wennesland,t...brown, hopper, hodges, bradley, wennesland, and yamauchi table i-(continued) hemato-...

9
Journal of Clinical Investigation Vol. 41, No. 12, 1962 RED CELL, PLASMA, AND BLOOD VOLUME IN HEALTHY WOMEN MEASURED BY RADIOCHROMIUM CFLL- LABELING AND HEMATOCRIT * By E. BROWN, J. HOPPER, JR., J. L. HODGES, JR., B. BRADLEY, R. WENNESLAND,t AND H. YAMAUCHI (From the Department of Medicine and the Cardiovascular Research Institute, University of California School of Medicine, San Francisco, and the Department of Statistics, University of California, Berkeley, Calif.) (Submitted for publication June 25, 1962; accepted August 15, 1962) In a previous study of 201 healthy men (1), red cell volume (Vrbc) was measured by a modi- fication of Sterling and Gray's radiochromium method (2), and whole blood and plasma volumes (Vwb and Vpl) were derived from venous he- miatocrits. The influence of factors other than body size on the variance of the data was studied, and standards for predicting normal volumes were derived. The present report describes a similar examination of 101 women. SUBJECTS AND METHODS The women, all of whom volunteered for study, were actively employed as housewives, laboratory personnel, nurses, or office workers, and most were white (Table I). None were taking medications regularly or were subject to dietary control other than mild voluntary caloric restriction, and none were pregnant. Although some engaged in sports regularly, none were trained athletes. All had been living at sea level for at least a year. Cases of gross clinical obesity were not included. No subject was a regular blood donor, and none had given blood within 10 weeks. Health screening tech- niques included a medical history, physical examination, chest X-ray, and urinalysis. A hematocrit below 37 per cent, the limit of normal as defined by Wintrobe (3), caused exclusion of only one volunteer. In no subject was the arterial blood pressure over 140 mm Hg systolic or 90 mm Hg diastolic. The method' of labeling the autologous cells with NaCr5O4 and of determining their volume of distri- bution (VCr"1) was as described in the study on men (1, 4). Tests were performed before breakfast or, rarely, in the afternoon when lunch had been omitted. Subjects lay down for at least 30 minutes before the labeled cells were delivered and until sampling was completed no less than 35 minutes later. Precautions were taken to * Supported by U. S. Public Health Service Grant H-1271 and by the Robert Harris Fund allocated by the Committee on Research of the University of California School of Medicine, San Francisco. tResearch Fellow, American Heart Association. prevent venous congestion during sampling. Hemato- crit readings were not corrected for plasma trapping, and it was assumed that Vwb = VCr"1 (no allowance was made for a difference between the hematocrit of venous blood and that of the body as a whole) (1). Cell and plasma volumes were calculated by the formulas: Vrhc = VCr`1 X hematocrit; Vpl = VCr5` - Vrbc. The data were treated as outlined in the study of men (1). Regression equations were calculated by the method of least squares to describe the relations between vol- umes (Vrbc, Vpl, and Vwb) and body measurements (weight, height, weight and height combined, and sur- face area). The differences between the observed vol- umes (Vrbc and Vpl) of each woman and the mean vol- umes found in women of the same height and weight vere calculated by means of Equations 3 and 7, Table II. These differences, or "residuals," wsere used to analyze the influence of factors other than body size On the blood volumes. RESULTS 1. Volumes in relation to height and weight Table I summarizes the data. In Figure 1, each of the 101 subjects is represented according to her weight and height. In general, the relation- ship between weight and height was fairly uniform. Notable exceptions were four women weighing over 81 kg, who proved to be 23 to 58 per cent overweight for height and age according to ac- tuarial tables (5). The weight: height ratios of these subjects were more than 2 standard devia- tions above the mean of the ratios of the other 97 women. For this reason and because the series included so few large women, regression equations describing the relationships of the volumes to body measurements were prepared only for the 97 women weighing less than 74 kg (Table II). The bivariate regression equations described straight lines and the trivariate equations, planes without curvature (see Figures 1 to 4). The lo- cation of the regression plane for Vrbc in rela- 2182

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Page 1: WENNESLAND,t...BROWN, HOPPER, HODGES, BRADLEY, WENNESLAND, AND YAMAUCHI TABLE I-(Continued) Hemato- Redcell Plasma Age IHeight Weight crit t volumet volume cm kg 170 57.0 168 60.0

Journal of Clinical InvestigationVol. 41, No. 12, 1962

RED CELL, PLASMA, AND BLOODVOLUMEIN HEALTHYWOMENMEASUREDBY RADIOCHROMIUMCFLL-

LABELING ANDHEMATOCRIT*

By E. BROWN,J. HOPPER, JR., J. L. HODGES,JR., B. BRADLEY,R. WENNESLAND,tAND H. YAMAUCHI

(From the Department of Medicine and the Cardiovascular Research Institute, University ofCalifornia School of Medicine, San Francisco, and the Department of Statistics,

University of California, Berkeley, Calif.)

(Submitted for publication June 25, 1962; accepted August 15, 1962)

In a previous study of 201 healthy men (1),red cell volume (Vrbc) was measured by a modi-fication of Sterling and Gray's radiochromiummethod (2), and whole blood and plasma volumes(Vwb and Vpl) were derived from venous he-miatocrits. The influence of factors other thanbody size on the variance of the data was studied,and standards for predicting normal volumes werederived. The present report describes a similarexamination of 101 women.

SUBJECTS AND METHODS

The women, all of whom volunteered for study, wereactively employed as housewives, laboratory personnel,nurses, or office workers, and most were white (TableI). None were taking medications regularly or weresubject to dietary control other than mild voluntarycaloric restriction, and none were pregnant. Althoughsome engaged in sports regularly, none were trainedathletes. All had been living at sea level for at least ayear. Cases of gross clinical obesity were not included.No subject was a regular blood donor, and none hadgiven blood within 10 weeks. Health screening tech-niques included a medical history, physical examination,chest X-ray, and urinalysis. A hematocrit below 37per cent, the limit of normal as defined by Wintrobe(3), caused exclusion of only one volunteer. In nosubject was the arterial blood pressure over 140 mmHgsystolic or 90 mmHg diastolic.

The method' of labeling the autologous cells withNaCr5O4 and of determining their volume of distri-bution (VCr"1) was as described in the study on men(1, 4). Tests were performed before breakfast or, rarely,in the afternoon when lunch had been omitted. Subjectslay down for at least 30 minutes before the labeled cellswere delivered and until sampling was completed noless than 35 minutes later. Precautions were taken to

* Supported by U. S. Public Health Service GrantH-1271 and by the Robert Harris Fund allocated by theCommittee on Research of the University of CaliforniaSchool of Medicine, San Francisco.

tResearch Fellow, American Heart Association.

prevent venous congestion during sampling. Hemato-crit readings were not corrected for plasma trapping, andit was assumed that Vwb= VCr"1 (no allowance wasmade for a difference between the hematocrit of venousblood and that of the body as a whole) (1). Cell andplasma volumes were calculated by the formulas: Vrhc =VCr`1 X hematocrit; Vpl = VCr5` - Vrbc.

The data were treated as outlined in the study of men(1). Regression equations were calculated by the methodof least squares to describe the relations between vol-umes (Vrbc, Vpl, and Vwb) and body measurements(weight, height, weight and height combined, and sur-face area). The differences between the observed vol-umes (Vrbc and Vpl) of each woman and the mean vol-umes found in women of the same height and weightvere calculated by means of Equations 3 and 7, Table II.

These differences, or "residuals," wsere used to analyzethe influence of factors other than body size On the bloodvolumes.

RESULTS

1. Volumes in relation to height and weight

Table I summarizes the data. In Figure 1,each of the 101 subjects is represented accordingto her weight and height. In general, the relation-ship between weight and height was fairly uniform.Notable exceptions were four women weighingover 81 kg, who proved to be 23 to 58 per centoverweight for height and age according to ac-tuarial tables (5). The weight: height ratios ofthese subjects were more than 2 standard devia-tions above the mean of the ratios of the other 97women. For this reason and because the seriesincluded so few large women, regression equationsdescribing the relationships of the volumes to bodymeasurements were prepared only for the 97women weighing less than 74 kg (Table II).The bivariate regression equations describedstraight lines and the trivariate equations, planeswithout curvature (see Figures 1 to 4). The lo-cation of the regression plane for Vrbc in rela-

2182

Page 2: WENNESLAND,t...BROWN, HOPPER, HODGES, BRADLEY, WENNESLAND, AND YAMAUCHI TABLE I-(Continued) Hemato- Redcell Plasma Age IHeight Weight crit t volumet volume cm kg 170 57.0 168 60.0

RED CELL AND BLOODVOLUMEIN HEALTHYWOMEN:CR51

TABLE I

Data in chronologic order from experiments on 101 healthy women

Residual

Hemato- Red cell Plasma Red cell PlasmaSubject * Age Height Weight crit t volumet volume volume volume

M.Ho.M.Va.V.Sc.K.Ha. (J)A.Ma.P.Ca.M.Jo.N.La.N.HuI.K.La.J .Ta.J.Mo.M.Iw. (J)J.Se.L.Bo.M.Sm.L.Fe.G.Ov.S.Ri.E.Fi.J.Ke.S.Di.N.McL.J.We.P.Pr.F.Ca.L.MacT.M.Me.J.Pu.M.La.C.B1.E.Ma. (sm)M.Go. (smi)D.Li.R.Ad.P.Fo.J.St.M.Sc.S.We. (smi)M.McG. (urn)A.Co.J.Be.V.Ma.B.Wi.P.Pe.L.Fo.Z.Jo. (1urn1)M.Co.B.Pa.Ejo.J.Ye.B.Re.K.McK.J.St.A.Mo.C.Ta.B.McK.N.Jo. (N)J.Ta.E.Fi. (sm)A.Ko.B.Gr.M.Bo.

years452829403328442325303826222728292620312122312523282120202129247552272844244154542522392825395023232648273122243231362377282427

cm kg169 58.0172 56.6168 60.3144 51.8162 53.0175 58.7173 69.5172 63.2176 56.8165 53.3178 72.3156 51.0156 52.6166 63.5162 55.2171 63.8171 50.0164 58.3163 54.2171 62.0161 53.4166 55.8166 53.5171 57.0173 60.6160 51.7171 54.9160 54.8171 70.11 77 58.9164 59.3157 61.3172 70.0168 63.0164 54.4161 55.6157 68.1159 49.5158 61.4173 57.7160 50.8159 51.0159 49.0168 57.6163 51.7162 51.7159 53.9162 55.8162 49.6171 53.4161 50.4164 54.3168 60.4167 54.1166 58.0169 56.0161 53.2174 73.3161 61.7157 66.0163 59.6166 57.4171 73.1

39.140.538.838.041.937.239.443.539.839.743.338.641.739.037.641.842.741.240.439.739.840.139.940.742.237.741.640.541.838.342.638.138.738.640.738.941.140.441.242.445.144.942.141.845.739.144.241.139.940.841.041.638.044.842.442.642.838.242.245.641.541.537.2

L L1.48 2.311.41 2.061.65 2.591.15 1.861.44 2.001.40 2.341.66 2.541.44 1.881.52 2.311.41 2.121.93 2.521.10 1.741.33 1.851.55 2.411.32 2.191.74 2.411.55 2.071.43 2.041.43 2.111.35 2.051.38 2.081.70 2.531.41 2.131.70 2.481.48 2.021.14 1.881.48 2.071.30 1.921.47 2.041.42 2.291.61 2.151.52 2.441.84 2.901.70 2.721.45 2.111.49 2.331.40 2.011.60 2.361.46 2.081.64 2.211.47 1.791.37 1.691.23 1.691.62 2.271.37 1.631.59 2.471.62 2.031.49 2.131.17 1.751.30 1.891.31 1.881.56 2.181.49 2.431.49 1.851.42 1.941.45 1.951.47 1.961.50 2.421.38 1.891.65 1.971.68 2.361.57 2.231.74 2.94

ml-10-90

+130-70+70

-150-30

-140-10+10

+160-200+10

0-80

+150+160

-30+40

-220+10

+2600

+210-80

-200+20-80

-210-150+140+70

+150+140+50+90

-150+300

0+120+150+50-60

+140+10

+240+260+80

-150-140-10

+160-30+70-50-10

+110-250-110+130+210+110+20

ml+150

-90+380+80+20

+110+70

-430+120+110

-70-130-60

+140+160+90+90-80

+100- 220+100+450+110+330-240-50-30-80

-430+40

0+310+420+450+80

+300-290+500

-60+20

-110-210-160+130-320+530+60+90

-140-180-20

+150+220-200-190-160-10

-150-290-270+220+110+400

* (j) Japanese, (N) Negro, (sm) spontaneous menopause, (nm) no menses, hysterectomy.t Uncorrected for trapped plasma and including buffy coat.t Weight:height ratio exceptionally high. See Figures 1 to 4.

2183

Page 3: WENNESLAND,t...BROWN, HOPPER, HODGES, BRADLEY, WENNESLAND, AND YAMAUCHI TABLE I-(Continued) Hemato- Redcell Plasma Age IHeight Weight crit t volumet volume cm kg 170 57.0 168 60.0

BROWN,HOPPER, HODGES, BRADLEY, WENNESLAND,AND YAMAUCHI

TABLE I- (Continued)

Hemato- Red cell PlasmaAge IHeight Weight crit t volumet volu me

cm kg170 57.0168 60.0171 63.2161 56.5172 64.3178 67.7168 66.5162 87.24173 63.4165 54.8167 51.9157 62.2167 58.6176 81.4t156 44.8160 51.7168 60.2175 94.24165 65.4159 59.9165 83.7t157 52.2168 44.5168 55.4169 59.3163 59.2168 60.8170 60.9160 56.8170 60.1166 53.2155 49.4171 67.4173 61.3164 58.4169 61.9179 64.0169 65.0

40.745.042.242.641.042.742.741.242.241.138.739.442.138.137.843.138.040.941.938.938.339.442.042.244.838.939.540.338.839.738.240.340.544.337.039.238.339.3

L1.341.731.761.491.341.661.621.851.611.371.261.341.601.651.001.231.461.861.751.361.441.261.331.371.591.331.401.491.511.471.250.991.761.681.191.461.541.61

L1.962.132.402.001.932.222.172.652.201.971.982.062.202.691.641.632.392.692.432.122.311.941.831.881.952.102.152.202.382.222.011.462.592.112.022.252.482.48

Residual

Red cell Plasmavolume volume

ml-150

+220+180+80

-270-40+10-10+10-50

-130-120+110-230-210-110-60

-200+180-100-390-60+40-80+80

-140-130-50

+100-60

-150-280+120+110-270-90

-110+20

ml-180-70

+100-50

-410-250-190-150-130-80-10-90+40

-100-80

-300+190-400+130

0

-430+30+10

-210-240-30-70-40

+3300

-10-370+190-170-100

0

+90+150

tion to height and weight (Equation 3, Table II)is represented in Figure 1 by solid contour linesprogressing from the lower left to the upper rightof the chart, and the regression plane for Vpl bydotted contour lines.

2. Analysis of residuals

The residual Vrbc and Vpl of each subject are

shown in Table I. A positive correlation (r = +0.67) was found between the residuals for Vrbcand Vpl.

Age. Table III shows the mean residuals ofthe subjects in various age groups. Comparisonof mean residuals with their standard errors indi-cates that age had little effect on blood volume.There was a slight tendency for Vrbc and Vpl per

unit of body size to be smaller in the youngerthan in the older women.

The menstrual cycle. Of the subjects whosemenstrual periods were regular, 17 were in thefourth week of the cycle at the time of the meas-

urement. They showed no evidence of hydremia.Mean residuals were Vrbc + 2 ml (SE 34) andVpl - 12 ml (SE 52). In seven subjects, aged47 to 77, who were no longer menstruating (seeTable I), the mean residuals were positive: Vrbc130 ml (SE 51) and Vpl 87 ml (SE 79). Thisgroup consisted of the six subjects aged 50 or

more (Table III) and one additional woman aged47.

Body build. In the group of 97 women used incalculating the regression equations, the mean ra-

tio of weight in kilograms to height in centimeterswas 0.350 (SD 0.032). Subjects whose ratioswere beyond 1 SD of the mean were chosen foranalysis of residuals. The residuals tended to be

Subject *

B.Je.

1r.Fl.C.1Re.L.FP.W.LeR.J.Wy.L.Se.F.Ta.J.Ew.P.Ju.M.Je.L.Gr.L.Br.D.Mi.G.Va.T.Ya. (J)E.Pe.M.Da. (smi)E.Br. (nm)P.Sc.N.Po.M.Au.C.Do.L.Te.G.Gu.C.Sc.N.Ni.S.Ha.A.Mi.B.Mu.N.MacK.C.Kl.V.Fr.B.Ha.V.Da.E.Ha.E.Mi.J.Ro.

years

3922284329284149163624433625232739634722271923242421212430232323312726262227

2184

Page 4: WENNESLAND,t...BROWN, HOPPER, HODGES, BRADLEY, WENNESLAND, AND YAMAUCHI TABLE I-(Continued) Hemato- Redcell Plasma Age IHeight Weight crit t volumet volume cm kg 170 57.0 168 60.0

2185RED CELL AND BLOODVOLUMEIN HEALTHYWOMEN:CR51

negative at both ends of the distribution, althoughthe differences were slight (Groups A and C,Table IV). The tendency to negative valuesamong subjects with high weight: height ratios ismore evident after four menopausal women overthe age of 50 (Group B, Table IV) are removedfrom consideration. The influence of excessweight is shown by Group D, Table IV. In allfour of the womenwith exceptionally high weight:height ratios, the residuals for cells and plasmawere negative.

DISCUSSION

Qualitatively, the results of this study bear manyresemblances to our findings in men (1). As faras the regression lines and planes fitted by the

190

k

zU

180

170

160

150

140

method of least squares are concerned, the co-efficients of variation again are smaller when thevolumes are related to height and weight com-bined than when they are related to either measurealone, and are smaller for whole blood than forcells or plasma. Further, the coefficients of vari-ation are exactly the same for the bivariate regres-sion of volume to surface area (Du Bois' formula)and the trivariate regressions of volumes to heightand weight combined (Table II).

Figure 1, a graphic expression of Equations 3and 7, Table II, also shows the range of weightsand heights in the sampled female population.The regression equations derived from the data arenot necessarily applicable to women whose weightsand heights are outside the area covered by the

40 50 60 70 so 90

90

190

1o

170

160

150

140

FIG. 1. RED CELL AND PLASMAVOLUMESIN RELATION TO HEIGHT AND WEIGHT. Each circlerepresents one woman, plotted according to height and weight. Solid circles indicate women

weighing less than 74 kg and open circles, women weighing over 81 kg. The solid and dashedcontour lines give the mean predicted red cell and plasma volumes (Vrbc and Vpl), respectively,to the nearest 0.1 L, calculated from Equations 3 and 7, Table II. The mean predicted volumesof a woman 165 cm tall and weighing 60 kg are: Vrbc = 1.45 L, Vpl = 2.13 L, and Vwb=

3.58 L. Values are uncorrected for trapped plasma and for differences between body hemato-crit and venous hematocrit. Vrbc includes leukocytes and platelets.

The contour lines were constructed by introducing the successive mean values for Vrbc andVpl in their respective regression equations (Equations 3 and 7, Table II) and computing theheight for a given weight, or vice versa.

.5IIII I~ ,, I ,,l I ,IllI,, I,,,I,, I,,T

_ _ *~~o\\\

- \s \\.A/S\_,, , \1, ,,, 0 0

- \ \ \ ~ \ *.\ \\e*\\*0

~~iii~~~~~i I-~~~

40 50 60 70 80WEIGHT IN KILOGRAMS

I

F

Page 5: WENNESLAND,t...BROWN, HOPPER, HODGES, BRADLEY, WENNESLAND, AND YAMAUCHI TABLE I-(Continued) Hemato- Redcell Plasma Age IHeight Weight crit t volumet volume cm kg 170 57.0 168 60.0

BROWN,HOPPER, HODGES, BRADLEY, WENNESLAND,AND YAMAUCHI

TABLE II

Regression equations of red cell, plasma, and whole blood volumes to weight alone, height alone,weight and height combined, and to body surface area in women

144 to 179 cm tall, weighing 45 to 73 kg*

Mean of Standard Coefficientall values Predicted values deviation of variation

ml ml ml %Red cell volume 1,470 177 12.0

1. (14.64 X height) - 957 153 10.42. (18.26 X weight) + 409 139 9.53. ( 7.49 X height) + (14.32 X weight) -603 134 9.14. (1,138 X surface area) - 397 134 9.1

Plasma volume 2,130 274 12.95. (21.09 X height) - 1,362 243 11.46. (28.89 X weight) + 455 213 10.07. ( 9.03 X height) + (24.13 X weight) - 766 209 9.88. (1,747 X surface area) - 733 209 9.8

Whole blood volume 3,600 426 11.89. (35.73 X height) - 2,320 366 10.2

10. (47.16 X weight) + 864 319 8.911. (16.52 X height) + (38.46 X weight) - 1,369 308 8.612. (2,885 X surface area) - 1,131 308 8.6

* Height in centimeters, weight in kilograms, and surface area in square meters as calculated from Du Bois' formula.Values are uncorrected for trapped plasma and for differences betweeen body hematocrit and venous hematocrit.

solid circles. Therefore, in finding the expectedcell or plasma volume of a given subject, it is de-sirable as well as convenient to locate her on thechart by weight and height and to make the predic-tion graphically. A subject of unusual weight or

height, like the four who were excluded from our

calculations, can be recognized easily when thisprocedure is followed.

The extensive data of Gibson and Evans (6)appeared to show that the amount of blood per

unit of body size decreases with increasing size(weight, height, or surface area), especially in fe-males. The present results, like our data for men,

fail to confirm this for subjects whose weight:height ratios are in the common range. Forwomen 144 to 179 cm tall, weighing 45 to 74 kg,and with body surface areas of 1.4 to 1.9 square

meters, sizes comparable to those of Gibson and

Evans' subjects, the fitted bivariate regressionequations are linear (Figures 2 to 4). The graphsand regression equations of Samet, Fritts, Fish-man, and Cournand (7), relating Vrbc and Vpl toweight and surface area for "hospital control"women and men in the same ranges of size as our

subjects, show results in agreement with ours.

For exceptionally heavy women, predictions basedon weight alone tend to be too high (Figure 3).The data for our four heavy women are in bestagreement with the remainder when the regressionto surface area is used (Figure 4).

The average hematocrit of the women was 40.7per cent (SD 2.1) and of the men studied undersimilar conditions (1), 45.2 per cent (SD 2.6).These values are lower than Wintrobe's (3) by1.3 and 1.8 volumes per cent for women and men,

respectively. Our blood samples were taken with

TABLE III

Influence of age on red cell and plasma volume

Residual Vrbc Residual Vp)l

Number of SE SEAge women Mean of mean Mean of mean

years ml ml ml ml20-24 33 -50 23 -91 3625-29 29 2 25 21 3930-39 17 36 33 81 5140-49 10 42 42 88 6650-59 4 133 67 110 10560-77 2 100 95 20 148

2186

Page 6: WENNESLAND,t...BROWN, HOPPER, HODGES, BRADLEY, WENNESLAND, AND YAMAUCHI TABLE I-(Continued) Hemato- Redcell Plasma Age IHeight Weight crit t volumet volume cm kg 170 57.0 168 60.0

RED CELL AND BLOODVOLUMEIN HEALTHYWOMEN:CR51

TABLE IV

Influence of weight: height ratio on red cell and plasma volumes. Analysis of residuals in the 30 womenwith weight: height ratios beyond ± 1 SDfrom the mean

Residual Vrbc Residual Vpl

SE SEGroup Description Mean of mean Mean of mean

mnl ml ?nl mlA 15 women

average age = 46 years -12 35 -20 54weight = < 74 kgweight:height ratio = > 0.382

B* 11 womenaverage age = 32 years -49 40 -64 63weight = < 74 kgweight:height ratio = > 0.382

C 11 womenaverage age = 31 years -31 40 -89 63weight = < 74 kgweight:height ratio = < 0.3 18

1) 4 women

average age = 41 years -207 67 -270 104weight = > 81 kgweight:height ratio = 0.46-0.54

* Group A minus 4 menopausal women aged 50 or more.

great care to avoid the effects of tourniquet stasisand only after the subj ect had rested in a hori-zontal position for an hour. The hematocritswould therefore be expected to be lower than those

of samples taken from ambulatory subjects underordinary conditions of collection (4, 8). The posi-tive correlation between residuals of Vrbc andVpl for women and men (1) shows that the he-

2.0

'4J

0

*dj

0

1.H _0

0

1.6 _

1.4H_

1.2 _-

0

0

0

0 _

1.0 _

* 0

*0

140 150 160 170 180

HEIGHT - CENTIMETERSFIG. 2. RED CELL VOLUMEIN RELATION TO HEIGHT. The solid line is de-

-scribed by Equation 1, Table II, fitted to the data for the 97 women weighingless than 74 kg (solid circles). The dotted lines represent 1 SD of themean Vrbc for any given height. The open circles represent the four women

with exceptionally large weight: height ratios.

2187

Page 7: WENNESLAND,t...BROWN, HOPPER, HODGES, BRADLEY, WENNESLAND, AND YAMAUCHI TABLE I-(Continued) Hemato- Redcell Plasma Age IHeight Weight crit t volumet volume cm kg 170 57.0 168 60.0

BROWN,HOPPER, HODGES, BRADLEY, WENNESLAND,AND YAMAUCHI

2.0 r0

0 0_

00

0-1

0

00

0

0

0 0

50I

60 70 80BODY WEIGHT-KILOGRAMS

90 100

FIG. 3. RED CELL VOLUME IN RELATION TO BODY WEIGHT. The solid line is described byEquation 2, Table II, fitted to the data for the 97 women weighing less than 74 kg (solid circles).The dotted lines represent + 1 SD of the mean Vrbc for any given weight. The open circlesrepresent the four women with exceptionally large weight: height ratios.

matocrit is regulated within closer limits than theblood content per unit of body size.' Thus, healthypersons with large cell volumes tend also to havelarge plasma volumes. This is in contrast to thesituation in anemia and polycythemia, where de-

1 The results of replicated measurements, separated byvarious intervals of time, in 15 members of the maleseries led to the conclusion that most of the observedvariation of Vrbc between individuals of the same sizewas biological rather than methodological (1, 4).

2.0i;:

R 1.8

1.6

1.4

; 1.2

Q

*Q1.01

ficiency or excess of cell mass is often balanced byreciprocal expansion or contraction of plasma (9).In this study, the coefficient of variation (SD as

per cent of the mean) was 5.1 per cent for he-matocrit and 8.6 per cent for Vwb after regressionto weight and height (Table II). Among themen, those with the highest hematocrits were aptto be short and heavy and those with the lowesthematocrits, tall and thin (1). The data forwomen showed no such relationship.

0

0 0

* .

0

0

*

0- 0

.-0 0

i

1.4 1.5 1.6 1.7 1.8 1.9SURFACEAREA-SQUARE METERS

2.0 2.1

FIG. 4. RED CELL VOLUMEIN RELATION TO SURFACE AREA AS CALCULATED FROm DU BOIs' FORMULA.

The solid line is described by Equation 4, Table II, fitted to the data for the 97 women weighing lessthan 74 kg (solid circles). The dotted lines represent 1 SI) of the mean Vrbc for any given sur-

face area. Open circles as in Figures 2 and 3.

_

(I,

W1.8

-4j 1.6

N 1.4

1.2

"J 1.0

_

_-

40

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RED CELL AND BLOODVOLUMEIN HEALTHYWOMEN:CR51

A comparison of the blood volumes of womenand men ought only to be made within comparableranges of heights and weights. Omission of thewomen under 160 cm in height and 54 kg inweight, as well as the four unusually heavy sub-jects, left 67 women who were within the rangesof heights and weights of the men previously stud-ied (1). A residual value for Vrbc and Vpl wascalculated for each of these women by means ofthe prediction equations derived from the data onmen.2 The mean residuals were Vrbc - 214 ml(SE 23) and Vpl + 85 ml (SE 29). The differ-ence in blood content between women and men ofthe same height and weight in our two studiesthus averages only about 130 ml. In contrast, thecompilation by Allen and associates (10) of dataacquired by various techniques in Boston, Stock-holmn, and Taipei shows an average difference of600 ml between the blood volumes measured innonpregnant women aged 20 to 50 and the pre-(icted volumes for men of the same heights,weights, and ages.

The lower content of hemoglobin (11, 12), redcells (13, 14), and blood (10, 15-17) per unit ofbo)ly size in women than in men is usually at-tributed to the higher fat content of the female.It has been reported that the difference betweenthe sexes becomes insignificant when Vrbc is re-lated to lean body mass calculated from body water(14) or when blood volume is related to total bodywater (15). Blood volumes of women were inthe range of those predicted for men when fatthickness and girth were included with height andweight as the bases of prediction (16). Data forboth sexes fell on the same linear regression linerelating blood volume, in milliliters per kilogram,to total body density in the study of Allen and co-workers (10). Huff and Feller's findings (13)for whole blood were similar, although at any givenbody density women tended to have lower cellvolumes and higher plasma volumes in millilitersper kilogram than men. The latter suggests thatsex-associated factors other than body density orfat content may influence the Vrbc andl relativecell volume.

To test whether differences in fat content couldhave accounted entirely for the sex differences

2 Vrbc (nil) = (8.6 X height) + (18.6 X weight) - 830(SD 190). Vpl (ml) = (19.9 X height) + (13.1 X weight)l-2,000 (SD 240).

found in our studies, we determined residual val-ues for Vrbc and Vpl for the 67 women over 160cm in height and 54 kg in weight, using the pre-diction equations for men as above, but multiply-ing the weight factor by 0.85. This factor waschosen on the ground that it would overestimateslightly the difference in storage fat betweenwomen and men, which probably is about 12 to 13per cent of body weight (18, 19). The meanresiduals calculated on this basis were Vrbc - 54ml (SE 23) and Vpl + 20 (SE 29). Althoughthe correction achieved through this artifice isvery good, the possibility still remains that factorsother than body composition may play a role indetermining the difference between the Vrbc ofmen and women. Drabkin has suggested that theloss of hemoglobin due to catamenia and gestationmay contribute (12). The finding of consistentlypositive residuals and higher than average vol-iimes in the older and nonmenstruating women ofour series could be attributed to the cessation ofcatamenia. It is conceivable, however, that post-menopausal changes in the endocrine factors in-fluencing erythropoiesis were responsible. Al-though the number of older people in both ourstudies was small, the tendency was for residualsto be negative in men and positive in women pastthe age of 50.

SUMMARY

1. Red cell volume was measured with Cr51-labeled cells in 101 normally active women whohad been screened for general health. Volumesof whole blood and of plasma were derived indi-rectly from venous hematocrits.

2. The data were collected and treated as de-scribed previously in a similar study on 201healthy men. In the women, the degree of residualvariation, after relation of the volumes to height,weight, height and weight combined, or to sur-face area, was about the same as that found in men.Trivariate regression equations relating volumesto height and weight combined were derived.A chart representing the equations graphically al-lows convenient prediction of red cell and plasmavolumes for a woman of given height and weight.

3. Sixty-seven women were of heights andweights such that they could be compared withthe men previously studied. The red cell volumeof the individual women was on the average 214

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BROWN,HOPPER, HODGES, BRADLEY, WENNESLAND,AND YAMAUCHI

ml smaller and the plasma volume 85 ml largerthan would be predicted for men of comparableheight and weight.

REFERENCES

1. Wennesland, R., Brown, E., Hopper, J., Jr., Hodges,J. L., Jr., Guttentag, 0. E., Scott, K. G., Tucker,I. N., and Bradley, B. Red cell, plasma and bloodvolume in healthy men measured by radiochromium(Cr51) cell tagging and hematocrit: influence ofage, somatotype and habits of physical activity onthe variance after regression of volumes to heightand weight combined. J. clin. Invest. 1959, 38,1065.

2. Sterling, K., and Gray, S. J. Determination of thecirculating red cell volume in man by radioactivechromium. J. clin. Invest. 1950, 29, 1614.

3. Wintrobe, M. M. Clinical Hematology, 5th ed.Philadelphia, Lea & Febiger, 1961, p. 105.

4. Wennesland, R., Brown, E., Hopper, J., Jr., Scott,K. G., Hodges, J. L., Jr., and Bradley, B. Ex-periences with the radiochromium method for de-termination of red cell volume. Scand. J. clin.Lab. Invest. 1962, 14, 355.

5. Build and Blood Pressure, 1959, vols. 1 and 2. Com-piled and published by Society of Actuaries, Chi-cago, 1959-1960.

6. Gibson, J. G., II, and Evans, W. A., Jr. Clinicalstudies of the blood volume. II. The relation ofplasma and total blood to venous pressure, bloodvelocity rate, physical measurements, age and sexin ninety normal humans. J. clin. Invest. 1937,16, 317.

7. Samet, P., Fritts, H. W., Jr., Fishman, A. P., andCournand, A. The blood volume in heart disease.Medicine 1957, 36, 211.

8. Thompson, W. O., Thompson, P. K., and Dailey, M.E. The effect of posture upon the composition andvolume of the blood in man. J. clin. Invest. 1928,5, 573.

9. Brown, E., Hopper, J., Jr., and Wennesland, R.Blood volume and its regulation. Ann. Rev.Physiol. 1957, 19, 231.

10. Allen, T. H., Peng, M. T., Chen, K. P., Huang, T. F.,Chang, C., and Fang, H. S. Prediction of bloodvolume and adiposity in man from body weightand cube of height. Metabolism 1956, 5, 328.

11. Sj6strand, T. The total quantity of hemoglobin inman and its relation to age, sex, bodyweight andheight. Acta physiol. scand. 1949, 18, 324.

12. Drabkin, D. L. Metabolism of the hemin chromo-proteins. Physiol. Rev. 1951, 31, 345.

13. Huff, R. L., and Feller, D. D. Relation of circulatingred cell volume to body density and obesity. J.clin. Invest. 1956, 35, 1.

14. Muldowney, F. P. The relationship of total red cellmass to lean body mass in man. Clin. Sci. 1957, 16,163.

15. Zak, G. A., and Earle, D. P. Blood volume and bodywater in normal hospital subjects. J. Lab. clin.Med. 1957, 49, 504.

16. Hicks, D. A., Hope, A., Turnbull, A. L., and Verel,D. The estimation and prediction of normal bloodvolume. Clin. Sci. 1956, 15, 557.

17. Berlin, N. I., Hyde, G. M., Parsons, R. J., Lawrence,J. H., and Port, S. Blood volume of the normalfemale as determined with P3" labeled red bloodcells. Proc. Soc. exp. Biol. (N. Y.) 1951, 76, 831.

18. Keys, A., and Brozek, J. Body fat in adult man.Physiol. Rev. 1953, 33, 245.

19. Johnston, L. C., and Bernstein, L. M. Body compo-sition and oxygen consumption of overweight, nor-mal and underweight women. J. Lab. clin. Med.1955, 45, 109.

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