THE EFFECT OF CHANGE OF ALTITUDE ON THE CORPUSCULAR
CONSTANTS OF WINTROBE*
ROBERT C. LEWIS, GLADYS M. KINSMAN,! ALBERTA ILIFF AND
ANNA MARIE DUVAL
From the Child Research Council and the Department of Biochemistry, University of Colorado
School of Medicine, Denver and the Oklahoma Agricultural Experiment Station, Stillwater
In 1929 Wintrobe 1 proposed certain corpuscular constants for universal use
as an aid to diagnosis when a blood is abnormal with regard to its red cell count
and hemoglobin content without having to resort to a comparison with standards
which had been established for the locality in question. Thèse constants
are the hemoglobin content of the average cell in terms of micromicrograms
(meàn corpuscular hemoglobin), the percentage hemoglobin content of a unit
volume of cells (mean corpuscular hemoglobin concentration) and the volume
of the average cell in cubic microns (mean corpuscular volume). The constancy or variation of thèse corpuscular constants has been studied in the past
principally by a comparison of values obtained by différent workers. The
data recently reported by Lewis, Iliff, Duval and Kinsman 2 on the number of
red cells, the hemoglobin content and the packed red cell volume of several
normal subjects at différent altitudes offer an excellent opportunity to study the
effect of altitude on the constants of Wintrobe, particularly as the déterminations
on the blood were made by the same workers on the same subjects at the différent
altitudes. Although the number of subjects studied is too small to warrant the
use of the data obtained for the establishment of normal values for the corpuscular constants at any of the altitudes, thèse constants hâve been calculated in
order to détermine their trends in changing from one altitude to another.
EXPERIMENTAL PROCEDURE
Five women and two men were the subjects of the study, and the observations
were made at altitudes of 910 feet, 5,280 feet and 8,720 feet above sea level.
The conditions under which the experiments were conducted are reported in
détail by Lewis, Iliff, Duval and Kinsman 3 . The methods used in the collection
of the blood for the déterminations of the number of red cells, the hemoglobin
content and the packed red cell volume are described by Lewis, Iliff, Duval and
Kinsman 2 .
* This report is taken from the dissertation submitted by Alberta Iliff to the Faculty of
the Graduate Sohool of the University of Colorado, June 1942, in partial fulnllment of the
requirements for the degree Doctor of Philosophy.
A preliminary report of this study was made at the meetings of the American Society of
Biological Chemists at New Orléans in Mareh, 1940 (Kinsman, G. M., A. M. Duval, A. Iliff
and R. C. Lewis, J. Biol. Chem. 133: liii, 1940).
t This author's participation in this study and its publication hâve been approved by
the Oklahoma Agricultural Experiment Station.
208
THE EFFECT OF ALTITUDE ON CORPUSCULAR CONSTANTS
209
RESULTS AND DISCUSSION
Tables 1, 2 and 3 give the mean, the standard error and the standard déviation
of the mean and the coefficient of variation for the mean corpuscular hemoglobin,
the mean corpuscular hemoglobin concentration and the mean corpuscular
volume, respectively, for each subject at each altitude. It may be seen that
there is relatively little intra-variation for any of thèse corpuscular constants at
any of the altitudes. The coefficients of variation never exceed 6 per cent and
average only 2.6 per cent.
TABLE 1
THE MEAN, THE STANDARD ERROR AND THE STANDARD DÉVIATION OP THE MEAN, AND THE
COEFFICIENT OF VARIATION FOR THE MEAN CORPUSCULAR HEMOGLOBIN
The first three of thèse values are expressed in micromicrograms
SUBJECTS
N(cT)
Stiliwater
(altitude
910 feet)
L(cf)
D(9)
K9)
K(9)
H(9)
B(9)
4
7
9
6
3
4
Number of tests
10
Mean
26.1 28.2 29.1 28.8 28.6 27.0 27.1
Standard error
0.76 0.33 0.25 0.34 0.44 0.70 0.37
Standard déviation
1.31 0.82 0.71 1.04 0.98 1.22 0.52
2.4
3.6
3.4
Coefficient of varia- 5.0
4.5
1.9
2.9
tion (per cent)
20
12
6
8
19
6
7
Denver (alti- Number of tests
tude 5,280 Mean
27.9 26.7 29.5 29.9 29.2 27.8 26.7
feet)
0.30 0.21 0.31 0.19 0.28 0.32 0.24
Standard error
0.66 0.56 1.35 0.80 0.69 1.05 0.53
Standard déviation
4.6
3.8
2.4
2.0
2.1
2.7
Coefficient of varia- 2.4
tion (per cent)
Eldora (alti- Number of tests
tude 8,720 Mean
feet)
Standard error.
Standard déviation
Coefficient of variation (per cent)
9
9
7
9
27.9 30.1 30.0 30.9
0.18 0.40 0.25 0.50
0.44 1.13 0.70 1.42
3.8
2.3
1.6
4.6
The changes in the means for each corpuscular constant with each increase in
altitude for each subject hâve been tested for significance, and the results are
given in table 4. The mean corpuscular hemoglobin shows significant changes
only in the case of subject L between Stiliwater (altitude 910 feet) and Denver
(altitude 5,280 feet) and between Denver and Eldora (altitude 8,720), but thés*
are in the opposite direction from one another. No significant changes in the
mean corpuscular hemoglobin concentration occur except in the case of subject
N in changing from Stiliwater to Denver. The mean corpuscular volume shows
greater variability by far than either of the other two constants. Significant
différences are to be found with a change from a lower to a higher altitude in
210
R. C. LEWIS, G. M. KINSMAN, A. ILIFP AND A. M.' DUVAL
eight out of eleven possibilities. However, thèse are divided equally between
decreases and increases. From thèse observations it is évident that no definite
trends for the corpuscular constants of Wintrobe occur with an increase in
altitude, and that the mean corpuscular hemoglobin concentration shows the
least variation.
Whether the illness experienced by subject L during a non-experimental period in Denver
just prior to his departure for Eldora had any effect on the corpuscular constants is problematical. Lewis, Iliff, Duval and Kinsman2 hâve suggested that the values for the number
of red cells, the hemoglobin content and the packed red cell volume found at Eldora for this
TABLE 2
THE MEAN, THE STANDARD ERROR AND THE STANDARD DÉVIATION OP THE MEAN, AND THE
COEFFICIENT OF VARIATION OF THE MEAN CORPUSCULAR HEMOGLOBIN CONCENTRATION,
EXPHESSED IN PER CENT
SUBJECTS
N(d-)
Stillwater
(altitude
910 feet)
L(o")
D(9)
1(9)
K(9)
H(9)
B(9)
4
Number of tests
7
4
3
6
10
10
Mean
30.9 33.2 32.0 33.6 32.5 32.5 32.2
Standard error
0.96 0.39 0.33 0.45 0.43 0.76 0.92
Standard déviation
1.66 0.87 1.00 1.34 1.06 1.32 1.30
4.0
3.3
4.0
4.0
2.6
Coefficient of varia- 5.4
3.1
tion (per cent)
Denver (alti- Number of tests
6
19
7
12
6
8
18
tude (5,280 Mean
34.6 33.2 32.5 33.4 34.3 32.6 33.0
feet)
Standard error
0.58 0.31 0.26 0.25 0.47 0.33 0.24
Standard déviation
1.30 0.81 1.09 1.04 1.14 1.10 0.54
3.3
3.4
Coefficient of varia- 3.8
2.4
3.4
3.1
1.6
tion (per cent)
Eldora (alti- Number of tests
tude 8,720 Mean
feet)
Standard error
Standard déviation
Coefficient of variation (per cent)
9
9
9
7
34.1 32.6 33.1 36.2
0.49 0.46 0.57 0.59
1.20 1.31 1.60 1.67
4.0
3.5
4.6
4.8
subject may hâve been affected by his illness. It is possible, then, that the significant
changes in mean corpuscular hemoglobin and in mean corpuscular volume found for him at
Eldora may hâve been due to the illness. However, it is interesting to observe that in
spite of the illness no such significant change occurred in his mean corpuscular hemoglobin
concentration.
•
Only a few studies of the corpuscular constants of Wintrobe hâve been made
for altitudes higher than 1,000 feet above sea level. Andresen and Mugrage4
reported the corpuscular constants on 40 men and 40 women, ail of whom were
résidents of Denver, Colorado (altitude 5,280 feet). Their average values for
mean corpuscular hemoglobin concentration of 34.2 and 33.4 per cent for men
THE EFFECT OF ALTITUDE ON CORPUSCULAR CONSTANTS
211
and women, respectively, were practically the same as the gênerai average of
33.5 per cent reported by Wintrobe 6 . However, their values for mean corpuscular hemoglobin of 30.5 micromicrograms for men and of 31.2 micromicrograms
for women, and their values for mean corpuscular volume of 89.2 cubic microns
for men and 93.3 cubic microns for women were somewhat above the gênerai
averages of 29.0 micromicrograms and of 86.7 cubic microns given by Wintrobe.
Nevertheless, the following observations indicate that other factors than altitude may hâve accounted for the increases found in thèse constants. Walters 6
and Haden 7 , both of whose studies were made at low altitudes, reported values
TABLE 3
THE MEAN, THE STANDARD ERROR AND THE STANDARD DÉVIATION OP THE MEAN, AND THE
COEFFICIENT OF VARIATION OF THE MEAN CORPUSCULAR VOLUME
The first three of thèse values are expressed in cubic microns
SUBJECTS
N(e?)
Stillwater
(altitude
910 feet)
L(d")
D(Ç)
K9)
K(9)
H(9)
B(9)
Number of tests
6
4
10
3
4
6
9
Mean
84.6 85.4 90.7 85.8 88.3 83.0 84.5
Standard error
0.19 0.14 0.38 0.31 0.74 0.21 1.12
0.33 0.31 1.06 0.92 1.66 0.37 1.59
Standard déviation
1.9
0.4
0.4
1.1
Coefficient of varia- 0.4
1.2
1.9
tion (per cent)
7
19
18
Denver (alti- Number of tests
12
6
6
8
tude 5,280 Mean
80.6 80.5 90.7 89.7 85.3 85.4 80.8
feet)
Standard error
0.49 0.36 0.23 0.29 0.29 0.31 0.19
Standard déviation
1.10 0.95 0.96 1.18 0.72 1.04 0.42
0.8
1.3
1.2
0.5
Coefficient of varia- 1.4
1.0
1.2
tion (per cent)
Eldora (alti- Number of tests
tude 8,720 Mean
Standard error
feet)
Standard déviation
Coefficient of variation (per cent)
9
9
9
7
81.9 92.5 90.8 85.6
0.29 0.45 0.36 0.34
0.71 1.28 1.02 0.95
1.1
1.1
0.9 " 1.4
for mean corpuscular hemoglobin and mean corpuscular volume on men that
were even higher than those found by Andresen and Mugrage at Denver. Furthermore, values only slightly lower than those reported at Denver were found
at élévations below 1,000 feet by Haden for mean corpuscular hemoglobin and
mean corpuscular volume on women and by Foster and Johnson 8 for mean
corpuscular volume on men.
Hurtado 9 has reported corpuscular constants for 132 maie Indian natives who
were lifelong résidents of the Peruvian Andes and on whom studies were made
at Morococha (altitude 14,890 feet). The mean of 96.2 cubic microns for mean
corpuscular volume found by him is markedly higher and those of 24.4 micro-
212
E. C. LEWIS, G. M. KINSMAN, A. ILIFF AND A. M. DUVAL
micrograms for mean corpuscular hemoglobin and of 24.9 per cent for mean
corpuscular hemoglobin concentration are markedly lower than the gênerai
averages reported by Wintrobe6. Andresen and Mugrage4 hâve called attention
to the possibility that diet, race and environmental conditions other than altitude
must be considered when Hurtado's observations are compared with Caucasian
subjects studied in the United States.
Smith, Belt, Arnold and Carrier 10 reported a small séries of déterminations on
the blood of six subjects studied at San Francisco, California (sea level) and at
Long Lake (altitude 11,000 feet) in the Sierra Nevada Mountains. Although
TABLE 4
SLGNIFICANCE OF THE DIFFERENCE BETWEEN THE MEANS OBTAINED AT A HLGHEB AND A
LOWER ALTITUDE, RESPECTIVELY, FOR MEAN CORPUSCULAR HEMOGLOBIN, MEAN CORPUSCULAR HEMOGLOBIN CONCENTRATION AND MEAN CORPUSCULAR VOLUME AS INDICATED
BY THE RATIO OF THE DIFFÉRENCE BETWEEN TWO MEANS IN EACH CASE TO THE STANDARD
ERROR OF THE DIFFÉRENCE.
DIFFERENCES IN MEANS
For
Between
N(cf)
Mean corpuscular Denver and Stillwater
hemoglobin
Eldora and Denver
2.1
Mean corpuscular Denver and Stillhemoglobin conwater
centration
Eldora and Denver
3.3*
m\ — mt\
• ÏOK SDBJECTS
LCc?) D(9) 1(9) K(9) H(9) B(9)
-4.0*
0.9
2.8
1.3
4.5* 1.2
0.5
2.9
1.1
-1.1
0.9
0.0
1.1 -0.4
2.8 0.2
1.7
0.1 -0.4
2.5
Mean corpuscular Denver and Still- -7.6* -12.8* -0.1 9.2* -3.7* 6.3* -3.3*
volume
water
Eldora and Denver
3.0* 3.6* 2.4 0.8
* The values so indicated are significant because the différence in the means is 3.0 or
more times the standard error of the différence between means.
f The values used in the calculation of this formula are: roi = the mean obtained at the
higher altitude, ra2 = the mean obtained at the lower altitude, ao = the standard error of
the différence or vVJ, + o-J,
the standard error of the mean of the values
at the higher altitude and
the standard error of the mean of the values at the lower
altitude.
they did not give the corpuscular constants, thèse hâve been calculated from
their data and are given at the bottom of table 5. The values for mean corpuscular hemoglobin are practically the same at sea level as at 11,000 feet. Furthermore, thèse values and those for mean corpuscular volume on women at both
altitudes and on men at sea level and for mean corpuscular hemoglobin concentration for men at both altitudes are within the limits found by Wintrobe6 at
Baltimore. However, the mean corpuscular volume for men at 11,000 feet has
a slightly lower minimal value and the mean corpuscular hemoglobin concentration for women at sea level, a slightly higher maximal value than the comparable
THE EFFECT OF ALTITUDE ON COKPUSCULAB CONSTANTS
213
values reported by Wintrobe. Moreover, the range for mean corpuscular
hemoglobin concentration for women at 11,000 feet is higher than that reported
by Wintrobe.
A comparison of the ranges of the corpuscular constants obtained in this study
with those of Wintrobe 5 , of Mugrage and Andresen4 and of Smith, Belt, Arnold
and Carrier10 are also given in table 5. Values for each of the corpuscular
constants found at Stillwater (altitude 910 feet) are within the limits found by
Wintrobe at Baltimore. Likewise the values for mean corpuscular hemoglobin
concentration and mean corpuscular volume obtained at Denver (altitude 5,280
TABLE 5
COMPAEISON OP THE RANGES POE MEAN COBPUSCULAB HEMOGLOBIN, MEAN COBPUSCULAB
HEMOGLOBIN CONCENTEATION AND MEAN COBPUSCULAR VOLUME or THE BLOOD FOUND
BY WlNTBOBE (5), BY ANDRESEN AND MuGBAGE (4) AND BY SMITH, BELT, ARNOLD AND
CAKEIEB (10) WITH THOSE OP THE PBESENT STUDY.
AUTEOR
PLACE AND ALTITUDE
MEAN
EAN
CORPUSCULAR CORM
PUSCULAR
HEMOGLOBIN
VOLUME
CONCENTRATION
a
C
c!
B
B
ai
1
g
o
O
micro-micro- per per
•s
cubic cubic
micro-micro- cent cent
microns
microns
grams grams
25-33 25-33 30-36 30-36 80-94 80-94
26-28 27-29 30-33 32-34 84-85 83-91
MEAN
NUMBEK OF CORP
SCULAR
SUBJECTS HEMU
OGLOBIN
d
1
Wintrobe
This study
Baltimore (sea level)
Stillwater (910 feet)
86 101
2
5
Andresen and
Mugrage
This study
Denver (5,280 feet)
40
40 27-34 27-34 31-37 30-36 80-100 79-100
Denver (5,280 feet)
2
5 26-28 26-30 33-35 32-34 80-81 81-91
1
4
3 28 30-31 34 32-36 82 85-93
2 28-31 30-33 34-36 36-38 79-88 84-87
4
2 28-32 30-33 33-35 34-37 85-90 89-90
This study
Eldora (8,720 feet)
Smith, Belt, Long Lake (11,000 feet)
Arnold and
Carrier
San Francisco* (sea
level)
* Thèse values from the report of Smith, Belt, Arnold and Carrier at sea level are
included in order that they may be compared with those obtained by them at 11,000 feet.
feet) are within the limits found there by Andresen and Mugrage. However,
the minimum for mean corpuscular hemoglobin found in the présent study is
slightly below the range reported by them. The basis of comparison for the
results found at Eldora is not as good as for the values obtained at Stillwater
and at Denver, as the only study available for such comparison is that of Smith,
Belt, Arnold and Carrier at an altitude approximately 2,300 feet above that of
Eldora. The values for the mean corpuscular hemoglobin observed at Eldora
(altitude 8,720 feet) fall within the range found by Smith, Belt, Arnold and
Carrier for 11,000 feet, as do the mean corpuscular hemoglobin concentration and
mean corpuscular volume for the man studied at Eldora. For the women at
214
R. C. LEWIS, G. M. KINSMAN, A. ILIFF AND A. M. DUVAL
Eldora the range for mean corpuscular volume has a higher maximal value than
that found by Smith and co-workers, whereas the upper limit for mean corpuscular hemoglobin concentration is the lower limit of their range.
As previously mentioned, the number of subjects used in the présent study is
obviously too small to warrant the use of the data obtained for the establishment
of standards for the corpuscular constants of Wintrobe at any of the altitudes.
However, the opportunity has been afforded to follow the effect of change of
altitude on thèse values on normal individuals. Although certain minor fluctuations are évident, there are no definite trends for any of the constants with an
increase in altitude. Furthermore, ail of the constants for each subject at each
altitude fall within the ranges reported by Wintrobe for sea level. Thus, support
is given to Wintrobe's contention that thèse constants provide a universal basis
for laboratory diagnosis when a blood is abnormal with regard to its red cell
count and hemoglobin content without resorting to arbitrary local standards
for comparison.
SUMMARY
1. The corpuscular constants (mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and mean corpuscular volume) of Wintrobe hâve
been calculated from the data obtained on the number of red cells, the hemoglobin content and the packed red cell volume of seven subjects, four of whom
were studied at altitudes of 910 feet, 5,280 feet and 8,720 feet above sea level
and the other three at the two lower altitudes.
2. No definite trend in any of the constants occurs with an increase in altitude,
and ail of the values found fall within the ranges reported by Wintrobe.
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hemoglobin content of the red blood
hemoglobin and packed cell volume
corpuscle. Am. J. M. Se, 177: 513,
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1929.
and Clin. Med., 19: 851, 1934.
(2) LEWIS, R. C , ILIFF, A., DUVAL, A. M.
(7) HADEN, R. L.: Clinical significance of
AND KINSMAN, G. M.: The effect of
volume and hemoglobin content of
change of altitude on the blood of
red blood cell. Arch. Int. Med.,
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(3) LEWIS, R. C , ILIFF, A., DUVAL, A. M.
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AND KINSMAN, G. M.: The effect of
(8) FOSTER, P. C. AND JOHNSON, J. R.:
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Oxygen eapacity and hemoglobin
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Red blood cell values for normal men
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Blood observations on the Indian
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natives of the Peruvian Andes. Am.
(5) WINTROBE, M. M.: Anémia: ClassificaJ. Physiol., 100: 487, 1932.
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H. P., BELT, A. E., ARNOLD,
différences in the average volume and
H. R. AND CARRIER, E. B.: Blood
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(1) WINTROBE, M. M.: The volume and