AIDS TO PATHOLOGY BY HARRY CAMPBELL M.D., B.S. LaND., F.R.C.P. SDlIOR PHYSICIAN, WES'l' END HOSPITAL FOR NI:RVOUI DISEASmI: LATE PHYSICIAN AND PATHOWGIST AT THB NORTH-WEST WIlDON HosPITAL FOURTH EDITION LONDON BAILLIRRE, TINDALL & COX 8, HBNRIETTA STRBET, COVBNT GARDBN Igao WORKS BY KE~JOrH CAMPBELL, M.B .. F.R.C.S. CONSULTING SUltGEON, WESTERN OPHTUAI.M1C HOSPiTAL; COMJfAND OPHTHALMIC SPECIALlST, SOUTHERN COMMAND; MAJOR, R.A.M.C. REFRACTION OF THE EYE S«Md llJin-. (I.. PreI_Ii.... ) TREATMENT IN DISEASES OF THE EYE lIIi p,q.,,,ti.,,:, LONDON BAILLIERE. TINDALL & COX, 8, HENRIETTA STREET, LONDON, 5931 NLVS/IVRI 1\\ \ \05931 \ \ \ \ ~\ \\\\\l\ w.e. PREFACE TO THE FOURTH EDITION THE demand for another edition of this book has afforded the Author an opportunity for the careful revision of its contents. Much new ma.terialhas also been added; many sections (notably those dealing with the Wassermann Reaction, Rickets, Vitamines, Wound-Shock, Gas Gangrene, etc.) have been entirely rewritten, and every effort made to embody the most recent views bearing on pathological teaching and research. HARRY CAMPBELL. 14, "WIMPOLE "ST:!EET, LONDON. W. 1. Septemlm, 1920. Huoh philosophy is wanted for the oorreot observation of things whieh are before our eyes. RO'D'99I11AtJ. CONTENTS .A.GB TIlE BRICKS 011' THlII BODY 1 6 • VARIETIES all' DlIIGlIINBlU.TIoll PIGHlIINTATIOlif 12 ~%t" 14, ATROPHY 15 HYPERraOPHY 17 'THlII BLOOD AND ITS DISBAS]IIS INII'LAMMATION 17 33 lI'BVIIlRS 36 IMIIIUNITY 38 lIfATUU'S LIlIfES 011' DlIIII'lIINC:III' 39 tEDlIIMA AND DROPSY--THRO)l:BOSIS--BM:BOLIBll 61 THE GRANULOMATA 71 - TUMOUBS (NBOPLASMS) DIIIE4.S1II9 OF THE V1IIJD DISEASES 011' THE ARTBRIlIIS WOUND-SHOOK 76 • 103 • 106 • - COLLAPSE DISBASlIIS OF THE PBBIOAJmIUlIiI 115 116 116 119 131 DISlIIASlIIS 011' THE HlIIART DISEASES 011' THE LUNGS DISEASlIlB 011' THE NERVOUS SYSTBH • LUMBAR PUNOTURiD 153 • 154 - 100 • DISEASES 011' THE KlDNlIIYS • DISlUSlIIS 011' m1ll. LtVlilR vii 140 viii PAOli J)IAlIETEB MELLITUS - 177 - 178 - 179 J)ISEABES Oll' TRill ENDOORINE GLANDS • 183 SYFBILIS FATIGUE - HEAT STROKE • 2i4 INDEX - 245 DISJllA.SES OF THE GALL-BLADDEB AND BILE-DUOTS DISEASES Oll' THE PA..NCBEAS CHBONIO ALCOHOLISM DISEASES Oll' BONE - DISEASES OF THE JOINTS DEli'OBMITIES SAPB1EMIA.-SEl'TIOlBMIA-l'Y./EMU AN'IMAL PARASITES - - 193 200 201 210 216 228 231 244 AIDS TO PATHOLOGY TJiIE BRICKS OF THE BODY. The Cell.-The organism is built up df -a. number of struc· tural units known as cella, which bea.r the same relu,t:!'lJl to the body that the bricks do to the house. The natural cell is composed of 'life·stuff,' technically known as oytoplasm (C)/toa-the cell). a Bubstanoo resembling in appearance the white of egg, and when magnified, seen to be studded with a number of minute granules. If treated with certain reagents (alcohol, mercuric chloride, formalin, eto.) the cell dies, and what was the oytoplasm becomes a coagulum showing a retioulated framework. Whether the latter exists as suoh during life, but in an invisible form, it is impossible to say. It may be a. natural condition or it may be an artefact. Recent researches suggest that the oytoplasm is colloid in com· position (=intermedia.te between that generally reoognized as sus.JlCnded in a :fluid and that in a true solution,l. In typioal cases the cytoplasm is surrounded by a cell wall, and contains a nucleus and nuoleoli. The whole substance of the cell is conveniently oalled bioplasm. The nuclel£8, the most highly specialized part of the bioplasm, is the dynamic oentre, for it direots and controls its many activities. Deprived of its nucleus, the cell can neither grow nor reproduce itself, and soon dies. Like the cell itself, the nucleus is bounded by a membrane, the nuclear wall, which is achromatic-i.e.. having no affinity for basic dyes (chruma= colour)-and oontains a. network of interlaoing fibrils. The nuclear network is achromatio, but embedded in it are oertain small granules, which, because they stain a oharacteristic yellowish.brown colour by chromium salts, are ca.lled chrumatin. This chroma.tin is regarded as the one indispensable'life.stuff,' Md the bearer of the hereditary AIDS TO PATHOLOGY qualities of the cell. At the points where the threads of the network intersect, the chromatin granules may be heaped up into larger masses, called' net-knots,' or karyosome8. The nucleol'U8, contained within the nucleus, is usually single, but there may be 8S many as five. It is oxyphil (i.e., stains with acid dyes). Within it is a minute body, the endonucleua, the function of which is unknown. The centrosomfl8 lie in the cell cytoplasm, just· outside the nucleus. Usually there are two pl~ side by side FIa. 1.--a, Cell wall; b. reticulum; c. nuclear wall; d. karyosome; e. J. nuolear reticulum; o. nuoleolus; k. astral system. with centrosomes. enclosed within a membrane from the exterior of which radiate delicate fibrils-the aatralSY8tem of the CeD.trosome. The centrosomes appear to be connected with cell reproduotion, iItitiat ng the prooess (by separa.ting to the opposite poles of the oell) in ~itotio division. Cell Division.-The nucleus dhides. This division may be-I. Dirf/!t (simple or amitotic). The nucleus becomes constricted at its middle, and then by simple fission separates into two parts. The cell cytoplasm now divides, each half carrying a nucleus. The result is the production of two cells. 2. Indirect or mitotic. The chromatin granules 001- THE BRICKS OF THE BODY 3 lect into threads (mito8=a thread), whioh subsequently undergo a oomplox series of ohanges (known as karyokinesis) prior to the ultimate division of tho cell into two parts. Mitotic division i8 the rule. amitotio division is the exoeption. It is said to occur in malignant tumours. The cells lie bathed in lymph, which, though at times tending to stagnate locally. as in the muscles during rest, may be regarded as more or less oontinually on the flux, flowing both through and around them. The lymph-fl0f) to the cell oarries the oxygen. proteins. oarbohydrates, fats. salts, hormones, vitamines. and other substanoes neoe3sa for the bioohemioal ohanges that oonstitute oell life:{ the lymph. ebb carries away from the oell the waste produots of cell metabolism. Note.-Oxyphil. }-a1D·t f 'd d Dl Y or 001 yes. eosinophil Basophil =afDnityfor basic dyes. A.mphophll =afDnity for both. Neutrophil =no afDnity for either. Cell Disease. The structure of thc various cells of the body depends primarily upon the oonstitution of the zygote (=fertilized ovum) which gives origin to them. Their behaviour during life dopends upon their struoture as thus hereditarily determined. and upon the inflllonces brought to bear upon them from witbout. These influences are plasmic and fW1I-plasmic. Hon-Plasmic Infiueuce3.-These consist for tbe most part of nerve stimuli, which, originating In sen~Qry end·organs, oither on the surfaoo, or in the deepor tissuOB, of the body, are continually reverberating throughout the entire nervous system, and thus influencing not only individual neurones, but nonnervous cells (such as muscle cells and gland cells) attached to tho ends of etlerent norvc fibres. It we refl.cct that tho humo.n organism consists essentially of a nervous systom from the onds of \vhose etlerent norve twigs so many musclo and gland cells depend, the wholo being held together by oonnoctivo tissue, and permeatcd by 0. complex system of ohannols for tlle oirculatlon of the body flulds, and that nerve stimnli aro oeaselossly reverberating throughout the nervous system, we shall tho bettor reall~e how potontly that system must influonoe the individual colis of tho body. Plasmio Influences.-These operate through tho lymph bathing tho oolls, and depond upon the composition of that IYlllph, which, again, Is ossontially determined by tho oomposl- 4 A.IDS TO PA.THOLOGY tlon of the blood·plasma. This is a highly oomplox fluid-the mOijt oomplex In nllturo-oontaining an endless variety ot sub· stanoes-food'stulfs, oxygon, hormonelJ, ferment&--most ot whioh defy tho most Ollrotul and dolicate mothods ot ohomical researoh; and let the faot over be remembered that it is in a fluid of this kind that, from the beginning to the end oUts eareer, every cell in the body lies bathod and is through it subjected to an endless variety of influences, both good and bad. Cell Environment.-E60h 0011 may be regardod as surrounded by three zones: (a) A zono ot lymph, whioh foods the 0011; (b) II zone of blood, whioh toods the lymph; and (c) a zone of air (= lungs) u.nd food pu.bulum (=alimentary c!anal), which feed the blood. Now, the oolls ot the body dJsplay little or no intrinsio ten· dency to disease: the cell environment, notably the plasmic en· mronment, is chieftll res-ponBible lor whateuer disease mall al/ect the ceu. Even senile 0011 dosoneration is largely extrinsio in nature, tor though doubtless it is in part intrinsic--due to the running·~own or wearing·out ot the 0011 microcosm-it. is even more the result of spooiflc changes in the plu.smio environment of the cell Senility is, in fu.ct, mainly of plasmio origin, the in(lividual being slowly destroyed by means of his plasma: not, indeed, by any suoll simple and pathologioal proooss as that suggested by lIIetohnikoff""""",-e., by the absorption of baotoria toxins from the large intestine--but by the operation of oomplex physiologioal mechanisms, the obJoot of which is to put II de:tlnite torm to tho vital cyole, and thus obviate the innu.te tendonoy to immortality bolonging to all living matter. In some animals -e.g., the dog-these meobanisms oome Into operation soonor than In othors~.g., maD. Sometimes in man they come into -prema.t\ue e-perat1en, the arteries becoming sclerosed, the skin wrinklod, and the hair grey as ea1"ly, it may be, as the second decade; at others their operation is dolayed, the nonogonarian boing as youthful, it may be, liS the average man of fifty or Sixty. If we exoept oases of intrinslo senile degeneration, it but very seldom hal'pens thBt a coli primarilll becomes diseased. Tho nearest approaoh to such a phenomenon Is afforded by tho family palsies, in which de:tlnite systoms of neuronos undergo early degeneration. HeDce, in every oase ot cell disease we should suspect the oxistence of some morbid influence operating on the cell trom without. This influeneo may be nerv01t8 or plasmic. Cell Disease from Nervous Causes.-A familiar instanco is the degenoration which takos place in the striped muscle flbre when its motor twig is disoased. All the instances of genl'lne trophic lesions are due to some interference with the normal flow of nerve impulses Into the colis ' trephically , danlagod. Degeneration from Plasmio Causes.-l\fuch the most common 06UIHI of disease ot the 0011 is 80me abnormality in respeot of the THE BRICKS OF THE BODY plasma bathing it. heads: 5 Abnormalities 01 tbJa kind tall under tlfo 1. Detects in tile O£reu.latiIm oJ tile PlaBma.-Those may bo oentml. as In heart and lung disease; or looal. as in embolism and degeneration of the smaller blood vossels. Any sudden and pronounoed interference with the 10001 elroulation leads to profound degenerativo oho.nges. as in Infarot (see p. 67). Moro ohronlo defoots of tho olroulation. as in ohronio hoort disease and senile degeneration ot the arteries, lead to gradual atrOPhy of tile parenehyma cells and increase ot the fibrous elements. In the former ooso the sluggish eiroulation oouses damage of tllo oopillary walls, with escapo ot tho chromocytes into tho tlssuos and subsequent staining at tho tlssuos from their disintegration. as iIIllstmted in tho well-known' nutmeg liver.' In the lattel case tba fibrous ohange may be tormed senile .fibroN, and it is ohiefly responsible for tho toughening of the tissues observed in old ago. 2. Detecta in the OompOBititm oJ t1!BPlaBma.-The composition of the plasma may depart from the normal In an untold number ot ways. Thus the plasma may vary in respeot of its nutrient constituents. its fermonts. its hormones. and its normal waste produots. Furthermore. It may be poisoned (0) as the result of morbid metabolism, as In diabetes; (b) by tho introduotion ot a poison, suoh as lead or aloohol, into tho body; and (c) by bactorial and other toxins formed within the body. Tho vast majority of non-traumatlo djsO&sos result from tho action of a morbid plasma upon tho tlssuo oells. How wido Is tho rlllo which tho plRsma plays in disease Is evident from the faot that a toxio stato of tho plasma Is tho sole oausa of inflam· ma.tion; and how largely this process bulks among the diseases whioh the physiolan is oalled upon to treat Is evident from a casual porusal of any text.book on medlolne. But morbid plasma. induoes many lesions other than the inflammatory. Thus tho blood may contain substances whioh exert a -noxious action chlofly or entirely upon oertain kinds or colis. ploking thom out. as we say. by solootive aotlon. mlloh as tho pigmonts usod for staining mioroscoplo seotlons pick out Bomo colIs rather than others. It.. famUiar instanco of this is aftorded by tabes dorsalis. This dlsoo.so is a sequela of syphilis. and is due to tho aotion of a polson whloh oauses degenoration In c~rtain sensory neurones; and It fs probable that most of the • systom lesions' of tho norvous system-i.e.. sypunotrloal losions of partioular traots--lI,ave a Similarly plasmio origin. In suoh oo.S08 tho degenerative ohanges a~ for the most Part chronio. Morbid plasma may, however, sot Ull acute dostruotivo changes in special kinds of oolls. Experiments have shown that the tissues of animals. such as the dog and the rabbit. can be made to elaborate substaneos eapable of oausing rapid destruction of speoial oell types. snoh as obromooytos, hepatic cells, and renal oelIs; and there oan be little doubt that substanoos at this kind play an important part in disease. Thus. aoute 6 AIDS TO PATHOLOGY yellow atrophy of the liver is producod by the action ot some toxin which is to all intonts and purposes a hepatolysin (soo p. 46), and oortain forms of • acute panoreatltis' probably own a similar pathology. DEGENERATIONS AND INFD..TRATIONS. Strictly speaking, degeneration is simI)ly the reverse of evolution; it is an undoing, so to speak, of evolution. Thus, when the dendrites of a neurone diminish in number, as they do in old age, or when the transverse strire of a muscle disappear, degeneration takcs place. The pathologist, however, uses the term 'dcgeneration • in the chemical rather than in the structural sense. For him it means, not the actual death of the cell, but the replacement of its complex cytoplasm, partial or complete. by a material of a simpler type, such as fat. As already stated (p. 4), cell degeneration is rarely spontaneous, but almost always due to some morbid influence operating on tho cell. Such morbid influences operate. above a.ll. through the cell environment. To trace out the various degenerative changes which may be produced in the tissues by morbid conditions of the plasma would be impossible, even did space permit. When we 'fejltd that eve:ry abnormality of the plasma must tend to produce its own parlitmIa'f chp.nge in the ti88UIl8 whicl& that plasma bathll8, it i8 obtJiO'UB that the degeneration8 which p'l"otoplasm undergoes mU8t be far more numerOUB than th08e a8 yet ducribed by pathologists. Degeneration must be distinguished from inliltrationi.e., tho deposition of some new substance in an otherwise unaltered cell. Some of the more common forms of innltration and degeneration will now be considered. I njiltf"ationB. Degenerations. Glycogenic infiltration. Cloudy swelling. Fatty infiltration. Chromatolysis. Calcincation. Fatty degeneration. Amyloid degeneration. Hyaline degeneration. Mucoid degeneration. Colloid degenerati<m.. Caseation. DEGENERATIONS AND INFILTRATIONS 7 Glycogenic Infiltration. Glycogen is normally present in the liver, in embryonio tissues, and indeed to some extent in most cells (absent from their nuclei), but not in the nervous system, pancreas, salivary glands, thyroid, hypophysis, adrenoJs, or bone-marrow. As a morbid process, infiltration of glycogen ocours in malignant tumours, and in the leucooytes in cases of suppuration, pneumonia, and other IIo01lte infections. In diabetes mellitus the convoluted tubule of the kidneys. the heart-muscle, spleen, and leucooytes, are loaded with it. Glycogen stains a mahogany-brown colour with iodine (the iodide of glyoogen). and a bright red with Bost's carmine method. FaitJ Inilltration. In fatty infiltration tiny globules of fat appear in the cell, the protoplasm of which, however, remains heaUhy. The globules may coalesce and push the protoplasm against the cell wall. Fatty infiltration is the nornial condition of many connectivo tissues (e.g., of the medulla of the long bones) and, to a less extent, of the liver. It i8 only when the number of fat globules exceerla the normal limit that the term' fatty infiUration • i8 applicable. The causes are excessive (liet, espeoially if coupled with insufficient exercise, and alcoholism, partioularly beerdrinking. Excessive deposit of fat may also occur from an anabolio habit of body, as in the monstrously fat people seen in shows, and in myxmdema. In all such oases the causo is probably a peculiar condition of blood, in consequence of which the fat is not properly metabolized. 'Adiposa doloroan.' 1s a condition in which a nodular deposit of fat is associated with considerable superfi.cial pain. An excesaive local deposit of fat may result from disuse, as in the case of the muscles of a fraotured limb which has been put up in splints. 8 AIDS TO PATHOLOGY Caloifioation. Caloification is the deposition of lime salts (phosphate Land carbonate) in degenerated or dead tissues. Aocording to Klotz, 0. necessary preliminary to caloification is the formation of 80ap8 in the degenerated or dead tissues. • Bites.-Arteries, especially the aorta and coronary (very rarely the veins), valves of the heart, old tubercular lesions, Icerta.in tumours (e.g., fibro-myomata. of the uterus), the capsule enclosing the Triek&na BpiraZis, adherent pericardium, the walls of old absoesses, the fcetus of an eotopio gestation (forming lithopmdion or peritoneal oalculus), the thyroid, oostal, and other cartilages in old people. Cloudy Swelling. In oloudy swelling the oells beoome swollen, their oytoplasm • oloudy' from the presenoe of fine granules, and their nuolei obsoured. 'l'he granules, whioh are probably albuminous in nature, are dissolved by acetio acid and alkalies, but, unlike fat, are insoluble in ether and do not stain blaok with osmic acid. If the degeneration has not advanced too far, the cloudiness may clear up and the cell resume its normal appearance, but if it continues to advance it may pass into fatty degeneration. Cloudy swelling occurs in connection with febrile states (pneumonia, diphtheria, soarlatina, enteric, eto.). It i8 prod/aced by tk6 action of bacteriaZ toxi7l.8, its distribution being detemlined by the nature of the toxin, the organs most frequently affected being the kidney, liver, and heart. Chromatolysis. One of the first signs of degenerative ohange in the neurone is the absorption of the stainable Nissl granules (ohromatolysis). The ohange begins in the neighbourhood of the nucleus. The granules are first converted into fine dust, and ultimately disappear. DEGENERATIONS AND INFILTRATIONS 9 Fatty Degeneration. Practically all the tissues of the body and, with the exception ....f the urine, all thc body fluids contain fat. In fatty degeneration the cell protoplasm is replaced by fat, the fat being split off from the protoplasm molecule. The fat first appears as minute, highly refractile gmnules, which gradually increase in number until, it may be, the whole cell is converted into a mass of fat. Thc fatty contents stain black with osmic acid, and reddish-orange with Sudan III., and dissolve in alcohol and ether, but not in acetic acid. In the majority of cases cf fatty dogeneration, the proBllnce of Zipoids can be demonstrated. These are fat-like bodies soluble in fat solvents, and normally found In minute quantities in all tho tissues and blood, being ebPeclally abundant in tho nervous system, particularly in tho myelin of the whitc matter. Thore are three classes: (a) Tho phosphailides, C, H, 0, N, and P; (b) the galacfocides, C, H, 0, and N; (c) tho choZesterols, C, H, and O. Leoithin, whioh belongs to (a), is the most important of all lipoids. Fatty degeneration is typically found: In severe and prolonged anremins-e.g., fatty degeneration of the heaI1 always occurs in pernicious anremia; as the result of certain poisons. notably alcohol, chloroform, iodoform, ~"ulf, &M &i"l!\l)b'.T, f."ti'm' jf-,n,. ,£\l'lt,\m .:Jl ol\l'l"lkl)r bacterial toxins-e.g., pneumonia, diphtheria, enteric, tuberculosis. It is also found in diabetes and jaundice, and is often an accompaniment of amyloid degeneration. Hearl, liver, and kidneys, are the organs principally affected. WUy, Lardaceous, or Amyloid Degeneration. This is a condition in which peculiar changcs occur in the cytoplasm of certain connective tissues, whereby they become homogeneous, translucent, and 'waxy.' The change involves more especially the connective tissue of the middle and inner coats of the arterioles, and the subendothelial layers of the capillaries. The endothelium itself is never affected, nor are parenchyma cells of any sort (muscle, gland). 10 AIDS TO PATHOLOGY Of 250 caeos examined by Litten. the frequency In whlch the various organs were aflocted was as follows: Spleen. 99 per eent.; kidfUlY. 98 por oont.; efidocardiJ"m. 76 per oent.; liver. 65 ler oont. ; imestifUl8. 67 per oont. The skin. bones. lungs. and oentral nervous system. are exempt from It. The waxy material stains a deep mahogany brown (quiokly fades) with iodine, turning blue or violet if 10 per oent. sulphurio aoid is afterwards applied. With methyl violet it gives a deep rose pink (normal tissues are stained blue). This degeneration is found in connection with chronic suppuration, when no free dr.unage can occur, particularly that due to tuberculosis. It also ocours in syphilis, both acquired and congenital. Of 189 cases quoted by Lubarsch, 98 were due to pulmonary tuberculosis, 25 to bone and joint tuberculosis. while 35 were due to syphilis. The waxy material is a glyco-protein, linked with chrondroitin-sulphuric acid (Krakow). It is not a. preoipitate from the blood or lymph. but in all probability results from the action of bacterial or cellular tOxins, for the organs most affected, (kidneys, spleen, liver, and intestines) are those most ooncerned in the elimination and neutralization of toxins. Some authorities hold that it is due to an enzyme found in the spleen, giving as their 'reasons: (a) the spleen is the first organ to be attaoked; (b) the disease cannot be produced in dogs whose spleen has been removed. In the Liv6T.-The organ is greatly enlarged, smooth, firm, and heavy, with its edges rounded. The out surface is pale, translucent, and wax-like. 'l'he change commenc68 in the subendothelial layer of the capiUari68 01 the intermediate zone 01 the l~ver lobule (flee Diseases of the Liver), the lining endothelial cells of the capillaries remaining unaffected. The pressure of the new material upon the liver cells causes them to become fatty and to undergo atrophy. In the KidneY8.-These organs become pale and enlarged, and the capsule strips off readily. The cut section has a translucent, bacon-like appearance. The ohange begins in the 1J688el8 01 the glomerular tults and in the arteriIB rectIB. Later on, the basement membrane of the tubules (especially of the oortex) may suffer. The lining DEGENERATIONS AND INFILTRATIONS II epithelium of the tubules tends to undergo fatty degeneration, owing to interferenoe with the oirculation. In the Sploon.-There are two varieties of lardaoeous spleen: The sago-spleen, commonest in phthisis. In this the organ is but slightly enlarged. On section it is seen studded with small, translucent, sago-like bodies, which vary in size from a millet-seed to a hemp-seed, and give the ordinary amyloid reactions. The change begins in the arterioles and capillaries of the Malpighian bodies. The d~ffuse waxy sploon, commonest in syphilis. The organ is greatly enlarged, and becomes hard and firm. On section it shows a uniform translucent appearance. The walls of the sinuses of the splenio pulp specially exhibit the .change. Hyaline Degeneration. This term is applied to those conditions in which certain oell elements are converted into a substance like glass (hyalU8, glass). When affecting epithelium, the Van GillSon stain is yellowish-brown; whe:Q. affecting connective tissue, it takes the red fuchsin stain. It is only of importance when it affects blood vessels, in which case it is the intima of the arteri!>les that shows the degeneration. Mucoid Degeneration. The glyco-protein mucin is a normal secretion of the mucous mem branes, and is poured out in inoreased quantity when they become inflamed. As met with as a degenerative process, it is probably a pseudo-mucin. It is found as part of a degenerative process in chondromata, sarcomata, carcinomata, and other tumours. The affected cells and fihres swell up, and become transformed into a jelly-like substance. In water the muoin swells up; it is soluble in dilute alkalies, from which it is precipitated both by alcohol and acetic acid. Thionin blue stains the mucin red and the surrounding tissues blue. In ovarian oysts an allied substanc6-j)seudo-mucinis found. This differs from muoin in not being precipitated by acetic acid. 12 AIDS TO PATHOLOGY Colloid Degeneration. Colloid (kolla, glue) is a normal constituent of the thyroid gland and the pituitary body, blling derived from epithelium, the cells of which become detached and glued together into a solid mass. As a degeneration, it is most frequently met with in cancers of the abdomen, especially of the stomach, intestinc, ovary, and peritoneum. In rare instances it occurs in cancer of the breast, and in congenital cystio disease of the kidney. The material resembles mucin in appearance, but is insoluble in water, and is not precipitated by alcohol nor by acetic acid. . PIGMENTATION. , Pigmentation' (pingo, paint) is the term used to denote an abnormal deposit of oolouring matter in the tissues. The pigment usually lies within the cells of the pigmented area. . Melanin.-This is the most common normal pigment of the body. It oontains nitrogen, hydrogen, carbon, and sulphur, but no iron. It is bleaohed by chlorine, a feature which distinguishes it from carbon. It is not a product of the disintegration of hmmoglobin, bu~ it is elaborated by oel~ action from an albuminous substance, and is normally present in the skin, hair, iris, choroid, and cardIac muscle. The quantity of melanin in the skin is augmented by solar rays, at the elimactello in women, and often during pregnancy; also in leucoderma, Addison's disease, Graves' disease,- granular kidney, rheumatoid arthritis, and chronic tuberculosis: Melanin constitutes the pigment met with in melanotio sarooma; in certain cases of this disease it may be found in the urine (melanuria). Lipochromcs.-These are pigmcnted fats containing melanin, and are normally found in the corpus luteum. Pathologically, they are present in xanthoma and ohloromao It is not yet decided whether the pigment in brown atrophy of the -heart is due to ordinary melanin or to the presence of lipochromes. (Lipochromes are also found normally in oertain ganglion cells, and sometimes in degenerated nerve oells.) PIGMENTATION I3 Oe'hronosiB.-In this rare condition a dark pigment, allied to melanin, is deposited in the cartilages throughout the body (sometimes also in the aorta and kidneys). rendering the patient conspicuous on account of the bluish colour of his nose and ears. It often accompanies alkaptonuria. It has been observed to occul" after the treatment of wounds or sores by carbolic acid. The 'hrematoge:nO'UB pigments are derived from the breaking up of the chromocytes. The hQlmoglobin meleoule is VIll"y complox. It is represented approximately by CrMHIII1l3NIIIIl021SFeSs (Mann). Whon of no further use, thc chrcmocytoa are broken down in the livor, spleen. bone·marrow, and kidneys, the residual pigment being decomposod into (a) the iron·containing Awfn08i,derin, which is uaod in tho manufacture of new chromocytes; and (b) the iron· free A_Iota'", whioh is ohiefly excreted as a waete product by the liver in the torm ot bilirubin. Hremosiderin. or iron·containing pigment. is found in those diseases (e.g., pernicious anremia and malaria) in which there is a pathological destruction of the chromocytes. In pernicious anremia large quantities may be found. in the form of minute granules. in the cells of the intermediate zone of the liver lobules. as well as in the spleon. renal epithelium. and bone-marrow. In the kidll&Ys it may be present in a diffuse form. Hamtatoidin, or ironJree pigment. is generally derived from ~xtravaBated blood, the hremoglobin being first converted into hrematin and then into hrematoidin. It is often seen in the remains of old blood-clots in the form both of granules and orange-coloured rhombic cry8tals. which may remain unaltered for years. Living cells appear to be neccssary for the elaboration of hll'mosiderin. but not of hrematoidin. Piumentation from Bile.-Jaundice is genorally due to come form of obstruction to the outflow of bile from thc liver and to its subsequent absorption into the circulation, by which it is carried throughout the body. The pigmentation is the result of a diffu8e 8taining of the tisRucs with bilirubin and biliverdin. and is specially marked in tho conjunctiva. the skin. and beneath the tongue. (The toxic effects of jaundice are probably referable to the bile salts.) AIDS TO PATHOLOGY Extrinsio pigment8 are those introduoed into the body from without. The chief examples areThrough the lungs {Carbon. cOld. Iron. or grit. depositod in tho lungs and bronchial glands. Through the ali-} " . mcntary tract Arsemc. silver. deposited in the skin. Through the skin: Tattooing. NECROSIS. The term 'necrosis' (neoru8i8, deadness) signifies death of a limited portion of the bodily tissues. (When a considerable area of tissue is involved, the term gangrene is cmployed.) l'he principalforrns of necrosis are: focal necrosis, fat necrosis, coagulation necrosis, and caseation. Focal Necrosis.-ln this condition numerous minute areas of tissue--generally in the liver, 8pleen. lcidneY8, or lymph glands-undergo a focal necrosis. The protoplasm of the part disintegrates. the cell walls disappear, and a 'granular substance replaces the original tissue. The necrotic foci may be pither absorbed or converted into fibrous tissue. The most probable cause is a toxin, which may act directly by killing the cells outright, or indirectly by causing capillary thrombosis. Focal necrosis occurs in enteric f('lver, diphtheria, and probably in most of the other microbic infections. Fat Necrosis.-This is a condition in which localized patches of necrosis are found in the fatty connective tissues of the abdomen. In a large majority of cases it is associated with pancreatic disease (e.g., hrcmorrhage, abscess, gangrene). It is supposed that tlu fat.splitting ferment (steapsin) of the pancreatic juice escapes, and acts directly upon the parts affected. It is met with typically in the BubperitoneaZ fat, in t,he omentulll, mesentcry, and under-surfacc of the diaphragm, and is most mal ked in the immediate neighbourhood of the I)ancreas, often occurring in that organ itself_ Occasionally it is found in the pericardial fat and the medulla of bone, in which situations it is probably due to emboli of dctachtd p'tncreat.ic cells. In all these maces are to be NECROSIS seen, scattered throughout the normal fat, small opaque foci, ranging in size from a pin's head to a pea. The affected areas stain with osmic acid and molt on heating. Coagulation Necrosis.-This ocours when an area of tissue suddenly dies and becomes converted into a homogeneous, solid, firmly-compacted mass. It is probably always toxic in origin, and the cells in dying give rise to coagulins, which, uniting with the lymph, cause it to coagulate. The tissue must be a very cellular one, and an abundant supply of lymph must be present. The cmbolio infarction in the spleen and kidney form the most typical example. Zenker's Degeneration is now regarded as a form of ooagulation necrosis. It aJleots musole fibres: theso swell and loso their transverse striation, while the muscle-proteim ooagulate into II. olear homogeneous material., whioh soon breaks up into shiny masses of irregular shape. Zenker's degeneration is met with in oontinued tevers, notably onterio, and is ohiefly met with in the abdominal musoles. Caseation (caaeua, cheeso).-This is a post-necrotio change in whioh the cells disintegrate, lose their outline and nuclei, and are converted into a yellow, homogeneous cheesy mass, composed of desiccated cells, fatty dbbris, and cholesterin orystals. It is most often met with in tubercular and gummatous formations and in certain rapidl~-growillg tumours, and is due in part to the cutting off of the blood-supply by thrombosis, and in part to toxio action. ATROPHY. By atrophy is meant decrease in the size alone, or in both the size and number, of the elements of a normallydeveloIl6d tissue. The condition has to be distinguished from hypoplasia, in which there is defective development. It affects essentially the functionating elements (i.e., tho parenchyma) of an organ. Thus, in muscles it is the contractile substance; in glands, the secreting oells; in n~rves, the nerve fibres. The connective-tissue stroma either escapes or 'becomes hypertrophied. Physiological atropby, Buch as ocours in tho thymus, in tho uterus after parturition, in tho ovaries atter tIle menopause, is known as inllOlulion. 16 AIDS TO PATHOLOGY The protoplasm of an atrophying oell becomes un. wontedly clear, staining less tha.n norma.lly, and the nucleus disappears. Often there is increased pigmentation __ phenomenon well seen in brown atrophy of the senile heart. Atrophy may be general or local. Causes of General Atrophy.-General wasting of the tissues may be caused either by: Decreased, anaboli8m, the result of impoverishment of the blood, such as occurs in starvation-e.g., that caused by cancer of the <Esophagus and stomach; or by: Increased, katabolism, such as occurs in severe fevers, tuberculosis, congenital syphilis. In these cases the general wasting is chiefly to be ascribed to the action of toxins in augmenting katabolism. The wasting which occurs in Graves' disease and from the administration of thyroid extract is also due to heightened katabolism, the thyroid yielding, to the blood some substance which plays the part of a vital bellows, causing the vital fire to blaze, as it were. The Causes 01 Local Atrophy ar&L688ened, Funr.tional Activity-e.g., atrophy of the muscles of an arm or leg encased in splints. EXC68Biv6 Functional Activity.-Usually this is pre· ceded by hypertrophy. Exo.mples are: the sterno· mastoids and other cervical muscles in emphysema, and the biceps hrachialis in file-grinders. P"688ure-e.g., atrophy of the bodies of the vertebrm or sternum owing to the pressure exerted by an aneurism; atrophy of the liver cells caused by the pressure of the fibrous tissue in alcoholic cilThosis. Defective Neurotrophic Influence-e.g., facial hemiatrophy. We are still in the dark as to the pathology of this curious affection, but it is probably nervous in origin. The cha.nges which take place in the muscles in consequence of disease of the lower motor neurones are rather of the nature of degenera.tion than atrophy. Dimini8hed Blood-Supply-e.g., atrophy of the testis caused by pressure on the spermatic artery by a tumour. Here, again, the changes are degenerative rather than simply atrophio. THE BLOOD AND ITS DISEASES 17 HYPERTROPHY. Normal growth is determined by impulses inherent in the zygote. By hypertrophy is meant an abnormal increase in the BUB of the tissue elements. If the tissue elements increase in number the term hyperpla8ia is employed. As a rule, hypertrophy and hyperplasia go hand-in-hand. True hypertrophy must be distinguished from pseudo· hypertrophy. In the. former there is hJPertrophy principally of the parenchyma; in the latter, of the connective tissue only. Thus, in pseudo-hypertrophio paralysis some of the muscles may appear to be enormously enlarged, but the enlargement is brought about by the increase of fatty and fibrous elements, the muscle fibres themselves having largely disappeared. The usual cause of hypertrophy is increased functional use, which is always accompanied by increased bloodsupply. Familiar examples are hypertrophy of the heart in valvular disease, of one kidney when the other is removed, of one leg when the other is crippled or paralyzed. Muscular hypertrophy, if excessive, is liable to be followed by atrophy. In some cases hypertrophy is due to the influenoo of an internal secretion (hormone), of which acromegaly and gigantism are examples (see Hormones, p. 190). THE BLOOD AND ITS DISEASES. The blood, which constitutes about 5 per cent. of the body-weight, consists of the plasma, in which Hoat the blood-corpuscles. The plaBma contains oxygen, nutrient proteins, carbohydrates, fats, and salts, as well as a multiplicity of other less-understood substances necessary to normal nutrition (such as hormones and vitamines), and waste products. It is continually oozing through the thin walls of the capillaries to replenish the lymph. The lymph, which is a diluts plasma, forms a vast irrigation system between all the cells of the body, being the medium of exchange between the blood and the tissues, conveying to these latter nutrient material, and carrying 2 18 AIDS TO PATHOLOGY off their waste products. It provides the cells of the body with a saJine medium reminiscent of that inhabited by their far-off ammboid ocean ancestors. The blood-corpuscles are of three kinds: The coloured, called Ck1'O'TllQCyt68 (or erythrocytes); The blood-platelets " The colourless, oalled leucocyt68. The Reds. The red blood -corpuscles are cBllod byvnriousna.m~hromo cytes, erythrocytcs, etc. For convenience tbey nre referred to 1I.8red& The reds of all mammals in health are non-nucleated (except in embryonic life and immediately after birth), I and their numbers approximately are 5,000,500 per cubic millimetre. The average diameter of each is 7·5 II(lr!hm inch), and in health does not vary more than 1 p in extent. (,]~ho micron [p] is the microscopic wlit of length _=0. micromillimetre=nllii'l part of a millimetre=nlioo inch.) Their shape in all mammals (except the camel) is that of a biconcave disc. This shape is due to· the fact that the original spherical body of the parent cell shrinks with the disappeaxance of its nucleus. Their average duration of life is about three weeks. Bource.-The immediate ancestor is the normoblast of the red bone-marrow. As it passes into the blood-stream the nuclous becomes extruded, and the original spherical body col\apses int) a biconcave disc. In the fmtus all the reds are normoblastB. Bt.ooa-Platelets (Thrombocytes).-These are discoid. bodies, measuring about a quartor of the diameter of the red blood-ceIl. Some regard thlllIl as a third kind of blood-ceIl, others but as artefacts. Probably thc latter view is eorrect, because in a recently-made blood-111m few are scen, whereas they inereaso in number after tho blood is shod. Pathological Reds. Undel' certain pathological conditions the rods oro subjeet to variations In sizc, shape, and structure. Also, tho eolour may vary-tile cell may be llndercoloured (hypochromasia), or overoolourod (hllPerch.romasia). 1Il0reover, witll the Roman- THE BLOOD AND ITS DISEASES 19 oskl's stains, Instead of a roddish·plnk (as with tho normal reds), it may be uniformly purplo (polttMromaBia), or show minute bluo granulos (punctate basopkilia). . Miorooytes. Megalooytes. Non·nuoleated{ Gigantooytes. Polkilooytes. NOrmOblasts. Nuoleated, or MegaJoblo.sts. erythrobl&sts { Glgantoblasts. Mioroblasts. M icrocytes vary in diameter from 3 p, to 6 p,. They are found in most forms of 8llIIlmia. M egalocytes vary in diameter from 8 p, to 16 p,. They are typically met with in pernicious a.n.almia, but they may be present in any kind of severe anremia. GigantOC'l,Jtes are enlarged forms of megalocytes. They may exceed 20 p, in diameter. Poikilocytes (oval, pear·shaped, or fiddle·shaped) are present in many varieties of anmmia. 00 FIG. 2.-REDS (DUGRAIIDlATIO). I, Normal red; 2, mlm-ooyte, 3, maorooyte; " polkllooyte; 5, normoblast; U, megaloblast; 7. glgantoblast. Nucleated Retl8 only display thoir nuolei when stained; they are present during intra·uterine life, but are never seo~ in healthy blood after birth, exoept for tho first few days of life. They are found especially in pernioious anremio., but thoy mo.y occur in any severo kind of anremia. They are of four varieties. according to their size: Normoblasts (blastos= bud} are of the same size as the normal reds. They are normal to the red marrow, and pass into the blood minus their nuclei, to become reds. In the faltus the reds are all normoblasfis. They are fonnd in allanremias, with the exception of chlorosis. Megaloblasts are of greater size, and even doublo that AIDS TO PATHOLOGY 20 ~f the normal chromooytes (10 '" to 16 '" in diameter). The nucleus. which may occupy two-thirds of the cell. stains faintly with the nuclear dyes. Megaloblasts occur in pernicious anremia. and in the anremia of Ankylostomum duodrmale and of Dib:JthriocephaZu8 latU8• •GigantoblaBts.-These resemble the preceding, but are larger. sometimes exceeding 20", in diameter. Microblasts are small nucleated chromocytes. They are found in all forms of anremia, and are of but little diagnostic importance. i Colour Index-Estimate of the Amount of Bmmoglobin. Decrease in the number of the chromocytes and decrease in the amount of hrem~lobin in. the blood do not necessarily go hand-in-hand. The severity of most anremio.s is better estimated by the quantity of hremoglobin than by the number of reds; in chlorosis, for oxample. the number of reds may be .but little, if at all. diminished, while the amount of hremoglobin in ·each individual red may be much reduced. The amount of hremoglobin (Bb) in each individual red (R) is called the colour index. It is the ratio of tho hremoglohin percentage to the corpusole percentage. The oolourindexis obtained by means of the formul_ o/cBb OJOR Percentage of Reds. In hcaltp - 100 In chlorosis 60 In pernioious 20 o.nllllIlio. - Percontage of H_oglobln. Colour·Indox. 100 30 t&S. or 1 1&, or 0-5 30 fS, or 1'0 Leucooytes (or Whites). In fmtallife the leucocytes make their appearance later than the reds. , In normal blood the proportion of leucocytes averages THE BLOOD AND ITS DISEASES 2I 8,000 per cubic millimetre. their ratio to tho reds being thus as 1 to 600 or 700. The lcucooytes dlaer amongst themselves both with regard to tho form of the nuoleus and the oharacter of tho cytoplasm. In some the nucleus is single aud the cytoplasm non-granular; in others the nucleus is multiple or polymorphic and the cytoplasm granuIa.r (either fine or coarse). Ehrlich has divided the granules into throe. according as they stain with o.oid. al.lmline. or mixed dyes. naming them respectively eosinophile, basophile. and neutrophile granules. Tho leueocytes are namod elther aceordlng to tho' cbaraotor of the nucleus or aocordlng to the oharacter of tho granules. so that more than ono name has been given to the same coIl. The following classitlcation is based on nucleation: Pe,. Oent. Small mononuolears = 22 to 25 1. Large mononuolears = 2 to 4 Neutrophilo =70 to 72 2. Eosinophile = 2 to 4 (,,) Dasoph!le(mastcolls)= -r5 Some authorities describe a hyallne leucocyte Intermediate between (a) and (b). (a) { (b) Mononuclears (4) Polymorphonuelears { (IJ) Thc 8mall mononuclear is 6 I' to 12 p. in diameter. Cytoplasm is non-granular. It contains a large. spherical. deeply-sta.ining nucleus. which oooupies almost the entire cell. It is non-amreboid and non-phagocytic•• .~ .. ......... . '.1 •.,::• 4 5 FIG. 3.-WHITES (DIAGRAMMATIC). 1. Small mononuolear; 2. largo mononuclear; 3. neutrophile; 4. eosinophile; 5, basophllo. The large mononuclear is 10 f.t to 20 p. in diameter (the macrophage of Metchnikoff). Cytoplasm is non-granular. Its nucleus stains less intenscly than that of the sma.ll lymphooyte. It is amreboid and phagoopw. In malaria QUs variety is usually abundant. The neutrophile (the miorophage of Metohnikoff) is 9 f.t to 12 I' in diameter. Cytoplasm is finely granular. the 22 AIDS TO PATHOLOGY Pathological Leucocytes, The mllelocute8. normally tound In bone·DUIorrow. but never present In healthy blood, are regardod as tho parent colls of all tho polymorphonuolears (00le diagram). Neutroph1le MlleIocute (15 to 20 ,...).-Tho parent 0011 of tho neutrophile. Contains numerous fine neutrophile granules. The nuoleus Is largo, single, and stains feebly. Charaoteristio of myelmmlu.. EosilllOph1le MlIeIOCl/le.-The parent oell ot the oosinophlle. Similar in size and shape to tho formor. but tho granulos are large and ooslnophile. Found in IDyelmmia. BaBOphile .lIf1lelocvte.-The parent cell ot the basophile. Smaller than tho two former. with basophile oytoplasm. Found in myolannla. Myeloblast (10 to 20 ,...).-Largo nucleus. cytoplasm non-gro.nu· lar, and dyes 0. • pigeon's egg' bluo with Leishman's stain. Probably tho parent coli of the myolooytos (Vide diagram). Found in abundance in myelrumla. Plasma Cell (' InfIammo.tory Leucecyte ': 10 to 20 ,...).Usually peo.r-shaped, with a single nucleus placed at one end. By the Unna·Pappenheim method the cell oytoplasm stains 0. brilliant red. Often found in largo numbers in subacute In· i'flammatory fooi. Probably derived frOm the lymphooyte, and iPorhaps elaborates a digestive terment. THE BLOOD AND ITS DISEASES 23 Origin 01 Blood-Corpuscles. According to Pappcnhoim, tho oommon ancestor of all the blood colls is the lymplwidocyte, the rods and most of tho whites being born In the marrow, the largo mononuoloars in tho spleen, and the small mononllclears in tho lymphatio tissue genoralllY Up to tho sixth month oUcetalllfe tho lympholdooyte is the onI blood-oell found in tho lymph nodos and marrow. After blrt it is nover tound In tho periphora.l olrculatlon in health, bu ma.y be present in certain dlsooses. Tho accQJD.panyln dfagram (Fig. 4) illustrates the pedlgrco of the blood-ooUs. Bone-Marrow. In Inlanoy and ohlldhood bone-marrow Is composed of a tissuo rosembling the splenio pulp, tho red or lymphoid marrow. By the ago of publlrty tho red marrow In the shafts of long bonos has beon largely oonvortod into fat-tho yellow or fatty marrow -that in tho epiphyses, tho flat and tho short bonos, still remaining red. Interspersed thronghout the reil marrow are Isolated oOIOnl08 01 oells, some composed 01 normoblasts and others of myoloo;rtes, In various stages of evolution. In old ago tho fat Is to a considerable oxtent replaoed by fibrous and gelatinous tissue, and the same r08uIt may be bronght about by dobllitatlng diseascs. Fuootions.-Bone-Inarrow Is tIm manufaotory and storehous6 for all the rod blood·oolls, and most of tho white. If thero Is an urgont call tor more reds, there Is an • er;rthrobIastlo' r08p0ll86; It the oallis tor moro whltos, thore is 0. ' loueoblastlo ' respODse. Pho.gooytlo--'.e., for I'neumoooool, streptooocci, staphylocoooi. oto. Leucocytosis. By this term is meant an increase in the total number of leucocytes in the blood. Any number over 10,000 per cubic millimetre may be regarded as constituting leucooytosis, so long as tho increase lasts sufficiently long. (A physiological leucocytosis occura from three to four hours. after every meal, when the leucocytes may reach from 10,000 to 12,000 per cubio millimetre, but this soon passes off.) It may also occur after the administration of certain drugs-e.g., salicylates, chlorate of potassium, and phenacetin. as also after giving thyroid extract, bone-marrow, and nucleic acid. It ha.s been observed after opemtions. Leucocytosis is natura.l in pregnancy and childhood (lymphocytosis), just before death, and after exercise and massage. AIDS TO PATHOLOGY 24 ~ NormoblOlst ® AmphOir;/OCY~ 1 Q) / CO) ~ I-otrge Q) \ I \ I!yel.&I.st MononucleClr (Q Mo~~nOlJ~/eer,. \OJ(§) Myelocytes @®~ 8Otsopl1i1e tleutrophile Eosinophile FlO. 4.-SCEBIlUTlO REPRESENTATION OF TlIIll ORIGIN OF REJ)$ 4NIl Wurms FROM Tum L nJPHOmOOYTIIi mm ,THE BLOOD AND ITS DISEASES 25. Apart from these conditions, it may be affirmed as a general principle that a leucocytosis means an infection. The presence or absence of loucocytosis may be of material aid in forming a diffcrential diagnosis, as, for example, between pleural effusion and empyema, a leucocytosis reabhing to 20,000 per cubic millimetre being indicative of the latter; again, a leucocytosis of 20,000 per cubic millimetre )Jas lcd to the deteotion of an hepatic abscess or a pyosalpinx. Again, a rising leucocytosis in a local disease like appendicitis means that the inflammation is spreading, and that an operation is imperative, even though the abdominal symptoms are slight. Leucocytosis may assume either (a) a. general or (b) a Bingle type. (a) General ltucocytosi8 occurs in all the general infections, except enteric (provided there are no complications), paratyphoid, measles, German measles, }lalta fever, malaria, mumps, influenza, miliary tuberculosis (when unaccompanied by a mixed infoction), and leprosy. The leucocytosis in all these cases begins early; its degree depends on tho severity of tho infection, on the nature of the infective agent, and it increases until the disease has reached its full development. If, however, the infeotion be of great severity, the leucocytosis may be slight or absent, owing to toxic paralysis of the leucoblastic function of the bone-marrow. It a.lso occurs in certain cases of malignant growths (especially of the thyroid and panoreas), and after hmmorrhages. (b) Bingle-type leucocyto8is : All local inflammations, cspoolally When accompaniod by suppuration; pneumonia; the incuba(I.) Neutrophile tlon period of the speeifio foVorB, { except thoso in whioh thoro is no louoooytosis. Whooping-cough, rickets, scurvy, himnophUia, s?'P~lis, ~ympho(Il.) Small mononu.,loar { sarooma, cortam infantile dlarrhmaB. This form suggests a protozoon disease, suoh as malaria, trypano(ID.) Largomonolluoloar somiaBie, kala-azar, ammboid { dyS8I1tory, relapsing tever. also 81JJ.allpox. 26 AIDS TO PATHOLOGY Asthm.a. emphysem~. eozema. urticarla, psoriaBis, lupus. pomvhlgus. triChinosis. ankylostomln.-J { sis. Hilbarzia hmrn.atobia. goutt IIrlllIDia, muoous colitis. Basophile leuoooytosis is unknown. / (iv.) Eoslnophilo i'he ,Purpose of Leucocytosis. L/ The essen~ial purpose of leucooytosis is to aid the resistance of the body against bo.oterial invasion by inoreasing the number of phagocytes, and the gr~a.ter !JIihe degree of leucocytosis the better the prognosis. It is (evident that during the course of an infection the bonemarrow (and in tha case of lymphocyto3is the lymphoid tissues) is stimulated to increased leucoblastic activity, and, accordingly, we must postulate that the bacteria give off a substance which, passing to the bono-marrow, induces there an augmented produotion of leucocytes (see Chomotaxis, p. 42). Leucopenia. In this condition there is a decrease in the Dumber of leucooytes. It ooours in pernicious an;emia, in very severe anmmias, in splenio an;emia, in the early stages of enteric, in measles, in pneumonia (if alcohol, or fatal), in kala-azar, in dengue, in Banti's disease, and in malignant disoase of the c.esophagus (= starvation leuoopenia). It has also been observed after the administration of large doses of quinine, atropine. otc. ~mia. The term' an;emia j·.-li~?a.lly means' want of blood.' but in the following it more partioularly refers to abnormal conditions of the red blood-cells. (l'he red bfood-celllives but a few week", and then, its duty done. its mission fulfilled, dies of senile deoay.) It is obvious that an anremia may result either from interfrgence with. h.omwgenesi&--i.e., dofective blood formation; or from lumnolyai&--i.e., blood destruction. These two faotors may co-operate. Oligmmla= a decroa.se In tho total qnantlty of blood. Oligooythmmia= a decrease In the number of reds. Oligoohrommmla==& deorease in the amount of hlllID.oglobln. THE BLOOD AND ITS DISEASES 27 Chlorosis. Chlorosis is almost entirely confined to young women. The disease commonly begins about puberty-that important period of lifo when the girl-child is being transformed into the young woman. Want of fresh air and sunlight, defioientexeroise, unsuitable feeding, ooourring at the most oritioal epoch in a woman's life, appear to be the most important contributory oauses. It is likely that the actua~. oause is an infection that throws out of order the bloodforming elements of the bone-marrow. Suehinfectio possibly originates in the alimentary tube. (Certainly many oases can be oured by the administrd.tion of purgatives alone.) Blood Changes.-The specific gravity and composition of the plasma are normal. The outstanding feature of the disease is that the amount of hremoglobin in eaoh in· dividual J:Bd cell is below the normal standard (anochro· masia), the hlllIIloglobin being ohiefly colleoted in a ring around the margin of the cell, the centrd.l portion oontaining but little. The colour index may fall as low as 0·3. Th~ plasma is increased in amount, the volume of blood. being greater than, in, health (plethora). Notwithstanding the faot that the number of ehromooytes per cubio millimetre is generally reduced (sometimes to as few as 2,000,000), their entire number must be increased, for, as Lorrain Smith has shown. the total quantity of hremoglobin in the blood is normal in amount. l'tIicrocytes and poikilocytes are often present, and in severe eases megalooytes, normoblasts, and even megaloblasts. Although the number of leucocytes per cubic millimetre of blood is reduced, there is no leucopenia in the proper sense of the word, owing to the increase in the volume of the plasma. Oomplicatio1Ul.--<Edema, venous thrombosis, fatty de· generation, visoera.l inflammations, optio neuritis. Pernicious Anmmia. This disease was originally described by Addison under the namo of idiopathic anremia, and is charaoterized by remarkable changes both in the blood and bone·marrow. :l8 AIDS TO PATHOLOGY Blood Changes.-These changes are of the nature of reversion to the embryonal type of blood. Specifio gravity is lower than normal; the total quantity of the blood is normal. The chromoeytea are much decreased in number; when the case first comes under observation they may number only 2,000,000, and towards the end may sink to 500,000, per cubic millimetre. In a case of Quincke's they were only 143,000 per cubic millimetre. The number, however, often oscillates within wide limits. Under treatment periods of temporary improvement may ollcur. Each individual red blood"ceil contains an excessive amount of hremog!ob·n (hyperchromaaia), the hremoglobin index sometimes being as high as 1·S. Every possible form of abnormal red blood-cell is to be found-microcytes. poikilocytes, megalocytes, megaloblasts, gigantocytes. and gigantoblasts. Megaloblast8 are generally abundant, and on this oircumstance the diagnosis of pernicious anremia is usually founded. The nucleated red cells may appear suddenly (= blood crisis). Leucocytea.-As a rule there is leucopenia, especially noticeable with respect to the decrease in the number of polymorphonuclear neutrophiles (occasionhlly myeloblasts are present). The number of leucocytes in somo cases is as low as 1,000 per cubic millimetre. HCBmOBide:rin (or iron-containing p;gment) is found in the liver, spleen, and kidneys (the kidneys may contain fifty times more iron than usual). Bloodve8sel8.-There is a great tendency to hillmorrhages in the skin, retina, brain, uterus, and sorous mombranE's. Bone-Marrow.-The yellow marrow of the long bones reverts to the megaloblastic fmtal type--i.e., is transformed into a red lymphOid tissue, suggesting red-ourrant jelly in appearance, and containing a large number of red ~nuoleatcd cells and megaJoblasts. The myelooytes are [diminished in number. Tho yellow marrow Jargt"ly disappears, and much of the surrounding bone is absorbed, so as to make room for the new marrow. Bean.-Fatty degeneration always oceurs, the' thrushbreast' markings usually being eonspicuous on the left ventricle 3 ~ THE BLOOD AND ITS DISEASES 29 Liver.-Usually enlarged from fatty degeneration. If the cut surfaco be treated with ferrocyanide of potassium, and afterwards with hydrochloric acid, the lobules become mapped out by TingS of Prussian blue, owing to the presence of free iron (hoomosi'derin) in the peripheral and middle zones. 8pleen.-Oocasionally shows the presence of hromosiderin. Kidneys.-Usually show fatty degeneration (especially of the convoluted tubules) and the presence of hremosiderin. Tho gastro-intestillal mucous membrane usually shows atrophy. N ervoua 8ystem.-Sclerosis of tho posterior columns of the cord may be present. The actual causo is unknown. It may be due either to somo form of malignant disease of the bone-marrow causing the Ied cells to be turned out higgledy-piggledy, or to some hwmolytic poison in the blood (in the infectious pernicious anremia of the horse the blood-picture is much the samo). The disease is generally fatal within two years Amongst the causes of Bevore anmmia. which may be BO intenso as to simulate pernicious o.nmmia. o.re--Long·standlng small 10ss68 of blood (blooding piles. bleeding' ftbreids,' otc.); chronie septio infection (ulcerative endocarditis septic bladders from enlarged prostate, eto.); carcinoma. of tho stomach; syphills; phthisis; mo.larla; infection with tho Bolh'l'iocephaJus latus a.nd Ankyloatomum duodenale. Splenio AnlBmia (or Primary Splenomegaly). This very chronic discase is characterized by a great enlargement of the spleen, progressive a.memia of the chlorotic type. and leucopenia. There is 0. tendency to; lumnatemesis. melama. and epistaxis. The lymphatic glands are not enlarged. The chromocytes are diminished in number, frequently fa.lling to 2,500.000 per cubic millimetre, and occasionally to a smaller number. The hremoglobin index is considerably below the normal, varying between 0·5 and 0'7. The leucocytes may fall to 800 per cubic millimetre. The enlargement of the spleen is uniform~ and may be 30 AIDS TO PATHOLOGY considerable; there is great increase of the stroma, and the Malpighian bodies are atrophied and transformed jnto fibrous tissue. Banu's Disease. This is a combination of splenic anmmia with multi· lobular cirrhosis of the liver, causing jaundice and ascites. Hremorrhages from the skin and mucous membranes are common. According to Bantl (who has collected fifty oases), thero are throe stages: (a) The pre-ascitic, characterized by splenomegaly. This stage generally lasts throe to five years. (b) The intel'· mediate, characterized by anmmia, leucopenia, with relative Increase ot the mononuelea.rs. The liver is somewhat enlarged, and diarrhroa may come on. This stage lasts trom twelve to oighteen months. (c) The final stage is characterized by ascites, shrinkago of the liver, general wasting, and gastrointestinal hremorrhages. The duration ot this stage varios from a tow months to a year. Leukmmia. Leukremia. is a disease characterized by an enormous 'and persistent increase in the number of leucocytes in the :blood as the result of pathological changes in the spleen. [bone-marrow, or lymphatic glands, or in any two or in all three of these. Hughes Bennett, in 1845, first drew atten· tion to it, describing his case as one of 'suppurationof the blood.' Later in the same year Virchow recorded a similar case. Two chief forms are recognized-Cal myelremia and (b) lympktBmia. and there are probably many in~rmediate forms. (a) lIyelmmia (Spleno-MedulIary). In some cases the blood is merely thin and pale, with coagulation imperfect. or it may look like a mixture of blood and pus, while in extreme cases it may resemble pure pus. The leucocytes are enormously increased. ranging in number from 50,000 to over 1,000,000 per cubic millimetre (but this is ro:ubjeot to fluotuations). All types are represented. both the normal and abnormal. At first the polymorphonuclear neutrophiles are the most conspicuous, but as thc disease advances myelocytes become predomin. ant (basophile. neutrophile. eosinophile myelocytes amI THE BLOOD AND ITS DISEASES 31 myeloblasts), constituting from 30 to 60 per cent. of all leucocytes present. Basophile leucocytes (mast cells) are also abundant. Sometimes the lymphoidocyte-the original ancestor of the blood-corpuscles--may be found. During the earlier stages there is no reduction in the number of reds, but later on they diminish, and normoblasts and megaloblasts appear on the scene. The 8pleen increases enormously, and may wcigh 18 pounds. It is often adherent to the surrounding viscera. On !fection it is pale, the splenic pulp and fibrous stroma are-seen to be greatly increased, and the l-lalpighian bodies are indistinct. Numerous yellowish necrotic areas of infarctions (probably thrombotic) may be seen in its substance. The bone-ma"ow is hypertrophied and highly vascular, and, owing to the presence of enormous numbers of myeloeytes (in all stages of development), it presents a oreamy appearance. '.rhere are accumulations of fat in the heart, liver, and kidneys. The urine contains an excess of urie acid-probably derived from the disintegration of the leucocytes. Charcot-Leyden cry8tals are sometimes found in the blood after its removal from the body. They are octahedral in shape, and are probably a crystalloid product of either the plasma or the leucocytes. Hremorrhages, especially from mucous membranes and retina, are common. Acute MlIelwmia.-This runs a rapid coursc, with a great tondonoy to profuse hromorrha.ges. The most striking bJoodohange is the predominance of myeloblasts. (b) Lymphmmia (Lymphatic LeukIBmia) This form of leukremia is associatcd with onlargement of the lymphatic glands throughout the body, and often of the lymphatic tissue of Peyer's patches. and of other parts where this tissue is found. These may attain the size of walnuts. Examined microscopically, the glands show a uniform hyperplasia of their lymphoid tissue, which is packed with lymphocytes. The spleen is also enlarged. There is a great increase in the number of leucocytes (100,000 to 500,000 per cubic millimetre), of AIDS TO PATHOLOGY which theZymphocytea constitute from 80 to 98 per cent.• in somEl cases the small mononuclears and in others the large mononuclears preponderating. In most instances the reds are reduced in number. and in the acute forms the hl8moglobin index falls below the normal (between 0'5 and 0'7). Lymphmmia may be either acute or chronic. but there are ~ransitionnl forms. The acute is much the more common, anti may occur at any age from birth to over se'fenty. more than two-thirds being maleS. The blood. picture is variable, and changes widely from week to week in many of the patients. The rule is that the moro acute t_he course, the more immature the prevailing typ3 of leucocyte; thus. in rapidly-fatal cases the prevailing type is the common parental form-the lymphoidooyte. The blood-platelets are strikingly few in most •oases. The bone-marrow is red and difRuent. There are often hmmorrhages into the skin, from mucous membranes, and into the various viscera. and there is little doubt that many oasos have been mistaken for the 'hl8morrhagio diathesis.' In many ways acute lymphmmia resembles an acute infection, or septicmmia, though. 8.S yet, no causal organism. has been detected. Hodgkin's Disease. Described by Hodgkin in 1832. Cha.ra.cterized by a 'progressive, painless enlargement of many groups of lymphatic glands throughout the body, with which is often associated the growth of scattered patches of lymphoid tissue in the spleen. liver, kidneys, testes, lungs, and medulla of bones. The disease genemlly starts in a single group of glands (frequently those of the neck). and then extends to other groups, more particularly selecting those in the axilla. groin, and mediastinum (but no group is exempt). The enlargement differs from inflammatory affections in that the glands generally remain free and distinct, forming smooth, rounded, or egg-shaped, firm, elastic swellings, the skin over them retaining its natural colour and remaining non·adherent. (In exceptional cases the glands fuse together to form a large lobulated mass.) THE BLOOD AND ITS DISEASES 33 On section, the gland appears greyish-white, and a microscopio examination shows that the normal tissue is largely replaced by a delicate reticulum, in the meshes of which are numerous mononuclears, eosinophiles, and endothelial cells. Occasionally a few giant cells containing one or two large nuclei (with nucleoli) are present. At a later stage the reticulum organizes into dense fibrous tissue. The Blood.-At the' commencement of the disease the blood is normal; later on anmmia of the chlorotic type develops. Except when the glands inflame, there is no leucocytosis. The disease is much commoner in men than in women, and is alwaIB fatal-either from pressure on important structures (veins, nerves, trachea, msophagus, etc.), or from asthenia. Judging by the way the disease begins in one group of glands, and then gradually extends to involve other groups, the probable cause is an infection. Chloroma. This is a very rare disease. A.ccordlng to Sternberg, It is distinguished by the following clml.'8cters: The presenco of lymphoid (:rowths In the orbits, temporal fOSSDl, dura mater, and mediastinum; the greenish colour of these growths; the studding of the bone-marrow, spleen, lympba.tlo glands, and viscera. with lymphoid deposits; an cnormous Increase of the lymphocytes. The growths resemble lymphosaroomata In structure (Ilide p. 88). INFLAMMATION. Inflammation is essentially a defensive prooess, being Nature's carefully-planned and cunningly-executed fight against the action of noxious irritants. In the large majority of cases the irritants are the soluble toxins of micro-organisms. Cases of inflammation resulting from the action of non-bacterial toxins-e.g., gout, and the pericarditis of Bright's disease (but even here it is impossible absolutely to exclude the presence of bacterial toxins) -may perhaps be explained on the supposition that the tissues mistake, as it were, a non-bacterial poison for a bacterial one. Such agents as heat, electrioity, Rontgen rays, mechanical irritation, initiat,e inflammation, probably by facilitating the play of toxic forces, especially 3 34 AIDS TO PATHOLOGY of those produced by the innumerable microbes which always lie buried between the celfs of the epidermis. (More than 100 different varieties of bacteria have been demonstrated on the skin.) Seeing that bacteria play such a dominant part in setting up inflammation, anything which diminishes the bactericidal power of the body necessarily predisposes to it. It is in this way that sbtes of so-called 'lowered vitality,' such as may result from privation, fatigue, chronic alcoholism, Bright's disease, diabetes, may coopero.te in the causation of inflammation (vide Immunity). Phenomena of Inflammation. (1) First an initial contmction of the arterioles, immediately followed by (2) Dilatation of the same arterioles (probably due to a toxic paralyzing of the muscular tunica mcdia) with flushing of the capillaries and widening of the venules, with acceleration of the blood-stream; then (3) Retardation of the blood-stream, with accumulation of the leucocytes along the walls of the bloodvessels, the endothelial cells of which swell up. (4) Active migration of the ltJUCOCytes, especially of the neutrophiles, into the surrounding tissues. (Metahnikoff regards this as the essential feature of all inflammations, because they ingest the causal bacteria.) (5) Synchronous with the escape of the loucocytes is the exudation of the lymph into the surrounding tissues in abnormal abundance· (' inflammatory redema '), the amount of which is determined by the nature of the particular toxin causing the inflammation. (The exuded lymph is richer in proteins than the ordinary lymph, and is usually coagulable.) , (6) Late in the process, the' :reds,' which do not possess the power of independent locomotion, are squeezed through the capillary walls. (7) Stagnation of the blood-stream. The blood-cells now cease to pass out. (To compensate for the loss to the blood of so many leucocytes tha.t have migrated to the inflamed area, there is an inoreased output of leucocytes from the bone marrow.) INFLAMMATION 35 Me.r.nwhile, the fixed tissue cells of the part swell up, dud may undergo cloudy 8'U!elli'tl{j, and even/atly and mucoid degeneration. Should the bacteria be easily exterminated, the e:mdate and leucocytes are absorbed by the lymphatics, passed on to the nearest glands, where they are disposed of; thc damaged cells of the inflamed area recover, and the part resumes its normal condition (r68olution, or r68fJitutio ad integrum). Inflammation i8 a defensive operation. The neutrophiles and the large mononuclears possess the power of ingesting bacteria. and for this reason they have been named by Metchnikoff phagocytes (phagein. to eat). • The phago. cytes, having arrived at the spot where the intruders are found, seize them after the manner of the amrebm, and within their bodies subject them to intracellular digestion' (Metchnikoff). Seeing that the purpose of inflammation is the extermination of bacteria, the migration of the leucocytes thus tends to remove the cause of the inflo.m· mation and bring it to an end. The exuded lymph serves two useful purposes-(i.) it dilutes the toxin, and also, neutralizes it by supplying antitoxins; (ii.) it acts as IL bactericide ("ide Immunity). Other Sequels 01 Inflammation: Fibrosis, Suppuration,. Absoess, Uloer, Slough. Fibr08i8.-If the. inflammation is mild but persistent, the fixed cells of the area proliferate-notably the connective-tissue corpuscles and endothelium (muscle and nerve cells do not proliferate, though their nuclei may); and in course of time the derivatives of these cells organize into fibrous tissue. Suppuration.-If the phagocytes and tissue cells are beaten and the fight won by the bacteria, then suppuration occurs. The phagocytes, notwithstanding their large output from the bone-marrow, are unable to cope with the virulence of the infection, and die; the vessels become thrombosed, the tissues are dissolved (histolysis) by the peptonizing action of the bacterial products, and pU8 is formed-i.e., a fluid composed of exuded lymph and of the liquefied and digested tissue, holding in suspension dead AIDS TO PATHOLOGY polymorphonuoleal'll (mononuolear pus is very rare). If the process now ends and the pus is evacuated, the cavity hea.ls up by the orga.nization of granulation tissue (see Repair). Probably suppuration is always due to bacteria. In the few oases in which they are not found, the likely explanation is faulty teohnique. The usual organisms causing suppuration areStaphlll0c0caua PlIogeneB aUreuB{ StaphlllocoOCUB PlIouenes albus 75 perce~t. ot PUB Staphlll0C00CUB PlIogenes cUreuB formatiOn. StreptocoOCUB p1/OUenes. Ba~us PlIOC1/aneus. BacUlus typ1&osus. BacillU8 coli communi&, GooocoOCUB. PneumoCOCCUB. In all cases of suppuration there is an early polymorphonuolear leucocytosis which is of great diagnostic importance, as it can often be discovered before the patient feels ill. To explain this leucocytosis we must asswne that some substance is given olf from the inflamed area which stimulates the bone-marrow to the production of large quantities of leucocytes (positive chemotaxis). This must be so, for an ordinary-sized abscess would contain all the leucocytes normally contained in the blood. Ab8ces8, UZcer.-If the pUB is pent up in the tissues, the condition is termed an ab8t;688. If, on the other hand, the Jnfiamed tissue yielding the pus abuts on a surface, and the Skin or mucous membrane breaks, the r.esult is an 'Ulcer. Slough, Gangrene, N6Cf'08i8.-H the inflammation is of such virulence that there is not time for the tissues to undergo liquefaction and they die qUickly en bloc, while still retaining their structure, the resulting condition is termed a 8lough. If the dead part be of large size, the term gangrene is applied. A portion of dead bone is called necr08i8. FEVERS. The body temperature varies in different species of animals: Man Monkey .. Horse Dog F. 98·8· 100'0· 100· 102'2· Rabbit Guinea-pig Hoo F. 108·1· 102'4· IDS· FEVERS 37 Leucooytosis ocours in all specifio fevers, with the excep-, tion of enterio, measles, influenza, German measlest malaria, Malta fever, dengue, and acute miliary tuberctJlosis. The absence of leucocytosis in lobar pneumonia usually means death. The rash of a fever is probably due to the irritation produced by the elimination of toxin by the skin, being thus similar to the rashes sometimes found after the administration of oertain drugs-e.g., bromides, iodides, and copaiba. Changes occnrring in Fever. Tho temperature is raised. Very exceptionally this classical symptom is absent-e.g., in certain cases of diphtheria, septicamrla, typhus, and enteric, when there is generally profound prostration, early coma, and doath. The elevation of the temperature is in part due to increased produotion of heat, and in part to defioient heat loss. The pu18e·rateis accelerated, the average being4i beats for each 1° F. The respiration. is accelerated, and usually maintaining the ratio in health-i.e., 1 to 4--except in pneumonia and pericarditis. The 8ecretions tend to dry up--i.e., those of the skin, mouth, alimentary tube, liver, pancreas, and kidneys. The urine is scanty, concentrated, of high specific gravity, deposits urates on cooling, and not infrequently contains albumin (febrile albuminuria). Metaboliam.-There is (a) i'llCreased kataboliam (the nitrogenous waste-produots, urea, uric aoid, etc., are increased in quantity, as likewise is the CO2 ); and (b) les8ened anaboliam (the tissue cells are less able to absorb nourishment). Tissue Ohanges.-The body fat tends to disappear, the liver loses its glyoogen, the muscles shrink, the're is cloudy swelling of the epithelium, and often focal necrosis of the liver, spleen, and kidneys. In some fevers, notably diphtheria, there is a marked tendency to fatty degeneration of the heart. In rheumatio fever the heart (espeoially the left ventricle) is probably always dilated. Death in fevers generally takes place from heart failure. AIDS TO PATHOLOGY Oontagion is probably conveyed via. tho secretions, and by these a.]on&-il.g., spraying the air during the acts of coughing, sneezing; by the evacuations, fmcal and urinary. . DDIUNlTY• No ono can be sa.ved unlos8 Na&lll'8 oonquers the disease; and no one dios unles8 Nature succumbs (Galen, A.D. 130). No ono recovers from a chronlo or acute bacterial disease unless it be by the production of protective substances In bis organism; no one acquires proteotion against disoase except, again, by the production ot protective substanoos; and, finally, no one llvosln the presenoo of infection and repels that infeotlon oxoopt by the aid of protective substances in his blood (Sir AJmroth Wright). In the technical sense in which the term is employed, immunity mea.ns the power the human body posseBBes of protecting itself against the invasion of certain microbial foes. 'rhe body, indeed, wa.ges a perpetual wa.rfare aga.inst these foes, and it is only by unceasing vigilance on the part of the tissues that their attacks can be repelled. (N.B.-In tho following description, the term • microbe' is used in the generic sense to include all micro-organisms, whether bacterial orprotozoal.) Infection is the term emPloyed When a dlseaso-producing microbe enters tho body and Inultiplies therein. Toxins. Tho influence of miore-organlsms on the body depends mainly upon the tozinB which thoyproduce. The bacterial toxins (~ polson) ara poisonous substances allied to colloids. Just as oormin plants possess their special allmloids (strychnine, morphin~. a.conltlne. otc.), so each species of bacteria elaborates its own particular products. Bome ot which may be useful to thoir host, Bome innocuous, and some harmful. It is to those latter poisonous produots that Brieger gave the name ot tozins. It is to be understood that in speaking at tho toxins of a particular bacterium IDe are re/erri1U} to solutions 0/ them, no toxin having as yet boon isolated and analyzed as the vegetable alkaloids have been. It is probable that there are two kinds ot baeterial toxins: (a) Those confined to the Interior of living bacteria, and only liberated on their death (imraceUular, or endo-toxins); and (b) Those yielded by living bacteria. to the medium outside them Ce:z:tracellulal'. or exo·toxins). IMMUNITY 39 (a) Intracellular TOJ:ins.-In this group, whloh Includcs tho toxins of tho greater number of baoteriogenio diseases (amongst others, thoso of lobar pneumonia, enterio fever, Malta fover, cholora, plague, and gonorrhtea), tho toxin is looked up in tho bodies of tho bactoria, not being liberatod till these degenerate or dio, and then only whon tho baoIlli disintegrato. It is found, In tho partloular diseases just roierred to, that It the baoterla oausing them are grown in a roitable oulture medium no toxin separates out 'by filtration through porcelain, whereas It the bacteria aro frozen at the lowest of tomperaturos, and then crushod, tho result is a highly toxio Bubstanco. (b) Eztracellular T0J:i1l8.-In this group, whioh Includos ·the toxins of B. diplotherim, B. telani, B. botulinus, too toxin appoors to be of the natur~ of an exoretlon. U, for examplo, the diphtheria or tho tetanus baolllus Is grown In a suitable modiwn, soluble to:Din8 am/ouM to pass rna into the medium• ./'I"Um which. theu can be separated by filtration thf'O'U(/h porcelain, tho inferenoo being that tho baoilli in question exorete them (unless we suppose that they produce thom by promoting some ohango in the extcrnal medium). Soma species of bacteria appear to produce both Intraoollular and oxtrooolluIar toxins-e.o.• tubercle baoillus (probably). Ehrlich assumes that 0. moleoulo of toxin oonsists of two groups of atoms: ono tho haptophore [(h)apto=I fastenl, which oombincs with the antitoxin; and another, tho to:t:Ophore, on which tho toxic action depends (soo diagram of Ehrlloh's sldechain theory, Fig. 6). J!'or example, if diphtheria toxin be kept for Bomo time it loses its toxic property, but retains its power of combining with antitoxin-it has lost its toxophoro, and retained Its haptophoro, group of atoms. Suoh a toxin Ehrlioh oalls a to:t:Oid. ACtiOn of1'"OZi'ns.-·l'"o~lils appear tio um't!e Wil:ii tiiie protiopihsm of tho tissues. In many of their properties, however, they resemble ferments. ThusThey are destroyed by a temporature or from 140,0 to 11111 0 F. They are preolpltatod by alcohol; they are unaffected by ohloroform and eth~r. Thoy can be swallowed with Impunity. Thoy do not aot until aftor a latent period. They aot Irrespeotlvoly of thequantityemployod--i.e.. an infinitesimal doso Is e1reotive; 6.11., r.A.. gramme of tetano-toxin will kill a horse 600,000,000 tlmoslts mvn woight. FaI.e 0/ To:i:lns.-Ultimately toxins are partly oxoreted as suoh (ohielly by tho kidnoys Bnd liver), partly burnt up in the tissuos, and partly neutralizod by antitoxin. NATURE'S DEFENCES. Against infection the organism puts forth supreme efforts. bringing into play various mechanisms which have been laboriously evolved throughout millions of years AIDS TO PATHOLOGY of time, Nature acting, so to speak, as her own physioia.n, treating eaoh infeotion in a different way. Local General 1. The physical resistance oflered by healthy and intact skin and muoous membrane. 2. The phagocytio aotlon ot the tissue cells at the site of infection. S. IntiaIDllUl.tlon at the site of infection. 4. The extinction of the invading mlorobes and their produots by the action of plmgocytos and { antibodies. 1 1. The Physical ReaiBtance offered by H.,et.utky and Intact Skin and Mucous Membrane.--80 long as the epidermis remains healthy and unfissured, bacteria may oome into oontaot with it almost with impunity. To a. less extent, the same remark applies to mucous membranes; microbic invasion of, or through, a mucous membmne is more likely to occur when there has been a preceding catarrh, or injury, of its I!Ilrface. (The gone<l0CCUS can invade the healthy urethral mucous membrane.) Epithelial cells may, in a minor degree, exert a phagocytic action. 2. The Phagocytio Action of the Ti88ue ceUl at the Site of lnfection.-Probably all tissue cells which contain oytoplasm are oapable of exercising a phagocytio influenoe. Certainly this is so in the case of endothelial oells, espeoially those at the !MOUS lnem.'on.nes, 'ol.oodvesscls, and lympha.tics. In fact, phagooytosis may be regarded as one of the primordial funotions of protoplasm, from the amc:eba upwards. • 3. Inflammation ooourring at the aite of Infection.As pointed out in 8. previous page, infla.mmation is to be looked upon as a local battle fought by Nature against infection, for its effect is essentially bacterioidal and antitoxic. 4. The E~inction of the I nvad;,ng Microbe by PhagOOyt68 and Antibodies. Should tho invadiog mforobe break through theee various lilies of defence and gain admlttanoe to the-Inside of the body, 'Nature brings into play various defensive agenoies. There wore tormerly two chiet theories to account for generallm.mUDit,.-the • ceUular' theory of Metchnlko1! and the • Immoral' theory ot Nuttall It Is now established that the NATURE'S DEFENCES body employs both her • oell•• and her • humour. ' fD dealing with Infectlollos. They are oommonly ]mown as phllgoo;vtes and antibodies. Phagocytosis. Phagocytosis (phagein=to eat; cyt08=a cell).-Metchnikoff believed that phagocytes ( = leucocytes and most timme cells) are the essential agents in the destruction of bacteria-the warriors which deal with the invading army of microbes-and that other agencies play but a subordinate part in the process. • It is the phagocyte,' he says, • which delivers us from our enemies. Sometimes the phagocytes devour at one swoop whole masscs of the organisms.' He admit", however, the existence of a complementary substance-cytase--which is probably iden. tical with the opsonin of Wright. The phagocyte, as it were, • recognizes in the microbe a foe to the organism; scents it from afar; hunts. seizes. and digests it; and then, its duty done, its mission in life fuHillei, it withdraws its pseudopodia and dies contentedly' (Adami). The bacteria. engulfed by the phagocytes either undergo intracellular digestion or are destroyed by a chemical poison, probably related to nucleic acid and secreted by the cell nucleus. H the invading bacteria are very, virulent, thQY may kill the phagocytes, or, if their spores have been taken up by the phagocytes, these may develop within the phagocytes and destroy them. All leuoocytes possess phagocytio properties, but the polymorphonuolears and the large lymphocytes are by far the most powerful in this respect. Beside tne_leuco. oytes, most tissue cells are phagocytic, especially the endothelial cells of serous membranes, bloodvessels, and lymphatics. Phagocytosis takes place chieHy in the blood. spleen, bone-marrow, lungs, liver, and lymphoid tissue generally. The number of the leucooytes in the blood increases (leucocytosis) in most infections, the bacterial toxin stimulating the bone-marrow to increased production of them. AIDS TO PATH OLOGY Chemotasis.-Tho migration of tho loucooytos from tho bonomarrow is oXplained on tho hypothesis of chomotaxis. by which is meant the property possessed by a cell ondowed with the power oC locomotion to move towards or away from a stimnlus • The phagooytes possess a kind of BOnse of taste. cr chomoto.xls. which enables them to distinguish the ehomloal composition of the substances with whioh they come into contact· (Metahnlkofl). In the case of the less vlrulentlnlootions. thelnvndingmlcrobos secrete a. substance which attracts the phagooytes (= positi'116 chemota:r:is). whereupon the latter ingest and destroy them. In the case of virulent InJections. such as tho acute septlcmmias. the microbes secrete a substance which ropels or paralyzes tho phagocytes (=fIeI1aH'OO chemotaa:i8). thus enabling the invaders to multiply witllout hindrance. Antibodies. -The antibodies are protective substances generated within the body a.nd brought into operation by the action of the antigen. The antigen (=antibody generator) is the agent which ca.lls forth the action of the antibody, and it may be either a. microbe, alien cell, or chemica.l substance. 1'he antibodies are named in reference to the mecha.nism by which they are supposed to antagonize the pa.rticular antigen, the following list comprising the ohief ones: 'I.'he upsonins. The Agglutinins. The Prooipltlns. Tm-..i.11t.lJ"oXMlR Bactoriolysins. { Hmmolyslns. Cytolnlns. Opsonins.-It was In Soptembor, 1003, that Sir Almroth Wright and ()Qptain Douglas, 1.1II.S., contributed to the Proceedings cHho Royal Socioty (vol. lxxil.) their now famous papor, In which they showed by a series of eXperiments that the rate_ and activity of phagooytosis are determined by the presenco in tho blood-plasma of a substanoe whioh aots on tho Invading bo.c~eria in It IDanner which renders thom 0. roady proy to tho pbago es.' To this substanoe they gave· the name of ()psooin (fro 0 Greek bl/l.,,,.., and the Latin opsono-I convert into pal le pabulum). and it is dlstlnotly to bo understood that the efleo"t thoy olah' for it is produced upon the bacteria. and not upon tho pho.gdriytos. Suppose thoro is an Infoction by one or other dlsease·oauslng miorobe; gradually the appropriate opsonin is elaborated In the plo.sma. and becomes attaohed to tho invading ntiorobes. rendering them palatable Qike sauce applied to foods). The { The LTSlns NATURE'S DEFENCES 43 phagooytes oan now 8wallow them greedily, and 80 make an end of tho invasion. Thus, while acoeptlng tho main theilis of Motohniko1f-vlz., that the final destruotion of tho baoterla is brought about by the phagooyt_they eOlltend that these latter are incapablo of ingesting bacteria unless thoso havo been aotod on by this pa.rtioular substanoo gonerated In the plasma; for they find that If leucooytes are separated from the blood and W8.shed they possess little or no power of Phagooytosis, but that, if to the wa.shed leucooytes blood-serum Is addod, phagooytosis at onco takes plaoo, thus showing that tho serum contains a •somothlng' which is essential to that process. MetobnikotT admits this, but ho affirms that this something Is derived from tho louoooytos: • Either the absorption of the miorobos may bo etTcoted without the help of the opsonin, or, should sueh help be indispensable, the opsonin may be supplIed by tho louoooyte Itself.' Normal blood-plasma contains opsonin, tho amount inoroaslng with every baotorial Invasion, and Wright goeS so far as to assume that the body POSBCSSOS tho power of elaborating a 8peciJlc opsonin for almost evary kind of bacteritun. It will thus bo soon that, aooording to this viow, tho rosisting power to baotoriogenio disease is largely determined by the quantity of the right kind of opsonin which the host can provide. Tho blood ot 0. patient sull'ering from bacterial Invasion may contain an army of lusty pbagooytos, and yet these may be powerless to attaok the Invaders. Their striking forco 'll'ill depond upon tho oxtent to whloh tho baotoria are first aoted on by tho opsonim. Just as the preliminary artillery bombardment in a battle, by demoralizing the enemy, r-reparos the way for the advanoe of the infantry, so do the opsonins prepare the way for the phagocytio attack. By injeoting the Infected pa~lent with a sterilized emulsion of the bacteria oausing a particular disease, the quantity of tho opsonin is increased, and the resisting power of the patient thus raised for tha.t diBeaso, but far 710 other. The • opsonio index' of a patient oxpresB6s the power of his agooytos opsonins to Infiuence the ingestion of miorobos by as compared with that of the opsonins ot a heslthy n. It is obvious then that, when an individual i8 8 Jug from a baoterlog6nio disease, a knowledge of bis opsoni ldex glvOB valuable Information as to his powers of combatl e discasc, and that this information is essential in our endeavo to assist him by tho Inoculation of a bacterial vaccine. The Opsonic IndtJ:IJ tm!y a Partial Mea8'Urll~hll.A. cterial IH/1l'IWtJ& of the Body.-Wright Is careful to nt out t it Is Impossible to estimate oxactly • all the facto which make up the resisting power ot the organism to bacter I invasion '; to enumerate all tho leuoocytos, to messuro their individual phagooytlc powers and the extent to whioh these powers are av:o.ilable for application, and to estlma.te all the known-to say nothing of the unknown-antlsubstaucea whioh havo afleoted the microbe 44 AIDS TO PATHOLOGY \v.blch the patient is su:fleriDg. The measurement of the DPsonic power of the blood leads admittcdly to only a partial estimate of the antibacterial defences of the body. He claims for It, however, (a) that it can be accurately measured, and (b) that it increaees and diminishes In responee to inoculation by vaccine and In correlation with the patient's clinical con-, dition. Wright's Law of the Ebb and Flow, Back Flow, and S'UBtai1l6t1 H{,gA TIde oJ Imm..,.Uy.-The lIrst eUect of a bacterial Infection Is to cause a fall in the opsonio index-the negativo·phase (ebb), owing to the taking up by the bodies of tho bacteria of Homo of the ava1lablo opsonin. This is followod by a rise to a point above its original level-the positive phase (flaw), owing to fresh supplies of opsonin being generated. A sooond, and this time moderate, fall then occurs (rejlow), after whioh the Index remains for a variable time at this higher level (maintained AiDA tide 0/ imm"nity): This law holds good both for oases of ordinary baoterial infection and also for oases In whioh the products of dead baoterla (vaooines) are Introduced into the body by inoculation. By a series of properly timed Inooulations with the appropriate vaooines, the opsonio index of the blood can be gradually inoreased to a lovol at which it tends to remain permanently ~om high. The property of the body in virtue of whioh it can guard itSll1f against infection V!{right oalls Its pk7llactic power (p"IwJasso= guard). The transport of the phylactio agents to the site of the infection he oalls kalaph7lla:t1ls, and any oondltion whioh interferes with SUch-e.D., stoppage of adequate arterial bloodsupply (oollapse, extreme cold, eto.~atapA7Ilazis, for undor suoh circumstanoos, the movements of leuoooytes and the transport of lIlood·f1uids being interrupted, pathogeniC organisms· can flourish unopposed. Agglutinins.-It the serum of a patient oonvalesoent from enterle fever bo addod to a living culturo of theBa.cUlw typkosu,s, the organisms lose their motility and become massed into clumps (Wldal's reaction). This phenomenon Is known as • agglutination,' and is supposed to be due to tho dovelopment in the lymphoid tissues, bone· marrow, and spleen, of a substanoe--agglutlnin-whioh, by aUectlng tbe surfaoo tension (=the foroe with whioh a fluid strives to recfuoe Its free surfaoe to a minimum), causes the olumplng. In this respeot it Is analogous to the running together Of bubbles on the surface of a fluid. The proooss of agglutination does not appear to play any, important part)n Immunity, for the ohange Is a physioal one, and the vitality. of tho bacteria is not a1lBcted by its occurrenoe, although their dissemination Is (and in this way it may favour llhagocytosis). Nor is it a certain test tor enteric fever, some oascs failing to give it; while It Is found In Malta fever, In the' dysentery due to Shiga's baoillus. and In Aslatio oholera. NATURE'S DEFENCES 45 PrecipitiDs.-If an old oulture of typhoid baoilli be filtered. and tho filtrate be then added to some typhoid serum. a precipitate forms. Suoh a precipitating substance is known as a • precipitin.' Preoipitins are allied to. 11 not identioal lvlth, agglutinins. and. like these latter, probably play no important part in immunity. 4ggressina.-It a mixture of tubercle bacilli with sterilized tubercular exudate is injected into the peritoneum ot a guinea' pig. the a.nimo.J dies rapidly. It, however, each be injected separately. nothing happens. From this Ball argues tbat there Is something in the exudate whioh increascs the virulence of the bacteria by paralyzing tho phagocytes (negative chemotaxis). and thus permitting the Invading microbe to exist without hindrance. To this speciflo substance. tormed by the bacteria to inhibit Phagocytosis. he gives the name of • aggressin.' In this sense, aggressins are to the bacterium what opsonins are to the animal. Antitollins.-An antitoa:in is a speoifio neutralizing substance elaborated by the blood. lymph, or tissue.s, as the result ot the presence in the body of a toxin, neutralizing quantitatively the toxin and thusouttingshortthedl~ The greater part of our knowledgo of antitoxins has been aequired with respect to dlphtherla antitom. whioh can be prooured in the following way: The diphtheria baoillus is oul· tivated bymilllons in beef-tello, and the fluid is then filtered. The filtrate is free of microbes. but loaded with their toxin. A horse is then injected with graduated doses of this filtrate. The tissues of the horse reply by the production of large quantities of antitoxin whioh flows into its blood. It the horse be now bled. and the blood be allowed to ooagulate. the resulting serum is rioh in diphtheria antitoxin, whioh then oonstitutes the commercial preparation. Tllat tile neutraJizlilg anti'toxin acts upon tile baoterial tOXJ'n~ and not upon the bacteria themselves, is proved by the faot tha the bacilli oJ diphtheria .mu grow readily in diphtheria amitomn It a similar oxperiment be performed, but tetanus toxin use instead of diphtheria toxin, it is found that the resulting tetanus antitQxin·fg not an antidote for diphtheria toxin. nor trice ~. Each antitozic serum. then, is apeciJlc. neutralizing only the toxin of the oorresponding organism. It Is to be olearly understood that by adminlsterlng an antitoxin the free tom only is neutralized. Henoe the urgent need oJ giving, the antitoa:in early. for tho toxin whioh has entered into combination with tho tissues is boyond the reach of tho remedy. In the treatment of tetanus, for example. antitoxin is of little praotiool value unless immediately lnleoted into the nerve leading from the wound. for the tetano-toxin rapidly disappears from tho blood and travels along the axis cylinders of the nerve to the central nervous system, to the elements of whioh It becomos • flxed,' thus being inaccessible to the action of the InJeoted antitoxin. With regard to diphtheria it has been demonstrated that AIDS TO PATHOLOGY when antitoxin has been administered on the first day of tho disease the mortality is praotically nU. and that it increases rapidly as oaoh suooecding day elapses. Lysins. These are substances whloh have a solvent (lvo= I dissolve) action on certain bacteria and certain cells. The chief are-Bacterio)Jsins.-These are formed in the blood and lymph. and possess the power of dissolving bacteria (IVO= I dissolve). The t'pooh'making experiment of Pfeill'er is the foundation of our k"llo,"ledge of the bacteriolyBinB. Pfe1Jfer's Reacti<m.-If a guinea·plg is immunized against oholera by injecting it with small and gradually increasing quantities of the cholera. vibrios. vibrios subsequently injected Into tho peritoneal cavity ot suoh an animal first become motionless. then die. and ultimately disappear. Seeing that tew. If any. leucocytes are present In tho peritonoal cavity. Pfci1l'er regards the substance causing these phenomena. as an cxoretion from the ondothellum lining the peritoneum. and Inasmuch as it dissolves the organisms. it is spoken of as a bacteriolysin. Hmmo)y$ins (haima= blOOd; 1'/10= I dlssolve).-If the chromocytes of one species of ma.mmaI~.o.• the horS&-a.re Introduced Into the body ot another species ot mamma.l~.g.• the dog-the latt~r animal elaboratos a serum oapable of dissolving the chromocytes of horses In general. Such a serum is said to contain hmmolysins. Oytolysins.-In a similar way the sorum may be made to acquire the property of dissolving other cells, Buch as those of the kidney. liver. and testes. and such sera are said to contain rrutolysins (kyto8. a cell; Ivo. I dissolve). ot which"llephro-. hupato-. and spormato-Iysins are examples. Mechanism of Lysis. Three factors are essential: 1. Antiaen{=antlbody generator). 2. Amboceptor (also known as Immune Body and Sensltlzer).This does not exist normally in the blood. but Is elaborated solely for the oceasion"""",.e.• no antigen, no amboeeptor. It Is specific """",.e.• for ollch different antigen present there Is produced the appropriate amboceptor. It is thermostabll~.e.• It is not destroyed by heating to 56· C. (Twenty hours heating to 00· C. scarcely injures it. Resists putrefaction. and has boon kept for as long as eight yoars. Non-dialyzable.) It has t,vo aftlnities, one for the bacteria and one tor the complement: hence thu name. 3. Oomplement (also known as Alexin or Cytase).-This Is always present In thc blood. both in health and dlseasc. and is non-speoUlc. It Is thermolablle-i.e.. it is destroyed at 50· O. Sei'um which has been so hee.to04. and there10re contains no NATURE'S DEFENCES 47 complemont, is said to bo inadillated. The complement is so named because it complotes tho action of the ambooeptor; one Is powerless without the other. Accordingly, lysis of the antigen takes plaoe only in the presence both of the speei1l.e amboceptor and the non,spooiflc complement. Neithor can produce It alone. Let A= Antigen, B= Amboceptor, and O=Comploment. Then A+ B+ 0= Lysie of A. A+B Dr A+O=no Lysis. An Illustration of these processes, and also of their practical value In diagnOSis, Is afforded by the Wasscrmann reaction, now to ·be desoribed. The Wassermann Test (Fixation and Deviation 01 Complement). The materIals required are-1. SIiPhilitio antigen (=A). This may be a solution obtainod oither from a syphilitio fmtalliver, or (slnee the antigen is really a lipoid) from cortaln other substances, such as human heut or that of a horse, ox liver, ete. II. Oomplement (=0). That "ontained in fresh gninea·plg's blood Is generally used. 3. Serum/rom the patient swpected ofsuphiliB. This, of oourse, contains oomplomont, but tho amount is uncertain and liable to wide variation. '.rhe serum is therefore inaotivated, the required complemont being mQre oonveniently supplied by (2). It the patient is syphllitlo, his serum will also contain the specifio amboceptor (= B). If not, thon thera will be no amboceptor '= 0). 4. Inaotivated sorum from a rabbit whioh has been rer tedly InJeoted with slleep's red oells. These oelie havo aotell' as an antigen, and the sorum, therefore, new oontalns a hmmolytio amboceptor (= Bg), whioh is speciflo for the reds, and whloh, in tho presence of oomploment, oan destroy them by hmmolytlc aotion. 5. Sheep's red reUs, ,vashed in isotonlo saline (= ~). Experiment-Incubate I, 2, and 3 togother for an hour at 37· C. Oase t.-The patient is syphilitic. Then A1+0+B1=(A10Bl). That is, thero is fixation of oomplement, all of which Is used up in the intoraotion between the three substanoes, and none is lelt free. Case 2.-The pationt ie non-syphilitio. Then AI + 0+ 0= Al + O. Here the oomplement Is not affeoted and is still available. Next, add (4) and (5) and Inoubate for another hour. In Case 1 we now havo-(AICB)+ B.+ ~~ no hrem.olysl~. 'l'he reds (~) are not destroyed by thc amboceptor in tho rabbit serum (B.), since there is no free oomplement. They sottle at the bottom, with a olear, oolourless 6upc!rnatant flilid. AIDS TO PATHOLOGY In Case 2-.4.1+ 0+ Bs+ ~ lUl!molysis of reds CAa) by speolflo amboceptor CBs) In presenco of fl'ee complement. There is no deposit of reds, beoauBo, the stroma of the corpuscles having been dissolved and their contents liberated, the test·tube oon· tains a olear, transparent, bright red solution of hmmoglobln (' laking 'I. Deviation of tho c01llploment hal! oocurred. After , Hour. CASE I (+) ~ ~ Syph,lit,c ilntigen(A,) o. After'/!. Hours No haemo- ~} ·Iys/s. Clem,. colou,.· lesslluid with deposi-t (A, C 8,) No free comp.ie- m!lnt. of unAlter'l1ll reda. Complement (e) ~" Syphllit'c Amlloceptor (BJ t3" tlllIemolytic Amlloceptor (Be) o " Sheep's reds . (Anfiqen, A2) CASED C-) A,+C No fiXAtion. of com- plement ~ 8o (A£C Bd "HAemolysis of reds, giving c/eDlrretJI. fluidlllnd no deposit. PIG. 5. The Wassermann rea.otlon is positive (but only after two to six weekS from the first appoaranoe or the primary sore) In syphilis as follows: 66·4 per cent Primary 100·0 Secondary (untl'Dated) 90·0 Seoondary (all cases) •. 99·1 'l'ertiary (untreated) SS'O 'l'ert!a.ry (all oases) 95·5 Congenital 9S'0 Geneml pa.mly1lis 64" 'l'abes dorsalis •• (Oolw:ted by McIntosh and Fildes.) NATURE'S DEFENCES 49 A positive WaBBermann Is also found in yaws, trypanosomJasis, relapsing tever, malaria, scarlatina, leprosy, and tropioal uloer. Ehrlich's Side-Chain Hypothesis, Bacterial tOxins are, as already statcd, allied to proteins, and as such possess a highly complex chemloalcomposltion, in contradistinction to the ordinary vegetable alkalolds--e.g., strychnine, morphine, etc. These two classes of poisons further dHler as regards their chemical action on the tissuos, the former entering into more intimate ohemical union with them than the latter--so much so that, while it is impossible to recover a bacterial tOxin, sllch as that of tetanus, from the tissues after death, it is qUite possible to recover such poisons as strychnlno and morphine. This, according to Ehrlioh, Is because the former olass of poisons enter Into firm chemical union with the living protoplasm, being FIG. 8.-P=Protein-receptor; O=carbohydrate-receptor; F= fat-receptor; T=toxln mol"culo, witn baptophore (A) and toxophore (e); P'=prote1n-recoptor linkod to haptophore; T'=toxin molooule dotaohed from oell, with protein-receptor linked to it. actually built up Into or assimilated by it, while the latter llIIite only with the fatty and other substanoes entangled In tho protoplasmio network, and not with the actual protoplasm Itself. Ehrlich assumos that the moleoules of which protoplasm Is oonstitutod oODsist of II central part furnished with numerous side-chains or • receptors,' adaptod to unite wlth-' fitting like a key fits a look '-and thus aSSimilate the various food-stulfs ciroule.ting in the lymph, there being protein receptors (P) for proteins, carbohydrate receptors (0) for carbohydrates, fat reoeptors (F) for fats, and so on. Now, when toxins are present, they, being aIllcd to certain food-stuffs, are, as it were, mistaken by the tissues for them, and are oaught up by tho recoptors. It tho reoeptor possess no affinity for tho toxin, the animal will be naturally immune. Imagine, howover, a cell to be 4 50 AIDS TO PATHOLOGY attacked by a toxin for which It has a1ll.nlty. As already explained (Ilide p. 38). the toxin molecule (T) consists of two groups of atoms: a oombining group. the haptophore (h). ane'{ a pois~n1ng group. the toxophere (I). The haptophoro booomes Joined to a toxophile receptor. Imd the toxophore then exerts its poisoning influenoe. In this way a oertain nwnber of the receptors are thrown out of action. and are no longer available to oarry on the nutrition of the cell. In addition to this. the 0011 is partially poisoned. Under the stimulus of the abnormal assimilation. the cell protoplasm buds olf fresh receptors to meet the extra demand, the collin oourse of time becoming cducated. so to speak. to produco an abundanoe of reoeptors. some of which are in oxoess of Its needs. The surplus receptors are then oast olf. and. though tree of the parent OI'JI. still retain their power of combining with toxin. These Il'Urplus reuptors it is that constitute the circulating antittXllin, whioh, by uniting with the toxin. neutralizes it. and thus protects the living protoplasm from Its aotlon. In this way lite tends to be prolonged until the organillIIl has had time t.o destroy the bacteria from whioh the toxin had Its origin. Should receptors not be formed In su1Dcient number. tIle animal dies. Susoeptibility• Natvtral SUSceptillUitll.-It a mouse is inoculated with anthrax at the tip of its tail. even though the tail bo amputated within one minute of the Inoculation. the animal will succumb to anthrax-a striking instance of natural susceptibility. Man Is similarly susoeptlble to certain bacterially induoed diseases, suoh as hydrophobia and syphilis. Acquired Susceptibilitll.-Tho hen is naturally insuscoptible to anthrax; when. however, its foot are Immersed in cold water It becomes susceptible. and experiments have proved that not only cold, but hunger, thirst. improper feeding. fatigue, and loss of blood, all tend to Increase susceptibility to bacteriogenic diseases. White rats. tor example. whioh are ordinarily insusceptible to anthrax. become susoeptlble after fatigue. or whon red upon a purely vegetable diet. Agai'n. while healthy swine ilo not oontraot glanders. young and debilitated pigs may some~lmOB be a1fected with it. Immunity may be(a) Natural, or (b) Acquired. (a) Natural Immunity.-This is the resistance to an infection that is innate. For example. pigeons and other fowl are quite immune from the pneumonococcus. Rinderpest is essentially a dise¥,.ltof rwp.inants; horses never oontraot it. Tubercu\ps4I/¢.ough common in cows and NATURE'S DEFENCES pigs, is very rare in horses, asses, sheep, goats, and dogs. Dogs are immune from o.nthrax, fowls from tetanus. Again, Algerian sheep are immune against anthrax, a.l though ordinary sheep are susceptible to this disease. In all these cases we must assume that when the specific microbe enters the system, it is at once exterminated, and so cannot breed there. Immunity, like susceptibility, is 0. relative term. With few exceptions, no animal which has been made the subject of observation possesses absolute immunity against any given microbial disease under every possible circumstance. For instance, the fowl, though immune to tetanus, if refrigerated, loses its immunity to this disease. (b) Acquired Immunity.-Of this there are two chief kinds: (a) Active or Direct. (b) Passive or Indirect. (a) ActivB lmmunity.-In active immunity defensive mechanisms have been created in response to a former infection. Examples of this are1. Immunity due to a previous attack 'of an infectious disease-B.g., measles, scarlatina, mumps-the patient acquiring freedom from the same disease for a certain period of his life. 2. Immunity induced by the inoculation of the virus of a disease which is either an allied condition or a weakened form of the disease against which protection is sought, as in the case of vaccination for smallpox. 3. Immunity due to repeated inoculations with sublethal doses of living micro-organiams, which in course of time produce an immunizing, substance in the blood, so that the animal can ultimately tolerate a dose which would at first have been fatal, as in the case of Pasteur's method for fowl oholera (now seldom employed). In all these cases the body is stimulated to elaborate its own antibodies. (b) Passive lmmunity.-If the blood-serum of an animal rendered immune against a partioular disease by any of the above methods is injected into a second susceptible animal, this animal also becomes immune against that disease. In such oases the process of immunization AIDS TO PATHOLOGY is :Pa8SiV8 80 far as the second anima.! is ooncernel!, for the antibodies are not elaborated by the animal itself, but are supplied ready-made_ An infant fed a.t the breast is less lialile to contract disease than one brought up by hand, one reason for this being that it derives immunizing substances from its mother's milk, and in this way is rendered passively immune_ Anaphylaxis (Hypersensitiveness). Riehm, Who coined the word In 19011, de.flnos allaphylu.xis as • the peculiar attribute posscsscd by oertaln poisons of Increasing, Instead of diminishing, the sensib!llty of an organism to their ILctton.' Delille describes It as ' a state of aoquired vuInera.bility in an organism to a second Injeotion of a SUbstance to which, at the time of Its first Injection, It was indlf'fepent.' The first injeotion is known as the se7lBitising dose; the second, as the reacting dose. The Injections may be made intravenously, intracardially, intrapllritonea.lly. or subcutaneously. As u. rule they are made intraperitoneally. OondititmBnecetJllarufO"ltheProductiono!Aflaph.ylazis.-(a) The substanoe used must bo a protein (serum, milk. egg-white, plant-albumins, bacterial extracts, etc.). (b) The protein must be foreign to the animal e:r:per.lznented on; e.g., guinea-pig slll"llm cannot hypersensitize either the same or another guineapig. (c) Between the first injection (' sensltiz:lng dose ') and the second injection (' reacting dose ') there must elapse a latent period. The shortest latent period Is ~ dan; ie., if a second dose be administered within ten days of the first dose, anaphylax:ls does not occur. (Il) The 'reacting dose' must be introduced by the same channel as the' sensitizing dose'; e.g., it the first dose be Injected Into the peritoneal cavity, and the second dose into the jugular vein, anaphylaxis Is not estabiished. (e) The ' sensitizing' and the' reacting' proteins must be derived from tho same souroe; e.g., If you start with horsegorum on a guinea-pig, yoU must continue with horse-sel'1lD>. (Thc serum of closely-related anlnaa.ls, however, can be used vicariously, as that of the horse and donkey.) Once established, ana.phylaxis may last for months or yea1'8. Anaphylaxis, 118 oliserved In the rabbit, Is thus described by &.rthus: • One or two minutes atter the administration of the !econd dose, the animal begins to shake Its head, and then lies iO'VD. Respiration Increases greatly In frequency, but there is [1.0 actual dyspncea. Solld f_l matter Is freely evacuated. The animalroUs over on Its side. and, a.fter taking foul' or five heavin8' breaths. dies within four or five minutes of the injection.' In the post-mortem examlna.tlon the blood Is noticed to be dark in colour, and to show little tendenoy to coagulate. The lungs are swollen and congested. The mucous membrane NATURE'S DEFENCE 53 of tho Intostlnes Is oongested, and numerous hl8lllorrhages are visible. Anaphylaxis can be induced by feeding on foreign proteins, though less readily than in the case of injeotlons, and this is how Hutlnel eXplains the toxio aocidents sometimes oaused in Infants by milk. (Alimentary anaphylaxis Is of great Interest, since there are people to whom moh things as eggs, shelltlsh, .eto., are anathema.) The mother oan transmit the anaphylaxis either through the placental olroulation or through her milk. If a pregnant guinea-pig be inooulated with horse-serum, and afterwards one of its o1fspring be Inoculated with tho samo serum, it will develop anaphylaxis. It has been suggestod that puerperal eolampsia is a manifestation of anaphylaxis evoked by some substance of placental origin. Epilepsy, urmmla, and diabetlo coma, oan be explained on muoh the BOome ground~. Also, It is probable that an attaok of spasmodlo asthma is an anaphylaotlo phenomenon. Mechanism. oj Anaphllla:riB.-This still remains somewhat of a blologloel puzzle. The simplest eXplanation is that suggested by Richot. Acoording to him, the • sensitizing dose' oauses the production in the blood of a new substance, whioh, while in itself non-toxic, yields an intensely toxio substance by combination with the' reacting dose.' Vaccines. A vaoolne Is a substanoe oontainlng the endotoxin of a particular mierobe, the microbe In question having been previou~ly Iso1ated and cultured.. The vaeoine must be »repared from tho oausal organism: e.g., In a streptoooccal Inteotion the vaccine must be prepared from !Po oulture of streptoooooi ;'In a staphyloOOCCIC lil!ecllfon, trom a cufture of stapftyCooooof. TIle action of tho vaooine is to stimulate the natural meohanlsm of i=unity inherent in the body~.e., to exoite the manufacture, by the blood and tissues, of the appropriate antibody. Most of the vacolnes are prepared from killed baotoJia; a few, however, are prepared from living haoteria whioh have had their virulence attenuated either by repeated suboulturing or by heat. Vacoines can be !Lffld De e pro,pludqc:HC to preyept intectiOD (e.o., smallpox, enterie, hydrophobia, and plague), er lor curativll ~8eA In the QMO of OJ) Aetnel integtj9~.a., furunculOSIS due ~ phylocoool, enterio, malignant endooardltls). With regard to the proteotion afforded by vaccination against enterio, note the faots given by Sir William Osler in a reoent speech (September 15, 1914): • Above all ether, one disease had proved most. ratall)). modern warf&l'O-illlterlc, or typhoid fever. Over and over again It had killed thousands before they over J;eaohed th'l fighting line. The United States troops had a terrible OXperienoe in the Spanish-Ameriean War. III six months, between June and November inclusive, among 107,973 officers and men in 92 volu!_1teer ~D1entjl. 20,738. praoticallv ou-flfth of the 54 AIDS TO PATHOLOGY cntfrenUDlber, bad typhoid fever, and 1,580 died. Fortunately, In this oountry typhoid tevor was not prevalent In the dletricts In which oaIOps were placed. The danger was ohlefly from per' eons who had nlree.dy had the disease, and who earrled the germs in their intestlnos, harmless messmates in them, but oapable of infooting barracks 01' camps. They could easily understand how flies oould convey the germs from theso oarrler. far and wide. It was hi this way probably, and by dust, that the bacilli werc so fatal In South Africa. There were 67,684oases of typhoid fever, of whioh 19.454, were Invalided and 8,029 dlcd. More died from the bacilli of this disease than from the bullets of the Boers. Let this terrible roooril Impress upon them the importanoe of carrying out with rellglous oare the sanitary regolations. lie Wished to ask them to take advan· tpge of the kno\vledge that the human body oan be protected b)r vacolnation against typhoid fever. Discovered through the resoorohes of Sir Almroth Wright, the measure had been Intro' dnood suocessfully Into our own Regular Army, Into the Army of France, the United States, Japan. and Germany. The appal· ling Incldonce of typhoid fevor in the volnnteer troops in America during the Spanish-American War resulted IB.l'l!'IllY trom the Wide prevalence of the disease In country districts, and the camps became Infected; and because we did not then know the Impol'tanoe of the fly as a oarrier, and other points of great moment. Hut In the ltuglilar Army of tbe United States. where inoculation had been practised now for several years, the number of cases had fallen from 3'63 per 1,000 men to prao, tloally nU. In a strength of 90.640 there were, in 1913, only 3 CaBBS of typhoid fev8l'. In France the enterio rate among the unvaco.inated was 168'44 per 1,000, and among the vaool· nat'ed 0'18 per 1,000. In Indio., where the disease had been very prevalent, the succesa of the meILmre had been remarkable. In the United States. In France, and In some other oountries. this vaocfnatlon against the disease was compuls017.' The property of tho body in virtue of whloh it guards Itself against inrootion is tOl'lDed by Wright its ph'Vlactic power (pllulll8BO=guard). The conveyance ot the phylaotlo agents to the slto ot the infootion is oalled kalaph'Vla:r:i8, and anything which Interfores with this transport ami·kalaphllla:z:i.s--e.g., diminution of tlifl artorial blood -supply (from oollapse, extreme oold, eta.). In anti·kataphylaxis t)1e transport of leuooc)'tes and antibodies is inton-upted, 80 that pathogenio organisms can grow unopposed In addition to phylaxis and Imtaphylaxla there are resei'Ve foroel -the epiphlllactic reinforcements or response. A response 01 this kind oocurs after the administration of an a.ppropriate vacoine (positive Phase). preceded, however, by a negative phase or apoph7l14ctic phase. (Yide lecture by Sir Almroth E. Wright, F.R.S.• reported in Lancet. Mareh 29, 1919.) NATURE'S DEFENCES S5 Sera. Tho action of a SC1'UJD. is to supply a ready·mado antIbody. In the easo or diphtheria, for example, the antibody (antItoxIn), prepared from the serum ot a horse (see p. (6). is used to neu' tralize the toxin of diphtheris. Somotimes a serum is ueed tor tho purpose of actually killing the causal microbe. such being caUed a bactericidal serum. 'The sick body Is itselt put to no expenso for its defenoe; It has no army to raise. equip, and train for the struggle upon which it is entering. We. so to speak, place at Its disposal an army ot meroenarles ready equipped. prepared. and trliincd, abroad. As the organism is at no troublo to prepare an antIbody. it is eaar to understand why it is not exhausted' (Profossor Louis mnon. • Lo Traitoment de Ie. Tuberoulose Pulmonaire par les Serums '). A serum may be employed either tor (a) proph'UlacUc or (II) eumti'DB purposes. In (a) it is Injeoted Into a healthy indf~ vidual who is likely to bo exposed to an infeotion. In (b) th~ sorum is Injected into a patient Ji'ho Is at tho tiDle suttorlng trom an attack ot the disease. Serllm-Siokness. Borum-siolmess develops In about a third ot all people Inocu· lated. and Is oharaoterized by rashes. joint-palm. adenitis. fever and transient albuminuria. The rash. which may be assooiated with violent itohing of tho skin. usually appears between the seventh and tenth days. and lasts tram three to seven, days. It Is oommonly urticarial. and Is usually first notioed on the tront of the abdomen. sometlmos spreading to tho tace. arms. and legs. Occasionally there Is redema of the lips and eyelids. Tho Joint-pains are ohiefly felt in the large joints (Imees. elbows and shoulders). Thoy are lIeeting In chlll'aoter. and as a rule there Is neither rodn~s nor swelling. The glands draining the area into whloh the serum was injected may enlarge and become tender. The fever Is usually lillght (rarely above 100· F.). and acoompanyfDe It there may be transient albuminuria. AIDS TO PATHOLOGY GANGRENE. By gangrene is mea.nt the dea.th of the mass. Olassification. 80le tissues in Bums, corrosive poisons, otc. (Infiam· matol'Y gan~Des are pro~ablY in pari due to the direct destructive action of the toxins on tho protoplaSm of the tissues.) RI1Pture. ligature, embolism, or thrombosis, of maIn IIo1'terYi Arterial arterial spasm (6,g., trom { ergotlsm, frost • bIte. Ray· From vascular ob. struction naud's disease). Tight bandage, plaster 01 Paris, { Venous { • splint· pressure, thrombosiH. strangula.tcd hernia. From acute Sllptio{Cla.rbUDale. cat;'crum oris, sloughing ~hage· inA mmations dmna, malignant cedema, mo.llllnant 0. pustllle. FromiDterruptionof{ Acute bedsores after injuries to spinal trophlo inlluenoo oord. From destruction of the tissues outright { Clinically there are two main varieties of gangrenethe' dry , and the • moist.' The former only ocours when the arterial afflux is obstructed, lIB when a main artery is thrombosed or plugged with an embolus; the latter when the venous efflux is obstructed, as from thrombosis of a main vein. .All gangrenes resulting from inflamma· tions are of the' moist' variety. Dry Gangrene is well illustrated ih the case of the ordinary variety of senile gangrene. The arteries of the leg, narrowed and rigid from calcareous degeneration, become gradually thrombosed, and the blood· supply being thus cut off, the most distal parts suffer fil'Bt. One of the toes (geners.lly the great toe) present.s a tallowy. white colour. La.ter on it becomes purple or mottled, owing to extra.vasation of hmmoglobin from the veBBels. In conse· quence of the evaporation which takes place from the surlace, the tissues become dry and shrivelled, and the skin assumes the appearance of parchment, u1ti~ately becoming covered with an oily film from transudll<ti.QI\ qi the underlying fat. GANGRENE 5'1 IJ tke prOC68S i8 arrested, the dead part acting as an irritant to the adjacent living tissues, a dusky red zone of infl.a.mmation forms, called the line oj demarcation. Finally, the dead part is separated from the living by ulceration. As a rule,. however, the Hne of demarcation is imperfect; the disease spreads from toe to toe, then advances up along the foot, and ultimately involves the leg. Constitutional infection is rare in dry gangrene, the dried up. shrunken tissues not proriding a suitable soil for the growth of organisms. Moist Gangrene is well illustrated in cases of septic inflammatory gangrenes. The veBBels are thrombosed as the result of toxic action, and the gangrenous part becomes soaked in an albuminous fluid containing many disintegrated chromocytes. The dissolved-out htemoglobin, diffusing itself through the dead tisBues, stains them a greenish-black (= FeS). Later on, buZZQl, containing a blood-tinged fluid, form. Still later, gases are generated from infection by *e BaciZhUi o,ij1"ogenes capsuZat'U8 of Welch, giving rise to emphysematous crackling. mti· . mate1y the part putrefies, and oonstitutional infection occurs. Senile Gangrene may be eitber (a) df'1l or (lI) moist. (a) Has been described on the previous page; (b) generally occurs as tho result of SOIDe slight injm'Y, suob as knooking the foot against 8. hard substanoo, wearing too tight boots. cutting a oorn. eic. The injured part becomes inlla.med. and a slough forms which Boon gets dry and blaok. The Infiammo.tlon spreads slowly, and all the phenomena ot moist gangrene supervene. Gas Gangrene.-This occurs in oonnection with wounds causcd by high explosive, trench mortar sholls. bombs. oto. (very rarely from rlfie bullets). and 1IIfually develops within forty-eight hours of the receipt of the injury-whieh Is most often of the lOlver limb. The spread of Infection varies considerably. The gangrene may be: (a) localized; (lI) SPread slowly; or be of the (c) fulminating t)~e. in which the spread is so rapid that the gangrene has boon lmown to rOllch the umbilicus from the thigh in eight hours from the tlmo of injury. It Is essentia.lly an alfection of muscles. and may be oonflned to a. single muscle or groUP of mUJIcles. 8.nd vory rarsly begins In tissues other than musoles. The injured musoles a.re stunned. bruised, present a crushed o.ppeo.rance, and look like 0. piece of uncooked meat, neither bleeding when out nor oontraoting when irritated (' musclestuDor • ot the Frenoh). In addition to the damaae caused by Its AIDS TO PATHOLOGY impact, thc missile drives in front of it a 'Volume of compressed air, which splits the muscle lIbres In the direction of their grain for some distance above and below the seat of inju.ry. Along these microscopic fissures aerobic and anacrobic organisms can travl.'l, and the medium being suitable for their growth, they Inultlply and generate toxins. These toxins, diffusing rapidly, cause tho dwth ot the tissues to whloh they gain aooese. Whilst those events are happening, the part qulokly swells, bocomes tense, and the skin discoloured (the hue varying from a brlck·red to u blo.ckish-green). Blebs contalnlng fiuld and gas form, and omphysematous craokling can soon be elicited. At the advancing edgo Is a pale zono, more translucent and firmer than the normal skin. In a certain number of cases, gas forms in the liver--made apparent by squeezing (' toaming liver '). An Intense toxmmia occurs in the later stages preceding death. EUolorll/.-The predisposing causes are (a) fatigue. and (II) In· llufficient ddbridement (= the Immediate and completo mechanical cleaning of the wound and the exeislon of o.ll devitalized tissue). Tho aotual eauso is the contamination of the wound with certain a,naerobic organisms. Bacteriolow.-From the oxperionoe gained in the recent war. I L hi generaJly admitted that the gangrene is caused by the combined influenee of a mixed infection. the most notablo organisms being: (a) BacUl'IUI welchii, (II) Bacill'IUI lBdematiem: and (I:) the Vibrion septique of Pasteur. Carbuncle.-Thisls due to inooulation with tho StaphllloctJCCU8 pyogenea aUf'eu8 of patlonts with lowered vitallty--e.q.• from undor·feedlng, over·feedlng, ohronlo alcoholism, albuminuria, and diabotos mellitus. It is most common In men over forty. and Is generally situated at the lower part of the nape t)f the neck. It begins with a primaf'1/ inflammation oj the subcutaneous tissues, the skin being secondarily Involved. At 1Irst there Is noticed a roundod dusky·red swelling, hard to the feel, and with well·deflned margin. SoOD a number of pustules form on tbe surface, whieh, bursting, loave the skin riddled \'I'lth pus-exudlng apertur~s. Many of the apertures ooalesce, and so exPo~e the underlying ashy·grey slough. This Is ultlmstely thrown otr, often laying bare musole or fascia. Healing is slow. The average size of a. (lsrbunole is about 2 Inches In diameter, but It Inay oover an area as large as a soup·plate. Bedsoros.-There are two kinds of bedsores-the ordinary and tho a.cuJe. The ordinaf'1/ bedsore forms In parts exposed to pressure when tho patlont is In the recumbent position, the usual positions being the sacrum, the troohnntors. the elbows, the spines of soapulro, the malleoli. and the heels. It Is partioularlyliable to develop in tho old and feeble. Negligent nursing (leading to oontamination With urine and flllOes) is an important oontributory oaU8e. The allected part becomes red. smo.ll blisters form, and flno.lly sloughing and ulceration supervene. In severe caBell GANGRENE 59 the underlying bone is exPosed. The dangers are from spinal meningitis and se"pticlIlIIlia. Acute Bed80re.-This OCOlll'S in 0. caso in which 0. part bas boen deprived of nerve influence. It is typically soon after fracture-dislocation of the spine, and in aoute myelitis_ The gangrene is moist; it comes on very suddenly, and spreads rapidly. Cancrum Oris.-This Is a quickly -spreading in1lammatory gangrene attaoking the inside of the cheek of unhealthy ohildron oonvo.1eseent from some speeifle fever, notably measles. The cheek beoomes rcd and brawny. On opening the mouth a slough is observed. This on separating loaves a. toul, excavated ulcer, whieh may perforate tho choek and destroy a large portion of It. The gangrene sometimes extends to the gums and tho floor of the mouth. It is a vBry fatal malo.dy. Should recovery take plo.ce, a serious deformity of tho face is 1IB11&lIy lotto Malignant Pustnle.-This, whioh is met with amongst workers in foreign wools and hides, Is due to the Inooulatlon of somo oxPosod part of the body with tho Bacilllull anthraci& Tho patient oither soratches 'Or prioks himself, and aftor a short period of Inoubation a red plmple-suggestive of tho sting of lin insooli-appeo.rs_ The pimple enlarges, and at Its oentre II vesiole fllrms whioh, bursting, leaves a scab. The margins of the • pustule' are now indurated, the surrounding tissuos oodematoUB, and the lymphatio glo.nds enlarged. A. second orop of vesicles soon form In the Indurated margin; the central biaok scab meanwhile beoomes dry and sunken below the level of tho surrounding parts. In the oourse of a few days the malignant pustule attains the size of a florin, and presents the following four zones: (a) A oentral depressed black scab. (b) A zone of vesioles. (c) A. zone of dusky-red Induration. (d) A. zone of mdema. The danger to life is from general infeotion (antAl'actUmia). Sloughing Phageena.-This, Which in the pro-antlseptio days was very oommon under the name of • :hospital gangrene,' Is now, happily, very rare. Although it may complicate any wound, it Is at tho prosent day ohiefly met with in IIasos ot venereal sores. The tissues at the infected site booome acutely Inflameil., and IL contral grey slough soon appears surrounded by an angry red margin. When the slough separatos, a toul, excavated ulcor Is lett. A. largo area ot tissuo may be destroyed in this way. Diabe&ic Gangrene.-Vide p. 182. Gangrene from Embolism.-This is commonor in the log than in tho arm, the latter having a freer collateral circulation. The embolus generally lodges at the bifurcation of the popliteal artery. The gangrene is at first always of the • dry' kind; tho 11mb assumes a tallowY oolour, and become" Clold_ numb. and 60 AIDS TO PATHOLOGY Insensitive. wjth arrest of pulsatIon In the ar~ below the _ t of obstruction. Should the part become septic. the gangreno changes into the' moist' variety. Gangrene from Ligature of III Arterr.-This. though possible, rarely results from a ligature per Be. there being asually an associated thrombosis of the oomplllion vein as the reBUlt of injury at the time of the operation. Henco the gangrene ill generally moist. RQnaud'a Diseaae.-Vaso-motor spasm affeoting the outlying cutaneous vascular regions (hands. foot, nose, ears) is very lommon. In the hands especially every dogree of spasm may be observed. from slight temporary blanohing to spasm so severe and protraoted as to cause aotual gangrene. Transient spasm of the 1Ingers causes them to become suddenly pale or tallOW-like. This condition Is known as • dead lingers,' and is common in women during the reproductive period of life. It Is probably assooiated with the vaso-motor fluctuations peeullar to menstruation. Spasm of the venules of the hands and teet causes them to become cyanotic. This is the condition obtaining in those who Illlffermuehfrom cold hands ando feet. It is nearly as common In mon as in women, and although a purely looal phenQmenon, is popularly supposed to indicate a • feeble ciroulation ' of cardiac origin. The oyanosis results from the sluggish capillary oiroulation consequent on the venular spasm; the sluggish flow allows deoxygenation to proceed beyond the normal. and the capillary blood thus becomes blue. In oourse of tlmo the soft tissues of the affected region thicken. apparently from flbrous overgrowth, lust as happens in the case of the sluggish eapillary oirculation oharaoterizing passive ocngostlon. It is only In minor degrees of this condition that ohilblalns are apt to ooeur. Raynaud's disBase was first described by Raynaud under the name of 'la gangrlme sym6trique des extrimit6s.· It is more common in women than in men, and occurs most frequently between tho ages of eighteen and thirty. Characteristic featuros are its symmetry and periodiolty. In typical oaBBS there are. as described by Raynaud, three stages: (a) Looal synCOpe (pale stage). (b) Looal asphyxia (blue stage). (c) Lo&.l gangrene. (a) Local S1/ROOP6.-In this. the affeeted region (hands. foot, ears, nose, eto.) becomes pale and exsanguine from spasm of the arterioles and venules. (b) Local ABphllxia.-In this, the affected region becomes swollen and blue. The condition may be brought about in two ways, either by arteriolar spasm and secondary vcnous regurgitation into the capillaries, or by spasm of the venules alone. In either oase, the blood stagnates in the capillaries, and conIIIderable efl'usion is apt to ooeur. (EDEMA (DROPSY) 6r (0) L~l Gant/t6M.- Blebs form, and these on bursting expose small superfioial sloughs, seldom extending deeper than the skln. The resulting uloers are slugglsh and slow to heal. The attaok may stop at stage (a) or (b). The attack is probably caused by the aotion ot some vaBO· constrictor toxin, generated either In the aUmentary oanal, uterus, ovaries, or Fallopian tubes, or as the result ot some violous metabolism of the tissues. Frost-Bite.-The first etreot or severe cold Is arterial spalllDt the part becoming bloodless and shrivelled. Should the ex posure oontinue, the result is complete freezing of the part, the tissues being sti1lened and the blood coagulated, BO that some· times portions can be broken 011 like glass. It, however, tho patient be brought into warm surroundings betore this occur!!, the blood may re·enter tho frost· bitten area, and aU the phenomena of infiammatlon then devolQP. Suoh infla.mmatlO11 may either end In resolution or in • moist' gangrene. Gangrene from Erlotism.-Thie is only tound in thoBO countries In whioh rye bread is eaten. It tho arterial spasm induced by the ergot oontinuos tor a long time, the gangrene i. dry; but should it bo succeeded by vaso·dilatation, or the part become septio, the gangrene is moist. (EDEMA (DROPSY). All the tissues are bathed in an alkaline tluid-Iymphwhich is a very dilute kind of blood.plasma (see table) The lymph is conttnually oozing through the thin capillary walls and diffusing itself slowly among the tissues, to w.b.ic.b .it .!Il1J\.lllw t.bto ,r.u.rlro;ul.lllllllltAlll'~.Ilf'nlfuI toO tJW.r vitality; it collects the waste products of metabo~ism, and ultimately flows into the venous system by the thoracic ducts. Though the question is not yet settled, we may pro· visionally assume that the separation of the lymph from the blood is in part Filtration, PliUBi.cal{ Osmosis. Dialysis; in part Yilal { The endothelial cells of tho capillary walls actively secrete the lymph from the plasma; and in part lIfbiticmal{ The tlssue cells suck fluid from 1m the ca.pillaries. AIDS TO PATHOLOGY An undue acoumulation of lymph in any part of the body is known as redema. It may collect either in a body oavity, or between the individual cells of 0. tissue causing it to swell and to beoome puffy. <Edema. of the subcutaneous tissues is known as :maaarca .. of the lateral ventrioles of the brain, as hydro. ~epkalu8 j of the peritoneum, as a8oite8; of the pleura, as ~ydrothorag;; of the pericardium, as hydropericardium; !Iond of the tunica vaginalis, as hydrocele. The degree of oodema is determined by the looseness or denseness of the tissue o.1fected; e.g., the subcutaneous tissues and the lungs are capable of great distension, whereas the solid organs possessing dense capsules, such as the. kidneys and testes, can swell but little. <Edematous fluids a.re much richer in proteins than is norma.llymph (see table). The following table from Halliburton shows the c(lmposltlon 01 dropsical fluids as compared with the normal :fluIds ot tho body: Pa.rta per 1,000. PIufd. Solids. .....__ Blood.~sma •__ Norma l)'lIlJ!h Pleuritic :flUId ___ Ascitio lI.uid Hydrocele fluici" .... -.--.-. ... 97"10 18-66 00'05 89-51 61"15 Wat.et". Proteid&. Salta. 909'90 986-34 968'96 960-49 988-85 82'89 8-55 8'87 8'78 7'55 ------ --28'50 29'78 60'05 6'94 9"26 Tl£oorWl tCJ ea:plai·1/, lEdema.-The whole lymphatics of a. limb may be ligo.tured without producing oodema, the explanation being that the powers of absorption pos· sessed by the capilla.ries is very great. <Edema was origina.lly thought to be due to an abnormally watery condition of the blood, but that this per 8e is no.t a. suffi· cient cause is proved by the fact that the injection of large qua.ntities of sa.lt solution does not produce it. It is highly probable that the essential cause of redema. is some ohange in the capillary wa.ll, so that it becomes abnormally permeable to fluid. This Dlay be due to (EDEMA (DROPSY) deficient oxygenation, as in the prolonged venous engorgement of heart disease; to the irritation of toxins; to impaired nutrition of the wo.lls of the capillaries from the absence of vitamines (which is the likely explano.tion of the' famine dropsies' of India). The chief conditions under which redema occurs are as follows: (a) inflammatory, (b) mechanical, (c) toxic, and (d) neuropathic. (a) Injlammatory.-Here the redema is due to exudation through damaged capilla.ry walls_ (b) Meehanical.-Examples of this are: tight bandages o.pplied to the arm or leg (and thus interfering with the return of blood from the veins, which are more easily compressible ~han the arteries); pressure of tumours on veins (e.g., mediastinal sarcoma on superipr vena cava); thrombosis of a main vein; obstruction to the portal circulo.tion in the liver (cirrhosis. co.ncer) co.using ascites. (c) Paxic.-This cause operates in such diseases as nephritis and beri-beri. It is supposed that the toxin causes some damage to the endothelium of the capillary walls, wltereby their permeability to fluids is increased, certain capillaries, such as those of the face, being more susceptible to this influence than others. Hence the early occurrence of redema. of the face in :J3right's disease (see chapter on Kidneys). The mdemo. of anremia is either toxic or due to impaired nutrition of the capillary wall. The redema of beri-beri is either toxic, or due to the absence of vitamines. (d) Neuropathic.-This is seen in herpes zoster (due to irritation of ganglion on posterior root of spinal nerve). Acute Circumscribed (Edema (Angioneurotic) is characterized by the sudden appearance of transient, sharplydefined, tense and shiny redematous swellings in the eyelids, and of the face, hands, genitals, or other parts. It was first desoribed in 1880 by Quincke, and would a.ppea.r to be due to some form of alimenta.ry toxremio., or a manifestation of anaphylaxis. AIDS TO PATHOLOGY Thrombosis. Thromboai8 (thromboa. a clot) means the coagulation of blood. during life, in any part of the cardio-vascular system-heart, arteries, capillaries, or veins; the resulting clot is called a thromb'U8. The essential primary change in the formation of a thrombus appears to be the aocumulation and fusion into a mass of blood-platelets, and their adhesion to the damaged vascular lining. According to Greenfield, the leuoocytes usually take no active part in thrombus formation. Oa'U8e8.-Changes in the vessel walls; changes in the oomposition of the blood; retardation of the blood-flow. Frequently two or all of these causes co-operate. OOOngea in the Vea8eZ WallB.-Damage to the IlUdothelial lining of the vessel walls is the most important factor here. Atheroma, primary oalcification, varix, phlebitis, eto.. do not cause thrombosis, um888 the endotheZiallining i8 injured or deBtroyed. OOOng88 in the Blood.-These are suoh as oause increaaed coagulability. For example. in lout of every 100 cases of enterio fever, and in lout of every 150 oases of lobar pneumonia, thrombosis of the femoral vein oocurs. This may be in consequence of increased coagulability of the blood, or, on the other hand, it may be the result of lI.amage \0 'lfJl6 en~o'l;'Jlellm. fuimg by 'lfJle 'oac\eiI1lJ. 'wxim. Certain poisons may also operate btl increasi.f&/I eM fibrin/erment--e.g .• toxins. proteosos, snake-venom. OOOng68 in the Blood-FlOtD.-Retardation, or even arrest, of the blood-flow is by itself incompetent to cause thrombosis, for it haa been proved that if a bloodvessel isligatured in two places under strict antiseptic precautions, and oare is taken not to injure the endotheliaJlining, the stagnant blood may remain fluid for weeks or even months together. Nevertheless, it is an important contributory factor in thrombosis. Witness the effect of oompressing or ligaturing the artery supplying an aneurism, and the tendency to thrombosis of the intracranial venous sinuses when the circulation is languid, os in the aged and moribund, and, again, the clotting of blood within the auricular appendices in mitral sten03is. EMBOLISM Thrombosis ocours most frequently in the veins. Venou. thrombosis is fifty times more common in the leg than in the arm. • Septicremia, pyoomia., and other infootive diseases,would appear tG oause thrombosis, in part by increasing the coagulability of the blood, and in part by damaging the endothelial lining of the bloodvessels. Appearance of a Thrombus.-If it forms slowly, it is laminated and of greyish-white colour (=pale thrombus); if it forms quickly, it is non-laminated and red (=red thrombus). Intermediate forms may occur. Post-mortem clots difier from thrombi in being softcJ, never laminated, and non-adherent to the vessel wa.lls. Sequels of Thrombosis: Absorption. Organlzation. Calcifioatlon (phleboliths). Disintegration. causing aseptic emboli. Septlo Infection. This rosults from mloroblc invasion of the thrombus and Its subsequent diSintegration. with the formation of septio emboli. EMBOLISM. Emboli6m significs the lodgment of some solid BUb· stance, or of an air-bubble, in a vessel too small to allow it to pass on. The impacting body is carried into position by the blood-stream. and is ca.lle9 an embolus. Emboli occur in the arteries, as these diminish in size in the direotion of the blood-flow; also in the intrahepatio branches of the portal vein which, within the liver, divides like an artery. They are most frequently observed in the splenic, renal. and cerebral arteries. An embolus of a systemio artery is derived from ijle left heart, or systemio arteries; an embolus of the pulmonary artery is derived from the right heart, or systemio veins. A very small embolus may pass through the pulmonary oapillaries into the general CIrCulation. Varieties. Embolus consisting of a detaohed portion of a thrombus. Embolus oonsisting of a vegetation detaohed from a heal t val ve. 5 66 AIDS TO PATHOLOG"F Embolus from detachment of an atheromatous patch in an artery. Embolus from detachment of a portion of a tumour (e.g., sarcoma). Embolus consisting of masses of vegetable parasites (e.g., Bacillua antkraeia). Embolus consisting of animal parasites (e.g., Fwri« Janguini8 lwmini8). FaJ, EmboZi.~All fractures and vlolont 3ars to bones produce. in all probability. Bome tat-emboli. by far the greater number of which Is IIltcred oft in the lUllgs, but In some ca80ll the emboli may be driven through the 11lllll'sinto the general clrculaUolI, to be held up In some distant organ_ Air embo'i. Eoeaa 0/ EmboliBm.-I1 the collateral circulation is sufficient to compensate for the obstruction, as in the case of the muscles, skin, and bone, secondary thrombosis takes place on each side of the plug, and extends up and down the blocked vessel as far as the nearest branches. Tho clot then organizes, and a small portion of the artery becomes obliterated. but the tissues do not Buffer in nutrition because the collateral vessels carry on the circulation. If a large and important vessel, such as the pulmonary or coronary artery, is blocked, sudden death may result. If the collateral circufation fs Insufficient to compensa.fe for the obstruction, the nutrition of the blocked area suffers, and the degenerated area. of tissue, thus bereft of ita normal supply of blood. is spoken of DB an infarct. INFARCTS. • Eud' or • Terminal' Artery.-By this Is meant an artery whloh, though it hilS capil!aru anastomosis, has no /'rei!. arlerl.aZ araastomoBis with flei(i/Kiourina _Belli. Such arteries exist In the spleen. kldnoys. Intestlnos. brain (base). spinal cord (grey matter). retina, heart (coronary arteries). The peripheral branohes of the pulmonary and superio:r mesenterlo arteries are also to som.e oxtent end-arteries. It should be noted that the hepatlo arteries are not ond-arteries. An end-artery genera.lly supplies a cone-shaped area. of tissue. the base ot the oone being au the surfaoe of the orll"an. INFARCTS An infarct (jarcio, I stufi) may be defined aa 8 mass of tiBBue that has undergone degeneration heeause the endartery which supplies it has been blocked by an embolull (and sometimes by a. thrombus). The aJfeoted area is usually cone-shaped, the baae of the CODe being at the surface of the organ, and the apex at the point of obstruction. An infarct may be red or white. Virchow regarded the latter aa a later stage of the former. Much controversy haa taken place on this still debatable question, whioh after all is of trifling importance except to pedants. Probably the changes which take place in an infarct ao;e somewhat as .follows: At the moment of ooclusion the artery beyond the embolus contracts and drives muoh of the blood out of the infarcted area.. The infarot is now. in a. sense, white. In COlI1'S6 of time the minute collateral ohannels enlarge, and blood in ~uantity enters the area in question, whioh is now • st~ed. Meanwhile the tissues. including the capillaries, having been temporarily deprived of blood, undergo 8. certain amount of diSintegration, and the damaged capillaries thus allow the inflowing blood to extravaaate into the substance of the infarot, whioh acoordingly beoomes red. The entire mass then becomes solid from coagulation of the blood and lymph contained in it. In course of time leuoooytcs absorb the colouring-matter and the infarct becomes white again. It is now dead tiBSUe. Eventually this dead tiBBue is removed and its place taken by fibrous tissue, whioh in time contracts into a small scar. Embolism oj an. e,nrl-artery in the brain (oommonly due to 0. detached portion of a olot formed in the dilated left auricle in connection with mitral stenosis) gives rise to necrosis of the blocked area, followed by , softening' and liquefaction and the formation of a oyst contaihing milky fluid. Infarot of the liver does not occur, because, although the portal vein is like an end-artery as regards its intra· hepatic distribution, and emboli may thus lodge within the liver, these intrahepatio branches connect freely' with the hepatic artery through the medium of the ca.pillaries. Infarct of- the heart is generally caused by tkromb08is in 110 diseased coronary artery. 68 AIDS TO PATHOLOGY Fat Emboli are composed of globules of liquid fat. They are most frequently met with in the arterioles and capillaries of the lungs, generally in connection with injuries of the long bones, especially of those nea.r the epiphyses, the veins in the cancellous tissue of which, being large and patent, allow the liberated marrow cells to enter·the circulation and thereby to reach the lungs. Some of the smaller particles may pass through the lungs and lodge in the brain, heart, or kidneys. Air Emboli may result from wounds about the root of the neok (the' dangerous area '). The blood. pressure in the large veins entering the thorax being negative, air is sucked into the right heart, and the bl'anohes of the pulmonary artery are found full of frothy blood. It is probable that most of the alleged cases of air embolism are the work of glIB-producing bacteria. 'fBE HEALING OF WOUNDS. An Incised Wouna.-:Blood and lymph escape from the severed vessels; in time the bleeding stops on account of thrombosis of the out vessels. This is followed by coagulation, which glues together the opposing surfaces. The' reds' disintegmte, their remains being carried away by phagocytes. The now decolorized elot is replaced by a new tissue, which consists of (a) fibroblasts and (b) newlyformed blood-capillaries. (a) Fibroblam.-These are large fusiform cells, having a single ovoid nucleus. AB they are concerned in tho formation of the future perma.nent tissue, they are sometimes called 'formative cells.' Though probably derived from the. pre-existing connective-tissue cells, by somo authorities their origin is ascribed to the endothelial cells lining the 'lymphatics and bloodvessels. (b) N e:wly-formed Blood-Oapillaries.-Coincident with the appeamnce of the fibroblasts, certain of the endothelial cells of the neighbouring capillaries throw out projeoting buds. These elongate, become hollow, join with other similar buds from a.djacent vessels, and so form loops of new thin-walled capillaries. In this way the original blood-clot is tmnsformed into a richly vascular material known as grtJnulation tiMue, THE HEALING OF WOUNDS 69 which may be aptly termed embryonic repair tissue. Later on the loops of the new capillaries on the opposite sides meet and unite, the fibroblasts enlarge, fibrils develop in their interior, and ultimately fibrous tissue forms. In oourse of time the newly-formed fibrous tissue contracts and obliterates most of its bloodvessels, a fact which explains the dead-white appearance of the ordinary soar. It was once thought that primary union-i.e., direot union of divided fibres and cells-took plaoe. It is now known that, in the higher animals at least, this docs not ocdur. In. all forms of wO'Il/nil-healing the prOC688 i8 Ju1filamentally the 8ame-i.B., by means oj granulation tis8ue. Healing by first intention ocours when the sides of an aseptio wound are brought into apposition and maintained there, and is the method of healing always aimed at by the surgeon in the treatment of wounds. The process is precisely the same as that described above under the heading of ' An Inoised Wound.' The repair of the divided epidermis takes place by a growth from the oells of the rete Malpighii. Healing by second intention occurs when the sides of a wound have not been brought into apposition, or when sepsis has interfered with healing by first intention, or when the pa.rts have been so damaged that suppuration or sloughing has supervened. As in healing by first intention, granulation tissue forms. The new tissue projeots from the base of the wound in the form of a number of small round red points, or granulations, eaoh granulation oonsisting of loops of oapillaries embedded in fibroblasts. The new tissue organizes in its deeper parts, and, pari pa88U with this, fresh granulations form on the raw surface, and in this way the wound heals up from the bottom. Finally, the epithelium grows in from the surrounding margin and covers the cioatrix, and contraotion of the newly-formed fibrous tissue then takes place. Hair and~andB are not regenemted 111.<1 In tke '1ieiiZing 0 fractured bOne the pJ,'Ocess is tne samo as in the healing of soft tissues, with the exoeption that ' 08teoblaBts from the periosteum and endosteum take the place of, and subserve the same function as, the fibroblasts,. a AIDS TO PATHOLOGY the result being the formation of dense osseous tissue instead of dense 6.brou8 tissue. The essential part of the cell is the nucleus, and when a portion of the oo]J-body is severed, the nucleus romaining, it tcndsio regenerate the part lost. When a musole flbre is out aoross, the divided ends oannot directly unite. Such lUlion -as takes place between the ends of a dividod muscle is efreoted by granulation tissue. Tho neurone Is peculiar in regard to its power of repairing injury (soo p. 146). ~a£,. is II mode o/_ f/1'OWtlt. Dot an inflammation. _ f i questIon wli6tnerrnflammation is a necessary part in the process ot repair ot wounds Is one ot historical Interest. Oldtlmo surgeons, notloing that inflllIIllD.ation frequently oocurred during the healing process, camo to regard infiammatlon as a necessary antecedent to repair. 'VIlen, however, with the advent of aSOPSIS' it was found that tho edges ot a healthy wound, if kept closely together, unite without any. ot the olasslcal Bymptons of inftllIIllD.atl0¥i t~o4 ruD~ ~d iffiitt eM heIIHnrnlt wOiiilds 18 sat18fl!!lt,ory n ~e~;!!f!!!:pto~.!! ~rii ibseiit", Qoubt arose as to whether inll8,lllmatlOn li Tn any wo~tio.I to repair. At the present time we may regard it as an acoepted canon that aseptio wounds heeJ without inflammation. Repair, then, is to be regarded as 0. mode of growth, and it Inflammation acoompanies it, it is to bo eonsidered an epiphenomenon resulting from bactorial oontaminatlon. In r Diseases of Scars• .E:rt1(Wlln- lWIt.r.scrJDD,- LlImIU.IIV pam aDd defl.l1'J.lJJtJ$ Keloid growth (= hyperplasia of fibrous tissue). IDoeratlon. Epithelioma. Varieties 01 Fibrosis. Hyperplasia of eonnootive tissue, or ftb1'ON, ooours under tho following oonditions: AS Part of II Reparati1l6 Process.-When·a tissuo has sutTered a solution of oontinulty, an ombryonio connective tissue (=granulation tissue) torms, and this, by developing into soar tissue, ro-establishes the oontinuity. 8econdarily to In/fammation.-Tho fibrosis whieh oecurs In this caso Is not to be regarded as part of the Inflammatory prooess, but as a soquel to, or aooompaniment ot. it. Examl,los: 'l'he generalized fibrosis whlel!. takes place in ohronlo infiamm",tlons (e.g., fibroid phthisis); tho formation of adheSions in pleurisy, pericarditis. and peritonitis; the formation ot a fibrous capsule round a foreign body, a ollronlo absoess, or tuberoular focus. THE GRANULOMATA 86COf1,darUy to Disappearance 0/ the Parenchyma.-Whenever the parenchyma (=epithellal cells, neuroncs, musclc cells) su1fers destruction, llyperpl.a.sla of the connootive tissu!) of the part occurs. Thus, In descending l.a.tcral solerosis in the spinal cord, the IIXOns, or nerve fibres, undergo atrophy, lind the neuroglia takes on lIotlve growth, thus filling up tho SPII008 previously ocoupied by tho axona. Agllin, in tho strugglo for existence whieh alWilYs takcs pilloe among the several elemellts of tho tissuos undor conditions of detective nutrition, the hardy oonneotive tissue displ.a.ys a marked tondonoy to inorellse at the exponse of the more delicate parenohymatous oells. This Is well shown in the progressive fibrosis and oonsequent hardening of the tlssuos which takos pliloe with IIdvllUoing years (=sonile fibrosis), and In tho fibrosis whioh ooours In passive venous con· gestion (= brown induration). It Is often dllHcult to determine how far fibrosis is of this 'socondary kind, and how far it is due to the direct IIction of an irritant. 'rhis difficulty prosents Itself in suoh II malady as granular kidney, for Instanoe. Somo hold thllt ovon in those oaSElS in whioh fibrosis mo.nif08tly ocours scoondarlly to atrophy of the po.renohyma (e.g., In tho symmotrioal spino.! SOleroS08), It is produoed by irrito.tlon---t.e., by tho ehemioal irritation caused by tho disintegrating parenohymo.. THE GRANULOMATA. 'rhe term granuloma is now more or less obsolescent, but is co:g.venient to retain as 0. generic name to embrace the following lesions. which bear 0. broad. genoml histological resemblance to one another: Tuberole. Syphiloma.. Leprosy. Glanders. Actinomycosis. The characteristio lesion in all these diseases is the presence of 0. tissue somewhat similar to granulation tissue, developed round a spot at whiM certain 8pecific organisms MV6 lodged. Tubercle. When fully developed, an individual or 'anatomical • . tubercle consists of(a) The giant· celled or inner zone, composed of one or more large cells, with radiating processes extending out· 72 AIDS TO PATHOLOGY wards between the cells of the next zone. The giant cell contains numerous large nuclei, which are disposed peripherally-often in the form of a crescent. The giant cells are most abundant in slowly-growing tubercles; they are rarely found in rapidly-growing ones. They are not distinctive of tubercle, being also found in ordinary granulation tissue, as well as in syp.!rllomata, in leprosy, in actinomycosis, in glanders, and in certain cases of Hodgkin's disease. (The giant cells of myelomata belong to a differentorder.) (b) The e:ndotltelioid-ceUed or middle zone, composed of several layers of large cells each having a large and distinct nucleus. (.c) The lymphoid-celled or outer zone, composed of. layers of cells identical with lymphocytes. .As regards the bacilli, most of them lie free between the cells, but some are seen lying inside the giant cells" and' in the endothelioid cells also. The anatomioal tuberole thus desOl'ibed is a minute rounded body scarcely visible to the naked eye (a pin's point), semitransparent, and' grey in oolour. By the fusion of several anatomical tubercles small millet-seed bodies are formed, and it is these that constitute the so-called' miliary' tuborcles. By the coalescence of largo numbers of miliary tubercles. a big conglomerate mass may form, such as is sometimes found in the cerebellum of children. Eooluticm oj the Tubsrcle.-This is probably somewhat as follows: The tubercle .bacilli, having gained entrance into the lymph-stream (fJ. p. 74), ultimately form plugs in certain lymph-capillaries. The latter now oonstitute so many incubating chambers, in which the baoilli proceed to multiply. Some of the bacilli die, and in so doing dis,charge their speoific toxin. This toxin, being highly irritant, induces a local tissue reaction, and causes(a) Swelling and proliferation both of the endothelial and connective-tissue cell~. (b) Lymphocytes to be attraoted to the infected area, forming ronnd_it a. belt, which is probably proteotive. By the further 'action of the bacillary toxins, the cells at the oentre undergo hya.line degeneration, lose their distinotness of outline, and fuse into a homogeneous mass, constituting the ' giant oell.' THE GRANULOMATA FIG. T.-DIAGRAM wlcijication may occur. 73. OF AN ANATOll[[OAL TUlIEROLE. Sometimes a tuberoular area. becomes infected with pyogenic organisms. which. by oausing suppuration. leads to the formation of an ab8C688. and thi!:'. if it happens to open on to a. surfa.oe. to an ulcer (skin. bladder. reotum, ileum, larynx). .A tubl!fl'cle MIII!fI' organiz68, for, apart from other con. siderations, no new tissue can organize unless it possesses new blood-capillaries. If the case be a chronio one, a. ca.psule of fibrous tissue forms outside and around the tubercle as the result of a chronio inflammatory proceBB, whioh is distinot from the tubercula.r process proper. This new tissue in course of time oontracts upon the tubercle, which finally COIneS to be represented by a lamina.ted fibrous nodule, in the interior of which a. giant oeIl mayor may not be distinguishable. 74 AIDS TO PATHOLOGY Bites.-Let it be clearly understood that tubercles only form in lymphatics, for the bacilli cannot survive for any time in the blood-stream, and, as before stated, each anatomical tubercle is to be regarded at first as an incubating chamber for living bacilli, and subsequently, if the disease is arrested, as the tomb of dead bacilli. The favourite sites for tubercles are-the tonsils, the lymphatic glands, the lungs, the synovial membrane of joints, the pleural, the peritoneum, the pia mater of the brain, the epididymis, the Fallopian tubes, and the cancellous tissue of bones. An important characteristio of tuberculosis is its tendency to difiusion, either locally, or by tranllferenoe to distant organs. There are two entirely different typos of tuberculosis in the human subject--{a) the human and (b) tho bo1line-the former havIng a predilection for the respiratory organs, and the latter (convoyed by milk) for the cervical and mesenteric glands, the peritoneum, the bones, the loiJl,ts, the skin, and the pla mater of the brain. It is significant that bovine tuberculosis occurs, par ezeeZlence, during the mllk·drinking period of llfe. • They lVould generally find the germs whioh caused consumption in one in every ten samples of milk taken at random' (Prof. Kenwood), Sometimes both types ocour together. PractiDally every man or woman over thirty·five on whom searoirlng post-mortams have been done (no matter what disease caused death) bears evidence of having suffered from tuberculosis. Acute Miliary Tubercu1D:r1S.-A primary deposit of lubcrcle-as, for example, in the bronchial glands, in ~he lung, bones, or epididymis-although it may remain ~ftOIl! .ocalized, yet at any timemali )f the s lit ,c arac the fo . n of thou .th . u II of them, ) ana omica tu lUore or leRs, -olthe same age. The tubercle baoilli in these Jases are probably distributed by the blood-stream (by ~rosion through the walls of Il. branch of the pulmonary vein )r thoracic duct), the bacilli subsequently passing through the thin capillary wa.lIs into the lymph-stream. When this happens, the condition is known as acute miliary tubercUlosia, of which there are two main types: that affecting the lungs. the pia mater of the brain, and the peritoneum and abdominal viscera in combination; and that a.ffecting the pia mater of the brain by itself. The indi- THE GRA.NULOMATA 75 vidual tubercles are of small size, because the progress of the disease is so rapid that there is no time for the fusion of neighbo11ring anatomical tubercles. Lupus. Lupus is ohronic tuberculosis of the skin (outis vera) and muoous membranes. Typical tubercles are presen~, but the baoilli are few and very diffioult to find. Tlie common situation of lupus is about the nose and oheeM, but it may occur in the skin and mucous membrane of almost any part. When .it involves the muoous membranes, it generally does so by extension from the skin. The lupus patch may cicatrize under treatment, or may ulcerate deeply, destroying the skin, mucous membrane, muscle, cartilage, etc., but not bone. The disease rarely begins after the age of puberty, but it may r6IJ'Ur at any age. Syphilis. For a full aocount of the lesions found in syphilis, see p.193. Leprosy. Leprosy is characterized by the formation of granulomata arising in connection with the presence of the Bacillus "leprm. The granuloma is composed principally of endothelioid cells, with oocasional giant cells, and may oocur either in the form of (1) distinct nodules, or (2) as a diffuse infiltration. The tissue tends to degenerate, being either absorbed or leaving a oicatrix. Therei", no ca8eation a8 in tubercle. Sites.-Skin, mucous membranes, nerves, testioles, liver, and spleen. Glanders. Glanders Is a highly oontaglous disease due to the BacUlus maUei, and attaoking primarily horses, mulcs, and asses, but also oommunicable to man from the diseased animal. In the horse two va~eties are recognizod--glandors proper and farcy_ch of whioh may occur in the samo animal ILt the same time. Tho lesion is a ~ra.nuloma. the oells of whioh are almost AIDS 'FO PATHOLOGY I101~~nUOlear leucooytes, bet'l1'c( n which are the specifio oaol ; no ti@e OfilIA Q,tft PmtlQDt" iu course of time necrosis takes place. GIa.nders proper begins (In tho horse) in tho septum nasi and neighbouring parts; the lymphatio glands of the neok and thorax soon become a:freoted, and subsequently the lungs, l1ver, and spleen. In the variety known as faEc)' the infeotlon takes place through the skin, the disease then beginning In the superftclallymphatio vessels 8nd glands. Seoondary nodulel\form In Internal orga.ns, 8S in glanders proper. In man tho diseaso occurs ohi&fly in grooms, knaokors, and those who work amongst horses, Infection taking place through an abrasion of the Skin, or through tho mucous membranes of tho mouth, nOBO, or eyes. The sYmPtoms may be either aouto or ehromo, wh1le, 8S in tuberculosis, a chromo attack may at any time take on the characters at tho acute form and rapidly prove entirely composed of fataL Actinomycosis. Actinomycosis is a disease usually of cattle (oxon), occasion: ally of man, and is due to the growth of tho actinomyces, or raytuDgns. It is probably seldom transmitted directly from ona animal to another. The fungus is common on Buch ceresls as barley, and a man may be inooulated by ohewing the raw grain or by inhaling the tuDgus during threshing, etc. Tho granuloma Is at first oomposed prlnolpally of lymphocytes. olymorphonuclear leuoocytes thon appear. and giant cells are ot infrequent. In the central part are olumps ot the ray·fungus. , Around the granuloma there Is otten considorable fibrous thickening, and thus the condition may be mistaken for a sar.ruuna. In OODrse of time softenilul:. Sllll.uuratioq. .and si.nwl formation occur. The pus Is oharacterlstic; It may be serous or viscid, and in either case contains the golden-yellow oolonies of the parasites. The most usual site In the ox is on tho tongue (and somotlmoS In the 3aws), where It forms large masses which soon break down and suppurate. In mIlD the common sites are tho face, mouth, 3aWlil, and neck. The infection may spread to the mediastinum. The intestines may also be attacked, and from them the disease may spread to the mesenteric glands. peritoneum, and lI"Ver. The lungs may be a primary Beat ot Infection, 118 In threshers. ~ TUMOURS (NEOPLASlIS). A definition should inolude everything pertaining to the thing defined and exolude everything'not pertaining to it. It is not possible. in the present state of our knowledge, to frame a definition of a. tumour which satisfies these TUMOURS (NEOPLAS~S) 77 requirements. It must suffice to say that UumQu.I .9_CID::. s~s1e of a, ,:oncentrated..JIIM!I of Jtew tissue, nOIl,-!nfl.a.Dup-atory in ongrn.. that lives a parasitIc Ure a~ the expense of its host, giving nothing in return for the nourishment it receives, and is outside the control of the nervous system. I There are two chief varieties-the innocent and the malignant-the main distinction between which is that the former va.riety, after a variable period of time, ceases to grow and does not reproduce itself in distant parts; while the latter alwa.ys oontinues to grow during the life of the patient, and does reproduce itself in distant parts. In the following classification it is assumed tha.t the tumours originate in tissues of their own nature. Classification of TomourL lnnocent MyXoma. Fibroma. Papilloma. Glioma. Chondroma. Mesoblastlo Connective-tissue Osteoma. Odontome. Irfowths Myeloma. Neuroma. Myoma.. Angion1&. Lymphangioma. Eplbla.stJo adenoma. HypoWIIIstlolld6llOlllIlI. [Cysts.) (Teratomata.] Sa.rcoma. esoblastl0 { Endothelioma?) Squamous OPithllllomal Epiblastlo Rodnet ulcer { Spheroidal oancer Th Malignant (M Duct ca.noer . e Hypoblastio: Columnar OPithelioma. JoarolDomata. Carclnoma.Saroomatodes i'he Innocent Tumours. An innocent t'l.lll1UYUr is one consisting of a. tiBBue for the ~ost pa.rt normo.! in type, ~b)iDg more or less the ,jwue of the part from whjch it originates, Its growth i8 generally slow; it is usually oircumscribed and encapsuled. AIDS TO PATHOLOGY does not involve the lymphatic glands. nor reproduce itself in distant pa.rts. Docs not recur after removal. A Myxoma is composed of stellate connective-tissue cells which by the union of their processes form a delicate network, within the meshes of which is a clear mucoid material containing a small number of round cells. The tumour thus resembles in structure the tissue which pre· forms all the connective tissues of the fmtus, also the vitreous humour of the eye a.nd the Whartonia.n jelly of the umbilic~l cord. Sites.-The suboutaneous tissues, bladder, rectum, nerves, and spinal cord. A myxoma may also occur in IIoBsociation with ca.rtilaginous tumou~ of the parotid and the testicle, and sometimes in conneotion with sarcomata. (The so·called 'mucous' polypus of the nose is probably a mass of hypertrophied and mdemo.tous muoous memo brane.) A Fibroma is a tumour composed of connective·tissue cells and white fibres arranged in wavy bundles. It is round or lobulated in form. and generally enclosed in 0 distinct capsule. On section, and viewed obliquely, it looks like ' watered silk.' Fibromata may be hard or 80ft, 8(lcording as the elements composing them are loosely or closely packed. Sites.-The hard fibroma is met with on the gums (fibrous epulis); the soft fibroma, in the skin. as a pedun. culated mass (molluscum fibrosum). Other situations are -fascim, tendon sheaths, periosteum, base of skull, nerves, and uterus. Most Bo-oalled neuromata. are in reality fibromata. involving nerve trunks. A Papilloma (sometimes olassed as an epithelial tumourl consists of a ma.in stalk of connective tissue, giving oft primary and sometimes secondary processes, the whole being capped by the normal epithelium of the part. This, however, never invcules tke u1u1e,rlying tissue (thus differing from carcinoma). The connective tissue of papillomata is more cellular than normal oonnective tissue, _being sometimes even myxomatous, and the blood vessels are more dilated. In certain situations-e.g., the bladder-pa.pillomata. arc prone to bleed. TUMOURS (NEOPLASMS) 79 8ites.-The skin (warts), larynx, rectum, bladder. A Glioma is a tumour growing from the delicate connective tissue (neuroglia) of the nervous system. (The true position of the gliomata amongst tumours is uncertain, inasmuch as embryologists have not decided whether the neuroglin.is epiblastic or mesoblastic in origin.) It is soft and translucent, not unlike the grey matter of the brain. and not sharply demarca.ted from the surrounding pa.rts. Structurally it consists of a large number of closely packed stellate cells, with numerous branching process s which interlace to form a network. It is often very vascular, and its vessE'ls, having thin walls, arl" liable to rupture; hence the frequeTICIJ of kmmorrhages within it. It is non-malignant and dangerous only on account of the pressure it ('Ixerts (v. Glio-sarcoma, p. bO). 8ites.-Brain, spinal cord. The so-called glioma of the retina is a tumour 8ui generis, and quite distinct in structure from glioma of the brain. It contains, among other cells, some which resemble epithelium, and for this reason the growth is sometimes classed among the epithelial tumours. It is very malignant, for it is liable to extend along the optic nerve and to recur after removal. It is only found in infants, and is probably always congenital, although it may remain undetected for some years. A Lipoma is composed of ordinary adipose tissue. It is the commonest of all the tumours in man, and may attain to an enormous size (60 pounds). and is most common in adult life. It may be either circumscribed or diffu8e. A CircftmlJC'ribed Lipoma (the usual kind) is a rounded, lobulated tumour of elastic or doughy consistency, contained within a distinct capsule: It is gen6l'll.1ly single, but two, ten, or more, may coexist. 8ites.--The common situation is in the subcutaneous tissues. (shoulders, back, and nates), but it may occur in the subserous tissues (e.g., of peritoneum, pleura), in the subsynovial and submucous tismes, between orin muscles, in tho periosteum, and in the meninges of the brain and spinal cord. A Diffme Lipoma is a diffuse syrnmetrico.l overgrowth of subcutaneous adipose tissue, not encapsuled, generally 80 AIDS TO PATHOLOGY occurring beneath the chin or at the back of the neck. It is said to be most frequently met with in beer-drinkers. A lipoma may oontain other tissues besides fatt.y. Exa.mples of such are myxo-lipoma., fibro-lipoDllL, DJ.9VOlipoma. Xanthoma.-Tbis Is a modified form of lipoma, Its substanoo rosembliJlg embryonio tatty tissue. with an admiXture ot small round oells. It oeOUrli on the eyelids In the fol'Il1 of 1lat elevations oJ: a yellow colour. It may also be tOUJId in diabetes (but rarely on the eyelids or faoo). A Chondroma is a tumour composed roainly of hyaline cartilage, though it may also contain a certain aJD,ount of fibro-cartilage. It Il18.y consist either of a single mass of cartilage, or be composed of lobules bound together by a. vascula.r fibrous tissue. Occa.siona.lly, caloification occurs in patches. Sometimes cavities are found filled with a gelatinous material. Site8.-The most common situation of chondromata. is the interior of the pha.langes of the band, where they are often multiple. forming rounded knobs, which may attain the size of walnuts, or even larger. They are alllO found attached to the extremity of the diaphysis of So long bone in young subjects (lower end of femur. heads of tibia and humeEus). They are only IJlet with in the bones which develop from cartlla.ge, probably originating eitber from misplaced islets of cartilage or from the epiphyseal cartilage. Chondromata. also occur in the parotid gland (where they prol: bly originate from Meckel's cartilage) a.nd in the iesti8; but in these situations tbe tumour is ~nerally associa,ted with an endothelioma, and occasionally 'With myxomatous or sarcomatous elements (or with both). Pure chondroma. of the testis is exceedingly rare. An OsteoDla is a tumour compcsed of bone tissue. There are two chief varieties: (a) Cancellous, or spongy; and (6) compact, or ivory. (a) OIJ/ItCeUO'UB.-TbiS is usually met with as a pedunculated, 'cauliflower' mass of about the size of a walnut, growing near the extremity of along bone. It appears to originate from the epiphyseal cartilage. and consists of II. mass of spongy bone limited by a shell of compact bOIle. During its growth the tumour ia encased TUMOURS (NEOPLASMS) 81 in a thin layer of oontinually growing hyaline O&l'tilage, and it is by the ossifioation of this that it inoreases in size. When the epiphysis beoomes united to the diaphysis, growth oeases and the tumour remains stationary. The affeoted bone, as a rule, loses in length what it gains in , new growth.' 8itea.-Lower end of femur, ungual phalanx of great toe, upper ends of tibia and humerus. Sometimes the tumours are multiple and hereditary.. Multiple Exostoses.-Accordiog to Professor Arthur Keith, these ought to bc removed from the catogory of tumours and placed amongst the disorders of growth. They are probably congenital in origin, but not usually becoming obvious until the child Is of fair size. (b) 1fJory.-This is composed of very dense bony tissue, of the consistence of ivory. It is rounded in form and usually sessile. 8itea.-Although a tumour of this variety may develop in any bone, its most frequent sites are-Frontal sinus, orbit, external auditory canal, anglo of the lower jaw, mastoid proceSB, ilium, and scapula. Odontomes (Tooth 'l'umoars).-· Odontomes are tumours oom· posod of dental UsBUeS in va.rying proportions and dilforent degrees of development, arising from teeth germs or tecth still In the progress of growth ' (Bland-Sutton). Tho two most important are-(a) Epithelial odontom08. (b) Follicular odontom09. (a) EpitluJliaZ Odontomes (Multilocular Oustic Tumours) are oomposed of 0. number of small cysts lined by cubical epithelium, and embedded in o.flbrous stroma. They oontain a viscid ftuld, and appear to originate in branehing columns of opithellal cells derived from the enamel organ, which cells break down in their more central parts. The jaw becomes expanded, but growth is slow. These cysts are non-malignant, showing no tendcncy to dect thc glands or to disseminate. (b) FoIZit:u.Zar Odontomll8 (=' dentigerous cysts ') arc oysts which form in connection with misplaced and non-erupted teeth. The expa.nded dental BOO represents tho cyst wall. The interior contains a viscid fluid and the crown of the non-ol'1lpted tooth. tho fang of which Is uBually ftx.ed to the cyst wall, though sometimes the tooth is loose. With rare exceptions follicular odontomes form only in connection with the permanent teeth, and morc partloularly with the canine of tho upper jaw. The 6 AIDS TO PATHOLOGY tUD10ur ~rows slowly. Owing to expansion of the surrounding bone. • eggshell ora.ckling· may In course of time bo felt on pressure. (These oysts must be distinguished from • dental cysts' which develop tram the tangs of normally erupted teoth.> A Myeloma is a tumour growing from the red marrow of bone and corresponding to it in structure. Characteristic of the growth is the presence of numerous large cellsmlleloP la:leB-the nuclei of which (twelve or more) are arro.nged centrally.or distributed throughout the interior. In appearance the cut surface often suggests a piece of liver, owing to the presence of extravasated blood which has undergone pigmentary changes. Cysts are common. The tumour is often very vascular, and as it enlarges and the surrounding bone becomes expanded, it may pulsate and thus be mistaken for an aneurism. (Myelomata were formerly classed am:mgst the sarcomata, under the head of C myeloid sarcomata,' but, inasmuch as they show no tendency to the formation of secondary deposits. they are , now classed amongst the innocent tumours.) Sitll8.-Upperend of tibia, lower end of femur, upper end of humerus, and the lower jaw. A Neuroma is composed of ne!""e cells, and is extremely rare. Cases have been described as occurring in the skin of children and in the sympathetic ganglia. (A • false' neuroma is a fibroma growing from the sbe&t.b of JI, nerve; JIJl • .a.mput.u.t.ion ' neurODlJl. .is' JDarely a mass of fibrous tissue on the cut end of a nerve.) A Myoma is a tumour composed of muscle tissue. Two varieties occur: the (a) rhabdomyoma, consisti;ng of striated muscle; and the (b) leiomyoma, consisting of non-striated muscle. The Rhabdomyoma is very uncommon and usually congenital. Its usual seat is the kidney, where it probably arises from inclusion of some of the fibres of the lumbar muscles during fretal development. The component elements rarely present the characteristics of normal striated muscle, but consist chiefiyof spindle-shaped cells, together with a large number of embryonio cells and only 0. few striated fibres. The Leiomyoma only develops from pre-existing unstriated muscle fibre, and occurs most commonly as the • uterine fibroid'; but it occasionally occurs in the I I TUMOURS (NEOPLASMS) oosophagus, stomach, intestines, and prostate. IfJ hap also bcen found in connection with the broad ligaments and the ovaries. When occurring in the uterus, this tumour is composed of bundles of spindle·shaped unstriated muscle fibres, which interlace in various direotions. In places the fibres are arranged concentrically, presenting the appearance of tiny balls of cotton. There is generally a fair amount of fibrous tissue present, so that the tumour is often called a fibro.myoma. The Angiomata are tumours composed of dilated bloodvCBBelS. They are of three kiI?-dsSimple nmvus. Cavr.rnous nmvus. Plexiform angioma. A Simple N retIU8 consists of a mass of dilated and t'lrtuous capillaries and venules bound tJgether by a scanty amount of oonnective tissue. It is nearly-always congenital, and usually tends to inorease in size for a few months after birth. A Caverno'lUl NaJlJU8 resembles in structure iihe corpus cavernOBum of the penis, and consists of a series of intercommunicating spaces lined by endothelium, and Qound together by a delicate connective tissue sometimes containing fat. Small arteries open directly into the spaces, and veins carry the blood away. It is generally subcutaneous, but sometimes is seated beneath a mucous membrane. Tlle tumour may be provided with a distinct capsule, or it may merge gradually into the surrounding tissue. It may be congenital, or may develop in later life. Sitea.-Lips, skin of face, scalp, trunk, limbs, and liver. Plexijorm, Angioma.--When a single artery becomes dilated, thinned, elongated and tortuous-resembling a varicose vein-the condition is known as arterial vam. When the same condition affects several neighbouring arteries, it is known as cir80id aneurism. The muscular and elastic elements in the walls of the affected arteries are partially atrophied. H the dilatation involves the capillaries and veins as well, so as to form a pulsating, bluish, spongy tumour (like a bundle of pulsating worms under the skin), the condition is termed plezijorm angioma. AIDS TO PATHOLOGY Sitea.-May be found on any part of the body, the usual seat being the soalp, where it affeots the temporal, posterior aurioular, and oooipital arteries. A Lymphangioma is a tumour oomposed of dilated lymphatios, with hyperplasia of the intervening oonneotive tissue. The dilatation may be so extreme as to oonstitute large oysts. They are mostly oongenital, and form a large proportion of the' oongenital oystio tumours.' Three kinds a.re desoribed-(i.) l{I.rmphatic nal1JU8 (ooourring in the skin and tongue); (ii.) cavemDuslympliangioma (ooourringin the neok as '·oystio hygroma' and 'hydrooele '); (iii.) lymphatic cyst, whioh may ooour anywhere. The Adenomata are tumours oonsisting of normal gland tissue (thus differing from the o8orcinom8ota., which consist of a perverted type of gland tissue) 80rising in oonneotion with, and constructed on the model of, the secreting gland from which they grow, but their duots do not onter those of the gland. and they contribute nothing to its normal funotions. Imitating the structure of the gl80nd from whioh it springs, an adenoma. consists, when growing from a. compound tuliular gland, of aoini and duots, and, when growing from a simple tubul80r gland, of tubules. The aoini 80nd tubules 8oliko are lined by regular epithelium which daea not infiUrate into. bu.t is sharply demarcated from, the 8'U"ounding tis8'Ue. Pure adenomata arc rare. The oonnective-tissue stroma varies in amount; in some cases it is so oonsiderable th80t the growth is oalled 80n adeno-fibroma. In the quioklygrowing forms, myxomatous and sarcomatous elements may be intermingled with the stroma.. Such mixed forms are known 80S my:r:o-adenoma, sarco-adenoma, ete. Further, the tubes and aoini may become distended into oysts, forming a cysto-adenoma, and oooasionally the stroma may projeot into the lumen of the acini. when the growth is known as a papillary adenoma. Adenomata are generally encapsuled and not infrequently multiple. They never reproduoe themselves in distant organs. Sitea.-Ma.mma, parotid, thyroid, ovary, rectum, and prostate. TUMOURS (NEOPLASMS) 85 Cysts. A cyst is a closed sac of abnormal development, the contents of which are fluid or semi-fluid. The different varieties areRetention Oysts constitute the majority of cysts; they are caused by obstruction to the outflow from a gland or cavity. Muoons, sebaoeous, mammu.ry, renal, and pancreatic cysts, and ranula, are examples. They are lined by a layer of epithelium. Oysts formed by the Dilatation of a FCBtaZ Tube which normally is obliteratedt-e.g., parovarian oysts, cysts in connection with the thyrogtoBll&I duct, urachus, Wolffian duct, and l\{iillerian duct. Oysts containing an AnimaZParasite-e.g., hydatid.l Distension 6ysla, resulting from hernial prot;;&iolls of the synovilil membrane of a joint, and hernial protrusions of tendon sheaths (ganglion). Also cysts of the thyroid. NPfUral Oysts. of which meningocele and spina bifida are examples. Oysts r68UZting from Degeneration in the OentraZParl of c4 TumO'lJ,r-e.g., in sarcomata. Oysts forming round Foreign Bodies. Blood Oysts.-These are due either to extravasated I blooa beoomlng.encapsulea. or to luemorraage occurrIng} into any ordinary oysts. Lymphatic Oysta (see Lymphangioma, p. 84). Implantation Oysts are caused by the implantation of tho epidermis. conjunctiva, or other mucous membrane. into the deeper tissues. after such an injury as 0. stab with 0. hatpin. fork. etc. In ~ts new situation the epithelia.l cells proliferate and form a oyst. Teratomata. The term teratomata (teras, a monster) is applied to tumollrs oomposcd of an aRsortmont of many difteront tissuos (eplblastio, mesoblastio. and hypoblastic), mixed in varying proportions. Somo oontaln dermal structuree--e.g., skin. 116ils. hair, and toeth {= dermoid oyst)---and others may oontain musole, cartilago, bone, nerve, visom'a, or, Indeed, any tissue of the body. They appear to result from tbe disPlaoement of a germ ooll within the tissues ot an embryo- 86 A1DS TO PATHOLOGY Dermoid O,sls ooOUl' most commonly in the ovaries, but aI€o" in tho testioles, about the angles of the orbit, oorneal JDal'gin, in tho nock, and elsewhere. The oyst wall is oomposed ot skin, a.nd insidc the Cyst are hair, na.!ls, or teeth, a.nd sebaceous matter. In many oases they se(lJIl to result from inclusion of the epiblast during tho closure of the embryonlo olefts. In the case of the ovary, thoy probably cl~her develop from the Woltrlan body-a.n cpl blastic strueture-i)r result from the a bort3d growth of an ovum. The • mixed' tumour of tho testiole (the so-oolled , fibro·cystlo ') is probably a. teratoma. '!'he Malignant Tumours. The distinguishing charaoteristics of malignant tumoul'll /trd: (r.J) unceasing local growth, and (b) repr.>duction in distant parts of similar tumours which develop from cells detaohed from the mother tumour. There are two chief kinds-the saroomata, which grow from oonnective tisaue; and the carcinom.ata, which grow from epithelium. Sarcomata. .A Sarcoma is a tumour which originates in one or other of the connective tissues (mesoblast), but differs in structure from the parent tissue in that the cells, instead of attaining to adult growth, remain permanently embryonal. Moreover, the cells, like those of all malignant tumoul'll, lJ1JQe~D jJlc.e.saant. .multJpl.iL'.a.tJOOJ,. whic.h LU!Jy c.eases (unless removed) with the death of the host. Furthermore, some of the cells, by becoming loosened from their bed, pass as emboli into the effluent blood-stream, and being arrested in the capillaries of the lungs, form secon· dary tumours there which repeat th!3 characters of the mother-tumour. These, then, are the cardinal facts of a sarcoma: Origin from mesoblast, embryonal nature of the composing cells with unceasing powers of multiplication, reproduotion of the tumour in distant parts. Broadly speaking, the more embryonic the cells, the more malignant is the tumour. Structure.-The varieties of sarcoma represent stages in the ordinary development of oonnective tissue, from the round cell to the spindle cell, but 8topping 8hort offully- formed c01~nective ti8sue. [ntlll'cellular sub8tance-is always present, but though TUMOURS (NEOPLASMS) very evident in some cases, it is difficult to distinguish in others. It may be fluid and homogene011ll, granular or finely fibrillated, and sometimes cartilaginous or osse011ll. Sometimes the stroma seems to consist of little more than thin-walled bloodvessels. Ths bloodv688els, owing to the active growth of the tumour, are usually very numerous, and generally embryo:lic in structure. Often they are mere channels or sp:wes between the cells of the tumour. This explains the frequent occurrence of hmmorrhage into the Bubstance of the growth; also the way in which the tumour cells can be carried into the circulation and deposited in distant organs, there to set up secondary growths. Owing to their rapid growth there is no time for a efinite capsule to form, but in a slowly-growing tumour here may be a condensation of the surrounding tissues, but this is generally infiltrated with the sarcoma, cells. Mode of Spreading.-Sarcomata spread locally by in-filtrating the surrounding tissues. At the growing border of the tumour there is a great excess of small round cells; these advance in all direct.ions, absorbing the normaf tissues (histolysis) in the immediate vicinity. The most common channel of dissemination in distant parts is the blood-8tream: detached groups of the cells pass into the circulation, and are carried by the veins into distant organs (notably the lungs), there reproducing the , structure of the original growth in all its details. They may also spread by the lymphatics; this happens in the case of melanotic sarcoma, sarcomata of lymphglands. tonsil. thyroid. testis. as likewise all quicklygrowing sarcomata. The classification of the sarcomata is based upon the prevailing type of constituent cell: Ordinary Forms. Special Forms. Small round-celled. I.ympho·ssrcoma Large round-celled. Alveolar. Small spindle-celled. Melanotic. Large spindle-celled. Myxo-sarcoma. Chondro·sarcoma. Osteo-sarcoma. Glio-sarcoma. EJldothelial sarcoma. ~ 88 AIDS TO PATHOLOGY Small Round~celled Sarcomata are the commonest form of sarcoma, and, next to the melanotic, the most malignant. They grow rapidly, infiltrating the surrounding tissues, often attain a great size, and disseminate through the bloodvessels. They are encephaloid in appeamnce, being to the naked eye very like the encephaloid carcinoma. Sitea.-They may occur in any organ: in the bones, glands (especially the mamma and testis), muscles, and subcutaneous tissues. Large Round~celled Sarcomata are rarer and less malignant than the last-named variety. l'he cells are large, and have a round and distinct nucleus. • Spindle-celled Sarcomata consist of oat-shaped or fUSi form cells, tapering to a point, which often bifurcates They are arranged in bundles, which take different direo tions, so that in section under the microscope some of them appear rounded, and others spindle-shaped. They are firmer than the round-celled sarcomata, and they may contain an admixture of myxomatous tissue (myxo- Barcoma), cartilage (f1umdo-ilarcoma), and bone (08teo-mrcoma). In slow-growing forms some of the spindles may be converted into fibrous tissue (fibro- .. j sarcoma). Sitea.-Bones, subcutaneous tissues, fasoilB. The L:vmph~Saroomata are com_posed of cells identical with. those of the round-celled sarcomata, and they contain a delicate, fibrillated, intercellular substance. Sitea.-Their common seat is in the bronohial and mediastinal lymphatio glands, but they are also found in thCl mesenteric and other lymphatic glands. The tumours found in chloroma (v. p. 33) are probably lympho-sarcomata. Alveolar Sarcomata, which are very rare, grow from the skin. Their round or oval cells are grouped in alveoli formed by fibrous tissue. Between the cells is a delicate, fibrillated, intercellular substance. Melanotic Sarcomata are usually oomposed of interlacing bundles of large spindlEl. cells oontaining an intracellular brown pigment in the form of highly·refracting amorphous granules (melanin), elaborated by the cells themselv.es, and differing in composition from the ordinary blood-pigments TUMOURS (NEOPLASMS) 89 in containing sulphur, but usually no iron. An ironcontaining pigment may, however, sometimes be found between tbe cells as the result of blood extravasation. They vary in colo.ur from a sooty brown to an intense black. Sometimes the urine contains melanogen. Most of the cells are spindle-shaped, but others are epithelioid, and sometimes the stroma is so distinct as to map the growth into alveoli. When 0. melanotic sarcoma grows from the skin, the alveolar structure with epithelioid cells is the rule, and, according to Unna, this form should be considered as a melanotic carcinoma. Although locally far less malignant than many other kinds of sarcomata, the melanotic sarcomata are the mos~ malignant of all tumours on account of their rapid dissemination. Thus, by the time the primary growth has reached the size of a filbert, secondary growths are generally to be found in the lungs, liver, kidneys, and brain. (The liver may contain hundreds of small tumours scattered throughout its substance.) They di88eminate by the Zympkatica as well as by the bloodvea8elB. They IIore 'Very rare, about one cllose each year being seen at a large London hospital. Bitea.-'l'he primary seats are the tissues which normally contain pigment-i.e., the skin and the uveal tract of the eye (iris and choroid). It is gener&l.ly aocepted that melanotio I!8l'COmata devoloD from cbromatophores, but it is not yet settled whether theso latter are derived from epiblast or b)'I>oblast, but inasmuch as it is unusual for mesoblastio oells to elaborate pigment, tbe InferenOil Is that melanotlo sarcomata belong to tho carcinomata. The Osteo-Sarcomata, as primary growths, are met with almost exclusively in bone. .As a rule, calcification is more common in them than true ossifioation, but spioules of true bone oan genera.lly be deteoted. In these mixed tumours it is most important to examine the growing pa11i at the circumferenoe, because this region always shows the true sarcoma elements. (For Sarcomata of Bone, see p. 205.) The Glio-Sarcomata grow from the neuroglia of the nervous system, a.nd a.re composed of cmbryonio neuroglia. They are a. oommon form of cerebral tumour. go AIDS TO PATHOLOGY Endothelial Sarcomata.-These are probably examples of simple endotheliomata which have undergone malignant transformation. Some parts show the structure of an endothelioma, and other parts that of a sarcoma. Endotheliomata. The Endotheliomata are tumours which appear to grow from the endothelium of serous membranes (pleura, peri. toneum, meninges of brain, synovial membrane of jOints, and tendon-sheaths), lymphatios, bloodvessels, and sometime!\ from the endothelium in the parotid gland, testicle, and .ovary. (Such tumours growing from serous membmm s are sometimes called mesotheliomata, and when growing from the perivasoular lymphatics peritheliomata.) The cells are large, round, and sometimes' epithelioid' in shape, with no intercollular substance, and they are contamed in alveoli formed by fibrous tissue. The structure of the endotheliomata thus resembles that of the oarcinomata. (If tho crolum theory bo correct, tho llnlng colis of tho plouro, peritonoum, etc., aro epltholial, and as In no case has the origin of a tumcur from ondotholium boon pre,·od, many of the reputod cases of cndotholiomata may bo examples of carcinomata.) The endotheliomata, as a rule, develop very slowly; they are only occasionally malignant, seoondary growths and recurrence after removal being rare. W.hen aficcting the dura mater, for example. they do not infiltrate the brain, but push it before them, compressing the nerveelements. Psammomata are endotheliomata which grow from the pia mater of the brain and the choroid plexuses. The cells are arranged in groups lying in a fibrous stroma. E~ch group of cells is composed of concentric layers, in the CI:>Iltre of which is a calcified sand-like particle due to the degeneration of the -most central cells. In the brain a psammoma rarely exceeds the size of a shelled wahiut. Many tumours classed as ondotlloliomata are probably not so, for, as Ribbcrt points out, the continuity of the tumour colIs with endothelium at the margin. is no proof that it springs from the latter. Som_s, for instance, the so-called peritheliomataare probably sarcomata. TUMOURS (NEOPLASMS) 91 The Carcinomata. A carcinoma is 0. malignant tumour growing from and oontaining as its essential elements epithelial cells (epiblastic and hypoblastic), and charaoterized by all the special qualities which pertain to 0. malignant growth-viz., continuous local extension, and reproduction of its own likeness in distant pa.rts. The epithelial cells-which constitute the malignant part proper-manifest extraordinary powers of reproduction and survival. No longer simply covering a surface or maintaining the arrangement of normal glandu. lar tissue, the cells (at one particular place) multiply and send out processes which, breaking their natural bounds (i.e., basement membni.ne), force their way into the surrounding tissues. l'his activity of the epithelial cells is aocompanied by a proliferation of the adjacent connective tissue, whioh is either the result of mere mechanica.lirritation, or Prc;'v0lnd b:iJsomo chomjgai Hub!ltiijlce liberated from the~oJ oe s. The bloodvessels are confined to the stroma-ill'Oonformity with the rule throughout the body generally that no bloodvesselslie between epithelial. cells. There is thus developed 110 tumour the architectural plan of whioh is a connective-tissue framework( =8troma containing irregularly-shaped intercommunicating oham bers (= alveoli) in which lie the essential carcinomatou elements, groups of epithelial cells. If II. thin section b made and gently brushed, or sha.ken in a test-tube hILl filled with water, the cells are removed and thl' stroma remains (v. Fig. 8). In general structure then, 0. carcinoma may be roughly compa.red with a sponge the spaces in the interior of which are filled with grains of sand; then the sponge-fibres would stand for the stroma, the spaces inside the sponge for the alveoli, while the graina of sand would represent the epithelial cells. The alveoli may be plLcked with epithelial oells, as is the case with the epibllLstic carcinomata, or they may be simply lined with epithelial cells, as is the case with the ordinary hypoblastio carcinoJllata. The'n rcommunicatin alveoli aTOm reali dilate ~ t ID.& w 92 AIDS TO PATHOLOGY and are directly continuous with tho neighbouring lymphatic vessels. This explains how it is(a) That the extension of the tumour peripherally takes IPlace along the course of the marginal lymphatics. (6) Tha.t the lymph which flows between the carcinoma cells can carry away some of these cells and lodge them as emboli in the lymphatic glands draining the tumour area, there to set up secondary growths which reproduce the features of the primary growth. From these, secondary growths in detached cells may be carried to other parts, such as the liver and bones, and so cause oancer growths in these places. The looser the cells, the greater will be Y.l!I. .lI•....,.'h'rulW OF f'.ARIllNlUU,. JIllI).\UNG ..u,vs.nr.r (CORNIL ET RANVIER). the tendency for them to be thus carried away; for example, secondary growths occur more n,adily in the case. of the breast and testis than in the case of epithelioma of the skin. Wherever these secondary growths occur, their composing epithelial cells are the genealogica.l descendants of the cells of the parent tumour. The stroma, on the other hand. is always derived from the local connective tissue. The secondary growths, developing as they usually do in situations with a free blood-supply. often attain to a size l!luch larger than the parent tumour. Thus the liver may be the seat of bulky seoondary tumours. while the primary one is comparatively small. The epithelil;\l cells of a carcinoma. within certain limits TUMOURS (NEOPLASMS) 93 tend ttl resemble those of the pa.rt from which they or:gina.te. Thus, a carcinoma of the lip contains squamcus cells; of the intestines, columnar cells. H, however, they are subjected to much pressure from abundant stroma formation, they are liable to deviate from the original type. When the tumour has reached a certain size, degeneration commences in, the central parts, while growth continues at the circumference. The most common is 'fatty' degeneration of the epithelial cells. The degenerated cells shrivel up, or are absorbed, and this often leads to a relative preponderance of the stroma, which, contracting, causes a. dimpling of the surface. When the tumour involves a surface, such degeneration leads to the formation of an ulcer. In this case (and often in cases of a tumour unattended with ulceration) a bacterial infection ta.kes place, leading to toxmmia. Cancerous cachexia (anremia, emaciation, and pigmentation of the skin) results chicfly from this, and partly from long-continued discharge, and pa.rtly also from the appropriation by the tumour of nutriment which should go to nourish the normal tissues. Whether the ma.lignant tumour before it degenerates, or becomes the seat of a bacterial infection, gives off poisons capable of producing cancerous cachexia is doubtful. Oolloid degeneration of the cells is not infrequent, and sometimes the stroma is tho seat of myxomatous changes. The transference of ,cancer from one human being to another has never been satisfactorily observed, neither h!l.9 Ii. tumour from man ever been inoculated successfully into a lower animal. • Primary cancers occurring in mice are similar in oliDical history and mlcroJccploally to those occurring In mell- Bomo of them may be transferred to other mioe by grafting the living tumour cells In suitable positions. Upon grafting from a primary tumour in the first Instance, only a small percentage of the grafts are as 0. rlllo suooessful. This peroentage Increases in subsequent grattlngs, and the tumour is said to become more .. viable," until a stage may be reo.ehed when the usual percentage of successes Is nearly or quite J.OO. The rapid passage of the tumour through successive hosts Inoreases the rapidity of the growth of the tumour. But these things only happen when the same broed of mice Is used. It unrelated breeds are used, tho percentage of successful graftings Is sma1l, If, Indeed, the tumour Is viable at all; though, If any grafts are 94 AIDS TO PATHOLOGY successful, thc same" viability" in thc new brced of mice may bo attained in the same \vay as before. These mouso cancers, no matter how readily they may be tranS]Jlantcd into other 1nice, can never be established in another spccies of animal. Though the cells may live and multiply for a short time in 'the body of another species oJ' animal--e.o.• a rat-they always die 0:6' eventuallY. and can never be established' (C. F.. Walker). The following are the chief forms of carcinomata, a classification based on the type of cell from which they grow and the shape which they tend to maintain: FIG. 9.-SQUAMOUS EPITHELIOMA. SIlO WING CELL· NESTS. A Squamous Epithelioma grows from parts covered by stratified squamous epithelium (skin, mouth, tongue. pharynx, <:esophagus, larynx, vulva, vagina,lower part of cervix uteri, bladder, penis, and anus). They also frequently originate from chronic ulcers, sinuses, and scars (particularly those from. burns). The tumour first appears as a small warty growth or tubercle, ·which soon breaks down in the centre, leaving an ulcer with hard, raised, everted edges and indurated floor (on the penis the tumour may attain a large size before breaking down). The ulcer slowly spreads. destroying all TUMOURS (NEOPLASMS) 95 the ti88ues in its p::l.th. Although differing in certain details, the structure of an cpithelioma i~. in the main, similar to that of cardnoma g~ner,~lly, being composod of a. oonnective-tissuestroma enclosingalveoli which are packed with epithelial cells. A nota.ble feature of epithe!iomah gr.:>wing from cutaneous surfaces (lip. anus, etc.) is the presence of cellnests, which are onion-like masses of ceils Ila.\rjng the following structure: In the centre are flattened, dried-up cells; around these are layers of crescent-shap3d cells. and on the outside columnar-shap3d cells resembling those of the rete Malpighii. (This order represents the tendency of the cells to undergJ their normal epidermic evolution.) In course of time the whole cell-nest becomes a mass of Battened cells arrang.:ld concentrically around the cornified centre. The fibrous stroma. is scanty, riC'h in cells, and often shows leucocyte infiltration. The group of lympha.tic glands draining the area of the growth are infected more rapidly when the primary growth is situated in soft vascular parts (e.g .• tongue) than when occurring in the skin. The affected glands enlarge, and if reaching the surfa.ce become adherent to the skin. which finally gives way, exposing an excavated foul ulcer. Although occasionally found in the viscera, as a rule the secondary growths are confined to the neighbouring lymphatic glands, probably because the intercepted epithelia, being comparatively large, cannot escape beyond the infected glands. When growing from scars, an epithelioma may remain localized for a long time. When preceded by a chronic irritation (e.g., leueoplakia), the growth is usually very malignant. Chorio-Epithelioma.-Thls occurs In the ull!rus after preg. nancy, and whon found is generally associated with hydatiform molo. It originatos from tho cpitllelium of the cllorionio villi, and is composed of similar coils groupod in columns, along with which are solid areas of protoplasm containing many nuclei. There may be abundant secondary growth in the lungs and other organs. Cystic enlargement of tho ovaries ofton accompanies it. A Rodent Ulcer (basal-cell carcinoma) is a species of epithelioma growing from the sebaceous glands. sweat glands. or hair follicles, and generally occurring above AIDS TO PATHOLOGY aline drawn from the angle of the mouth to the lobe of the ear. Common situations a.re the root of the nose and inner canthus of the eye (does not develop at mucocutaneous junctions). The growth begins as a small pimple in the skin, and may remain as such for yea.rs. In process of time this breaks down into an ulcer with a smooth, depressed fioor, and a hard, mised, everted, sharply-cut, sinuous edge. The ulcer extends very slowly, and may go on for many years, but gradually destroying the tissues both superficially and in depth. In this way it may eat its way through bone, and even penetmte the bra.in itself. It is not uncommon for thc ulcer to make abortive attempts at healing. but the scar tissue :which forms BOon breaks down. Structumlly a rodent ulcer resembles an ordinary epithelioma. It differs. however, from it in that thereat are sma r nd rounder, an at the ro h supe cia ra er an • e stroma is a wa.ys i WI sma roun cells. In most ~mens cell. nests are absent, or, when R~;I:t, {ledrn! "'Its mlthgnancy IS purelYoc ,and although it slowly invades and destroys all structures in which it comes into 'contact, it never infects the nei hbourin 1 m hatic nt :l.rts its epl e 801 lands re ce s eing fixed.' Spheroidal-celled Carcinoma only grows in oonnection with glands, and is typically represented in cancer of the breast. A fibrous-tissue stroma (Fig. 8) encloses welldefined intercommunicating alveoli packed with epithelia.l cells, spheroidal or polygonal in shape. according to the pressure of adjacent cells upon each other. In course of time the growth invades the pectoral fascia and skin, eventually ulcemting on the surface. There are two chief varieties (with intermediate forms), depending upon the relative proportions of oellsand stroma. n the stroma is dense and abundant, while the cells are not plentiful, the tumour is hard and is called (a) scirrhu8 ,if the stroma is sparse and the cells are abundant, the tumour is soft. and from its resemblance to brain tissue is termed (b) encephaloid. Although from the clinical signs the growth may TUMOURS (NEOPLASMS) 97 appear localized, yet widely beyond the limits of the actual tumour the tissues are found to be infected with small masses of epithelial cells; in faot, in all cases of carcinoma of the breast, and from an early period, the entire mammary region is to be regarded as sown with the cancer cells. (a) Scirrhus is the commonest form, constituting about 95 per cent. of a.Il oases of carcinoma of the breast. When first coming under notice, it forms an indurated lump with long processes extending in various direotions. As it enlarges, the skin beoomes adherent, then gives way, exposing a foul ulcer. When removed, the cut surface of the tumour has been aptly compared to that of an unripJ pear in tint, and is slightly concave from shrinking of its fibrous elements. The stroma is especially abundant at the central pa.rt, and here the tumour often shows but little else than a dense feltwork of connective tissue, with a few a.trophied cells enclosed in shrunken alveoli. At the oirference, however, the typical carcinomatous structure is evident. ..J.t1'Opkie So€IT1ws.-In. this very ram form. tho stroma. is very abundant and contraots to such an extreme degroe that the breast becomes largely replacod by a puckcrcd. scar·like InBSS. With perhaps a small superficial ulcor in thc position of tho nipplt'. It is very ohronio. tho patient often living many yoars (evon up totwonty). (b) Encephriloiil is the opposite extreme to soirrhuB, for it is much more rapid in its growth, quickly developing into a bulky, soft, and elastic tumour, which soon becomes adherent to the skin. eventually protruding from the surface as 0. bleeding fungating mass (fungu8 luBmatodea of Hey). The out surface resembles brain-substance, and shows here and there dark-coloured blotchos due to blood extravasation. In conformity with its rapid growth, the amount of stroma is small and the colIs numerous; the . stroma, moreover, is less fibrous and more vascular than that of scirrhus. Encephaloid is very much less common than scirrhus as 0. primary growth. being most often met with as 0. secondary growth-e.g., given a primary scirrhus, the secondary growths are encephaloid. In addition to glandular involvement, these secondary growths may occur 7 98 AIDS TO PATHOLOGY in the liver and the interior of bones (more particularly the femur and the lumbar vertebrre). Cancers ot the breast have metastasing spoeds whioh vary with the activity of thc primary growth, encephaloid ot the lactating breast, for example, metastasing very rapidly, aud atrophic scirrhuB very Blowly; 12·5 pcr cont. ot all recorded cases ot cancers of the breast appeared betwoon thc twentieth and thirty· fifth year of life. Duct Cancer (or Villous Cancer) grows from the epithelium of the ducts of the breast (generally not far from the nipple). It is composed of a fibrous stroma enclosing alveoli. The alveoli are lined with (i.e., not, as in scirrhus and encephaloid, entirely filled by) columnar epithelium, and into their interior vascular papillary processcs are seen to project. Owing to the rupture of the bloodvessels in these processes, the alveoli often oonta.in much extra. vasated blood, which may escape by the nipple. Duet cancers are of slow growth; they are not so liable 8S other forms of carcinoma to affect the glands or to recur after removal. Paget's Disea.se 01 the Nipple resembles chronic eczema in its naked-eye Iloppearance, but is· in reality a slowlygrowing carcinoma, commencing around tho orifices of the lactiferous ducts, and gradually spreading along the skin and into the deeper structures. A Columnar-celled Carcinoma is a tumour growing from the positions where normally columnar cells are met with-e.g., the mucous membrane of the stomach, intestines, liver, pancreas, and uterus (body and upper part of the cervix), the cells retaining their morphological resemblance to the epithelium in which their growth bega.n (hence the name). It consists of alveoli lying in a fibrous stroma; but, instead of the alveoli being pa.cked with cells, as in ordinary epiblastic carcinoma, they are, as in ' duct' cancer, lined with columnar epithelium enclosing a central space; a columnar-cellcd carcinoma in this respect resembles an adenoma; hence the old name of adenoid cancer applied to it. (If the growth be rapid the alveoli are Med up with cells.) It differs, however, from an adenoma in that it lacks TUMOURS (NEOPLASMS) 99 definition, is devoid of a capsule, infiltrates the neighbouring tissues, ulcerates early, tends to recur after removal, and gives rise to secondary growths. In the alimentary traot it generally grows as a ring around the canal, constituting the so· called 'ring carci· noma.' Columnar-celled carcinomata show a marked tendency to coUoid degenemtion, especially when occurring in the stomaoh. FIG. lO.--cOLUMNAR-I"1I:LLED CARCINOMA •• Colloid Cancer is simp'y one of the preoeding forms (generally the encephaloid or columnar-celled), the epithelial cells of which have undergone colloid degeneration. This is common in the cancers of the stomach; intestines, and ovary. Carcinoma.-Sarcomatodes.-Thesll aro mixed tumours in which the stroma is saroomatous and the remaining part carcinomatous. They arc extremely raro. I1ertheimer publishod the history of a caSe oocurring in the (Esophagus. Saltykotr demonstrated three cases betore the German Pathological Sooiety at Munich, 1914. The PaJholoOl/ of Malignant .1JiBease.-Pcrilaps tho greatest problem confronting the pathologist is the nature and causation of malignant disease. The one thing t.hat stands out pre'emlnently is tho influence of chronic local irritatirm. As instances: Caroinoma of tho alimentary tract occurs mOJ!t frequontly in those parts whlch are most subjected to irritation -e.g., the lower lip, the tongue, the oosophagus (at its beginning and end, and where it is crossed by the lett bronchus), the pyloric 100 AIDS TO PATHOWGY orifice of the stomaoh, the large intestine, espeoially at thll.:fto:xurell (tho liability inoreasing trom omoum to reotum----i.e., \vlth the increasing hardness, and tendenoy to stagnation, ot the fmoos; wWlo, on the other hand, oaneer ot tho small intestines Is rarely met \vith, the oontents being :ftuld. .Acoording to Bland·Sutton, in ovary 100 eases ot intestinal cancer, 76 occur In the reotum, 23 In the large intestine, and only II In tllC small intestine). Cancer of thG gall-bla.dder Is almcst unknown except in connection with gall-stoncs. Witness, again, the occurrence of chimneysweop's canoer in the sorotum, and tho frequenoy 01 oaneer in tILe cervix uteri. 'Out of 1,876 cases of carcinoma of thc cervix utari investlgatod at the Middlesox Hospital Research Laboratorics, no less than 1,796 had been married. Of thcsc, only 9 per cent. had not borne children. Cilnically, a cllse in an undoubted virgin was a.lmost unknown. Tho roason ot tlLis remarkable relationship between the diseaso and sexual lifo \Vas found by pathology to be due to tILe fact that oVllry caBO of carcinoma of the oervix appeared to bo founded on a elLronio oervicitis' (Bonnoy). Fournier says that ollithelioma of the tongue Is raroly found except In those who havo syphilltlo leuooplakla and who at the sam~ time smoko In excess. Few syphilitics, ho\vover, who do not smoke ever develop lingual canoer, and still fewer cases of this disease ar~ found In smokers wlLo are non"llYPhllltic. Dr. Chalmers, In his paper' On tlLo Inoldence of Canoer in Ceylon,' says that tile Cingaleso women are almost without oancer of tho brca.st, and Ile attributes tho great di:fference between them and European \vomen in tlLis respect to tho proper use of this organ, and the entire disuse of corsets. External canoer most ofton grows from cicatrices, warts and moles-parts specially liable to chronic irritation. Per comra, in tho case of organs protected from chronic irritation, primary malignant growtlils rarc. 'Vltness the caso of the liver. This organ is a hugo mass of about 50 ounces of epithelial cells (an outgrowth of tllo alimentary hypob"last), and yet if wc takc 100 cases of hepatiC carcinomata, only a1.lOut 4, por oent. of tllese aro primary. Again, primary sarcomata of the liver are so rare that but fow authentic oases are on record. PrCQisoly the same argumcnt applios to the sploen, kidneys, ctc. 'l'he irritation, in many cases at loast, would appear to act by inducing a ohronio Intlammatlon, and somo olinicians have spoken of a 'precanoorous inflammatory' phase. It should be observed that the various forms of looollrrltatioll mentionod morely act by preparing tho solI. Once the malignant proccss is startod, It goos on independently of such irritation. Some of the sq.liont facts in the pathology ot malignant dlsea~e will now bo oonsiderod. . (a) The rapid multiplication and survival, at the expellSO of the normal tissues, of tho • malignant' cells (epithelial cells in tho case of the oarcinomata, ombryonic connective-ti881.1e cclls In tho case of tho sarcomata). It is by virtue of this rapid and TUMOURS (NEOPLASMS) IOJ unceasing multiplication, and tho ability of the now-born oells to shift for themselves, that oonstitute the phenomonon of mallgnanoy. (b) The 'looseness' of the malignant cells. The rapidly multiplying malignant cells aro not, liko tho fixed oells of a normal tissue, seourely held In place. On tho eontrary, thoy are more or less loose, and are thus liable to be eonveyed to distant parts. 8'10h loose oells can, in the case of carolnomata, pass straight into the Iymphatlos (whloh are oontlnuous with tho intercellular spaoes throughout the body), or, In the ease of saroomata, they onter tILe blood-stream through tho walls of Imperfeotly·formed bloodvessels. (c) The brooding true of the seoondary growths. These always reproduce, tILe same typo of oell as that belonging to tho parent tumour;' a squamous epithelioma of the tongue produoos a similar growth in the local lymplLatlo glands, whloh normally oontaln no epithelial oells: carcinoma of the reotum, oontalning tho charaoteristio columnar colls of tho part, gives rise to secondary growths displaying tho samo type of ooll, whether thoy form In the lIvor, Insldo the slLatt of a long bone, or else· whero; a melanotio sarooma of tho skin or tho eye reproduCDs itself as a melanotlo sarooma of tho lungs and liver. (d) Tho transferenco of the clLaracteriatlc malignant cells to secondary s(l;es. This is r!lI1dorod posslblo by the loosenoss of the cells. Tha.t the transforonoo ooours Is sho\vn by tho fact that the tumour breeds truo. • (e) The faot tlLat tho transferred malignant coils can survive and multiply in thc secondary slto, giving rlso to a tissuo similar to that of the primary tumour. It is very doubtful It a oell of tho normal tissuo--say tho IIver--oven If it bocame dotached and convoyed to a distant tlssuo, oould Burvive In its new habitat, much less multiply and form new tissue. The ability of maligna.nt cells to multiply In distant tissues is on a par with Its abillty to multiply in the tissues Immediately surrounding a malignant tumour. . (f) Tho multiplication of malignant colIs is associated with a solvont action (histolysis) on tho normal collii of the part. Fat and mnsoIo, eto., disappcar. In tho oaso of the carcinoma, woll·markod hyperplasia of tho Invadod oonnoctivo tissuo occurs. Evidently there arc developed, in connection with thc malignant cells, (a) solvcnt and (b) irritant substances, and it scorns probablc that by tho disturbing action which thoso exert on thc normal colis of thc part tho survival of thc malignant ceUs is sooured; otherwise it is doubtful whcther thoycould snrvivo In thc struggle for exlstenec with the normal cells. (g) The fact that malignant tlssuc Is a morbid tlssuo, nowhore normally mot with In thc body: that of tho sarcomata is a pormanently embryonio form of connectlvc tissuo; that of tho carcinomata a porvorted type of epithelial tissue. (h)'The tendoney tor malignant tissue to degencrate. (i) The tendenoy for malignant tissue to be Invaded by 102 AIDS TO PATHOLOGY bacteria. 'Owing. no doubt. to that defootivo rosistanoo whJoh seems to be a looturo of all neoplastic tissuos, canoor. very oorly In its hJstory.long beforo It has burrowed its way to tho sul."face. booomes the soot of a staphylocoODus infcction_D infection by the so·oallod Microc0CCU8 moformalllJ cf Doyen. And thero is rcason to belicve that muoh of thO pain and swelling and ill' tlammation in connoction with tho tumour. and much. it not all. of tho so-called oaneereus cachexia. is due to this micro· organism' (Sir A. E. Wright). To sum uP. it maybe said that tho malignant cells. at one time orderly members of the ocll community and harmoniously co· operating with tho other tissues of the body for its welfare as a whole, become Bolsheviks. and traitorously turning on that of which they were fonnerly useful parts. cause its ultimate de· structlon. and incidentally they sign tholr own death!warrants thereby. So far as the above statements are concerned. we arc on fairly certain ground coneernlng the pathology of malignant diSOBse. How far do they give us an insight into tho real nature of tho malignant process' ;rt Is obvious that the crux of the problem of malignanoy is how to explain the abundant multiplioatlon and survival of the malignant cells. It is noteworthy that the only fixed cells of the body which nOhllallyarc capable of multi· plying are 'ust the very cells wbich qonstltllte 'malignant· oclls --GJ)ithOlial cells. connective· tissue cells. and endothollal cells. The neuronos and musele flbJ,'Os are inoapable of proliferation. and se malignant growths can nevor originate In them. What wo have to ask Is. how theso cells come to multiply so extrava· gantly as they do in malignant diseaBO. and how they are ablo to survive at the expense ef the normal tissue. Their rapid multiplication can cnly be due to one of two causes: olther (a) to som~ ooll. or a fow cells. spontanoously boooming endowed with unwonted reproduetive activity, and so giving riso to colonIos of malignant cells (we can concolve that a cell. or a limited number of oells. might. under speoiallnflucnces. throw back to somc remote phylogenetic ancestor. and. dissociating themsolves from thc vast cell community of which thcy form part. assume tho rOle of rebols. which would virtually constltutc parasitos); or (b) to the action of some irritant in their interior constantly mshing the malignant cells into Inordinate reproductive activity. The kind of irritation whieh sometimes initiates malignancy \vould not sufficc; \VO should need to postulate a contin'U01I8 irritant acting on each indi11idual cell in tho grO\v:!ng portions of both the prlma.ry and secondary tumours. Corta.in It is that many of the phenomona of mallgn&nt dlsoasc can be explained on tho parasitio theory. Thus: local irritation. by loworlng vitality. diminishes resistance to parasitfoin vasion; the paraSites provide alastinglrrita.nt(probably of a chomiOal nature). Under this continued specifio irritation t.hO malignant colIs undergo a ceaseless multiplication. produolng a degraded typo of tissue. containing loose cells. and dlsplo.ying a liability to degenerate; DIS"EASE:l 0.[< THE VEINS 103 the loose cells are carricd away with the parasites to the secondacysltes, and, being thus subjected to the samo kind ofirrita.tion as in tho primary growth, behavo in the same way; tho chGmical irritation causGd by the ,Parasltos so disturbs tho nutrition of tho normal tissues that tho malignant cells aro able to survivo in tho struggle for oxlstenoe with tho normal colls. The Incidence of Cancer in Relation to Age, Sex, and Situation. On analyzing 6,732 casos of cancer occurring at the Middlosex Hospital bctween tho years 1746 and 1904, Dr. Lazarus-Barlow found that tho mean age of incidenco in malos woos 65·2 years, and In females 49·9 years. In malos 80 por oont. of all cases of cancer oocurred in tho alimentary traot, while IJl females 80 por cent. were found in tho generative organs aud breasts. Cases of cancer of the alimentary tract wore soven timos as froqucnt In males as in females (soo Fourth Report from tho Oancor Research Laboratories, r.nddlosox HospltaI). After tho ago of thirty-fivc, ono In olght fomalos, and aDO in twelve males, die from carcinoma. DISEASES OF THE VEINS. Varix (Varicose Vein). Varix consists of 0. permanent yielding of the venous wall, both laterally and longitudinally, in consequence of which the vcin becomOB dilated and elongated-it may even become as large as the wrist, and three times its normal length. The dilatation is specially marked where the intermuscular veins open into the superficial. In consequence of the elongation the vessel is tortuous. The walls undergo a. compensatory thickening, and when cut crosswise the vessel gapes like 0. divided artery. Occasionally, calcareous plates are met with in the thickened walls. It is probable that the essential cause of va.rix, when it OCCUIS idiopathically, is a defect in the venous muscular coat, which normally, by its tonic contraction, resist8 the di8tending action of the blood-pressure more effectually than any mere passive tissue can. This is, indoed, the essential function of the venous muscular coat, which is thickest where venous blood-pressure is greatest-i.e., the lower limbs (Campbell). Either we must suppose that there is a congenital defect of the musoular ooat in those predisposed to varicosis, or that its muscle fibres remain unduly AIDS TO PATHOLOGY relaxed, and thus fail to brace up the venous walls in normal fashion. The mpst notable change observed in the wall of the varicose vein is the replacement of its normal elements (especially the muscle fibres) by fibrous tissue, which is chiefly located in the middlo coat and to a loss oxtent in the outer. Here and there tho wall is thinned and dilated into pouches, over which the skin may become adherent. The valves undergo cicatrioial con· traction, ultimately shrinking to mere ridges or fibrous cords. In course of time there may be no competent valves between the affected vein and the right heart, and this explains the' impul86' on coughing then to be felt in a varicose vein. ' OomplicaUlms : Pigmentation of overlyiug skin. Thrombosis. Pblebitill. AdhesiOn to skin. Ulceration (varioose ulcer). Perforation. Eezema. <Edema of the ankle. A dilated poueh adherent to the skin (whioh is thinned by pressuro) may give ,val' by ulceration, or evon' by bursting without previous uloeratlon. Dangerous bleeding then onaues, "hiob may prove fatal In a few minutes. This bleeding takes place in a di1l'erent way from ordinary hlllIllorrhago; for, tho dilated vein being rigid Md not collapsing, and the valves being Inoompetent, the blood eomes largely--indeed, ch.ieftU--/rOm the cardiac Biil8 of the perforated vessel: it is a reflux. Occasionally calcareous plates are met with In tho thlekenl',l waJJl of a varicose vein, and In rare cases p'AlebolUks may fo'rm In the Interior. The volns commonly afteoted by varix are the Internal and external saphenous, tho pamplnilorm plexus of the spermatio oord, and the hllllJlrrohoidal veins. Sometimes a varicose vein is not muoh lengthened: e.o., the internal saphenous vein may stand out as a more or less straight dilated tube from the ankle to the groin. In suoh oases we must assume that the lOngitudinal musole flbres are funotlon' atJng normally. Phlebitis is inflammation of the venous wall, and is aJways associated with thrombosis. There are two classical forms of phlebitis-Cal the inJective or suppurative, and, (b) the simple or non· suppurative. DlSEASES OF THE VEINS 105 (a) In In!edi"e Phlebiti8 the venous wall becomes inoculated with pyogenio organisms. and a clot soon forms inside the vessel. The cause ma.y be I\, septio woun4. extension of inflammation from some neighbour. ing septic focus. such as acute infective osteomyelitis. middle·ear disease, or carbuncle-especially when it occurs on the face. The vein wall, the surrounding tissues, and the thrombus inside the vein. arc crowded with scptio micro· organisms. The clot breaks down. and scptic emboli may be dis· charged into the blood-stream, and so lead to pymmia. unless a ligature be placed on the proximal side of the olot. in favourable cases infection of the blood·stream is prevented by the portion of the olot at the proximal end remaining firm instead of disintegrating. (b) Simple Pltlebiti8, like tho infective variety. is always associated with thrombosis. The thrombosis may cause the phlebitis. or the phlebitis may cause the thrombosis, but the two pathological conditions always coexist. The causes are thrombosis (see Thrombosis), injury, extension of surrounding inflammation, and certain blood states-the 'gouty phlebitis' of Paget, for example. Varicose veins, espccially when superficial, are more liable to inflammation than healthy ones. The coats of an inflamed vein are infiltrated with small round cells, the endothelium is swollen and may become detached, and, in the case of superficjal veins. mdema. of the surrounding iissue- is observed. In all inflamed aroas the walls of the small veins are involved in the inflammatory process. Terminations oj Phlebitis : Resolution. Organization of the olot and obliteration of the vessel. 'fnnnelling-i.e.• the axial part of the thrombus is absorbed. and the peripheral part organizes. Embolism. Suppuratlun. The formation of phlebollths. 106 AIDS TO PATHOLOGY DISEASES OF THE ARTERIES. Aoute inflammation of an artery may be the result of trauma, infeotion from septio wounds, or by emboli. Excluding these. the olaBBioal forms of arteritis areAcute endarteritis-Acute aortitis. Arteritis in Inflamed area. Atheroma. or {!!eoondaey calolficatlon. endarteritis Atheromatous absoesll. detormans Atheromatous ulcer. Chronio endarterItis Primary oalolfication. EndartorltlP ( Endarteritis syphlllti08. obliterans. Endarteritis tuberoulosa. Acute Endarteritis.-The best example ot this rare disease Is acute aorlUiII, which Is usually the result at Wootlon tram the aortlo valves in mallgnant 8lLdocardltis. In other oases it results from blood Infection (e.g., enterlo). Ita uBUaI situation is at the beginning ot the aoUa and round the oriBin ot .•tll b~nohes. Tho prooess commences as B small round-oelled Inllltratien of the inner coat, producing sharply-defined. raised. gelatinous patches. eireul",r or ovoid ill outline. and soft and elastlo in oonslst8llce. The infiltrationlUay extend into the middle and outer ooate. in whioh oase the Dew elements may orgBllizeinto fibrous t;ssue. The endothelium, as a rule, remains intact. Tho disease maY lcad to aneurillDl. or pass into ondarterltlB deformans. Arteritis in Inflamed ArelL.- Wh811 an area. of tiBSUe is iII1I.aIDed, the tissues oonstitutlng the walls ot tbo arteries &lid veins within the infiaIDed area share in the iuftamma tory proccss_ Tho tnfio.mmatory ohanges are ovon more marked in the venous walls than in tho arterial. Tho arterial and venous walls. notably the adventitia &lid intima. beoome infiltrated with cells. and in this way the lumen ot the all'eoted vessels beoomes narrowed. and eveD obliterated. thrombosis being thereb, induced. At a later stago the new oell formation may organize into oonneotive tiSaue. causing a PllIDlanent hardening ot the vessels. Atheroma* (Endarteritis Deformans 01 Virchow).~ome authorities designate this disease arteria-8clerosis, but inasmuch as the torm embodies the conception of 0. strengthening instead of a weakening of the vessel-wall, the name arterio-sclerosis is best employed in the sense as described on p. no. Another objection to the term is that, during lifo. the affeoted parts are not hard, but soft, the hardening being a post-mortom process. u8~P1I= 1,l0rrldgo or moaJ. DISEASES OF THE ARTERIES 107., Atheroma is common in men over forty; in fact, it is very rare after middle life to find it absent from the large arteries. The disease has a notable conneotion with high bloodpressure (espeoially in aBBOQiation with granular kidney). Except as a senile change, it is, indeed, rarely lnct with in subjects displaying low blood-pressure. The conneotion between atheroma and high blood-pressure is further shown by the fact that the former is seldom met with in the pulmonary artery, exoept when, from disoase of the Jeft heart and obstructive disease of the lungs, the bloodpressure in that circuit has been chronically augmentede.g., mitral stenosis and emphysema. (According to the French teaching, the most likely cause is sonle poisonous agent acting on the intima.) The- disease occurs in those arteries which are exposed to the greatest strain, as in the aroh of the aorta, and it shows a special predilection for the points at which largo branches are given off, or where a trunk bifurcates. the most frequent sites beingThe aortic arch. Round the orifice ot Its largo branches. Tho oorono.ry arteries. Round the orifice ot tho omlJao axis. At tho bifuroatlon Into the lIlaos. The eerebral arteries. The ronal arteries and tholr branohes. As u affecta tlle Aorta and Large V888el8.-Bmall round coIls and branched coIls containing fat infiltrate the intima in tho form of scattered foci, replacing the normal clements of the part. In course of time these foci coalesce. At this stage, when we examine the interior of the vessel, wo see it studded with hard, yellowish, circumscribed patches, slightly elevated, which range in size from mcre pin-points to plaques as large as a shilling, with more or Icss abrupt edges. (In the arch of the aorta the appearance sometimes suggcsts a crocodile-skin.) On careful inspection the endothelium is generally found to be intact, however advanced the process. The further progress may bo in one of two direotions: the patches may (a) calcify, or they may (b) soften and break down. (a) In the former co.sc fatty degeneration of the cells 108 AIDS. TO PATHOLOGY takes place; the contents afterwards dry up, and limesalts and oholeBterin are deposited in the shrivelled mass, which is thus ultimately converted into a hard, calcareous plate. (During life the material is of soft, putty-like consistency.) This is !mown 0.9 8econdary or laminar calcification (so called to distinguish it from the primary calcifioation found in the middle ooat of suoh arteries 3S the radials and tibials). (6) On the other hand, the contents of the patches, instead of drying up, may liquefy and form an atheromatoUB ab8eeBB, which, upon the endothclium giving way, may become converted into an atheromato'U8 ulGer. In the lattercaso, a small coagulum forms over the roughened part. Later on, cellular infiltration into the middle coat takes place. similar in character to that which started in the intima, resulting in the slow destruction of its muscular fibres. (Some conaider this to be the primary change in atheroma.) The outer coat usually shows 110 varying amount of compensatory fibroid thickening. The middle coat is the Btrong coat of an artery, for it is by the active contraction of its muscular fibres that the vessel is prevented from expanding to the blood-pressure. Once it is seriously damaged, the vessel-wall yields slowly to the blood-pressure, the artery becomes dilated, elongated, tortuous, and a fUBifarm aneurism is liable, to develop. AB it aflectB the Smaller Jl1J88el8 (Oorona1'1J, Oerebral, Renal, etc.).-The process here is essentially the sapIo as in the case of the huge vessels. The patches. however, are often in the form of nodes, sometimes suggesting' in appearance a' signet-ring,' whioh may projeot so far into the lumen as partially to occlude it. It is specially to be noted that in atheroma there is no formation of new bioodvIJ88els in the patches; this explains why the new tissuo degenerates and does not organize. in this respeot being in marked oontrast to syphilitio endarteritis, where the opposite is the case. Effects 01 .A.theroma on the Ciroulation.-Tho diseaso causes (a) rigidity of tho vessal walls, o.nd (b) narrowing of the lumen. Rigidity of the aorta causes hypertrophy of tho left ventricle. Narrowing of tho lumen has a spoeial significance with respect to suoh arteries 88 the ooronary and cerebral on acoount of tho Interforonce with the oirculation which it entails. DISEASES OF THE ARTERIES 109 Primary Calcification affects the medium-sized arteries --e.g., those distributed below the elbow and knee, and the circle of Willis. The process begins in the middle coat, tlie muscle fibres of which beeome infiltrated with limesalts, and, as these fibres run circularly round the vessel, the deposit takes the form of a suocession of rings, causing the artery to assume the appearanoe of ipecacuanha. lTItimo.tely the artery may be converted into a rigid tube. In the oase of the tibial arteries, the intima may aotually beoome detaohed, and as a result of this, thrombosis and gangrene may ooour (see Senile Gangrene). Symmetry is a markeiJ Jeature oj the di8eaae. Endarteritis Sypbilitica.-Disease of arteries is the most important manifestation of syphilis. The usual pathologica.l change is identical, in prinoiple, with the syphilitio affeotions of other mesoblastic structures (v. p. 196). There may be either (a) a diffuse gummatous inmtration of the intima extending both around the veseel and along its course for some distance, which in process of time develops into ooncentric l~inm of fibrous tissue; or (b) small greyish-yellow patches may develop on the intima; these are tiny gummo.ta. In both instances the intima. becomes greatly thickened, and the lumen oorrespondingly narrowed. Owing to the development of capillaries in the new tissue, fatty or calcareous degenemtion does not occur. The disease is most oommon in the arteries at tke base oj the brain and in the arteries oj gummata (see Gummata). In consequence of the narrowing of their channels. thrombotic occlusion is liable to occur; this is the most frequent cause of hemiplegia (especially in men) under forty years of age, and also explains the tcndenoy of ordinary gummata to slough, by deprivation of their blood-supply. In another class of case the disease begins in the tunica media, setting up a -mesarteritis which, by destroying the muscular fibres (the chief source of the strength of the middle coat), leads to the formation of 110 'sacculated' aneurism, the common site of which is the arch of the aorta. and the big vessels which arise from it. So there are three ways in whioh syphilis may affect arteries, viz.: (1) diffuso gummatous, infiltration of the intima; (2) gummata of tho intima; and (3) mesarteritis. IIo AIDS TO PATHOLOGY Endarteritis Obliterans is probably aD advanced stage of endarteritis syphilitica. There is great subendothelial proliferation, the change involving also the middle and external coats. New capillaries are formed, and the final result is the formation of fibrous tissue, which narrows the lumen and may ultimately occlude it. In some cases occlusion is brought about by thrombosis. Endarteritis Tuberculosa generally involves the peri. vallCular lymphatic sheaths, but tubercles may also develop in the arterial walls themselves. Under these circumstances the intima becomes greatly thickened, and the lUDlen reduced in size, and even obliterated. Arterio-Sclerosis. Apart from the disea~os just doeJt With, there is a condition of tho arteries as~ooillted with adV61lcing years which i~ commonly known as arterlo·8CIef"oriB. Old age Is a relative term, and, mel\1oally considered, Is to a large extent detormlned by the condition 01 the arterl~e., wllethor thoy are soft a.nd elastlo, or hard and rigid. After a oertaln period ot lite the arteries, In common with tho other tissues, tend to barden. This results trom 0. general fibrosis, whioh impairs the nOl"IIla.l elastiCity of tho vcssel walls and makes them rigid. This inorease in the fibrous (J]ements of tho vessel wall is espeoially obscr"ed In the intima, the thick· noss 01 which tends to increase from about the ago of thirty until tho end of life. The test of 0. healthy artery is that, If suoh 110 vcssel as the radial or temporal be pressed by the fIn~'(lr,itmelts away into, o.nd oan be scarcely differentiated from. the surround· ing tissues. whereas a thiekened vessel can be distinctly felt under the examining finger. Sometimes the arterio·fibrosis sets in early. (It may bo peculiar to certain families.) A maJi of thirty. for iJistanee. may have arterios as rigid as those whieb are natural to I) man at Sixty, and tJice _ . lIonce tho aphorism • • A man is as old as his arterie~.' Thomas Parr is said to have had artories wluch at tho time ot death showed nothing abnormal. Premature arterio·sclerosis is due to some abnormal bloodstates. either a detect as rega.r(ls the hormonlc content (It is known. e.o.• that athoroma can be artifioially induced by tho inJeotion of adrenaJin). or an actual toxremia--sueh as may result. 6.0•• from defective Intestinal digestion. tho toxins in this case boing duo to the abnormal transformation ot food (Indol, scatol. phenol)-or to bacterial agency. Tho morbid blood·state. what· evor bo its nature. may act upon tho vessels in one of two ways: (a) It may oause fibrosis by Its direct action on the arterisJ tUllics; or (b) It may. like adronalin. cause vaso-oonstrletloD. which. it long continued, would cause hypertrophy of the mus- DISEASES OF THE ARTERIES III culal' IDIdla, and in proeess of timo the hypertrophicd mnscle fibres would be replaced by fibrous tissue. in accordanco with tho law that. wilen muscular h)'llcrtrophy rcaches a oortahl timlt. the musolo fibros atrophy and are rcplaood by fibrous Issuo. Probably both theso mechanisms arc operative. In connection with thls subjoot of artcrio-sclel'osis. the student Is referred to pp. 160. 161. dealing with the arterial ehanges observed in granular kidney. ANEURISM. An aneurism (aneurisma. a dilatation) is 0. cavity com· munioating with an artery and containing blood, either fluid or coagulated. The walls of the cavity are formed either of the expanded portion of the vessel wa)l, or of the tissue around. It is during the middle period of lifo, between tho ages of thirty and fifty. tho.t non· traumatic aneurism is most frequently met with. Thore are but few cases recorded in medical literature as oecurring before the age of twenty and most of theso are probably due to embolism, which sets up arteritis. , Dissecting' aneurism is more common in women than in men; aneurism of the carotid is equally common in the two sexes; otherwise aneurism is thirteen times more common in men than in women. OlasaitioatioD. fusiform. Spontaneous Traumatlo S~ceulatod. Dissecting. { Miliary. {Ci.rCUmBCrlbed. Dilruso. Artorio.venous {An~riBmal va~IX. Varloose aneurIsm. A Spontaneous Aneurism is one that develops in con· sequence of pre·existing disease of an artery. A Fusiform Arteuriam is a dilatation involving the entire circumference of the artery. the result of.exte7l8ive atheromat0'U8 di8ea8e of its walls. The usual seat is the arch of the aorta. As a rule. the vessel is involved for a considerable portion of its length. In addition to the dilatation there is elongation. whieh may be considerable lIZ AIDS TO PATHULOGY Thus, the arch of the aorta may be increased in length by some inches. From the main dilatation small • saccular' aneurisms may spring. On examining the strueture of a fusiform aneurism, it will be found that the iuternal eoat shows widespread atheromatous changes; it is stiff and rough, calcareous plates are frequently scattered over the internal surface, and in places where the endotheliwn is injured shreds of fibrin are adherent. The middle coat is atrophied in proportion to the dEgree of dilatation. The outer coat is compensatorily thickened and strengthened by the _formation of new fibrous tissuc. It is owing to thh. thickening that the course of an uncomplicated fusiform aneurism is usually chronic-either remaining stationary or increasing very slowly, and thus oontinuing for many years without causing death. A Sacculated. Aneuri8m is one in which the dilatation involves only a part of the circumference of the artery. the result of a localized. disease of its middle coat, which is degenerated. The arterial wall now having lost its support, yields at this spot, and a bulge forms which tends to get larger and larger (viele Mosllrteritis). When the aneurism is of very small size, the three arterial coats are spread out over it; when larger, the internal and middle coats are wanting, Ilnd as it increases in size the sac comes to consist almost cntirely of the thickened and condensed surrounding connective tissues (the aneurism acting as a foreign bedy). Usually the interior of a saccubted aneurism contains fibrin arranged in concentric, overlapping layers, no single layer reaching over the whole sao. l'he older layers on the outside are of a pale buff colour; those towards the interior are darker. Organization of the clot is rare, because of the forcible stream of blood through the aneurismal sac. No organization can take place in the aneurism unless the artery from whick it springs is occluded.. Occlusion may occur either by extension of the clot from the sac into the artery, by 0. detached. piece of clot plugging the artery, or as the result of surgical compression or ligature. Complete arrest of the circulation leads to the formation of an ordinary soft blood-clot (clot en ma88e); this is very .rare, however, and is only possible when the mouth of the DISEA5ES OF THE ARTERIES 1I3 aneurism, or the main trunk of the artery immediately beyond it, becomes plugged by a detached piece of clot. 00,11.868 oj Death from Aneuri8m.-Tho tendency of aneurisms is to rupture, either into the perica.rdium, plema, tmchea, msophagus, peritoneum, or externally (vers rarely). Aneurism of the intrapericardial portion of the aortic arch (a favourite site) may be so small as to elude the most careful examination, and may causa unexpected death by rupture into the pericardium. EmbOlism (e.g., of the cerebral arteries) may occur in consequence of the detachment of a portion of the olot into the blood·stream. Death may also result from p7"68sur6 on vital parts. lEtiolotm 0/ Spontaneous Aneurism.-It can bo dc1lnitely stated that the essential cause ot lVIIi/arm aneurism Is a preoedlng wldespread athercmatous change in the artery (especially such as destroys the middle coat), for evidence of this is always present in the walls of the dilated portion. Syphilis appears to be tho ossential cause of sacculated aneurism, alcohOl and physicsl strain sometimes acting as coefficients. The trepo· nemes probably settle in the tunica media (the vasa vasorum roaching thus far), a.nd thoro set up a. 81/P"ilitic mesarterUia. Tho tunioa. media being the main support of the artery, and this being locally destroyed, it can readily be understood how the vessel yields to the Intravascular pressure at thet partieular spot. In tho grcat majority of cases of spontaneous aneurisms of the smaller o.rteries. such as the radial, ulnar, and tibials, as well as aneurisms under the age of twenty, ombolism (by settlug up a local softening of the arterial wall) is the cause. Suoh Is especially likely to be the esse If the embolus be septio, as in mal.lgn&nt endooarditls. A Dis8ecting Aneurism is one in which there is a.longitudinal rupture of the internal coat, the blood being forced between the layers of t_he middle coat. It is generally the result of the bursting of an atheromatous abscess. The blood may escape by an aperture in the outer coat and become diffused externally, or it may open again into the lumen of the artery through another atheromatous spot. It is most common in the arch and thoracic portion of the aorta, and occurs more frequently in women than in men. Miliary .A.neurismB are about the size of a &maJI pin's head, and arc met wlth In the cerebral artorlos, more especially those coming oft trom the olrclo of Willis-i.e.• t·he central as disS I I.. AIDS TO PATHOLOGY tingutBhed trom the cortU:al arteries. It is trom rupture ot sueh miliary o.neurism toot ' spontllolloous ' corobrol hmmorrhage is practioe.lly always duo. (When this oocurs In a child. howover. it is generally from an lIoIlourism which has developod socondarily to a septie embeJism.) The pathology ot miliary anourisms is still somewhat doubtful. Charcot taught that they do not occur secondarily to o.thoroma; that. whereas this condition sto.rts in the intimo. and spreads outwards, the artorial chango which leads up to miliary aneurism begins in the external eoat ot the artery and spreads inwo.rds. Certain it is that athoroma of·the corebral vessels may be extensive o.nd mllio.ry aneurisms conspicuous by their o.bsence trom them. and tJice 11erBa. One clinloal fact stands out prominently in connootion with miliary lIoIleurisms: they never occur in o.ssoclatlon with low blood-pressuro. Hence the low bloodpressure individual does not die from "orebral hromorrhage. MIliary lIoIleurisms. if they do not rupture. tend In course ot time to become occluded. trom thrombosis ot their contained blood and subsoquent shrinkage. 0. A Traumatio Aneurism is a cavity oontaining blood, either :O.uid or coagulated, oommunicating with an artery. and produced by an injury dividing all the coats of the vessel. If the blood escapes slowly, compression of the tissues around leads to the formation of an adventitious 110.0-, and the result is a circumscribed traumatic aneurism. On the other hand, if the blood escapes quickly and in o.bundance, it finds its way along the oonneotive tissue planes, travelling in the direction of leastresista.nce, and, the distending force being too great to allow of the formation of a sao, a diffu8e traumatic aneuri8m results. An Arteria-Venous Aneurism is the result of a oommunication between an artery and a vein lying in juxtaposition. It is generally of traumo.tic origin-e.g.• when the braohial artery and the medio.n-basilic vein at the bend of the elbow are wounded simulto.neously. H the two vessels are in close contact and become adherent, the blood passes directly from the high bloodpressure artery into the low blood-pressure vein, and the latter becomes dilated into a pulsating. fusiform, or globular pouch, with thickened walls, the dilatation extending also into the venous tributaries, which become varicose and tortuous. This is known as aneurismaZ varix. Instead of the blood passing directly from the artery into the vein, it may well out between the two tubes, o.nd WOUND-SHOCK XIS become enclosed in a.n adventitious so.o communicating with both. This condition is known as variC086 aneurism. (For Oirsoid Aneurism, ete., t.. p. 83.) W01JN])-SBOCK (TRAUMATIC TOX.2EMIA). Shock is characterized by a. lowering of the a.rterial blood·tension, thready and quickened pulse (sometimes intermittcnt and irregular). pallor, cold and olammyskin, with rapid and shallow breathing. There is usually, in addition, a general state of museular limpness, and the sphincters may relax. It may be either (a) Primary, or (b) Secondary, (a) Primary.-This immediately follows the in1liction of the wound, and is allied to 'fainting.' It is probably due to a reflex inhibition of the vaso-motor centres govern: ing the splanchnic area, which allows more blood than usual to determine to the portal system of veins (' bleeding into one's own veins '). The accumulation 'of a large quantity of blood in the abdominal veins reduces, pro tanto, the amount of blood in the arterial tree. This involves both a decreased output from the left heart, and Ilo decreased flow through the coronary arteries. The arteries are therefore underfilled and the hearl's action weakened. (b) Secondary.-This may follow the primary shock, or occur independently. In either case it is of slow development, and only appears some two or three hours after the infliction of the wound. but too quickly to be due to bacterial infection. According to recent investigations, secondary shock is the result of the absorption from the wound area of an injury toxin, histamine. formed from one of the amidoacids, histidine. present in nearly all proteins. (H Justamine be given in minute doses it produces a condition practically identical with shook.) The first effeet of the diffusion of the histamine throughout the body is to cause a universal dilatation of the ca.pillaries, with partial stagnation of the blood in thom (but no dilatation of the arterioles). In consequenoe of this the heart is relatively empty and less blood flows through the lungs, and BUb-oxygenation 0/ tM ti8BUe8 is n6 AIDS TO PATHOLOGY tke result. The second effect of the histamine is to make the capillary walls more permeable, thus allowing muoh of the fluids of the plasma to escape by filtration into the surrounding lymph-spaces, the patient, in a sense, bleeding into his own lymphatios. (Dale and Laidlow have shown that by the action of histamine there may be in this way a loss of as much 0.8 half the volume of plasma in five minutes.) In consequence of the great loss of plasma-fluid there is a redaction of the volume of blood in effective circulation-hence the low arterial tension and the other phenomena. In all cases of shook thore is great sensltivenoss to ethor and ohloroform anmsthesla, the administration of whioh would ca~ a further tall In an already low blood-preasure. Per ormlira, there is a tolerance of nitrous oxide and oxygon 'anmsthesia, without a furthor tall of blood -pressure. N.B.-Shook is not to be mistaken for the symptoms of latombolism, whioh Is so particularly oommon after jars to bones Ilnd fraotures. (BUrger, in 100 oonsecutive oases of death from accidonts associated with fractur~s, found tat-embolism In the lungs in all of them except one.) COLLAPSE. The pathology of collapse, which is much the same as that of shock, consists essentially in the 1088 of fluid from the blood. In the one case the fluid passes into the ~jssues; in the other, out of the body. Collapse accompanies such diseases as are attended by constant vomiting or diarrhma, examples bcing the diarrhma of young ohildren, Asiatio cholem, and the profuse and prolonged vomiting of stmngulated hernia and acute peritonitis. It may also result from severe hremorrhage. Owing to the abstmotion of such largo quantities of fluid, the blood becomes inspiBSated and resembles tar, and the muscles, liver, spleen. and kidneys, become tough and leathery. DISEASES OF THE PERICARDIUM. Tho pericardium oonslsts of two parts: (a) A fibrous part, analogous to the capsule of a joint; and (b) a serous part, 0.11610goUB to tho synovial membrano. DISEASES OF THE PERICARDIUM II7 By AcutePericarditi&is meant an inflammation beginning in the aeroU8 pericardium, spreading to the fibrous pericaJidium, and often to the surface of the heart. It occurs in about 20 per eent. of oases of rheumatio fever (beginning about five to seven days from the onset of tho attack). About 70 per cent. of cases of perioarditis are duo to this oause, about 50 per cent. of the cases occurring before the age of twenty-one. (Endooarditis is about three times more common than pericarditis in rheumatic fever.) Other causes anr-septieromia, pymmia, the speeifio fevers (notably scarlatina), pneumonia, tubercle. It also occurs in Bright's diseaSe (when it is very fatal), and as the result of extension of inflammation from surrounding parts, as from burns on the thorax, a. mammary cancer that has ulcerated, fractured rib. In the following description the pericarditis of rhcumatio fever is taken as the type: The inflammation starts at the base of the heart, travels downwards, and involves, more or less, the entire pericardial sao. Tho smooth, glistening serous surface becomes dull and sticky from swelling of the lining endothelium (many of the cells of which are shed) and the exudation of inflammatory lymph. Coagulation of the lymph now takes place, fibrin is deposited, and by the rubbing together of the opposed surfaces, the interior of the pericardium. comes to present & 'shaggy' appearance-not unlike tripe. 'rhe fibrin is usually thickest over the heart surface. It is whitish in appearance and of soft, gelatinous consistence. The pericarditis may be 'dry,' or fluid may collect in the pericardial sao. The effusion rarely exceeds 2 to 3 ounces in quantity. (The increased area of cardiac dulness found in rheumatic fever is mainly due to cardiac dilatation, and not to pericardial effusion.) Although the fibrin may become absorbed, yet in the great majority of cases after a timc new bloodvcssels penetrate it, and connective tissue forms, so uniting the visceral and parietal layers of the pericardium. The adhesions thus formed may be of mere spidcr'a-wob consistency, or so extensive as to obliterate the entire pericardiac sac (about 17 per cent. of the cases). These adhesions are most ma.rked at the base, lea.st at the a.pex. 118 A.iDS TO PA.THOLOGY They are specially liable to form when the patient is allowed to get up too soon. From repeated attaoks, the perioardium may beoome greatly thiokened-even to the extent of 1 inch. The preBBure of the fibrous tissue on the ooronary arteries, by impeding the circulation may give rise to fatty degenera. tion of the myooardium. In rare oases the pericardium becomes calcified. Sometimes there is an 3BBociated mediastinitis, and when this happens the pericardium may beoome matted to the lungs, diaphragm, sternum, and ribs, and the phrenic nerves may lie embedded in the newly.formed tissue. The adhesions in such cases may so hamper the movements of the lungs lJ.)ld diaphragm that cyanosis, dyspnma, enlargement of th~ liver, ascites, and even general mdema, may result. The heart, Il8peciaZly the left ventricle, is alway8 dilated in rheumatic pericarditis, and thi8 constitutll8 its main danger. This has been asoribed to direct extension of the inflammation to the myooardium; others with more probability, attribute it to the paralyzing action of the rheumatic toxin on the cardiac muscle, for dilatation is absent in other forms of pericarditis (e.g., tubercular, suppurative), while it is always present in rheumatic fever, even when there is no periea.rdi tis. Should the patient be allowed to get up too soon, there is great risk of the dilatation becoming permanent. (It cannot be too much emphasized that tho heart has least, work to do whcn a person is lying down.) Such dilatation of necessity leads to hypertrophy, as, the oubic capacity of the ventriole being increased, more work is required of it. TIllS dilatation with secondary hypertrophy mainly accounts for the enormous hearts sometimes found ill adherent pericardium, the adherent perioardium, per 8e, playiItg but a subordinate part. If, on the other hand, . the patient has been allowed adequate rest in bed, so that tho dilatation and the hypertrophy which it entails have had time to subside, and if the perioardium is not greatly thiokened, there may be no permanent cardiac enlargement. To Bum up, then, the cardiac enlargement some· DISEASES OF THE PERICARDIUM 1I9 times found after an attaok of rheumatio fever may be due to-(a) A dilatation remaining permanent. (6) A muoh thiokened pericardium. (c) A oombination of both. It is to be remembered that endocarditis and myocarditis often ooexist with pericarditis. PuruI8IIt pericarditis is raro. It oooasionally OOOUl'll in oonnootlon with empyemo., septlolllmio., pyremia, pneumonia, oud scarlatina, or It may rosult from extension of malignant growths. It Is extremely rare in the rheumatlo pericarditis, and is thon Ilrobably due to a • mixed' Infeotlon. Blood is sometimes found In the pericardium as the result ot JlUlcarditls, septiOOlIllia, pymmio, sourvy, and purpura, as also from rupture or an aneurism. Tuberculosis of the Pericardium.-Thls is very rare, evon when tubercles abound elsowhere. When fonnd, It generally ooeurs In assooiatlon with tubercular pleurisy, and tubercular mediastinal glands. Tho effusion may be serous, purulent, or hmmorrhagio. In old-standlng cases, caloifled plates may torm In tho wolls of the pericardium. Milk-Patches.-The pericardium is locally thickened, opaque, and dense. The patches are most oommonly found in elderly persons, especially over the right ventricle, and are probably caused by the ·movements of the hea.l'b against the sternum and ribs, as they are very rarely found on the parts covered by the lungs. DISEASES OF THE HEART. Weight 0/ heart: Adult malo, 101 ounoes. Adult fomole, 9t ouncos. • The thloImIlR of the walls of tho various cardioo ohambers is as follows: • That of tho Zeft 'D6'1ltricle varies from :t Inoh at the apex to I or t inoh at tho auriouio-ventricuIa.r furrow. • That of the right ventricle va.ries tram l inoh at tho a.pex to ! inch at t.ho auriculo·ventrioular furrow. • That of tho Wt auricle measures about! inch. • That of tho right aur!ck measures about ,,\ inch' (Box). The hoavIest hoart on record weighed 66 annoes; the lightest vrll-S lJIlder II ounoos. J20 AIDS TO PATHOLOGY Cardiology.-The sino-auricular fIOde, or • pacemaker: lies in the wAll of the right auricle (the part which correspends to the sinus venosus in the frog) at its junction with the superior vena co.va. A seeond and similar node--the auriculo-1le1&triculal' nodc--lies in the coronary sinus at the base of the interalll'feular septum. The two nodes arc connected by muscle fibros. They both censist of aOoemplioo.tcd network of very na.rrow musclo fibres with numerous nuolel, transverse striation, and rioh ill glycogen. The sino-aurioular node recelvos Important :fIJamonts trom tho vagus nerve_ The aurioulo-vontrioular node below is conneoted with tho (invertod) v-shaped bundle oj. His, whioh, beginning in tho intorall.rioular septum, passes down to tho Interventrioular septum, at the bettom of ,vhioh It bifurcates, one portion BPl'eadlng over the interior of the loft ventricle, and the other over the Interior of the right vontriole. The fibres of the • bundle of nls' oonneot with the general heart museulature through tho medium of Purkinie's network of fibres (which are only striated on their periphery). The various links In this anatomlcalohain, then, aro--(a) Tho sino-aurioular node; (b) the aurlculo-vcntrlcular nodc; (c) the' bundle of His '; (d) Purklnje's fibres; (e) the heart musoulature. The myogenUJ hypothesis of Gaskell assumes that the rhythmic aotlvlty of. tho hoart resides In the fibros of the oardlac muscle themselvos, and that the nervous system possesses merely the secondary function of rogulation. It also assumes that the transmiss:on of stimuli botween the Individual parts of the heart does not occur through nerve fibros, but through mus<.'UIar fi bros. What happens is supposed to bo this: Tho slno-aurloular node generates (at tho rate of about 70 per minute) rhythmical impulses, which, desccndlng along tho • bundle of llis,' oventually flow into the general myocardium via Purkinje's 'fibres. Tho result Is tho oontraotion, in ordprly sequonce, of the cardlao chambers, from the base to the apex of the heart, culminating in the contmotion of the musouli papiilares. It is further assumed that tho myooardia.l flbrOtl manufacture and storo up a • stimulus substanoe' which, when under suflicicnt tension, evokes their contraction. This' stimulus substance' Is used up during systole, and reaooumlllatos during dlastolo. The hoart muscle fibres, evcn When relaxed during diastolo, are ahvays in a stato of slight permanent oontractlon (=' tonicity'). The motto of the hoart is • All or nono '; In health it oontracts to its fullest possible extent. During rest the heart uses but a BUlall portion of its energy to earry on the oirculation. That kept in roservo Is known as • reserve energy.' It is this reserve NlOl'8'Y whloh diminishes in heart fa.lluro. DISEASES OF THE HEART 121 Simple Endocarditis. This disease is usually confined to the endocardium of the valves, and may be either(a) Acute, or (b) Ohronic. (a) Acute Simple Endocarditis.-Except when occurring during fretallife, it is almost alwa.ys confined to tho valves of the left heart. It is 0. disease mainly of early life, and probably 90 per cent. of the cases are due to rheumatic fever. (In the case of children it is not improbable that acute endocarditis may be the sole manifestation of rheumatic fever.) Each succeeding attack of rheumatic fever involves an increased risk of endocarditis. Any other infection, however-e.g., scarlatina-may cause it. . The liability to endocarditis in rheumatio fever may be expressed thus: It begins at the age of two years (it is almost unknown in infancy), is crescendo from two to ten years, and diminuendo from ten to forty years, after which period the liability practically disappears. A first attack is rare after thirty. Order of Incidence: Mitral valve alone. Mitral valve and aortic valve. Aortic valve alone. It begins on, and is generally oonfined to, that surface of the valve which faces the blood-ourrent-i.e., the aurioular surface of the mitral and the ventricular surface of the aortic valve. At first there are scattered foci of subendothelial infiltration (probably caused by micro-organisms brought by the lymph-stream), which raise the surface of the valve into rows of minute glistening beads situated a short distance from its free edge. Later, the endothelium over the beads swells up, becomes sticky and covered with fibrin, which, owing to the swinging to and fro of the valves, assumes the appearance of vegetations. By continued acoretion of fresh fibrin the vegetations may attain a large size, and by detaohment of partioles. from their surfaoes, emboli may pass into the blood-stream. 122 AIDS TO PATHOLOGY Result8 of Acute EndooarditiB : Resolution. Organization, contraction, and hence regutgitation. Fusion of valve edges, and hence stenosis. Aneurism of valve. Rupture of a valve aneurism. Detachment of vegetations, and so embolism. Contraction of chordre tendinem. (b) Chronic Endocarditis.-(This condition must be distinguished from the damaged condition of the valve left by acute endocarditis.) It is a chronic, progressive process from the start, leasling to fibrosis and often atheromatous changes. It is rarely found under the age of thirty. The Aortic Valv68 are those par e:coeJ1tmC6 affected. The causation may be expressed thus: SyphiliB, alco. holi8m, physical strain, acting either singly or in conjunction, and high arterial blood-pressure (an almost constant factor). The valve segments, more particularly at their free margins, become thickened, opaque, puckered, and distorted from the formation and contraction of scar tissue. This causes the valve to ' leak.' Calcareous material may be deposited in the valves, especially near their a.ttached margins. Disease of Individual Valves. Mitral Valve.-Disease ot this valve is generally the result ot rheumatie fever in a person under thirty, the usual sequel being retraction of tho valvo edge. with consequent ' back-wash' of the blood-i.e., mitral regurgitation. MUrat Reourgitation.-This is 0. residual condition resulting from former acute endocarditis. The left auricle is dilated and somewhat hypertrophied; the left ventricle is dilated and hyp_ertrophicd. If, in course of time, cempensation fails from degeneration of the heart tissue, the result is that the lungs have 0. difHculty in emptying thoir blood into the Jaft heart, 8lld thoro result--venous congestion of the lungs (with' red' or 'brown' induration from fibrosis and pigmentation); dilatation and slight hypertrophy of the right ventricle; triouspld regurgitation: dilatation of the right auricle; impeded portal circuIo.tion, oausing venous congestion of the liver (' nutmeg' llver), which may pulsate; asoltes; congestion of the mucous membrane ot the gastre-intestinal tract; consrestion of the kidneys (and thus DISEASES OF THE HEART 123 albuminuria and dimlnished flow of urine); mdemo., beginning in the lower limbs and mounting upwards. As the redemo. increases so the urine decreases. 'AurieuJruo fibrillation' may now be noticed. Should the valve guarding the junction of tho internal jugular and subolavian veIns 'leak,' t:qare is pulsatien ot the veins in the neok. As tho venules are badly emptied tho p.l.tlents tend to cyanosis. The splocn Is generally small, tough, and firm. Sometimes it is enlarged, but this Is usually the result of Infarction. In tho dilated right heart a thrombus may form, which, if it breaks up, causes embolism of the lungs (pulmonary apoplexy). It is a ourious faot that pulmonary tuberculosis is exception· ally rare in mitral regurgitation. M;tral Stenosis.-WJ!<m ooming under obsorvation tho plLtient is generally 0. young woman. As in mitral regurgitation, the ohief oause is rhoumat.ic tever, although a history ot this disease oannot always be obtained (the joint symptoms in the rheumatio fever of ohildren are otten vague, and may be entirely absent). The valves are thiok, smooth, ll.brotio, free from vegetations, and glued together at their margins, produoing eit.l:\er the • button-hole' orill.ce or the • funnel-shaped' orlll.oe of Corrigan. Tho orill.oe may bo so oontracted as soarcely to allow the Insertion of the tip of one finger (instead of the index and middle finger,s as far as the ll.rst joint). The apox of the funnel looks in the diroction of the blood-ourrent--i.e., into the ventriole. Tho ohordlll tondinem are oommonly thiokened. The obstruotion at the mitral orifice oauses hypertrophy (whioh In early oases may be oonsiderable) of the left auriolo; la.ter dilatation, often oxtreme, OOQUl'S; finally, • auricular fibrilla.tion' Is established, A clot is liable to form In the left aurioular appendix. a portion of whioh, if it beoomes detaohed, givos rise to ombolism. (This is the oommonest causo of ombolism of tho middle oerebral artery.) Tho lungs o.ro congested, as in mitral regurgitation. but the tendenoy to hlllllloptysis is muoh greater. (Sometimes suoh cases of hIlIm.optysis a.ro mistakon for phthilris.) The pulmonary arteries aro ofton atheromatous. The right vontriclo is dilated and hypertrophied. In ooursoof time trlcnspid regurgitation ensues with all its sooondary oonsequenoes on the abdominal viscera and legs. (The most pronounced instances of •nutmeg' liver occur in mitral stenosis.) Asoites may be the first sign of cardill.O dropsy. Many contradlotory statements have been made regarding the condition of tho left ventricle in mitral obstruction. In pure oases it is of normal size. The fingers are more apt to become olubbed than in mitral regurgitation. Patients rarely reaoh the age of forty-live. It is a well-known taot that pulmonary tuberoulosis is praotically never found in oonnection with mitral stenosis. (Rokltansky taught that all eonditions which brinll about passive congestion of the lungs impart an immunity against pulmonary tuberculesis.) 124 AIDS TO .PATHOLOGY Mitral stenosis is forty-five. 0. common CAuse or dea.th undor the ago of The Aortin Valve.-Dlsea.se of this valve alont, though som.,· times & sequel oI rheumatio tever. Is more otten of tile nature or a ehronie ondooardJtls, in which ease tIloro is usually atheroma of tho aorta a.t tho saUle time. Isolatod aortio valve disoase (i.6., Without a:l!eollon of the mitral valve) is raro as the result at rheUDlatie fever; it present. In a young woman, it. Is noorly always of syphilitio origin.. Aortic regurgitation is the usual sequel, aortio stenosis being rare. In aortlo regurgitation the blood is not only suoked back into the left ventriole durlog diastolo. but is also squirted baokwards into the heart by the recoil at the stretched aortic walle. thG initial rosult being dilatation of the loft ventriolo (more room having to be found for the additional blood, the ventriole ha.ving to aooommodate both the auricular blood and tho locgurgltant blood). to be immedJa.tely foIlo,ved by compensatory hypertrophy. This dilatation and hYJIortrophy tend to be progressive, ond it is for this reason that the heart may assume enormous dimensions (cor bovinum). A.s the result of ineroosed intraventrioulo.r pressure, the mitral orifice may 'le&k ' (oither from stretching of the orlfios or curling up 01 the valve Ol1l'tains). whon all tho sequolm of mitral regurgitation onsuo. The endooo.rdium lining the septum of tho left ventricle at tho point of impaot of tho regurgitant blood often shows patchos of thickenillll. The arch of the a(lrta is usually atIleromatous. The OBpillo.ries belog badly filled. the patient tonds to p&llor. A.t a lo.tcr stage fibroid degeneration of tho hoort muscle is liablo to ooeur, in aceordanoe with the genora.I law that a muso1o is capablo only of a oert.ain amount of hypertrophy, WId \vhoJl tllis limit is reached musouIar atrophy and fibroid degeneration follow. As 0. result, do-compensation ensuos. As in. aU disuz8eB oj the huJrl. the mea8'111'6 oj the patien.Qs danget' U t1l6 cmtdition oj the eardiac muscle. IIeart.failuro proooede muoh more rapidly in aortio than in mitral regurgitation, owing to the greater burden thrown on the left vontriole . .4arfiic stcnosis.-This by itself is rare, and when found results from either an acute endocarditiS or from atheroma.tous thickoning. ThO loft v6Iltriole Is hypertrophied, dUo.ta.tion bolng superadded in course of timo. (N.B.-Wha.t is olinl0811y ofien called aortic stenosis Is generally nothing more than 0. murmur. caused either by 'roughening' of tho valves, or atheroma of the a4rtie arcll.) Tricuspid Valve.-' Leakage' at the right aurioulo-vontriculo.r orifice Is generally the result of the 'book-wash' of mitral disease (regurgitation or stenosis). or of chronic lung disoasee.1I•• emphysema and bronohleotaals. Slmplo endocarditis of the valve rarely (I()(lUl'B exeept during footal llfo. U tho triouspid DISEASES OF THE HEART 125 booomes dIsoased during oxtra-uterino life, It is generally from Dl&lignant endocarditis_ The Pubnonary Valve.-Tho OODlDlon lesion of this valve Is sknosiB, whioh is praotioally always oongenital, the result either of a fmtal endocarditis or of a dovelopmental defeot. If occurring _Zu in fmtal life, It Is liablo to be associatod with a doficiency of thll upper part of the intervontriouln.r septum (pars i~ema), the two ventrlclos thon cODlDlunlcating. Endocarditis of the pulmonary valvo ocourrlng during extra-uterine life is almost always of the malignant variety. Summary of the Heart AftectiOD9 in Rheumatic Fever. Pory,arditis oocurs in about 20 por cont.; 60 pcr cont. of tho cases eocur under the- age of twenty-one. Dilatation.-The heart, especially the lett ventrlele, Is dilated (toxlo). The dilatation may bo temporary or permanent. Endocarditis (aoute) Is oaused by rheumatio fever in about 90 p~r oont. of cases. Praotlcally all children with rhoUDl&tlo tever, up to the age of ten, have endocarditis. After this age the tendenoy to endocarditis Is diminuendo up to forty, after whloh It dies out. In the typical rheumatic heart of a child dying from the disease, there will generally be found mitral reglll'Q'itatlon, mitral stenosis, aortio regurgitation, an adherent perioardium, and the heart may weigh as muoh as dve times the normal. .Malionant Endocarditis may occur in rheumatlo fover. Tho degree of damage Inflioted on the heart largely depends upon the patient being allowed to get up too soon. Auricular Fibrillation. When oompensation is tailing In an old-standing case of mitral disease, the lungs, right heart, and vonous syetem generally become engorged with blood, and ovontually dropsy supervenes, with scanty urine. Under suoh oircumstances tho pulse Is noticed to become markedly irregular, tho sphygmogram ~howing that two beats of the Bame length or oharacter rarely follow.each other. At the same time, in the majority of casos, the rato Is much too frequent, the average being between 90 and ltO, strong and weak beats being mixed up in complete oontusion. A pulse of this eharacter was oaiIcd by the older writers the' mitral pulse,' and, when In an exaggerated form, •delirium eordis.' Thanks to the introduction of the polygraph and the electrio eardiograph, the mystery of tho • mitral pulso' has at last been oleared up. It Is now known that the auriolo in £heso cases Is a spent force, being In a condition of semi-paralysisi.e., it oannot oontract properly, but makos, as it wore, abortivc attempts to do 80, its walls merely quivering, like the tongne ot a patient with • bulbar paralysis'; oo-ordtnate contraction Is I2.6 AIDS TO PATHOLOGY replaced by inco-ordinate contraotlon. the ohamber IIdl a whole not ccntracting_ The condition is well summed up by Lewis_ • The muscular walls are maintalncd in a position of diastole; systole, either ccmplete or partial, is never accomplished; the structure as a wholo rests Immobllc, but o1oso observation of the musclo surfacc revoals Its extreme and Incosso.nt activity; rapid and minute twttchings, and undulatory movements are visiblo ovor tllO whole.' This inactivity ot tlle auriole is responsible tor tho irrogular beating of the ventriole. and the irregularity of tho beating of the lattar exPlains the irregolarity of the pulse. Tho loft auricle is much dllated-sometimes to twioe its natural size. As tho result of the impaired action of the heart. thero·is usually mdema. ot the feet and legs, enlargement of the liver. ascites. and albuminuria. Auriou.la.r ftbr.ill&tlon is present in aboqt 65 par cont. 'ot all pationts admittod to hospital su1ferillll from cardiac fallure, and in about half of those mitral sl8fW8£s is tound. In all these casos tho commonest pathological change Is a chronio myocarditis going on to a patchll ftbrosi8. most marked in tho auricular wall. but also as a rulo involving tho ventriclos. In tho rheumatio CBSOS, degoneration ot the • bundle of His ' is !!roquent. Fibrillation of tho ventricle is fatal In a fow minutes, but fibrillation of the aurlclo may continue for weeks or years; few patients. however, survive its onset for more than ten years. (Aurioular ftbrmatlon is oocasionally found in pneumonia. diphtheria, and othor infections. Here the oouso is tCDC.) Malignant Endocarditis. This disease is due to the implnn~tion of pathogenic organisms on the endoca.rdium, the most important of which are pneumococcu8. Streptococcus pyogene8 aur6U8, gonococcus, and tho influenza bacillus. (There appears to be a malignant form of rheumatio endooarditis, but whether this is duo to tho organism of rheumatic fever or to a mixed infeotion is unoertain.) Special Oharacl6T8.-The disease attacks by preference damaged valves (i.e., those affected by an old endocarditis); the vegetations are large, numerous, and highly friable; tho valves may become aneurismal, and even rupture. Sometim68 the valV68 oj the right heart are involved. The infeotion ma~ spread to tho walls of the hoart, the aorta, and the chordal tendineal. There may be burrowing abscesses in the heart walls. Owing to the brittleness of the vegetations, portions are very liable to become detached, causing embolism of various organs, notably of tho Bpleen, kidneys, and brain. DISEASES OF THE HEART 127 The heart tissue genemlly shows a polymorphonuclear infiltmtion, with cloudy swelling and granular degonemtion of the muscle fibres. Diseases of tbe Beart Musculature. The myocardium Is tho vital part 01 tho heart. Diseases 01 tho valves and pericardium are relatively trivial compared witll dlseaso 01 the myocardium . • It is In the vital and anatomico.l condition of tho muscular fibres that we find tho kcy 01 cardiac pathology. for no matter what tho alfectlon may be. its symptoms mainly dopend on tho strength or weakness. the irritability or tho paralysiA. tho anatomic health or dis6llso of the cardlne muscle' (Stokes. 1836). Atrophy.-Thili occurs in old age and in certain wasting diseases. such as phthisis and diabctes. The muscle fibres shrink, granules of golden· brown pigment aro deposited in their interior (chieft.y around the nuclei), tho heart assumes 0. brownillh colour-hence the name brown atrophy 01 the heart applied to this oondition. The nature of tho pigmcnt in brown atrophy of tho heart Is a disputed point. It appears to be either melanin or II plgmentod fat (Zipochrome). Bypertrophy.-This develops in response to the neccssity for increased work on tho part of the cardiac pump. and i8 orily p08sible when the nutrition of the heart is good. Hypertrophy without dilatation is rare. Apparent hypertrophy with diminution of the oardiac chambers is a post-mortem effect. Hypertrophy of the Heart as a Whole.-Tbis is typically seen in certain ca.ses of adherent pericardium. Aortic regurgitation. Aortic stenosis. causes of hypor- Mitral rogllrgitation. . trophy of tile Increased perlpll?ral roslstance--e.g.. In leIt untriclB ohronlc renal dJsoase. { Exoessive muscular exorclso. Exophthalmic goitre. Aneurism. Mitral dlsoase. Causes of hypor- Emphysema } An~ othor ohronio hlllg trophy of tile Bronohlectasis dlBeaSOll. fWntricZe lDlsoo.ses of the pulmonary valvos. Pressure on pulmonary artery (anourlsm, cto.). t,g'" f 128 AIDS TO PATHOLOGY Pure hypertrophy of tho right ventricle never lasts long. This is probably due to the comparatively low reserve power of its musoulature. Hypertrophy of the ventricles is said to be concentric when it occurs without dilatation, and, except in pure aortic stenosis, is but rarely seen. When the hypertrophy is associated with dilatation, it is said to be eccentric, and such is the usual form. Hypertrophy of tho auricles is always associated with dilatation, the left auricle being most affected in mitral stenosis, and the right auricle in emphysema and disease of the mitral valve. Dilatation, or increase in the cubic capacity of one or more of the heart chambers, may either precede or succeed hypertrophy, the two conditions then coexisting. If a heart of good reserve power is exposed to conditions imposing on it increased work, the initial result is hypertrophy, followed by dilatation if the cause be long continued. For examplo, the greatly hypertrophied left ventricle of chronic Bright's disease tends in colirse of time to dilate. (Most cases of hypertrophy are, however, from the very beginning accompanied by some degree of dilatation.) If, on the other hand, a heart of low reserve power be exposed to conditions of increased strain, the tendenoy is rather to dilatation pure and simple. Sudden cardiac dilatation may occur. For example, it is probable that the acute pain of an attack of angina pectoris is due to the stretching of the heart walls arising from a sudden mechanical dilatation of the left ventricle. Acute toxic dila.tation of the left ventricle is the rule in rheumatic fever, and particularly so in the case of children. Mechanism of Cardiac Dilatation.-The essential factor in the mechanism of cardiac dilatation is excessive distension of 0. cardiac chamber during diastole. (It is manifest that a cardiac ohamber cannot yield during its systole.) The causcs of such excessive diastolic distension are-(a) Regurgitation of blood into a chamber, which thus receives blood from two direotions. (b) Inadequate systole, leading to an excess of residual blood in the inadequately systolizing ohamber. This is the great cause of cardiac dilatation in failing heart-e.g., in the later stages of granular kidney. Degeneration ot DISEASES OF THE HEART 129 the cardio.o walls leads to dilatation in this way. and also by rendering them liable to yield. (I:) An excessive supply of blood from the normal direction-e.g., in sprinting, the blood may be driven into th9 right heart by the rhythmical contractions of the musoles more rapidly tho.n it can be delivered into the lungs. The dilatation of the left ventricle in mitral regurgitation result!! from the extra supply of blood this' ch!l.lllber reoeives from the dilated left auriole. Diseases of the Coronary Arteries. Althongh the artories of tho heart anastomoso to 0. slight oxtent. thoy ma.y. for a.ll pmoti0011 purposes. be l'(lgardod a.s 'terminal.' AtkeromtJ.-The ooronary arteries are espeoially liablo to this disease. Their channels are narrowed, and the heart substance, receiving an insuffioient supply of blood, tends to undergo fatty and fibroid degeneration, (In angina. pectoris the cor.:>no.ry arteries are generally ath')romatous. particularly at their orifices.) Thromboaia.-This is a. not infrequent comp iC'l.tion of atheroma. Its results are the same as those of embolis'U (see below). EmboUBm.-If a large vessel is blocked, the usua.l result is srdd3n death; if a small vessel is blooked_hort of causing dcath~ infarct results. Should the rati( nt live suffioiently long, the infaret is oonverted into fibrous tissue. This, subsequently yielding to the ir.tracarJia\ pressure, causes an aneurism of the heart, the common site of which is in the region of the apex of the lelt ventricle. 8yphilitit; Endarteritia.-This causes great narrowing of the channels of the affected vessels, and, like atheroma, is liable to be complicated by thrombosis. Acoording to Osler, it, is the commonest lesion to be found post mortem in angina pectoris. Fibroid 'Bearl, This form of ~Iao degeneration ooours as 0. termln..'l.l evont In the hypertrophy and 'dUatation of vlI.lvltlnr disoose, general arterial IIbrosls. 6B wall 68 tn syphilis. When IOCI.IU?.e(l. it Is generally ot BflIhillGic origin and a.s8ociated with the pr080UOO 9 of 130 AIDS TO PATHOLOGY definite gummllta. In the~e c~sos thoro Is usually syphllitio ondarteritls ot tllo surrounding arteries. Fibrous tlssuo forms· botWOOD the muscle fibres, in part roplaeing them. Thc change is usually confined to the lett ventrlolo, and occurs mON particularly In tho neighbourhood of its apox. It Is one of the causes of sudden death. F~tty Degeneration of the Heart. In this disease fa.t globules, often a.rranged in transverse a.nd longitudinal rows, appear in the muscle fibres. The condition is most common in the left ventricle, less so in the right, and rare in the auricles. The left ventricle suffers most in the anromias and aortie valve disease. In phthisis and mitral disease the right ventricle is chiefly implicated. In typical cases the heart looks 'mottled.' like the thrush's breast, or presents tho • faded leaf' appearanoe. Three main faotors (whioh may act singly or in 0011· junction) are proba)'ly concernod in its causation-the action of some toxin, interference with the blood·supply, from diselllle of the coronary arteries, and the want of an adequate supply of oxygen. It is to be remembered tha.t the heart requires more oxygen than any other tisj:luo in the body. Chronio a.lcoholism is perhaps the commonest of 0.11 causes. Alcohol is not only a protoplasmio poison-it has been called the • genius of degeneration '-but it interferes with the oxygena.tion of the tissues. Other causes are: prolonged a.nd severe anrelpias (it is aJways present in pernioious anmIDia), phthisis, and phosphorus· pOisoning, and as a termina.l stage in valvular disease. Ail am acute condition, it is found in diphtheria. Heart-Block, By k(!o'rl·bloc1c is meant that condition in which the oontraction wa.ve from auricle to ventricle is 'blocked,' the rhythm of the auricle being maintained, .but tha.t of the ventricle not following in proper sequence. The' block' may be slight, the ventricular beat merely lagging behind the auricular, or so marked that the a.uricleBIand ventricles beat quite independently of oach other. For example, the jugular tracings ma.y show tha.t the auricle beats twice DISEASES OF THE LUNGS 131 to the '\'entriclo's once-that is, every alternate oontractit,n wave is blocked, or only one of every three may get through. Temporary hcltrt·block may occur in certain fevers, notably rheumatic fever, pneumonia, and enteric, in whioh cases it must be regarded as toxic. PersiBtent heart· block implies 0. gross pathological lesion of the' bundle of His,' but not necessarily limited to it, forit may bo widely spread throughout the heart. Gummata, fibrosis, atrophy, calci· fication, and diseaae of brancluu of the coronary arteries, are the most constant lesions. In exoeptional cases 0. neo· plasm may be the cause. The Stokes-Adami S:vndrome.-ThiB oonslsts of persistent slow pulso (bradycardia), with occasional attacks ot synoope, vertigo, and opileptlform fits. 'rhe Stokoe·Adams syndrome always indicates heart-block. but it is to be clearly understood .that only 0. minority of the cases of hoart·blook exhibit the syndrome. DISEASES OF THE LUNGS. The. lungs are devoloped as outgrowths of the (l)soph. agus. 'rho epithelium lining the air cells, bronchi, and trachea, is derived from the hypoblast, and the rest of the lung tissue from the mesoblast. .CoUapse of the Lung. Ato\oo\a81B 18 'Lbo cunMUun u\ 'Lbo rongs in 'LbD s\;JWDom. SUell IUDgs are completely alrlcss and sink in water. The causes of collapse of the lunge areair, serum, 1. Pressure from without the lungs blood. aneurism, tumours. 2. Obstruction from within the lungs, caused by blockage of the bronchial tubCII. The chief cause of such obstruction is ' capnIary bron· chitis,' in whioh the small tubes become plugged with visci~ mucus. Tho imprisoned ~ir is absorbed by the blood, and the alveolar walls, faIlmg together, ultimately 110 in contact. f tPUS' AIDS TO PATHOLOGY Collapsed lung is reduced in aize, of a dark red colour, and non-01'6pitant; it sinks in water. Pulmonary Emphysema. TI:.ere are two main varieties-the spurious and the true. SpuriO'UB emphysema (insumation, acute emphysema) occurs chiefly in children, as the result of capillary bronchitis and broncho-pneumonia. In these diseases excessive stretching of the uncollapscd air vesicles occurs as the combined result of widespread vesicular collapse, and of the thoracic expansioll (from prepondcrating action of the inspiratory muscles) resulting from dyspnrea. As a. result the vesicles arc so greatly stretohed as temporarily to lose their power of recoil, and the lung tiBBue involved may remain unduly oxpanded for somo days; but there isno rupture of the vesicles. Of true emphysema there arc two kinds: the interZobular, in which, under the influence of a violent expiratory e1fort, such as occurs during 0. paroxysm of whoopingcough, actual rupture of tho vesicles takcs place, the air c:Jcaping into the interlobular spaces, \vhenco it may gain aCC099 to the mediastinum, and thence to the subcutaneous tissue of the neck and chest; andVesicula, Emphysem!l.-This is the varicty whioh is generally meant when pulmonary emphysema is referred to. It may ocour in a localized or gonoralized form. In the former it is met with in the neighbourhood of pleuritic adhesions, or in parts of the lungs which have been rendcred airlcBB-e.g., by tuberclo or collapse-when it is generally known as compe1UJatory emphysema. In these localized forms the essential cause is unduo traction on the vosioular walls, in consequenco of which their nutrition fails and the sopta botween adjac~nt vesicles give way. In generalized vesicular emphysema a degcnoration of the vesicles takes place throughout tho entiro lungS; their bloodvessols and epithelial lining atrophy; they lose their elastioity; and the septa between adjacent vesiclos give way. At tho same time the vesioular walls lolle their wavy outline, presenting under the microscope a stretched appearance. DISEASES OF THE LUNGS 133 This variety of emphysema. is essentially due to prima'71 aerop'h,ic degeneration. Suoh degeneration takea plaao in everyone with advanoing years, quite independently.of cough, but in some it is met with in early adult lifo or even before this. Its occurrence is favoured by certain diseases, suoh as gout and granular kidney. The second, but much less imPortant, factor in the production of this form of emphysema is long-con.Unued over8tretching 0/ the vesicular wal18. Such overstretching may result from (a) exoeasive pressure from within, as happens when a powerful expiration is made while egress to the air is impeded, as by a completely or partially elosed glottis (muscular effort, coughing), or in blowing wind instruments. Or it may result from (ll) excessive traction from without. We have seen that the latter is the chiof factor in determining localized emphysema. Such traction may alae be a minor factor in causing generalized emphysema: in all forms of breathlessness other t·han those due to obstruotion in the respiratory passages (as by the diphtheritio membrane or by throttling), the mean size of the chest is increased by the preponderating action of tho inspiratory muscles (the expiratory muscles remo.ining in partial or complete abeyance). This is because the inspiratory position of the chest is the one most favourable to the pulmonary circulation and the aeration of the blood. Hence what· ever promotes breathlessness predisposes to emphysema, whether it be physiologica.l breathlessness, suoh as results from athletio pursuits, or patbologioa.l breathlessness, such as ocours in asthma and heart disease. In generalized emphysema. the lungs may be unduly expanaed (hypertropholIs, or 'large-lunged,' emphysema), or (much leBS frequently) not more than their average size (atrophous, or • smaJl-Iunged,' emphysema). In the latter case it is probable that tho disease has not occurred until the thoraeic cage has undergono senile fixation. When it occurs before this. the mean sizo of the chest (owing to the favouring influence of tho inspiratory position on pulmonary circulation) undergoes steady increase from overaction of the inspiratory musoles. AS a result, these latter shorten (just as the overacting muscles do in talipes). and ae fix the chest in the inspira~ry posi. tion. Moreover, the bones and joints of the thorax tend 134 AIDS TO PATHOLOGY to become 'set' in this new position. In this way the chest, in the latter stagcs of the disease, may be fi:l:ed in a poaition of BUper ea:traordinary inapiration-i.e., the patient is unable, by the most powerful oxpiratory effort, to reduce his thorax to normal dimensions. Under these circumstances the chest appears barrel-shaped and the neck short. . It will be observed that the enlll1"gement of the chest in ' hypertrophoUB' emphysema is compensatory. A reduction of the chest to the normal size in this condition would soon cause death. It wm generally be found that the chnst expands as middle life is reached, especially in stout people. Men arc apt t.o pride themselves then on possessing a 40-inch chest, ignorant of the fact that such 0. mcasurement gcnerally indicates degeneration. The progressive enlargement takes place in obcdience to the principle already cnunciatod, and is in large measure due to loss of pulmonary elasticity. In order to maintain physiological conditions it is necessary that the pulmonary tissue shall be kept in a certain degree of tautnCBB (for otherwise not only will 'pulmonary suetion ' fall below the normal; but the slack, wrinkled vesioles will unduly encroach upon the air spaces), and lUI the pulmonary fibres length6n they need to be tightened up-tuned up to the nermal pitoh, so to speak-by an increase in the mean size of the chest. Though generalized vesioular emphysema involves the ontire lungs, the emphysema is usually most marked at the parts least supported during occasions of heightened intrapulmonary prossure - i.e., the apices, anterior margins, lower and posterior margins (which may present an appoamnce which has been likened to the fur on a lady's mantle). It must not be forgotten that under ordinary conditions the lungs, far from being supported by the structure eircumjacent to them, actually exercise suotion upon them. Owing to the 10BB of their elast.icity, the lungs in generalized emphysema. collapse but little when the thorax is opened, or when they are removed from the body. The anterior borders are found to have lost their sharp edges and to be rounded, showing emphysomatous bulb ('frog's lung'). They may also overlap in front, and DISEASES OF THE LUNGS 135 by covering the hcart obliterate the area of superficial cardiac dulness. The pulmonary tissue is palo and blo.odless, pits more easily than healthy lung tissue, and feels like eiderdown. The &ir can be squeezed from one part to another with greater facility than normally. As the emphysemo. progressea, tho obstruction to the pulmonary circulation resulting from obliteration of the amaller vessels causes the branches of the pulmonary artery to dilate, and its main trunk often to become atheromatoUII. Eventually tl,e rigke heart becomes dilated. and general vonous congestion supervenes (enl&r&oment of liver, redema of lower oxtremities, albuminuria, eto.). Bronchiectasis. In this condition there ito permanent distension of the bronchi, which in consequence may bccome: Cylindrical, Fusiform, or Saccular. The IIltiology of bronohiectasis is much tho same as that of emphysema - viz., increased stretching of the bronchial walls, cither from augmented internal pressure (an unimportan~ factor) or increased traction from without (the eBSential factor). In bronchiectasis, however. another factor comes into operation--i.e., weakening of the bronchial walls from degeneration of their muscular fibres which (as in the case of all tho muscular tubes of the body), by their o.otive contraction, normally tend to prevent overstretching. Bronchiectasis is the usual aocompaniment of all ohronio diseases of the lungs. and is typically met with in fibroid phthisis. I~ this disease the contraction of the fibrous tissue, attached, on the one hand, to the adherent pleura, and to the bronohi on the other, has been hold to be an important factor in causing the dilatation. Though such contraction plays its part, the chief traction comes from the powerlul action of the inspiratory musoles. which. in accordanoe with the prinoiple already mentioned, are in dyspnrea continually striving to inorease the mean. size ot 136 AIDS TO PATHOLOGY the chest. It is evident that, were the normal amount of vesicular structure present without any fibrosis, such inspiratory action would simply lead to emphysema, because the delicate vesicul&- walls would necessarily yield before the stouter bronchi. When, however, the lungs &"e seamed with comparatively non-yielding fibrous tissue, the effect of the constant inspiratory efforts will be to expand the bronchi as well as the vesicles. . In bronchiectoais the muscular coat of the dilated bronchi is in large measure replaced by a fibrous tissue, and the muoous membrlUle tends to lose its sensibility_ As a result, the secretion of the tubes is apt to accumulate IPdld to undergo putrefaction:, not being expelled until it reaches a level at which the mucous membrane is sufficiently sensitive to excite the act of coughing. Bronchiectasis may give rise to abscess in the brain. Pneumonia. There are two classical forms of acute pneumonia, which have different exciting causes, run different olinical C01lI'88B, and present different morbid appearances. These are: Lobar pneumonia, and Broncbo-llneumonio.. Lollar Pneumonia (CroupoasJ.-Pi\e pneumoooccus oj Fraenkel is eke eB86ntial cau8e, though occoaionally the pneumo·bacillus of Friedlander, streptococci, and staphylococci &"e also present. The pneumococci are constantly found in large numbers in the mouth, pharynx, and nasal cavities, of man in health, and it is orily when vitality is depressed (e.g., by chronic alcoholism) that they' can set up inflammation of the lungs. They are most numerous in the advanoing area of disease. The lesion usually begins at the root of one l)Ulg, extending thence to tho base, and in typica.l cases involves tho whole of the lobe in a uniform manner. Exceptionally, it may occur in scattered areas. The constitutional symptoms are the result of absorption of the pneumo-toxin into the system. Lobar pneumonia. is alwa!J8 a pleura-pneumonia, arm passos throu$h tile follo~ stages: DISEASES OF THE LUNGS 137 The Stage o/Oongeation.-The affected area of lung is swollen, of a deep red colour from vaacular engorgemont, and it is less orepitant and less elastic to the feel than normally. It floats in water. The capillaries in tho 0.1 veolar walls are distended, the lining epithelial cells swell up, lI.nd exudation of inflammatory lymph begins. Signs of pleurisy are evidl'nt. The Stage of Red Hepatization.-The inflamed portion of lung, usually a whole lobe, is now solid, like 0. piece of liver; the inBo.mmatory lymph hIlS completely filled the alveoli and undergone eoagulation, the clot being com· posed of a fibrinous network. entangling in its meshes polymorphonuoleo.l'B, chromocytes, and shed epithelial cells. In consequence of this the inflamed lung is distended, a.nd its p]eumlsurface may ije indented by the ribs. (This is probably a post-mortem phenomenon, as during life the inspimtory muscles enlarge the chest on the affected side, a.nd thus proteot the in1l.amed lung from pressure.) The affected tissue does not crepitate, is very friable, and sinks in water. On section it looks like red granite, being dry and granular. Tho pleura is sticky and covered with a dolicate layer of fibrin. The Stage of Resolution is the normal sequence to red hepatization if recovery takes place, in which case the coagulum disintegrates, to be in part absorbed by' the lymphatics, and in part removed. by expectomtion, after which the alveolar walls become relined with epithelium. Instead of resolution the stage of red hepatization may pass on toThe Stage 0/ Grey Hepatization.-The lung remains solid; is still more friable than in the second stage, and sinks in water. Ou section it looks like grey granite, and may yield a purifOJ/lll :fluid. The fibrinous network has partially dissolved, the chromooytes ho.ve disintcgmted, and the alveoli are packed with granular leucooytes. If at this stage a section of the lung is made from apex to base, the organ will be seen to bc mapped out into zones. At the bottom is the zone of grey hepatization, while above this are three others-first, a. zone of red hepatization, above tho.t a zone of congestion, ILIld above that, a.gain, a zone of ccdcma. AbBCe88.-In some cases of pneumonia the alveola.r walls AIDS TO PATHOLOGY disintegrate, leaving a cavity filled with dead leucocytes. This is 110 very rare phenomenon. Gangrene.-In persons whose tiBBUes are very muoh weakened by, e.g., alcoholism, the intensity of the inflammation may be such as to cause gangrene. Oomplicati01l8.-The pneumococoi entering tho circulation may set up pericarditis, malignant endocarditis, meningitis, peritonitis, synovitis, or otitis media. The pleurisy may pass on to empyema (whioh is generally on the left side). The absence 0/ leucocytosis in pneumonia usually J;Ileans 0. fatal termination. The expeotoration of prune-juioeooloured sputum is also a bad sign, as it indicates much pulmonary mdema. At the time of the orisis the opsonio index undergoes a matked rise. BroDcho-Pneumonih (Catarrhal, Lobular Pneumonia).This is par excellence a disease of the e_xtremes of life (childhood and old age) and of influenza. It is also the essential lesion of pulmonary tuberculosis. It is alwaya preceded by a preliminary capillary bronchitia, of whioh it is the direct outcome. It is microbic (pneumooocci, streptococci, and staphylococci) in origin, and an example of point-to-point infection. Thus, it occurs in children as the result of measles, whooping-cough, and scarlatina, and in adults after influenza and operations on the mouth and windpipe (' aspiraLion' and 'deglutition' brancho-pneumonia). The inspired air rendered septio by passing over the infected mucous membrane of the mouth, nose, or pharynx, sets up a capillary bronohitis; subsequently, patches of pneumonia devolop around the affected bronchioles, in consequence ofDirect extension of the inflammation; or Inoculation with septic material sucked in from the bronohioles; or Collapse of the alveoli from plugging of their bronohioles with tough mucus, and subsequent absorption of the air imprisoned in the alveoli. Possibly all thcse factors co-operate. A seotion of suoh a lung in an oarly stage of the disease shows small, dark red, ill-defined patches, ranging in size from a pin's head to 0. pea, and Il'Urrounding inflamed DISEASES OF THE LUNGS I39 bronchiolfl8, separated by healthy intervening lung tisBue. At a. later stage neighbouring patches may coa.lesce into !lone-shapecl areas (with the base of the cone at the surface of the lung and the apex at the aff~ted bronchi). Still later, by furthcr coalescence, such large areas of consolidation may result that the appearance suggests loba.r pneumonia. Pleurisy is le88 common than in lobar pneumonia., and is found only in those cases in which the pa.tches lie adjacent to the surfaee. The bronchiolcs a,re inflamed. and choked with muco-pus and shed epithelium. The ait-vesicles are filled with large mononuclea.rs and swollen epithelial cells; also loucocytes in variable numbers, and a few chromocytes. During resolution, the collapsed portions may remain uninfiated, ca.using much shrinking of these areas of the lung. In some cases tho inflammation involves the connective tissue of tho hmgs, resulting in much perma.nent induration. Moreovor, tuberculosis may develop out oE a bronoho-pneumonia, but this is exoeptional. P~ercular Broncko-Pneumonia is par excellence the leSion of phthisis. Broncho-Pneumonia and Inftuenza.-Tho tcrm bronchopnournonlals otton uscd to Includo all oases of pulmonary complications occurring in influonza. Many cascs sho\v post-mortem oxtensiVt' oonfiuent bronoho-pneumonia; others SlIO\V bronchiolitis, extremo oongestlon of tllo lungs, oollapso, Illdema, plllurlsy, and consolidu.tion. OtlLOfS would bo mora oorrectly termed streptococcal soptllll'Omla. In all those O"S08 tho mechanical obstruction to tho Intako or oxygen oxplains tho cha.ra.otorJstlo • holiotrope cyanosis.' Bactorlal culturas llBb.ally show tho prescnooof FriedlAnder's bacillus,streptococci,and sto.phylooocci. Chronic Pneumonia.-Thls is a merc frequent soquonoo to brancho-pneumonia tllan to lobar. Tho alveolar \voJls bocome Inllitrated with small raund oolls, wllich by organizing Into fibrous tIssue may load to progressive obliteration of tho airspaces. It is generally assoolated with vosioular omphysema and bronohlectasls. Phthisis, or Pulmonary Tuberculosis. Tubercle bacilli are expelled from tho body of II. tuberculous patient: (a) in the sputum (and perhaps with the expired air during coughing and sneezing); (b) in tho urine; (c) in the freces; (d) in the discharge of a tuberculous sinus. The lungs may be infeoted: AIDS TO PATHOLOGY (1) Via the inspired air. (2) Via the tonsils. the cervical glands. the mediastinal and the bronohial glands. and thenoe to the peribronchial lymphatics. (3) Via the alimentary tube and thoracic duct. Babies are born free of tuberoulosis. but post-mortems of 'ehildren nearly ahvays reveal the prosonee ot tuberole. ne matter \vho.t disease oaused death; post-mortems of adults praotioallyal\vo.ys sho\v healed lesions. The comparative immunity of adults to new infection,may perhaps be aecounted for by the immunizing effect of the arrested infeotion acquired in early litc. • It one develops active tuberoulosis, it is not a new infection. but an activation of latent tuberoulous losiens he has been oarrying since ohildhOod' (Woodruff). Something has happened to weaken the defenoes of the bedy against the tubercle baoilli. It wo.s formllrly taught that pulmonary tuberculosis bogan at the apex, the 'line ot march' being down\vards; but recent pathological observations. ooupled with radiographie evidence showing heavy reot shadows with distinet mottling In the neighbouring lung tissue, indica.te tho.t the diseaso often begins in the bronchia.! glands at the root of tho lung (the largo majority of all bodies examined post mortem reveal tho presence of old-standing disease of these glands), the infection thence spreading along the hilus to the peribronohial lymphatlos. Whon the o.pex is reaohed, the disease here may progress 80 rapidly that this region appears to be the aotual startingpoint of the disease. (Also. it is te be romemborod that the lung apex is comparatively superfleial. and 80 with the stethoseope fine Bounds can readily_ be detected.) The tubercle bacilli at length settle in the lymphatics of the lung (peribronohial. perialveolar. and perivascular), where. liberating their toxins. ano.tomical tuberclos form as explained on p. 72. The cardinal initial lesion in all casu 0/ phthisis is probably a tubercular broncho-pneumonia. Although no two oases of phthisis are ever precisely identical. we may in a general way describe four chief types: 1. Ordinary phthisis. 2. Acute phthisis. 3. Aoute miliary tuberculosis. 4. Fibroid phthisis. 1. Ordinary Phthisis.-This is the oommon form of pulmonary tuberculosis. There are four stages: DISEASES OF THE LUNGS I4I (a) Deposition of tubercll's in the peribronohial perialveolar, and perivascular lympho.tics, the presence of which casues the setting up of 80 chronie broneho-pneumonia. This is the initial lesion. (b) Consolidation.-As a consequence of the bronchopneumonia, the alveoli and bronchioles of the affected area become choked with intlamm.a.tory products and the part becomes solid. (0) E:t:cavation.-The pressure exerted by the perivascular tubercles, plus the aotion of the bacterial toxins. cause thrombosis of tb.e bloodvessels in the con~J'jd"\ted area. From the cutting off of the blood-supply there results necrosis and ca.seation. By the softening and. brea.king down of the caseous material a cavity (=lIomioa) is formed. (A ca.vity ma.y also be ea.used by the yielding of the softened tuberoular bronohial walls-bronchiectasis). Recently-formed cavities hllove irreglllll.r walls of softened necrotio tissue, while older ones are lined with a smooth pus·yielding membrane, often da.rkly pigmented. They oontain pus, degenerated endothelial oells, lung debris, and caseous ma.tter. A cavity sooner or later opens into a bronchus adll its contents disoharged. (d) Fibroo8.-Pari plU8'IJ with excavation new fibrous tissue forms on the outside of the diseased 0.1"(1.10. tho adjacent pleuta thiokens, and by beooming adherent to its opposite layer seals up the intrapleural space. The disease may now beoome arrested. Then more fibrous tissue forms which, contracting. partially or complet3ly soals up the cavity,oonverting it into a pigmented fibra-cicatrioial mass enolosing calcareous matter. If, on the othcr ha.nd, the disease progresses, fresh areas of lung tissue are infectcd in succession, the processcs of consolidation. excavation, and fibrosis are repeated a.gain and again, the lung is o~ively hollowed out by adjac~nt oavities mnning into one another. and sooner or later the other lung beoomes similarly affected. If a branch of the pulmonary artery passcs along the wall of a cavity or across its lumon, it is generally obliteratcd by thrombosis. Sometimes. however. it remains plI.wnt, and in this case an aneurism may form in the vessel, and by rupturing give rise to severe. even fatal. hillmorrhage. AIDS TO PATOOLOGY 2. Acute Phthisis (GallopiDg CODSumption).-This is 0. form of pulmonary tubetoulosis that runs a rapid oourse, the patient dying within a few months. Tho tubercular broncho-pneumonia is intense from the start, and numerous small cavities soon form, the interior of which ~onsists of softened, necrotic, and caseous material. There is little or no tendenoy to the formation of an organized wall, the time being too short. Suooe88ive areas of pulmonary t·is8ue are rapidly affected. If a oavity lics close to tho surface, it may ulcerate into the intraplcural Bpace and cause pneumothorax and pyopncumothorax, the process being too rapid for proteotive pleural adhesion, to take place. 3. Acute Miliary Tubercnlosis.-In this disease an cruption of innumerable tubercles in the form of minute grey dots (especially numerous bencath the pleura) ocours throughout the Bubstance of both lungs, from apex to base. lt is probably never primary, but alwa1P a final stage oj a pre-existing tubercular lesion. In this sense it is an auto· infeotion, the source of infection being, as a rule, caseating bronchial glands in the case of children, and in the case of adults an old tubercular deposit in the lung. • In acuto millney tuborculosis the b~illi nla thougllt to be carried by the blood-stream. thuB differing trom other ferms of tuberculosis, in which infeotion is conveyed by the lymphu.tics. The baeilli roaoh tho blood oither by tho caseation of n gland tlll'ough the walls of an adherent pulmonary voln, or'1ly the perforation of a tubercle which has formed on the outside of a vessel. Sometimes tho orosion Is through tho thoru.cio duct. The bacilli cannot multiply while ill the blood-stream, but only after coming to rest in tho lymphu.tlcs of Bomo organ. Patches of broncho-pneumonia are scattered throughout the lungs, but death occurs before any marked dcstruction of tissue can take place. Owing to the rapidity of the process, no giant cells can usually be seen in the anatomical tubercle. :Many other organs may be affected simultaneously with the lungs, notably the liver, spleen, kidneys, peritoneum, and membranes of the brain. Tk6 dis(J(J86 is liable to be mistaken lor enteric lever. 4. Fibroid Phthisis (Cirrhosis of the Lung) is a very ohronic form of pulmonary tuberculosis, not usually developing until after the age of thirty. and lasting from ten to twenty years. DISEASES OF THE LUNGS 143 Fibrosis predominates over necrosis, the affeoted lung tissue being replaced to. a greater or less extent by connective tissue, embedded in which are tubercles-often difficult to detect on account of the density of the new tissue; in most cases, indeed, the only evidenco of their presence is the ocourrence of one or two giant cells. Thi8 form of pAtkiBis i8 always associated with marked lrronckieetasis, and, to a leBB extent, with cmphysema. In a. fully-developed case the lung is shrunken, hard, fibrous, and pigmented; the pleura is thickened and adherent over the affected parte, whioh nearly always includes the apexwhich is then usually covered by a dense leathery ca.pand the organ feels like 0. cirrhotic livcr. On section, the fibrous tissue is found to havc penetrated both the alveolar walls and tho interlobular septa, obliterating many of the air-vesicles. In the midst of the new tissue, ai'OlloB presenting a honeycombed appearance are often seen ( .. emphysema). There is marked -dilatation of the bronchi, and this is the most active factor in the formation of the cavities, the bronchi often opening into spaces lined by a smooth, pus-secreting membrane. The pleura outside these bronohiectatic cavities is flattened, for banda of fibrous tissue pass to it from tho walls of the cavities, and by contracting cause depression of its surface (see Bronchiectasis). The shrinking of the lung, combined with adhesions Of the pleura, often gives rise to drawing in of the ohestwall. In all cases of phthisis the lym phatic glands at the bifurcation of the trachea and those at the root of the lung are tuberculous. The liver and heart arc usullolly fllotty in all forms of active phthisis. T1/pelf 0/ Ba"uzi met with in Tuberculosis.-In a total of 938 cases In which tho sputum was examined, only four bovine types wore found. tho rest being human. In primary abdominal tuboroulosls the !>ovlno typos constitnte about 50 per cent. Tubercular adenitis of the cervJcal glands In cbildren give '" percentage of BOV8llty-ftve bovine: In adolosconco, 50 per cent. (Abridged from Cobbott's Oawes oj Tuberculosis.) Pneumokoniosis (leonis, dust). This la a form ot ohronlo interstitial pnoumonla sot up by tile inhalation of Irritating partiolos-coo.l-dust In miners (anthracosis), motllol-dust In noodle and knife grinders (siderosis), stone- AIDS TO PATHOLOGY dust In stone-masons (silicosis), which, passing into tho perlbronchiallymphatics of the lungs, is deposited in various parts ot these organs_ Dronchial catarrh, patehos of chronlo catarrhal pneumonia, an inerease--Bometimes considerablG--Ot the IIbrous tissue, pigmentation, pleural adhesions, and bronchiectasis, arc the chief pathological features. These cases are lia.blo to be compIicated by tubercle, and arc then examples of IIbroid phth's!s. Dr. J. S. Haldane, at the annual mooting of the Institution of Mining Engineers, 1919, In an address on • The Health of Old Colllors,' said the phthisis doath-rate among colliers was not only much lower than In nearly all other occupations, but WlLS evon lower than In the exceptionally healthy occupation of fann-labourer. Coal-dust cor4l.inly did not kill germs, buL It had come to be regarded by medical men as a preventive or phthisis. Syphilis of the lung Is very rare, and, when found, is usually In the form of gummata in tho neighbourhood of tho root. White pneumonia is the name given to the condition met with in Infants with congenital syphilis. Extensive tracts of lung tissue are condensed and inmtratod by a new formation o~ connective tissue. Glanders.-The Baci1.l'UII mallei may cause a bronoho-pneu-' mcnia. The consolldated arOlLs resemble soptio infarcts. • Actinomycosis oonsists of grey nodules oontalnlng pus, In which arc found the yellow grains of the streptothrJT. It ma.y extend to pleura, pericardium, muscles of the chest, ~kin, etc_ Tumours of the lung may be primary or Booond&ry, and are practically ahvays malignant_ Primary tumours are: carcinomata, which grow from the bronchial epltheliuni, and sarcomata, which grow from the lymphatic glands at the root, and inmtrato tho connective-tissue planes of the lung in all directions. Secondary growths (caroinomata and sarcomata) are multiple, and causo tho lungs te assume B marbled appearanoe. Acute Pulmonary <Edema. The outstll,nding features of this disease are dyspnooa cyanosis, and incessMlt coughing, accompanied \>y a continuous frothy discharge from the mouth and nostrils. The cause is sudden failure of the left ventricle, the right ventricle continuing to aot. Hence the capillaries,of the lungs beoome engorged Mld the alveoli filled with exuded serum, the patient being' drowned in his own secreti9n.· The predisposing factors are: Aortic dissase, ohronic nephritis, and arterio-sclerosis, the exhausted loft ventricle losing its driving power and suddenly ceasing to act. DISEASES OF THE NERVOUS SYSTEM 145 DISEASES OF THE,NERVOUS SYSTEM.. & cell proV:lded with one or mol'S process08 and traversed by neuro-fibrUs. which oonstltute the strands along which • nerve currentlJ' travel. Each nauro-fibrll enters the neurone through one of its prooeSS8IJ, traverses the oell-body. and leaves the oeD by anothor process. or, If there Is but a single prOC88S (as in tho case of the sensory neurones of sensory nerves). by the same process. It will thus be seen that the essentlel elements of the neurone prooesses are neuro-ftbrlls. Two kinds ot such prooesses are met with: (a) Shorter naked proeessos, or dendrites, whieh, after arboresolng. terminate in tree extremities within the grey matter of the brain and spinal oord: and (b) longer medullaooated procosslfS. or wrons. TI10SO latter oonstitute the ordinary medullated nerve tlbros mot with in the white matter of the A. DeuroDe is .eml-orytl'n in Iltln. de. _nr:I., 3-~Ar.i~'~~nmt~~n~BU~~~~~i~"~~ I" ~1IIfNII:Y 11.",&. S';"D~OfIt ganglia cIa li'Ia. H.-This diagram mows tho ClOurso of tho nerve impulses In & simple spinal reftox_ For the ·sake of slm.pUeity, the sensory root-gangUon oell (proteneurone) is represented 80S having two proOS8Ses instood of one procoss, and the Intermedlo.ry cell between the sensory root-ganglion cellsnd the anterior horn motor ecll Is omitted. brain and spinal eOI'd, and In the cerebro-splnal nerves. In the tatter case, the medullated fibres have an additional sheath in the shape of the nettrllemma. whioh. unliko the neurone proper (which 18 of epiblastio origin), is derived from tho mesoblast, and Is of the nature of oonnective tissue. The function of the modullary sheatllIs probably partly to protect, o.nd partly to'ald In the nutrition of, thB nouro-tlbrlls oonstltuting the oentral. "lm! or axis cylinder, ot the long axens. The neurJlommll has slmllll' 10 AIDS TO PATHOLOGY functions, and, further, ailis in the regeneration of nerv;: IIbrue atter their division, whether by trauma or by disease (e.g., anterior poliomyelitis). Neurones are contigDOUB, but not continuous; tho neuro-flbrH.s do not pass from one neurone to anoLhe... Each neuro-flb1·j) begins at the extremity of a neuro2te prooess, tJoiIverses the cell body, and ends at tho extremity of 8 neurone process. One of these extremities Is rOOllIltive (a1lerent) and adapted, to be sUmulated... the other is emissive (efferent) and adapted to simulate. The afferent extremity Is proVided with an end -Ol"ll"BD, whioh i~ adapted to be stimulated by a. specifl.ctorm otstimulus, and,thus to start a nerve current a.Jong the lleuro-flbril, Thore arc two chief olo.1Ises of suoh a.fferent end-orgaw: those belonping to the neuro-flbrils 01 the sensory and special-sense nerve fibres. and LllOse belonging to the dondritio nem-o-flbrlls situated in the grey matter of the brain and spinal oord. The efJerent extremities have simllarly two modes ot termination: The neuro-flbrlls belenging to the axons fi.I efferent nerves terminate in muscle fibres. or epithelial oells; those belonging to DXons whicl end in the grey matte! ot the brain BDd spinal oord have lIec extre:nities, whioh are plaoed in relation with the reoeptive end-organs of neighbouring dendritic neuro-flbrlls. ' Observe that on this view tho funcGlon of tho terminals ot efferent nouro-fibrils (tho~e. i.e.. which I'un in efferent axons) la to initiate a chemioa.J process (for the most part of a disruptive natlIPO) either in a muscle fibro or gland cell, or In the reoeptlve cnd-o-rgan ot a dendritiC neuro-fibril pe-rta.1nfng to a neigbbouring neurone. The interval between the trca extremity of an ctrehmt axonlc neoro-fibril and the end-organs of its related dendritlo neurafibrils Is spoken of as a synapse. It 1s hore that the real mystery of narvous reaction resides; it is here that the complex prooesses ot co-ordination (ineludiDg inhibition) are offeotod, and It is probably in this region also that the physical 001Te1ativcs ot psychio processes take place. Nerve currents, it wUl be observed. originate In tho endorgans ot afferent neuro-flbrils. The old View or the oell-body of the neurone being a kind of battery discharging nerve currents a.J.ong its processes must be abandoned. It should bc observed that some authorities do not bellevo In the o:Dstenoo of neura-flbrils.lnasmuoh as these cannot be detected In the liVing neurone. Strong argumonts can. howover, be advancod in tavour of their existence. Changes in Neurones which fonow upon Division of Cerebro-Spinal Nerve. Peripheral Portion_-The changes here have for their object the emptying of the neurilemmal sheath, so as t.o DISEASES OF THE NE'RVOUS SYSTEM 147 make way for a new down-growing axis-oylinder from the central end_ The contents are gradually absorbed by the action of substancea (ferments, lysins) developed within the sheath; the neuro-fibris of the axis-oylinder beoome separated, break up into granules, whioh are absorbed; the medullary sheath breaks up into blooks ( =fragmentation), and these into smaller particles, whioh beoome absorbed; the nuclei of the neurilemma multiply_ Tkese changes constitute Wallerian degeneration_ Gentral Portion-Cal Gell-Body.-Within twenty-four hours of the seotion changes in the oytoplasm of tho oellbody are observed: it and its processes swell somewhat from the imbibition of fluid; the chromophyl particlcs (Nissl's granules) break up into fine dust, and may disappear (chromatolysis). The nuoli'us moves towards the periphery of the cell-body. Changes similar to these have been observed in the large oortioal motor cells of Betz after transverse section of the cord. (b) The A:.:on.--Just above the point of section nota.ble changes occur: tho neuro-fibrils become separated, presenting the appearance of a tress of hair; soon they take on active growth, throwing out branches ha.ving bulbous extremities. The growing fibrils are directed by chemotaxis through the new-formed granulation tissue, which unites the divided ends of the nerve, towards the emptying sheaths of the distal portion. By the time the fibrils roach the neurilemmal aheaths, the latter have rid them, selves of their oontents, and are ready to reoeive them. The fibrils penetrate the sheaths, forming new axis. cylinders; thereafter new medullary sheaths are formed. This remarkable power of :repair possessed by the medullated fibrea of the cerebro-spinal nerves is not shared by those of the brain and cord, a cireumstance whioh has been attributed to the faot that the latter laok a definite ne:orilemmal sheath. These fibres are probably endowed with some power of repair, however, for when severed by disease the neuro-fibrils of the oentral end ahow a tendency to sprout and form terminal bulbs, as in the case of divided nerves. In acute aDections of the neurone body--e.g., acute anterior poliomyelitis-the ohanges are very similar to those AIDS TO PATHOLOGY just described, but more pronounced; there occur tume· faction, vacuolation, complete chromatolysis, distortion and dislocation of the nucleus, which may be extruded from the cell, in which oase the entire neurone suffers permanent dissolu~ion, and can never be replaced. Every neurone in the organism is laid down in the embryo, and is adapted to last a. lifetime : it ma.y thus outlast a century. In chronic affections of the neurone body (e.g., chronic anterior poliomyelitis) there is simple atrophy-diminu. tion in the size of the cell and its processes, ending, it JDI_y be, in complete dissolution of the entire neurone. In such oases • pigmentary atrophy' may ocour, the body of the cell being reduced to a maas of pigment, bordered by a layer of protoplasm. The neuronic changes, both central and peripheral, which occur in peripheral, neuritis are similar to those whioh occur after soction of a peripheral nerve; also the secondary degenerations of the cerebro·spinal medullated fibres, save that in this case there is -no neurilommal shea.th to share in tho changes. The name periazial neuritis has been given to a disease of the axon involving the medullary sheath in parte, but leaving the MOns intact. It haa been observed in the neuritis produced by lead and diphtheria, in the posterior spinal roots in cases of tabes, and in the sclerosed nodules of disseminated sclerosis. Secondary Sclerosis.-When the proper nervous tissue of the central or peripheral nervous system degenerates and disappears, a secondary hyperplasia of the connective tissue takes place. In the case of the central nervous aystem this is spokon of as sclerosis. A familiar instance is the secondary lateral sclerosis of hemiplegia or para.plegia: the peripheral portions of the severed motor MOns disintegrate, and the neuroglia grows into and fills up the spaces left by them. At fil'Bt the new tissue consists of a large.meshed reticulum, but this in time is gradually converted into dense tiesue. Weigert's stain tints the myeline sheath deep blue; therefore, if a section of sclerosed cord is stainedDY this method, the sclerosed patches show up by their absence of coloration. Marchi's method of staining is b88ed OD the faot that osmic acid stains fat black. DISEASES OF THE NERVOUS SYSTEM 149 Toxic Degenerations of the Nervous System. A large number of diseases of the nervous system, both functional and organic, are due to the selective action of toxins on neurones. Thus, the convulsions of rickets are due to the action of a toxin (or toxins) probably generated in the alimentary tract, while all the organic 'system' lesions (e.g., tabes dorsalis) are the direct result of specific toxins. Indeed, putting aside the primary senile degenerations of the neuron.e--those, naInely, due to a genuine wearing.out process-neurone degeneration is very rarely spontaneous. It is practically always refcrablc to an ext$lsic cause, such as cireulatory defect-e.g., syphilitic endarteritis-or toxic action. Selective Action.-Tho selective action of toxins on tissue elements is in no case so remarkably displayed as in that .of the neurones. Not only is this selective action displayed as regards different groups of neurones, but also as regards different portions of the same neuronecell·body, axon, axonic terminal, dendrite, dendritic endorgan. Thus, progressive muscular atrophy is due to tho action of a toxin upon the cell-body of a lower motor neuronef lead palsy, to the action of lead upon the axon of such a neurono; while curari causes paralysis by acting upon the motor end-plate. The distribution of toxic nervous lesions is, however. not due merely to a selective action between neurone and toxin. but may result in Il,Lrge measure from a concentration of' the poison in certain parts of the nervous system. l'hus, in lead palsy the muscles chiefly affected arc situa~ed below the elbow, possibly because the poison is • largely absorbed from skin of the hands. Again. the subarachnoid space appears to offer a favourable breedingground for the Treponema pallidum, and it is probable that the concentration of thesc organisms in the cerebrospinal fluid determines the occurrence of syphilitic meningeal affections of the brain and spinal cord, and possibly also of general paralysis of the insane and tabes dorsalis. Okannel8 of Toxia lnfection.-(a) Through the blood. This is the usual mode of infection. Thus, the toxins which produce acute and subacute myelitis are transported in this way. (b) Through the cembro-spinal auid AIDS TO PATliOLOGY Ce) Along the spinal nerves; there is evidenoe that infeotion of the spinal oord may take l'lace in this manner. Homen injected streptooocci into the sciatic nerve of the rabbit. Some days after he found the miorobes in the spinal roots and the spinal oord; again, after injeoting the virus of tetanus and hydrophobia, the transferenoe of the poison to the oord oan be cheoked by dividing the nerves between the seat of inoculation and the cord. Experiments also tend to show that the diphtheria toxin reaohes the oord by way of the nerve trunks. Trophic Lesions. By 0. trophlo leBlo~ Is understood 0. gross structural oha.uge brought about by faulty nervous activity. The norvous meoha.niBms by whioh trophio lesions are produood Q,re ot severQ,l di:i!erent kinds: 1. Interruption of e:trorent nervous itnpule6S to muscle or gland oells oauseB the oells. thus bereft ot their nervo·BlJ.pply. to atrophy. Thus division of 0. motor nerve to a muscle oausos atrophy of the musole; diviSion of the chorda tymp8Jli oanses atrophy of the subm.a.xilllu'y gland; division of tho tostioular nerves, atrophy of thO testis. II. Intorruption of derent IronulBes a:l!eots nutrition in II. twofold way: (0) The a:i!ecteil res;ion. boreD all itt ia of the defensive rooobJmism atrorded by sensibility. ls'lla.ble to burns. cuts, and bruises. whioh readily become Infected and undergo ulceratIon. Similarly. a 'oint whIoh has lost sensibility to pain is liable to injurious oonoussions and twists. a olrownstanoe whIoh may help to ex:plain theartbritio ohanges whioh ooour in tabes and syringomyolia. (b) Owing to interruption ot the a:i!erent portion of thevlIoBomotor aros. tho normal reflexes oan no longer take plaoe in the a..I!eeted region. This mlilY lead to olrculatory disturbanoe. and thus to nutritional deteot. 3. Irritant nervous lesions are more apt to CBllSe trophio lesions than others. Suoh are neuritiS. partial. as distinguished from oomplete, section of a outaneous nerve. Inflammation of a root ganglion (resulting in herpes zoster). 4. Disturbed Vaso-motor action. by modifying tho olrou1a.tion locally. may give rise to struotural ohanges. Thus protracted hypermmia gives rise to hypertrophy; protraoted ischlmllia to overgrowth of the oonnectlve tissues, or if pronounoed to-necrosis. as IDay happen in Raynaud's disease. 6. Nutrition may be modill.ed locally as the rosult of psyohlc Influence. It 1s a.n Incontestable fact that concentration of the attention upon-a. portion of the skin may cause II. blister t'o form there. DISEAS.ES OF THE NERVOUS SYSTEM 151 The following a.re among the more common eXlloIllples of trophlc loslons: Glossy skin; sclerodormia; overgrowth of bair; alopecia; bianohlng ot hair; redema; ulceration; herpes zoster; thinning, splitting, thiokening, striation, lamination of nails; thickening and nodulation of aponeuroses (e.g., palmar fasoia) and synovial sheaths. Rarefaction and overgrowth of bone, polypoid ovorgrowth of synovial mombranes, degeneration of cartilage. The aClIto bedsore (whioh may dovolop a fow hours after the onset of myelitis). homl hemiatrophy. Cerebra-Spinal Fluid. Composition o! Cerebro-Spinal Fluid.-This fluid surrounds the brain, spinal cord, and origin of nerves in unbroken oontinuity. Total quantity, about 3 ounces (60 : 80 0.0.; hence abstraction of more than 10: 15 o.e. is held to be dangerons, unless, as in oerebro-spinal meningitis, the amount be increased). It is secreted by the ependyma covering the two ohoroid plexuses of the lateral ventrloles. Thenoe it runs through the foramina of Munro into the third ventriole, then into the fourth ventricle by way of the aqueduot of Sylvius, and eventually Into the subamolmoid spaoe through the foramen of Magendie and the foramina of Lusehka. The subarachnoid space is thus oontinuons with the 'lateral ventrioles, and, aoeordingly, any increase of pressure inside the lateral ventricles will be registered in the spinal subarachnoid space, unless thero be olosure of the aforesaid foramina.. (Acoordlng to some authorities, the oerebro-splnal lluid IB also sooreted by the endothelial lining ot tho subaraohnold &paee.) In hoalth the lIuid is of orystal olearness, with a speoiflo gravity of 1006 to 1008, and sllghtly alkaline in reaotion. It oontains a faint traoe of sero-globulin and of albumose, in quantity equal to about per cent. (with variations from .~, to .~~ per cent.). There is also 0. trace of a copper-reduoing substance which yields gluoosBZone crystals and a few endothelial cella, with an occa.sionallymphocyte. It is therefore of very low immune value. Its ohlef salt is sodium ohloride; thel'o al'e tl'aces of carbonateA and phosphates. The normal pressure of the lluid in the recumbent position supports a oolumn of water 2 inches high (or about 15 mlllimetres of Kg); in disease the pressure may incroa.se ten times. When withdrawn with the trochar and oannula, the :flow should not be in a steady stream, but • drop by drop,' generally at the rat!! of one drop per seoond. Anything approa.ohing a oontlnuous stream indicates all abnorma.l pressure. Morbid Conditions of the Fluid-P1'e8suu-Doos the lluld come away from the end of the cannula drop by drop, or does it eaeape quickly' In hydrocephalus, all forms1lf aoute meningitis, seme tumours (if large), obronio meningitis, the :fluid may run away in jets. or even pshos. '1:" 15 2 AIDS TO PATHOLOGY Oolour.-Is the 1luid clear. bloody. opalcscent. or purul~nt , Blood.-It towards the start of the 1low. it may be due to aocidental rupture of a vessel. It. howevcr. it Is intimatoIy mixed with thc cerebro-splnal 1luid. then it IDBY be due to injuries to the skull or spinal column causing rupture of a vessal into the subarachnoid spaco. or to hmmorrho.ge Into thc ventricles. or hromorrhago from tumours. ctc. Opalescence.-This IDBY be due to the presenoo of cells or bacteria. and a microscoplo examination must bo made to determine their nature. Pus.-If the 1luld Is distinctly purulent. tho causo Is a purulont moningitis, or a ruptured abscess. In rare eases of extreme jaundico the fiuid may be bllestained. In urmmia. urea. ammonia, and other nitrogeneus, products may be found. In diabetes mollitus, an appreciable amount of sugar IDBY be detected. Oyt0si8.-After staining. noto the following: Presenoe of red blood-colls, and thoir number. Is there a preponderanoe of polymorphonuelears or of mononuclears' Are bactoria prosont , Polymorphonuclear oytosls is usually present in acuto meningitis (pneumoeoocal. mon,1ngocoooaI. staphylococcal. streptococcal. etc.). and in aeute anterIor poliomyelitis; while lymphooytosis (small mononuclear) is usually a marked feature of tubercular meningitis. cerebro-spinal syphilis, general paralysIs of the insane, tabes dorsalis, trnIanosomillsis. and Is sometimes f011I!d in herpes zoster. Bacteria.-It bacteria are found. their morphologloal oharaoters should be noted-i.e.• whether ooeol or baoillI. diploooool. staphylooooei, streptococci, long bacilli or short baoilli. etc. In sleeping sickness. trypanosomes are found In the later stages. Prote:ins.-As before stated. in nOrIOBl cerebro-spinal1luld the amount of protein present is Infinitesimal; in disosse it may rise very high. In most acute a1fections of the nervous system -e.g., acute myolltls, acutc anterior poliomyelitis-thore is a oomparatively large amount of albumin present. assoclatod with a lcuooeytosis (polymorphonuclear- and lympho-cytosis). whoreas in syphilitic a:ffections of the nervous system tho ineroase in albumin is usually accompanied by a lympho-oytosis alone. In tabes dorsslis and general paralysis of the insane. choline, a produot of ncrve dogoneration, may be detected. A positive Wasserm8lUl's reaction of the fluid is invaluable In diagnOSing syphilitio a:ffeetions of the nervous system. It is found In about 97 per cent. of <lBBOS of goneral paralysiS of the insane. and in about 70 per coot. of cases of tabes dorsalis. (The reason that the vercentago Is not higher in tabes is that this disease may become stationary. whereas in general paralysis of the insane the disease is always a.etive.) LUMBAR PUNCTURE 153 LUMBAR PUNCTURE. Surgical A'Ultom1l.-The oord in early fretal Ufe extends the entire length of tho spinal oanal At birth it tormiI14to6 at tlLo level of the .third lumbar vertebrm; in the adult, opposite the lower border of the first lumbar vertobrro, more raroly opposite the border of the sooond lumbar vertebrlll. The depth of the spinal subaraohnoid space from the surface varies in ohildren and adults. In children it Is about 1 inch; in adults 2 to 21 inchos, or even 3 inches in some cases. Lumbar puncturo is done botwoon the third and fourth lumbar vertebrm (or botwoon the fourth and fifth) for the following l'OOosons: The spot is well below the termination of tho spinal cord; any pathologioal elements tond to gravitate in this region; tho dura mator is horo more firmly attached to tho laminm than it is higher up, and thorefore the needlo more easily pieroos it. Operation.-'I.'ho procedure is quite harmless. The instruments roquired are a stout oxplorlng needle about 4, inohos in longth, provided with a platino-iridium point, and e. stilette, several sterillzod test-tub08. The patient is either pla.ced on hls loft side, close to the odge of the bed, with his back :flexed as much as possible by drawing up the knees towards tho chin, or, it his condition permits It, in the sitting poeture, with the head dopressed botween tIm knees. Flexion at the spino slightly elevates the cord, widens the space betwoon the neural archeR, and makos taut tho ligament~ and membranes to be pierced by the noedle• .A generalanmsthetic Is advisable in both adults and children. The operator having sterlllzed bls hands. and tho skin over tho area. having been painted with. tincture of Iodine (so as to bottle up the organisms burled in the opidcrmiR), selects a point in tho spaoe between the fourth and fifth lumbar vertebrre. Tbls is easily found by taking the highest points of the iliae orests: a line joining these orosses tho fourth lumbar spino. The third or fourth lumbar spine having been do:ll.nod, the thumb of the loft hand should be placed on the one or the other, aocording to whioh space it is propesed to enter, and used as a guide. The needle, having been sterilized, is held firmly and entered i ot an ineh to the lett of the middle line, and i of an ineh below tho selected spine, boing pushed, but not stabbed, in a direction towards the umbilious, upwards, inwards, and torwards. Altel' tho needle has been inserted 2 to 2i inches in an adult (and 1 inch in ohildren), it will bo felt to go suddenly through a resistant layor, and if tho stilette be now withdrawn, oerebro-spinal fluid should drip from the oann1llo.. If the point strikes against bone, it should be withdrawn for e. short distance, and again pushed forwards in a slightly e.lterod direction. ' If, after several attempts, the operator falls to gain tho interior of the canal, it is advisable to withdraw the needle altogether, and to insert it, either between the second and third. 154 AIDS TO PATHOLOGY or the third and fourth lumbar vertebrro. Somc prefer entering the necdle in the middle line, as here there is no risk of hitting the bonc. It no fluid oomes away whcn the needle is apparently within the subarachnoid space, It may mean that Its bore is blooked; the stilette should then be pushed gently along it, and any obstruction thus removcd. In some cases failure to obtain fluid may arisc from the fact that the needle has not pieroed the meninges, but has pushed them in tront of it. Assuming this to be so, it is a good plan to perforate the membranes by means of the stilette, thus allowing the needle to entcr along the tract opencd up. The fluid withdra.wn should be received into sterilized testtubes. A fow drops of blood derived trom the accidental puneture of II> vessel may come away with the first drops of fluid; If Sll,. it should bc oolleotod in a separato test-tUbe, as for mioroscopical cxamination It is desirable that the fluid should be tree from blood. Aftor withdrawing the fluid and the needle, the wound should be closed with a dab of oollodion and ootton-wool. The patient Is then to rest for some hours. DISEASES OF THE KIDNEYS. The normal kidney is about' inches long, 21lnohes brood, 11 inches thick, and its weight is about 41 ounces. The corle:1; oonstitutes a little less than a third of its substance. As regards structure, the main point tu understa.nd is that there are not two kidneys, but thousands of kidney&-in the sense that eaoh individual tubule is in reality a separate kidney. This Is important in view of the foot that disease may desvGT many tubules and yet leave others unharmed.' Another- Item of interest is the faot that there is no Intertubular oonnoctlve tissue, tho tubules lying in oontaot with eaoh other. The kidneys are essentially tllters, their principal function being the oxoretion from the blood of the nitrogenous w&s~ products of the tissues--urea, uric aoid, eto. Thoyalso eliminato sulphates, olilorides, phosphates, and other salts; these, however, do not represent tissue metabolism, but are simply the sruts contained in tho food swoJlowed. The urea, urio acId, etc., are not manufaotured in the kidney trom raw material, but preexist as such in the blood, and are removed trom it by the renal epithelium (chiefly of the oonvoluted tubules) by a vital prooOBP of excretion. The salts and water are passed through the glomeruli by a biophysical prooess of tlItration. Uroto:J:ins.-The kidneys are also concerned' in the elimination, both in heruth and disease, of a largo munber of di1l'crent toxins. Thus, according to Bouohard, normal urine contains (a) a diuretio, (b) a narcotic, (c) a salivant, (d) a pupll-oontracting, (6) a heat-reduolng, if) an organio convulsant, and (g) an inorganlo ocnvulsa.nt. AnythiDg whioh interferes with the proper action of the kidneys may oause the retention of ono or more 01 DISEASES OF THE KIDNEYS 'ISS these substances. The toxins ot tho various infeotious diseases are largely excrotod in tho urine. It is, moreover, suggested tha~ a groot number of other diseases-e.g., epilepsy, aoute maniasare toldc in naturo; it this view is oorrect, we may suspect that their specific toxins may be presont in tho urine. and itis probable that one day suitable tests will be devised for their detection there. The existence of an internaZ BeC7"etiIm has not been satisfaotorily proved. nor has that of secretory nerves, but the kidneyS are abundantly supplied with 'IlaBO-motO'l" nenes. FIG. n.-CORTIa OJ/' KIDNEY. I, Interlobular artery; 2, Malpighian body; 3, convolutod tubule. Nephritis. The term 'nephritis' is used in the generic sense to include in:fl.a.mmations of both kidneys, whether acute or chronic. It is probable that all forms are caused by the action of poisons (distinot for each variety) oonveyed by the bloodstream to the kidneys. Quickly-aoting poisons oause acute nephritis; slOWly-acting poisons chronic nephritis. These poisons may be derived from baoteria, be absorbed from the oro-a.limentary tube, or they may be produot of a. vicious meta.bolism of the tiBBues. 15 6 AIDS TO PATHOLOGY Inasmuch as acute nephritis is a frequent sequel of scarlatina, and sometimes of other fevers, it would indicate that in other cases of acute nephritis a bacterial toxin is the probable cause. As the tubular epithelium is more especially involved, we must assume that these poisons are particularly irritating to it. Possibly the great exoretory oapacity of the kidneys may lead to an &ooumulation of suoh poisons in the renal substance. In both acute and chronio nephritis the most conspicuous morbid changes are to be seen in the cortex of the kidney, especially in those parts of it where physiological aotivity is greatest-that is, in the glomeruli and C01woluted tubules. The wdema which is assooiated with many forms of nephritis is due to the circulation through the tissues of an aldema-produoing toxin. (Renal aldema is more marked in the early morning; cardiao aldem.a in the evening.) Various subdivisions of nephritis have been made by different authors, which has rendered the subject very complicated, but it is doubtful if the disease ha.s not been over-classified. Au lond, inflammation of the kidneys is the same in principle as inflammation of other p&fIIs of tba body, the dlfferenoes in the phenomena arising from the peculiar struoture of the kidney substance which is composed essentially of a closely-packed mass of epithelial oells. Reduced to simple principles, &oute nephritis is characterized by hyperremia, exudation, and swelling up, with subsequent detachment of the epithelial cells; and chronic nephritis by fatty degeneration of the epithelial cells and the forma.tion of new connective tissue. Acute Nephritis (Acute Parenchymatous, Desquamative). -The kidneys are swollen, their capsule!! stretohed, sometimes bursting. The swelling is the outcome of: (a) Congestion, (b) exudation, (c) swelling of the tubular epithelium. The exudation is partly intertubular, but ohiefly intratubula.r (this being the path oflcast resistance). ~he intratubular exudate, by coagulating, forms a cylindrioal mould, or ' cast,' of the interior. If the cast oonsists solely of the coagulated colourless exudate it is known as a DISEASES OF THE KIDNEYS 157 hyaline ca8t; if detached epithelial cells adhere to its outside, it is termed an epithelial Ca8t; if the adherent epithelial cells have undergone fatty or granular degeneration, it is called aJatty or grantda'l' cast. The damaged tubules a.llow the esoope into the urine of the serum-albumin and serum-globulin of the blood (but never :fibrinogen). The casts and shed epithelium tend to block some of the tubules, and this largely explains the scanty urine of acute nephritis. . There are two classical forms of acute nephritis, each varying with the nature of the partioular toxin that causes it. (a) Glomerular Neph'l'uia.-The stress of the inflammation falls more espooially on the glomeruli, the vessels becoming much distended and often rupturing (so allowing blood to pass into the urine). The cells inside Bowman's capsule proliferate, in some cases to such a degree as almost to fill up its interior, and by compressing the glomerular tuft cause it to atrophy. (b) Tubular Nephriti8.-Here the stress of the inflammation falls more espeoially on the epithelium of the oonvoluted tubules, the cells lining which swell up, proliferate, and beoome detaohed. The tubules are sometimes choked with these detached cells. The swelling of the epithelium often oauses the tubules to present a v~ricose appearance. By dislodgment of the epithelium, portions of the tubules may become ohoked with the cells. When recovery scts in, the inHammatory produots are in part expelled into the urine and in part absorbed. Some of the tubules are rendered kor8 de combat and atrophy, whilst others, hitherto imperfeotly developed, attain full physiologica.l maturity, and functionally com. pensate for those irreparably damaged. !rhe Large White Kidney.-lf, however, recovery does not ensue and the disease becomes chronio, we have the condition known as 'large white kidney,' which is also known as chronio parenrilt/llmaJoU8 nephritia (as it is a further stage of acute parenchymatous nephritis). The organ is now enlarged (the two kidneys together may weigh 28 ounces, as against 9 ounces in health). The surface has a pale appearance and the capsule readily section, the cortex is seen to be enlarged. strips off. On 158 AIDS 7'0 PATHOLOGY and bosides a general paleness there is an opaque mottling. The convoluted tubules are much dilated and filled with detached vacuolated epithelial calls in a state of fatty and granular degeneration; fatty and grnnular casts occupy the straight tubules, and proliferated epithelium is seen within Bowman's caspule. Smo.ll embryonal cells (which may later develop into fibrous tissue) make their appearance between the tubules. Albuminuria is profuse, but cardio - vascular changes are not a pronounced feature. The patient is water-logged, and generally dies within two years, either from urmmia or some visccral inflammation (pericarditis, pneumonia, pleurisy). If, however, he continues to live, the embryonal cells lying between the tubules organize into connective tissue, and the disease now passes into the stage ofThe Pale Granular Kidney (Secondary Chronic Interstitial Nephritis)_ In a typical case of this disease the organ is pale, fibrous, shrunken, and granular on the surface. The cortex may be of normal thickness, or much reduaed in size, according tQ the time the disease has lasted. The fibrous tissue is chiefly intertubular, many of the tubules and glomerular tufts are atrophied, whilst other tubules are blocked with detached epithel~al cells. It is very rare, the writer having seen but three cases, all of whom died from acute urremia within a few months of the development of' albuminuric retinitis.' (Ede:rna is generally absent, and so the disease is often overlooked until the onset of urremia, or failure of vision. (Sir Rose Bradford contends that the pale granular kidney is a chronic disease from the beginning, and not a development from a preceding stage. If this is so, it is .manifestly due to the action of a chronic renal poison quite distinct from that causing the next form of Granular kidney.) Red Granular Contracted Kidney (Primary Chronic Interstitial Nephritis).-Red granular contracted kidney is not a sequel to acute nephritis, but is ab initio a chronic disease, due to the long·continued action of a. specific renal poison, generated either within the alimentary canal or from some faulty metabolism of the tissues. The poison in question appears to operate coincidentalty both on the DISEASES OF THE KINDEYS 159 kidneys and the cardio-vascular system. The kidneys are small, sometimes remarkably so, Hilton Fagge quoting 0. case in which the two together weighed under 1t onnces. The colour is usually 0. dark red. The capsules are thickened and adherent, and, when removed, portions of kidney tissue are pulled off with it, the exposed surface to showing small granulations, varying in size from 1- inch. On seotion, the cortex is seen to be shrunken, often being reduced to 0. mere shell of but I to t inch in thickness. Cysts, both macroscopic and microscopic, are often fo_und in the shrunken cortex; they arise by obstruction of the tubules. The pathological changes are essentially: A fibr08is, with tubular and glomerular degeneration. Concerning these changes two explanations are offered: (a) That the renal poison causes a primary fibrosis, the tubular degeneration being due to the pressure-effect of the newly-formed tissue; (b) that the renal poison causes a primary tubular degeneration, and the cpithelium, in process of disintegration liberates So poison which, diffusing through the kidney substance, provokes a seoondary fibrosis. The fibrosis is markedly different from the normal connective tissue, being tough and coarse, and is specially charaoterized by its tendency to oontract. It has tile following distribution: (i.) Periarterial. (ii.) Periglomerular. (iii.) Peritubular. (i.) The periarterial fibrosis occurs especially in conneotion with the interlobular arteries. The strands of fibrous tissue aronnd these vessels contract, and this explains the depressions between the granUlations on the surface of the organ. The arteries are sometimes so greatly compressed by the shrinking connectivo tissue as to become almost obliterated. (ii.) The capsule of Bowman is greatly thiokened by the formation of ooncentrio layers, and in advanced oases the entire glomerulus is oonverted into a laminated fibrous ball. (iii.) Instead of the tubules being in direct oontact, as .n- zoo AIDS TO PATHOLOGY in the normal kidney, they are separated by bands of fibrous tissue. Many of the t.ubules are a.trophied; others sllow an enlarged lumen, the epithelium of whioh is either doto.ohed or degenerated. The oysts seen in tho oortex are caused by the distension of tubules, the ohannels of whioh have been oonstrioted by fibroid contraotion. Tho diseaso is of froquont occurrenco aftcr tho o.go of forty, and very insidious in its courso, sometlmos not boing dlagnosod until noor its fatal tormination, whioh is usually from cerebral i&mmorrhag6 or from cardiac Ia:UW6 (dllo.ted loft ventrioio). The patient may go first to the ooulist booause of faJluro of his eyesight (albuminuric retinitis). Many oases of cardlo.o tnllure arc ofton regarded as oo.se9 of primary heart disease, and not due t.o reno.l disease, iuasmuch o.s during lifo the ma.1n symptoms o.ro cardlao. Urmmio oonvulslons arc rare. (Of 126 oases oollected by llilton Faggo, only 15 ended iu oonvulsions.) Correlative Pathological Changes in Chronio Nephritis. Whcn onoo nephritis ho.s boooomo chronic, there occur, with rare oxceptions, cardio·1JQ8ctdar changea, whioh are most markod in tho 'Intorstitial' forms. Tho loft vontriolo of tho heart becomos hypertrophlod, tho smallor arterics are thiokened by inoroaso In their musoular and flbrous tlssuo, and atheroma is ofton presont in tho larger o.rtorios, and in those a.t tho base of the brain. Theso ohanges are most oharaotoristlcally soon In tho two kinds of granular kidney. 'l'heir pathology has exoitod muoh controversy, and no two authorities appear to o.groo OD the subJoct. It is, perhaps, somowhat as follows: In tho oarly stage of granular kidney a substanoo having a vaso·oonstrictor aotion olrculates in the blood. What this Bubsto.noo Is, or whether it is the OUll whioh is responsible for the progJ"OSsive renal disorganization \vhioh oha.racterizes this diseaso, it is impossible to say; but it is probably not the result of defeotlve ronal excretion, Booing that its oJloots are observecl long before tho kidneys arc seriously disorganizod. The substanoe in question Co.usos 0. widespread constriction (hyportonus) ot tho systemio arterioles, the intraronal arterioles roDUlining relaxed. Now, those are the vaso·motor oonditions most favourablo for diurosls--i.e., an Inoreased pressure in tho systemio artorios, IIoIId 0. diminution in tho resistanoe otrered by the Intro.ronal arterioles, tho oonjoint efCeot being to oauso a great augmentation in the pressure, and a oorrespondlng In' oreased rato of blood·fiow. within the renal capillo.rles. In DISEASES OF THE KIDNEYS 161 short, the vaso-oonstriotor substanoo, whioh Is ever present, brings about lust those vaso-motor oonditions whioh aro most favourablo to its elimination. (It Is 0. mistake to IIoBsume, as many writers do, thll.t mere inorell.8o In the systemlo blood -pressure neoossarlly inoroll.Bes the urinary tiow_ A genera.lized arteriolar oonstriotion, including tho renalaroo., would oause a diminished flow In spite ot tho augmented blood-pressure. Hence, to explain the polyuria of granular kidney we must assume that a generalized arteriolar eOWltriotion oausing the high blood·pressure is acoompanied by a dilatation of the intraronal arterioles.) The constriction involves the arterioles essentially. It Is hero that tho augmented vascular resistance of ronal disease resldos; the view that it is situated In tho oaplUo.ries is untenable. Both under physiological and pathologioal conditions' periph· eral rMistance • resides ossentlally In the region of the arterioles. Tho writer has shown that the oontribution of the capillaries to peripheral resistance Is pra.otlcally negligible. The hypertonus tends, however, to Involve the entire systemio arterial tree, the pro·arteriolar oonstriction--i.e., of the arteries proximal to the artorioles--being probably of a compensatory no.ture, tending as It does to protect the arteries fl'om the distending effeot of the heightened blood·pressure. One ef the most important functions of tho mnsoulo.r eloments of bloodvessels is by their active oonstrlctlon to provent tl)e vessel walls from undergoing 0. progressive dilatation and elongation. Thus. tho radial artorios In granular kidnoy often feel small, • tlghtenod up,' and incompressible. Those may. however, be largo and Incompressible, and In suoh oases the hypertonus, in the upper oxtremities at least, Is llmited to the arterioles. Th!s oondltlon ot arterial hypertonus loads to hyportrophy of tho media of tho hypertonic arteries, and to 'hypertrophy ot the left ventrlole, whioh. owing to the augmented peripheral resistance, has inoreascd lvork put upon ft. On tho othor hand, the media of tho hypotonio intraronal art.eries tends to atrophy (W. Russell). In the hyportonio arteries tho intima IDld adventitia stand in sharp contrast as regards the induenoes they are subjected to, for wbile a hyportonio melUa protects the onvoloplng advontltia from tho augmented blood-pressure, tho intima recoives the full brunt of that pressure. as does also the endocardium of tho left ventriele. This state of things eontlnulng hour by hour, by day and by night, year aftor yoar, it is not SUl-prising that both those struotures should undergo some responsive change; b1'lolly, they tend to thicken. whUe the largo arteries and the loft Vllntriole, espeolally II. the region of th('l valves, booomes atheromatous. A further effect ot tho augmented blood-pressure is that the lett vontrlcle and entire systemic arterial tree tend to dilato, the extent to which they do so depending upon the bebavipur of their musoular eioments. 11 162 AIDS TO PATHOLOGY So long as t.he musouIar tissue of the heart remains sound, it is oapablo of otfeotual systole; but when it dogonerates, as in procoss of timo it does, the degeneratod musele tlbres being replaood by fibrous tissue, the left ventricle falls to empty itsclf adequately during systole, an oxcess of residual blood romaina after systole, and thus by dei:roos it comes about that the left ventriele, overdistended during its stretchable llhase of diastolic relaxation by this load of residual bloed plus toot flewing in from the lungs, boccmes unduly stretched, and yields--i.e., dilateB-sueh dIlo.tatien being 0. oemmen oause of death after tlfty. In like manner, the extent to \vhieh the IIrteries become stretched, giving rise te tertueslty and dilatation, depends upon the cendltion of the muscular media. Let us suppose hypertonus to be maintained fairly generally throughout tile arterial tree; It is probable that In such a case little or no perftJ.u.nent yielding wID occur until the muscular elements have been to a large extent replaood, as in advanced oases they tond to be, by a hyaline fibrOid material. In thoso arteries, however, which do not become hypertonic, carly yielding is likely to occur. Thus, In the cases in which the radiu.larterios aro tightly eontraoted, those vossels may long remain quito straight and undila.ted.-even, Indood. throughout the entire ClOurse of the disease; but In those oasos in which the radials tend towards 0. state of hypotenus, they early become dilated and tortuous. It is probable also that the oceurrence or absoneo of a dIlo.tcd aorta In granular kidney largnly· depends upon the dogroo ot tonieity of the vossel. The adventitla tends to romaln unalreotod in granular kidney so lOng as it IS proteeted--i.e., so long as the blood-pressuro is borne of! from it by a hypertonie media. If the media does not· beoome hypertenio, or if, In preeoss ef time, a hypertonlo media degeneratos, the adventitia yiolds before the augmonted bloodpressure, and undergoes compensatorythiekenlng. Among the other rosults of the heightened blood-pressure in granular Iddney are the formation of miliary aneurisms In tho oorebroJ arteries, • granular kidney' being the cause par excellence of cerebra.l apoplexy. The <edema of granular kidney is genorally a torminaJ ovent, and Is then usuaJly • cardiac ' .i.e., duo to dilatation of the left ventriele. In any form of ohronic nephritis, but especially in granular kidney, there is 0. marked tendency to hmmor,hags. AB Hale White puts it: 'A per80n with nephritiB may bleed from anywhere-e.g., from the brain, retina, lobe of the ear, nose, lungs, alimentary and urinary tratlts.' Patients with' granular kidney' generally have emphysematous lungs. Pleurisy, pericarditis, and pneumonia are common DISEASES OF THE KIDNEYS 163 complications of Bright's disease, whether acute or chronic. Albuminuric retinitis is met with in about 28 per oent. (Gowers) of all cases of Bright's disease; it is muoh com· moner in the ohronic forms of ranal diseasc. The prog· nosis is very unfavourable, most of the pa.tients dying within a few months of the first appearanoe of retinal changes. The condition suggasts some virulent form of toxremia. Scarlatinal Nephritis. In this torm ot Bright's dlsoaso the genoral phenOlnono. are the sarno as those described unde\' acute glomcrular nephritis, but thore o.ro somo special pOints to be mentioned ill oonnectlon with it. Tho scarlatinal polson has a special atHnity for tho lIalpighian bodies and tho small artorlcs connccted thero\vlth. The intima ot theBO arterioles undergoos hyaline degencratlon Bowman's oa.psule is swollon, a.ml the cells ot its epitbolia.llillillg proliferate, In some cases to suoh a. degree as almost to till up Its Intorlor, and, by compressing the glomerular tuft, to causo its atrophy. Should the diseaso become chronie, by ono to throe years' time, tho wholo Me.lpighlan body may be seen to be oomposed of concentrlo lamlDm of fibrous tissue, with complete obliteration of tho glomorular vesscls. The branches of the renal artery become thickened from abronie endarteritis and periarteritis. War (Trench) Nephritis. An acute disease which takes the form of blocking of the glomerular capillaries with changes in tho epithelium of the convoluted tubules, In association with this there Is often desquamation of the eplthslium of the terminal bronchioles IUld the connooted alveoli, a tact which explains tho important BYIDptem-dYBPnrea. Hugh l!oIac'\ean adduces evidence suggestIng the oonveyance of an infcotion by moans ·of body·vermin, probably lioe. Tuberculosis of Kidney. This is usuBlly B diseBse of 2arly adult life, and in the largo majority of cases is primary-due, i.6" to infection throllgh the blood-stream. It is unilateral in 92 per cent. of cases (KrOnlein). Sometimes it is associated with tuberculosis of the epididymis. the vas deferens, the vesiculro seminales, and the trigone of the bladder. It may begin in any part of the organ, but more com- AIDS TO PATHOLOGY monly starts near the apices of the papilllll (this accounts for the hiematuria, which is often the firat sign), sprcading thence into the kidney substance, on the one hand, and into the calices, pelvis, and ureter, on the other. Caseatiop and ulceration take place, and the curdy pus and necrotic debris thus resulting are expelled with the urine. If at this stage the interior of the bladder be viewed with the cystoscope, the opening of the ureter is seen to be everted and to ' pout,' and the urine trickling from it to be turbid. If the thickened and contracted ureter becomes blocked by the caseous material, pyonephro8is results, and this in tum may be complicated by the formation of a perinephritic absces8 in the loin. In many cases the urine contains, in addition to the tubercle bacillus, the Bacillus coli, the staphylococcus, and the streptOi!occus. At the post-mortem examination of an advanced case the following changes are found: The kidney is greatly. enlarged; the perinephritio fat, thickened by chronic infiammation, is adherent to the capsule; the cortex is represented by a toughened shell; the medulla and papilllll have disappeared; the pelvis is dilated; its walls are thiokened, and its interior may present a characteristic 'mouse-nibbled' appearance. 'lhe dilated cavity is filled with a curdy pus, which in some cases is transformed into a putty-like mass. The ureter is adherent to the neigbbourjng parts; its walls are infiltrated with tubercles, and its lumen is contracted. Proteinuria without Nephritis. The chief prctein present In the urine of nephritis Is serum albumin; globulin-cf which there are two kinds: (a) ouglobulin o.nd (b) pseudoglobulin-also occurs, but the amount is relatlvoly low. The term • proteinuria without nephrit,is' Includes all thosc conditions described as functional albuminuria, physiological albuminuria, Intermittont o.lbuminuria, transient albuminuria, orthostatic, cyclic, adolesccnt, etc., in nono of which are there any signs of organiC kidnoy disease. In all these casos thero Is poth albumin and euglobulin present in tho urine (in tho ra£io of about 2: 1). In that form of functional protoinuria, howevor, known as • leaky' kidney, the condition is essontially that of olobinuria (the globulin being euglobulin, with whioh is assooiatod lipolds and fatty acids), the ratio of albumin to glo· bulln being 1: 2 to 6. The turbid urine somotimos found in • leaky , lddney is due to the presenoe of lecithin-globulin, DISEASES OF THE KIDNEYS 165 TraDBitoQ' Nephritis. In the albuminuria of pneumonia, enterlca, diphthoria., and other febrile disorders, a toxin must In Homo way damago the tubules, allowfng the escape of the albuminous oonstituonts or the ·blood. When this happeWl, the condition Is known as transitory nephritis. The ingestion of turpentine, oantharides, mer01ll"Y, and other poisons, may e.lso cause albumlnmla. Cantharides in somo oases Induces a marked glomerular nephritis, in many resp60ts rosembling soa.rlatlnal nephritis. In aeute alcoholism temporary albuminmia Is common. Syphilis of the Kidney. In secondartllll/Philis there may be albuminuria (often in tho form of looithin-globulin), due, probably, to an injury Infliotod on the renal epithelium by tho sp60iflc toxin. In tertiary B1/Philill thero may be elthor a diffuse gummatous infiltration ot the kidneys, or the development in them of definite gummata (as in the oa.so of tho liver). Tho urine in thoso syphilitic oases may oontain abundant albumin. yet dropsy amI the other symptoms of Bright's disease may be absent. Congenital Oystic Disease. This is a oonditlon met wfth In new-born children, In whieh the kidneys are greatly enlarged and eonverted Into a ma.ss of oysts, suggQstlng In appearance a bunoh of grapes. Tho cysts, separated by the remains of the ronal tissUll, are lined with epithelium, and oontaln an albuminous fluid. The propor kidney substanoe Is atrophiod. The dlsoase has boon attributod to somo anomaly in developmont, or to an Inflammation of tho pa.pl11l1), oauslng occlusion of the duots. It often oooxists with other oongenltal defeats, Bueh as hydrocopha.lus. defeotive urinary bladder, oto. A similar oondition Is sometimos, but very rarely. mot wfth in adults. In this form also the kidneys are greatly enlarged. and may weigh from 1 to 6 pounds. Hydronephrosis. Hydronephrosis is tho oonilition in whioh tho kidnoy is oonvertod, partially or ontlrely, into a oyst, as the result of some obstrnotlon to the urinary outflow. A sudden and absolute bloek never causes it; the obstruction must be Blowly applied. 'l'ho pelviS IUld the oa.lloos undergo dilatation; the medulla beoome~ atrophied, the proeess of atrophy starting at the papillm and spreading outwards; and ultimately tho kidney is transformed Into a ~ero oyst. whioh may be either small or of o!lnslderablo 166 AIDS TO PATHOLOGY size. The ureter is dilated, and In extreme Cll.B<lB mo.y resemble a portion of the small intestine. The condition may be congenital or acquired, and, according as the obstruction affects ona or both Sides, unilateral or bilateral. Tho oongenital causos arc dovalopmontalabnormalitios of the ureter and imperforate urethra; the causes in lator lite are such conditions as the presence of a oalculuB In the ureter, cicatricial contraction of the ureter, prossure on tho ureter by a growth (e.g., carcinoma of the uterus), enlarged prostate, and strieture of the urethra. Tumours 01 the Kidneys. Theso are very rare. They alO adenomata, rhabdomyomata. sarcomata, and composite tumours. '!'hOBO la.ttor contain fat, unstriated muscle, myxomatous tissue, and epithelium; they may attain an enormous size and metatasize. Hypernephro. mata, composed of a tissuo similar to that of tho oortox of tho suprarenalB, may be found embodded in the cortex ot tho kidnoy (thoy are also found In the suprarenoJs,llvor, panereas, spermatlo oord, epididymis, eto.). The larger ones are vary malignant-. DISEASES OJ' THE LIVER. Avarage weight In adult= 50 to 60 ouneos, being ono'fortieth of tho body·weight. At birth=one·twontieth ot bodY'welght. Tho liver is doveloped as a diverticulum of tho primitive gut. Tho liver colIs are therefore hypoblastic, and the stromata moso. blastio in origin. The orga,n is composed of lobules, each 01 which is about r. inch in dls.meter. Botween the lobules is a IlUppon.ing eo1mOOl:.ive t.issue ca.rrying the lymphll.tl.IlB, b100U.vwsels, and blle-duots. Within thG lobules 1\1:'0 th~ liver colIs, closely packed. in form polyhedral from mutUal Pl'OSBure. and separa.ted from one another by a sparso and very delioato tiBBue, oontinuous with the interlobular connective tiosue. The portal vein drains the blood from the capillaries of the wholo of the alimentary mucous membrane between the lower end of tho cesophagus and tho lower end of the rectum. It terminates in the capillaries of the liver lobules, where a junotion is effooted with the eapillarios of the hepatic a:.;tery. The blood is carried from the liver lobules by the hepatic system oj 'IIeim, and thence to the right heart. The portal circulation is pecuIiarin that it begins anq ends in capillaries, and is destitute of valves. All the substances absorbed from the gastro-intestinal tube (with the excep. tion of most of the fat), pass into the portal system, aud therefore have to be subjected to the influence of the liver before they can enter the general circulation. DISEASES OF THE LIVER 16'] Tho livlll' ill the groo.t biochomioa.lla.boratory of the body. It normallyreduces IIlIIJlY nitrogenous wa.ste produots to substanoea ur08, uric a.cid) which the kidneys oxcrote; it destroYB ptomaines and other poisonQus bodies, is strongly Phagooytio, and. ia the greoI. deto3:inaJIBr or blood-purifier. lnterteronoe with those tunotioIUI l~ds to Buto·lD,toxioa.t1on a.nd impa.irment of tho general health. (e.g., SulJLPbultlr Tle~"6_ .f.I I I r..rerlor I I CcJvR.. Inl:t1'ttobut ..r TIeL". . FIG. IS.-DIAGRAM SHOWING CIRCULATION OJ' THE PORTAL BLOOD THROUGH :t'HB LIVER. The portal vein ia soon to diVide and subdlvldo, and to br~k up into tho interlobular veins which run betwoon the hepatic lobulos. From the interlobular veins capillarIes (portall pa.ss to tho Intra.lobular veins. Theac a.re gatlaered up into the sublobuJa.r which enter the hepatio veins (of which there 'lm1~~,""II'lMIu ~ ~ 'My, 'i1la. ~'ml __"'ft>. 'iUb intralebular brnnchos of the hepatio a.rtoriea form capilla.ries, whloh unite with the pOrtal oa.plUaries. latmdice. Ja'ltndics is a condition in which the bile enters the geneml ciooula1iion, and stains the fluids and tissues of tho body yellow. It may be due to: (a) Bome ob8t1"lldicm td the O'Utjlow oj bile i"to tke duodenum, in consequenoe of which it is fh'St absorbed by th& lymphatics of the liver, and thence passes into the blood·stream through the iympha.tic duct. The obstruction may arise from (i.) caUBeS acting within the lumen of the ducts (gall.stones); (ii.) causes primarily involving the duct waJls (ca.tarrh of the muoous lining); (iii.) pre9SUre from without (tumours, espeoially malignant disea8e of the liveror panorelloli). and hepatio oirrhosis. 168 AIDS TO PATHOLOGY (b) Some affection of the secreting cells of the liver, as in hypertrophic biliary cirrhosis, alcoholic cirrhosis, the various forms of toxic jaundice (delayed chloroform poisoning, phosphorus, etc.). Toxic Jaundice produced by the Action oj Chemical Poisons. DUring thE' war cases of toxic jaundice were brought to light amongst munition workers and those engaged in work involving the use of dangerous poisons, absorption taking place through the skin. Amongst the most important poisons are: tetrachloride of ethane, trinitrotoluene, dinitrobenzene, dinitrophenol, and picric acid. Post·mortem examination showed that an invariable condition is intense degeneration of the liver-colis with great deposit of fat in them, similar changes being also found in the kidneys and heart. Fatty Degeneration. For pathological purposes the liver lobule may be divided into three zones. Fatty degeneration begins in the outer zono, amyloid disease in the intermediate zone, and' nutmeg' liver in the central zone. The organ is enlarged, light brown, and in advanced cases even yellow in colour; on section it presents a greasy appearance. In the slighter cases the fat globules are limited to the cells of the peripheral zone; in fullydeveloped cases the fatty degeneration affects all the cells of the lobule. The liver may become markedly fatty in phthisis; chronic alcoholism; phosphol'1ll.s, arsenic, or chloroform poisoning; in pernicious anremia, and all other forms of severe anremia. Fatty livers may be caused, like the foie gras of Strasburg geese, by over-feeding, underexercising, and a heated atmosphere. Cloudy swelling is liable to pass into fatty degeneration; hence fatty degeneration of the liver may be found in diphtheria and all other acute infections. Lardaceous or Waxy Liver. The organ is much enlarged-even to three times its normal size-and though its general contour is preserved, the edges become thick and rounded, and the whole mass DISEASES OF THE LIVER 169 is 110 compact toot it outs like raw baron. The out surfaoe has a waxy appearano&-henoe the name. The neighbouring livel' oella are often atrophied, and fatty degeneration is oommon. A wlllLk solution of iodine renders the amyloid material mahog~y- brown, while gentian v.iolet stains it a deep rose-pink and the normal tissues blue. The ohange begins in the intermediate zone. The disease is always associated with lardaceous de· generation of the spleen and kidneys. Chronio Venous Congestion (' Nutmeg Liver '). This condition is caused by obBtruction to the free flow of the blood from the hepatic veins, as the result either of heart disease or of primary obstruction in the pulmonary circuit-e.g., emphysema of the lungs. or fibroid phthisis. (The most pronounced forms are found in mitral stenosis.) A fact to boar in: mind in connection with this disease is that no va;lves intervene between the central intralobular hepatio veins and the right heart. Thus, when compensation fails-6.g., mitral regurgitation-the ' backwash' from the left heart will produce its effects first on the lungs, then on the right heart, and then very readily on the ValTelOSS hepatio veins. Oour8e of Ihe DiBease.-The central intralobular vein becomes much distended and thickened, and the capillaries opening into it become dilated and tortuous. The liver cells atrophy from the centre of the lobule outwards. The centrol zone of the lobule becomes pigmented (the pigment being derived either from the blood or the bile), while at the periphery of "the lobule the cells tend to undergo fatty degeneration, so that on section there is seen a dark innor zone alternating with a pale peripheral one. Hence the liver presents a marbled, or 'nutmeg,' appearance. Soon or later some fibrosis occurs, first in the contre and then at the periphery of the lobules. In advanoed cases the cells of the inner zone are completely destroyed. In the early stages the liver is enlarged as the result of the mechanical congestion; later on it becomes smaller from atrophy of the liver cells, and the capsule undergoes thickening, and may present a wrinkled appearance. AIDS TO PATHOLOGY On section much blood ma.y gush ou1l; on washing the surface the characteristio 'nutmeg' appeara.nce is displayed. Abscess of the Liver. Ab8IJes8 oj eke Liver is always due to infection by microorganisms. The two principal types are the PYOJmio and the Tropical. Pymmic Absce&se&.-In ordinary pymmia. abscesses rarely occur in the liver. the more usual Bites being the lungs and the joints. When pyremic abscesses do involve the liver. they are small and multiple, and contain a putrid yellow pus. In 81J,ppurative pylephlelJitiB (' portal pyOJmia ') the infection comes from some part drained by the portal system of veins, generally from an ulcerated portion of the alimentary tube; abscesses ma.y also follow operations for hremolThoids. They are small and numerous, and lie in the course of the distribution of the portal vein, the bra.nches of which are seen to be filled with puriform clots. Tropical Abscess.-This disease is due to infection by the Entamwba hiBtolytioa, conveyed by the portal circiJlation, and in lihe majority of cases is secondary to a dysentery owning the same cause. "Alcohol is probably the most important' soil preparer.' The pus is of a. slimy, gummy consistenoe, of chocolate colour, and composed of necrosed and liquefied liver cells, with an admixture of blood, ordinary pus cells being either few or absent. II i8 8terile, no cultures of bacteria being obtainable by the ordinary methods. As pointed out by Manson, the entammbm are numerous in the spreading margin of the abscess, and though absent in the pus when first drawn off, they make thoir appearance in the discharge about three days later-that is. when the walls of the abscess begin to granulate and to contract. The abscess is generally situated deep in the right lobe, and may contain several pints of fluid. After a time the pUB tends to make its way to the surface of the liver, oausing adhesiorus to neighbouring structures; and if the condition is untreated, the pUB ultimately escapes into the pleura. lung. peritoneum. or externally through tho DISEASES OF THE LIVER IilI abdominal walls, and in rarer cases into the stomach, gall-bladder, hepatic duct, portal vein, inferior vena. oava, pelvis of right kidney, perioardium, or other parts. Oocasionally the abscess becomes surrounded by a thick fibrous ca.psule_ In rare instances absoesses in the liver are caused by a auppuratt'1l{l hydatid, and by the 8treptothriz aonnomycea. Subphrenic Abacess. Owing to the cruoitorm arrangoment of the laloitorm, ooronary. and Iateralllgaments ot the liver, there are six possible situo.tlons whloh a subphrenio absooss may ooonpy-four intraperitoneal and two extraperitoneal (between the layers of the coronary ligament). The following table (takon from Barnard's • Contribntions to Abdominal Surgery ') gives the position in seventy-two cases: Duo. Gastrto Ap'l'OD- Hepatio denal mcer. diCltis. Abscess. moor. Intraperitoneal, right anterior Intraperitoneal, fe1ht posterior Intraperitoneal, 1 t anterior Intraperitoneal, left ~sterior Extraperitoneal, ~h Extraperitoneal, Ie t --- - - - - --4 1 16 2 0 1 10 6 1 0 l' 0 7 1 1 0 15 0 1 2 1 0 2 0 Cirrhosis of the Li'ter. Of this disease there are three classical forms. The oause in each would appeo.r to be some irritant, probably toxic in nature, _present in the liver, and brought thereBy the porta}, blood (alcoholio cirrhosis); By the bile-dulJt8 (hypertrophio cirrhosis); or By th..e general circulation (syphilitic cirrhosis). Alcoholic Cirrhosis (' Hobnail Liver,' 'Gin-Drinker's Liver,' Chronic Interstitial Hepatitis, Atrophic CirrhosiB).--The esaontia! pathological change in this disease is an 172 AIDS TO PATHOLOGY inorease in the oOIUleotive tissue around the inteTlobulot bro/TWMs 0/ tke portal vein. An irritant, oirculating in the portal blood, first starts a periphlebitis " there then ocours a small round-celled infiltration, which ultimately beoomes organized into fibrous tissue. This tissuc tends to surround groups of several lobulcs rather than to envelop each individual lobule. In course of time the new tissue contracts and strangles the branches of the portal vein within the liver, and as a consequence there results great distension of the portal radioles in the gastro-intestina.! tract and mesentery; hence ensue hrema.temesis, melama, ascites, and enlarged spleen. (Aooording to some pathologists, the irritant primarily acts upon the liver cells, these cells, in process of disintegration, liberating a diffusible poison which excites the growth of the connective tissue.) The irritant which provokes the cirrhosis consists either of the alcohol itself, impurities in the alcohol, or of certain toxins liberated in the alimentary canal as the result of chronic gastro-intestinal cata.rrh-a. condition so common in drunkards. The oirrhotio liver varies considerably in size, aocording to the stage the disease has reached. The organ is always enlarged at first. sometimes to more than twice its normal size; on the other hand, it may ultimately be reduced to less than half its normal size, but in most CBses this stage of contraction never arrives, the patient dying oither from pneumonia. pulmonary tuberculosis. fatty degeneration of the heart, Illsophageal hmmorrhage. pertal thrombosis, or from some infeotion-pneumonoccal, streptococcal. • As seen in tbe post-mortem room, the typioal oirrhotic liver presents the following appearances: Its surface is irregular, boing marked by elevations whioh suggest the hobnails of a boot (' hobnailed • liver), and often by large round bosses as well. The capsule is usually thiokened, and adherent to the surrounding peritoneum. On sco· tion the organ shows bands of fibrous tissue• ..which form a network throughout the liver substance. dividing it into , islands' of various sizes, each of which contains sepa.ra.to groups of lobules: hence the name of 'polylobular' oirrhosis applied by Charcot. The fibrous bands from the DISEASES OF THE LIVER t73 interior can be traced to the peritoneal Burface, where they are seen to pass to the depressions between the 'hobnails.' The' hobnails,' in fact. are portions of liver substance which have been thrust outwards by the oontraction of these fibrous bands. The new tissue consists of round cells, delioate spindle cells (fibroblasts), and wavy bundle!! of fibrous tissue, the rcl.ative proportions of which vary with the duration of the process. ' In the fibrous bands are numbers of new-formed bloodvessels, which anastomose with the branches of the hepatic artery. In some cases double rows of cubillal cells are seen, suggesting a new- formation of bile-ducts, but the significance of these is still doubtful. The liver cells undergo atrophy, and in beer-drinkers fatty degeneration of the peripheral zone of the lobule is common. Wheft the atrophy of the cells is advanced, toxic symptoms supervene not unlike those which occur in acute yellow atrophy. The oollateral vessels between the portal and systemio veins beoome dila.ted, and thus relieve tho oongostlon of the porta.l area. This oompensa.tory ana.stomosls is carried out principally between the following sets of veins: The (Bsopha.goal and gastric; the epigastric and internal mammary; the inferior mesenterio and hmmorrhoidal branohes of the Internal ilIao; the portal branohes In the round Iigl10ment of the liver, and the epigastrlo and internal mammary at the umbilious (oaput MeduslB); branohes of the portal vein in the mosentery, with the inferior vena. cava &nd its branohes (veins of Retzius). Bypertrophio or Biliary Cirrhosis (BanDt's Disease).In this very rare disease the liver is greatly enlarged, firm, and smooth. The newly-formed. connective tissue is more delicate than in the other kinds of cirrhosis. and surrounds each individual lobule.. hence the name of , unilobular' cirrhosis applied to it by Charcot. In tho new tissue are numerous so-called 'bile-ducts' -remarkable for the absence of any regular lumen. .As there is no obstruction to the portal circulation, hrematemesis, melama, and ascites, are not present, unless there is an associated portal cirrhosis. Jaundice, on the other hand, is a oonstant feature. The cause is unknown. The theory has been advanced thai it is due to a microbic infection of the bile-ducts I74 AIDS TO PATHOLOGY aacendingfrom the duodenum, cauaingretention witWn the liver of bile, wWch, in conjunction with the infecting agent, irritates the interlobular tissue. Obstruotive BililL1'J Cirrhom.-In certain CIlB08 of biliary obstruction, Buoh as thoso duo to impacted calculus, cancer of the lIvor or pancreas, lUI interlobular oirrhosis is mot witll, B'ISOeiated with dilated ·blle-ducts, and the tormat.lon ot what look like bllo-oapillaries, but whioh probably oODsist simply ot double oolumns ot altered liver cells. There is marked jaundice. Syphilitic Cirrhosis-Oongenital SyphiliB.-In infants dying three or four months after birth it is not uncommon t) find an interlobular cirrhosis uniformly affecting the whole liver. In ma.ny cases the new tissue penetrates into the lobules, and so bllCOmes peritJellular. The liver cells are degenerated. Gummata may also be present. Acquired Syphilis.-In this disease tho liver may become infiltrated with 0. diffuse gummatous matorial, which by organizing causes it to be seamed with fibrous bands. Definite gummata may also occur. but these are always connected with a preceding syphilitic cirrhosis. The gummata form pale yellow. well-defined. rounded masses, generally springing from the surface, which is often adherent to the neighbouring structures, such as the dillphragm. They are surrounded by a fibrous eapsulu_ When fresh they may be soft and pulpy; later they ml'y become hard, like cartilage. Sometimes a gumma undergoes absorption, and in such a case the surface of the liver shows a characteristic puckering. The Drunkard's Liver. This subject has given rise to much confusion, soma authoritics maintaining that the liver is enlarged. and othets that it is contracted. As ordinarily seen in thc out-patients' department of a London hospital, it is certainly milarged. and oftcn very much so. This ep.largement is proba.bly the resultant of three distinct pathological conditions: (a) Blood and lymph engorgement ; (b) Fatty infiltration and jatty degeneration: (0) A small embryonGl-oelled infiltration. DISEASES OF THE LIVER 175 The drunkard usually dies from some complication (as previously explained, p. 172) before (c) can organize into connective tissue and contract. Tuberculosis of the Liver. Tubercles form bcth beneath the capsule and in the interior of the liver. By ooalescence they may attain tile size of a hazel-nut (rare). Sometimes they develop along the walls of the hepatio ducts, Md, by compressing them, oause jaundice (very rare). Tumours 01 the Liver. Oavernoua Angioma is the commonest of the non· malignant tumours of the liver. It may rangl3 in size from a pea to an orMge. Aden01TUlla are very rare. They occur in the form Qf nodules, composed of acini lined with cubical epithelium. Primary Sarcomata are also very rare. Secondary sa.rcomata, particularly the melanotio variety, are not uncommon. Halo Whito reoords that not a singlo MBO of primary sarooma of tho liver was Jnot with at Guy's Hospital during the twonty years. 1870-89. both Inclusive. Byrom Bramwell and Leith were only able to collect twenty-five published oasos. and they came to the ooncluslon that. few of those were genuine examples. Primary Oarcinoma is rare, constituting only about per cent. of hepatic cancers. Secondary Oarcinoma is common; indeed, it is the only hepatic tumour which is at all common. ' Of all persons in whom at death malignant disease of My organ is found. about 60 per cent. have secondary deposits in the liver' (Hale White). The primary growth may be situated in any part of the body (and is often overlooked clinically), but its usual seats are the alimentary tract, the head of the pancreas. the gall-bladder, the uterus, or elsewhere. AB the cancer-cells are sown in every part of the liver, these secondary tumours are usually multiple; the superficial ones occur in the form of bosses, or large nodules, and often present an umbilicated appearance from the breaking down of their central parts. Owing to the great vascularity of the liver, they grow quickly, the dura4, AIDS TO PATHOLOGY tion of life being seldom more tha.n eight months after the diagnosis is first established. The liver is sometimes so enormously enlarged as to weigh as much as 10 or 12 pounds (tho heaviest livers on record are cancerous). Hmmorrhago into the interior of the tumours often takes place. Jaundice is present in about half the cases. Acute Yellow Atrophy. This is a very rare disease (not more than 300 cases on record). It is probably toxic in nature, due to the action of a hepato-lysin--i.e., a substance capable of dissolving the livereells (see p. 46). This causes so rapid an atrophy of the liver that in the course of a. few days the organ may be reduced to half its original bulk. The malady is commonest in women, usually occurring in conneotion with pregno.ncy. As seen after death, the liver is much shrunken. No longer preserving its norma.l shape, it flattens out when placed upon the table, lying loose in its wrinkled capsule (like a half-filled ba.g). On section the surface presents a bright yellow colour-hence the name-the outlines of the lobules are indistinct, and the liver cells are for the most part broken down and replaced by a granular debris, though here and there olumps of oomparatively healthy cells are to be seen. The disease bears a olose resemblance to phosphoruspoisoning. As Vivian Poore pointed out, it is found in young pregnant prostitutes who have oommitted suicide by phospliorus-poisoning. and a.ceording to him ms.ny alleged cases of acute yellow atrophy have been in reality cases of phosphorus-poisoning. Acute yellow atrophy has been observed to succeed gas-poisoning. Enlargements of the Liver. Reoultu'=nutlJ16g liver, tatty inftltration, lardaceous disease, biliary cirrhosis, Polylobular oirrhosis (early stage), louklllD1ia, lymphadenoma, diffuse OBIloeroUB inftltration, portal pymmla. lweoular= malignant growths (secondary), hydatid, abscess, guUlIllata. DISEASES OF THE GALL-BLADDER 177 DISEASES OF THE GALL-BLADDER AND BILE-DUCTS. Inflammation of the gall-bladder is tenned cholecY8titis, and of the bile-duots. cholangiti8. The oause is a miorobio infeotion. whioh probably travels up from the duodenum, the oommonest organism being the BaciUu8 coli. next to whioh appears to be the B. typh08U8. If oholeoystitis be suppurative, the condition is known as empyema of the gall-bladder; in suoh oases there is gener. ally impaotion of the oystio duot by a gall-stone. FIG. U.-l and II. Right and left hepatlo ducts; 3. the hepatlo duot; '. the oystio duct; 6. tIle common bile-duct; 8. the duot ot the pan_B; 7. the ampulla and papilla ot Vater. In old-standing oases of oholeoystitis the gall-bladder is usually muoh thiokened and oontraoted, being drawn up and buried under the liver, and adherent to the surrounding parts. Oarcinoma of the galZ-bladder, when found. is almost invariably assooiated with gall-stones. Gall-Stones (Cholelithiasis). In a typioal speoimen a gall-stone is found to be oomposed of three zones: (a) A small oentral nucleus, dark in colour, oontaining epithelial cells, muous, bile-pigments. and dead microbes, the presence of whioh is, strong evi· 12 AIDS TO PATHOLOGY dence in favour of the hypothesis of infection; (h) a middlo zone, composing 90 per cent. of the entire sUbstance of the stone, and formed of cholesterin; (c) a peripheral zone, very thin, and formed of lime salts, but insufficient in amount to throw a. definite sha.dow with the X rays. In most cases the stones are formed in tho gall-bladder (even when found in the hepatic ducts); in rare instances, however, they may form primarily in the ducts. Gallstones vary in size from small grains of Band to masses as large as a walnut. They are often multiple, and as many as 7,802 (Otto) have been found in the go.ll-bla.dder. 1£ multiple, they often present smooth, flat facets froUl mutual friction. When dry, the calculi float in water; otherwise they sink. They are most common in women over forty_ • The first stage in the production of gall-stonos is a microbial infection which sets up a catarrh of the mucous membrane. As the result of this catarrh, the epithelium becomes shed, and this, in conjunction with the infecting microbes, forms a nucleus round which thedlard matter is deposited. 'Gall-stones are tombstones ereeted to the memory of dead bacilli lying within them.' They are three or four times as common in women as in men, and their incidence reaches its maximum between the ages of thirty and forty-five. COIII,plicatioM : Obstruotlve Jaundloe. Empyema of tho gall-bladder. Ulceration into duodonum (Intestinal obstruction). Ulceration into hopatlo tlexuro of oolon. carolnoma of gall-bladder. Stenosis of the oommon' duot. Olrrhotio changes in liver and pancreas. Subphrenlo absoess. DISEASES OF mE PANCREAS. Acute Pancreaiitis.-As the panoreatio duot (In oonjunction with the oommon blle-duot) opons into the duodenum (Vide FJg. 14)-whioh Is ofton tho soat of bactorial aotivity.-it is probablo that this disease Is genorally due to an Infootion dorived from this source. ThOBe not so oocasioned must be due to blood Intootlon. Gall-stones. by fretting tho epithelial llning of tho terminal part of the duot. strongly prodlspose to it. There aro three ohlef forms. oaoh of Wllioh probably OVillS 0. dlll'orent infecting agent: DISEASES OF THE PANCREAS 179 Acute Bannorrhagio Panoreatitis.-In thiS disease the greater portion. It not the whole, of the gla.nd bocomos InOltra.ted with blood, and its oells undorgo QCorosis. Them may also bo tilt nocrtllJis in the panorea.s, ementmn, and olscwhoro. Suppurative PanereaWis.-This Is oharactarizod by the prosonee at either a single abscoss or or sm"ll multiple onos. Gangrenous PanareatitiB.-This may elrClet a part or tllo wholo of thCl gland. the tissue being oonvertod Into a dark s1l1OOcoloured mass. In Chronic Pancreatitis thore is IIIl ovorgro,vth of tho tl brous tissue ot the e-rge,n, with a.trophy ot t.he glo.ndula.f elements. In extreme casos the oondltion is known as cirrhosis oj the pancreaB. The usual caUBO is III partial obstruction to tho outflow ot tho panorootio juice, arisiDgtrom thO lodgment of a gall-stono In tho torminal part of tho OOIDIDOll bUe-duot. TumoUl'S of the Panoreas. Pancreatic Cysts may be of soveral kinds: &Jtention. cysts, whioh may be as big WI a ohild's lUlO.d, rosult-from obstruction to the outtlow ot tho pancreatiC sooretion--e.o., from Impaotecl jlRlculus or prossure, from wl.thout. as trom chronic paneroo.tltis; cysts in connection w~ (lI"OW~.o., adenoma. carcinoma: hOJ11l()1'rhall'i4; q/st8 ; hydatltl cysts. Adenomata may oeour, but they arc extremely rarc. Carcinoma is by:tar tho most important tumour of the pan- creas, and occurs usua.lly as a dense growth at fibrous appoo.rance (soirrhus). Its most oommon slto Is the hoad, rarely in tho body or tail. Bomo 01 t.ho CIlBOS start In tho neighbouring glands, and involve the panoreaB sooondarlly. (Of 2,005 OOB08 of oaroinoma oxaminoo post mortem by Biaoh ot Vionna. tho pancreas was the seat at the di_so In 29.) Pancreatic CalouU are somotimos met with. Thoy consist prinCipally of oalcium oorbonate, and they mllY (lanSIl obstruotion in any part at tho main panoreatlc duet. Thoy are usually mulUp1e.. DIABETES MELLITUS. Normal urino contruns a BUliIoll quantity at de:elrose, tho total amount excretod par twenty-tour hours bolng about 1 grammD. (Exoess or sugar In tho blood= hyperolycannia. Excess of sugar in the urino= OlYOO8Uria.) The blood in health contains on Wl a.veroge 0·10 per cent. of sugar (0·16 pez: cent. is to be regarded as the maximum normal blood-sugn.r level; anything over that amount cOllBtitutes hyperglycro.mia), and to this amount the renal apparatus is impermeablo. In health, the formation Wld consumption of sugar in the body are ovenly balanced, 180 AIDS TO PATHOLOGY for a.e it is.metabolized by the tissues it is concurrently raplenished from the glycogen stored in the liver; in this way there is Ill3intained a state of stable sugar equilibrium. Diabetes mellitus is that morbid condition of the system in which the blood and the urine habitually contain sugar in excess (hyperglycremia. and glycosuria), whioh excess is not the consequence of any excess in thc consumption of sugar-forming foods. rhe essential fa.cts of the disease a.re that the carbohydrates of the food are not stored up in the liver and muscles as glycogen. but circulate in the blood as sugar, and that the tissues are unable to utilize this sugar placed at their disposal. It thercfore aecumulates in the blood. whence it is exereted by the kidneys. (U the sugar in the blood exceeds 0·15 per oent., the patient should be regarded as a potential, or actual, diabetic.) The tissues then, in spite of an abundance of sugar lying at their door, are sugar-starved. How is this to be explained f According to Minkowski. diabetes is due to the absence of the hormone of the Pan"crcas. This hormone is the co-ferment which aotivates the ferment proper that metabolizes sugar in the tissues. This failure of activation results in the accumulation of sugar in the blood. and its consequent appearance in the urine. Forsbach has shown that if two dogs a.re united by skin. muscle. and peritoneum. and the pancreas of one is removed, the glycosuria that would otlierwise occUl'is checked; on separating them, however, sugar appears in the urine of the depancreatized dog. Carlson and Drennen, who experimented with pregnant dogs, found tha.t when the panereas is removed from an animal towa.rds the end of gestation, glycosuria does Dot occur. The subsequent extraction of the faltus is, however, followed by diabetes. suggesting that the hormone of the faltal pancreas can replace that of the mother. Ryporglycmmla without glyoosuria Is oommon in obesity. Joslin found decided obesity to ha.ve Pl'IlOedod tho ol18et of diabetes in over 40 per oent. ot his cases. ExPerimentally glyoosuria CIUl be induoed in animals by any of tho folloWing mothods: Puncturing the Floor oJ lhe Fourlh Yentricle.-DiBbotes thus "induoed is thought to 1fo duo to w.mage of 0. centro in tho JnedullB which oontrols the gJ.yeogenio o.ctlon ot the liver oel1!. IUld resUlts fll q. ~oo rapid oonVlll'llion of glycc1Ben fllto dextrose. DIABETES MELLITUS (GLYCOSURIA) 181 • Thora aro oxperimonts recorded wlliob show that tbo livor nerves hn.vo a dIreot inftuonoo on the liver colls, quito apart from thoir Infiuonco on the bloodvessoIs' (Halliburton): in othor words. that tho liver Is provided with' trophio • nerves; Re1IIOI!i1\jl U\e Pancreas.-Remava.l at too entire paneroa.a in alli.ul61a causes severe and total gIyoosuria: if. hO"-OVDr. even R very small portion of the gland is loft behind. glyoosuria does not ensue. _ Administerlnu PAlotitbi'l&.-By tho administration of this glucoside a very severo form of diabetes is Induoed. characterized by the prescmoo of abundant sugar in the urine. though tho blood oontalns DO more than the normal quantity; it is gl1/cosuria 'W'itlwut glycrmniq. the sugQr being formed in tho kidnoy by somo Bubsta.n('o brought to it by tho blood. • If tho phloridZin is directly injected into one ronal artory. sugar rapidly appears In the socretion or that kidnoy. and, lawr. ill that of tho other kidney' (Halliburton). Admi1loiBterina AMeoolin.-In the diabetes thus induoed thore ia both gl1lCfEmia and UI1lCOS'Uria. Ad...in.isterina 'J'h'llf'Oid Emacl.-Glyoosnria Is oo08sionally noticed after tho administration of thyroid extraot. IGlyoosuria also sometimes oecurs in oxophthalmic goitre.) HlIPoglUcannic Glucosuria.-This Is a condition in whlcb. with a subnormal quantity of sugar in the blood, there is exoess in tho urine. It is apparently due to an eXOOBslve pnrmeability of tho kidneys as rega.rds sugar. Paekological.-As regards the pathology of diabetes. the only fact definitely known is that in tIo certa.in proportion of oases (about 75 per cent.) the panoreas, post mortem, is found to be diseu.eed. In these ca.ses the che.nges consist of an increase of ehe connectille-tiasu6 8troma, aecom· panied by atrophy of ehe parenchyma. It is quite impossiblo to make anY dogma.tic statement a.s to whother a disturba.noe of the funotlons of the • islands ot LalJgorhans' is to bo roga.rded as a taotor in tho prQduction of glyoo· suria. MallY observers oonsider these • Islanlis' .to be merely exhausted groups of ordinary secreting aoini. The liver is devoid of glyoogen, or contains but a. tra.co. Exoept the heart. glycogen is absent from all the musoles. Glycosuria is uncommon in carcinoma. of the pancreas, the reason being that the growth mrely destroys the entiro gland. In the earlier stages of diabetes the urine contains an excess of urea and uric acid; in the later stages, when the system is breaking down, there is a progressive diminution of thc urea a.nd uric acid. AIDS TO PATHOLOGY Diabetic Coma.-The occurrence of this symptom is probably due to the presence in the blood of the fatty acid. {:J.o:tybutyric acid. This aold Is a normal product of fat DlotaboUsD1; It Is n()t. however. found In hoolthy urine. It is probably exidizod into dJo.ootio aeld. whloh. by losing C<>z, beoomos aoetone «AHaOa00.,= OJlftlO). Of the~ various bodiO$. acetone alono is fOlln<l In healthy urine. (Tho term acetonuria Is only applied whon tho amount of acetono Is ~s8ive.) In diabetio coma tho oxidation of ,g·oxybutyrio acid seams to tail, and it thcreforo aocumulo.~os In tho system (Wte Aoldosls). In diabetes, wOlmds heal badly; inflammations nre generally very BOvero. often going on to suppumtion and gangrene; phthisis pulmonalis often oloses the sceno; and double cato.mct is not uncommon. Diabetic Gangr8ll.8.-This takes place chielly in elderly diabetics (about the age of sixty). and it is often the first indication of the existence of diabetes. Its exciting cause is commonly a slight injury, such 0.8 may result from wearing tight boots. or pressure on a corn. Its most frequent sito is the foot. The1'6 are two chief types: Mummification. Perforating ulcer. Mummification.-The toes become cold and discoloured, and in course of time mummified. They may now be cast off, tho'parts healing ur' In other cases the gangrene extends to thc dorsum 0 the foot. Perforating Ulcer.-·Jn this form the disease usually starts in the ball of the great toe, often around a com. The corn suppurates and leaves & painless ulcer, having stoep edges. bordered by heaped-up and thickened epidermis. a condition very similar to that sometimes met with in tabes dorsnlis. A dusky purple areolo. Boon surrounds the ulcer, which in time becomes gangrenous; the gan· grene slowly spreads along the foot, until it may even extend as far as the calf of the leg. Whilst confined to the foot it usually remains' dry,' but once it invades the soft tissues of the calf it tends to become' moist,' and may at any time lead to septio infection. In aU 00888 o/diabetic gangrene tAe arteriea 8'/J.pplyillU DIABETES MELLITUS (GLYCOSURIA) 183 ths part ars di86a8e1i, the endothelium tieing greatly thickened and the arterial channels reduced in size, or even obliterated. In oerta.ln disooses, such WI meningitIs, S'!IgM is found in the urine. It may also be present in oaeos of Graves' disoase, ""hooplng-oough, and disease of the hypophysis. As 0. transient phenomenon it may ooour In indigestion. but horo it is probably dao to 0. sllgllt attack of pancreatitis. Acidosis. 'fho normal reaction of ~he blood is neutraL Though Its reaotion te litmus paper is slightly alkalino, oiootrloa.l and othor tests provo it to be praotloe.lly noutral. By aoidosis is meant tho oondition in which thoro Is an alteration in tho reaotivity of the blood owing to tho proeonoo therein of abnormal quantities of II-oxybutyrio and diaaetio ooids (wbloh fail to be oxidized Into aootone). Thero arc two oxpIo.no.tions of the roeulting symptoms: (a) Under ordinary olrcumstanoes the alkalies of the blood oo.rry the COg from the tissues to tho air in the lungs. Should, hOWBvor, tho aforesaid aolds be present, they, by oomblning with tho alkalies, prevent tho removal of tho COg. Aeoordingly, the COg stag· nates in tho tissues, setting up tlssuo-asphyxla. (b) The respiratory contro in tho modulla, owing to tho reduced. alkalIno reaotivity of its neurones. becomes hypersonsitivoto tho aotion of C02 (whioh is their norma.l sthrtulus). If alkalies are admln' istered. tho oondition is rolieved. Aoidosis is present In dlabotio coma, In tho oyolical vomiting of ohildren, in the pnetuiLonias of ohlldren, in the pernleious vomiting of pregnanoy, In doiayod chloroform-poisoning. in poisoning by salicylio acid, phosphorus. tetanus. ohronio nophritis. In starvation. and In oortaln casos of oa.ncor. DISEASES OF THE ENDOCRINE GLANDS. The activities of tho body-oolls are largely oontrolled by hormones. Those a.re spooifto substanoos olaborated by partlcu· lllr glands \'V'hlch have the funotIon of oxorcislng 0. controlling influenoe on (a) metabolism; (b) tho aotion of ocrtain tlssuos (~.U., uustripod musole·flbres); (c) tho devolopment of Important structures; (Il) the sooretion ot other glands; (e) the psyche. A good oxample of hormonlc action Is affordod by pregnanoy. It a watery extraot of 0. rabhit tl»tus be Injooted Into a virgin rahbit, rapid growth of its mammm takes plaoe. and mUk is formed. To olimlnate the possible offect of norve Influenoo, the mammary gland of u. rooontly pregnant guinea-pig was trans· planted to the region of Its ear: hypertrophy of tho gland ensuod. and milk was secrotcd. Thl) Inference Is that the fmtus in utero oiaborates II somethi.'I&{} whloh. ofroulating in the mother's blood, AIDS TO PATHOLOGY excites tllo growth and functional activity of hor mammary glande. This somothing is oalled a hormone, • chemical m0880nger,' or endocrino. .Again, if an animal bo castrated in early life, tho malo seeondary sexual characters' fall'to develop, owing to tho doprivatlon of the testionlar hormone. For example, Jolm Hunter shewed that thO antlers do not groW on stags eastrated when quite young. Also It is woll known that, if a boy is castratod In OIIrly lifo, he approximates, when grown up, to a type intermedlato betwoon the two BQXOII. The hair on the face is eitller a.bsent or scanty, thl.' voice remains hoy-liko (in past timl.'s castration was practised in order to preserve tho voice of ohorIsters; tho choirmaster in Vienna. wanted Haydn to be gelded so that he would retain his tine soprano voice). Thcre ill a tendoncY to tho laying on of tat, the disposition booomes moro placid, and thoro is a IMk of courage to meet danger. According to Hlgler, tho interstitial SUbstance of the testicle is conccrned in tho SOOl"Stion of a lilJidogenoiJ,s hormone, which Inspires tho instincts of solfpreservation and race propagation. Tho Influence of the ovarian hormone is oqually proneunced. Removal of tho ovari~s In early lifo prevents tho developmcnt of the female • secondary soxllal characters'; tho individual, when grown up, approximaws to a type intormodiato betwoon tbo two SOXOII, wblle tbo uterus and IllAlIlIDAry glands do not dovelop. (It is thought that the Interstitial cells [embcdded in the ovarY]lJroduce one hormone and the corpora lutca anothor. The ovary also controls tht! functions of the uterus.) 'The action ot hormonos on tho PB7/CM Is equally potent. Consider, for oxamplo, tho apathY of tbo myxcedematoUB patient, tho Intense JlOl"VOUsneS8 and agitation of the sufferer from Graves' disease (whiob Dlay change the most caIm,level-holldod, self-diSCiplined, strong-willed woman into an exoitable, nervous being, startled by tho loost noiso), tbe vIolent emotionalism exhibited at tbo period of the rut, tho altered emotional tone at tho menstrual periods and the epoch of the climacterio. In taot, the action of tho thyroid hormono bas exeroised a vary potent infiuenc!) upon thc history of tho human raco. • La genese ot l'oxercise dcs plus hautes tacult6s de l'homme sont conditionn6s par I'Mtion lJuremo:iJ.t ohimiquo d'uu produit de sooretion. Que lea psyebologuos m6dltont 00II faits' (M. Gloy). Normal growtb is largely controlled by hormones, Which are poured out at definite perJods (infancy, childhood, and pubcrty), and determine the developmontBI changes incidcntal to these periods. It tbese particular hormonos are not duly seoreted, development may be arrested at anyone of thorn, giving I.'i&c to infantilism, arrestod puberty, and aJllcd condltions. On Lhe other band. it thoy are formod In OXCOSB, or aro perverted, they may lead to hypertrophy; both aoromegaly and gJgtmtJsm Bra to be explainod in this way. Hormcnes are known to bc elaborated by the following DISEASES OF THE ENDOCRINE GLANDS 185 organs: tho thyroid. tho parathyroids, tllo thymus (I). tho pituitary, the pineal gland (l), tho panoreas, the duodonum, tlto suprarenals, the testos, and tlto ovaries. Chemical Nature.-HormoDos aro orJranlo bodios, in composi· tlon less complex titan protoins. They are dialyzable, readily soluble In wator, insoluble in aloohol, and "are net destroyed by boiling. Tho hormono derivod from tho modulla of tho supraronals (adronalin) has boen proparod synthotioally. The Thyroid Gland. Tho thyroid, which weighs about] ounoo, III a duotloss gland, oomposed ot acini lined by a single layor or cubical opithollum, and tlllod with the so-oalled 'colloid matorlal.' Tho stroma is abundantly supplied both with bloodvossols and lymphatlos. The gland is developod from the ventral wall of the mnbryonle pharynx, and In fretal lile is a eompound tubular gland, It&vlll8 a duct-the thyro-glossal-whioh opens into tho foramen CUlCtlm ot the tongue. The oooasional porsistenoo ot this duot oxplains many ef tho oysts whioh dovelop In tho middlo lino of tho nook. Tho gland attains its full development at puberty, and tends to atrophy in old age. From the ' colloid material ' of the acini Kendall has isolated a pure crystalline substance which is to be regarded as the active principle of the gland, having the formula CuHIOOaNIa. It contains an organic nucleus (indol) and oxygen. which he calls thyro-oxy-indol, shortened into thyroxin. Plummer's observations show that the thyroxin is a.most active factor in bodily metabolism, stirring up the fires of life everywhere, the metabolic ratc being raised or lowered by the activity or non-activity of the thyroid (measured by the intake of and the output of CO2 in respiration). The total amount of thyroxin in a normal person is approximately 13 mg.. Each increase of 0·033 mg. (approximate) of the thyroxin increases the rotc of energy output 1 per cent. Accordingly, in hyperthyroidism there is a.n increase in the metabolic ra.te, and in hypothyroidism a. decrease. ° Julian IIuldey has found that by giving a propara.Mon of the tbyroid (from any animal) to tadpoles lie could change them Into frogs in thrao weeks or so, inst,cad of three months odd, whloh is the natura.l period. On the other hand, they (lould be kept as tadpoles till he gave them thyroid. wben they began to develoll Into frogs. Also, by giving thyroid to tho axolotl he has macio it develop Into a sort of frog or salamander, and to produoe oertain joint obaractoristios never before seen. 186 AIDS TO PATHOLOGY Exophthalmio Goitre (Graves' Disease, Hyperthyroidism, etc.). The most probable explanation of the symptoms of exophthalmio goitre is that they result from an excessive formation of the normal, or the formation of an abnormal, secretion, which increases the katabolism of the tissues, causing an increased output of carbonio acid and Ul1la, together with losll of weight. Most of the characteristio symptoms-the emaciation, the sweating. the pigmentation of the skin, the tachycardia, the nervous agitationare referable to this augmented kabbolism. The commonest time for the disease to develop is be· tween twenty and forty, and there is a vast preponderance of women over men. Cretinism is a physical and mental defect of develop. ment associated with a oongenitally defective thyroid. The gland may be either smaller or larger than normal, but in all cases the acini are ill developed. The symptoms are rarely noticed until the child has reached the age of six months. The teeth erupt late, walking and talking are long delayed, and by the time adult life is reached the cretin may be mentally and physically as undeveloped as a child of five. The head in cretins is large and broad; the hair is scanty, coarse, and lustreless; the nose flat; the eyes are widely separatcd; the lips greatly thickened, as is also the tongue, which usually protrudes from the mouth. The skin is dry, coarse, and rough. The nails are brittle. The abdomen is pendulous, and there is often knock-knee. The genital organs remain infantile. Myxmdema (hypothyroidism) was first described by Gull as 'a cretinoid state supervening in adult life in women.' In it the thyroid is always diseased, the acini being atrophied and the oonnective tissue hypertrophied. The symptoms are due either to auto-intoxication, the result of the accumulation in the blood of substances normally destroyed by the thyroid, or to abl{ence of the secretion. The latter view is the more probable. The organism tends towa.rds lion anabolic rather thllon a katabolic condition; the vital fire glimmers rather than blazes (as in exophthalmic goitre), the output oI carbonia DISEASES OF THE ENDOCRINE GLANDS 187 acid and urea being diminished. H a. large amount of sugar be ingested. no glycosuria results. She bccomes much stouter, and her whole disposition changes. The skin of the body becomes dry, hard, and rough, and pads of fat forming the clavicular regions, over the cervical area, lower ribs and flanks. The alre nasi, eyelids, tonb'lle, and lips, become swollen, as also the fingers and toes. These changes depend upon an inorease in the connective and adipose tissues of the parts. As Halliburton points out, the mucin is not necessarily in excess in the tissues, for in only two out of ten cases of myxoodema examined by him did he find an excess. Hence the name by which the disease is genemlly known is not well chosen. Tho following Is Sir WillilU'\ Gull's description of his original case: Miss D., after tho oessation of tho oatamonial porlod, bocamo insensibly more Bnd marc languid with goneral inol"CBSO of bulk. TWs ohango went on from yosr to yoar, hor face altering from oval to round, much like the full moon at rising. With a complexion soft and fair, the skin, presenting a pecullarly smooth and fino texturo, was aimost PQreelalnouB in aspect, tho oheeks tinted of a dolicate rose·purple, the collular tissuo under the eyes being iooso aDd folded, aDd that UDder tho jaws and in tho nook becoming heavy, thickoned, and folded. The lips largo and of a rose·purple, aIm Jl4I.si thick, oorneo. and pupil of tho oye norma], but tho dlstanco' botWOOD tho oyes appearing dislJrOportionatell' wide, and the rest of the nose depressed, giving the wholo faco a flattened broad charaoter. Tho hair llaxcn and soft, tho whole oxPresslon of tho taco remarkably placid. The tongue broad and thlok, voico guttural, and tho pronuncIation as It the tongue were too largo tor tho mouth (oretinoid). The hands peculIarly broad and thiok, spade-liko, as it the wholo textures ,vcre inftltratod. The IntcgQJDonts ot tho ohest and abdomen loaded with subcutaneous fat. Tho upper and lower oxtremitlos also largo and fat, with slight traees of aldoma ov~r tho tfbiw, but this Is not dlstlnot, and pitting doubtfully on pressure. Urine normal. Heart's aotion and sounds normal. Pulso 72: broathing 18. Cachexia Strumipriva is the condition which results from complete extirpation of the thyroid. The symptoms closely resemble those of myxoodema, but run an acute course. Parathyroids.-These were first described by Sandstroom in 1880, and are four minute bodies, each being of tho size of a pin's head, and embedded in the posterior ilurfo.co 188 AIDS TO PATHOLOGY of the thyroid. They are developed from the epithelium of the third ahd fourth bronchial clefts, and are composed of 0. connective-tissue stroma in which are embedded closely-packed polygonal cells. Their hormone exerts & powerful influence on the nervous system. If removed, tetany results, and from this it must be inferred that occupation-tetany, tetany of children, tetany of maternity, stomach-tetany, tetany in infectious diseases, depend upon insufficiency of the parathyroids. . Suprarenal Capsules, or Adrenals. The adrenals belong to the cllromaJlln Bystem, a namo applied to various cell-aggregates bocsuse with ohromium salts thoy stain a yellowish-brown e010ur. (Other members of tho systom are: Tho Intercsrotld body, the aortlo paraganglion of tho f03tUS, the accessory adrenals, and some oells in the anterior lobo of tho pituitary.) Eaoh gland is composed of (a) corIe:l:, and (b) medulla. (a) The eurte:e oonstitutes 90 per oent. of tho gland, and is derivod from the mesodermal tissue ot tho embryo. It is thought to seorete B hormone whioh influences the development of the sexual glo.nds (the oortex and sexual glands originate trom groups of oells in juxtapOSition). Aooording to some authorities, tho oortex also acts as a dotoxinator, partieularly with regard to tho wasto products of muscular activity. (b) The medulla oonstitutes 10 per cont. of the glandJ and is derivod from tho 8ame blastema. as the 00311ac plexus of the sympathetlo. It is stated that in man it Is Dot found untll Bome little time birth. .&dl'efWlin is the actlvCl principle of the medulla, its secretion being under the control of the splo.nchnio sympathetic. (AccordIng to Takamine its constitution Is: Ortho-dioltY-phonyl· ethanol-methylamine.) The action of adrenalln is to ra.lse tho blood-pressure by Musing an intense contraction of the musculo.r fibres of the peripheral artcrioles (by stimulation of the sy:tnpa.thetic nervo-endings). The kldnoy-artorlcles at the same timc dllato-hence diuresis; also tho coronary a.rterioles dllo.to-henoo more blood is supplied to the heart musculature. (Tile pulmona.ry vessels are refractory to its influence.) It Is thus seen tha,t the adrenals. like the pituitary. aTo of double origin a.nd repretent two distinot sots of organs (in certain fishes tho two pa.rts are separate), having quite di1ferent functions. alter Addison's Disease is characterized by great mUSQular weakness, low blood-pressure, rapid, feeble pulse, a tendency to syncope, vomiting, and pigmentation of the skin, which varies in intensity from & hue &s da.rk as tha.t of the negro to a faint sunburn. while sometimes it is absent. DISEASES OF THE ENDOCRINE GLANDS r89 In the grea.t majority of cases, if not all, the change consists in a tubertJ'Ular tkstruction of the gland tissue, and especially of the medulla. New growtha sometimes oceur, but they are rare, a.nd it is very doubtful if they are ever the cause of genuine Addison's disease, inasmuch as they do not, like tubercle, destroy the suprarcnals on both sides, The pigmentation of Addison's disoose must not bo mistaken for tho pigmentation ot pregnancy, of ohronlo tuberoulosls, of arsenio, or silver, of vagabond's disease, of von Reoklinghausen's disease, of hBsmocllromatosis, of exophthalmic goitre, of workers in oertain kinds of ohemical factories (especially a.nthracene compounds), of mela.naBma in connection with melanotic sarcoma. AccesSOry AdrenalJ are not uncommon. They nre In the form of solid lumps, near the main glands, or In the capsule of tho kidney. They havo also been found in difforent parts of the abdominal oavity (liver, broad ligaments, spermatio oord, epididymis). Tumours may devolop from these accessory alirellllols,luore ospecially \vhen they are situated In the kidney. The Pituitary Body (HypoPhysis). This BtruOturo is peeullar In being developed in part from tho alimentary oanal, and in part from the brain. It oonsists of throe parts: (a) Anterior, (b) intermediate, and (c) posterior. (a) and (b) are derived from the pharynx (' Rathke's pouch '); (c) Is a diverticulum. of the third ventriolo. (a) and (b) are composed of a reticulum onclosiDg masses of epithelium-like oells (some of whiclL belong to thecllromafDn system); (c) is com· posed almost entirely of neuroglia with an entire absencc of ncrve-elements. In the meshes of the fibres Ie a hyaline material. Extracts from the anterior lobe are without effect. Extracts from the posterior lobo and pars intermedia raise the blood· pressure by vaso·constriction (after an initial fall) and slow the heart's action; at the same time the rellllol arterioles dilate (= diuresis). (The activo prinoiplo of tho pesterlor lobo may be B·lmlnozolyl-ethyIamine. In the anterior lobo Robertson considers tetholin the active principle.) Tho rapid growth (especially of the skeleton) which takes place at puberty Is largely due to the hormone secreted by tho anterior lobe. In some obseure way the pituitary sooms oloeoly related to the genital glands, for its destruotion causes amenorrh<ea and arrest ot spermatogenesis. Defeotive aotion of the pituitary ooming on before puberty causes stunting of the staturo, arrest of development of the sexua.l glands. greo.t obesity, and high sugar tolerance. 190 AIDS 1'"0 PATHOLOGY Diabetes inslpiduB appears, in most 'Clloses, to bo due to Borne lesion of tho pltuitllory. Acromegaly is a disease ohamcterized by hypertrophy of certain bones, notably of the face, hands, and feet. In the face, the lower jaw especially is affected, projecting in advanced cases beyond the upper. The soft part of the nose, the lobe of the ear, the lips and tongue, the hands and feet, also become thickened, and the patient in many respects reverts to the simian type. In all cases which have been examined after death, the pituitary body has been found hypertrophied, or the seat of a tumour. Probably the disoose results from an excess of, or some alteration in, the secretion of this, gland. (GiantiBm is due to an enlargement of the pituitary body in the growing years of youth, and acromegaly to an enlargement when the normal period of growth has ceased.) The pituitary gland, in fact, appears to be one of the most important factors in determining mcial ohamcters, suoh as stature, oast of features, texture of skin, peculiarity of hair, etc. The acromega)ous man takes on many of tile features of the anthropoid ape, tile former resembling the latter In the following among other particulars: In the possession of cranial crests, prominent supra-orbital ridgeS and maIars, and rnllosslve jllows; in tho prominence of the oyes, wrinkling of the lids, furrowing of tho forehead, breadth and fleshiness of the nose, and thickness of the lips; in tho shortness and thickness of the neck; in the backward convexity of tho cervico-dorsalsplne and consequent stoop; in tho long sagittal diameter of tho thorax and the abdominal character of the breathing; In the bowing of the legs and massivenoss of tho skeletal and muscular systems; in ihe existence of pads, separated by deep furrows, on the palms and Boles, and In tho longitudinal striation of the nails; in the coarseness and looseness of the skin and tendency to pigmentation, and in the coarseness and excessive growth of bair; In the depth of the voice; In the aetlvity of the outaneous glands, and susoeptibility to cold (H. (',ampboll). Frohlich's Syndrome (Dystrophia Adiposo-geDitalis).-Thls is an example of hypopitUitarism. Adiposity is marked (especially over pectoral regions and hips). Hair is absent from the faco and scanty over the body. Sexual activity is subnormal. If beginning before puberty, the stature is small. Napoleon I. wa8 probably lJU:fI'ering (rom hypopituitarism during the latter period of his ute. DISEASES OF THE ENDOCRINE GLANDS .I91 The Thymus Gland. This gland is devoloped 80S Do bilateral hypoblastio dlvortlcuhun mo.lnly from tho third visoeral arch, and when fully formed is ehiefly composed of lymphoid tissue, the corpuscles of Hassal ropresenting the original hypoblastio elements. Eosinophile leuoocytos are fairly abundant along tho fibrous septa. (In Ulan and rabbit it Is ontodermal in orfgin; in tho mole oetodermal; in the guinea-pig and pig It has a dual origin.) 'rhe gland attains Its full development at puberty, after whleh It undergoes a gradual Involution. and after about the twenty-ftfth year is represented by a mass of fatty cmmcctlve tissue spread out over tho superior mediastinum and front of the pericardium. • Of the functions of the thymus nothing definite is known. According to some authorities, it is concerned with the regulation of the lime-salts of the body. Hypertrophy of the gland is found in Graves' disease, Hodgkin's disease, leukmmia, acromegaly, 'thymic asthma,' and myasthenia gravis (90 por cent.). In none of these, however, can the hypertrophy be regarded as essential, because it is not always present. Status Lymphaticus is the condition sometimes met with in children and young adults, characterized by delayed involution of the thymus, hypertrophied lymphatic gla.nds, and increa.se in the lymphoid tissue of the tonsils, base of the tongue, of Peyer's patches, and of the Malpighian bodies in the spleen. Fatty degeneration of the heart sometimes coexists. The condition has been found in a number of cases in which sudden death had oceurred during the administration of anresthetics, as well as in certain cases of death from trivial causes, but there is no actual proof that tho sudden death is connected with the existence of a persistent thymus. Lympho-Barcoma.-The thymus gland iii a not uncommon site tor mediastinal sarcomo.ta. • Weights at DiJlerent A(168 (Hammar): New-born 6 to 10 years 11 to 15 111 to 25 66 to 66 66 to 76 Grms. 13·110 26·10 37·62 24·73 10·08 6·00 192 AIDS TO PATHOLOGY Other Hormonic Affections. Premature PubertJ".-Puberty may make its appearance 8S oarly as the second year, owing to tho premature entrance into the blood of some hormone or hormonos which nornwJly bring it about. In somo of these cases there may bo consider· able musoular dovelopment and a largo deposit of fat. Infantilism.-In this condit.ion dovclopmont does not proceed boyond tho infantUo stage. Ib is probably due to the absence from the blood of somo hormone or hormones necessary to normal dovelopment. Premature SenilitJ".-This is due to the premature ontrance iuto tho blood of subsLancoa which promote senile ehanges in tho tlssuos. or to tho absonoo from the blood of substanoes which koep tIlO tissues youthful. Deforo tho patient has reachod the ago of t,vonty, it may bo, tho skin beoomes wrinklod, the hair blanched, the spine rigid, tho arteries thiokonod. and tho tissues genorally exhibit other featuros oharacteristic of old age. The degonerative ohanges oocurring in what may be termed normal Benil'Uy aro not so mucll due to a wearing out of the tissues as to tho presence ill the blood of substu.nces which bring tllem about. Goitre (Bronchocele). Goitre is a clinical rather than a pathologica.l term, and embraces a.ll enlargements of the thyroid gland of non· neoplasmic origin. ClD.SSi1loatiOIl{pareIlChymatous { ~r:!~~. Exophthalmle. Parenchymatous Goitre consists of an overgrowth of the acini of the gland, and to Borne extent of the stroma. The acini may become cystic (' cystic' goitre), or the stroma may be abundant (' fibrous' goitre). It is usually bilateral. The iodine-content is low, and this is probably the chief cause of the disease. Exophthalmic Goitre is largely a re"erBio1~ to the fmtal Btate, being characterized by three sets of changes: (a) Alteration in the alveoli. (b) Increase in the connective-tissue stroma. (e) Dilatation of the bioodvessels. (a) The outline of the acini, instead of being uniform, are irregular-due to the cubical epithelium lining their interior becoming cylindrical and so being larger and requiring more room, causing an infolding of the walls. SYPHILIS I93 New acini are formed by diverticula from old ones. Thero is little or no colloid, its place being taken by a thin, granular coagulated fluid. (b) In the newly-formed connective tissue of the stroma nodules of lymphoid tissue arc often found. ' (c) The blood vessels (more particularly the veins) become greatly distended and their walls friable, so that during an operation on the gland hromorrhage is apt to be copious. The gland presents a solid, almost homogeneous, appearance, not unlike the pancreas. The Blood.-The polymorphonuclears are reduced, and the small lymphocytes increased in number. The Thymus Gland is peraistent and enlarged in about 75 per cent. of the cases (Capelle and Muth). Tumours.-Adenoma of the thyroid is characterized by the formation of large acini, which are enclosed w'ithfn a distinct capsule separating them from tho rest of the gland. In some cases the acini are converted into cysts containing a thin brownish fluid. The tumour is generally unilateral. As tho thyroid gland contains both mosoblastic and hypoblastic elements, sarcomata and carcinomata may occu~, but thoy arc extromely rare. SYPHn.IS. 'Syphilis constitutes one-third of human pathology' (Gaucher). Schnudinn and Hoffmann were the first (1905) to show that syphilis is due to the presence of the Treponema pallidum. The organism is foundIn the primary soros. in tho skin losions. in tho mucous membranolesions. Acquired iu the lymphatic glands. syphilis in the blood and lymph. in gummata. ( in .the brain in general paralysis of the msano. ,in tho spinal cord in tabos dorsalis. In congenital syphilis tho treponcmes aro found in tho blood and in noarly all tho organs and tissues of tho body. In the livc~ and sIl1cen moro Ilarticularly thoy congregate in enormous numbers. They are also found in the urino, frocos, bile, bronchial secretion, and n:1sal dischargos. 13 194 AIDS TO PATHOLOGY The organisms are found most abundantly in situations where infectivity is most intense-e.g., mucous tubercles and oondylomata. Metchnikoff and Roux discovered them in the syphilitio lesions of the higher apes inoculated with the virus taken from human beings. Neisser was the first to demonstrate their presence in tertiary lesions. At the Lisbon Congress he exhibited a specimen showing five or six treponemes in the periphery of 0. gumma of the liver. Noguchi was the first to demonstrate their presence in the local lesions of general paralysis of the insane and tabes dorsalis. The Treponema pallidum (so named by Schaudinn) Is supposed to be a prolozOOI1., and, as seen In the living condition by means ot the dark· ground illumination, Is a long thrcad·like organism, about 20,. In leQgth and 0'25,. in broadth, tapering at both ends, with eight to sixteen corkBorow·lIke spirals, which are viBiyle both while inmevement and atrost, and whichgivo It a' twisted' appoaranoo. It moves slugglshly across the mlcrosoopie 1I.eld (most other splroohetes move morc rapidly), the movements being ot feur kinds-viz., rotation onltslong axis, bending and lashing, flexion and extension of its spirals, slow progression. The organism has been kept alive In a drop ot Its own serum under a cover·glass In tho laboratory of tho military hospital, Chlseldon, for a period ot torty·three daYR. Nogucbl has grown them in pure culture, with which he produced BYllhilitlc lesions In rabbits. The majority ot observers considf.>r that multiplication takes place by transverse division, though others asse~ that longitudinal division Is the rule. It is killed by exposure tor halt an hour to a temperature of 51 0 c. Although the customary division of syphilis into throe stages is in a sense misleading, inasmuch as all the lesions contain and are caused by the treponemas, yot it is so generally used that it may be allowed to stand, especially in view of the fact that it has 0. distinct olinicalsignificance. Primary LeBion.-An abrasion of tho surface is necessary for the introduction of the treponemes into the system. Even the mucous memb:ranes. if intact. resist inoculation. 'The orifices of the sweat-glands and hair follicles. into which staphylococci and streptococci easily penetrate. do not in their normal state appear to 0llen the door to infection' (Neisser). The chancre. or 'hard Bore,' occurs at the site 9f inoculation, being the local SYPHILIS 195 ' expression of the reaction of the tissues to the Trepone.ma pallidum. (Of 10,000 cases seen by Fournier, 850 were on extra-genital regions, 50 per cent. of which were on the lips.) It is generally in the form of a papule, with an indurated base. (In men it is generally single; in women it is often multiple.) Slight ulceration of the surface takes place, and in about six weeks' time (under treatment) the cntire chancre disappears by absorption, leaving little or no scarring. Inasmuch as it is painless, and yields but a slight discharge, it may pass unobserved by the patient. The chancre is composed of mononuclears, prolifcrated connective tissue and endothelial cells, with occasional giant cells, between which arc great numbers of new blood vessels. Should the sore become phagedrenic, it indicates a mixed infection. (A genital sore may be syphilis, chancroid, scabies, herpes, or traumatic.) General infection of the system takes place by the lymphAtics and bloodvessels long before the appearance of the primary lesion; it is probably a matter of a few hours from the time of infection. Neisser failed to arrest general infection of the system by excision of the inoculated area after only eight hours from the time of inoculation. The Wassermann roo.ctlon is of no value in the diagnosis of oo.rly syphilis, as it does not beoome positive for from two to six weeks after the appoorance of the primary sore. During the period of quioscence which precedes tile secondary stal,re, tho parasites are chiefly located in the bone·marrow. sploen. and testicle (Nelsscr). Secondary Le8ions.-These are essentially epithelial (epiblastio and hypoblastio), being oharacterized by cutaneous eruptions, mucous patches, and shallow ulcers on the tonsils. tongue, soft palate, and pillars of tho fauces. They are to be regarded as breeding-grounds of the specific organism. The' mucous patches' are the commonest of all secondaries, and their discharge the most contagious. During this stage the blood contains the treponemes in small numbers. TertianJ LesionB.-By the time this stage is reached, which may be as early as six months after the primary infection, the treponema has probably undergone some ohange ill" form, and produces a different toxin. This would account for the difference in the lesions of the 196 AIDS TO PATHOLOGY tertiary stagi? as compared with those found in the secon· dary stage. Although Neisser and OtheN have found the treponemes in various tertiary affections, yet in tho great majority of cases their presence cannot be detected. 'l'hey are certainly absent from the blood in any recognjz. able form during this stage. Experimental an~ clinical obllervations have shown tho.teontagion, though less probable, is still possible during the tertiary stage. Ter~iary lesions affect par ucellence the mesoblastic tissues, and the history of this stage of the disease is the history of a particular form of granulation tissue, the 61JPMloma or gumma, composed of lymphoid eells, con· nective-tissue cells, endothelial cells, a.nd sometimes giant cells; between the cells a.re new bloodvessels. This granulation tisaue may occur in two forma: (i.) in concentration, when it is called the gumma .. or as (it) a diffused gummato'U8 i'lljiltration. (i.) The gumma is most liable to form in parts exposed to injury-e.g., round about the knee and on the liver. Its future ca.reer varies according to circumstances-e.g., it may resolve under treatment (if begun early), or it may undergo necrosis from syphilitic endarteritis and subsequent thrombosis of tho supplying arteries. A gumma. situated on an exposed surface is specially liable to ulcerate and to destroy the tissues deeply. Living treponemes Dore only sometimes found, in gum. ma.ta.. The expla.ns.tion of their absence may be that a. gumma is the tomb of numerous treponemas, which melt away and'so diss.ppear from the soene. (ii.) A diffused gummatous in.1iltration may involvo any of the viscera, the bloodvessels. bones ann joints, and nervous system. Its tendenoy is to organize into fibrous tisBue, but, like the gumma, it may resolve under treatment if begun early. The two conditions may coexist; for oxample, there may be a diffused gumma.tous infiltration of the livor, and gummata. on its surface. a.nd this applies to all th~ viscera, to the nervous system, to the bones and joints, and to the bloodvessels. Shakoopea.re describes syphilis when he makes Timon of Athens say t!l the two prostitutes, 'Oonsumptions sow in hollow bones of man; strike their sharp shins and mar SYPHIUS 197 men's spurring. Orack the lawy~r's voice that.he may never more false title plead, nor sound his quillete shrilly; hoar the tlamen that scolds against the quality of flesh; down with the nose, down with it tlat; take the bridge quite awa.yof him that smells from the general weal; make curI'd pate ruffians bald, and let the unscarred braggarls of the war derive some pain from you; plague all; that your ootivity may defeat and quell the source of all crection '-o.s it docs when syphilis is followed by tabes dorsalis. According tc tho statIstics of ins1ll"&noo offioos. syphllls sliortons lIfe five to six years. Of 1.009 persons of ntnatoon years and upwards who visited the London Hospital for reasons wholly unconnected with syphilis and on whom Fildos performed the WassCl"lllann tost. 8·3 per oent. were positive. Excluding 197 aliens with 13 positivos. thoro remain 803 Dritisil CIlSOS with 7111ositlv6 rosults= 8·8 per cent. Syphilitic affections of the various organs are doalt with under their respective headings; those of the nervous system 00.11 for special notioe. Syphilis of the Nerveus System. Syphilis may attack the nervous system a.t any time between three months and twenty-five years (or even longer) after infection. According to 1\[ott, 'it most frequently occurs within the first two years after infootion, and the frequency of its ocourrence diminishes with each successive year.' All the syphilitic diseases of the central nervous system are due to the direct action of the treponeme. They fall into two sharply-sepa.rated olasses-the interstitial and the parenchymatous. In the former the treponemas infe!~t interstitial structures, such. as the walls of the arteries and the meninges, producing such lesions as ondarteritis and chronic meningitis. In the latter tho parasite takes up its abode between the individual neurones, causing a. primary parenchymatous degenemtion. Geneml paralysis of the insane, tabes dorsalis, and syphilitic prima.ry optic atrophy belong to this category. Clinically, the interstitial differs from the parenchymatous variety in being amenable to the action of mercury and arsenio administered through the blood. This difference is probably due Iq8 AIDS TO PATHOLOGY to the f3$lt that the oapillaries whioh supply the neurones of the central nervous system with blood q,re impermeable to both of these drugs. Among the :p1ore important forms of the interstitial variety are the following: Syphilitio Enilarleriti8, either in the form of nodular thickeni~ (gummata), or of a diffuse gummatous infil· tration of the arteries of the brain, especially at the base (which, if complicated by thrombosis, may give rise to hemiplegia), and of the spinal cord. , I have not seen a case of syphilis of the oentral nervous system post mortem in which the vessels have been per· f3ctly healthy; usually they were extensively diseased' (l\lott). In fact, endarteritis may be said to dominate the histo.pathology of all stages of syphilis. MyelitiB.-Eighty per cent. of oases of myelitis (so called) are due to syphilis. The disease begins as llJl endarteritis: this may go on to thrombosis and end in • softening.' Gummatous MeningitiB, espeoially at the ba.se of the brain (involving the oranial nerves, more particularly the oculo·motor), and of the spinal cord. . GUlmlnmta, beginning in the meninges and spreading to the brain surface, are specially (lommon at the base, notl!.bly in the region of the chiasma, but they may be found in any part. General ParalYsis of the Insane.-Syphilis is the essen· tial cause of this disease. Mott has been able to demon· strate the existence of the specific organism in 66 per cent. of the cases examined by him. He adds:. Sometimes they oan be found In ten mlnutos, sometimes only after a day's searoh; but inasmuoh as looking for these minute organisms in a largo organ like the brain may be llke looking lor the proverbial needle in 0. haystaok. it is not surprising that they cannot be found in overy oase. The oxistence of tho positive Wassermann reaotion in the cerebro-sPinal fluid in every case. however, strongly supports this oonolusion. The essential pathological changes occur in the oerebral . cortex, and consist of: Thickening and adherence of the meninges. Thickening of the neuroglia. Thiokening of the walls of the arteries. SYPHILIS 199 Atrophy of the neurones. (This is thought to be a primary ohange.) On removing the membranes, the surfaoe of the brain tears away with them (, deoQrtization '), leaving a oharacteristio worm-eaten appearanoe, especially marked over the frontal and oentral oonvolutions. Changes in .the oord similar to those met with in tabes dorsalis are generally found. They would doubtless be still more frequent and pronounced if the disease did not run such a rapidly fatal course. Thore is always lymphooytosis of the oerebro-spinal fluid. Tabes Dorsalis.-This also is a manifestation of syphilis, the treponemes being found in the local lesion. The morbid changes are, mutatis mutandis, the same as those found in general paralysis. The disease uBUlIolly starts as what appears to be a. meningo-neuritis of the posterior roots in the dorso-Iumbar region of the oord, a.lthough the process is probably to a. large extent a primary atrophy of the sensory nerve fibres oonstituting the posterior roots. The continuations of these fibres in the posterior columns of the oord undergo seoondary atrophy. Other regions of the oord are also sometimes involved. In oourse of time the posterior roots, like the posterior oolumns, lmdergo marked atrophy. The Argyll Robertson phenomenon (= pupils react to accommodation, but not to light) is thought to be due to a lesion of the oiliary ganglion within the orbit. (With very rare exceptions, it indicl).tes syphilis of the nervous system.) Lymphooytosis of the oerebro-spinal lluid is always present. In oases complicated by • Charcot's joint disease' and • perforating' ulcer of the foot, the nerves supplying the affected parts have been found degenerated. Lymphooytosls of the oerebro-splnal fluid ooours In cerebrospinal syphilis, in tabes dorsalis, and in genoral paralySis ol the insane. Wassermann Reaclitm in 8I1philis.-Up to t-wo to six -weeks tram tho first a.ppoaranoo of tho prima.ry BOfe tho rea.otion is genemlly nega.tive. It is in the ea.rlll sooonda.ry (untrea.ted) stage that the highost poroentage at positive roa.otions is found, in whioh it ra.nges from 96 to 100 per oent. (For further partloulars, 11ide p. 48.) 200 .AIDS TO PATHOLOGY CHRONIC ALCOHOLISM• .Alcohol has been termed the' genius of degeneration.' The morbid changes obseryed in chronic alcoholism are: An increase of the fibroUB at the expense of the higher e1ements of the tissues. This is particularcy marked in the liver, arteries, and nervous system. A tendency to fatty degeneration, especially of the heart. At the coroners' inquests held in London, the common cause of sudden death in drunkards is found to be fatty degeneration of the heart. A tendency to inflammations, notably to catarrh of the mucous membranes, alimentary and bronchial. .Alcoholic peripheral neuritis is not uncommon. .The tendency of alcoholics to inflammations is largely due to their diminished resistance to pathogenetic bacteria. It is for this reason that the mortality from such diseases as pneumonia is so high among them. The above·mentioned changes may be caused either by the direct action of the alcohol on the tissues, or by bac· terial toxins developed in the oatarrhal alimentary tract. Probably both factors co-operate. 'When the eot hae dll60el1dOd through hie ohoson oourso of ImbeoUity or dropSY to the dead-houso, l\{orbtil Anatomy is ready to reoeivo him-knoW's him well. At tho post-mortem ahe WQuld eay: .. Liver liard and nodulatod; brain dllD.BO and small, Its ooverings thick." And if yay would listen to hor unattraotive but interesting taw, she would traco througbout tho sot's body Ii series of ohanges whioh leave unaltered no part of him worth s:peaJdpg of. She would tell yOU that the onoo dolloate, filmy texture whlob, when he was young, had surrounded llko a pure atmollPhore overy fibre and tube at his mechanism, making him lithe and supple, has now beoome rather 0. dense fog tllan 0. pure o.tmoSllhere-denso stu:tr whioh, Instead of lubricating, has closed In upon and orushed out ot existonoo moro and more of tho fibl."OB and tubes, espooially in tho brain and Iive__whenoo the imbeoility and the dropsy' (Moxon). , Alcohol aots partloul&rly on the higher centros of tho b!'lloln, and a drunken man may exhibit the abstraot and brief ohronlole of Insanity, going through its successive phases In a short period of tlltle ' (Ma.udBley). DISEASES OF BONE 201 DISEASES OF BONE. The struoture of bono is that of a specialized connective tissue impregnated with lime-salts_ The periosteum on the outside of a bone is continuous with the endosteum (marrow) of the inside, and numerous bloodvessels pass _ from the one to the other_ This vascular continuity explains how inflammation, beginning primarily in either periosteum, bone, or endosteum, is lia.ble sooner or later to involve all three_ Osteitis. Osteitis is always due to microbic infection of the soft tissues of bone, the usual organisms being: Staphylococci, 8treptococci, pneumonococci, BacillUB typho8U8, bacillUB of tubercZe, and the treponemB8 of 8yphili8. Fir8t Stag e.-The bloodvessels dilate, then exudation begins accompanied by the escape of leucooytes, the bone assuming a pink colour. Second Stage.-Exudation continues, the lime-salts are dissolved out, and the bone-substance is partially absorbed, the compact tissue becoming eaten away,as it were, and the cancellous becoming still more cancellous. 'l'his ' rarefying' process is effected in part by the action of phagooytes, in part by the peptonizing action of bacterial toxins, and possibly in part also by the solvent action of the inflammatory lymph imder high pressure. In the dry specimen the bone at this stage presents a 'wormeaten' appearance. 'l'hird Stage.-Osteitis, like inflammation of soft parts, may terminate in one of several ways. Thus, resolution may take place, and the bone resume more or less its normal condition. On the other hand, should the • rarefying' process continue, the whole of the affected bone dissolvcs away by a process of molecular death, or cariB8. If, after this has occurred, the inflammatory exudate, consisting largely of pus, becomes imprisoned by the surrounding bone, the result is an abSCes8. If, however, the exudate poured out during the period of rarefaction organizes, sclerosis results, the cancellous spaces and the medullary 202 AIDS TO PATHOLOGY canal becoming ill this way obliterated by the formation of hard, dense bone resembling ivory. This is the usual condition of the terminal portion of bone in stumps after amputation. Acute Infective Osteomyelitis (Pan-Osteitis). This disease attacks the long bones, the larger more frequently than the smaller. In the great majority of cases the Staphylococaus aurew is the oause (other causes =pneumonococcus, BaciZZ'1J8 typhosu8, etc.), the organisms entering the body either through an external wound, or in consequence of some infeoting focus in the mouth, throat, or other part. It is essentially a disease of young people (thirteen to seventeen years), and lowered vitality is an important predisposing faotor. The disease is characterized by the rapid formation of pus. It presents three types, according to the position of the initial lesion, which may be either: 1. In the periosteum, 2. In the interior of the shaft, or 3. In the epiphysis (aoute epiphysitis). 1. If the disease begins in the periosteum (favourite site = femur, usually starting at baok part oflower end), the pus spreads over a wide area and strips the periosteum ftom the bone. The latter, having its blood-supply cut off, dies, unless the pus is let out by a timely incision. In this way a portion, or, it may be, the whole shaft, of the bone perishes, the condition being known as acute necroN 0/ bqne. This form is generally limited to the shafll, for the disease does not usually spread to the epiphysis, which is protected by the intermediate cartilage; for a like reason the neighbouring joint also escapes as a. rule. 2. H the disease begins in the interior of the shaft, necrosis is brought about partly by a strangulation of the bloodvessels and partly by the toxio action of the baoteria.l products. This is the ordinary Acute Infective OsteomyeZitiB. Should it remain untreated, pymmia is very likely to occur, as the infective thrombi in the veins are liable to disintegrate and be discharged into the blood-stream as septic emboli. DISEASES OF BONE 3. If the disease begins in the epiphysis, it is genemUy localized to this part, and is known as Acute Epiphysitis. In these cases the head of the humerus and the upper and lower epiphyses of the femur are the parts most usually involved. The disease often spreads to the joints, giving rise to acute septic arthritis. It is essentially an affection of infants and very young children. Infections of the middle ear are genorally caused by' the 8treptoCOCC'UB. Caries. Caries is the molecular dissolution of a portion of bone, resulting from the continuation of the rarefying proccss of osteitis, being analogous to ulceration of the soft tissues. It may occur in any bone, but is commonly met with in tke ca7lCelloU8 tiBBtt6 of the epiphyses, the bodies of the vertebral, the carpus, and the tarsus. By far the commonest cause is tubercle, and when thus originating it may be regarded as a phthi8iB of bone. When dead bone separates, it does so by caries taking place in the adjacent portions of the surrounding living bone. Dru Caries.-The absorption ot bone resulting from presSllr&B.g., ot an aneurism-is sometimes spoken of as • dry caries.' The prooess is of tho nature of a simple atrophy. Necrosis. Neorosis is the death of bone in mass, and is analogous to gangrene of the soft ·parts. It commonly affeots the compact ti8sue of bones, particularly of the tibia and femur; also lower jaw, bones of skull, and phalanges. In all cases the cause is a cutting off of the blood.supply, either by injury or inflammation (periostitis, osteitis, or osteomyelitis, syphilis, scarlatina, mercury and phosphorus poisoning). Necrosed bone is bloodless, dry, and white in colour, but on exposure to the air it· often becomes brown. Separation of Dead Bone.-The surrounding bone becomes inflamed, caries results, and the loosened dead bone, now called a sequfJ8trum, lies bathed in pus in a cavity bounded by granulation. tissue, and lined with a • pyogenic membrane.' The periosteum covilring the 20 4 AIDS TO PATHOLOGY sequestrum may form a new Ia.yer of bone over it-the involucrum. This is perforated by holes-cloacal-to allow of the escape of pus. Tuberculosis of BOlle. Tubercle may form in the p~riosteum. in the epiphyses, or in the diaphyses. Its favourite position is the cancellous tissue of the epiphyses, the bodies of the vertebrm, the carpus, and the tarsus. The bones of the skull are rarely involved, and those of the face and jaws praotically never. The disease runs a ohronio oourse, shows a marked tendenoy to suppuration and progressive destruction of the parts, with but little tendency to repair. The bovine ba.oillus is the probable oausal organism. Syphilitio Diseases of Bone. In the Becondary Btage of syphilis there may be 0. fleeting periostitis. In the tertiary Btage the bone affeotions are similar to those oharacterizing this stage of the disea.se elsewhere. Gummatous material may form in either the periosteum or the bone. and give rise to caries, necTOBis. or 8dflTOBi.s. Caries and necrosis may oocur together (cario-ntlCr08iB). Gummata are most likely to form on parts exposed to injury. and hence they are most often met with on the subcutaneous surfaces of bones, leading to the formation of 'nodes.' Syphilitic caries is commonest in the skull. Syphilitic sclerosis may be widely diffused throughout the whole shaft of a. long bone, and it may also occur in the bones of the oranial vault. In both acquired and congenital syphilis the fingers and toes may be affected with periosteal gummata, giving rise to the condition known as Byphilitic dactylitiB. In congenital ByphiliB the diseases of bone, according to Parrot, assume two prinoipal f{)rms: Golatlnltorm. 1. Atrophlo { Ostoochondritis. _. {Osteoid. 9. Hypertrophlo. or Ostooph...10 Fibro-epongiold. 1. In gelat1:nllorm atropl'1I the bOlle tfssue fs replaoed by a gelatinous substance. DISEASES OF BONE In osteochondritls (sometimes oollod syphilltio epiphysitis) the cartilage between the epiphysis and tho diaphysis becomes abnormally thick and loses Its rogular outline; ossification stops short at oololfloatlon, tho zono of oaloltlod matorlal being dense and brittle. As 110 result, fracture Is liable to occur, and, as the symptoms may resemble paralysis, Parrot has named this oonditlon SlJPhilitic pseudo-paralysis. 2. In the hypertrophio varioty the new bone of the growing child :m.ay be hard and ivory-like, when it is termed osteoid; or it may be fibroid In struoture and vory vascular, when it is tormed /i/n"o-spongioia.. The two conditions may be combined; thus, the osteoid and spongioid material may be arranged in alternating layers. The most eommon sites for these ohanges 0.1'0 the ends of the humerus, femur, and tibia. In the skull • bosses' of new bone may form around the fontanolles (. Parrot's nodes '), and these may become bridged over, and so give rise to the rounded, prominent forehead observed in later life in the subjeots of this disease. In the occipital and parietal bones circumscribed areas of extremely thin bone, or evon of membrane only, arc sometimes met with. To this condition the name of craniotabes has been given. (In the Museum of the Uoyal College of Surgeons, London, are specimens prosonted by M. Parrot showing all those ehanges.) . Tumours of Bone. The m08t common primary tumours of bone are the enchondromata, the osteomata, the myelomata, and the sarcomata. Secondary tumours may be either sarcomatous or carcinomatouB. Saf'Comata oj Bone.-These may be either periosteal or endosteal. Peri08teal 8arcoma is of extreme malignancy, so muoh so that, of sixty-eight cases collected by Butlin, a oure was effected by amplltation in but one case, and even here there was an element of doubt as to whether the growth did not start in the endosteum. DEFICIENCY DISEASES (AVITAMINOSES). Besides the erdlnary food oonstituents, such as protein. fats, carbohydrates, IIpoids, and inorganlo salts, 0. number of Bubstances oan be found In small quantities whleh are as indispensable to life 0.8 the former constituents. These substances I have designated vitami1le8, and the diseases whioh arise from their laok as' de.!l.olency diseases,' or aVitaminoses (Casimir Funk). Vitamines are the product of the plant world on whleh ultimately all animals Uve. So far as is known, animals are una!;le to synthetize them. Their absence from food eauaes eertaln 206 AIDS TO PATHOLOGY diseases, the following being thoso definitely known: rlckots, BOl1rVY, berl.-berl, and pellagra. There are different kinds of vitamlnes, Dach playing a definite rOle in metabolism, and they are dilforently distributed amongst natural food-stutrs as instinotively oonsumed by men amI o.nimals. Their chemical composition is unknown. Three olasses bave boon dltrerontiatod: 1. Fat Soluble A.-COntained in the :majority of animal fats (boof fat, fat of kidney, ete.), abundant in buttcr (but destroyell by hcat1D.g to 100 C.l, egg·yolk, :fish oUs (eod-liver oU), heartmuscle, liver, and the raw green leavos of plants. Not present ill lard, and only in small quo.ntlty In margarine made from vegetable oils. Its absence causes riokets. 2. Water Soluble B.-Present In the cuticle of the husked grain of rice. Yeast is rich in it; also eggs. Its absence causes bert-beri. s. Water Soluble C.-The antiscorbutic vitamine present in lemons, oranges. raw cabbage-loaves. the raw juiee of swedes. germinated sCQds. and most edible vegotables. Destroyed by moderatcly high temperatures, alkalies, desicootion. and canning processes. Ronoe the importanoe of fresh fruit and salad. It is important to emphasize that drIed vegetables have lost almost tho whole of their antiscorbutic properties. 0 Rickets. Riokets, first desoribed by Glisson in 1650, is a' defioienoy disease' affecting the nutrition of the entire organism, being due to the absence from the food of the antirachitic vitamine (fat soluble A). Deformities are the later and graver manifestations of the disease, and occur in but a small proportion of all cases. (Schmorl's histological investigations on ehildren dying before the age of four showed that 90 per cent. had rickets.) Lawson Dick found 80 per cent. of the children in the L.C.C. schools had rickets. The condition commonly attmcts attention at about the sixth month after birth. The child is anromic; it is very irritable, and cries when handlell on account of a diffuse tenderness of the body; it is restless during sleep, sweats freely about the head, and a slight degree of fever is often present; besides being irritable, the child is nervous, and liable to 'fits.' There is also a much lowered resistance to infection. (In the West of Ireland, where rickets is very mre, the infantile death-rate is only 30 per 1,000. In the poor urban districts of England, where rickets is common, the infantile death-rate varies from 100 to 300 per 1,000.) DEFICIENCY DISEASES 207 The most characteristio bone changes ooour at the epiphyses and beneath the periosteum of the long bones. Thus, the cushion of oartilage between the epiphysis and the diaphysis is thicker than normal, and the plane of ossification on the diaphyseal side of the cartilage, instead of being even, is irregular. The cartilage cells divide with cxcessive rapidity, suggesting the action of an irritant. The newly-formed bone is unduly soft, chemioal examination showing it to be very deficient in lime-salts. Similar changes take plo.ee beneath the periosteum, the new bone laid down by this membrane being softer and more spongy than in health, and as 0. consequence the bones bend, giving rise to various charo.eteristic deformities. These are molO marked in some bones than in others. although the entire osseous system is affected. The anterior fontanelle remains open longer than the normal eighteen months after birth, and the teeth erupt late. ]j'rom pressure by the pillow, soft, deoalcifi.ed areas arc liable to form in the occipital and parietal bones ( = craniotabes), though this oondition generally (some say always) indicates congenital syphilis. H the child lies much on its back, the occipital bone is liable to become flattened and the frontal bone to become prominent; for the bones of the cranium are easily displaced on account of the late closure of the fpntanelles and the yielding nature of the sutures. The oranial vertex is often.fiat, and the coronal suture may be 'keeled.' In the spine there is usually some kyphosis, and the child may not begin to sit up until after tlie first year, instead of, as normally happens, at about the seventh month. The sternum is thrown forward (' pigeon-breast'), and there is considerable thickening of the ribs at their junction with the cartilages ('beaded' ribs). It should, however, be remembered that a small degree of beading is normal. Rickets is the commonest oause of deformed pelvis. The sacral promontory projects forwards from the downward pressure of the weight of the body, and the brim is • kidney-shaped.' Sometimes the symphysis pubis is pulled backwa.rds by the a.bdominal recti, giving rise to the' hour-glass' pelvis. The most notable ohanges in the long bones are: enlargement at the junction of the shaft with the epiphysis 208 AIDS TO PATHOLOGY from swelling of the epiphyseal cartilage, exaggeration ot the normal curvatures, and the developmen~ of curves due to the traction of powerful muscles-e.g., an outward curve of the humerus, corresponding to the insertion of the deltoid. The bones of the forearm are bent outwards in their lower thirds. The femur shows a long forward curve. The bones of the leg are bent outwards and forwards in their lower thirds. Strong bony buttresses usually develop in the concavities of the curvatures, where the new rickety bone is laid down most abundantly. Caloification at the human teeth oontinues till the eighteenth year, and this caloification depends largely upon an adequate supply at tat soluble A in the diet. Henoe dental oaries is often evidence of riekets. Infantile Scurvy (Scurvy-Rickets; Barlow's Disease). This disease is unknown in breast-fed infants. It is probably a 'deficiency disoase' due to the absence of vitamines in the food. There is acute tenderness of the limbs, the child screaming when moved. HlIlmorrhagio effusions take place beneath the periosteum of the long bones, more particularly of the femur and tibia. Hmmorrhages may also .occur in the interior of the long bones and ribs. Sepamtion of the epiphyses is not uncommon. Spongy gums, and hmmorrhages from mucous membmnes. and into the skin and the joints, are usually also f~und. Achondroplasia. This disehse is due to a deteot in development at the bODes whioh are tormed from oartilage, more partieularly of the long bones and those of the base at the slrull. It is sometimes inaccurately called treta! rlokets, diflering from ordinary riokets In that it is always congenital. The bones whioh develop tram membrane are unaffected. Tbe development in length. of the diapbyses at tbe long bones is defootive, though they are normal in thiokness; bence the limbs are short and stunted. There is no bending, and there are no abnormal CUl'Ves. The bones at the base of tho skull ankylose early, and as those at the valdt grow naturally, tJ,le holtlt looks unusually big. The bridge of the nose ill depressed. The boneS which develop tram membrane being unaffected, the ol,tvicles, ribs, sternum, and vertebral column, Bra all at normal size. Death ocours in most cases a tew days after birth. Those who survive grow up dwarfs, but with tho intolllgelloe unimpd.lred (thus d11fering tram cretins). OSTEOMALACIA-ACROMEGALY 209 Osteomalacia (Mollities Ossium). This disease is essentially one of progressive decalcification, the lime-salts being absorbed and the bones in consequence becoming soft, bent, and liable to spontaneous fractures (which do not unite)_ . It occurs only in adults, is almost entirely confined to women, and generally develops during pregnancy. The bones usually affeoted are those of the pelvi8, the vertebral column, and the rib8. The morbid ohange begins in the interior of the bones, the medulla being replaced by a tissue resembling the splenic pulp. The decalcification proceeds gradually from within outwards, until all that is left of the original bone is a thin layer of compact tissue beneath the periosteum. The pelvi8 is flattened from side to side, the acetabula are approximated, and the symphysis pubis projects forwards in the form of a beak. Osteitis Deformans. This disease was first described by Sir James Paget. 'The disease affects most frequently the long bones of the lower extremities and the skull, and is usually symmetrical. The banes enlarge an~ soften, and those bearing weight yield and become unnaturally curved. Th!l spine may sink and seem to shorten, with greatly inoreased dorsal and lumbar curves; the pelvis may become wide; the necks of the femora may become nearly horizontal, but the limbs, however misshapen, remain strong and fit to support the trunk' (Paget). The calvarium may become enormously thickened, the patient notioing that he has to use larger and larger hats, while his stature becomes less and less. The disease begins after middle life, and its progress is very slow, sometimes lasting as many as twenty years. The enlargement and softening of the bones are due to the development of soft, spongy, and highly vascular new bone. Acromegaly. This disease is charaoterized by excessive growth of the bones (as well as the soft tissues) of the hands, feet, face, and other parts. The lower jaw is inoreased in eize and projeots forwards; the supra-orbital ridges are prominent (see p. 190). :uo AIDS TO PATHOLOGY Leontiasis Ossea. In this disease the bones of the faoe and cranium become greatly thiokened. Hypertrophic Pulmonary Osteo-Arthropathy. This disease is oharacterized by enlargement of the terminal pkalange8 of the fingers and toes and neighbouring bones. with incurvation of the nails. It is assooiated with bronchieotasis, empyema, and pulmonary tuberculosis, and is probably caused parMy by absorption of toxic material from the diseased lung or pleura. and partly by the sluggishness of the circulation resulting from the pulmonary obstruotion. DISEASES OF THE .TOINTS•. Tuberculosis of the .Toints. Tuberculosis of a joint may be compared with tuberculosis of the lung. The disease may begin in the synovial membrane. whioh is the morphologioal equivalent of the pleura (tubercular synoviti8); or in -"the liead of tho bone, which is the morphological equivalent of the lung (t-ubercular o&teitiB). It never begins in the a.rticular oartilage. The disease is generally chronic. and resembles tubercle elsewhere in its course and termination. ending either in recovery by the formation of fibrous tissue, or going on to abscess formation and the destruotion of the joint. Tubercular synovitis affeots, o.s " rule, the hinge-joints -viz., the elbow, wrist, knee, and ankle. Tubercles form in the synovial membrane, causing it to beoome thickened, gelatinous, and pulpy. The synovial fringes spread over the artioular surfaces. covering them like a veil, and from the under-surface of this veil small processes penetrate into the underlying cartila.ge, a condition compared by Billroth to ivy creeping over a wall and becoming gradually attached by its roots. The cartilage now beoomes ulcerated. and, finally, unless the tubercular process is a~ested, the underlying bone is inva.ded and becomes canous. Should the disease progress, tubercular fungoid· processes, derived from the synovial fringes. burrow through DISEASES OF THE JOINTS 2II the capsule and infect the tissues around the joint. causing periarticular abscesses. the contents of which generally find their way outwards. A fistulous canal. lined with exuberant granulations. and forming a communication between the inside of the joint and the skin. is the result. In an early period of the disease recovery may take place under treatment. but after the occurrence of suppuration tho jOint becomes partly or completely obliterated, and fibrous ankylosis occurs. if in the meantime the patient does not die from the lighting up of tubercle elsewhere. or from lardaceous disease. T1Ibercular o8teitiB affects the ball-and-sooket joints, and is well illustrated in the case of tubercular disease of the hip-joint. The process here usually starts in the epiphysis of the femur. either olose to the intermediary cartilage or just beneath the articular cartilage of tho head. Caries supervenes. ILlld the inflammatory products escape into the cavity of the joint. The synovial membrane and ligaments become secondarily affected. and the whole joint IDldergoes disorganization, the acetabulum being inoculated by contact with the carious head of the femur. (It may even become perforated.) In some cases the epiphysis gets detached and lies loose in the joint. The pus generally escapes through the thinnest part of the capsule-i.e., 0.& its posterior part. It then burrow!! forwards beneath tho gluteus minimus, the medius, and the tensor vaginm femoris, ILlld Ultimately forms 0. swelling beneath the anterior superior iliac spine. Oomplications of Tubercular Arthriti8.-If an abscess bursts and becomes septio. amyloid di8ease is likely to develop. At any tim~ during the progress of tubercular arthritis acute miliary tube.rculosia (either of the pia mater, lungs, or abdominal viscera) may be set up. As previously stated, complete disorganization does not of necessity follow tubercular joint disease. In favourable oases, espeoially if treatment has been begun early, the disease may be arrested, the inflammatory produots being absorbed; ankylosis (fibrous, or bony), however, is often a sequel under these circumstances. In rare oases tubercular arthritis starts from a ttWerculous periostitis or from a tubercul0't&8 b....sa. Tuberculosis of joints. like that of bones. is probably d1l6 to thc bovine bu.oUlus. 2I2 AIDS TO PATHOLOGY Arthritis Deformans. This is a generic term, and embra{)cs severa'! types illstinot alike in their etiology, pa.thological features, and clinical course. The cause, in certain of them at least, is probably a toxin, which may be generated in t,he nasal sinuses, around the teeth, in the aliment,ary canal, in the uterus, or in the FalIopi::tn tubes, and operating through the synovial fluid. As seen in museum specimens, the disease gives the impression of having boon a chronic one, but the clinical history of cases suggests that whatis seen pest mortem is the result of the frequent recurrence of acute or subacute a,Uacks. The disea,se presents two main types (though numerous intermediary forms are Dlot, with): DSleo-Arthritis, in which the changcs are most. ma.rkcd in the articular cartilages and bones; and Rheumatoid ArtJlritis. in which the synovial membrane, ligaments, and periarticular structures, are most affect,ed. DSleo-Arthritis is a chronic and progressive disease of middle and advanced life. The morbid changes invohroThe articular cart£lages. The underlying bones. 1.'he synovial membrane, The iniemrticula·r ligaments. TIle sU!rrmmdin(J muscles. The hyaline matrix of the articular cartilage becomcs fibri'lat,ed, and the cartilage cells proliferate and escape into the joint. The surface.of the cartilage now loses its polish, assuming a velvety appearance, and in course of time its central part is worn down, and the tmderlying bone, highly polished like porcelain or ivory, is exposed. While these chang(ls are in progress, the marginal cir· cumference of the cartilage becomes irregularly tlrickened (' lipping '), sometimes dcveloping flange-like outgrowths or ecchondroses, which have been likened to the guttl'rings of a wax candle. These ecchondroses may in course of time beeomo ossified, when they are known as o8ieophytes. (In a carwus joint the {)steophytes have the jagg8d form of staJactitcs.) The 8ynovial membrane thickens, its fringes hypertrophy, and eyentuaf[y the whole membrane nmy assume a shaggy aplIeamnce. Oooasionally oartilago develops in DISEASES OF THE JOINTS 213 the fringes, forming pedunoulated nodules. and thos.e may subsequently become detached and form 'loose bodies' in the joint. Tho interarticular Zigamtmt8 in oourse of time degenerate and wear away. In this way the ligamentum teres dis· appears from the hip-joint, the intrascapular par~ of the long tendon of the biceps from th~ shoulder-joint, and the crucial ligaments and interarticular cartilages disappear from the knee-joint. AB a final result, the contour of the joint becomes considerably altered. This is most characteristically seen in the hip, the acetabulum being widened, tho head of the femur flattened and expanded at the oircumferenoe, its neck shortened and sct more at right angles with the shaft. The muscles around the joint tend to atrophy, a ohange often well marked when the disease attacks the shoulder, hip, or knee. The disease generally attacks the large joints, such as the hip, knee, and shoulder, but it may involve a numbcr of joints. When the spine is attacked (8pondylitis deformans), there is often so much new bone formed that the individual vertebroo become fused together. Rheumatoid Arlkriti~ generally comes on in early adult life, involving many joints symmetrically. It is much commoner in women, and is probably caused by an infection, for it is often associated with uterine or tubal troublo. All the joints of the body may be affected. (N.B.-In gout and rhewnatic fever the temporo-maxillary joints and cervical spine are practically never attacked.) Those of the fingers are apt to be involved early, causing these latter to be fusiform from swelling of the interphalangeal joints. There is great thickenipg both of the Rynovial membrane and ligaments, as well as a periarticular effusion, which in time tends to organize. 'Lipping,' ehondrophytes, and osteophytes. are absent. The muscles about the affected joints undergo marked atrophy. and the contractions of the wasted muscles may cause oonsiderable crippling. A feature of this malady is its oonstitutional nature. It is manifestly a blood disease. for the p:ttiont is aDoomio, her vitality is low, and she is apt to be febrile-o.ll of whioh suggest an infeotion. AIDS TO PATHOLOGY Still's Disease is allied to the last, if it is not aotually the same disease, but, in addition to the joint affection, enlargement of the spleen and of the lymphatio glands is apt to ooour. It occurs in children. Neuropathic Arthritis. This group of joint diseases is found in oonnection with certain diseascs of the spinal cord and nerves, the most notable being-tabes dorsalis, syringomyelia, sl>ina bifida. hemiplegia, paraplegia., periphera.l neuritis, and injury to peripheral nerves. Charcot's loint Disease develops in connection with tabea dorsa i8, generally during the pre-ataxic stage. The disease may affeot one jOint only, or may oocur successively in several.. Tho usual joints to be involved are those of the knee, hip, and shoulder. The onset is generally sudden; there is considerable swelling of the part (which is sometimes enormous), but neither pain nor fever is present. A patient may go to bed well, and wake up in the morning with the joint dilltended, without any apparent cause. After a few days the general swelling disappears, but the joint remains distended with fluid. This swelling is due in part to effusion into the joint, and in part to Gldema. of the soft tissues outside it (the , Gldema without pitting' of Char~ot). Although in a. few cases the effusion may be absorbed (the 'benign' form of Charcot), the articulation returning to its normal state, it generally proceeds to rapid and complete non-inflammatory destruction of the articulation (the' malign • form of Charcot). and culminates in the production of a. • flail joint,' movable in all directions. Dislocation of the joint may take place. especially in the hip or shoulder. It is essentially a trophic lesion, the nerves going to the jOint being found diseased. The morbid changes characterizing it are--effusion into the joint, early disappearance of the ligaments and carti· lages, and great atropky of tke articular ends of tke 6ones. OstetJphytes may form, sometimes in large numbers. In Cha.rcot's disease of the knee it is not Uncommon to find bursal 8Welling8, espeoially of the bursa which so DISEASES OF TilE JOINTS 215 frequently communicates with the joint--viz., that under the semimembranosus tendon. Syringomyelia may be associated with 0. form of joint disease similar to that occurring in tabes dorsalis, but the seat is 'U8ually in the upper limb. In this disease trophio lesions may be also found in tho skin, such as whitlow8, ulcer8, and gangrene of the fingers. The pathology is the same as that observed in Charcot's joint disease. A similar condition of the soft parts occurs endemically under the Mme of' Morvan's disease.' GonorrhreaI Rheumatism. This disease, sometimes called young man'8 rheumatiBm, is caused by the entrance into 0. joint either of the gonococcus, the gonococcus-toxin, or the organisms, or toxins, of a • mixed' infection. One or several joints ma.y be affected, as also sometimes fascim, tendon sheaths, bul'llre, and the fibrous sheaths of nerves. The knee is most often attacked. (Of 376 cases recorded by Finger, the incidooce was as follows: Knee 136, ankle 59, wrist 43, fingers 35, elbow 25, shoulder 24, hip 18, jaw 14, other joints 22.) A very troublesome form is that which affects the ankle, the tarsal joints, and the fibrous struc~uree in the sole, causing a severe form of fiat-foot. In some cases there is • iritis.' The disease seldom sets in until the third or fourth week after contagion. It may be acute, BUbacute, or chronic. In the acute form there may be suppuration (very rare), and even complete disorganization of the joint. Sometimes it simulates rheumatic fever. The more oommon aubacutll or chronic form is o4aracterized by a plastio exudation involving the ligaments and periarticular 8tructUTIl8, with but oomparatively little effusion into the joint. This accounts for the oharaoteristio solid feeling of the joint. The exudation shows a marked tendenoy to the formation of new" fibrous tissue, which leaves the joint permanently stiff. In those cases in which the larger joints are affeoted the patient may become quite crippled. Affection of th~ fourth metatarso-phalangeal articulation is said to be diagnostio of gonorrhma. 216 AIDS TO PATHOLOGY In a oortain number of cases of arthritis and tonosynovltis following gonorrhma, pure cultures of the gonococcus can be ob· tained from the local parts; in other cases, no organisms can be found. Gout. Arthritic gout is characterized by the deposit of mono· sodium urate in the matrix of the articular cartilage. P,st mortem it is found in the form of crystals lying just beneath the surface, not extending deeply, and but exceptionally involving the underlying bone. In advanced cases the surrounding ligaments, tendons, and synovial membranes and bursro may be likewise involved. The sites of election are the great toe, the fingers. and knee. Occasionally, the deposit affects thc ears, eyelids, larynx, and kidneys. The most common complications of gout are emphysema of thc lungs and granular kidney. DEFORMITIES. Branchial Fistula, Cleft-Palate, and Bare-Lip. In order to understand the nature of these deformities, it is necessary to recall some points in the normal develop. ment of the upper jaw and neighbouring parts. In early FIG. 16•. fmtallife the anterior portion of the alimentary tube com· municates with the exterior 011 either side by 0. number of slit-like openings-the branchial defts,. between wh;ich are the branchial arc"h68. The first branchIa.l cleft persists as the external auditory meatus, the tympanum, and the Eustachian tube. All the others should close. In some DEFORMITIES rare cases, however, the third or fourth remains partioJly unclosed, the result being a. fistula (branchial fi,Btula) opening on the surface of the body near the sternal head of the sterno-mastoid muscle. Similar nstulw have also been met with below the glottis. As development proceeds, the (irst branchial areh on either side divides, fOrming the two superior and the two inferior ma.xillary processes_ The two inferior processes unite in the middle line to form the lower jaw and the lower lip. The two superior processes grow forwards to form the superior maxillw, with the hard and the soft palate, tho cheeks, and ihe lateral parts of the upper lip. They do not, however, unite anteriorly, but between them there grows downwards from the front of the skull the 1IIJ80frontal pr0Ge8s. from which are" developed the nose, the vomer, the nasal septum, and the premaxillw carrying the incisor teeth and the central portion of the upper lip. These various parts should unite by the ninth week of freta) life; should union be defective, tho following deformities, which are always situated in the linos of fissures norma.lly present in intra-uterine life, may oocur: Blfld uvulo.. FislJUre ot the soft palate, with bl1ld uvula. ]!'ilsure ot both the soft and the hard palate. Fissure ot the hard Dala.te only (very rare). FIssure ot the hard and the 80ft pft,Iates, combined with fissure of the alveolus and the lip on one side_ The same as tho preceding, with fissure 0t the &lveolus and lip 00& both sides. Simple hare-lip. Double hare-lip. In the rare case of oleft of the hard palate the nasal septum is usually attached to one side of the palate, shutting off the nose from the mouth on that side. In only very rare cases is the lower border of the nasa) septum free, so that both nasoJ cavities communicate with the mouth. In double hare-lip the premaxillw and the central por. tion of the upper lip may be oarried forwards &8 an appendage of the nose. Very rarely the fissure of the hare·lip extends upwards on one side of the nose towards the inner side of the orbit (patenl orbilal gtOO'lJs). 218 AIDS TO PATHOLOGY Meningooele and Enoephalooele. A meningocele is a protrusion of the dura mater and the arackfUJid through a congenital aperture in the skull, .where it forms a. soft Huctua.ting swelling, which conta.ins cerebra-spinal fluid, and which increases in size on expiration, coughing, or crying_ The most common site is the occipital bone, just a.bove the foramen ma.gnum, but it may also oocur in the anterior fontanelle, at the root of the noae, at the base of the skull (protruding into the nasaJ. passages or pharynx), and a.t the external angle of the orbit. It is often assooiated with hydrocephalus. An encephalocele is a meningocele conl;aining brain mbstance. It pulsates with the heart-beat. A hydrep,cep1udoceJe is an encephalocele enolosing a oavity filled with fluid continuous with that in the ventrioles. Spina Bi1ida. Spina bifida is a congenital defect of the posterior part of the spinal canal, due to arrested development of the laminoo of one or more vertebne, and generally accompanied by protrusion of the meninges and cord through the gap. in the form of a oystio tumour varying in size from a walnut to an orange. The usual position is the lumbo-sacral region. the laminal of this part being the last to olose in fretallife. It is sometimes aasooiated with hydrocepha.!.us and ta.lipes. Varieties.-Meningocele, meningo-myelocele, syringo. myelocele, myelocele. A meningocele consists of a protrusion of the dum mater and the araohnoid through the gap in the spina.!. oana.!.; it contains cerebro-spinal fluid. A meningo-myeJoceJe is the most common form of spina bifid&. It consists of a meningocele plus a portion of the spina.!. cord and nerves. A syringo-myelocele is rare. It is similar to the last, but the centra.!. canal of the spinal cord is distended, the posterior part of the cord being spread out over the interior of the sac. A myelocele is the condition resulting fram non-olosure of the primitive medullary groove, the central canal opening 011 the surface. DEFORMITIES 21 9 Torticollis. Tortioollis is a deformity caused by contraction of one of the sterno-mastoid muscles (often of other muscles also), by which the head is drawn downwards towards, and rotated away from, the afiected side. The deformity may be congenital, or it may appear soon after birth. IIi the former case it is due to an arrest of development, and in the latter to partial rupture of the sterno-mastoid during the second stage of labour. In childhood it may come on after measles and scarlatina, usually as the result of inflamed cervical glands. In some cases it arises.from irritation of the spinal accessory nerve. Occasionally it is spasmodic, disappearing when the patient is a.nresthet.ized. If torticollis lasts for any length of time, the sternomastoid, the deep cervical muscles, and the anterior portion of the trapezius, become shortened, and the cervical vertebne rotated, and lateral curvature of the spine may set in. The congenital variety, unless surgically treated, ,tends to produce asymmetrical growth of the head. Cervical Rib.-This is mainly composed of cartilage. The condition is commoner in women, and in only 5 per cent. of cases does it give rise to symptoml!l. It arises most frequently from the transverse process of the seventh cervical vertebra, and passes down oehind the nerves of the brachial plexus to unite with the central portion of the first rib. It may compress both the branches of the brachial plexus (often giving rise to atrophy of the small muscles of the hand) and the ilubclavian artery. The condition is usually bilateral. Lateral Curvature 01 the Spine (Sco6osis). This deformity commonly results from weakness of tke spinal muscles, and commences in almost all such cases at about the period of puberty. It may also be due to the shortening of a limb, or the falling in of the ribs after an empyema.. There is a primary curve, generally in the dorsal region and convex to the right, with secondary or compensatory curves above and below, in a direction opposite to that of :220 AIDS TO PATHOLOGY the primary ourve, and with the object of ma.nt&ining the body in the upright position. In addition to the lateral curva.tute, the verteiJrm are rotated on their vertical aa:e8, the front of their bodies moving towards the convexity of the curve, and the spines towards the concavity. In this way the ribs on the convex side, together with the shoulder (. growing-out shoulder ') are thrown baokwards and widely separated, while on the concave side they are thrown forwards and crowded together. If the oondition remains untreated, the intervertebral disos become permanently wedge-shaped, the base of the wedge being directed towards the convexity of the curve. In old-standing and advanoed oases the bodies of the vertebrre also become wedge-shaped. Lateral curvature is common in Friedreioh's disease, a.nd in syringomyelia. Angular Curvature 01 the Spine. This deformity, also oalled Pott's ourvature, is caused by the destruction of one or more of the bodies of the vertebrre by tubercular earill8 before adult life is reached. The disease may occur in any part of the spine, but its usua.! sta.rting-point is the dorao-lumbar region, the caries beginning either beneath the periosteum on the anterior surface of the vertebral bodies, or in the cancellous tissue at their intmior. The a\Ieuted bodies and. adja.cent intervertebral disos being destroyed, a. ga.p is left, and in the case of the growing individua.l the upper part of the spina.! oolumn then bUs forward upon the lower to form an angle-the so-oa.lled • a.ngular curvature' of the spinewhile the lower portion moves backward in compensation. Tubercular disease of the spine rarely oauses a.ngular ourvature in the adult. If repair takes placo, the gap is :filled in by a. buttress of new bone or by fibrous tissue, and at the same time the laminre and spines of the neural arches usua.lly become ankylosed, and so a.ct as a kind of splint. Spinal abacll8s is the usual accompaniment of oaries of the vertebroo. As the pus accumulates it travels aJong the lines of least resistance, either following the COU1'Be of 110 bloodvessel or burrowing beneath fascioo. When the disease is seated in the cervical region, the pus may point DEFORMITIES :221 in toe pharynx (post-pharyngeal absce8s), or pass along the back of the cesophagus into the posterior mediastinum, or it may work its way' into the posterior triangle of the neck, and even sometimes extend into the ILXilla. Whfln the disease is seated in the upper or the mid-dorsal region the pus usually passes baokwards along'the posterior branches of the intercostal arteries, and forms a swelling olose to the spinous processes (dorsal ab8Ce8s). When the disease is seated in the lower dorsal or lumbar region, the pus may pass backwards and form a swelling just external to the erootor spinal muscle (lumbar ab8Ce88). As a. rule, however, when the disease attaoks the dorsolumbar region, the pus burrows into the psoas muscle and forms a P80as ab8Ce88, the oourse of which is determined by the attachmenta of the ilio-psoas fascia.. The ilia-pseas fasela. whieh invests beth the psoas and the iliaeus musoles. Is attached above to the ligamentum arcuatum Internum.. below to the iliac orest and brim of the true pelvis. internally to the front of the bodios of the lumbar vertebrm. externally to the transverse processes ot the same vertebrm. amI it ultimately follows the ilio-psoas tendon to its insertion Into the small trochanter at the femur. The abscess destroys the psoas muscle, extends downwards into the false pelvis over the iliaous musole, and forms a large fluctuating swelling in the iliao fossa. Travelling still farther, the pus passes by a narrow neck beneath Poupart'li ligament, just external to the femoral vessels, and then works its way behind the femoral vessels towards the insertion of the ilio-psoas tendon into the small trochanter of the femur, pointing at or olose to the saphenous opening. A typical psoas abscess, then, when fully developed, consists of four parts: a narrow track in the psoas muscle. an expanded. portion over the iliac fossa, a narrow neck beneath Poupart's ligament,and a second expanded portion in the upper part of the thigh. Oooasionally the psoas abscess is double. In some oases th" pus tracks down the thigh. and it has been known to travel as low down as the popliteal space, and even as far as the side of the tendo Achillis. Oocasionally the pus may enter the true pillvia, pasil 222 AIDS TO PATHOLOGY through the grea.t sacro-sciatio notoh, and form a gluteal abscess, or it may work its way along the side of the rectum and point in the ischia-rectal fossa. Paraplegia occurs in but a small percentage of cll8es of angular ourvature, the spinal oord generally ellcaping compression because the bending of the vertebral column takes place slowly; also beca.use the spinal canal is considerably larger than the cord, which, moreover, is protected by the dura mater. When paraplegia does occur it is due to the pressure of inflammatory products which cause an oodema of the spinal cord. These products tend to beoome absorbed in process of time; hence the paraplegia is rarely permanent. Coxa Vara.-The normal angle of elevation of the neck of the femur varies between 120 and 140 degrees. Coxa vara. is that condition in which the angle is le88 than 120 degrees. In marked oll8es the head of the bone lies below the level of the great trochanter. The anterior surfaoe of the neok of the femur becomes oonvex, so that the whole of the lower limb is rotated outwards. The deformity is generally due to separation of the upper epiphysis of the femur, partial or complete, and the subsequent reunion in a faulty position. It may also be due to rickets. Coxa Valga is the antithesis of coxa vara, the angle of elovation being over 140 degrees. It may result either from separation of the upper epiphysis and its subsequent reunion in a. faulty position, or from rickets. Genu Valgum, or • Knook-Knee, • is a deformity in which the tibia is de:B.ected outwards from the femur, so that the external angle at the junction of the leg with the thigh is smaller than normal. The deformity is alway8 acquired, and usually double. Knock-kn,ee develops at two periods of lifoDuring early childhood. During adolesoence. During Early Ohildhood.-The oause here is ric'fceta. The lower end of the diaphysis of the femur and the upper endof the diaphysis of the tibia, being soft, bend inwards. The result is an OIJYlK'renl lengthening of the internal condyle of the femur. DEFORMITIES 223 During Adoleacence.-The strength of the knee-joint, like that of the arch of the foot. depends not only upon the ligamenm, but also on tho bracing o.ction of the surrounding muscles. Normally, the weight of the body is transmitted more through the outer than through the inner condyle of tho femur; if tho muscles are weak. the weight is thrown still more upon the outer condyle, the growth of which is retarded, while that of the inner is accentuated. This inoreases the downward and inward obliquity of the femur. In whichever way the deformity of knook-knee is produced, stretching of the internoJ lateral ligament. occurs, while the extemal lateral ligament, the ilio-tibialoand of the fascia lata., and the biceps, undergo shortening. The patella is thrown outwards. Genu Varum.-This. deformity is the antithesis of genu valgum. It is {lro.ctically aJways bilateral, and is due to riokem. Talipes. Deformities of the foot may be congenital or acquired, and they may occur in both extremities or in one only. T he following are the different varieties: Talipes Equinus, in which the heel is drawn up so that the patient walks on his toes, which are at a right angle to the foot. This condition is rarelyoongenital . .A oommon oause is infantile paralysis of the dorsi-flexors of thefoot, oausing a seoondary shortening of the musoles at the baok of the leg. It may also occur in connection with hemiplegia, lateral sclerosis, abscess in the calf, or even simply lying in bed. Talipes Calcaneus, in which the anterior part of the foot is drawn up, forcing the patient to walk on the heel. It may be congenital, or .the result of infantile paralysis of the muscles of the calf. It is rare. Talipes Varua, in which the anterior part of the foot is twisted inwards at the calcaneo-cuboid and astragaloscaphoid articulations, the pationt walking on the outer border. ~ It is generally associated with talipes equinus, pure talIpes varus bcing of extreme rarity, and, when found, usually congenital. Talipes Valgus, in which tho anterior part of the foot is twisted outwards at the oalcaneo-ouboid and astragalo. AIDS TO PATHOLOGY scaphoid articulations, the plantar arches being obliterated and the sole flattened. It may be either congenital or acquired, and when the latter is generally the result of infantile paralysis. Talipes Equino-Varus is muoh the most frequent variety of talipes. The hoel is drawn up and the. foot twisted inwards. the patient walking on its outer border, where a bursa tends to form. The twisting takes place at the oalcanea.cuboid o.nd astragalo-scaphoid articulations. In ordinary cases there is an inorease in the obliquity of the neok of the astragjlolus. Seconjary contraction of the muscles, ligaments. and fasoim, ta.kes plaoe on the concave side of the foot. The tendo Achillis, and the tendons of both the tibalis anticus and the tibialis postious, are shortened. With the exoeption of the altered obliquity of the neck of the astragalus just mentioned, the tarsal bonea are at first quite normal. In old-standing oases, however, those on the inner side of the foot, being compressed, remain undeveloped. The most frequent cause is infantile paralysis. It may also be congenital when it affects both feet. The most probable explanation of this latter form of talipes is that, owing to some malposition of the fretus in utero, or to deficienoy of liquor amnii, or the presence of adventitious ba.nds, there is an a"est of the 1.£nfoldi1lfJ pr0C688 of the feet. , If the inversion of the foot, which is normal during the early periods of fretal life, be maintained beyond the normal period of time, the musclcs and ligaments will as a. consequence be adaptivoly short on one aspect of the limb, and too long on the other; a normal position of inversion will finally become a. deformity' (Parker and Shattock). Talipes Calcanea-Valgus, in whioh there is a combina.:tion of talipes calcaneus with talipes vo.lgus. It is a very rare deformity. Talipes Cavus, in whioh the main arch of the foot is a.bnormally developed. It is always an aoquired condition, and is due to paralysis of the interossei musoles, with towo contraotion of the opposing musoles, in oonsequenoe of whioh the proximal phalanges beoome hyperextended upon DEFORMITIES the metarsal bones, and the two distal onosflexoo towards the sole. The deformity is almost always combined with either talipes equinus or talipes equino.varus. Flat-Foot, or Talipes Planus.-The plantar arches do not exist in the infant, but are acquired by exercise of the deep muscles of the calf (flexor longus digitorum, tibialis pomcus, and flexor longus hallucis) and that of the tibialis antious and the peroneus longus. The ligaments (more particularly the inferior calcaneo-scllophoid and the long and short plantar ligaments) simply help to koep the bones in position when the arch is finally established. The primary oause of flat-foot would appear to be m'U8cular weakness; this throws an extra strain upon the ligaments, which, lengthening, allow the instep gradually to sink, 80 that the sole becomes quite flat and displays 0. tendency to eversion. The head of the astragalus, which forms the keystone to the main plantar arch, is displaced downwards, and in bad cases may rest upon the ground, the internal malleolus being perceptibly lowered. The inner side of the foot becomes lengthened. The deformity frequently comes on in early adult life, when the body-weight increases out of proportion to muscular development, and it is especially liable to occur in those who have to carry heavy weights, as for instance, in the girl who has to carry an infant. BaUus: Valgus consists ~f an outward displacement of the great toe, so as to form a sharp angle with its metatarsa.l bone. It results from wearing fa.ultily-shaped boots. As a consequence, the toes are crowded together, and the distal end of the first metatarsal bone becomes prominent, being usually covered by a burs~ (bunion). Hammer-Toe is the deformity in which there is hyperextension of the proximal phalanx, with flexion of the second and extension of the third. Corns or bursro usually form over the points of pressure. The deformity generally Involves the second toe. Although sometimes congenital, it is usually acquired aa the result of the toes being crowded together from wearing pointed boots or high heels. Dupuytren's Contraction is & shortening a.nd thicken· ing of tho digital processes of the palmar fascia. inserted 15 AIDS 'I'O PATHOLOGY into the middle phalanges. It oommonly begins in the little finger, thenoe extending to the ring and middle fingers, all of which Me drawn down into the palm. The cause is generally some long-continued pressure on the palm of the hand, such as ma.y result from the use of oerta.in tools, from pla.ying golf, rOwing, or from lea.ning on a walking-stick. In some ca.ses contraction occurs without any apparent exciting cause, and it is then ascribed to gout or rheumatism. 'On examining the hand, projecting ridges can be felt extending from the palm to the fingers and if an attempt is made to strengthen the fingers these ridges become taut. The skin over them is at first free, but subsequently becomes adherent. The deformity can be readily diagnosed from contraotion of the flexor tendons by the fact that the tendons above the wrist do not become tense when an attempt is made to stra.ighten the fingers. Volkmann's Contracture.-This is the result of auremia of certB.in muscles due to the pressure of bandages or splints applied in the treatment for: (a) separation of the lower epiphysis of the humerus j (b) fractures of the radius and ulna.. Contraction of the fingers occurs, and some· times of the wrist. The contraction and paralysis come on simWtane0U8ly, a circumsta.nce that differentiates it from the condition arising from injuries or diseases of the nerves of the brachial plexus. Adenoid Disease. A.denoid disease (. adenoids ') consists ot a hypertrophy ot the adenoid tissue in the naso·pho.ryn:s:. The growth may entirely fill this cavity, causing 0. blobko.ge of the Eustaohian tubes and ot the posterior nares, thus oompelliDg the patient to breathe through the mouth. The diseaso, though in rare instances oongenital, does not generally begin until atter the first year of life. It seldom begins after puberty, and, if already existing at puberty, tends spontaneously to get well after this period. . Should tho nasal passages be ohronioally blocked before the upper :law (maxllla) has 1Inlshed growing, this latter fails to develop properly, and there results what may be termed • the mouth-breather's ;law.' The MouJh-lJreather's JatD.-This deformity essentially In,"olves tho ~la, the mandible being a1fected only In so far DEFORMITIEst as Its shape Is moulded by that of the maxilla. Thill falll to II'1'Ow to its normal dimensions, and it is oompressed laterally, so that the front portion proJeots unduly, while the palate is vaulted, and, though aotually less than the normal height, appears abnormally high. The alveolar ridge being less than the normal length, while the teeth tend to grow to their normal dimensions, these are unable to take up their proper pOSitions, and are thus irregularly disposed. Proo01£nud dental i,.,.egu!ari!lI, indeed, is palhoUnoinonio 0/ tke momk-bf'ea!ker'B law, and in nineteen oases out of twenty (like the mouth-breather's :law itself), Is indicative of the existenoe of adenoids, past or present. Defeotive development of the maxilla leads to alteration in the shape, not only of the mandible, but even of the skull. Though adenoid disease Is muoh the most frequent oause nasal blockage In the young, and thus of the mouth-breather's ' Jaw, ohildren may, of oourse, sWfer from nasal obstruotion from other oauses, so that a typioal mouth-breather's jaw may sometimes bo met with In a person who has never su1fered from adenoids, but this Is rare. Congenital syphllis, being a oause of nasal obstruotion, may lead to the deformity; In this oase, however, owfng to the Imperfeot development of the teeth, dental Irregularity is less apt to ooeur. The pathology of this deformity has exolted muoh oontroversy. Probably the ohief faotor In its production Is a negative on--'.fl., the absence of the normal stimulus supplied by nasal breathing. Clearly, ~e dally passage of some 1Ifty thousand respiratory currents through the nasal passages must ln1Iuence the development of the surrounding parts. Another oausatlve factor which has been suggested Is the unduly low Intranasal negative pressure produoed b,.. inspiration through partially obstruoted nasal passages. Palholow 0/ AdenoidB.-Adenolds Is essentially a disease of olvfUzed pooples. That it must be very rare among primitive oommunlties Is shown by the faot that, amoug the vast oolleotlon of skulls of non-clvfUzed raoes In the Hunterian Museum, the writer oould not lInd a single mouth-brea.ther's Jaw. One known factor In the produotion ot adenoids Is oatarrh of the naso-pharynx, and, this being otten the result of mlcroblo Infeotion, the frequency of adenoids among the olvillzed may perhaps partly be explained by the prevalence among them of Infective' colds In the head,' In oonsequenoo of their being so orowded together. There is, however, a muoh more potent cause of catarrh In children-namely, Improper feeding,leading as It does to toxmmfa of gastro-Intestinal origin-' alimentary toxmmia,' as we may call it; Improperl'y-fed children su1!er greatly from gastritis, enteritis, bronohitis, pharyngitis, and rhinitis. The chief defeot In the modern syStem of feeding ohildren is that their food oontains an excess of pultaceous starchy material, whloh both faUs to a1ford su1llolent exerciso for the jaws and allows the stomach to be swamped with 8.Il 0' 228 All>S TO PAT.ttOLOGY excess of starch whioh has not been properly Insalivated. In oonsequence of thls, not only does the chUd suffer from perennial alim.entary toxremla, whloh !,"enders him liable to catarrh, but the jaws and neighbouring parts, Including the nasal apparatus, faU to develop properly. Now, an ill·developed naso-pharynx, lined by a catarrhally-disposed mucous membrane, affords conditions peculiarly favourable to the growth of adenoids. A further faotor In causation Is the absence of the stimulus to the flow of blood and lymph in this region normally aftorded 'tIy vigorous mastication; the close proxlmlty to the nasopharynx of the powerful pterygOid muscles is worthy of note In this oonnection. Adenoid disease Is, In short, essentially a dietetio disease (R. Campbell), and mlght be practloally eradloated by the adoption of a rational system ot feeding ohildren. BAPRl£MIA-SEPTIC.2EMIA-PY1ElIIA. The baoterla whioh, living on dead organio matter, cause putrefaotion are known as saprophytes (sapros, putrid, rotten), and are described as non-pathogenic, beoause they are unable to grow on or In healthy living tissues. The baoteria whioh develop in living tissues are known as parasites. and are do· lI<'.ribed at path.ogenic. Bactlll'ial Proaucts.-The most important of these are the tomns, whioh are the essential oause of the symptoms- of baoterially·induced disease. 8epsis.-Thls term is generally ased In oonnection with wounds. A wound is said to be In a oondition of sepsis. or to be septic, when it has become Inoculated with pathogenic or non-pathogenio bacteria. In/ecIlion is the term applied when pathogenic organisms, having entered the llvlng body, develop therein. Sapremia. or Septic lDtomation. If putrid blood. serum, or the fluid of decomposing tissue, is carefully filtered, and injected into an animal, there resultr-rigor, pyrexia, muscular twitchings, vomiting, diarrhcea, and eventually, if the dose is sufficiently large, death from cardiac failure. On examining the dead anima.!, the blood is found to be tarry and imperfectly coagulated, but free from micro· organi81ll8 : the endothelium of the heart and bloodveBBels is stained by pigment derived from disintegrated chromooytes; small petechia.! hmmorrhages are noticed benea.th the serous membranes; the lungs are engorged; the liver, spleen, and kidneys, are soft, pulpy, and friable; and the intesliiDal mucous membraD,!l is intensely congested. SAPRlEMIA-SEPTIClEMIA-PY lEMIA 2%9 l'he term Saprremia is applied to the constitutional symptoms similar to those just indicated resulting from the absorption into the system of toxins generated by organisIIls, either pathogenic or non-pathogenic, existing in a. septic wound. No organisms entering the body, the poison is not self-multiplying therein, and its effects are strictly proportional to the dose absorbed. As found in man, examples are: Absorption of poisons from the pent-up discharges between the flaps of an amputation stump, and the decomposed retained matter in the uterus after parturition. POllt-mortem Ohange,.-Death rarely results. The post-mortem changes are similar to those found after injecting putrid blood· serum into an animal (see above). Septicamtia., or -Septic Infection. If Wllfiltered putrid fluid is injected into an animal, the result is the setting up of a train of symptoms·very similar to those found in saprmmia.; but the animal soon dies, even after very smaJl injections, and large numbers of micro-organisms are fownd in· the blood. The term Septicmmia is applied to the condition which results from the entrance into the system of pathogenic organisms from a. septic wound. The wound may be of the most trifling nature, but if it permits pathogeniC organisms to enter, these may multiply in the system ad infinitum, and this being so, the symptoms are not proportional to the dose absorbed. In man septicmmia most frequently results from punctured, dissecting, and post-mortem wounds, and from infection during the puerperium. Most cases are due to streptococci. P08t-mortem Ohange8.-These are the same as those observed in saprmmia. Pymmia.. If a. putrid fluid, holding in snspension not merely pathogenic micro organisms, but decomposing solid particles, is injected into an animal, death takes place, and secondary abscesses are then found in the lungs, spleen, kidneys, and brain. The term' pyremia ' is applied to the condition in which AIDS TO PATHOLOGY there occurs the passage of septic emboli into the bloodstream, giving rise to rapidly-forming scattered abscesses. These emboli are derived from the breaking down of a septic thrombus in a vein, the .sequence of events being: (a) Septic phlebitis in connection with a wound. (b) Inoculation of the contained thrombus with pathogenio organisms. (c) The breaking down of the thrombus into emboli. (d) Dissemination of the emboli by the circulation. (8) The plugging up of the terminal arterioles of the lungs, spleen, kidneys, etc., by such emboli. (/) The formation of septic infarcts, in whioh are reproduced the conditions existing in the original wound (= pYlelD.ic abscesset;). The mioro-organisms are the same as those found in septicmmia, streptococoi being the most abundant. Py.mia WILB, in pre-Listerian da.ys, a very common cause of death after operations and oertain injuries, especially those implicating veins, bones, or joints; now it is but rarely seen, except in the form of .eptic tkrombosia of the ZatsraZ Binu. in conneotion with middle-ear disease. Po.t-mortem Cha.ngBB.-The veim lea.ding from the infected wound show suppurative phlobitis and periphlebitis, and they contain thrombi in various stages of deoomposition a.nd disintegration. The lungs are congested, a.nd scattered thrqughout their substance are septio infarcts, ra.nging in size from a pea to a walnut, and having their bases beneath the pul, monary pleura. In the neighbourhood of the infarots are patohes of bronoho-pneumonia. The pleural sacs contain a quantity of a dark-coloured turbid fluid mixed with pus. The heMt muacle is flabby, and often the seat of small abscesses. The pericardium may contain fluid similar to that found in the pleura. The interior of both the heart and the aorta is generally deeply stained with pigment derived from broken.down ohrcmocytes. The spleen, kidney8, and brain usually show septic infarcts similar to those found in the lungs. The joints, particularly those of the knee and shoulder, are often affected, and contain a thin purulent liquid. ANIMAL PARj1SITES 23 1 Abscesses may form in other parts of the body. such as the parotid gland. and interior of the eye (panophthaZmiti8). Portal pyamia, or suppurative pylephlebitis, is that form of JlYEmia. which ooonra in connection with ulceration of the gutro· mtestinaJ. traot or gaJ.I·blo.dder, or infia.mmation of the uuibilica.l vein in newly-born infanta. Multiple septio info.rota are found scattered throughout the liver, corresponding in situa.tion to the terminaJ brancliea of the portal vein. ANIMAL PARASITES. OllUrijicatiOfto { 1:=:a':m~~ihiBtOZytica. TrypaflOBoma.. Malarial para.Bite,. Treponema. "allidum. Leishman's body. Tami" ,olium. Oestoda, or Tamia. medioc"nellatll. taLpe-worma{ Tcmia echinococcus. Bothriocephalus lGtus. .AscariB lumbricoides. ProtOJloa· O~uriB tlermicularia. TnchocephalUIJ dispa.f'. .Ankylostoma duodeaaf.e. thread-worms Trichitsa Ipir..ZiB. { Filari• • a'll(JUiwi8 Itominis. Dracunculus medinensi,. m.._ t d or {SClti8toSomum, or BilAar:na ItlBmMo5ia. "'~uka. 0 a., Schiatolomllm callo;. .. e-worms SchiBtosomumjaponicum. Nema.toda., or ProtOZOa. The term Protolloa is applied to the lowest group of the animal kingdom, a group which is sharply distinguished iTom others (M8tasoa) by the fact that its members are simple unicellular maSBes of protoplasm. Most of the parasites found in circulating human blood a.l"e protozoal; the only metazoal are the embryos of the order Filariidre (FiZ. Banerofti, etc.). Ammba coli is found in the upper part of the la.rge intestine; it does not penetrate the mucous membrane,. and is probably quite harmless. AIDS TO PATHbLOGY Entamceba. histolytica. is found in the dejeota and in the ulcers of the disea.sed bowel in Asiatio dysentery, also in the walls of a tropical absoess of the liver. The erganism measures 25 " to SO ". in diameter, and consists of an outer translucent part, the tleto,arc, and an inner granular part, the tmdOBarc. It is colourless, throws (lut pseudopodia, is actively motile, and in its general charaoters resembles the ordi,nary ammba. Reproduotion is by fission. Trypa.nosomata. are minute protozoal organisms shaped like an elongated spindle, with 110 long la.sh or flagellum at one end, and 110 delioate finlike swimming membrane running from the attachment of the flilogellum to the other end of the spindle. .They swim very aotively in the blood-plasma, with a wriggling sorew-like movement, the flagellum being usually in front' (Manson). They are never contained in the blood-cells. Their average size is three to four times the diameter of me red blood-oorpuscle. One speoies, the Trypanoaoma Gambitm,c, is probably the cause af tho.t scourge of Africa, the aleeping Bicknell (in which disease there is a well·marked cerebro.spinal meningitis), as it is found in the blood, cerebro-spinal fluid, and lymphatic glands of patients suffering from this disease, being conveyed from the sick to the heo.lthy by means of a biting l1y-the GIOBSina palpali,. (Another fly, the Glol8ma mor8itana, ill now also suspected. 1$ is found much farther south-as far as Rhodesia.) ~other speoies, the Trypanosoma Bruoei, causes the tsetse-l1y disea.se of horses, dogs, sheep, and the large game of Africa, the l1y aoting as the intermediary which carrieG the pa.rasite from one mammal to another. A third species, tho Trypano,oma Lewisi, infests the mt. Mala.riaJ. Pa.ra.sites.-Malarie.l fevers are caused by the presence in the blood of small, colourless, amreboid proto.zoa. The para.sito has two cycles of existence, one pa.ssed in man, the other in the mosquito. Into. the human host the organism is introduced by the }lite of the mosquito. Taking up its habitat in the red blood-corpuscle, it lives at its expense, and 'lJlultiplies asexually by simple division. In a.ddition ,to this method of a.sexual reproduction, the parasite a.lso produces orescent - shaped sexulll forms which ANIMAL PARASITES 233 under ordinary circumstanccs perish in the blood (being probably engulfed by phagocytes); but if they are transfcrred into the stomach of the mosquito, Il.S when the insect bites a man whose blood contains these foms, they undergo further development there, and reproduce themselves sexually. In the proboscis of the mosquito thero are t1vo separate tubes. one UP. which blood Is sucked, the other down which the intooted So.lIvu. Is injected. Of the three to four hundred described species of mosquito. only a limited number arc malaria-carriers. and these belong to the subfamily .4 nophelina. In common with other Insects. the mosquito passes through the follo\vlng stages of development: The adult female lays her eggs in still water. In tho course of from two to four days thoso arc hatched Into laM/aI. which in about ten days' time are transformed Into the pupm. these two days later becoming full-grown insects. or imagos. Atter hatching they must have air, which is breathed through 0. hole near the tall. The normal position of the little animal is lust below the surface with the tail pointing upwards. Eventually they burst their pupa-casos. and flyaway from the water. The female impreonated aneplloles is tho blood-sueker. and then Only during night-time. The vitality and growth of the mosquito aro favourod by warmth, and retarded. or altogether arrested. by cold. The malaria.! parasite, once introduccd into the blood of man, may persist for months. sometimes for a year or two. After this it dies out, unless reinfection by the mosquito ~s place. Whilst in the blood, it lives entirely at the expense of the red corpusQles of its host. The life-history of all is pJ'8.~tica.lly the same, and consists of two cycles: (a) The human cycle, and (b) the mosquito cycle. (al The Human Cycle.-At the time of infection by the bite of the mosquito, minute rod-shaped bodieB-8porozoiteJ (IS)-are introduced into the blood of the human host. Each sporozoite at once bores its way into 110 red bloodcorpuscle (I), in the interior of which it develops ~ally in the following manner: The rod-shaped sporozoite assumes a spherical shape. forming a minute unicellular mass of protoplasm, 8ckizont (2). exhibiting ammboid movement and occupying but a small po.rt of tho corpuscle. Gmdually it increases in size until it occupies nearly the whole 234 AIDS TO PATHOLOGY (\ 3 :$' _.~~~~ O n e~.! ~:;:: I 74, 4;1J;(j(@ie~@~ .I ~~ I~ f S !ljf./flfl 'I) 1{JffJ/rf~f I ~.IJ,J(JI3 ~ @ ....... '" ~" ~ ••;..,~ .•• .G) Iliff ~11{f,/1/ II" ~.;. /f/Jlflilly J • (@D@"":II .,.' l~, 1 MOSqU'Tl/ I ...... ~ " ~ ®. 0;~ .~_~r""':'~ cYeLl! ..... :,~, .... . . . :0 .( I ./ FlG. 16. 1, Boa lIoEpnaele with sporozoite entering; 1', red OOl'pllscle with merozoite enle.riD(; SI. 8••tagtS of developJDeut within red corpuscle (lIIlhinll;t); 4, rosette body; 6, Jorma.tlon of merozolteai 6~ libere.tlon of merozoite. into I!ls.sma by bllHting at rea eotp1llCle; S', merozoite, whiclJ 6_8& (7) erescenti body; 8. meJe _cent; 9, female creacent; 10. male ga.tJIetocyte; 11. female gametocyte; 12, forma.tion of microgWletes in male gametocyte; 1S. formatiOli of me.crogametll in female gametocyte; 14. fertiliza.tiOli of macrogamate of female gametocyte bye. microgamete of the male gametocyte. whiob now becomes a zygote i 15. O(lkinet· 16. oocyet; 11, developlllGnt of aporoblsatB; 1S,llbeta.tion J sporozoite•• corpusole (3). the hlllllloglobin of which is oonverted into gmnules of pigment, whioh ultimately collect into clumps. ANIMAL PARASITEs 235 The parasite now undergocs segmentation, arranging itself in a cluster of minute spherules (15 to 25), and form. ing what is known as the rosette body (4). These segmented bodies soon break up into separate parts, merozoites (5), and by the end of forty·eight hours the corpuscle ruptures and liberates these into the plasma (6). Eachmerozoite then inva.des a fresh red corpuscle (1), in which it repeats the same forty-eight hours' cycle of development. This asexual process of multiplication by simple division is known as sckizogony. The setting free of the merozoites into the plasma coincides in time with the onset of the febrile attack, and it is proba.ble that a fever-producing poison is also liberated when the corpuscle bursts. The completion of this asexual oyole takes forty.eight hours in tertian fever, and seventy·two hours ill quartan. (b) The Mosquito Oycle.-In addition to the above asexual multiplication, some of the parasites in the red corpuscles develop (as before explained) into crescent· shaped sexual forms (7). The crescents contain pigment, and are of two distinct kinds: The female crescent (9), 0. long and narrow cres· cent, round the centre of which the pigment is arranged in a circle; the male crescent (8), Do shorter and thicker crescent, throughout which the pigment is scattered irregularly. , Each of these bodiee remains enclosed within the thin shell of its respective red blood-corpuscle, and if left in the blood of man does not proceed to segmentation, and undergoes no further development. Should, however, a mosquito bite a person in whose blood these crescents exist, they are then conveyed int:> the insect's stomach, where, escaping from the red blood·corpuscles: they become free. The crescents now beooIlle spherical, and are known as the female (11) and male (10) gamel.ocytes respeotively. From the outside of the male gameMcyte (12) whiplike filaments (microgame!e3) now protrude, and becoming detached, swim about in the stomach of the mosquito until. meeting a female ga.metocyte (13). one of them fertilizes the large cell (macrogamete) oontained in it (14), and gives rise to a zygote. AIDS TO PATHOLOGY The zygote, at first spherical, becomes ovoid with Il pointed end (ookinet, 15). and, acquiring powers of locomotion, burrows through the epithelial lining of tho stomach, a.nd comes to rest between the epitheIia.1 and the muscular layers. Here it forms a capsule round itself, becomes spherical. and begins to grow (oiieyst, 16), until by the end of from ten to fourteen days it has attained a comparatively large size. 'During this time the contents have become converted into a number of rounded masses (8poroblaat8, 17), each of which, when the process of subdivision is completed, becomes covered with a pile of thickly-set, minute, elongated, spindle-shaped rods (8porozoites, 18), arranged like the spines on a hedgehog' (l\:[anson). Finally, the capsule ruptures, a.nd the sporozoites, escaping into the lymphatics on the outer surface of the stoml!-ch, enter tho oircull),tio~, and are ultimately convElyed to the salivary gla.nd. When the mosquito bites a man, the spqrozoites travel down the probosois with the salivary or poison fluid and are injected into their human hest (1), and there meeting red blood-cells, function as the merozoites did. There are three kinds of malarial parasites: 1. Plasmodium malqritB. 2. Plasmodium fJif)lJ3; (tertian). 3. Plasmodium Jalciparum (malignant). Variations in oyoles may be produced by mosquitoes biting on sucoessive nights, so that one crop will mature and sporulate twenty-four hours before the other= quotidian type of fever. Summary of Sexual ·Cycle. The Jemak gameWcyU encloses a. single cell, called tho macrooameie. which Is the homologue of the ovum. The male gametlJC'Ute develops ,upon its exterior whipliko proccsBOs. oalled microga:tlUllu. whioh are tho homologue ot tho spermatozoa. One of these mlorogam.otes fortiliJI:es a. maorogamete. the result being a. Z1Ig~. The zygoto. when It has acquired powers of looomotloJI, is termed an o(Jkinet. The enoysted oilkinet in the stomach wall is called an OIJC1/Bt. In the 06cyet aro developed tIle 8JlorOOlastB. and from these lInallY are formed the BpCfI'Ozoite8. ANIMAL PARASITES 237 In the oourse of a report on the risks of the spread of malaria in relation to demobilization. Lieutenant-Colonel James says that tho factor whioh determines whether the disease will spread or not is neither tho number ot anopheline mosquitoes in tho district nor tho number ot human malaria oarriers_ It depends on the closo and oontinuous association between the malariB carrier. the anopheline. and tho susoeptlble porson. This is only IIkoly to ODDur in the type of dwolling ,vhioh tho mosquito solects as its pormanent feoding Bnd J:ostlng place. It has been found that tho malaria-boaring mosquito does ROt stau in a ~1'-lightM house or modem hOBPital. Clean baro walls and ooilings. large windows. and littlo furniture Bro not suited to it. On tho contrary. it selects cottages or old-fashioned houses. where the rooms are ' stufJ'll • and hot, ill-lilJllkd. il'-1lemilated. 1I1iO& dark recesses. C1I.pboards. old drapery. and much furniture. Hero tho mosquito takes up its abodo. and it there is restrictod living or sloeping acoommodation. intootion is very likely to bo oBrriccl from tho malaria-oarrier to tho susceptlblo porson. Treponema Pallidum.-Vide p. 194. • Leishman's bodies (or Leishman-Donovan) are found in the spleen and bone-marrow of tropiCBI splenomegaly, or 1cala-aza,.. Each is ovoid in outline, with a. large deeply-staining nucleus, and a tiny rod-shaped, still more deeply-staining nucleolus_ Tho disease is transmlttod by tho blto ot the common bug Captain Patton (!.llf.S.) has sucoeeded in observing tho oomplete dovelopment ot tho )mIa-azar parasite both In Indian bedliugs Bnd in the European SpOOiOB. Species: Leishman-Dono'Vani, causes kaIa-unr (India); Leisl~man tropica, oauses Delhi lioU; Leishman infantum, oauses infantUe splenic anlllIllla. Cestoda (keltol, a girdle). The members of this group have a life-history whioh is peculiar in tha~ it embraces two dis~inct stages of exis~ence -the adult BtagB, generally found in one species of animals (the host), and the embryonic dagB, found usually in another species (the intermediate host). The adult tape-worm occupies the intestines. It consists of a head, a narrow neck, and a series of lIattened segments, or proglottides. The head at its widest part is provided with four suokers, by means of which it fastens itself to the intestinal mucous membrane of the host, and anteriorly it is pro- AIDS TO PATHOLOGY longed into 80 f'08tell1,m, or proboscis, surrounded by two rows of hooklets. Commencing at the a.nterior part of the body and running ba.ckwards aJong each side are two 10ngitudinaJ tubes-the water fJa8cular Bystem. Tllere is no aJimenta.ry C&naJ. Ea.c.h progiottill is bisexuaJ, the respeetive senaJ ducts opening at the genital papilla, which is placed at one edge of each proglottis, the papillm being at alternate sides of successive 86f,ments. The teats8 consist of smaJl vesioles, the ducta of which uuite into a vas deferens, whioh enters the penia. The uterua is branched, having a centr-.J, canal with lateral diverticula; it is connected at one end with two ooariea by means of two oviducts, and at the otlaer end with a vagina. The Bpermatozoa travel from the pellis, enter the vagina. at the genitaJ pore, and then fertilizo the ova. The di8taJ proglottides, holding the embryos, become deta.ched, ,.and escape from the intestines with the fmces. I The proglotlis then decomposes and liberates 'he embryos, each of which is provided with six hooks and surrounded by a capsule. If the embryos are now swallowed by another animal (ths intsTmetUate koat) , their capsules are dissolved ~~x!ts digestive juices, and the embryos esoape into the . entary canal of the new host. They then bore their way through the walls of the alimentary canal, and finally settle in the viscera, or the musclE\ll. After this, the further development of the embryo is as follows: The hooklets disappear, and at the caudal end a cavity develops, in the interior of which an immature head (.cole",) appears, the whole organism being afterwards enclosed by 0. fibrous capsule formed by oondensation of the surrounding connective tissues of the host. This intermediate stage is known as the Oysticfff'CUI CellUWBtB, or bladder-worm. Should the flesh of the animal harbouring the Oy8tic6TCUI ceUulo.tB now be consumed by another animal, the head of the cysticerous becomes everted, and, losing its bla.dder-like appendage, fastens itself to the .intestine of the new host by means of its foUl" BUckers, and develops proglottides frdm ita caudal end. Hydatid Cyst.-The intermediate stage of the TtBnia. "MnoOOCCUI is known as the hydatid. The embryos, ANIMAL PARASITES 239 proviaea witb tbeir six books, enter tbe alimentary canal of some animal-aay man-and their capsules being dissolved by the digestive juices of the bost, they are set free. They then bore their way into the tributaries of the portal vein, and so reach the liver or other organ, where they come to rest. FIG. 17 .-BROOD OAPSULE. 'Ea.cb embryo now loses its booklets, and is connried into a cyst, the wllllll of which are composed of concentrio lamina lined by granular cells-the gernWnal memll'rlm6and filled with a non· albuminous lluid rich in sodium TABLB OF CBIBF POINTS OONCBRNING THB TAPE-WORMS. Name. Tamla aolium. Tami.. medio· canellat.&. Lendh ••• - ProiJ,ottldes 10 feet 800 15 feet 1,000 ninch present 26 -n inch a.bsent o.hsent 4 Pig 4 Ox Read .•• Rostellum Booklets ..• ... •• , .. . Suckers... .. . Intermedia.te hOlt TIIID.ia echfno· oocous. linch 3, B%clu· sive of head Bothrio- cephalus liLtus. 20 feet 8,600 irinch hfnch present a.bsent present abient 4 2 Me a.nd Sturgeon, eheep pike, trout N.B.-Avenzgelength a.nd number of proglottides given. 240 AIDS TO PATHOLOGY chloride and containing the hooklets, which are of great diagnoltic va.1ue. They are insoluble in acids. Within the cyst are b"ooa CapBUle. j these are small vesicles which, originating from the germinal membrane, contain immature heads (,colicell) orowned with hooklets, and are analogous to the Oy.tiCfJf'()'U' cellulo.tB of the other tape. WOrllls. Tile entire hydatid oyst is surrounded by an adventitious capsule of fibrous tissue. Nematoda. (nema, a thread). These "are slender, elongated worms tapering at the extremities. Each has an alimentary oanal, with mouth and anus. The sexes are distinct, the female being the larger. A few typioa.1 members of the class alone need be described. . Ankylostoma Duodenale. - The female is about ! inch in length, the male slightly shorter. The mouth is furnished with teeth, by which the worm fastens itseU to the duodena.1 muoous membrane of the hosr. The egg ill enclosed within a thin transparent capsule, and is voided with the freces. It then matures in d~p earth the ep:l,bryos invading the body of the new hoat, probabiy by penetrating the skin, generally that of the feet or leg!!. From the likin they enter the blood, ultimately rea.ching the lungs. Up to this time they retain their original size, but once in the air.passages of the lung!! their growth Is rapid. They then travel up from the air· vesicles into the bronchi, trachea, and glottis, whenoe they pass into the resophagus, and thenos into the duodenum, where they attain maturity. These parasites, in virtue of their leechlike habits, suck a great quantity of blood from the duodenal mucous membr~e, causing 8 serious form of aDlemia (oooli6 antBmia), which is associated with a great increase in the eosinophile leucooytes in the blood. The worm in 1908 made its appearance amongst the miners engaged in the Da.1coath tin.mine in Cornwall. It is oommon in Egypt, Brazil, Italy, and other hot countries. Trichina. SpiraJis.-The fema.1e is about 1 inch long, and the ma.1e about inch. The mature worm is found in the intestines of man and other anima.1s; the n ANIMAL PARASITES Immature form is found in the mUsoles. The ova aN hatohed into embryos in the uterus, tM 'Y0'IIII'IfI bmt,g born in tke free stGte. The life-history of this para.site is BI follows: When infected pork, e.g., is eaten, the capsulel containing the em bryos are dissolved in the stomach by the digestive juices, and the liberated young worms pails into the intestines. Here, in the course of a. few days, they atto.in. maturity and pm. the females afterwards boring their wa.y through the mucous membra.ne into the lymphatics, where they liberate their young (each female giving birth to thousands), whioh are then oarried into the general circulation. Ultimately they reaoh the voluntary musoles (especially the abdominal, thore.cia,. pharyngeal, and tongue), and piercing the sarcolemma, coll themselves up in the interior of the fibres, and become encysted, in this position undergoing no further development until the infected flesh is eaten by a new host. After a time the cyst wall may calcify. The cysts are visible to the naked eye as minute whit,e speoks, firs' observed by Sir James Paget, when a student in the disseoting-room of St. Bartholomew's Hospital. They have been found in all striated muscle except that of the heart. The disease is conveyed to man by. the ingestion of imperfeotly oooked trichinosed .pork. The pig is usually infeoted by eating triohinosed rats. FUaria Sanguinis Hominis.-The adult form of this worm is known as the Fila.rio, BamoroJU, and the ombryonio form as the FilairiG noohwnG. FiZtvriG BcmoroJti.-This form is confined to the lymphatios. The female is about 81 inches long, the' male only about half this size. Reproduction is viviparous, the female disoharging her embryos into the lymph, by which they are carried into the blood-stream by way of the thoraoio duct. FilaJriG NootumG.-The snakelike embryo is about ..\ of an inoh long, its breadth about the diameter of a red blood-corpuscle. The head is provided willi a ahort spine, and a circlet of hooked lips. The organism is imprisoned within a long loose SBO, inside which it oan be seen to wriggle, but from which it 16 2042 A.IDS TO PA.THOLOGY is powerless to escape, BO long lIB It remains in its human host. The embryos are present in the surface bloodvessela during sleeping hours only-whence the name F. nooturna; when the patient awakes they gradually retire to the lungs and larger bloodvessels. The cause of this remarkable periodicity is unknown. If a :filarial patient changes hiJI hours of sleep from nigh~ to day, the periodicity changes correspondingly. As theae :filarilB cannot further develop in the human host, they probably soon die, unless they are removed to an intermediate hoat. This latter is a species of mosquito (OuZez ft£tigrLns), which swallows the filaria. when sucking humm blood. In the mosquito's stomach the embryo escapes frOID the Bac which has hitherto enclosed It, and bores its way through to the thoracic muscles, where it comes to rest. By about four weeks' time it has grown considerably, and then, resuming its travels, it reaches the proboscis, and returns to another human host when the insect stings. Ii now passes to the lymphatios, where it matures into the Filaria Ba;ncrofti. The sexes then come together, and the young are born. Yllariasis.-In the large majority of CaBes the presence of filarilB in the human ,!>ody gives rise to no obvious symptoms. Occasionally, however, the mature worm may block the lymphatics, or the femaJe may disoharge, instead of embryos, unhatched Qva which are large enough ~o obstruct the lymph-streloID, and 80 give rise to lymph. ,ta..U. When this happens, any of the fonowing tropicoJ disease. may result: OhIY7luria, due to ruptured lymphatios in the urina.ry tract, the urine beooming milky in appearance and coagu· lating into • jelly after standing. Analogou. conditions are: OhyloUl dianT'hma. OhylOUl IUcite•• Lymph .erotum, characterized by the presence in the scrotum of dilated and varicose lymphatios; these some· times bunt. ElepAantituU .drabum, characterized by hypertrophy of the tissues, the result of blocked lymphatics. It is most CIOD1IDOIIly met with In the legs aDd genitals. Enormous ANIMAL PARASIT;ES tumours may thus form, the scrotum alone, for inlltance, having been-known to weigh as muoh as 100 pounds. Vanoole ligmpn.afM glMr.l", giring rise to soft, painless tumours, over which the skin oan be freely moved. AbBC6IBIJI, from the irritation caused by blooked lymphatics or by dead filaril1!. In a.ddition to the FilMia BMJtJrofti and its emblyonio form, FilMia noet"ma, which are found all over the tropics, there are at leut three other a.llied s~ found in the tropics-viz., Filaria diuf'fIG (West Africa), Filaria _pll1'stans (Africa. and Demerara), and Filaria demarqvcIi (West Indies and Demerara). Trematoda. The only member of this group at &ll oommon in man is the BiZhalrna, n.mma,tobia. The parasite is found in Natal, the Transvaal, Egypt, Madagascar, and the West Indies (particularly Porto Rico). The female worm is about 1 inoh long, the male about l inch. They inhabit the portal vein and its tributaries, also the ve~caJ veins. The ventral surface of the male is concave, and during oopulation the lateral borders become infolded 60 lioii to enclose the female in a 'gynlllcophorio cana.I.' The ova are shaped like melon.seeds, being provided at the pointed end with a spin., by means of whioh they work their way through the walls of the &mall veins; they thus gain entrance into the rectum or bladder, whence they are discharged with the flecee and urine. A good deal of oozing of blood from the muoous surfaoes may be caused by the migration. The Ova cannot mature)whilst in the body, but if placed in water, or if the urine oontaining them be diluted with water, the oapsules burst, and the ciliated embryos are set free. As regarcls the intermediate host nothing iI brown. Analogy with the history of the other nematodes would suggest that the embryo antere lome fr~lh-w&ter animal, in whose body U undergoes a further developmental change.. Infeotion in man is probably through drinking contaminated water. Some maintain that the embryo. enter the urethra or anus during the act of bathing. 244 AlpS TO PATHOLOGY The effect of the parasite is to cause mdemic /r,m_ tUM, as also the passage of blood from the rectum. Condylomata may develop both inside and outside the anuB, and for 1.hiB reason the condition ma.y be mistaken for syphilis. The period of incubation which elapses between infection and the appea.ra.noe of ova in the urine, would appear to exoeed feur months. FATIGUE. Fatigue is due to (a) using up of tho enorgy pabulum within the musole; (II) to the aocumulatio,n of fatlglle produots, whioh are acid in nature, chiefly laotlo acid. If a muscle is made to oontmot in the presenoe of oxygen,laotio aoid does not appear, and the onset of fatigue is retarded or absent altogether. BEAT-STROKE. Tho oauses are the aooumulatlon of fatigue produots, produced by exoessive musoular exertion, aoting in oonjunotion with Insu1ll.olont oxygenation of the blood. Those addiotcd to alcohol, or who are over-indulgent in feeding, and su1l'erers from malaria, are particularly prone. Previously healthy men are rarely a1l'eoted. Tho post-mortem findings are: mdema. ot the leptomeninges, braiD, and lungs; oloudy swelling of the myocardium, liver, and kidneys; fatty ohanges in the liver; peteohialluemorrhages in thc brain, viscera, and skin. Rigor mortis sots In early, and the body decomposes qulokly. INDEX ABSOEIIS 36 of liver!. 170 Acetone, IBlI Achondroplasia, 208 Acidosis, 183 Aoromegaly, 200 Actinomycosis, 76 Acute yellow o.tropby, 178 AddiBoIt s disease, 188 Adenoids, 228 Adenomata, Sf. Adrenalln, 188 Agglutinins, 44 Aggressins, 46 Ague, 232 Albuminuric retlnltls, 183 Alcoholism, 200 Alexln,46 Amboc~tor, 46 Amitotic, 2 Ammba coli, 281 Amphophil, 3 Amyloid degeneration, 9 AUlllmia 26 Anaphylaxis, 62 Anasarca, 62 Aneurism, 111 • Angina pectoris, 129 Angiomata, 83 Angio-neurotic cedema, 63 A_ngular curvature, 220 Ankylostoma, 240 Anopheles 233 Anthracosis, 143 Antibodies, 42 J..'"lt~ 4.'1. AntitoxIns, 46 Apoplexy, 114 Arteries diseases of, 106 Arterlo-sclerOllis, 110 Arthritis, deformans, 212 Ascaris lumbricoides, 231 Ascites, 62 Astral s,f3r.m,-2 Atelectasis, 181 Atheroma, 108 Atrophy, 16 Auricular ftbrlllation. 125 Avitaminoses, 205 Dactp.rlolyslns, 46 Bantl's disease, 80 Basophil, 22 Bed-sore, 58 Berl-berJ, 208 1illharzla hromatobla, 243 Blood,17 Blood-platelets, 18 Bone, 201 Bone-marrow 23 Bothtiocepiiaius latus, 239 Branchial ftstula, 218 Bronchieotasis, 135 Bronchocele, 192 Broncho-pneumonia, 188 Cachexia stmmiprlva, 187 CalclOcatlon, 8 Cancer Incidence, 103 colloid,99 duc~, 08 Cancrum oris, 69 Oarbuncle, 68 Oaroinomata, 91 columnar, 98 encephaloid, 97 scirrhus, 97 spheroidal, 98 squamous, 94 Carles, 203 CaBeation, 16 Cell,the,l Cell-nesta, 96 Centrosome, 2 Cerebral hremorrhage, 114 Cerebro-spinal ftuid, 161 Cervical rib, 219 Cestoda, 237 Chancre, 104 Charcot's joint disease, 214 Chemotaxis, 42 ~_,'L'I> Chlorosis 27 CholeliihIaSis.t 177 Chondroma, 110 Chorio-epithelloma, 06 Chromaflln system, 188 Chromatin, 1 Chromatoiyais, 8 Chromocytes, 18 Chyluria, 242 Cirrhosis of liver, 171 CIrsoid aneurism, B3 Cleft palate, 218 Cloudy swelling, 8 Coagulation neorosls, IIi ColiapRe, 116 CollOid cancer, 09 degeneratioD, 12 Colloids, 1 COlour-Index, 20 Oolumnllr-oelled carcinoma, 98 245 A.IDS TO PA.THOLOGY Oomplement. 48 Ooronll1'Y arteries, 129 Ooxa vaiga, 222 vara, 22.2 Oraniotabes, 207 OretinlRm, 186 Oulex fatlgans, 242 Cysts, 85 dermold,86 Oytolysins, 46 DefIciency diseases, 205 DeformltteB, 218 Degenerations, 6 Delhi boil, 237 Dermoid cysts, 86 Dextrose, 179 Diabetes mellitus~ 179 Diabetic coma, 11S2 gangrene, 182 Diphtheria, 45 Dropsy, 61 Drunkard's liver, 174 Duct cancer, 98 Dupuytren's contraetlon, 225 Dysentery, 282 Echinococcus, 288 Ehrlich's theory of Immunity, 49 Embolism, 65 Emphysema, 132 Encephaloid carcinoma, 97 Endarteritis, 106 Endocarditis, 121 Endocrines, 183 Endotheliomata, 90 "Endo-toxins, 88 Entammba hlstolytioa, 232 Eoslnophlles, 22 Eosinophilia, 26 Epithelioma, 94 Ergotism, 61 ErythrocyteR, 18 ExophthalmiC goitre, 186 Exostoses, 81 Exo-toxlns, 88 Fat embolism, 66 necposis, 14. Fatigue, 244 Fatty degeneration, II Inftltration, 7 Fevers, 86 Fibroid phthisiS, 142 FIbroma, 78 Fibrosis, 85, 70 Filariasis, 241 Flat-foot, 226 Focal necrosis, a Fractures, repair 01, 89 Frost-bite, 61 Frohlich's syndrome, 1.0 Gall-stones, 177 GametocyteR, 236 Gangrene, 66 Gas gangrene, 67 . G~n'ra1 paralysis of inso.ne, 19S Ganu valgum, 222 Giant cells, 71 Giants, 190 Gigantoblasts, 20 Glgantocytes, 19 Glanders, 76 Glioma, 711 GUo-sarcoma, 89 Glossina paJpalis, 232 monitan8, 232 Glycogenic infIltration, 7 GIYcosurio.~ 179 Goitre, 1911 Gonorrhmal rheumatism, 21& Gout, 218 GranUlation tissue, 68 Granulomata, 71 Growth,190 Gumma, 196 Hmmatoidln, 13 Hmmoglobin Index, 20 Hmmolf!ius, 46 Hmmoslderin, 13 Hallux valgns, 226 Ho.mmer-toe, 22'; Hanot's disease, 178 Haptophore, 99 Hare-lip, 217 Healing, 68 Heart, 119 Heart-block, 129 Heat-stroke, 244 Hepatolysin, 48 Histolysis, 36 Hodgldn's disease, 32 Hormones, 183 Hyaline degeneration, 11 Hydatlds, 238 HYdronephrosla, 165 Hyperplasia, 17 Hypertonus, 160 Hypertrophy, 17 Hypophysis, 190 HypopltlJ1tarilm, 190 Hypoplasia, 16 Hypotonu~, 180 Immune body, 48 Immunity, 98 Infantilism, 192 Infarcts, 86 INDEX Infection, 88 Inftltmtiona, 6 Inllammation, 88 Influenza, 139 Involniaon, 16 JSllI1.dJ(J8; Joints, 11J'I diseases of, 210 Kala-azar, 2ST Karyosomes, 2 Kelold,70 Kidneys, diseases of, 164 Lardacoous degeneration, II Lateral curvature, 219 Leiomyoma~ 82 Leishman's DOdy, 237 Leontiasis 0888&, 210 Leprosy, 76 Leucocytes 10 Lencocytosis 23 Leuoopema, 26 Lenkmmia, 30 Lipochromes, 12 Lipoids,9 Lipoma, '19 Liver, diseas08 of, 166 Locomotor ataxla, 199 Lumbar_puncture, 153 Lungs, diseases or, 131 Lupus~ 76 Lympn,61 Lymjlhmmia, SI Lymphangeioma, 84. Lymphocytes 10 Lymphocytosis, 26 Lymphoidocyte, 23 Lympho-s&rcoma, 86 Lyslns,46 l\Ialarla. 232 Mal1IIinant pustule, 69 Mamma, 97 Marrow 29 Mast ceils, 22 HogJiJol1bI.fU, 19 lIlegalooytes, 19 Melanin 12 Melanotio sarcoma, 88 Meningocele, 218 Menlngo-myelocele, 218 Merozoltel 235 Mlcroblasr.s, 20 Miorocytes, 19 MlUary aneurislllll, 113 Milk-patches, 119 MitotlC,8 Moist gangrene, 57 Mollities ossium, 209 Mosquito, 238 Mucoid degeneration, 11 Myelmmla, 80 L& t' Myelitis 1'18 1...- u Myeloceie, 218 Mye'/ocrtBB. .BlI Myeloma, 82 Myoma, 82 Myxmdema 186 Myxoma,7il NlBvu. 88 N ecr08is, lOS Nematoda, 240 Neoplasms, 76 Nepbritis, 166 Nerve degeneratiOll, 146 Nervous system, 145 Neuroma, 82 Neurone 145 NeuropathiC arthritis, 2U NeutrOpblle, 21 Normoblasts, 19 Nutmeg liver, 169 Odontomtlll, 81 <Edema, 61 anglo-neurotic, 63 Ollgmmia, 26 OIlgocbrommmiaL 26 OligocythlBmia, l!:6 Opsonlns, 42 Osmosls,62 Osteitis, 209 deformans, 209 Osteo-artbropathy, 210 Osteomalacia, 209 Osteomata, 80 Osteomyelitis, 202 Oxypbil, 3 OxYUrIs vermloulat1s, 231 nlf Paget'. disease of pl8, 98 Panoreas, diseases 0 , 178 Papillomata, 78 Parasites, 1191 Parathyroids, 187 Pericardium, 116 Pernicious allIBmia, 27 Pfeiffer's reaction, 46 PbagedlBna, 69 Phagocytosis, U Phlebitis, 10"' PhthiRis,189 Phyluis, " Pigmentation, III Pituitary body, 189 Plasma cell, 22 AIDS TO PATHOLOGY Pn~umokODfoaia, 148 Pneumonia, 136 Poikilooytes, 19 Polymorphonuclean, 111 Port&!. pymmi.., 2S1 Preclpitlns, 4& Premature puberty, ]92 Benillty, 192 Proteinurl.., 164 Protozoa, 231 PBoas abscess, 221 Pulmonary tllberculOllla, 139 mdema,l44 PUB,35 PYlllmla, 229 Ranul.., Jl6 Raynaud's diileaae, 00 Recet>tolBii 49 :ll.epall, I> Rhabdomyoma, .82 Rbeumatold arthritis, 218 Riokets, 206 Rodent llicer, 95 Rosette "ady, 23& Saprlllmia 228 Saprophyte8L 228 Sai'eonmte, 1:18 Sean, 70 Schizont, 235 Sclrrhus, 97 Sourvy rlcketAl, 208 SeDlitizer, 40 SepRIS, 228 SeptiCQImia, 229 Tabes dorsalis, 199 Taluia ecllinococcus, 239 medlocaneUata, 239 solium, 239 Talipes, 223 T ..pe-wormB, 239 Teeth, 208 Teratomata, 86 Tetanus, 39 Thrombosis, 64 Thymul gland, 101 Thyroid gland, 186 TortlcolllA, IUD ToxIus, 38 Toxophore, 89 Trematoda, 248 Trench nephrltla 163 Treponema p ..llldum, 193 TrlChinat!lfaliB, 240 Tricboce alua diapar, 231 Trophic. lous, 160 Tropical abscllIl8, 164 Trypanosomata, 232 Tubercle, '11 Tuberculoeia l .139 acute mulary, 74 TomoUl'll, '16 Ulcer, 36 rodent, 96 Union, prImary1 69 secondary, .,9 Sera, &5 ~~l:' ~~;ness, 55 Uro-toxlus. 164 Side·o~ theory, 49 Uterine ftbroid, 82 Slderosil, 143 Silicosis, 144 Sleeping sickness, 232 Spina biftda, 218 Splenic BnIIImia, 29 8pleno-medullary, 30 Splenomegaly, 119 SqUAmous epithelioma, Status lymphllticus, 191 StlU'B dl!jfABe, 214 Stokea-A ~ syndromo, 131 Subphre1.lc abscess, 171 Suppuration, 86 SuprarenaIs, 188 Surface tenSion, 9' « JlJLLJNO SUBCeptibUity, 50 Synnl!se, 13' Syphilis, 193 Syringomyelia, 215 ByilngolllYeioeeie, 218 Vacoines,63 Veins, diseases at, 103 VilloUB cancer, 98 Viteminea, 206 Volkmann'S contracture, 226 WaaBarmann rea.ctlon, 47 Waxy degeneration, II Widal's reaction, 44 Wound shock, 116 xanthoma, SO Zenker's degeneratiOll, 16 Znote, 8 I'Blln'IID Jlf GUA.T BBl'l'AIIII JJI' llrD., Gtm.DI'OBD A.IIID IIIIBlIR. .um SOliS,
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