Atomic bomb radiation and the oral regions

ATOMIC

BOMB

RADIATION

AND

THE

ORAL

REGIONS

Introduction N ANY consideration of changes in the oral regions that, result from esI posure to atomic explosion it is necessary to have as background a knowledge of the changes throughout the body. M’hen the entire body is radiated. the effect on the int,egrated organism is largely determined by the effect on its most radiosensitive system. the lymphopoietic and the hemopoietic apparatus, descendants of reticulum cells. The effects of the atomic bomb on human beings are on the basis of trauma from flying debris, thermal radiat.ion. and ionizinSq radiation. The ionizing radiation effects of the bomb cause only a small part 01 the total injuries; the changes produced are widely varied, depending on distance from the explosion and amount and character of shielding. C?linieal I>and pathologically the patients affected by radiat,ion were easily separated intcl four distinct cat.egories based on the degree ot’ clisease (ver\- severe! sevc~. moderat,e, mild) with close relation bet,ween severity ant1 time and inciderrer 01 mortality. The outstandin g svmptoms . were l~usca atit1 vonliting on the (la\ of the bombing, followed soon by fever, leukopcnia, diarrhea. and a Fter IW Dr. Averill Liebow of Yale at Hiroshima, and by (‘apt,ain Shields Warren a11t1 me. representing Navy and Army, at Nagasaki.’ Most, of the gross descriptions of early cases are the work of Japanese pathologists. but preserved organs and tissues for histologic study were arailable to us for onr review. M7e ~~ri’orrnr~ti autopsies after our arrival. In reviewing the effects of radiation on the systems of t.he body t,hc rcla tionship of lesions to time of death must be consideretl. In patients dyilig during the first two weeks after exposure, there was histologic evidence of ratlia tion effects in the bone marrow, gonads, gastrointestinal trac.1, and skin, whicll. however, were not manifested clinically. In t,he persons dying from the thi)*(i to sixth weeks, bone marrow changes predominatrtl and nerrt ropenic ulceration+ and hemorrhagic symptoms were spectacular. General nutrition derline(l. Gross changes were approximately at their peak. In those dying in the S~H)II(1 and third months, beginning recovery in bone marrow and rrgeneratiori of h;li 1’ were apparent, but testicular and connective tissue changes persisted. Thct,? was often emaciation. Malnutrition, however, was not based entirely on sh(~l~rages of food; intestinal lesions and other factors were largely responsible. Presented at the Fifth Stevens Hotel, Chicago, Ill., *Armed Forces Institute

Annual Meeting Feb. 4, 1951. of Pathology.

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180 Pathologic Changes From Atomic Bomb Radiation Bone Marrow.-The

~llular picture of irradiated bone marrow was tremendously changed during the first week after the bomb explosion. There was almost total depletion of blood-forming elements, with the exception of small islands of era-thi~opoiesis. By the c~tl 01’ the week reticulum began to proliferate and at first differentiated into lymphocytes and plasma cells rather than myeloid cells: Those forms pretlomillated until the fourth week when m.veloid differentiation way seen. The hone marrow of most of those dying before six weeks was bypoplastic; hut in a few, islands of hyperplasia with arrest of maturation were observed. Most of the fatal cases of the third and fourth months showed hvperplasia, which in the femur was grossly evident as grayish pink marrow extending through a t,hird or half of the shaft; in these the maturation defect decreased and more nelltrophils were found in the peripheral blood and in infected tissues. In a few of the cases of longer duration, however, aplasia was prominent, with the ma~ow of the femur pink and gelatinous. Some marrows which grosslv appearetl h,q)erplastic were actually hJ-poplastic, the pink color coming from dilated blood vessels. Whatever the marrow picture, there was usually profound leukopenia at some time in fatal cases. Lymph No&.--The high degree of sensitivit.?- ot’ Iym])boid tissue to ionizing radiation resultetl in tremendous atrophy seen as early as the third day. Lymphocytes almost disappeared, leavin, v ;I lacy framework that was spectacular Necrobiosis n~ay have ac&conntcd for changes in in microscopic preparations. t,he germinal centers, but departure frol11 the normal architecture was marked only when the germinal centers tlisappcaretl, as they did in three-fourths of those who died during the first, two weeks. The peripheral sinuses contained many red blood cells. l~r~thropllagoc’tosis was somet,imes striking. The large atypical mononuclear cells which appeared by the second week were considered lymphoblasts by one observer, but could logically be pathologic forms whose sensitive nuclear ehromatin was deformed by the radiation. The lymph nodes from Japanese patients dyin, w about the fifth week were usually large and almost devoid of 1,vmphorytes. and germinal centers. Bizarre large cells were more numerous. Plasma cells, eosinophils, mast cells, and increased numbers of reticulum cells were present. Tn the fourth month Iymphoqvtes were more numerous but were still reduced. Spleen,-The lymphoid elements in the spleen reacted to radiation as did those in the nodes. Early, the spleen was usually small, but an occasional one reacted very promptly by swelling. On section it was dark red and pulp adhered to the knife; the follicles were indistinct and the trabeculae somewhat prominent. In addition to the near absence of lymphocytes, large mononuclear cells were seen in greater numbers, ergthrophagocytosis was evident, and hemosiderin deposits were also present. 1)uring the second month the spleen was small and organized follicles were absent. A syncytial reticulum seemed to surround the regenerating follicles in which the slight lymphocytic content of the organ was obvious. Atypical large mononuclear cells were found in about 25 per cent of

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.\T’)JII(’ B().\lfj KAI)IA’I‘I’).~ .\su ()%\I. f(E’d”? rrllrollgh tile f()nrl h ~non~h there ws still the material examined. atrophy; (jct:asio1~al germinal c~ettters ij~)llCillYYl ;IllCl t 11” I>-lll]~ll()V~t show-ccl some evidence of rccoreq-. Secondary

Effects of Radiation on the Histiocytic

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~~ritrc~i~~~~i lesions, Ieuliopctiic~ necrosis, and bacterial itirasioti r.~[rrc~~ntccl tilt effects 011the irradiated body ahout the end ol’ the first rttontit. I,eulioptlttia ~1s tlxt rettte in &f&ted Japanese. The pharylts” ant\ its c~onttr~etiotts. 1/I(’ Xitst I’,*itttest inal tract, the respiratory organs, ant1 the skin mattil’estt4 h0t11 c*l~att~:c~*. In addition. petechiae, purpuric patches, or Iargr ccch\-tttoses wer(? SCUMin 01 II(,). ~01’1 tissttes, partict,tlarl)- the: urinary tract, tnesothelial litrings, ~(1 IIII~SV~~+. The lymph channels draining these areas were etigorgecl witii t~lootl. ‘i’l I(“($’ ~~h;lJlgW were outstattding clitticall;v, and their severit\. tlepettded Ott t Ire lo~at ilzll of the larger hetttorrhagic lesions. Hemorrhages in the linings of tile ph:tr;ctI~:c~;ii regions, the bowel. or the urinary tract gave signs ~~xterttall~. llnrtror,t~li;iul,s brcakittg tht~ottgh epithelium of ljactcria-ladett surfaces often itlit iatcl! tl(arli 1’0 pertic nect*otizin$ lesions. Such ulc*erations were sc)trtctintes itt~lf~p~~tirl~~titII/ hemorrhagt!. It is probable that, ordinarily nottpalhogettie bactrrin trr;t;\. c’;ltist, serious c.onsryurttces after suficient t~eticuloetttlothelial reserves ale 10~1. ?I,tsi! ulcerative lesions throttghout the stottrach ;ltl’l intestinal 1rac.t \vtlt*c OII it sirlhi!;lrS basis.

Oral Regions.--Lesions in the oral regions wt’rc of uttiiosl c*littical ittlIn thr posterior ph;rt’\ IIX portance in the third to sixth weeks after explosion. grayish bnllae appeared. These were followed b;- pctccltial or ccchytttot ic IICIII~II rhages in the mucosa. lYlcerations over these hemorrhages ol’i en a~)pea~'~ d. ()ther nlcerations sitnilar to those of agranuloc~~t ic. 2lIl~ilM l)Wam~ ;l~)~il~TIlt. partic!ularlover the tonsillar areas, and iu increasing trmpo ot’ scvc>i’ity ;I!I(! spread jumped front one lytnphoid island to anal-her to invol\-c the tottgtl’*. 'l'lrc, gingivae tvere hrmorrhagie and ulcerated. the tissue ttcstructioti sorntt ir!lcs spreading to the baccal membrane to involve the entire c*heek and give tlrt> I)ic, tnrc ol’ adult noma. Almost all patients wit11 such lesions tliecl. ‘I%(~ cbulirc. picture was similar to that of agrattuloc~ytic~ an?itia, lcitkcmia, 01' ilI)lilS!iC' ;!t~c’!!li;i from other causes. Lungs.--Only the slight edt~ttta. prt~ivasc~ular or plural. that appt~arcci it! ion t#rvt, the lungs in the first t,wo weeks tttight have been a pritnary Kldi:lt Hemorrhagic attd nerrotizittg pneumonia wets caomnton secondary IGotts a ~IPY the first, few weeks, and were probably part 01’ the pro~ss whic~h rvsnlt (vi in ulcerative lesions of the gastrointestinal tracat. Gastrointestinal Tract.-This t rwc4 was altlut1,1) the first iti M.hivh Irsicbns were g~~ossly visible. Ttt some cases tlvett hefore hemorrhagic* tn~ttlifestittirltis, the sensitive ileum, particularly, prescxntetl i’ocal c*hangvs charac~tcrizecl b\ swelling, greenish and pellowish gray coloration, and induration of the rnuws:J. Some of these foci beeatne confluent attd widespread. with a tliphthcriti~ tncmLater, tiiucosal heniorrhagc~ at branotis effect and much subtttucosal edema. times initiated another c*yclr of sitttitat* (~h:tttgt: in thta stomach (II’ intcbstincx. 116~

182

ELBERT

DE COURSEY

ginning with ulceration of the mucosa at the site of the hemorrhage and progressing to an ulcerative or pseudomembranous process. In the small intestine init,iallp only the tips of the folds were involved , giving the appearance of having heen dipped into boiling water; later? they became greenish or yellowish gray. again in the third and fourth months, enteritis, most often in the large intestine, but sometimes affecting also the small intestine or occasionally the ,stomach, was the most prominent lesion at autopsy. The large intestine at this stage wa.s usually the seat of a widespread process that extended from the ileobeecal valve to the rectum, the involvement being most prominent in the distal portion. Thickening of the wall was a feature, A diphtheritic membrane and ulceration were sometimes present to give a pathologic picture resembling that of bacillary dysentery. It would seem t,hat the process represents not onI> changes due to irradiation of the sensitive intestine, but also the results of decreased resistance to omnipresent intestinal microorganisms and, prob,ably more important, lowered antibiotic capabilities of the blood. Microscopically, the epithelium early contained extremely bizarre cells with giant hyperchromatic nuclei and multipolar mitoses. The swelling appeared to be ca.used by edema, and the peculiar coloration by the absence of infiltrating leukocytes. In the late stages prominent features were areas of mucosal ulceration with much fibrinous exudate, few leukocytes, and in the remarkably edematous submucosa a considerable numb,er of hist,iocytes, a few lymphocytes, and occasional eosinophils. Plasma cells of the lamina propria remained numerous. Testes;--The changes in the testes were, in almost every instance, intense. Bs early as the fourth day when the parenchyma had a normal appearance grossly, the histologic sections exhibited remarkable evidence of damage to the germinal epithelium, numerous cells of which were necrotic and free in the tubules, some having been carried into the rete test,is. The number of mitoses was small. Sertoli cells began to increase in number. Mature spermatozoa were found even in later specimens when spermabogenesis had ceased, and apparent15 uninjured spermatozoa were noted in the seminal vesicles. 1)uring the second month gross examination revealed little. Histologirally, a few necrotic germ cells remained, but most had disappeared. and phagocytic or infiltrating inflammatory cell act,ivity was absent. A fen- bizarre cells approximating the basal membrane appeared to be spermatogonia. Sertoli ccljs cells were more numerous. The tubules had begun to shrink, and the interstitial of Leydig were so prominent that some interpreters regarded them as hyperplastic. The most extreme vascular change in any part ot’ the body was seen in some of the small interstitial vessels; beneath the distinct thin endothelium was an eccentrically located mass of eosinophilic homogeneous refractile material that almost occluded the lumen. This change, difficult to ascribe to radiation, was often best seen near the tunica albuginea and it seemed to persist, for it was present also in autopsy material from the third and fourth months. At that time the interstitial tissue was somewhat less prominent: the basement membranes were thick, wavy. and acellular: the tubules. which were more atrophir,

Klsewhere Sertoli cells had wplaced the gerlll ~~1~. were often hyalinizrd. which had become rare. Before attributing these changes ent,irely to radiation, one must give consideration to the poor state of nourishment during thv i.llrr (1 and fourth months. In this connection, similar testicular* changes have l~rr ~lcscribetl in autopsy material from victims ot’ the I)achnn pr*ison camp. Ovaries.-C’hanges were much less striking in the ovaries than in t tic! testes. C~~YNSchanges. except as l)art of the hemorrtrag& l)henomena, WOW absent. Histologically. primary ova were usually present, and only o(*cirsiorl~rI I)evclo-ping follic~les wt’!‘fb specinretrs hat1 R few atretic primary follicles. seldoni found. A ’ ‘ resting phase ’ ’ of the endometr*iunr reflected the ov;lr.i;t II picture. Clinical observat,ion in Nagasaki indicated that amenorrhea W:LS ciefinitely increased and that the rate of premature tet.nrination of prt’grr;1rr~*>~ :Irnotrg won~en nithin a LiOO-yard radius of the explosion was significant i> higher th:rrr rrsual. Skin.-- -The quickly visible changes in Japanese esposed to an atort iv I~onrl~ were the pigmented areas that appeared in the first few weeks :rr~tJ I)ersistetl. These hat1 such sharply demarcated outlines that t-hey were c*(rtrDevelopment of what is usually recognized as ionizitttr siderecl flash Inum. ray skin bum was not seen. In a few early cases there \Vas said t,o I)(&l)11110~1s (~d~rrlir that ~rr:j;\.ha\-e l)eerr caused by g~nrma 1*:1p. Epilation al)pearetl on the scalp, occasionally- being IIIOW severe OII orw sitle than the other. Axillary epilat,ion was an accoml~animent~ in 16 I)t’r WII~, pubic iii 12 lwr cent. illld eyebrow in 8 per vent. Mic.r.c,H~ol)i~all~-. the hair follicles showed distinct ehanpes both in the rpidermic alid tler~mic coats. Early specimens were not obtained, but in those of the foruth week the internal yoot sheaths could not, be identified, t ht. external sheath (continuous with the Malpighian layer of the epiderm) hcirtg continuous with the hair shaft. Vascu1arit.y of the papillae was reduced :rrrd ~lunip~~fl. the adjacent epithelium wits atrophic. Pigment WilS irregularly Then in the tlrrrnic~ coat the inner hyaline membrane arrtl the cellular lihror~s layeta both l)ecartre thickened. The base of the follicle apparently untlervtqrt continuous shrinkage. pushin g the base of the hair toward the surf’avc, until regeneration began with new cells over the papillae. This process ntirni(~kt~tl normal hail replacement. There was also atrophy of the sebaceous g:.l:rn~ls in some eastx Some of the sweat glands were small, their cells oc*c~asiotr;r~l~\~acrrolatecl anal pyknotic, and the basal mernbrane thickened. Evidence of radiation effect, on the epidermis was not conclusivr. ‘I’hi~ti degree flash ~WIWS co~zld be expected to include some radiation effect. Itut, interpretation was diffitic~ult. In patients (lying on the fifth day, there was necrosis of vessel walls and thrombosis. 1Iyperpi~Smerlt:rtion in b%iiil (‘cl Is and chromatophores were common at the edge of burned areas. So1ne IRlrllning of epidermis, hyperkeratosis, ironing out of ljapillae. and hyperpigmtbntation of basal cells were found in the scalp ithe most usual specimen). J3rytliema or pigmentation from ioniziiig radiation Tl’ilS not recognizetl in 1ht. Japanese.

Adrenal Glands.-During

the first two weeks there seen~etl to he a IOHS

of lipoid in the adrenal cortex, and in fatal cases it was thin and exhibited a progressive loss of its orange-yellow coloration. ~lic:i~oscol~ically, most cells were granular rather than foamy, and atrophy was itlost Inarked in the outer zona glomerulosa. \\‘hen foam cells were present. they \vwc ns~rally in the inner layer. The medulla was ~~ormal

Urinary Tract.-Except for hemorrhagic manifestations there were no apparent lesions. In the bladder during the hemorrhagic stage of the radiation disease, nrucosal hemorrhages tended to result in necrotizing ulceration without evidence of leukocytic infiltration. The prostate and seminal vesicles were not remarkable except for a raw necrosis and the presence of a few morphologically normal sperma.tozoa. Other Organs.--The organs were radioresistant hemorrhagic, or infectious

brain, liver. kidneys, bone, endocrines, and ot,her and were affected in proportion to their vascular, complications.

Summary The lymphoid and hematopoietic tissues, skin, genital organs, and gastrointestinal tract were most severely affected by ionizing radiation. There was atrophy of lymphoid elements in lymph nodes, tonsils, spleen, and gastrointestinal tract. Atrophy of the bone marrow was evident early, and it either, continued or was followed by focal or diftuse hyperplasia with maturation Hemor~hapes. necrotizing inflammation, and ulceration of the oroarrest. breakdown led to pharynx were prominent and severe. The oropharyngeal many deaths from the third through the sixth week following exposure. The scalp showed the surest external gross sign of ionizatiotl-alol,eci~l, which? with appeared ahont the same time as the throat hemorrhagic manifestations, lesions. The testes showed 1)rominent microscopic changes, with alluost every sex cell destroyed itI all men who died. The ovaries showed very little more t,han In all time l)eriods the intestinal extreme scarcity of proliferating follicles. 111ucos:~was the seat .of changes which varied from ulcerated hemorrhagic foci to focal or widesl)read necrosis and ulceration with formation of diphthpritiv MCIII hrwles.

References of -1tonlic Boml, C8sualtirs. I. Lieborn-, ri. A., \Varren, H., and DeCoursey, E.: Pathology Am. J. Path. 25: X.31027, 1949. The Effects of Atomic Etadiation on thr* Oral and Pharyngral .\I11 2. Bernier, Joseph I,.: co';:,.

.T. Am.

Dent.

A. 39:

6-I-7-657,

1019.