THE DISTRIBUTION OF ELECTROLYTES BETWEEN

SERUM AND TRANSUDATES

BY CARL H. GREENE, JESSE L. BOLLMAN, NORMAN M. KEITH,
AND E. G. WAKEFIELD
(From the Division of Medicine, The Mayo Clinic, and the Division of Experi-
mental Surgery and Pathology, The Mayo Foundation, Rochester,
Minnesota)

(Received for publication, November 3, 1930)

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That there is a disturbance in water metabolism in cases of
edema or ascitesis obvious. Many investigations have shown that
there is a simultaneous disturbance in the metabolism of the
inorganic salts. In consequence,the cause of the edema has been
sought in the chemical composit,ion of the pathologic fluid or in
the physicochemical relationship between the composition of the
fluid and the blood serum.
Previous analyses of the blood serum and transudates in human
subjects have indicated a distribution of electrolytes between the
two solutions similar to that obtained after the equilibration in
vitro of horse serum and artificial salt solutions across a collodion
membrane. These results have been quoted widely by the pro-
ponents of a physicochemical theory of edema formation. Un-
fortunately only a relatively small number of such analyses have
been made and the results of experiments with serum from different
speciesof animals have been compared directly. In the present
report we wish to present the results of a considerable series of
analyses of serum and ascitic fluid in dogs and in clinical cases.
The diskibutions obtained have been compared with those which
occur between the serum and the in vivo dialysate previously
reported by Greene and Power (5).

Electrolyte Distribution in Dogs

Experimentally produced edema or ascites, in a dog, ordinarily
is transitory. The spontaneous development of ascites, however,
has been observed in dogs after experimental ligation of the com-
203
204 Electrolytes in Serum and Transudates

mon bile duct (12), and Bollman (3) has shown in these animals
the intimate relation between the diet and the appearance of the
peritoneal effusion. Because the ascites can be maintained in-
definitely under these conditions, such animals afford an op-
portunity for the study in dogs of the distribution of electrolytes
between serum and ascitic fluid, and for t,he comparison of the
results, both with t’he data obtained in clinical cases and with the
in vivo dialysate of the blood obtained experimentally in dogs.
Material and Methods-The common ducts of ten dogs were
doubly ligated and sectioned aseptically, ether anesthesia being

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used. 1 to 2 months later, ascites was produced by the feeding of
considerable quantities of meat or meat extract,, as described
by Bollman (3). Samples of the ascitic fluid, obtained by para-
centesis, were collected over mercury without exposure to the air.
Samples of blood were drawn from the jugular vein without stasis.
They were collected under oil and centrifuged immediately so
that the corpuscles were thrown down before coagulation occurred.
They were then put on ice until coagulation was complete, when
they were recentrifuged and the serum was removed. The
analytic methods were those previously.described (5).
Results-The results of these analyses in dogs are given in Table
I, Series 1. The protein cont,ent of the serum in these dogs was
slightly reduced below that seen in normal animals. The ascitic
fluid on the other hand contained very smdl amounts of protein.
Compared to the serum, the protein, calcium, magnesium, and
phosphates in the ascitic fluid are reduced. The sodium and
potassium are essentially the same as the serum and the chloride
and carbon dioxide in the a&tic fluid are greater than the serum.
The values obtained for the different inorganic constituents of
serum and for the distribution between the serum and the transu-
date agree well with those previously reported by Loeb, Atchley,
and Palmer (9), as well as by Hastings, Salvesen, Sendroy, and Van
Slyke (7), and by Gollwitzer-Meier (4).
Electrolyte Cisttibution in Clinical Cases
Material and Methods-Samples of ascitic or pleural fluid were
obtained by paracentesis from ten patients. Samples of blood
were drawn from the median cubital vein without stasis. All
samples were collected under oil, and were handled rapidly and
 Greene, Bollman, Keith, and Wakefield 205
with care to prevent loss of carbon dioxide. Some of the patient.s
had been treated by the administration of ammonium nitrate;
the nitrates present in the serum and fluid were determined by the
method of Whelan (15).
Resdts-The analytic results are given in Table I, Series 2.
The protein content of the serum was essentially normal in these
cases although it was reduced to 3.7 per cent in one case. The
a&tic and pleural fluids contained considerably more protein than
that found in the animal experiments. Clinical acidosis was not
present in this group of cases. The amount of nitrates present

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in the serum depended on the previous medication received by
the patient. In those cases in which ammonium nitrate was
administered, the nitrates in the serum varied from 0.10 to 5.55
mg. for each 100 cc., with an average value of 3.51 mg. The
fluid usually contained somewhat more, the values ranging from
0.17 to 6.95 mg.
The distribution of the different ions between the serum and the
pleural and ascitic fluids in these cases in general is the same as
that observed in the dogs, Compared to the serum, the protein,
potassium, calcium, and phosphates in the transudate are reduced;
the sodium and magnesium are essentially the same as in the
serum, whereas the chlorides and nitrates in the transudate are
greater than in the serum.
General Comment
A study of the equilibrium between the serum and the tran-
sudate is best made on the basis of the data given in Tables II and
III. In Table II, the various constituents are expressed as milli-
equivalents for each kilo of water in the serum or transudate. The
amount of water was determined directly in all cases. The equiva-
lent bicarbonate was calculated on the assumption that one-
twenty-first of the carbon dioxide content represented free carbonic
acid. This method of calculation dots not take the variation in
hydrogen ion concentration into account, but there was very little
difference in each case between the hydrogen ion concentration of
the serum and that of the transudate, so t.hat this omission does
not introduce any significant error. The concentration of in-
organic phosphate was converted into its equivalent base-bind-
ing power at pH 7.4 (1.8 times t,he millimolal concentration of
phosphate).
 TABLE I
Composition of Blood Serum and Transudates
Na, K, Ca, Mg, chloride, phosphate, and nitrate N are measured in mg. per 100 cc.
- -
N5-S K Ce, Cl(NaC1) PO4 (P) COZ, P” Cent Nitrate N
Series 1 Serum Fluid Serum Fluid T Mg by volume
Dog No. water water proteir 1 I noteil
I
3-
Ehln Fluid 3erum I Fluld .I Serum I Fluld .I Serum I Fluld .I- Serulr Fluid leruml Fluid I Serum I Flwd .I- Serun
;?ic”,” gm. per gm. pel rm. pe T
. 1oocc. 100 gm ‘00 gm
1 95.24 99.27 5.40 0.31 335 332
-I-I-l-/-l-l-
18.9 20.2 9.26 6.42 2.70 2.10 683 733 ,,,,,,,,I-
2 94.20 99.03 5.03 0.40 329 337 17.3 8.78 7.04 2.4 2.30 673 731 3.88 3.60 38.2 48.9
3 94.76 98.89 5.20 0.17 350 345 17.6 15.310.76 8.20 2.59 1.70 638 687 4.64 5.03 57.6 71.1
4 94.53 98.92 5.20 0.34 350 349 18.5 18.6 9.70 6.91 2.69 2.13 691 746 3.86 4.49 49.9 51.3
5 95.06 98.64 4.50 0.35 369 353 23.0 23.4 8.28 6.40 2.70 2.0 759 793 7.31 5.15
6 94.18 98.81 6.20 0.27 356 350 19.5 21.9 8.56 6.68 1.56 2.70 684 734 3.70 3.94 55.1 59.5
7 95.12 99.27 4.55 0.10 347 346 19.9 16.5 9.16 6.64 1.85 1.85 645 700 4.12 4.60 61.0 69.1
8 95.24 99.12 5.22 0.24 345 328 19.5 20.0 9.60 6.62 2.41 2.06 695 739 4.12 4.10 58.8 64.9
9 93.10 98.78 7.09 0.65 333 330 22.6 19.1 9.51 6.70 3.25 2.02 646 708 4.49 3.53 51.8 61.8
10 93.56 98.25 7.10 0.75 339 331 19.0 20.1 9.53 7.29 2.69 1.81 660 722 4.88 4.26 51.8 57.5
~__~ _- -- ____~
Average. 94.50 98.90 5.54 0.36 345 340 19.5 19.8 9.31 6.89 2.48 2.07 677 729 4.50 4.34 52.7 60.4
--- ~--
Series 2
Patient No
I I
93.02 97.12 7.24 3.10 307 311 13.1 12.610.04 7.63 2.39 2.09 518 566 4.49 4.68 71.3 71.0 0.4: 0.59
93.81 95.46 6.15 4.57 320 320 18.3 14.8 9.64 8.58 3.09 2.80 600 623 2.00
94.00 95.22 6.76 5.00 335 333 18.6 12.510.18 9.35 1.31 2.35 577 590 2.80
93.44 95.99 7.38 3.82 316 318 15.5 13.7 9.40 7.97 2.21 2.05 555 571 4.80

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 56 93.30 95.92 7.22 4.01 333 319 15.0 14.8 9.42 7.94 2.24 1.99 561 586 3.18 3.02 66.2 63.8 3.78 4.45
‘511 95.11 99.02 3.52 1.95 305 301 20.2 12.5 7.52 5.24 2.17 1.92 609 651 2.40 2.34 50.2 51.3
77 93.48 97.80 6.73 2.12 308 331 15.7 12.6 8.11 6.62 3.1 2.6 560 640 2.38 3.10 62.2 66.7 0.10 0.17
87 93.23 95.98 6.67 3.34 315 317 17.2 14.0 9.10 7.80 1.94 1.97 542 573 4.02 3.76 64.0 63.6 5.55 6.95 0
gt 93.84 96.65 4.99 2.49 361 332 20.0 12.0 9.70 7.87 2.56 2.58 582
620 3.90 4.00 60.1 55.9 2
1olT 93.41 98.28 5.80 0.56 333 320 17.4 10.811.08 7.82 2.55 2.36 508 544 3.27 3.02 79.5 85.8
___~- g
Average. 93.66 96.74 6.25 3.09 323 320 17.1 13.0 9.42 7.68 2.36 2.27 561 599 3.52 3.46 64.6 64.8 2.51 3.11 .t”

* Hydrothorax; cardiac. al
t Carcinomatous ascites.
3 Carcinomatous hydrothorax.
# Ascites; cardiac failure.
I/ Hydrothorax; nephrosis.
7 Ascites; portal cirrhosis.

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208 Electrolytes in Serum and Transudates

TABLE II--Electrolyte Equilibrium b

Values are expressed in milli-equivalents per kilo of water.

Series 1 Fluid
Na
7
Ii
T Ca -I-
-- -
Dog No. a a a
!5
2F 2h c
u) 4h
-___

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_
gm. per gm. per I im. per
100 cc. 100 gm >100 gm.
1 95.24 99.27 5.67 0.31 153.0145.3 5.1 5.2 4.9 3.2 2.3 1.7 I
2 94.20 99.03 5.34 0.40 151.7147.8 4.7 4.7 3.6 2.1 1.9 1
3 94.76 98.89 5.49 0.17 160.4151.7 4.8 4.0 5.7 4.1 2.2 1.4 1
4 94.53 98.92 5.50 0.34 160.9153.5 5.0 4.8 5.1 3.5 2.3 1.8 1
5 95.06 98.64 4.73 0.35 168.7155.6 6.2 6.1 4.4 3.2 2.3 1.7 1
6 94.18 98.81 6.58 0.27 164.3154.0 5.3 5.6 4.5 3.4 1.4 2.2 1
7 95.12 99.27 4.78 0.10 158.7151.7 5.3 4.2 4.8 3.3 1.6 1.5 1
8 95.24 99.12 5.48 0.24 157.4143.9 5.2 5.2 5.0 3.3 2.1 1.7 1
9 93.10 98.78 7.61 0.66 155.6147.4 6.2 5.0 5.1 3.4 2.9 1.7 1
10 93.56 98.25 7.60 0.76 157.8146.5 5.2 5.2 5.1 3.7 2.4 1.5 1
_-
- __- -~ __--
.____ -- ____
Average. 94.50 98.90 5.88 0.36 158.9149.7 5.3 5.0 4.9 3.5 2.2 1.7 1
_- -- - -
Series 2
Patient

1
No
I ~ II I
93.02 97.12 7.78 3.19 143.5139.0 3.6 3.3 5.4 3.9 2.1 2.0
2 93.81 95.46 6.56 4.79 148.2145.6 5.0 4.0 5.1 4.5 2.7 2.4 1
3 94.00 95.22 7.19 5.25 155.2152.2 5.0 3.3 5.4 4.9 1.2 2.0 1
4 93.44 95.99 7.90 3.98 147.0144.7 4.2 3.7 5.0 4.2 1.9 1.8 1
5 93.30 95.92 7.74 4.18 155.2144.7 4.1 3.9 5.1 4.1 2.0 1.7 1
6 95.11 99.02 3.70 1.97 139.5132.2 5.4 3.2 4.0 2.6 1.9 1.6 1
7 93.48 97.80 7.20 2.17 143.0147.3 4.3 3.3 4.3 3.4 2.7 2.2 1
8 93.23 95.98 7.16 3.48 147.0143.4 4.7 3.7 4.9 4.1 1.7 1.7
9 93.84 96.65 5.32 2.58 167.3149.5 5.5 3.2 5.2 4.1 2.2 2.2 1
10 93.41 98.28 6.21 0.57 155.2141.7 4.8 2.8 5.9 4.0 2.2 2.0
-____ ~- -- _- _-
Average 93.66 96.74 6.68 3.22 150.1144.0 4.7 3.4 !5.0 4.0 2.1 2.0 1
- - - - -
 Greene, Bollmsn, Keith, and Wakefield 209

een Serum and Transudate

Cl / Bicarbonate / P Nitrate Total cations / Total anions / Cation excess

a
e
d -- -

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6 125.8 22.7 25.5 2.5 2.8 165.3 155.4 147.8 154.1 17.5 1.3
0 126.2 17.3 21.0 2.4 2.1 163.2 158.0 141.7 149.3 21.5 8.7
0 118.8 26.0 30.8 2.8 3.0 173.1 161.2 143.8 152.6 29.3 8.6
0 128.8 22.6 22.1 2.4 2.6 173.3 163.6 150.0 153.5 23.3 10.1
4 137.4 24.0 26.1 4.5 3.0 181.6 166.6 164.9’ 166.5 16.7 0.1
2 127.0 25.0 25.8 2.3 2.3 175.5 165.2 151d 155.1 24.0 10.1
9 120.5 27.4 29.8 2.5 2.7 170.4 160.7 145.81 153.0 24.6 7.7
9 127.5 26.4 28.0 2.5 2.4 169.7 154.1 153.8/ 157.9 15.9 3.8
7 122.6 24.8 26.8 2.8 2.1 169.8 157.5 146.3/ 151.5 23.5 6.0
5 125.6 23.7 25.0 3.0 2.5 1644.5 156.9 146.31 153.1 17.3 3.8
-- -~ .-
5 126.0 24.0 26.1 2.8 2.5 171.3 159.9149.a/ 154.6 22.0 5.3
-

-/l-i-
3 99.6 32.8 31.3 2.8 2.8 0.32 0.44 154.6 148.2 131.21 134.1 23.4 14.1
4 111.6 27.7 26.1 2.8 2.3 0.93 1.50 161.0 156.5 140.81 141.5 20.2 15.0
0 106.0 28.2 27.1 2.6 2.4 2.13 2.10 166.8 162.4 137.9’ 137.6 28.9 24.8
5 102.2 31.8 31.9 1.8 1.8 2.83 3.59 158.1 154.4 137.91 139.5 20.2 14.9
8 104.4 30.4 28.5 2.0 1.8 2.90 3.32 166.4 154.4 138.11 138.0 28.3 16.4
112.3 22.6 22.2 1.5 1.4 3.7
4 111.7 28.6 29.1 1.5 1.8 0.79 1.24 12.4
4 102.0 29.3 28.4 2.5 2.3 4.25 5.18 14.9
0 109.6 27.4 24.8 2.4 2.4 22.2
0 98.3 36.5 37.3 2.0 1.8 13.1
---__-
4 105.8 29.5 28.7 2.2 2.1 1.92 2.32 14.6
-
210 Electrolytes in Serum and Transudates

When the composition of the serum and transudate are com-

pared on the basis of the data in Table II it is apparent that the
concentrations of t,he various bases are uniformly higher in the
TABLE III
Ratios between the Electrolyte Concentration oJSe~um and Transudate

Series 1
Dog No.

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1 0.949 1.020 0.644 0.743 0.940 0.9740.8900.897 0.960
2 0.974 0.767 0.910 0.968 0.9680.8241.132 0.950
3 0.946 0.834 0.730 0.630 0.931 1.0500.8440.963 0.942
4 0.954 0.961 0.682 0.754 0.944 0.9701.0230.899 0.977
5 0.923 0.984 0.744 0.715 0.917 0.993 1.472 0.991
6 0.937 1.067 0.744 1.653 0.942 0.9770.9690.985 0.977
7 0.956 0.794 0.694 0.954 0.944 0.9620.9190.934 0.953
8 0.914 0.984 0.662 0.822 0.908 0.9790.9431.045 0.974
9 0.934 0.798 0.664 0.588 0.927 0.9680.9251.346 0.966
10 0.929 1.013 0.728 0.641 0.954 0.9590.9481.200 0.961
~~~___
Average. 0.943 0.944 0.715 0.773 0.934 0.9720.9201.120 0.965
Series 2
Patient Nc

1 0.969 0.917 0.722 0.952 0.958 0.9571.0481.0000.7401.979

2 0.976 0.800 0.883 0.889 0.972 0.9801.0611.2180.6200.996
3 0.981 0.660 0.908 1.666 0.974 0.9911.0401.0831.0101.003
4 0.985 0.881 0.840 0.948 0.976 0.9940.9971.0000.7900.989
5 0.933 0.951 0.804 0.850 0.928 0.9861.0661.1110.8701.000
6 0.947 0.593 0.650 0.842 0.926 0.9741.0181.071 0.983
7 1.030 0.768 0.791 0.815 1.012 0.9170.9830.8340.6400.926
8 0.978 0.787 0.837 1.000 0.966 0.9751.0321.0870.8200.982
9 0.894 0.582 0.788 1.000 0.882 0.9671.1041.000 0.993
10 0.913 0.584 0.678 0.910 0.895 0.9460.9791.112 0.957
---- ~~-___~~
Average. 0.961 0.752 0.790 0.987 0.949 0.9691.0331.0520.8300.9798

serum, whereas the concentrations of the various anions tend to

be higher in the transudates. These ratios are given directly in
Table III. In dogs the average base ratios range from 0.942 for
sodium to 0.71 for calcium, whereas in clinical cases t,he ratios are
 Greene, Bollman, Keith, and Wakefield 211

slightly higher, 0.961 for sodium and 0.79 for calcium. In both
instances the base ratios are higher than those obtained by dialysis
in viva. This is to be expect.ed as the difference between the
protein content of the two solutions is less in the case of these
transudates than it was in the case of the dialysates.
The distribution of the various anions was somewhat less
regular than that of the various bases. In both dogs and man the
phosphates were higher in the serum than they were in the transu-
date. This result, again, is in harmony with the results of dialysis
in vivo, which indicated that some of the inorganic phosphate in

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the serum was held in non-diffusible combination. The chlorides
uniformly were greater in the transudates than in the serum and
were of approximately the same magnitude as those obtained
by dialysis in vivo. The bicarbonate ratio in the experiments
with dogs was approximately the same as that of the chlorides but
in man the transudate contained less bicarbonates than the serum.
Loeb, Atchley, and Palmer (9) found the same relationships to be
present in their comparison of t.ransudat,es with blood from the
arm. One of the difficulties in studies such as this is that of
obtaining a sample of blood truly representative of that with which
the particular transudate in question is in equilibrium. The
true equilibrium in the case of ascitic fluid may be either with the
blood from the mesenteric artery, the portal vein, or the interven-
ing capillaries. In either case, blood from the median cubital
vein at best could indicate only the approximate state of the
equilibrium present. Such considerations probably will serve to
explain t.he apparently anomalous bicarbonate ratio present in
these cases.
Seven of the patients had been taking ammonium nitrate. The
concentration of nitrate in the serum and in the ascitic fluid of
one patient was the same, but there was a great excess of nitrate
in the ascitic fluid of the other six patients, so that the avera.ge
serum-fluid ratio was 0.83 (this may be due to the time at which
samples were taken, for it is possible that the nitrate content of
the ascitic fluid tends to lag behind the serum, both when the
amount in the serum is increasing during the administratJion of
ammonium nitrate and when the amount in the serum is decreas-
ing after administration of this drug has been stopped). Hastings
and van Dyke (6) have found that after sodium bromide has been
212 Electrolytes in Serum and Transudates

given there is an irregular distribution of bromides which concen-

trate in the erythrocytes at Dhe expense of the chlorides, but that
if the sum of the two anions is considered the expected diskibution
ratios between cells and serum are found. The same may be true
of the different anions present in these transudates.
In a consideration of the dialysis of the blood, in viva, the distri-
bution of the chlorides was assumed to represent the best measure
of the shift in concentration produced by the membrane equilib-
rium present, and the chloride ratio was used for calculating the
state of the various cations present in the serum. It was further

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shown for the purposes of this discussion that the serum could be
considered as a diphasic system, consisting of colloidal micelles
dispersed in the intermicellary fluid or free dispersion medium
present. The collodion membrane theoretically serves to separate
the two phases without altering the equiIibrium already established
between micelles and fluid. In consequence the dialysate may be
considered to represent the composition of this intermicellary
fluid.
The same general considerations apply to the relationship
between the composition of the serum and transudate. Both
solutions contain protein but in varying amounts. The membrane
separating the serum is assumed to be freely permeable to water
and to all ions except the protein anions. To maintain osmotic
equality the ratio of osmotically active molecules and ions to water
must be the same in both serum and kansudate.
A, + B, = A/ + Bf (1)
Complete dissociation of the electrolytes being assumed,the
cations in either fluid may be considered as the sum of the cations
paired with diffusible anions and those bound by protein. We
t.hen have
2A, + BP, = 2A/ + BP, (2)
The concentration of the different electrolytes in serum and
transudate is so nearly the same that these relationships still
hold, even if we assumenot complet,e dissociation but equal dis-
sociation of the various salts. Dividing the equation t,hrough by
~4~ and rearranging, we find that,

- = 1 - BP, - BP/
Ts, = A8 (3)
A/ 24
 Greene, Bollman, Keith, and Wakefield 213

According to this calculation the protein in 6he fluid may be

considered as the equivalent of a diffusible anion which neutra-
lizes the effect of a corresponding amount of protein in the serum.
If one assumes that Dhe protein in the two solutions is ionized to
a like extent, then the distribution ratio between the tota, deter-
mined inorganic anions in the serum and transudate is a measure
of the Donnan effect produced by the excess of protein in the serum.
Accordingly the state of the various bases present in the serum
may be calculated from t,he composition of the serum and the
transudate, in the same manner as previously was done in t.he

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study of the serum and the in vim didysate. The average base-
binding power of the serum proteins, when so calculated from the
data given in the present series of analyses, compares favorably
TABLE IV
Base Bound by Serum Protein
M.-eq. per 1 per cent protein 2

Experiment Be&s

per cent
Dialysate. ................... 2.550.1660.355 0.10 3.16 0.276 27
Ascitic fluid, dogs. ........... 2.600.0850.297 0.11 3.07 0.633 67
Transudates, men. ........... 2.550.3880.329 0.06 3.29 0.567 53
---
Average. . . . . .. . . .. 2.570.21 0.327 0.09 3.17 0.482 49

with that previously obtained. The average results for each gm.
of protein are shown in Table IV. The values obtained were all of
approximately the same magnitude in the three series of experi-
ments and t.here was very good agreement between the figures for
the total base and the sodium combined with protein. The results
for calcium and magnesium were less uniform and the greatest
variation was present in the figures for potassium. These differ-
ences, however, are no greater than is to be expected from a
consideration of the analytic errors in each case. We have previ-
ously considered the difficulties in the use of a figure such as this
for the base-binding power of the serum prot’eins. Nevertheless
for the present, the average values given in Table IV may be
214 Electrolytes in Serum and Transudates

regarded as the most satisfactory figures available for the calcula-

tion of the base-binding power of the serum proteins.
It was pointed out (5) that the anions in the serum, with the
exception of the phosphates, probably all occur in the free state.
The results of the present series of analyses accord with this view,
with the sole exception of the bicarbonate ratios in the transudates
from man. We have already considered this point and have given
our reasons for thinking t,hat this ratio does not represent the
actual bicarbonate equilibrium. The concentration of anions in
the dialysate or transudate is increased over that in the serum by

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virtue of the Donnan equilibrium that is present between the two
solutions.
The data in Table IV indicate that the amount of the different
bases bound to protein apparently is a constant, and is independent
of the type of membrane, whether it is a collodion or a living mem-
brane, that is responsible for the equilibrium from which the base-
binding power of the serum proteins is calculated. The apparent
degree of ionization of the base proteinate varies considerably in
the three series of experiments as does the amount of water held
in the protein micelle. Both these constants represent calculated
values which were not determined directly, and small experimental
errors will produce considerable variat,ion in this calculation. A
collodion membrane immersed in serum usually carries a negative
electrical charge and it is recognized that variations in this charge
will affect the electrolyte equilibrium across a dialyzing membrane.
The charge on the capillary wall or on other living animal mem-
branes is not known and a comparison of the effect of this charge
with that on a collodion dialyzing membrane is not possible.
Differences in the electrical charge of the membranes, however,
may well affect the apparent degree of ionization of the serum
protein when calculated by the method used here.
The dialysate may be used as an index to the composition of the
intermicellary fluid or free dispersion medium present in the
serum. On the basis of this assumpt,ion the apparent difference
between the composition of the two solutions may be explained by
some of the water present in the serum being held within the zone
of electrostatic attraction of the protein micelle. The amount of
water so held for each gm. of protein is shown in Table IV. The
average is 0.5 cc. Depending on whether the specific volume of 1
 Greene, Bollman, Keith, and Wakefield 215

gm. of serum protein is taken as 0.75 (13) or 0.80 (14) this gives a
value of 1.25 or 1.30 as the specific volume of the protein micelle.
These values agree well with those of 1.2 and 1.3 previously re-
ported by Polanyi (11) and Augsberger (2). Similar values have
been obtained by Moran (lo), and by Adair and Callow (l), in
the study of gelat’in gels. Hill (8) also has found that 2 to 3 per
cent of the water in blood and other protein solutions is bound by
the colloid.
In a previous study (5) it was pointed out that certain modifica-
tions in the application of the currently accepted physicochemical

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laws relative to the properties of protein solutions were necessary
to explain the relationship observed between blood serum and the
dialysate in vivo. If these modifications are kept in mind, t,hen
the results reported here confirm the earlier studies of Loeb,
Atchley, and Palmer (9), of Hastings, Salvesen, Sendroy, and
Van Slyke (7), and of Gollwitzer-Meier (4) in indicating that the
distribution of the various electrolytes between blood serum and
transudate is governed by the same physicochemical laws which
determine the distribution of these ions between serum and its
dinlysate across a collodion membrane. In consequence, the re-
lative amounts of protein present in the two solutions det,ermine
the relative distribution of the various ions between the serum and
transudate. The fact that the distribution across the living
membrane, whether this is capillary wall or pleural or peritoneal
serosa, or the combination of the two, is the same as that across a
collodion membrane is perhaps without direct biologic significance.
Although physicochemical laws will determine t,he composition
of the transudate while it is in equilibrium with the blood serum
they do not explain either the development or the resorption of the
transudate. Changes in the permeability of t,he living membrane
must be assumed to explain the varying amounts of prot,ein in the
different transudates. Many conflicting hypotheses have been
advanced to explain the causation of edema and ascites and a
review of this question is beyond the scope of this report. We
wish rather t.o point out t,hat the explanation is not to be found
in the composition of the transudate alone for at equilibrium this
is determined by physicochemical laws.
216 Electrolytes in Serum and Transudates

SUMMARY

A study ha,s been made of the distribution of electrolytes between

blood serum and experimentally induced transudates (ascitic
fluid) in dogs and pathologically occurring transudates in clinical
cases. There was no physiologically significant difference be-
tween the two series of experiments.
The distribution of the various electrolyt,es between blood
serum and transudat,es was apparently governed by the same
physicochemical laws which determined the distribution of these

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same ions between the serum and its in vivo dialysate. Under
these conditions, the relative amount and character of the protein
present in the two sohrtions seemingly is the factor which primarily
determines the relative distribution of the various ions between
6he serum and transudat.e.
The base-binding power of the serum protein calculated from
the electrolyte equilibrium between the serum and transudates
is approximately the same as t,hat calculated from the composition
of the in vivo dialysate.
It is pointed out that although these physicochemical laws will
determine the composition of a kansudate while it is in equilibrium
with the blood stream they do not explain either the development
or the resorption of the transudate.
BIBLIOGRAPHY

1. Adair, G. S., and Callow, E. H., J. Gen. Physiol., 13, 819 (1930).
2. Augsberger, A., Ergebn. Physiol., 24, 618 (1925).
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387 (1928); Proc. Staff Meetings Mayo Clinic, 3,137 (1928).
4. Gollwitzer-Meier, K., 2. ges. ezp. Med., 46, 15 (1925).
5. Greene, C. H., and Power, M. H., J. Biol. Chem., 91,183 (1931).
6. Hastings, A. B., and van Dyke, H. B., J. Biol. Chem., 78, p.xxxv (1928).
7. Hastings, A. B.,,Salvesen, H. A., Sendroy, J., Jr., and Van Slyke, D.
D., J. Gen. Physiol., 8,701 (1927).
8. Hill, A. V., PTOC. Roy. Sot. London, Series B, 106,477 (1930).
9. Loeb, R. F., Atchley, D. W., and Palmer, W. W., J. Gen. Physiol., 4,
591 (1922).
10. Moran, T., Proc. Roy. Sot. London, series A, 112,30 (1926).
11. Polanyi, M., Biochem. Z., 104, 237 (1920).
12. Snell, A. M., Greene, C. H., and Rowntree, L. G., Arch. Int. Med., 40,
471 (1927).
13. Svedberg, T., and Sjorgen, B., J. Am. Chem. Sot., 60, 3318 (1928).
14. Van Slyke, D. D., Wu, H., and McLean, F. C., J. BioZ. Chem., 66,765
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15. Whelan, M., J. BioZ. Chem., 86, 189 (1930).
 THE DISTRIBUTION OF
ELECTROLYTES BETWEEN SERUM
AND TRANSUDATES
Carl H. Greene, Jesse L. Bollman, Norman M.
Keith and E. G. Wakefield
J. Biol. Chem. 1931, 91:203-216.

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