile cell. Stain reaction of the granules is not constant. Eosinophile granules and intermediate gradations of stain reaction occasionally present. Eosin and hematoxylin usually fail to demonstrate the presence of granules. Fixed hy Flemming’s solution, karyokinetic figures may be pres- ent. Probably identical with ‘‘cellules medullaries of Cornil.’’ Cabot considers them inter- mediate between the hyaline cell and the finely granular oxyphile cell. While found in other diseases, it is in spleno-medullary leukemia that the presence of myelocytes assumes the most diagnostic importance. : modified and extended, and reproduced from ‘‘ The Jeffersonian.”’ 431 432 SPECIAL PATHOLOGY. to the cubic millimeter, we shall find that not uncommonly the number of leukocytes will exceed this artificial boundary without there being, of necessity, any evidence of disease. On the other hand, if we adopt a standard above this point, or at least very much higher, we find that in certain well-recognized morbid con- ditions the associated leukocytosis falls within the artificial limit decided upon. It will thus be seen that it is quite impossible to draw a fixed line and to say that beyond this the accumulation of leukocytes is abnormal, while under this quantity the number is essentially normal. A standard of 10,000 to the cubic milli- meter has been generally accepted as the maximum normal leukocytic count. There can be no objection to the figure, provided we understand that it is arbitrary and open to the objections just pointed out. In a general way it may be said that leukocytosis may be physiologic or pathologic. The leukocytosis that follows diges- tion, the leukocytosis of the new-born, which not uncommonly persists until the end of the first year, and the leukocytosis at times associated with pregnancy are taken as examples of the so-called physiologic leukocytosis. Digestive leukocytosis is sometimes quite marked; thus, after a meal, particularly a meal rich in proteid food, the number of leukocytes may approach 50,000. The cellular elements in excess are the lymphocytes and finely granular oxyphile cells; sometimes the increase is more marked in one than in the other. This point is of value, as a blood examination made during digestion might, as a result of the large lymphocytic count, lead to erroneous conclusions, and the finding of an excess of finely granular oxyphile cells might also mislead. When gastric digestion is deficient or greatly delayed, it occasionally happens that there is no digestive leuko- cytosis, and, hence, the absence of digestive leukocytosis is not uncommonly regarded as an evidence of gastric disorder. Inflammatory Leukocytosis.—This form is most frequently associated with suppurative, septic, or other inflammatory pro- cesses, and hence is occasionally referred to as phagocytosis. The term is misleading, as the same word is used in an entirely different sense. This form of leukocytosis is not uncommonly preceded by a brief stage of leukopenia, the extent and duration of which depend upon the promptness with which the body tis- sues react, and also on the virulence of the infecting factor. The prompt occurrence of this form of leukocytosis in acute infective disorders—such as pneumonia, acute bacterial conditions affect- ing serous membranes, streptococcal and staphylococcal infec- tions, scarlet fever, and allied conditions—is taken as a favorable THE BLOOD. 433 omen ; the occurrence of a leukopenia that persists is held to be an evidence of weak resistance or of overwhelming infection. Not uncommonly the count in inflammatory leukocytosis may approach 35,000, 40,000, or 50,000, and in rare instances the number of leukocytes present may be considerably greater. The leukocyte most abundant in this condition is the finely granular oxyphile cell. The large numbers of these cells present in the blood may so alter the percentage that repeated accurate obser- vations may show that from ninety to ninety-five per cent. of the leukocytes are of this type. In some cases there is an increase in the number of lymphocytes and hyaline cells. As in other forms of leukocytosis, various opinions have been held as to the source of the added leukocytes and the essential etiology of the condition. It has been held that the leukocytosis is the result of nothing more or less than altered distribution ; the finely granular oxyphile cells leaving the celomic cavities and entering the blood in response to infection. While it is not improbable that such a cause may be active, the large number of leukocytes destroyed at the point of infection,—as, for example, in abscess formation,—and the evi- dence of increased leukolysis, as shown by the excretions, point to the occurrence of increased leukocytic production. The leukocytosis of malignant disease, syphilis, rickets, and the leukocytosis following hemorrhage, as well as the leuko- cytosis that not uncommonly precedes death (agonal leukocy- tosis), are by some writers grouped with the inflammatory in- crease of leukocytes. The leukocytosis observed in connection with malignant disease usually consists of an increase in the mononucleated forms of leukocytes (lymphoid and hyaline cells) ; the same is true of rickets, syphilis, and agonal leukocytosis, while leukocytosis following hemorrhage is usually of the finely granular oxyphile type. Leukocytosis is usually more marked in the presence of sar- coma than in carcinoma, and is particularly evident when the former disease attacks the lymphatic structures. Hemocytolysis.—Dissolution of the red blood-cell with lib- eration of the hemoglobin and endoglobular changes in the cell cytoplasm not infrequently occur in a sufficiently marked form to deserve consideration as a distinct pathologic process. Blood destruction is, in a sense, anormal process. The liberated blood coloring-matter resulting from cell dissolution is converted, in the liver, into bile pigment, and possibly enters into other normal chemic processes. When the process exceeds the normal or when cell destruction assumes an abnormal type, the resulting condition is spoken of as hemocytolysis, hemoglobinemia, or 28 434 SPECIAL PATHOLOGY. by some writers as hemolysis. In the condition under consid- eration the cell elements primarily involved are the erythrocytes ; when the cell destruction involves both red cells and leukocytes (erythrocytolysis and leukolysis), the term hemolysis is more appropriate. Of the many causes presumed to be active in the production of hemocytolysis, no one satisfactorily explains the occurrence of the manifestation under all circumstances. When foreign blood is introduced into the circulation of an animal, and particu- larly when such blood is from an animal’ of another species, the added hemal cells promptly undergo fragmentation. The intro- duction into the circulation of large quantities of fluid may give rise to destruction of normal erythrocytes. _Hemocytolysis occurs in connection with certain infectious diseases, among which may be mentioned smallpox, scarlet fever, diphtheria, enteric fever, and, possibly, to a varying extent, all the acute exanthemata. Bacteria and bacterial products circulating in the blood, as in septicemia and pyemia, may bring about the change. Malaria always induces more or less blood destruction, and in certain forms the process assumes grave proportions. Many poisons induce a similar change, and hemolysis arising from such causes is called toxic. A long list of poisons possessing the power might be given, the most important of which would be chlorate of potash, arseniureted and phosphoreted hydrogen, carbolic acid, pyrogallic acid, and various coal-tar derivatives other than those mentioned, such as anilin, antifebrin, antipyrin, etc. The blood destruction associated with poisoning by various fungi, and, in- deed, the destruction associated with the introduction of venom, might properly be grouped with this class. Extremes of tem- perature seem to be influential in the production of this condition, and local tissue destruction from burns or frost-bites may bring about the change. The condition is sometimes associated with Raynaud's disease. A form of hemocytolysis is clinically recog- nized as paroxysmal hemoglobinuria. Whatever may be the cause of the cell dissolution, liberated hemoglobin may be excreted by the kidney (hemoglobinuria) as methemoglobin or oxyhemoglobin, or the latter may be con- verted into the former by more or less prolonged retention within the bladder, and a sufficiently long stay in this organ may lead to the final conversion of oxyhemoglobin into acid hematin. An examination of the blood usually shows that it is dark in color, and the serum secured by coagulation or by the centrifuge may show a hemoglobin tint. Blister serum obtained from the patient may show the spectroscopic lines of free hemoglobin. THE BLOOD. 435 There is usually a marked reduction in the number of erythro- cytes, associated with the presence of degenerating, fragmenting cells, chlorocytes, andachromocytes. Poikilocytosis, microcyto- sis, and megalocytosis are present to a varying degree. The reduction in hemoglobin may be marked. As a rule, there is little change in the number of leukocytes, although evidence of leukolysis may be present. The liver may be unequal to the task of removing the large quantity of hemoglobin, even with the occurrence of polycholia. The liver cells may show granu- lar change and bile-staining ; free pigment is not uncommonly present in the hepatic tissues. No constant renal lesion is demonstrable, although the kidney shows, for the most part, considerable staining, and the secreting substance may be brown or brownish-red in color; granular, desquamative, and other degenerative changes may be seen in the renal epithelium in marked cases, and free pigment may be present in the tubules; the Malpighian tufts are said to escape the deposit. Mention has already been made of the hemoglobinuria. Hemoglobin infarcts occur in the kidneys, and infarction is occasionally present in other organs. Regeneration of the Blood.—After extensive hemorrhage, and from other causes, direct loss and blood destruction may re- duce the number of red cells to 1,000,000 or less. Usually, with the subsidence of the cause regenerative processes rapidly ensue. After the loss of blood a temporary hydremia is brought about by the abstraction of fluid from the tissues. It is not improbable that the temporary hydremia, so induced, alters the specific gravity of the plasma and favors the actual solution of erythrocytes. Favorable to this view is the fact that chloro- cytes and achromocytes, as well as fragmenting erythrocytes, may be found in the blood. Later, the mean diameter of the erythrocytes falls, and normoblasts are present in varying quan- tities. The fall in hemoglobin is at first proportional to the reduction in the number of red blood-cells, but later the color- index drops, and may fall as low as 0.5. During the process of erythrocytic regeneration nucleated cells may appear in varying numbers. The erythrocytes increase more rapidly than the hemo- globin, and, hence, the color-index remains low. With the occurrence of hemorrhage a rise in leukocytic count is found. The leukocytosis rarely exceeds 25,000; in some cases it is absent. The white cell proportionately increased is the finely granular oxyphile. The length of time necessary for complete regeneration of the blood varies with the recuperative and hematogenic power of the individual and with the extent of 436 SPECIAL PATHOLOGY. the hemorrhage. Repeated hemorrhage weakens the regenera- tive powers more rapidly and to a greater extent than a single copious hemorrhage. Attempts to establish a definite period within which hemal regeneration will occur are not well founded, by reason of the uncertainty in hematopoiesis in different indi- viduals. Anemia.—The term anemia has been variously defined, but, so far as a definition goes, nothing better has been offered than to call it ‘a poverty of the blood.” In certain classes of cases the anemia is apparently dependent upon defects of the blood- making or blood-destroying organs, or, possibly, it would be better to say faults of hematogenesis or hemolysis, or both, Anemias in which no sufficient cause can be recognized in the organs or tissues are commonly referred to as primary anemias. In another class of anemias the blood condition is dependent upon some more or less evident lesion. These are the so-called secondary anemias. As our knowledge of pathology pro- gresses we will, no doubt, class as secondary some of the anemias now regarded as primary. When we have demonstrated the factors influential in the production of an anemia, it becomes secondary to its demonstrated cause. Secondary Anemia.—lIt is proposed to consider with this class those anemias in which it is possible to demonstrate a cause believed to be a sufficient explanation of the recognized change. As blood production is dependent largely upon the general nutrition and health of the individual, as well as upon the hema- togenic functions, properly so called, it becomes evident that a large number of etiologic factors, often not even remotely associated, can be classed with the causes of symptomatic anemia. Unsani- tary surroundings ; improper, poor, or scanty food; overwork with insufficient food ; emotional conditions influencing the appe- tite, sleep, etc., may all possess a varying importance in the pro- duction of anemia. Hemorrhage, copious and single, or scanty and repeated, may also be a cause. Painful affections, by reason of their influence upon the primary and secondary assimilation, may also favor the occurrence of an anemia. Intestinal parasites —such as anchylostoma duodenale and bothriocephalus latus— may induce anemia by interfering with the digestive process, by inducing hemorrhage, and possibly by elaborating some absorba- ble poison that influences unfavorably blood production or destruction. Anemia may depend upon the presence of parasites within the blood ; the most conspicuous of these is the organism of malaria. Acute infectious diseases commonly impoverish the blood. THE BLOOD. 437 During the activity of such processes the anemia may not be con- spicuous, but with convalescence it not uncommonly becomes evident. With this group should be classed anemias following typhoid fever, scarlet fever, smallpox, etc. So-called chronic in- fectious diseases are also associated with the occurrence of anemia, which may of itself be a striking symptom; the anemias of syphilis and tuberculosis are most typical. The anemia of scurvy and purpura should be mentioned. Certain of the secondary anemias are called toxic, and are dependent upon poisoning by lead, arsenic, phosphorus, mercury, etc. Malignant tumors (car- cinoma and sarcoma) usually give rise to a form of anemia that may constitute an important factor in the diagnosis of such con- ditions. Diseases of various organs influencing the general nutrition are not uncommonly associated with anemia. The anemias of chronic nephritis, of heart disease, and of chronic intestinal inflammations belong to this group. The Conditions in Secondary Anemia.—tThe table on pages 448 and 449 gives in a general way the blood changes in this condition. It is probable that the disease ordinarily referred to as simple anemia is truly an example of secondary anemia, and that it should be considered with this group. It will be observed that the blood changes in secondary anemia possess nothing characteristic, and depend more upon the intensity of the anemia than upon any other factor. The reduction in red blood-cells varies within wide limits. A fairly evident secondary anemia may show a blood count of 4,500,000, while, at the other extreme, a count below 1,000,000 may occur. The corpuscular changes also depend upon the extent of the anemia. It may be said that in the milder anemias there is little distortion of the erythrocytes, and but few abnormal cells are present. In more marked anemias poikilocy- tosis and microcythemia occur, while in the graver forms megalo- cytosis and nucleated erythrocytes are found; megaloblasts are rare ; normoblasts are more abundant. Polychromatophilia (ab- normal stain reaction) is usually proportionate to the degree of the anemia. The hemoglobin always shows greater reduction than the cor- puscular count would justify (low color-index), and may not ex- ceed twenty per cent. The leukocytes are but little, if at all, influenced by the mere occurrence of secondary anemia. The condition that produced the anemia may determine a leukocy- tosis the character of which will depend upon the cause. It is usually stated that when the blood counts are low, a leukocytosis is likely to be present ; this is not, however, an invariable rule. 43 8 SPECIAL PATHOLOGY. The visceral lesions associated with this form are dependent upon the cause and upon the extent of malnutrition. Granular changes occur in glandular viscera, notably the kidney and liver. A similar change is seen in the heart. Degenerative changes in the capillary system are indicated by the concomitant edema. The degenerative lesions are-probably dependent upon overwork of the organs involved, associated with poor nutrition, and possibly to a limited extent upon the toxic effects of poisons generated within the blood or arising from other causes and acting them- selves as causes of the existing anemia. CHLOROSIS. Synonyms.—Febris Amatoria; Greensickness; Morbus Vir- gineus ; Chloremia, Chloranemia,; Bleichsucht (German). Chlorosis is primarily a disease of young women, marked by more or less reduction in the number of erythrocytes and still more evident oligochromemia. Causes.—As just,stated, the disease is practically restricted to women, and is most frequent between the ages of fourteen and eighteen years, although it occasionally appears later in life (chlorosis tarda). A condition closely resembling chlorosis is sometimes seen in men. A family history of tuberculosis, faulty hematogenic power, or heredity, as indicated by cases appearing in successive generations, may be predisposing factors. Emotions, such as grief, fear, anxiety, homesickness, and disap- pointed love, have been regarded as causes. Hypoplasia of the heart and greater vessels, and sometimes of the generative organs, has been observed. Autointoxication, constipation, men- strual disturbances, unsanitary surroundings, overwork, and faulty or insufficient diet may cause or predispose toward the condition. Hemorrhage, as by epistaxis, menorrhagia, and bleeding from hemorrhoids, intestines, or stomach, are often assigned as etio- logic factors. Race and climate, particularly among civilized nations, seem to have no influence upon the occurrence of this malady. Lloyd Jones believes that the disease is more common in girls belonging to large families, and that it not uncommonly constitutes part of a general condition one of whose manifesta- tions is unusual fertility. Dyspepsia and constipation associated with the disease are generally not regarded as etiologic factors, although one of the toxic theories (autointoxication) is based upon the belief that the blood condition is due to copremia or some allied state. In the present state of our knowledge infec- tious theories are not to be regarded with favor. THE BLOOD. 439 Blood Changes.—The blood is easily obtained, flows freely, and is usually bright red in color. The specific gravity of the serum is normal or higher than normal, while the diminished hemo- globin gives an unusually low (1030) total specific gravity. Alkalinity seems to be increased. There is an oligocythemia that varies within wide limits, and is not commonly marked. The oligochromemia is usually the most evident change. In mild cases the erythrocytes fall to eighty per cent. of the normal and the hemoglobin to fifty per cent. ; in more marked instances the erythrocytes approach fifty per cent. of the normal and the hemo- globin thirty per cent. or less. Hayem has reported a case in which the red blood-cells fell to twenty per cent. and the hemoglobin to sixteen per cent. It will thus be seen that the reduction in hemoglobin is always greater than the corpuscular reduction (low color-index). In about forty per cent. of the cases the number of red blood-cells does not fall below 4,000,000. The erythro- cytes show a mean reduction in diameter, and are strikingly pale. Microcythemia, poikilocytosis, and polychromatophilia are present to a varying extent. Nucleated red cells are rarely abundant, although occasionally a few normoblasts occur. The presence of macroblasts is usually regarded as an unfavorable sign. The plate- lets are slightly increased. There may be no important change in the leukocytes, with the exception of the occasional occurrence of myelocytes. While it is commonly stated that these cells are absent, there can be no doubt of their occasional presence in grave cases. (See table, pp. 448 and 449.) Associated Lesions.—The panniculus adiposus is usually abun- dant, and the general nutrition, aside from the pallor, seems fair or even good. The pallor of all the tissues may be striking. Granular and fatty changes occur in the heart, and aortitis is occasionally present. Hypoplasia of the heart and aorta has already been mentioned. Fatty changes in the capillary, renal, and gastric cells have been noted. In spite of the fact that the blood coagulates less rapidly than normal outside the vessels, venous and capillary thrombosis and thrombosis within the cranial sinuses may constitute important lesions during life. The morbid anatomy and blood changes fail to explain the peculiar venous hum observed during life. Changes in venous caliber, and in the blood itself, as causes of this important phenomenon deserve men- tion, although the demonstration is by no means satisfactory. 440 SPECIAL PATHOLOGY. PERNICIOUS ANEMIA. Synonyms.—Addison’s Causeless Anemia ; Idiopathic Anemia ; Essential Anemia; Progressive Pernicious Anemia; Myelogenic Anemia; Ganglionic Anemia ; Anematosis ; Biermer’s Disease. Pernicious anemia is a morbid condition associated with exces- sive hemolysis and inadequate hematogenesis (West), and for which no sufficient cause has been demonstrated. While an adequate cause has not been recognized, certain predisposing ele- ments are regarded as important factors in the production of disease ; of these predisposing causes the following may be men- tioned: pregnancy, parturition, starvation, hemorrhage, degene- ration of the mucous membranes of the alimentary canal. The disease is more frequent in adults, although cases in children have been reported. Blood Changes.—The blood is often difficult to obtain, pale, and watery, although occasionally it assumes a coffee or choco- late color. A drop forming at the point of puncture is usually not rounded and elevated, as normal, but flattened, and may spread over adjacent surfaces. Oligocythemia is marked ; blood counts below 1,000,000 are not infrequent, while a count as low as 143,000 has been reported by Quincke. Occasionally, blood counts may, for a time, approach the normal, rising to or exceed- ing 5,000,000, followed by relapse and death. The average size of the erythrocyte is increased, and may approximate 9 yw. The large cells (megaloblasts), which markedly increase the mean diameter of the erythrocytes, may constitute from three to twelve per cent. of the red cells. Megalocytes possessing diameters between 10 and 16 » occur. Microcytes are not, as a rule, abundant. Nucleated red cells are usually, but not constantly, present. So-called crises occur in which an unusually large num- ber of normoblasts may be thrown into the circulation, followed by an increase in the number of red cells. Free nuclei are some- times present in the blood, and occasionally one sees a nucleus with shredded protoplasm containing hemoglobin, attached to its periphery. Both normal and abnormal sized red cells may show polychromatic reactions. The presence of unusually large nucleated cells (megaloblasts) is regarded as unfavorable. By reason of the irregularities in the size and contour of the ery- throcytes, rouleaux formation is peculiar. Oligochromemia does not approach in extent the oligocythemia. The relatively high color-index is usually held to depend upon the large number of red cells the diameter of which exceeds that of the normal cell ; and as the more marked the anemia, the more abundant such cells THE BLOOD. 441 become, it is commonly found that the fall in corpuscles is not associated with a corresponding fall in hemoglobin, and that the corpuscular count may be ten per cent. of the normal or less, and the hemoglobin from fifteen to twenty per cent. of the nor- mal or more. The specific gravity of the total blood is decreased ; the platelets are said to be increased, and occasionally show pe- culiar and excessive agglutination. No change especially worthy of note regarding the leukocytes occurs, with the exception of the usual presence of myelocytes. These are not abundant, and rarely exceed two or three per cent. of all the leukocytes. There is sometimes a slight increase in the number of lymphocytes, and occasionally a proportionate diminution in the number of finely granular oxyphile cells. Leukolysis and tinting of the proto- plasm of the white cells by hemoglobin may be recognized in some cases. (See table, pp. 448 and 449.) Associated Lesions.—In spite of the extreme anemia, emaciation is not present. The skin is pale, but may show a faint icterus ; the peculiar lemon hue may be manifest in the conjunctiva. Petechiz are occasionally present. There is not uncommonly a small amount of edema, particularly on the lower extremities. The panniculus adiposus may be abundant; it is usually yel- lowish in color, contrasting strongly with the red muscles. Coagulation of the blood in the great vessels and in the heart may be delayed or absent. The presence of free hemoglobin in the blood serum and in the serous fluids may be marked and may be sufficient to stain the hands. Fatty and granular changes occur in the heart. Similar degenerative processes are occasion- ally seen in the arteries and capillary walls. Atrophy of the gastric mucosa has been described. The spleen and kidneys may show pigmentation. Tracings of sclerosis have been de- scribed in the central nervous system. The bone-marrow usu- ally shows reversion to the fetal state, and contains a large num- ber of nucleated hemoglobin-containing cells (erythroblasts) ; the larger cells may show evidence of phagocytic power. The liver is usually enlarged and may be fatty, and constantly con- tains an excess of iron. Normally, the percentage of iron is from 0.078 to 0.12, while in pernicious anemia it not uncommonly reaches 0.7. The iron is distributed in the hepatic cells at the periphery of the lobule, where it is usually abundant. (For demonstration of iron in tissues see p. 230.) Occasionally, an excess of iron will be found deeper in the lobule, and at times the interlobular tissue may contain a trace. It is generally conceded that, essentially, pernicious anemia is due to an excessive hemolysis. This is indicated by the 442 SPECIAL PATHOLOGY. occurrence of disintegrated cells—microcytosis, polychromato- philia, plasmorrhexis, etc. ; the hepatic changes offer additional support to this theory, and also indicate that the hemolysis occurs within the portal circulation. The large percentage of iron in the liver supports this view, and the absence of hemoglobinuria . would indicate that the hemocytolysis did not occur in the gen- eral circulation. LEUKEMIA. Synonyms.—Leukocythemia ; Lymphadenia. In this disease there occurs a most marked increase in leuko- cytes, which, while it varies within wide limits, is usually a con- stant feature throughout the disease. Leukemia occurs in the lower animals, notably the cat, dog, ox, sheep, and hog. Causes.—Leukemia may occur at any age. It is most fre- quent during middle life—thirty to fifty years. It is twice as frequent in man asin woman. A history of malaria is present in a certain percentage of cases. Injury to the spleen is sometimes followed by leukemia. Pregnancy, lactation, rickets, and syphilis sometimes antedate the appearance of symptoms. The scanty evidence of heredity does not favor the view that it is an important factor. Certain facts in the history of some cases would indicate the possibility of its being an infectious dis- order, and while protozoa and various bacteria have been de- scribed as present in the blood in some cases, and while it is claimed that the disease has been communicated to lower animals, the evidence must be regarded—for the present, at least—as incomplete ; experienced investigators have failed to demonstrate the presence of bacteria in the blood, and inoculation in animals has proved futile. By some the process is regarded as allied to tumor formation. This view would regard the blood as a tissue the intracellular substance of which is fluid, and the added cellu- lar elements present in the blood would be considered tumor cells. The fact that the cells invade the organs, or at least are found infiltrating various organs and tissues, is adduced to sup- port the theory. Nothing satisfactory in the way of demonstra- tion has been given, and at best the view can be looked upon merely as a working hypothesis. Theoretically, three forms of the disease are admittedly possi- ble—splenic, myelogenic, and lymphatic. The coincident presence of the blood changes of two forms may give rise to what is usu- ally considered as mixed leukemia. Clinically, but three forms are usually recognized—the sflenomedullary, lymphatic, and mixed. With regard to time of invasion and duration, the THE BLOOD. 443 disease is said to be acute or chronic. The splenomedullary cases belong to the chronic type of the disease. Lymphatic leukemia usually runs a more acute course. The Blood Condition.—When the number of leukocytes is large, the blood may be pale, and even slightly turbid, and marked oligocythemia, with associated reduction in blood color- ing-matter, may give rise to a thin, watery consistence, and, as a result of the presence of a large number of leukocytes, a yellow- ishtint. Thealkalinity is lowered. The statement that the blood is acid appears to be unsupported by facts. Coagulation is delayed, and this delay is most marked in the presence of marked oligo- cythemia and oligochromemia. The actual quantity of fibrin present is said to be increased. The two statements are recon- ciled by the belief that peptone is present, which, as is well known, delays coagulation. Splenomedullary Leukemia (Medullary or Myelogenic Leu- kemia or Leukocythemia ; Myelemia ; Myelocythemia).—Asa dis- tinct marrow-form of the malady has not been shown to exist, and as it has not been established that the disease begins in the marrow, the term myelemia or myelocythemia with’ splenic engorgement is generally conceded not to be acceptable. The total number of leukocytes may approximate 500,000; usually, the count does not exceed 1,000,000 or 2,000,000, and at times may fall within normal limits. The enormous addition of myelocytes is the most conspicuous change in this form of the disease. These cells may constitute from twenty to fifty per cent. of the leukocytes present—a percentage never ap- proached in any other form of leukocytosis. The smaller forms of myelocytes may manifest ameboid movement. There is a marked increase in the finely granular oxyphile leukocytes, although the preponderance of myelocytes materially alters the percentage. Instead of from sixty to seventy per cent. of the leukocytes belonging to this group, the percentage varies between ten and fifty. The uninuclear cells, the lymphoid and hya- line cells, are uninfluenced or are slightly diminished. Myelo- cytes showing karyokinesis are occasionally present. The red cells are usually diminished in number ; the extent, however, of the reduction varies in different cases, and more or less at different periods in the history of any given case. Some- times the count may be normal ; in other cases the oligocythe- mia may be most marked. Eichhorst has reported a case in which the red cells were reduced to 316,000 to the cubic milli- meter. The reduction in red cells proportionately reduces the hemoglobin ; marked alterations in the color-index are not un- 444 SPECIAL PATHOLOGY. commonly present. A conspicuous morphologic change is the abundance of nucleated red cells. Normoblasts are rarely absent ; microblasts and megaloblasts are never so abundant. Poikilo- cytosis is not commonly conspicuous. The blood platelets show no constant change, being sometimes diminished, sometimes in- creased. Charcot-Leyden crystals are occasionally seen. (See table, pp. 448 and 449.) ; Lymphatic Leukemia (Lymphocythemia ; Lymphemia).—Leu- kocytosis is not so marked as in splenomedullary leukemia. The proportion of leukocytes to red cells rarely exceeds 1 of the former to 12 or 20 of the latter, and the total count of leuko- cytes ranges between 40,000 and 400,000, rarely exceeding 200,000 or 250,000. The leukocytes most abundant in this form are the uninuclear cells; in some cases the lymphocyte predominates ; in other cases the hyaline cell. The finely granu- lar oxyphile cells are diminished, and the coarsely granular oxy- phile cells are scanty or absent. Myelocytes, if present, are never abundant. Oligocythemia is more conspicuous and constant in this form of leukemia. The count of the red cells may show from 1,000,000 to 2,000,000. Abnormal forms of red cells are less frequent in this form of leukemia, although they are occa- sionally present. (See table, pp. 448 and 449.) Mixed forms of leukemia partake of the blood changes of both forms described, and do not here merit special con- sideration. The names given to the different forms of leukemia are not based upon changes in the organs; enlargement of the lym- phatic glands is not a constant feature of lymphatic leukemia. Changes in the organs usually depend upon the duration of the disease rather than upon the character of the blood-cells, being more marked in chronic cases. The spleen may be greatly enlarged, weighing as much as eight kilograms. The capsule may be fibrous or even cartilag- inous. The shape of the organ is not altered. Infarcts may be recognized upon the surface or on section. Associated infectious processes produce less softening in the leukemic organ than in the normal spleen. The color of the pulp is further influenced by the number of red blood-cells, and as leukemic patients are prone to hemorrhage, a pinkish or pale pulp may be induced thereby. In the absence of such condition the pulp is usually redder than normal. Ina uniformly red organ the Malpighian bodies may not be recognizable. The extensive intercalation of leukocytes may, even in the paler pulp, obscure the Malpighian bodies. As already stated, the density of the organ is more THE BLOOD. 445 marked in the chronic form of the disease. Under the micro- scope the splenic reticulum may show some increase, although it is not commonly much in excess of the normal. Occasionally, it shows more or less hyaline change. The most striking feature is the abundance of leukocytes. These are usually of the form in excess in the blood. The more chronic the case and the greater the splenic enlargement, the more marked the leukocytic intercalation, The changes seen in the bone-marrow usually assume one of two types, although intermediate grades are occasionally noted. Both of these types have received inappropriate names. Pyoid marrow is yellowish in color and soft in consistence. The mar- row usually present is firm, pink or pinkish-gray in color, and is called adenoid or lymphoid marrow. The abnormal marrow dis- places the fatty marrow of the long bones. Histologic changes of the splenomedullary form consist of an enormous increase in the number of normal marrow-cells. Erythroblasts, normal in size, and cells of the larger and smaller types, are usually found ; large phagocytic marrow-cells are present. Evident cell prolif- eration is not uncommonly present, and in a few cases has been conspicuous. The gross appearance of the marrow in lymphatic leukemia does not differ from that observed in the splenomedul- lary form. The leukocytes present are, however, of the hyaline and lymphocytic types—normal marrow-cells being displaced by the lymphoid infiltration. Lymphatic Glands.—In nearly all cases of lymphatic leukemia enlargement of these glands occurs at some time or other in the progress of the disease. In some cases the enlargement is re- stricted to an anatomic group; in other cases different areas may be involved ; and still less frequently the condition may be gen- eral. On section, the glands are pink or grayish-pink in color, soft, and juicy. Confluence is not common, and even where a large group of glands has apparently merged into a single mass, differentiation of the nodules may be possible. The enlargement of the gland seems to be due to engorgement of its channels, including the peripheral sinuses. In the less frequent glandular en- largement of the splenomedullary form the lymphatic sinuses are distended by leukocytes presumably coming from the. blood. The Liver—The organ usually shows considerable enlarge- ment, and may weigh as much as six kilograms. It is commonly pale, and the pallor may be most conspicuous along the course of the portal channels. The extreme pallor is frequently due to the intercalation of leukocytes, the distribution of which may be patchy, local, or general. 446 SPECIAL PATHOLOGY. The kidneys may be enlarged, and lymphoid intercalation may be marked. Increase in the lymphoid tissue is always noticed in the thymus and lymphoid elements of the alimentary canal, as well as in the lungs, and even in the skin. The tendency toward hemorrhage, previously remarked upon as a clinical phenomenon, is further shown by the occurrence of visceral hemorrhage and of hemor- rhage into the newly formed areas of lymphoid tissue, into the joints, and even into the brain. No satisfactory explanation has been offered for the increase in leukocytes and the associated intercalation of these cells in the various organs. It has been held that the leukocytic increase is dependent upon proliferation of the lymphoid tissue from which leukocytes are thrown into the general circulation. It has also been maintained that the lymphocytic infiltration of the various organs and tissues represents the accumulation of leukocytes de- posited from the blood. White and Hopkins favor the belief that the increase in leukocytes is dependent upon diminished destruc- tion of the cells. Pseudoleukemia (Hodgkin's Disease).—This morbid condition resembles leukemia in its anatomy, but differs materially in the character of the blood changes. Like leukemia, it may assume a chronic as well as an acute form, and, like leukemia, splenic enlargement may predominate over the changes in the lymphatic glands. Splenic anemia—sometimes called pseudoleukemia splenica —is regarded by some as a splenic form of Hodgkin’s disease analogous to the splenomedullary form of leukemia. The changes in the blood in leukemia and in splenic anemia, and their differ- entiation from leukocythemia, will be found in the accompanying table. (See pp. 448 and 449.) For further consideration of the morbid anatomy of Hodgkin’s disease see Diseases of the Lymph- glands. Mycoses of the Blood (see Intoxications and Infections, pp. 385 and 389).—The possible infections of the blood may be greater than is at present believed. The organisms of anthrax, tubercu- losis, glanders, typhoid fever, and relapsing fever, also the pyo- genic and a few other bacteria, have been identified in the blood. Care must be used in drawing conclusions from the presence of bacteria in the blood postmortem, as it has been satisfactorily demonstrated that in the agonal period—the final moments or, it may be, hours of the death agony—bacterial diffusion is favored by the lessening bactericidal action of the blood and the proba- ble increasing permeability of the vessel walls. The demonstra- THE BLOOD. 447 tion of bacteria in the blood does not materially differ from their demonstration elsewhere. Trustworthy conclusions are rarely possible from an examination of a drop of blood obtained by simply pricking the skin, as already directed. The method of Sittmann is to be commended. A vein, preferably one in the arm, is exposed under the most rigid aseptic methods,—previous sterilization of the skin, instruments, operator’s hands, etc.,—and a sterile cannula is thrust into the vessel, which may be caused to distend by proximal obstruction, as by pressure by the finger or a fillet applied above the point elected for opening. The blood flowing from the cannula is received in a sterile container (flask or test-tube sterilized by heat), and the subsequent examination is conducted upon principles laid down in chapter 11, part 1. Animal Parasites.—The animal parasites found in the blood are broadly classed as hematozoa. The most important are the malarial organism (p. 211), the embryo of the filaria sanguinis hominis (p. 199), and the distoma haematobium (p. 196). The last named is really a parasite of certain vessels—the portal vein and its branches and the venous ramifications around the bladder and rectum, (See Animal Parasites.) TABULATION OF BLOOD Gross APPEAR- HEMOGLOBIN AND NUMBER OF S1ZE OF, AND PRIMARY ANEMIAS. DISEASES. d E Form CHANGES ~ + ANCE AND Sp.Gr.| CoLor ]NDEx. RYTHROCYTES. | Ww Rep CELLS, Blood flows read- ; ily. Pale red wa- I 4 tee aes | Decreased in size. slow; intravascu- | Greatly reduced. | Normal or slightly ae in CHLOoROsIs. Color index con- only in severe lar, frequent. Sp, reduced. cases, and rarel gr. of total blood | Stantly low. snarked y decreased. Sp. " gr. of plasma slightly increased. Blood flows scant- Marked variation ily, often difficult P 7 in size. Macro- Pri to obtain. Watery,| Marked reduction.| Pronounced oligo-) cytes predomi- ERNICIOUS | pale red (often cof-| Color index usu- | CYthemia. Rou- | nate, Poikilocy- ANEMIA. fee color), Coagu-| ally high. leaux formation | tosis more marked lation slow. Sp. scanty or absent. | than in any other gr. decreased. anemia. ‘Paler red than Sienn oe . | Moderate reduc- . Primary * latign lightly tion. Ee index Moderately ieieeane| slightly Aseria, more rapid. Sp. Dorma or nearly diminished. ecreased in Size. gr. decreased. ; Light red or milky Less fluid, coagu- _ . + ge Tation:slow. Siren oughly reduced. Usually only a See reduction; EDULLARY! decreased. Alki- | Color index below slight reduction, | POV! ocytosis a LEuKEMIA. linity usually di- normal, ‘ slight. 5 minished. a a x ResemblesSpleno- a medullary type, | Reduction more Reduction in size, 4H L except that marked than in Reduced. Always! and distortion fore changes are not so| Spleno-medullary | ™°re pronounced | more striking than UKEMIA. | pronounced. Al-| type. Color index| than in Spleno- in splenomedul- kilinity usually low. medullary type. | lary type. diminished. Paler red than | normal, depend- | Reduced, depend- Psrupo-Lev- ing on severity, ing on severity Diminished, de- ae bene EMIA/OR Coagulation more | and stage. Color | pending on sever- | 1260, + 0!Kilo- Hopcxin’s i i P e cyt rapid. Sp. gr. index normal or | ity and stage. ioe ere Disgase. normal or slightly | lower, coeee decreased. Pale red, more Normal; usuall Spence watery. ? Coagu- Reduced. Color Reduced, some- slightly 1 duced. ANEMIA. lation’ more rapid,| index normal or | times to one-fourth Poikilocytosis Sp. gr. decreased. lower. of normal. seldom excessive Pale red, depend- Reducti E ing on severity; ae anes SOMES Usually decreased. SECONDARY | watery. Coagu- sete Beal Diminution varies| Poikilocytosis in ANEMIAS. lation usually flex Oe a or | with condition. a number ofsevere eat Sp. gr. below natel conditions. ecreased, - 448 * By some authors not recognized as a primary anemia. CHANGES IN ANEMIAS. N N LympuHocytes | Finery GRAN- Res Gere, L EAE ES OF AND HyaLinE /ULAR OXYPHILE, MyELocyTes. geen ED CELLS. EUCOCYTES. CELLS. Leucocyrss. LATES. Rarely found. Normoblasts are Generally Occasionally rela- | Normal or rela- present in severe normal. tively increased. tively dimin- | Rarely found. Increased. cases. ished. Microblasts, nor- : moblasts and A moderate leu- Usuall 2 Commonly Small number megaloblasts pres-| copenia may be| /SU2 y relatively decreased, nearly always Diminished. ent. The latter | present. increased. relatively. found most numerous. : z Fi Sometimes Only in severe Generally Sometimes in- decreased Absent or rare. Increased. cases, normal, creased relatively. relatively. : . Myelocytes form More frequent Enormous in- a Taree percent: than in any other | crease. Inno | Yncreased, but rel-| Increased. but | age of the leuco- form of anemia. | other anemia atively diminished relatively cytes, often 60%. Increased. Normoblasts pre- | are leucocytes diminished. (Basophilic cells. dominate. so abundant. included.) Greatly in- Greatly increased creased, but not| (as high as go per to the extent cent. or more. Relatively Rarely; present found In the Sometimes small decreased. Absentior:tarey Spleno-medul- | and other times lary type. large are increased Usually absent. Normal or May be present slightly Generally normal. Generally Rarely found. Increased. when disease is jnereased. normal. marked. Normal or Generally normal, Generally Rarely present. slightly Usually increased ‘normal. Rarely found. Increased. increased. if fever is present. Rarely met with | Generally in- in mild anemias, | creased. Sel- Usually “Usually May be found Usually but not uncommon) dom normal or diminished. increased. in some cases. increased. in pronounced cases, decreased. 29 449 CHAPTER II. SPLEEN. The spleen, in the course of the postmortem, is the first organ examined in the abdominal cavity. It varies greatly in size and weight, usually weighing between 150 gm. and 350 gm., and measuring from Io cm. to 15 cm. in length, 6 cm. to 10 cm. in breadth, and 2.5 cm. to 4 cm. in thickness; the rela- tion to the weight of the body is about 1 to 360. The color varies considerably, even in health, and undergoes important changes after death ; the same may be said of the consistency. Postmortem Changes in the Spleen.—In the presence of any engorgement or necrotic process the spleen quickly undergoes postmortem disintegration. As a result of attachment to the stomach, digestion may give rise to disintegration of the gastric wall which may extend into the splenic tissue. Sulphureted hy- drogen passing through the wall of any adjacent hollow viscus gives rise to precipitation of the iron present in the splenic tissue, as a result of which the organ shows pseudomelanosis, at first re- stricted to the area of contact, but in time, and particularly where decomposition is in progress, involving the whole surface of the organ. The layer of postmortem pigmentation is usually thin, rarely extending to a depth of one centimeter. Emphysema of the spleen is usually held to be a postmortem process, and depends upon the evolution of gas in the splenic pulp as a result of infection by some gas-producing organism, such as the bacillus capsulatus aerogenes, colon bacillus, etc. Malposition.—Splenoptosis, wandering or movable spleen, arises as a result of relaxation or stretching of its normal attach- ments. The extent of the displacement may be very marked, the viscus at times becoming a pelvic organ. It is probable that the lengthening of the suspensory ligament may be caused by an in- crease in the size of the spleen, and, most certainly, the organ dis- placed becomes larger, the increase in size being partly due to the obstruction to venous return, brought about by the tension on the splenic vein impeding the flow of blood on its way to the liver. The condition is more common in women than in men, and is most frequent in women who have borne a number of children. Relaxation of the abdominal walls favors displacement of the 459 SPLEEN. 451 organ by partial withdrawal of its normal support. The splenic malposition is frequently but a part of the downward displace- ment of nearly all the abdominal viscera—a condition receiving the name wsceroptosis, enteroptosis, splanchnoptosis, or Glénard’s disease. The spleen may be forced from its normal position by spinal curvature, tumors and swelling in the retrosplenic area, and assumes a lower level asa result of inflammatory effusion, morbid growths, etc., in the left pleura. The organ is sometimes pulled out of place by attachment to an adjacent prolapsed viscus, as the colon, stomach, kidney, or spleen. The long pedicle neces- sary for such marked displacement as is seen when the spleen is located in the pelvis or in the right iliac fossa is usually made up of the splenic artery and vein, with a certain amount of connec- tive tissue, in which may be embedded a part of the pancreas. The danger in wandering spleen is twisting of the pedicle and obstruction to the blood supply of the displaced organ. Inter- ference with the venous circulation may be brought about, slowly inducing congestion, with marked induration of the spleen (cyanotic induration). It is alleged that the interference with circulation may give rise to atrophy, although the author has never observed such a condition. When the obstruction, either venous or arterial, is complete, necrosis, which may be mani- fested as a general softening of the organ or as gangrene, occurs. The liability of wandering spleen to circulatory disturb- ance is further evinced by the fact that it not uncommonly contains infarcts ; these may be of different ages. Asa result of localized peritoneal inflammation and capsulitis, the wandering spleen may become attached in some abnormal position, and has been mis- taken for a neoplasm arising at the point of attachment. In addition to the wandering spleen, there is occasionally seen, as in the liver, a partial rotation of the organ on its long axis, thus presenting an edge for percussion and other physical examina- tion, and misleading the clinician as to the size of the organ. In the sztus znversus the organ is on the right side. Malformation.—The spleen may be absent. Aypoplasia of the organ is more common. Splenculi, or accessory spleens, are quite frequent. The number of splenculi varies. Usually one or two are found. Instances have been reported, however, in which as many as forty accessory spleens were present. Theac- cessory organs may be situated near the hilum of the normal organ, in the splenic pedicle, in some peritoneal fold adjacent to the spleen, or even upon the opposite side of the abdominal cavity. Rarely, they are found in the spleen itself, and are occa- sionally embedded in other organs, as the pancreas. Histologic- 452 SPECIAL PATHOLOGY. ally, the structure of the accessory organs is identical with that of the normal spleen, the former being nothing more than miniature reproductions of the normal. They are probably physiologically accessory to the normal spleen, and may undergo hypertrophy after removal of the fully formed organ. It has usually been found that where animals show no disturbance of health as a result of splenectomy, accessory spleens have hypertrophied and have assumed the function of the organ removed. Multiple Spleen.—Instead of a single organ approaching the normal, with a number of accessory spleens, there are sometimes found two or more smaller spleens of approximately the same size. Garrod has observed nine spleens in one cadaver. Multiple and accessory spleens are liable to the same diseases as the normal organ. The normal splenic notch may in rare instances be absent, and in other cases a number of notches are found. Occasionally, the normal notches are deep, and practically amount to incisures or fissures, giving rise to the so-called lobulated spleen. Atrophy of the spleen is said to occur. In the very old the organ is likely to be small. The typical seve spleen is usually small, with a wrinkled capsule, which may be considerably thickened. In the absence of any preceding or associated con- dition giving rise to pigmentation the organ is usually pale. The Malpighian bodies and splenic pulp are atrophied, and the fibrous septa are thickened. A closely allied, but by no means identical, condition is found in large spleens with atrophied Malpighian bodies and intensely hyperemic pulp. As a result of fibrous change, a certain amount of contraction may be present. Hypertrophy of the Spleen.—Little is known of true hyper- trophy of this organ. By some the enlargement of the spleen seen in splenic anemia, Hodgkin's disease, and leukemia is held to be an example of hypertrophy. The increase in size seen in malaria is surely not a true hypertrophy. With regard to the others, they will be considered more fully with the diseases in question. Pigmentary Infiltration.—In chronic malaria the spleen may acquire an enormous size and be intensely pigmented. The viscus may weigh as much as five kilograms, or even more. During the earlier infections the spleen is soft, the pulp being almost diffluent and of a dark-brown chocolate color. Throm- bosis of the smaller blood-vessels and areas of necrosis are not infrequently present. Later, or after repeated infections, the or- gan becomes greatly enlarged, firmer, cutting with considerable resistance, as a result of a decided increase in the fibrous tissue SPLEEN. 453 (‘“‘ague cake’’). It may be of a dark slate-color, due to the con- tained pigment. Histologically, the fibrous septa, the trabecule, and the pulp will all show an abundant increase, with wide- spread deposit of melanin throughout the connective tissue and pulp. The parasite of malaria may be found in the spleen, and leukocytes containing the parasite are not infrequently present. Lardaceous Disease.—The spleen is large, and may be voluminous, weighing five kilograms ; itis lighter in color and of. high specific gravity, with deposits of amyloid material in sago- grain-like bodies; hence the name, sago-spleen. The iodin reaction renders its recognition clear. (See Lardaceous Disease, p. 228.) Under the microscope the amyloid material will be seen to occupy the Malpighian bodies; in the earliest stage it probably occurs as an involvement of the arterial branch that the Malpighian body surrounds. There is a form of amyloid spleen in which the infiltration is more diffuse, not in the distinct sago grains, as just described, but involving the pulp and fibrous septa. The chemic reaction is equally well marked, but is more diffuse and less punctiform than in the sago-spleen. (See Plate I.) sis already described, amyloid disease arises in a number of organs almost simultaneously, but the spleen seems to suffer most in the early stage of a wide-spread morbid condition, and, for this reason, any large, rather pale organ should be carefully tested with iodin to differentiate clearly between the enlargements, due, for example, to leukemia, and those of amyloid disease. The occasional deposit of hyaline material in the septa, vascular twigs, and reticulum has been regarded as a form of degeneration. It is possibly but a step in the evolution of lardacein. Calcareous infiltration is seen in the spleen as a result of past necroses, inflammations, or chronic infections. Lime salts are not infrequently deposited in the thickened capsule of chronic capsulitis, which may extend over a considerable area and assume a bony or stone-like hardness. The periphery of quiescent tu- bercular areas, cyst-walls, and the cicatrices of old infarcts may show calcareous infiltration. Splenic Engorgement.—lIn acute sepsis, and in many of the acute infectious diseases with bacteria or their products circulat- ing in the blood, the spleen seems to become distended with blood; its pulp grows soft and diffluent, and the whole organ becomes edematous and enlarged. This has been considered an acute engorgement,—an acute hyperplasia of the organ,—the re- sult of the accumulation of broken-down elements, and by some a reactionary phenomenon by which the spleen, accessory to other organs, is enlarged in an effort to elaborate a power—to 454 SPECIAL PATHOLOGY. be manifested through the leukocytes or antitoxins, or in some other way—which may successfully combat the noxious agents circulating in the blood. As we are not fully aware of the func- tions of the spleen or of the organs at work in resistance to in- fections, the precise cause and process can not, for the present, be definitely explained. In addition to the gross changes previously noted, the tension of the capsule may be striking, and during life it may be so great that, with the softening, the spleen may rupture. Postmortem, such an organ is rarely removed without a tear in its capsule through which the abnormally dark, grumous pulp is easily squeezed out. Such an organ will show, under the microscope, a pulp distended with blood, an enormous number of leuko- cytes, and the red cells advancedly fragmented. If bacteria are circulating in the blood, the splenic interstices may be distended by the invaders. The pulp-cells may be found in all stages of their life history—karyokinetic, active, cloudy, granular, and fragmenting ; the displaced and softened fibrous network mani- fests the separation of fibers incident to edema and vascular dis- tention. Commonly, the splenic pulp contains a large number of phagocytes in which may be found bacteria. That the condi- tion is not always an infection is shown by the fact that it can be produced by abrin, ricin, and by large doses of nitrate of sodium. These considerations, with other clinical and experimental data at hand, would lead us to regard the change as depending upon a toxemia. That all toxic conditions do not bring about the change ‘is shown by its absence in uremia. That such organs recover there can be no doubt, as the fact of the splenic enlargement of typhoid abundantly bears out; but the exact method of repair, of restoration, and of regeneration is not known. The condition has been called acute diffuse splenitis. The term engorgement is not the proper one, and the term zzfectious splenitis has been offered as a substitute ; the objections to the latter will be apparent when considering splenic infarctions. Chronic Inflammation of the Spleen.—The fibrous thick- ening observed in the spleen as a result of capsular inflammation, chronic engorgement, malaria, syphilis, etc.,is sometimes described as a chronic diffuse splenitis. In the earlier stages the organ is somewhat enlarged and is usually pigmented ; the splenic pulp shows whatever alterations the associated cause may have induced. Later, there is marked increase in the amount of fibrous tissue, which fact renders the organ dense and gives to it the name fibroid spleen. Perisplenitis.—In general peritoneal inflammation the serous SPLEEN. 455 covering of the spleen is, of course, involved; by extension of inflammation from some adjacent tissue or viscus—such as the stomach in chronic ulcerative processes, the diaphragm in pleurisy of the left side, perinephritic inflammations, and chronic colitis involving the splenic flexure of the colon—the capsule of the spleen may become inflamed and thickened, and may form adhe- _ sions. Rarely is this observed as an acute process, but, rather, the results are seen postmortem. The whole of the capsule may be involved (capsular fibrosis), or only a small area; the past inflammation is marked by a layer of inflammatory tissue from 2 mm. to 10 mm. in thickness, rarely thicker, and usually adhe- rent to some adjacent structure, diaphragm, colon, stomach, or posterior abdominal wall. On external examination the white area, if small, may resemble the scar of a past infarct; but on section its purely capsular relation will be apparent. In some instances the newly formed fibrous tissue is piled up in layers, constituting the so-called /amellar or corneal fibroma of the spleen. In rare instances the new tissue is cartilaginous. Sometimes the capsular inflammation and its associated thickening extends along the fibrous septa downward into the spleen. When the capsulitis has been uniformly disseminated over the whole organ, the mass, before section, may not resemble the spleen: during an opera- tion it has been mistaken for a tumor ; its position, relations, and attachments during life should prevent such an error, and an incision postmortem quickly exposes the characteristic splenic parenchyma. It is possible that the uniformly thickened capsule might, by contraction, lead to atrophy of the splenic structure, but it is not known that such a process ever occurs to a suffi- cient extent to involve the function of the organ. Congestion of. the Spleen.—lIn cirrhosis of the liver with obstructed portal circulation, in prolapsed or wandering spleens, in cardiac or pulmonary disease associated with venous engorge- ment, and during or after thrombosis of the splenic vein, more or less passive congestion of the spleen occurs. The organ becomes large, soft, sometimes semifluctuating, and nearly always dark in color; later, it may be rather fibroid. The conditions are anal- ogous to the changes in the cyanotic kidney. There is usually a decided increase in the fibrous tissue, distended blood-vessels, edematous and rather fluid pulp, and considerable pigmenta- tion. Hemorrhage into the splenic pulp occurs in nearly all infec- tions that prove fatal, and is, therefore, usually demonstrable in any spleen showing engorgement of the kind described on page 453. Asa result of injury during delivery, and sometimes 456 SPECIAL PATHOLOGY. in the infections that follow splenic hemorrhage is seen. It also occurs in the new-born as a manifestation of congenital syphilis. The hemorrhage may be diffuse or focal. The focal hemorrhages are commonly multiple, and vary in size from 1 mm. or 2 mm. to accumulations as large as an orange. Little is known of the changes that take place in areas of hemor- rhage occurring in patients who recover. It is probable that the blood is absorbed, and that more or less fibrous tissue results. We certainly find marked increase in the pigmentation, but this is usually not sufficiently circumscribed to enable us positively to identify the area. Splenic Infarction.—In no organ more clearly than in the spleen are to be seen the results of lodged emboli. The vessels to the spleen are characteristically terminal, and their distribution and ending in the splenic pulp are such that no embolus is likely to traverse the organ without being arrested. Szmzple cmbolt in- duce infarcts, distinctly conoid ; on section, wedge-shaped ; with, in the early stages of the process, an elevated surface; in color purplish (Aemorrhagie infarcts), black, or of a combined tint ; soft at first, later firm, and, again, after coagulation has terminated in liquefaction necrosis, soft, semifluid, or even cystic in consistency. Later, if not too large, organization and cicatricial tissue formation convert the mass into a pale and eventually white cone of scar tissue extending more or less deeply into the parenchyma of the organ; sometimes such a scar may extend down to the hilum, almost dividing the organ into two parts. In other cases the in- farct contains but little blood; it does not become purplish or black, as in the foregoing, but is of a light pink, pinkish-white, or whitish hue, and hence is called anemic or white infarct. There is the same coagulation necrosis, followed by liquefaction necrosis, and probably the result is the same as in the area of the hemorrhagic infarct. The number of infarcts may be so great as to preclude counting ; as a rule, there are more than one. While usually on the surface, they are not always superficial, and, while most frequently the area involved is cone-shaped, the blending of a number of infarcts may offer so misleading a picture as to require careful study for positive identification. Infected emboli quickly produce an entirely different picture. Possibly, in the early development of the infarct, the appearance is the same ; soon, however, the area involved is converted into an abscess, and as such abscesses are usually multiple, the spleen becomes studded with small pus cavities, or may show, by con- fluence, one or more of much larger size. It is well to remem- ber that the soft, juicy, splenic pulp, with its open-mouthed SPLEEN. 457 blood-vessels, may contain a pus so loaded with broken-down tissue and extravasated blood as to mislead the unwary. Splenic abscess may also arise from direct injury of the spleen and from extension of suppurative processes from adjacent organs, such as perforating ulcer of the stomach, and at times without any discernible cause. The occurrence of splenic abscess in typhoid fever and other acute processes must be looked upon as resulting from pyogenic infection of an area of necrosis, itself caused by the activity of toxins circulating in the blood. It is admitted, of course, that the typhoid bacillus might possibly ‘induce suppuration without the presence of pyogenic cocci. Actinomycotic and gummatous lesions occasionally suppurate. Splenic abscess may be single or multiple. Embolic abscesses are usually, although by no means always, multiple. Abscesses resulting from trauma and from direct invasion of the splenic tissues are commonly solitary. An abscess may be superficial or deep ; its shape is largely dependent upon the cause; embolic | abscesses are usually more or less irregularly conic, and trau- matic abscesses are commonly ovoid or spheric. An abscess may rupture into the peritoneal cavity, into some adjacent hol- low viscus, or, where the process is limited, inspissation and encapsulation may take place. Thrombosis of the splenic vein, while rare, may occur, giving rise to edema and distention of the organ resembling the congested spleen; there is commonly more edema, and, as the process is acute, less fibrous tissue is present. The thrombus may be an extension backward from the portal vein, or, arising: in the splenic vein, may extend into the portal. Gangrene of the Spleen.—The wandering spleen may, by the twisting of its pedicle, cut off the blood supply and blood exit ; the poisons produced by the disorganization of the splenic tissue favor the migration of bacteria from the adjacent alimentary canal, and, by this infection, the dissolution of the organ ter- minates in gangrene. The author has known two cases, undiag- nosticated during life, and both found with evident infection postmortem. Leukemia and Pseudoleukemia.—In these diseases the spleen is often much enlarged, pale or bright red, with tense cap- sule, and not uncommonly with adhesions to the adjacent organs. The largest spleens are found in splenomedullary leukemia, in which disease the weight of the organ may approach 8 or g kilo- grams. Accessory spleens are likely to show enlargement. The density of the organ seems to be dependent more upon the duration of the process than upon the kind of leukemia. In- 458 SPECIAL PATHOLOGY. farcts are frequently present, and are often of different ages. In some.cases the Malpighian bodies stand out as lightly colored nodules on the incised surface, so clearly enlarged as to be most prominent features; in other cases the cut surface is uniform. Under the microscope the hyperplasia seems to involve the entire splenic parenchyma as a lymphoid cellular growth, either shown, as previously indicated, by overgrowth of the Malpighian bodies and pulp, the former in excess, or of both structures without apparent differentiation. In leukemia the splenic enlargement may be largely due to the intercalation of leukocytes, the added white cells being of the same kind as those found in excess in the blood. In other cases the spleen contains tumor-like masses, sometimes called lymphoid growths. Such tumors vary in size from purely microscopic bodies to nodes two or three centime- ters in diameter; they sometimes project on the surface of the spleen. (For blood condition in leukemia and pseudoleukemia see pp. 443 and 446, and table on pp. 448 and 449.) Rupture of the Spleen.—As a result of violence—either directly applied, as by a blow or fall, or indirectly applied, as by the sudden arrest of the body, as in falling from a height— the spleen may rupture ; when enlarged, the most trifling acci- dent may be followed by laceration, and, when intensely en- gorged or softened, as in infectious diseases, the rupture apparently occurs without trauma—so-called spontaneous rupture. The hem- orrhage is likely to be severe, but is not invariably fatal, and in rare instances, with small stellate tears, a clot may form and the organ may undergo repair by the subsequent formation of cicatri- cial tissue. Rupture may occur in areas of septic infarction, splenic abscesses, and cysts. Chronic Infections of the Spleen.—The most frequent of these is tuberculosis. It is at least questionable whether primary tuberculosis of the organ occurs. In acute miliary tuberculosis, with wide-spread visceral invasion, the spleen rarely escapes. At times the spleen may contain a few, or more rarely many, tuber- culous areas, 5 mm. to 2 cm., or in rare instances larger, caseous areas of apparently quiescent tubercle. The acute form may consist of an almost uniform invasion of all the splenic tis- sues with typical miliary tubercles located near the arteries, in the pulp, in the Malpighian bodies, or even in the capsule of the organ. In the larger, caseous areas of chronic tuberculosis cal- careous infiltration is not infrequently present. Syphilis of the spleen occurs in two forms—congenital and ac- gured. The congenital type may be manifested in one of two ways: (1) Diffuse splenic fibrosis with some enlargement, which, SPLEEN. 459 however, is not usually marked, although Ziegler records an instance in which the enlarged spleen weighed 100 gm. at birth ; (2) in other cases true gummata are found. The splenic lesions of acquired syphilis vary with the stage of the disease during which the organ is involved. In the earlier stages of syphilis the spleen may participate in the hyperplasia found in a number of the blood-making organs ; in the late secondary or early ter- tiary period a diffuse fibrosis is not infrequently present ; later, the characteristic lesion of tertiary syphilis—the gumma—is oc- casionally seen. Commonly, the lesion is solitary, but in very rare cases two or more gummata may be found. The size varies greatly ; the mass is spheric or oval, of a pearly-white or grayish- white color, and is sometimes translucent, particularly at the margin. Like chronic tuberculosis, the masses are sharply de- fined at their margins, but, unlike the tubercular nodule, casea- tion is not a characteristic. Leprosy of the spleen manifests itself as leprous nodules loaded with the bacilli in quite characteristic clusters. Actinomycosis of the spleen occasionally occurs; with the de- velopment of the actinomycotic node, suppuration is most likely to ensue, engendering an actinomycotic abscess of the spleen. Tumors of the Spleen.—Splenic tumors are not common. The primary tumors in an otherwise normal spleen are, of course, connective-tissue neoplasms ; of the adult or typical series, hem- angioma, fibroma, and lymphangioma are the forms usually met. Sarcoma is less rare. Secondary tumors are more fre- quent than the primary growths, and as sarcoma travels by the blood-stream more frequently than carcinoma, it is the usual secondary neoplasm of the spleen. Cancer, however, does occur, Cysts of the Spleen.—Cysts are found in the spleen oftener than primary neoplasms. They may result from the encapsula- tion of massive infarcts, which, by reason of their size, have failed to organize and have not been absorbed. The usual cyst is, however, of parasitic origin, and may attain considerable size ; rarely, the parasitic cysts of the spleen are multiple. CHAPTER III LYMPH-GLANDS.* The lymph-glands, or, more appropriately, the lymph-nodes, are structurally composed of a peculiar form of cells that, massed together, constitute lymphoid tissue ; these, in the gland, are retained in place by a reticulum of connective tissue. The gland lies loosely in the connective tissues, and, in addition to its blood supply, receives through its capsule the afferent lymph- vessels, draining lymph from the area beyond; after passing through the gland the lymph finds its exit by way of the efferent vessel, eventually reaching the blood through the vein into which the lymph-vessel empties. The capsule of the gland is made up of fibrous tissue, with some unstriped muscle-fibers ; from the capsule run septa that converge at the hilum, dividing the gland into follicles. Each follicle is made up of a reticulum, scaffolding, or sponge-like network of connective tissue, in the spaces of which are lodged the lymphoid cells ; toward the periphery of the ovoid follicle the lymphoid cells are smaller than in the center, in which many of the larger form show active karyokinesis. The lymph, in passing through the gland, comes in intimate contact with the cells of the parenchyma, and in this way is probably altered in composition and cellular contents; at the same time the gland structure is exposed to whatever deleterious influences the lymph, in its return to the circulation, may bring. It will thus appear that the glands are liable to be influenced by the blood brought to them and by the lymph of the area drained. Lymphoid Atrophy.—In the old this process is normal. It may be a metaplasia, the gland being more or less replaced by adipose tissue. Such glands are usually firmer and paler than normal, and may be pigmented. Pigmentary Infiltration.— Whatever pigment the lymph may find in the tissue of the area drained is brought to the gland, and may be deposited (p. 233). Thus, in the removal of blood ex- * The examination of the lymph-glands during a postmortem is regional : that is, the glands of an area are examined with other organs of the region, so that the consideration of their special pathology at this point, near the spleen, is due to the intimate association of their lesions with those of the spleen rather than to any special propriety of considering them at this time. 460 LYMPH-GLANDS. 461 travasated into the connective tissue, the blood coloring-matter carried to the gland may be found in the cells of the gland. In anthracosis—indeed, in all forms of pneumoconiosis—the pig- ment from the lung is carried to the adjacent lymph-glands, where it may be deposited to such an extent as to make the gland brown, gray, slate-colored, or even black. Some of the infiltrated material, as certain calcium salts, may be removed ; other solid or insoluble bodies may remain as a permanent part of the gland. The infiltrated material may induce a chronic fibroid change in the gland, with the production of fibrous tissue, thus rendering the gland more firm, larger, and less efficient in physiologic activity than normal. Whether or not normal lymph-glands are likely to be invaded by calcareous matter can not be definitely settled, but certainly an inflamed or infected gland is exceedingly prone to the deposit of lime in its interior. Lardaceous disease affects lymph-glands as it does other tis- sues of the body. At times it would seem that there may be lardaceous deposits in the glands of an area without manifest gen- eral deposition in other tissues. This is said to arise as a result of the lymph bringing to the gland a material, or irritant, which leads to the change, and which, being arrested in the gland involved, permits the other tissues to escape. (See Amyloid Disease, p. 228.) Of the degenerative changes in lymph-glands but little can be said. They are usually due to irritants brought to the gland, and occupy positions of secondary importance. It would seem, however, that hyaline degeneration, and possibly colloid change,. may occur in lymph-nodes without any apparent or discoverable antecedent disease. Infections of Lymph-glands.—The lymph-glands, probably more than any other tissue, possess a remarkable susceptibility to the influence of bacteria or their chemic products. There is hardly a known infection, from bubonic plague, which seems to explode its virulence on the lymph-nodes, to the most chronic infection, such as leprosy, which does not either directly or indi- rectly modify the structure and function of the lymphoid tissues. The change in most cases is an inflammation, a Lyinphadenitis, which may extend to the tissues around and give rise to a perz- lymphadenitis. As to time, the process may be fulminatingly acute, or may extend over months or even years. In the lymphadenitis arising from the ordinary infections, such as those produced by the pyogenic bacteria, the appearance of the gland is greatly modified according to the stage of the dis- ease. At first it is swollen, tense, and tender, and the obstruc- 462 SPECIAL PATHOLOGY. tion to the passage of fluid through the gland may be evinced by a surrounding or overlying edema, or a swelling in the tissues of the area drained. On section, the surface is gray, grayish- white, or pink, or, rarely, there may be enough contained blood to give the incised surface a darker hue. Ina gland not previously indurated the parenchyma is soft, and may be diffluent. Under the microscope the lymph-channels are distended by leukocytes, and commonly contain fibrin; in the follicles areas of coagula- tion necrosis, with fragmented cells, are usually abundantly shown. Later, the processes of degeneration extend beyond the follicles, involving the septa, and eventually the capsule and circumglandular tissues. Such an inflammatory process is spoken of as a bubo. It is common in the groin during in- fectious lesions of the genitalia and superficial infections of the lower extremity ; it is seen in the axilla from similar lesions of the upper extremity or mamma, and in the neck when the initial process is in the superficial, tissues of the scalp, face, mouth, or pharynx. One must not forget possible unusual lymphatic distribution: for example, cases in which involvement of the supraclavicular glands follows disease of the breast, the corre- sponding axillary glands escaping. Suppuration of the lymph-glands fails to occur in many in- fections, particularly those in which the infecting organism does not possess the faculty of pus production. In these cases there is a degenerative change, a necrosis of the lymphoid tissue, with corresponding interference with function. Thus, in diphtheria the toxins absorbed from the diphtheric area give rise to edema of the lymph-gland, coagulation necrosis, and periadenoid edema, and probably lessen the phagocytic, bactericidal, or other protec- tive powers of the lymphoid tissues to such an extent as to per- mit of suppuration should pyogenic ‘bacteria be carried into the gland. The somewhat dense capsule of lymph-nodes permits the occurrence of a rather prolonged intraglandular inflammation without infection of the surrounding tissue; such a battle be- tween the invading organism and the gland-cells may terminate in a victory for the latter, or in a drawn battle, in which case periade- noid induration and subsequent dense fibrosis, with possible cal- careous change, may so surround the area of danger as perma- nently to include it as a ‘‘healed-in” focus. It is a limitation of this type that occurs in tuberculosis. The gradual delivery to a gland of irritant bodies, such as may be taken up from some permanent area of infection or from dust, as occurs in pneumoconiosis when solid particles are being con- stantly thrown into the gland, induces a more or less subacute or LYMPH-GLANDS. 463 chronic productive change, during which new fibrous tissue may be formed in and around the gland, constituting adenztis chronica or periadenitis chronica, or the two lesions combined. Of the chronic infections occurring in lymph-glands, tubercu- losis and syphilis are the most important, although leprosy may involve the lymphatics. Tuberculous lymphadenitis, the scrofulous lymphadenitis or scrofula of the older writers, arises from invasion of the lymph- glands by the bacillus of tuberculosis brought to the gland by the lymph-vessels or blood-vessels. That it is usually lymph- ogenous can not be doubted; but this would not account for those occasional cases, really rare, apparently no system of glands. in the body escaping, and in which they all develop tuberculosis at so nearly the same time as to preclude the belief that the initial lesion was in any one area. It may be possible that these cases are general infections directly by the blood : that is, tuber- cle bacilli carried throughout the organism reached the lymph- spaces, and from these were transferred to the lymph-glands. Whatever may be the cause, undoubted cases of almost universal lymphatic tuberculosis occur. The frequent form of tubercu- lous lymphadenitis is that of some chain of lymph-glands with a fairly clear source or route of infection. Under this head come cervical, mediastinal, mesenteric and retroperitoneal, axillary, and enguinal lymphadenotd tuberculosis. The route of invasion, or, rather, the portal of entry, can often be surmised, and, although rarely, at times demonstrated. A mucosa weakened by inflam- mation is the most frequent route ; thus, we see tuberculosis of the cervical lymph-glands following catarrhal processes of the nose or throat or inflammatory lesions in the mouth. The frequency of mesenteric tuberculosis in bottle-fed children, in whom indigestion and catarrhal lesions pave the way for the entrance of the bacillus of tuberculosis (admittedly not an infre- quent milk contaminant), is largely explained by admitting the increased permeability of an already diseased mucosa. The frequency of tuberculosis of the mediastinal glands after influenza rests upon a similar basis. As already stated, the point of entry of the bacillus can sometimes be more or less accurately determined. Senn reports a case in which a nontuberculous girl wore the ear- rings of a tuberculous sister, and later developed a local tubercu- lous outbreak. The author saw a case of axillary tuberculosis follow a wound made by a corset steel on the outer margin of the breast in a young girl nursing a sister in an advanced stage of tuberculosis of the lungs; the glands were removed, and no further evidence of tuberculosis has been observed. 404 SPECIAL PATHOLOGY. Morbid Anatomy.—The gland is very much enlarged, swollen, and, at first, not attached to the surrounding tissues; the gland capsule is thin and tense. On incision, early in the case, the gland is more or less hyaline, translucent, and very mark- edly swollen; scattered throughout its structures will be shown tubercles in different stages of development and in all degrees of necrosis and degeneration ; later, these tubercles may become fibroid, caseous, or calcareous. In the mean time the gland shrinks in size and grows fibroid, with a dense and thickened cap- sule. Such glands as the last-described represent a ‘“ healed-in”’ tuberculosis, or gutescent tubercular lymphadenitis. In less favor- able instances the process of caseation involves the whole gland ; eventually, a periadenitis is induced, and the gland becomes ad- herent to the surrounding structures ; masses of such glands may coalesce. These either break down singly or a number case- ate at once, giving rise to a tubercular abscess, the contents of which are free from pyogenic bacteria. Ina small percentage of the cases pyogenic bacteria may have gained ingress either with the tubercle bacilli or as a secondary infection; under such circumstances the inflammation will give rise to more marked sys- temic phenomena and the suppurative processes will be more active. On the whole, it may be said that tuberculosis of the glands has a tendency toward the conservative processes of sclerosis and limitation, and that general dissemination is not likely to occur; exceptions to this statement are not infrequent. With the deposit of the tubercle bacilli in the lymph-node the evidence of infection begins. There is quickly developed an epithelioid cellular accumulation arising by a proliferation of the endothelial cells of the lymph paths; to these are added a few polynuclear leukocytes, which, with the accumulation of lymphoid cells, produce the anatomically mature tubercle. A number of these become confluent, and caseation occurs, followed by local diffusion involving the whole gland and later a periadenitis that binds the glands of the areatogether. The infection may spread to the circumadenoid tissues, and eventually, by the route of least resistance, may reach the skin. During this time it is pos- sible that some of the bacilli may have passed the gland and assured further extension of the process by a second incursion through the lymph stream. (See Tuberculosis, p. 366.) The course just described may be arrested at any point. The bactericidal action of the lymphoid structures, including the leuko- cytes, may terminate the process by a victory for the protective forces, the bacilli succumbing or becoming so surrounded by a protective cordon of leukocytes as to limit the lesion to the area LYMPH-GLANDS. 465 involved, or, possibly, to a single gland, or even to a part of a gland. This “ healing-in” of a gland, part of a gland, or a mass of glands does not represent a cure, but merely a quiescent in- fection, which may, when the protective power is weakened by some secondary or intercurring malady, break out anew. Syphilitic Lymphadenitis.—The nearest anatomic lymph- node draining an area in which there is an initial lesion of syphilis shows, as a rule, a reaction to the invasion, which is quickly fol- lowed by surrounding glands, and eventually, inthe vast majority of cases, by the lymphadenoid tissues at large. This initial or primary glandular involvement seems to be almost purely a pro- liferative change in the cells of the lymphoid follicle and further blocking by leukocytes. The change is usually transitory, and disappears in a few days under treatment, and, often, in a few weeks without. In addition to this primary involvement of the glands gummata may be present in an active stage of develop- ment, or gummatous changes represented by atrophied, cicatrized, or caseous areas of a practically cured tertiary glandular change. Under the name of lymphadenia, lymphadenoma, lympho- sarcoma, progressive lymphadenoid hyperplasia, malignant lymphoma, simple adenia, Hodgkin’s disease, pseudo- leukemia, and other more or less synonymous terms, there ex- ists a peculiar form of lymphoid change in which one or more of the lymphadenoid tissues of the body are involved, including not only the lymph-glands, the spleen, and the tonsils, but even the lymphoid tissues of the various mucosze. The tendency at present is to regard the change observed as truly sarcomatous, and but little effort is being made at the present time to separate such glandular enlargements from the admittedly malignant growth— sarcoma of lymphatic glands. The glandular enlargement follows no law: each case differs from all others. As a rule, the first glands to enlarge are the cervical. A cluster of glands may become prominent in a comparatively short time, may remain quiescent sometimes for months, and then may suddenly take on renewed activity. Fol- lowing the cervical glands in order of frequency come the axillary and inguinal glands. In extremely rare cases the disease begins in some of the internal glands, such as the mediastinal, retroperi- toneal, or bronchial ; and later in the affection all these groups may be implicated. Some of the glands may show caseous areas accurately circum- scribed, and probably the result of a past tuberculous infection. The disease, however, bears no relation to tuberculosis—the asso- ciation of infections is mentioned only to indicate the possibility 30 466 SPECIAL PATHOLOGY. of combined lesions. The process is not restricted to the lym- phatic glands properly so called, but the lymphoid tissues through- out the body show acertain amount of involvement. The splenic changes have already been considered. (See p. 457.) The adenoid tissue of the alimentary canal becomes conspicuous, and lymphoid growths in the liver and pancreas are occasionally found. The thymus and thyroid bodies and the suprarenal cap- Fic. 245.—HODGKIN’S. DisEASE.—(From a photograph taken a few weeks before the death of the patient from mediastinal involvement.) The lymphatic enlargement in both axillee is shown, as well as the unusual collar-like gland- ular involvement in the neck. The glands of the left axilla show the tuberous or nodular character of the enlargement, as they have not as yet matted together. In the right axilla the individual glands are not easily outlined. The right arm is swollen from pres- sure on the axillary vein, and possibly from obstruction to the lymph flow through the in- volved glands. At postmortem examination the mediastinal, retroperitoneal, mesenteric, and inguinal lymphatics were all found to be involved. (Patient of Professor J.C. Wilson, in the wards of the Jefferson Medical College Hospital.) sule may be involved; rarely, lymphoid growths occur in the central nervous system. The enlarged glands are white or grayish-white, and are either firm or soft, depending upon the rapidity of their growth ; in rare cases there may be evidence of necrosis in their interior. Asa rule, they remain distinct until reciprocal pressure or peripheral growth has coalesced them, and not until they have attained con- siderable size do they show evidence of marked periadenoid ex- LYMPH-GLANDS. 467 tension ; to this rule there are notable exceptions, and occasion- ally, in a group of glands, many differences in consistency, in color, and in evidences of infiltration may be present. When examined under the microscope, great difficulty will be experienced in at- tempting to classify these growths. In some there may be hothing but the usual structure of a lymph-node on a large scale,—a true lymphoid hyperplasia,—while in others but little resemblance to anormal gland can be observed. Between these two extremes all stages of lymphoid tissue proliferation may be demonstrable ; the gland capsule may be intact, or it may be infiltrated and the same cellular texture may be demonstrable from one gland to another. Tumors of Lymph-glands.—If we except the foregoing enlargements from the tumors of lymph-glands, the only primary tumor of the lymph-node is the sarcoma ; the alveolar, round-cell, melanotic, and mixed-cell forms occur in the order given. Sar- coma may be secondary as well as primary, but is less commonly so. The frequent secondary tumor of lymph-glands is cancer. In all its forms carcinoma involves the lymph-spaces ; the extent of this involvement of the primitive lymph paths, and the port- ability of the invading cells, together with the resistance of the individual, determine the rapidity with which the tumor cells reach the lymph-gland. Thus, the rapidly growing, almost spheric, cells of the encephaloid spread more rapidly than the squamous or flat irregular cell of the epithelioma. (See Tumors, pp. 319 and 356.) When the lymph-node is reached, the histology of the primary tumor is usually as fully reproduced as the gland and its sur- rounding structure will admit. CHAPTER IV. THYMUS BODY. In the last months of intra-uterine life and during the first two years of infancy the thymus body may be justly called a gland, as it contains epithelial elements arranged in lobes, with subdi- vision into lobules, and a minute structure resembling that of certain glands. Even before birth displacement of the epi- thelial structures by lymphoid tissues is marked, and this substi- tution persists to the second, third, or fourth year. After this time atrophy progresses, and by the tenth year the adenoid struc- ture has been replaced by fat and fibrous tissue, and at puberty, or shortly afterward, the gland can rarely be identified, or at most but a small vestige may be found. Malposition and Malformation.—The organ may be absent, and there may be no evidence of its ever having developed. In other instances even in infancy it may be scarcely demonstrable. Accessory lobes, and even fully formed accessory glands, are occasionally observed. Rarely, the gland may be out of place, approaching the thyroid, or, less commonly, anterior to the heart and below its normal position ; in some instances a lateral displace- ment may be present, and still less frequently the thymus vestige may be found in the peribronchial connective tissues. Persistence of the gland, either with or without enlargement, is occasionally observed. In the absence of any distinct overgrowth it may be questioned whether any symptoms or lesions result. Atrophy of the thymus, as previously stated, is a normal process. Hypoplasia of the fibrous tissue, with increase in the lymphoid structure, giving rise to considerable glandular enlarge- ment, sometimes called thymic hypertrophy, is occasionally seen. Normally, the thymus gland varies in weight between 5 and 10 gm. at the stage of its fullest development. The en- larged thymus may weigh from 20 to 40 gm., and may retain a weight of from 20 to 25 gm. in the adult. Very often this per- sistence or enlargement of the thymus gland arises without any associated phenomena. In other instances it is observed in con- nection with goiter and with the lymphoid and adenoid enlarge- ments of leukemia and Hodgkin’s disease. Hérard, Bontemps, 468 THYMUS BODY. 469 Grawitz, Marfan, Brouardel, and others believe that enlargement of the thymus may have something to do with the occasional occurrence of sudden death, particularly in children—so-called thymic death. Following thymic death, as well as asphyxia from other causes, ecchymoses and marked congestion are com- monly found in thethymus. Petechie, ecchymoses, or even hentor- rhagic infiltration are occasionally observed in the gland in scurvy and in acute infections occurring during infancy. Little is known of inflammations, degenerations, and necroses that occur in the thymus. That the body is subject to embolism is indicated by the occurrence of abscesses in pyemia, and some- times in septicemia. .In common with other tissues it is liable to invasion by mili- ary tubercles, and at times shows the caseous nodules of chronic tubercular infection. Gummata have been met with. Primary tumors of the thymus gland are rare. By reason of the presence of epithelium, carcinoma is probably the most fre- quent tumor; however, sarcoma of the round-cell type is seen. Lymphoid proliferation occurs in Hodgkin’s disease and leuke- mia. CHAPTER V. SEROUS MEMBRANES. The normal serous membrane is composed of a flattened layer of connective-tissue cells (endothelium) resting upon a sub- serous network of loose connective tissue in which ramify the blood-vessels, lymphatics, and nerves. The membrane produces no secretion, but is lubricated by a transudate of serum that probably passes out between the connective-tissue cells through the open mouths of the lymphatics; these openings constitute what are known as stomata of the serous membranes, and, by making the serous cavity continuous with the general lym- phatic circulation, render the view that these cavities are only immense lymph-spaces probably correct. The statement that the fluid normally present in the serous cavities is a transudate rather than a secretion is based upon the view that lymph is not a secretion; this matter has been already discussed, and need not be reviewed. (See Edema, p. 264.) The blood-vessels to the serous membranes are derived from those supplying the or- gans that the serous membrane covers; it is also probable that the lymphatic system of the serous membrane is intimately asso- ciated with that of the subserous tissues. These views, if correct, explain the inflammatory processes that occur on the serous surfaces as secondary to inflammations of the underlying organ: é.g., the pleurisy of fibrinous pneumonia. The serous cavities of the body are the peritoneum; the pleure, the pericardium, the serous covering of the brain and cord, the synovial structures of the joints and tendon sheaths, and the burse. When we examine one of these in its normal condition, we find that it is moist, smooth, shining, and transparent. The color is uniform with that of the tissue which it covers, and where two layers of the serous membrane have nothing between them but the fibrous or fibro-elastic network on which they rest, it may be practically true that the membrane is colorless. The normal serum of the cavity is a clear fluid, usually of a light straw- color ; it may, however, be stained by osmosed coloring-matter, as the coloring-matter of the blood, which may pass through the heart postmortem and stain the pericardial fluid. The amount of 470° SEROUS MEMBRANES. 471 fluid present in any given serous membrane {s dependent upon the amount in the connective tissues elsewhere, as well as the sur- face area of the membrane in question, and must, therefore, vary in quantity. Ifthe patient has died slowly, and a general lymph stasis has ensued from the gradual slowing of the circulation, more fluid will be found in the serous sacs than under conditions of rapid death. The amount of fluid that can be collected will approximate, in the peritoneum, from 8 to. 50 c.c.; in the pleura, from 30 to 100 c.c.; in the pericardium, from 4 to 30 c.c. If during life, for any reason, there is slowing of the circula- tion leaving a serous membrane on the organ which it incloses, there will be a disposition for fluid to accumulate in the serous cavity, just as obstruction to the onward flow of blood in any part of the body leads to the infiltration of the lymph-spaces with serum. (See Edema, p. 264.) Such an accumulation constitutes what is often spoken of as dropsy of a serous cavity. Ascites, or hydroperitoneum, from obstructive lesions in the liver is an ex- ample of this condition. The accumulation of fluid in the pleura (Aydrothorax) in pulmonary edema and general dropsy is a second instance ; similar conditions may cause hydropericardium. The accumulated fluids interfere mechanically with the function of the organs in the cavity at fault, and increase the venous congestion, which may have been the original cause. Accumulations of serum, without any evidence of inflamma- tion, occasionally occur in serous cavities where the membrane is infiltrated by miliary tubercles. The tubercles surrounding and obstructing the small vessels—arteriole, capillary, and vein—lead to extravasation exactly as would any other obstructive lesion. The process is most frequent in the peritoneum, where not un- commonly gallons of fluid may be, at different times, drawn off, only to reaccumulate, as in the ascites due to obstruction of the portal vein radicles in the liver. In addition to the dropsical conditions arising from chronic disease of the heart and of the kidneys, and the local obstruction to the circulation secondary to cirrhosis of the liver, chronic or persistent irritation of any kind affecting a serous membrane is likely to induce more or less serous accumulation within its cavity. Such persistent irritation is occasionally observed in the joints, giving rise to Aydrops arthrosis, sometimes called joint dropsy. The fluid present in dropsical conditions of serous membranes differs materially in composition from the inflammatory exudates. Its specific gravity is usually low—1io10 or lower. Asa rule, it is clear; occasionally, however, it may be cloudy. Cloudiness 472 SPECIAL PATHOLOGY. is more frequent in hydroperitoneum than in dropsies of other serous cavities. When the accumulation is due to obstruction of the lacteals, as it may be in the peritoneum, the milky opacity is to be attributed to the presence of fat globules. These are usually easily recognized under the microscope, and may be further identified by the usual tests for fat. (See p. 243.) It has been the custom to believe that the abundant presence of leukocytes arose only in connection with inflammation, but Polja- koff * has reported a case in which the milkiness of the transudate was apparently due entirely to the presence of white blood-cells. In Poljakoff’s case the low specific gravity (1009) favored the exclusion of inflammation. In true milky ascites the fluid, on standing, usually evinces partial separation into three layers: the uppermost layer is milky or cream-like, and contdins fat; the sediment is composed of leukocytes and cellular detritus, while the intervening layer may be quite clear. The order in which the serous cavities of the body are exam- ined is: (1) Peritoneum ; (2) pleura; (3) pericardium; and (4) the serous membranes covering the brain and cord. The pro- cesses in each of these, when affected by disease, vary so little— the variation depending not so much upon the membrane as upon the surrounding structures—that we may study in detail disease affecting one of the cavities and apply the knowledge thus acquired to any or all of the other serous membranes with but slight modification: ¢.g., the brain, being inclosed in a rigid covering (the skufl), will never be surrounded by the accumula- tions of fluid so constantly found in inflammations of the pleura. Remembering these variations in the process, as affecting different membranes, we will consider the most convenient serous mem- brane: namely, the pericardium. Malposition of the Pericardium.—Whatever malpositions affect the heart, the pericardium will accompany the heart in its abnormal place. As the development of the pericardium is de- pendent upon the development of the heart, the sac never occurs without its enveloped viscus. Malformation of the pericardium occurs but rarely, and usually consists of partial or complete absence of the membrane. Do not be misled by considering universally adherent pericardium as illustrative of absence of the organ. Normally, the phrenic nerves are widely separated by the pericardium, but in those cases of absence of the pericardium that have been reported the two nerves are almost side by side.’ This will, therefore, aid in dem- * «Berliner klin. Woch.,’’ 1900, No. 1, p. 9. SEROUS MEMBRANES. 473 onstrating that the pericardium was present at one time, and that inflammation sealed its walls together. Evidences of past in- flammation are usually to be found. Adhesions to the surround- ing structures, thickening of the adjacent pleura, and sometimes induration of the mediastinal tissues will offer further aid in recognizing the essential character of the process. Macule albidz, tendinous patches, or white or milk spots on the pericardium, are occasionally found, and are usually due to the heart thumping, at each pulsation, against some hard body, such as a prominent costal cartilage, or, more rarely, the vertebre. These spots are to be differentiated from the deeper lesions of fibroid change in the cardiac muscle by the former being thin, superficial, and not in the muscle, but on its surface. It is gen- erally admitted that the so-called milk spots do not have their origin in any acute inflammatory condition. Each spot is essentially a localized fibrosis, commonly restricted to the pericardium and sub- pericardial tissue, and rarely involving the myocardium. When the fibrosis extends into the muscle, it is usually only a very super- ficial invasion, although, in rare cases, local extension of the newly formed fibrous tissue into the cardiac wall may be observed. In such instances it is quite impossible to say that the condition did not first involve the muscle—an interstitial myocardial fibrosis. The spots are pure white, grayish-white, or even pearly in color; rarely, of a pinkish hue. Occasionally, a spot may be slightly calcareous. They are usually situated in the visceral pericardium near the base or exterior surface of the right ventricle or near the apex of the left. They are infrequent in childhood, and are more often present with advancing years. They are more frequent in males than in females. Enlarged hearts are more commonly affected ; particularly is this the case in hyper- trophy. Infiltrations.—Pigment is rarely found in the pericardium. Fatty infiltration is occasionally observed. Calcareous areas may be seen, particularly if the membrane has ever been the seat of inflammation. Sometimes in fibrous areas resulting from past pericardial inflammation extensive calcareous infiltration is found. At times this calcific deposit may be so great that one can but wonder how the heart has maintained its contractile power; the whole of the pericardium may show more or less calcareous infiltration, and at points the calcific layer may be five millimeters in thickness. Such extensive calcareous. infiltration is usually to be regarded as evidence of past inflammation, and it is doubtful whether calcification occurs in a serous membrane that has not been the seat of some inflammatory lesion. \ 474 SPECIAL PATHOLOGY. Degenerations.—Fatty, myxomatous, hyaline, and granular changes occur, but not frequently. Inflammation of the pericardium (pericarditis) is analo- gous to inflammation of the peritoneum ( ferdtonzts), inflammation of the pleura (p/ewrztzs, or pleurisy), inflammation of the men- inges (meningitis). Acute Pericarditis.—Clinically, pericarditis is said to be acute or chronic ; pathologically, it would probably be better to refer to it as simple and infective, the simple form being separable into the acute or chronic, the infective depending upon the character of the infection running a rapid or a prolonged course. As all the infections are not as yet fully worked out, the clinical classification must, at least for the present, be accepted. Inflammations of the serous membranes are said to be primary and secondary. The primary inflammations are sometimes called idiopathic, based upon the impossibility of definitely ascertaining the essential etiologic factor. Nearly all the inflammatory con- ditions affecting the serous membranes are secondary in point of origin, and therefore are practically always associated with some other morbid process. One of the most frequent causes of in- flammation of the serous surfaces is extension of the inflamma- tory process from adjacent structures. Of the many examples that might be given for this condition, the following should be mentioned: Meningitis secondary to disease of the ethmoid, sphenoid, and mastoid sinuses, and from diseases of the middle ear or cranial bones ; pericarditis secondary to pleurisy or medi- . astinitis or ulcerative lesions in the esophagus ; pleurisy second- ary to diseases of the underlying pulmonary tissue ; peritonitis resulting from. perforation of the intestine as well as from sup- purative, perforative, or gangrenous processes in the appendix ; and extension of infection from the pelvic viscera, particularly in the female. The circuitous route usually taken by suppurative and ulcerative processes occurring in organs adjacent to the dia- phragm may lead to unusual, or even extraordinary, combina- tions of pathologic conditions. Thus, a hepatic abscess may in- duce a peritonitis or pleurisy, or both, depending upon whether its extension is directed toward the diaphragm, through which it may perforate, extending even into the lung and discharging its contents through a bronchus. Gastric ulcer and carcinoma of the stomach may perforate the peritoneum, pleura, or peri- cardium. Inflammations of the serous membranes may also arise as a re- sult of specific agents circulating in the blood. Thus, we see in pyemia and septicemia inflammations involving the joints, peri- SEROUS MEMBRANES. 475 cardium, pleura, meninges, and peritoneum. Inflammations of serous membranes are sometimes said to be chemic or aseptic, in contradistinction to inflammatory conditions arising from demon- strable infection. Thus, it has been held that the inflammation of the joints and of the pericardium in rheumatism, for example, was due to the presence in the circulating blood of irritants probably the result of faulty metabolism. The trend of opinion at present seems to be toward the belief that rheumatism is a bacterial disease, and if such origin can be satisfactorily demonstrated, its time honored use as an example of a nonbac- terial cause of inflammation of serous membranes will not be justified, and the possibility of distinctly chemic or aseptic serous inflammation must appear less admissible. Of the various causes given for pericarditis, the following may be considered as important: Rheumatism probably leads the list. In about fifty per cent. of the cases there is a distinct rheumatic history. With the rheumatic cases are to be included pericardial inflammations attributed to cold and exposure, as it is found that these factors are often influential in determining the occurrence of pericardial inflammation in rheumatic patients. In from five to ten per cent. of the cases of chronic renal inflammation peri- carditis occurs. It is sometimes a part of uremia; at other times it precedes uremia, and in some cases it occurs without other uremic phenomena. Blows over the pericardium, crushing of the chest-wall, penetrating wounds, fracture of the costal carti- lages, and other forms of thoracic injury may cause inflamma- tion. Pericarditis resulting from extension of inflammation from adjacent structures has been considered. Myocarditis, particu- larly of the acute suppurative form, is usually associated with a certain amount of pericardial inflammation, although the latter may be absent. Aneurysm of the heart or of the aorta—the latter presenting in the pericardial cavity—may be associated with pericarditis. Malignant growths and chronic infectious processes attacking the pericardium usually induce inflammation. In mycoses of the blood the serous membranes rarely escape, the pericardium par- ticipating in the general infectious process. Pericarditis is occa- sionally seen in diphtheria, measles, and smallpox, and is not an infrequent complication in erysipelas. Gout and diabetes are present in a small percentage of the cases. Of the many bacteria influential in the production of pericar- dial inflammation, streptococci, staphylococci, and the pneumo- coccus deserve special mention. The tubercle bacillus is usually present in pericardial inflammation secondary to tuberculosis of 476 SPECIAL PATHOLOGY. the lung or pleura ; but as pulmonary tuberculosis is often accom- panied by a mixed infection, it is possible to have an associated pericarditis not of itself due directly to the tubercle bacillus. The bacillus coli communis may be found in pericardial inflammations, alone or with the typhoid bacillus, and is not infrequent in inflam- mations of the pleura ; it is a frequent cause of peritoneal inflam- mation. Inflammations of the endocardium and of the peritoneum may be due to the gonococcus; it is not improbable that with more general infection the pericardium and pleura might suffer. Of the less common organisms, the bacillus pyogenes fcetidus, the bacillus pyocyaneus, and the bacillus aerogenes capsulatus may be mentioned as causes. Morbid Anatomy.—In the first stage the membrane is dry, red and injected, slightly opaque, and much roughened. It may be sticky, and it always presents, over the inflamed area, a dull or velvety surface, in contrast to the shining luster of the normal. Histologically, at this stage the subserous capillaries are dis- tended with blood. The areas of capillary hyperemia are scat- tered over the membrane irregularly, and look as though a smear of carmin stain had been daubed over the surface at irreg- ular intervals ; the diffuse character of the discoloration has been likened to a blush; rarely, if ever, is the hyperemic capillary dis- tention universal. The morbid physiology is shown in the friction sounds discernible on auscultation, and due to the roughened and dry surfaces rubbing against each other; the pain of this stage is probably due to direct or mechanical irritation of nerve fila- ments, and partly to the irritation of the nerves by the applica- tion of the chemic bodies engendered by the changes in cell metabolism ; it seems not improbable that the fever of this stage is due to the same bodies entering the circulation by resorp- tion. The second stage is brought about by the blood-vessels relieving themselves of those materials that ordinarily escape in any inflammatory process. The liquor sanguinis escapes from the distended capillaries, and passing through the stomata of the serous surface, reaches the cavity. Immediately upon reaching the surface of the membrane it splits into fibrin and serum, the former coating the surface of the serous membrane, the latter finding room in the cavity. With the transudation or escape of the liquor sanguinis the leukocytes pass by diapedesis directly into the fibrinous and serous exudate. It is also probable that the flattened connective-tissue cells are to some degree detached. Should the exudate be slight, and should the serum be rapidly absorbed, but little remaining in the cavity, clinically, the inflam- SEROUS MEMBRANES, 477 mation is spoken of as plastic or fibrinous ; if, however, the exudate Fic. 246.—HEART SHOWING VILLOUS PERICARDITIS ; ASCENDING AND TRANSVERSE PORTION oF ARCH OF AORTA, SHOWING ANEURYSM WITH CONTAINED CLOT, AND RUPTURES INTO PULMONARY ARTERY AND PERICARDIUM. A. Part of the parietal pericardium, showing the fibrinous deposit and minute villi. A simi- lar appearance is present on the visceral pericardium. &. Innominate artery. C. Left common carotid. D. Left subclavian. £. Catheter passing through the clot in the aneu- rysm of the aorta and into the pulmonary artery, following the course of the rupture into the last-named vessel. /. Continuation of the same catheter into the right ventricle through the orifice of the pulmonary artery. A section was cut out of the catheter in order to show position of aortic cusps. G. Catheter parse from the aneurysmal cavity through the thrombus and pericardium and entering the pericardial cavity into which the aneurysm ruptured. There were clinical and pathologic reasons for believing that the rupture into the pulmonary artery was old—probably several weeks. The rupture into the pericardial cavity was recent, and had been the immediate cause of death. WA. Inferior thyroid artery. /. Wall of aneurysm. /. Laminated thrombus, through the center of which the circulation had been maintained. Above the leader from the letter_7 are shown four slit-like areas that contained dark clots of blood (red thrombi). The remainder of the thrombus was white. be abundant and the serum be not taken up, the process is spoken of as serofibrinous. If the first stage be called the stage of 47 8 SPECIAL PATHOLOGY. engorgement or hyperemia, the appearance of the exudate initiates the stage of exudation. In this stage the membrane will be found either partly or com- pletely covered with fibrin, the degree of cohesion being depen- dent upon the thickness of the layer and upon its age, as will be evident further on. The serum in the serous sac differs from the normal in that it is opaque and contains flocculi of fibrin, the opacity being due in part to the fibrin, but largely to the abundant presence of leukocytes. The soft, downy mass of fibrin hanging in shreds has led to the heart at this stage being called the cor villosum, it is also known as the cor iursutum. (See Fig. 246.) Laennec compared the appearance to that resulting from the separation of two smooth surfaces of wood between which had been pressed a pat of butter, and hence the term “ bread-and-butter appearance.” The thick, shaggy layer may remain adherent to the membrane, or the fibrin may be whipped off to a greater or lesser degree by the movements of the inclosed organ. The color varies. Commonly, the inflammatory exudate is white or yellowish-white ; sometimes, however, it is brown, yellowish-brown, or even brownish-red. These modifications in color are due to the dissolution of hemal elements in the exudate. In the earlier stages the exudate may be readily stripped from the serous surface, and may even show lamination, as though suc- cessive layers had been thrown out, the lowermost and overlying layers being pushed upward by the succeeding layer. The amount of serum present in the cavity determines whether inflammation should be called in this stage dry or moist. Where absorption has been rapid and the serum has thereby been removed as rapidly as formed, or nearly so, the pericarditis is said to be dry, plastic, or fibrinous. On the other hand, the amount of accumulated serum may be from 100 to 200 c.c.; rarely as much as a liter, and: occasionally more. The morbid histology of this stage will be found to be a reduc- tion in the size, and a less crowded condition, of the subserous capillaries, they having been largely relieved by the outpouring of those materials that have gone to form the exudate. The layer of fibrin, on section and in teasings, will show the abundant presence of leukocytes and a few red cells, while the endothelial cells will be seen to be desquamating, the process at points being laminated, masses of these elements being discernible far up.in the fibrinous layer. The morbid physiology of this stage is shown in the resistance offered to the functional activity of the encumbered viscus. If an abundant exudate be present, pressure will influence the action SEROUS MEMBRANES. 479 of the environed organ and will mechanically impede its function. Friction sounds disappear if the exudate be sufficient to force the two layers apart and the fibrin covers the roughened serous sur- faces. The fever may be kept up by the absorption of the meta- bolic products ; these also induce, not uncommonly, phenomena not usually due to pyrexia alone: ¢. g., suppression of excretion and nervous symptoms. The fibrinous exudate may so conceal and obstruct access to the lymphatic and vascular exits as to pre- clude absorption of the serum or its pyrogenous constituents, and hence no systemic phenomena due to their absorption may be manifest. When percussion and auscultation can be brought into play, the phenomena associated with the presence of solid or liquid materials may be found: ¢. ¢., dullness. Exactly how long these two stages may last can not even be inferred ; their duration varies, the conditions inducing the varia- tion being but indifferently understood ; thé cause, the severity of the attack, the condition of the patient, whether weak or strong, are undoubted determining factors. The stages may be prolonged or brief, and just what determines this can not always be definitely stated ; sooner or later, if the patient survives, repair proceeds as follows : In this stage the connective-tissue cells, and possibly the leuko- cytes, present in the wall of fibrin proliferate and convert the layer into embryonic tissue ; young blood-vessels are developed from the subserous layers, and lymphatic connection is reestab- lished. The facility with which young blood-vessels shoot up into the new tissue is marvelous, and to the rapidity with which this process of organization develops, modern surgery owes many of its great achievements. The proliferated leukocytes and young connective-tissue cells, the progeny of the endothelial lining, constitute a small, round-cell mass known as embryonic tissue ; when the young blood-vessels permeate this structure,—in other words, when it becomes vascularized,—it is known as granula- tion tissue. The next step is the organization of this into fibrous connective tissue, which, becoming smoothed, gives a surface functionally normal; but as all organizing tissue manifests a ten- dency to contract, grave results may ensue in the structures beneath. Following meningeal inflammation, pressure upon nerves leaving the brain may, by constriction, lead to degenera- tion and entire loss of conducting power (paralyses), blindness or deafness being thereby produced. Over the lung the con- traction may preclude reexpansion and favor the continued pres- ence of the serous exudate. A band around the intestine may cause narrowing, and eventually obstruction. In the pericar- 480 SPECIAL PATHOLOGY. dium, however, it is not believed that the contraction does suffi- cient harm to merit consideration. Adhesions between two layers of a serous membrane—z. g., the pericardium—are brought about by the two fibrinous surfaces coming together at any stage of the inflammation before organi- zation is well under way. In the recent state the fibrinous layer of one side will adhere to its duplicate if they come in contact, e x aket py “td ee a 4 : . Ag A a NS OE Geel £PRO Fic. 247.— VERTICAL SECTION THROUGH AN INFLAMED SEROUS MEMBRANE AFTER THE FORMATION OF THE FIBRINOUS EXUDATE.—(Schmaus.) X 250 diameters. a, Subpericardial fat. 4. Swollen membrane, the surface of which is contiguous to and blends with the overlying fibrinous deposit c. c. Layer of fibrin in which are numerous leuko- cytes, d, and into which, at e, are developing blood-vessels. and it is not improbable that in the embryonic tissue stage of the inflammation, or even when vascularization is well advanced, cohesion of the two surfaces, followed by an organized adhe- sion, is possible ; after agglutination of the surfaces, the young blood-vessels anastomose and pass from one side to the other, organization into fibrous tissue ensues, following the lines already SEROUS MEMBRANES. 481 indicated, and an adhesion is the result.* The constant movement of the heart probably precludes the general union of the peri- cardial layers at a single attack, but in the pleura it is not im- probable that the entire sac may be obliterated by a single inflam- matory attack. Whether adhesions form or not, the serous membrane remains permanently thickened. Into this new tissue lime salts or fat may be deposited. In the former instance the con- dition is known as calcification ; in the latter, as fatty infiltration. An opportunity to study the formation of adhesions is afforded in almost all surgical operations upon serous surfaces. A wound of the intestine has the two serous surfaces brought together by sutures ; along the line of contact an exudation of liquor sanguinis and the migration of leukocytes occur; the former breaks up into fibrin and serum, the fibrin forming a temporary cement and binding the two apposed surfaces together ; embryonic tissue is formed, followed by granulation tissue, and later by a cicatrix that binds the surfaces together along ‘the line of suture. This cicatrix is an adhesion, the histology and mode of development of which are practically identical with the formation of adhesions in pericarditis, pleurisy, inflammations of tendon sheaths, etc. The closing or obliteration of the sac of hydrocele is brought about by inducing an inflammation of the serous membrane and favoring adhesion of the walls by withdrawal of the contents, thereby per- mitting collapse. The surgeon withdraws the contents and brings about an inflammation of the lining membrane by gently scratch- ing the serous surface or by injecting an irritant, such as iodin. There is redness (hyperemia), followed by the development of a fibrinous exudate with agglutination of the collapsed walls ; pro- liferation of the connective-tissue cells leads to repair, just as indi- cated in the foregoing description of adhesion formation. In this case adhesions are expected, and, as in the union of two serous surfaces when sutured, the success of the operation depends upon the development of new fibrous tissue through which union is secured. Suppurative pericarditis results from the infection of the serous membrane by pyogenic bacteria. Whether these were. present from the beginning, as after a wound of the pericardium, or whether infection followed the initial processes, matters but little. The peptonizing influence of the organisms manifests itself as soon as the development of embryonic tissue occurs ; this is liquefied as rapidly as produced, and pus is thereby engen- dered. Vascularization is impossible while the process of lique- * See p. 470; also compare with union by first intention, p. 298. 31 48 2 SPECIAL PATHOLOGY. faction is going on, and the protracted character of the pro- cess has given the infected membrane a name descriptive of its pus-producing faculty it being known as a pyogenic mem- brane. Structurally, such a membrane is composed of cellular elements not unlike those found in. the wall of an abscess (p. 291); later, the free surface continues to be rich in leuko- cytes, and therefore largely cellular. Within this cellular accumu- lation the conflict between the bacteria and the cells will continue, as manifested by the associated phagocytosis, necrosis, and pus- formation. Below this wall there is sooner or later developed a layer of fibrous tissue. As this fibrous tissue, in conjunction with its overlying cellular layer, presents a certain resistance to the further invasion of the underlying structures by the bacteria, Park has proposed the name prophylactic membrane. The thick- ening may exceed one centimeter; the membrane is usually tough, the surface being soft and downy and bleeding upon the slightest injury. The deeper layer not infrequently contains cal- careous material. In the suppurative inflammation of serous membranes the fever-producing element present in the noninfec- tive forms has its activity augmented by the addition of the py- rogenous products of bacterial life. (See p. 385.) The accumu- lation of pus in the pleura constitutes what is kown as empyema or pyothorax ; in the pericardium, pyopericardium ; in the perito- neum, pyoperitoneum, peritoneal abscess, suppurative peritonitis, etc. Inflammation of the serous membrane is sometimes accompa- nied by a hemorrhagic exudate ; at such time the term hemor- rhagic inflammation is used. It occurs most commonly in connection with debilitating conditions, such as tuberculosis, asthenic states, cancer of the serous membrane, and, rarely, with- out any apparent cause. Trauma may lead to hemorrhage in the exudate. Tapping may rupture some of the delicate vessels of an organizing exudate, or the withdrawal of the serous exudate may remove the support to the delicate newly formed capillaries, which rupture, and thereby give rise to blood in the fluid. The hemorrhagic phenomenon may show in the serum, or it may exist as petechiz or areas of subserous rhexis. The hemor- rhagic inflammations are most frequent in childhood, although not unknown at any age. The pleura is oftenest affected. The frequency of the hemorrhagic form of pleurisy is variously given by different writers : Lewin found the effusion hemorrhagic in 4 out of 50 cases; Reimer, five times in 121 autopsies ; and Israel,* twice in 206. * “ Jahrbuch fiir Kinderheilkunde,’’ Bd. xLv, 1898, No. 16. SEROUS MEMBRANES, 48 3 Inflammations of the serous membranes are spoken of as localized or circumscribed when only a part of the serous surface is affected ;.as general or diffused when the process invades an entire membrane. Localized peritonitis ig common ; localized pericarditis probably never occurs. Diaphragmatic pleuritis is a localized inflammation of the pleura at the base. When the localized process is accompanied by the development of a walled- off accumulation of fluid, the inflammation is said to be encysted ; rarely, such inclosed masses, when they contain pus, are referred to as’abscesses : ¢. g., of the pleura or peritoneum. They are not really abscesses, but purulent accumulations in existing cavities. Chronic pericarditis consists in the presence of the results of the acute form, and is known as adhesive or adherent peri- cardium. The condition present may be that of: (1) Partial or complete adhesion ; (2) large masses of fibrin whipped off in the serum may not have undergone absorption, but may remain as caseous or semisolid collections too large to be vascularized ; (3) caseous areas resulting from the absorption of the fluid por- tion of a past pus collection or from tuberculosis of the membrane ; (4) calcareous masses in the newly formed inflammatory tissues. When these forms exist, the only morbid physiology that is likely to be present will be increased work for the heart. Tubercular inflammation of the pericardium or other serous membrane may exist in two forms—acute and chronic. The source of the infection is usually tuberculosis of some organ or tissue adjacent, as mediastinal tuberculosis and tuberculosis of the lungs, acting as causes of tubercular pericarditis and pleurisy respectively. Tuberculosis of the middle or internal ear may cause tubercular meningitis. Tuberculosis of the alimentary canal or mesenteric lymph-glands may be followed by tuberculosis of the peritoneum. Again, tuberculosis of one or, it may be, two or more serous membranes may occur as a part of an out- break of acute disseminated miliary tuberculosis. (See p. 371.) In acute tuberculosis of a serous membrane the phenomena described when considering acute simple pericarditis will usually be found present ; fibrin and serum will be found, as in the acute inflamma- tions already described, and only after the most careful search may the tubercular origin of the process be demonstrable. Tubercle bacilli are rarely demonstrable in the serum, but may occasionally be found in the fibrin layer; at times distinct miliary tubercles may be found in the new tissue or in the membrane beneath ; when, however, miliary tuberculosis exists in a serous membrane, sections, or occasionally stripping, will usually show the presence of the tubercles. 484 SPECIAL PATHOLOGY. Actinomyces, glanders, and other bacterial chronic infections may occur. Air in serous cavities is always regarded as a dangerous occur- rence, and gas or air in the sac of the peritoneum has long been recognized as a certain precursor of suppurative processes. The reason is apparent : all sources of air ingress give rise to infection, the import of which need not be explained. The presence of air or other gases in the pericardium (pneu- mopericardium) results from one of three causes: (1) Injury . (50 per cent. of the cases); this includes wounds of the chest- wall or esophagus, thereby assuring the direct entrance of air. ¥ AE Fic. 248.—ACUTE TUBERCULAR PERICARDITIS, VERTICAL SECTION OF INFLAMMATORY Ex- UDATE.—(Schmaus.) X 250 diameters. a. Subpericardial fat. 6, Layer of granulation tissue that extends to the layer of fibrin, d. c,c. Tubercles containing giant-cells. Other tubercles are shown, in some of which de- generative changes are beginning to evince themselves. (2) Penetration of the pericardium by ulcerative or necrotic pro- cesses originating in or invading an adjacent gas-containing vis- cus. With this class of cases would be included the pneumoperi- cardiums resulting from tuberculosis or other lesions in the lung, as well as like extension from the esophagus; ulcerative pro- cesses in the stomach, and possibly in other intra-abdominal vis- cera, may also reach the pericardial cavity. (3) Infections of the pericardium by gas-producing bacteria. The demonstration of this source of gas in the serous cavities is now complete ; the organisms found in this condition are the bacillus coli and the bacillus capsulatus aerogenes of Welch. As further proof of SEROUS MEMBRANES. 485 micro-organismal gas-production in the serous cavities during life, if such be needed, is the occurrence in these infections of inflammable gases containing hydrogen, and therefore not derived from inspired air.* In the large majority of cases in which air is found in the peri- cardium it entered postmortem ; in raising the sternum, the least puncture, so smallas to escape recognition, may permit air to enter the pericardium. By remembering this possibility, one is not likely to be misled. Blood in the pericardium (hemopericardium) may follow rupture of the heart or the first part of the aorta, aneurysm, can- cer of the pericardium, rupture of the pulmonary artery or veins, or atrauma that injures or lacerates the parietal pericardium. The quantity may be slight or excessive. In scurvy, pernicious anemia, blood mycoses, purpura, phos- phorus-poisoning, leukemia, and allied conditions, the serous membranes may be studded by pinhead-like dots of subserous hemorrhage—petechiz. Hydropericardium may accompany dropsy from any cause. (See Dropsy of Serous Cavities, p. 471.) Tumors of the serous membranes may be primary or second- ary. The primary tumors must, of necessity, be of the con- nective-tissue series, and nearly all the members of this group have been found in the serous cavities and springing from the serous membranes. For some reason not known, the omen- tum seems to be the most common seat of this class of the nonmalignant.or adult-tissue type of the connective-tissue series : myxoma, lipoma, fibroma, chondroma, and even osteoma may occur. The embryonic connective-tissue tumors—sarcomata— are not infrequent in the serous membranes. Quite a number of sarcomata of the omentum and mesentery have come to the author's notice. Endotheliomata may arise from any serous membrane, but are most frequent in the pleura, pericardium, and meninges. The cancers or carcinomata are always secondary, as they never rise in a pure connective tissue. The carcinomata of the uterus and alimentary canal not uncommonly invade the peri- toneum, multiple nodules of secondary cancer developing on the serous surface. Cancer of the esophagus, stomach, or medias- tinal glands may invade the pericardium direct or by metastasis. Of the cysts, dermoid may occur in the cavity of the pelvis. Purely serous cysts have been noticed, but their pathologic sig- * For further reference see ‘‘ Deutsch. Arch. fiir klin. Med.,’’? Bd. Lx1, p. 532; «6 Wien. klin. Woch.,’’ Feb. 16, 1899; ‘‘ Phila. Month. Med. Jour.,’’ Oct., 1899. 486 SPECIAL PATHOLOGY. nificance has not been definitely determined. ematomata in the serous Cavities are of not infrequent occurrence, especially in the peritoneum. The blood mass may be absorbed or it may be walled in by inflammation or a laminated circumferential clot ; occasionally it may become infected. In the first instance but little evidence of its presence may in time remain. At other times absorption may be accompanied by clotting and organization of the fibrin, leaving a permanent tumor. The laminated circum- ferential clot may organize and inclose a cyst containing the more or less disintegrated blood. Parasites in the Serous Cavities.—4chinococcus or hydatid disease has been observed in all the serous cavities. Cysticerci are at times met with in serous cavities, but give rise, in most cases, to no discernible disturbance. 7richinge may be found in experimental /vzchznoszs in the serous cavity, but the author has no knowledge of their occurring in the ordinary form of the disease. They probably never induce any disturbance of the serous mem- brane. Grosser parasites, such as round-worms, have been found in the peritoneal cavity associated with a fulminating inflammation, suppurative in character, infection having occurred as the result of the opening in the intestinal wall that permitted the escape of the worm. CHAPTER VI. VASCULAR SYSTEM. HEART.* Normal Structure.—The heart is essentially a hollow mus- cle divided by partitions into two distinct sides, not communica- ting with each other ; each side is further divided by a perforated septum into two cavities, known respectively as an auricle and a ventricle. The opening through which the auricle communicates with the ventricle on each side is known as the auriculoventric- ular opening or orifice, and is guarded by valves that open toward the ventricle ; on the right side the valve is known as the tricuspid, on the left, as the mitral. The right ventricle commu- nicates with the pulmonary artery and the left ventricle with the aorta, the two orifices being guarded by valves opening toward the vessels. These valves are each composed of three cusps, crescentic or semilunar in outline, and known as the semilunar valves of the pulmonary artery and of the aorta respectively. The exterior of the heart is covered by the pericardium, to which reference has already been made (serous membranes) ; the interior is lined by a flattened layer of connective-tissue cells (endocar- dium) applied almost directly to the cardiac fiber, with but little, if any, loose connective tissue intervening ; the valves are composed of two layers of the endocardium, reinforced by fibrous tissue, in which are a few elastic fibers. The valves of the right side, having less work than those of the left, are much the thinner, containing relatively less fibrous tissue. The endocardium, including most of the tissue that enters into the formation of the valves, is nonvascular, probably receiving its nutrition from the blood flowing over it. The cardiac muscle is of the striped variety, but differs from voluntary striped muscle; the fibers have no sarcolemma, and they inosculate by branched filaments, passing from one fiber to another; there is no bundling of the fibers, and the individual fibers are smaller than those of the purely voluntary muscle. Size of Normal Heart.—The heart is about the size of the fist * For method of removing the heart and completing its dissection see p. 28. 487 488 SPECIAL PATHOLOGY. of the individual ; its weight in the male varies between 285 gm, and 450 gm. (10 and 16 ounces), with a mean between 340 gm. and 375 gm. (12 and 13 ounces). The heart of the adult female weighs between 200 gm. and 400 gm. (7 and 15% ounces) ; mean, between 285 gm. and 300 gm. (10 and II ounces). The taller the individual, the heavier the heart. The left ventricular wall is about 1.25 cm. (1% of an inch) in thickness, the right about 0.4 cm. (1% of an inch). The ventricular wall is thickest at its middle and thinnest at the apex. DIAMETERS OF CARDIAC ORIFICES.—( After Hamilton.) Male. Female. Greatest. Least. Average. Greatest. Least. Average. Inch Inch Inch Inch Inch Inch Aortic, ess RS 0.9 1.0 1.0 0.8 0.9 Mitral, . 1.8 I. 1.4 1.5 1.0 1.2 Pulmonary Artery, . 1.5 1.0 1.2 1:3 1.0 II Tricuspid, st a BB 1.3 1.8 1.7 1.4 1.5 The taller the subject, the larger the orifices. MALPOSITION OF THE HEART. (A) CONGENITAL. 1. Cervical Heart.—Heart in the neck; the condition may be complete or partial, and is more frequent in the lower animals than in man. 2. Abdominal Heart.—Through faulty development of the diaphragm the heart may sink into the abdominal cavity ; occa- sionally, the diaphragm does not develop immediately under the pericardium, and where the heart can not sink through the open- ing, an abdominal viscus may partly pass through into the peri- cardium, as a result of the difference between the pressure within the two cavities. 3. Pectoral Heart.—The heart may be developed anterior to the chest-wall ; the wall may be absent, or it may have developed behind the misplaced heart ; in rare instances there may be no pericardium, and less frequently the heart may be extracorporeal, —i. ¢., outside the body,—the integument having partly closed behind it. Such conditions are not compatible with life, and are usually associated with fissural malformation of the thoracic and abdominal walls. 4. Dexiocardia.—A heart on the right side is compatible with life, and is recognized by insurance companies as not in any VASCULAR SYSTEM. 489 way, of necessity, increasing the risk. Vehsemeyer states that but twenty cases of true dexiocardia have been reported up to March 18, 1897.* It is usually associated with transposition of the abdominal viscera, the liver going to the left side, etc., the combination of transposed organs being known as the situs inver- SUS. Any one of these malpositions may be partial or complete, no two cases being equally marked. (B) ACQUIRED MALPOSITION. The heart may be displaced by pressure applied by neighbor- ing or adjacent organs: ¢. g., by hydrothorax pushing the organ toward the unaffected side; under this head come the malposi- tions due to,aneurysm and mediastinal disease. Emphysema of both sides pushes the heart downward ; emphysema of one side displaces the heart to the opposite side. Pleurisy, with contraction or a contracting fibroid pneumonia, may pull the heart toward the affected side. Hypertrophied hearts have their axes more nearly parallel with the axis of the body and nearer the median line. MALFORMATION OF THE HEART. 1. Walls, including the septa: (a) Single cavity. (2) Arrest of cardiac development with a single auricle and a single ventricle, a condition permanent in the chelonia and scaly reptiles. (c) Single auricle with perforate septum between the ven- tricles. (zd) Single auricle with normal ventricles or a patent foramen ovale, an attempt at closure of the septum between the auricles. 2. Blood-vessels. As in intra-uterine life the vessels are developed from five branchial arches, it is possible to have innumerable malforma- tions of the great vascular trunks. The following are most frequent : (a) Patent septum between the pulmonary artery and aorta, a condition permanent in the crocodile. The fact that the aorta and pulmonary artery develop from a single trunk renders the condition possible. * <‘ Deutsch. med. Woch.,’” March 18, 1897. 490 . SPECIAL PATHOLOGY. (6) Transposition of the vascular trunks, the pulmonary artery arising from the left heart and the aorta from the right. (c) Double Aorta——In development there are two primitive aortas, a right and a left; ordinarily the right disappears, but it may not do so. (d) Patulous Ductus Arteriosus—When a stenosis of the pul- monary artery develops before occlusion of the ductus arteriosus, the communication between the aorta and pulmonary artery may remain permanent. There is little difference between this and a, except the location, the latter being immediately at the heart. (e) Stenosis of the pulmonary artery is probably the most fre- quent cardiac abnormality, excepting, of course, patulous foramen ovale. The degree of stenosis varies, and may be situated: im- mediately at the valvular orifice or slightly beyond this point, or may be manifest in the trunk some distance from the orifice. Occasionally, stenosis is manifested in the conus arteriosus. Stenosis may involve the aorta. (f ) Atresia of the pulmonary artery or of the aofta is possible only with persistent communication between the two vessels beyond the point of occlusion. 3. Valves.—These being developed from the endocardium, may be in excess as to number of leaflets, or the reverse; a leaflet may be redundant or deficient. Care must be taken not to confuse the results of antenatal endocardial disease with mal- formations. : Hypoplasia of the heart occurs. The organ is small,—may be less than one-half the normal size and weight,—and_ usually has proportionately small vessels. The vessels may be hypo- plastic without the heart showing marked abnormality. The organ may be absent. Causes —Malformation of the heart is dependent upon arrest or perversion of development. The stage in its evolution at which this occurs largely determines the character of the mal- formation. When cardiac development is arrested early, the organ shows the widest deviations from the normal. When it is delayed until later in intra-uterine life, or when the usual cir- culatory changes at birth fail to take their normal course, mal- formation is usually not marked, and commonly gives rise to no phenomena leading to a suspicion of its presence later in life. Aside from arrest of development as a cause of cardiac mal- formation, there can be no doubt that antenatal endocarditis may give rise to changes in the valve leaflets or in the orifices closely allied to those seen as a result of postnatal endocardial in- flammation. : VASCULAR SYSTEM. 49I Course and Termination— Aside from those malformations which mechanically preclude the possibility of postnatal circu- lation, almost no cardiac deformity has been described that may not be compatible with a more or less prolonged extra-uterine existence. The accompanying lesions and associated phenomena are due to circulatory inefficiency, as manifested by tendency toward stagnation and the occurrence of faulty aeration. The mere mixing of arterial and venous blood may be unassociated with symptoms or alterations in other organs or tissues. If the blood can be kept circulating with sufficient activity to secure aeration and to prevent venous distention, the patient may escape any manifestation of the condition. The clubbing of the digits, cyanosis (morbus cceruleus), thick lips, and stubby nose with thickened ala, may all be taken as evidences of disturbance of nutrition. The polycythemia may be truly remarkable, as in the case reported by Baunholtzer: pulmonary stenosis was present, and the blood examination showed 9,447,000 erythrocytes and 160 per cent. hemoglobin. The relatively high specific gravity of the new-born (1060 to 1070) often persists. General atrophy of the heart occurs as the result of general wasting, with or without lessened work, the organ being very much decreased in size and weight. A specimen in the writer’s laboratory weighs less than three ounces. The condition can usually be differentiated from hypoplasia by the fact that the blood-vessels remain approximately normal in size, while the cor- rugations of the pericardium and endocardium indicate the dimi- nution in volume. Local atrophy of the heart occurs in the left ventricle, and is probably a result of disuse. A stenotic mitral orifice permits but little blood to flow into the left ventricle and gives it but little work. The nutrition is also in most cases below the normal. The condition is usually accompanied by an unusual dilatation of the right side, which may also show hypertrophy. Wasting of the left ventricular wall, under the foregoing circumstances, is comparable to the hypoplasia observed in the left ventricle as a result of atresia of the aorta, or of the right ventricle when the pulmonary artery is similarly affected, in both cases the auricular septum being patulous or absent. Brown atrophy of the heart is due to persistent congestion of the muscle, and is associated with old age, inanition, and allied conditions. The organ is of a dark chocolate or maroon color, hard and tough, diminished in size and weight, with tortuous vessels and wrinkled endocardium, due to diminution in surface. Hematoidin or hemofuchsin is deposited in the muscle-cell as a 492 SPECIAL PATHOLOGY. granular pigment, near the ends of the nucleus (polar pigmen- tation); the fiber is shrunken, and there is also, probably, a numeric decrease. The muscle-fibers may waste to the point of disappearance. The fibrous tissue may be notably increased, and occasionally distinct areas of induration may be observed. (See Chronic Myocarditis.) Hypertrophy will be considered after valvular disease. (See p. 512.) Fatty infiltration of the heart occurs in general obesity ; after the permanent changes incident to pericarditis ; in chronic alcoholism ; occasionally, in the aged and the insane. There is enormous increase in the subpericardial fat; fat-cells infiltrate between the muscle-fibers, and probably incommode their action. Some believe that atrophy of the fiber may be induced; during the early stage of the process this is not probable, as the fibers in the mass are, usually, histologically normal. The condition is sometimes spoken of as Zpomatosis of the heart. It should not be forgotten that this condition constitutes a most frequent cause of sudden death, the overcrowded muscle-fibers failing to contract, or the fat, having penetrated between the muscle-fibers, may have weakened the interlacing network and led to rupture. The columns of fat may extend through the cardiac wall. A marked ‘overgrowth of the fat, and persistence of the causes that lead to its accumulation, not infrequently terminate in an associated degenerative change in the muscle-fibers. Lardaceous Disease.—Albuminoid or amyloid infiltration of the heart may occur in the blood-vessels of the heart and in the myocardium. The heart is undernourished and anemic; milky opacity of the endocardium of the right auricle is usually the most common macroscopic phenomenon, although any of the cavities may exhibit the change. It responds to the usual stains, but can rarely be detected except by the microscope. Asa rule, the alterations in the muscle-fiber are inconspicuous, the amyloid deposit being restricted to the blood-vessels and the connective tissue between the fibers. Calcareous infiltration of the heart may occur around the auriculoventricular orifice, usually of the left side, in the valves, in the heart muscle, and under the pericardium. If any of these structures have been inflamed, infiltration of the inflammatory products with lime salts is likely to ensue. Deposit of lime salts is not infrequent in areas of myocardial sclerosis and in old in- farcts and other necrotic areas. It is also a frequent occurrence in connection with tuberculous and syphilitic lesions of the myo- cardium. VASCULAR SYSTEM. 493 Pigmentary Infiltration of the Heart.—By some, brown atrophy is considered as a form of infiltration and is described under this title. Granular degeneration of the heart, or cloudy swelling, is probably an initial stage in a form of fatty degeneration. (See Fig. 181, p. 242.) It occurs in infectious processes, such as septicemia, erysipelas, diphtheria, scarlet fever, and typhoid fever ; in hyperpyrexia, as that of thermic fever; and in exhausting diseases generally, such as pernicious anemia. It may be associ- ated with pericarditis or endocarditis, either as a result of the inflammation or dependent upon the same cause. The heart muscle is softer than normal, is slightly edematous to the touch, and is grayish and cloudy, in striking contrast to the bright red of the normal. Rigor mortis is absent in advanced cases. The muscle-cells are more or less loaded with granular debris, albumi- noid and not fatty, at this stage, as is shown by the granules clearing up when treated with acetic acid, and not being soluble in alcohol or ether. (See p. 241.) Fatty degeneration of the heart occurs: (1) As a general process invading the whole heart or the whole of one ventricle ; (2) secondary to some local lesion, and restricted to a small area ; (3) due to poisons, as phosphorus. I. Diffuse or General Fatty Degeneration of the Heart.—This form arises from the same causes as, and is probably merely a later stage of, granular degeneration. The papillary muscles and columnz carnez of the left ventricle show the change to the best advantage ; they are light brown in color, and running across them are yellow striz, giving them a brindled, streaked, or flecked appearance—‘‘ tabby-cat”’ or “tiger”? heart; at times the mus- cle is pale yellow rather than brown, at other times brownish- yellow—the ‘‘faded-leaf’’ color; in the cut wall the fiber lines just below the pericardium are lost, and the tissue appears, as a rule, uniformly yellow. Looking through the pericardium, or, better, the endocardium, the muscle shows yellow and red striz, the latter being the unaffected fibers. The process is diffuse but not universal, comparatively normal fibers lying next to more or less altered ones. The cardiac wall may be thinned as a result of dilatation, and the orifices may be dilated. The specific gravity of the muscle is lessened. The myocardium can usually be readily pinched through. Microscopic or even macroscopic hemorrhages into the heart-wall may be present. Under the microscope the affected fibers are loaded with minute oil globules not larger than a red corpuscle. They differ from granular fibers in that the fat 494 SPECIAL PATHOLOGY. is darkened by osmic acid, and may be dissolved in ether. (See Demonstration of Fat, p. 243.) r The termination of the granular and fatty metamorphoses is likely to be the same: (@) sudden syncope and death from failure to contract ; (4) gradual failure by reason of increasing incom- petency to maintain the circulation. Rupture of the heart is not common in diffuse or general fatty degeneration of the organ, as the cardiac muscle has not the power so to raise the intracardiac pressure as to endanger the weakened walls. It is probable that, in the granular stage, regeneration and recovery may ensue; this becomes less likely as the fatty stage advances. Clinicians commonly maintain that repair is possible even when fatty change Fic. 249.—FaTTy DEGENERATION OF THE HEART. (Specimen fixed in osmic acid, rendering the fat globules black.) Near the center of the drawing are a number of red blood-cells. (From a case of pernicious anemia in the Jefferson Medical College Hospital, service of Professor J.C. Wilson.) is advanced. Under such circumstances it is held that the de- stroyed fiber is absorbed and the adjacent fibers undergo hyper- trophy, and in that way compensate for the tissue that has been lost. As it is not improbable that in cardiac hypertrophy new fibers are formed, with the associated enlargement of existing fibers, the possibility of a similar change following the subsidence of the disorder at present under consideration must be admitted. 2.. The second form of fatty degeneration is sometimes spoken’ of as partial or /ocal. It is due to a local ischemia, such as results from atheroma, calcification, embolic plugging, or throm- bosis of some branch of the coronary arteries, which are, toa VASCULAR SYSTEM. 495 certain extent, terminal. The lesion is manifested by the presence of a softened spot in the ventricular wall, pale yellowish-brown in -color, frequently greasy to the touch, and occasionally containing oil globules, visible macroscopically. Sometimes the degenerated area is surrounded by a zone of hyperemia. The rapidity with which the process develops varies in different cases, depending upon the promptness with which the cause acts. When there has been a sudden occlusion of the blood supply, the process will com- monly be rapid. On the other hand, when the local change is brought about by gradual encroachment upon the lumen of the coronary artery or a branch, the lesion will be delayed, and oppor- tunities will be afforded for an associated overgrowth of fibrous tissue. As a rule, the degenerative change is limited to a single focus, which is located on the anterior aspect of the left ventricle near the apex. Less commonly, a corresponding point on the wall of the right ventricle is involved. The degenerated area will rarely be large, as the conditions that bring it about, if affecting a con- siderable extent of the cardiac wall, would cause death before the manifestation of any degenerative lesion. Occasionally, more than one area is involved. Microscopically, the changes already described are more marked than in the general variety, as the patient usually lives longer, and the small focus advances further. The process may be followed by: (a) Rupture, which is rare in the general degeneration; (4) aneurysmal bulging; (c) fibroid processes may convert the mass into cicatricial tissue ; (@) the area may be so small as to give no determining phenomena. 3. The third form of fatty degeneration,—that due to poison- ing,—toxic degeneration of the heart muscle, results most com- monly from phosphorus, but occasionally from arsenic and an- timony. It presents the changes already given, and responds to the general stain and chemic tests of the ordinary fatty de- generation ; if an opinion is to be given in a suspected poisoning case as to the presence or absence of fatty degeneration, it must be formed, if it is possible to form such an opinion, while the tis- sue is fresh. The term soxic degeneration is not altogether appro- priate, as the degenerative changes resulting from various infec- tions are essentially of toxic origin. Hyaline degeneration of the heart differs from the albu- minoid or granular change in that the heart muscle-fibers are converted into a hyaline, vitreous substance resembling the mate- rial that results from the vitreous change in other muscles, known as Zenker’s degeneration. When present, hyaline degen- eration has been discovered by the microscope and not by macro- scopic evidences. In hyaline degeneration the muscle-fibers may 496 SPECIAL PATHOLOGY. be fragmented ; the separation of the fragments may be at the junction of the muscle-cells or directly through the cell-wall. When this condition is present, Renaut has proposed the name segmentary myocarditis. Strekeisen believes that the fragmenta- tion is dependent upon violent cardiac contractions during the agonal period. He holds that a preliminary weakening of the muscles is not necessary to the occurrence of fragmentation, as shown by the frequency with which it occurs when death has been due to accident and when no associated. lesions can be detected. Peculiar patches of a yellowish or grayish-yellow color, situated immediately under the pericardium, have been noticed. They usually contain bacteria, but not the tissue reactions incident to an infection. The change resembles, in a limited way, an embolic process. Weber regards the condition as a postmortem change in an area of infection, which infection occurred just before death. Acute Myocarditis.—By some the degenerative and necrotic changes seen during acute infectious diseases, and occurring either as focal lesions involving the cardiac fibers or as a more dif- fuse process amounting practically to a granular or fatty change, are regarded as inflammatory, and have received the name paren- chymatous myocarditis. Inmost cases myocardial inflammation is infective in point of origin, arising from the presence in the myo- cardium of bacteria brought by the blood or infiltrating the mus- cle from the adjacent pericardium or endocardium. Acute suppurative myocarditis—vnyocardial abscess or metastatic abscess of the heart—usually results from infection of the cardiac wall as a result of the lodgment of infected emboli. The condition is most frequent in pyemia and septicemia, and particularly in such mycoses of the blood as commonly accom- pany osteomyelitis, suppurative thrombophlebitis, and endocar- ditis due to pyogenic organisms. In other cases the infection results from extension of bacteria from the endocardium or myocardium. The foci of suppuration are usually situated in the anterior portion of the left ventricular wall. In the earlier stages they present the gross characteristics of an infarct ; later, pus may be evident, and may burrow toward the endocardium or the pericardium. The abscesses are rarely large, are not infre- quently microscopic, but may attain a diameter of 0.25 to 0.5 cm. The adjacent heart muscle usually shows the changes incident to infective processes independent of actual bacterial invasion. Chronic interstitial or sclerotic myocarditis (also called productive myocarditis, fibrous transformation, fibrous degenera- tion of the myocardium, and fibrous infiltration) is a chronic pro- VASCULAR SYSTEM. 497 cess associated with thé formation of fibrous tissue in the myocardium. Causes—Chronic endocarditis, either associated with or inde- pendent of valvular incompetency or stenosis. Chronic inflam- mations of the pericardium, congestion of the cardiac veins, in- creased venous tension, such as is seen in emphysema, interstitial pneumonia, and chronic pleurisy. It isa more or less constant lesion in failing compensation, and constitutes one of the mani- festations of syphilis and of malaria. It is maintained that the Fic. 250.—CHRONIC MYocARDITIS.—(Schmaus.) X 150 diameters. m. Cardiac muscle-fibers. 4,4. Newly formed fibrous connective tissue. This can often be demousttated to be of different ages, and in the older parts calcareous change may have occurred. sclerotic changes of myocarditis may be consecutive to myocar- dial degeneration and necrobiosis brought about by various bac- terial toxins. The fibrous increase has been experimentally pro- duced by pyocyaneous toxin (Charrin), and the poison of the diphtheria bacillus is believed to lead to lesions of the muscle- fibers followed by fibroid increase (Mollard and Regaud). It is generally conceded that the fibrosis is secondary to alterations in the muscle-fiber and not the reverse. The statement that it 32 498 SPECIAL PATHOLOGY. may be brought about by rupture of the muscle-fibers is not accompanied by any satisfactory proof. Morbid Anatomy.—Two forms of the lesion are recognized: (1) local or circumscribed, (2) general or diffuse. Local or cir- cumscribed fibrous myocarditis is usually attributed to a cause that has affected only a part of the cardiac wall, such as the anemia following gradual occlusion of a branch of the coronary artery, infarction, and local fatty degeneration. The fibrous area may be small, irregularly outlined, and less than one centimeter in diameter. It may or may not extend through the heart-wall. In other cases the area of fibrosis may equal one-third of the ven- tricular wall, and in some instances larger areas have been found. The process is most frequent at or near the apex of the left ven- tricle. When fully developed, the fibrous area is dense, like a cicatrix, constituting the so-called ‘‘heart-scar.” Such collec- tions of fibrous tissue probably represent efforts at repair in areas of past degeneration or necrosis. The fibrous tissue may contain pigment and calcareous matter, and muscle-fibers may be absent. When the entire thickness of the heart-wall is involved, and even sometimes when only a part has become fibroid, aneurysmal bulging may occur. The more or less sharply outlined margin at times observed has led to the belief that many of these heart- scars are really gummata. The finding of scars of evidently dif- ferent ages, associated with the presence of absorbing gummata, would certainly seem to be conclusive. Diffuse Interstitial Myocarditis —Al\though diffuse, the fibrous tissue increase is commonly not uniform. The abundance of fibrous tissue between the cardiac muscle-fibers has to a certain ex- tent justified the appellation fibroid infiltration. Most observers, as already stated, do not consider the increase of fibrous tissue an evidence of past or existing inflammation, but rather a sub- stitutive fibrosis, the fibrous tissue having replaced atrophied, degenerated, or necrotic muscle-fibers. Morbid Anatomy.—The cardiac muscle is usually firmer than normal; this abnormal density is not uniform in distribution. Occasionally, whitish areas of fibrous tissue may be recognized in the ventricular wall. White lines are frequently shown on the columne carnee; the tendons of the papillary muscles seem to be projected as whitish streaks, often extending nearly to the base of the papillae. Under the microscope, fibrous tissue can often be demonstrated in various states of development. Not infrequently calcareous infiltration may be present, and the mus- cle-fibers usually show some granular change, and occasionally pigmentation. Interference with function is always probable ; it VASCULAR SYSTEM. 499 may be slight, but in most instances dilatation comes on rapidly and gradual failure of the heart takes place. Aneurysm of the heart results from any of the preceding conditions that lessen the resistance of the cardiac wall at any one point. Bulging occurs, the wall of the aneurysm being either a saccular mass without constriction or a large sac communi- cating with the ventricle by a small opening. A specimen in the writer's laboratory possesses a sac as large as an egg, its wall being made up of the endocardium, a layer of fibrous tissue, and the pericardium ; the cavity of the aneurysm communicates with the ventricle by a small opening near the apex about one centimeter in diameter. In over sixty per cent. of the reported cases the aneurysm is in the left ventricular wall, usually near the apex. Rarely, the aneurysmal dilatation begins in the septum. When the aneurysm is composed of a dilated pouch communicating with the ventricular cavity through a smaller opening, thrombi are not infre- quently present. As a result of roughening in the wall of the aneurysm a thrombus may form even when there is no oppor- tunity afforded for stagnation of the blood. Sometimes the aneurysmal wall is intensely calcific. The author has observed a case in which the whole of the aneurysm was attached to the parietal pericardium, suggesting the possibility of pericardial adhesions dragging the fibroid wall outward, and in that way favoring the local dilatation, the cause of which must be princi- pally the intraventricular pressure. Rupture occurs in nearly all cases, and death almost instantaneously follows. Diseases of the blood-vessels supplying the heart do not commonly differ from similar alterations observed in the arteries elsewhere. The fact that the coronary arteries are more or less terminal, in the sense that abundant anastomosis is not afforded, leads to changes in the cardiac wall differing somewhat from tissue alterations secondary to vascular lesions in other organs. Atheroma of the coronary arteries, obliterative arteritis, and fatty degeneration of the intima and media occur under the same con- ditions and from the same causes as observed elsewhere. Athe- roma and obliterative change are frequently associated with syphilis, and may constitute a part of the fibroid change occur- ring in the organ in this disease. Both atheroma and oblitera- tive arteritis lessen the carrying capacity of the vessel, lower the nutrition of the cardiac muscle in the area beyond, and favor the occurrence of fibroid change. Huchard analyzed 145 cases of angina pectoris in which the postmortem showed that in 128 of the cases the coronary artery was diseased. Fortunately, the coronary arteries are rarely the sites of _500 SPECIAL PATHOLOGY. thrombosis and embolism. Atheroma and obliterative change favor the occurrence of thrombosis. Embolism is less frequent. With the occlusion of the artery, the nutrition of the area beyond is suspended, and later that portion of the myocardium involved undergoes necrosis and fatty degeneration, leading to rapid softening, the resulting condition constituting a form of what the older writers called myomalacia cordis. (See Local Fatty Degeneration, p. 495.) With the presence of infected emboli in the blood, and possibly as a result of mural implanta- tion of bacteria circulating in the coronary vessels, metastatic abscesses are engendered in the myocardium. (See Embolism, p. 275; also Acute Suppurative Myocarditis, p. 496.) Aneurysm of the coronary artery is rare. It may result from atheroma or degenerative changes in the arterial wall, and is said to occur as a result of inflammation or degeneration involving the adjacent muscle. Occasionally, coronary aneurysms are multiple. Syphilis of the heart-wall usually manifests itself as fibrous or sclerotic myocarditis ; some of the cases of fibrous myocar- ditis are probably cured gummata. A form of fibrous myo- carditis, due to congenital syphilis, has been described as occur- ring in the new-born. Gumma in the heart is most frequent in or near the ventricular septum, although it may occur in the ventricular wall. It is nearly always associated with a marked increase of the fibrous tissue in the adjacent muscle, and may not be sharply outlined from the surrounding structures. Tuberculosis of the heart may occur; it is usually miliary, and is seen most commonly on the right side, immediately under the pericardium, although the bacillus has been demonstrated in the myocardium and valves. Areas of caseous tuberculosis are infrequent. Tumors of the heart are very rare. The primary tumors are the fibroma, myoma (usually congenital and of the rhabdo- myoma class), lipoma, and sarcoma. The secondary tumors are the sarcomata and cancers; the latter can never be primary. Hydatids occur in the heart. Rupture of the heart may be caused by a number of conditions already considered, among which the following are deserving of special mention: Fatty infiltration ; fatty degene- ration, particularly the local form; embolism or thrombosis of the coronary arteries ; and aneurysms. Ruptures resulting from blows upon the chest and crushing are more frequent on the right side or in the auricles, as the sudden rise of pressure brought about by the accident leads to yielding of the weaker walls. The ruptures depending upon changes in the myocardium VASCULAR SYSTEM. sol are most common in the left ventricle, as its wall sustains the relatively high systemic arterial tension. The rupture may be szzgle or multiple, complete or partial. As many as Six or seven distinct ruptures may be present. With a rupture extending through the wall or from the pericardium nearly to the endocardium, or in the reverse direction, there may be purely intramural breaks in the muscle, as shown by hemorrhages into the myocardium at the point of rupture. Ruptures are not of necessity fatal; and even when multiple, death may be delayed for days or weeks. A rupture of any size, permitting rapid evacuation of the ventricle, leads to sudden death. In the smaller ruptures that merely leak recovery is possible. The great obstacle to recovery from rupture of the heart is the fact that the conditions that bring about the rupture lessen the reparative power of the organ. Wounds of the myocardium may not prove fatal even when the heart cavity has been penetrated. Union occurs by a fibrous tissue repair, and not by muscle regeneration. It is probable that regeneration of cardiac muscle does not occur, and that the fibroid areas occasionally found postmortem are points at which cicatrization has followed some destructive lesion involving the myocardium. ENDOCARDIUM. The xormal endocardium is made up of a flattened layer of connective-tissue cells—histologically, a serous membrane. The continuous flowing of blood over its surface, and the difference in function from other serous membranes, render a separate descrip- tion of its diseases necessary. The membrane is nonvascular even in its reflected layers, which, reinforced by fibrous and elastic tissues, form the valves ; the valves are rich in lymphatics ; imme- diately beneath the endocardium ramifies the plexus of nerves de- scribed by Krause. Recent investigations seem to show that the bases of the mitral and tricuspid leaflets contain some capillary ramifications ; the blood-vessels do not, however, approach the free edges of the valves. : INFLAMMATION OF THE ENDOCARDIUM—ENDOCARDITIS. Sites.—That part of the endocardium having the most work, other things being equal, will first suffer and suffer most. This explains the infrequency of the process on the right side, in adult life, and the rarity of intra-uterine disease of the left side; again, it explains those cases of secondary endocardial inflammation of the right side, in adult life, when extensive obstructive or regurgi- 502 SPECIAL PATHOLOGY. tant lesion of the left side leads to backing of blood and increased work of the right side. When the inflammation is in the valvular endocardium, it is known as valvular endocarditis, or valvulitis ; when on the auricular or ventricular wall, itis spoken of as mural endocarditis ; the latter is rare except in the malignant and athero- matous forms. In the adult about one-half of the cases of en- docarditis occur on the mitral leaflets ; of the remaining fifty per cent., about ninety-four per cent. occur on the aortic cusps; the remaining cases are divided between the valves of the right side, the tricuspid being the more commonly affected. Forms of Endocarditis.—Inflammation of the endocardium may be acute or chronic. It has been customary for pathologists and clinicians to divide the acute inflammations of the endocardium into sample and malignant. It was believed that the acute simple endocarditis was noninfective in origin, and that it was not asso- ciated with the presence of bacteria. The tendency at present is to regard both forms as dependent upon infection, but in that type previously called simple endocarditis, the infection differs in degree, or possibly in character, from that seen in the ulcerative variety. Both pathologically and clinically, cases are not infre- quently seen in which the clinical history and morbid anatomy justify the term simple endocarditis. It is equally true that we occasionally find extensive lesions, affecting the valves and mural endocardium, associated with pyogenic infection, and also, al- though less commonly, with other mycoses, clinically and ana- tomically meriting the name ulcerative or malignant endocarditis. Between these extremes there is a middle ground, occupied by a not very small number of cases, in which it is quite impossible, either anatomically or clinically, to separate and group them with one or the other of the foregoing divisions. The possible iden- tification of differences once believed to be clearly recognizable is further complicated by the more recent introduction of the term acute malignant rheumatic endocarditis, * and applying it to a form of endocardial inflammation of rheumatic origin, and usually termi- nating fatally, without the tendency to suppurative lesions in other viscera, and unassociated with the rather characteristic temperature-curve of that form of endocardial inflammation that we have been in the habit of calling malignant endocar- ditis. It is to be presumed that the easily recognized differences between the typical, clearly defined, acute, simple endocarditis and the admittedly malignant endocarditis must depend upon the character of the infection and upon the resistance of the tissues * Litten, ‘Berlin. klin. Woch.,”’ July, 1899. VASCULAR SYSTEM. 503 to the infective agent. Thus, infection associated with the pres- ence of staphylococci will usually be ulcerative in type, while the endocardial inflammations associated with rheumatism rarely manifest the phenomena heretofore grouped as essential mani- festations of the ulcerative form of endocarditis. Bearing the foregoing facts in mind, and remembering that the so-called acute simple endocarditis may or may not terminate in the malig- nant, we will adhere to the customary division, based upon the belief that it is possible to recognize an acute simple endocarditis and an acute malignant endocarditis. The chronic, indurative, sclerotic, or interstitial endocarditis is still to be regarded as an entity, although it often is nothing more than a terminal stage of an acute process. Acute Simple Endocarditis.— Causes —(1) Acute articular rheumatism (twenty per cent. of the cases), The growing be- lief that rheumatism is infective in origin offers a better expla- nation for the associated endocardial inflammation than the older view that the endocarditis was due to the presence of a nonbac- terial irritant in the circulation. (2) Tonsillitis, which may be rheumatic, and hence involve the first. (3) Infectious diseases of childhood—scarlet fever, etc. (4) Rarely, typhoid fever. (5) Chorea. (6) Pneumonia. (7) Diseases associated with general debility and blood dyscrasiz, as gout, cancer, diabetes, and inflam- mations of the kidney, especially the interstitial form; the last of these acts also by increasing cardiac work. Previous attacks increase the liability to the disease. Various organisms, mostly micrococci, have been found in the valves and exudate ; the frequency with which bacteria have been demon- strated in the lesions, and the fact that the disease is constantly associated with processes admittedly of micro-organismal origin, lends weight to the belief that endocarditis in its acute form is always of bacterial origin. In order to avoid repetition the vari- ous organisms that may be present in the form of endocarditis under consideration, as well as in the malignant type of the dis- ease, may be named at this point. Heiberg and Winge (1869) first demonstrated bacteria in the lesions of endocarditis. Harblitz* has analyzed the records upon the subject, and presumes to differentiate some of the infec- tions by the character of the lesion ; streptococcus-infections pro- ducing large vegetations that progress slowly and are accom- panied by nephritis. In the pyemic endocardial lesions contain- * Harblitz,““om Endokardit, dens Pathologiske Anatomi, og Aetiologi,’? 1897. Harblitz, ‘‘ Deutsch. med. Woch.,’’ Feb. 23, 1899. 504 SPECIAL PATHOLOGY. ing the ordinary staphylococci the course of the disease is rapid and the valve destruction is great and is associated with more wide-spread infection. The organisms found include the streptococci, staphylococ- cus pyogenes aureus and albus, micrococcus endocarditidis ru- gatus (Weichselbaum), micrococcus endocarditidis capsulatus (Weichselbaum), gonococcus, and the diplococcus of pneumonia ; among the bacilli occur the bacillus pyogenes fcetidus (Passet), Fic. 251.—AorTIC ORIFICE LaiD OPEN, SHOWING THE VALVE LEAFLETS, ACUTE ENDO- CARDITIS.—(Redrawn from Schmaus.) A. Line of contact with beginning formation of vegetations. &. More advanced and larger vegetations closely simulating in appearance an ulcerative lesion. Between the leaflet A and the leaflet immediately above the letter B is seen a single vegetation on the leaflet B ; should a similar Jesion occur at the corres; onding point on the leaflet 4, the two, coming together, could coalesce, or the continued de osit of fibrin might fuse the adjacent masses, and, by organization, would produce an adh 5 : i esion between t rowing the orifice. e two leaflets, thereby nar- bacillus endocarditidis griseus (Weichselbaum), bacillus endo- carditidis capsulatus (Weichselbaum), the bacillus of pneumonia (Friedlander), the bacillus typhosus, and the bacillus diphtheriz. Those cases in which the bacillus of tuberculosis has been found are believed to be instances of secondary infection, the bacillus having been implanted upon a preexisting endocardial lesion. Morbid Anatomy.—This will depend upon the stage. First stage: Redness and injection are not present, as the tissue is VASCULAR SYSTEM. 505 nonvascular. (@) Milky opacity of the membrane, due to serum and leukocytes infiltrating the lymph-spaces and to slight roughening of the connective surface, just as grinding the surface of glass renders it more or less opaque. (4) Bogginess or edema of the valve is discernible at this time, and is due to the infiltra- tion of the valve tissue by serum and leukocytes. In this soft- ened and boggy condition, the valves pounding against one an- other at the rate of from 120 to 150 times a minute, (c) abrasion or even laceration may occur. The line of friction is the line of contact, and in this line the roughened points develop. A microscopic examination of the valve in this stage will show more or less proliferation of the endothelium, associated with des- quamation, and in some cases hyaline degeneration or distinct coagulation necrosis. The subendocardial connective-tissue cells are not infrequently swollen, and the lymph-spaces of the valve may contain fibrin. Lhe Production of Vegetations——The blood passing over the roughened line of abrasion has fibrin whipped out upon the rough points ; to this are added proliferation of some of the con- nective-tissue elements and a further infiltration of leukocytes into the affected valve. These being most abundant in the focal area, increase the size of the so-called vegetation or cap of fibrin. The deposited fibrin may be granular, fibrillar, or, less frequently, hyaline. The distinctly hyaline form of fibrin is usually absent ; when present, it occurs as small irregular collections in the forming vege- tation. It should be observed that struc- turally and genetically the developed : vegetation is essentially a thrombus. It yg. 252 Acure Enpocarpr- may contain all the bodies commonly 71S OF THE MITRAL VALVE, ‘ i SECTION AT LINE oF Con- found in thrombi,—fibrin, leukocytes, TACT. (Partly diagram- or ae matic.)—(Rindfleisch.) X10 erythrocytes, and platelets,—and is liable diameters. : : S , a’. Endocardium, which at to secondary changes identical with those “ has ‘become swollen ane . s ‘ be abraded and covere the oo \ thrombi. (See Thrombo cap of fibrin d. ‘ by the sis, p. 2 7s stitial tissue of the valve : n with newly formed blood- With firm vegetations of moderate vessels. ¢. Free margin of m 2 sa: valve leaflet. size the lesion is called endocarditis verrucosa; when the collection of fibrin is large and flabby, the term polypous or villous endocarditis is at times applied. Changes in the Fibrin Cap or Vegetation—The vegetation may increase by layers and show distinct lamination ; it may be re- dissolved ; it may soften, from being too large to organize; if 506 SPECIAL PATHOLOGY. near a corresponding mass on an opposite leaflet, especially at the valvular attachment, cohesion may occur (see Fig. 255); or- ganization of the mass is the last process, and by some is con- sidered as a third stage. Unless the process be fulminatingly rapid, organization has begun, at the point of attachment to the valve, by the time the vegetation is visible to the unaided eye; as organization progresses, new blood-vessels may develop from A Fic. 253 NARROWED MITRAL ORIFICE SHOWING RESULTS OF ADHESIONS WITH CONSID- ERABLE FIBROID THICKENING (BUTTON-HOLE MITRAL). A, A,A,A. Papillary muscles and tendons. £8 to C. Area of adhesion and fibroid thickening. D to &. Second area of adhesion and fibroid thickening. The whole free margin of the valve is intensely indurated, rendering the leaflet too stiff to close readily and, as a result of the adhesions, unable to open to its normal lumen, giving rise to both stenosis and regurgitation.—(From specimen in author's collection.) the base of the valve. The presence of pyogenic and some other bacteria may limit or prevent organization and favor disin- tegration and softening. Results—(1) At an early stage the thickening or swelling muffles the valves and alters their sound ; (2) fenestrations may occur if not prevented by the cap of fibrin; (3) laceration of the VASCULAR SYSTEM. 507 valve leaflet, a further process than fenestration; (4) adhesions of valve leaflets (see Fig. 253); (5) induration, as organization occurs ; (6) contraction of the valve (see Fig. 255) ; (7) calcare- ous or atheromatous changes (see Fig. 254) ; (8) dilatation of the valve or orifice may occur early, from the softening and edema of the initial stage, or it may follow the atheroma; (9) a single valve leaflet may relax, producing what is sometimes termed ancurysiut of the valve. Acute Malignant Endocarditis. —(Synonyms, Ulcerative, Mycotic, Bactertal, or Pustular Endocarditis; Arterial Pyemia. L Endocardite Vegetante Ulcereuse ; Endocarditis Pyemica ; Diph- theric Endocarditis, etc.) Causes.—(1) Simple ; may become malignant, and the chronic valve lesions are believed to predispose to this form. Goodhart found that 61 out of 6g cases had been preceded by chronic en- docarditis. (2) Croupous pneumonia is the most frequent cause ; in Osler’s collection of cases, in 54 out of 209 recorded obser- vations the endocardial inflammation developed during an attack of croupous pneumonia. (3) Erysipelas. (4) Septicemia and pyemia. (5) Osteomyelitis, probably due to this condition being commonly accompanied by septicemia or pyemia. (6) Puerperal fever. (7) Gonorrhea. (8) Enteritis. (9) Rarely, tuberculosis, typhoid, diphtheria, rheumatism, or chorea. The bacteria present : Streptococcus pyogenes ; micrococcus pyogenes aureus, also albus, cereus albus, and cereus flavus ; the diplococcus pneumoniz, bacillus foetidus, and the alleged micro- coccus endocarditidis. (See microbic causes of endocarditis on Pp. 504.) Injury or previous disease of the valve favors the occurrence of infection, and therefore predisposes to this form of endocardial inflammation. Site.—(1) Contact line of valves ; (2) at base of valves ; (3) mural. There is a form secondary to myocardial infection pre- sumed to be due to infective embolism of the coronary artery. As to orifice, Osler, Sansom, and Hamilton accept the following. order: (1) Mitral ; (2) aortic ; (3) aortic and mitral ; (4) heart- wall; (5) tricuspid; (6) pulmonary. The valves of the right side of the heart are more frequently affected in this form of en- docardial inflammation than in the acute simple endocarditis. This is to be explained by the fact that in such infectious diseases as suppuration, erysipelas, osteomyelitis, puerperal fever and other infections of the genito-urinary organs, ulcerations of the intestine, suppurative processes in the liver, and otitis media, the venous blood returns to the heart charged with the bacteria, and * 508 SPECIAL PATHOLOGY. hence the valves first subjected to the danger of infection are those of the right side. Following Virchow, most observers are inclined to believe that the infection is the result of direct implan- tation of bacteria upon the valve segments, although Koster has strongly urged the possibility of infection through the blood-ves- sels of the leaflet. The almost complete absence of blood-ves- sels in the normal leaflet, and the fact that bacteria are most abundant in the periphery of the lesion, would favor the view first given. : Morbid Anatomy.—Whether preceded by simple inflammation or not, necrosis, ulceration, and loss of tissue are almost con- stantly present. Ulceration in the sense that a distinct recogniz- able or anatomically perfect ulcer must be developed is not at all necessary. Bacteria are invariably present during the active stage of the process, and are usually most abundant in the superficial layers of the vegetation, although they are not infre- quently present at the bases and in the interstices of the valves. Vegetations are usually large, although well-marked cases are found in which they are small. They usually show evidences of necrosis, soft- ening, and fragmentation. As a result of these changes, embolism, with the development of sup- purative processes in other viscera, usually accompan- ies this form of endocarditis. The necrotic processes are not restricted to the vegeta- tion alone, but may involve the valve leaflet, which Fic. 254.— ADJACENT AorTIC Cusps, SHOWING A SMALL VEGETATION DEVELOPING JuST BE- 1s sometimes totally de- LOW THE POINT OF AN OLD ADHESION. stroyed. Mural lesions are Calcareous areas are indicated by the white areas on the valve leaflet. A case of acute endocar- not infrequent they some- dial inflammation ingrafted on chronic lesion. times depend upon direct inoculation from bacteria in the blood ; in other cases their. location would indicate that the vegetation had, by contact, inoculated the ventricular, auricular, or aortic wall. Cases occur in which it is possible to believe that the infection involved the heart muscle as a result of dissemina- tion through the blood by way of the coronary artery. Microscopic abscesses are sometimes to be recognized in the valve tissue, and similar areas of a larger size are occasionally VASCULAR SYSTEM. 509 observed in the myocardium. The extension of the infection to the myocardium may lead to penetration or perforation of the ventricular septum, aneurysm, or rupture of the heart. The calcific deposits occasionally observed in this form of endocarditis may be due to the fact that the lesion is ingrafted upon an old endocardial change in which calcification was present. In other instances there is reason to believe that the infiltration is second- ary to the acute process with which it is found. Results —More or less destruction of tissue ; infected embolic and disseminated infarction processes throughout the organism. Rarely, if ever, the patient recovers ; if so, cicatrization and de- formity of the affected area result. Chronic Endocarditis. — (Synonyms, J/udurative, Fibrous, Sclerotic, Adhesive, Interstitial, or Permanent Endocarditis.) Causes.—(1) The result of the acute forms; (2) alcohol; (3) syphilis ; (4) gout ; (5) excessive work for any one valve, rarely all the valves, and usually only those of the left side. The results of acute endocarditis have already been described. The true chronic endocarditis consists essentially of a progressive fibrosis involving the valves and sometimes the mural endocar- dium. The interstitial fibroid change develops slowly, showing as a milky opacity first at the margin of the leaflet, gradually extending, increasing the thickness and lessening the pliability of the valve, sooner or later contracting, and undergoing calcareous change. The newly formed fibrous tissue frequently shows necrotic and degenerative processes, and commonly contains areas of calcareous infiltration. Degenerative changes in the overlying endothelium may expose the calcareous plaques ; the presence of pro- jecting spicules of calcific matter leads to Fic, 255.—ApueReNT AND THICKENED VALVE the deposition of the blood platelet fol- Leae cers — (Rind . i is eisch. lowed by fibrin, so that, even in this form view obtained by looking of endocarditis, small fibrinous collections downward upon the 2 i aortic valves from the are occasionally seen. As_ contraction aorta. Two leaflets are . a adherent, all are con- ensues, curling of the valve edges, insuffi- tracted, thickened, e . fi everted, and unable to ciency, and stenosis may develop. In fig- open widely or close ure 250 the valve leaflet on the extreme aa right is beginning to show slight eversion. The chorde tendinee thicken, agglutinate, or shorten, so that the muscle may appear to be inserted immediately into the valve cusp; narrowing and adhesion leading to such conditions, for example, as the button-hole mitral, funnel mitral, etc. As 510 SPECIAL PATHOLOGY. the sclerosis advances, the calcific changes become more marked, and eventually the valves and walls of the orifices are converted into hard, calcareous, fibroid structures, with scarcely a normal element remaining. The mural form of chronic endocarditis is secondary to atheroma or interstitial myocarditis, and shows merely as hard, fibroid, or calcareous areas on the cardiac wall. Results of Endocarditis.—When the valve does not return to the normal, which in rare cases may occur, the changes already described lead inevitably to one of two conditions or to both. 1. Narrowing, Obstruction, or Stenosis.—This condition may be brought about in any of the following ways : (2) Vegetations pro- jecting into the lumen when the valve is open ; (0) stiffened valves that do not open; (c) contracted valves that can not open, but subtend the orifice like a cord ; (a) adherent valves, the adhesions preventing opening ; (ce) eversion or inversion of a leaflet either as a part or a whole; (/) a lacerated leaflet hanging in the cur- rent; (g) contraction of the orifice incident to a circumferential inflammation at the base of the valve, or, in the mitral, the free margin ; (/) loss of elasticity of the orifice owing to fibrous or calcareous change, or to both, without of necessity contracting, but being inelastic, it is practically a stenosis ; (2) combinations of these processes. 2. Lusufficiency or Incompetency of the Valves, Permitting Re- gurgitation.—(a) Valves may be propped open by a vegetation ; (2) valves may be too stiff to close; (¢) contracted valves can not close, for the same reason that they can not open ; (@) inverted, everted, or lacerated valves can not close the orifice ; (e) fenestra below the line of contact permit regurgitation ; (/) contraction of the orifice leading to wrinkling of the leaflets is by some sup- posed to be a cause; (g) relaxation, distention, or dilatation of the orifice beyond a size that the valve will cover or close. Lnfluence of Stenosis and Insufficiency on Cardiac Work.—lIt matters not which of the above processes occurs, the inevitable consequence will be increased work for the heart, and this must lead to either hypertrophy or dilatation. It is not possible, in the space available, to take up in detail the physics of the normal circulation, with which it is presumed that the student is familiar, nor can the disturbances brought about by stenosis and in- sufficiency be fully considered. It is, of course, evident that either of these conditions affecting the orifice through which the ven- tricle is normally emptied more profoundly influences the function of that structure than when it is the orifice through which filling occurs. With the occurrence of aortic stenosis the work of the left ventricle must be increased, as it necessarily requires more VASCULAR SYSTEM. SII force to deliver 100 gm. of blood through an orifice 0.9 inch in diameter than it would if the orifice possessed a diameter of 1.3 inches. Were there not so many factors to be taken into con- sideration, it would be theoretically possible to calculate the amount of increase in cardiac work that would result from a one-tenth reduction of the sectional area of the aortic orifice. The cardiac work is also increased by insufficiency or regurgita- tion, for if 100 gm. of blood have been delivered into the aorta during the previous systole, and if 25 gm. return to the ventricle by reason of insufficiency in the aortic valves, the ventricle at the same time receiving its normal inflow from the auricle, it must be apparent that one-fourth of the blood is being pumped into the aorta twice in order to assure its progress. It of necessity follows that the heart is doing one-fourth of its work over, which, of course, implies-an enormous increase in cardiac labor. The same hypotheses applied to the auricles would not yield the same con- clusions ; the auricular cavities communicate directly with their respective venous systems, so that the venous system of the side in question must always be considered practically as a part of the auricle. Nevertheless, it is evident that regurgitation through the mitral orifice must increase the work of the heart, as when the left ventricle contracts, a part of its force loses its effective- ness by the fact that the insufficient mitral permits a backward flow into the auricle. During the next diastole the ventricle should receive its normal quota of blood plus the blood. that was re- gurgitated into the auricle through insufficient mitral. This, of course, means increased work for the ventricle. Mitral stenosis acts differently,—at least, when marked,—as already referred to when considering local atrophy of the heart. (See p. 491.) In the presence of increased cardiac work brought about in ways that have just been mentioned, hypertrophy or dilatation must of necessity follow. HYPERTROPHY AND DILATATION. Hypertrophy— Dilatation— Simple. [Simple. ] Eccentric. | With thickening. hConeenedes With thinning. . ‘Simple hypertrophy is increased weight with increased func- tional power, without evident alteration in the cavity. Eccentric hypertrophy is assumed to be increased weight, with increased (?) functional power and increased cavity; in other words, it is the same as dilatation with thickening ; during life the 512 SPECIAL PATHOLOGY. symptoms, if any presented themselves, were those of dilatation rather than hypertrophy. Concentric hypertrophy is assumed to be hypertrophy at the expense of the cavity: that is, increased weight, etc., with dimi- nution in the size of the cavity. It is a postmortem change, or is dependent upon the conditions that determine death. How easily one may be misled is illustrated by the following ex- periment : Obtain three bullocks’ hearts immediately on slaughtering. In one heart all the vessels should be ligated before the animal is bled or the vascular system opened ;-let the second heart remain empty. The third heart is to be distended by ligating the pulmonary veins and attaching the aorta to a hydrant. It is best that all the hearts have about the same weight. Ina few hours, when rigor mortis has ceased to act, the following will be found: The first heart is an example of hypertrophy with a normal cavity ; the second, hypertrophy with diminished cavity; the third, hypertrophy with increased cavity. As death may arrest the heart in any degree of distention, or rigor mortis act to any degree, the foregoing conditions may all be found in any hyper- trophied heart. Simple hypertrophy therefore remains. Dilatation with thickening is admitted, as is dilatation with thinning; but szmple dilatation implies a larger cavity, with wall of normal thickness, and as such a heart must weigh more, it requiring more muscle to surround a large cavity with a wall of a given thickness than a smaller cavity, as the normal, the condition is one of dilatation with increased weight or thickening. Causes of Hypertrophy and Dilatation.—Increased work with abundant nutrition are followed by hypertrophy. Overwork—that is, work beyond the nutrition and muscular power of the organ —leads to dilatation. These may be due to conditions zztracardiac or extracardiac. Intracardiac Causes—({1) Any of the valvular lesions already given that increase the cardiac work (p. 510); (2) myocardial sclerosis ; (3) overstimulation of the cardiac muscle, as may re- sult from the excessive use of alcohol, tea, and tobacco. : Extracardiac Causes —(1) The various forms of chronic peri- carditis—adhesive, caseous, etc. (2) Diminished caliber of the vessels transmitting the blood: ¢. g., narrowing or hypoplasia of the aorta ; contraction of the arterioles, as occurs in Bright’s dis- ease. When the blood-vessels lose their elasticity from any cause, the work of the heart is increased. (3) Increased muscu- lar work demanding extra supply of blood, as in laborers and athletes. Hypertrophy is a physiologic process in gestation. VASCULAR SYSTEM. 5 1 3 Hypertrophy of the left ventricle is by far the most common, but hypertrophy of the right occurs not infrequently. Those of the preceding causes that may here act are apparent, and to those may be added: (1) Stagnation of blood due to mitral dis- ease ; (2) narrowing of the pulmonary blood-vessels, as in con- genital stenosis of the pulmonary artery ; reduction in the vas- cular area of pulmonary artery, as in emphysema, interstitial pneumonia, etc. ; (3) valvular lesions of the right side; (4) tumors and aneurysms pressing upon the pulmonary artery. Morbid Anatomy of Hypertrophy —The apex is broadened, the wall implicated is extended and forms the apex, the conic shape is lost, the muscle is red and firm, cutting with more than the normal resistance. The test is increased weight; hearts weigh- ing over 1800 gm. have been reported. Reference has already been made to the unreliability of measuring the cardiac wall. Histologically, there is probably a numeric increase of muscle- fibers, and during the active stage an increase in the size of both the new and old fibers. Life History of Hypertrophy.—Hypertrophy is not a dis- ease, but a definite physiologic process with the distinct object of meeting a demand for more cardiac force: just as any muscle responds to an increased demand for power, the heart may respond. It is, however, imperatively necessary that the demand be not too suddenly developed, and that abundant nutrition be supplied to attain the desired end. It will be noticed that most of the causes already given are progressive in character and per- manent in action, and will, therefore, indefinitely increase the de- mand for work; or advancing years, with the concomitant changes in general nutrition, or the inroad of other diseases, such as Bright’s disease, will reduce the nutritional value of the blood and lessen the available food supply forthe heart. In either case the compensation that nature has attempted may be overthrown by the wasting that the new changes will induce. In the earlier stages of stenosis and insufficiency abundant nutrition and slowly increasing work favor the occurrence of hypertrophy, with which there may be a certain degree of dilatation. The hyper- trophy, however, exceeds the dilatation; with the increased cavity there is a proportionate increase in the volume of muscle. Later, dilatation gains on the hypertrophy, compensation fails, and the circulation, possibly for the first time, begins to manifest evidences of embarrassment. Hypertrophy then passes into dilatation. ‘Acute dilatation, or dilatation not preceded by hypertrophy, un- doubtedly occurs, and merely shows that the initial nutrition can 33 514 SPECIAL PATHOLOGY. not supply the initial demand; ordinarily, this is met by the re- serve force of the organ, but this may be deficient as the result of general malnutrition or local disease, as occurs in granular degeneration and myocarditis, or the work suddenly thrown on the heart may be beyond the power of the reserve force; in either case the inability of the organ fully to perform its function leads to a gradual accumulation of blood within the cavity, and dilatation results. Acute dilatation occurs in mountain climbing, after severe exertion, and sometimes during excitement; sud- denly developed valvular insufficiency, as from laceration or rup- ture of a leaflet, may bring about the same result. Chronic dilatation usually follows hypertrophy, as previously mentioned, when compensation can no longer be maintained. Morbid Anatomy of Dulatation.—Most common on the right side, and most marked in all the cavities in aortic incompetency. The auricle never hypertrophies without dilatation, and may attain an enormous size. Dilatation of a cavity leads to dilatation of the orifices that communicate with it, and hence to incompetency. Opacity of the endocardium has been noted. The muscle-fibers not uncommonly show advanced degenerative change, and in some cases a well-defined interstitial myocarditis may be present. Degeneration of the cardiac ganglia has been observed. Influence of Cardiac Inefficiency on Other Organs.— Lungs.—Edema, congestion, brown induration, pulmonary apo- plexy, bronchitis, croupous pneumonia. Liver—Congestion, red or cyanotic atrophy, occasionally fatty. Kidney.—Cyanotic induration ; infarction. Spleen.—Congestion may render the organ black or scarlet, and is usually attended with more or less induration ; infarction is not uncommon. The mucous membrane of the stomach and intestine becomes edematous, and may contain punctiform hemorrhages. BLOOD-VESSELS. ARTERIES. Normal Structure of an Artery.—(z) Tunica adventitia, or areolar sheath of fibrous tissue. (2) Tunica media ; (@) in the larger blood-vessels this is largely composed of elastic tissue with but little muscle-fiber ; (6) in the arterioles the involuntary fibers predominate and but little of the elastic tissue is present. (3) VASCULAR SYSTEM. 515 Tunica intima is histologically identical with the endocardium, and is known as the endangium ; it lines the interior of all the blood-vessels and constitutes the wall of the capillary. Arteritis.—Inflammations of the artery may be manifest in the external coat and surrounding tissues—periarteritis ; in the in- ternal coat—endarteritis ; and in the middle coat—vesarteritis. Many of the conditions ordinarily described as inflammatory and grouped under the term arteritis are composite processes, partly degenerative and partly inflammatory. In other instances inflam- matory lesions may precede degeneration or degeneration may occur in the cellular accumulation of past inflammatory pro- cesses. I. Atheromatous Arteritis.—(Synonyms, Exdarteritis Chron- tca Nodosa, Endarteritis Deformans.) Causes.—({1) Kidney disease, particularly chronic interstitial nephritis ; (2) old age, men more commonly than women ; (3) syphilis ; (4) gout and rheumatism. Sttes—(1) Arch of aorta ; (2) thoracic and abdominal aorta ; (3) iliac arteries ; (4) cerebral arteries, especially at the base; (5) rarely, arteries of the limbs ; (6) occasionally, in the pulmonary artery ; (7) in almost any of the large arterial trunks, particularly around the orifices of smaller branches given off; thus, in the aorta the exit points of the coronary arteries and each intercostal branch may be surrounded by a rim of atheroma. Morbid Anatomy.—(1) Milky opacity of the tunica intima, never universal, but confined to patches here and there ; (2) ele- vation of these patches, due to cellular infiltration and thickening ; (3) fatty change in the patch, showing as a pale-yellow spot in the center of the patch, which spreads throughout the entire area ; (4) deformity of the vessel, such as button-like elevations, usually most marked where a branch is given off; (5) changes in the spot—ulceration or calcification. All these processes may be evident in the same vessel. Morbid Histology —"Excess of fibrous tissue without blood- vessels ; hence the tissue tends to become fatty. The degenera- tion commences near the media. The new tissue disintegrates, forming a small cavity filled with granular debris, oil globules, and occasionally cholesterin. Degeneration may spread to and invade the media; the intima may give way, causing an athero- matous ulcer. The cellular infiltration of the arterial wall may be first manifest or most marked around the branches of the vasa vasorum. Lffect—Loss of elasticity, weakening of the wall, and in- creased liability to aneurysm. The arterial tube being made rigid, 5 16 SPECIAL PATHOLOGY. increases the cardiac work. When the process develops around the exit of branches,—as, for example, the coronary artery,—it may lessen the carrying capacity of the branch. II. Arteritis Obliterans.—Causes——(1) Tertiary syphilis ; (2) contracting kidney ; (3) it is present in areas of tuberculosis : (4) physiologic process in the vessels of the fetus, which become c a Fic. 256.—OBLITERATIVE ENDARTERITIS.—( The tissue from which drawing was made was removed from near a cancer of the face, and prepared in the laboratory of the JSefferson Medscal College Hospital by Dr. Thomas Leidy Rhoads.) 1-inch objective, t-inch ocular. Specimen fixed in corrosive sublimate, infiltrated with paraffin, stained with hematoxylin and eosin, and mounted in balsam. a. Adventitia. 4. Media. c,c. Elastic lamina. d. Irreg- ularly thickened intima. The gross specimen was hard, cord-like, but net nodular. useless at birth, and in the arterial supply to the parturient uterus ; (5) complete or partial occlusion of the vascular lumen. Stte.—Arteries of the brain and in the blood-vessels in areas of chronic infection: ¢. g., gummata and tuberculosis. Morbid Anatomy.—(1) Universal cord-like hardness ; (2) lumen barely discernible, or the vessel may.be closed. Outline of the vessel, as a rule, uniform, but may have annular or nodular thick- VASCULAR SYSTEM. 517 enings. There are none of the yellow patches of the atheroma- tous variety. Baumgarten regards the annular and nodular thickenings as perivascular gummata. Intima becomes milky, as in atheromatous endarteritis, but does not become fatty; the sclerosed areas are uniform; thickened intima encroaches on the lumen ; young blood-vessels develop to supply the new tissue ; hence fatty degeneration is absent. Differs from the atheroma- tous in that (a) it is a disease of small arteries, not large ones ; (4) thickening is circumferential ; (c) thickening becomes vascular and not fatty; (@) obliterates and does not favor aneurysm ; (e) other signs of syphilis or other chronic infection are not un- commonly present. Liffects.—(1) Cuts off blood supply to tissues. In the brain softening and paralysis ensue ; neuralgia, if the root of the fifth nerve be implicated. (2) In the fetus destruction of an organ, as the kidney, results from cutting off the blood supply during development. (3) Prevents hemorrhage, as in tubercular and other ulcerative processes. III. Arteritis Infectiosa.—Includes the suppurative, malig- nant, or ulcerative inflammation of the arteries. It may be (@) mural and (6) interstitial. Causes.—Introduction of pathogenic bacteria into a blood- vessel : ¢. g., from wounds, periarterial infection, septic thrombi, septicemia, pyemia, etc. . The mural variety is due to the direct implantation of bacteria on the surface of the intima; the changes that ensue are analo- gous to those of malignant endocarditis. The implantation may , be primary or secondary. The zuterstitial form may follow injury with infection or may occur as the.result of a general infective process. It may follow the mural form. In some instances it probably represents infec- tion by the vasa vasorum. Inflammation terminating in pus- formation occurs in the media or adventitia, or both. There is also proliferation or, it may be, necrosis of the cells of the intima, producing roughness, which favors deposition of platelets and leukocytes, and in turn leads to fibrin formation or deposit on the vessel-wall. Thrombi so formed are prone to break down and give rise to infective emboli. The same process occurs in the veins: @. g., infected uterus ; infected cranial sinuses from mastoid disease. When an inflammation involves an artery by extension from contiguous tissues, the process is spoken of as a secondary arte- ritis, and partakes of the essential features of the inflammatory process that caused it. 5 18 SPECIAL PATHOLOGY. IV. Endarteritis Verrucosa, or arty Endarteritis.—The condition is rare, and is probably the result of organized thrombi on the vessel-wall ; it is usually found in the larger vessels—the aorta or the iliac or femoral arteries. Morbid Anatomy.—Smooth warty growth on the interior of the vessel, the same color as the intima, and projecting into the lumen of the vessel. Morbid Histology.—The mass is at first composed of young cell elements, and later, for the most part, of fibrous tissue covered by endothelium. V. Periarteritis Simplex (Charcot)—This condition is non- suppurative, occurs in the vessels of the brain, and leads to mili- ary aneurysm. It first attacks the adventitia as a small cell infil- trate, which invades the media later, and the intima last, if at all. The softening weakens the vessel and leads to aneurysm. The disease is most common in the smaller arteries, but may invade the capillaries or the larger arteries of the base. While the cause is not established, syphilis seems able to induce the change. VI. Periarteritis Nodosa.—This condition has been de- scribed as occurring in the vessels of the heart (coronary artery), stomach, kidney, spleen, and muscles. As a rule, the smaller vessels alone are involved. Macroscopically, the irregular nodu- lar enlargements vary in size from I or 2 mm. in the smaller ves- sels to 0.5 cm. in the larger. It has been thought that the affection did not involve the blood-vessels of the brain, but recent studies by Schrotter * would indicate that the cerebral vessels may be affected. The vessels are at points dilated, and at other points contracted. An abundant cellular infiltration occurs in the outer coat of the vessel; the media becomes fatty, but the intima is not affected. The small sac-like dilatations not uncommonly contain clots. Arteriosclerosis.—Under the name arteriosclerosis have been considered a number of conditions, either associated or occurring independently. Many writers on the subject have grouped the lesions already described, and, by reason of the fact that they are occasionally associated, assumed that they were but different expressions of a general process. Gull and Sutton apparently intended to restrict the process to changes in the capillary and arteriole walls associated with an increase in fibrous tissue; to this condition they gave the name arteriocapillary fibrosis. As the clinical studies of the condition were extended, it was * « Wiener klin. Wochen.,’’ April 15, 1899. VASCULAR SYSTEM. 519 observed that atheroma, periarteritis simplex, etc., were not in- frequently associated with the change in the arterioles and capil- laries. This led to grouping all these conditions under the one term—arteriosclerosis. Thoma concluded from his studies of the process that it was not to be restricted to the arteries, but that it involved the whole circulatory apparatus, and hence he termed the condition angiosclerosis. Having considered the changes observed in atheroma, arteritis obliterans, and the forms of periarteritis, an idea may be formed as to what is meant by arte- riosclerosis in the clinical sense, if it is assumed that all of the foregoing are but different manifestations of the same process. Old age is said to be one of the causes; the presence in the blood of the poisons of gout and rheumatism, and of the irritant bodies, whatever they may be, which induce ‘chronic interstitial inflammation of the kidney, are important factors. The excessive use of nitrogenous food, the abuse of alcohol, poisoning by lead (chronic form), and the poison of syphilis are active causes. That atheroma, obliterative changes, and arterial degenerations are largely due to increase in the blood pressure is indicated by the fact that under normal conditions the pulmonary artery is rarely involved, but in mitral stenosis, with increased intravascular ten- sion in the lung and marked rise in the blood pressure of the pulmonary artery, the vessel not infrequently shows atheroma ; and in cases in which the right ventricle hypertrophies, and thereby further raises the pressure, atheroma may be widely distributed in the pulmonary artery and its branches. Exactly what raises the blood pressure of the left side is not always easily determined. The method by which it is raised is, of course, more readily comprehended. Thus, if it is assumed that the heart increased its output of blood into the aorta, and at the same time there was no yielding in the arterioles throughout the body, the arterial tension must rise. Onthe other hand, if the heart continue its normal output, and there be contraction of the arterioles throughout the body, a similar rise in pressure must be brought about. The fact that in certain forms of renal disease (see Chronic Nephritis) there is a widely distributed increase in the fibrous tissue of the arterioles, led to the belief that the renal lesion was secondary to the changes in the arteriole and capillary. There has been a decided tendency of late to include too many conditions under the general head of arterio- sclerosis; a recent writer considers aneurysm as one of the manifestations of the disorder. Calcification of blood-vessels occurs (1) as a result of atheromatous endarteritis or other inflammation of the vessel ; \ 520 SPECIAL PATHOLOGY. (2) when lime salts are deposited in the vascular wall, without any. discernible antecedent disease, the condition is called crypto- genic calcification. Ossification, or true bone formation, is said by Orth to bea possibility ; exactly what induces it, or how it may be brought about, is not known. Hyaline, vitreous, or diaphanous degeneration, allied to that form of degeneration described by Zenker as occurring in the muscles, has been found in the vessel-walls, usually in the arterioles. (See p. 246.) Amyloid infiltration has been considered when dealing with lardaceous disease. (See p. 228.) Fatty degeneration of the blood-vessels is a disease of the capillaries, the small arteries, and, rarely, the veins. It occurs most commonly in the capillaries of the brain. As to cause, it is observed in connection with (1) old age, (2) pernicious anemia, (3) phosphorus-poisoning, and (4) general debilitating conditions. The change in the intima resembles the degenerative lesion of atheroma, but is not accompanied by any fibrous tissue formation or other phenomena so constantly associated with atheroma. fitstology —The vessel-walls are converted into a fatty cellular debris without any preceding inflammatory process like that of atheroma. An aneurysm is a tumor-like sac, containing blood and com- municating with an artery. (See Fig. 246, p. 477.) The sac may be made up of one or more coats of the blood- - vessel, when it is known as a true aneurysim—arterial ectasia ; when the sac is formed by the condensed tissues around the vessel, the walls of which have entirely given way, the condition is spoken of as a false aneurysm. Causes of Aneurysm.—Aneurysms are said to be (z) traumatic or (2) tdiopathic. As nothing occurs without a cause, it would be better to call the latter cryptogenic. Further, the causes of aneurysm are said to be (z) predisposing and (2) exciting. Of the former, many of the degenerations of the vessel-walls that have been studied, and that weaken the artery, are eminently predisposing ; atheroma is doubly dangerous in that it renders the vessel rigid and at the same time weakens the wall. The fact that syphilis favors or often brings about arterial disease or degeneration makes it a predisposing cause of aneurysm. Be- tween the thirtieth and fortieth years of life the arterial changes described in the preceding pages are likely first to evince them- selves ; the heart is yet in full power, in most individuals, and, with the maintained cardiac force and diminished strength of the VASCULAR SYSTEM. 521 diseased arterial wall, rupture or dilatation of the blood-vessel is likely to ensue. Suddenly developed, powerful cardiac force— such as may occur from a hard lift, sudden spring, or vault— doubles the demand on the semirigid and weakened vessel-walls. FIG. 257.—SYMMETRIC ANEURYSM OF THE ABDOMINAL AORTA.—(Specimen in the museum ' of the Jefferson Medical College.) A. Sacrum. #. Fourth lumbar vertebra; the anterior part of the body has been eroded by the aneurysm. At the inferior margin calcareous material has been thrown out; ante- riorly, this covers the cartilage. C. Body of third lumbarvertebra. At D the aneurysmal sac has been cut away to show the absorption of the body of the vertebra. &. Cavity of the aneurysm. At the lower part of the cavity, between the points of exit of the two iliac arteries, a sharp spicule of a calcareous plaque will be seen projecting upward. F. Left iliac artery; the right iliac artery will be seen as a short stump at the lower part of the aneurysmal wall. : The male is more liable to these sudden exertions, and hence aneurysm is much more prevalent in that sex. Injury to the blood-vessel may be an exciting cause or a predisposing element ; if the injury be a puncture, it may be followed immediately by a 522 SPECIAL PATHOLOGY. false aneurysm ; a contusion may give rise to arterial changes that weaken the wall and cause it to give way when subjected to a strain that would not influence the normal vessel. Stretching and twisting of vessels, as in dislocations and fractures, or in their reduction, have been followed immediately by aneurysmal dilatation. Form of Aneurysm.—(A) Classified by the shape: (1) Cylindric, uniform distention of the vessel. (2) Fusiform, or spindle-shaped. (3) Crsoid, a number of arteries irregularly dilated. When a single artery is involved, the term aneurysmal varix is used. (4) Saccular, in which a distinct pouch is formed. If on one side of the vessel and communicating by a small opening, it is spoken of as asymmetric, if the sac be uniformly distributed around the vessel, as in the miliary aneurysm of the brain, it is symmetric. (5) Arteriovenous aneurysm, where injury has established com- munication between an artery and a vein. When the wall sharply defines the aneurysm, it is spoken of as circumscribed ; when the blood cavity terminates in infiltrated tissue, the term diffuse is applied. (B) Classified by the cause: (1) Traumatic—an aneurysm arising suddenly, as from an ulcerative endarteritis or trauma, is some- times spoken of as an acute aneurysm ; (2) idiopathic or crypto- genic; (3) embolic, due to proximal distention in occluded vessels, usually terminal ; (4) dissecting aneurysm due to blood dissecting between the layers or coats of a vessel’s wall; (5) verminous aneurysm, one containing a parasite such as is found in the mes- entery of the horse. (C) Classification based on duration and changes in the wall: (z) An acute aneurysm or recent aneurysm is one quickly devel- oped, and is usually traumatic ; (2) chronic or old aneurysm, an aneurysm that has persisted longer, as shown by the changes that its walls have undergone. Results of Aneurysm.—(1) Disturbance of blood distribution ; (2) pressure on surrounding tissues and organs; (3) rupture ; (4) cure and arrest of further circulation through the altered vessel, Cure of Aneurysm.—(1) Clotting or fibrinous deposit must occur; this may be in layers (laminated) (see Fig. 246, p. 477), or it may be a central clot apparently formed as one mass. By occluding the point of exit the circulation is arrested. (2) The coagulum may remain unaltered for years. The writer saw a case in which all symptoms except the presence of the tumor had been absent for eight years, the proximal and distal ends of the vessel having undergone obliterative arteritis. (3) In time, blood- VASCULAR SYSTEM. 523 vessels may permeate the clot and organization of the mass may ensue. (4) The young blood-vessels may dilate and canalization may occur, reestablishing the circulation. (See Canalization of a Thrombus, Fig. 186, p. 273.) (5) A mass of fibrous tissue may remain and mark the site of an aneurysm. Hypertrophy of Arteries.—When a large arterial trunk is obstructed, the blood supply to the part beyond may be main- tained by enlargement of branches, rising above the point of ob- struction, and anastomosing with branches from below; the latter may also increase in size. The condition is one apparently of true hypertrophy. The anastomotic circulation eventually be- comes as competent to carry on the functions of nutrition as were the normal vessels. When this occurs, it is said that a collateral circulation has been established by anastomosis. VEINS. Normal Structure.—Veins have normally the same structure as arteries, except that the tunica media is very much less devel- oped, and hence the walls are thinner. Many of the veins are supplied with valves, and thus differ from the arteries. Inflammation of Veins (Phlebitis)—Inflammatory pro- cesses analogous to those already described as occurring in the arteries take place in the veins, the most important of which are the infective forms—infectious phlebitis. As in the veins the current is from the smaller lumen to a larger one, dislodgment occurs, and emboli are thrown off in large numbers. When considering thrombosis and embolism, this point was mentioned. (See p. 267.) The source of the infection in veins may be by (1) direct infection, as in wounds ; (2) mural implantation ; (3) continuity of spread (that is, passing directly along the vessel-wall); (4) by contiguity, from periphlebitis. As examples of the last two may be cited the spread from infected uterine sinuses to pelvic veins and the extension of suppurative mastoid disease to the adjacent intra- cranial sinuses respectively. Pyemia and other systemic septic conditions may result. When the inflammation begins in the intima as a result of ex- tension of an inflammation along the wall, a thrombus commonly follows the progress of the inflammation. In other cases a propagated thrombus invading a vein may give rise to inflamma- tion, justifying the term ¢hrombophletitis. The presence of bac- teria in practically all these thrombi is usually admitted ; in many of them pyogenic organisms are almost exclusively the cause, and such venous inflammation has received the name suppurative 524 SPECIAL PATHOLOGY. phlebitis. In other cases neither suppuration, softening, disinte- gration, fragmentation, nor dislodgment occur. The absence of such changes indicates that the condition is not suppurative, but by no means excludes infection, such as typhoid fever, influenza, and, more recently, rheumatism. The simple, bland, or xonn- fective phlebitis, such as follows injury of the vein without infec- tion, is inconsequential, and is usually unattended by secondary processes. Chronic phlebitis or phlebosclerosis is a morbid entity studied by Thoma, who believes it to be part of a general vascu- lar disease (angzosclerosis). The wall of the vein, usually imme- diately beneath the intima, shows a marked increase in the fibrous tissue, which may undergo hyaline degeneration ; thrombosis is not infrequently present. Varicose Veins, or Phlebectasia (Synonyms, Var7x, Varicos- aty).—This condition consists of more or less irregular dilatation of the veins; as a rule, associated with alterations in their walls and nutritive changes in the area involved. Sites—Veins of the leg and thigh; plexus pampiniformis ; hemorrhoidal veins ; occasionally, the veins of the abdominal wall, and, rarely, intra-abdominal veins— peri-uterine, renal, or mesenteric. Causes.—(1) Obstruction to the onward flow of the blood: ¢. g., tumors of the pelvis, pregnancy, etc., inducing varicosity of the veins of the leg and of the rectum; cirrhosis of the liver, obstructing the veins returning from the alimentary canal ; tight garters or other constricting bands are also Fic. 258.—Varicose Veins Causes. (2) Diseases of the central organ OF THE LEG.—(Gould.) . A . of circulation, leading to venous stasis. (3) Pulmonary obstruction, leading to stagna- tion of the blood in the veins. (4) Inflammation of the veins, (a) leading to softening of the walls, and thus favoring expansion, and (4) obliteration or narrowing of a large vein, such as the femoral, by a thrombus or by contraction, and thereby increasing the intravenous pressure in the vessel beyond the point of obstruction. forms.—(1) When the dilatation is regular, symmetric, and not associated with lengthening, the condition is known as szmple dilatation ; (2) when the vein is dilated and tortuous, owing to apparent lengthening as well as to dilatation, it is spoken of as VASCULAR SYSTEM. 525 cirsoid dilatation ; (3) when the distention is irregular, saccular, or upon alternate sides, the condition is called varicose dilatation. Results of Phlebectasia—The slowed circulation, passive con- gestion, lessens the nutrition of the tissues in the area drained by the vessels involved ; as a result of failure to remove effete mate- rials, degenerative or even necrotic processes may ensue ; edema may occur; clots may form in the veins; the stretching of the walls usually renders the valves inefficient; as a result of the lowered vitality, slight bruises or superficial excoriations are fol- lowed by infection in the diseased area, and extensive ulceration commonly ensues. In the testicle lessened nutrition undoubtedly results, and in some instances this may be followed by atrophy of the organ. In the rectum clotting may occur in the dilated hemorrhoidal veins, and violent inflammatory processes may fol- low, or the venous mass may ulcerate and bleed, or may, by its size, cause more or less obstruction to the passage of fecal matter. Tumors of Blood-vessels.—Primary tumors of the blood- vessels are rare. They must be of the connective-tissue series. Sarcomata invade the vessels rapidly, and particularly the veins, by which they not uncommonly spread. The cancers can impli- cate the vessels only as secondary growths or by direct extension of the growth into the vessel-wall. (For tumors of the blood- vessels, blood-vessel tumors, see Hemangiomata, p. 342.) Tuberculosis of blood-vessels occurs as a result of the mural implantation of the bacilli or by invasion of the blood-vessel wall by a tubercular process from an adjacent tissue. Asa result of studies by Weigert, Weil, Orth, and others, it has been recognized that one of the most frequent causes of miliary tuberculosis is a prim- ary infection of the wall of a vein. Such a lesion may occur in the pulmonary vein as a result of its proximity to active tubercu- lous glands. In other cases tuberculosis results from mural im- plantation; as is shown by the occurrence of a distinct tubercular endarteritis, of which about nine cases are on record. Syphilis of the vascular system has been considered under each condition in which it may occur. LYMPH-VESSELS. Nutrition of the tissues is largely maintained by the lymph circulating in the interstices or primitive lymph-spaces ; this lymph is derived from the blood-vessels. (See Edema, p. 264.) At first the lymph is free in the reticulum between the cells, the 526 SPECIAL PATHOLOGY. cavities within which it is lodged being called the primitive Lymph-. spaces. From these lymph-spaces there arise the lymph capil- laries, which join to form the lymphatic vessels. The larger lymph-vessels possess walls structurally resembling the walls of blood-vessels. The lymphatic capillaries, or lymph canaliculi, are structurally like the blood capillaries, except that they show great irregularity in diameter, often exhibiting saccular, cylindric, and fusiform dilatations. Malformations of the lymph-vessels are usually manifested as congenital tumors (dymphangiomata), which have been consid- ered elsewhere. (See p. 344.) As in the blood-vessels anomalies of origin and course are occasionally found, so in the lymphatic vessels evidences of abnormal distribution of the channels are sometimes exhibited. Thus, carcinoma of the mamma, which normally invades the axillary glands first, may show initial glan- dular involvement in the supraclavicular glands, thereby proving that, in some instances, at least, the lymph stream from the breast passes in a direction at variance with the normal. Obstruction of a lymph-vessel may result from pressure, as when adjacent tumors, aneurysms, and cicatrices collapse its walls ; inflammation, thrombosis, tuberculosis, and animal parasites (such, for example, as the filaria) may also occlude its lumen. Cancer spreading by the lymphatics may plug the vessels. The changes resulting from occlusion of a lymph-vessel depend largely upon the importance of the vessel and upon the possibility of collateral anastomoses. The distribution of the lymphatic system com- monly affords abundant opportunity for the lymph to pass through some circuitous route when obstructed in its normal course. When passage in this way can not be provided, the resulting obstruction is associated with edema in the area in- volved. (See Edema, p. 264.) In other cases, either with or without edema, the lymphatic vessels distal to the obstruction dilate. The dilatation may be restricted to a small area, in which case a lymphangioma results, or it may be diffuse, and manifested by the occurrence of small cysts in the area involved. In still other instances, either with or without any of the fore- going conditions, more or less edema, with marked proliferation of the connective tissues, occurs, giving rise to elephantiasis and elephantoid conditions. Manson’s statistics show that in 96.84 per cent. of the cases of elephantiasis the lower extremities are in- volved ; in 5.86 per cent. the upper extremities ; and in 2.3 per cent. the scrotum manifests the change. The enormous over- growth of the connective tissues may be appreciated by the fact that the scrotum sometimes attains a weight of 200 pounds. On VASCULAR SYSTEM. 527 incision, the tissue involved is found to consist largely of white fibrous elements superficially ; and deeper, of a ‘‘ blubbery-look- ing dropsical tissue.’’ The lymphatic glands of the area involved are commonly enlarged and fibrous. Occlusion of the thoracic duct affords a slightly different picture by reason of the fact that the vessel contains and trans- mits chyle. It may be obstructed from the same causes as those already given for lymphatic trunks elsewhere. Thrombosis in- volving the left innominate vein occludes the duct at the point where it empties its contents into the venous circulation. As in obstruction of other lymph-channels, it is possible to have abso- lute occlusion of the thoracic duct without any untoward mani- festation, in which case the fluid that it normally transmits must enter the circulation through some circuitous route. Asa result of obstruction, chylous ascites may occur. (See p. 472.) Similar effusions are occasionally observed in the pleural cavities, and chylocele—an accumulation in the tunica vaginalis testis—at times follows obstruction to the course of the intra- abdominal lymph. In other cases there is an accumulation of chyle in the lymphatics of the scrotum, constituting so-called lymph-scrotum ; and in still other instances the obstruction to the onward flow of the lymph is manifested by the occurrence of chyluria. Asa result of obstruction to the flow of the chyle along its normal course in the vessels of the mesentery, cysts are occa- sionally formed. Not infrequently these cysts closely resemble abscesses, for which they have been mistaken. A microscopic or chemic examination of their contents prevents this error in diagnosis. Obstruction to the onward flow of chyle materially interferes with nutrition, leading to more or less anemia, and eventually, in many cases, to emaciation. Lymphangitis, angioleucitis, or inflammation of the lym- phatic vessels occurs in two forms—acufe and chronic. The acute form is usually due to infection by pyogenic organ- isms, and is, therefore, most commonly suppurative in character. It may accompany erysipelas or may result from the extension of infections, such as abscesses. The dissection and postmortem wounds of common occurrence and great mortality before the proper injection of anatomic material were typical examples of acute suppurative lymphangitis. That acute inflammation of the lymphatic vessels is not always due to bacteria is indicated by the occurrence of a typical form due to filaria, and of another variety, brought about by the introduction of venom into the lymph- spaces. Severe bruises and burns, the former often without any 528 SPECIAL PATHOLOGY. solution in the continuity of the skin, may be followed by acute lymphangitis. ; The morbid anatomy of the condition depends largely upon whether the process is restricted to the lymph-spaces or passes beyond these structures and invades the vessel properly so called. In the former instances (acute reticular lymphangitis) there is dila- tation of the blood-vessels, giving rise to redness, which often shows a peculiar mottling due to its irregular distribution. More or less edema (swelling) is present. In the acute tubular lymph- angitis the lines of hyperemia and swelling follow the course of the lymphatic vessels ; usually they are broader than the duct, as a result of the presence of an associated perilymphangits, or, rather, a reticular lymphangitis surrounding the inflamed vessel. On microscopic examination, the lymph-spaces will be found to contain numerous leukocytes, and later, in pyogenic infection, the accumulation may be sufficient to justify its. being called a distinct pus collection. Fibrin is nearly always present at some stage in the process. In the lymphatic vessels swelling and des- quamation of the endothelium occur, associated with more or less marked leukocytic migration, and not infrequently with thrombosis. The extent and termination will depend largely upon the character of the infection and upon the resistance of the individual. In areas of lymphatic obstruction—such as lymph-scrotum and elephantiasis—the absence of sufficient pro- tective powers on the part of the tissues may lead to disastrous infections. In other cases the virulence of the infecting agent may be overwhelming, and associated with the production of poisons that rapidly destroy life, or by the diffusion of bacteria into the lymphatic glands, and eventually into the blood-vessels, septicemia or pyemia may ensue. In still other cases the viru- lence of the infection may be slight or the resistance of the tis- . sues marked, and in either case the process may quickly subside. Chronic lymphangitis may follow the acute form or may result from gradually developing obstruction to the onward flow of lymph. It is frequently observed in lymphangiomata. It is man- ifested by more or less dense edema of the area involved, with proliferation of the connective tissue, leading to a true fibrous in- duration. Lymphangiectasis and lymphangioma have been referred to in considering tumors. (See p. 344.) Tumors of the lymph-vessels, aside from those resulting from lymphangiectasis, either congeni- tal or acquired, are usually secondary, and are due to invasion of the adjacent tissues or primitive lymph-spaces. Exdotheliomata of the serous membranes are usually regarded as primary tumors VASCULAR SYSTEM. 529 arising from the endothelium, and are allied to, if not identical with, similar tumors the origin of which is the endothelium of smaller lymph-spaces or lymph-ducts. The extension of cancer by the lymph-spaces has already been considered. (See p. 319.) In connection with or independent of associated tuberculosis of the lymph-glands the process may involve the vessels. Exten- sion onward to the nearest glands or to the blood stream is possi- ble. When tuberculosis occurs in the thoracic duct, either as a result of mural implantation of tubercle bacilli, which have found entrance near the periphery of its distribution, or when an adjacent tuberculosis invades the structure, disaster due to systemic dissemination is prone to follow. 34 CHAPTER VII. MUCOUS MEMBRANES. Normal Structure.—A mucous membrane consists essentially of three parts: (1) Upon the surface, a layer of epithelial cells ; (2) a basement membrane, upon which these cells rest ; (3) the submucous connective tissue, in which ramify the blood-vessels, lymphatics, and nerves essential to the life and functions of the layers above. 1. The epithelial layer varies in two particulars: (a) in the character of the epithelium and (4) in the number of layers. When the function of the epithelium is largely protective in character, it is found in a number of layers; when secretion is the essential function, there is commonly but one layer: ¢. g., on the tongue numerous layers are found, while in the tubules of the stomach, the acini of glands, and the tubules of the kidney, etc., but a single layer exists. When, in addition to protection, pro- pulsive force is needed, or when the latter alone is demanded, the epithelial cells are supplied with cilia, as in the bronchi, Fallopian tubes, etc. In all mucous membranes possessing a stratified epithelial layer there lies immediately adjacent to the basement membrane a genetic layer analogous to the cylindric-cell layer of the rete mucosum of the skin. When the epithelial covering is simple (nonstratified), a distinct genetic layer may not be de- monstrable, as in the vesicular portion of the lung and the tubules of the kidney. Mucous membranes so constructed must, after exfoliation or destruction of a single layer, recoat the connective- tissue basement membrane from the viable cells at the margin of the area involved, exactly as the epithelial regeneration progresses over the surface of an ulcer undergoing repair. Epithelial cells possess the remarkable faculty of manufactur- ing from supplied, nutrition new chemic compounds not enisting, as such, in the pabulum supplied: ¢. g., the secretions of the salivary glands, the gastric follicles, the pancreas, the kidney, etc. Every mucous surface is, therefore, a laboratory, and this peculi- arity has given the membrane the name specialized, indicating that it possesses characters eminently its own. While all mucous membranes elaborate something, the most constant element 530 MUCOUS MEMBRANES. 531 is mucus; when altered by disease, it not uncommonly is the sole product of a tissue the function of which is the manufacture of a material to be further utilized by the economy, or the ex- cretion of an agent for which the organism has no further use ; and when such perversion of cell activity exists, the evidences are not slow to appear. As the function of the cell is dependent largely upon the pabulum supplied, and as this supply is con- trolled by the subepithelial layers, it becomes evident that the alteration of the basement membrane or of the submucosa must affect the activity of the superimposed epithelium. 2. The Basement Membrane (Membrana Propria)—This struc- ture is mesoblastic in origin, composed of fibrous tissue and, in some situations, a scant supply of unstriped muscle-cells. The thickness of the basement membrane varies greatly ; thus, in the mouth and nose it is of a discernible thickness, while in the wall of the pulmonary alveoli it is demonstrated with difficulty. When great changes in the volume and surface of the organ are likely to occur, the basement membrane may be thrown up in irregular ridges. By some it is claimed that the nerves and lymphatics penetrate this structure and present themselves immediately in the epithelial layer. It is not, however, probable that such is the case ; the basement membrane being the line between the con- nective and epithelial tissues, it seems extremely probable that it is merely pushed as a thin layer ahead of the nerve-fibers, and that the lymphatics open by stomata immediately beneath or into the genetic layer of epithelium when such exists. 3. The submucosa, or submucous connective-tissue layer, is of the greatest importance, and varies more than either of the preced- ing. In a part of the nasal fossz it is erectile; where an organ is subject to great alteration in surface, like the stomach, it is especi- ally abundant ; where it is not to be called upon for such altgra- tions in surface at such rapid intervals, it may be wanting, as in the uterus, where it is extremely scanty, if present at all. As the nutrition of the epithelium is largely dependent upon the condi- tion of the submucosa, lesions of this layer influence the func- tion and structure of the overlying membrane. In many mucous membranes collections of lymphoid follicles are to be found. For the most part these nodes occupy the submucosa, although in numerous situations the membrana propria contains a quantity of lymphoid tissue. The lymphoid elements may be somewhat diffuse, agminated in nodules, or grouped in patches. In certain infectious processes—for example, typhoid fever—the essential lesion involves, to the greatest degree, the lymphoid elements of the mucous membrane. 532 SPECIAL PATHOLOGY. DISEASES OF THE MUCOUS MEMBRANE. Hyperemia may be a physiologic process, as in the increased blood supply sent to the stomach during gastric digestion. (For Pathologic Hyperemia, see Inflammation of the Mucous Mem- branes. ) Congestion of a mucous surface is dependent upon conditions that interfere with the return or exit of the blood. Congestion is seen in the lungs and upper air-passages and in the alimentary canal, as a result of cardiac disease associated with interfer- ence in the onward flow of the blood, and in the stomach and intestinal mucous membranes in obstructive hepatic disease as well. It may or may not be the precursor of inflammation, and its permanency is dependent upon the condition that causes it. The function of the membrane is materially altered by the faulty metabolism that always attends a stagnant circulation. In time an increase in the fibrous tissue of the submucosa occurs, usually preceded, accompanied, and followed by a catarrhal process manifested in the epithelial layers above. In obstructive diseases of the lungs or heart the congestion of the gastric mucous membrane may be so great as to resemble the lesions resulting from poisoning. Hemorrhage from the mucous membrane occurs as a physio- logic process in menstruation; hyperemia and congestion not uncommonly terminate in hemorrhage, as in yellow fever, con- gestive malaria, and allied conditions. It is not always an evidence of any serious malady, as is shown by trifling epistaxis without apparent cause. In hemophilia and scurvy epistaxis is a common occurrence. As to severity, the hemorrhage may con- sist of the trifling escape of a few red corpuscles in an abundant mucous exudate (serosanguineous) or it may be alarming; the escaped blood may pour out on the surface as in epistaxis, or it may infiltrate the submucosa (interstitial or purpuric hemorrhage) and be found postmortem in the intestines or elsewhere as pur- puric spots. During life, in purpura, exposed or visible mucous surfaces may exhibit the discolorations in a typical manner. These spots, if large, may give rise to sloughing (gangrene) in very exceptional cases, and, if the patient survive, ulcers may develop, although this is rare; asa rule, if recovery occur, the blood is absorbed without any septic or gangrenous process. Atrophy of the mucous membrane. (See Inflammation of the Mucous Membranes.) Hypertrophy of the mucous membrane. (See Inflammation of the Mucous Membranes.) MUCOUS MEMBRANES. 533 INFILTRATIONS OF THE MUCOUS MEMBRANES. Pigmentary Infiltration.—(A) Pneumoconiosis.—Solid particles may gain ingress to or through the mucous membrane from the surface, as in laborers whose occupation exposes them to the constant inhalation of suspended solid matters: c. g., the inhalation of coal-dust by laborers in anthracite mines leads to a condition in the lungs known as anthracosis ; in the grinders of metal instruments, in nailers, etc., iron inhaled leads to an allied condition, known as siderosis (when the disease occurs in nail- ers, it is also known as xavler’s phthists); in stone-cutters and the ‘makers of grindstones, etc., the disease is known as lithosis or chalicosis. Similar infiltrations occur ‘in laborers in cotton Fic. 259.—SECTION OF THE LUNG, PNEUMOCONIOSIS.—(Rindfletsch.) The deposited pigment is shown in the connective tissue of the vesicular wall. and shoddy mills and in the handlers of grain. These pigment particles do not seem to be able to penetrate the stratified epithe- lium, but gain ingress further down in the air-passages ; the alveoli being permeable, the epithelial cells not arresting all the pigment, it enters the lymph-spaces of the basement membrane and from there diffuses by the lymphatic channels into the sur- rounding tissues. The deposited material finds lodgment in the following structures (Hamilton): in the subpleural and interbron- chial tissues ; in the peribronchial glands ; in the lymphadenoid interspaces of the alveoli. After the disease is well advanced in the pulmonary tissues, the substernal and general mediastinal glands may be infiltrated. Weigert asserts that the circulation may be reached by the pig- 534 SPECIAL PATHOLOGY. ment passing through the peribronchial glands, which attach themselves to the pulmonary veins, into which they may rupture. The presence of foreign solid material induces inflammation of the mucous covering—at first acute ; but from the continued ap- plication of the irritant, the changes incident to chronic inflamma- tion occur. In the deeper tissues fibroid hyperplasia ensues, with the abundant production of new fibrous tissue in the infiltrated areas. The catarrhal processes denude the epithelial protecting layer, and the lung tissue becomes exposed to the dangers of Fic. 260.—SECTION OF LUNG SHOWING CHALICOSIS.—(Schmaus.) a. Collection of infiltrated material Jodged in the pleura, c. A capsule of fibrous tissue has formed around it. a@’.Similar nodule in the lung tissue. Other nodules are shown. 6. Unaffected pulmonary tissue. c. Pleura. g,g. Blood-vessel, around one branch of which a nodule is forming. i. Interlobular septum, showing some thickening. infection by bacteria. Pyogenic organisms lead to infective in- flammation and softening in the fibrous areas, and eventually to cavity formation ; or, what is much more common in susceptible individuals, tubercular infection terminates the case. Aside from the lung, a similar pigmentary infiltration is occasionally seen in the vomer and turbinated bones. Occasionally, metallic substances taken as medicines or other- wise may be precipitated in or on the mucous membranes with which they come in contact. Examples of this are seen after MUCOUS MEMBRANES. 535 the administration of iron or bismuth. (See Pigmentary Infiltra- tion, p. 231.) (B) Pigment Deposit from the Blood.—Brown induration of the lung is in part a pigmentary infiltration, secondary to chronic congestion. The disease is most marked in the lung in chronic heart disease. The alveolar epithelium contains altered blood pigment, and pigmented cells are found in the interalveolar wall. The capillaries are distended, and the fibrous tissue of the lung is increased in amount. The lungs, on opening the chest, do not immediately retract; they are at first brownish-red in color, but on exposure to the air they become livid red from the oxidation of the excessive quantity of hemoglobin; as a result of the increase in fibrous tissue the organs are denser than normal, cutting and tearing with considerable resistance. Deposition of coloring-matter is found in other mucous mem- branes, where constant or repeated congestions occur, as in malaria ; the intestinal, gastric, and hepatic tissues showing the change in the highest degree. Fatty infiltration seems exceedingly rare, if it ever occurs, in a mucous surface. The author has never seen it. In the glands of the mucosa it may occur, and in the liver it is rather frequent. (See Fatty Infiltration of the Liver.) Albuminoid or amyloid infiltration, when the general dis- ease is present, invades the mucous membrane (submucous blood- vessels) of the stomach and intestines, rarely the gullet or the air-passages. (See p. 228.) Calcareous infiltration is usually secondary to chronic inflam- matory changes. DEGENERATIONS OF THE MUCOUS MEMBRANES. Granular degeneration, or cloudy swelling, occurs in the various epithelial structures as the result of high temperature, overwork, or beginning inflammation and necrosis ; it is seen to the best advantage in the epithelium of the kidney and liver. (See p. 241.) Fatty degeneration, or fatty metamorphosis, representing, as it does, a later stage of the granular process, will be seen when the latter condition has lasted for any length of time with persis- tent or progressively increasing causes. It has been noted in pernicious anemia. (See p. 242.) Coagulation necrosis is a composite degenerative process that occurs in mucous membranes under certain conditions. If the blood supply to an area be cut off, the area dies, if collat- 536 SPECIAL PATHOLOGY. eral nutrition be insufficient. Fibrin is found matting the ele- ments together, and, later, granular, fatty, and infective changes lead to its absorption, separation, or ulceration; the infective changes, if pyogenic, lead to ulceration or abscess formation, and occasionally, on mucous surfaces, a wide-spread lymphatic infec- tion finds entrance through an area that has undergone coagu- lation necrosis: ¢. g., streptococcus-infection of the lymphatics, accompanying or following diphtheria. Coagulation necrosis most commonly is associated with or follows infective processes, FIG, 261.— GRANULAR DE- Fic. 262.—FAaTTY DEGEN- Fic. 263—GRANULAR DE- GENERATION (CLOUDY ERATION OF THE LIVER GENERATION OF THE SWELLING) OF THE CELLS.—(Schmaus.) KIDNEY EPITHELIUM LivER CELLS. (CLoupy SWELLING) .— —(Schmaus.) (Schmaus.) such as typhoid fever, diphtheria, etc., but may result from emboli lodging in the vascular supply of the submucosa, the in- farcted area disappearing by coagulation necrosis. By some this process is called a hyatine or fibrinous transformation. Coagulation necrosis is also classed with the degenerations, but as it occurs almost exclusively in consequence of inflam- mation, it is separately considered. INFLAMMATION OF THE MUCOUS MEMBRANES. There is probably no tissue in the body so prone to inflamma- tory processes as the mucous membranes, and as these inflam- mations occur as the result of many and complex causes, and are modified by the character of the membrane, as well as by its function and by the cause, to describe each anatomic and eti- ologic form would require more time and space than is allotted to the present volume. For convenience of description the in- flammations are divided into the (1) catarrhal, (2) pseudo- membranous, (3) hemorrhagic, (4) gangrenous, (5) suppurative, and (6) chronic infectious. MUCOUS MEMBRANES. 537 1, Catarrhal inflammations are clinically spoken of as (@) acute and (4) chronic ; pathologically, they occur as more or less acute processes, becoming chronic by prolongation of one stage of the acute; or by repeated attacks changes are induced that are, in many instances, permanent. (a) Acute catarrhal inflammation arises as a result of many complex causes applied from without or exerting their influence from the circulatory side of the membrane. Inflammations of the mucous membrane result most commonly from some form of infection. Nearly all the acute infectious diseases—such as measles, scarlet fever, typhus fever, diphtheria, etc.—are accom- panied by, or may incite, a catarrhal inflammation of one or more mucous surfaces ; the same is true of the chronic infectious dis- eases, such as tuberculosis and syphilis, if they occur in the mucous membrane. The application of other irritants to the mucous surface is, next to infection, the most common cause, and embraces a multitude of subcauses: ¢. g., foreign bodies ; heat, as by hot air, steam, or a liquid such as hot water; irritant gases, as chlorin, bromin, am- monia, sulphurous acid; poisons, such as escharotics like the mineral acids, arsenic, etc., in dilutions too weak actually to de- stroy the surfaces with which they come in contact. Inflamma- tory conditions in the mucosz may also arise from irritants due to chemic changes in foods, whether the irritant be preformed when the food is taken or develop subsequently by fermentation or other change; as examples of these may be mentioned the ptomain poisonings and gastric catarrh. due to fermenting food. Alcohol is also a cause. While rapid thermic and barometric changes and excessive humidity are alleged causes, they probably act by altering the secretion or circulation, or both, thereby lessening the normal resistance to infection; it is not improbable that many of the previously given causes act in similar manner. Pure mycoses of the mucous surfaces may incite a catarrhal inflammation, often violent in‘character ; as an example of a mycotic infection, appar- ently restricted to the mucous membrane, thrush is most fre- . quently cited. Bright’s disease, rheumatism, gout, and allied dis- eases may be causes or predisposing factors. The young and the aged seem more susceptible to diseases of the mucous mem- branes than those in middle life. While it is not assumed that the foregoing include all the causes, the great majority may be embraced under some of them. All inflammations of the mucous membranes are accompanied by 538 SPECIAL PATHOLOGY. a catarrhal element, just as all cutaneous inflammations are asso- ciated with some tendency to desquamation. Morbid Anatomy.—In the first stage of the inflammation the surface is dry, or is lightly covered by a thick, sticky, adherent mucus; during life hyperemia is shown by the intense redness, which, in violent cases, may assume a dusky red; a little later will be added evident submucous edema, from the pouring out of serum in the submucosa. The histologic changes of this stage are engorgement of the submucous vessels and infiltration of the submucosa with serum and leukocytes ; the epithelium is cloudy, swollen, and desquamating. The morbid physiology is shown in excessive dryness, giving rise, in the vocal organs, to the husky, rough voice or toa cough; in the nose, to the ‘‘ stopped- up”’ feeling, which is intensified by the erectile tissue becoming far more distended by blood than the ordinary submucosa; in the stomach, the absence of secretion causes anorexia and nausea ; in the intestines, constipation, etc. Immediately following the first or dry stage—which may be brief or prolonged, rarely the latter—an abundant secretion of mucus occurs. The epithelial cells desquamate with the greatest rapidity, and the surface, instead of being dry and sticky, becomes flooded with mucus. The rapidly desquamating cells undergo fatty degeneration and desquamation with such promptness that the special secretion of the part is not elaborated: ¢. g., in the stomach, pepsin production is arrested; in the salivary glands, there is a lessened output of digestive ferment, and the production of mucus is excessive. The mucous membrane may fail to pro- duce, even in small quantities, the agent which normally it is the function of the mucosa to elaborate ; the apepsia of gastritis may be taken as an example. The inflammatory mucus is composed of the debris resulting from the degenerating cells, a varying quantity of serum, epithelial cells, free nuclei, and leukocytes ; more or less of the serum infiltrating the submucosa may osmose through the basement membrane, and. may be sufficient in quan- tity to justify the inflammation being called serous; in very severe cases a few red blood-corpuscles escape. The patient is usually relieved, the submucous circulation being reestablished and the perivascular exudate finding some exit by the surface and the lymphatics. If the cause be now withdrawn, the circulation gradually returns to the normal, absorption of the submucous exudate is completed, and restoration of the epithelial covering from the genetic layer of the basement membrane grad- ually takes place. Ulceration rarely occurs. The basement membrane is probably never destroyed by a simple catarrhal pro- MUCOUS MEMBRANES. 539 cess ; when such destruction results, it is most likely that, during the hyperemic stage, stasis occurred in some of the vascular twigs and an ulcer followed by the process of coagulation necrosis. (b) Chronic catarrhal inflammation of a mucous membrane results from the continuance of the last stage of the acute condi- tion or eventually persists after a succession of acute attacks. The chronic inflammations are due to more persistent causes, usually acting from within the body : e. g., the slowed circulation of chronic heart disease, the vascular and blood changes of Bright’s disease, gout, rheumatism, malaria, chronic alcoholism, etc., by weakening the resistance of the mucous surface, favor repeated attacks of infection or the persistence of a single attack once developed. The continued presence of irritants also favors the process, as in the forms of pneumoconiosis already men- tioned ; repeated libations also weaken the mucous membrane. Morbid Anatomy.—The continued infiltration of the submucosa with leukocytes and serum leads to permanent. alterations in tissue ; the leukocytes and fixed connective-tissue cells prolifer- ate and form embryonic tissue, and this, organizing into fibrous tissue and contracting, alters the nutrition of the submucosa so that proper functional activity of the epithelial surface is more or less permanently impaired. During the earlier stages the super- abundance of the submucous inflammatory products gives the membrane an appearance of thickening, and is often spoken of as an evidence of hypertrophy, or the inflammation is said to be hypertrophic ; the persistent softened condition of the tube may favor dilatation in this stage. Occasionally, from obstruction of ducts, mucous glands and follicles—as in the mouth, pharynx, and trachea—become distended and prominent. The prom- inence of these structures has given to the process the name follicular inflammation. As the inflammatory process advances,—grows older,—con- traction of the newly formed submucous tissue ensues, leading to lessened blood supply to the surface and to faulty or perverted function of the mucous membrane, associated with thinning— an atrophy, giving the present stage the name atrophic inflam- mation, by reason of the absence or diminution in secretion the process has been called dry catarrh. The hypertrophic and atrophic stages of the inflammation may be seen in the same subject at the same time, or the atrophy may be observed to follow the chronic inflammation without the development of very marked thickening, contraction exceeding in rapidity the process of infiltration. Whatever may have been the cause of the inflam- 540 SPECIAL PATHOLOGY. mation, the bacteria of decomposition find lodgment in the dry and slowly removed secretion, and fetid or poisonous products are developed. This is illustrated in ozeva and in neglected chronic inflammations of the ear. Sites-—Catarrhal inflammation may occur on any mucous membrane. Of course, the accident of location gives rise to differences in the character of the lesion, but the essential phe- nomena will be but variations of the stages and processes indi- cated. The site and name for some of the accompanying catarrhal FIG. 264.—SECTION OF WALL OF BRONCHUS, CHRONIC BRONCHITIS. Specimen hardened in corrosive sublimate, infiltrated eel pee stained with hematoxylin and eosin, and mounted in balsam. (From slide loaned author by Professor Harris.) a. Diagrammatic representation of the normal cylindric cells arranged normally. 6. The line runs just under the membrana propria into a mass of newly formed fibrous tissue, which extends downward to c. Just beyond the line from ¢ are several blood-vessels dis- tended by blood. ad. Mucous gland surrounded by considerable fibroid thickening of the submucosa. e. Cartilage. . Distended blood-vessel. g. Part of the chronically inflamed mucosa, showing inflammatory exudate and progressive fibrosis of the submucosa. The normal cylindric cells that should cover the area are seen to be advancedly degenerated and ee and those remaining are fragmented. To the left of the lower end of the line from g (1.5 cm.) is a depression which marks the exit point of a duct from one of the mucous glands. #. Denuded surface of the mucosa. Under this point the more recent inflammatory changes are less marked than at g. (%-inch objective, 1-inch ocular.) processes are as follows: Nose, rhinitis; mouth, stomatitis ; tongue, glossitis; tonsils, tonsillitis ; pharynx, pharyngitis ; trachea, trachitis or tracheitis; bronchus or bronchi, bronchitis; in the capillary bronchi and the air vesicles, catarrhal pneumonia (a condi- tion in which the catarrhal inflammation differs from that observed in other localities in the tendency to accumulation, in changes in the inflammatory products, and in other phenomena, which demand that the process be considered more in detail, as will be done when the forms of pneumonia are described); esophagus, esophagitis ; MUCOUS MEMBRANES, 541 stomach, gastritis, or, on account of the symptoms of indigestion, dyspepsia ; ileum, zéezts ; colon, colitis ; ileum and colon, zeoco- 4itis ; rectum and mucous surface of the anus, proctitis ; urethra, urethritis (when due to the gonococcus and involving the urethra, the process is called gonorrhea ; the same cause acting on other mucosz produces what is termed gonorrheal inflammation) ; blad- der, cystitis; ureter, ureteritis; pelvis of the kidney, pyelitis ; gall-bladder, cholecystitis ; biliary ducts, cholangitis. Catarrhal in- flammation occurs, no doubt, in the hepatic structure, but here, as in the lung and kidney, other associated phenomena demand that the condition be considered separately. 2. Pseudomembranous, Fibrinous, Plastic, or Croupous Inflammation.—Of the many names given to this condition, the first-mentioned is to be preferred. The process consists of an inflammation, attended by the development, on the surface of the mucous membrane, of a false or pseudomembrane composed of a solid or semisolid matrix and entangled cell elements. Causes.—That it can be induced without the intervention of bacteria is established, but that such is often the case is extremely doubtful. Heat, irritant gases, such as chlorin and ammonia, escharotics, which do not destroy the basement membrane, and allied agents, may possibly induce an inflammation attended by the development of false membrane. The local application of lactic acid and other medicaments has led to pseudomembrane formation. Of the many alleged microbic causes, two are estab- lished: (1) the bacillus of diphtheria and (2) a streptococcus identical morphologically to that found in suppuration and ery- sipelas. The pneumococcus has also been found as the only demonstrable organism present. Investigation into the cause of pseudomembranous rhinitis, which often lasts for months, has demonstrated, in a large percentage of the cases, the presence of the bacillus diphtheria. It would, therefore, appear that the chronic as well as the acute pseudomembranous inflammation may be, in some cases, at least, due to the Klebs-Loffler bacillus. Pseudomembranous inflammation of the intestine has been ob- served in pyemia and allied septic conditions ; also in pneumonia and typhoid fever, as well as in Bright's disease, cirrhosis of the liver, and cancer (Osler). The same writer has observed membranous bronchitis in pulmonary tuberculosis, and de- scribes a fibrinous bronchitis that arises independent of any known cause. Morbid Anatomy.—Two forms are recognized—an acute and a chronic; so far as known, the histology and process of devel- opment differ only in the chronic form occupying more time. 542 SPECIAL PATHOLOGY. Of necessity, the process begins as a catarrhal inflammation, with hyperemia and infiltration of the submucosa; liquor sanguinis passes through the basement membrane, and, reaching the sur- face, the necessary ferment is supplied by the bacteria or the epi- thelial cells (probably the latter, as the bacteria may be introduced FIG. 265.—VERTICAL SECTION THROUGH THE PSEUDOMEMBRANE AND PART OF THE WALL OF THE LARYNX IN PSEUDOMEMBRANOUS LARYNGITIS.—(Schmaus.) a. Cartilage. 5. Submucosa, rich in glandular elements, also swollen and with some lymphoid- cell exudate. c. Line of the membrana propria. d. Pseudomembrane made up of fibrin- ous elements. in which are entangled leukocytes and desquamated fragmented epithelial cells. e,e. Gland-duct. into the circulation of an animal without immediate coagulation of the blood), and coagulation occurs. That all pseudomem- branous processes are due to the deposition of a fibrin-forming body has been strongly controverted. It has been shown that the membrane contains mucin, and that it often fails to give the charac- MUCOUS MEMBRANES. 543 teristic stain reaction (p. 251) of fibrin. It must not be forgotten that on various mucosz rapid alteration in the fibrin may occur, and that digestive or like changes may rob it of its specific stain reactions. The fact that mucin is present in the membrane is not astonishing when the frequent entanglement of epithelial cells containing this body is considered. Still, it must be admitted that, with the tests at our disposal, membranes apparently mucig- enous and failing to give the fibrin reactions often occur ; that fibrin had no part in their formation is not so easily. established. The membrane may be fibrillar,—that is, the fibrin coagulated in fibrilla, or branching lines,—or the result of the coagulation may be a hyaline, homogeneous film, almost, if not quite, imper- ceptible. If the exudate be fibrillar, the membrane is clearly dis- cernible during life; if hyaline, it may be quite invisible, even in the throat. Intermediate between the fibrillar and hyaline forms of the membrane is a finely granular deposit, resembling to a certain extent fragmented cells rather than a distinct fibrinous product. The hyaline and granular forms of the membrane— particularly the hyaline—resemble in stain reactions the mucin- containing bodies. The membrane may be laminated, especially in chronic cases; two, three, or even four distinct layers may be shown on section. Sometimes these layers do not adhere to one another and may be separated or separable; the lamination is probably due to a layer of membrane forming, followed by a pause, in which mucus forms below, and then a second layer of membrane forms and another layer of mucus, and so on, until the cavity is freed of, or is filled by, the rapidly forming exudate. Occasionally, a rather extraordinary periodicity is observed in the appearance of the membrane; this is especially true of the chronic form, in which, exclusive of the pseudomembranous processes that may accompany menstruation, the membrane appears once each week, once each month, or at almost stated intervals. Its appearance may be attended by fever or other symptoms ; in the acute pseudomembranous inflammations this always occurs, but in the chronic types no symptoms, except the extension of the membrane, may precede, accompany, or follow its formation. At times a few red blood-cells may be found in the membrane. Exfoliation or casting-off of the membrane may occur as rapidly as it forms, or it may remain and be pushed off by devel- oping mucus or demanded functional activity. When removed, the surface of the basement membrane is exposed ; but that tissue is not destroyed, so that the pseudomembrane may be immediately reproduced, or, if the process be in a condition to terminate, the cause withdrawn, a catarrhal inflammation of the mucous surface 544 SPECIAL: PATHOLOGY. ensues, and recovery follows exactly as in simple acute catarrhal inflammations. The tendency to redevelopment of the mem- brane in chronic cases is manifested by repeated attacks, as in membranous endometritis and membranous proctitis. Of the Fic. 266.—FIBRINOUS CAST FROM THE BRONCHI, CASE OF CROUPOUS PNEUMONIA.* —(Schmaus.) chronic form occurring in the bronchi Osler says, ‘‘ We know of nothing which can prevent recurrent attacks,” Sites—There is no anatomic reason why pseudomembrane should not occur wherever catarrhal inflammation may develop. * Pneumonia is not a frequent cause of fibrinous bronchitis. MUCOUS MEMBRANES. 545 The acute pseudomembranous process is most frequent in the larynx, throat and nose, intestine, rectum, and middle ear, in the order named ; the chronic form is most common in the uterus, rectum, bronchi, nose, and intestine, in the order given. 3. Hemorrhagic inhammation is not common on mucous surfaces. It accompanies intense infective processes, such as pyemia and septicemia, and specific blood mycoses, such as anthrax ; it is not infrequent in violent intoxications, such as oc- cur in fulminating septic peritonitis secondary to a perforation in the alimentary canal (perforating gastric and duodenal ulcers) ; it may follow the application of escharotics, such as carbolic acid, etc. Morbid Anatomy.—There occurs a violent hyperemia of the mu- cous surface, attended by interstitial hemorrhage and plugging of the entire capillary area involved ; there may be hemorrhage on the surface of the membrane or into the inclosed cavity. In all cases that have come to the author’s knowledge death from other causes must have ensued, the present process being no doubt an important factor in hastening the fatalissue. Should the area involved be small, it is probable that the process could ter- minate in the gangrenous form. The stomach and intestine are most commonly involved when the accompanying septic process is in the peritoneum. The presence of a similar condition is recognized in diphtheria, and occasionally in smallpox, occurring in the throat, trachea, nose, or mouth. The condition differs from the simple purpuric interstitial hemorrhage in that the latter, if recovery takes place, is absorbed in most cases without destruc- tion or cicatrization of the mucous surface, while in the hemor- rhagic inflammation destruction invariably occurs and a scar usually forms to mark the site of the past process. 4. Gangrenous inflammation occurs as a result of the hemorrhagic process, or may arise from the same causes. It probably most commonly accompanies diphtheria, and hence at one time was known as aiphtheric inflammation, in contrast to the pseudomembranous or croupous inflammation—diphtheria and croup being assumed to be different diseases. We now know that the bacillus diphtheriz may cause both, and other inflamma- tory processes as well. The gangrenous sore throat and gan- grene of the fauces of the older writers, were types of this inflamma- tion, and were most likely cases of diphtheria. Gangrenous in- flammation also follows burns, scalds, escharotic injury, and trauma of the mucous surface. Embolic cutting-off of the blood supply to an area of the mucous membrane may lead to gan- grene. The author saw a most extensive gangrenous proctitis 35 5 46 SPECIAL PATHOLOGY. follow the continuous use of opium and morphin in a patient who used three to six grams of the latter each day by rectal suppository. Administration of mercury, antimony, or arsenic has been followed by gangrenous processes involving the mucous surfaces. It is probable that cancrum oris, noma, or gangrenous stoma- itis is due to a bacteritic factor, although Lingard’s bacillus is not generally believed to be the cause. (See Diseases of the 3 ie i 3, Be Fic. 267.— VERTICAL SECTION OF Mucous MEMBRANE, SHOWING DIPHTHERIC OR GAN- GRENOUS INFLAMMATION, FROM A CASE OF DySENTERY.—(Schmaus.) X 40 diameters (?). a,6. Muscular layers. c. Submucosa with widely distended blood-vessels, swelling, and leu- kocytic infiltration. d. Adherent portion of the mucosa in which degenerative and necrotic changes are in progress, and which fades off into e, the necrotic layer of the mucosa. /- Part of a gland in the necrotic tissue, the structure of the gland elements not having been, as yet, destroyed, although separating with the necrosed layer. g. Distended blood-vessel. Alimentary Canal; also Gangrene, p. 255.) This disease occurs in debilitated children, and usually follows one of the acute infec- tious diseases, and most commonly (fifty per cent. of the cases) measles. The necrotic processes affecting the mucosz and due to infec- tion by the streptococcus, or, less frequently, the pneumococcus, occasionally manifest a clearly gangrenous tendency. In tissues MUCOUS MEMBRANES. 547 weakened by any associated lesion, and often when reduced resistance is not demonstrable, other bacteria, as the colon bacil- lus, typhoid bacillus, and the staphylococci may give rise to gan- grenous processes. Morbid Anatomy.—Whether the initial cause be infection or not, the circulation is arrested in the area involved, and coagulation necrosis and gangrene ensue ; infection (primary, secondary, or multiple) is now assured, and breaking-down follows. As the necrotic area extends into the submucosa to a varying depth, the lymphatic system is widely opened and absorption of microbic poisons follows, with all the phenomena of grave septic intoxica- tion. The plugs that occlude the vessels become infected and break down, and hemorrhage may result ; or bacteria (most com- monly streptococci) gain ingress to the lymphatic system, and enlargement, and even abscess formation, in the nearest lymphatic gland may follow ; or, bacteria reaching the blood, may give rise to septicemia. The gangrene may assume phagedenic characters, followed by wide-spread destruction ; this is probably due to a sec- ondary infection, although, of course, it may have been primary, and is typified in noma—gangrenous inflammation of the labia in the female, and of the glans penis in the male. The initial process in the latter cases may have been a chancre or a chancroid. Sites.—Gangrenous inflammation is most common in the tonsils, pharynx, mouth, external genital organs, rectum, and colon, but is not infrequent on other membranes as well. The author has observed a severe gangrenous cystitis that followed prostatic abscess with urinary infiltration. 5. Suppurative and pustular inflammations occur on the mucous membranes in pyemia, septicemia, smallpox, and, rarely, in other infectious febrile processes. Erysipelas of the mucous membrane may be followed by suppuration. Diphtheria may, by rendering mixed infection possible, give rise to pus formation in the submucosa. Pyogenic infection of the submucosa results from abrasion or destruction of the protective epithelium, or from the accumulation of infective material in a mucous gland with obstructed duct ; the basement membrane of the gland being less resistant than the overlying tissues, rupture of the distended gland into the submucosa leads to infection and pus-formation. This is probably the process giving rise to suppurative tonsillitis and allied conditions. Abscess in the submucosa of the urethra may follow or accom- pany gonorrhea. Pus, being a connective-tissue product, de- velops in the submucosa, and secures egress, if left alone, by rupture, through gangrene or other necrotic process involving 548 SPECIAL PATHOLOGY. the basement membrane. Dissemination of the poison may occur through the lymphatics, as already stated when considering Gangrenous Inflammation. Suppurative processes are usually situated in localities liable to injury and accompanying infection, or in membranes rich in sulci affording lodgment for materials that subsequently lead to infection; aside from the specific diseases, such as smallpox, in which the suppuration occurs in the form of pustules in the mouth and adjacent membranes, the most common sites are in the rectum and the appendix. In the latter the infection and pus- formation in the submucosa may find less resistance to egress toward the peritoneum than the mucous tract, and hence appendi- citis not uncommonly gives rise to infection of the peritoneum. Similar obstructive conditions may occur in the Fallopian tubes, and rupture into the peritoneum may afford a more favorable route for the infection and emptying of the distended tube than escape into the uterine cavity. While the foregoing reference to appendicular and Fallopian disease is made under Suppurative Inflammation, it is not to be forgotten that accumulated catarrhal material contains abundant infectious agents, and that its escape will be as certainly followed by septic inflammation as though an abscess had poured its contents into the serous cavity. Suppura- tive and gangrenous processes are not uncommon in the appen- dix, and it does not seem probable that the Fallopian tube, once infected, should be less liable to the same processes. 6. Chronic infectious inflammations of the mucous mem- branes are of the greatest importance, and deserve the closest study. For the most part they, from the beginning, involve the essential function of the mucous surface by invading the submu- cosa. Included under this head are tuberculosis, leprosy, syphilis, glanders, actinomycosis, and rhinoscleroma. Tuberculosis of the mucous membranes, independent of pulmonary tuberculosis, is not a rare condition. In the upper air-passages it is a most frequent occurrence in tubercular patients, arising in the larynx, in the bronchi, and occasionally in the nose. Tuberculosis of the alimentary canal has been noted in every structure from the lips to the anus. The cause is the bacillus of tuberculosis, which has been considered in the section on Bacteri- ology. (See p. 180.) Morbid Anatomy.—Miliary tubercles develop in the submucosa —as a rule, around a blood-vessel ; and in marked cases of gen- eral miliary tuberculosis the tubercles can be seen at many points in the mucous membrane. A little later these tubercles coal- esce and, by the obliterative changes induced in the blood sup- MUCOUS MEMBRANES. 549 ply, cut off the nutrition to the basement membrane and epithe- lium above; by this time, through confluence, necrosis, and softening, a cheesy area develops, and with the breaking of the basement membrane the caseous material is discharged and an ulcer results. The long axis of the ulcer is usually transverse to the long axis of the membranous tube—a condition due to the blood-vessels being distributed circumferentially rather than longitudinally. External to the area of ulceration new fibrous tissue develops and contracts in many localities, giving rise to Fic. 268.—MARGIN OF TUBERCULAR ULCER OF THE INTESTINE. Specimen hardened in corrosive sublimate, infiltrated with paraffin, stained with hematoxy- lin and eosin, and mounted in balsam. a. Mucosa that,as it approaches the ulcer, is swollen and thickened, with Pasmuptited and desquamating cells. 6,d,and e. Tubercles situated in the submucosa; 4 and d, and a tubercle just under and to the right of d, each show a central giant cell. The tubercle e shows central softening and beginning casea- tion. Note the extensive infiltration of the submucosa with small lymphoid cells, which, immediately under the ulcer, at /, have invaded the circular muscle-fibers. c. The longi- ae layer, which, at g, contains a solitary tubercle. (4-inch objective; 1-inch ocular. stenoses. When examined in its earlier stages, the condition is known as miliary tuberculosis; and later, when ulceration has ensued, or in the stage of caseation, as ulcerative or caseous tu- berculosis, respectively. Rarely, calcareous changes may occur and, as a result of infiltration with lime salts, the tubercle becomes quiescent, the process being arrested. The anatomy of tubercles, their method of infection, etc., have been considered with tubercu- losis in general. (See Tuberculosis, p. 366; also tuberculosis of 550 SPECIAL PATHOLOGY. the various mucose and organs—alimentary canal, respiratory apparatus, liver, kidney, etc.) Leprosy of the Mucous Membranes.—In purely anesthetic leprosy the only involvement noted by observers is in the colon, where ulcers are said to develop without leprous tubercles. Tu- bercular leprosy is prone to attack the mucous membranes, especially the conjunctiva, cornea, larynx, and nose. The leprous tubercles, like those of tuberculosis, occur in the submucosa and around the blood-vessels ; as the process extends, the blood sup- ply is cut off by the obliterative changes in the vessels, and a fibroid area may result. Ulceration is not inevitable, or even frequent, as in the tubercle. Sometimes, however, the leprous infiltration is followed by pyogenic infection, softening, and ulcera- tion. The disease is due to the bacillus leprae, which has been considered when dealing with bacteria. (See p. 188.) (For pathology of leprosy see p. 379.) Syphilis of the Mucous Membranes.—In primary syphilis the lesion is far more frequent in the mucous membrane than in the skin. The submucosa becomes infiltrated with small round cells, in which epithelioid and giant cells may be found; the blood supply to the surface is cut off by obliterative changes in the arteries, and ulceration, or rather coagulation necrosis, ensues. The roseolar rashes of the secondary stage leave no discernible lesion. The mucous patches and ulcers are the result of coagulation or liquefaction necrosis, and occur in the mucosa of the tongue, pharynx, tonsils, palate, gums, and cheeks, and also on the mucous membrane of the anus and genital organs. The lesion of tertiary syphilis affecting the mucous membranes is the gumma occurring in the submucosa, developing like the previously considered infective granulomata, and, when untreated, usually breaking down and ulcerating. As the ulcer heals, con- tracting cicatrices give rise to strictures; these are most com- monly seen in the larynx, rectum, and esophagus. (See illustra- tions of syphilitic stenosis of the larynx and trachea, Fig. 271, chap. vi.) Should cicatrization occur, without ulceration, con- traction is equally sure to follow, but is less obstinate. (For pathology of syphilis see p. 363.) Glanders.—This disease, due to the bacillus mallei (p. 179), manifests itself usually in the nose as ulcers brought about by the development of glanders nodules, made up of lymphoid and epi- thelioid cells in the submucosa, which, breaking down, give rise to an ulcer. Inthe acute form gangrenous and septic phenomena not uncommonly accompany the process; in the chronic form MUCOUS MEMBRANES. 551 the ulcers may be mistaken for those due to protracted catarrhal, tuberculous, or syphilitic disease. The finding of the bacillus is essential to an accurate diagnosis. (For pathology of glanders see p. 375.) Actinomycosis is most common in the walls of the oral cavity, and is due to the ray fungus or actinomyces (p. 160), entrance being brought about by food containing the parasite coming in contact with an abrasion in the mucous surface. A granulation tumor develops; this is made up of structures re- sembling, in a crude way, the tubercle. The new formation is usually surrounded by a zone of proliferating connective tissue, which, in the jaw, has been mistaken for sarcoma. Sooner or later suppuration ensues. The diagnosis can be made only by finding the fungus in the tissues or discharges. (For pathology of actinomycosis see p. 377.) Rhinoscleroma consists in the thickening and tumefaction of the submucosa of the nose, rarely extending to the pharynx or larynx. The tumefaction usually begins inthe nose. The tume- fied areas are at first red or pink, and are very tender ; later they become white. The disease is due to a bacillus (see p. 178) found in the tumefied area, usually in the hyaline cells of the fibrous meshwork. The disease is rare in this country, and clinically resembles lupus. It is essentially chronic as to time, requiring years fully to develop. The tumors, which may occur on or in mucous membranes, are numerous, and, as certain localities seem liable to given tumors, it is thought best to record the neoplasms and cysts with the special pathology of each region. CHAPTER VIII. ORGANS OF RESPIRATION. Anatomic Divisions.—From an anatomic standpoint the organs of respiration are divided into the xose or nasal cavities, larynx, trachea, bronchi, and lungs. For physiologic considera- tion these are divided into the conducting part, including all but the lungs, in which the essential chemistry and vital phenomena of respiration occur. Incidentally, other functions are performed by the various parts of the whole, one function being accessory to another,—e. ., olfaction in the nose, vocalization, etc., in the larynx,—all aided by and dependent upon the various muscular and bony structures of the chest with its complex innervation. NOSE. Malformations.—The nose may be absent or may be repre- sented by a teat or a snout-like projection in cyclopia or synoph- thalmia—a malformation attended by a single orbital ‘cavity, centrally located, and containing one or two eyeballs in varying stages of development ; rarely, no eye may be present. Other malformations of the nose consist in absence of one or more muscles, clefts of the ale, deviations and faulty development of the septum, incomplete development of some of the bones enter- ing into the formation of the cavity, constriction of the nares, more or less complete, and clefts in the floor of the nasal cavity, usually associated with faulty development of the lip, palate, or other soft parts. (See Malformations of the Mouth.) Hemorrhage from the nose (epistaxis) occurs as the result of injury, either directly applied to the nasal structures, or falls and blows severely jarring the head; fractures involving the base of the skull; extreme plethora is asserted to be a cause ; hyperemia, either premonitory to inflammation or secondary to overexertion and forcible cardiac action, may be a cause; violent respiratory acts, like strangling, coughing, or sneezing ; intra- cranial congestion and hyperemia ; in the passive congestions of heart disease and obstructed return of blood from the head, as in tumors pressing on the veins of the neck; occasionally the hemorrhage is vicarious, as in arrested menstruation and suspended 552 ORGANS OF RESPIRATION. 553 excretion (¢. g., sweating and suppression of urine); severe vomiting may cause it; tumors, ulcerations, etc., of the nasal mucosa ; blood diseases, like hemophilia, scurvy, leukemia, etc. Epistaxis is also seen in the early stages of some of the acute infectious diseases, most commonly typhoid fever. Renal dis- ease, associated with a rise in blood pressure, and cirrhosis of the liver are also causes. Death from epistaxis is rare. The quantity of blood lost varies, but usually stops short of danger. When bleeding is repeated, there is not infrequently some local lesion to account for it, such as erosion or ulceration, most commonly situated on the septum. Varicosity of the veins of the nasal mucosa may sometimes be recognized. Inflammation of the nasal mucosa is spoken of as rhinitis. (For pathology of acute and chronic forms of inflammation and changes in inflammation of the mucous membranes see chap. vu, part 111, p. 536.) Any of the already described mucous membrane inflammations may occur in the nose. The acute catarrhal inflam- mation—acute catarrhal rhinitis, acute nasal catarrh, coryza—is the most common. Of the many conditions believed to be opera- tive in the production of acute catarrhal rhinitis, infection must be presumed to be predominant. Cold and exposure, irritants, such as ammonia, and superheated gases are said to be etio- logic factors. Cold and exposure are practically of secondary importance, probably only increasing the liability to infection. There is, at times, evidence that might lead to the belief. that the condition is contagious. The inflammatory process secondary to infectious diseases, such as influenza and typhoid fever, merits nothing more than mention. Fibrinous and gangrenous inflammations of the nose may be primary, but are more frequently associated with or secondary to a primary pharyngeal lesion. Pseudomembranous rhinitis is, in a certain percentage of cases, a nasal manifestation of diphtheria. This statement applies not only to the acute forms, but to the more chronic cases as well. Some of the latter show a persistent, rather long-continued pseudomembranous inflammation; the diphtheria bacillus is present in the exudate, and, in rare instances, may constitute the starting-point for an epidemic of diphtheria. Pseudomembranous rhinitis from other causes occurs, but is in- frequent. Chronic nasal catarrh usually follows repeated acute attacks of acute inflammation, although occasionally it comes on insidiously and may induce lesions of considerable magnitude before symptoms appear. Inhalation of irritants and dust and the presence of coarse foreign bodies are also causes. Various constitutional vices—such as chronic heart disease, tuberculosis, 554 SPECIAL PATHOLOGY. syphilis, anemia, etc.—are also important causes. The extreme aridity of houses heated by modern methods undoubtedly pre- disposes to catarrh, The presence of tumors, particularly of polypi, is said to favor the condition, or may be an im- portant determining cause; in other cases overgrowth of the mucous membrane may assume polypoid characteristics, a fact supporting the view that the inflammation leads to tumor forma- tion. Inflammatory processes may be hypertrophic or atrophic, and may or may not be associated with fetid discharge (ozena). There is a form of nasal inflammation that has received the name purulent rhinitis, by reason of the pus-like character of the dis- charge; an inflammation of this kind not infrequently follows the presence of foreign bodies, nasal tumors, suppurative pro- cesses in accessory sinuses, acute infection, such as gonorrhea, and the ulcerative stages of the chronic infections, particularly glanders, tuberculosis, and syphilis. Tuberculosis and syphilis are the most common chronic infec- tious inflammations; g/anders usually manifests itself here, as does riinoscleroma ; leprosy and actinomycosis may occur. The mucosa being continuous with that of the sinuses of the superior manilla, the frontal and ethmoid bones, and by the Eustachian tube with the middle ear, inflammation once estab- lished in the nose may extend to these structures, where, by reason of faulty drainage and inaccessibility, chronic processes ensue. The sinuses lying in proximity to the brain may afford means for intracranial infection, as seen in middle-ear disease lead- ing to cerebral abscess, and in the tubercular meningitis asserted to follow tuberculosis of the nasal cavities and their appendages. Tumors.—dAdult Epithelium — Adenomata of the nasal mucous membrane occur more commonly as the pharynx is approached, but, on the whole, are not frequent; they are mostly cystic, owing to inclusion of a mucous gland, ordinarily by inflammatory tissue. Papillomata or warts occur in the vestibule. A hairy papilloma resting on a base of fat (lipomatous tissue) has been described. It is believed to be congenital (Arnold). Carcinoma of the nose is rarely primary, usually extending to the nasal cavity from the mouth or face ; it is generally of the epithelioma- tous type rather than glandular. Fidromata, chondromata, osteo- mata, and myxomata occur. True myxoma is rare, but fbromyx- oma and pure fibroma are of not infrequent occurrence ; xasal polypi are most commonly one of these two varieties. Sarcomata occur in the nasal cavity, arising from the fibrous tissue of the submucosa, the periosteum, or, rarely, the bone; they occasion- ally develop in the sinuses: ¢. g., the antrum of Highmore. ORGANS OF RESPIRATION. 555 Erectile tumors (telangiectatic polypi) are made up of numer- ous thin-walled blood-vessels embedded in a fibrous, mucoid, or adenomatous matrix containing more or less myxomatous tissue. They are infrequent. Postnasal Adenoids.—There must be some doubt as to the advisability of regarding these enlargements as true tumors, and as the new growth is most frequently the result of an increase in preexisting lymphoid tissue, the term postnasal adenoid hyper- trophy has been applied. The disease is one of infancy and childhood, and is most frequent in tuberculous families, com- monly associated with some form of rhinitis, with defects of de- velopment in the osseous walls, causing stenosis, and with con- comitant pharyngeal or postnasal catarrh. The growth is most marked on the posterior rhinopharyngeal wall. The masses are usually sessile, with uneven, granular, or lobulated surfaces. Histologically, the new growth is composed of lymphoid tis- sue. So faras the growth itself is concerned, it usually atrophies and disappears at or about puberty. In the mean time, however, the mechanical interference with respiration, and the associated catarrh, induce a drain on the patient’s general health, embarrass respiration, and may be accompanied by tuberculous infection ; involvement of the Eustachian tube and an infective otitis media, with consequent deafness, may also occur. Rhinoliths are calcareous masses occasionally found in the nose ; they arise from the deposit of lime salts around a nucleus, usually a foreign body, or, rarely, from inspissated secretion. Anosmia, or loss of the sense of smell, may be caused by (1) central lesions or (2) chronic catarrhal thickening, and con- traction may pinch the filaments of the nerve, and thereby de- stroy them ; a similar result may follow periosteal thickening, as seen in syphilis. When the sense is not destroyed, but perverted, the term parosmia is used. Hyperesthesia of the olfactory nerves, also called hyperosmia, is usually dependent upon central lesions or is a part of some neurosis. Exclusive of the abundant exu- date seen in inflammations, and independent of any recognizable change in the membrane of the nasal cavity and accessory sin- uses, there is, at times, a most marked serous discharge, consti- tuting a true rhinorrhea. The cause of the condition is not known. LARYNX AND TRACHEA. Normal Structure.—The epithelial layers of the mucosa vary as to depth and variety of epithelium ; the epiglottis and the true cords are covered by squamous epithelium, lines of which 556 SPECIAL PATHOLOGY. extend between the epiglottis and cords. The greater area is covered by ciliated epithelium. Malformations.—Adsence of the larynx is rare. Occasion- ally, it is small and poorly developed (Aypoplastic), a condition said to attend testicular hypoplasia and to follow castration. Abnormal largeness is at times noted. Combinations of the last-named conditions, giving rise to asymmetry, are more fre- quent. The ventricles may be abnormally large, or aberrant sinuses or pouches may extend into the perilaryngeal tissues, giving rise to a condition known as emphysema of the neck. From faulty union of the branchial arches fistulas may result. Clefts and fissures of the epiglottis occur. Defects in the laryn- geal cartilages are sometimes observed, but are rare. Hemorrhage from the larynx accompanies injury, severe in- flammations, tubercle, and tumors, particularly the highly vascu- lar papillomata and carcinomata ; it rarely occurs from vascular distention and vicarious function. Hemorrhages into the sub- mucosa, and even on the free surface, are sometimes present in scurvy, leukemia, pernicious anemia, and allied blood dyscrasias. Suffocation and strangulation are also causes. Intense hyper- emia and extreme congestion may cause laryngeal hemorrhage. Hyperemia occurs in the initial stage of inflammation, after violent exercise, inhalation of irritants, etc. Congestion is noted in heart disease and lesions obstructing the return of blood from the larynx, as goiter and mediastinal tumors. Inflammations.—Inflammation of the larynx is called laryn- gitis ; of the trachea, trachitis or tracheitis. Catarrhal, pseudo- membranous, and gangrenous inflammations occur in the order given ; the last is infrequent, and the catarrhal is common. The catarrhal inflammations may be either acute or chronic, the former depending upon exposure, inhalation of irritant gases, extension of inflammation from adjacent mucose, infections and infectious diseases, such as measles, influenza, etc. Follicular distention and superficial erosions occur, but are infrequent. The vascular distention of acute inflammation, with even slight edema, interferes with the function of the vocal cords, narrows the orifice, and is the anatomic basis for the so-called spasmodic laryngitis, which is also known as spasmodic, false, or catarrhal croup. Chronic catarrhal laryngitis is usually a sequence of re- peated attacks of acute inflammation. It is favored by continu- ous exposure to irritation, by the presence of constitutional vices,—such as syphilis, tuberculosis, contracting kidney, gout, etc.,—and by local disturbances of nutrition, such, for example, ORGANS OF RESPIRATION. 557 as are seen in the stagnant circulation of chronic heart disease and in long-continued pulmonary inflammation, emphysema, etc. Epithelial thickening (pachydermia laryngis) of the vocal cords, submucous cellular infiltration, and even papillomatous excres- cences may result. Rosenberg regards singer’s nodes as a result of inflammation involving the duct of Frankel’s glands, and not true epithelial indurations (pachydermia), as believed by Virchow. Pseudomembranous_ inflamma- tion is almost exclusively depen- dent upon the bacillus of diph- theria, which here rarely induces the gangrenous lesions seen on the pharynx and tonsils. Hemor- rhagic inflammation is less frequent. Suppurative inflammation occurs as pustules, as in smallpox, or as a purulent infiltration of the sub- mucosa, most commonly secondary to an antecedent edema of the sub- mucosa. Pus-formation may be diffused in the submucosa or may be circumscribed (abscess), in which case it may rupture into the lar- ynx, infiltrate the perilaryngeal tis- sues, or dissect into the esophagus. If evacuation be established and drainage secured, repair may fol- low. Catarrhal, pseudomembran- ous, and gangrenous inflammations have been noticed in typhoid fever, Fic. 269.—Tusrrcutrar ULcER oF THE Mucous MEMBRANE OF THE as have the suppurative and peri- TRACHEA. VERTICAL SECTION . “ 3 OF THE TRACHEAL WALL.— chondroid inflammations. (Schmaus.) X10 diameters. The chronic infectious inflam- K- Cartilage. ¢,e. Epithelial layer of 4 the mucous membrane. ¢. Tuber- mations are extremely prone to cles in the mucous membrane. . “0 {oubrntcersy) g. Ulcer extending invade the larynx; syphilis and rom ¢ to e. tuberculosis are the most frequent, but when leprous infection or glanders occur, the larynx rarely escapes. (For morbid anatomy, etc., see chap. vill, part 0; also chap. vu, part ur.) Primary tuberculosis is rare, but does occur; tubercular ulcers usually are posterior, and begin low and ascend, in contradistinction to syphilis, which is higher and descends ; cicatrization and contraction take place in syphilis, 558 SPECIAL PATHOLOGY. but rarely in tuberculosis. Although rare, syphilitic and tuber- cular ulcers may be side by side * and differentiation of the gross lesions may be impossible. The finding of anatomic tubercles containing the bacillus affords the necessary diagnostic evidence. Fic. 270.—PERICHONDRITIS WITH LARYNGEAL ULCERATION.—(Specimen from patient dead 3 of typhoid fever.) The area shown near the center indicates the outline of an ulcer, the floor of which was smooth and healing. Near the center is seen a black necrotic mass of exfoliating car- tilage. Perichondritis, or inflammation of the perichondrium, occurs as the result of acute inflammations of the mucosa; more com- monly, however, it follows tuberculosis, syphilis, or inflammation, * Griffin, ‘‘ The Laryngoscope,’’ No. 4, 1897. ORGANS OF RESPIRATION. 559 extending from surrounding structures ; typhoid fever, smallpox, and, less frequently, other acute infectious processes may cause it. Pus forms in the perichondrium, escapes through the sub- mucosa and mucosa, and an ulcer follows in which exfoliation of the cartilage takes place; the necrosed cartilage falls into the larynx and is expectorated, or it-may, acting as a foreign body, reach a bronchus, or, lodging in the air-passage at any point, may give rise to acute obstruction. After exfoliation, in non- tubercular cases, the ulcer tends to heal. Calcification of the cartilages is seen in the old, rarely in the young or middle-aged. Edema of the glottis is in most cases aninflammation. Acute edema follows or accompanies (1) inflammations of the mucosa, as already described ; (2) inflammations of adjacent tissue (¢. g., pharynx) ; (3) erysipelas and other infections not included in the previous list. It tends toward suppuration, and is therefore a true inflammatory process, probably an infection of the sub- mucosa, Chronic edema may follow or precede the acute form, or may arise independently, and this is by far the most common. It may occur as a result of venous distention, as seen in valvular heart disease, and from compression of the veins returning from the larynx by tumors, cysts, goiter, etc. Pulmonary emphysema, dropsical affections associated with kidney diseases, or obstructive heart lesions may terminate fatally through an attack of edema of the glottis ; chronic infectious processes in the vicinity are not in- frequently associated with a mild degree of edema. In either form édema may threaten life by occlusion of the passage—in- flammatory stenosis. Stenosis of the larynx occurs in two forms, exclusive of the malformations—(1) functional and (2) organic. Fanctional stenosis results from paralysis of the muscles that open the larynx or from spasm of those that close it. The former most commonly results from faulty innervation, due to central disease of the nerve, trunks, or brain, or from pressure on the nerves by tumors, aneurysms, etc. That paralysis may follow degeneration of the muscle without antecedent nerve change seems doubtful. Organic stenosis follows contraction in healing ulcers, notably the syphilitic ulcerations ; laryngeal tumors, edema, and inflamma- tions; pressure from without, as in tumors and enlargements of the surrounding glands, and aneurysm; hemorrhage into the mucosa, fracture, or other injury to the laryngeal structures, as in throttling. Laryngeal obstruction depending upon the presence of false membrane, congenital hypoplasia, and foreign bodies is 560 SPECIAL PATHOLOGY. not correctly considered among the stenoses, although the influ- ence upon respiration is practically the same. Tumors of the Larynx.—Adult Epithelium.—FPapillomata are by far the most common. They may consist of fibrous as well as epithelial increase in the papilla, and may be soft and dendritic, or they may be pachydermatous or dense from the FIG. 271.—TRACHEAL AND PARTIAL LARYNGEAL STENOSIS FOLLOWING CICATRIZATION OF A GuMMa. The syphilitic lesion has evidently destroyed parts of two tracheal rings, and extended upward into the larynx. The cartilage on the right shows results of a slowly progress- ing Se aatitiss with beginning necrosis, although the overlying mucous membrane is not involved. thickening and subsequent hardening. All forms of papilloma are likely to undergo transformation into cancer. Limbryomc Epithelium.—Epithehoma involving the larynx is usually of the squamous type, and may be dendritic, like papil- loma. Papillomata occur in childhood and in adolescence ; the cancer, in middle life or later. The cylindric-cell and tubulated ORGANS OF RESPIRATION. 561 varieties of epithelioma also occur. In rare instances a papilloma may accompany or may even follow a cancer, while the develop- ment of cancer from papilloma is not uncommon. Adult Connective Tissue —Fibrous polypi, like those described in the nose, both hard and soft, may occur in the larynx. Like the papilloma, the location is most commonly on the vocal cords. Myxomata are rare in the larynx, but may occur. Chondromata have been observed. Embryonic connective-tissue tumors (sar- comata) are exceedingly rare in the larynx and trachea. BRONCHI. Normal Structure.—The bronchi consist of a series of tubes lined by columnar epithelium, which is ciliated down to the ter- minal tubes, where it becomes cuboid and nonciliated; the wall of the bronchus is composed of fibrous and elastic tissue and of a small quantity of unstriped muscle, the latter being most abundant where the cartilaginous rings fail to surround.the tube completely. The mucous membrane of the larger bronchi con- tains numerous mucous glands. Malformations.—When arrest of development has occurred previous to the structural completion of the lung, the bronchi may terminate as blind pouches or may be absent. Congenital narrowing or the reverse may be found. (See Bronchiectasis, Pp. 563.) Hyperemia and congestion manifest themselves under the same conditions and with the same changes as have been else- where noted in the trachea, etc. Hemorrhage.—(See Hemoptysis, p. 567.) Inflammation.—Catarrhal inflammation, both acute and chronic, is one of the most frequent diseases of the bronchi. In the larger tubes the glands of the mucosa may stand out promi- nently, constituting a follicular bronchitis. When the inflamma- tory products are abundant, clear, serous fluids, the name dron- chorrhea is given ; bronchoblennorrhea is the term applied when a puriform expectoration is present. These probably represent only different stages of the inflammatory process. Putrid or fetid bronchitis is due to decomposition of the bronchial secretion by saprophytic bacteria ; it is usually associated with bronchiectasis, the dilated cavities affording storage sufficient to permit the de- velopment of decomposition. Similar facilities are present in pulmonary gangrene, in empyema with perforation of a bronchus, in tubercular cavities, etc. By some it is held to be due to a specific organism ; by others, to the colon bacillus. Actinomyces, 36 562 SPECIAL PATHOLOGY. oidium albicans, and possibly other organisms may bring it about. Chronic bronchial inflammation tends toward the development of fibrous tissue around the bronchi—the peribronchitis chronica of German writers; in other cases atrophic changes occur in the mucosa; bronchiectasis may follow ; emphysema is an almost constant accompanying lesion. Of the chronic infections, tubercu- losis is the most common ; it may occur as a miliary process or as a caseous area around the bronchus, which, breaking down, forms a cavity which can be only with great difficulty differentiated from bronchiectasis. Gangrenous and hemorrhagic inflammations FIG. 272.—CHRONIC CASEOUS BRONCHITIS, TUBERCULOUS BRONCHITIS, CASEOUS SOFTENING OF THE BRONCHIAL WALL, WITH THICKENING OF THE PERIBRONCHIAL TISSUE, PERI- BRONCHITIS CHRONICA.—(Schmaus.) a. Bronchus with thickened and caseous wall surrounded by a layer of fibrinous tissue. Several other bronchi are shown, but representing slightly different degrees of the pro- cess. 6. Transverse section of interlobular septum. c. Blood-vessel. of the bronchi are rare, and follow or accompany pulmonary gangrene, the inspiration of powerful irritants, etc. The jibrinous or pseudomembranous inflammations of the bronchi are usually chronic, although an acute form is abundantly present in laryngeal diphtheria, in fibrinous pneumonia, and, less commonly, in other acute infectious diseases. (For pathology of the acute, chronic, and infectious inflammations of mucous mem- branes see p. 536.) Suppurative inflammation of the peribronchial lym- phatics may follow pleurisy,—more especially the suppurative ORGANS OF RESPIRATION. 563 form (empyema),—abscess, gangrene, septicemia, pyemia, and allied infectious diseases. It is not recognizable during life, and postmortem shows as a purulent infiltration of the peribronchial tissues, at times extending to the lymphatic glands; if not due to, it is usually followed by, septicemia or pyemia. (See Pulmo- nary Suppuration, p. 574.) Pigmentary infiltration of the bronchial mucosa and the effects of congestion have been studied. (See Infiltrations of the Mucous Membranes, p. 533.) Stenosis of the bronchi may be due to swelling of the mucosa (bronchial turgescence, such as occurs in bronchial asthma); to occlusion, more or less complete, by fibrinous exudate or mucus; to pressure from peribronchial exudates, as intuberculosis, or to contraction of newly formed cicatricial tissue, as in syphilis ; to intrabronchial tumors ; or to pressure from neoplasms of the lung or peribronchial glands or from aortic aneurysms, mediastinal tumors, and tumors of the esopha- gus. Foreign bodies may obstruct or occlude the bronchi. * Atelectasis and atrophic or inflammatory changes occur in the lung tissue beyond the point of stenosis, while bronchiectasis may develop in the bronchus back of the strictured point. Bronchiectasis, or, dilatation of a bronchus, occurs in two forms—(z) congenital and (2) acquired. (1) The congenital form is unilateral, usually general, affecting many or all of the bronchi of that side (dronchiectasis universalis, Grawitz). The condition is a tubular or cylindric dilatation of the bronchial tubes. It is very rare, and the cause is but poorly understood. (2) dAcguircd bronchiectasis arises as the result of chronic bronchial inflamma- tion, interstitial pneumonia, atelectasis, adhesions of the pleura, tuberculosis, peribronchial inflammations, usually tubercular, or accumulated bronchial secretions. Two conditions are necessary in bronchiectasis: (1) Some lesion leading to softening of the bronchial wall; (2) a distending force. All the foregoing offer these, and any condition inducing them may bring about dilata- tion. The inflammatory conditions soften the walls, and the attending cough offers the distending force ; where an area of the lung is collapsed, the bronchus delivering air to that part is sub- jected to inspiratory distention, and commonly dilates. A num- ber of observers have described a form of bronchiectasis involv- ing the bronchioles, and hence called bronchiolectasis. The condition is said to develop acutely, and hence is termed acute bronchiectasis, or bronchiolectasis. As a tule, the bronchiectatic cavities are fairly evenly distrib- uted within the lung. In over fifty per cent. of the cases but 564 SPECIAL PATHOLOGY. one lung is involved. Any part of the lung may contain dilated bronchi, but apparently they are most frequent in the lower and middle lobes. Statements to the contrary probably arise from failure to differentiate the cavities of tuberculosis from bronchi- ectatic cavities. The bronchiectatic cavity may be uniform, cylindric, or tubular, as in the bronchiectasis universale ; fusiform, or spindle-shaped, saccular, globular, or irregular in outline ; the last is found in bronchiectasis due to interstitial pneumonia. As one part of the bronchial wall is nearly always weaker than some other point, the cavity is rarely symmetric. The cavity of a dilated bronchus may be eight centimeters, or even larger, in diameter, and from that size down to almost inappreciable dilatation. The cavity may be differentiated from a tubercular cavity by the following points : In bronchiectasis the wall may be smooth and lined with epithelium, and may contain, at points, if not throughout, rem- nants of the normal bronchial wall; if the cavity be roughened by ulceration, it is at the most dependent point. The points of entrance and exit of the bronchus may be seen. No shreds of blood-vessels or of other bronchi or bronchioles are to be seen in the wall or extending into the cavity. Recognition of the cause may aid in differentiation. The absence of tubercle bacilli and of anatomic tubercles in the wall, of course, excludes tuber- culosis. The cavity contains accumulated secretion, and this is proba- bly fetid, owing to saprophytic infection and decomposition. Ulceration may open the peribronchial lymphatics and infection of the pulmonary tissue may ensue, with pulmonary abscess, gangrene, etc. Tumors of the bronchi are exceedingly rare as primary growths. LUNGS. Normal Structure.—The bronchi, by dichotomous division, eventually terminate in the infundibula, around which are ar- ranged the air vesicles. The ciliated epithelial cells lining the bronchi become low, nonciliated, and eventually flat polygonal cells, which, in turn, are transformed into flat, pavement-like cells in the air vesicle. The wall of the air vesicle is composed of fibrous and elastic tissue, in which ramify the capillaries derived from the pulmonary artery. The nutrition is dependent upon the bronchial circulation. Malformation.—Absence of a whole lung or of a part of a lung occasionally occurs ; absence of both lungs has been ob- ~ ORGANS OF RESPIRATION. 565 served. Additional lobes have been found present in numerous instances. Aberrant lobes, or even a miniature lung uncon- nected with any normal or patulous air-passage, have been observed. Hypoplastic or underdeveloped lobules or rarely lobes have been found, and the reverse may occur. Arrest of development involving part of a lung, or it may be all of one lung, is usually associated with the corresponding overdistention of the developed portion of the lung, constituting a compensa- tory emphysema. (See Emphysema.) CIRCULATORY DISTURBANCES. Hyperemia (active congestion or active hyperemia of some writers) occurs in violent exercise, in the initial stage of acute inflammations of the lungs or pleure, in the chill or cold stage of malarial and septic paroxysms, and in allied conditions that incite powerful cardiac action ; excessive heat or cold is also said to favor hyperemia; pulmonary hyperemia is said to precede death from disease of the coronary arteries; disease and injury of the pons or medulla are possible causes. Localized hyperemia occurs around diseased areas that interfere with the circulation, such as infarction processes, circumscribed catarrhal or croupous pneumonia, and areas invaded by any of the chronic infectious diseases to which the lung is liable. If the lesion be purely a hyperemia, the condition to be noted in the initial stage of fibrinous pneumonia will be found. Congestion (passive hyperemia or passive congestion of some writers) is dependent upon the slowing of the pulmonary circula- tion from (1) deficient force from the right heart ; (2) from non- aeration of the lung; (3) from backing of blood from the left heart, as in valvular disease of the mitral orifice, associated with obstruction or regurgitation, either condition permitting of in- creased blood pressure within the lung. In the vast majority of cases more than one of these causes will be found acting. Two forms of pulmonary congestion are constantly observed—(1) brown induration and (2) hypostatic congestion. Brown indura- tion has already been referred to. (See p. 535.) It results from disease of the left heart most commonly, but may be brought about when any obstacle beyond the pulmonary capillaries im- pedes the circulation. Pulmonary edema is most commonly associated with chronic congestion. Hypostatic congestion arises as the result of weakened heart action, deficient respiration, and the influence of gravity. It is found in febrile conditions (¢. g., typhoid fever), in the aged, and 566 SPECIAL PATHOLOGY. after prolonged stay in the recumbent posture, as when a fractured limb is treated with the patient prone. This form of congestion has also been noted in morphin- poisoning and associated with, or following, disease and injuries of the brain; in the latter case the condition is further favored by deficient movement or innervation of the side affected, and will therefore manifest itself most likely when paralysis is present. All forms of coma favor the development of hypostatic congestion, Being influenced by gravity, the dependent part of the lung shows the change; this is most commonly the posterior part. The affected area is dark in color, often almost black, much heavier than normal, pits on pressure, and when cut into, blood or bloody serum streams from the cut surface. The blood may be retained in the vessels and the serum in the intervesicular structure, in which case the affected area floats in water; not uncommonly, however, the serum, and even some blood, per- meates the vesicular wall and involves the air vesicle, in which case areas may be selected that sink in water. This latter con- dition has been called splenization and hypostatic pneumonia. When hemorrhage or infiltration of blood occurs in the vesicular wall, the changes observed may resemble those seen in diffuse pulmonary apoplexy. The anatomy, as just given, indicates the histology. In poorly marked cases, after hardening, very slight histologic changes may be evident; a few leukocytes and mucous cells in excess will be present in the vesicles ; the vesicular epithelium will be found cloudy and often desquamating. In more marked cases, in addi- tion to the foregoing, the vesicles will contain more or less blood; and infiltration of the pulmonary connective tissue by serum and blood may be demonstrable. Pulmonary edema occurs, as already indicated, in any pro- longed hyperemia or congestion, certainly in the latter. It is brought about by a slowed or impeded circulation, aided by some poorly understood alteration in the blood, and, probably, an associated degenerative change in the capillary walls. It also accompanies blood dyscrasias, such as the various forms of anemia, Bright’s disease, and cancerous disease of the lung or mediastinum, and occurs as a terminal event in the death agony when the latter is, from any cause, prolonged. Why it does not always occur in congestion, and in the other conditions just given, is not apparent. Aside from the general edema, a local process, similar in kind, manifests itself around neoplasms, infarction, and inflammatory and tubercular areas in the lung, and is spoken of as collateral, circumscribed, or localized edema. ORGANS OF RESPIRATION. 567 Morbid Anatomy—The edematous lung is swollen, wet, and boggy in appearance, pits on pressure, collapses slowly, if at all, and is heavy, but does not sink in water ; on section, serum flows from the cut surface, and if congestion be present, the serum is bloody. Hemoptysis (Spitting of Blood; Bronchopulimonary Heim- orrhage)—Causes.—(1) Trauma; severe falls; blows upon the chest ; wounds of the lung, bronchi, etc. (2) Tuberculosis: (a) primary, miliary, or ulcerative lesions of the passages ; (6) rupture of vessels, whether aneurysmal or not, in cavities. Tuberculosis is by far the most frequent cause. (3) Laryngeal, tracheal, or bronchial ulceration, arising from any cause, opening a bronchial artery. Bronchiectasis is rarely a cause. (4) Pulmonary conges- tion, such as accompanies valvular heart disease; hyperemia, as in the stage of engorgement of acute fibrinous pneumonia. (5) Malignant tumors of the lung or tumors involving the bronchi, trachea, or larynx; papillomata of the larynx, rarely from other simple neoplasms. (6) Hemoptysis has been ob-. served in leprosy. (7) Necrotic processes in the lung: @. g., abscess, and notably gangrene. (8) Aneurysm (a) of the pul- monary artery or its branches, as occurs in tubercular cavities ; (0) of the aorta ; (c) of the innominate artery ; (d) of the internal carotid ; (e) of the subclavian. (g) Vicarious hemorrhage. (10) Hemoptysis in arthritic diathesis. (11) Blood dyscrasias, as seen in purpura and scurvy. (12) Parasitic hemoptysis, or endemic hemoptysis, a disease common in China and Japan, due to an in- vasion of the lung with the distoma westermanni or pulmonale. (13) In a certain number of cases no assignable cause can be found ; in a few of these the hemorrhage may recur a number of times without any discernible organic lesion preceding, accom- panying, or following it. To this class properly belong vicarious hemoptysis, as well as that which may accompany pregnancy ; in the latter instance cases are recorded in which successive preg- nancies have been accompanied by recurring hemoptysis. The effect of hemoptysts may be local or general. Locally, a slowly manifested hemorrhage may be aspirated into the air ves- icles and gradually inundate the bronchial system ; a marked or severe hemorrhage may rapidly inundate and be immediately fatal. The hemorrhage may develop so slowly that no phe- nomena during life may be observed, and postmortem much of the lung may be found filled with the effused blood. If large cavities are present in the lung, a fatal hemorrhage may fill them and cause death without any blood-spitting. The general phe- nomena are those of shock. The lung postmortem will be found 568 SPECIAL PATHOLOGY. more or less distended or inundated with blood if death occur during the attack ; antemortem and postmortem coagula will be found in cavities, when such are present, and in the bronchi. As the patient does not commonly die from the hemorrhage, the causes may be of more interest than the condition. Hemorrhagic infiltration, or infarction ( pulmonary embolism, or pulmonary apoplexy), consists in the arrest of the circulation ina given area of the lung, vascular rhexis with infiltration of the intervesicular structure, and effusion of blood into the air vesicles. Causes.—Blocking of the pulmonary artery by a thrombus (autochthonous embolism) or an embolus. The latter usually reaches the heart from the venous circulation, as in phlegmasia alba dolens, or arises in the heart, notably the right auricle. The processes of thrombosis and the origin of emboli have been con- sidered. (See p. 267.) Where a thrombus forms, fibrinous plugs occlude the vascular supply to the affected part, and a cone-shaped area marks the outlines of the infarct. With clearly formed areas of hemorrhage, not to be differentiated from known areas of infarction, sometimes no embolus or thrombus, or source of either of these bodies, can be demonstrated. Feebleness of the circulation favors the occurrence of pulmonary infarcts. Morbid Anatomy.—Postmortem, the changes found depend somewhat upon the extent of the area involved and upon the age of the infarct and its character. When the lodged embolus is massive, occluding the pulmon- ary artery at its bifurcation, and when death occurred immedi- ately upon its lodgment, the lung does not show the condition here considered as pulmonary apoplexy ; it may show almost no change. In typical cases of recent embolism the infarct appears, under the pleura, as a dark-red, almost black, spot, varying in diameter from one centimeter to five centimeters, rarely larger, and on section is found to be wedge shaped, truly conic, with the apex of the cone directed toward the center of the lung. The color will vary from a gray, in extremely leukemic blood, to a black ; as the process grows older the color passes from black to reddish-brown, and, with the gradual resorption of blood col- oring-matter and resolution, the normal color may be, in favor- able cases, resumed. While the typical pulmonary infarct is conic or wedge shaped on section, the extensive anastomosis of the pulmonary circulation often affords so abundant a collateral blood supply that the area may be almost globular, pear-shaped, and ovoid on section. The pleura over the area is at first normal, but soon shows a beginning exudate. There is usually considerable edema surrounding the infarct. If the ORGANS OF RESPIRATION. ~ 569 process is not infected—it is the noninfected variety which is now under consideration—and the area is small, it is possible that absorption may occur. It is probable, however, that a certain amount of cicatricial tissue always develops, and, in not a few instances, a fibroid area remains. Histologically, the area consists of plugged vessels, with blood infiltrated into the septa and vesicles. Ina short time after the infiltration the blood coloring-matter is yielded up by the red corpuscles, which also break down. The leukocytes increase in number, and, if the area involved be small, the products may pass off by the lymphatics, which, in many cases, become per- manently pigmented by the process. If the area be larger, the tissue reaction greater, some fibrous tissue results; in more marked cases a puckered, pigmented, fibrous area forever marks the site of the lesion. If the bronchial artery, as well as the branches of the pulmonary artery, be occluded, the area may undergo a simple softening, fibroid change may occur around it, and lime salts may infiltrate it. The embolus causing the process may organize 7” szé« and permanently occlude the ves- sels, or resolution may occur. If the embolus contained bacteria, or should the area of the infarct become infected by the cocci of suppuration, an abscess results ; if the saprophytic bacteria gain ingress and survive, gan- grene may be engendered ; if the embolus represented a part of a malignant tumor, a new focus of development is assured. Emboli containing the specific infectious agent of the chronic infections engender those processes in the lung. The emboli associated with the latter processes—abscess, gangrene, neoplastic growth, and chronic infections—are so small that little hemor- rhagic infiltration may accompany them. Pulmonary atelectasis occurs in two forms—the congenital and the acquired. 1. Congenital atelectasis, or apneumatosis, is that con- dition of the lung resulting from failure to expand following birth, the organ retaining its fetal characteristics. Causes.—Feebleness ; extremely feeble infants may not be able to expand the whole lung; plugging of a bronchus by aspi- rated solids, or even fluids, during delivery ; imperforate bronchi associated with the collapse will usually show dilatation in the affected area, the extent of the dilatation depending upon the duration and force exerted. Morbid Anatomy.—The condition may involve a part or the whole of one lung, or may be scattered as irregular masses in both lungs. The areas of atelectasis are usually most abundant 570 SPECIAL PATHOLOGY. and largest posteriorly in the lower lobes. When the collapse has been due to inefficient respiratory efforts, a blowpipe inserted into the bronchus will usually lead to expansion. When the atelec- tasis is due to mechanical obstruction by foreign bodies, the col- lapsed areas can not be fully expanded in the manner just given. The areas are darker in color than the surrounding expanded portion, do not crepitate, and sink in water. When the areas are small and not abundant, the infant may recover ; under such cir- cumstances gradual distention may be brought about, or degener- ative or proliferative changes may lead to connective-tissue sub- stitution, followed by contraction, and, in time, but little evidence of the lesion may remain. 2. Acquired atelectasis, or collapse, is the condition ob- served when a part of the lung which has once expanded loses its air and does not refill. Causes.—Gas, fluids, or solids occupying the pleura, the first arising from puncture of the lung or chest-wall, or both; the second from pleuritic effusions, dropsical or inflammatory, or hem- orrhage into the pleura; the third from tumors. Bronchial obstruction is a most common cause; the obstruction may be a foreign body, a plug of mucus, pressure from without, as in en- larged peribronchial glands, tumors, or aneurysms. The influ- ence of pressure may be shown in aortic aneurysm, pericardial distention, mediastinal tumors, spinal curvature, etc.; the pres- sure may be insufficient and the atelectasis partial at first, but if the cause continues to act, the collapse becomes complete. Morbid Anatomy—When the collapse affects the whole lung, as in pleurisy with effusion, the organ is squeezed up against the spine, is pink or pale gray in color, is firm and airless, is tough, tearing with difficulty, and often can not be distended ; firm ad- hesions may bind it down, and the pleura may have become so thickened, fibroid, and resisting that reexpansion can never occur. When small areas of collapse occur, as in bronchopneumonia, in the recent state, they present themselves as small depressed spots immediately under the pleura, bluish-purple or bluish- brown in color ; occasionally lividity develops on exposure to the air; surrounding these areas the vesicles are distended (compen- satory emphysema) and are pink or reddish-white, in contrast to the darker collapsed portions. If the collapse be recent and the occluded bronchus not too firmly obstructed, a blowpipe, or even firm pressure on the surrounding areas, may refill the points of collapse. Later, from stasis in the vesicular wall, the color be- comes much darker, and blood escapes into the connective tissue ; the mass is soft and resembles the spleen in texture (splenization). ORGANS OF RESPIRATION. 571 Later, the blood is absorbed to a certain extent, the vesicular walls coalesce, proliferated connective-tissue cells and leukocytes form new fibrous tissue, and the mass is now in the condition known as carnification. With the completion of contraction and organization a firm fibroid area results, known as the cirrhosis of collapse; these areas contain a relative excess of pigment, are pink at first, later gray, and are said to show gray indura- tion. Emphysema.—(A) Interstitial emphysema, also called interlobular emphysema, is a condition in the lung comparable to subcutaneous or surgical emphysema, as seen by the surgeon in the subcutaneous tissues in fracture of the nose, or to the gas generated in the tissues in some forms of gangrene. Causes.—(1) Ruptured air vesicles, as occasionally occurs in violent coughing, as in whooping-cough or in vesicular emphy- sema ; (2) wounds of the lung, resulting from fractured ribs and penetrating wounds of the chest. In the latter condition intersti- tial emphysema may occur without pneumothorax, provided air does not gain ingress through the thoracic wall. It has recently been shown that pneumothorax may result from infection of the pleura by the bacillus aerogenes capsulatus of Welch. It is probable that in a similar manner an interstitial pulmonary emphy- sema might be induced. Morbid Anatomy. — Interstitial emphysema may be readily detected postmortem by the large blebs found immediately under the pleura, differing from overdistended air vesicles in that the former can be pushed around from place to place beneath the pleura. When the rupture occurs near the root of the lung, not only does the air reach the surface of the organ by the inter- lobular connective tissue, but it may find access to the con- nective tissue of the neck. (B) Vesicular emphysema is a condition in which the alveoli and infundibular passages are dilated. When the emphysema consists of overdistended vesicles in one area to occupy the space and to receive the air intended for another area, the condition is spoken of as local, vicarious, or compensatory emphysema. As the condition may be acute,—e. g., around an atelectatic area,— the withdrawal of the cause may terminate the emphysema; when the cause persists, the acute dilatation becomes permanent ; at first there may be no wasting, but eventually the intervesicular septa atrophy and this form passes into true emphysema. Substantive, substantial, idiopathic, hypertrophic, or large-lunged emphysema is a well-marked condition, readily 572 SPECIAL PATHOLOGY. recognized clinically, and possessing pathologic lesions eminently its own. Causes.—There seems to be necessary a hereditary tendency, a congenital deficiency in the lung tissue, before this disease is likely to establish itself; exactly what this hereditary deficiency is has not been determined ; the view that it is a defect in the elastic tissue is entirely consistent with the facts, but probably is not demonstrable. The disease is, in this sense, hereditary, it being one of the “soil” conditions transmitted from the parent. Given the first element,—congenital weakness of the vesicular wall,—the second is heightened intravesicular tension. This may be brought about in two ways—(1) zspiratory and (2) expiratory. I. Inspiratory Distention.—The vesicular distention of com- pensatory emphysema is, of course, inspiratory; and as true vesicular emphysema is almost always associated with catarrhal lesions, which favor atelectasis, the possibility of inspiratory dis- tention acting as the cause must not be forgotten. The constant association of catarrhal inflammatory lesions and the plugging of bronchioles, attended by collapse in the lobules supplied, leads to compensatory dilatation of adjacent vesicles, and there- fore to their overdistention ; the plug of mucus now shifts, and another series of vesicles become overdistended. These pro- cesses, frequently repeated, so overdistend the elastic tissue of the vesicular wall that the normal retractile power is lost or modified, and the air vesicles are thereby rendered incompetent fully to empty themselves. The foregoing views with regard to the inspiratory hypothesis have been largely supplanted by the theory to be next discussed. 2. Expiratory distention acts by increased pressure applied to the lung by the bony walls, and resistance to free exit from the lung by narrowing of the laryngeal chink, glottis, epiglottidean lumen, etc. The costal cartilages and sternum are pushed forward, the extreme normal obliquity of the ribs is altered, and the pulmo- nary space at the apex is increased, thus permitting distention of the lung at the apex or upper lobes and the anterior margins, these points showing the most marked change. The causes active in increasing the expiratory effort are : (1) coughs, as in chronic bronchitis, the violent cough of pertussis, etc. (2) Increased pulmonary tension, as induced by playing wind-instruments, heavy lifting, etc. Morbid Anatomy.—The chest is barrel-shaped ; the cartilages are calcific and rigid ; when the sternum is raised, the lung does ORGANS OF RESPIRATION. 573 not show the normal tendency to collapse—indeed, it may not retract at all; its anterior margins extend over the pericardium to a varying degree; when removed, it does not collapse ; the pleura over the affected area is pale, anemic, dry, and the un- affected areas are congested; white patches occur on the pleura —the pulmonary albinism of Virchow ; the emphysematous lines may follow the intercostal spaces, but the disease is most marked along the anterior margins, at the apex, and, less commonly, around the margin at the base; large bulla may be seen under the pleura, varying in size up to 0.5 or I cm., and at the free margin they may attain the size of 2 cm. or more. The lung fails to crepitate where the emphysema is most marked. The absence of elasticity is indicated by the fact that pits are obtained FIG. 273.—PULMONARY EMPHYSEMA.—( Fliitterer.) a. Emphysematous enlargement of the infundibulum. 4. Atrophied intervesicular septa, * improperly called absorbed alveolar walls. c. Pigment in the fibrous septum. almost as in edema, although edema is usually absent. The color depends upon the amount of pigment. Usually, the organs are pale and the pigment is conspicuous. As a rule, the lung contains less blood than normal ; and even when death has been delayed, marked congestion and conspicuous edema are frequently absent. The lung, when handled, feels like a pillow stuffed with down (Laennec). The smaller bronchi may be dilated ; more or less bronchitis and peribronchial induration are always present. The longitudinal bands of elastic tissue may be traceable in the bronchial wall. Morbid Histology.—lf the lung be blown up and dried, the enormous size of the distended vesicles may be apparent; even 574 SPECIAL PATHOLOGY. on section in the recent state, the atrophic remains of the vesic- ular walls may be discernible with a hand lens; hardened and examined, the elastic tissue will be found diminished, the vesic- ular septa atrophied, permitting coalescence of adjoining cells ; in the process of atrophy the capillaries disappear, and this, with the loss in septa, diminishes the aerating capacity of the lung. Changes in Other Organs ——The increased work demanded of the right heart in emphysema leads to hypertrophy and dilatation, the former in rare cases affecting the entire heart; atheroma of the pulmonary artery with or without dilatation may occur. Other organs liable to the alterations of structure incident to venous distention usually manifest that change. (C) Atrophic or senile emphysema (senile atrophy of the lung, small-lunged emphysema of Jenner) is, as its name indicates, a dis- ease of advanced life, and is essentially an atrophic lesion of a lung in which very little, if any, distending force has been exerted. The chest is small, the ribs are oblique, thus decreasing the diameters and diminishing the capacity of the chest ; the respira- tory muscles are atrophied and the lung is smaller than normal ; the changes in the vesicles and septa already noted in substantive emphysema occur. The enlargement in the size of the vesicles is held to be due to atrophy of the intervesicular walls. The bronchi frequently show some dilatation ; large bullz are usually absent ; the lung commonly collapses on opening the chest, and, in contrast with large-lunged emphysema, not infrequently shows areas of congestion, edema, and infarction. There may be some doubt as to the propriety of classifying this condition with emphysema. The fact that custom has established the prece- dent does not, of course, prove its correctness. A better knowwl- edge of atrophy as it occurs in the lung would probably lead to the recognition in this form of emphysema of some atrophic manifestation analogous to that seen in other tissues in advanced life, Acute vesicular emphysema is said to be present in acute bronchitis and after death from asphyxia ; there is also reason to believe that vesicular distention is present during life in these cases. That the condition is unassociated with atrophy of the vesicular walls is admitted. In the absence of such atrophy it consists largely of functional overdistention, and is not a disease of the air vesicles. Pulmonary Suppuration.—This condition is commonly de- scribed under the head of purulent pneumonia, suppuration pneumonia, etc., names indicating that it is some special type of ORGANS OF RESPIRATION. 575 pulmonary disease rather than the usual form of suppurative lesion, : Etiologically and pathologically, and to a certain extent clinic- ally, suppurative processes occurring in the lung possess no im- portant difference from suppurations arising from pyogenic infec- tion in other organs. Primary pulmonary suppuration is an exceedingly rare condi- tion ; pyogenic infection may be brought to the lung in one of four ways: (A) By the air-passages ; (B) from contiguous struc- tures; (C) by the blood ; (D) by the lymphatics. (A) By the Atr-passages (Bronchogenic Suppuration).—Al\though we are constantly inhaling large numbers of bacteria, many of them undoubtedly pyogenic, and in other ways pathogenic, the bactericidal action of the extruded epithelium, leukocytes, mucus, serum, etc., prevents ingress or pathogenic activity except the tissues be weakened by (1) general debility, (2) previous local dts- ease, or (3) accompanying injury. As examples of these may be mentioned : of the first, the probability that fibrinous pneumonia in drunkards will present a mixed infection ; of the second, pyogenic infection of tubercular areas, or pyogenic infection of the areas involved in lobar or lobular pneumonia, or the pyogenic infection in pneumoconiosis. In lobar pneumonia abscess formation is rare ; the so-called purulent infiltration is not really pus, as it not uncommonly contains no pneumococci, and rarely, if ever, con- tains the bacteria of suppuration. If abscess formation takes place in pneumonia, it usually begins as scattered foci of infec- tion, and, as such, is found postmortem ; rarely, however, these foci extend and run together, the infection lessening or obliterat- ing the circulation in the area, and more or less of a lobe may be converted into an abscess. Abscess formation in acute lobular pneumonia is still rarer. Suppuration from injury with infection may occur as any sup- puration following an infected wound. Exploratory puncture of the pleura has caused pulmonary abscess. But the form of in- fection with injury which brings infection with the injury, and both through the air-passages, is typified in the so-called aspira- tion pneumonia. Foreign bodies in the air-passages ; suppura- tive processes in or around the larynx, trachea, or larger bronchi ; deglutition pneumonia, in which, from altered innervation, food particles gain ingress to the air-passages ; and allied processes, all may give rise to abscess formation by depositing an irritant, no matter how small, and with it the bacteria of suppuration. (B) Pulmonary suppuration arising through extension of the infection from contiguous structures is not common, in the sense 576 SPECIAL PATHOLOGY. that the abscess extends by necrosis of the lung tissue; but in the lymphatics such extension may occur. Localized or circum- scribed empyema, or pleural abscess, particularly when situated between the lobes or at the base, between the diaphragm and lung, may penetrate the pulmonary tissue by a gradually extend- ing necrosis, and eventually may find evacuation through a bronchus. Abscess of the liver or suppurating echinococcus may perforate the diaphragm and infect the lung; mediastinal abscess and other forms of peripulmonic suppuration may like- wise induce pulmonary abscess. Cancer of the esophagus may lead to direct infection of the lung tissue or to infection of the air-passages. (C) Pulmonary suppuration from infection through the blood (hematogenic infection) was the common sequence of preantiseptic surgery and obstetrics. Emboli containing the cocci of suppura- tion lodge in the lung and give rise to centers of infection, fol- lowed by abscess formation. These abscesses are small, usually multiple, superficially located, not uncommonly cone-shaped, with the base of the cone toward the pleura, into which they not infrequently rupture, giving rise to suppurative pleurisy (empyema or pyothorax), or, if communication has been established between the abscess cavity and a bronchus, thereby admitting air to the pleural cavity, there quickly results a pyopneumothorax. (See Metastatic Abscesses, p. 278.) (D) Infection of the Pulmonary Structure through the Lymph- channels (Lymphogenic Infection).—An interstitial, peribronchial, or interlobular suppurative process may result from invasion of the lung tissue by way of the peribronchial lymphatics. Thus, in suppurative inflammation of the pleura the lymphatics passing through the lung structure may become clogged with infective material, or material eminently adapted to infection, and cocci accompanying this or gaining ingress to it may give rise to sup- puration, which, being in the lymphatics around the bronchi, is spoken of as peribronchial suppurative lymphangitis. The condition can not be diagnosticated during life,and is recognized only postmortem. Pyogenic agents reaching the lung or its lymphatic system from the mediastinum or elsewhere may give rise to the process. Morbid Anatomy of Pulmonary Abscess.—When solitary, the abscess may attain the size of a lobe; when multiple, the abscesses are usually small. The contents, in addition to pus, will be made up of epithelial debris and remnants of lung tissue, the finding of which in the sputum is a valuable aid to diagnosis. If evacuation has occurred during life, the walls may be gangre- ORGANS OF RESPIRATION. 577 nous and the cavity exceedingly fetid; if the mass be small and the patient in good condition, a fibroid protecting wall may form ; ordinarily, however, the wall is made up, from within out- ward, of a layer of (1) necrotic breaking-down lung and inflam- matory tissue ; (2) a layer of solidified lung infiltrated with leu- kocytes and young connective-tissue cells, and commonly show- ing hemorrhages into the alveoli and interstitial tissue ; (3) edematous lung tissue. Ifthe pleura has not been opened, the abscess wall formed by that structure will show an abundant exudate of fibrin, and some cloudy serum, varying in quantity, will probably occupy the cavity; purulent pleurisy (empyema) may occur without rupture of the abscess, but invariably occurs if rupture takes place, and is usually accompanied by pneumo- thorax, the latter depending upon whether the abscess commu- nicates with an open bronchus. Rarely, a pulmonary abscess may encapsulate, as previously indicated ; in lobar pneumonia, when the evacuation is complete, cicatrization has been known to occur; the same thing has taken place in hepatic abscess dis- charging through the lung. The majority of cases terminate fatally. Sometimes infection is wide-spread and is not associated with distinct abscess formation. Under such circumstances the condition is one of peribronchial suppurative lymphangitis, such as previously mentioned. Attempts have been made to classify pulmonary abscesses from the cause, as, pyogenic, tubercular, actinomycotic, pneu- monic, etc., but these are essentially mixed infections in the vast majority of cases, and the primary infection does not materially alter the true character of the developed malady. Gangrene of the lung consists of two factors: (1) Death of a part of the pulmonary tissue (necrosis) or a material lessening of its blood supply and (2) infection, which must be, in all prob- ability, a mixed infection. Infection alone does not induce gan- grene ; obliteration of the blood supply does not insure gangrene ; the two must be present. If pyogenic infection occur in a lung whose blood supply is abundant, suppuration is induced, pus being a product of vital reaction to pyogenic mycotic invasion ; if, however, the tissue be dead, if vital processes be materially weakened, the tissue resistance reduced, the nutrition greatly modified by existing lesions, or, it may be, arrested, infection gives rise to gangrene. The causes of pulmonary gangrene, then, embrace all those conditions that materially lessen or arrest nutrition and permit infection—lobar pneumonia, aspiration pneumonia, foreign bodies in the bronchi, pulmonary embolism, bronchiectasis, suppurative 37 578 SPECIAL PATHOLOGY. conditions in the lung, pressure, as from tumors and aneu- rysms on the bronchi and blood-vessels, etc. The cases of pulmonary gangrene that accompany, or, more commonly, fol- low, severe febrile processes are probably infections in areas of hypostatic or hemorrhagic pneumonia. Brain abscess and middle-ear and mastoid disease, by infectious thrombosis of the sinuses, may induce pulmonary embolism, which, being infected, will be likely to be followed by gangrene or abscess. The same is true of infectious processes in the venous system elsewhere. Morbid Anatomy.—Two forms are recognized: ‘the diffuse or disseminated form and the circumscribed form. The division made, independent of any surgical view, seems aptly adapted to the modern surgical divisions of gangrene, circumscribed and spreading. The diffuse, like spreading gangrene, is rare, and fol- lows most commonly pneumonia, and, rarely, obstruction of the pulmonary artery. There is not a sharp line of demarcation between the healthy and diseased tissue ; a whole lobe, or the greater part of a lobe, is involved, the process being well marked at the center of the diseased area, but gradually fading into the surrounding zone of highly inflamed pulmonary tissue. In the circumscribed form there is a sharp line of demarcation between the dead and the inflamed tissue, and, although the foci may be multiple, each focus is distinct from the living pulmonary tissue. The gangrenous mass in either case is, as a rule, extremely fetid, and during life this foul penetrating odor is imparted to the breath, and persists for hours in the sputum. The latter, when left in a conic glass, separates into three layers: the uppermost is ‘thick, frothy, yellow or green or greenish-yellow in color; the middle layer is a clear serous fluid, but slightly tinted ; the sedi- ment is greenish-brown, occasionally pus-like, and contains the characteristic odor in its fullest concentration. Elastic fibers are not always present, although they usually are to be found. The color of the diseased tissue is dependent upon the stage and, probably to a large extent, upon the character of the infection. Early, it is brown or reddish-brown; and later, quite black. The color-changes are in part brought about by the presence of blood pigment, to which the brownish hue is to be attributed. The blackening is partly due to changes in the hemal iron as well as to the presence of iron-free pigment. The occasional greenish hue, which may be marked, may be due to changes in normal pig- ments or to the presence of the bacillus pyocyaneus. In the earlier stages the gangrenous tissue may retain its structure, but disintegration rapidly ensues, and a cavity with ragged irregular ORGANS OF RESPIRATION. 579 walls forms, inclosing a green or reddish-yellow mass of softened necrotic tissue. Passing into, often across, the cavity are remains of blood-vessels and bronchi. By reason of the infec- tious character of the lesion, the blood-vessels are not occluded, as normally, by an organizing thrombus; the thrombus forming in the lumen being infected, is easily displaced, permitting of hemorrhage, which may be recurrent, and in rare cases fatal. Around the gangrenous area there is a zone of deeply’ congested or intensely hyperemic tissue, which is usually solidified, and outside of this an area of marked edema with leukocytic infiltra- tion. Cicatrization and recovery may occur ; the disease is more commonly fatal. PNEUMONIA. The term pneumonia is used to embrace all the inflammatory lesions of the pulmonary tissue, often including some of the pro- cesses already considered ; for example, pulmonary suppuration is sometimes spoken of as septic pneumonia or suppuration pneu- mona. When the term pneumonia is used alone, without any qualifying statement, croupous pneumonia is usually meant. The forms of pneumonia commonly considered under this heading are lobar or croupous pneumonia, catarrhal pneumonia, or bronchopneu- monia, tnterstitial or fibroid pneumonia, and, by some writers, the desquamative pneumonia of tuberculosis. Lobar, Croupous, or Fibrinous Pneumonia (Pxeumonitis ; Lung Fever).—The fact that the pleura is usually involved has led to the name /Pleuropneumonia. This disease is an acute inflammatory affection of the lung due to infection. Causes.—That pneumonia isa disease due to bacterial invasion is now universally admitted. That it is, however, the result of a single organism seems no longer probable, although not abso- lutely disproved. The organism most frequently present is the diplococcus pneumoniz, which was described by Sternberg as the micrococcus of rabbit septicemia, and named by him the micro- coccus of Pasteur. This organism was later studied by a num- ber of observers, and was found by Frankel and Talamon in the lung in croupous pneumonia. (For description see p. 168.) In 1882 Friedlander described an organism associated with pneumonia, to which he gave the name pneumococcus. As a result of later studies the organism is now held to be a bacillus. (For description see p. 177.) Croupous pneumonia, clinically and anatomically not to be differentiated from croupous pneu- monia produced by the pneumococcus of Frankel, may result from infection by streptococci, and possibly staphylococci, 580 SPECIAL PATHOLOGY. although it is usually held that the présence of the latter organ- ism is to be attributed to a mixed or secondary infection, and that, even when found alone, the primary pneumonia was due to the pneumococcus or other organism which has disappeared. The bacillus typhosus, bacillus of influenza, colon bacillus, plague bacillus, and possibly a number of microorganisms may bring about that form of solidification usually regarded anatom- ically characteristic of croupous pneumonia. The anatomic dis- tribution of the lesion would indicate that infection usually takes place through the bronchi. Atypical distribution, and occasion- ally associated lesions, would lead us to admit the possibility of hematogenous infection. Certain predisposing causes are recognized. These act in one of two ways: (1) By altering the saliva, and thereby the culture medium in which the organism is growing, and these changes in the pabulum increase the virulence of the micrococcus ; (2) the predisposing elements so weaken the tissues as to permit of ready infection. The latter is illustrated by the frequency with which pneumonia occurs in drunkards, in the debilitated, in Bright’s disease, after contusions of the chest, etc. The latter view seems the more reasonable, and but little importance is to be attached to the first given. All ages are liable, but pneumonia is most frequent in three periods—early childhood, between twenty and forty, and after sixty. It is more common among males than females ; where both are subject to the same influences, there is little difference. Conditions disturbing the equilibrium of the pulmonary cir- culation, as chronic heart disease ; retention of excrementitious matters, as in uremia—in other words, any process reducing the vital powers and enabling infection to occur favors the de- velopment of pneumonia. Unhygienic environment acts in two ways—(a) by reducing resistance and (0) by favoring the ac- cumulation of infectious material in the surroundings. The specific cause elucidates the occasional occurrence of epidemics in crowded or unhygienic quarters. There seems to be an in- dividual susceptibility, as manifested by the frequent recurrence of pneumonia in the same individual, twenty-eight attacks having been observed in one patient (Loomis). That relapses do not occur seems to indicate a condition of acquired immunity ; that such is of brief duration is also presumable from the liability to recurrent attacks. Experimentally, it has been shown, in animals, that an induced immunity may be secured by the injection of filtered bouillon cultures of the pneumococcus or a glycerin ex- tract prepared from the growing organism. The immunity is ORGANS OF RESPIRATION. 581 temporary, lasting but a few months, but during that time is transmitted, in gestation and by nursing, to the offspring. The serum of such animals has been used with apparent success in the treatment of pneumonia. Morbid Anatomy.—Pneumonia involves, asa rule, either a whole lobe or a whole lung, most commonly the lower right lobe; the lower left lobe is next in order; third in point of frequency is double pneumonia, while pure croupous pneumonia of the apices is rare. The right apex is more frequently involved than the left. The pneumonia is double in from twelve to fifteen per cent. of the cases. The whole lobe or lung is usually in the same stage, although wandering, creeping, or migratory pneumonia, involving one lobe after another, will show different stages in different lobes; the lower lobe is most frequently involved first. In rare instances one lobe and part of another may be involved, and in different stages. Occasionally, central changes precede peripheral lesions, and the center of the lung may be gray while the periphery is less advanced —central pneumonia; rarely, the reverse may be demonstrated. In double pneumonia one lung may be further advanced than the opposite organ. In infancy and in old age the apex is more frequently the initial point of invasion ; in the aged death occurs earlier in the attack than in the adult. When the disease is one-sided, the unaffected lung is commonly deeply hyperemic and congested. Three stages are recognized : (1) Engorgement, (2) red hepa- tization, and (3) gray hepatization. State of Engorgement—When the chest is opened, the organ does not retract or collapse with its wonted rapidity; there may be a slight shrinking in volume, but the general contour of the organ is likely to be retained. The lung, or the area involved, is red, often a scarlet hue. Crepitation is present throughout, but is less distinct than normal; the specific gravity is greater than in health, as is shown by the fact that while the lung floats, it does not float so “high” as the normal organ. Occasionally, the pleura shows evidence of beginning inflammation. (See p. 476.) On section, the color is uniform; asa rule, blood oozes from the cut surface, and while in the majority of the cases the blood is thick, flowing slowly, in some cases an abundant tran- sudate of serum appears immediately on section, which, mixing with the blood, bathes the incised surface, and drips, or even runs, from the dependent edge. Histology of this Stage-—On microscopic examination the capillaries of the vesicular walls are found enormously distended, tortuous, and even saccular; the epithelium of the vesicles 582 SPECIAL PATHOLOGY. is swollen and, in places, desquamating ; in the few vesicles with marked desquamation some leukocytes and red blood-corpuscles may be demonstrated. The subpleural and interlobular con- nective tissue shows also the engorgement, and the lobules may be outlined under the pleura by the intensely engorged vessels. This stage lasts from a few hours to two or three days ; rarely the latter. It seems reasonable to suppose that in the last moments of life, or even after death has apparently occurred, solidification may develop, or, having already developed, may extend. Thus, the author has made postmortems after the most . experienced clinicians had, but a few moments before death, out- lined the area that seemed solid; in not a few of these cases has the solidification been found far beyond the outlines in- dicated by the physical examination made just before death. ° This offers some consolation for undiagnosticated areas of solidi- fication, but it is also explained by assuming that, after death, the lung rises, as a result of retraction or partial atelectasis of the unsolidified areas above. Death rarely occurs in this stage except when great exposure, an alcoholic debauch, or other pre- viously debilitating conditions are incident to the attack. The stage of engorgement is often found in one part of the lung when another area is more advanced, or in one lung when its fellow is solidified. It seems reasonable to assume that, in very rare cases, recovery may occur without further progress of the morbid process. Stage of Red Hepatization.—The stage of engorgement termi- nates by the distended blood-vessels pouring out the inflammatory exudate into the air vesicles, and thus, by excluding the air, bringing about the stage of solidification. The lung, or affected area, on opening the chest, shows absolutely no tendency to re- tract ; it is voluminous, and may be marked by the ribs; the color is darker than the first stage, or rather more of a brown or reddish-brown ; the area involved is solid, and the absence of air is shown in the entire freedom from crepitation, in the absolute dullness, great weight, and, when thrown into water, the rapidity with which the part involved sinks. On section, the organ is dry, rough, and granular; a finger passed over the scraped sur- face gives to the observer the impression of a rough surface, not unlike ground glass; this and the granular appearance are due to the plugs of fibrin that occlude the vesicles and on section project ; they may be scraped out or picked out with a needle, and often an infundibulum with attached cast of the vesicles, or a bronchial plug, may be removed. The area is friable, and gives way when the finger is thrust into it; a slice cut from the Puate II. Lung, Croupous Pneumonia. Stage of red hepatization. ( Fox's Atlas.) ORGANS OF RESPIRATION. 583 surface may break when bent; there is nothing more character- istic than this fact. The weight of the normal lung may be 600 grams; the lung in croupous pneumonia may weigh three or four times as much. (See Plate II.) Morbid Histology —On microscopic examination the blood- vessels are less distended than in the preceding stage, although they are still fuller than normal. The inflammatory exudate poured out from the vessels now occupies the vesicular cavity. When the exudate passed from the vessel it was liquid (liquor sanguinis), but in the vesicle coagulation of the fibrin has solidi- Fic. 274.—THREE ALVEOLI FILLED WITH FIBRINOUS EXUDATE. CROUPOUS PNEUMONIA, STAGE OF HEPATIZATION.—(Schmaus.) 250 diameters. @,a,a,a,a,a,a,a,a. Alveolar septa with somewhat distended capillaries,as at 5,5. ¢. Mesh- work of fibrin occupying the cavity of the air vesicle. Two other air vesicles, also filled, are shown. In this solidified exudate are entangled desquamated epithelial cells, c, from the alveolar wall and leukocytes, d, d. : fied the intravesicular contents and entangled the cellular ele- ments present. With the transudation of the liquor sanguinis leukocytes (by diapedesis) and erythrocytes (by rhexis) escape into the vesicular cavity. Thus there are found in the vesicle’ leukocytes, red corpuscles, and a few desquamated epithelial cells entangled in a meshwork of fibrin fibrilla. This fibrin may run as a net from point to point or may traverse the vesicle in straight lines; the fibrin lines may be parallel. The number of leuko- cytes present in the vesicular cavity increases as the process advances. The small amount of epithelium contrasts strongly 5 84 SPECIAL PATHOLOGY. with the abundance of that element in the air vesicles in broncho- pneumonia. The demonstration of the presence of fibrin is best accomplished by Weigert’s method. (See p. 251.) The solid exudate extends into the bronchiole, and may, in rare instances, reach bronchi of considerable size. The connec- tive tissue of the lung also shows some change. The vesicular a a Fic. 275.—Croupous PNEUMONIA. SINGLE AIR VESICLE IN THE SECOND STAGE, WITH SLIGHTLY CONTRACTED ExuDATE. (¥%-inch objective, 1-inch ocular.) Much higher magnification than in figure 276, with the object of bringing out the fibrinous network. Specimen fixed in corrosive sublimate, infiltrated with paraffin, stained with hematoxylin and eosin, and mounted in balsam. a@,a,a,a,a,a. Vesicular walls. 6. Exudate in the air vesicle; during life the unoccupied area around the exudate either contained serum or the contraction may have occurred during fixation and hardening. wall contains a number of leukocytes, but they are less abundant than in catarrhal pneumonia. The bronchial wall is also infil- trated. Suitably prepared sections usually show abundant pneu- mococci, with the occasional presence of other organisms, to which reference has been made. FLATE ILI. Lung, Croupous Pneumonia. Stage of gray hepatization. The pleura on the right and at the base shows the fibrinous exudate, modified from Bollinger. ORGANS OF RESPIRATION. 585 If evidence of pleurisy did not develop in the earlier stages, it is certain to do so now. A thin plastic layer or a marked fibrin- ous exudate may be present. When a past pleurisy has obliter- ated the sac by universal adhesions, the exudate may be poured out into the adhesions, when these are not too firm. Serous exudates are rare, and, from the very nature of the me lesion, can not be extensive. Whether a desquamative process preceded the stage of exuda- tion at present under consideration or not, there is now induced desquamation of the epithelial lining of the vesicles. The fibrin contracts, and free fluid collects in the vesicle or is taken up by the lymphatics. The red blood-cells undergo fragmentation, are broken up, and bronchial inflammation with some of the features of a bronchopneumonia occurs. The desquamated and fatty epi- thelium leads to liquefaction of the coagulum in the vesicle and to the conversion of the mass into an emulsion favorable for absorp- tion or expectoration. These changes alter the color of the organ from red to gray, and the condition is spoken of as gray hepatization. The duration of the stage of red hepatization no doubt varies; in three days after the onset of symptoms the lung may be gray ; ; on the’ other hand, the author has examined a lung thirty-nine days after the initial chill, and thirty-seven days after the clinical diagnosis of solidification, and found the organ still red. Gray Hepatization.—When this stage is reached, the lung no longer resembles, in its gross appearance, the previous stage, just described. As indicated, the organ is reddish-gray, gray, or yel- lowish-gray, depending upon the degree to which the stage is developed; the organ is softer and less tense than in the red stage, tearing with the greatest ease, but is less readily broken by bending. The surface is moist and smooth on section, in contrast to the dry and rough surface observed in the red stage. (See Plate III.) In gray hepatization squeezing the organ leads to a rather free flow of the partly emulsified inflammatory exudate. The peribronchial glands are enlarged, the pleurisy is more advanced, and occasionally the lymphatic channels, running from the pleura toward the mediastinum, are swollen and show as light yellow or yellowish-red streaks. The involved area is still air- less, at least in the earlier stages of the gray change, as may be shown by the tests already given when considering the airless condition of the organ in red hepatization. Under the microscope no fibrin is to be demonstrated, but the vesicles are filled with cellular elements resembling those of bronchopneumonia ; there are more leukocytes and desquamated epithelial cells in varying 586 SPECIAL PATHOLOGY. stages of granular and fatty change, and there is less serum than in the bronchopneumonic exudate. The coagulability of the fluids that bathe the cut surface in the gray hepatization can be shown.by thrusting the organ into strong alcohol, aqueous solu- tions of picric or chromic acid, or boiling water, thereby coagu- lating the albuminous constituents of the vesicular contents. The firmness and resisting density of the red stage can not, how- ever, be redeveloped, as the material becoming solid at this stage is albumin undergoing coagulation, and not fibrin. Terminations —It is reasonable to suppose that the gray stage is the beginning process of resolution. The softened vesicular exudate, by fatty changes, eventually becomes transformed into an emulsion that is absorbable and sufficiently liquid to permit of being displaced from the air vesicles and expectorated. The amount leaving the lung by absorption may be in excess of that removed by expectoration, or the reverse. The amount of the exudate (estimated by weighing the normal lung and deducting its weight from that of the inflamed organ) varies for the entire lung between 1 kilogram and 1800 grams; by observing how little may be expectorated, the capacity of the absorbents can be, in part, appreciated. It is probable that this absorbed mate- rial is largely cared for by the lymphatics, as such exudates are not likely to pass through even capillary walls. The termination of lobar pneumonia in interstitial pneumonia will be considered with the latter. (See p. 593.) Occasionally, croupous pneu- monia apparently terminates in tuberculosis. In such cases the tubercle bacillus may have been in the lung in some quiescent nodule, or the lesion may be the result of a secondary infection in the tissues weakened by the pneumonic process. (For the formation of abscess in lobar pneumonia see p. 575. Gangrene resulting from lobar pneumonia is also there described.) Lesions That May Accompany Croupous Pneumonia.— Fleurisy is always present in a pneumonia that reaches the sur- face of the lung. Pleurisy of the base with pneumonia of the apex, inflammation of the opposite pleura, are combinations of patho- logic interest. While the pleurisy is usually one of slight plastic or an abundant solid exudate and little serum, it is not invariably so; abundant serous exudates occasionally occur, and empyema (suppurative pleurisy) is not so infrequent as was once believed. It is now established that the pneumococcus is the essential etiologic factor in the various forms of pleurisy, and that it may, without mixed infection, induce suppuration is probable. Pericardial inflammation accompanying pneumonia partakes of the same general characteristics already described as present in ORGANS OF RESPIRATION. 587 pleurisy, and is due to the same cause. It occurs most com- monly in pneumonia of the left lung, and especially when that part of the lung overlying the pericardium is the seat of the dis- ease, The blood changes that occur in croupous pneumonia, although not characteristic, are important. There is a notable in- crease in the number of finely granular oxyphile leukocytes ; poi- kilocytosis is occasionally present ; the alkalinity of the blood is decreased. Although not of unvarying import, increase in the leukocytes is considered a favorable prognostic omen. The heart muscle may show cloudy swelling ; less commonly, advanced granular change; and, rarely, a well-marked fatty de- generation may be in progress. Myocardial infective processes have not been observed. Cardiac thrombi on the left side develop rarely, except immediately preceding death, and when associated with endocardial inflammation. Just preceding death, in the agonal period, the slowed and greatly obstructed circulation of the right side may be embarrassed by clots extending from the right ventricle into the smaller ramifications of the pulmonary artery, and, at the postmortem, these may be pulled out as long tree-like or whip-like masses. £ndocarditis, both acute simple and acute malignant, occurs. The acute simple form has been found without the observer being able to demonstrate pneumococci in the blood or cardiac lesion ; they are, however, commonly present. In the malignant form of endocarditis accompanying pneumonia the pneumococcus is invariably present, and in a small percentage of the cases the organisms of suppuration occur in the vegetations and blood. Monarticular joint inflammations have been frequently noted, and are extremely likely to terminate in suppuration. It is inter- esting to note that pneumococci have been found in the affected joints, in the pus from the joints, and that arthritis has been in- duced by the intra-articular injection of the organism. The extreme selection of serous surfaces by this organism and its products is further illustrated in the occasional feritonitis and inflammation of tendon sheaths that have been observed. Meningitis is another illustration of the liability of serous sur- faces to suffer; while it may occur with malignant endocarditis and be accompanied by embolic processes, both may be absent. All the intracranial serous structures may be the seat of the disease, or it may be restricted to a single fossa or region or to the base. Infection occurs through the blood or from the nasal or aural spaces, and the seat of the lesion may indicate the source of the infection. The process may be restricted to the meninges 588 SPECIAL PATHOLOGY, or the brain structure may be involved. Involvement of the spinal * meninges has been observed. A number of mucous membranes that may be infected by the pneumococcus, either during pneumonia or independently ; the most frequent are the ear (otitis media) and mucous surfaces of the nasal appendages: ¢. g., abscess of the frontal sinus, containing the diplococcus and followed by a diplococcus-meningitis. Swppura- tive parotitis (the pus containing the diplococci) is occasionally ob- served. Fibrinous inflammations of the stomach, colon, and other mucous surfaces may occur ; hemorrhagic and gangrenous pro- cesses are less frequent, except in the embolic phenomena which accompany malignant endocarditis. The epithelium of the mu- cose, liver, and kidneys is usually cloudy. The renal lesion in croupous pneumonia, manifested by the presence of more or less albumin in the urine, rarely passes on to an inflammatory condi- tion which persists after the disappearance of the initial cause. Bronchopneumonia.—This disease is also known as lobular pneumonia, a name objectionable in that it does not indicate the bronchial association that is always present, and also in the fact that embolic processes may be essentially lobular and still bear no relation in point of cause or pathology to the condition under consideration. The name catarrhal pneumonia indicates the character of the exudate, but not all of its component parts are catarrhal in point of origin, and the changes to be noted in the vesicular wall make the process more than a superficial inflam- mation. The designation capillary bronchitis is objectionable, as it does not indicate the accompanying vesicular change. The term disseminated pneumonia indicates the wide distribution of the process in contradistinction to the more or less circum- scribed lesion of croupous pneumonia. The term catarrhal bronchopucumonia seems no better than bronchopneumonia alone. The various other synonyms that have been given in attempts to indicate the location or character of the lesion, the cause or termination, are either objectionable or obsolete. Causes.—Bronchopneumonia is not, as a rule, a primary disease, but arises secondarily in some other process. In nearly all, if not all, the cases of this disease the bronchiole or the passage above is the initial seat of the lesion, and the vesicle is second- arily affected. When the inflammatory process follows disease of the intervesicular wall, such as tuberculosis of that structure, one can conceive the initial process to have been in the vesicle; but, aside from this factor, contiguous disease, bronchopneumonia, as the name indicates, begins essentially as a bronchial inflamma- tion. ORGANS OF RESPIRATION. 589 While no specific germ has been adduced, the phenomena are those commonly attributed to infection or infectious products. The pneumococcus of Frankel is present in a relatively large per- centage of the cases ; it may occur alone or be associated with other organisms. The condition is so constantly a part of various infections that it would seem that the definite anatomic alterations to be described might arise from a multitude of causes, a few acting singly, or the combination of two or more factors. The fact that bronchopneumonia occurs most constantly, as an im- portant process, in the young and the aged seems to indicate some peculiarity of tissue at those periods ; this has been assumed to be, in part at least, an inability of the terminal air-passages to evacuate themselves, owing to the faulty or poorly developed elastic tissue in the lung of the young, or muscular weakness of the respiratory apparatus in the two extremes of life; further, the epithelium of the infant, in the transitional stages of development, is most abundantly thrown off as a result of an irritation that adult tissues would resist. That such excessive susceptibility of the mucous surfaces exists is shown in the gastro-intestinal dis- eases of childhood equally as much as in the pulmonary lesions. A similar susceptibility is manifest in old age. Unsanitary surroundings, crowding, poorly ventilated sleep- ing or living rooms, are all predisposing elements. Exposure, cold, dampness, and other incidents of the winter months show a most marked influence, the disease being most prevalent from November to May, inclusive, reaching its acme in the uncertain, varying, climatic conditions of the early spring months. _ Its rela- tion to the infections is shown in the constancy with which it develops in the presence of those conditions; of the acute infec- tious diseases, measles is the one with which it is most frequently associated, although diphtheria, both pharyngeal and laryngeal, especially the latter, is commonly the immediate precursor or accompanying lesion. Scarlet fever and whooping-cough are usually, and typhoid fever and suiallpox may be, accompanied by bronchopneumonia. When the respiratory apparatus is the seat ofany of the specific infectious diseases, whether acute or chronic,—anthrax (as in wool-sorter’s disease), tuberculosis, glanders, leprosy, etc.,— bronchopneumonia is extremely liable to occur ; and when one of these processes involves the lung, catarrhal ‘pneumonia is in- evitable. The bacillus of tuberculosis in the lung, whether in the cavities of the alveoli, as when aspirated from above, or in the vesicular or bronchiole wall, as when brought by the blood or lymphatics, always incites a bronchopneumonia, which is modified 590 SPECIAL PATHOLOGY. by the tubercular process, but is, nevertheless, a characteristic lesion. (See Tuberculosis of the Lung, p. 596.) In syphilis of the lung bronchopneumonia may be present. When infectious materials are drawn into the lung, as in the deglutition and aspiration pneumonias, to which reference has already been made, bronchopneumonia and other accompanying infective processes ensue; that bronchopneumonia is not the whole of the process is shown by the frequency with which sup- puration or gangrene may follow. (See Pulmonary Suppura- tion, p. 574.) Bronchopneumonia also terminates fibrinous or lobar pneumonia when resolution is gradually reestablishing the normal. In conclusion, it remains to be said that any condition that lowers the vitality of the individual, that weakens the avenues open for infection, that depresses or debilitates, favors the de- velopment of bronchopneumonia. To this group of causes belong Bright’s disease, chronic heart disease, convalescence from acute processes, or the debilitating influences of more chronic ones. Bronchopneumonia always accompanies, to a varying degree, pneumoconiosis. Morbid Anatomy.—In recent cases, acute in time, the lung is more voluminous than normal, and does not collapse with usual promptness, and may not shrink in the least when the chest is opened ; there is not that dense firmness of the tissue involved, so constantly present in fibrinous or lobar pneumonia, and on super- ficial examination the lung appears to crepitate throughout ; ex- amined more closely, areas that do not crepitate are easily found; while firm, they are not dense, and are small nodules in contrast to the large areas of fibrinous pneumonia. On the sur- face of the lung near the base, as a rule, are areas sunken below the surface, blue or bluish-brown in color, usually isolated and small, although in rare instances almost, if not quite, all of a lobe may be involved in the atelectatic process. Usually, such areas can be reexpanded by forcing air into the bronchus. The area joining that of collapse is not uncommonly emphysematous, as are the anterior and apical margins. At scattered points will be found projecting areas, over which the pleura may be rough or even show a beginning exudate. On section, the surface is usu- ally dark or reddish, although in adults it may be gray at points, not unlike the gray stage of fibrinous pneumonia. The surface is smooth and moist, and drips blood or bloody serum. The outline of the affected lobules can be seen, or, where a number have run together, they will usually be found in different stages, and can in that way be made out. A suitable lobule, on longi- ORGANS OF RESPIRATION. 59I tudinal section, shows the grape-like structure of the lung, with alveoli, infundibula, and bronchiole filled with puriform mucus ; a transverse section reveals the central bronchiole, containing a tenacious plug of mucus, surrounded by distended vesicles and the adjacent collapsed lobules. Adjoining the inflamed area the areas of collapse may be well made out, or they may be indistinct; if defined, they are dark, smooth, airless, and instead of bulging when cut, apparently retract; when imme- diately subpleural, there may be ecchymosis in or over them; when not well defined, the outline will show as darkish bands traversing the lobes in an irregular manner. The peribronchial lymphatic glands will be, not uncommonly, swollen and edema- tous, owing to the effort made to carry off the degenerative pro- duct of the bronchial and vesicular inflammation. Morbid Fiistology—lf a drop of the fluid that fills the air- spaces be squeezed out upon a slide, it will be found composed of germinal, granular, and fatty epithelium, with a varying number of leukocytes, rarely any red blood-cells. The fluid exudate must be solidified before making sections for histologic examination ; this may be accomplished by thrusting a part of the affected tissue into boiling water, and thus coagulating the albumin in the serum and incarcerating the cellular elements ; such a process alters the surrounding structures too profoundly to be commendable, and the same object may be secured by using absolute alcohol or Flemming’s or Hermann’s fixing solu- tions. (See pp. 48 and 49.) Infiltration is imperative in order to retain the histologic structure in place. Examination: of properly prepared sections will show the alveoli filled, not with a fibrin-bearing exudate, as in lobar pneu- monia, except in a very few scattered vesicles, but a mucoid exudate containing the cellular elements previously indicated, the epithelium being especially predominant. The bronchiole lumen will be found occluded by the same exudate, and the wall infiltrated by young cells, its integral elements pushed apart, typifying the swelling that was present. Longitudinal sections reveal, in the bronchiole, more or less irregularity in the trans- verse diameter—saccular dilatation. The infundibulum and its sur- rounding vesicles are filled with a similar exudate, and the same cellular infiltration of the vesicular walls may be found. Toward the margin of the affected lobule the distention will be less marked, and the alveolar epithelium will show desquamation and marked fatty changes. The capillaries of the walls, both vesic- ular and bronchial, will be found distended and surrounded by leukocytes. The lymphatic channels leading from the affected 592 SPECIAL PATHOLOGY. areas are usually engorged. In the peribronchial lymphatics more or less swelling and, infiltration are manifest. In the bronchopneumonia accompanying the aspiration of foreign bodies into the bronchi the bacteria present infiltrate the connective tissue, abundant leukocytic infiltration occurs, and, if the processes have sufficient time, suppuration or gangrene may ensue, Terminations.—Acute bronchopneumonia undergoes resolution rapidly once the process begins; upon the withdrawal of the cause the lymphatics and blood-vessels care for the unexpec- torated exudate, epithelium rehabilitates the denuded walls, and organization of cellular products in the vesicular and bronchiole walls follows the removal of the liquid exudates that caused the swelling to which reference was made while considering the his- Fic. 276.—Two ALVEOLI AND a PART OF A THIRD FROM LUNG IN CATARRHAL PNEUMONIA. u,a,a. Walls of the alveoli. 4. Desquamated epithelial cells from the walls of the alveolus. c. Alveolus filled with catarrhal exudate. d. Leukocyte. tology. The feebleness of the respiration and the reduced resist- ance may enable deposited bacteria to secure a more or less per- manent abode. That pyogenic and saprophytic bacteria may in- duce suppuration and gangrene, as has already been stated. In the distended vesicles or lobules tubercle bacilli may lodge, and the characteristic phenomena of tuberculosis ensue, constituting a tubercular infection secondary to the bronchopneumonia. This, while possible, is no doubt rare, and where caseation with fibroid encapsulation of the caseous area is found postmortem, it is prob- able that the disease was tubercular from the start, but that the conservative elements limited the process; these areas may be- come calcareous, and exhibit the other phenomena so constantly associated with quiescent tuberculosis. It is possible for the tubercle to follow by a more wide-spread infiltration, or a wide- ORGANS OF RESPIRATION. 593 spread infiltration of tubercle may have induced the broncho- pneumonia. At one time it was believed that caseation and fibroid change were a legitimate termination of bronchopneumonia, and recognized as a frequently occurring condition. While, as already stated, one can conceive of a simple nontubercular area of consolidation becoming fibroid and limited, independent of the bacillus of tuberculosis, still when caseation and calcareous infil- tration are found, the evidence is clearly that of a ‘‘ healed-in” tuberculous focus. Interstitial pneumonia, chronic interstitial pneumonia, pulmonary cirrhosis, or, more properly, pulmonary sclerosis, foroid induration, fibroid lung, with various other synonyms, is a chronic productive inflammatory process, involving essentially the connective tissue of the organ, with increase of the fibrous elements and more or less contraction of the newly formed tissue. The degree to which the change may progress is dependent upon many factors, and the fact that the process is secondary to other conditions has led toa multitude of names, each assuming of heart, 490 of spleen, 451 of thymus body, 468 Hypospadias, 614 perineoscrotalis, 614 Hypostatic congestion, 263, 566 of lungs, 565 Hypothermia, 384 I. Icterus gravis, 672 Idiopathic anemia, 440 aneurysm, 522 emphysema, 571 ° Tleitis, 541 lleocecal valve, intussusception at, 656, 657 Tleocolitis, 541 Immunity, 154 absolute, 156 acquired, 157 active, 157 artificial or experimental, 158 cellulohumoral theory of, 156 induced, 158 local, 159 natural, 157 theories of, 154 units, 112 Implantation of tissue into animals, 52 109 817 Impulse, congenital, 218 Inclusion theory of Cohnheim, 306 Incompetency of heart valves, 510 Incubation of hanging-drop cultures, 101 Incubator, 105 Indirect division of cells, 296 necrosis, 248 Indol, production of, 102 Induced immunity, 158 Induration, brown, of the lung, 565 gray, of lung, 571 Indurative endocarditis, 509 pancreatitis, 687 parotitis, 644 Infantile hemiplegia, 773 meningeal hemorrhage, 770 paralysis, 698 Infarct, 277 Infarction, anemic, 278 hemorrhagic, 278 of the spleen, 456 pulmonary, 568 splenic, 456 Infarct, anemic, 277 white, 277 Infarcts, uratic, 615 Infected emboli, 456 thrombus, 269 Infection of mouth by bacteria, 642 secondary, 388 Infections, 382 chronic, of larynx, 557 local, 387 of the lymph-glands, 461 Infectious edema, 266 granulomata, 363 processes in intestine, 658 splenitis, 454 Infective embolus, 276 thrombus, 269 Infiltration, 225 albuminoid, 228 of heart, 492 of liver, 669 amyloid, 228 amyloid, artificial production of, 229 amyloid, causes of, 228 amyloid, morbid anatomy of, 230 amyloid, of heart, 493 amyloid, of liver, 669, 670 amyloid, sites of, 229 and degeneration, 225 bacony, 228 calcareous, 237 calcareous, causes of, 237 calcareous, of heart, 492 calcareous, of pancreas, 686 818 INDEX. Infiltration, calcareous, of spleen, 453 of suprarenal bodies, 695 morbid anatomy of, 237 seats of, 237 cholesterin, 240 fatty, 225 causes of, 226 of heart, 492 of liver, 226, 227, 668, 669 of muscle, 227 of pancreas, 686 of pericardium, 481 of serous membranes, 481 sites of, 227 fibrous, of myocardium, 496 glycogen, 239 glycogenic, morbid anatomy of, 240 growth of neoplasms by, 309 hemorrhagic, 261 hydropic, 240 into joint structures, 732 lardaceous, 228 methods, 51 of kidney, 615 of lung, hemorrhagic, 568 of mucous membranes, 533 of muscle, 701 of pericardium, 473 of thyroid gland, 692 of tissue with celloidin, 59 of tissue with paraffin, 51 pigmentary, 231 of heart, 493 of liver, 670 of mucous mem- branes, 533 of spleen, 452 of lymph- glands, 460 purulent, 293 waxy, 228 Inflamed serous membrane, 480 Inflammation, 280 acute, 293 acute catarrhal, of biliary passages, 682 and repair, 280 changes in the blood-ves- sels in, 282 in the perivascu- lar tissue in, 286 chemic, of serous mem- branes, 475 chronic, 293 Inflammation, chronic catarrhal, of the bile-ducts, 682 of spleen, 454 circumscribed, of pericar- dium, 483 circumscribed, of serous membranes, 483 croupous, of mucous mem- branes, 541 diffuse, of pericardium, 483 of serous mem- branes, 483 diphtheric, of mucous membranes, 545 discoloration in, 295 disordered function in, 295 dry catarrhal, of mucous membranes, 539 etiology of, 280 exudate in, 288 fibrinous, of mucous mem- branes, 541 fibrinous, of pericardium, 477 fibrinous, of serous mem- branes, 477 follicular, of mucous mem- branes, 539 > gangrenous, of larynx, 557 general, of pericardium, 483 general, of serous mem- branes, 483 gonorrheal, 541 heat in, 294 hemorrhagic, of larynx, hemorrhagic, of mucous membranes, 545 hypertrophic, of mucous membranes, 539 interstitial, 294 intravascular changes in, 283 localized, of the serous membranes, 483 morbid physiology of, 294 of arachnoid, 758 of arteries, 515° of biliary ducts, 682 of bladder, 629 of bone, 717 of brain, 773 of bronchi, 561 of dura mater, 756 of endocardium, 501 of esophagus, 647 INDEX. Inflammation, of heart, 496 . of intestine, 658 of joints, 733 of kidney, 617 of larynx, 556 of liver, 673 of mouth, 638 of mucous membranes, 536 of muscle, 701 of nasal mucosa, 553 of nerves, 790 of pancreas, 686 . of pelvis of kidney, 628 of pericardium, 474 of periosteum, 709 of pia, 758 of serous membranes, 474 of spinal cord, 783 of stomach, 651 of suprarenal bodies, 695 of thyroid gland, 692 of tongue, 641 of tonsils, 642 of veins, 523 pain in, 294 parenchymatous, 294 plastic, of mucous mem- branes, 541 of -pericardium, 477 of serous mem- branes, 477 productive, 293 pseudomembranous, of mucous membranes, 541 serofibrinous, of pericar- dium, 477 serofibrinous, of serous membranes, 477 simple, 293 subacute, 293 suppurative, of larynx, 557 suppurative, of peribron- chial lymphatics, 562 suppurative, of serous membranes (see Sup- purative Pericarditis), 481 swelling in, 295 systemic phenomena of, 295 white corpuscles in, 285 Inflammations, acute catarrhal, of mucous membranes, 537 aseptic, 294 aseptic, of serous mem- branes, 475 atrophic, of mucous mem- branes, 539 819 Inflammations, catarrhal, of mucous mem- branes, 537 chronic catarrhal, of mu- cous membranes, 539 chronic infectious, of mu- cous membranes, 548 pustular, on mucous mem- branes, 547 suppurative, on mucous membranes, 547 Inflammatory edema, 266 enlargement, 304 leukocytosis, 432 process, terminations of the, 280 processes as atrophy, 223 Influence of cardiac inefficiency on other organs, 514 of stenosis on heart, 510 Influenza, bacillus of, 185 Inguinal lymphadenoid tuberculosis, 463 Inherited hemorrhagic diathesis, 260 Injections, intraperitoneal, 108 Inoculated animals, after-treatment of, causes of 109 postmortem exam- ination upon, 109 Inoculation of animals, 107 into the anterior chamber of the eye, 108 intravenous, 108 subcutaneous, of animals, 107 Inoma, 337 Instruments for postmortem, 17 postmortem, case for, 18 Insufficiency, influence of, on cardiac work, 510 of heart valves, 510 Insular sclerosis, 779 of cord, 787 Intention, first, union by, 298 second, healing by, 301 third, healing by, 302 Interlcbular emphysema, 571 Intermittent fever, 391 Internal causes of disease, 139 congenital hydrocephalus, 754 examination of the body, 23 genitals, postmortem examina- tion of, 34 Interstitial arteritis infectiosa, 517 emphysema, 571 endocarditis, 509 gastritis, 651 glossitis, 642 growth of neoplasms, 309 inflammation, 294 pneumonia, 593 820 Interstitial pneumonia, chronic, 593 termination of, 596 I. Intestine, actinomycosis of, 662 hernia of, 654 infectious processes in, 658 inflammation of, 658 leprosy of, 662 malformation of, 654 malposition of, 654 obstruction of, 655 structure of, 654 syphilis of, 661 tubercular ulcer of, 549, 662 tuberculosis of, 662 tumors of, 662 varicose veins of, 663 Intestines, postmortem examination of, 37 Intoxication, septic, 386 Intoxications, 382 auto-, 387. microbic, 385 Intracorpuscular plasmodia, 212 Intracystic warts, 313 Intraperitoneal injections, 108 Intravascular changes in inflammation, 283 Intravenous inoculation, 108 Intussusception, 655 at ileocecal valve, 656, 657 Inversio versicz, 613 Involucrum, 722 Ischemia, 257 Ischemic edema, 266 Itch-mite, 209 Ixodes ricinus, 210 Jar staining, 61 Jaundice, 234 hematogenous, 235 hepatogenous, 234 malignant, 672 Joint inflammation in croupous pneumo- nia, 587 Joints, ankylosis of, 739 Charcot’s disease of, 738 chronic infections of, 738 dropsy of, 267 hemorrhage into, 733 infiltration into, 732 inflammation of, 733 loose bodies in, 733 malformation of, 732 INDEX. Joints, malposition of, 732 neuropathic diseases of, 737 postmortem examination of, 44 K. Kalteyer’s cover-glass forceps, 95 Karyochromes, 744 Karyokinesis, 296 Karyokinetic figures observed in the epithelium of the mouth of a salaman- der, 297 Karyolysis (see Blood, Karyolysis of White Cells), 429 Karyomitosis, 296 Kelis, 339 Keloid, 339 cicatricial, 339 true, 339 Kettle, farina, 77 Kidney, absence of, 612 amyloid disease of, 628 urine in, 628 atrophy of, 614 calcareous infiltration of, 615 calculi or concretions in, 615 chronic interstitial nephritis, 623, 624, 625, 627 cirrhotic, 623 cloudy swelling of, 616 congenital cystic disease of, 632, 633, 634, 635, 636 congestion of, 616 contracted, 623 contracting, 623 cyanotic, 616 cystic disease of, 634 cysts of, 633 degenerations of, 615 diagram of blood supply to, 609: diseases of, 614 epithelium, granular degenera- tion of, 536 fatty, degeneration of, 615 infiltration of, 615 fibroid, 623 floating, 613 gouty, 623 granular, 623 hobnail, 623 horseshoe, 611 hydatid cysts of, 634 hyperemia of, 616 hypertrophy of, 614 in enteric fever, 660 infiltrations of, 615 inflammation of, 617 of pelvis of, 628 in hemoglobinemia, 435 in inefficiency of heart, 514 1 INDEX. Kidney, in leukemia, 446 large fatty, 620 white, 620 leprosy of, 632 malformations of, 610 malpositions of, 610 medical diseases of, 614 movable, 613 Senate degeneration of, 15 pigmentary infiltration of, 615 postmortem examination of, 33 prolapse of, 612 retention cyst of, 633 single, 611 small white, 620 solitary, 610 structure of, 608 surgical diseases of, 614 syphilis of, 632 tubule, cloudy swelling of epi- thelial lining of, 242 tuberculosis of, 630 Killing agents, 48 Kitasato’s filter, 111 Knife, brain, graduated, 34 Koch-Ehrlich anilin- water solution, 94 Koch’s alkaline-beef-peptone bouillon, 76 law, 149 L. Labels, 65 Lactic acid, bacillus of, 152 Lamellar fibroma of the spleen, 455. Landry’s paralysis, 785 Lardacein, 229 histologic examination of, 230 Lardaceous disease of heart, 492 of lymph-glands, 461 of spleen, 453 of suprarenal bodies, 695 infiltration, 228, Large fatty kidney, 620 -lunged emphysema, 571 mosquito, 211 white kidney, 620 Laryngeal stenosis, 560 ‘ Laryngitis, 556 chronic catarrhal, 556 pseudomembranous, 542 spasmodic, 556 Larynx, calcification of cartilages of, 559 chronic infections of, 557 gangrenous inflammation of, 557 hemorrhage from, 556 hemorrhagic inflammation of,557 inflammation of, 556 821 Larynx, malformations of, 556 perichondritis, 558 postmortem examination of, 32 pseudomembranous inflamma- tion of, 557 stenosis of, 559 structure of, 555 suppurative inflammation of, 557 syphilis of, 557 tuberculosis of, 557 tumors of, 560 Large spindle-cell sarcoma, 350 Larva of trombidz, 210 Latent osteomyelitis, 719 tuberculosis, 370 Law,’ Koch’s, 149 Muller’s, in relation to neoplasms, 309 Virchow’s, in relation to neoplasms, 309 Leaflets, thickened, 509 Left parotid, section of, 645 L’Endocardite vegetante ulcereuse, 507 Leontiasis of bone, 713 Lepra mutilans, 381 Leprosy, 379 anesthetic, 379 bacillus of, 188 gangrenous, 381 mixed forms of, 381 nodular, 380 of bone, 727 of intestine, 662 of kidney, 632 of liver, 680 of lung, 604 of mucous membranes, 550 of nasal mucosa, 554 of spleen, 459 of urinary organs, 632 smooth, 379 trophoneurotic, 380 tubercular, 380 Leptomeningitis, 758 acute, 759 chronic, 759 fibrinous, 759 suppurative, 759 Leptus autumnalis, 210 Lesions that may accompany croupous pneumonia, 586 Leukemia, 442 blood changes in, 443 bone marrow in, 445 kidney in, 446 liver in, 445 lymphatic, 444 lymphatic glands in, 445 mixed forms of, 444 spleen in, 444, 457 822 Leukemia, splenomedullary, 44 Leukocytes, 428 counting of, in blood, 417 differential counting of, 418 melaniferous, 429 migration of, 285 normal number of, 428 of a frog, 285 Leukocythemia, 442 Leukocytopenia, 429 Leukocytosis, 429 inflammatory, 432 physiologic, 432 Leukoderma, 236 3 Leukolysis, 429 Leukontyelitis, 783 Leukopenia, 429 Leukoplakia, 642 Life history of hypertrophy, 513 Limitations of hypertrophy, 220 Lingual abscess, 642 Liomyoma, 341 Lipemia, 422 Lipoma, 333, 335 diffuse, of the neck, 334 simple, 335 Lipomata, diffuse, 333 Lipomatosis, 227 of the heart, 492 Liquefaction necrosis, 250 morbid of, 250 sites of, 250 of gelatin by bacteria, 149 Liquor puris, 290 sanguinis, 420 Lithopedion, 238 Lithosis, 232 Litmus paper as an indicator, 78 Liver, 664 a actinomycosis of, 680 acute yellow atrophy of, 668, 672 albuminoid, infiltration of, 669 amyloid, 228 infiltration of, 669, 670 atrophic cirrhosis of, 674, 677 beginning cirrhosis of, 675 carcinoma of the, 325 ‘ -cells, cloudy swelling of, 242 fatty degeneration of, 243, 6 anatomy _ 33 infiltration of, 227 granular degeneration of, 536 showing fatty infiltration, 227 cirrhosis of, 674 coagulation necrosis of, 673 coccidial disease of, 680 congestion of, 666 INDEX. Liver, contracted, 674 contracting, 674 cylindric-cell carcinoma of, 681 cystic adenoma of, 680 cystoma of, 681 cysts of, 681 fatty cirrhosis, 677 degeneration of, 672 infiltration of, 226, 668, 669 fibroid, 674 floating, 666 function of, 665 gin-drinker’s, 674 glandular carcinoma of, 330 Glissonian cirrhosis of, 678 granular, 674 ‘*hobnail,’’ 674, 676 human, coccidium oviforme from, 194 hydatid cyst of, 681 hyperemia of, 666 hypertrophic cirrhosis of, 678 hypertrophy of, 667 in enteric fever, 660 inflammation of, 673 in inefficiency of heart, 514 in leukemia, 445 in malarial fever, 670 leprosy of, 680 lobulated, 678 malformation of, 665 malposition of, 666 nutmeg, 667 parenchymatous degeneration of, 671 pigmentary infiltration of, 670 postmortem examination of, 36 pressure atrophy of, 667 pyemic abscess of, 674 red atrophy of, 666 scirrhus of, 330 showing results syphilis, 679 simple atrophy of, 667 slate-colored, 671 structure of, 664 syphilis of, 678 syphilitic cirrhosis of, 680 traumatic abscess of, 673 tropic abscess of, 674 tumors of, 680 Lividity, cadaveric, 22 Livores mortis, 22 Lobar sclerosis, 780 pneumonia, 579 Lobular pneumonia, 588 Lobulated liver, 678 spleen, 452 Local anemia, 257 atrophy of the heart, 491 of congenital INDEX. Local effects of bacteria and bacterial products, 154 immunity, 159 infections, 387 Localized glanders, 375 inflammation of the serous membranes, 483 Locomotor ataxia, 787 Léffler’s alkaline methylene-blue, 67, 94 blood-serum mixture, 74 method of flagella staining, 96 methylene-blue solution, 400 Loose bodies in joints, 733 Loss of tongue due to noma, 641 Louse, common, 210 Lung, abscess of (see Pulmonary Sup- puration), 574 actinomycosis of, 604 acute disseminated tuberculosis of, 370 anthracosis of, 232 brown induration of, 535, 565 carnification of, 571 chalicosis, 534 cirrhosis of collapse of, 571 collapse of, 570 congestion of, 565 cysts of, 607 emphysema of, 571 fever, 579 induration of, 593 tuberculosis, morbid anat- omy of, 602 gangrene of, 577 glanders of, 604 gray induration of, 571, 594 hemorrhagic infiltration of, 568 hyperemia of, 565 hypostatic congestion of, 565 in inefficiency of heart, 514 leprosy of, 604 malformation of, 564 morbid anatomy of chronic ulcer- ating tubercu- losis of, 601 of miliary tuber- culosis of, 599 parasites in, 607 postmortem examination of, 32 senile atrophy of, 574 showing chalicosis, 233 splenization of, 570 structure of, 564 suppuration of, 574 syphilis of, 603 tuberculosis of, 600 tuberculosis of (see Secondary In- fection in}, 601 tuberculosis of, mode of infection, 596 823 Lung, tumors of, 605 white hepatization of, 603 Lupus exedens, 327, 374 nonexedens, 374 Lutein, 235 Lymphadenia, 442, 465 Lymphadenitis, 461 quiescent 464 scrofulous, 463 syphilitic, 465 tuberculous, 463 Lymphadenoma, 465 Lymphangiectases, 643 Lymphangiectasis, 528 Lymphangioma, 344, 528 Lymphangiomata, 526 Lymphangitis, 527 - acute, 527 reticular, 528 suppurative, 527 tubular, 528 chronic, 527, 528 peribronchial, _ suppura- tive, 576 Lymphatic glands in leukemia, 445 leukemia, 442 plethora, 259 Lymphatics, peribronchial, suppurative inflammation of, 562 Lymphemia, 444 Lymph-glands, 460 adenitis chronica of, 463 atrophy of, 460 bubo of, 462 carcinoma of, 467 degenerative changes of 461 diseases of, 460 infections of, 461 lardaceous disease of, 461 periadenitis chronica, 463 perilymphadenitis, 461 pigmentary infiltration of, 460 sarcoma of, 467 syphilis of, 465 tuberculosis of, 463 tumors of, 467 Lymph-nodes, 460 Lymphocythemia, 444 Lymphogenous tuberculosis, 598 Lymphoid atrophy, 460 cells from meninges, 287 Lymphoma, 344 malignant, 465 Lymphosarcoma, 344, 465 Lymph-scrotum, 527 -spaces, primitive, 526 -vessels, 525 tubercular, 824 Lymph-vessels, malformations of, 526 obstruction of, 526 tuberculosis of, 528 tumors of, 528 M. Macroblasts, 425 Macrocheilia, 344, 643 Macrocytes, 423 Macrocythemia, 423 Macrocytosis, 423 Macroglossia, 344 Macrostoma, 638 Macule albidee on pericardium, 473 Madura disease, 162 organism of, 162 Maggots, 211 Malacosteon, 716 Malaria, plasmodia of, 211 method of demonstrating plas modia of, 212 Malarial fever, liver in, 670 organisms, forms of, 213 Malformation, 138 of bone, 707 of brain, 749, 752 of heart, 489 of joints, 732 of liver, 665 of lungs, 564 of muscle, 697 of pancreas, 685 of pericardium, 472 of spinal cord, 749 of spleen, 451. of stomach, 650 of suprarenal bodies, 695 of thymus body, 468 of thyroid gland, 691 of trachea, 556 Malformations of biliary passages, 682 of bladder, 613 of bronchi, 561 of esophagus, 646 of larynx, 556 of lymph-vessels, 526 of kidney, 610 of mouth, 637 of nose, 552 of ureter, 613 of urethra, 613 Malignant adenoma, 323 edema, bacillus of, 175 goiter, 693 jaundice, 672 lymphoma, 465 neoplasms, 310 Mallet, 37 Malposition, 137 INDEX. Malposition of heart, 488 of intestine, 654 of joints, 730 of liver, 666 of pancreas, 685 of pericardium, 472 of spleen, 450 of suprarenal bodies, 695 of stomach, 650 of thymus body, 468 of thyroid gland, 691 Malpositions of kidney, 610 Marasmic necrosis, 249 thrombus, 270 Marchi’s fluid, 244 Mayer’s albumin, 56 carmalum, 64 Maximum temperature, 103 McCrorie’s method of staining flagella, 97 Measures of capacity, 19 Meckel’s diverticulum, 654 Mediastinal lymphadenoid tuberculosis, 463 Medical diseases of kidney, 614 Medium, culture-, 73 Elsner’s differentiating, 185 reaction of, 150 Medullary carcinoma, 331 Megaloblasts, 425 Megalocytes, 423 Megalogastria, 650 Megastria, 650 Melanin, 233 Melanosarcoma, 352 Melanosis, 234 pseudo, 231 Melanotic carcinoma, 333 sarcoma, 352, 353 Membrana propria, 531 Membrane, normal serous, 470 prophylactic, 482 pyogenic, 482 Membranes, serous, 470 Meningeal hemorrhage, infantile, 770 Meninges, .anemia of, 758 lymphoid cells from, 287 syphilis of, 762 Meningitis, cerebrospinal, 763 chronic alcoholic, 763 demonstration of diplococcus of, 169 en plaque, 762 in croupous pneumonia, 587 organism of, 169 tubercular, 761 Meningocele, 751, 754 _ encephalo-, 754 myelo-, 751 myelo-cysto-, 752 INDEX. Menorrhagia, 261 Merorachischisis, 750 Mesenteric glands, postmortem examina- tion of, 37 lymphadenoid 463 Mesonephron, 613 Metamorphosis, 241 fatty, of mucous mem- branes, 535 hyaline, 246 myxomdtous, 245 parenchymatous, 241 Metaplasia, 217, 221 examples of, 221 of cartilage, 732 Metastasis, 310 by the blood, 310 growth of neoplasms by, 309 Metastatic abscess of the heart, 496 abscesses, 272, 278 Method, Friedlander’s, ofstaining diplo- coccus of pneumonia in tissue, 168 of bacteriologic examination, postmortem, 45 of collecting sputum, 131 of conducting urinary examina- tion, 118 Widal’s test, 113 of demonstrating ameeba coli, 195 of demonstrating bacillus lacu- natis, 188 of demonstiating bacillus of lep- rosy, 189 of demonstrating bacillus pestis, 186 of demonstrating echinococcus- hooklets, 208 of demonstrating nerve degen- erations, 761 of demonstrating spirillum of re- lapsing fever, 192 of demonstrating the plasmo- dium malarize, 212 of demonstrating trichina spir- alis, 198 of demonstrating tubercle ba- cilli in milk, 182 of filling test-tubes, 182 of holding tubes during inocula- tion of liquid me- dia, 89 tubes during inocula- tion of solid me- dia, 88 of infiltration, 51 of inoculating tubes, 88, 89 of mounting paraffin sections, 56 tuberculosis, 825 Method, of preparing antitoxins, 110 pure cultures of ac- tinomyces, 161 toxins, I10 of preventing stored media from drying, 84 of removing paraffin from sec- tions, 58 of staining bacteria, 94 the capsule of the pneumococcus, 169 the diplococcus of pneumonia in tis- sue, 168 tubercle bacilli in urine, 181 tubercle bacillus in sputum, 181 Pianese’s, of demonstrating col- loid degeneration, 247 of demonstrating hya- line degeneration, 247 the Pitres-Nothnagel, of exam- ining the brain, 43 Ziehl-Neelsen, for staining tu- bercle bacilli in tissues, 181 Methylene-blue, 67 Loffler’s alkaline, 67, 94 Unna’s alkaline, 67 Methyl-violet, 67 Metrorrhagia, 261 Microblast, 425 Microbic intoxications, 385 Microcephaly, 755 Micrococcus cereus albus, 171 flavus, 172 pyogenes albus, 171 aureus, 170 citreus, 171 tenius, 171 tetragenus, 172 Microcytes, 423 Microcythemia, 423 Microcytosis, 423 Micromyelia, 752 Microorganisms in croupous pneumonia, 580 Microscope, use of, 71 Microscopic examination of stained mounts, 98 examination of unstained mounts, 98 examination of urine, 118 scissors, 56 Microsomia, 708 Microsporon furfur, 163 826 INDEX. Microstoma, 638 Microtome for celloidin-infiltrated tissue, 55 Minot, 58 Ranvier’s, 57 Ryder, 57 Migration of leukocytes, 285 Milk as a culture-medium, 74 coagulation of, by bacteria, 150 spots on pericardium, 473 tubercle bacilli in, 182 Minimum temperature, 103 Minot, microtome, 58 Mitral valve, acute endocarditis of, 505 Mixed-cell sarcoma, 351 cultures, 85 forms of leprosy, 381 hemorrhage, 259 tumors, 357 Modified Virchow postmortem knife, 24 Moist chamber for potato culture, 75 heat, sterilization by, 83 gangrene, 254 Mold fungi, 159 Molecular layer, 748 Mollities ossium, 716 Molluscum contagiosum, 194 fibrosum, 339 Monarthritis, 733 Monarticular arthritis, 733 Monilia conidia, 165 Morbid anatomy of acquired pulmonary atelectasis, 570 of active hyperemia of brain, 765 of acute catarrhal in- flammation of mucous membranes, 538 of acute malignant en- docarditis, 508 of acute parenchyma-~ tous nephritis, 618 of acute poliomyelitis, 785 of acute simple endo- carditis, 504 of acute simple serous synovitis, 734 of acute suppurative ar- thritis, 735 of amyloid disease of kidney, 628 of amyloid infiltration, 230 of amyloid infiltration of liver, 669 of anemia of brain, 765 of arteritis obliterans, 516 Morbid anatomy of atheromatous ‘arte- ries, 515 of atrophic cirrhosis of liver, 675 of bone-necrosis, 721 of broncho-pneumonia, 590 of calcareous infiltra- tion, 237 of caseous tuberculosis of lung, 601 of cerebral hemorrhage, 769 of cerebrospinal menin- gitis, 763 of chronic catarrhal in- flammation of mucous membranes, 539 of chronic infections of joints, 738 of chronic interstitial nephritis, 625 of chronic meningo- encephalitis, 777 of chronic pancreatitis, 688 of chronic parenchyma- tous nephritis, 620 of chronic productive osteitis, 722 of chronic ulcerating tuberculosis. of lung, 601 of coagulation necrosis, 250 of combined lateral and posterior sclerosis of spinal cord, 790 of congenital pulmonary atelectasis, 569 of congestion, 263 of congestion of kidney, 616 of congestion of liver, of cyanotic kidney, 616 of diffuse interstitial myocarditis, 498 of dilatation of heart, 514 of edema, 266 of edema of lungs, 567 of endarteritis verru- cosa, 518 of enteric fever, 658 of fatty cirrhosis of liver, 677 of fatty degeneration, 243 INDEX. Morbid anatomy of fatty degeneration of liver, 672 of fatty infiltration of liver, 668 of fibroid phthisis, 602 of gangrene, 255 of gangrene of lung, 578 of gastric ulcers, 653 of glycogenic infiltra- tion, 240 of hematemesis, 651 of hemorrhagic inflam- mation, 547 of hemorrhagic inflam- mation of mucous membranes, 545 of hereditary ataxia, 789 of hypertrophic cir- rhosis of liver, 678 of hypertrophy of heart, I of inflammation, 282 of interstitial emphy- sema, 571 of interstitial pneumo- mia, 594 of liquefaction necrosis, 250 of locomotor ataxia, 787 of miliary tuberculosis of lung, 599 of myelitis, 783 of neuritis, 792 of pancreatic hemor- thage, 685 of parenchymatous de- generation, 241 of passive hyperemia of brain, 765 of pericarditis, 476 of pigmentary infiltra- tion of liver, 671 of primary lateral scle- rosis, 789 of ‘ progressive spinal muscular atrophy, 786 of pulmonary embolism, 568 of pulmonary abscess, of rickets, 731 of simple acute focal encephalitis, 775 of simple atrophy of liver, 667 of suppurative cerebritis, 776 of syphilis, 364 827 Morbid anatomy of thrombosis of veins and sinuses of brain, 773 of tuberculosis, 368 of tuberculosis of lung, 99 of tuberculosis of mu- cous membranes, 548 of vesicular emphysema, ; 572 histology of parenchymatous de- generation, 671 physiology of inflammation, 294 Morbus anglicus, 730 Virgineus, 438 Mother’s mark, 342 Mosquito, 211 horse, ‘211 large, 211 Motility of bacteria, 147 Mounting sections, paraffin, method of, 56 technic of, 63 Mounts, stained, microscopic examina- tion of, 98 unstained, microscopic examina- tion of, 98 Mouth, diphtheria of, 642 infection of, by bacteria, 642 inflammation of, 638 malformations of, 637 sore, putrid, 638 tumors of, 643 Mouse, apparatus for holding, 107 Movable kidney, 613 Mucoid carcinoma, 332 degeneration, 245 Mucorini, 159 Mucous membrane, congestion of, 532 diseases of, 532 hemorrhage from, 532 hyaline transforma- tion of, 536 hyperemia of, 532 membranes, actinomycosis of, 51 acute catarrhal in- flammations of, 37 albuminoid _ infil- tration of, 535 amyloid infiltra- tion of, 535 atrophic inflam- mation of, 539 atrophy of (see Inflam mation of), 531 calcareous infiltra- tion of, 535 828 Mucous membranes, INDEX. catarrhal inflam- mations of, 537 chronic catarrhal inflammation of, 539 $ chronic infectious inflammations of, 548 cloudy swelling of, 535. coagulation ne- crosis of, 535 croupous inflam- mation of, 541 degenerations of, 535 diphtheric inflam- mation of, 545 dry catarrhal in- flammation of, 539 : fatty degeneration of, 535 . fatty infiltration of, §35 fatty metamorpho- sis of, 535 fibrinous inflam- mation of, 541 fibrinous transfor- mation of, 536 follicular in- flammation of, 539 glanders of, 550 hemorrhagic _ in- flammation of, 545 hypertrophic —in- flammation of, 539 infiltration of pig- ment from blood, 535 infiltrations of, 533 inflammation of, cee in inefficiency of heart, 514 leprosy of, 550 pigmentary infil- tration of, 533 plastic inflamma- tion of, 541 pseudo-membran- ous inflamma- tion of, 541 rhinoscleroma of, 551 Mucous membranes, structure of, 530 suppurative in- flammation on, 547 syphilis of, 550 tuberculosis of, 548 Muguet, 165 Miiller’s fluid, 49 law in relation neoplasms, 309 Multiple sclerosis of brain, 779 spleen, 452 Mumps, 643 Mural endocarditis, 502 thrombus, 269 Muscle, amyloid infiltration of, 701 atrophy of, 697 chronic infection of, 703 cloudy swelling of, 701 degeneration of, 701 fatty degeneration of, 701 infiltration of, 227 -fiber, granular degeneration of a, 242 hyaline degeneration of, 701 hydropic degeneration of, 701 hypertrophy of, 700° in enteric fever, 660 infiltration of, 701 inflammation of, 701 malformation of, 697 parasites of, 703 pigmentary infiltration of, 701 syphilis of, 703 tuberculosis of, 703 tumors of, 703 voluntary, structure, of, 697 Muscles, voluntary, 697 Muscular atrophy, progressive spinal, 86 paralysis, pseudo-hypertro- phic, 227, 698 Mycetoma, 162, 378 Mycoid degeneration of bone, 732 Mycoses of stomach, 651 of the blood, 389, 446 Mycosis, 272 Mycotic endocarditis, 507 stomatitis, 639 Myelemia, 443 Myelin, 746 Myelinic neuromata, 317 Myelitis, 783 central, 783 disseminated, 783 focal, 783 transverse, 783 Myelocythemia, 443 Myelogenic anemia, 440 leukemia, 442 INDEX. Myelocystocele, 752 Myeloid sarcoma, 350 Myelomeningocele, 751 Myelotome, 42 Myocardial abscess, 496 Myocarditis, acute, 496 suppurative, 496 chronic interstitial, 496 diffuse interstitial, 498 parenchymatous, 496 productive, 496 sclerotic, 496 segmentary, 496 Myocardium, fibrous degeneration of, 49) infiltration of, 496 transformation of, 496 wounds of, 501 Myoma, 340 Myomalacia cordis, 500 Myopathy, primary, 698 Myosclerosis, 698 Myositis, 701 acute poly-, 702 chronic, 702 ossifying, 702 . suppurative,. 702 Myxedema, 692 congenital, 691 postoperative, 692 Myxolipomata, 335 Myxoma, 344, 345 Myxomatous degeneration, 245 degeneration, demonstration of, by Pianese’s method, 247 degeneration, sites of, 246 polypi, 269 metamorphosis, 245 N. Nailer’s phthisis, 533 Nanosomia, 708 Naple’s paraffin bath, 54 Narrowed mitral orifice, 506 Narrowing of heart orifices, 510 Nasal mucosa, actinomycosis, 554 glanders of, 554 inflammation of, 553 leprosy of, 554 papilloma of, 554 rhino-scleroma of, 554. syphilis of, 554 tuberculosis of, 554 tumors of, 554 polypi, 554 _ Natural culture-media, 73 immunity, 157 829 Necrobiosis, 241 Necrosis, 248 caseation, 252 causes of, 254 cheesy, 252 causes of, 254 coagulation, 250 morbid of, 251 of liver, 673 of mucous mem- branes, 505 sites of, 252 termination of, 252 colliquative, 250 direct, 248 fat, 252 forms of, 250 indirect, 248 liquefaction, 250 morbid anatomy of, 250 sites of, 250 marasmic, 249 neuropathic, 249 of bone, 720 results of, 249 senile, 249 toxic, of bone, 720 Needles for handling sections, 60 for postmortem, 46 | platinum inoculating, 87 platinum, sterilization of, 88 Negative chemotaxis, 287 Neisser’s differentiating stain for bacillus diphtheriz, 174 method of staining, 96 Neoplasms, 304 atypic, 311 benign, 310 causes of, 306 classification of, 310 of, based on histogenesis, 311 connective-tissue, 311 growth of, by dissemination, 0 of, by infiltration, 309 of, by metastasis, 309 interstitial growth of, 309 malignant, 310 Muller’s law in relation to, 309 parasitic influence in, 307 parasitism of cells in, 308 pigmentation in, 310 typic, 312 Virchow’s law in relation to, 399 anatomy 830 Nephritis, acute, 617 catarrhal, 617 diffuse, 617 interstitial, 623 parenchymatous, 617 tubal, 617 chronic desquamative, 620 diffuse, 620 interstitial, 623, 624, 625, 627 interstitial, changes in urine in, 627 interstitial, changes in vascular system in, 628 parenchymatous, 620, 621 parenchymatous, changes in urine in, 622 tubal, 620 fibrinous, 617 tubal, 617 Nephroptosis, 612 Nerve-cells, arkyochromes, 744 arkystichochromes, 744 demonstration of, 745 gryochromes, 744 karyochromes, 744 somatochromes, 744 stichochromes, 744 degeneration, method of demon- strating, 761 Nerves, 742, 790 axis-cylinder of, 742 bodies of Nissl, 744 circulatory disturbances in, 790 ganglion cells of, 743 in alcoholic multiple neuritis, 792 inflammation of, 790 nodes of Ranvier, 749 olfactory, hyperesthesia of, 555 primary lateral sclerosis of, 789 regeneration of, 793 tumors of, 793 Nervous system, 740 anatomy of, 740 basket cells of, 748 glia cells of, 746 granule layer of, 748 gray matter of, 746 histology of, 742 molecular layer of, 748 substantia gelatinosa centralis, 748 Neuritis, 790 acute interstitial, 791 Neuroglia, 742 Neuroma, 316 INDEX. Neuromata, amyelinic, 317 glionic, 317 myelinic, 317 Neuron, 742 Neuropathic atrophy of bone, 715 diseases of joints, 737 edema, 266 necroses, 249 Neuroses of the stomach, 652 Nevus flammeus, 343 prominens, 343 vinosus, , 343 Nissl bodies of nerves, 744 Nodular leprosy, 380 Noli me tangere, 327 Noma, 255, 546, 640 loss of tongue due to, 641 Nonintective phlebitis, 524 Nonpathogenic fungi in urine, 121 Normal, definition of, 137 serous membrane, 470 Normoblasts, 424 Nose, carcinoma of, 554 hemorrhage from, 552 malformations of, 552 Novy’s apparatus, 99 Nucleated red blood-cells, 424 Numerical hypertrophy, 219 Nutmeg liver, 667 Nutrition of bone, 705 O. Oat-cell sarcoma, 350 Obesity, 227 Obligate bacteria, 151 Obliterative arteritis of coronary arteries, 499 endarteritis, 516 Obstructing thrombus, 269 Obstruction, esophageal, 648 of bowel, 655 of heart orifices, 510 of intestine, 655 of lymph-vessel, 526 pyloric, 652 Occlusion of vessels of brain, 770 Oidium albicans, 165 Old aneurysm, 522 Oligocythemia, 426, 428 Oliver’s hemoglobinometer, 404 Optimum temperature, 103 Organic stricture of esophagus, 647 Organism of favus, 162 of Madura disease, 162 of thrush, 165 Organisms, malarial, forms of, 213 Organized sediment in urine, 119 Organs of respiration, 552 INDEX. Organs of respiration, anatomic divisions of, 552 reserve force of, 218 urinary, 608 Oris, cancrum, 640 Orth’s fluid, 50 Osseous apposition, 707 resorption, 707 Ossification of blood-vessels, 520 Ossifying myositis, 702 periostitis, 711 Osteitis, 717 chronic nonsuppurative, 722 productive, 722 Osteoarthropathie hypertrophiante pnev- - monique, 713 Osteoarthropathy, pulmonary hypertro- phic, 713 Osteoblasts, 707 Osteoclasts, 707 Osteoma, 336 cancellous, 337 compact, 337 eburnated, 337 spongy, 337 Osteomalacia, 716 Osteomyelitis, 717 bacteria in, 717 chronic, 719 tuberculous, 724 Osteophytes, 715 on the popliteal aspect of lower end of femur, 714 Osteoporosis, 715 Osteosarcoma, 355 Ostitis, 717 Otitis media due to pneumococcus, 588 Oven, drying, 59 Oxyuris vermicularis, 197 Ozena, 554 P, Pacchionian bodies, 741 Pachyacria, 712 Pachydermatocele, 339 Pachymeningitis, 756 chronic internal, 757 hemorrhagic, 757 suppurative, 756 Pain in inflammation, 294 Palate, cleft, 638 Panarthritis, 733 Pancreas, 685 atrophy of, 686 calcareous infiltration of, 686 cloudy swelling of, 686 congestion of, 685 cystoma of, 689 cysts of, 689 831 Pancreas, fatty infiltration of, 686 hemorrhage into, 685 hyperemia of, 685 inflammation of, 686 malformation of, 685 malposition of, 685 postmortem examination of, 37 structure of, 685 syphilis of, 688 tuberculosis of, 688 tumors of, 688 Pancreatic apoplexy, 685 calculi, 689 fibrosis, 687 gangrene, 687 hemorrhage, 685 ranula, 689 sclerosis, 687 Pancreatitis, 686 acute henforrhagic, 686 suppurative, 687 chronic, 687 interstitial, 688 indurative, 687 Papilloma, 311, 312 of nasal mucosa, 554 villous, 312 with tendency toward villous formation, 313 Paradoxic embolus, 275 pyrexia, 391 Paraffin bath, Naple’s, 54 infiltration, 51 flat -iron- shaped table for, 51 method of removing, from sec- tions, 58 Paralysis, acute ascending, 785 glossolabiolaryngeal, 787 infantile, 698 Landry’s, 785 muscular, pseudohypertrophic, 698 progressive bulbar, 787 pseudohypertrophic muscular, 227 Parasites, animal, 193 in blood, 447 in bronchi, 607 in lung, 607 in serous cavities, 486 of muscle, 703 ~ quartan, 214 tertian, 214 Parasitic cysts, 362 influence in neoplasms, 307 stomatitis, 639 Parasitism of cells, in neoplasms, 308 Parasynovitis, 733 Parathyroids, 690 832 Parenchymatous degeneration, 241 degeneration, causes of, 241 degeneration, demon- stration of, 242 degeneration of kidney, 615 degeneration of liver, 671 degeneration, termina- tion of, 242 hepatitis, 672 inflammation, 294 metamorphosis, 241 myocarditis, 496 Parietal stream, 283 thrombus, 269 Parosmia, 555 Parotid bubo, 643 fibroid, 644 left, section of, 645 right, section from, 644 sclerosis, 644. Parotitis, 643 chronic interstitial, 644 indurative, 644 suppurative, due to pneumococ- cus, 588 Partial, giant growth, 218 hypoplasia of brain, 755 Passive atrophy, 224 congestion, 263 hyperemia, 263 of brain, 765 immunity, 158 Patch, smoker’s, 642 Pathogenesis, 138 Pathogenic bacteria, 149 cocci, 167 fungi in urine, 121 Pathogenicity of an organism, demon- stration of, 107 of yeasts, 164 Pathology, general, 137 of blood, 420 of ganglion cells, 766 Pelvis of kidney, inflammation of, 628 Peptic ulceration, 652 Perforating gastric ulcer, 652 Perforation of esophageal wall, 648 Pericystitis, 629 . Peri-esophageal suppuration, 647 Persistence of urachus, 613 Persistent fetal kidney due to anasto- mosis, 612 Phagedenic gingivitis, 639 Pharyngocele, 648 Pharynx, tumors of, 643 Pigmentary infiltration of kidney, 615 Prolapse of kidney, 612 INDEX. Ptyalism, 644 Putrid sore mouth, 638 Pyelitis, 628 Pyelonephritis, 628 tuberculous, 631 Pyloric obstruction, 652 Pylorus, stenosis of, 650 Pyonephrosis, 633 Pearl epithelioma, 322 Pectoral heart, 488 Pediculus capitis, 210 corporis humanus, 210 inguinalis, 211 ordinarius, 210 pubis, 211 vestimenti, 210 Pentastoma denticulatum, 210 Peptone solution, Dunham’s, 85 Peptonizing ferments, 152 Periadenitis chronica of lymph-glands, 463 Periarteritis nodosa, 518 simplex, 518 Periarticular abscess, 710 Peribronchial lymphatics, suppurative in- flammation of, 562 suppurative lymphangitis, 6 57 Peribronchitis chronica, 562 Pericarditis, 474 acute, 474 tubercular, 484 chronic, 474, 483 in croupous pneumonia, 586 suppurative, 481 Pericardium, adhesions of, 480 air in, 484 blood in, 485 calcification of, 481 circumscribed inflammation of, 483 diffuse inflammation of, 483 fatty infiltration of, 481 fibrinous inflammation of, 477 general 483 infiltration of, 473 inflammation of, 474 maculze albidze on, 473 malformation of, 472 malposition of, 472 milk spots on, 473 plastic inflammation of, 477 a se examination of, 2 pus in, 482 tendinous patches on, 473 tubercular inflammation of, 483 inflammation of, INDEX. \ Perichondritis of larynx, 558 Perihepatitis, 678 Perilymphadenitis, 461 Perilymphangitis, 528 Periosteum, hemorrhage under, 709 inflammation of, 709 Periostitis, 709 acute simple, 709 suppurative, 709 bacteria in, 710 albuminosa, 711 fibrous, 710 hemorrhagic, 710 ossifying, 711 Periostoses, 715 Perisplenitis, 454 Peritoneal abscess, 482 Peritoneum, pus in, 482 Peritonitis, suppurative, 482 Perivascular tissue, changes in, in inflam- mation, 286 Permanent endocarditis, 509 Pernicious anemia, 440 blood changes in, 440 Persistence of thymus gland, 468 Petechize, 261 of thymus body, 469 Petri dish, 86 plates, 86 Petrifaction, 237 Petrification, 237 Phagedenic ulcers, 292 Phagocytosis, 155, 432 Phagolysis, 156 Pharyngitis, 540 Phenolphthalein as an indicator, 78 Phenomena, systemic, induced by hem- orrhage, 262 Phlebectasia, 524 results of, 525 Phlebitis, 523 chronic, 524 noninfective, 524 suppurative, 524 Phlebosclerosis, 524 Phlegmonous cholangitis, 682 hepatitis, 673 Photogenesis of bacteria, 151 Phthirius pubis, 211, Phthisis, fibroid, morbid anatomy of, 602 nailer’s, 533 Physiologic atrophy, 222 hypertrophy, 219 leukocytosis, 432 Pia-arachnoid, cysts of, 764 tumors of, 764. mater, 740 circulatory disturbances of, 758 53 833 Pia-inflammation of, 758 Pianese’s method of demonstrating col- loid degeneration, 247 of demonstrating hy- aline degeneration, 247 of demonstrating myx- omatous degener- ation, 247 Pigmentary infiltration, 231 of bronchi, 563 of heart, 493 of liver, 670 of lymph-glands, 460 of mucous mem- branes, 533 of muscle, 70r of spleen, 452 Pigmentation, 231 bacterial, 236 in neoplasms, 310 Pigment, demonstration of, in tissues, 236 Pigments, autochthonous, 231 extraneous, 231 hematogenous, 233 Pineal body, diseases of, 782 Pitfield’s method of staining flagella, 97 Pitres-Nothnagel method of examining the brain, 43 Pituitary body, diseases of, 781 Plasmatic stream, 283 Plasmodia, epicorpuscular forms of, 212 intracorpuscular, 212 Plasmodium malariz, 211 crescentic form of, 215 estivo-autumnal form of, 215 extracorpuscular form of, 215 flagellate form of, 215 method of demon- strating, 212 sporulating, 212 Plasmolysis, 426 Plasmorrhexis, 426 Plastic inflammation of mucous mem- branes, 541 of pericardium, 477 of serous mem- branes, 477 Plates, blood, 86 . . Esmarch’s tube (see Esmarch’s Tube Plates), 87 Plating by Blake bottle, 86 methods, 85 834 Platino-aceto-osmic mixture, 49 Platinum inoculating needles, 87 needle, sterilization of, 89 Plethora, 259 corpuscular, 426 general, 259 hydremic, 259, 421 lymphatic, 259 vascular, 259 vera, 259 Pleura, localized inflammation of, 483 pus in, 482 Pleurze, postmortem examination of, 27 Pleurogenous interstitial pneumonia, 594 Pleuropneumonia, 579 Plexiform angiosarcoma, 353 hemangioma, 343 Pneumobacillus in sputum, 133 Pneumococcus, 579 abscess of frontal sinus due to, 588 in sputum, 133 otitis media due to, 588 parotitis, suppurative, due to, 588 Pneumoconiasis, 232, 533 Pneumonia, 579 bacillus of, 177, 579 bacteria in, 579 broncho-, 588 terminations of, 592 catarrhal, 540, 588 alveoli from, 592 chronic interstitial, 593 croupous, 579 endocarditis in, 587 joint inflammation in, 587 lesions that may accompany, 586 meningitis in, 587 microorganisms in, 580 pericarditis, 586 stages in, 581 staphylococci in, a streptococci in, 579 terminations of, 586 diplococcus of, 168, 579 fibrinous, 579 Friedlander’ s bacillus of, 177 hypostatic, 566 interstitial, 593 termination of, 596 INDEX. Pneumonia, lobar, 579 , lobular, 588 pleurogenous interstitial, 594 purulent, 574 septic, 579 tubercular, 597 tuberculous, 598 Pneumonitis, 579 Pneumopericardium, 484 Poikiloblasts, 425 Poikilocytes, 424 Poikilocytosis, 424 Poisons as causes of disease, 146 Poliomyelitis, 783 acute, 785 Polyarthritis, 733 Polyarticular arthritis, 733 Polycythemia (see Blood, Polycythemia), 426 Polyemia, 259 Polymyositis, acute, 702 Polypi, cardiac, 269 fibromatous, 269 myxomatous, 269 nasal, 554 Polypous endocarditis, 505 Porencephalia, 754 Pork tapeworm, 203 Portal thrombus, 270 Positive chemotaxis, 287 reaction of Widal’s test, 114 Posterior spinal sclerosis, 787 Postmortem blank, 21 clot, 267 examination of abdominal cavity, 26 examination of abdominal viscera, 33 examination of aorta, 37 examination of bladder, 34 . examination of bones, 44 examination of brain, 42 examination of coronary ar- teries, 31 examination of duodenum, 35 examination of esophagus, 37 examination of head, 38 examination of heart, 29 examination of inoculated animals, 109 examination of internal gen- itals, 34 examination of 37 examination of joints, 44 examination of kidneys, 33 examination of larynx, 32 examination of liver, 36 intestines, INDEX. Postmortem examination of lungs, 32 examination of mesenteric glands, 37 examination of pancreas, 37 examination of parotid gland, 44 examination of pericardium, 28 examination of pleurz, 27 examination of receptaculum chyli, 37 examination of retroperito- neal glands, 37 examination of salivary glands, 44 examination of spinal cord, 43 examination of spleen, 33 examination of stomach, 35 examination of sublingual glands, 44 examination of submaxillary glands,» 44 examination of thoracic cav- ity, 26 examination of thoracic duct, examination of thymus gland, 32 examination of thyroid gland, 2 de minette of trachea, 32 instruments, case for, 18 instruments for, 17 knife, modified, Virchow, 24 needles, 46 saw, 27 Postmortems, technic of, 17 Postnasal adenoids, 555 hypertrophy of, 555 Postoperative myxedema, 692 Potato as a culture-medium, 75 culture-medium, preparation of,75 moist chamber for, 75 plug-cutter, 76 sterilization of, for culture-me- dium, 65 Pott’s disease, 725 Predisposing causes of disease, 139 Prenatal tuberculosis, 367 Preparation of antitoxins, 110 of bouillon, for use as a cul- ture-medium, 76 of bouillon from beef-extract, 78 of potato culture-medium, 75 of toxins, IIO of urine-agar, 80 Preservation of tissues, 46 of urine, 119 835 Pressure, atmospheric, alterations in, as causes of disease, 145 atrophy, 222 of bone, 715 of liver, 667 Primary anemia, 436 lateral sclerosis of nerve, 789 myopathy, 698 spastic paraplegia, 789 thrombus, 269 Primitive lymph-spaces, 526 Probes, 36 Proctitis, 541 Production of bacteria by alkali, 152 of gas, 150 of indol, 102 of ptomains, 153 of putrefaction by bacteria, 152 of toxins, 153 Productive inflammation, 293 myocarditis, 496 Progressive bulbar paralysis, 787 lymphadenoid hyperplasia, 465 muscular dystrophy, 698, 700 pernicious anemia, 440 spinal amyotrophy, 697 spinal muscular atrophy, 786 Propagated thrombus, 269 Prophylactic membrane, 482 Proteolytic ferments, 152 Proximal thrombus, 270 Psammoma, 354 Pseudarthrosis, 730 Pseudohypertrophic muscular paralysis, : 227, 698 muscular paralysis, section of, 699 Pseudohypertrophy, 219 Pseudoleukemia, 446, 465 spleen in, 457 Pseudomelanosis, 231 Pseudomembranous bronchitis, 562 infammation of larynx, 557 inflammation of mu- cous membranes, 541 laryngitis, 542 Pseudoreaction of Widal’s test, 115 Pseudotrichinosis, 702 Pseudotuberculosis, 375 Psorosperms, 193 Ptomains, production of, 153 Pulex canis, 211 felis, 211 hominis, 211 irritans, 211 minimus cutem penetrans, 211 836 Pulex penetrans, 211 serraticeps, 211 Pulmonary albinism, 573 apoplexy, 568 atelectasis, 569 cirrhosis, 593 edema, 566 embolism, 568 emphysema, 573 hyperemia, 565 hypertrophic pathy, 715 infarction, 568 sclerosis, 593 suppuration, 574 Pure cultures, 85 Purkinje, cells of, 748 Purpuric, hemorrhages, 261 Purulent accumulation in gall-bladder, 684 . arthritis, 735 infiltration, 293 pneumonia, 574 rhinitis, 554 suffusion, 293 Pus-cells, 286 composition of, 290 in pericardium, 482 in peritoneum, 482 in pleura, 482 in urine, 120 Pustular endocarditis, 507 inflammations on mucous mem- branes, 547 Putrefaction, 22 production of, by bacteria, 152 Putrid bronchitis, 561 Pyelitis, 541 Pyemia, 272, 389 arterial, 507 Pyemic abscess of liver, 674 abscesses, 272, 278 Pyogenic membrane, 482 . Pyonephroses, 292 Pyopericardium, 482 Pyoperitoneum, 482 Pyopneumothorax, 576 Pyosalpinx, 292 Pyothrax, 482 Pyrexia, 384 paradoxic, 391 osteoarthro- Q. Quartan parasite, 214 Quiescent tubercular lymphadenitis, 464 tuberculosis, 370 INDEX. R. Racemose aneurysm, 343 Rachiotome, 19 Rachischisis partialis, 750 totalis, 750 Rachitis, 730 Rachitismus, 730 Ranula, 645 : pancreatica, 689 retromaxillaris, 645 sublingualis, 645 submaxillaris, 645 Ranvier, nodes of, 749 Ranvier’s microtome, 57 Ray fungus, 160 Raynaud’s disease, 255 Reaction of medium, 150 of stains, 150 positive, of Widal’s test, 114 Recent aneurysm, 522 Receptaculum chyli, post-mortem exami- nation of, 37 ° Records, systematic, for the study of bac- teria, I15 : : Rectum, tubercular abscess of, 662 Recurrent embolism, 275 fibroid tumor, 350 Red atrophy of liver, 666 blood-corpuscles in sputum, 131- softening of brain, 772 thrombus, 268 Reeves’ rapid method of fixing and infil- trating tissue, 54 Regeneration, 303 of blood, 435 of epithelium in repair, 301 of nerves, 793 Regurgitation, congestion of, 263 Relapsing fever, spirillum of, 191 Remarks on hemoglobin methods of esti- mation, 413 Remittent fever, 391 Removal of brain, 41 of heart, postmortem, 31 Renal sclerosis, 623 Repair, 296 by first intention, 298 epithelial regeneration in, 301 of bone, 728 Repletio, 259 Reproduction of bacteria, 147 of cells, 296 Reserve force of organs, 218 Resorption of bone, 707 osseous, 707 Respiration, anatomic divisions of or- gans of, 552 INDEX. Respiration, organs of, 552 Results of endocarditis, 510 of necrosis, 249 of phlebectasia, 525 of thrombosis, 274 Retention cyst of kidney, 633 cysts, 359 of liver, 684 Reticular, acute, lymphangitis, 528 Retrograde embolus, 275 : Retroperitoneal glands, postmortem ex- amination of, 37 lymphadenoid _ tubercu- losis, 463 Rhabdomyoma, 342 Rheumatoid arthritis, 736 Rhinitis, 540, 553 acute catarrhal, 553 atrophic, 554 fibrinous, 553 gangrenous, 553 hypertrophic, 554 purulent, 554 Rhinoliths, 555 Rhinorrhea, 555 Rhinoscleroma, bacillus of, 178 of mucous membranes, 551 of nasal mucosa, 554 Rickets, 730 Right parotid, section from, 644 Rigidity, cadaveric, 22 Rigor mortis, 22 Rodent ulcer, 327 Rosolic acid as an indicator, 102 Round-cell sarcoma, 348, 349 ulcer of stomach, 652 worms, 197 Rupture of bladder, 630 of heart, 500 of spleen, 458 Ryder microtome, 57 Ss. Saccharomyces albicans, 165 Saccharomycetes, 164 ; cerevisice, 164 Saccular aneurysm, 522 Safranin, 67 Sago-spleen, 230 Salivary calculi, 645 glands, 643. diseases of, 643 hypersecretion of, 644 postmortem examina- tion of, 44 tumors of, 646 Salpingomyelus, 752 Sand-flea, 211 837 Sapremia, 386 Sarcoma, alveolar, 352 angiolithic, 354 is fasciculated, 350 . giant-cell, 350, 351 large spindle-cell, 350 melanotic, 352, 353 mixed-cell, 352 myeloid, 350 oat-cell, 350 of lymph-glands, 467 of thymus body, 469 round-cell, 348, 349 small spindle cell, 350 varieties of, 345 Sarcoptes hominis, 209 Saturated solution of eosin in water, 68 Saw-cut, circumferential, 39 undertaker’s, 38 wedge-shaped, 40 double, for sawing through lamine, 44 for postmortem, 27 Scalds and burns as causes of disease, 142 Scalpels, 42 Schizomycetes, 165 division of, 165 Scirrhus, 328 atrophic, 331 degenerative changes in, "330 of liver, 330 Scissors, 31 microscopic, 56 Sclerosis, gastric, 651 nisular, 779 of spinal cord, lateral and pos- terior, 790 pancreatic, 687 parotid, 644 posterior spinal, 787 primary lateral, of nerve, 789 pulmonary, 593 renal, 623 Sclerotic endocarditis, 509 myocarditis, 496 Scrofulous lymphadenitis, 463 Scrotum, lymph, 527 Seats of calcareous infiltration, 237 Secondary anemia, 436 growths of cylindric-cell epi- thelioma, 325 infection, 388 in tuberculosis, 371 Second intention, healing by, 301 Section cutting, 51 of bone-marrow, 706 of left parotid, 645 of pseudohypertrophic muscular paralysis, 699 - 838 Section of right parotid, 644 of squamous epithelioma, 322 through a part of a vein with its organizing thrombus, 271 through border of healing wound, 302 Sections, paraffin, method of mounting, 56 Sediment from acid urine, 122 from alkaline urine, 122 organized, in urine, 119 unorganized, in urine, 122 Segmentary myocarditis, 496 Senile atrophy of bone, 715 of lung, 574 emphysema, 574 necrosis, 249 spleen, 452 Septicemia, 272 Septic intoxication, 386 pneumonia (see Pulmonary Sup- puration), 579 Sequestrum, 721 Serofibrinous inflammation of pericar- dium, 477 inflammation of membranes, 477 Serous cavities, 470 air in, 484 cysts of, 485 dropsy of, 471 hematoma of, 486 parasites in, 486 membranes, 470 adhesions of, 480 aseptic inflammations of, 475 calcification of, 481 chemic inflammations of, 475 chronic infections of, . 484 chronic inflammations of, 483 circumscribed inflam- mation of, 483 degenerations of, 474 diffused inflammation of, 483 endothelioma of, 528 fatty infiltration of, 481 fibrinous inflamma- tion of, 477 general inflammation of, 483 infiltrations of, 473 inflamed, 480 inflammation of, 474 localized inflamma- tion of, 483 serous INDEX. Serous membranes, plastic inflammation of, 477 serofibrinous inflam- mation of, 477 suppurative inflam- mation of (see Sup- purative Pericar- ditis), 481 tubercular inflamma- tion of (see Tuber- cular Inflammation of Pericardium), 483 tumors of, 485 Shake cultures, 98 Sherrington’s solution, 418 Shower, embolic, 276 Sialorrhea, 644 Siderosis, 232, 533 Simple acute focal encephalitis, 774 adenia, 465 atrophy, 223 of liver, 667 dilatation of veins, 524 embolus, 276 fibroma, 337 hemangioma, 342 hypertrophy, 219 of heart, 511 inflammation, 293 lipoma, 335 meningitis, 758 nevus, 342 thrombus, 269 ulcer of stomach, 652 Simplex, periarteritis, 518 Single kidney, 611 Sites of amyloid infiltration, 229 of coagulation necrosis, 252 of fatty infiltration, 227 of hydropic degeneration, 244 of liquefaction necrosis, 250 of myxomatous degeneration, 246 Situs inversus, 489 Skin, tuberculosis of, 374 warts, 312 Slate-colored liver, 671 Slide, drop-culture, 101 Small-lunged emphysema, 574 spindle-cell sarcoma, 350 white kidney, 620 Smear culture, 90 Smooth ependymal sclerosis, 780. leprosy, 379 Smoker’s patch, 642 Soft cancer, 332 fibroma, 338 Softening, cerebral, 771 Solid, artificial, culture-media, 76 blood-serum, 73 INDEX. Solitary kidney, 610 tapeworm, 203 Solution, Dunham’s peptone, 85 Gram’s iodin-iodo-potassic, 96 Koch-Ehrlich anilin-water, 94 Sherrington’s, 418, Toisson’s, 417 Somatochromes, 744 Soorpilz, 165 Sore mouth, putrid, 638 throat, gangrenous, 545 Spasmodic croup, 556 laryngitis, 556 Spatula, 109 Specific gravity of blood, 412 Spermatozoa in urine, 121 Sphacelation en masse, 254 Spina bifida, 708, 752, 753 Spinal cord, 741, 782 anemia of, 782 circulatory disturbances of, 782 column of Clark, 748 cysts of, 790 hemorrhages into, 782 hyperemia of, 782 inflammation of, 783 insular sclerosis of, 787 lateral and posterior sclero- sis of, 790 malformation of, 749 postmortem examination of, 43 showing posterior sclerosis, tuberculosis of, 790 Spindle-cell sarcoma, 350 Spirals, Curschmann’s, 132 Spirilla cultivated outside the body, 189 Spirillum not cultivated outside the body, 191 of Asiatic cholera, 190, 191 of Finkler-Prior, 189 of relapsing fever, I91 fever, demonstra- tion of, 192 proteus, 189 tyrogenum, I90 Spirochzta obermeieri, 192 Splanchnoptosis, 451 Spleen, 450 ‘“‘ague cake”? of, 453 actinomycosis of, 459 atrophy of, 452 calcareous infiltration of, 453 capsular fibrosis of, 455 chronic infections of, 458 inflammation of, 454 congestion of, 455 corneal fibroma of, 455 839 Spleen, cyanotic induration of, 451 cysts of, 459 emphysema of, 450 engorgement of, 453 fibroid, 454 gangrene, 457 hemorrhage into, 455 hemorrhagic infarcts of, 456 hypertrophy of, 452 hypoplasia of, 451 in enteric fever, 660 in inefficiency of heart, 514 in leukemia, 444, 457 in pseudoleukemia, 457 lamellar fibroma of, 455 leprosy of, 459 lobulated, 452 malformation of, 451 malposition of, 450 movable, 450 multiple, 452 pigmentary infiltration of, 452 postmortem changes in, 450 examination of, 33 rupture of, 458 sago-, 453 senile, 452 syphilis of, 458 tuberculosis of, 458 tumors of, 459 wandering, 450 Spleens, accessory, 451 Splenculi, 451 Splenic abscess, 457 anemia, 446 engorgement, 453 infarction, 456 leukemia, 442 Splenitis, acute diffuse, 454 chronic diffuse, 454 infectious, 454 Splenization of the lung, 570 Splenoptosis, 450 , Spondylitis deformans, 736 Spongy osteoma, 337 Sporadic cretinism, 691 Sporozoa, 193 Sporulating plasmodium, 212 Spreading gangrene, 256 » Sputum, bacillus of leprosy in, 133 Charcot-Leyden crystals in, 133 Curschmann’s spirals in, 132 demonstration of tubercle bacil- lus in, 180 elastic fibers in, 131 fibrinous casts in, 133 method of collecting, 131 pneumobacillus in, 133 pneumococcus in, 133 red blood-corpuscles in, 131 840 Sputum, technic of examining, 131 tubercle bacillus in, 133 white blood-corpuscles in, 131 Squamous epithelioma, 321, 322 section of, 322 epithelium, 131 Stab culture, 90 Stages in croupous pneumonia, 581 Stained mounts, microscopic examination of, 98 Staining bacteria, 93 blood, 399 by Gram’s method, 96 by Neisser’s method, 96 jar, 61 of actinomyces, 161 of capsule of the diplococcus, me- thod of, 169 of Friedlander’ s bacil- lus pneumoniz, 177 of diplococcus of pneumonia, in tissues, 168 of flagella, 96 by Léffler’s method, 97 by McCrorie’s meth- od, 97 by Pitfield’s method, 97 : of tissues by hematoxylin, 64 technic of, 63 Stain'reaction, 150 Staphylococci in croupous pneumonia, 579 Starvation as a cause of disease, 140 Stasis, 264 causes of, 264 Steam sterilizer, Arnold, 83 Steatoma, 337 Stenosis, influence of, on cardiac work, 510 laryngeal, 560 of bronchi, 563 of esophagus, 646 of heart orifices, 510 of larynx, 559 of pylorus, 650 tracheal, 560 Sterilization, 83 by moist heat, 83 of platinum needle, 89 of blood-serum, 74 of culture containers, 81 of egg for culture-medium, 75 of potato for culture-medi- um, 75 Sterilizer, hot-air, 81 steam, Arnold, 83 INDEX, Sternberg’s anaerobic culture tube, 99 flask, III Stewart’s cover: glass forceps, 93 Stichochromes, 744 Stomach, 649 congestion of, 650 cylindric-cell cancer of, 324 dilatation of, 652 hemorrhage from, 650 inflammation of, 651 hyperemia of, 650 malformation of, 650 malposition of, 650 mycoses of, 651 neuroses of, 652 ‘ postmortem examination of, 35 round ulcer of, 652 simple ulcer of, 652 structure of, 649 syphilis of, 651 tuberculosis of, 651 tumors Of, 653 vertical, 650 Stomatitis, 540, 638 aphthous, 640 fetid, 639 follicular, 638 gangrenous, 546, 640 mycotic, 639 parasitic, 639 ulcerative, 638 Stratified thrombus, 269 Streak culture, 90 Stream, axial, 283 circumferential, 283 corpuscular, 283 parietal, 283 plasmatic, 283 Strength of antitoxin, estimation of, 112 Streptococci in croupous pneumonia, 579 Streptococcus erysipelatis, 172 pyogenes, 172 Streptothrix madure, 162 Stricture, organic, of esophagus, 647 Stroke culture, go Stroma, fibrous, 318 Strongylus, 199 Structure of alimentary canal, 637 of arteries, 514 of bones, 704 of bronchi, 561 of endocardium, 501 of heart, 487 of intestine, 654 of kidney, 608 of larynx, 555 of liver, 664 of lungs, 564 of mucous membranes, 530 of pancreas, 685 INDEX. Structure of stomach, 649 of thyroid gland, 690 of trachea, 555 of veins, 523 of voluntary muscle, 697 Struma, 693 Strumipriva, cachexia, 692 Strumitis, 692 Styrone, 68 Subacute inflammation, 293 Subcutaneous inoculation of animals, 107 Subdivisions and forms of bacteria, 159 Sublingual glands, postmortem examina- tion of, 44 Submaxillary glands, postmortem exami- nation of, 44 Subnormal temperature, 384 Substantial emphysema, 571 Substantive emphysema, 571 Suffusion, bloody, 261 purulent, 293 Suggillation, 22, 261, 264 Suppuration, 290 diffuse, 293 hepatic, 673 of cellular tissues, 293 of lung, 574 peri-esophageal, 647 pulmonary, 574 Suppurative, acute, lymphangitis, 527 pancreatitis, 687 cerebritis, 775 hepatitis, 673 inflammation of larynx, 557 of peribron- chiallymph- atics, 562 of serousmem- branes, 481 inflammations on mucous membranes, 547 leptomeningitis, 759 meningitis, 760 myositis, 702 pachymeningitis, 756 peribronchial, lymphangi- tis, 576 pericarditis, 481 peritonitis, 482 phlebitis, 524 Suprarenal bodies, atrophy of, 695 calcareous infiltration of, 695 cysts of, 696 degeneration of, 695 hemorrhage into, 695 inflammation of, 695 lardaceous disease of, 695 ‘ malformation of, 695 841 Suprarenal bodies, malpositon of, 695 pigmentary in filtra- tion of, 695 syphilis of, 695 tuberculosis of, 696 tumors of, 696 Surgical aseptic fevers, 387 diseases of urinary apparatus, 614 Swelling, cloudy, 241 of epithelial lining of the kidney tubule, 242 of liver-cells, 242 in inflammation, 295 Symmetric aneurysm of abdominal aorta, 521 gangrene, 255 Symptomatic anthrax, bacillus of, 176 Synophthalmia, 552, 755 Synovitis, 733 acute simple serous, 733 Syphilis, 363 acquired, 363 bacillus of, 189 congenital, 364 liver showing re- . sults of, 679 of blood-vessels, 525 of bone, 725 of brain, 778 of dura, 757 of esophagus, 647 of heart-wall, 500 of intestine, 661 of kidney, 632 of larynx, 557 of liver, 678 of lung, 603 . of lymph-glands, 465 of meninges, 762 of mucous membranes, 550 of muscle, 703 of nasal mucosa, 554 of pancreas, 688 of spleen, 458 of stomach, 651 of suprarenal bodies, 695 of thyroid gland, 693 of urinary organs, 632 Syphilitic cirrhosis of the liver, 680 fever, 365 lymphadenitis, 465 Syphilomata, 365 Systematic records for the study of bac- teria, 115 Systemic phenomena induced by hemor- rhage, 262 of inflammation, 295 842 T. Table of blood diseases, 448, 449 of temperature changes, 384 | Tzenia echinococcus, 206 flavopunctata, 205 lata, 205 mediocanellata, 201 saginata, 201, 202 solium, 203 head of, 203 Tapeworm, armed, 203 beef, 201 broad, 205 dog, 206 pork, 203 solitary, 203 Tapeworms, 201 Technic, bacteriologic, 73 histologic (see Histologic Meth- ods), 48 of blood examination, 397 of chemic disinfection, 104 of mounting, 63 of postmortems, 17 of sputum examination, 131 of staining, 63 Telangiectatic polypi, 555 Telangiectoma, 342 Temperature changes, 382 maximum, 103 minimum, 103 optimum, 103 subnormal, 384 Temporary mounts of bacteria, 95 Ten-day-old fracture, 729 Tendinous patches on pericardium, 473 Teratoma, 357 Termination of coagulation necrosis, 252 of interstitial pneumonia, 596 of parenchymatous degener- ation, 242 Terminations of bronchopneumonia, 592 of croupous pneumonia, 586 of the inflammatory pro- cess, 289 Tertian parasite, 214 Testing gases, 106 Tests, chemic, for amyloid infiltration, 229 Test-tube basket, 80 tubes, method of filling, 82 Widal’s, method of conducting, 1:3 pseudoreaction, 115 Tetanus, bacillus of, 182 method of demonstrating bacil- lus of, 183 The microscope, 69 INDEX. Theories of immunity, 154 Theory, cellulohumoral, of immunity, 156 inclusion, of Cohnheim, 306 Thermal causes of disease, 142 death-point, 103, 150 determination of, 103 edema, 266 Thermic disinfection, 103 Thermolysis, 139 Thickened leaflets, 509 Third intention, healing by, 302 Thoma-Zeiss hemocytometer, 414 Thomsen’s disease, 701 Thoracic cavity, postmortem examination of, 26 duct, postmortem examination of, 37 Throat, sore, gangrenous, 545 Thrombophlebitis, 523 Thrombosed blood-vessel showing organ- ization and canalization, 273 Thrombosis, 267 causes of, 270 of cerebral veins and sin- uses, 773 of coronary arteries, 500 of splenic vein, 457 of veins and sinuses of brain, 773 results of, 274 Thrombus, 267 annular, 269 arterial, 270 ball, 269 bland, 269 canalized, 269 changes in a, 271 channeled, 269 distal, 270 gray, 268 infected, 269 infective, 269 infective, changes in, 271 marasmic, 270 mural, 269 obstructing, 269 parietal, 269 portal, 270 primary, 269 propagated, 269 proximal, 270 red, 268 simple, 269 stratified, 269 valve, 269 venous, 270 white, 268 Thrush fungus, 165 of esophagus, 647 INDEX. Thrush organism, 165 Thymic death, 469 hypertrophy, 468 Thymus body, 468 atrophy of, 468 carcinoma of, 469 diseases of, 468 ecchymoses of, 469 hemorrhagic infiltration into, 469 hypertrophy of, 468 hypoplasia of, 468 malposition of, 468 petechiz of, 469 sarcoma of, 469 tumors of, 469 gland, persistence of, 468 postmortem examination of, 32 Thyrocele, 693 Thyroglossal cyst, 690 ‘Thyroid gland, adenoma of, 694 anemia of, 691 atrophy of, 691 congestion of, 691 cysts of, 694 degeneration of, 692 hyperemia of, 691 hypertrophy of, 692 infiltration of, 692 inflammation of, 692 malformation of, 691 malposition of, 691 postmortem examination of, 32 structure of, 6go syphilis of, 693 tuberculosis of, 693 Tin foil for use in sealing tubes, 34 Tissue, embryonic, 298 granulation, 300 cellular elements of, 299 implantation into animals, 109 Tissues, cellular, suppuration of, 293 demonstration of pigment in, 236 preservation of, 46 Toad-head, 753 Toisson’s solution, 417 Toluidin-blue, 67 Tongue, inflammation of, 641 loss of, due to noma, 641 -tie, 638 Tonsillitis, 540, 642 Tonsils, inflammation of, 642 Tophi, 736 Toxic degeneration of heart, 495 edema, 266 necrosis of bone, 720 Toxicogenic bacteria, 149° 843 Toxins, method of preparing, 110 production of, 153 Trachea, hemorrhage from, 556 malformation of, 556 postmortem examination, 32 structure of, 555 Tracheal stenosis, 560 Tracheitis, 540, 556 Trachitis, 556 Trachomcoccus, 167 er sled fibrous, of myocardium, 49 Transudates, 267 Transverse myelitis, 783 Trauma as a cause of disease, 144 Traumatic abscess of liver, 673 aneurysm, 522 edema, 266 Trichina spiralis, 198 demonstration of, 198 Trichiniasis, 198 Trichocephalus dispar, 201 Trichomonas intestinalis, 195 vaginalis, 195 Trbmbide, larva of, 210 Trophic arthritis, 736 atrophy, 223 edema, 266 Trophoneurotic leprosy, 379 Tropic abscess of liver, 674 True aneurysm, 520 keloid, 339 Tubal nephritis, 617 Tubercle bacilli in sputum, 133 in tissues, Ziehl-Neelsen method for staining, 181 in urine, 121 bacillus, 180 in butter, 182 in milk, 182 in urine, method of demonstration, 181 method of staining, in sputum, 181 Tubercles, confluence of, 253 Tubercular abscess of rectum, 662 inflammation of pericardium, 483 of serous mem- branes, 483 leprosy, 380 meningitis, 761 pneumonia, 597 ulcer of intestine, 549, 662 Tuberculin, 182 Tuberculosis, 366 avian, bacillus of, 182 axillary lymphadenoid,. 463 844 Tuberculosis, bacillus of, 180 bronchogenic, 598 cavity, wall of, 602 cervical lymphadenoid, 463 chronic ulceration of lung, morbid anatomy of, 601 extension of, 371 healed-in, 370 inguinal lymphadenoid, 463 latent, 370 lymphogenous, 598 mediastinal lymphadenoid, 464 mesenteric lymphadenoid, 463 miliary, of lung, morbid anatomy of, 599 of bladder, 630 of blood-vessels, 525 of bone, 724 of brain, 778 of bronchi, 562 of dura, 757 of heart, 500 of intestine, 662 of kidney, 630 of larynx, 557 of lung, 600 mode of infection, 596, 601 ot lymph-glands, 463 vessels, 528 of mucous membranes, 548 of muscle, 703 of nasal mucosa, 554 of pancreas, 688 of skin, 374 of spinal cord, 790 of spleen, 458 of stomach, 651 of suprarenal bodies, 696 of thyroid gland, 693 of urinary organs, 630 prenatal, 367 quiescent, 370 retroperitoneal lymphade- noid, 463 secondary infection in, 371 Tuberculous lymphadenitis, 463 pneumonia, 598 pyelonephritis, 631 Tubes, method of holding during in- oculation of liquid media, 89 of holding during in- oculation of solid media, 88 of inoculating, 88, 89 INDEX. Tubular, acute, lymphangitis, 528 adenoma, 315 epithelioma, 327 Tubulated epithelioma, 327 Tubule, kidney, cloudy swelling of epi- thelial lining of, 242 Tumor albus, 725 fibrocellular, 339 Tumors, 304 adult connective-tissue, 333 epithelial, 311 benign, 310 classification of, 358 connective-tissue, 333 embryonic connective-tissue, 345 epithelial, 318 epithelial, 311 granulation, 365 mixed, 357 of biliary passages, 683 of blood-vessels, 525 of brain, 780 of cord, 790 of dura, 757 of esophagus, 649 of heart, 500 of intestine, 662 of larynx, 560 of liver, 680 of lung, 605 . of lymph-glands, 467 of lymph-vessels, 528 of mouth, 643 of muscle, 703 of nasal mucosa, 554 of nerves, 793 of pancreas, 688 of pharynx, 643 of pia-arachnoid, 764 of salivary glands, 646 of serous membranes, 485 of spleen, 459 of stomach, 653 of suprarenal bodies, 696 of thymus body, 469 of thyroid gland, 694 of urinary organs, 632 Typhoid bacillus, 183 fever, 658 diagnosis of, by Widal’s test, 112 ulcer, 660 of intestine, 659, 660, 661 Typic neoplasms, 312 U. Ulceration, 292 peptic, 652 Ulcerative endocarditis, 507 INDEX. Ulcerative stomatitis, 638 Ulcer, gastric, perforating, 652 rodent, 327 round, of stomach, 652 simple, of stomach, 652 tubercular, of intestine, 662 typhoid, 660 Ulcers, phagedenic, 292 Undertaker’s saw-cut, 38 Union by first intention, 298 Units, immunity, 112 Unna’s alkaline methylene-blue solution, 68 glycerin-ether mixture, 68 Unorganized sediment in urine, 122 Unstained mounts, microscopic examina- tion of, 98 Urachus, cyst of, 614 persistence of, 613 Uratemia, 422 Uratic infarcts, 615 Uremia, 422 Ureter, malformations of, 613 Urethra, malformations of, 613 Urethritis, 541 Uric acid deposits, 238 Urinary apparatus, surgical diseases of, 614 casts, 121 examination, method of conduct- ing, 118 fistulas, 630 organs, 608 leprosy of, 632 syphilis of, 632 tuberculosis of, 630 tumors of, 632 Urine, acid, sediment of, 122 -agar, preparation of, 80 alkaline, sediment from, 122 as a culture-medium, 75 casts in, 121 changes in, chronic interstitial ne- phritis, 627 in chronic parenchyma- ~- tous nephritis, 622 collection of sample of, 118 demonstration of tubercle bacilli in, 181 distoma heematobium in, 122 epithelium in, 121 filaria sanguinis hominis in, 122 gonococcus in, 122 in amyloid disease of kidney, 628 microscopic examination of, 119 nonpathogenic fungi in, 121 organized sediment in, 118 pathogenic fungi in, 121 preservation of, 119 pus in, 120 845 Urine, spermatozoa in, 121 tubercle bacilli in, 121 unorganized sediment in, 122 Use of microscope, 71 Uterus showing uniform myomatous en- largement, 340 Vv. Vacuolization, cellular, 244 Vaive thrombus, 269 Valves, aneurysm of, in acute simple en- docarditis, 507 Valvular endocarditis, 502 Valvulitis, 502 Varicose veins, 524 of intestine, 663 Varicosity, 524 of esophageal veins, 646 Varieties of adenoma, 315 of cocci, 165 of edema, 266 of emboli, 275 of neuroma, 316 of sarcoma, 345 Varix, 524 Vascular goiter, 693 plethora, 259 system, 487 i changes in chronic in- terstitial nephritis, 628 Vegetation of aortic cusps, 508 Vegetations in acute simple endocarditis, 505 ‘4 Vein, splenic, thrombosis of, 457 Veins, 523 cirsoid dilatation of, 525 esophageal, varicosity of, 646 inflammation of, 523 simple dilatation of, 524 structure of, 523 varicose, 524 of intestine, 663 Venous congestion, 263 hemorrhage, 259 hyperemia, 263 thrombus, 270 Verminous aneurysm, 522 Vertical stomach, 650 Vesicular emphysema, 571 Villous disease, 312 endocarditis, 505 papilloma, 312 pericarditis, heart showing, 477 warts, 312 Virchow’s law in relation to neoplasms, 09 icseed, abdominal, postmortem exami- nation of, 33 846 Visceroptosis, 451 Vitreous degeneration, 246 of blood-vessels, 520 Volkmann’s canals, 705 Voluntary muscles, 697 structure of, 697 Von Fleischl’s hemoglobinometer, 401 Ww. Wall, esophageal, perforation of, 648 of abscess, 291 of cerebral abscess, 776 of tuberculous cavity, 602 Warts, intracystic, 312 skin, 312 villous, 312 Warty endarteritis, 518 Water, bacteriologic examination of, and other fluids, 90 -bath, agate-ware, 77 centrifuge, 119 Waxy infiltration, 228 Wedge-shaped saw-cut, 40 Weigert’s method for demonstrating bac- teria in tissue, 95 Whip worm, 201 White blood-corpuscles in sputum, 131 corpuscles in inflammation, 285 hepatization of lung, 603 infarct, 277 softening of brain, 772 INDEX. White substance of Schwann, 746 swelling, 726 thrombus, 268 Widal’s test for the diagnosis of typhoid fever, 112 method of conducting, 113 positive reaction of, 114 pseudo-reaction of, 115 Wooden-tongue, 377 Worms, round, 197 Wounds of myocardium, 501 Wright’s method for anaerobic cultiva- tion in liquid media, 100 X. Xerostoma, 645 Y Yeast fungi, 164 Yeasts, 164 chromogenic, 164 pathogenicity of, 164 Yellow softening of brain, 772 Z. Zenker’s fluid, 50 Ziehl’s carbolfuchsin, 67, 94 Ziehl-Neelsen method for staining tuber- cle bacilli in tissues, 181 Zymogenes, 149 Zymogenic bacteria, 149 ORCS PSSA Wk ea ok ORS ree Ea RSA RS Kh Nn a Aas an artes : Q peat aaah hc aieae tc iat’ EPR RED AS EAR ASS Beth RA tre teeta Berens mie Sa Sahat OS ASN echt p EES REEEES EEN? Meee Ce ee aA KEE hk Re VM MMe Oe LER TT IIIA Sactens can ; on ae n oe EEE exceed Ae ed eRe ah paca eR RN HARA Res Roe aac CII AH ESL = RAE RARER EAR EAS - : a a G Pe AeA! EERE Se AN at ey ae eS ae os ELPr OS PEPE BSE RES ap aiats Beet ise Kirby eh a bteovuran ans Pit tetas: ter? ie, és a wes on see r Py Br ARE ag CoP e OK En Lah en Bal Ce U 5 (Soares Oe