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Les diagrammes suivants illustrent la m^thode. 1 2 3 1 2 3 4 5 6 MICROCOPY RESOIUTION TEST CHART ^SSI and ISO TEST CHART No ? 1.0 m ,2.2 I.I 1- 2.0 1.8 1.25 ^■\ 1.6 ^ /APPLIED INA4GE Inc A Method for the Determination of Plasma and Blood Volume X. -M K 111 il, M I) 1- <■.. \< < I W X T k i; j-. Ml) AM) .1. T i; I", k \ I. II T >-, M h h\-rniil,;l in. Ill ih,- .hrliitrs ,l\ l',>!. xi-i. /-/>. ^47-^71, AMtuirAN Mkdicai AssoriAT li^' Hrv,,,, ,. T Minvl-ivi Nmbtm I), vk I'llS '■'"' .^TRtF.T I A Ml-.TilOD I'(_)R TIIF. DETERMIXATlUX AXb BLijOD volume* OF PLASMA X. M. KEITH, M D., L. G. ROWXTREE, M.D. AND J. T. GI-RAGHTV, M.D. ISALTIMORi; Rrnuinc red cell (.ount^ and iR'innfjldliin dcterniinations yield iiit'or- niation that is valuable but \ery incomplete. This information con- cerns on.ly the concentration of the blood. The.-;e routine methods do not furnish us absolute \alues for hemofjldbin, for red cells, or for the oxygen-carryinrj cajiacity of the blood. With them, an anemia may be more aii]iarent than real, as it may be dependent on or associated w ith a marked increase in plasma volume, while a polycythemia does not necessarily indicate an absolute increase in reil cells, as it inay be dependent on a decrease in plasma. In order to obtain absolute values for either red cells or hcmoi^dobin. data relative to plasma volume or total blood volume are essential. The volume as well as the concentration of the blood must play a role in ])atholos;ical physiology. Absolute values are essential to the ]>roper intcri)retation of certain pathological findings. Is an increase in the blood mass with overfilling of tin- vascular system m any way responsible for hypertension? Is the large heart frequently seen in pernicious anemia due to a large blood volume? Is the large heart sometimes seen in myocardial insufticicncy (unassociated with hyper- tension or nephritis) due to an increase in blood mass? Questions such as these must remain unanswered until data concerning absolute \aiues are correlated with pathological findings. \\ ith so great variations in size and weight of in(lividuals, the normal xalucs f^r plasma and blood are best expressed in percentages cir fr.iclion- i.f the body \veit;ht. or a^ the numi)er of cubic centimeters ])cr kilogram of b(jdv weight. Since the work of W'elcker. tiie bloo.I has been considered to constitute one-thirteenth of the body weight. Recently, the values obtained by Ilaldane and Smitii (one-twenty- lust), and by Plesch (one-nineteenth) have been frequently accepted. The methods affording these la>t values are not without serious draw- backs from the jioints of view of inherent technical error, complicated nature of apparatus re(iuired and the possibility of injury or discom- fort atiendintr their use. * From the Modiral ;in(l J.imes riiuhaiMii Br.iily Urclogical Clinics of tlie [lilin^ Hopkins Ho-pitnl. TIrtc i- a (li-liiul uvlA inr a >iiii|ilc iihiIkhI fcr tlic (k'lcniiinaliuii of pla.-iiKi and MiukI miUiiih', |i,inicularly lor a iiKilnMl thai can lie rcpcatt'ilh' a|ijilicil witlmnt iniur_\- ti> the patient. I 111. n;iM iri.r i the inlr(]nia km,!,' encju^h for ihorou.u'h niixint;, and the deter- mination of its concentration in tlie pla-ma colorinietrically by coni- pari-on with a -iiitahle >tamlard mixture of dye and -enim. A d\e whicli would fiillil the>e conditions wa- r-ouj^ht. Certain of the plilhaleins were tried and di-carr. lierl)ert M. I'van.-. of the Anatiiliiical 1 )epartnieiit. when coiiMilled in re;;ani to dye- reinaiiiin.t,' for a loiii; time in the «. irculation, -iit^i^e-led the ]io--.ihilitie- ol vital red. ami -llp])lied ii- with tiie d\e ii-etl in thi:^ work. It i- with yreat p!ea--ure that we acknowledi;e our indebtedness to him. soMi- I'Koi'ijM ir.s OF Tin: i)\i-: \ ilal red i- di-odium di-ulphoiiaphlhol azolelramelhyl tri[)hen}l melhane. C!In V . CHa XaOSV/ so X.i H ] ■C- CM,, ^.^ n, >C = X i ID xao,.s\y\y -^L'N'a It i- water -olulile to die exlent of 1 ' .■ per cent, in dilute solulioii> of cud jier cent,, it doe- not dialw.e at;ain-t water tliroii^h collodion -ac- e\eii in fort\ ei;^ht hour-. I'lider -nch condition-, the dye i- practicallv ad-orhed h_\- the dial_\zini;- memlirane. When it.- toxicitx' wa- delerniincij hy iiitraxenou- injection into animals, it was found thai do-r- exceeding; from .^ to Id nii;. per kilo sometimes resulted in .a -lii^hl tf.in-ient alluuuiiiuria. Smaller di,-e- wcre harnile--. -o f;ir a- could he a-certained. 'I'hree m'^. ]ier kilip w,a- cho-en as tlu' mo>t -uilahle amount for our jmrposes. I'rolocol- of cat- and doi,'- -tudid! for loxicitv appear helow. ToXK 1 1 ^ I \ri:i;i .\ii:n l.s rR'Ti'c iii.s C\T ! — \\\ii;lit. 2 4 kir. : given 750 ni;;. intravenously; kilUiI in tlinr Imiirs. C.\r 2. — \\\ii:bt. 2.75 kg.; given "Id nip. intravrnmi-ly : kilKil in twenty hours. C\i ^ — W'li'jtit, k".- ki;.; iziven 6 mv.. tn kik'grain intr.aveniiii-ls' : i:n effect; urine free frmn .illmniin afierward DiKi 5. — W'cinlit, " lig X'lv. 4, 1''I4: (mmp COO mg. ; vitally ^tniiud ; iii) toxic manifestation?. One wctk later, 41) per cent, of (l\e still in circiilaticn. Dec. 17, 1914: lilood .still contains consiilerablc ilv.-. M;irrh 1, IOI.t- .\nimal still slightly vitally staim d after a period of fonr iiionth-. On only one occasion during this whole period was a trace of albninin found in the urine. Dog 8.— Weight. 6.8.^ kg. Xov. 17, l'yl4; Given .3.^0 mg. Xov. 18, 1'I14: C'on^iilerahle alliiiniiii in urine; tm casts; some red hlood celK. Xov. 22. 1'I14: Advanced distemper. Urine free from alhiimin. Xov. 26. 1914: Dieil with disteuipci. Do,; ').— Weight. '1.0 kg. Xuv. 21. 1''14: fiiven '■') mg. Dog was normal except for a l:iint traee uf allnunin fmnid in tlie urine mi lir^t and --I'eond clay-;. Dog 10. — Weight, ,^.5 kg. Xov. 21, 1914: Given 55 mg. ; normal; no alhumin. Til orck'r tu \ itallv siaiii tin ii-^ucs t-vcti sjitrlitlv, it was loutnl ticecssary to ii'C at loast 10 m^ per kilo. If a strong soltitioii is injected locally into the subciitaneou.s tissues, the ti-sucs are stained a licaiitifi'l l)rii;lit red ccilor, which iiersist, tmaltercd tor ir.any months. This accident happened with patients on two or three occasions early in this work, hut since has been avoided by ascertaining with certainty tli.'it the needle was in the liinien of the ve'iti 'elore the cl_\e was injected. Traces of the d\e ;ippe;ir in the urine ;ind in the Ivinph llowitig from tile thiir.icic duct at the end of ten niimite^. The dye coiuimies to be excreted in the urine of patients for from three to lour days fol- lowing a (l(jsc ^f .S mg. per kg. Following this amount no evidence of the dye in the tissue cell> or white blood cells could be found with the oil immersion. I'he fate of all the dye li;is not been detenuined, iiul con>ider,'ililc amount- can be found in the plasma for three or four days following il> inicclion. TI-CHMC .\ 1..^ per cent, -ululinn nl the dve in frohlv di-tilled water i> p,rc- [lared and sterilized bv boiling for from live to ten minutes, and nsep- licallv -till perrd in a sterile I .rionnieyer tlask. liii- snluli.iti is made u]) as rei|uireil. Ihe patient is wcigheil i-triiiped) and the do-e dete'rniined on a .5 mg. ]ier kiln basis. 'I'hc skin ove'- the anterior surf.ace of both elbows is cleaned up in the usual manner fur \ eiiepunelure. L'nder aseptic teclmic. ;i small platimim-iridium needle (20 gauge I to whicii is allaclied ;i -hurt ]iiece of rubber tubing ( from J to ,i cm. in lengdi ) is inserted into the \ein. Ten c.c. of blood are withdr.iwn iiUo a ]iipet and emptied into a ?0 c.c. centrifuge tube containing iust sufticient powdered -mliuni ox.alate to prevent coagulation. The pkisma so ol'.tained i- u-ed in the ptLiiaralion of the standard which is described later.' Tlu- nililiir tuliins; i-> rL-niovcd from the iicciUf, tue latter liein.i:; left in the \eiii and a 31 e.c. Recnnl >yrini:;e containing; the exact dose- ot the (iye is attaehed. and its e()ntent^ injected, after ^\•hiell the needle is withdrawn. Three minutes later, a needle is inserted into the \ ein of the oppo-ite ,inn. Wiihoul iniiiedinj,' the venous return, 10 c.e. of blood art withdrawn iniinediately hy means of a iiipet; two or three niinu'e- later, h' e.c. more are witiidr.'iw n. The lir^t i.-' placeil in a 50 c.e. i-enlrifu,i,'e tuhe. the .'-eeond in a 15 c.c. s,Madiiated ceiUrifusc tuhe. To each, MitVieient dry oxalate is added to prevent clotting, and the tnlie> .are eapjied with rnl)her to prevent ev.iporatinn during' cen- trifn,L,'aliz,i'Li diluted with thnc jiarts valine and ii'aced in the cup of th ■ colorimeter and read ;,,i,'ainst the above standard. C:.\LClLATI(l\ ul- KK.SLLTS The method described above furnishes volume \;dues for plasma and total blnod. When it is desired to express values a^ ])er cent, of body wci,L;ht. the formulas ^iven bebjw can be utilized. Since the s]K'cilic gravities of tile pla.-ma and of the blood were not ascertained in this study, one of 1.050 for the whole blood and of l.U30 for the ]ila~nia have been used. Inli.\u;i..\S I'Idsimi i'fluinc. — Weight of pati!.-tu in kt;. = W. Standard prepared su that amount oi dye injected i~ diluted in -iil c.c. for every k^. of body weight. Reading of standard prepared as directed = 1(HJ. Reading of patient's plasma against standard = R. The number of c.c. of plasma in patient's Iiodv = 100/ R X 40 \V = 4.1 iOO W/R. Percentage of BoJy li'eiijhl. — Plasma volume in c.c. X Sp. G. of pla-ma/l.OOO := u eight of plasma = M. X X 100/\V = per cent, of body weight. Cubic centimeters of plasma per kg. = Xo. c.c. in body/W. Total Blood I'olume. — Let hematocrit reading of the volmnc occupied by corpuscles = P. Volume of plasma = 100 — P. Total blood volume = iilasma volume X 100/100— P. Total Blood as Per Cent, of Body \\'ei(jht. — Total blood volume in c.c. X Sp. G./1,000 = weight of total blood" = Y'. V X I00/\V — " per cent, of body weight. Cubic ccn'imctcis per kg. ;= number c.c. in body/W. VMii;s!K.\i;i.i: ii:.\TLRi.s OI" tiik .Mi;Tiion llciuolysis. — .'sometimes the colors do not match perfectly in qual- ity. This is the result (jf hemolysis and of necessity makes the (|uan- titati\e determination more difticult. It is extremely infrequent, how- ever, to lind this failure with lioth s])ccimeiis. and on the one or two occasions when this has occurred, the determination was not attempted. Records have been kept throughout as tn the matching of the colors. In ,-i large jirojiortion of instances the ef)lors in both specimens were perfect. Where the matching was only slightly imperfect, readings were m.ade and in m.anv instances tliese have closclv apprriximated readings of the other specimen in which the color was perfect. In sj-ito 111' the iiK-l i-:irvful tixliiiii.-. incxiilicalilc iiciiidlyM-; (HTurK-d at tiiiK'-. It i- O'iiM.k-i-ahly ntdfc fR'i|lK'iil in tlu- iiarruw Ljraduatud cciitrit'iim' lulir ii-i'il inr tb.c iRiiialocrit valiK'-. I.il^rui'ui. l.i|i(.iiiia, if \lv\ niarkcil, make- tlic iKlornimatirn\,^v altiiitioii tn ilii'l aii.l l<> the time Hi" niakiiii; tlio (knermiiialinii. ihi- cliftk'ulty can he reaihty ,,h\iale(l. In (lur -erie- il ha- iml heen suUieiently IroiiliK'M.nie \o rei|nire -leh niea-lire--. I>iSi-,>iiif,>it tc l\itii)it. AM(k' fnmi the -hght I'ain nt the venc- piinetine. tlie iialiiiil n-na!ly Miller- nci ih-ecinldrl (if inennvenienec. In aii|ir(i\nnalelv 'i per cent, (if llie ea-e-, ehillv -en-alion- (icelirreil. wink- ill Ir.e iii-laiue-. ehill-, wilh fe\er reaeliini; In ll'l. wife -een. X.me of th.- maiiial ea-e- e\hihite.l tliermie re-iioii-e-. iliey are appareiith nmre em ihe i ir eillalidii (Iiiiiiil; llie lime "f diU rminalii m, hut al-n in. hi ale- that ihi III-, 1- HI, ..ii-lanl and -mall ' hi rare (Hia-Kni-. maiked di-ire|ianeics in ihe \\\n reailinu- (Haur ^m h del' 1 ininal 1..11- -hdllld he discarded. I'.eldw is shown the r,il( d di-appe iraiice dl ihe (i\« fn.iii pla nia in a mail inR Hour;, Minutes 13 30 2 20 3 • 6 24 ; IVr Ciiit. 'n i)2 65 60 52 26 Uoi; 2.— Weiglit. ''.5 kn ; \''0 me. ilye injectcM. Time I^lapiiiiiK Hours, Minutes * 10 , 12 , 15 1 (i 1 s I'er Ci'lit Sii SI "3 Tlie-r (lata lUiiion-liMle ill. it llii aKMiriitjoii from tin liloo,! -trr.im i~ >l(i\\ . .111(1 m-lif\ 11- 111 an'e|(liiiL; (IcUi illill.il i( dl- ni.idi- williiil -i\ niilimt- ((f the lillli of inintioll of llie dvr 1 llllliil ](r((((l (d tile -lowiie-- of lln' ali-((r]'li((ii i- -liowii li\ llir l.i't tliil n\\ -imimI i)cc;i- -jod^ tlu- )(1 i-ni.i ill 111 to f((iir (la\ - ,ifur tnie. lioii -li((\\i (1 a i oii-ickT- ;iMe ai ml ol llir (Ui II ' illi'u .il-o -liow- tl.m- lor -((llir d.'N - after llic iiiie(lioii /: i'iiliirs loiiiii! on A'i7'i((/('(/ Pi-t,-i niiiiiititiiis lselie.Hi(| deltr- mm.ilKdi- .(|| llie -.iliie indi\idll.d vieM pi ,(( tu ,dl\ idiiHi. 'I re--nits, |,iii\ i,l( (1 11(1 .i|(|(M ( i.ilile , liani;e in llie iialieiir- ( on(|itioii li.( oo lirred, >nnie ol llic-e pel ( (11- are IMdm.il .ind (dlh 1 - .He -lllli 1 llli; I idll i ar((llic ilisea-e m \\lii( li no .ippreeiaKU' < li.inue o( ( iirie(| dm in- ilie ml< run 5. The first rcailinK nt two inirutci was lower than siiliscqucnt ones. Mixing was protialily not eimipKii' m tun iiimnti -. 8 TABLl". 1 — Ri:pi:ati.d DktkkminaTiONS on Mkn Cubic- Snim' Date Woight Volumi' ccnti- in e.c. meters ptr Kg. CI 2; 2,15 M 2.I122 50 2, 4 15 OS J.ii:iil ;V.' Fl . 2' 2 15 <'.; 2.!«;'.i 41 2 4 15 lit 3.037 t:, |. 3 1115 57 2,(ai5 47 3 12 15 67 2.liM 17 r, 3 1115 M 3.171; r-o 3 12,15 M 3.0S3 4.- U 1' 7,15 61 3.03« 4!i 2,' li 13 04 3,11)5 lU T 2 •215 50 1.H75 4u 2, 25, 15 50 I.IW 4U Kr 120 15 (VJ 3.0.V1 411 3 18, 15 t)3 3.I(iO 50 I , 1 12 15 81 3.172 3il i,' 3,15 N) 3.0ii4 :» w 4,22,15 1-4 r..:',r, ,^3 6/ S/I5 '..-, ".1'-' ."3 1 )(iy- lid iKil L;i\f -o ri.ii-laiit ii-iill- liiit il i~ all' i^llii r innliahlc ill, it llu' ilii^-' ],la-ni:i \(ihiinr i^ -iiliU'it I'l r''lali\cl\ i;ri.attr .iml ill'. re -U'l'Un iliaiiL;i- lliaii ili.al of man. ."^i.iiic inuri.>li;i^' lindiiii;- uu dw^i ail itU'l:iiK(l in I .alilf J, T M'.l.l-'. 2 — RllMMIIi III 1 I UMIN \ I MN-- (fN I )(ir,S riiiMii::, Ce, per .Nil, liuir WciKlil c.l'. Kc UiiiKiiLr 1 1 l:< 111,,'. (Ot 911.3 1,27 ■' :". (12S mii |ii.|.lii|.iT 2/ 1 ,■• 1 ,-.72 70,1. 2/ a 7.I1S 4D1 02,'- I'.illiiKinK immnllnK'lv a lili'edlng til 11;:. tvc, 1/ 4 T.BS lal S55 Ni-,\t liny l»8 120 .\((iT infilrliill •>( 32'. 11 2 1 2T ».(» OOS tKl ■ 15 U.02 033 111 4 1/11) 15 1.202 Ml lilnifiuirtT bliil .iMi le. »is iMlniilf* Itefuro tint fiainple 1,'21 15 1.137 70 4 ( . I'ht.uuti I'i'liiiif,- / 'rli-i iiinu-il T> i//( rinviiii .liiu'ioil of P\r. 'I'lio '..■inu' \;ilii<' fur lilnm! \(ilii!iu 1- ulit.iitu.i \\liillnr im".- wmk^ willi J. .? 1.1 1 Ml:; I'll kill. '^r.ini I lua < |ir.i. li. .illx ninin.il nu n w < n -Uiilu.l • in tlii> coniKclicin. I Jiicniini.itinn-- mailc after injection ni 2 and .^ nit;. (IdNC-- yic'liif(l \ahii.'> within 7i^ c.c. in two instances, while in the tiiird. J and -i nij,'. per kiit>L;rain were used, the resuUs agreeinjj within I per cent. Three nit;, per kt;. is ciinNidered nbscjlutely ^atistac- ti^ry, xu'liUnt; culur^ well adajited tn culcirinietric determination. /'. ('I'Htruls till the Colmiiiicti'r. In the jja-t. in niakini; ]iarallel -•eric- of reaihnL;- witii \ariotis phtiialein- and with l''ohn'> niicro- isji'ldahl nuihod. practically identical reading;- were obtained with iwci in-tniiiient--, the linlio-ci| and our colorimeter. In a >niall -crie- of ]iarallel reacliiiL;- made in thi> investigation, identical readini;-. were .aNo (ilii.'uneii with both. /;. 'I It,- /.'M-.v (i/ I'ltiiu! at rnirsrctiiiii /''LHUiii.itidtril. The nicUiod \\a- applied to three men before .ind after phlebotomy, ihe re-illls appear in 1 able .v \o- 1 and _' were normal donor- lor Iran-fn-ioii and Xo. ,1 w,i- a hypcrten-i\i' p.atient. the -nbjcct ol .i ihcr.ipetitic \ene-eclion," T Mil.H 3. — Lnss MK Bi.iion at Vi msictihv Xeme Volume Bctore Amt. Bled Volume After 1. (i . l'I;>siim, 3.180 SIX) riiifliin. 2.S«2 •:. ii I'liisin.i. e.Tao 620 Plasma. ;,:t3 Bli.o.l. .i.osa Bloud. 4.2T4 3. A. . I'lil-illUl. 3,STL' SOO rin.«imi, :i.cri Ill 1. li.U.I lil.i,,.|. .434 A dccua-c corr( -ponding t.uilv well to the aniolliu of blood rcniii\cd i- d( nion-tr lied in ,ill ihrcc cases. /■ I Iriihil.u I :l The wlioU- IiIihhI \cilnmc i- c.ilciilated from the [ilasina \ohime on ihe b.i-i- of the 1 .'m.iiocni tindiiii;-. .ifiir ceil- triftlRali/.ition ni !,'radn,ile'! tnbe- for ,\n< im ihc same normal \u'<"l d'lls.' I'-arly in the Cdur-r nt ihi- work it i.r. aii.e e>.iauil that ihr dvc wa.- iini rcadilv taken U]. kv ti--ne erlK nr tlie .-ell- in the l'k"'l -treani, iMan,! ike fN]ierimem~ with eulkHhini -ae- in-e\i(mdy mentuMK-.i an.l I rum tke faet tlial neilkrr ilie er\tkrne\u- nn,- irnknevle- were -lained. when nkM-i\e.l in (re-h hi 1 i.rq arali'in-, it -ernieil fair U, -nrmi-e 'hat most nf the ihr ninanie.l in the pkiMna .Inrinu ;lu -Iiorl lime oi the (lelerminati.ni. In "ulrr to u:<'l at llu- (|nr-linn (|nantnati\ ely, it was lir-t ne>a->ar\- to ik.terinine ihe rrlaio.e amiuml- oi ]il.i-ni,i ,in.l veil hloi.il eurpttMle- in tke wlmle IiImm,!. Se\eral metko,]- ha\e keen cm|ilii\eil lor thi- pm-]iii~e, amonu- other-, the \ariou~ form- m the liemaluen; .nal the nilro!,'eii mellunl ile\i-eil ky k.Kiklren' I ho hematoeril metko, 1 de-eriked ahovc was loimd tn he tke nrnM -ali-lao- lurv fur our liur|io-e. \ie!dinL; li^itre- that agreed eki-il) with those (ihlained hv other wnrker- uilk iki- melkod. In two dillrrenl -anijile- of kluod. tile relative aniolint- oi |.la-ma and erythriKXU- wrre deter- mined kv llie kemal.ierit and ky tke nitro^m method. Ihe latter ,i;ave a lila>ma \alue 4 Jier eeiit, t" " per emt, hiuher than liial ot the liemaloeril i'deihlrelt's liuma- were .d-n kiuk enni]iar'd wnh iki-, ,,i dlher iih-erver- iimul; the hemaliiein melhud. In nnr wirk". tke hematoeril value- only were taken In onler to delerminc whella r llr. ii\e i- ak-oiki-d h\ the kinod eell-, and. if -o. to what extoil. the folliiwin- iivoeednre wa- ad.Mi.ud: I'ifty c.e. of blooil were taken from a lieallhy man and rendered incoai;ulnl)le with jMnvdereil sodinm us. date. Ten ... ni tin- hlond were ll-ed for hemaloirit ik lerniinalion, 15 e.e. heini: eeiilrilnued and the pla-nia pijietled olf. Ihe remainder wa- ai;ilaled mitil mea-Uied out for the exiieriilieiils i;ivcn helow : lixfi-rimeiit i.— CcntrifiiRc Tiilio 1. liiiLcn c.c. of lliis wlmle Iilooil pus 2 o.e. of live solution pli'S 13 c.c. of saline. CentrifiiKC Tulie -'.— Five c.c. ot plaMHa plii" 1 c.c. of dye sclutioii plus 4 c c. of valine. After Tiilie I \v;n ctntrifntjalizcil.' llie pl.Tsnn was pipetted olT and coin- parol with llie plasma ilyc mixture from Tiilie 2, which was placed as the standard in pri-iii of the colorimeter. The readiiiK was 80. Therefore, in dilu- tions used. Tiilie 1 contained Wl per cent, as much dye per cubic centimeter as Tulic 2. The relative amount of plasma in the blood in Tube 1, as shown by ihe hemalocril. is fiJ.S per cent. Then IS X (>ii = 9-37 c.c. plasma in Tube 1. m 7. nieibtrcu. M. ami I..: lane Mdhode xur RestimniunK dcs Vailiinis der korperlichen Klenieiite im Itlut, .Arch. f. Physiol. ( rilJuer's l, IfWJ, b, 151 8. Three thousand revolutions per minute fcivcil. Si pt r cent. Ex/'criiiictit S. — E.xperinient 1 was repeated with the IiIih.iI t.ikrn I'r'in a tliird normal individual. Colorimeter reading, as calculated t'rom lKniat"crit data. 814 lur cent. Colorimeter reading observed, 81 per cent. Ill coii^-iilcriiii,' the fia'cyniiii^r v.xiicriiiuiital ilata. several tactors slieuiM I'c iiciicd. riic lictiiali icril iiiit-t iicce^^arily ;;i\c ti> the iiiiiii- mtiiii vahic for llic ainmiin of iila--nia in the hlooil, a^ the eiir|ittseles ,ire wet and tlie iiiter-lices are filled with tlitid. Therefore, the hem.-iloerit lliidiiij,'s for plasma imi-t be slightly low. and the ealeulaled eolorimi'ter rcadiiii; sliyhtly lii,i,di. If tlic dvc is alisdrbi'd liy or dilTuses into the eor|Jtl-ele-, the oli-er\ed colorimeter ie:idiii,L;s will he low, that i-, the iil.i-m.a Mihime lar<;e. .\s the ealeulaled atid observed litjttrcs ai^ne x i with the blood v.iltte- ai'pear in l'ii;itrer. I .and _'. The x.isocon-trietion was obtained b\' eoiitinitou^ a(ltnini--tr,ition of ( pineplirin, ;i fairlv e--nrc cban'.^e- were ni -burl 'Itir.il i' 'ii. JJr. I'. IJ. i.am-iiM.' wiukin^ in Mr. Xbel'-. l.ibi'V.iinrv. b.is liiund that the polycylhen'.ia which de\-li:|i-- .ifler epiiupbrin iineclion doe- nut ri acb It- inaMinnm fnr finni linieii i.. l\\cnl\ in'mUe- NUlnme drieiinin.ilii in- ni.ide "ii two iln'j^^ .liter tin- inler\.il -Imwcd a .-!i;;ht bnl (Kiinile deciea-e m pla-in.' \ulnine. 9. Personal cotmminication. 1 f-i 00 ^ lA, CJ « c^ aa cc i fr CO i C C 1 14 # mi;tiiiiijs rki:vicK sl.^" i;.Mri.MVi;ii aM) \ \i.ri:> hihaim;!! Ai'cordini,'- to \\'(.lcki.'r,'" iIk- carlit'st altcmiil to dctcrniinc the IjIuoiI \oliinic was made liy Ilaller." It i,iin-i>ttjcl of bleeding t.vo criminals to in\-t Method. — Welcker, in 1S54, bled aninial< to death, washed out the blood vessels with water, minced and washed the tissues thoroughly, brought the blood and wa-hing^ togelher and detcrniined their hemoglobin content, lie concluded that the blood constituted one-thirteenth c]ioll '- ;qiplied tlii-- method to two criminals .and obtained the same \.ibie. .Modificiitious of the method were ma. and b\' Kottniann,'* who emplo\ed the hematocrit. 2. Indirect Mrtlu'ds.- \. Infn-ion metlio.l : i ,; i llirb-t,'' in 1S22, injected the \,i-cular ciilar >\>tciii and bled a,i,'ain (bi. The >()lid> of a and b were detennincd, the difference hein^' due to the number of cubic centimeters of water injected. \\ eber and I.ehmanii,-" utilizing- tiiis method, concluded that the blood con- >tituted one-ei,L,dith of the body weight. ((/| Quincke-' utilized the method of Malla--e/.-- Red couiUs were made in ca-e- of ])ernicious aneftna. A kiii>\\ii amount of blood with a known cell count was traii-fu-ed. follnwini,' which tlie ])atienl'.- red celN were a^ain counted. From the-e dat.i, the \(jlume was calculated. 1!. Inhalation Method: (irehant and Or |Uaud-' .ijave doi;s by inbal.iticm :i nie.iMired Milume of carlxjii UKmo.xid and deternnned it- liercer,ta,i,'e content in a -m:.II >:un]ile of the animal'.- blooil. I laldane ar.:l .'^mith-' modified thi- mcthed apparatus. A .-.ample of bI(jod is remined .and its carbon miaidxid c njent e-limated by the carmin titnilion method of llaldane. I'le-clr ;nid t >eruni-" have em])loyed this uiciIkhI, but the former determined the carbon monoxid volumet- rically. ('. .\ntil(ixin Method; I'.ehrinii'' noted that tetanus antitoxin remained in the circulaticm for lon^ periotls and made this the basis fur the e-timatinn of blood \olnme. Ili> .-Indies showed the blood to con-titiite 1 ll.S of the body weight. With it, Kammerer and Waldmamr" in MnllerV clinic. olitaiue -i'i!.]gi-rlic Cheiiiie. 1S.=II. li, .Xullam- ii. -'.-''. Jl. Qiiii:okL'; WVitirc lkijbaclitun;;^ ; 1881, xxiv. .-.'.- _'(i, Oiium. lb 1' T. : (JuaiUitatne IMiitiintrrsiuhunKin, Dciit-eh. .\rch, f. klm M.'d,. l'-08. xriii. .W' 27, v. Ikhrini;. I-",.; Die .\ntitoxiiiniet!iode yur liUitnuimr r.c-liinniun.i,', Minuiun. incd, Wkdinsclir., 1011. Iviii, 65.^. JS, Kamnirrrr, II . and '", .ild.Tn.inr. .A ; I'.iiilnunL'i'lii'-timnuinncn naili v. lltliriuL; mill :uidii-e i|n.iiililalu r unur-iiidimm.ii (kr l'.hitlie-.taniltcilo. Dcnt-idi. .\rili, f, klm Mol.. I'd. I nx. ,-J4 2'' I'm-. II,: I'rlur \k i anddimmii di r I'.liitinriik'e in Si-Inv:!n};erschalt, C.l.nii mid W.ulirnk.rt. /.l-.hr. f Geh. n ("i>ii. I'dl. Ixjs, .^40 • 16 Tabltj 4 indicates the wide \ariatinii^ tliat lia\e Iteeii obtaiiR-d liv the (HtYereiU methods. Tlie total niimher ct normal eri^e^ has heen >maH. In t!ie re]>ort of Haldane and Smith.-' the Hniits for normal are very wide, ihey ^tate sjieeilicallv, h(jwe\er. that one of the ea-^es was verv obese, that i-^. the one in which tlie blood was only one-thiriieth of hi< bodv weis to ISSl Taichannw' SuiMtintr and coimtini: K. B C. and llh. before and aftt r sleani b:.th 1 n.T I 21.8 1,15 Viornrdt Nn. v.c. put nut by ht.Mt miiltiplii'd by No, of M'con'Js re- quired for lunipltte eircuJation 1/13 W o r k (^ d (>u )i o r s e s an-I (ioRS. Krror, riu percent. Weber and Infnped waltr, ua?-ln'd Lehuianu ont vessel-: drier mined dry •;Mb>-tanee of bloiiii Haldaneand <."0 intmle iniMhnd. 'I'nrai u.n ii ui.nn i, wdn earniiQ sid'itinn 12 iiu'ii Cf I niiMliud. Titratinii •.' nien \\u\i larnnn soliitiou 4 uniiK'n I Intn-ii'p Mill; lib, d«MernMnai;itii«^, ■'. ( > ' inhalation uitti khii biistiun 3.3(>.27 3.7-8.31 2.5-6.ti![ 1 -.ni i*;.5 1,19 4.t;iM>.o:> i/--'o-l/iii.o 1/18 r>.o--'-t;.nj r. '; error K a h; Ml ' r- r lleiii int' n^eihud. and W;ild uiaiin Fries BeiirinK iiietlntd.. 1/17.5-1,11 i;l2.t> • Arch. f. ptiy>i(d,. is^n, xxil. 5t8: 1S81, xxlv. 525. t Arth. t. e.vpir. Tatli. ii. I'luirinakol.. vjcti. liv, 3j«. : Tr. I'ath. Nnc. I nndon. Im«'. li, 311. • iT. per IHt Krnins of body ueight. O t !i e r praeti (ally normal patirnts gave similar vain*"- f 17 NdKMAI. AND I'AT 1 1 ( ll.( ICKAL \AK 1 ATK i.NS IN lil.lidK AND I'LASMA VOLUMK IN MAX Results { Xonual) At k'a^t 14i) ik'lcrniiiiatinn^ *or ]ila>nia voluiiK- lia\c l)(.'cn made (HI iiKirc than Ino iiuli\ iiiiiaN. In the rarlicr wurk. licniatocrit -tudies were not made, mi that the \ akies for t(jla,l hluud volume are con- siderahly fewer. Xoniuil / '(i/;(i\s-.- -1 he resuUs here reported are fur normal men. heinj,"- obtained from jiatients attendin<; the outpatient dejiartment of the t;enito-nrinarv elinie for some minor local condition, such as chronic urethritis, chronic prostatitis or verumontanitis, etc. The as^'e, weitiht. height anil hlood ]iresstire, as well as the blood values, will be seen in the accompanvinsj tables ( .^ ;ui). T.ABLF. ? — Plasma Values in Twenty-Four Subjects So, X:imc Diiti' Ad.' WeiRlit, .■*.8 Ho Fl. 5 Kiit. la. 3 H. v. Sys- tolic 125 Vchiiiie, c c. Co. |.ir Kf. Frao- lion Ho.ly W.)fc.|it Per Cent Bo.iy Wi'ignt 1 F. .1. ... I 2 31) 3,100 45 1,21.(1 4.0 i; K. M. . 1 <; 22 6<.l.5 5 10 2.T75 47 1,20.7 4.S 3 G. 1'. 1,7 40 511.1 5 6 115 3.050 53 1 1S.3 5.4 4 .M 1 7 39 .-1.8 5 11 2.70O 52 1 18,11 5,3 5 P i.y 34 73.5 5 3 138 3.050 42 1,23 4,3 6 V 1,9 23 .\S.fi 5 : ;io 3,050 52 1 is.r, 5,3 - c 2 2 2/4 .53.4 53 2.iH5 3.025 55 1 17.« 1, 17 5.6 5.8 s F 2 '2 2/1 67 67 3!i>50 43 15 1 22 1 21.G 4.5 4.6 9 S 1,29 2,'. IIS, 4 h r, 3.100 45 1 21.(1 46 10 If S. .. I-', 28 3.i .>.!) -, 5 :o 2.1175 .'/> 1,20 5 11 H, .. 12 2S 51 -.1 5 1. 122 3,275 4,'p 1 21,0 4 6 12 J. J.... 12,28 22 57.5 5 ... 2,HiO 41) 1 i;i,s 5 13 .T. .S. ... 12 28 4''. liS.lj 5 3 142 3,075 48 1 20.4 4.9 \{ J. C... I2,2i> 43 Tl 5 1! 130 3,325 4S 1, L'0.4 4.D 15 u.o. .. 12 2« ."u 71 5 in 3,l,-.0 45 1 21.11 4.6 Ifi I!. S. ... 12,:(1 32 1)5, 3 5 6 145 3,100 47 1 2u,7 4.8 i: (i. 11. .. 12 31 .3(i (;2.5 .-, 10 120 3,100 M 1 20 5 IS G 12 34 60.1 4 8 130 3,300 48 1 20.4 4.9 I'.i F. I,. . . 1,2 32 --CO 5 5 105 2,51.10 41) 1 i;).s 5 :o F. .s. ... 12,30 49 6(1.8 fi 130 3.200 4.S 1 2(1.1 4.9 21 K..I. ... 1,5 70.5 G 2 S.7."K) 53 1 1S.3 5.4 "2 J. M.S. 3,11 3,12 52.3 62.3 2.(175 2,1175 51 61 I 10 1, 1'.' 5.2 5.2 L'3 D ] 22 70.* 5 11 130 3,375 48 1,20.4 4.9 24 s !,-I2 5r i 5 - 2,s;3 ia :,2o 5 f SagSSSi!iJ5J;z"S3SX-2 3i; i) S 8 8 i- l-'T 3 !^ 51 S 'T " S I §K S g ¥i '; ^ y I- i-^_ & Ti^ K © X I- ■^l c -.1- '-'= « I- '^ — irt ^^ >.* o lO 'C >n o h !' -c' -c -ii oi X s ■?! -t ci t2 — — 'r '2 "C ^- !r is I?. in ^ '" — O I.* O O -S *-. »■- "-- •— >.. '— III c> A U> I- •^ M OC — c; o ~ ^_ X zi '- '-* >-•: -t> CO itt oo •-; x i--_ 1- •»• V ^ -»• f -* irt" o •- a- o — r: I- M or;?' Ct ») C. Ci Cl -^ ^ CO 5' -^ I'. X T. = 19 I'la.uud I'dhii-s. l''nrty-ciL;lU ilftcTinitiation- witc iikuIo on furlv- t\v(i ]i:itii-m-. Tlio larL;i--t {^.77r c.c. i and snialk---t ( J,45U ca. , \cihnnc-. wcru riu-nnnti'icd in llir hca'.ioi ( S5 ki,'. ) ami lii,'lite>t (47.4 ki,'. > palicnt> ( Xcj-. 2(> and M> rc--|iL'cti\ els l . TIk' mean weight was (i\.2 kt;. and tlu- mean Vdlumc 3,123 (.'.o. ; tlie a\ iTa,i,'(.' weight, fxv.i ki,'. and till.' a\(.Tai;e \iilunic .i,05i) c.c. 'I'lic i^la^ma \aried frum 4_' to rh ex. \K-v kilo^rani. wliilc the frartii.n ut l)(idy \veit,dn \aricd t'rdin 1 2.i III 1 17. the axirat^e lieini,'- 1 1'*.4. ( l-'fum ihi^ it a])]iear:- ll'.:il ;i normal man of 140 ]Miunii- ha-- .i liter-- of pla-m.'t. or ,^l) e.e. per kt,'. ) 'I'he i-on-.lanev in the r'kition ot' i)l;i>ma to body \veif,dil in health i- slrikiiii;, there hein^ no i^re.il extreme.-;. IUih',1 I'tdiirs. The niimher ot' determination- of tot.d blood \alue> li:i< not heeii -o lafi^'e. 1 w enl \-i me determination^ im (.ii^hteen norm.al iiii|i\ idn.d- were made, the whole hlond \ahle- lieint^ caleu- lated friiin the pla-nia \iihime .-md hematoerit I'indini,'-. The plasma eonbtitnie- on the a\ eraije ."' i.' ' ]ier eeiit. of the total hlood, the i \t rentes Ileitis,' .^1 Jier cent. ;md d-'.ii per eenl. d'he lars^e-t and >malle-t Ndhtnie ('i/i7,^ e.e. .and 4._'iWl e.e. ) were ohtained in the two patient- mentioned .alio\e a- h:i\ ins; the l,ir^e-t and -malle-t ]ila-m,a \olnme-. Ihe-e patient- -iiowed /S..- .am ])er kilo,i,'ratn. re-peeti\ely. The aver.iL;e Moiid \ohnne wa- .^..i.-d e c or appro.\inialely ^^.^ e.e. jier kilo- t;ram. < hi a ,t^ra\ inietric ha-i-, die iilood e,dit. The eon-t.iney of tlie-e \alue> i- in .-irikint; iontra rel.ition-hip e\ieedini;ly xaria'ije. llie re-nlt- here reported -upport the litiitre- of \\ eleker and I'.i-ehol'f. \ ierordt. Kotlmami, I'.ehrint,', l-'iies, and Kamiiierer .iiid Waldmann. Cliii'h\}l Studies { Palhohuiicid) Si\t\-li\e jialieiit- were studied, the determination- mimherinj,' ei^hty'eii;lit. I'or purpo-e- of di-eussion the cases are .^roitjied aeeordiiis; to elinieal eondition-. It i- to he le^retted th.it the mttuher of ea-es in eaeli ^roup i- nui lart^er. dhi- wa- im]io-silile. since the dntt; is ot ( lernian origin and ile-|iite repeated ellort- it wa- imiio--ihle to secure .a fttrther supply. " d'he ,-co]ie of the work ha.- been limited by the -mall .■inionnt ot d\e available. ,^n It i- iinil.;iMf that many ilve; will an-«or the purpn-e ciinall;, ur!I Stmlies al'iii).; ihi-c Hiu- arr ii"W m priii^ress. i l-J « M C" i^ ;i^ 5 "^ :,^ — X « W -M .- ^i2 58 ill; £ ? « 3 3 i ;: « I.- ^ eo 1- n I- " '"30 Ti > Sr: rfS3 SSi SSS S3 S3 fiS SS Si5 i='i 21--= ^3 ?TS':^ S^ sr: M ?l OSM-r elffl P? « ^J MCI M?) M 51 IS 3J S 0-2 1 cc ore C-; -1 1.1 k.-? TI r^ifi lA S5 sm 3 K '~ — ;^S 1 .•0 » : f? : : - : S §; ^ s; a;; ?i i • 1 13 ; 8 — S!;- « •- £1 • lA •— ^3 I- SS • f' I • k • t • r • 21 I'rcmaiu-y.--^ )1,.crv;ition. l,.ivc Uecn nuulc bciurc an.l aia-r deliv- ery in ckv.n' ca.u.- (Tabic 7). In tho latter months ..1 pregnancy, the Mood nla^^ in pro,>.,rti.m t(. the body \veii,dit is .letinitely increased. Whereas norniallv. bln,,d constitutes S,8 per cent., in twelve pregnant Nvonien prior to l;ibor the blood averaged 9.50 per cent., which corre- .,H,nd, to the highe.t limits of normal v.alne In tour in.tance^, the 1,1, ,„d valuer rose con>ider,ably above normal linntv The plaMua vol- ume^ were c.rre.^pondingly increased, averaging .-S.4 c.c. per kilogram, in^tea.l of .^H c.c. Determinations made .i week ti; ten days .after P.lH.r d.owed tiiat a great decrease in the blood ma^s liad ,.ccurred xvhich .unld n,.t be accomned for bv lo,. of weight (child, placema ,,„,, ;„„„„„„. iluidi or kw, of blond .at ,.artnrit,on. .\fler labor, the blood and plaMUa lormed " per cent, and 4" ,.er cent, of the body is-ht. respectixclv. The average lo^> of biocul, .according to the ub-t^elrical report of these ea>es. w.a. only .^(Hi c.c, wherca^ bloo.l xdlnnie Mu.lie> -houcd an average lo- of l.bHi e c. l.;,,,,,!- have been made, but uidmut -ncces-. to lind the dye in ,hc placenta, i; tiie .nnnioiic ihi.d .and in the .hild^ urine. folkiwing ,hc admimMralion nf the dve mtrav en. ai-ly to the mother during labor. Abnormal ab-ori^no,, of ilu .l\e would not -ecm lobe the explanation „f the high blond x..hic^ re.orded m pregnancy. Ihi^ . ipinmn i-li-.^d „„ ,,,^. ,-.,„ ,|,.„ ,„e decrca-c m blond ma~. ,^ imt fnund imme.hately after p.arturitinn. fnr ni t \\.. ca^e- (J and 4 I it will be -ccn that deter- w 1 w i nnnatinn^ ma.lc tbirlN -ix hnur- in one c.a-e, .ni.l four d.ays .ilier deliverv in the other, dnrvsed the -ame high v.diu^ for plaMua .md l,lno,l. ' Snb>ec|tiem detcrminalion-. ten day^ alter labor, dmwed m l,ntl, ca^e. the marked decrease recorded m the oihcr c.a^^e. ot (he series. ■ITc consideration of blond volume in relation tn 'pregnancy 11 innn die subiecl ni a sejarate cnninmnicalinu m cnliuburatiun th I'r, I. U. Miller, with wlmm this part nf the unrk was earned ,,ut in the wards nl I'ml. J. Whnrid^c WiIIkmiis n,ese lindini^s .nulirm ihe uidcsprci,! bebcl .inmng nbstelriciau- that pregnaiU wnnun s,.,„,! lKinorrhaL;e mri-nallv uelb fomp.ara- tivelv verv iarL;e bb edin.^s m eclnnpsia ,are uell bnrne. It unuki .,,,,,e'.,r th.U N.unre h.is here a f.utnr ..f ^al'ety. tlic large blood vohune, saleL;u.ndinL; .c.;a.nsl the effc, ts nf hemorrhage before, duriiiK or after l..il„,r Or u ni.o. b.- ih.ii the l.ua^er blood supply is necessary for pinper nnlrilion nf the chiid Case II ".I- .nnipb>,ited by secondary lues and luphritis It doc-^ not accord with die oiher caves nf the sitics. t • 22 I- iihh-ial'uni. Two ca^c^ (1 and J. 'i'aMc S) are iiK-link'tl: 'I'he tir-t i-- in a Wdniaii wim hail lo-t 1_' to 13 ki;. llir(iu;,'li \lar\a- linn. Tin- ]'la-nia \cilniiu' i~ ab-nluU'h niirirja!. and ^in^■l.' reel ccll^ were 4,1 K i(i.( i( i( I. Iiir lilocid vcilunie wa-, in all proliability, nnl much below nurnial. 'I'he ^eecind ]iatient. \ery lall an.d lliin, aK( i -lidwed strictly normal \ allies. Obesity. Six ea-e- i Xo-. .\ 4. 12. _'(.. .^1 .md M. 'I'al.le Si >l!owed in e\er\' m-lanee a ]ila-ma \ulume decidedly liejuw thai o' ib.e a\eraL;e normal. 1 he average wa- .^7 .\ e.e. I'er ki;.. or .xS per eenl. ol body weight, \\hieh i- le-- lli.in ihree-l'ourlh- of llu' nnrmal \alne. In llic, line ea-e i .■iJ i in wbieli a hent:itoerit reailini,' wa- oblaineii, .~ 1 e.e. jier kiloi;ram oi blnMii \s,i- found. 'liii> jialient had onl\ .i- niiuli blooil |ier kiloi,'rani a~ the unrm.d indixidiial has ]ila-ma jier ki!oi,'ram. Case .^ i~ of eNlreme inlere-t. ina-nuuli a-- the |ila~ma lovmed le-- than ,> |ier eenl, of ihe limh' \\eii;lu. I'be-e tindinu:- are in barmone wilh tbo-e of I hildane and .^niilb, l-iiuhuitiiiti ,tnil .li:rii:'ii. I'en eases ( Xos. 5 to 14. inelu-i\e, 1 able Si exhibiiinii I'Uiaeia 'on. in i i inibin,:lion with nindrr.-iie or ~e\ere -eeondary anemi;'., w e •-tudied. In tbrei' of tlie-e. in.di^nant i,eo|ila-m- were pre-enl. In -i.\. ibe ]ila-ma Miluine \\a~ bii.;hi.r lli.aii the ;i\erai;e normal, .and if. tline. ;tl morin.dK hit^h. ihe .i\er.aL;e in eiv;hl ea-e- \\.a- r' ' e e. per ■-ili.;;ram. wbieli Midiiale< a -i fon- plrtin ir.i. In four. llu total blou.l \oinine wa- -ludiid and three :'.i\e low \alue>. It i- e\iiUiit. llureiore. th.at in -iieh eondition- In--, nf pl.i-ma doe< tioi ;^ii h.ind in b.iiid with In-- of \\eiL;bl and deerea-e ol rid bl 1 cell-. I iifortmi.iIeK , In in.ili niit -ludie- were not m.ide in the ear- eiiiom.i ea-e-. With the dii^ler ■.! .memi.i mdii aled in the table, it i- evidetil. however, lb, it the toi.il lilmid Milnnii- nin-t ha\e bn n appro.xi- iiiatelv ni inn.d Siliei the .i\eraj;e bl 1 \.ilue w.i- 7S e.e i 1 1 .i J ol biid\ weiijht ), instead ot S.^ e.e. ]ier k^'., it beeome- apiiamit tli.at the anemia is fairly aeeurately itidieated by the tiloml eount In I ,i-i - S and 11, tlierc is a dcereasc in the vdIuiik', as well ,i- in the cell eoiiieiii of the bldcid. /'(■i»iii-|(i|(.\- .hltliiia • 'nl\ three e.i-e- i Xo- 1.-. bi atiil 17, 'I'anle 7) were studied, .\o. ]? -hi. wed ,in i \tieinely liiL;li pl,i-m,i Milimn' of 72 C.e. per kj;.. the biuhe^t eiieolinlireu olll-ide of preun.iiky. Ihe lilooij voluiiM' wa> normal, but sli;;hlly lulnw the .i\er.iue In the other twi), ])la-in;i values were normal, and the intal Milume i ..n-ider,ililv (Uvreased. \\ illi -o y;re.it :iii iiierea-e in ]il;i-m,-; \olumi i.i * .i e I,-. It was tbiiiiLiht th.at the whole blood m;i-- mii^ht be kiiu" f th.in nnrm.d .ind be briiu;;lit into e.iit-.d lel.itinn-lnp with die inl,irL;id lu.irt -muelime- 23 r ■-ccn in lurnicious aiR-mia. 'I'la- two Mibscqucm ca^^•~ -hnwcd kiw M,„„l vahK'. and no caniiac enlargement. FurMicr data in this con- nect inn are necessarv. y>„/v.-v//,.-,»u;.--Mnlv two ca^e^ , Xo~. IS anal 1". Tal.le S, with iH-h hl.Hul counts were >tu.!ied. Patient IS, thron,t;hout several weeks -tav ii, the uar.P. rrc-ented a ^er^i-tent!y hii;h red cell cotint ( S,(X)0.- (KHM. Two deteniiination-. a week interv enin-. yieldo identical results, that i~. hoth iila-ina and M-.od volumes were decide,-/c.v. 'If die f..iir patients v.h.-e cases were -ludied ( -\'os. M to J.v nichisixe. 1 ahlc Si, three were moderately thin nun and one ,„ ohe~e woman. nie three men lu'wed .a sn^ar content m ihe hlood l,elwecn D IS per cnt and -N... -'-' ' showed hlno.i volmne dccidedlv l.elow normal. M, tlMl llie ohesitv exerted a -n ater nitliunce on ihe hlouddiody-mass relationship than did the i;l\co~nvi;. hro,,, tiu-e l-iir ,ases it appears that an incre,a-c' m the hi 1 \olnnu d..e~ not ie~nh i torn or accom- pany hyperL;lycemi,i. \lxoa\rd\a\ l>L<,itiu'inuy. Nnu (Ti-ma delcnmnalion - were made on .iwen eases , No.. JT to Mk nuhi-ue. lahle S, of ni>oeard,al insumciencv. Nepl'nti- \^.'- •'''-"'• '"■ l''T^cd a \ . rv minor role m this s^.rics,' >e\eral of thc-e patients had marked edeiii.!, and thf aver- age \..llimc, 17 c- per kiloi^ram, was slighllv low, m, th.at, in general, edema is not associated will, .m increase in plasma eorrespondln^; to the increase in weight. Hi^ih values may occur, as is seen in I'atient Mt Ihe lowest plasma value (Case 27) is associated with .i liiyh r.d lilood count. Xo. Niiiiie Uato lli.-iury Agt So. TABLI". S.— Clinical ( Pathological i- I'lilfllOSiS Red liloD.l Hfh. Ci'lls S:lhli. Wclglit A tual I!c'-t 1 A. K. 1,15 33381 32 1 . .1 1 5 33514 ii ;i li. -M 1 1.'. 33.-« a 4 1 N. 1 li :a-io U 1'. .S. ■J iJ ;!37H 31 i;, 1'. .1. U. 33433 4-' w T. A. 33770 33 17 W. .M. •■. 11. 1. tu lu F. O. 1 3 3;i.-.2ii 2j ■Jl) (i. V. H. 3 18 ■xviia 23 •Jl 1-: X. V. 3 11 337S7 <» •£! .M. H .1. 1 Jl 33487 37 •-•3 1 w : 12 33617 ■::i 54 11. .s. 1 12 33.-.71 41 •a <). O. M. 2 17 3373.-. IX) 26 W ,I.R, 1 l.i 33M4 70 27 .I.S. 1 u G. No. 1«72» 48 28 w. 123 29 ,1. .S. SI. 1 « 33521 59 3i> .1. F. I 12 I 22 :av!i I ' 31 K. W. S. 54 33i;:- t'liriinic panorcatilis. Malnutri- 4.022,000 82 linll. VisrProptOSiS .\..ldiiil. l';iill ia siilo S.UlO.nOO 100 .Syphilis. Olii-sitj- 4.200.000 84 i:>hi'sity. Myncarrtial Insufflcl- ,i,noo,000 SO I'Dty. hypt'rti'n.sion CnriiQonui sioiiinc'li 2.i:oo.COO 4."i Ailiylia KMslriiii: malnutrition. 4.ii0'-i.o00 80 .Vrti'ridsftrrogi!* t'ul'i'innlMa prostali". Mi-tnstascs 2. 120.000 4.'j .siviiM.lnry ani-inia. Ulnrrlii'a. S.iKxi.ooO 01 INyrliosis. .Miyraiuo Cariinuiim stolii:'.i'h 3.600.000 «.» llnlantiilMini cdI:. .Si'con.l.iry 1.072.000 20 anfiilJa Si'couilary ani'lnia. Leg uleiTs L.'OO.OrtO 31 Anaildlly. Malnvitriluin. Sec- 4.ri. t'olim Dialieifn mellitu!!. Pulmonary 1.700.000 82 tnliert'iiln<«iit. Arterioseleriipis .Viirtie Insulllriency Ulabeien mellitus. Oboslly... .S5 niabeli's mellitus 5„" lOO mnnary tuberculosis Ar,.ri .r.ler,..!- Myocardial In- 4.700.000 94 -UlluH'IU > Myocarilial ln»iifllclency .-.,000.000 84 Syphllii". Aortic Insuflielency. ii.jOO.OOO 107 niyoeanliril insutflejency Myoearillal Insullleiency » ArterloMlerosls. Angina pec. 5,000.000 3U K.rln Myoearillal iuHolBileney syplillH ot lorla. Aortic In- *iitlleieney Pulmonary ttibrrciilotit. Afrrlo- 5,000,000 79 •cirruili. Chronic Mphrltli 36.8 48 70.5 05.4 100 107.7 i:u 43.0 43.9 55.9 50 44.5 :,9.5 13 ('.8.2 r.1.1 53 .li BO.l 72 :2.5 53 58.2 70 80.9 SO 51.1 67 7">.2 8i a:. 3 73.4 89.5 H8,8 TJ.2 88.5 112 00.4 59.1 00.2 r r — Studiks UN Bloou V'dLCMI. Edema l!lo.„l I'rtssure Cardlnc l:iilart;e- liieul ■ I'Uifina e.e. r,e. I'er Hema- 1 toerit I'er Cent. riasma lilooj Vol uine C.C. IHT Per lent, li.. i«i Noil.' LS'iO 50 None l-JO M) None o,7r>t> 53 60 6,250 89 U.3 1 10.!) 6 feet '■) inelii'-^ in hi'iglit None 1-J(i TO None e.T-.'.') 28.6 Slight 210 110 Mo.liTiite i,:M 45.S None 100, 60 None 2,j7J 66 70 3,425 88 1'.2 IIO.S Xune IM 100 Non.' 2,375 45 Kight leg 130 c:, None 3,l.'iO 64 77.2 4,075 H 6.8 1,11.4 Nune 100/ 6j None ■:,17J 4'J 65.3 3,325 76 8 1/12,5 None no 6j Sjiiiht 3.725 0« ModiTiite lii.V 4,-. Mlflit 3.42:. 60 80.6 4.025 70 7.3 1,13.6 None None 2.'.iOO 57 78.8 3.675 72 7.5 1 13.2 None i;o, IK) MlKht 2.120 47.6 1.7.3 3.150 71 7,1 1 13.5 Nunc 1(10 or, Slifllt 3.400 57 70.6 4., 'too SS U.2 1,10.8 Ni,llf ]■'-■ 70 Mitllt 3.225 .-.1 61.3 5.025 80 8.4 1,12 Nn:,' ii>> .•,:. None 4,1)50 72 ao :,.:m 81 8.5 1 11.7 None l-JO, 70 JSligllt 3.450 04 $4 4.250 66 0.0 1,14.4 Iniprove.l None None 2.850 53 Ule.l .None lai 70 None l.'.CS 3'J 53.2 3.725 73 7.7 1 13.5 2.000 3a 53.2 3.750 73 7.7 1,13.5 None I3j; 00 Sllgllt 4.125 00.7 52.5 7.hK) 113 11.0 1 8.4 >Mne HO' [10 None 2.175 51.3 57 3..»00 8U 9.3 1,10,7 Bloo.l gluec^e 0.25.)). 3 None 11X1, IH) SliKiil :;.275 56 62.1 5.375 92 9.0 1,10 Neerop!»y Blr)Oil glllcos" 0.45-O.lS None IL'O 70 None 2.825 35 BUto.l gl)ico?»e 0,1"' None l-.'O w None 2.775 51 11 loo. 1 glucose 0.4^1.34 None 120 70 None 2.825 35 None 120 SO N.,no 2.775 51 .Morke.l !«) rni M.i.l. rale 3.!W .'« Murke.l 120 HI Mark.-.l 4.375 M 51.3 s.o:.« Might .Marke.l 3.900 .03 M(.ileriite 170 120 Moilerate 3.HI0 42.5 .M.i.lenite 130 ' 90 Mirkeil 3.II.',-. 3.170 40 43 45.6 c.uoo Mn.leratc 150 115 Markeil 3.975 43 Sllghl 130' m 115,' ? Slight 3,3sn 2.8U 6fi 48 Slight 100/ w Blight S,300 36,7 9.0 1,10.3 Necropsy 0.1 1 u Nerrr.psy NVrropsy Weight 131) lb(, la 1903 TAI'.LL'. t<.— Cl.lNIl -M- ( rATHOl-OiaCAL) — Nil. Niilili' Iniii- Hi^liiry Nil. Age 32 I., .1. 33777 47 S3 i:. K. 1 20 3. IS 33757 36 2. i:. (1. 2 '21 33697 47 X, (1. 1.. 1 20 33310 63 sa R. A. 2 17 33643 45 37 F. W. 2 17 S3722 47 M M. 1 . 1 23 C. U. I. 39 .1. K. A. 2 12 2,18 2 2.-) 30283 4U t'l H, (1 •■. 1 It 3fiOS2 55 41 N I'. I'. 3 18 36551 51 *:' i:. s. II. 2 12 3(tt'J8 71 43 M. P. 1 12 2 3 33510 32 41 W. I.. I. 1 12 2 3 33424 38 4') T. K. 1 12 33,V14 ■29 4i: A. T. 1 3 33472 22 47 1 \V. 1 7 33479 71 48 !■ k > 1 12 33.572 .11 46 F. N 1 20 333'.iO 40 ■ii) U. 1 7 33333 43 1 K •!■. 1 14 33545 n 62 M. 1 14 :a»r,i 18 .-.3 s II. .1 o» 3 U 36426 48 Diagnosis Bed Blooil IlKh. I'flls S;lllli. Weight Ailuiil Bi-t • HypiTtcnsiiin. Chrnnip nei)liritis. • i-iii..;irttiritis of spiue SyiOniis. ArUTiosi-lerosis. Ilyppr- lensioii. Cliriinif lifpliri'is AitiTiosderusis. Ctironit? in'i'li- ritis. IlyptTtension. I'oly- tytlK'Uiia Syphilis. Hypirtonsiuu Clironic nephritis. Hypertension. MvooEirdial insuSicienoy Cliroiiii: nipliritis. Hypertension. I i'ri'!ir:il liemorriiage Uypern-ii?iiin Chronie nephritis. Hypertension. Arteriosclerosis. Hematuria Arteriosclerosis HypertenBion. KnlHrgeil prostate Arterioselerusis. Hypertension. (.'areinonia of blaililer Arteriosclerosis. Uyperten^ion .. Chronic nephritis. Hvperlension. Myucarilial insoHlclency Chronic nephritis (■lirnnic nephritis Chronic prostatitis Chronie infi'itinm' ^irtliriiis Cerelirnl arierioseliTosis. Brain tumor? Kniphy-ema. Chronic lironehitis s\iiiiili>. .Vneurysm of Ihoraiie aiirla Chronic iippeniliciti* Typhoiil fever Carcinoma bladder. Secondary anemia 5.111*1.0(10 90 79.4 3„')0().000 05 62.3 05 5.'.'00,00i) 105 72 80 6.000,000 S3 (10.7 70 3.000,000 W 65.D 5,S0O,00O 92 X.H a.m., 78.3 4.oiHl.(iO(\ 80 76.4 p. in., 3,700,000 75 75.9 70.1 3.800,0(10 72 OS. 4 50.1 4,4iK).lKN) 03 S7.3 70.3 4.000,000 82 80.9 79.5 4.20O.0OO 93 l!2.7 73 4.300.000 10() 52.3 61 4.st«l.()()0 75 72.7 73 .-16.4 ,5,000,000 90 51.9 4,2iiO.iKl0 92 (il.4 ii3 . . 5,000,000 iiO 4* 6 4,500,000 .■« OO 3,300,000 33 ,58 .58.4 Stuuii's ON Bi-iion \'n]X-\ii:—i Continued) i I I Kdoma blood Pres-bure Cardiac Kularge- uient Plasma e.t. C,c. Per Kg. Bema- tocrit Prr (.ent. Plasma Blood Vol- ume C'.e, per Kg, Per Cent, Uudy Weight Fr,ic- tion Hody V. eight Remarks Slight ls(i 100 Moderate 2.70O 34 66,7 4,o:)0 51 5,3 Me.7 Ntine L'oo i:*) Slight 3.050 3.150 49 51 None ■JM loO Slight 3,050 42 56.1 5,475 70 8 1,12.5 Wood glucose 0.12 4S 01 5,675 78 8,2 1 12 None ls5 105 Slight 3.025 50 Slight ■IV) 130 Slight 3,175 4ti 63 4,913 74 7.8 1,12,7 Blood gliicose 0.14. Wed None I'J.j, 130 Slight 2,950 52 54,3 5.425 90 10 1.10 None 180/ ? Slight 1.S2') 43 1 None :2r. 11(1 Moderiue 4,0,50 3.875 .59 51 d 0,150 81 s,s 1/11.9 SO*J e e. blood lenioved e35,'155 3.425 45 63 5.125 At 8.4 1,13.1 220, 125 4.150 55 75 5,500 72 7.0 1,13,1 None 175 no Slight 3.500 ,50 60.S 5,750 81 8.5 1 11,7 None i;'5, no Slight 4.325 44 60,4 6,525 65 O.S 1,14.7 Died None 210' 'A) Moderate 3.150 53 Con=i'ler- ISO 100 Marked 3.S75 44 64.1 li,025 09 7.2 1 13.9 Slight 115 75 Slight 4.047 53 Moderate i."o so Slight 3.172 3.0cr kilogram iiiav iinl Ijc incrca^cil alici\c iiiirmal. llic tulal lilood vnhiiiie iiiav lie larm' in rclaticm tn the iinrnial IkmIv weight. Case 25 luul a liloiid ma-s ive am! t'lhrnus in l\|'e, with h\ p'crtropln- nf muscle and small scattered scars everywhere. The heart wa- df tremendous size. It is (|uite ])0ssible that in this instance the Iari,'e hldud itiass stood in caudal relalidtiship to the large heart. 1 1 y^oii-Hsioi! aiui i lirciiii- \ , ["In ills. - In nineteen determinations dti thirtei'ii cases ( .\'d<. M to 4.i, inclusi\e. Tahle 8), a ]ilasma volume greater than nortnal wa- foimd onlv diice. while tiic total blood volume was nut fcitind incri'.i-ed in nine detcnnitiatiotis uu '-ix cases. Tills would appear to demoii--trate tliat in the-e ca>e- tile hypertension was nut dependent on an increase in hldiid ni.i-^. in hyperten.-ioii, the hlddil \iilunie is normal and I i"e>|iii niK' low. Ilic incrca>cd tcn-ion wiiuli! appic.ir. tlien.'fdri\ tn lie tlepeiidciU dn a \a-cular s\.~teni that is tdu -mall, r.itlur th.in dii ;i lilood \olnmc th.it i- too liruc. The a\eraL;e value for jiki-ma w,i- 42,8 c.c. per kilogr.im. and fdr the \vhiile hlood, 7r c,c, per kilogra.m, in both in-tance-- the lower limit of iidrmal. The sm.dl \,\lue- ,ire not dependent on edenin. as will be ascertained fvdiii the table, -ince in onlv three ca-e- was even ^liijlil eilein.i |'re-ent, ami in onl\- one w.i- there u:reat cardiac enl.irgcment. The rc-iilts are in -triking coiitra>t with i!io-e of I'lesch.'* Scxer.d df the-e ca-c- arc of peculiar intcc-l. r.itieiil .^'>. who, on one deterniination -hdwed, .an iiu rca-cd I'Li-ma \olunu. h,id a marked hematuria -o that lunidrrhagc iiiav lia\e accoimtcd fdr this linding. .'^iiii-ei|ncnt delermni.ilidii-. ~hdwt'd tlu' pla>nia \dluiiK> td be iidrm.al. I'dlldwini; \ene-e< lidti with remocal of StXI cc, there was no decre.a-c in blood iires-nic. but immediate decrease in pla-ma \(iliinie. \ Week later, there wa- an inirea-e in ]ila-nia to abd\e tli.it fmind befdrc the \ene-eitidn. but wilbdiil ,i cdrre-l'diiding increa-e in the bk idd \ dlnnic. i hat h\ pevtcn-idi, can e\i-t in ;i--dci,itidn widi ,a IdW bluod \dluinc is clearlv indic.ated b\ ^'.i-e .U. the p.itient -lidwiiig i -y-tdlic blood pressure of 1S<1 and dia-tolic of pK), Ihe pla-iiia w,a- .U c.c. per kilo- L;r,aiii ami the total bl 1. .^1 c i-, per kilo^i.nn. The hypertension 29 exi>tol .Ic^piU' the tact thai the i)atient's total WuiM mass was not greater than the jila-ina vohinie is nurmally. (Jbcsity and a sHght edema were in i>art respiin>il)le lor these low values. Case 4;^ is al-o of great intere>t. The patient is the only one of the serie:, presenting marked edema at the lime of determination. At this time, he had 40 c.c. of plasma per kilogram. Following a loss of 11 kg, ( disippearance of edema), the [.lasma volume was found to be slightly lar^. r, 4,().=l) c.e.. eoinpared with .\S75 e.e. It is evident that tlie Vilasma volume remained ihe same throughout, not being influenced by the presence or disappearanee of the edema, d'his does not always occur, a- will be seen by contrasting with Ca-e i.->. From' thei^e ci-e-, it would appear that true plethora is not present in hvpertenMon, ;nid that a small or contracted vascular system and not ini incre.a-e in liln.)d ma^:, i-. re.ponsiljle lor the increased blood pressure. Clir.'iiic .W-l^lu-itis iniliout llyfnti'iisioii. < )nly two cases ( Xos. 44 and 4.= , Table Si fall into lhi> group. I'atient 44 w.as an instance of chronic ii.arencbx matous nephritis, wilh slight edema and very marked .albumiiiuria. The i.|;i~nia w.as e-timated twice, three week.- iiiter\eniiig. iM.llowing a \ .'? kg. decrea-e in weight, the ]ilasma decrea-ed ItMl c.c. I'.oth ca-es gave v.alues below the normal average for pla>iiia. Miscellaneous Gii'itp. .\ -mall -erie^ of miscellaneous unrelated cases (No-. 4«i to .= ,\ inchi-ive, T.able S) were -tudied. Case H). an instance of aneury-in of the a-cemling arch of the aorta, and with a moderate tirade of aiieiina, -hi.wed identical roults on two occasions- an aNera-e normal v.ilue for the plasma, ratieiits 4'>. -uttering wuh chronic bnuuhiti-; r\. with diroiiic appendicitis; 4o. a neurasUiemc. .-md 4S. with cerebral arteri(r-clero-i>, all showed value- within the limit- of normal COM Ml' NT Exiept in pregnancy. hyi)eneii-ion and obe>ity. the number of cases sui.lic.i in any one con.iition has been so .mall that far-reaching conchi-ion- .are ini'iios-ible. SutVicienl evidence has been adduced to convince us n\ i ,; i an increase in blood volume just before term in uncomplicated prc-nancy. ( /' ) absence of a causal relation-hip between increa-vd bln...| volume .and hvperlen-ion, and ( c ) of a relativel\ small blo..,l m.a-- in obe-itv. Inirther blood v occur in any one disea-e. Com- plication- of anv kind mav al-o exert a great inlUience on ihe bl 1 vohune. ,1- evidence,! bv Ca-e -' in T.able 7. It become- evident llial 30 wo cannet lake t'dr j^ranU'd llial tlio blood Nnlumc i> iiKTcaM-'d or dccrca^til in any <,'iviMi disca-c, lull inu-t ainually dticrmiiK' il in each individual i-a-u. In ihc prc-cnt --talc (jI i1k- ina \nhinie i^^ described. I'roni tbe plasma volume and hematocrit \alue- the blood volume can be calculated. _'. W ilb tlii> mellind, duplicate determinatidiis on normal subjects yield identical \alue>. ,v I he amount nt decrease in blood \nlunie a- the result of henior- rhai;e and "f increase following; iiUravenou-- infu-inn of ,-alnie has been denn in-traled. 4. Chanije- in blmul \iilume are in-i,L;nilicant in experimentally induced Inpcrlen.Mon and li\ pnten>ii .n. and cannot be bron,i;ht iiUO cau-.il relalinn-hip with iheni. .-. Tlie ]'laMiia nnvmallv c(in>titules apiimximately ,^ per cent, or one-tuenlielh nf tbe b<"ly weight. Ndrnial iiidi\ idu.iV- liave ai)!)roxi- niatelv rt> k-.k:. of pla-ma per k^., the extremes beini; irdui 4_' to .~0 c.c. per kiliii;r.nri. (.. The normal heni.itdcrit value- (iblained were apprroxiuiately 8.^ c.c. <>i blood per kild^ram, llie extreme- bcin^ 7S and *'" per kileigram. 8. In prei^nancv, before term, the 1)1 1 and plasma \iihnne< are increa-ed, .\ iimditinu nf -eiou- plethora exi-t.-. Within a week or iwu after deli\ery. the bbni.! value- return to ncjrmal. '». In nbe-ii\-. the plasma and bb^od \olumes are relatixely .-mall. Ill, Manv ca.-e.- of anemia, exhibit a relatively lart;e plasma volume. II. I', ilvcythenna in the sense of a hi-h blood count may be dependent nii a liiw plasma Mnnme. Il may be a-socialed with a large plasma \iilume. in which ca-e true jilelhora i- indicated. IJ. 1 lyperi;]\cemia exists wilhcut increase in blood volume. l.v In anasarca accompanying in}oc,ardial insuhiciency the blood \olnme inav be absolutely increaseil. 14 .\ small \ Illume i- -Imwu in many eases of marked hyperten- -ion. Therefore so far as these studies go it would apipear that hyper- ten-ion is not dependent on a large blood volume. I I I