BLOODVOLUMEPRECEDINGAND FOLLOWINGSPLENECTOMYIN HEMOLYTICICTERUS

ANDSPLENIC ANEMIA'BY HERBERTZ. GIFFIN AND GEORGEE. BROWN

WITH THE TECHNICAL ASSISTANCCEOF GRACEM. ROTH

(From the Divtision of Medicine, The Mayo Clinic, Rochester)

(Received for publication December 26, 1928)

Very little investigative work has been published concerning therelationship of the spleen to blood volume. Barcroft, Harris, Ora-hovats, and Weiss allot to the spleen a function that correlates wellwith its anatomic structure. They demonstrated that the spleenacts as a reservoir in the normal resting animal, and that blood isexpressed into the general circulation as a result of stimulation to aneed for oxygen. The presence of a storage function is further demon-strated by the observation that carboxyhemoglobin disappears lessrapidly from the spleen than from the general circulation, indicating thathemoglobin is, under normal conditions, stored in the spleen. Theseworkers demonstrated the greater susceptibility of the splenectomizedanimal to carbon monoxide intoxication. Cruickshank's experimentson the cat indicate that the capacity of the spleen is from 2 to 5 percent of the blood volume when calculated by fluctuations in hemo-globin and in changes in the volume of the spleen.

Observations concerning the spleen and splenectomy in relation toblood volume in man have not been found in the literature. Thestudies carried out previously have dealt largely with variations inthe concentration of the erythrocytes and the hemoglobin, the mor-phology, and the chemistry of the blood. Weknow that splenectomyis curative in certain diseases and markedly beneficial in others, anddefinitely untoward effects attributable to splenectomy have not beenobserved in man, although there has been some question as to whethera factor of safety is removed by this operation.

'Read by title at the meeting of the American Society for Clinical Investiga-tion, Washington, D. C., April 28, 1928.

283

BLOODVOLUMEFOLLOWINGSPLENECTOMY

Our study was undertaken to determine: (1) the blood volume andplasma volume in patients suffering from certain diseases associatedwith splenomegaly, (2) the effects of splenectomy on the blood andplasma volume, and (3) whether in certain forms of splenomegalythe anemia is apparent rather than actual. The cases selected forthis study fall into four groups:

number of cases1. Normal subjects ................................... 742. Primary splenomegaly without anemia:

Preceding splenectomy ................................... 5Following splenectomy ................................... 4

3. Hemolytic icterus:Pteceding splenectomy ................................... 11Following splenectomy ................................... 9

4. Splenic anemia:Preceding splenectomy ................................... 18Following splenectomy ................................... 7

The dye method was used to determine the blood volume and plasmavolume. Congo-red was employed and three to four minutes allowedfor the mixing time. Determinations were made under resting condi-tions without breakfast (8).

It has been shown in anemia that with a decrease in the hemoglobinand cell volume there is usually an increase in plasma volume. Thisis doubtless a compensatory phenomenon designed to maintain anadequate volume of circulating blood. The increase of plasma variesin different forms of anemia; according to Rowntree and Brown, it isabsent or slight in the anemia of glomerulonephritis with edema andin the anemia associated with myxedema and Addison's disease.In this connection we have employed the term "replacement index"to represent the ratio of the percentage increase in plasma to thepercentage decrease in cell volume.

For example, if the plasma volume is 61 cc. for each kilogram(normal 51.2 cc.) there would be an increase of 9.8 cc. (19 per cent).If the cell volume is 21 cc. for each kilogram (normal 36.5 cc.) therewould be a decrease of 15.5 cc. (42 per cent). The ratio is ii = 0.45;the replacement index is 45. This indicates roughly that for every100 cc. loss in cell volume there is approximately an increase of 45cc. in plasma.

284

H. Z. GIFFIN, G. E. BROWNAND G. M. ROTH

NORMALSUBJECTS

Dreyer and Ray have maintained that blood volume is a functionof surface area rather than of body weight. Wehave, therefore,expressed our data according to both surface area and body weightand the statistical treatment of these data has shown a slightlyhigher correlation of volume to surface area then to body weight innormally built subjects.

The results obtained in seventy-four normal adult subjects (forty-nine males and twenty-five females) have been reported by Rowntreeand Brown. The ages varied from, seventeen to sixty-three years.The mean weight was 65.9 kgm. The mean value for the blood volumefor each kilogram of body weight was 87.7 cc. (with a range of from70 to 100 cc. in 98 per cent of the cases). The mean value for theplasma volume was 51.2 cc. (with a range of from 42 to 60 cc.). Themean value for the cell volume was 36.5 cc. for each kilogram. Themean value for the blood volume for each square meter of surfacearea was 3278 cc. For the plasma volume it was 1920 cc. for eachsquare meter of surface area. The mean value for circulating hemo-globin was 13.8 grams for each kilogram of body weight, or 508 gramsfor each square meter of surface area. The cells by hematocrit were41 per cent2 by the dry oxalate method, and the hemoglobin for each100 cc. was 15.7 grams. These values closely approximate thoseobtained by Keith, Rowntree and Geraghty in their original reportbased on eighteen subjects. Many of the normal subjects variedconsiderably from the accepted average weight for height and age,but could not be classified as underweight or obese. When a classi-fication of this group was made on the basis of a 10 per cent variationabove or below the average standard for height and age, the meanvalues for the blood volume and plasma volume were only slightlydifferent.

PRIMARY SPLENOMEGALYWITHOUTANEMIA

Cases of primary splenomegaly without anemia, when all etiologicfactors have been excluded, such as syphilis, malaria, hemolytic icterus,

2 In subsequent work it has been found that hematocrit values obtained by thedry oxalate method should be corrected by the addition of 3.4 per cent. There-fore, 41 per cent, as used here, should read 44.4 per cent.

285

uaalds jo lqs2Ak00 VI)

alznbsq-iojsuxm £- 00 0U U) \0 0 C

.m m %~

- --- - - - - -m

nUIBIs I s ~~~~o \0 n C o+I

4

o % 0ooo00\0 U 0azawtu aIUnts nOBA CN U) i)n oo0 CO 0 0 t 1 C

tnUIBI3OII1f tj)'-a lo.a>- 00 - 00 '0 '-a -

d°<Cou °U) 04 U) ) "1E ° I4 4O 4aumbsrpv o o 4 OC,400000 0I

' In c 00 0 0 000n a-n -iol.ilatuiluao 3iqnD______ ___

uituSolp[ pra M r- 00 -4 -4 -4 oc I

jop} alatut uao otqnD tn ' t m m ;!t m .dc4

.N dZ ON I" 00 °n CD \ o

;)tunl0,A, - ) 1> 1> U)d f 00CD\ 00 I0

o- 0U)00000U) 0o o 00walaruennbs qava 80 '.0 '.0 4'.0O'

UIU1O~~tpU00Cl0 00qn0 00_^^^___o

.~io; SjaunuflDU) Diqn: - - - -'

.0 1oj solalun ux) xlqnD I~I

.00 n 0 ' Ch O QO0QuilnOA t -U) 00 Cl u) U) U00oo '

0 t

Ca in CaCa) a)~ U)1 ta - Uaolsurannb sq:ea D C\ 1t C) \ tn t c soo\ *c

- t-O-O 4 e4 U-) t_ u-) \-o O -4 1-4

q:,'ea . IN C) C14)08 000 00CO' )O1O)0

. n dq ) O oo oOCD CD Ln0 C U

aquinMa m oo 0n omoI

. * b o ~~~C,m t- U-) 00 \osoI

CN

lC 4

'NoCi S cs

Cloo-

.0~C"

Ul U)~o .ea No

'Us I* ~~~*i *g *

2-8 Cl l U-)

286

4) . .

O 0

... .-

4) A&u

.e.

CS

En

0o

"0

"0

cS

cS c

~4

<0

H. Z. GIFFIN, G. E. BROWNAND G. M. ROTH

chronic infectious splenomegaly and various blood dyscrasias, haveordinarily been regarded as potential splenic anemia in the pre-anemicstage, and the splenic enlargement has been the outstanding clinicalfeature.

There were six cases in this group. Three were studied both beforeand after splenectomy. Two cases were studied preceding splenec-tomy and one case only after the operation. The results of thesestudies are shown in table 1.

Comment. The blood volume preceding splenectomy was 101 cc. andthe plasma volume was 59.6 cc. These values are high. While theratio of cell to plasma volume, as denoted by the hematocrit value of41 per cent, was normal. This state has also been disclosed in cases ofchronic passive congestion and in arteriovenous fistula, conditions inwhich a compensatory increase in the volume of circulating bloodseems to be necessary for circulatory efficiency. This leads to thepossibility that in primary splenomegaly without anemia, the increased.circulatory bed due to the splenomegaly and enlarged blood vesselsnecessitates a larger blood volume for circulatory needs.

The comparison of the average values of the two groups of casesbefore splenectomy and after splenectomy does not show significantchange in blood volume, plasma volume or in the percentage.of cellsby hematocrit. In case 5, with an interval of nine days, there was adecrease of 20 per cent in total blood volume and of 3 per cent inplasma volume. Since the weight decreased 5 kgm., the changes involume for each kilogram were not so marked. This could be ascribedto operation and loss of blood. The large blood volumes in the caseswith long intervals, one year and one and a half years after splenec-tomy, are probably more significant; these patients have a largevolume of normal blood, an unusual condition in subjects of normalbuild.

HEMOLYTIC ICTERUS

The clinical features of hemolytic icterus are well known. Thefundamental process is abnormally active hemolysis and the patho-logic basis is probably chiefly concerned with increased fragility of theerythrocytes and microcytosis (Giffin). In the diagnosis of hemolyticicterus care must be taken to exclude cirrhosis of the liver with

287

uaalds jo lqa!al 00 _

O) n o o en o0q if) 9 0 0n00 0% iLO oq i)

ax~~nbsq~ioj sui~~ 0 0%1 tI- (11 0% 00 'IC 11 0 0 C% 0aivnbs q:),uaioj suirif) to° N C14 if) 0 00 ON% 0) - 00 0, en

0~ ~ ~ ~ ~ 0~ ')0 0\% -0 00C1.tb uIvsCp0 0 0_e p0 -o;0Sltu, 3!qnj 00to f) i) 1>. 0% t 00-n4

V% v c'e -4c i

0V-4

i) 't- C., 0't t 000

aTunlOA 0O000' 00 00Om 000

.ial; ui axenbs qpra 00 0 00in ) 0oCo) CDo 0

J~~iu~~fl?flS~in 00 in" V-J4 00000%-' 0If)

JOj0 JWalauiua3 xqnDjOO

I, __________ e~~~~~~U, t- e' oeq U t- (D., -- --

joj WaEJauiua o0q%3a 00a 000 0 ON0 It 00

*Q 10J 1O1}U1I)U~Z) z)iqnJ 00 if) if) 0 00C) ifC) \0 C) C) C0if COi)uiflnOA 0 ON) Cf)-0 t-00 0% m0 C' 1_ b ~ ~000000-oen 4ON r_ oo d oo i oo - -n

-- 000~~~~~~~~~~~ ~~~~~ 0 C)0-) ) t 0

IaTu airnbs 0 00_____ _ 0~ooooa o Jo o00eO U") o-- 9£JOi 000%0lua0:)0qnD- - -) - - - - - -

~ J0 1~13W!~U~) ~!qn3 0 - 0-0 C) to 0%-00 i) C 100000 00joj ialatuilu;D3 3iqnD |0 f )_ o00u s0s Ee° oo

000 0O O O O O Q O O O O Q O -)qZosotooc Uro hNs

::i at no0 ° S 9 C) C) C) O 8 C) dqC)oo

00 to ONi4n inf to

atunlIAac ,Cqe ° N m ag -t oo u 0

2 JO1 waIatuXqsfl3 00'x ) 00o 00 0f )0 %C)) 0 O o C)np aeb r-r CN tn ey CS (7s CS 00

900 \0 00 el0 - 0% I4.

X 0 UtRelOIla q3sa| 0000 00'o o f00 e 00o00 E o00iojjalatiluaaoinD - - - - - ---- - - - - -

x~~~~~~~~~~~~~~e en oo " m N u el- CN C1 C14 ooou

i - a- 0 0' ON mU00O -

Ooj IalatuiltuaD3qqn- X-|- oo0-- r- 0o 0 00 000-

00 in _Iifif)n C,i if)

..~~~~~tnO "i to cs a, m iNNOC -0

00 san 0 to , m C) Or oN- 0

LO-- - S 0 0 0 n 00

-~~~~1 ~ ~en4 4 m e*o ~~~~~~~~~C.) >' >oo

mbbeo o

aSy t'. - if)~~~1 fE)X- ) if 4 0%0

*t ~~~~uiqolRotuaH tx

C* o'1ooo Xo 00 0oo

$~~~~~~~~~~~~~~r C)J uvfJs$++ooo- *nt 0 C) 00 00 oo t

4 4 di \0 +V % -N cs c

utoinin 6 u

b o084) I4 )

I2 U- Mt ON>n A

xas

ase3 .q4 f) 'IO t-~

288

mtC

U)1eqU)- 8 u

00e04o LO0

-~~~~~~~U)J o- -eNU q

0 00 LO0 --

U) 00 >14 % -4 00

mL00 )O _4

r o- N Ot- C 0%

-4 e1 E)t_4

A t- \0 e

4 U U U) U0

'0

ll 0 00 0

t- NoX4-0\ X - ) -

C4 _

C> _4 CsON

* 0 *C- - L ON

rN so S XI

'> d4CO t4 m°4-~4 t 4m

.N\. C

%o \ 0 00C

CS CSN4N0\ \ S0 C'_se >

O4-4 0 >0

_4. _4-4 _4 00 w

d4C- 4 0 End

v 2 2 ~~dce

* O _4 Cd*># 4 2~~~c

289

BLOODVOLUMEFOLLOWINGSPLENECTOMY

secondary hemolytic characteristics. Splenectomy is a curativemeasure. Following operation the jaundice disappears, the excessivehemolysis ceases and, in some instances at least, the erythrocytesbecome less fragile. As Moynihan stated: "The spleen, if not theexclusive cause or seat of the disease, exerts the profoundest in-fluence on its pathogeny."

Preceding splenectomy. Eleven cases of hemolytic icterus werestudied (table 2). The body build in this group was subject to widevariation; none of the patients were overweight, but the youngerpatients were underweight. Studies of the blood volume were madeone or two days preceding operation, and from nine to seventeendays following operation. Anemia was present in all of the cases.The patient with a blood volume of 153 cc. was the only one with avolume above the upper range of normal; she was an emaciated girlaged six and a half years, and according to surface area the bloodvolume was less than the normal mean. According to surface areathe mean plasma volume for the entire group was 2200 cc. for eachsquare meter, about 15 per cent higher than the normal mean.

That anemia was actually present is shown by the amount ofcirculating hemoglobin. The mean value for hemoglobin was 8.1grams for each kilogram of body weight (normal 13.8 grams). Themean value for the cell volume was 21.7 cc. for each kilogram (normal36.5 cc.), a decrease of 14.8 cc. (45 per cent). The mean value forthe plasma volume was 73.1 cc. (normal 51.2 cc.), an increase of 21.9cc. (43 per cent). The ratio was, therefore, - = 0.95. This replace-ment index of 95 is high, almost twice that seen in primary and simplesecondary anemia.

The hemoglobin in grams and the blood volume when separatelyplotted against the weight of the spleen did not correlate. The cellvolume calculated for each kilogram of body weight plotted against theweight of the spleen did not show definite correlation. There was afairly high correlation of 0.87 between plasma volume and weight ofthe spleen.

Following splenectomy. Estimations were made from nine to seven-teen days following splenectomy in nine of the eleven cases (table 2).The plasma volume according to body weight and surface areashowed a smaller percentage variation since the body weight decreased

290

H. Z. GIFFIN, G. E. BROWNAND G. M. ROTH

after operation. The total hemoglobin volume increased in all butone case, the range of increase being from 57 to 327 grams, averaging

90oF

80o

600Hul

Wa

q-

400

I I I I I

5 o10Days after operatio

FIG. 1. CEANGESIN TH CIRCULATING HEMOGLOBININ CASES FOLLOWINGSPLENECTOMYFORHEMOLYTICJAUNDICE

183 grams (fig. 1). The percentage of cells by hematocrit and thenumber of erythrocytes increased in every case, and the hemoglobin ingrams for each 100 cc. showed a significant increase in all but two cases.

291

BLOODVOLUMEFOLLOWINGSPLENECTOMY

Comment. The status of the blood volume in hemolytic icterus,according to mean values, is that of decreased cell volume withnormal blood volume. The cell volumes and the hemoglobin volumiesaccording to body weight and surface area were decreased, which isindicative of the existence of an actual rather than an apparent anemia.With the exception of one case, that of a child, the blood volumeconformed closely to the normal range, which is 70 to 100 cc. for eachkilogram. The plasma volume, however, was greatly increased, theincrease amounting to a mean of 21.9 cc., 43 per cent for each kilo-gram above the normal mean. The replacement index was high, 95;in other words, when compared to normal values the increase of plasmato replace the decrease in cells was almost complete. This indicatesthat in hemolytic icterus the replacement of the diminished cell volumeby plasma is effective and adequate, much more so, in fact, than inprimary anemia and simple secondary anemia without splenomegaly.

The increase in the blood volume and cell volume following splenec-tomy in cases of hemolytic icterus is most striking and correlates wellwith the clinical improvement following operation. In every case butone the cell volume increased significantly within three weeks and theactual volume of hemoglobin showed comparable changes, the increaseaveraging 183 grams. In case 2 (table 2) the increase in the bloodvolume was more than a third of the preoperative value, and the actualincrease of hemoglobin was 327 grams in ten days, or over 30 grams aday. This increase of hemoglobin represents only the demonstrableincrease of pigment and does not include the amount necessary tocompensate for that which is normally destroyed. Figures for thenormal amount of hemoglobin formed daily in man are not available.Whipple, Robscheit and Hooper have shown that in the dog afterunit hemorrhages, the amount of hemoglobin regenerated dependslargely on the type of diet. In one experiment with beef heartdiet, 43 grams of hemoglobin were formed daily over a seven-dayperiod.

The rate of recovery from anemia after splenectomy is not correctlyshown in the concentration values for hemoglobin and erythrocytes.For example, in case 2 (table 2) following operation there was anincrease of about 9 per cent in the grams of hemoglobin in each 100 cc.and a questionable increase in the number of erythrocytes. The

292

H. Z. GIFFIN, G. E. BROWNAND G. M. ROTH

increase in the blood volume, however, was 1970 cc. (40 per cent)half of which was cells. The increase in the actual volume of hemo-globin was 327 grams, or about 50 per cent. The plasma volumeincreased 940 cc. while the cell volume increased 1030 cc., that is, cellsincreased in greater proportion than plasma, thus affecting the ratioof cells to plasma.

Hooper, Robscheit and Whipple have shown that in the recoveryfrom experimental anemia, the increased plasma volume caused by theanemia gradually disappears with the regeneration of cells. In therecovery fromll anemia in hemolytic icterus, the plasma volumedecreased in five cases with the increase of cells, and increased in fourcases.

The status of the blood volume as indicated by the mean value in aseries of eleven cases of hemolytic icterus preceding splenectomy isthat of decreased cells with normal volume. The anemia of hemolyticicterus is an actual rather than an apparent anemia and as the plasmavolume increases to cause a slightly high blood volume a small amountof dilution occurs. The blood volume is maintained within a normalrange since the replacement of cell volume by plasma is almost com-plete, as shown by a replacement index of 95. Following splenec-tomy there is an immediate rapid increase in the cell volume andhemoglobin volume which is not adequately demonstrated by theordinary clinical estimations for determining the concentration ofhemoglobin and erythrocytes.

SPLENIC ANEMIA

Splenic anemia is a useful term to indicate a poorly defined clinicalsyndrome rather than a disease entity, and the diagnosis is chieflvmade by exclusion. Cases included in this group have two features incommon: primary splenomegaly, and a secondary type of anemia.Cases of questionable diagnosis are always present in a group of casesclassified as splenic anemia, and the difficulties of arriving at conclu-sions concerning observations on the blood volume are correspondinglyincreased, especially in those cases in which secondary hepatic cirrhosisis present.

Preceding splenectomy. Estimations of blood volume were madepreceding splenectomy in eighteen cases classified as splenic anemia,

293

\0000%uaalds jo jiq2ioAj

lalaw~~~~~~~~~~~- | tn Oo oo \0 oOo 00 O) cO O\ I- ta inbs tqeJio; stIi g 00C0 C0 o0 0O - - 00 00 -I, - -A

______ d' C04c_t 4 4 Cl Cl 00bo ~ ~WJMT1 .:.: .:bo

oOO_toqo-% O00sCmwo0000 t- 0s d

amnlOA "-4) 0%0if 0 ) 0 '0 \0 000 Cl c %014 00

0 000 t 00 Po \0 0 00-04a0\0 no t- oo m 00 t- VI t- m m 00 t" oo r- W) 0 o 8- 0 U)0 OaaI malvnbs tpva 00 0 00 0 -4 00 d 0- 14 00 - 00 °O

10oJ SI 104o tIUa 3iqnl O% O1 \0 -0 00 0000 0- -- -- -

- urei2oRjpjq:)sI-ea t- \0 'ft i) -t 0 -4 in \0 -14 t- tou0JSaloun ua:U3qnD 00n0-NCl Cl 0 C"l Cl 0 0 0 00 Cl Cl 't

O880> c, o u) <> o:° °*_mn_A_\______ - - -t ' ClC C-4 4_ '-4 c\Cc

8 ~0 0 0)0 000 in0 0oisXlam aanbs q:sea |- 0% 0 C m

°00% oU) °

'u 3.io; sialounjuxo :)iqno) Cl-- f 00- 00

_____ _ ClC14 - mC14 CNc> CNC4C14C14c clC ClIN Cl

- aresopll oveaA lo; sialau05lu Z)qno) I- 00 0 0% 1- 0 0 00 in 0 ' 00 t-dawlAe~oq \0 \0 r- ofi \ \0+meyo u) e N m u) lt) tds e X8 C) "nIOA W- 000o Co 0%o -o Co -o U)oo o- I)

lo;sJalaluao olqns oe~~~~~-4~- ol 8 l clo l .4eXeo el el cN X__________ ~~~~~~~~~~~~~4 0000 %0 0 00 Cl 00000 C)

00 000 0000aumo^ .0g000 0 00O 000003t°)0000

jalaw o.xnbsq3-coV-sp 0% '14" C O - t- mn 4Ur.Ioj s SluY!1uSZ) 1iqno) ~ 0 Cl %0 --'1 o \0 0C1 N0

*~~ LU~I~OjUj t~~1~5 Cl 5'- t-145- 00 \0 Cl4 C4 00'- t-- - 00 \0o o10S55uaai ua:): 1~n3 - 0 00 0 0% 00 0 0) 0 0 0% 0 0 0

- - -------- - - - -- -mA000 00-4 00 Cl 00r O ' 400 00000 C'-

ouCq\a \000 0 c-cc0-0- 04U- )i0 v C r01"l5lC 0 00 C4 0 0' 05 '-M M M In d4C

Ct .41 * m EP !; C)\ O CN C\ C1 0 e Ne

saltOlqlD: .,.;

00 Cl\0 Cl0Nin C) 00000000 \l \l 0 \0

u!qol2ouxaH 00doobo0 oo 0\ 000\ 1 0k 1-\ C4C000\0 Cll -IC'00000 5-0%U-) C\ \0 C 00%0

.~~~~~~~~~~~~~~~~~~~~~~~~~~q 14 stq V-4 v.I 4 _- v- 4

*OoA e 0 C> - L- rq 4 Z- to 0\ mo

u~~~qo~~~otus~~~~~ ~ U) - \00- 0 - t--1 -n - -'0 - 0l 0 Cl C Cl 0

-----S -- Cloo b $ i -I -C\ N o °

Y e o ,' > o 3 r 9i~~~~~~~~=$3

0%0%> %0C t° ° %

0%'-Cl c'' :%% 04 0% 0%

Z~~~~~~~in',0 0 00 0 \

laStldfi4Z4}qZ43

. :?f ._.

294

E-qA

-0b

S& Ss j s !..m 1-14 t- V-4 1-4 §

1. 1.4 .' -;,

0

W4'.

ifCh 0n 0 -f)

00 00n es00 I) 000 Q- CV)

S Xua r oO 0 g\00\ °O oO 4 0 \0 00OQ\0 I 0%0if eq0% 00 ,-4 0 %Q%0 0%_%0 t- 4 if)i )4 i f)

O 0 00I)0 00 0000CV)

WI)If Qi)-4 if8 '.%0 C4 t- 00 00 00

- - -- -- - -

t- C4%C%O4'-.%0if)000 C) CV) 00

00l~00 0I 0 000 00 1

r No od4 if (0V)O

%- \ % - 0 0 - 0 001

t-4 U-0 4 0Q f)

m 11 - --- - W

If) 0

OC400000 %-.-. 0%so vo v) oo CV) o

\0 r- t0 "ov ou

00 0\ 00-4CV)%4- 00%- -- - --nU) O X-

C4 m m C4 m m oo U

\0-4CC4 \0 -4 m 0-

Ol~~ ~o-Zld 0 t

m C4 4 m00 Ct w) mos toto en oo t- t-4, 00 0

eq, ~ ~ _.0 -, D

Uf)if)00 '-.%Q ifto iU) o

C4 C14 00ON Ch C, N C'

CD

4-4- -44 OQ. -qC'smPS_ o

y y4

O 0% ui) 00o ) 0 oft --Ii O U)

.

eo. 600

U)*-. 4)

,L -4

>

0

0bo -

C) Cd

id44)

bo o

._.

e of

4i)

CB 04o) if

U) U

- 4b44

C.)44

- U)Q

*> 14iOO

bOU) 440

o cd_ d

° CXa0 04O COa

(n

5-4 Ca

>O

* -- .*- l

295

-4 - - - r- oo- -

U

00§ § lold4 §Iz

BLOODVOLUMEFOLLOWINGSPLENECTOMY

seven of the Banti type (table 3). It will be noted in table 3 that inthe seven cases of the Banti type there was approximately the samehigh blood volume as that in the cases without advanced hepaticcirrhosis.

The body build of this group of patients was fairly uniform. Nonewas obese or emaciated. The mean figure for body weight was64.2 kgm.

Following splenectomy. In seven of the cases observations weremade both before and after splenectomy. Estimations of bloodvolume were made from two to three weeks after operation (table 3).

Comment. The mean value for the blood volume according to thebody weight and surface area is increased in splenic anemia approxi-mately 10 per cent above the normal. This increase is largely due toplasma volume since the cell volume is reduced 18 per cent. The meanvalue for the plasma volume according to weight and area is approxi-mately 30 per cent above normal. The plasma volume is muchhigher in splenic anemia than in the chronic secondary types of anemiaand in pernicious anemia with comparable hemoglobin and cell values.This fact suggests the question whether the anemia is actual or whetherdilution factors play a r6le causing apparent anemia. The circulatinghemoglobin in grams for each kilogram preceding splenectomy was9.7 grams, or for each square meter of surface area 355.6 grams com-pared with a normal of 13.8 grams and 508 grams, respectively. Thiswould indicate that actual anemia exists which is diluted by theabnormally high plasma volume. The anemia is due both to dilutionand to actual loss of hemoglobin. The plasma not only replaces thelost cell volume but increases to a point beyond the original bloodvolume. The replacement index is very high, as is demonstrated bythe following calculation: A mean cell volume of 30 cc. for eachkilogram, compared with a normal of 36.5 cc., is 6.5 cc., 17.8 per cent,less than normal; the mean value for the plasma volume of 68.6 cc.(normal 51.2 cc.) is 17.4 cc., 34 per cent, above normal. The replace-ment index would then be 191 (1348 = 1.91). The replacement indexas demonstrated in sixteen cases of secondary anemia was 42 and inten cases of pernicious anemia was 30.

The reason for the increase in plasma volume in cases of splenicanemia is not clear although there is a close correlation between the

296

H. Z. GIFFIN, G. E. BROWNAND G. M. ROTH

plasma volume and the weight of the spleen. It has been suggestedthat in the cases of enlarged spleen and a presumably active reticulo-endothelial system the dye is removed from the blood with abnormalrapidity. Information on this point has been obtained by the followingexperiments:

1. In two cases of hemolytic icterus volume determinations weremade 'on the operating table just prior to removal of the spleen.Twenty to thirty-minutes after the injection of the dye, samples ofblood were taken from the splenic artery, splenic vein and spleenpulp. It was found that the concentration of the dye in the threesamples was exactly the same. These experiments seem to demon-

TABLE 4

Percentage of variation in the plasma volume within six minutes after injection of the dye

Time after injectionCase

2 minutes 3 minutes 4 minutes 6 minutes

1 100 100 100 1002 100 101 1073 100 100 101 1024 100 100 100 1045 100 99 100 966 100 97 100 100

* The two-minute determination is taken as 100 per cent.

strate that the dye is not abnormally removed by the cells of thespleen in hemolytic icterus.

2. The rate of disappearance of the dye from the blood was ascer-tained by determining the plasma volume at periods of two, three,four and six minutes in a large series of normal subjects and in sixcases of splenic anemia (table 4), demonstrates that an increased orabnormal rate of disappearance of the dye was not present in the casesof splenic anemia. Moreover, dye was not excreted in the urinewithin one hour after injection, as has been demonstrated in certaincases of nephrosis.

The effect of anemia on the increase in plasma volume was con-sidered. Only rarely in cases of secondary anemia were high plasmavolumes found. In thirty cases of primary and secondary anemia there

297

BLOODVOLUMEFOLLOWINGSPLENECTOMY

was a moderate increase in the relative volume of plasma with meanvalues of 60 and 58 cc., respectively. This would indicate that theanemia is probably not the sole factor in the production of the highplasma volume in splenic anemia. It was demonstrated in the seriesof cases reported in the first portion of this paper that cases of spleno-megaly without anemia also show a high plasma volume. It ispossible, then, that a high plasma volume may be one of the funda-rmental changes in cases of splenic anemia, and that it may precedethe development of anemia.

j6050 ..-I.

z00 400 600 600 1000 1200 1400Weight of spleen in grams

FIG. 2. PLASMAVOLUMEANDWEIGHTOF SPLEENIN SPLENIc ANEMIA

t6oo+

Following splenectomy a decrease in the total volume of the circu-lating blood occurred in every case. This decrease was slight in oneinstance but definite in all the others. The maximal decrease was1230 cc. and the average was 656 cc. The decrease in the total bloodvolume was more constant and marked than that occurring in therelative blood volume for each kilogram because of variations in bodyweight. On the basis of surface area a decrease occurred in all butone case. The plasma volume likewise decreased in every instance,with a range of decrease from 145 to 910 cc., the average decrease being

298

H. Z. GIFFIN, G. E. BROWNAND G. M. ROTH

442 cc. Slight increases and decreases occurred according to bodyweight. The cell volume decreased in five of the seven cases, but wassignificant in only three cases. In only two cases did the cell volumeshow an increase. The total amount of circulating hemoglobin ingrams showed a decrease in five of the seven cases, averaging 50 grams.

The total blood volume for each kilogram of body weight wascharted against the weight of the removed spleen. The curve shows arough correlation between these factors. It is apparent that largervolumes of blood occurred in the cases in which the spleen was largest.A closer correlation is brought out when the plasma volume for eachkilogram is plotted against the weight of the spleen. The curveapproximates a straight line (fig. 2). Between the cell volume and theweight of the spleen definite correlation could not be demonstrated.

The moderate reduction in the blood volume after splenectomy incases of splenic anemia would, at first thought, be attributed to lossof blood. The studies in these cases were made two and three weeksfollowing operation; this interval would ordinarily be regarded assufficient for adequate blood regeneration. There is great variation inthe amount of blood lost at operation; in some cases it is negligibleand in others large. There does not seem to be any correlation be-tween the amount lost at operation and the decrease in blood volume.Likewise, the drop in the volume of blood after operation consistslargely of plasma, indicating a readjustment following splenectomy.A relationship could not be established between the reduction in bloodvolume and plasma volume and the weight of the spleen; in fact, thepatient (case 5, table 3) with the smallest spleen, showed the greatestdecrease in blood volume. Surprisingly small amounts of blood wererecovered from the enlarged spleens; the amount ranged from 100 to500 cc. Either the contraction of the spleen eliminates much of theblood before it is removed, or its actual capacity is reduced, possiblybecause of fibrosis. One would infer from these observations thatloss of blood due to removal of the spleen, although it may affect theresults to a certain degree, does not account for all of the reduction involume of blood, nor could it account for the disproportionate loss inthe plasma volume and the relatively high plasma volumes remainingafter splenectomy.

Summarizing these results in connection with splenic anemia, it has

299

BLOODVOLUMEFOLLOWINGSPLENECTOMY

apparently been shown: (1) the plasma volume, and therefore the totalblood volume, is high according to body weight in spite of a decreasedvolume of cells; (2) the increased plasma volume estimation is notdue to an abnormal affinity of the cells of the spleen for the dye, to lossof the dye in the urine, or to an abnormally rapid rate of disappear-ance from the blood; (3) while the existence of anemia is usually asignificant factor in the production of the high plasma volume, it isnot the important or sole factor as it seems to be in cases of secondaryanemia and pernicious anemia; (4) the enlarged spleen is probably anadditional factor in the increase of plasma volume and total bldodvolume; even in splenomegaly without anemia the plasma volume isslightly increased, and (5) a fairly high correlation exists between theweight of the spleen and the plasma volume for each kilogram.

SUMMARY

The figures obtained in blood volume studies in seventy-fournormal adult subjects reported elsewhere by Rowntree and Brown areapproximately as follows: for both sexes, mean value for the bloodvolume for each kilogram of body weight, 87.7 cc.; plasma volume foreach kilogram, 51.2 cc.; cell volume, 36.5 cc.; circulating hemoglobinfor each kilogram of body weight, 13.8 grams, and for each squaremeter of surface area, 508 grams; hemoglobin for each 100 cc., 15.7grams, and cells by hematocrit, 41 per cent. On the basis of eachsquare meter of surface area the values are approximately as follows:volume of blood, 3278 cc.; volume of plasma, 1920 cc., and volume ofcells, 1358 cc.

In cases of primary splenomegaly without anemia the mean value forthe blood volume was increased to 101 cc, for each kilogram, the plasmavolume was increased to 59.6 cc., and the ratio of the cells to plasmawas normal. After splenectomy there was no significant change in theblood volume or in plasma volume, the values still remaining abovenormal.

In hemolytic icterus the blood volume was normal and the cellvolume decreased; the replacement of the diminished cell volume byplasma was complete. After splenectomy there was an increase inblood volume and a very striking increase in the volume of cells andhemoglobin. These increases were much greater than were indicatedby the ordinary estimations of hemoglobin and erythrocytes.

300

H. Z. GIFFIN, G. E. BROWNAND G. M. ROTH

In splenic anemia blood volume was increased and cell volumedecreased. An increase in the plasma volume was found which couldnot be accounted for solely on the basis of anemia. The anemia wasdue both to dilution and actual loss of hemoglobin. Followingsplenectomy a moderate decrease, which was largely in the plasmavolume, occurred in the total blood volume, yet the increased plasmavolume persisted. A high correlation has been demonstrated for therelative plasma volume and the weight of the removed spleen.

Most of these observations were made within three weeks of thetime of operation. The number of observations made at longerintervals subsequent to splenectomy have been too few to warrantdiscussion.

BIBLIOGRAPHY

1. Barcroft, J., Harris, H. A., Orahovats, D., and Weiss, R., J. Physiol., 1925, lx,443. A contribution to the physiology of the spleen.

2. Cruickshank, E. W. H., J. Physiol., 1926, lxi, 455. On the output of haemo-globin and blood by the spleen.

3. Dreyer, G., and Ray, W., Proc. Roy. Soc. Lond., 1910, Series B, lxxxii, 545.The blood volume of mammals as determined by experiments ftpon rabbits,guinea-pigs and mice; and its relationship to the body weight and to thesurface area expressed in a formula.

4. Giffin, H. Z., Surg., Gynec., and Obstet., 1917, xxv, 152. Hemolytic jaundice;a review of seventeen cases.

5. Hooper, C. W., Robscheit, F. S., and Whipple, G. H., Am. J. Physiol., 1920,liii, 263. Blood regeneration following simple anemia. V. The influence ofBlaud's pills and hemoglobin.

6. Keith, N. M., Rowntree, L. G., and Geraghty, J. T., Arch. Int. Med., 1915,xvi, 547. A method for the determination of plasma and blood volume.

7. Moynihan, Berkeley, G. A., The spleen and some of its diseases. Philadelphia,WV. B. Saunders Co., 1921.

8. Rowntree, L. G., and Brown, G. E., Blood volume in health and disease.(In press.)

9. Whipple, G. H., Robscheit, F. S., and Hooper, C. WV., Am. J. Physiol., 1920,liii, 236. Blood regeneration following simple anemia. IV. Influences ofmeat, liver and various extractives alone or combined with standard diets.

301