Boston University

OpenBU http://open.bu.edu

Theses & Dissertations Dissertations and Theses (pre-1964)

1963

Protein losing gastroenteropathy: A

disturbance of albumin metabolism

Bagnoli, Thomas C.

Boston University

https://hdl.handle.net/2144/25760

Boston University

PJlOTSIN L081NG OASTILOENTD.OPATHY:

A J)lftftBANC& OJ' ALBVUIN MZTABOUSM

'111 "' •• c. ....,u JWaNm

Yrll-\i"-i G i..l 'TI?C1::··.n~ . ..-:· ... ! V:OT2U~.

~.,.T' •. J t

JVli;)i03i'·i c,o JCOH':

TA!tLE OF C';ON'J'ENTS

t. Iatroelaction 1

n . ........ 3

m. N•'IID&l A~ia W.bctliull 10

IV. Proteia•lo•iac O&.tb\Oea'-~"•,..,. 17

v. A!W~~aaiou ia l:adopaou AltliJP'ia w•beli11m zo

VI. s lllU'Y 33

vn. B~play i

-

I

ea ••• of "idiopathic hypoft&'ote.iaeml&" have appea,ecl ill the

wpdd J,Ue;q,wre for y•••· 'l'Jteee pau.-. ede:re4 maiDly from

...... ,.,.~ia~q~~l& with .... e··~ of both ••nm albumi~ aacl alo•

t,NUae •. 'l'bH hypo.p:roteia-Ja wae ut eqtlaiuble - the baeie of

.·,~ .

-.._able to del$ae a •••• pOr._ ttl the ••••• pr4JY•ely ela .. ified1 ......,.

• be tbe ••u• of lew protei& lwei• ia then pali•ta, ancl th• 1•••414

that. ••ec•l•• Pl'oeeia loee ialO the Ptf.\l'oiateeliu1 tract wae reepon•

-1·

LIBRARY sos·.-oi": '-'~liVERSiiY

SCI--iDJL_ c::- i<':::DICINE

al'bumta rnetaboU8111, the paper deale with normal alb11111iD metabollem

&Del with "idiopathic hypercataHllc bypoproteinern ia ", which evea­

W&lly becCIIIIDee ''pi'Otain lo.._ peboeateropathy". Finally, there te

-~of the bocly'e ,.tfort!l to c:ompeaeate for it. exceulve

albumS. lo••••·

II

To uaclerstaad a syndrome lCM "protein-losial 1aetroeteropathy",

which looeely defiaed is a aynd...,e ltlvol9ba albumin metabolism, it

l• nec:eHary to measure c:ertaia paru:netere of albumia metabolism.

Ul I taBled albumin (R.lSA) le the _.lnstay of the common cllllical

(TEA}, &ncl albumin wruver. Two.lilaeic methode ueed are Sterlinl'•

Extrapolatioa Met)a.ocl, aad the ••tenilill&tiea of urinary radioactivity

a;creti-, baeed. oa Be:reoa 4tt al. '• ....Uibri~am conc:ept. A diec:uerioa

of theee metlaod.a ta tmportaat to tudicate some of the faetore that com-

pltoe.te the b•etaee• of quadtadaa albullin metaboliem, and to lay the

fo.-uoa for aome :rema:rka c:o-ernilll alb~~min metaboUam that w.ill

follow. Oitlin aud .r..-ay(l), -"* more rec:etly, Beeke et al. (Z)

uaclerly tll.-.

-3-

If R.IIA i1 to play ncb u important role in the common medt.od•

uecl to m•nre albumin metaboKIDI, ceraia a .. nmption• muat be

va.lW. Ia the firM place, the la.'Deled potein mu1t act Sa vivo a• ado•

1..-ou• a.l'Dnmin. Mcl'al'lape(3) elaowecl that uacler defined condittou of

fl'ac~tion ucl. labellq, kJUSA bebavecl idatieally in vivo with albumin

W.•yathotically labelecl with c14. (Tile lllbltla&tton of c14 for a&mral

carbon 4oe• aot .qaifk&Dtly alter protein moleculea.) Othen o'Dalnecl

eim.l.lar renlu ln experiaaenu COII!III&rlnl R.JIJA a.ncl c14 in ra~tt.<4) &ad

rat1 (t). J'lna.Uy worun com,.... eel the fate of R.I8A and a commerclally

IJ'.,..red -man ,_... 'It tamia ia a patiat with conaenital -.lbumi•

alalia, a.ncl fouDil tb&t tbl• pat._ a m.WUc apparame wa• UD&ble to

4Ufw•t&ate be&ween the two prot._,,, 7). A IICOM requir.., .. t i1

tM.t "'- «J .. raclatioa pi'Otiucta ot R.I8A mut aot be lncOJ'por&tecl into new·

ly fol'llllecl .acio1.-u1 a.lb\I!ID.in. Cob• reporu that there ie ao detectable

incorporation of tl:sl lnto MJWly 1yathe~laecl proteln(4). L&1tly, the

radioactive tal muat be exol'ltecl rapidly and completely. II one admi·

abten lod .. lNlere the injecUoD of !tiiA, oae can block thyroid uptake

of t 1U eo that the body will excre.te 84,. of an &dmi.nllterecl do•• of NatlSl

in 24 ho\ara(9), ancl v.r .... Uy all of ... in, .,.uo). Thil •mall las ln

uzUa&ry excrettea ot 1'131 11&1 eome *eoretical eiliill'icance in tho11

matJaode of m••arlq albumln metabollem that dapend on determi•tioa•

of l&l'iaary rad-ctlvity. H-~~rer, tlte du•ation of the cli.nlcal emdie1

unally mitiaatea, for practical fiiU'ptN.ea, aay error introduced by

dlia· -...u laa ia 1131 uereu...

~ lirat method <IW.loped to maaure TEA and allNmia tul'll•

-•r with JUSA waa SterU..'• &.tn.polatioa Method (11). Sterliaa

«Nal•• altu aet dlffv.•ioa of !USA ftom the ~ama baci cealtldl __.

tla&t lUSA '• bac:U.Ol•ate of ... .,dlltioa appared to be oq•l to ita

frat$io~l·•ato of di•pPaQD.Ce fii'OQt plaema, ~ theae obe.,..a•

~. be dll'riaed a m-.. of a~>•~l aa&ly1ia IH. ealc1&latta1 dle

.-raqacular • lat._,...w.ar &w.i'-tioa• the total exc-..able al ..

lM!am<la, pel the ralf of allNmia d .. nilatioa. He plotted the lo• of tile

pia...., coHeatqti,oa of liUIA ow.•• aa a .fqctiq of the total ....

......... va. time. Aft .. tiUJ thlrcl to aiath clay, the pia-a diaappur•

of 1101••$$• of IU8A. The M1f life of !USA cu be calculated from

•• ltnipt llae ~-of the C\lft'e b., aelactbll a Ji'f'OD pl&ema COD•

• ...,..,._ - the .._ .pd m•n•iaa the time it aha for the coaoentll'&"

U.. to fall to eaa _., thi• • .-.. 'l'lte lracti-.1 rate of llear&Uti- .or ~

I'Tll. o. 69J X TA I 't l/2.

-5-

tho at-.dy alate the J'ato of 4oa.....,Uoa 811ual• tho rate of aynthoala,

eo that a: meaauro of albumia ca:tatioUem ie aleo u indeX: of ita ayn•

thule.

. ~ ~

time, the lntercopt become• tho .-.ceton of tho total JUSA pool that le

111 tta• plae~Da. · ftl.a ia true oaly if oao a .. um .. that illataat&Deoua

diatJ".iltution of lUSA throuahout the lV aa4 EV apace• take• place lmm•·

dlately after llljectiea, i. e. , at aei'O· time. U oao kaowe the traeUoa of

TEA coatailled ia tlao piaoma pool. tho TEA ie tile amount of al1Nlraia ill

tho plaema di'riclod by thie ~rMUoa. Plaema albumill concentratioa

multiplied by plaem& YQNmO &ivoe the amOUDt of albumln ill plaem&.

neoua a .. umptioa that after tho lflaema c•rv• beco. .. a etnlpt line,

alellDiia aa4 IUIA flllfueo iato *• EV epaco, c&ualna a riee in EV

IV pool. 'bat in the mOIII&Whtlo, two tlliaa• occ•r. Tho body d .. ncloe la·

llolod albumia.,.. ,,_. .. 1.,. now ..a.bolod abl\ilmill th&t pae••• direct• ~

ly iato ••tv pettlwitho\U ftret a•lna to tile EV pool(l). Thue the apocl•

-6-

!USA. AI thia pMCeae datlml .. , .... apecifie activity of tlle EV

actiYity fall• wtt1l tile •••••ttn IUld tla• replacemeat of IUSA, tlla

apeeUle activity of Cbe albtamla 4Uifuaiq from the plaama peol ltlto

tlle J1:V •PM• will f&lla aa4 aa ·~ ll'..Wto the apecific activity of the

J1:V apace wUl f&ll. How ... u, -.c• .... EV apec:Uic activity •c..U

IIlah" the a.,..ti.-e elope of dae ..a..liii!IU- actiYity curve, eo daat EliSA

Furthermore, the. latueept cl . .mecl hom Cbe atl'&i1bt portioa of. tllta

C"tJrve will bulicate a apuri-•ly low ftlue for dle fractioD of _.,,..,_.

al~laeiattq ia tll.e IV epue. 'l'llle, ia tara •. will t.rce tile ¥tim&-

tiOD of TEA up .. ~eely hip \f&luea.

A aecoacl .....,., tile ~~tWlilt!'lwla metho4l(S), via\lali .. a tile albamia

pool" a two ceaa,..nmeat opea ..,.tem. The tr&(ler l• iatncl\lucl bat o

tile cemr-nmeat Cllat ia opaa -that la, iato tile ilr.tr&Y&ac\llar ar-ce.

eMI'&•\f&....._:r .U !aln...,•Mlazo al'"-mia ia reU&We ~ &lbtii!Dia Q.ux

betwe• the ..,o comr-l'tas•t• doe• Mt OCCNil'. P.aoa(lZ) -rked out

-7·

time and to use thie fact to plet the illtravaacular and extravaacular

albumin coneatratioas, and the total exchaqeable albumin.

Thel'e are diMdvantaa .. to thie method. In the firat place it

aeeumee rapid mixl.q of lUSA· ift the ..Uavaecula:r albumin pool to

aive a ~lform epecific activity in tit pool at equilibrium time.

However etiuiie• oa ~ah indicate that there are multiple extra­

veecular compartmeate excU.nataa with plasma at dHferet ratee< 11• 14).

Othere conelucled from tacer experiment& with RISA that a kinetic

aystem for JliSA meW.boli~m coataine at leaat three exchanaiaa com­

partmeata aad that evea dlie 18 preb&bly an ove\_,eimplifieation(lO).

C...aicleriq the di1tribution of RlSA ae occurrina in a two compart•

meat ayetem meallB that the meth04l averaae• the equilibrium time

for all pu;ta o£ the extraY~t.ecular eye*-· Thoulh the error iatrociuced

will be 81DIIll in the normal m--. it •Ul Jl'OW increaainaly lal'ae a•

RISA half•lile become• ahorter.

Oae can determine R.lSA turnever ratee by meaeurtna the amount

of radioactivity excreted per clay in the urine. Iodide dietribution i8

relatively rapid(U), aad urbl&&-y excretioa relatively prompt, eo dlat

urbl&ry ra4ioactivlty will parala.l.the 1-el of radioactivity in the com•

partment in which R.ISA dBJriUiation occure(Z). Since urinary radio­

aotivity eurvee cloeely foll- c11rvee of plaema radioactivity, catabo•

Uem proRbly oc:cnare at a eite cordlJUOU• or in rapid exch&nae with

·•-

the plauna computmeat(lO, 16). Taa only aeeumptioa iavolvecl

ie that the epeclfic activit)' of al'INmift ca1&bolisecl is the •~e ae

.,._., of lliSA 'bnku dowa 1ft the maia eite of alaumia cataboliem,

'bollylUSA • PTlt(T) • a-rial Ia tile uriae per clay. A'b..U.te

1)

2) J'TIL(T) x TEA lOCI

Cohen et al. (11) nowecl that tu.II'IIOver ratee, d&teJ!ftliQed by m•-

a\lrlat ariaary radloactivlt)', eom•u lavora'bly with ratu calcalatecl

by other methode. Tile meaa ..Uu lor alaumla turaover rate by four

m...- locWiaa the uriftary excretioa mctho4 ie 185 ma/KJ/day

whit a ra111• of 116 • 157 ati/KJ/ayC17J. Thle aa:re•• with Beekea'e

-·-

.-_.,;,_

&ad wa&abel.S al-.,ia -.ad dlereloll'e will ao~ al~er epec:iflc activity »y

i~e.U. The ..Uea~ to wl'ddllUSA la 4tlut..S depeado on the ra~• of

Tlae uility to m•••n bedl .,. •• ,. aad ..... dation ill patieate

aot ill -.atllttrium •• m&de it po11lW. loll' iav••tlp.W:n to eacly eevere ..

ly JWOt• 4ql•ed p&tieah. Pl'eviou~y it wae aec .. eary to keep aa

ladWidtaal .ill equllt'-rlum to ~ We albumin metabeli1111, nt til!• wae

di«tnlt 1o J..s&fy ia a dePl41M4 paU .. t. N9w tr..-eat &ad etlady may

'IMaia ........ .

-ao-

m

The adv._t of radlot..-pee,..,_e made lt po .. ible for workeu

to laveettp-.~aumaa prot.m m•'b4llt.em. Ia 1914, Miller aad hi1

co•worken ttltclwed tlt.at Uvel', pel'faled wltll blood eoataiaiat cl4

ly1t.ae, pl'Ciftced N•ma protem• labeled with c14• He couluded tlt.at

liver pnclucee tile pl&ema &lbumia. totetller with the alpha aad beta

tlo\Jidt.ae, &ad fllwtut• ( 19). I'I'Om ito iatl'allepettc •it• of eyath .. ie.

&lbamia pe•••• clb:ectly lato tbe $abavaecular epace, where it il

ettblr Hat oa to the extl'~ular 1pace, or cletradecl.

The wicleace for the -traneeular lliltributioa of albumia ie

maailold. SterU., •tudied tile rate of dilappearaace of IUSA flrom

tbe plaema, a.cl 10111ld tlt.at altar • iatrauecular iajectiea of lllSA,

tile labeled albumia will dtaapp.- Ia nch a way that ita rt.te of decUae

le moet rapl4 at the oaeet aa4 clecrea••• aradully with time. The

lr&cU.. of lllSA let.Yiq the pla--. .,.. •• peraait time il areateat

aoea after iajecttoaaad llecrea ... t.lymptottcally to • eoa1taat nlve

-lo-A

:r•che4 •om-ure between tile ~d aDd aiath day after b1jec:un.

DllriaJ the firat f.., df,ya, the fractional rate of diaap,.raace of lUSA

bom die plafll)a ia ar•te• tJiaa the fruuoaal rate of diaa,.ruce

of total retaiaed !USA, wldc:ll iatllcat .. that the rate of 1o .. from the

plum& la r.Iatively jr•tu thaa tile rate of total body loa .. a. :Diffu•

••- of JltSA lato dle at;ravaacular ait- aceouta for the rel&Uvely rapid.

pla81!& loaa. (11) UaiaJ the Coo&• aatibod.y tec:batrtue, Ciitlia aave a

albliiiDia &1111 odler ,.,_.,. proteiDe ia the cODDectlYe ti.ane, inter•

atiti.al a~ea, aa4 the lym ..... tlca ia eectioaa of vadoua humaa tianeatlct).

Furthermore, JUS.\ hae be• '-1IDCl botb ill die tianea<U) &lid ill aamplea

of lymp~~(l-&) fir- aabnala lll&t had beea atvea iatravaoua iajectiOila of

lUSA. At the aama time, l'ecerat atu4iea iadicate that the ratio of ..._1

atl'&vaacular to W.avaacular .U.Umia ia ia the aetpborhood of 1. 5,

a.d. wriee between 1.1 &lid 1. '7, d..,ead.iaa Oil the ••Qaod of d.etermiatioa

4«<..17, ~1) •

.an........-r >epace ia a reveralble .... &lid tllere i.a ardyaamic: equl·

ll\1riW111 betweea tile two proteiD poole. Ciitlla aDd Janeway ehowed. that

wltea epMiflcl aat&bofllea were r-..M from rabbite 1 blood eitlter by

.--...e tr&aef1&eioa or 1Jy re&ctioa witlt lte uttaea. th4l ooaceatratioa

of dae uttbo4r nee to ... half lte fwmer le¥el widaia 18-14 heura(22).

-11-

p&111Deld wtU make lte.U f.U ia dae eilh•r compt.l'tmont. Taylor

ebowecl that dae aiMu:nla rearnecl to tJa. pla.ama tp&ce via tlao lymph&•

tiu, whea he wa1 alll• to cuaUect f&'Om the tlaoracic net 90S of -

emOIU\t of JUSA '-lectecl bdftmutc:ularly lato aa ilulivt4v.al<U).

Al.U.p alW.la mov• '-,elY 'b...,.•• the EV aacl IV apace• aacl

a dyaaratc -.wubrhalll •l•u betweea the two protem poola, data equi-

albvmia occ11n either ia U.o iatftvaec•lar apace or in a compa7tmlftt

ia l'&pill equillbdUI&l wltla it(S, U, lO). :.:..actly where clearaclati- takea

place ia ~ tlefialt., ,tbnP tholddaey, the liver, the reticlllooado·

thellal aya&on~, aad ru.Uy, dle p.atrokrteatlaal tl'&ct have boea Uftder'

'1'ho role of dae lli••Y ie mi,. ... al, Kat& allowecl dla& DOt oaly clid

nepilS"ectomlaecl l'&U 001atiaue to 'break clewn 1\ISA (U) witho.at any cle•

cr••• ia thl uto of cata'boUam<16l, wt that a perfuaecl kidney prepa­

l'&tloa decR4ed oaly 0. lY. of tile ltadtoal!Nmla preaentecl to u(ZS).

Tllellvor'• l'olo ia al'bUI&lia...V.'boliem ia not cloar. The work of

Oltlia aacl Jaia aro.p ilulicatecl .... the U.u waa an important alto of

ct.,,...tioa. ll•ection of 40fa of 11a• liver dopre1aecl cata'boliam by

&04Jit. •·• liv.., recODer&tecl, allmmin cataboliam returnecl to normal(Z7),

Oa tho ••r haacl, •timatiDaa of tile liver' a part Ia al'bumla 'br•kclowa

-ll-

ba1ecl on .,_fu•loa ~e• do aot •pport a .. e fiacliq•. A perfu111Ci

rat U..er pre,.-.tt.oa. with 10841 liver fuaotloa •• ••timated by BSP

'""' accouatecl for oaly 1 ~ of 6e cact!laa1ea'ble albamill tv.noYer<la).

U•iaa differ.u teolual41tu aad •tHNIIlptioa•, Coaa &ad Qorclon were

able to fortUy alaeae l'e.-ak• wfA ._.lt•tltq tU.t aa appareatly faac•

tioe'•• l't.t liver anCN!lted fer lW. of a11Nmia tv.raover(29). Eva if

OM JI'Utl a 50~ tldelt ta alae fuaetJon of a pe:rfuaecl Uve:r •peelma.

the U..er'• role ill allrimmia u•hollaJD uco:trtliq to the•e •tu4l•• -w

1till aceowtt for no more tU.Il '""·

Blockacle of alae l'.eicnaloeada•·•U.al 1ypem by either thoretra•t(lO)

or ...,,._(Sl) dou aot U.•• aay .U.Ct • the nte of homolopu• alw•

'nle pt beeaae impllcata4 ill allNmia metaboll- who '-••ti­

pton attempted to 1 1 pl•la •• llypoproteiaemia oftea a .. octatecl with

varW.• ..ee...,..iu .. the lllut..Qf p•t:rotat .. tlftal p:roteia lo••·

n ........ their .U.II't• it •• 'becolle, ........... *t.t there is e-.idvahle

ht•e of plaama , ....... iato the ,.. ill aonnalladhtldual•. aad that

neb twoteia l_,..Je i• put ol•ftllal alhmla metaboU•m.

AlbGmia ,.. ... tato ae ,. fi'Olll the ... uvary 11aad •• (U, ss, !4)

the biliary taou. (SJ) the 1a1'1e bowel. (S6) &ad ,,._ the •tomaeh aJMI •mall

~tial. TIM lr.tte:r two •IMa aaoe tho•• "'"peaei'ble for the major

............... , -'1Nmta ..... ia Ja•ltb aU 41•--e.

·IS·

Holllulcle:r's -:r~ m&de it clear that the stomach was capable of

excrettnc al'b\lmin. Uo us eel a.eetyleholiae to stimulate mucue eec:retion

in dot• with Heicl..-il!V !)O!Itlles. ·Oa paper alectropho:resis, the moat

promiaent sone -• that ot Jl'e&test anoclal mobility, which be deeit·

nated the leacllq.aaedal peak (LAP). Comp&:rieoa of tlleae stripe With

elec.tropho:reUc strips for clot ••rum suueatecl that eerum albumin

formed dae llM.jOr part of the LAP. The intravenous bajection of t 131

tf.Hed ftJ&lae .alMullin, foU..ecl &ty the determiaation of protein baud

ra41oaotivtty on paper electrophonlic strips, and imm\lllOc:hemtcal

proceclur.ea c:Oilflrm.ecl the P&'eseace of a.llmmia iasaatric eac:retiooa

(IT, S&,S9).

W'ettorlors worked with a sort .. of ulcer p&tleata and waa aW.

to thow that the etomacdl we.ll conc-.&ted RI8A and that aamploe of

petl'lc juice buff~re4 ill vivo to pt.n .. t proteolytic euyme activity,

c:•~Qaiaecl al\Nmin(40), Maay odael'e have feuad alttuDin in DOa&cid

pat:ric: J•lce<34• 41• <d.).

Attempts to f&a&llltit&ta. aa.atric allNminloa .. s have been made oa

aab:a&la aad man. HolJaiMiel' fOIIIMI that ACH·m•C\11 from dol• contain•

eel 6. 4 m1 of a.l\Nmin per mJ, (l9) Wetterlor't -rk on11lcer p&tieat:J

11!.Citcated that 4:. 4'l of the ..... "* .. doee of RlSA wa.s elimmated via

tho 1tom&eh ba 24 bollra. 0. ~ . .t tile retaiaN dose W&l eUmiaated as

pl'Oteia bcNDd UMtine wlt.lcb corn ...... s to I. J 1 of albamia in 24 hwre.

hrtlaOJ!more. if tb.e activity p&'eellft in aay form otbel' than l'adio&ctlve

·•·

iodide rep:real!lnia b:reakd-11 p:rod.lcta of albumin, then 4 11 of

albumin per ;14 laou.:ra ia a fair oathllato of 1aetric albumin lou. 140)

The amall ioteatlne i• al•o ao important 1ite of pt"Otein 1o ...

Al'mltroaa et al. fowld lliSA ia the amall int .. tme• of rabbit• that

had been injected previou•ly 'With 1111 albumio(fJ). Ullbera &lUi

hi• auociatea 1kdied tho c:Uetributtoa of RISA in cat• &lUi mice uaina

an antoradio1raphlc teclaaique. with aectlone thrO'II}Jh whole frosen

animale. Not only did !USA concentrate in the gaat!'l.C muc:oaa and

lumen, but it al•o -• vieible in Jlea•y concentration• in the emall

inteetinal wall and lwnen. Te preclude the pouibility of RISA leakina

from the biliary tract into tho ~~mall \!owel, the duodeawn of one ani•

mal -• llaated bel- the comm- duct; the aame reeult1 were ob·

taiae41(.U). Finally W etterfo:ra ekdie4 patlentl undercotna Bill roth ll

procedure• and fnDd tltat int:ra¥eaoue injection of RJSA wu followed

by a high •peciflc uptake of IU$A tty the duodenum and jejunum, aa

well a a by the ato~eh. Aleo .-all bowel eecretiona contained albumta<40).

The qu&atity of allNmin lon via the amall bowel ie lianifloant.

Glflle:rt'• group attribute• 50·'" of the total albumia deara4ation in

eke clot to patrolat4t.atiaal leahat•(4!1). W etterfora eetimated that 4. S'A>

of the i_.ra¥.-v.a radioactivity waa elimiaated by the jejuniUl'l and

a.• at leaet 4 1 &lUi poulbly ap to 6. 1 of albumin were n:cretecl by

dUa rollle in 14 ~,., ... <40>. JeoJottMia and OoJhill eeUmatecl dlat

iate•tU.l albumin leall&ae aecounttld for 50" of hwnan albumin

?

ctea~radatioa occurriaa over a 24 hour perioc1(46).

From Wetterfo~r!.w work(<tO) lU• apparant that at leaat 4 arama

of alblsmin are loat fi'OIII tile a&emull~Uld amall bowel ill 24lloure,

aad thla fipre m•y be oloaer to 9 ar~~ma, if the raclioactivity preallllt

1a foi'Ula otllor thaa fr- t 131 repraa.U !liSA metebolltea. Tile nqr­

mal rate of albumia ctearactatioa in a 70 Ka male ie 16.5 am/day<47),

eo that it ia coD.Ceivable that eaterlc &lbumill ctearadation ie reaponaible

for 25')1. of alwmia 4earMatlOD. aal probably more.

Na .. et(48) aulyae4 1aabie • jej\Jaal ammo acida ud 19\lftCl

tll&t the com~aition of p;etl'ic &D'IIM acida varied accordilll to the

.teat meal liven, but that the jej\IM.l -tonta remained conataat. He

CO!tAluded that eadOi411101l8 amiao acida diluted the maoated amiM

acid pool a• it pa••*' thrwp the. amall bowel, obacurin1 -y of ita

dia~abinl f•tuna. Tile eD~~ueDOua amino acida come partly

from the diaeatiea of pl&ama pl'oWna includiaa all:tumin. Na .. et

poimaJ.&tea tlllPot thie llllteric pHt'li.n lo .. ia a bomeoatetic mecllanlam

t~t-.• -•urea the U.vel' a coaetaftt mixture of &D'Iino acida fer further

proteia ayntheeia.

Til•• it ia apparut that a aipiftcant portion of albumin cataboli.sm

occur a Ia. t1u1 aaeuolateetiaal tract. via a vie the action of proteolytic

eaaymea.

At the nme time, t,lloup, it ia well to keep in miad that a lara•

p&l't of album ill cat&boliiiD'I occurl at aome unknown llite.

lV

h-.ltll -• pocl, b\a who ha4 p..,lorbUal edema in tlle mornin1 tllat

eubalcled duriJaa tlle day, only to rMppear at the ankle• in the even•

ina. Hypoproteinemia, wltll 84(u&l auppreeaiou of the alb\tmin and

l~in fracUoua, w&a preeent. but ita cauae waa unknown. There

waa no e\ljcl•c• of anemia, ma!Dutrition, liver, or klclney cliaMae,

and dle au&llou tllel'efore ••11 .. ted that tlle defect iD thil caae of

idiopadaic ll,_lbumiaemia lay ia proteill ayatheail o• catabolilm (49).

1a 1949, AJ.bl't.pt and JU• 1rwp carried out metabolle atucliea

on a patientwhla icli.Qpathic llypoproteiaemia(SO). They rMaoaed

that the bocly coulcl haadle an intravenoua illfualon of albumin in one

of tllree waya. lt mill" \Nralt to excr.te tlle de&r&dation product•

aa u:riaary aitJIO&en• It mtallt convert allNmia to protoplaamic pro·

taiD. (The fo~&Uoa of preto.plaem require• pboapborua frOQI the

atncellular pool ao that U proto,-em ayatheaie diet OCCllr, uriQ&ry

pboaplaorua excretion would fall). J'iQ&Ily the body mipt uae albumia

to maiataia or reatore ita alltumia pool, ill wklch ca .. tllere woulcl

trnP lutller r••••acl that a pati•t with biiopathic hypoproteinemia

wwl4 ••• bafu•ecl..tQwmia to r•etore Jai• al'bamia pool, •o that the

caW •t the oppe•lk wa• tl'11e. •• barned. albumia coaetlwted. 651ft

Utl11DCUDfed alhllalla 81Jit ctf dle laW.- tlo•e.afte:r 16 days. The

:relatiYfiy lara.• &JIIl~t of al'bllmla d.,.,.aclecllet!Allllript et al. to

ngeet dlat bypercatabollem ,... ree,.aeible for the. hypeprotelaemia

••eruia dleir P*tleDt. The fellowf.Dt , ..... Klasell ••ed. s35 l&bfied

coulued dlat syathe•l• wa_e aot bl.)par..t bllt that catabolism wa• ·~

-....JeJ&ted.(Sl), FID&Uy ia 1957, lobwarta aDd Tllompeea(ll), ueiat

rUt labeled. albllmia, foud .. , lte half life ia plaama wa• reduced.,

ud dlat the allNmla • .,_..~,,i!H' clay calculated. after Sterliaa.

wa• iauea .. 4. Tbla•, it eeom ~ thM lc dlese patieats bypo&l"-mi·

It b...._e .,..,eDt te iave...,atore dlat idiopathic bypoalbumi•

U~Pi& wa• 4ivlJ.We lato Pro l&rp ll'9•pe ba•ed. oa the cief•t ia pro·

tela ••ta-liem reapoae~ for the low albumia levlll•(SJ). Eidt.er

bt.Mfficien& eyatheel!ll or rapid .._radation of albumin .miJht leaclto

hypoallMm:liaemia wldl a low total bcMly albumia. In oae II'CNP, the

-18-

latpaaubolk aroup, daere l• miaSmal ei.ma with aeYere :hypo&lbu•

miatmia, al~ia leYela b.mt ia tile r&IIIJe of 0. !S'ft. There l• al10

hypertuDm&J!Gk ...... ta, hypereYleiMrolemia, aad an elevatld

aellba•ta~ M.te. Tile 4l••~b pniUD&bly due to an iaela.tlli

defect ia the body• a abWty to foq~~ albuaia. The aeeou ar-p, au

the JI'OIIP 1!ldUoh COMeraa ••• h&a lt.ypO-.ibiUDla-ia oa dae ba.1ia of

hypeM&taboU- ef.albumia, wf.tlaout. impaired ayatheai1. Tlaere ia

aiplfkUd e4ema 'llldth 1- ,..,_ alhuaia leYel, but DOt •• '- •• tho••

ae• ia the hypOI•hUc JI'OIIP• hrthennore, the ~ 1lo1Nlla la

cl.,._.eaaeal, iMl~ the patiM; •lob\tlial. SelMim elutleaterol i1 1-

pS'e.- ia low ca._-.atratioa•, w~er the meclt.a.al1m that ia rei•

pequ.&e ... tile...,... cl'ldlt,tioa of preteial, lt ia llOt •peclf~c for

al~ia. Molt of Ae WMk .._ oa tbltl ella•••· howe¥er, waa a.e

witll ~alWmia or albumia ~imUea like :PVP. A• a reault,

.U.n .. ioaa of ldio,.&laic taype._..~ hypoprotelatmia are ia term a

of aUNmia. HnapmmaclobeaUt~;~uta 4•••ocnr, •-ah. but it i• com·

fortlac to llOte •• there are llO cUaic&l f•ture• ••.ociated wida dae

low ilo\Nlilllevela(W).

~"'""..,..__.liRa waa I'MOCDiaed •• dae cauu of tlae

low, .11-ta level• &MD ia a ial'le 11'0\tP of .-u•t• with ltiopatlaic

~ ........ dae r••oa ... tllf _.,ae•ate4 proteiD dea•adatioa

·19-

,._..._. wU!aowa. Ia 1957, Cltl'i11. stulilla. aDd. Halateacl atadi.ct

a pau.t wlao had JW•••* .. wWa 011..-4-t ...tema aacl hypopi'Ot.tll•

cni& a yMr 'b•r• 4•.t•ptaa p....._teatl.a&l aymp&oma of aao•aia

11&\l .... &ad YGmiUIIII(SS). a .. a---.rapbic ......,l.a&tloa of her int ...

tlal .. ti'&Ot •lafa••teci a cli&aao•t•·of t*t hyputropbtc palritta. No••· OYer, • •wi .. of "'- lite ..... • ytel4M four ca•• Ia which the ~Y11!»·

alllumtaemia aa ... lateci wltll ,... 1ly,..U.p]aic paultb Nbaicled

at~ n~ or total aaatnctomy~ They au:rmtaecl, th•retore, that

She petrtc le.aioa . .,.._. •••ect&Mcl wUb thellypoalbumiaemi&. Uaizla

IUlta"'ed •• ..._albumin ta c__,.ttoa wltla sterliq'• method of-­

.-..lyau, the•• au6.or• fcMaad tJ1N •• total ••n•1•1tle albui!Dta pool

waa low ._.. that til• ~1ate4 **• o,f .albumia tl.,l'&dation -• l'&plcl.

FollowiRJ ia,•a• ... u injectloa• ., lt.ISA, there waa Ul appreciable

&DIIOllllt of P"t•la b•'l.acl iocllae 1a a.. ,..tric juice, aacl electreplao•.UC

a.al.,.J• of She pdric ....._. rw.U...t lar1• am~t• of aenm ~w­

mla. llU•~~·u wa• reJa.,.ely lit/de aitro1- in the atoola, the authon

aaeumed that iaua.luml.a&l al--ijl waa cUI••*"· ancl that the r"ulttq

amiao &eiQ were rea'beo:r1t... JW .. umably to ..... uua...t ill pJ'Otein

l)'llflleiJIIIi _.to be_...._. ta the Vine. If excret...t ia the ul'lae, uri•

nary aitJ'Ot• .....W riee. It ta coracetya1tle that thia aame • .._uence of

.,. ... •••••• hip leYel• of ••l.a&ry aitJ'•I ... ta Albrlpt'a patteat•

...... --~ .... lafulioa ., &BiaDtla.

Al._.p Ct.._ aatl llla eowuk•n cllcl aot relate their flaclizlaa to

-10-

bl ••.-rial albluaia lo.ae• late~~~~~ le tile fact that proteolytic

_.YID•• 4-'&.-t tile a11ed ~bllmla, aa4 the re••ltiaa taaJed am lao

Ht.cle or free 1131 paee back lato til• pertal clrculatioa. For tllle r•·

aoa tt i• .,...u.a. to , ... wate autaU iate•ttaal alltumia 1• .. •• by

m•nl'ial f"&l radlou&t.Yity or by -.1r•iat pceua •tel'ieu• lor •. . - ·,,,,.

al)llupla. Gorcloa a&ttlmP' .. to ~--- llUIA '• dl*Yaataae• by

..... ._~ tUl PVP lor tl3l labeled ._tlNJDtaC56), PVP ie a macro•

IIIOloctale wU~ a raoleeulaw Weicht of~'"· 000 (&lamia weipa 68, 000),

that ie ••bl• ba tho pru.ace ol,psoo~ic ••vm•• &ad ie aoa-abaer• .. · ·

tin of PVP w&a c•••• la pe.tt.,_ ha\lia1 ldiopatlllc hyperc&tabollc

A)'pepi,Ot~llt. tMa ill coatrol •'lbJ"'- qr;lth or without ec~.-. He

coaclalded tllerefon tM.t tile l~•tlll&l tract• of p&tiftte with

llUef!ttldc bypere&tabollc bypopi'Otoiaarallt. were peau•ble to. mac.ro•

m.oloeule.a Uke &lllaala. ~· .-lrmed ble re•ult•(51, sa, 59, 60)

&ad f....t ~ lt.lP fecal PVP lftela conel&ted well with low eerum

·Zl·

alblamia'c•c•U&Uo!l•(53).

SchwaPa Mad Janwm 4.,iae4 tile r.tieaa.kip betweea hyper­

calabolic hypoprcnciaemi& aa4 exceuiYc albumillleakal• laW Qlc

pt(60). Tbey etadlcd f patieata wUb idiopathic kypoproteiaemt.a

ueial JlJSA aJU1 lUI PVP, aJU1 -- that all of them laad hypcrcala-

liloUfln& aad hip fce&l PVP levt!U r..,calcd pro-1UlCe4 aaetroiatcetillal

pcn:n•'bllity- to a hip moU.Ular wciabt nbetaace. T- of the••

&wo had aiaat hypcrtropllic P..nti•. Ja three of the four, Qle edema

precttel41!Ci the -••* of clycpeptic eeraplaiate wlaich, when they occurred,

vomlu.&, '-l..tbcr with a tw.tve P~"~ad wcl&ln locc, wac foll-ed ia

a '"" •-*• by depud• ....... Tlaic !act patient had hypertrophic

cubt:ot&lpctr•t.omy, hie ee:nun 1\U...:Sia roce to aormallcvelc. ')llc

e4cma di .. ppearcd, aad a II) I PVP ... t clone three mcmthe poctopcra• -'

tiaaJ. cympt4lmc had bee leolu1d for, aad found. In fourtea of til••• pe.Uatc the compla.kc laacl 'bea cwcre, ucually concictins of ccvcre

cliall'rh•.

the hyponote4De~Di&. It waa &PP"'eat, dloap, that lcllopathic:

l!oypercat&llolic: h,:poprotela .. i& wu aa.oci&tri with diae&ae of dle

pnaoobdoeU..-1 tract.

MakiJai uo of a.ISA, 11Sl PVP, &ad electaoophoretie aad imm~-

petroiateatill&l c:liaordora fo• a....,.m&lly hip p:roteia loa .. • iato

die pt. 'rho Uat of auk diaaua coa.pltcated. 'by hypercataboUem

..a m&l'kod p.-.,.iat .. till&l aJ'bumi& loakaa• ta a loq oao(54), j1aati-

fybla tile -.mo, "protei& loaW, poti'Oeataro}*thy", PJ.'Opoaed by the

!Wet ia 1959(-61). It i&4 .. 4~ ....-ophlc patritia(.fll, adOIIOCI&raioma

of tho o~h(6J.J, .&l&at ".,.nropllic patdtia(!l5, 57), and dutuae ulcora­

tioa of dlo l&•t:rlc muon(!f), S.&U bowel dian•• lac:lucloa roaioa&l

oatodtia(6J), ..... pati'Ooatod*<54), araatalom&tou• ell•••• of Wl•

dotermiatld otioloty(!T, 64), aDd ti'Oplca1<65) &all noa-t:ropi.c&l aprue (66, 6?).

Pati••• wi* ~o:rutvo colUM .,..., &leo lo .. la•t• amoaata of albumia

.tlai1N,Jh •• bowel(6J).

A fiaa1 Jl'oap of patl•w with Jayparcatabollc hypopNteiumla

&all •c .. ave eatut,c proteta.a..a .... ·aot Jaave evi4leace of_, knowa

pltMiateetiaal .U.•••• dlooap their aymptoma uaually iac:lde di&nh•

or atatora-. o...ttmo ct.rialeta. •-u• ef their cllle&a.o<68).

Tiano are two couleMat ,..._lotic&l fi.Ua,a i& •••• ca ....

a eqq3eatal .-ed .. bJrOWa to yellow-br-a pipent involve• the c:­

temal muec~ala:rie(S9, 60, 6&). Micl'OecopicaUy, thie pip eat coa•

eiet!l<l of larae 4epoei&e of yel"-•DI'OWD pip eat iaei4e Uae mueele

cella aad •WUD pb&Jocytee ill the -*•r-1 mv.ecle 1ayer(60). By

hietocbemical•ll&lyeie, tile pitmeat le certti4 or Upofuecin(6S),

1&&'.!1Qm ~- p..._.._ f~.tlmila• pipeat in ekel•l muecle and

ill llvel' celle. Tlltly &leo poiat ••• ill .tllelr brief revi- of piiJrlent.

..._, Pa.ppuhimer aa4 Victlcir(69) d .. uieed a similar pipeat in

"'"of liMl' cirrJloeie, a caee ef cell&c die ease, aad one of mv.co­

vuJa.aie. Dubia('fO) IOliH U4e p~p:~ .. t ia the llnr of patieate with ----alu'oaic Wiopt.thic ~Mice. Jar .. aad Petenen coaclv.de, theu­

fou, Qat *be pr .. -e of the pip .. ia other dieorden aad ita

u,c.e ie a e...-ry ........ aad t.e a!Qc~elated to the pat:ho1eaeeie of

prouia-loeiaa aatttreeatwopa-.,(~9).

~ 17om patl..U w~t typloalaaavointeltilt&l dieeaee, ie the pre-

(!w.my llpo....,ae(6a). Doora r.,orted the preaaee of lar1e hietio~

cytee "With loamy cytoplila.u iD tiM mueclllar layer• of the jeJ-um

J:niKO ... mtalat be t&ktaa •• .pro$cia •• it leaked tbrotap tlae gut wall,

._. f01Ul4'~ lh.oi'CfCeiae t&altd alblunia<W&I lMeed ooncatratad

m tlae .. ceuaC71).

pMtltiua:nta. .U e!aowed dl&t elpte• Jaad ohylou affu•i-• into

tJaa perltelleal or ~nl ca¥ttiae, or "both(6t). Thie fiadma, toaetJaer

lympbatic ey!Kem •u•e•. Chi• dieerdeJ'. They propoee the tei'Dl

"iahltiftallymplall .. i•taaia" for tllla aroup(S9). At the eame time,

..... whh. mucla laueaeed iahatblal lympla n-. "Which, by itaelf

mlaltt accout for tile Iii.._ lymJ1raU.• (T2}.

-as~

v

If patieat• with l4iopat1Uc hypucataholic hypoproteinemia lo ..

pl'Oteia lAte the-pt, l• it &ppl'opriate to deacribe them aa bavin1

"hypercatebolle hypoprokbaemia" • a term aUIIHtiriJ me&eboUc

deetRotloa wbllla tlae UeRee? 'EJUe .-.. uoa w&e poaed at a eym­

po•i- aiveo oa thelcliopatlaic hy,.plotelnemia• at the NatioMl

la.U.tute• 011 H•lth(U), aDd ••"•• te remiad ua that. althoup a•

tel'ic pl'OteiA lo•• i• r .. poa.tltle lor a •ilaiticant part of 110rmal

&llturaia cl.,...4attoa. there ia &lao a. 1ooc1 part of albumi.D cataboUam

ocnniq entlot..,.•ly. The term 'fit.ypercataholic hypop.-otei.Demia"

odaiMted with lov .. tfpteu who la.a.ct the m••• to diati.Dpiah

betwe• a.ot••u• or p.atroiatea.._l protela deatruction, aDd endo­

laGile cataboliem carried o•t by U•••e ... ym••· Therefore, aay•

oae Wbo ct .. -u.ted a qpWly lal .. l R.liA pla•ma coac•tratioa

C\li'Ye ,.., ._.wered to have "Jaypetcat&boUc hypjaprotelnem ia".

Jettl • ..._.y aDd Colhlufi6) denkpod a tec~e that made it

I ... .... I

) )

l,fl,!ill ~!!!!lli ~ffi~i f J e l l "· .' i ! t I J:. ,. I ; f I ! a. r- I ; I = ~~~~; 1 .· ~, ·ll't== .. ·:J ,. 1 '< 1 · • ,. : i I : . f · 1 1 r .. ,-'<'1 i&( ~., ....... .. l ! . : , J I r : • r ! ! i i f ~ ! t : I ~

: i 1 r 1 ~ 1 t 1 ~ 1 i r f ! : i ! t , c & · • 1 I t ~ ' ~ ·1~ ! • I J [ ' i 1.. ;. 1 ' i ~!. a.a. ... fi. a.J

1 ~ I r [ ! 1 ~. i I I r ~ l ~ I i l ·r... J I :I ·' :•!l•:fl•;JIJ 0 : •8 ~ " " I ~ : . • r ' r l ~ • g l f .. I a • ' r .t • = . . . r .. • t .. • ft .. g ! ~ i

• s[ tl!ol •=••f.e•sea"· 1 !' I i i !fF ~ 1 l!i~it. !1 ~~ • i l" • e ;-(i :,.'l!J ·~r;- !.: :. r~ , • o. • -.c s yo I e. • ; ~ e r 1 • ... • fli' t&i••"' ~-~·· • ft. .... ;: = i :' ': ....

I I

\

.·.--

pe:rceat of the ia,IMted lloae of. ralllloe.ativity. EDiio&ellOU• turnover

W&e to.uui. ~y IIUbW&elSAJ the exos.-oua tllrDOVel' from the total

ai'DO!I!er. lilduoee ,.u .... with activeoprotela ~Qaiq saatrooatero•

pathy, the aer'lim &~ill a_. TEA •••• within ao:rmal limite, but

the total turDO'ter w ... lacr•aec! ... there waa a hip aoaenoua

tunover (inllllcative el •••••lY• •'IJv•tn leakaae). Eadoa-ua

turaoYer w&a u.-m&l ·o• elevated..

J:eeJ-obll.oy r•aoaed tt.M ill o:rcler to maiatala a no.-mal or

el..,.ted ......,._ua tllrM~Hr (knply11la lll•r••ed .,atheaia a•• de·

1~). aad a aormal TEA S. the face of MO auive eaterie l.eaaaa,

the 'body muet aave aywdh .. iaed •"-•Sa at a more rapid rate thaD

aoJ"llllal. To lilt it .uther .,.Y• tlbeltody •emed to maintaia aonnal

alltumia levela by iacr••h• eyatlleela.

Tw.We pati .. ta bad low tcttal -.cu"'•ble albumill &ad eerum

a1Mim1a. Se,_ of •-• Ucl 1Uth eateric pntein loe ... , bv.t 1-

eadOI..,_, tu•..,.••· FiYe oeber• 1Wd a aowmal aoaeaou• cle1ra•

datioa b!at ap.i!l low n4oleaoa• tun.overa. lil both fi'OUJNI with de•

pre .. ecl alMunhllevola. .......,,_. turCIOYer waa low. He eoaewded,

dwlrll!f•ra. tall lt le poutW. to repJ!!t laJ1'o&lbamiaemia aa u effect

of t)ae 'body' a ta.WHay to ,,.. .. ue _..p albv.mia to malataln a

ae..al _..,...., .......,..... lil pntela loalaa aaatn-teropathy,

the body '!lllakaa al1Nm1a D~Jrm&Uy, 1:nat moat of thie allmmla paaeoa

late dl.e pt. laviq little to be d .. •adecl ...S••-••ly. Th•alora,

-aa-

thoro are low ...aoaeao•• tllrn-•1' rate• ia Ch••• patioate. At the

~· time, ._ .-c••••• protela Joa .. a CAllOI a taU ia TEA. Tlaie

of eadoleiiOil• tlll'aOVor. Tlao aatllro of thb meclaaaiam ia apparent

wh• Jee,le.aDiloy ohowa ~ thel'e ia excellent correlation between

tho TEA aad tho n.to of ndos_..• tlli'DOVer(TS).

with a decr••• 1a tho TEA. ~ ad H&a- carried o.t allnuuia

........ otla4lee ill awen childr• with Kwaahiorkor, before aad

after .U.etary then.py(Tf). Ia hotla Aalltaac .. , albu.mia metaboliom

aerum al\Nmia aiMl total bocly aU....ia -• aaeoclated with a couido..WO

tar...,er, tJa•• iae•••ed •- bocly &lbuaaia lft'ele roee. J:aoseno~&a

tu'DOVer wu aot a proW- a .... patiete. Similarly, Picoll aad

Waterlow(?S) fowui .._, the lr~ tllrii&Wer l"atee ia iafante nlfer•

bat 1"- pJ'O.aa•...,la!ltdd.oa wore re4uced by almo•t balf. Apia

the ....... t•' ............... ia .... ••Ill•• probably reflect eado· "'c, •o\,,1\J:-, .. , "/,

Ia all of th .. o ...u ... •• pad_. were aypoallnuuiaeml& with

1ow TEA. ud hacl.a ro4llcod nto of ..,.._•-•• albuaaia taracwer. It

/

~·· th~f{ore, dlat oae ot the W&J'e dlat tbe bMy compeaeatee

lor 1!11\u~tp 4epletten le by depr"aiq ..us..-• cataboliem,

Tlaie t• couletem: 111rith dte eoacept dilat the rate ot albumin break•

fo~r ... ym&tlc br•H-• clecr••••· the rate of breakdown clecreae ...

Tlaue, ... 1e..Je•bii9J poetulatee(?S), --·1' there ie & aeaative

a laMe lHit.w.- ey:atlleaie .&JI4 cl-.raau.. • •• in proteillloelaa

aaetneate:ropathy • a fall oecu• in T.EA. Thie f&U reeulte in a

clecre&ee in eadoa..-e e&t&bo.._, to tile point whore eyadleale can

Thi• ieiiOt to Ay ~.eyatlaeeie cloee ut play a role in the

'bNT'• clef••• aaaiaet allNmla clepl.ti41Jl, Ill fact, a euiee of pa-

tleate 111ridl r.,ioaal tlf,teritle or ulurative colltie &Del hypoalbuminemia

eho111r..S incre&e..S n.tee of alW.ia eyat11 .... (6J), ac:corclllla to detell'll'li•

•tioaa of -.lbwzlla tu...,er' rat,. ..... at .. llWbl'ium. Odaere have

-..,. ._, alhamla turaover le well witbla aormalllmlte(62, 59) in

lwele ia n.~h '-Y pla-apbaneie, • oaly reault..S ia clapl'eu..S

ru.e of cl~tloa, bat u.n ..... tiM rate of albamia eyadt.oaie<76l.

-so-

ie llO:rm&lor .taor ... ed ill paUeate wida pl'otela lo•U.. petroeatuo•

,..,., it • .,. ... iaer••e• to dae nMIPim\IID nt e of 4 ma/Kt,/d&y(??, 78).

1t JD&y be, daerefore, t1aa.& tlltallver r .. pea4• to low alb\unin level•

by lae•••iD& ito eyatluttie Hti..,.ty, IMd tlaat to reepoad maximally,

it ..... \tire• e..Utei• amMat• of ,.. •. tela ill dae bocly pool. U dale

wen.talljt, r .. toriaa dae U! ... l of TEA ill alb\unin cleficiea.t patieate

..,..,...,.. a.lbllaaU. tlanaover • ia eyatlaeeie uc! c!Oirad&tioa. of &1·

bmabl. J .. jeQJlo.y ..... four acla patleate wida albumia aud

' edly aa4 ..._t •..-ua al'b\IIDia aa4 TEA level• were uo:rmal. ID dane

of dae four pati•t• daOI'A wae evWuce of a euet.a.iaed iaer••• iu

~ability, 'b.ecauee aenm a""'-ta level• remataell coaeaat

... , ..... w•••e ia allNIDiu tu ........ (?S).

Ia euJINDary, it appear• tlaat eace..tve eatel'tc proteilld.,rad&• '. ' .

tioa deplete!i tlae wtal body alllumia •. 'l'lle fall ill TEA aacl eenm al·

lNIDia ie r.QMNII ill taae el..._, of eU.a.-ou.• caa'bollem. Thie ie

eoaeiat;jllat ,.,itll Ciao c-.ep& tlaat _..,_. 'br-.kdowa ie a firet '

OMOI' reaotte. Low TEA levele &leo pnll&bly illlai'bit &a otherwiee

amltttW.e ~ill eyNb,eeie, ao tiiiU allMamill eyadauie, ia paUu.te ?

Tbie com~lioa of a .t- ...... ....,ua eataboliem aad an aolive

eyalbeela "•wally· reetoree t.lbaltln metaboliem to equilibrium.

-u-

VI

Radioll,din lMwpeell&n ~e tt ,.eelble to etacly the clpa•

... .._ ol albumia m*"Uem. Tlut ...,. ... ••eel Ia ••ala eaclt .. are

complex. tNt two etaad CNt ae b!t.etc. -.ruaa'• ExtrapolaU- Methocl,

a.d. Bereoa•e ~rium Metlaocl Ia coaj..etiOQ ••• cletermia&tiou

of.,......., re4toutl•ltr II&•• pl'OY14ecl mtach of the iaformatlon COQ•

cualac eyallteeie, 4letriWUon aJid 4qraci&U.. of albumin.

A.lbliunta eyntJaule takM place Ia tile u,. .. , ea4 dietrib\ltlon

belweea the.,.. .. .,.. .... a.d. •travaeeul&l' compartmeata occura

alowly. At .. 'lliUbl'W. tile ratio •' •*ra•aac11l&r to iatra.vaacular

ellowDta le iD \he .,qW.Ol'lloo4 of 1~ 5. CataMllan la lD a. com part·

meat CIOiltf,pou or lD rapid "'lliU11ol'&tiOil with tile iatr&vaecular epece.

Tlle ki41aey &lad retiulo..-tll-*1 -.•tem, •cluai•• of tl:le li·nr, do

ut play aalmportaat part lD allMtml& .-tahollam. The u .. er'• part

ie ~1, blat at mon. it pi'OMWy aocoute lor 1 ... tJaaD SOIA of

~. 1. •kat• of al)Umla bato the pt&roi&&eetlaal tract

.... .-.,for Uti to lOY. of DOrm&l tl'*mia e&t&Mliam. G&etroiatoetiD&l

...,-me• tia .. , the PNttla. ... ea.. ree'lll_, ammo acid• paee

llaek to tile liYer 'ria tile portal ci......_,

Ia PI'C!t.a Joiii•IP*oea&eropt.tlay, tkel'e are exceeeln

allnaDJa .,.,, .. iMD tiM pt ,.,.,.. al'e .... poaelble t.• .._ ... auy

npf.d. ntea .S ~ia ._..._. •• _.low ._. exc ... Hble e.lbumia

!Mala. CJialceUy. thie elS.•doa r..-lt• ia cluoalc fhaetuatS.,

ect ... , itithar eloac or ia ••••••atoa ••• peuoiateeU..l eymp-

-••rdl•--••· Bolly e.lbznia IM.ele etaltllQe ... _.. exce•ln aterlc lo ....

bee_.• .......... ah•ia dep,.,.u~, a flret ollie.- r-.ctioa.

•low• •• .total _..._,.ble u-.ta (lt.Ue. Syatll .. te le aormal or

aUptly iac••aed. ltle peealW. daM tlle depre .. loa of total lMMly

~RD:Iia .............. .,.., .. ........... ,.._ .... ., it ,.....,

Utillt "'UdiDaUy to r .. tel'e uaou aU..ia leYele.

-34-

''

1.

a.

3.

4.

5.

6.

7.

CUtlbl. D., &U Ju..ay, C. A, Some ieoto,a. etuJU,M 0a tlte fliftrib\1-oa &ad me•boliem of, .. .., •. ,..tea., A ... Btol. Wee~, J\lkye. 1!149. 1960.

B"ko, W. L., VelwU.el'; W,, Ool4.,.6y, P. D., Oarby, L. E., •er-We, W. E., -.e.cliU, It,, aacl. Stemler, 1\, S.

••••• oltlU.atliNarla.atabeUea:a u4 dlal'ibutioa la DHDial ,_., a:aale ........ . J. cu.. ttw .. t. 4l:Ullo 1961.

Wchrlaae, A. s. l.OelUnt ftl plaea:aa pi'Ott4U widl "*'•lA*'•• lodlae. lHMa....,, J. 6.1:115, 1911.

Clollea. I. , HoU....y, lt. D., ............. C. M. , aad Mc,....lue, A, I.

m.utb\1-oa u4 elimiaata of tlU aa4 c 14 l&Nled pl&ema ,....._.,.._.. ... uwt. · Btoolua. J. 61:143, 1916.

ca.pbell, It, M., C.dlbertellll. D. P., Natthewe, C. M., aa4 Mcii'UIMe, A. S.

&th"rior of cl4 ... 1111 aboUed plaea:aa pl'OteiD.e ia l'&t. lat.._._ J. 4ppl. lta•U.C. aacl.leotopee 1:66, 1956.

BtatoJ4, H. __. Kallee, E. · eo.,._... et:ulke Oil dle.a.&lf·We of tUl.labeled alb\la:abae _.. ••dioac.We IIMmaa e..Na:a al'INmba baa caee of IIUI&l­.,_.._.,.. J. ~. 11weH. Ska63, 195,,

Fl'e••••• T., ............ C, M. E., W4J'arlal!.e, A. S., BeDbltlcl, H., &ad teallee, J:;

Ala...mta ITI'o•v.t wta tlSl Ia - ualtnuniDeasio lhl'bject. Na.f:luo• 18S.. .,.,.

i

9._, Bereoa. S. A., v..-., R. $., Schrelb4Jr, S. I., aad Poet, 1. / 1'ncer ....... ..._ wlda tUl labeled hva:aaa eel'\11111 albu·

mba: dietd'blaUoa ............... lltadl••· z. ella. ••n. sa•'"'· 1951.

10. X...• II•, C. Q,, a+-. M., u.cl Rall, 1. E.

11.

/

lka4t .. of i .... l ... lll aetabolYm. I. A madaemaSical .,._. to .. Jdutioe;. J. cu. ...... 11:66, 1959.

lterJiat. K. fte .........., ... r.a. ot .. .._alb-ia la maa •• meaaured by tlll ..... allllii.ala. . J. ella. ~~w.-. MtllU, 19$1.

JZ. Peu1-. J. D., Veell• N., &IUl Vder, H. St-ah1 ... erapt., lo .. .-. Sl:lto, 19!1. TUlia . .,_, ~ D., ... .ThiiW&J', C. A.

A ... Blol .• "*'· PhT•· 7:249, 1960.

11. l'l'i .... n, 1. 1. V.~•e&tR\'&1_.1' tlllW4bntioa olr&dloac:tlve iodoll&lecl *""'-la.iamiee.

~ii-:•,lt.m· J. ~ylt.ol. 191:115, 1957.

14 ......... J. A., Jr., Kim, K, S., au Bollmaa, J. L. ·· .................. dll6aaioa ol pNtelD.

Aa. 1. Playeiel. 11.1.:117, 19fl. .

15. ......... N. B., C.."-' B. J),, Hoaour, A. J, , &ad Pochla, E. E. Dl.Uibutf.oa of .Ui•i.i•• ie aaa. Olia. let. , ...... 19$0.

16. Wei'& ... , A. 1. . ,..lMtMYior o11111 Iabell .. pla-a proteiD la vtvo. All!&• N. Y • .Jt.d4, W. 'JO:lt, 1957,

1'1. Cohea, 8., l'lrM¥,1~ 'I'~· aad•J'&•laae, A. S. W•' halil• .... M;klllllt•' u ahmta. Ollll· ... &0:161, 19(.{;.

u

18. Matthew•, C. M. E. m .. t. of pla•~:rellia on.alkmin poo18 in rabbit•. J. Clla. la¥elit. 40t60 3, I 961.

19. Miller, L. L., aad Bale, W. F. lyntllleai• of•U pla-. proteia fra•Uon• except gamma pol!Nlia ttyltvert u•eOt-.. eleetrop}Aore•ia and lydne-cl4

to ~ pla•ma pi'O~ ay.alaeaia.ecl by i•olatecl pel'fu•ecl liver. J. Jbper. Med. t9t1ZS·U1, 19!54.

10. Oitlia. D. , Landini• B. , &114 Whip~ A. · ~- louUAUoa ef 1l.o u lltJ!sau• plaema protem• in the

1\<.t't;., . .-ea of~ IPeu ll!tlat• a• cleaoutnted with fluo­r ... eeai a.otihfMH••· J. Bxp ...... 9'7:163, 195).

· 21. Cohea, S., apdiGhaQiroth, L. MetaWiuD of I U 1-laltele4 a.lltumin in Afl'ic&n •ubjecta. Bdt. w..r. J. 1: 1&91, 1951.

az. Oitlia, D., aacl J...,a.y, C. A. TJJe . .,..._lc ~IJI'ium b.., ... circulatinJ and extrava•­cuJ4,r .,.._..._ pl'ot•••; Scieaee UI:SOl, lWJ.

Z3. TayloJ', ~. w., Kiomo-. J. B., .R.olUuon, E., .R.otlalat, J., uc~ r.,._,,, o . .,,

Lymphtic obftlaUoa atucli..t with raclioactive pla•ma pl'olein. Brit. Wed. J. l:lU, ltl7.

24. Benoa, s. A. , aad YU., .R.. S. n. &lell'lhUiea ottlll i!lbell.-1 humaa •enm alkmin iatro­cluced iato &Mitlc fladd: ¥&!yale of the kiaeti .. of a three c:ODJpar ..... t ... ,....,., tr•e.tu ayat- ia maa aacl epecula­tioa1t ea ,.._ible ..... ol 4-a.....,tlon. J. ClJ,a. lave1t. nzU7, 1.4.

25. Katl, J., .R.o•alold, S., aacl Seller I, A. L. R••• of kiAII!teY ill plaama a---Ja eataltoli-.r~. Am. J. J!llly:.Wl. 191:114, 1960.

1li

16. Kata, J., lloeufold, s., aad S~en, A. L. Ske of pia•- al1Nmta b1-•1111Dwa in tbe body. Fed. ~. 18c251, 1959.

27. Gitlin, D., Kleila'be~ra. J. a.., alld Hqhea, w. L. Site of oatalllolia:n of p.la-a albumia. J. Clia. Iaveat. 37:897, 19tt.

18. Kata, J. , lloeufeld, s., aad Wlera, A. L. Situ of pie fill& al,_.t.p u.lallollam in tbe rat. Ainu. J, Phyaiol. ltOtUCU, 1961.

29. C.ken, s. aad Oordea, A. H; C&ta111olta:n of plaama al,.._l.al by perfuaed rat liver. Blo::kem• J. 70:$ .. , 1918,

)0, Thol'\tecke, C. J., s•uty-. )(., Beaacerrat, B., &ad Ore-. H. I.n.•c;• of reti.-.eaclotll .. l blockade on turaover rate of

:llp!AAii>·~~~Ololou• pla._& pl'ot.iae • mice. ~. Soe. Zllp. Blol ... d Med. 99:439, 1958.

31. Freemaa, T., O.rdola. A. ·H., aad H11mphrey, J, H. . Bl'it. J. m.p. Padt. S9t419, 1958.

sa. O.Uer, J, H. aad lloreletad, O. H. lllMtropho.:ute of ..,u,.~ J. DataUlea. n:n, 1958 •.

JS. J:Uieoa. S. A. , U..elt.lmo, P. A., and Maadel, I. D. latm..-lt.eadcal ••iN of launan aaliva. I. Demonatratto• of eer- t>Hhiae ia ltlaole _. parotid ealiva. J. Deaeal IUe. 19189~. 1CJ61t.

34. Collen. N., Ho.-.wita, M. I., __. Hollaader, F. S..nm allnlalia __. pmma ~bulla i• aormal hUJDan aaetric j'eiee. Proc. Soc. Bxp. B!ol .... Ne4. 109:4U, 1962.

JS. Kata\UU, T. , Aimul'&, H. , .J4111aetoa, C. 0. , and Miyalte, H. C01aeti*"'loa of \tile proNiU.

~ Proc. Soc. m.p. Biol. M~, UU:ZTZ, 1960.

iY

36. SoerJel, K. H., aao lJltlefiUJU• F. J. PJ>oteiu la eenm aad r.-1 mueue of patieata with ulcera­tive coliua. Gut~enlou 40:57, 1961.

37. MeU&atler, F. Tile play:11iolo1Y alll4 tile c~latry of the 1ecretton of a&etric mucue. OaatroeaterolOJY 41:304, 196Z.

38. Hollander, F., aad H--ihl, N. I. Serum pi'otew ia pab~acoue and other eecretioae. Im-

;: He·,;; pUu.tioae ia !'elati .. toc. · er protem loa ia1 petroeateropatlliee. Gaetn•torolol)' 43:75~ 1962.

39. Hol~r, F., UICI Horowita, N. I. hi'UJ &11Miamia ia caaiae p.._.ie aoetylcholiae-mucue aad wJao1e etomac\ aapir&tee. Fed. PI'OC. 19:181, 1960.

40, Wettel'for1, J., Gullbera, It,, LilJedahl, S•O,, PI&.Qtia, L., Blrk.. O., u,cl OUwt.t.a. B.

llo1e of ate.uh UICI amd iat .. tiae Ia all>umia breakcl-n. Acta Med. S.ueMMv. 1Qd47, 1960.

4l. o...lllterc. ll., an4 Olhaaa. a. lDIAictn ... Meie of llam&aiaaetl'ic juice. ~-.. (IAUon) 11411.MIJ 1959.

41•, Olate. Q. B. J. • and IAU..ri, A. '""'" ... e ef a-.n &ltlumia,Jbto the etomach: ite detectioa by pap. elt.;tl'o)llaor .. ie of·pl1tic juice Ia proteia•loeta1 eate.,.pathiee ud P•tr.ic ctac•· Amel'. J; ~;»., .... Die, .:llJI, c.f961. . '

43. Al'metroa~,l'. B., W&raea. S,, aad Taner, H. P-..,a PI'-*M· Vtl. st• ef delr&ciatloa of eei'UDI albumia. PJ'OC. s... Exp. Ntll. U1C1 MM. 103:592, 1960.

44. Ullber1• s., au--. Q •• Jlwal4eND. :e., Hau11oa, E., LilJe!I&JU, s-o. , Plaiatia. L. •0. • aad W.ntedore, J.

The role ol the petHJat.-tta&1 tr&et in *be .elimiMtioa of .. rum -.lbumia. ·

Aeta Ned. s.Htaav. 10?:421, 1960.

v

.r--:

45. Clle-.rl, G., Janaum, S., Riemer, S.

r·

The ~48 traaafer b.,., bloM to Jaetroiat .. tiDal tJ:&Ct in dOJII• Acta Chir. hudiaav. 1Z<~j6l, 196Z.

46. J•~etmoy, K. ¥t•: ucl ~ill. N• 11' • . MeaOIIr-.ent• olgaet"'fttotUsal proteia lo88 by new meduHI. Out l:lU, 1961. .

4 7. Stelaf.td, J, L. Ditt_.'&'.,-~ in t!aUJ albumia eyath .. ie betwe• 110nnal men uctw••• ae ••••He~ witla tl31 labeled a1~in. J. Let., aacl CU:u. Mee-. 55:904, 1960.

48. Nuaet, .-.:. s. Rt>le of cUao•ttve tract ia •Ulisation of protein aacl amino acid•. J. A. M. ~· 164.:1U, 1957.

49. Cope, C. L., ucl 0•6f• H. K, Sttuly of caae of l41111l.daic llJPOIII'OteiaJRnia. Lucat 1:10J8, 1915,'

50, AlbdDt• 11'., .ta.-ttar, F. C., h~, A. P. • The fa.te of 1aw:lau ,.._, &1-.ia admillieterecl intravenouely to a .-tiant wU}l idlo .... tc h,..lblaminemia aacl hypoa·lobulinemia • • ~,..., Ae.a. AIDer. ~ .... 61:1041 1949.

51. Kiae.U. J,., vr., Mara-. S., Tarver, H. McB., l"raata, J,. "-•p.a. E. K., Rtltc)da. .M. J:,, M!oh&ela, 0. D., I.M McCallie, D. P.

SUuliae ia aetlaloaine m _.,Uam. IU. The fate of intrav ... ue • ly ..._Watwecl sU ... !WII!'•mettaloatae 1-. ,aonnal adult malea, ia pMi...&a "Wtb clluale 1!, 41.!."• clieeaee, "iclio,.thic hypoprotei• ~ia" aad C:Uell4al•e eya1d •e. J. CUa. Iaveet. 19aU8, 1950.

5Z. ~rts, M., a.- noaa.-. B. I41ei!Mhic; cu• h7Pucat&~ llnoproteiaemia: by jlJl.Ja~ alb 1 Jill. Brit. M.,_ J. 1:14, 191'7.

IS. lcUo.pe.tllic ll''*"'lllaallaemiu: •14•'•1 •t&U coa(ereace at NatieNl laetltJata• of ~-lth.

Aaa, lat. Mecl. 5·1:551, 1919.

vi

' . .r"..

. 1'"'·

54. J'.Uriel, Q, H., .. lmaa. H. R., Slel•Aier, M. H. Pia-a pntefiu au the J&ttroiateetill&l tract. Mew EJ~~. J'. Mecl. 166:652, 1961.

55. Cltrill, Y., S&erlUal• K,, aS¥J Haleteacl, J'. A. Meehaalem ofhypqprototaemla a•ociatecl with atant hyper~ troplt.y of petric m•••· N_, J:lat. J', Mecl .• 157:,.., 1957.

56. OoNo-, R. S., J'r. I:Jrllldativ. Ateropa41Ly: abaol'mal permMbility of aaetro• latuatu.1 *"'" IO!il••trablo. with labollecl polyviaylpyrrolt~ .... ~cet 1:135, 1959,

57. SclHMrta, M., aDd J'arollnt, S. Protem•1o.mt aaetro411ltvopadl.y: hypoprotela-ia clue to p.llt'OilltoetiMJ.· proteila t.ee of n.ryiaa a.Uol•JY• cliapoeecl by m .... oftUI • a11Maa!bl.. Da•'-t& N. B.t1. 8:1, 1961.

SS. WeW.••n, T. A., ltoiafeld, J', L., Dlatcher, T. J'., D&vicleoa, J. D. , IMMl Goi!Cloa, R. S. , Jr.

Rolo of aanrolate .... l •Y•*-' ill "idiopathic hypoproteiaemia. " Oaetro•hrolftcy dtl97, 1961.

59. J&II'AOIIl, S., &M Peteree-. V. P. how.a•lou1 atoropMit.y. Laacet bU'r, 1961.

60. Seftarta, M., aa4 Jal'lai&Q'I, S. Qaatrolateedaal proteiD lo .. ia idiopathic: (hyperc:atabolic) hypoP"t•iD1t-•ia· Laacet l:JU, 1959.

61. Edlt~~Jri&l. Proteia-lo.U.aca•trooater•dl.y. J.Aacet l:Jil, 1959. .

6&. Jaraum, I., aM lclnrarta, M. Hypoalblmtluml& ia Petrie ca.rclaoma. o ............... ., Slt169, 1-.o .

vii

U. Stoiaf.W, 1. L., D&YiclfODt J, D., Gordon, R.. s .. Jr., &ad or--. T. z.

MeeUat.oo ot byPOpr••• 1 ia I.D p&tleat• with re1ioD&l ................. ...U .. 'colitil. Am. J. w..s. att4M. 1960.

U. Ho--., H., Nlelql, W. T., J•., &H Slel .. Dier, M. H. llypop•oteia..,ia -*edatilaa iate•till&l le.toae, allcl po11lbly ae Ill ao...t.• IQQm proteia loea iatoiat..Une . ..\Dl. J, Mill~ &7:961, 1959.

65. R.llhlalo M. E. , lheelay, 1. W. , Meroaey, Yl, H. , &llcl Louro, J. _.uve eldi'IOp&tlly. II• Obae...-.tioDe I.D tropical eprue. J. La'b. aa4 Clla. Meet. 581902, 1961.

66. Pa•kla1, R.. A. ProMia•loailll eatvopathy Ia •prua 1yllclrome. L&Met &:IJ66., 1960.

67. Loadon, D. R.., Bam,_.., J., &lUI Cra..,er, 8 • ._ .. Rll• .-... u.c •• ,.....oiateetiaal pa-otei.D lo11. lAMet Z:18, 1961.

68. WaWmau, T. A. , -.w.w. J. L. , Dutch••· T. r. , Davtd•oa. J o J), t 4lp4 Ool'4oa. Jl, So t J'l.o

'l'lae m• ., .. autroiateati&Ml ayetem Ia "lcllopatllic hypo­.. ~,:l!ll~-.. ~~,,~'$~i .... 41tl97, 1961.

69. ~--··· A. M., allll Vlclll'l, J, Cenl4 plpeld Ia ...,._ tlln ... ,bt. J. Pa&Ja, &2tl91. 1H6.

70. Dubla, I. N. CJuooalc icllo .... lc j& ....... .bt. J, Meet. Z4cU8, 191t.

11. 9oo• ... L. J,, v&a O.Wer ... H. H., aDd ViDk, C. L. J • ......... ........ ,. Acta Paeclt&t. S0c249, 1961.

72. Jaraam, I. Ua~-- data. 1961. From .Ta..a...i, 1. aU Petuua, v. P. L&Met h4l7, 1961.

·~ ?J. Je-.feebat.oy, Jt, N. ea .. olllypoa.\blUitill ..... ia patieatewith •••noiateatblal ..... , ........... . l.aac« hlotS, 1961.

74. ca-. s. , · .... H&a•-· J. D. L • . ~bt'i"" of albumia ... ..-•• 1loblalirain kawalliorkor. CU.. Sci. 2lrS51, 1961.

75. Pieou, D •• _. WawJ'low, J. c. Tbe .U,.t ot maltnaUiU.. oo the rnetaboliam of plaama &Ul!uDin• cu.. S.t. n:•n. 1962.

76. .......... c. w. 11:. Ueeta of plaama,.ereala •• a~in poola in rabblta. J. cu.a. Jayut. •et60S, 1961.

11. Na~raaa. 1., ~ Tal'Yelt, K. C:O.~ 1t1uliu. oa - tunuwer of aer!Qll alblQllia ia DOnn&l ltrw~ qbJeeta. · · J. ou.. .... t. J5:1161. 1956.

71. Wa ........ , T • .It· P. ....................... . O...etl .,_, ,.., ....... .,, IC. VI.

~- hUS. 1961.

ix