1482
`
`Cl'l1'\l'Tl:A 70
`
`t.lrn i1oh1l~!H pr~»,t•:nt., nr u11 one th:\~ m11hitt1illH nt. lenllt, on1i
`$Olutc C'.OtH:c,ntm1:ion 1:rndim1t 1tcm1:11:1 i1;;olf. Oinno~is, (.hem,
`iii tlu! ciiff'liHioo ill' wol.cr l.11rm11(h v mt1mhr1111ct t.hnt, mnintnins
`11t lc!Ol!t, ono 1ml11\.o c<mccnl,r11Li1111 !{1'11dient. 11crnKs it.11clf.
`AHK111110 o 8nlutfon A on 0111: nid,1 of 1.h<: memhrmw, nmJ 11
`Solut.ion B of tho l,lllmr. Kolu!A: b11t. or ,1 higlwr cm1~'.,!J11.1'11lfo11
`on thc ot.her ~icfo, t,hr. ~olvc!lll, \Viii tom] Lo p11s11 into l,hll 111(,r<,
`<">JlC(>)l(,t(tl.C1d nolutfon unLil c>.quilihrium hull bcM 111:1li1h(cid:173)
`'l'hci prc:,i:uu·e l'cquired l.o 1m:vont. U1i!i movu1ncnL h;
`lh1hecL
`t,hc os11'1(1l:ic 1n·o11sm·o. lt is d<ll'ill()d 1.\ll the cxc•~~s prel:ll:l11t(1, rn·
`pr<>s:mr\! ,;rMto1· than Lhnt uhovo t he purn ~olvc?nl,, whh:h
`must be n1>J)lh\d tel Solution B Lo pn)v(1llt Plll!l!Ogc o{ t.l<.•lv<mt
`through n perfect 1:ll!mipc:rmenble memhnmo from A to J3,
`'l'h0 conceutrntion ,,f 11 "olution wit.l1 n•~1>cict io effect. on
`,,11motk 1>1·ossur<1 ii; r(!lnt.cd Lo the 11wnbol' of pnrticle!:1
`(unionilr.od mok~r.Ul(!I:\, i()n11, m11cromoleculc11, n11t11·cgntcs) ,lf
`1;1vh1(.(1(,;) in solut:ion mid thu11 is nffcctcd by th4' d1,l(l'CO of
`io11i:,,;11lion 01· nggregl\l:ion of tho 11olutc;. Sec ChapLcir l.(l fol'
`revi(!W of <:<,lliw1tive pro1>m'ti1i~ of .:1)lutiorn1.
`B()dy Ovid11, including blo<>d imd lticl'imnl fluid, 1wr1MIIY
`huvc m1 rn,mof.ie 1mi8surc which vft,tm iii clm;<:l'ibed 111;1 (;c.1J·t0·
`i.pmHli1111 t.,, U111t. elf ,t (>.~% 11oh.1~ioo ,.,f !\Odium chloride. 'l'hC!
`body ul1;10 t,1t.l,1;mpl.ll to lrn<~JJ t.111! ,,1:1rn0Li,1 prnsm1rn of thc, \'.Oil·
`t:entn of l:h,.,, g,,1H(.rnint~i:it.in11I (J•uct. 11(. 1.1br'n1I. f.hiR level, lmt·.
`there l,h<~ norn111I rnngo is mud, wi1kn: ~han Lh11tofmo:it body
`t~> bu
`fluidll. Tlw O.H% :IO<lium d1J11rid1• H1,,l11ti,111 is !111i<l
`isoasmoti.,: wit.h phygiolo1iicnl fluidt1. 'l'hc L111·m isot1Jn£c;,
`meaning eq111tl l,(rn(l, is in nw.dic11I 1.u:1i1tt(1 <;<irnmonly used
`intorchnn[{eably with il'loo~motic. However, i<:rm11 1mcb nt1
`isotonic nnd t.onidty 1:1hollld be used only with rnl'cmmcc t~, n
`phy&iologic fh1Jd , hookmotic nct:mllly it1 !l phy1<ico.l term
`which com pure~ ~h,i o~moiic pres:mn1 (or ttnOl,her colligntiv{\
`property, such 111:1 fr(i<Jv.ing-point dcpre~l:lic\U) of two liquids,
`noit.hor of which n,uy boo. physiological fluld, or which mny
`b11 o phy11iologi<:1~l llohl only under ccrt.nin circu111»t1rn<:I).'\,
`T•'c1l' exnmplc, u solulfol\ oi' hol'ic acid thnt is ii;oo~motic wit.h
`l)()l,h bl(lod nnd lncrimal nuid 11< i11ot.onic only with 1.ho loeri•
`m11l r111id. T his Holut.i.ou cnu><os homoly;;b of tt\d blood coll,.;
`b1ic1ws1: molcculc!i; of hori<: acid pnss freely 1.hro1J1,:h t.ho
`(iryt.hrncyl:11 mcmbnurn rtiglilrdlc.w; of concenl,rat.i(>Jl,
`'l"h1u1,
`i11ot.onidty h1fe1·11 u 1,eui;e of phy11iologic comp11tibilit,y whorci
`i.H(u)i,mot.icity nmid ,wt.. A1;11\JW\,hc,r c,xmnplii, n "ch1:111iMll:y
`<fofinHd oltimcntnl diet." 0 1' e111.,m1I nut.riU01111l fluid cn11 be
`ii;oo~motic with the conl,<.\nts of the 1rn:;t1·oink:1U11ul 1.mc.:t.,
`but, would nol he wm1id<in~d ,, phy11iolnr{ic11l fluid, or ij\li\.11bk
`for Plll'<mternl mu,.
`A l:ll)h.11.ion is isotm1ic with a Jiving <mil if llumi iii no <11!,t
`gilin (11' 101:1~ of woter by the er.II, or <)thot· chnngc in thti cell
`whv.11 it i11 in C()ntuc~ with thi,t, ,;oluti()n. Physiolo1iic 1:1olu·
`tio111;1 with 1111 01nnotic prcssul't! lowtit• 1,h,m tl111t of b(1dy J'l\l·
`idr;, cu· of 0.9% aoclium chloride 1;oh1tio11, oro 1·cforn1cl \.(l
`commo11ly 1111 boing ltypol:cmi(;. Phyiiiolo,:iicnl nolutiorn, h11v(cid:173)
`inl{ 11 gro,nti1· osmot.ic prcs:mrc ure t.(!Ylll(id h)1perlo11ic.
`Such qu11Ht11iivi1 Lorms urc of limiLud vol uc, Mel it, hm1
`beC(\lllC ne<:1li1$MY t(> >';t,nte 011moti<: prop~1.rti<ill in qu,mtlto.tive
`tet11111. 'l'o do 110, ,t t.orn1 mu~t be uHecl t.l1«t will ro1,>rcllcnt. 111l
`the p1irticlc11 whid1 mny he tHesent ln a giv(m 1:<y~!R.m. The
`tcl'JJI \laod is c1s1nol. An omnol ill defined H8 the wc:ight, i11
`Kl'llms, of 11 tiolut.c, cxh,Ung in o 11oluLio111\ll 1:0uleculc.1J1 (nnd/or
`ions, macromolccukis, o.gr,reigntos, etc), whic:h i$ 111,motic111ly
`oquiv11kini to 11 mole of an i<loolly bchuvlnti 1ionoll!ctrolytc:.
`'J'huK, U1ti omnol-wcight of ti nouelc:ct:rolyt.r., i11 ,1 dilute 11olt1••
`t:ion, gcmirnll:, il'i <iquul \,IJ ik• 11r111n·nwle(;\1h1r-woit{ht.
`/\
`millim•mol, nbhf<ivinted 111O~m. ill Um wciy.ht: 1:1tutci1I in milli•
`1:1·tum1.
`If one e;,;,t.rnpol,1l(:ll l,hiK co111)cpt of r~1lu~i11i; 11n ()ijmol oncl n
`mole of u nm1(!l(1drolyt.c1 1111 h11inl{ ct111iv11lonl1 Ll11111 one nlso
`may defi11e nn o~mol in thu followi 111~ way~. rt i,:; the.\ 11mount.
`of l!olut.ci which will providu 1m<i Avog11<11·0'1:< numbc,1· ((1.02 X
`102:1) ()f 1>t1rl:idou in solution 1111d it iii t.Jw 11mo\111\, of 1:<ol.\1(,t!
`
`which, on di~~()h1lion in I. kg of wt•ter, will 1·1i1111ll in 1111
`osmoli(; prc,~l{\lr!I incromie of 22.-1 a(,mo1:1p hcir(,11, 'l'hir; i11 <fc ..
`l'ivud from Lhr. l;'M cqu1.1Lion, PV = nH.'l', 11,:;,;uming id(:o.l
`cCJ)1di~io1111 ,md iit1rnd1ll'<i l.c:m1>11r11tur<i of o•. 'l'his is oquivR(cid:173)
`lun\, l,11 ,111 im:rn,tse of l'l ,000 IJ»T m· l !l,:l()O tori· 11t. :!7°. On<i
`m01.1)t1ol ill ono-thom11rndth of 1111 01:111101.
`l~ol' mrnmplc, l
`mole of ,mhyclr<lUI.I d<ixL1·o~e is cq\111) l:o l.!:IO g. Ono Omnol of
`tJ)iK non(!l(lc:trolytc is 111!m J.80 K, One mOamol W<mld be 180
`m11, Th\11J l80mg-oftJ1iM1Jolut.edisHolvodin I kgofwotenvill
`produ('.(i 011 in<:1·011sc in o:unotic 1m.1~1:1urc of 19.3 torr at body
`tmnper11t\n·e.
`f<>r a e<•l\11,i(m of nil electrolyte such us sodium chl()ridc,
`one 1110l.eculll of ~odium chloride repteaent~ one 1;(11lium nnd
`one chlor.ide i(m. Honco, one mole will reprellellt,?. <,umol11 of
`sodium (:hlorido l.hool'ctically. Accordingly, l m,mol N11Cl "'
`58.51t/?. 01· 29.25 g. 'J'hill qu1mtity reprcij\!lltl.l the, 1;1\11n tolill of
`6.02 X 10n i()n~ M t.h<, totul number of 1mrtide~.
`ld<-ml
`i!OlutiomJ iufor vlll'Y di111Lc ~olutions OJ' infinit.e dih,ti1m.
`Hownver, nil th(: c1)11conf.rntio11 is incrca~cd, ol:luir fuc:l,cir;;
`enlor. With t4tron1: d1!1'.t1·olyto:,, intl\rionic 11U,1·iwtfon C}Hll:l(!11
`11 clocrr.osc in t.l1<iir <iffccit. <,m eolligntivo p ropcrt.iut<. In ncldi(cid:173)
`tfon, mu\ in 01>p11~itfon, for 11ll ilofnt(!:., incluclinr, nonelc,c\.t0•
`lyt<!fl, 1;11lv11tion und J)o~sibly of.t\l}r footors opC\1·111'.c to inte1111i·
`fy thdr <:olligotivc effect:. Therl/.for.o, it i$ vo1·y diffic11lt and
`oft:cn imJ)O$lliblc to 1>1:edict. 11cc:\ll'8l,(!ly the oMmotidty of a
`>.1ol\1t.ioi1. It mny be posKible. t:11 do so for II dilntc 1;oluti()n of a
`11iuKle, pw·c iHHI wcll-chnrnctcri7,cd tl())\11,ci, but not for moist
`p11nmt(m)l ,rnd ontorol medicinnl :iml/or 111,1,ritionol fluids;
`cxpcl'itn<mtul dct(lrminflf.ion likely•~ t'e(l\1ir1id.
`
`Osmolallty and Osmolarlty
`
`111
`
`II. i8 11"1:eJ!l!Ury to use severnl addi~ioMl l.<mns to dcfiJll:!
`cxpre31.1foll$ c,f conccmtrntion in refloctii\fl lht oi;moticit.y of
`solutiom!. T ho t(!l'tnB h1cl11dc m;molulit.y, tho c:xprcsMion of
`11Hm11l1\l C(>11<:011trntion 1111d osmolority, 1.h(! (1Xpl'ci1nio11 of tlll•
`molnr wn~\!ll~<•i1linn.
`Otm10JI\Jil,:Y-···A i!Olutiml lul8 un 081nc,J11I ccmcQnl..rntion of
`01w whcm it ~:cmt11i tlA l o~mol of 1:1nl\1Udkt( of wntc,r. A 110l u(cid:173)
`tion lrn1:1 1111 uHmolnlity of n when it; co11t.11i111, ii <'>~mols/kr: of
`wnt(•r. O1;1uH►lnl l'loh1tionA, like t.heir t:O\lll~1l'pMt mol11I :iolu·
`~ionii, renec:l a W<>.i/:ht: to w<:ight. 1·c•lut:ion~hip lrntween Um
`solute 1111d tht! ij(l)v,mt. All ~olutiom:1 with the 1111mo molol
`concent,rntfom,, irrcHp1:ic:tivc 01'2olutc, ccml,11in 1.h11 i\1)111<: mole
`fraction (!,.,) of ijolute, 111 w11tc1·
`I .,, .... _,,,,,,, .. ,. ........ , ........... , .. _. __ , .. __ ......... _ .. _,
`mole11111,l\Jl,11
`Jl1()1\u; 1:11>1\1!.I! + moloH flolvent
`thus, for II one molul 1:1olution
`. ..... .... I_ 1nClle. .s.<.>l.~!~.e .. .......................... ., .... ,L
`f ..
`'"
`l mole solute+ 55,[1 Jl\l)loa wl'.ltm· per l1g
`66.f>
`Since nu osmol of tmy nolloler.trolylo is cquiv1c1Jc,nt. t<> l mole,
`t\f that com1>otmd, tbell 1\ I oim1olol ~olution ii; ~ynonymoue
`t:o ~l l molal 1mlution for 11 typical nonolcctrolyu,.
`Wit:h II typical clect:rolyl,(• lil10 r,odium chlor.id11, l. oti!IIOI ia
`nppl'Oximotoly 0.5 mole o( l!Odi11m chlnridc. 'l'hu11, ii, rollow6
`t.hul n I osmolul tmlut,ion of >i<'i<lium chloride CHl:l\lnl,iolly i~
`e(111ivolont 1:o 11 0.5 mol11l i;oluti()n. H.c,cr1l1 th111. 11 l 01:11no!t1I
`1m)11tion of dci>c.t,rone or 11odi1J111 c:hloricle 1:11ch will c11nl,1)it1 th(!
`1:1nm<1 pnl'ticle concont-rutic)U. In the dext,ro11r. soh1!.ion Ui.11·0
`will b(1 (l.M, X JO?.~ molecol\1~/lc1~ nfw11tcr nnd in l:lw ~odium
`chlorido 11olution onc will hnv(, 6.02 X l()?.:i t.ot,11' fo11s/ltg of
`w1~t<•lr, 011e0 half' of which at·a N,1+ ion!l 1111d t.lie ot.h<ir ht\lfCI"
`'l'he molo fructioo, i11 tc-:nns of' totnl ptwticlel!, will bC1
`i ()ll!I.
`the 1Jnme 1111d, h<mcci, ~he Mmo oR.motic prel!llure.
`/\c1 in molnl ~ol~1Liot1lf, o~molol 11olutim\s u1:1utdly rno. Olll•
`ployed whe,:t! qo1rntitotivo prc,cision i11 rC!quitod, ow ln t.110
`
`FRESENIUS EXHIBIT 1013
`Page 305 of 408
`
`

`

`·1
`
`'f(lNICITY, ()(lMO'r'ICll'Y. or,MOI.ALl'fY ANI) OSMOI .. Al~ITY
`
`,m<1raHuri•11uiu1. of l)hy!.1k11l 1111,l chcmic11I p1:0J11!rl,irn, of' 8<>ll1•·
`~ion:◄ (i,?, eolliwitivc p1:opu1·1.iui,), "l'hc 1.1dvn111.111(<: of 1.h1, 11,/w
`l'()lflti011~hi1> fa t.hnt l:lw 1?011c,int1·11ti,:,n of Lhe sy~t(\lll h, uol:
`i111'Jum1c<·id hy L1-:11111ernt.111·c.
`O,imohwiLy ..... 'J'ht• n+Juti<mllhiJ> ,,1b,:1Jrv,,d h<itw<,cn molnl,
`ity und rn1mol11l.il;y iH sh11n1d Himil1\T')y bct,w,)t:11 mol,u•it,y ,rnd
`/1. l'!olutfon hnH 1m <1>>111olm· conccmt.ratiou of 1
`osm1.1J1.1rH.y.
`wlwu it co11l~1in,1 I. o,1mol of ,11.1Jut;c/L of' uolution. Ukcwiij(i, u
`,;1)!11!.ioll hm, ,m <>.~rnolurity of II whon ii. contai utj II vHmohs/L
`of Minlfon. Ot:mnl111· 1mh1tio1111, unlike <111mol1il Aoluti on,
`l'Oflc,cf; ,1 wcir,ht, ill v(1l11111t• ml111.ivnuhit) lu!twi,on I.he ~ol11t<:
`uud final 1iol\1ti,>1I, A <Intl m()l1.1r imd J. Ol'lmolur llolut.inn
`w<.11.ild he ~ynonymous for 1101wl11d.rolyt.<1:;. 1<'01· :.odium thin,
`dd,: (1 I f1Hmo)n)' 1-1,ih)tion would conwin I omnol of sodium
`c:hlnridt: pc!' lit,t,r whid1 upprox.iniat.c~ 11 o,:; molnr uol nt.ioJ1,
`The ttdvant,111~<! of' 1-1rnployi111.( oi;1nolm· ,:ou<:c11l,1·u!.ion!-I <>Ve•·
`Ofinwlnl c:onccintrn1'.ion11 it1 tlw Hhlli1.y t:o rnl11to 11 spedfk mun ..
`h1:r 1>f OKmols (ii' mi1Ji,,1:1mol~ to a vohuno, :mch rn; a Iii.er OJ'
`mL. Thu~. U.w o~mnlo1• con<!I/J)(, i1;1 i;i1111)lc,r: ond mo1·r. prncti (cid:173)
`cal.
`'.l.'be cn111H)h1l ,:011ci1p1. do(iK 1)of. 1dlow for thi,; l!t>I\VII·
`niclllC(l hr{c:/11llit! o.l' I.ht} w /11: t ii Iii 1.i on:,h i I), AJi,o, t11.l<1 if.ion,, I 1111 !.11
`!Jll<;h 111; 1.h<, dm1Hi1.y 11r11111lly nre not uvui!11hlt1. V1>hm1m; of
`ijoh11.io11, m tJwr Lhon w<d1tht,,1 of K•.ll\11-ioa, ,.,,.,i morn l)l'fl<.'l.i<:nl
`in l.hc-1 clolivory of liquid dm1111:ci 1'01·rnH.
`Mony hc:1111.h pr<}fot1gion:-1 ll1 dn 1101. h11vo II d<1m· uud1m!l:1md·
`i111: oft.Ii~: diff<:l'l\llt:e bet.W(!!!ll oslllol11li1;y 11nd 0Hn10l111·ft y. 111
`lit<t, Ul\1 t.crm~ h11v1, h~1,,11 u~c,d int111·ch111111e11bl?, Thi~ i8 (hie
`purtlv 1.0 UH! 1~i1•c11mi.Lirncc thr.11,, until l'l<l':cnt.ly, llli)!,t ol' t.ho
`,;yl!li!11l!l involvt►.cl W!:l'(I h1>dy fl uidll, in whid1 tho diffm,;nco
`botw~ml thl\ numeric.1.11 val1.1(~i.1 of 1.h(l t.wo c:onc1mf,l'lltion n:x ..
`p1·1,~i.ion:i is l!mull 1111d >1imil111• i11 11m1;nit.1.1dc, 1~, Utt• ~ 1·1\11·
`involved in t.l.11.!ir del:(.!l'Jllhilltion. T ho prnhlom p11rtl.y muy
`cont.N ar111,m1I Ow i11 t.11,p1·1iluf.ion by some 1.1) vi<!.W om1 kilo(cid:173)
`grnm of w11l:(1r hi 1.lw omnolol cooccpf, w, bciu1~ ~,11uivnh1111. to I
`l,, 1111d, n1111·,: imr>o1·l.,111t,)y, tht1 i11tr,?1-pr<,tuf.ivn 1.11111. Lo n111lrn up
`(;,1 v(l)Omt, of I L, o~ in osmoh1rity, i!:l eQ~1i111,iully t,hc ,mnw 1m
`t,iw w<ii1.:h1. of snluu, phu; ·J lil,,t<' (11 d i11fm•1.io11 of llw o~molnl
`1)11)1<:<rpl), Tiw pi·imnr~• di1T,1r<mr.<1 ••~ii:idm, in t.he <:rror in\·,1·0•
`duct!d whkh 1·cvulwii; 111·m111<l thn volume of w1:1t:er oc<:upi(?1.I
`by tlrn imluk. A I 11Mllltll111' 1:olution of r, Bol1.1t" t1lw11y,; will ho
`more 1:onr:11111.rntc:d thnn a J. <.mnvlal ,,oh1tion. Wil.h dilute
`:,oh1tio11~ I.he diffcnmcH may bi: ,a:MJ)l.,ihl,Y imrn ll. Niue
`,itnms of :,odium chl <1ri<h1/L of 1uJtl<:ou~ :iol11tlon ht ,11>proxi
`i111ll.cly tiq\1iv11l,:nl, l.o 9 J; ln 9HH.I> mL o!' wntu r.
`'l'hi!! r<!pru(cid:173)
`mmts 111111trv1' 111'11nd1)l' J %, when co11>p111·i111r Uw o,;11101,i<;i1.y (JI'
`0,9f;'., m/11 MOl111:i1m t.o :.1 ~,,l11{:ion o f \) I( plu,; l kg o/' vmt:m·.
`\J1;1i111< d,ixf.ro:;i.; in a j)m'alinl comp,11·i1<on, ,-:rrorn 1·11nfJ(> from
`apprnximntely ;1,;\% i,, o,;111,.,ti~:il,y with fill I{ d~x,.rn~c/L v1ir ..
`1;1•" f>O 1: ph.18 I. kJ~ o/' w,11.c,1· t.o n tliffol'once of obnut W% in
`0111110Uc:it.y wif.11 21i0 ~ chixlro:.r./L VCH'l\US 2/iU g phi,; J. kg of
`w11lcr. The ,:0111'1t1,i<,>1 111.iptuu·u t.o he, wif'.hout cm.nm for coJl•
`cem ut l,hia 1.i11w, Hownvi.r, illl\\ ij)wuld b11 ul~•·t<.1d t o Llm
`1)i¼N)bl~ m·rnrs which muy o,:c\m' wil,h w1we11Lr11t.1ld oolut.ion~
`or floi<l ~. auch ••~• l,ho,;<: t►. mployc:cl il1 tot.111 f.11-11·011f.n1·11I nul.l'i•
`1.in11, 1mteml hypemliment.ot,ion und ornl n111.ritionol n uid11
`ft>1· infonliJ.
`Hcfc1·cm:1J ha8 hem> nwdt:l IA> (,h<i 1-01·1rn1 hypt:rtoni<: mid
`hypoto11i,:. A1111lo1t<111:; l.1m11a 111·1; hy1.111ro11mo(,ic 1tnd hypo0ij·
`m1.1t.ic.
`' l'hc 11i1:nifie11nce of hypca•,, ,rncl lly1J1H>~ll\ol.ii:i1.y f'1l'
`1m,did11ol ,m<I n11t1·itioual fluids will be, dis(!(ll;st!d lot{)r, 'l'h,;
`vuh111:1 which Ct>l'l'l.!:ipond l.n tho, e tcnn:1 for ~m·um rnny lm
`vi1mnlill:l.!d a1>p1·oximul~1ly from Um followi1111, ex111npl<:, A~(cid:173)
`i:;1,1,mi11t{ norn)1.tl :111r11m o,1mol11lit.y to lm :?Hf> m.Oh·11w//J111, 1111
`11c,rurn omnololtt.y int,1·1,a1<es d111-i f:o wat1:1· d,•fic:il, 1.hii follo\v (cid:173)
`il\l( Hi g1rn uml l!ympt.oms utt11ully m:e fo1.111,l 1.11 11c1:\1rnu\11tt,
`1.1roi:rc:!r.\i V!Jiy 111, ll!)p1·oxiin,1lHly UHs:.<o val11c-,:1:
`?.!M to
`:J!J!! ....... t,hir11I. (if t.lw p11!fo11L is 11lcrt 01id comm1mimt,i v11); ?,fli)
`t,o a1.a, ,,dry IIIUMIII, mmn bl'IIJl(·II!; :114. l.o :Wf) .... W(·!l•llUWHK,
`<10111:hy Hld11: i1bove :?;JO .. -di!l,,rionl.,ltion, po:.t.1tl':II hypoU>ll·
`i;ion, M.wcre w,mlnwi;s, foi11ti11g, CNS (:h1u11!('\\, ,)l,tlJ)OI' ,rnd
`
`c,1mo, AH s,in.,m 01Jmol1.ilit.y rlucrm,lni111 d1w t.o Wtlt.<:I' c.ri:r.,;s
`:?'Iii l.o 2G J ...... Jrnnduchc; :m2 to
`the followi1111 m11y •>c,:ur:
`~rn ..... t1rowr1i1101;,1, wMknclll-li 2fJO 1.0 2:l:l----dit<ori1mt1.1l,io11,
`1:rnmp»; I.IBlow :1.:~a .. ,111"1i1.m·(:i1, i;t:upor 1md comn.
`Ai1 i11di1:111,1,d v•·<•vi()w1ly, t.lw m,1ch:111 i1;1111, of t,htJ body nc(cid:173)
`tivt\ly ,~ombr.11. 1111ch mnjor d1al\w1~ hy limif.in1{ t.hci v111'i11tion
`Ju rnnnvlnlit .. y J'<ir 1·11irnli1I indivicluob l.o le:!¼~ thon about l %
`(app1·0:xim11l,t1ly ir1 1.hc: 1·,mrc11 2112 t.> 2HH m01m1ol/k1;, hn~ccl 011
`Uw <1h<'lV<I 1lsn11mpt.ion).
`'l'hc: v,ilu<) f~ivo11 fol' no,·rm,l iwr1m1 o8mololity nllv~'I! w1tij
`de:11:rihcd us 1111 ,1ssuinJ)t.io11 b<~cuui,c or Lh<i v111·iu<,~ ()I' v11luw1
`found in t.lw lit1m1i:1m>. S1!1·um o~molulit.y ofHm i~ slAlt1,id
`loo:;dy t.,, be 1.1b,111f; ~lOO 1110 m11111/L. Ap111'1. f'rnm t:hnt, nnd
`mol'(i ~p<icil'icnlly, (,wn refonm,:m; stulo it 111; WO t.o :wn mO,.t ..
`mol/1.,; 1,1t,h1,r t<ifon: rn;1J~ tiivc it: m; i?(i to :i{)() mOi1111())/[,, WO
`m(hunvl/L, :ioc; rnOm1wJ/J, nncl ?.'lrt to !W5 m01;11111,i/kg.
`'!'horn i~ 11 Hl.rnng tund,mc:y 1·,11 crill ii, ,,i;owlalily hu1, t,o ~l,111,(! it
`111; m.O.,m•>IIL (not 11s mOsnwl/hg).
`l11 Ult'> liKhl, (ll' lhf>fiP.
`v111•yi11n w1h11!ll, one mt~V Mk abo111. I.he, 1·,:tH'oducibility of the
`,:x1>~:ri11rnnt11I mcmim·emtm tH. It h,11; b11c11 HU~tod thnl most
`01m10111cl.cr:i nrc 11cc11mC{; t,o !; m0:111101/L. Wit.h t hat. t,yJ>C of
`)'HJll'(,d uci hil il,y, th 1, i1 hovc-1 v,.n·i,_1 l,iom.1 pm·h11pi1 nuw he ex1>od-
`1:d. Thu diff~,1·1?1l(!<i ht>l.\vec:11 1i li Lr,>t 1111d l1ih>({rnm prob11hly i,;
`r,. i,; dil'f'i<:11lt t.o lllll/1>;\lt(!
`inoigDiric111)l, fol' ~(·ll'lllll ,mcl Ill-in(,,
`kilownnin pf w,1t.cii· in t1 11oh1t.ion, 1.111d <lllf!Y t~> 1~xpr(;H11 llody
`fluirl 111111111.it.ie:1 in lit.ct-s. Perhnp~ no hurm hns bt•.011 dotlll l.o
`dul.t! hy l.hi:1 pmcti.ct, for bod,v f'luid11. H.owcviH\ h1(1Kei ter(cid:173)
`minology here m11y lend l,o looi;c? l,,(~1·111i11oio1:Y wlwn dealing
`with tho 1·at.he1· coc1co111.1·111.()(I !'lui<I~ llfii•Jtl 111. \.imo,; in p1.11·1,n-
`1:ernl and c11t.1<nll nu1.1•i1.io11.
`Rcft•r<:n(!<l h1lH hc-Hm 11111<11, to confusion in 1:hu nsc of I.hi!
`1:r.rm~ v~moh1H1.y ,m<I oiimolnrit,y, n distinction of apociiil
`i11'1Jlilrt,rn1:o J'or 1H1tritio1wl tluidn. Awu1·1•11r:,;,; ol' bir;h con(cid:173)
`contmtion,; of. info11{; .. f1.1f11H1l111:1hi)11lcl 1(ivo w111·11i11g a:<; t.o J>Ol'i"
`~iihln l'i~lu,. Unfort.11naldy, 1.h,i Oi;tru>t.id{.y of infonl fornw(cid:173)
`lm11 tul.w fo11di111?i; and t.11u1 I f11H'1,:ntornl 1111t.l'itio11 ~oht~io111;
`hn~ not be<m •fo6c1·ihcd 1.1d,,q11atcly nilher in t:exl;book,; m· i,1
`!;hi: li U-1rnl.u1·0,:11111d th<i lnh<lls of 1111111y r.om n1-m:i11I 111t~ril.ion-
`11I f'luidi; <In 1.iot, in ,rn.v wtiy, ~t.at:c (.)l(!ir rnauof.idt.y. Only
`r1:1:1,11t.ly haw cnt.cnd lluidn bcl¾n clu,1·11,:t(!J'iv.<:d in tt!YJ11ij of
`o:i111otidt.y. 8011·,e prndoc:L liM11 n<>w 1m: ncccntin1: it-011~mo-
`1.ic 1•11!.111·0I 1111[,ritionul ,mppli:nwnlli. Often, wlwn l1111 (,1H'll1
`o:m1ol11ril,y ill 11n11d, ono c:,n11wtdiscc:1·11 wlrnt.Jwr I.hi~ i;imply i~
`incvrr11,;t ,~,rmillt)log,V, or ii' 0~1111.1lnl'ily 111;f,1111lly ho11 bec.n
`<.:11k11l,it..cd from omnolulit.y.
`A11n1.hc:r c1nTen1, prnctic11 which <a,11 c,11111c, ,:ont'w:Jon, is t.ll('
`Ull<I of 1:lw \.(!fill~ nornwl 11nd/or phy.~i'.o/01:ica/ for l1:1ot,oni1:
`i,odium diloridc t1oh1tion (0.9%).
`'l'hcr solutkm 8uruly jij
`foomnnol,ic. Howl;lvCr, O!i t.o h(Jing phy:1iolor,ical, U1<\ (!IJ)l()(!ll•
`irat,iml (>f io111; tll'<l <·>flC.h <)fl/ill ml~q/J., whilt, !itlrum 1:,mti1in~
`11hot1t HO ml!:,, of 1:odium (llt<l 11b,rnt 1.03 111Rri of c:h\ol'ido.
`'l'hc rnnr,c of mOsmol vt1hwij fmwd fo,· i;cl'um l'Uit:os t:bc
`qllc~tfo11 tin l,o wlmt trmlly ii, mcm\L b;v the. tcrnrn hypot:ooi1:
`1u1d hyt)Cl'toni(! for 11w1Hdnul 1\11d nuLrit.ionnl l.1uid~. One,
`Cl\l.1 find 1.1111 l,1:rH,Ct11/Jtl1, t.hot. J1uitlri wit.h 01\ (ll:llllOlalit.y or r;o
`1110im1ol 111· iruirc 11bovr: 11ormol al'c hypl.!rl,011i1! und, if r,O
`mO,,.,n,,1 or morn below 1101·m11l, m·c hypoto11i1:. 0110 Llfoo Ctlll
`fin d tho statc:me.:nL tfo11: 1>c,·iphernl inn,~iom; >1hould 110\, lmvc
`flll ,,nmolnl'it,y cxc<11idinK ?00 t,o /lOO mOsnnol/L:1 gxo111plo~
`of 011mol c{mcm11.rnt.io111:1 ol' ill)lutionk uHc,cl in periphi;ml infu.
`siotrn m·e: DbW·-·W2 1110~m,)I/I.,; DJ()W .. ,, ... t,rlf\ mOsmol/L;
`LaclHt•Jd 1-tillH<il''l'I Ii% Dexll•ogc .... ,.(i:!ti mO!Jnlol/L. When n
`ihiid i:; hypnrtonic, undm,irnble off'w:1,k c,ftt\ll (!1111 b~ dti•
`i::rnr-18c:d by u:;in1, ru lnf,ivel;v ~low r·;.it,H:; of i11f'11,iic)1), m,d/or
`rdutivoly ohor(, pui·iodll or inf11Hion, n21;w ..... -~.?..!i% Amin v
`Ackb i6 tt roprcN:e{ml.111,ivci m:,1mple of 11 highly 0~11101.ic hypm·(cid:173)
`oli11111nl.11t.io1, 1,11(111.ion. 11. hlljl hcon i;U1t.e.d 1,11111. whun o~mofol
`hw.l inK ili nr,r,rlc:d, a rnoxim11111 xlil'c: t olc\ral\ t!tl for fl 11m·n1111ly
`hydmtod :mbjcct. woold b~: un 11pproxim~~1.c hm·<,01.u,.' of 9,(i
`mO!:llllOl/ktt of wul.1-11· ovo.- ,J h r.:'
`
`FRESENIUS EXHIBIT 1013
`Page 306 of 408
`
`

`

`111011
`
`CliAP1'El'-I 19
`
`(0
`
`(2)
`
`Computation of Osmolarlly
`Sevornl 1m1thod6 Mt'l U!!~d oo ohtnin 1l\n1HiJ'ic1\I v11lu,;11 of
`onmolndty. ' l'ho 011molnr conccntmt.ion, ~nnwt.inw~ rnforrcd
`to ns U1e " l:he(1r<)L1(,11l 08rnol11rit.y", iB cnlculatcd ft<.Htl th,1
`wt:/vol C(l))('.l:1H,tu\.ion ui;lng orni of the followin11 oq1;nLio11s:
`l~or a mm(de(:\.rolyt,11
`... X/!~ ..... x JOOO 00 1110umol/L
`mol wl,
`I 1'01: a st,rong 11l(11:t.rol;v~1l
`({/L X lllllll her of ion:1 X 1 O()(l ..• 0
`I/I
`·;~~;j~-;~
`form11d
`··• m
`:<;mo
`'
`l•'oi: individonl ion.;, if dol4ired
`,r ,,r i<>n/L
`.
`1':-····:··-· ··· X 1()()() r~ mOsmol (of rnn)/l,
`10111C wt
`'l'hcsc ore simple ('.11l.cult1U1m~, hnwc:vor, they omit consider·
`11tfon or f1.1ct<.►ri, such llfl nolvnt.ion and inlm·ioni(: 1.'orc<:!ii. By
`t h ill met:hod ()f cnl1:ul,1 tion O.H% sodium chlmidc, hue ,u, 01;(cid:173)
`molM <;<>)W(rntrill.ion (If :!08 mOMmol/J.,.
`Two ol,h1ll' 1Mthod1> ()(Impute osmolarity from vi1h1es (1f
`osmolality. Tht! d.t!tcrminntion of rnunolrility will be dis(cid:173)
`cussed lalur. One nwt.hod h11fi 11 $f.r<m11 t.h,~01·cti<:11l bnsis of
`physicnl .. r.hemical pri11(:i1>le~'· u~in1; vi1luoi. of t.hc pmti,d
`molnl volume(~) of t.lw i,vh1 t.\l(~). A ().\1% 1iodiurn chloride
`solut ion, fotmd t~:i1.pc,riin<mh1ll:v IAJ huvt{ ,:111 oAmolulit:y of 28(\
`mO1m10l/kg, wat1 mkul11t.ed 1,() ht1v1) an or;rnol,uity of 280
`mOsmoln .• , t'llt.lrnr dilfor-0111, from t,lHi vah10 of !:JOH mO~rnol/L
`1.:olcul11l.nd 1,s llbcwe. The m~t.hod, u~ing pur1.i11l molnl vol(cid:173)
`t11n,,11, i;i ml11Livtdy l'igorm•B, hut mun y ~y11t.11fn11 I.IJ)fli1l.ll' f.o he
`1.c,11 cc1mplox 1111d/or U►o poorlv defined to li11 c.lvt1ll. wit.h hy
`tbi1;1 nt<l th1)tl.
`Tho oi.hor m(.11.hod i:-. bn:ci(~d (lJI t:he followin1i rel11(.ionKhip:u:1
`11cto1\I Oijnwfol'ity ''" lll<',ll!llll't: d oumolnlity x (dtm,.ily -
`1-(
`solulc/ml ,). 'l'hhi ,ixprn~~ion can be wl'itt.!m
`m()~m(1l/L 90Jution ,,, mOsmol/lOOO 11 wn\.er
`>< g w11te1'/ml .• ~olt1Lio11
`The cxperiment.ul v11l1)({ for thl) osmoh11it.y of 0.9% sodium
`ehloridcl!olution w11i, ?.99..7 m(hmol/lq_i; U\o vuluc comp\1ted
`for osmolal'ity ww; 2fll A m()1;mol/L. Thb method doe!! not:
`lrnvc as firm II t:lwore\:icul ba1;i1;11~(< Uw pre(:orlin:.: mothncl bu(:
`it hnll the ndv11nta1w that it. u~m; (ru:::ily obtohicd v11luc11 or
`d cnfiity of the :solut.ion and of il.1;1 soh1t.() 1:onu>nl.. J\ppnrcnt(cid:173)
`ly, ii: cnn be u8ud with 1111 syiit:(•m~. For llX1rn1ph), thr.: (Ji,mo(cid:173)
`lnlity of a 1111tritionnl m·odud, wni; dl;l l,on11i11c1d by Lh1: l'rn1.,:t,•
`ing point d ep roKsion method to be 626 1n01,111ol/l11~;'' il$ 1),;.
`moli1rity wua calc11lillcd o:. (l25 X 0.839 = !5:H mO,mwl/L.
`'f'h<'l USP 1·,"111irn11 t.hr.1t. l11hcls of phormui:op1!iul !:loh11.ion~
`whi1ih nrovi,h! i11t.r,1v1mou:; rcpleni~lumm(·, nf Ouid, Jl\Jtri-
`1m1.(11), Ol' 11hwt.rolyto(R) 1 Ill! well 11s of the o~mo\:i(; di111·citit:
`Murmit.l',I Jnjc111.io11, tttatu thr: 1):m10l11r <:011cm1tr11t.ion, in mil(cid:173)
`lio~rnol11/L1 c,xcopt. th1il. whe1·c the contont11 ni·t\ Jess tlmu .100
`ml,, (II' whcrn tlw l11b1•!l ~L11tu~ the urticlCl ii:1 not for direct;
`inject.ion but. in to ho dih1kHI br.foro nAc, t:ho loh1il llltornnt:ivc••
`ly mny !ltn\.~ t.ht'! t1lt.11l oi:i1t1(1lm' 1'.(lll~'.Ctltl'(1ticrn in milliosmol!!/
`mL. Thio ii, 1.1 rcn:mnnblo ra,il"Jllt l'rnm jjr.voml ~{:1mclpoint.'l,
`1rncl iutt·av(!llO\lll fluid,i nrn bcin1~ li)h<•:liid in accordnnco with
`this slipulat.ion, 11/l shuwn in t.h<: ll<,xt. 11c,ction.
`J\11 ~x11111plo of U11\ 1.1s<1 of l,lw firs1- m«lhutl (lni:,:l'ihc:il 11linv11 i~ 1.hc
`~tllll\)llll\U(>li or I.ht• ll))J)rtlXilll/1111 1)<lllc)h1r c:l))K'Clllm\.itlll ("thCQ)'<.:lfo11I
`1ll<moloriL.V") ,,t ll l..11,'.1(111,d rUu1;1w\ :i-t. DC'xlvo~1, &,lulion (/11,/u,lt),
`whir:11 iH lnh~lod 111 wnlnin, 1wr I.,, 1fox1.1·,,~,, (l1y,lro11~) (,o tt, ~1.11lil111,
`chh1ri~I<; 1; K, r,,11111,.ium ~hlorid11 :,()0 m1i , mlch1111 chlorido :.lOO mti nntl
`Rmli11m luclnlo :j,I I\, Alo;o ntuh\l.l i• 1hn~ th~ (.(>\111 <.>1m1olor ,'.mw,,111.r,11.im1
`<ifU1,i 1mh1tio11 iM llf.)prnximo\dy ~2•1 mOKnwl lll•r I,, in p111•t, 1:11111,ril,111,1<1
`li:,- 1:JOml•~t uf Nn' . JO!) ml•:C1 orc1 ··,1 ,11R,1 (11' K', !l ml•:(1 uf'Cu' '' llllll :l,J.l
`ml.~t vf' lnvlnl-<• i1.,,1.
`
`'J'hr, 1lc)th11,Uon t,f fJu~ 1)t1m1)l11'r 1:m,r.Nlfl'nt.ionH from Uut ~C"lud <:\Hill>"·
`• ii.ion of 1-lw .,,lu1foll m•1.1' hi, vi:ril'i~d l,y (>ll<iuloli,,u~ n~in~ l•:q I nbovo f<1r
`1,hr. 11(,11r.l1ir.1.r11lyf., ded.mHu, nncl 1,:,1 2 for ihc d <)dtoly l,\!1.
`
`$(11, X I()J.)O
`... · {iiii:-i'i ··· ~ 21i2.3 mO~moVI.,
`
`.
`
`S11dium C:/1/orid1:
`
`{0U2.H<lm0•nllll Nil'}
`(I ,, X2X lll\JO
`,
`. •
`····"··- ··········· ··'····· ··· "' 20fi,.M 1110Rt1tul/L
`00?..CiCimOsmol Cr')
`lill.44
`
`1'11/,ossitw1 C/1/ul'i<h:
`~,:,.~.>.<?)( .l!~~) ~ !l,CH 1110.1110)/l, {{4,02 111(),1111,,1 !(I)
`'/4,!.i!;
`{•1.0,. ,11()11mol Cl")
`
`().,2.r, l< :l.f ~.91~.> ~ :i.4 mOi;m1.1I/J.. {(l ,ll mOamol C,1" 1
`
`(:).G m()~nwl Cr-)
`
`)
`
`Cah·ium U/1/(,t/(/11
`
`UO.\J!)
`.'i(lfiitllll /,(1t:U1W
`
`1
`~:J .1/ ... ~t.l<J(_ll'.~I .., r,r,,;i~ mO~m,,l/1, {(27 .M mO:mwl No
`)
`(?.7.li(l mt}s111(>I h1,:l 11!(;)
`112.(){i
`
`'l'ht C,1(111 o,Jm11!Ar c1111cl•11Ltnt.im1 1.,f t.ll(t fi~e $l)lul.1!a in th,, Holulfon is
`li2!i,1, in J(Cllxl 111trt•c1n,:u1. with 1h11 l,1lw,l1,d lilt nl o~lllolnt t1>,11•{:11(.mlir,n 1,f
`111>1w1,xim11tt,ly /i7A mOamtMI,.
`The mOanllll<if 111)cli11m in I I., of the aoh1(.ion i~ U,,,,111rn llf Lhl: mO~m,iJ
`,l( J.h,, i1m fr6m •od ium d,loridc 1111d ~l)dium lndntc, ic, 102.<Sf, + W/,6Ci -
`J.:IO.:l:! ,nOmnnl. Chlorid~ ion~ 1:onw frmn th1, •1vtli1m1 chk,ridc,, pot,tssi(cid:173)
`um ch!orid111111d ct1ll'i11111 c;h111rid1\. 1.h,1 l11lfil osmolnr co11c1111t.rutio11 hr.ill/!
`Hl:.!.6fi •I· 4.0i + :rn ~ I Io.a 1110•1m>l, Thi: ,1,O1:nh·,1 w,lu~~ of poh1aaiu111,
`,~1lch1111 nml luchtk or(, c:,1l1~11lu1ecl u, be 4.02, \ ,IJ 1111d 'l.'l.ll<>, tc~11cd i,•~ly,
`'l'h11,:, with 1.lu, poRsibl~ 01u:01,tio11 ul' r.1,lr.hlln, tho1·c is clo~c 111:n•~mct\l.
`with 11111 lnbclcd mr•;q ,;~mll!111 or ,1:1ch or th1ts~ iou~.
`The osr11olutity of 11 mixture of complex compoflitkm, such
`au nn ent.eml hyp<!l'olimcrntation fluid, probubly ('.Q.nno1. be
`l:1.1kulat,ecl wit.h Qny 1wcoptublo dc,:ree of c-Ottllilll,y smd,
`therefore, th11 oxmofolit_y of such pr~pnml,ionij prob11bly
`nhould Im dHtern1iMd 1)XJ)Mimonl.11\ly.
`']'he opproximnte OijJ11oh11·i\.y of mixt111·cx of two ~Q)utfona
`cnn he computed from 1.l1(l tollowing rnlnlionship (I.Jw 11H1t.h(cid:173)
`od i,1 lrnown mi 11./lig(lli11n medi11/.)
`·
`C)ljl)\" X v" mnnb X Vi,
`osmnn•i = ····· ............ ··········· + -·--·······-··-·
`V,;,.,.1
`Vu,1111
`
`V., "' volume of componeii(. a
`V,, •• vo lu me of compornmt b
`Vn,. .. 1 ,., voltmrn of fillnl 1mlulfon
`0lllYI., ,., IIKmlllllrif.y of compoJU)IIL a
`oHm1, "- o~molaril.y of co1111>011e11t b
`oamri»nl r.:t o~molnrity of finnl 1;o)ut,i1.111
`J.•'ot c~1>111plt,, to ,:11k11IBI,~ Lhe o,m1ol11rit.y ,,f u 111ixt.ur1, (of liO0 mL of 11
`!!OIUl,ion of o~molurit.y lli.i\J 1111,.I !jlll) 111I. ,1f ,1 ,<o1l11t,ion nf' oMmolor((.y 2f,2:
`81i0 X liOO
`252 x 50(1
`o~m.,.,.i "' •-' ··1oiio . + - ··i.ooo···
`"' 425 mOijll)OI/L + 12(\ mOKm1)!/L "' fl(>I mOHmol/L
`T hi~ t1x11mpll• il1U1,t\;1•1~lc11 the e@c of c11k1llt)tin1( t.h1i 011mo•
`ti.city, by u~e 1)r (1amolarity, whon uolulioni, m·H mixed. Such
`11 cnlculution would be much lc»u vnlid if nsmoh1lity v11h10~
`were \tsccl. }i'rom the 1>r<wiom1 oxnmplo one cm, IJ()C how to
`colculnte t.he npp1'(lxirni1to effect if an 1)ddit.io111il 11oluto is
`oddcd.
`
`Undosiroble Effects of Abnormal Osmotlclty
`
`011hth11lmic Mcdicutio.o-·-lt gcncrallv h11ij been MC0pt(cid:173)
`(:d thot ophthalmic prepm:atio1111 iutemfod for im;tilliltiim
`
`FRESENIUS EXHIBIT 1013
`Page 307 of 408
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`

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`TONICITY, OSM01'1Cl1'Y, OSMOL/\1,ITY ANO OSMOLARll'Y
`
`1485
`
`into the cul-de•·~m: 1Jf tlw <IYO i:houkl, if pn1~1ible, b<i upproxi.,
`JI, nh10
`mutely i1mtonic (,o ow,id irl'italion {~ee Cl111ptcr 813)-
`hn~ IHH"1 l!f,nt.t!U lhot the nlmomrnl tonicif,y of c1111t1wt 1!!1\H
`l10luf,iom, cun cn,rnc the len~ to ndh1we t.o t.hc l!y<\ ,llld/or <:11111\<:
`bur11i11g or <l~yncns mul photophc1hi11.
`P11ronto1·al Mcdit:aUOJ\·-•-01;1motici(,y iij of grn11t, impor(cid:173)
`tance in pnrcnteral i11je1:tioni::, ilsi <iffecw dD1>cnding on t.he
`clegrt:c of clcviation t·ro,11 lmiicit.y, t:he 11,mccut,rntion, (,he
`locution of t,he inje1:t,io11, tho volume inji,cted, t he ijl)l!!!d of
`th<: inject.ion, 1.he ropidi1.y of dilut.1011 ,rnd diffu11io11, (\I.e.
`When forn1ull\tit11t po1·1mf:or11l1,, 1<1>ILtUc)1ll! otherwi110 hy))O·
`tonic u~unlly hove ~hoir tonicity 1Hliu11t.11d by Uw i1dditfon of
`l·lyp1;1rtonic pnrenl,eMI drut-i
`dextrose <1r eodium c;hloriclo.
`Bolul.ion1:1 tnmwt, be 11djuntecl. Hypot.onic m\d hyp<o·tirnic:
`solutioi11; utiually ,u•1., ndmini11t1:r~d ,;lowly in Hm!lll v\>himcff,
`or int.o u httg,i v(iin i;uch llff Uw 8\lbcl(lviun, wh,~l'l! dift1ti()n
`11nd d il1trihution oc:<:ur mi>i<lly. Solutions thllt dil'fo1· from
`tho 6ti.rum in tonid1.y i.:1nw1·tdly nni 11l.1itcd t.o cl1~1~a t.i~ijllli
`irritation, p1iii1 ()ll inj<,c:Lfrm 1)11(1 ol<'lc:1,l'Olytc shift:!, tho (!ffoct
`d<'p<'ndiol{ (Ill iho de~•'lil<i or (fovi11l,1()1l from toukity.
`l~)C(:eijt;ivo infoeion (lf hypo(.C)1)i(: 11uirls mny cause swelling
`nf rnd blo11d <:dli;, h,im11lyi;i11 Mui ,v111.,~1· invtmion of tJw b!Jd,v\;
`C(illH i1, Jfl:lllllrt1l. Wlum thh, ia l)(!,YOncl I.he body'.~ t.oloranc,i
`for wute1·, W/l.t.cr intollir,111.ion rc1iults, with co1wul1,i()n~ ,1,,d
`<1domo, euch 1111 pulmon11ry edema.
`llxcc11i1ivo infunion of i.~o1:onk fluid~ <:till couMc nu incrcnMe
`in cxlrncollulm tluid voluml.l, whid1 1)un l'C!llll ~ in ci>·c1.1latory
`1>v()rlo,~d.
`Excc.'l!livl• iufrn,ivn vf /i.yp,1r1.ouic. lluidll le1-1d1, lo a wide~
`variety of cot))J)licutionl'I.
`l~ol' example, the ije\jul!IJ<!<i 1,f'
`events whmi tho body ;,. pre~<mkd wit-h a lnrtic intr,).vc1nou11
`load of hypcrt.oni<: lluid, rich in dcxt rmw, i1:1 m1 follow11: hy(cid:173)
`pcrglyctimin, !{ly1!oeurin nnd inl,mculluJro· dchydrt.,tion, <)~ (cid:173)
`motic diutmiis, 101:1~ of wntnr nnd \ll1,<:trol~•t,e1:1, dehyd rnt.ion
`and <:0111t1.
`One Clll.l!!<i i>f orm1otic diurc~is is t.bc illfuaiun of dcxt.rn~ci at.
`11 1·111.e rll/11,er t.hnn tho nhilit.y of the Jl1ltfo111. t.o motllholizc it
`(llfl ((l'Mt~,r t.h1111 pcrht11>s 400 l-<> 600 m,;/k!C/h r for on ndult on
`1.01.111 l)t\l'<.ml<lrol nutrition). A h1mvy load of nonm1!t11boli:m•
`ble dextrose increnBci; t,h<'. o~m111.idt,y M blo1)d and nft,s 111:1 n
`di uretic; t.l,c i11crct1ijt1d ,;oh.11.~, loud rnquiro~ more lluid for
`oxcroti1.,11, 10 to 20 mL of Wl,ltllr being required t.o cxtt(!l,e
`co.ch Jil'O.m of de~t.rllij(;), Solulion:1, such 11~ those for tol,t\l
`pnrcnternl nutrition, .,h,,uld be 11dminiHl.t•r<•d by 11),11u11:1 <>f 11
`mctcl'cd coo,;t.11nt.-i11fw1ion ar,1>t1mtus VVl!r a hmgt.hy JHll'iocl
`(u11u111ly more thon 24 hr) to nvoid ~udden hypln'1.11.1iuof.i<:
`d<~xtrose 1011<111. Such il<1lutiom1 m11y <:nusc o~mot,i<: diurni.is;
`if thit1 occu1'8, w11ter balt111ce l:i likely to bo(:ome norrotivc
`bc<;tl\lllC •>f tho incn,nsecl urinary volu1m1, and eltllH,i·olyl.H
`duplet~Oll may occur bec11uae of exc1·et,io11 of' 1wdium 11nd
`p<Jl-t11.1i;iu,11 i1Mondt11·y I-<> th.\! t>1:1motil: diurelji,;. If sueh cliurc ..
`iii~ itt l'J'Hltk<,d, body wt1i1Ihl• fall,; 11bn1pt.ly mid !litJll!l of doby ..
`dr1.1t,ion 11ppflllr. Urio(:l i,ho1,ld be m11111~m•(1d for lli i(nr, of
`oftmoti1i dim·c.:sis, stu:h 1\/:1gly(;08llri11111ut i111:rn1ij\cd m'ino vol•
`lllll(l,
`It' tho intravr.noua injection 1·11to of hypm'Lonic solution i!-1
`too ropid, thorc mny be c,1t.1111t,rnr,hk: offcclol! on l,he drculr1-
`(4l'Y and rospirntot y ,;yi;tomu. Blood prossure may full lo
`dnngerou~ levels, c11rdiuc ilTer,ulariti.cs 01· ancst; mny e11!;\te,
`respiration muy b(lcom<, J1h111low nnd irrcri11lur !llld thel'(, muy
`be henrt foihmi nrid pulmonury odcmn. Probnbly tho pm(cid:173)
`cipitnth1l{ foot<>•· i1;1 11 bolus of c1lllccmtrnted l!olut(; ~ud<lenly
`re!lchil1g the myocnrdium Md tlui che111oroce1>tm·oi in the
`1~()1'1.ie 1m:h tind <ini·ot.kl jlim11c<.:1
`Abrupt ch1111171cs in llcrnm l)ijt\loticity 1:11n fo11d t(/ ecrcbml
`homorrhnuc. It ho~ been !!howu oxpc,:imcutnlly that rnpid
`infuc.io1111 of Uwrnpevt.i(; do!J~J; of hypcrt.onic !\Aline wH,h os(cid:173)
`mo tic londtt producf. l.>I >'.111ddcn rise in cer<ibrospinuJ fh1id
`(CSI~) pnii;ijllrC, ,rntl vonou~ prC6ilUrt> (VP) follow1Jd hy 11
`procipiwu11 f111l in CSP r>ressure. Thil'l J>m·timlnrly may ho
`
`conducive to i11lrncr11ninl hemorrhnr,<:, 11~ the rnpid infui;ion
`p roduct•s 11n tll(!rnnar. in plmimu voll1me and vc~,wua pr<lkAuro
`nt t:he sl\ll1(1 f.itnCl the CS1" p1·tts~urii ii; fnllinff. Dming t he
`C!e:W prc~surc rill<:, t.he1•(, iij u drori in hc,moglobin ,111d hcmnl,(cid:173)
`o<:rit., tt\flec;t.itlg II mnrk(!d i11cre11Ao in blocid w,ftmi<i.
`