Paper - On the development of the human diaphragm (1901)

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Mall FP. On the development of the human diaphragm. (1901) Johns Hopkins Hospital Bulletin 12: 158-171.

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On the Development of the Human Diaphragm

Franklin Mall (1911)
Franklin Mall

By Franklin P. Mall.

Professiir of Anatomy. Johns Hopkins University.

In a paper on the development of the human cadoni, puljlislicd several years ago, I was not able to give a detailed description of the separation of the body cavities from one


' Mull, Jour, of Morph., vol. la, 1897


another, because the specimens at my disposal did not include all the necessary stages. For that study I used 19 human embryos between 2 and 2-1 mm. long, in which various stages of the development cf the body-cavities were shown, but a number of the important stages were missing.


During the past three years the collection of human euihryos in the anatomical laboratory has grown very rapidly anil all the missing stages for the study of the formation of the body-cavities have been supjilied. The following table gives a list of these embryos. It will be seen from it that

TABLE OF EMBRYOS.




Time






tJrL'atost


between tln' be^innill;:' or tbe la.-^t period and


Direction




Ni).


lenji:th in mm.


of the seetion.


Fi


iin whom obtained.




the abortion.





XII


2.1


41 days


Transverse


Dr


Ellis, Elkton, Md.


CLXIV ...


3 . .5



"


Dr


MaoCalhmi,

Baltimore.


CXLVIII .


4.."


3S days


"


Dr


Hoen, Baltimore.


I.XXVI. ..


4.. 5



"


Dr


.Vliteliell, Cliieago.


LXXX ...


.5



(1


Dr


Brauham,

Baltimore.


CXXXVI .


5


.56 days


Sagittal


Dr


Campbell,

Halifax, N. S.


CXVI


6.5


5.5 days


"


Dr


Ryan,

SpringHeld, 111.


II


7


53 days


Transverse


Dr


C. O. Miller,

Baltimore.


CXIII


S



Sagittal


Dr


Gray, Washington.


CLXIII ..


9


5 weeks


Transverse


Dr


Lamb, Washington.


CXIV ....


10



Sagittal


Dr


Gray, Washington.


CIX


11



Transverse


Dr


Cusliing,

Baltimore.


CXLIV ...


14



Sagittal


Dr


Watson,

Baltimore.


XLiir ....


10



"


Dr


liookei',

Baltimore.


LXXIV...


li>



Transverse


Dr


Irving Miller,

Baltimore.


the series from 2 mm. upward is very complrir with the e.\ception of stages between 11 and 14 mm. long. Fortunately, the missing stages are not important. All the embryos given in this talile are practically perfect, the imperfect ones liaving been excluded. The present study is based u|hiii !•") embryos, only 3 of which are included in the 19 specimens considered ill (he earlier communication.

Il has often been stated thai Ihe development of lln diaiihrngin, i'S]i('cial]y in the Inmian embryo, is one ol' III!' iiiiisl (liHiciill |ii'ol)lenis of embryology, fiarty because (if the dilliciilty ill obtaining the iiecessaiy s|ii'ciiiii'ns ami partly heeaiisi' there are no fixed points rioni whiih In enleulate. Ill its (h'\i'loi)ment the wliole ilia|ilii'aeiii wiuiilers rrom the head (o the abdomen, passing Ijy as well as iiinilil'vino the structures and organs along the way. Sn. while vmi Baer recognized that the diapjliragm wandered in its development, picking up its nerve in so doing, a fairly clear pic tiiiv of the whole process was not given until Ilis studied eaicfiilhthe develo|iiiieiit of the iieelc, heart, lungs and intestine. In his studies His recognized the Aiihiijc of the diaiihiagin in a mass of tissue located with thi' liearl ainniiesl struct iiics lieloneing to the head and eonlaining within it the \'eiiis to the heart as well as the An/age of the liver, 'i'his mass of tissue ITis termed tbe septum transversuni. Ilis's studies


were made ui)on the human embryo, mainly by the method of reconstruction, and .shortly after they were published Uskow made a very careful study of the further growth of the septum transversuni. Uskow recognized the great importance of two additional structures in the formation of the pericardium and adult dia])hragm from the septum transversum; these he termed the iileuro- pericardial memhranc, containing the phrenic nerve, and the pillars which form the dorsal ends of the diaphragm. The pillars of Uskow have been termed the plcuro-periioncal memhranes by Brachet, and as the lattiT lei'in is more appropriate than the former I shall employ it in the present paper.

j\ly own studies show that the pleuro-pericardial and pleuroperitoueal membranes arise from a common structure, which extends from the lobe of the liver along the dorsal wall of the ductus Cuvieri to the dorsal attachment of the mesocardium. Ijater this structure grows towards the head to complete the jileuro-pericardial memlirane and then towards the tail to complete the pleuro-peritoneal mendirane. This stiiietnre, which I shall term the pulmonary ridge, is located in the sagittal plane of the body-cavity with cephalic and eandal horns on its dorsal side. The ductus Cuvieri lies between these horns (Fig. 29).

The purpose of this paper is to follow carefnlly the fate of the septum transversum and the origin and fate of the liulmonary ridge in the human embryo. In so doing il is of course necessary to consider the division of the body-cavity into the pericardial, pleural and peritoneal cavities. According to liis, the body-cavity in early embryos is divided into the Parietallwhle and Bumpflwhlen. The communicati-ou between these spaces he has also termed the recessus parietalis. The parietal cavity from its earliest appearance contains the heart and is destined to form the pericardial cavity. T shall term it the pericardial coelom. A portion of the recessus ]iarietalis forms the pleural cavity; it surnninds the lung bnd throughiuit its development and I shall term it the pleural eoeloin. The revnainder of the recessus |iai-ielalis to the origin of the liver has developed in it the liver and stomach; this is added to the general peritoneal cavity and I sliall term it the periloneal cculom. In the early embryos the whole eieloni lies far out of place; in F.mbryo XII nearly Ihe entire cadoin lies in the region of the head and iieek ami in the further develn|inieut of these parts the cadom with Ihe surrounding organs wanders away from the head to its |iermanent location. .\s long as the serous cavities arising from the codom are in tlu' process of wandering and are mil fnlly separated from one another I shall term them ]ileuial, pericardial and peritoneal coelom: when they are fnlly established I shall call tlieiii cavities.

Ill Embryo .\li, lig. 1, the cceloni of the embryo forms a fi'ee s|iaee eueiicling the heart and extending on either side of the body over the om|ihalo-mesenterie veins to the root of till' nmhilieal vesicle. This canal of commuuieation has ile\ elo|ieil wil hill il t he lung, stomaeh and li\'er, nml I hroiighoni its eai'lier ile\elo|iiiienl it measures in length ahoiit one-fourth of thai of Ihe hoilv (iMiibrvos XII, (IXLVIII, LXXVI,


IGO


JOHNS HOPKINS HOSPITAL BULLETIN.


[JJos. 121-122-123.


LXXX,, II and C'J.Xlll). The appearam-i' of the lun,;;- and liver marks the sul)divit;ion of the (•(I'loni iiiio the jileural and jjeritoiieal cadojii. W'ilh tlie dexeldpnient of tlie liver, limy and stomacli tlie e(eliini einilainiiiL;- them gradually dili:te>' until the emhryo is ahout !• nun. long, when the canal evaginate.s, so to speak, and Inrns the liver and stcnnaeh ont into the general pei'iloiienl cavity. The Wolllian liody, which (iniqiiod the dorsal A\all of this canal, gradnally degenerates and the Inng takes its place. From these statements it is readily inferred that the canal extending from the pericardial cceloni, Ilis's recessns parietalis. gives rise to the ]ilenral codoni on its dorsal side and to the peritoneal cielom on its ventral side. The line of division is formed hy the plenro-jieritoneal memlirane extending from tlic ductus ( 'uvieri to the adrenal.


am



Ar.



<•« 


0'

Fig. 1. — Pniiilc recmistnictiou of tliu eiiibryo 2.1 mm. loug. No. XII X liT times; m/i, amnion; iii\ optic vesicle; nc, auditory; vesicle hc, umbilical vesicle; h, lieart ; I'om, omi>lialo-meseuteric vein; mr, septum trausversum ; Oj, tUird occipital myotome; t'j, eiglitli cervical myotome.

The earliest emhryo in my collection in which the sejitum transversnm is well formed is No. XII, 2.1 mm. long, and about two weeks old." The specimen is very valuable for the .study of the beginning of so many structures that it also Ijecomes a good starting [loinl fur I lie study of the dcNclnpment of the diaphragm.

Figs. 1 and 2 give the external fcuin and oulline id' Ihe neural tube and alimentary canal drawn from a reconstruction. It is seen that the c(el(nH sends two canals into the


■-' Ditfereut pictures of this emliryo will be fimiul in the; .ImiiiiMl of Morpli., vol. 13; Ilis's Arcliiv, IS'.lT; .lolins Iloplviiis Hospital Hnllctin, IS'.IS; and the Welch Festschrift, .lohus llopkius Hospital Heports, vol. '.I.


head on either side of the neck which comniuiiicate with each dlhei- ill tile immediate neighliorhood of Ihi' nKUith. This U-slia|ied canal is sepaialed fidiii the exocielom on its ventral side by a Ijridge of inesodermal tissue connecting the umbilical vesicle with tlij embryo at the juncture of the head with the aiimion. It follows that this liridge of mesodernial tissue, the sepliim transversuni, is also U-shajied, as is shown in l-'igs. 1 an<l 2, iST and ilA//. ll forms a jiortion of the ventral wall of the pericardial cadom and sn]iports the omphalomesenteric and nmliilical veins. Sections of it are shown in Figs. 3, 4 and 5, which are from three sections through the head end of this embryo in the neighborhood of the first cervical myotome. The Aiilage of the liver is shown in Fig. t. which is located in this stage in a region belonging to the head.



>>„


'C


o


Fui. 2. — Parlial dissection of the reconstruetiou of the embryo 2.1 mm. long. No. XII x 37 times; dm, amnion; m, mouth; Hi', Br", lirst and second braneliial pockets; /, thyroid; p, pericardial coelom ; .■i^ septum transversuni ; I, liver; kc, nQibilical vesicle; /«•, neurenteric canal.

Figs. G to 9 are from an emhryo (CLXIV) slightly more advanced in development than No. XII. The embryo is from an ovum measuring 1 T x 17x111 mm., found in the uterus at an autop.sy. W'lii'ii the uterus was cut o])en the knife entered the ovum and |Hissil)ly distorted tlie emliryo, for when it came into my hands it was foimd that the emliryo was lloating in the cavity nf Ihe ovum Imt il was still adherent to its walls. This mechanical injury iindoiilitedly caused the body nf the embryo to straighten and at the attachment of the iiiiibilical vesicle the body <if the embryo is bent towards the \entral side, as is the case in a number of the His embryos (for instance, I'>H). The ventral wall over the heart, was also slightly torn. The entire uterus and ovum had been


ArRIL-MAY-JuXE, 1901.


JOHNS HOPKINS HOSPITAL BULLETIN.


161


liTcservod on ice fni' 2[ linurs, mid wlicn it was jiiven io iiie Iiy l»r. ^lacCalhiiii tiic i.'iitiic s|MMiiiic'i\ was iila<Til in sti-on>^ formalin. The si't-tioiis dl' tlic ciiilirvo sliiiw thai the tissuesi ore slightly iiiaceiTited Imt in i^cncral they arc well ]ire?orv<'(l. The spinal ecinl is (■l(ise<l ihnui.uhont its extent Iml thi' iiourcniore is still open. The thyi'oiil iiland. ii]i(ic and otic



UV


'W


Fig. o. — Section tlirougU tlic lirad <if tlie embryo '2.1 mm. loiii;-. No. XII X 50 times; rue, coelom ; /</i, pluiryiix ; /, liver; xl, seiitum transversura ; irr, umliilic.il vesicle.

vesicles, heart and veins, are but slightly more developed than ill N^o. XII. If this enihryo were curled up as No. XII it would measure froni 2.5 to 3 mm., whih' if the two had lunn hardened in the same way (Xo. \ll was hardciicil in ahohdl) they would ])rolialily measure alike.



Fig. 4, — Section tlnnnu'li tlie tliird occipital myotome of the cmhryo 2.1 mm. Ions. -"I mm. nearer llic lail tlian Fii;. 11 x .">(! times; (l.j, tliirel occipital myotome ; c«c, coelom ; /■, vein ; .■</, septinn transvcrsnm ; !, liver; pli, pharynx; "c, umbilical vesicle.

The figures given sliow the general relation as sei'ii in I'lmliryo .Xll with e;u-h id' the st laict ui'cs hut slightly iuhaiii-ed. The septum transversum is much the same as it is in .Xll, while the pericardial co'lom is puslied more to the ventral side of it and (he diverticidinii to tnini the liver is more marked. The iindiilical vein has extended somewhat (Fig. 9) and the jugular vein has made its appearance (Fig. T).


The tissue of the septum transversum in the two embryos is formed of irregular round cells, between which there are numerous vessels, of irregular diameter, which commnnicate freely with the veins to the heart.

The next stage of the develupment of the septum trans


'A ' ' !'


3-^-c.


Coe ;'




■^vu

(-VOM


Fig. 5.— Section throusli the first cervical myotome of the embryo

i.l mm. lonic, .'IS mm. nearer the tail than Fiir. 4 x .iO times ; f\ lirst cervical myotome; toe coelom ; ;■», umbilical vein; ;"'/», omplialo-mesenterie vein; iiiiib, umbilical vesicle.

versnm is found iu an embryo 4.3 mm. long (CXLVII), obtained from llr. Iloen.' The specimen is perfect and normal, as it was obtained through uiechanic;il means. The entiro



(S^^-:^


Fig. (i. —Section throun-h the head of the embryo 3. .5 mm. long. No. CLXIV X .'iO times; y</(, pharynx ; i«, bullius aortae ; cc/j/, ventricle.

ovum was hardened in S(i |ier cent alcohol shortly after it was expelled from the uieiais. This of course fi.xed the embryo in its natural shape, as was the case with No. XII. iioth embryos are cnrved, but in the emliryo 4.3 mm. long the lii-aiiehial region occupies relatively more space than it


'A photograph of this embryo is given in the Welch Festschrift.


1(52


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nds. 121-122-123.


does in the embryo 2.1 mm. long. In proportion to the length of the embryo.? this distance h;is inerensed 3 times, Tlie pericardial cfrlom has receded i'roni the head in |)r()]iortion to the inerenso of the growth of the branchial arches. In the emliryo 2.1 mm. long i\\v kead end of the |ici-ieardiai crelom is oiiimsHe (he otic vesicle, while in the end)rvo 1.3



Fig. 7. — Section tlirdiiuli tlu' embryo o..5mm. loiiir. .14 mm. nciirur the tail tb.au Fis;. x ."'O t mcs ; p/i, jiljai-ynx; lui, auricle; rent, venfiicle; .■it, septum tr.ansversum ; <;/, jugular vein ; /'», umbilical veiu.

mm. it is o])]iosite the first occipital myotome. The puint u\' comnnmication between the peritoneal coelom (encircling the liver) with the exococlom has also receded. In the embryo 2.1 mm. lung it is opposite the second cervical myotome; in embryo 4.3 mm. long opposite the second tlioraeie myotome



Fig. S.— Section tlirougb the embryo S.6 mm. long, .'2 mm. nearer the tail than Fig. 7 x .50 times ; I, liver; wiit, ventricle ;.«»■, siuus renuieus; coc, coelom.

(compare Figs. 1 and lU). Ilis's embryo Lr (4.2 mm. Imig) is intermediate between the t\V(i embryos just compaicil. In Lr (see liis's Atlas, Pis. IX and XI | llie ]ierieardial. |ileural and peritoneal creloni encircling tlie liver extends from tlie first occipital myotome to the sixth cervical, and the omphalomesenteric veins jirotrnde into these canals of the co'lmn. The liver has extended into the septum transversnm but does not yet encircle the omphalo-mesenteric veins as it does in


my embryo 4.3 mm. long. This detailed descri])tion is given to show the fate of the ccelom ' of the hea<l and neck. It gives rise to the pericardial and ]iit'ural cavities, and tliat portion of the ]U'ritoneal cavity encircling tlie liver of (he adult. Sections of the embryo 4.3 mm. lung ( Xo. C.XIjVIII. Figs. 11 and 12) show the livei' sprouts growiiio' in all dii'cc


FiG. 9. — Section through the embryo 3..'> mm. long, .is mm. nearer the tail than Fig. S x .50 times; rvw, coelom; ii:l, intestine; rum, (^mphaln-mcsenteric vein ; /■//, umlulical vein.

tious tlinuigli the sejitum transversum. encircling and ramifying through the omphalo-mesenteric veins, making a condition slightly in advance of that in Ilis's embryo Lr. The sections of this embryo show clearly that the heart, lungs, liver and li'Wer peritoneal cavity arise in tissues surrounded by that portion of the cadom extending into the head in Embrvo XII,



Fig. 10. — Outline of the embryo 4.:! mm. long. No. CXI.VIII x 1.5 times. ,, first cervical myotome; r',, ei!?t cervical myotome, 'llie line imlieates tlie dii'ection of the sections.

Fig. 1. Fig. 11 is taken from a section through a plane cutting the root of tlie arm and the otic vesicle, and can readily lie placed in the outline, I'ig. 1(1. It is seen that the lung.-arise wlicre the pericardial ecelom goes over into the pleural, /. ('. high up in tlie region of the head. Immediately on the dorsal side of them is the beginning of the lesser ]ieritoiieal


' Kopfbohle ; ITalsboble; I'arietallioblc ami recessus |i;n-iel:ilis.


Ai'hil-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


163


cavity, and the intestinal tnbe struck in this section is the stoniacli. All these stnietnrcs lie on the cephalic side of the first cervical myotome. Projecting into the peritoneal ccelom, encircling and penetrating the omphalo-mesenteric veins are the projections of the liver. Figs. 11 and 13, L. The two lohes rrai-h I'rom the tip of the Inngs ami the foramen of Winslow to the point wliere the entodermal cells of the liver arise from


X







ryj)


YC


n


Via. 11. — Section tlirougb the embryo 4.3 mm. Innsr x 2.5 times; T,, lirst tlioracic myotome; C, C,, and (\, cervical myotomes; .s', stomacli ; fti, brdnchus; /i, heart; (, thyroid; /<■•, pericardial cavity; I, liver; />, foramen of Winslow.

llic aliinentaiy canal, or in this ease the iluodcimm. The lobes of the liver lie entirely within the canals of the coelom on either side of the head. The caudal ends of these coelom canals have migrated from opposite the second cervical myotome ill Emliryo XII, Fig. 1, to opposite the second thoracic




.. ^T^


/




UV /



J



-'#^^


-5^)/,



L *



■-■/


Fig. 12.. — Section throush the embryo 4.:i mm. loun, .4 mm. deeper than Fis;. 11 x 2.") times; /, thoracic myotomes; ;, intestine; /, liver; /', ventricle; bii, bulb of the aorta; nm, amnion; iii\ umbilical vein.

myotome in Embryo CXLVIII, Fig. 10. It has moved towards the tail eight segments, while the cephalic end of ilie canal, the ]iericardial ccelom, has been kinked over to correspond with the bending of the head, has dilated to correspond with the growth of the heart, and has receded from the otic vesicle to (lie extent of the gi'owlb of I he linincliial arches. We have in this embryo the necessary stage to Imnte tlie organs which arise in the neighborhood of tin; sepiiim tiaiW'


versnni, as well as to give the fate of the ccelom in their immediate neighborhood.

A stage somewhat in advance of CXLVIII is ]A.\^M. The embryo is slightly larger, measuring 4.5 mm. in greatest length. It was obtained from the uterus 7 hours after death. The entire ovum was placed immediately in aljsolute alcohol.




Fig. 13. — Section through the embryo i.n mm. long. No. LXXVI x 2.5 times; /'c, cardinal vein; l/jc, lesser peritoneal cavity; <lc, ductus Cuvicri; xc, sinus vcnosus.

It was impossible to obtain a picture of the embryo before it was cut. but the specimen proved to be an excellent one. The direction of the sections is more nearly transverse than



l


H


Fig. 14 Section llirougli the embryo 4.5 mm. long, .il nnn. deeper

than Fig. IS x 25 times; we, cardinal vein; u, aorta; nnii. omphalomesenteric vein; fii, umbilical vein; /i, heart.

in CXLVIII. In CXLVIII the neuropore is closed with a thickening of the e|iidermis just over the point of closni'e; the umbilical vein entei's the liver and its direct connection with the ductus ('ii\ieri through the body wall is cut oil'. In LXXVI the neiiid|ioic is completely closed and the eiiilii'yo is somewhat lai'ger than hefore (compare Figs. i:i and I I with II and 12); the umliilical vein, however, coiiiniiinieates with I ill- (liictus Cuvieri tiirough the body-wall on the left


164


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-1^2-123.


side. This Ls an instaiifc nf rctardcil (li'vclii|inii'nt of a part, as tlie left iimliilical vein t^liniild lia\r \alli^lu■d liy lliis time. Fig. 13 gives a seel ion lliniiigli llie tdi-anien nf Winslow imniediately on tlie caudal side (if tlie lung liuds. as shown in a lateral view of the nuidel of the eniljvyo. Fig. 1-"). The



Fig. I.


se]ituni transversuui and liver have increased in fpiantily. as a e(nn|iarison of tlie dilVerent tigui'es will show. In tliis



Fig. 1G.

Figs. 1.5 .iiul Ifi. — Riirlit aud left views o( ,t roconst ruction of the embryo 4.. T mm. long x 2n times; n, aort.i ; ph, pli;ir\ii\ ; Im, hulbus aort;e ; me, coelom ; /), purieardiiil coeloin ; /, lung'; li, liver; Wb, Wolffian body ; ■«, stomach ; ./>, foramen of Winslow ; .«■, sinus veuosus ; "I, septum transversum.

stage we have the extreme bending of the head, which throws 'the heart to its most ventral ])oint with the septum transversum aliout parallel witli long axis of the embryo. The

PC DC



Fig. it. — Lateral view of the reconstruction of an ciuliryo .5 mm. long. No. LXXX x 17 times; I, hinir; li, liver; s, stomach: dc, ductns Cnvieri ; pr, pericardial coelom which communicates fully with pi euro- peritonea I coelom.

position of the heart, lungs, liver and their relation to the cadom is much the same as in the younger embryo with the


exception of the lesser ]ieritoiieal cavity, which is now more to the i-audid side i.if the limits.

While ill the embryo 4..'! uini. long llie niyoiomes were well formed and hollow, in the iMuliryo 4..") they are solid and contain embrvonic muscle ii'nes. The dorsal ganglia are also



._DC



Fin. Its. — Section through the nceU and heart of embryo LXXX x 2.T times; ,, fourth cervical nerve: iv, cardinal vein; </(-, ductus Cuvieri; Of, oesoi>liagus ; //-, ti'achea : .sr, sinus renniens.

more developed. In the I'lubiyos ."i mm. long (LXXX and ('.XXXVI) the myotomes are still further difTerentiated with nerve tiimks. composed of lioth dorsal and ventral roots, which are growing into the body-walls of the embryo. Figs. IT-.'O give the general form of this embryo, in reconstruction





Fig. 111. (Section through embryo LXXX .:.'•_' mm. deeper than Fig.

IS X ;i.") times; C, fifth cervical nerve ; fv, cardinal vein ; .i, subclavian vein; ih; ductus Cuvieri ; I, lung; pli, phrenic nerve.

as well as in section. The se]itum transversum is not as perpendicular as in either younger or older stages (LXXVI and II), but in general this embryo is intermediate between them. A separation between the jiericardial and ]ileural ca^lom now Viegins to make its appearance by means of a constriction in its walls, the ductus Cuvieri encircling the cwlom at this point. The hing buds hang free into the pleural ccelom,


Apkil-May-June, 1901.]


JOHNS HOPKINS HOSPITAL 15ULLETIN.


1G5


iiiul the liver and stomacli into the peritoneal eo'lmii. Tli.^ dnctus t'livieri lieb in a riilue of tissue eneirclini;- tiie lanal di coniniunieatitin lictween the pericardial and pleiiial iddniii. In this eniliryo the ridge has no mesentery, as descrilied by His {V\g. 18), hut in sagittal sections of the same stage (CXXXVI) tlie mesentery is yiresent. As yet there is no




KiG. 20, — Section tlirousili embryo LXXX, .2(i mm. deeper tli;iii Fiij. li) X 2.5 times; <',.,. si.xlli cervieiil myotome; <i, aorta; iv, eardiual vein; .«, stomach; ", iiinljilical vciii ; //«•, lower peritoneal cavity.

indication of a line of se|iai'ation between the plciiial and peritoneal cceloni in LXXX. Imt in ('XXX\'l ihei-e is an elevation on the d(ii>;d wall (d' llie |il('iiial cii'lniii, lig. 21, wliieh encircles the long ami joins the dnrsal end of the s('|itnni li'ansversniii, 'i'his is one of the ]iillars of Uskow



FiG. :ll. — Sa'jiltal section tliroii2;li an embryo, ."> mm. lonii;. No. CXXXVI X 2'} times; /i, lieart; i-i\ cardinal vein; xl, septum transversuni ; ', hoii;-; .s, stomacli; k, arm; jir, pulmonary rid:;'e.

(ir the beginning <>( a ridge which I shall term the juiliiioiiiiri/ ridi/e.

Fig. 20, coni]iared with Kig. 1o. shows that tlu> foramen ol" Winslow has moved more lapidlv Inwards liie tail than the Iieart. A section through it strikes the heart sqnarely in one case, while in the nther it does not tmieh the heart hwi strikes the li\cr mily. This is in [lai't i\\tt' ti> the direction of the sectiiiii in thi' Iwd specimens, and in |iiii'l to the shifting of till.' fdrameii uf Winslow with (lie recession of the


stomach. The cervical nerves are sefiarated in No. LXXX with the exception of an anastomosis lielween the fourth and the liltli. j-riim this piiint the pliri-nic nerve arises. Fig. 19, and passes to the lateral side of the parietal ccelom and lung. In a later stage it reaches the se])tum transversum through the plenro-]iericardial menilirane of I'skow.

I have now followed the transformation of the relatively sim]ile C(el(iiii of the head and neck from the time it is well I'diiiied ill an embryo of the end id' the second week to the end of the tiiird week. During this time tiie pericardial cadom has moved away from the head and the pericardial cavity is well lUitlined. but the membranes which divide the ccelom intii pcriearilial. pleiiial and jieritnncal spaces have not yet



FiQ. 'J2. — Rccoustnictiou of embryo No. II x 30 times; 7>, bronclins; X, liver; P/i, plirenic; 1, ,?, ,?, 4 branchial pouches.

appeared. During the foui'th week both of these membranes a]ipcar, but llicy are not well delined iiiilil the fifth week.

Fig. 22 is from a profile rcconslniclinn of I'hnbryo 1 1, showing the relation of the organs to tme another. A cast of the colon of this embryo is given in Fig. 23. The extreme ventral kinking of the heart is shown in this stage and from now on it begins to sink more and more into the body as the liver recedes, 'i'lie cinnmunieation lictwecii I lie pericardial cielniti and the |ilciiral eoelom is reduced to a narrow slit lietween the Cephalic end of tlie lung bud and I lie iliictus Cuvieri. It a)i]iears as if a simple adhesion of the walls of the slit would. com|ilctr the closure of the pericardial space. Fig. 24 is a .section Ihroiigh this space, striking the seventh cervical myo


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[Nos. 121-123-123,


tome and the tip of the phrenic nerve. It shows that the nttachnient of the ductus Cnvieri is no longer hroad, as in rnibrvd IjXXX, Ijiit is narrow, formino- a mesentery as de


fiG. 23. — Cast of coelom of embryo II x 20 times; /', perieiirclhil coelom ; L, coelom encircling to liver.

scribed by His. On the dorsal side of the ductus there is a ridge wliicli liegins as tlie ductus projects into the coelora and gradually I'luis over into tlie lobe of the liver. Tliis ridge is very pi-ononiiced and is also well shown in llu> sections of


CV



-:^^4-U


Fig. 24. — Section tlirousb the seventh cervical segment of the embryo 7 ram. long. No. II x 2.5 times; ('., seventh cervical myotome; rv, cardinal vein ; ili; ductusCiivieri ; ?<)•, brachial iilexus; /(/•, pnlmi>?i;ny ridge; ///(, jihrenic nerve; h, bronchus; h, heart; hn, bulbns aorta'.

His's emljryos. A and 1>, as given in his Alhix. The relation of this ridge to tlie phrenic nerve as well as its form in older endiryos makes of it the Anlfuje of both the pleuro-])ericardial and pleuro-pcritoneal membranes. It lies in the sagittal plane


of the coelom and as it passes the region of the fourth and fifth cervical noi-ves receives into its substance the phrenic nerve which ]iasses on tlie caudal side of the ductus Oiivieri. Soon the lung bud grows against this ridge, causes it to bulge. and with the rotation of the liver towards the head the ridge



Fig. 35. — Section through the embryo 7 ram. long, .6 ram. deeper than Fig. 24 X 2.5 tiraes ; T,, first thoracic myotome ; ci\ cardinal vein: Tl'fi, Wolffian body; .<:, stomach; Ipc, lesser peritoneal cavity; ?, liver; //, heart; kI, septum transversum.

is divided into two parts; (1) the cephalic end which retains the phrenic nerve and ductus Cnvieri and forms the pleuropericardial membrane, and (2) the caudal end which remains attached to the tip of the dorsal end of the septum trans


Ph :'^



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, ^ Li.


Fig. 26. — Sagittal section through the embryo (>..5 mm. long. No. CXVI X 25 limes; /jA, ]>haryn\; /j/-', first branchial arch; 6'(, bulbns aorta'; (f, auricle; /'. ventricle; ^ Inng ; //, liver; />i\ pulmonary ridge.

\ersum and the liver mi the one hand, tlie body-wall on the other, til f<iriii the ]ilcui(i-|ieritoneal membrane.

Figs. 26-28 show tliis ridge in sagittal sections in Embryo rXVI. a specimen not (piite as large as No. II, but somewJiiit


Ai'eil-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


IG'i


more advanced in developnu'iit. In P^ig. 26 its cephalic end a])])ears as a broad menibiaiie which in a section nearer the middle line extends to the liver on the ventral side and'



k


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A


Fig. 27.— Section tliiougli tlic embivo 6..5 mm. louir, .1 mm. deeper than Fig. 26 x 2.5 times, /i/i, pbarvux ; <(, arm; pi; ijulmonary ridge ; I, luug.


it begins to widen at its dorsal end hand in hand with tlu rotation of the liver. Fp to this time the se]itnm transversnm is pai-allel witli the vertebral eohimn. with the heart


a


H





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wb'pr" "~"'

Fig. 28. — Section tlirough tlae embryo 6..5 mm. long, .13 mm. deeper tliau Fig. 27 x 2.5 times; <«■, oesophagus; n, aorta; I, lung; li, liver; 11'/), Wnltliuu body ; jir, pulmonary ridge.



Fig. 29. —Lateral view of the iniliiionary membrane and surrounding parts of the embryo 7 nun. long. No. II x 30 times; «, auricle; , ventricle; /, lung; /(, liver; II A, Wolllian body; ///•, pulmonary ridge; ., eighth cervical myotome.


aecoiMpaiiics the ductus Cnvieri to the body-wall mi tlic dorsal side, I""ig. 21, pr. Stil more towards the midlino the ridge ends as a decided elevation iiuiiicdiately to the eainhd side of the ti]) of the lung.

After the lailnionary ridge is well formed (as in I'hnbryo IT)


on its venti-al siiU' ami tlie liver on its dorsal side projecting into the ]ici-itoiieal eodom, as shown in No. H. This eondition was hruught about at the time of the bending of tln' head when the viscera were forced towards the tail and into this position. The cejihalie end of the pericardial crelom


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[Nos. 121-122-123.


is tluis Lent over the septum transversum but the nuiin part of the head (•<vloiii remained parallel with the si)iiial eoliiiiin on either .side ol' llie liody. This process may he termed tlu: rolling over of the heart.

In the next stage the heart rolls in a dorsal diret-lioii and the liver in a ventral direi-lion. 'i'his process has already hegnii in endiiyo CLXIII and C^XllI. In so doing the lung buds become Ijuried deeper in the body of the embryo and the liver gradually changes its |iosilion from the dorsal side



Fig. 30. —Lateral view of the pulinoniiry membraue and siinomuliii!;parts of tlie embryo '.I mm. lont;; No. CL.XIII x 13i.< times, (\, eiiihtli cei-vical myotome; //.liver; I, liiuir; ■■-■, stomach; 1I'6, Wolfliaii botly ; y>/(, plirenic nerve; y«', pleuro-perieardial membrane ; ^/yj. pleuro-peritonuMl mcnihraue.

of the septum transversum to its ventral side. The septum transversum undergoes almost a half-revolution. The cudom containing the liver lobe evaginate.s and becomes incorporated with the general ahdiuniual ca\ity.



I'"iii. 31. — Section through the filth cervical myotome of the embryo '.I mm. Icing, No. CLXIII x l-}^ times; (',,, llfth myotome; (•<■, cardinal vein; tir, ductus cuvieri ; br, brachial ple.xus; jih, phrenic nerve; /ir, cephalic end of the pulmonary ridge forming the beginning of the pleuro-pericardial membrane.

\\'itli (lie rolling of the heart the cielom connecting the pericardial with the pleural space is kinked at the points of juncture between these cavities. At this point the duct of ( 'uvier enters the heart. Soon fi-om its dorsal boi'iler the ]nihnonary ridge arises which is semicircular in form and reaches from the liver to the dorsal walls of the credom as ilescribed under I'hid.iyo II. It is shown in section in Fig. 'H, and in a lateral reconstruction in Fig. 20. The pulmon


ary ridge is really an extension of the septum transversum from the lobes of the liver to the tij) of the AVolffian body. ,Vs the heai-t nio\'es in the dorsal direction and the liver in the ventral dii'ection it is the dorsal end of the septum trans


'^•^'HCoc/— -^ ^^e^, — ' — Ph


PCoe



Fig. 33. — Section through the embryo '.I nun. louir, -Wi mm. deeper than Fig. 31 x 12,'.; times; ('„, si.xth cervical myotome; •■/•, cardinal vein; p/i, phrenic nerve; jjc, pleuro-pericardial membrane; ////, plcuroperitoneal membrane; pl-cve, pleural coeloni ; /j-mc, peritoneal coelom.

versum which moves most ra])idly in the cbrection of the tail. In so doing the pulmonary ridge grows rapidly and divides at its dorsal end into two memtiranes, one containing the



Fig. 33 Section through the embryo '.I mm. long, .10 mm. deeper

than Fig. 33 x 13)^ times; C^, eighth cervical nerve; pp, pleuro-peritoueal mcmbi-anc.



Fig. 34.— Section through the embryo !) mm. long, .84 mm, deeper than Fig. 33 x 13).^ times; y,,, third thoracic myotome; //«■, lower peritoneal cavity ; 117), Wolfliau body.

duct of Chivier ;ind phrenic nerve, and the other still encircling the lung bud. In this division we have the beginnings of the jdeuro-pericardial memhrane of ITskow, and tlie pleuroperitoneal mendjrane of Brachet.


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'Pill' iiiiliiiiiiiary ridpo is well formed in Embryo II. It appears as a ridge of tissue passing towards the head from the lobe of the liver on tlie dorsal side of the ductus Cnvieri and then aloui;- th.e dorsal walls ol' the rcrhim to the meso





^f."-'



^LPC


Fig. 3.5. — Sagittal section tlirnuijli the unibrvo s nini. loiii:. No. C'XIII x 10 times; J, lower jaw ; .s-^z-uc, siuus lu-aecervicalis ; ;, fouitli cervical nerve, /)/(, phrenic nerve; st, septum transversuin; ih\ iluctus Cuvieri ; /)<•, pleuro-pericarilial membrane; pp, pleuro-peritoiieal membrane; /, lunif; ,v, stomach; 'yjr, lower peritoneal cavity ; T'/i, Wolffian body.

(■ai-(liuiii. \\liere it ends in the pillars of Uskow. As the einhryi) gidws larger tlie ductus t'uvieri separates more and mnic friiiu the latei'al liody-^all. and in a incasurt' sliifts intn the [lulmonary ridge, whieh at its nidst emne.x point grows in the form of a ridge towards the heart. This secondary ridge, which is present in C'LXIII. linally se|)arates the ]ilenral from the pericardial cavities and comiiletes the jilcnro-pericardial membrane.



Ki<i. :i(I. — Section through the embryo S mm. lony nearer the mitldlc line tliau Fiif. 3.5 x 10 times; ;/'■, ductus Cuvieri; I, lung; .«, stomach; Pli, pleuro-peritoncal membrane.

Tile piilniiiuary ridges from thcii' beginning to tlieir separation into the pleuro-pericardial and pK'urn-pri'itcnu'al niemliranes a]ii)ear as two ears to the se[)tum transversiun, c-\tending along the ducts of Cuvier in tlie sagittal plane id' the body and at right angles to the phiiie of tlie septum trnnsversnm. Judging by tlie relatimi n\ the phrenic iier\c to the ])ulmonary i-idge tlie poi'tion (d' it I'n tlie dorsal siih' (if the ductus Cu\ieri Clint, Lining the phrenic nerve, the pnrtimi containing the ductus Cuvieri. and the sccimdaiy ridge nf the


ventral side of tlie ductus Cuvieri, form the pleuro-pericardial membrane, 'i'he portion of the pulmonary ridge on the caiuhil side nf tlie ]ihrenic nerve gives rise to the pleiirnperitiiiie;d mend ii a lie. In so doing it gradually shifts over


PP


■Sl;


Fig. S7.— Sagittal section through the embryo 10 mm. long. No. CXIV X 10 times; /(/j, pleuro-peritoneal membrane.

the lung hulls and iinally t'omplctely separates the jileuial rriiui the peritoneal cavities.

The growth of the plenro-pericai'ilial meiiihr;ine towards



Fig. 3S. -Lateral view of the embryo 11 mm. long, showing the pleuro-pericardial and pleuro-peritoneal membranes. No. CIX x S.'.j times; /-, lirst rib; /, lung; 11, liver; p/i, phrenic nerve in the pleuropericardial memljrane; .s, stomach; ir6, Wollliau body; (ip. pleuro-peritoncal membrane which is not quite completed.

the head ami the ]ilenro-peritoneal towards the tail widens the dorsal projection of the septum transversuin and iiiin this wide hasi' the lung Ijurrows throwing the jileuro-ii.'ricard-ial membrane with the phrenic nerve to its medial side. The fate of the pulmonary ridge is shown in Fig. 3(1. which is from lOmbryo CL.XIII. Sections of this embryo are shown in l-'igs. 31 to 31. They show again that the pulmonary ridge reaches rroiii the diietus Cuvieri to the ti|i of the lung, and the phieiiie nerve. It is readily seen from Figs. 30 and


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[Nos. iai-122-123.


o2 liow the ])lirenic nerve is pushed to its permanent position liy the further rotation and recession of tlie septum (ransversum and livei'. ajid the lateral growth of the lungs to encircle the heart.


PC .


"it \



iMmMiK




Fig. 30. — Section through the body of the embryo 11 mm. long. No. CIX X 10 times; /i/i, plirenic nerve; yjc, pleuro-pericardial membrane; .s7, septum transversum ; //. humerus; .;, tirst rib; .', second rib; /, third rib.

Figs. ;J.j and 3lj are from sagittal sections of iMnlu-yo (.'XIII, which is of the same stage as CLXIII. The iihrenic nerve is shown throughout its whole course from the fifth cervical nerve to the pleuro-])ericardial memhrane. The nerve receives a second hi'anch a few sections deeper frmn the sixth cervical which unites with the main trunk hefore it enters



(^


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/


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Fio, 40. — Section through the embryo 11 mm. Ion;;; .IS mm. deeper than Fig. .39 x 10 times; /;/<, phrenic nerve; st, septum transversum; P'-, pleuro-pericardial membrane; pjj, pleuro-periloneal membrane; J, ,.-', ,)', 4, ribs.

the pleuro-pericardial nienil)rane. Hanging from the pleuropericardial memhrane is a section of the pleuro-|ieritoneal, which in Fig. 36 unites with the dorsal wall of the cndom at the head end of the Wolffian body.

About this time the portion of the ])ulinonary ridge des


tined to heconii' the plcuro-]ieiicardial membrane unites with the root of the lung hud and com]iletely closes the pericardial cavity, Fig. 37. By this union the course of the duel us Cnvieri is from the body-wall to the heart throtigh the pleuropericardial mendirane, and the plane of the pleuro-pericardial



Fig. 41 Section through the embryo 11 mm. long, .46 mm. deeper

than Fig. 40 x 10 times. The pleuro-peritoueal membrane is incomplete on one side, .;, j, .7, i:, ribs.

membrane is jiractically that of the septum transversum, the two together being transverse to the body of the embryo. The phrenic nerve at this time is in the plane of the septum transversum and reaches its dorsal tip through its projection, the pleuro-pericardial membrane.

Immediately aftei the completion of the pleuro-pericardial


v3^^^



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Fig. 42. — Sagittal section through the embryo 14 mm. long. No. CXI.IV X 10 times, ///>, phrenic nerve; /'/, tenth rib; .s, stomach ; /,-, kidney; 11', Wolllian body.

membrane the rotiition id' the liver and septum transversum is accelerated, and by the time the embryo has grown to be 11 mm. long (CI.X). tlie liver is practically in its adult position. The rapiil rotation of the liver, especially at its dorsal end, has elumged the relation of the planes between the


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JOHNS HOPKINS HOSPITAL BULLETIN.


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pleuro-pericardial membrane to tlie septum transversiim from parallel to right angles. Now the septum transversum is in ^ the plane of the plenro-peritoneal membrane (Fig. 38). With' the recession of the septnm transversum, especially at its


i


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rU


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Fio. 43. — Section tlirough tbe opening between tlie pleur-il and peritoneal cavities in the embryo 14 mm. long x .'50 times; .s, stomach; I, hing; /<p, pleuroperitoneal membrane; nr?, adrenal.

dorsal end, the evagination of the co?lom containing the liver and stomach is complete, throwing them into the general peritoneal cavity.

Figs. 39, 40 and 41 are sections through the plenro-peri


■ mi




M \


Fio. 44 Sagittal section through the body of the embryo 10 mm.

long. No. XLIII X 10 times; .9, ninth rib.

cardial and plenro-peritoneal membranes of Embryo CIX, Fig. 38. They give the relation of the pleuro-pericardial and plenro-peritoneal membranes to the surrounding structures. The heart is now in its permanent location in the thorax and


the liver is in the abdominal cavity. The septum transversum with its extension, the pleuro-peritoneal membrane, stretches across the body from the tips of the embryonic ribs. But in the thorax lie the lungs, and their further growth into the lateral walls of the embryo and septum transversum will make them encircle the heari:, thereby enlarging the pleuropericardial membranes and changing j)osition of the phrenic nerves.

After the heart, lungs, liver and stomach are located in their permanent positions the plenro-peritoneal membrane grows rapidly and soon closes the opening between the pleural and peritoneal cavities. Fig. 42 is from a section lateral to the opening showing the phrenic nerve throughout its greatest extent. In this specimen the marked growth is in the pleural cavity. Fig. 43 is from a section through the opening on a larger scale, including also the adrenal. A stage slightly more advanced is shown in Fig. 44. In this specimen, as in the one above, both pleural cavities communicate with the peritoneal. In Embryo LXXIV, Fig. 4."i, the iileum


FiG. 4.5. — Transverse section through the embryo 14 mm. long. No. LXXIV X 10 times; 7, seventh rib. The plenro-peritoneal membrane ; pp, is incomplete on one side.

peritoneal nienibrane is complete on the right side and incomplete on the left side. The reconstruction of this embryo shows that the opening is very large and extends from the seventh rib towards the tail. It may be an instance of retarded development, because in embryos 19 mm. long the membranes are as a rule complete on both sides of the body. To what extent the permanent diaphragm is formed from the pleuro-peritoneal membrane it is difficult to determine. Undoubtedly the portion of the diaphragm on the caudal and dorsal sides of the pleuro-pericardial membrane is formed from the pleuro-peritoneal membrane. That portion of (lie diaphragm on the cephalic side is formed from the septum transversum. Itut the diaphragm is greatly extended on the lateral sides of the heart after the embr}'o is 20 mm. long by the extension of the pleural cavities around it. It appears from the models that this portion of the diaphragm is also formed directly from the periphery of the septum transversum.


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OBSERVATIONS ON THE PECTORALIS MAJOR MUSCLE IN MAN.

By Warren Harmon Lewis, M. D., Assistant in Anatomy, Johns Hopliiis University.

The Adult Muscle.


The peculiar twist in the sternocostal portion of the pectoralis major muscle is described in the various text-books on human anatomy. In general, the descriptions would indicate that the posterior layer of the tendon of insertion is formed in such a manner that its highest fibres have the lowest origin on the thorax, and the lower the fibres at the insertion the higher their origin on the thorax. There must thus be a crossing of fibres. This crossing is generally represented as


direction of the fibres which form the apparent twisting. For this purpose specimens were taken from the dissecting room, from 1)odies embalmed with the carbolic acid mixture.' The muscles were placed in equal parts of glycerine, water and nitric acid for 24 to -18 hours. In most of the specimens thus treated the direction of the fibres was easily obtained as the connective-tissue elements were partially disintegrated and easily torn.


.— Gq


— h



Fio. 1. — Diagram of an adult peetoralis major muscle, c p, clavicular portion; s <• p, sternocostal portion; 1, 2, 3, 4, 5, 6, are overlapping bundles of fibres of the same ; 6 u, portion of the posterior layer of the tendon of insertion comirg from fi; /i, humeral end of the muscle.


taking place at or near the concave portion of the lower or axillary border of the muscle. I have found many anatomies incorrect or very incomplete in their description of the formation of the posterior layer of the tendon of insertion as well a.s the direction taken by the remaining sternocostal fibres, which go to the anterior layer of the tendon. These descriptions correspond fairly well with the direction the fibres appear to take when one examines the muscle superficially.

I have examined carefully twelve muscles to ascertain the


My dissections have shown in every case, (1) that the lowest fibres of origin go to the lowest end of the posterior layer of the tendon of insertion (Figs. 1 and 2), (2) that there is no crossing of fibres forming this posterior layer, and (3) that a peculiar fan-like arrangeuuMit of the bundles of fibres in the whole sternocostal portion is present (Figs. 1 and 2).

After the maceration, I found the muscle had a tendency

IF. P. Mall, The Preservation of Anatomical Material for Dissection, Anat. Anz., Bd. xi, p- TBO, 1836.


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to split into several overlapping bundles (Figs. 1 and 2; 1, 2, 3, 4, 5, 6). The number aijd size varies in different muscles. It will be seen from the diagram (Figs. 1 and 2) that the overlapping is more and more marked toward the humeral insertion.

The clavicular portion and upper five bundles form the anterior layer, and the sixth bundle the posterior layer, of the tendon of insertion. The lower fibres in each bundle, wliich are the superficial overlapping ones, reach to the lower end of the tendon, while the upper, deeper ones are more and more overlapped and pass to the u]iper edge or near to the upper edge of the tendon. Each bundle, as it approaches the tendon of insertion, spreads out and becomes thinner.


Development.

I have attempted to trace the development of the muscle in a series of human embryos and to explain the origin of the peculiar arrangement of its fibres. For this purpose I have studied the muscle carefully in embryos varying in length from 9 to 40 mm. The first indication of the muscle I have been able to note was in an embryo of 9 mm. in length. In an embryo of 40 mm. the adult form is present. Reconstructions of the younger and dissections of the older embryos were made to study them.

In a human embryo measuring 9 mm. in length (No. CLXIII),^ the pectoralis major and minor muscles are repre



FiG. 2. — Diagram of cross-sections ot tlie muscle talcen at //;, ; 1. ,1, auterior laj'er of tendon ; P, posterior layer.

Tlie distance to which the muscle fibres go outward toward tlie humerus decreases from above downward and thus aids in keeping the distal end of the muscle thin.

The posterior layer of the tendon is continuous with bundle 6 (Figs. 1 and 2). It gradually spreads out and becomes thinner on approaching the luimerus. As in the other bundles, its lower fibres reach the lower and its upper fibres the upper border of the tendon. The size of this bundle varies greatly, especially in the amount of overlapping toward the origin. Most of its fibres constitute the abdominal portion into which the muscle is sometimes divided. The accessory bundles of muscle having, as a rule, costal origin and which lie beneath the main muscle, arc inserted into this posterior layer.


i; op; and rij, in (Fig. 1). Numljers and letters remain as Fig.

sented by a mass of closely packed cells without sharp limits. As there are no muscle fibres in this tissue I shall call it premuscle tissue. The other muscles of the arm and shoulder girdle are also represented more or less clearly by this premuscle tissue. There are, however, muscle fibres in the muscle-plate system. Here the muscle plates have fused into a continuous column and in the costal region extend along the intercostal spaces, partially surrounding the ribs and fuse together beyond their tips into a ventral plate. This muscle-plate system contains fibres, is farther advanced


'The numbers here given correspond with those in the catalogue of the collection of human embryos in the Anatomical Laboratory of the Johus Hopkins University.


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[Nos. 121-122-123.


and has a different appearance from the premuscle tissue, which is lateral to it and in the arm. In Fig. 3, which is from a wax reconstruction of the right arm region of this embryo, the costal portion of the mnscle-plate system is seen (m.pl.s). Lateral to this is the lateral premuscle mass {t.pin). At the level of the first rib (cI.) the pectoral premuscle mass ip.pm) leaves the lateral to join the general arm premuscle sheath (a.pm.) along the ventral side of the proximal half of the condensed tissue which represents the humerus. The proximal end of the humerus lies opposite the interval between the fifth and sixth intervertebral disks (dVc, dVIc), the distal end opposite the first rib {cl.). The


tion into masses, such as the pectoral, latissimus dorsi and levator scapulfe and serratus anterior. It is impossible for me in the case of the pectoral mass to determine how far caudally into the lateral premuscle tissiie it extends, or just where to draw the line between it and the neck premuscle mass. Its humeral end is lost in the general arm premuscle tissue. Its location and correspondence with the muscle in the next stage and its nerve supply lead me to believe this to be the pectoral mass.

The pectoral premuscle mass is supplied by three nerves, from the brachial jdexus, the fibres of which come from the 1'/, VII and VIII cervical and I thoracic nerves. It will


apm



Fig. .5.— Ventral view of a wax reconstruction of tbe arm region of a liumaii embryo measuring 9 mm. in lengtli (No. CLXIII). Enlarged TM times. AB, median liiie; c I, c II, <■ HI, -■ IV, ribs one, two, three and iour; d IV <■, (/ V c, d VI c, d VII c, fourtli, fifth, sixth and seventh cervical intervertebral dislis; a. iiiu, premuscle mass eusheathing the arm; I. pin, lateral premuscle mass;

j. pin, pectoral premuscle mass; s. /)»i, scapular premuscle mass.


scapula lies imbedded in the scapular premuscle tissue (s. pm). The clavicle is not present at this stage. The intervertebral disks are of condensed or closely packed cellular tissue {dIVc, etc., to dIVt). The ribs are of condensed tissue and project ventrad from the adjoining parts of the intervertebral disks and vertebral bows.

It is very difficult to determine the exact limits of the premuscle tissue; in a few places it is very sharply marked off from the surrounding mesenchyma as at the ventral end of the neck premuscle mass. The entire arm between the central skeletal core and the integument is filled with this tissue. At the root of the arm there are signs of a separa


be seen at this stage that the pectoral mass is mostly cervical and lies in the region of its nerve supply.

The fibres of the brachial plexus are directed laterally and have scarcely any caudal inclination.

In an embryo measuring 11 mm. in length (No. CTX),' there is great advance in the musculature of the arm. Many of the arm muscles, especially the proximal ones, can be


3 Mall, (F.). The value of Embryological Specimens, Maryland Med. Journal, October 20, 18!)S. A Contribution to the Study of the Pathology of Early Human Embryos. Contributions to the Science of Medicine, dedicated to William H. Welch, Johns Hopkins Hpsi)it«l Reports, vol. ix, I'.IOO.


Apeil-May-Juxe, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


175


recogiiizi'd. Insti'ad uf premusole tissue we liiive distinct fibrillation.

The pectoral nuiscle mass extends from the rejiion lateral to the ends of the first three ribs cephalolateracl to the cephalic border of the humerus. Its cephalic portion is closely associated with the medial end of the clavicle (Figs. 4 and 5, cp.). There is no definite attachment of the mnscle to the ribs. The pectoralis major and minor are closely united. The latter is indicated by a bulging toward the coracoid process {p.min., Figs.. 4 and h). I have with difficulty traced the general course of the fibres in the major portion of the mass, as will be seen in Fig. -5. The fibres from the clavicle do not appear to overlap the sternocostal fibres but occupy the proximal part of the insertion, whih' the sternocostal fibres occupy the distal. See Fig. 6, which is a diagram of the relation of these fibres close to their insertion into the humerus.


It is also worthy -of note tiiat the pectoralis muscle has extended caudally to the level of the tip of the third rib.

In an embryo measuring 16 mm. in length (Xo. XLIII)/ the two pectoral muscles are eutii-ely sejiarate. The pectoralis major muscle assumes much more the adult form than in the previous stage. The entire arm has migrated caudally and with it the pectoralis major mnscle. It now extends to the sixth rib (Fig. 7, cVI.). The clavicle has extended to the tip of the first rib, where it joins the cephalic end of the sternal anlage (si.. Fig. 7). The clavicular portion of the muscles is carried with the clavicle toward the median line. The humeral end of its filjres are seen to overlap the sternocostal fibres near the himrerus (Figs. 7 and 8). There is a distinct gap between the clavicular portion (Fig. 7. cp.) and the sternocostal portion (Fig. 7, scp.) near their origins, The fibres of the sternocostal portion present a slight tendency to separate into bundles in which their is an overlap


lacar



N.Y.C


d.VIC


d.YHC


Fig. i. — .Mediau view of a wax reconstnictiou of tlie arm i-«;;iou of a human embryo measui-iiig- 11 mm. iu leni^th (No. CIX). Eularged 30 times. .1, acromiou; c II, second rib; c, coracoid process; riii\ carpus; ': p, clavicular portion of the pectoralis major; cZ, clavicle; i;h, chorda dorsalis split in the median line; d VI c, d VII t, sixth and seventh cervical intervertebral dislcs ; d I (, first thoracic intervertebral dislc, from which the first rib is seen arising; inrnr, metacarpus; p. m, pectoralis major muscle; p.miu, pectoralis minor bulging toward the i'or.acoid process; n,\ c, fifth cervical nerve going to join the brachial plexus; bp, brachial plexus ; c, radius; id, ulna; .•;, scapula.


Figures 4 and .) are from a wax reconstruction of the right arm region of this embryo. All muscles but the pectorals are omitted.

The ])ectoral muscle mass is supplied by four branches of the i)raehial plexus, two from the outer and two from the inner cord, the fibres of which can be traced to the Vf. VI f andVIII cervical and / thoracic nerves.

It is of special note at this stage, that the larger portion of the muscle lies above the first rib, reaching about to the level of the fifth cervical intervertebral disk; that there is no overlajiping of its fibres; and that the clavicle only reaches about one-half the distance from the acromion to the first rili.


ping of the deep portion of the lower by the superficial portion of the u]iper ones. This is more marked toward the insertion, as will be seen in Fig. 8, where the overlapping is quite complete. I liave not been able to make out at this stage anything which corresponds to the deep or posterior tendon and, as will lie seen later, it probably does not exist at this stage.


' .Mall, (F). Development of the Human Coelom, Jour, of Murpli., vol. xii, No. 2. Development of the Internal Mammary and Deep Epigastric Arteries in Man, Johns Hopkins Hospital Bulletin, Nos. 90-111, 1898. Development of the Ventral Abdominal Walls iu Man, Jour, of Morph., vol. xiv. No. -i, 1S08.


170


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-132-123.


The nerve supply is as in the adult.

Embryo No. XXII,° measuring 20 mm. in length, shows aboiTt the same condition as in Embryo No. XLIII. The separation of the sternocostal portion into various bundles is especially well marked. They have no relation to the ribs so far as the number and position is concerned.



Fig. 5. —Ventral Tiew of a portiou of the model sliowu iu Fig. 4, showing the pectoral muscle mass and its relations to the scapula, clavicle and humerus. A, acromion; c, coracoid process; cl, clavicle; /(, humerus ; p. m, pectoral miiscle mass ; c p, clavicular portiou \ » e p, sternocostal portion; p. min, pectoralis minor bulging; s, scapula.

In an embryo 32 nun. in length (No. C'XXIX)," we find that the j^osterior layer of the tendon of insertion has made its appearance (Fig. 9). The fibres which go to this tendon come from the most caudal portion of the rnuscle. This posterior layer is about one-fourth the width of the anterior layer of the tendon of insertion. The embryo was studied with a dissecting microscope and so far I could determine


?


-C,p

scp.


Fig 6. — Diagram of a cross-section of the pectoralis major fibres near their humeral insertion. Enlarged 50 times. P, proximal end of the same; c p, clavicular fibres; s c p, sternocostal fibres.

the arrangement of its fibres was otherwise similar to the adult.

In an embryo 36 mm. in length (No. XC). we find the posterior layer of the tendon of insertion nearly three-fourths the length of the anterior (Fig. 10). Otherwise the muscle appears to be much as in the adult. The pectoral region was studied with a dissecting microscope.


s Mall, Maryland Medical Jour., October 3'.l, 1S!I,S. Ibid., .Tour. Morph., vol. xiv. No. 3, ISOS. Ibid., Johns Hopkins Hospital Reports, vol. ix, 1900.

"Mall, Contributions to the Science of Medicine, dedieated to William H. Welch, Baltimore, liiOO, Johns Hopkins Hospital Reports, vol. ix, 1900.


In an embryo of 40 mm. in length the posterior layer of the tendon exceeds the anterior in width, and the muscle presents the adult form.



Fig. 7. — Ventral view of the pectoralis major muscle in an embryo measuring 16 mm. iu length (No. XLIII), taken from a wax reconstruction of the arm region of the same. Enlarged 30 times, hi c p, sternocostal portion, various artificial divisions of which a, h, c, cl, are shown near their insertion in Fig. s ; ,■ I, c II, <• V, c VI, euds of first, second, fifth and sixth ribs, which, with the third and fourth join together to form the left half of the pectoralis major muscle; A, humerus, p. m, pectoral muscle mass; scp, sternocostal portion ; s, body of the scapula; M, sternum; c p, clavicular portion; <■;, clavicle"; !i, humerus.

Summary.

It is thus seen that the pectoralis major muscle arises in common with the minor from a premuscle tissue which is



Fig. .s. — Diagram of cross-section of the pectoralis major muscle seen in Fig. 7, near its insertion into the humerus. Enlarged .30 times. P, proximal; ant, ventral surface ; c p, clavicular portion ; a, b, c, approximate position of the corresponding muscle bundles of Fig. 7.

located for the most ]uirt aliove the fir.^t ri1:i. It gradually migrates or sliifts to the costal region, as has already been noted by Dr. Mall.' During the course of this migration it splits into bundles. The clavicnlar portion i.s the fii'st to split off. Later the sternocostal portion splits into the major


■ Mall, Development of the Ventral .Abdominal Walls iu Man. Jour, of Morph., vol. xiv, No. 3, IMIIS.


April-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


17


and minor. The major becomes arranged into a series of overlapping bundles. As we have seen, the clavicular portion is the upper and most superficial. During the migration the overlapping of the sternocostal Inuidlus is such that superficial fibres of each l.iundle have descended farther than the deeper, owing perhaps to the greater friction of tiie


-a


Fig. 9. — Diagram of tlie insertion of the peetoralis major muscle in an embryo 30 mm. in lengtli (No. CXXIX). Enlarged 16 times. A, anterior layer of the tendon; 6, posterior layer.

latter against the chest wall or to their earlier attachment. The lower bundle seems to be the last to be differentiated, and its tendon, the posterior layer of the tendon of insertion, appears to gradually spread out toward the proximal end of the humerus after the superficial or anterior layer is well formed.

The early entrance of the nerves into the muscle while still in the cervical region explains the adult nerve supply.


Explanation of Varieties. It would seem that in the conditions existing between an embryo of 9 and 11 nun. in length might be found a partial explanation of such varieties as absence of the sternocostal or clavicular portions and of the peetoralis minor with the sternocostal portion. We have here a condition in which


-a


I

Fig. 10 Diagram of the tendon near

its insertion of the peetoralis major muscle of an embryo 36 mm. in length (No. XC). Enlarged 16 times. A, anterior layer; 6, posterior layer.

the clavicle is absent and no attachment to the ribs exists. The subsequent attachment to one or the other might not occur and that portion of the muscle found wanting in the adult. With absence of the sternocostal portion would be associated that of the peetoralis minor owing to their early fusion. In the tendency to split into bundles, with the shifting of the muscle and fibres, the muscular bands which are often found as the costocoraeoidens, sternalis, chondroepitrochlearis, etc., may have their origin.


ON THE BLOOD-VESSELS OF THE HUMAN LYMPHATIC GLAND.


By AV. J. Calvert, M. D., U. S. A., Palhological Laboratory, Board of Health, Manila, P. I.


The lynipliatic glands removed at autopsy from pest cadavers have enabled me, on account of the extreme congestion incidental to the disease and the reduction in the density of the nuclear elements of the gland, to follow in detail the course of the smaller vessels; the pathological changes referred to are not of sufficient degree to destroy the landmarks of the organ or to change the general relationship of the parts.

In an earlier communication I showed the course of the blood-vessels in the lymph follicle in the dog, and the present report is made because it demonstrates that the same arrangement is present in the human lymphatic gland.

The glands were fixed in Zenker's fluid, hardened in alcohol, sectioned in celloidin, stained in hematoxylin and eosin and mounted in balsam.

The illustrations show the origin and distril)ution of the follicular artery, the arrangement of the capillaries in the follicle and the origin of the veins. The course of the


arteria; and vena; lympho-glandulae and the vessels of the cord have been illustrated.'

From the above illustrations and the many typical pictures seen in the slides the following scheme for the blood supply of the human lymphatic gland may be described: The arteri* lympho-glandulffl enter the gland at the hilus, pass through the hilus stroma to enter the trabecule. In the trabeculae arterial twigs are distributed to all portions of the gland. On reaching the portions of the gland near the proximal ends of the follicles small arteries arise which run in the lymphatic structure more or less parallel to the surface of the gland. These arteries give rise to the follicular artery (Figs. 1 and 2) and supply the adjacent portions of the pulp cords.

The follicular artery runs a straight course in or near


> The Blood-vessels of the Lymphatic Gland. By W. J. Calvert Anatomiscber Anzeiger, xiii. Band, Mr. 6, 1897, p. 176.


178


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


the centre of the ]yiii]ih cord of its particiihir follicle, to ahont the junction of I lie jiroximal with the middle third of the follicle. The ftillicular artery may give off branches to .«u])])ly the adjacent jmrtions of the cords. Near the centre of the follicle the artery breaks np into a number of small, straight, long capillaries which diverge to the periphery of the fdllicle. In some cases these capillaries branch, in others they do not.

Just beneath the periphery of the follicle these capillaries turn and branching form a rich plexus of capillaries wdiich in turn unite to form small veins (Fig. 6). The ])Iexus of capillaries in the follicle is continuous with a similar plexus in the cords.

The veins formed in the follicle run toward the jjroximal end of the follicle to join a rich plexus of veins.

The arteries supplying the cords are, as a rule, quite short.


run in or near the centre of the cords and rapidly end in a rich capillary plexus near the surface of the cord. This plexus soon unites to form snudl veins which also run in or near the centre of the cords, but in a |iortion of the cord other than where the artery is found. The veins of the cord soon join veins from neighboring cords, through the anastomosis of the cords, to form larger veins which leave the cords to join the vensE lymjilio-glauduliP.

The veins from the follicles and adjacent jiortions of the cords unite to form a rich venous plexus, which lies within the lymphatic structure. This ])lexus may bo considered to be the origin of the ven;B lymjiho-glandula', which, like the arteries, run in the trabecula? to leave the gland at the hilus.

The lymph channels are free from blood-vessels.

This arrangement of blood-vessels is also found in the lymph gland of the monkey.


NORMAL MENSTRUATION AND SOME OF THE FACTORS MODIFYING IT.

(PRELIMINARY NOTE.)

By Cleli.v Duel Moshee, A. LL, M. D.,

Gi/nwcolor/iral E.rlcrne in the Johns Uopl'ins Ilospital Difiiciisarij.


The conclusions stated in this note are liascd on two kinds of data — clinical and experimental. The first consists of serial menstrual records of more than 300 women, collectively extending over more than 3000 nienstnud periods. A large number of these records were made by the writer, month by month, when the women Avere under her personal observation in the Stanford University Gymnasium, and then were continued by the women themselves during holidays and vacations away from the university. The records were supplemented by preliminary statements, careful intermenstrual notes, and subsequent letters. The usual physical examination for admission to the gymnasium was made by the writer in many cases; to this was added an intimate knowledge of the conditions under which the women were living and working. Second. laTioralory experimental data on the i-es])ii-alioii,' urine, tcm])erature, pulse and l)lood — blood |)ressure, blood counts, hemoglobin estimations and so on. Experimental work on the effects of clothing was also included. This work luis been done in the physiological laboratories of the Stanford and the Johns Hopkins Universities, and in Dr. Kelly's laboratory. The first work was done in May, 1893, in California, has been continued as o|i|iortunity offered and is still in progi'css.

Some of the more important conclusions, which are based largely on the blood-jiressure experiments and clinical data will be reported at this time.


• "Respiration in Women," Preliminary report as thesis for M. A. degree, Stanford University, May, 1.S94. Also paper presented at California Science Association, .Ian. 3, IS',16.


McthuiL — Daily records of the blood pressure were made on 14 persons— woincn and .'J men. The \vomen were selected as representing normal conditions of menstrual health. The iiK'U were all healthy adults and 4 were athletic, ^n attempt was made to continue the records long enough to cover at least two periods of change in pressure; in some cases the observafions extended over 49 days and some are still in progress. The blood-pressure records were made with the sphygmomanometer of Mosso. The tracings were taken daily at the same hour and under uniform conditions, perfect rela.xation being secured and all varialile factors excluded as far as possible.

Conchisions. — That a rhythmical fall of bl(jod pressure, at definite intervals, occurs in iKith men and women. The daily records of the blood-pressure with the sphygmomanometer of Mosso on men and women inider similar conditions of life and occu|)ation give curves apparently indistinguisliahle in chai'acter. The fall in pressure in women occurs near or at the menstrual period. In all of the 14 series of records the fall of blood-pressure was gradual from the mean average pressure. This from day to day shows oscillations .within rather definite limits. The maximum fall of ]iressure may extend over two or three days and the coi-responding rise to the normal average jn'ossure is gradual. There is usually a jireliminary rise, above the normal average jiressure; this occurs from 3 to 5 days before the onset of the main fall of pressure, wdiich constitutes the principal feature of the rhythm. Tn every case there was a preliminary fall, abrupt and definite, but usually not so extensive as the main fall of pressure; this preliminary fall was followed by


THE JOHNS HOPKINS HOSPITAL BULLETIN, APRIL-MAY-JUNE, 1901.


PLATE XXXi


Fig. 1.— The follicular artery and its capillaries. One of the long capillaries is seen to join a venous capillary in the periphery of the follicle; on either side of the follicle small veins are seen. Transverse sections of several veins are also seen.

Measurements: artery before dividing. 41 microns; and capillaries from 8 to 10 microns iu diameter


^«^« 



^-'ny^'^f^f


(^rr,




Fig. 2. — The origin, course aud distribution of a long follicular artery.

Measurements: at origin, o4 microns; and before dividing, 31 microns; capillaries in follicle, from 7 to 8 microns.


^5gft-.




■~^&




■A:


Fig. .5.— Two follicular artery an artery is seen end of the follic


follicles with their veins. The follicle on the right shows a portion of a entering the centre of the follicle. Below the proximal end of the follicle running parallel to the surface of the gland to turn toward the proximal

le ; here it is lost.


Fig. 3. — An artery arising some distance below the proximal end of a follicle, running toward the follicle to turn at a right angle aud run to the centre of the proximal end of the follicle; here it again turns at a right angle to enter the follicle, where it divides iu the usual manner.


^S??Sf^?SQ3:?'SWfS9i%.


%^'




$



l«^


Fro. 4. — A double arterial siipjily to the follicle.


Fig. 6. Long curved capillaries, c, near the periphery of the follicle.


Apbil-May-June, 1901.]


JOHNS HOPKINS HOSPITAL BULLETIN.


179


a return to tlie iiimiuil or hijrhcr })ressurc' Ijet'ore the iiriiieipal i'all oeeiirred. In 4 cases tliere was a distiiiet rise above normal after the main fall of pressure before the return to the normal daily oseillations. These variations were not peculiar to either sex.

A curve constructed on tlie subjective observations of the sense of well lieini;'. shows ups and downs eorrespondiiii;' to the marked vai'iations in pressure; the sense of maximum efficiency of tlu' individual corresponding to the time when the pressure is hii;]i. and lessened efficiency to the ]ieriods of low pressure. Tiie observations were carried on iiulopendently of each other. In no case was the change sufficient to incapacitate the indixidual. The time of low pressure appears to l)e, in Loth sexes, a jjeriod of increased susce]iti])ility. If symptoms of any kind are shown they are apt to he given by the point of least resistance. For exauqile, if a man oi' woman having a tendency to digestive disturbances, the symptoms from the digestive tract are likely to occur at the jjcriod of l(]\v blood pressure: or when a slight chronic catarrh exists, as so fre(|uently ha])pens in this climate, there may be marked increa-e of symptoms from the resjiiratory tract.

In Women the fall in blood jiressure most frecpiently occurs before the menstrual How. the maximum fall being coincident witli the onset of the flow; there is a gradual ret^irn to tlie lujrmal mean pressure by the time the menstruation ceases. Occasionally llie fall oecui-red during the flr.w.

Wliile true dysmenorrlnea is far too fretpicnf. much of the so-called menstrual sutfering is not dysmenorrhcea but simply coincident functional disturbances in other organs, induced, l)ossibly, by 'the favoring conditions of a lowered general lilood pressure occurring near or at the time of menstruation, ((.ioodman's restricted definition of menstruation is adhered to — ^" A periodic sanguineous defluxion from the genital tract.")

When tile attention is of necessity directed to so obvious a


l)rocess as the menstrual flow, untrained women, especially if without absorbing occujiation, naturally refer their lessened sense of w'ell being and diminished sense of efficiency, which may accompany the lowered general blood pressure occurring near or at the menstrual flow, to the fnnctiou of nu'iistruation. When we remendier how firmly fixed is the tradition that a woman nuist sufl'er and be incapacitated by this normal physiological function, it is .readily understood how many women would call the depression due to lowered blood pressure, menstrual suffering.

All statistics, however extensive or carefully taken, arc likely to exaggerate the percentage of women suffering fi'om dysmenorrhcea, because the errors just mentioned are so difficult to eliminate.

The conception that functional disturbances in other organs are considered and recorded as dysmenorrhcea was first derived from the study of the clinical data and later strengthened by the blood-iiressure experiments supplemented by tlie notes of the ]ier,sons studied.

The conclusions of this paper would have been impossil)le had my clinical data consisted merely of isolated statements ba.sed on the general impressions, as to their own conditions, of individual women filling out a single menstrual record, and without a personal acquaintance with, and an intimate knowledge of, the haliits of life and conditions of work of the women studied.

Although S]iace forbids detailed acknowledgements at this time, I wish to state my obligations for many favors received at Stanford University in the earlier work; to Dr. Howell and his associates, Dr. Dawson and Dr. Krlanger of the Pliysiological Department of the Johns IIoi)kins ITniversity; to Dr. Kelly's lilierality and generous encouragement which have made possible all of the later work. The intelligent cooperation of my former students and many friends and of the nu'U and wcunen who have recently given and are giving so much of their valuable time, has made this work possible.


RETROJECTION OF IIILK INTO TIIK I'AXCKEAS, A CAUSE OF ACUTE IIEM01II!11A(IIC

FANCREATITIS.


I;v W. S. II.\L8TED, M. D.


Mr. T., aged 18, a cor|julenl and robust looking man, Jiad been subject to attacks of " indigestion," attended with pain in tlie epigastrium and a feeling of distention, for several years. These attacks would .sometimes incajiacitate him for business, lie had a severe attack of this kind la-st Christmastide. He described also attacks of "vertigo," which had laid him U]) for S or 10 days every spring, with perha]is one exception, for the past ten years. At the end of April, 1901, be arrived in Baltimore after a hard railr(ia<l trip of about S days. On the way, suffering with indigestion, he bought a two-ounce package of bicarbonate of soda, half of wbieb lie consumeil. After Inneheon on the dav of liis arrival he


was seize<l (piite suddc^nly with a severe pain in the abdomen; he was nauseated and expressed his desire to be relieved of the "gas in the stomach." His physician administered calomel, and later nux vomica and carminatives. For 2-1: liours he was relieved; then, -after eating buckwheat cakes, the pain returned. Occasionally driiddng large quantities ■^of water, he forced himself with difficulty to vomit. He suffered almost constantly more or less pain for a week, Init took his meals regularly and slept about as well as usual. About noon on the Htb of May, the pain became very severe; morphia administered hypodermically three times during the afternoon. J grain in all, did not give much relief.


180


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[Nos. 121-122-1S3.


Inhalations of chloroform had to be given. At 9 j). ni. I was asked to sec him by his attending i)li3'sicians. As I entered liis bedroom, lie was walking al)out in his pajamas, excited and iiervous, and his teeth chattei'ing; he seemed to be in great pain. His pulse was full and regular, 92 tlie first count and 87 the second. When I attempted to examine him he made an effort to keep quiet but in a moment had to spring up again. He was sensitive to pressure over the epigastrium, but not exquisitely, the point of greatest tenderness being a little above and, I thought, to the right of the umbilicus. He was "somewhat cyanosed. My attention was called to the cyanosis by the print of my fingers on his abdominal wall. His condition was so good tliat I tliought, with his physicians, he was jirobably suffering from gall stones. He refused to go to tlie hospital. Hot baths during the night relieved him, I am told, for the time, but he had to be chloroformed frequently. In the morning he was anxious to go to the hospital and was operated upon immediately after his arrival, about 11 a. m.

Operation. — The cyanosis of the patient was much more striking as he was laid on the ojierating table, and lie vomited as he was being antesthetized. The abdomen was not distended, but the panniculus was very deep. On opening the belly through the middle line blood-stained fluid escaped and at once it was noticed that the omentum showed abundant fat necroses; these necroses were to be seen in the subperitoneal fat, in the mesentery, along the lesser and greater curvatures of tlie stomach, etc. In order to explore more fully the pancreas and to make sure that a certain hemorrhage in the wall of the stomach, near the pyloric end, had not produced any serious lesion, the omental bursa was rapidly opened. Nothing that could be designated as a tumor mass was made out; the entire region of the pancreas could be palpated. The tissues over the pancreas were slightly infiltrated with blood-stained scrum. The common bile duct, however, was distended to the size, perhaps, of an index finger. The presence of a stone in the diverticulum was of course suspected, and a careful though luirried search made, but none could bo felt; the fluid in the abdominal cavity was rapidly sponged out and a gauze pack placed over th(' head of the pancreas. The abdomen was then closed. The patient died within 23 hours.

Pain, vomiting, distention of the abdoiiien, sometimes an clastic swelling in the region of the pancreas, fluid in the peritoneal cavity, pulse 140 to IGO or higher, cyanosis, collapse -tliese arc the symptoms which the surgeon calls to mind when he pictures to himself a case of acute hemorrhagic pancreatitis, and hence it is that this disease has so many times been considered acute intestinal obstruction. My patient was strong, restless and walking about the room, not collapsed; his pulse was 92 the first count, 87 the second; the abdomen was not only not distended but. according to the patient, had greatly diminished in size during the few weeks preceding this illness; the reduction in the size of his waist, as evidenced by the considerable space between the band of his trowsers pnd his abdominal wall, was a matter


which ajiparcntly gave him some concern, for he referred to it more than once. Vumiting, it' present, was so inconspicuous a .symptom that it had not been noticed; the ]jatieiit had perluqis 3 or -1 times tickled his pharynx because he tluiught it relieved him to gag and bring up a little mucus from his stomach. When I saw him about 13 hours before the o])eration and again an hour before it, pain in the epigastrium and slight cyanosis were his only symptoms. But the pain must have been intense and seemed greater than I had ever seen it in cases of gall stone. I had the misgiving that I was in the presence of an unfamiliar affection and was prepared for a surprise when I opened the abdomen; and yet acute pancreatitis did not occur to me, my conception of the clinical picture was so different. But I shall not soon forget this case; the excruciating pain in the epigastrium and the cyanosis; altogether, a clinical picture difEerent from anything that I could recall. To save my colleagues and students the humiliation of making the same mistake, I have thought that it might be well to represent graphically the only sign which this obseurc case ])resented, the white print of fingertips in a slightly cyanosed field just over the site of greatest pain. Attacks of acute hemorrhagic pancreatitis, mild and severe, are probably much more common than is generally supposed, and I am sure that the clinical picture is sufficiently definite to be easily recognized by the general practitioner.

The autopsy was most carefully made by Dr. Opie, whose description of it will follow. The .stone, which I could not find in my hurried search at the operation, was almost too minute to have been detected under the circumstances, and even at the autojisy it was only after prolonged handling and probing of the papilla itself outside of the body that the presence of a stone was determined. Opie has found that gall stones have been present in the majority of the more recently reported cases of acute hemorrhagic pancreatitis. In some instances they were, imdoubtedly, not carefully searched for, in a few they may have been overlooked and in others they may have passed the papilla, having been arrested in the diverticulum long enough to produce the lesion in the pancreas. If it is true, as this case and Opie's experiments recorded below prove almost beyond question, that acute hemorrhngic j^ancrcatitis may be caused by liile retrojected into the pancreatic duct, the inference that milder lesions and subacute and chronic changes may be produced in the pancreas by the mere presence of bile in its ducts is natural. The fact that the entire pancreas is not always or even usually involved, normal areas being found here and there among the hemorrhagic ones, makes it seem not unlikely that quite small patches may at times be afEected and that the symptoms after very limited involvement might be overlooked or misinterpreted. Epigastric pain, rapid pulse, nausea, vomiting and possibly hematemesis coming on either soon or long after operations upon the common duct might in some instances be attributable to lesions in the pancreas.

The Mechanism, — The arrangement of the parts concerned


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in the production of acute hemorrhagic pancreatitis reminds me of the liydraulic ram in its primitive form. The ductus clioledochus is the feed pipe, tlie pancreatic duct tlie delivery pipe and the calculus the ball valve or stop cock. Although I know of no experiment to determine the force with which bile may be ejected from the gall bladder, it is conceivable that the sudden and complete interruption of the flow of bile during digestion by a calculus might give rise to a retrojection spurt of considerable volume and velocity. But whether this force is considerable or not, since the pancreatic juice and the bile are secreted at almost the same, quite low (3j^ini. of water) pressure, it would probably be suflicieiit, as Dr. Opie will show, to drive the bile into the pancreatic duct under the proper conditions.

Why is pancreatitis hemorrhagica acuta such a rare disease?

1. That bile may be retrojeeted into the pancreatic duct, the stone must be (a) too small to occlude the pancreatic duct or interfei'e with the force of the jet aud at the same time (6) too large to pass the papilla.

2. A narrow papillary orifice, such as we found in my case (a rare condition), would predispose to this affection, because many stones small enough to fulfill (a) the first condition are too small to fulfill (b) the second.

3. One calculus would be more likely to cause the pancreatitis than several, for other stones in this duct, unless very small, would weaken the force of the bile-spurt which drives the ball valve against the papillary orifice. I have elsewhere called attention to this fact.'

4. The gall bladder must perhaps be normal or nearly so; not thickened, shrunken or weakened by inflammation. Accordingly, one must have a calculus or calculi which have produced insignificant changes, if any, in the walls of the bladder.

5. The anomalies which Dr. Opie will consider protect a certain proportion of cases.

6. A predisposition may be necessary, as is given by adiposis and excessive use of alcohol.

Apropos of what I have said as to the possibility of mild attacks of hemorrhagic pancreatitis after gall stone operations. Dr. Finney has just told me the story of a most interesting and perhaps not wholly unique case. Four months ago he did a choledochotomy for 2 large soft stones in the common duct. The duct was enormously dilated, the gall bladder atrophied. The stones were almost as mushy as damp salt, and crumbled to pieces in the duct. The detritus was removed with extreme care and the duct afterwards repeatedly flushed with the physiological solution; notwithstanding this it seemed to Dr. Finney that some grains still remained in the duct. The incision into the common duct was sutured and the convalescence was entirely uneventful except for a trivial leakage of bile beginning about the 7th day p. o. A few days ago, when in robust health, the patient was seized with excruciating pains in the


' Halsted. Contributions to tlie Surgery of tl\e Bile Passages. Tlie Johns Hopkins Hospital Bulletin, .January, 1900.


epigastrium, unlike any that he had ever experienced. Dr. Fiuney was telegraphed for promptly and reaching the patient in a few hours found him vomiting, collapsed, cyanosed and suffering pain so severe that morphia in large doses did not control it; tb.e pulse was aliout 160, pressure over the pancreas was unendurable, the abdomen was distended. Acute pancreatitis was suspected, and operation, considering the collapsed condition of the jiatient, deemed inadvisable. The following day the patient was brought to the Johns Hopkins Hospital, his condition was greatly improved and 48 lioui's later he seemed perfectly well.

Is it not probable that in this case one of the fragments increased in size may have been responsible for the attack? Was the fragment passed? What were the lesions in this attack ? Acute pancreatitis just beginning to be understood will probably soon become a household word.

Trealmeni. — We must learn to make the diagnosis pronijith-, and to distinguish gall stone attacks per se from those attended with pancreatic complications.

To search for and remove the stone in the diverticulum as soon as possible after the appearance of the first symptoms would be the correct procedure in some cases if the true nature of the attack could be recognized early enough. If this patient of mine had been operated upon and the stone removed at some time prior to the onset of his severe symptoms, perhaps at any time within the first seven or eight days of his illness, it seems probable that his life could have been saved. Without operation there was little if any hope for him, for the conditions responsible for the lesions would have persisted. It was evident at the operation that the common duct was obstructed but the patient's condition absolutely eontraindicated prolonged search for the cause, which probably could only have been determined by opening the common duct or the duodenum, so minute was the calculus. Operation should not be undertaken upon cases in collapse, but the bloody fluid, probably highly toxic,' may he hastily evacuated by laparotomy (local anaesthesia) in cases too ill for radical operation.

Of 25 cases of acute hemorrhagic pancreatitis operated upon only two have recovered,' a case operated upon by me eleven years ago" and Hahn's case recently reported.*

In his recent article Prof. Hahn expresses a desire to learn if the operation performed by me in the case which recovered was prolonged by the usual search for some cause of intestinal obstruction, and the hope that, in future, inoculations of culture media will be made from the blood-stained abdominal fluid. It gives me pleasure to be able to reply and to state that fat necrosis was at once observed, the diagnosis promptly made and the operation, therefore, probably a short one: drainage was not employed. This patient is alive and apparently well. In the second case, inocula


sHahn. Deutsche Zeitsehr. f. Chir. Brt. 8.5. Heft 1. 3 Kortc. Die Chirurgisehen Krankheiten unci die Verletzungen des Pankreas.

Hahn, 1. c.


182


.JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


tious from the bloody abdomimil Ihiid wore made, aud witli negative results.

It seems not improbable that, as Hahii states, the rapid evacuation ol' the bloody tluid in the abdominal cavity may in some cases be benelicial. llahu believes that this fluid is highly toxic and perhaps inlectious, and emphasizes the fact, e.\emplified by one of the cases which he reports, that large retroperitoneal extravasations of blood cause incomparably less disturliaiice than we see in these cases ol' hemorrhagic pancreatitis in which the loss of blood is insigiiilicant. I had read llalurs article only a few days prior to the o])eration upon tliis case and was acting u[ion his suggestion, but coming so quickly upon the dilated common duct 1 lelt myself compelled to make a hurried scari'h for the cause of the obstruction. I have little doul)t that my operation hasteiu'd the death of the [latient.

If a stone in Venter's diverticulum was the cause of the pancreatitis in my first case, the one that recovered after oj)eiatiiin, we must conclude that it passed the |ia)iillii, prolialily dnring the attack, for it had [u-oduced no symptoms fronr the time of the operation, May. 1890, until June, 189."), when he was examined in the hospital by Dr. F)loodgood. I fiml that I misinformed Dr. Korte' when I wrote hiui that my recovered case had had a subsequent attack. The attack referred to oecu"]i'e(l in aiiotlier case, one of suppui-ative pancreatitis, operated upon and cuied by my associate. Dr. I""inney.


TTTE ETIOLOGY OF ACUTE HEi\IOKRTIAGIC PANCKKATITJS

JjY Eugene L. Orn:, M. D. fiislruf/iir ill Paihologij, Johns IlopMn.i Uiiiirrsilji.

(Fi-inii III, l;il/i„lv,/ir,i/ Liihiiiiitfiri/ of l/ii .h.hiis lli'iikuis C.iiviKil,/ ,n,d J[..s,nl.,l.)

Pathological Eepoht.

In many reported cases of hemorrhagic and of gangrenous pancreatitis symptoms of cholelithiasis have been associated with the fatal illness and at autopsy calculi have been found in the gall bladder or in the bile jjassagos. In a recent article ' I collected from the literature thirty-one cases of this character and described an additional instance. In eight of these cases, including the one which I reported, a gall stone was found at autopsy lodged near the orifice of the common bile duct or there was evidence that one had shortly before death occupied this position. Since the common bile duct and the duct of Wirsung unite to form the diverticulum of Vater before they enter the intestine, a calculus so located might occlude both ducts. In the greater number of these collected cases though calculi were found at autopsy, none


' Opie. Amci'. Jmir. of tlie Med. Se


I'.Kll,


exxi. [1.


were situated near the junction of the two duets. Nevertheless since, as was pointed out, death with intense hemorrhagic inflammation of the gland has in several instances followed within forty-eight hours the onset of symptoms and a ealeulus has been found near the duodenal orifice of the eommiin duet, it is readily conceivable that a stone tein|)oi'arily lodged in the position indicated might produce grave alteration of the gland before its final expulsion into tlie duodenum. In seven of the thirty-one cases death followed the onset of symptoms, intense abdominal [)ain, vomiting and profound coflapse, within forty-eight hours, and at autopsy the jiancreas was the seat of hemorrhagic infiltration. In seventeen instances in which tlu' fatal illness was of longer duration, seven days to four months, the paiu-reas was gangrenous and there was often evidence of pi'evious hemorrliage. There can be little doubt that gangrencuis p;ini-r('atitis is a late stage of the hemorrhagic lesion.

That acute pancreatic disease is fre<pieiitly iissociaied with ebolelilhiasis has been conliiined by cases ie[iorted since the preparation of the article referred to. The two conditions were |)resent in three cases recently described by Lund," in two by Bryant' and in one by Stockt(Ui and Williams,' by Struppler ' and by Ilahn. The relative frequency with which acute pancreatitis is accompanied by cholelithiasis is dillicult to estimate. In some cases the lesion has been tbagiiosed upon the operating table and, no autopsy being obtained, the condition of the bile jiassages has not been determined. In a very large proportion of the cases the nntojisy report is so meagre that the presence or aljsence of gall stones is not evident. Lund records the relatively large number of six cases of acute pancreatitis, one siqipnrafive, five hemorrhagic or. hemorrhagic and gangrenous. Two of the five cases he describes as hemorrhagic peripancreatitis. ill three of these live cases the gall bladder or the bile passages contained small calculi in large number, wliile in the remaining two no autopsy was obtained. In the two cases reported by liryiint hemorrbngic pancreatitis was associated with gail stones. In only one of the five cases of Ilahn were gall stones present, but in one of his cases hemorrhagic infiltration of the gland followed a pistof shot wound and in another recovery followed operation, (lall stones were, therefore, present in six of eight cases with autopsy described by three writers who have recently reported more than one instance of the disease.

In view of the fact that in several instances a calculus has been found at autoj)sy so lodged as to occlude the jianereatic duct, there can be no douljt that the frequent association of the two conditions is the result of an etiological relationship. The common liile duct and the larger pancreatic duet lie side by side as they penetrate the wall of the duodenum and are often separated near their junction only by a thin mem


'I^iiiid. Boston Med. and Surg. Jour., 1!>00, exliii, p. M?y.

' Hrynut. Liinoet, IflOO, ii, p. lo41.

■•Stoclcton .ind Williams. Philadelpliia Med. .Tour., I'.lOd, vi, p. (;4!l.

'•Struppler. Dcutsehe Arcli. f. Ulin Med., liieo, Ixix, p. JOC.

«Hahn. Deutsche Zcitschr. f. Cliir., Umo, Iviii, p. 1.


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branous septum, while before entering the duodennm at the suiumit of the bile papilla they unite to form a short channel, the diverticulum of Vater. From a study of the case previously reported it seemed not improbable that a calculus lodged in the common bile duet near its termination might cause partial occlusion of the pancreatic duct and subsequent changes in the pancreas as the result, possibly, ol' bacterial invasion. This case, as well as those recorded in the literature, alforded, however, no explanatirm of the pathogenesis of hemorrhagic inflammation. Tlie autopsy recently performed upon the case described Ijy Dr. Halsted has dciiionslruted a mechanism by which this lesion is produced.

Aulopsij. — The body, which is still warm, is tliat id' a large man with very abundant subcutaneous fat. The skin has a bluish cyanotic appeiU'ance. Passing downward from the right costal margin to a point 10 cm. from the symphysis pubis is a longitudinal incision, closed in great part by subcutaneous silver wire sutures. Crossing tiie epigastric region and meeiiug the hrst at right angles is a second incision. At their angle of junction the wound is unclosed for a short distance aiul gauze packed aboid by rubln'i- protective passes into the abdonunal cavity.

The jiei'itoneal cavity contains a moderate excess of l)ioodstained serous lluid. The general peritoneal surface is smooth. l<'at is present in very great amount in tlie omentum, in rnml (it the peritoneum of the ant<i-i(ir alidoniinal wall below tlie umbilicus, in the mesentery, in the retroperit(}neal tissue and as appendices epiploic^ upon the surface ol the large intestine. Studding the fat in the various situations named and conspicuous upon its translucent surface are small usually round opaque white, areas 2 to 3 mm. ^n diameter, often surrounded by a narrow zone of injection: They ai-e sujjerficially situated and extend usually less than 1 mm. below the surface. They are most abundant in the omentum and in the retroperitoneal fat adjacent to the pancreas. The gauze drain previously mentioned passes between the stomach and the transverse colon and lies in contact with the retroperitoneal fat immediately below the head of the pancreas. Here tlie tissue has a reddish-black discoloration.

The pancreas is represented by a blackish sw(dleu mass extending from the descending part of the duodenum to the spleen. The fat in contact with its splenic end has a similar blackish color and is soft and friable. The pancreas is greatly increased in size, is irregularly cylindrical in shape and measures 5.2 cm. antero-posteriorly, 5.5 em. from above down, and 16 cm. in length. The anterior surface is smooth and has an almost uniform black color in places with a reddish tint. On section the gland substance is found to be in great part transformed into black and reddish-black material. The head of the organ for a distance of 2.5 em. from the duodenum is firm, gray yellow, with well marked lobulation, and has the appearance of the fresh normal pancreas. Tissue « hicli is in immediate contact with this well preserved gland substance is soft and black in color, mottled here and there with small areas of dull red; gland lobulation is still very


obscurely marked. The distal half of the organ shows a similar mottling of black and reddish areas with in places small islands of yellowish, relatively preserved tissue. The largest of these, which is of reddish-yellow color, gradually passing into the surrounding reddish-black, is 1.5 cm. in diameter and is situated near the middle of the body. At the splenic extremity is a slightly smaller mass of intact gland substance. On opening the splenic vein where it lies in contact with the jiancreas the intima is found to lia\( a mollled yellow, blackish and red appearance, due to cbanges iu the underlying tissue. Occupying a portion of the lumen is a mixed red and yellow thrombus mass, fifin in consistence and adherent to the intima.

The duodenum was opened and the common orifice ol' tlir bile and pancreatic ducts examined. The papilla is prominent but its orifice is of small size measuring 1 mm. in diameter. The common bile duet which near its termination is completely embedded in the substance of the pancreas is slightly distended. By very firm pressure on the gall Idadder .-everal drops of liile can be squeezed with dithculty into the duodenum. The gall bladder when opened is found to eontain a moderate amount of viscid blackish bile; no concretions are present. The termination of the pancreatic duct, which is surrounded by the well preserved pancreatic substance in contact with the duodenum, was exposed by dissection and found to unite with the common bile duct 10 mm. from the summit of the bile papilla. A probe passed dow^n the common duct was stopped -1 mm. from the latter point, and it was not possible to touch it with a second probe passed into the narrow orifice. Careful examination disclosed a small graywhite, very firm concretion 3 mm. in diameter, snugly filling the diverticulum of Vater from which it could not escape through the narrow duodenal orifice. The pancreatic duct, where it passes through the intact tissue of the head, is like the common duct stained firight green with bile.

The heart and lungs are -apparently normal. The liver weighs 1350 grins. The surface is smooth and of yellowish color; upon the upper surface of the right lobe are conspicuous slightly depressed dull red areas which are irregular in ■ shape, the larger about 2.5 em. across. The cut surface of the organ has a bright yellow color, the periphery of the lobules being golden-yellow, the central part reddish. Corresponding to the superficial red areas the liver substance has a similar dull red appearance, the periphery of the lobules being marked by narrow yellow zones. Such altered tissue has at times an irregularly wedge-shaped outline and within it are found portal veins distended and plugged with red thrombus material. Following the vein in one of these areas toward the main portal trunk, the thrombus stops abruptly and near its end is of yellowish-white color, representing probably embolic material from the thrombosed splenic vein. The spleen is not enlarged and weighs 140 grms. The organ is flaccid but fairly firm in consistence.

The stomach contains a small amount of blackish semifluid material. The duodennm and remainder of the small intestine contain similar material. The kidneys, weighing


184


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


together 290 grms., appear to be normal, except for the presence of opaque yellow striations near the apices of the pyramids. The adrenals, the bladder, the seminal vesicles and the prostate are normal. Upon the intima of the aorta are a few slightly raised opaqiie yellow patches of small size. The urine contained in the bladder does not reduce Fehling's solution.

Microscopic examination of the pancreas. — A section passing through tlie line of demarcation between the intact parenchyma in the head of the gland and the adjacent necrotic tissue shows a very abrupt transition from the one to the other. On the one side the pancreatic tissue is well preserved, the secreting cells are normal in appearance and their basal zone stains deeply with haimatoxylin, while islands of Langerhans are fairly abundant and appear to be normal. The loose interlobular areolar tissue is everywhere infiltrated with red-blood corpuscles; polynuclear leucocytes are present in large number and often form collections of considerable extent. Eosinophilic leucocytes are numerous and fibrin is abundant. Between the acini are a few polynuclear leucocytes. Within the margin of the intact tissue are several small areas where the parenchyma is undergoing necrosis. The secreting cells no longer stain with hfematoxylin, but assume a homogeneous clear pink color with eosin; the nuclei which are still preserved are much smaller than those of the normal cells and unlike the latter are irregular and distorted and stain homogeneously. Small hemorrhages have taken place into the interacinar tissue of such an area, and polynuclear leucocytes are present in moderate number. Nearby in similarly localized areas the process is more advanced and the parenchymatous cells are replaced by formless material which staining faintly is mingled with a few nuclear fragments and is densely infiltrated with polynuclear leucocytes and red-blood corpuscles.

The transition from relatively normal parenchyma containing a few islands of necrosis to wholly necrotic tissue is very abrupt and is marked by a zone composed of nuclear fragments, polynuclear leucocytes, red-blood corpuscles and fibrin. That part of the section which corresponds to the black and reddish-black material seen macroscopically is necrotic, nuclei are no longer present and though the architecture of the gland is still obscurely definable both parenchyma and connective tissue stain only with eosin. At intervals in areas of varying extent the tissue has a dark brown discoloration due to the presence of brown pigmented material which appears to be changed blood.

Sections from the body and tail of the organ present the appearance described above. In the intact tissue of the tail well preserved islands of Langerhans are particularly numerous. In a section from the body nuclei still persist immediately about an artery, though the surrounding tissue is universally necrotic. Its endothelial cells are swollen and in places are almost cubical. In the media and adventitia, of which the vasa vasorum are preserved, polyaiuclear leucocytes are very numerous.

In sections stained by Weigert's method for the demon


stration of fibrin was noted a histological detail inconspicuous by other methods. Capillary vessels in the living tissue near the margin of necrosis as well as in the immediately adjacent necrotic part liave undergone hyaline thrombosis and form conspicuous deep blue, often branched, lines as though injected. Examination with high magnification demonstrates at times a close meshwork of fibrils in these vessels. In sections stained with hannatoxylin and eosin their contents take a homogeneous briglit pinkish-red stain and red-blood corpuscles are no longer seen, as in adjacent capillaries.

lu sections stained for bacteria with niethylene-blue, with gentian violet, and by Weigert's method, none were discovered.

Bacteriological e.vamination. — Plate cultures in agar-agar were made at autopsy from the heart's blood, peritoneal cavity, pancreas (aerobic and anaerobic on hydrocele agaragar), gall bladder, liver, spleen, and kidney. They were studied by Mr. V. II. Bassett to whom I am indebted for the following report. Cultures from the heart's blood, spleen, and gall bladder gave negative results. The anaerobic culture from the pancreas showed no growth after an incubation of seventy-two hours. The aerobic agar-agar plate from the pancreas contained at the end of twenty-four hours a single superficial colony of a pigment forming coccus whose cultural characters indicated tliat it was a contamination from the air. The streptococcus pyogenes and the staphylococcus epidermidis albus were isolated from the peritoneal cavity. Tlie colon bacillus was present in cultures from the liver and kidney.

Anatomiral diagnosis. — Cholelithiasis; calculus impacted in the diverticulum of Vater partially filling it and occluding its duodenal orifice. Aeule hemorrhagic pancreatitis; disseminated abdominal fat necrosis. Partial thrombosis of the splenic vein; embolism and thrombosis of branches of the portal vein.

The preceding autopsy has disclosed a condition which explains, I believe, the pathogenesis of those cases of acute hemorrhagic and gangrenous pancreatitis which are associated with gall stones. The diverticulum of Vater was 10 mm. in length. Lodged at its apex, blocking its duodenal orifice, was a small calculus only 3 mm. in diameter, but too small to pass the narrow opening. Though it occluded the duodenal orifice of the diverticulum it was so small that the orifices of the common bile duct and pancreatic duct were unobstructed. The two ducts were therefore, converted into a continuous closed channel from which it was not possible for either bile or pancreatic juice to escape.

On dissecting the pancreatic duct where it passed through the unchanged parenchyma in contact with the duodenum it was found, like the bile duct, to be stained bright green with bile. Where, as in this case, the two ducts become a closed channel, the entrance of bile into the pancreas or of pancreatic juice into the bile passages would depend upon the relative pressure in the two ducts. The pressure at which bile and


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paneroatic juice are secreted being small, any slight difference tliat might exist would be overcome by the gall Ijladder, a ijiuscular organ Avhicli at intervals forces bile in considerable quantity along the common duct.

A small calculus only partially tilling the ampulla of Vater can convert the two duets into a continuous channel, while a larger stone might simultaneously oTistruet the duodenal orifice of the diverticulum and the orifices of the two ducts wliicli enter it, thus damming liack bile and pancreatic juice upon their respective glands. In the present case, as previously mentioned, the diverticulum measured 10 mm. in length, the calculus 3 mm. in diameter. In many cases of hemorrhagic and gangrenous pancreatitis gall stones found in the gall bladder and bile passages at autopsy have been small and are often described as pea-sized. This statement is made in the reports of Pay,' Cutler,' Ivennan,° Simpson," Chiari " (two cases), Smith," Ehrich," Fraenkel," Korte," Morian,'" Eolieston," Grawitz," Opie,'° Bryant =° and Lund" (three cases).

Anatomical peculiarities of the diverticulum of Vater miglit favor or prevent' the conversion of the two ducts into a closed channel. The description of the ampulla given by Sappey,™ Testut," Henle'* and Quain '° does not differ materially. It may be described as a somewhat conical cavity into whose base open the two ducts; the apex situated at the summit of the diverticulum is their common duodenal orifice. Its length varies from 6 to 7 mm. according to Testut, from 7 to 8 mm. according to Sappey. Occasionally the two ducts have no common channel, but open by separate orifices upon the summit of the bile papilla. Claude Bernard '" described a variety of termination which has since been observed. The bile duct is prolonged as far as the mucosa of the duodenum, upon which it opens by a circular orifice. The terminal part of the pancreatic duct embraces the bile duct like a gutter and its. orifice has the outline of a crescent. Where the ampulla is very short or the two duets open separately into the duodenum it is evident that an impacted calculus could not render continuous the lumina of the two ducts.


'Day. Boston Med. ;iiul Surg. Jour., ISOi, cxxvii, p. .563.

Cutler. Ibid., 1S95, cxx.xii, p. 354. "Kenn.in. Brit. Med. Jour., 1806, ii, p. 1443. '"Simpson. Ediuburiili Med. Jour., 1897, ii, p. 24.5. " C'liiari. Wiener Med. Wocliensch., lS7(i, xxvi, p. 3iU ; Ibid., 1880, XXX, pp. 139, 164.

I'Smitli. Brit. .Med. Jour., 1897, ii, p. 468.

"Elirich. Beitrii^e z. lilin. Cbir., 1S98, xx, p. 316.

" Fraenkel. Miiuch. med. Wochenscli., 1896, xliii, pp. 813, 844.

isRorte. Arcli. f. klin. Cliir., 1894, xlviii, p. 721.

".Morian. .Miinch. med. Wochenscli., 1899, Ixvi, p. 348.

" Ilolleston. Trans. Path. Soc. of London, 1893, xliv, p. 71.

'«Grawitz. Miincli. med. Wochensch., 1899, xlvii, p. 813.

lii in 81 x,„. ,.if

■^■Sappey. Traite d'anatomie descriptive. Paris, 1889. '■'Testut. Traite d'anatomie humaine. Paris, 1894. =* Ilenle. Handbuch der Systematischen Anatomic des Mcnsclien. Braunschweig, 1873.

■'■Quain. Elements of Anatomy. London, 1896. '5 Quoted by Sappey.


I have recently examined the diverticulum of Vater in a small number of cases available. In three specimens (Nos. 3, 11 and 13) the ducts opened into the intestine by separate orifices. The following figures represent the length of the ampulla in these cases:


5 mm.


No.


1

2


.... 5 mm.

(; "



3


... "



4


4 "



5


.... 5 '*



6


. . . . 7 "



7 . . . .


... 10 "



8


.... 7 "



9


... .5.5"


Jo. 10 ...


3.5


" U



" 13...


6.5


" 13


...


" 14 . . .


. ..55


" 15


1.5


" 1()


1


" 17


11


No. G is from the case previously reported, No. 7 the one described in the present article. The figures are cited to show that the length of the so-called diverticulum varies considerably.

Another anatomical factor of considerable importance is the size of the duodenal orifice of the ampulla. Ilyrtl " states that this opening is narrower than the lumen of the gall duct at any point or is at least less distensible so that gall stones often remain here im]iacted. In the autopsy describetl the opening measured only 1 mm. in diameter. In most instances it measured 2 to 2.5 mm.; in specimen No. 9 the diameter was 4 mm.

EXPEHIMENTAL StUDT.

Hemorrhagic pancreatitis has been produced experimentally by the injection of a variety of irritating substances into the iiancreas, but no attempt has been made to reproduce the lesion by the use of bile.

Thiroloix "' injected several drops of deliquescent chloride of zinc into the duct of Wirsung in a dog. Death occurred suddenly after a short interval and the pancreas was represented by what appeared to be a blackish clot. Hlava " injected artificial gastric juice into the pancreatic duct. This fluid, containing hydrochloric acid in the proportion of 1 to 1000, caused death in three days; the pancreas was hypersemic and in the fat of the omentum and of the mesentery were numerous foci of necroses. Death on the tenth day followed the injection of 5 cc. of artificial gastric juice with hydrochloric acid 4 to 1000; the pancreas was the seat of hemorrhagic infiltration and the omentum and mesentery contained foci of fat necrosis. He suggests that in human cases hyperacid gastric juice may be forced by antiperistaltic action of the intestine into the pancreatic duct, thus causing the condition. Hlava has produced a hemorrhagic lesion of the gland Iiy injecting cultures of the bacillus coli communis, lincilliis lactis aerogenes, and bacillus capsulatus of Friedliiuder, but thinks that the change is the result of the acid products of these organisms.


"riyrtl. ITandbuch der Topographischcn Anatomic. Vicuna, 1882. '"Thiroloix. Quoted by Carnot (see below). "Illava. Quoted by Flexner (see below).


186


JOHNS HOPKINS HOSPITAL BULLETIN.


[Nos. 121-122-123.


Oser '" records the injection of 4 cc. ol ^'u normal sulphuric acid solution into the pancreatic duct of a dog. Deatli followed in twenty hours. In the duodenal part of the gland was a hemorrhagic area the size of a pea where the tissue was destroyed and its structure no louger recognizable. By tlie injection of tiie fi'rment, papaine (0.2 grnis. in 30 cc. of water), inio |]ie duel of a ilog, C'arnot '" caused the deatli of the animal in twenty-five hoiirs; the pancreas was every wlierc inllltrated with blood but there was no necrosis of fat. Smaller doses did not produce hemorrhagic lesions. The same wi'ilcr pi'odueed hemorrlnxgic pancreatitis by the injci-lidii 1)1' the diphtheria toxinc into the pancreatic duct of a rabbit. A suspension of the bacillus coli connnunis (12 cc.) caused a similar lesion fatal in twenty-four hours. Subsequent injections of the same organism caused inllanimatory rliaiigcs wilbnut hemorrhage.

More varied ami successful experiments have been performed by Dr. Klexner^" in this laboratory. In ten experiments pei'l'iirnied ujiim ddgs bydnu-hloric acid varying in strength in dilfcrent instances from 0.5 to 2 per cent, and in amount from 3 to 8 ec, was injected into the pancreatic dui't. In six instances there resulted hemorrhagic inflammation of the gland, accompanied in five by focal fat lu'croses. In three of these cases death followed the operation within twenty-four boni-s; in [wo the animals wei'c killed. In tlie remaining experiments purulent or chronic inteistitial inflammaticni resulted. Hemorrhagic lesioms were produced in two dogs liy the use of nitric acid (1 cc. of a 2 per cent solution and 5 cc. of a 1 per cent solution); in one, by the use of chromic acid (8 cc. of a 1 per cent solution). In a second series of experiments sodium hydroxide solution (21) to .5 cc. of solutions varying in strength from 1 per cent to 2 per cent) was employed. Hemorrhagic lesions resulted in three cases and were accompanied by fat necrosis in at least two. Suspensicnis of bacteria were used in a third series, llenmrrhagic inflammation was caused liy the bacillus pyoej^aneus and in three experiments by the bacillus diphtheria' but was unaccompanied by definite fat necrosis. In two ex|ieriinents the lesion followed the injection of 5 cc. of a 2 [ler cent solution of formalin into the duct and was associated with fat necrosis.

The experiments cited show that a variety of substances injected into the duct of the pancreas cause hemorrliagic inflannnation. How far they can he used to explain the pathogenesis of human cases is doubtful. The suggestion of Illava that gastric juice may be driven by antiperistaltic action of the intestine into the duets is not supported by any evidence. The relation of hemorrhagic pancreatitis to bacterial invasion from the intestine has not been demonstrated. The condition observed in the autopsy described has suggested a mechanism by wliich an irritating substance can make its way into


3" Oser. Die Erlii-aukuugeu des Panlireas. Nntliuagel's Spec. I'ntli. u. Ther., xviii, ii, p. 2S6. Vienna, 1S'.)S.

3' Carnot. Paris Tliesis, 189S.

■'■ Flexncr. Contrilmtiiius tn the Science of Medicine, Dedicated to Wm. H. Welcli, M. D., p. 74;). Baltimore, I'.IOO.


the organ. Can the hemorrhagic inflammation observed in human cases and produced in animals by means of various irritants be reproduced by the injection of bile into the pancreatic duct?

In the following experiments the duodenum of dogs was opened for a distance of several centimetres opposite the larger pancreatic duet. Tlic blunt pointed nozzle of a syringe was inserted into the orifice of the duct and bile obtained from the same or from a second dog was injected into the organ. The ojierations were performed with the usual antiseptic precautions and the duodenal wound was closed by submucous nuittrcss sutures. I desire to express my thanks to Mr. Bassett, Mr. Haskell and Mr. W. Marshall for assistance in the performance of these operaticuis.

Experiment 1. — Into the larger pancreatic duct was injected ■") cc. of bile obtained from a second dog. The animal was killed seven days later. The peritoiu'al cavity contains a small anu)unt of bloody Hnid and the surface is injected. 1'lie large and several loops of the small intestine are firndy adherent to the splenic arm ol' the pancreas, and on separating them are exposed pockets containing very thick viscid fluid ol' dull red C(dor. The walls of these pockets have in places the opaque white aiipearance of necrotic fat. The splenic ]iart of the gland and the duodenal part, above the duodenal orifice of the main duet, is firm in consistence and both ujion the surface and on section shows a mottling of opaque yellowish-white areas se])ai'ated by dec]) hemorrhagic red. Over a considerable area at the junction of the duodenal and splenic parts of the gland the tissue is almost uniformly grayish-yellow and is in places softened and disintegrated. Cultures and coverslips from the peritoneal cavity and from the substance of the pancreas contain no bacteria. Microscopic examination of the splenic and duodenal parts of the gland show that wide areas of parenchyma including entire groups of lobules are necrotic and the -secreting cells, whicli have a homogeneous hyaline appearance and are stained deeply with eosin, contain no nuclei. At the margin of such areas red-blood corpuscles and polynuclear leucocytes are present in great number and fibrin is abundant. In places the bodies of the secreting cells have been converted into formless detritus mingled with red-hlood corpuscles ami leucocytes. The interstitial tissue may be implicated in the general necrosis but often it has undergone very active proliferation and has in small part replaced the disintegrated acini. Islands of intact parenchyma still persist in places and are surrounded by newly-formed fibrous tissue, containing red-blood corpuscles and polynuclear leucocytes.

U.rperimeiit 2. — Bile (.5 cc.) from a second dog was injected as before. The animal was killed at the end of five days. Lightly adherent to the part of the pancreas which is in eontact with the duodenum are several loops of small intestine. In the omental fat are several opaque white areas of fat necrosis, while near the splenic extremity are several inconsjiicnous foci of a similar nature. In the duodenal part of the gland in the neighborhood of the orifice of the larger duct for a distance of 3.5 cm., there is extensive henun'rhagic infil


Apeil-May-June, 1901. J


JOHNS HOPKINS HOSPITAL BULLETIN.


187


tratiou separating islands ui' paruuchyma. In places the gland substance is soft and of gray necrotic appearance. The .splenic part is lirm in consistence and at several points are areas of hemorrhagic inliltration. Microscopic examination of sections from the hemorrhagic duodenal part shows wide areas of necrosis implicating both lobular and interstitial tissue. The pareiiehynuUous cells are hjaliue and without nuclei. Copious hemorrhage has taken place into these areas and at the margin of intact tissue polynuclear leucocytes an; numerous. I'^ibrin is abundant in the necrotic interlobular tissue. Where widespread destruction has not occurred there has lieen active proliferation of interstitial tissue replacing in part destroyed parenehyina and containing numerous red blood corpuscles and polynuclear leucocytes. The remaining acini are often separated by newly-formed interstitial tissue and there is the appearance of advanced chronic inhamniation. In the splenic part of the gland foci of necrosis with hemorrhage occur and in small scattered areas there is newlyformed connective tissue.

Experiinenl 2. — After opening the duodenum o cc. of biK^ obtained from a second dog was injected into the pancreatic duct. Death followed within twenty hours. The peritoneal cavity contains several cubic centimetres of bloody Muid anil the peritoneal surface has an irregularly distributed, deep red injection. The entire omentum is studded with conspicuous oi)aque white areas of fat necrosis, usually round, 1 to 1.5 mm. in diameter, and surrounded by a zone of injection. They are most abundant in the neighborhood of the s])leen, where superlicially and on section they occupy about one-half the exposed surface. In the mesentery of the duodenum near the pancreas they are numerous, but in the remainder of the mesentery of both large and small intestine they are sparcely scattered. Similar foci are present in the retroperitoneal fat and in the properitoneal fat below the diaphragTii. The splenic arm and the upper half of the attached duodenal part of the pancreas are swollen and osdematous in appearance and the lobulations are separated by tissue iidiltrated with blood. The cut surface has a mottled dull red and gray color, the interstitial tissue being hemorrhagic, wjiile minute heaiorrhages wrv. in places seen within the lobular substance. The left lung is the seat of a mucopurulent bronchitis. A culture made from the peritoneal cavity remained sterile. A short bacillus was grown from the pancreas. Microscopical examination shows that the dull red areas of the ])ancreas represent foci of necrosis where the parenchyinMti}Us cells stain only with eosin and no Imigi'i contain nuclei. The blood-vessels hero are widely dilated and abundant hemorrhage has frequently taken place. Polynuclear leucocytes are present but are not very numerous. Such an area of necrosis and hemorrhage is at times limited to the central part of a lobule group, while the acini furtbeiU-inn the central duct are intact. The interstitial tissue particularly of tlie duodenal part of the ghiud has an (edematous appearance and contains red blood corpuscles, polynuclear leucocytes and fibrin.

Experimenl J/. — iiy means of a sliai-p pointed needle 3 ec.


of bile was withdiawu from the gall bladder and injected into the larger pancreatic duct. The animal was killed at the end of seven days. Upon the surface of the pancreas where it is in contact with the duodenum are a few sparcely scattered opaque white areas of small size. In the omentum near tlie gland are a few suuilar foci of necrosis. The pancreas is normal in consistence aiitl no change is noted macrosco2jicall3^ Microscopic examination sliows the interstitial tissue of the splenic and duodeual parts of the gland modeiately iufiltrateil in iilaces with blood corpuscles, while here and there it is distended and has an oedematous appearance. The pareneliyma is normal in tlm sections examined.

ExiJCiiinenL 5. — The operation previously described was repeated and 2.5 cc. of bile was withdrawn from the gall bladder and after opening the duodenum injected into the larger pancreatic duct. The dog was killed at the end of four days. The pancreas which is not adlierent to the adjacent structures is hrm in consistence and has throughout a reddish-gray color, but is nowhere hemorrhagic. (Ju the surface of the duodenal part in contact witii the duodenum are sparcely scattered opaque white areas of fat necrosis. Microscopic examination of a section from thi- duodenal part of the gland shows that newly-formed celhdar eonnecti\e tissue has in a small area replaced the glandular elements. I'roliferation of cells has occurred in the adjacent interlobular tissue which contains in abundance red" blood corpuscles, polynuclear leucocytes and fibrin.

Should bile enter the pancreas after occlusion of the distal end of the diverticulum of Vater, its only opportunity for escape would be by way of the lesser pancreatic duct. In order to reproduce this condition, in the following experiments the duodenum \vas not opened, but the duet was exposed wdiere it approaches the intestine, ligated close to the' duodenum and partially cut across. JJy means of a syringe with a blunt nozzle, bile was injected into the distal end of the duct which was then ligated.

Experimenl 6. — Into the larger duct was injected 5 cc. of bile obtained by puncture from the dog's gall bladder. The animal died twenty-four hours later. The peritoneal cavity contains no excess of tluid. Opaque white areas of fat necrosis are numerous upon the surface of the duodenal part of the pancreas and in the immediately adjacent fat of the duodenal mesentery. Similar foci are present in both layers of the )nesentery near the stomach and pancreas and in the fat in contact with the splenic part of the gland. The interstitial tissue of the duodenal part over an area near the orifice of the larger duct, 2.5 cm. in width, shows deep red hemorrhagic infiltration. The parenchyma throughout the gland is mottled, .small dull red areas alternating with more normal gray yellow gland substance. This hemorrhagic appearance of the parenchyma is most marked in the duodenal part of the gland wdicre there are homogeneous dull red areas of considerable extent. Both lungs contain extensive deep red areas which are feirly firm in consistence and exude very abundant frothy serum. Microscopic examination of all parts of the pancreas shows the presence of numerous foci of necrosis. The ghind cells have assumed a hyaline appearance and have lost their nuclei. The blood vessels in these areas are widely distended and at times there is abundant extravasation of red blood corpuscles. Polynuclear leucocytes in moderate number are seen between the necrotic cells. The interlobular tissue is in many places much distended, containing red blood corpuscles, poljmuclear leucocytes and fibrin.

Experiment 7.- — The operation already described was repeated and 3.7 cc. of bile obtained from the gall bladder of the same dog was injected into the larger duct. The animal was killed three days later. Upon the surface of that part of the pancreas which is in contact with the duodenum and in the fat immediately adjacent to the splenic part are a few opaque areas of necrosis. Tlie pancreas is very firm throughout. On section the glandular lobules are found to be separated by septa of interstitial tissue which are firmer and thicker than usual and near the termination of the larger duct infiltrated with blood. In the duodenal and splenic parts of the gland microscopic examination demonstrates within the lobular tissue numerous small areas where newlyformed, very cellular interstitial tissue replaces groups of acini. The interlobular tissue is infiltrated with red blood corpuscles and often contains in great abundance polynuclear leucocytes and fibrin.

SYNOPSIS OF EXPERIMENTS.


I. — Duodenum Opened and Duct Injected.


Amount Mode of bile. of death.


Pancreas.


No. 1. . . .5tc.

No. 3 5cc.

No. 3 5cc.

No. 4 Src.


Killed in Hemorrhagic iuflamma 7 days. tion and sclerosis.

Killed in Hemorrhagic inflamma 5 days. tion and sclerosis.

Died in Hemorrhagic inllamma 30 hours. tion.

Killed in Slight hemorrhagic


Fat.

Eat necrosis near pancreas.

Fat necrosis.

Extensive

fat necrosis.

Slight

fat necrosis.


J, > o t;.. Killed in Slight hemorrhagic in- Slight "■ ■ 4 days. tiltration and sclerosis. fat necrosis.


No. 6.


. 5fc.


II. — Duct Opened, Injected and Ligated. Died in Hemorrhagic iullamma


24 hours.


tion.


^Fat necrosis. Slight


„ r. o 7,. Killed in Hemorrhagic intlamma ■ ' "' 3 days. tion and sclerosis. fat necrosis.

The injection of 5 cc. of bile into the pancreatic duct caused hemorrhagic inflammation of the gland in four dogs, two of which died within twenty-four hours after the operation. Death did not follow the use of smaller amounts and the changes produced in the organ were less wide spread and severe. In every case necrosis of the adjacent fat accompanied the lesion of the pancreas, and in the two instances in which death occurred spontaneously foci of necrosis were abundant and disseminated. In Experiment No. 1, though the entire splenic arm of the gland was the seat of an intense inflammatory reaction, eoverslips and cultures demonstrated the absence of bacteria. The presence of bacteria in the pancreas of dog No. 2, which died twenty hours after the


operation, is not surprising since the injection was made through the duodenal orifice of the duct.

Microscopic examination confirmed the diagnosis of hemorrhagic pancreatitis and demonstrated the identity of the experimental lesions with that which occurs in human cases. The injected bile first causes necrosis of the parenchymatous cells with which it comes into contact. They loose their nuclei and their protoplasm assumes a homogeneous hyaline appearance and stains deeply with eosin. The injurious action of the irritant upon the blood-vessels is manifested by the occurrence of hemorrhage into these necrotic areas. An inflammatory reaction now ensues and is characterized by the accumulation of polynuclear leucocytes and fibrin in the interstitial tissue and in the necrotic parenchyma. Tlie necrotic material undergoes disintegration and a rapid new growth of interstitial fibrous tissue in part or wholly replaces it. Where death docs not rapidly follow the primary effects of the operation opportunity is given for the occurrence of secondary changes in the gland. The experimental lesion is not in all cases so extensive as that recorded in the accompanying autopsy report. In these experiments a single injecy tion of bile is made, while in the human case bile is repeatedly poured into the organ.

Conclusions.

(1) A small gall stone impacted in the diverticulum of Vater may occlude the common orifice of the bile duct and duct of Wirsung and convert tliem into a continuous closed channel. Bile enters the pancreas by way of tlie pancreatic duct and the pancreas becomes the seat of inflammatory changes characterized by necrosis of the parenchymatous cells, hemorrhage and the accumulation of inflammatory products. Anatomical peculiarities of the diverticulum of Vater do not permit this sequence of events in all individuals.

(2) Injection of bile into the pancreatic duct of dogs causes a necrotizing hemorrhagic inflammation of the pancreas resembling tlie human lesion, and like it accompanied by fat necrosis. Necrosis of the parenchymatous cells and hemorrhage represent the primary action of the bile; an inflammatory reaction rapidly follows.

(3) The frequent association of cholelithiasis with hemorrhagic and gangrenous pancreatitis is the result of impaction of gall stones at the orifice of the diverticulum of Vater and penetration of bile into the pancreas.



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