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THE EQUILIBRIUM BETWEEN CEREBROSPINAL FLUID AND BLOOD PLASMA

III. THE DISTRIBUTION OF CALCIUM AND PHOSPHORUS BE- TWEEN CEREBROSPINAL FLUID AND BLOOD SERUM

BY H. HOUSTON MERRITT AND WALTER BAUER

(From the Neurological Service and Neurological Laboratory of the Boston City Hospital and the Medical Clinic of the Massachusetts General

Hospital, Boston)

(Received for publication, September 9, 1930)

The first conclusive experiments demonstrating that calcium does not exist in the serum solely in the form of a simple solution were performed by Rona and Takahashi (1). They found that only 65 per cent of the calcium in the serum was capable of diffus- ing through a membrane. Cushny (2) obtained similar results when ox serum was filtered through a collodion membrane under 150 mm. mercury pressure. Determinations of the diffusible serum calcium by other investigators (3-5) have varied consider- ably from those quoted above. Such differences are probably due to the use of different methods. Cameron and Moorhouse (6) first suggested that the cerebrospinal fluid calcium represents the diffusible calcium content of the serum. Except for the studies made by Cameron and Moorhouse (6), Hamilton (7), Pincus and Kramer (S), and Cantarow (9), there are very few data in the literature on the distribution of calcium in the serum and the cerebrospinal fluid. Pincus and Kramer (8) and Hamilton (7) have published the results obtained from a few such determinations.

In our studies of calcium and phosphorus metabolism we have accumulated much data on the distribution of calcium and phosphorus in the serum and cerebrospinal fluid. It was thought advisable to present such of these data as would give us more information concerning the diffusible serum calcium. These studies were made on adult patients1 admitted to the Medical

1 Lumbar punctures were performed in all of these patients for diagnostic purposes, thus enabling us to obtain spinal fluid samples for analysis.

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216 Cerebrospinal Fluid and Blood Plasma. III

Service of the Massachusetts General Hospital and the Neuro- logical Service of the Boston City Hospital. We are also record- ing here the results of determinations of the calcium content of the serum, aqueous humor, and cerebrospinal fluid of rabbits and cats.

The majority of the calcium determinations were made after the method described by Fiske and Logan (10) but a few of the earlier values were obtained by the Clark (11) modification of the Kramer-Tisdall method. The two methods were found to give similar values but the Fiske-Logan method yielded more consistent results. Results with this method have been published by Hamilton (7) and by Blackfan and Hamilton (12). The phosphorus determinations were made according to the method of Fiske and Subbarow (13). Serum protein was determined by the Kjeldahl method (14), and protein in the cerebrospinal fluid by the method of Denis and Ayer (15).

We have made simultaneous determinations of the calcium content of human serum and cerebrospinal fluid in 126 instances, and of the phosphorus content in thirty-nine instances. In experimental animals we have determined the serum calcium content in twenty-three instances, with simultaneous cerebrospinal fluid calcium content in eight. In eighteen animals simultaneous determinations were made of the calcium content of the serum and the aqueous humor.

I. Relation of Serum Calcium and Cerebrospinal Fluid Calcium in Normal Individuals

The normal serum calcium content is generally stated to vary from 9 to 11 mg. per 100 cc. (16). While there has been some disagreement in the reported calcium content of the cerebrospinal fluid most of the recent observers, Pincus and Kramer (8), Can- tarow (9), Hamilton (7), and others, agree that the normal varia- tion is 4.5 to 5.5 mg. per 100 cc. The results of the above authors are more reliable than those reported by other workers as they made simultaneous determinations on the serum and the cerebrospinal fluid.

Table I shows the simultaneous serum and cerebrospinal fluid


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H. H. Merritt and IV. Bauer 217

TABLE I

Normal Cases

The calcium content of the serum and cerebrospinal fluid from forty-nine cases without any disease of the central nervous system or any disturbance of calcium metabolism.

D. W. A. P. J. G. D. L. R. c. J. F. W. H. S. D. E. c. F. R. F. R. S. A. A. J. R. 0. A. T. M. N. E. G. M. A. ( W. B. F. A. J. W. / w. s. B. D. R. N M: D.

a e G?

% r i% :: 9.48 4.60

10.33 5.23 9.93 4.88

10.25 5.05 9.88 5.13

10.06 5.01 9.65 4.62 9.35 4.52 9.46 4.82

10.03 5.18 10.00 5.20 10.06 4.79

9.91 5.23 10.32 5.16 10.08 4.99 10.53 4.79 10.00 4.90 10.33 4.93 10.10 5.00 9.90 4.95 9.85 5.10

10.20 5.07 10.15 5.13 10.01 4.90

9.80 5.00

Calcium T - I

a e d

0.49 0.51 0.49 0.49 0.52 0.50 0.48 0.46 0.51 0.51 0.52 0.48 0.53 0.50 0.50 0.45 0.49 0.48 0.50 0.50 0.53 0.50 0 .50 0.49 0.51

P. P. T. S. A. D. J. D. Y. A. P. M. N. T. D. B. w. u. T. I,. A. M. E. A. G. J. W. H. R. C. B. M. G. F. S. W. N. D. G. R. B. M. McD w. s. P. B. B. H. T. I,. C. E.

l;& :LF 10.30 10.20

9.90 9.85

10.10 9.90 9.95

10.00 10.20 10.15

9.99 10.08 10.14

9.89 9.96

10.16 10.00 10.11

9.80 9.95 9.97

10.03 10.26 10.05

Average............................ . . . . . . . 10.09 5.00 0.50

Calcium

ng. pe, IOOCC.

5.05 4.98 5.20 4.96 5.05 5.01 5.05 5.10 4.90 4.79 5.07 5.11 5.02 4.94 4.99 5.13 5.03 5.01 5.05 4.89 4.96 5.08 5.01 5.09

0.49 0.49 0.52 0.50 0.50 0.51 0.51 0.51 0.48 0.47 0.51 0.51 0.50 0.50 0.50 0 .50 0.50 0.50 0.52 0.50 0.50 0.51 0.49 0.50


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calcium determinations from forty-nine patients who showed no disease of the central nervous system or other disease in which there is a recognized disturbance of the calcium metabolism. The protein content, of the cerebrospinal fluid was normal in every instance and the fluids contained less than five cells per c. mm., thereby eliminating the possibility of increased cerebrospinal fluid calcium due to increased permeability of choroid plexus or meninges.

In this series it will be noted that the serum calcium varied between 9.35 mg. and 10.60 mg. with an average of 10.00 mg., and the calcium content of the cerebrospinal fluid varied between 4.50 and 5.23 mg. per 100 cc., with an average of 5.00 mg.

Mestrezat (17) considers the cerebrospinal fluid to be a dialysate of the serum through the choroid plexus and he showed that the total osmotic pressure, as measured by the freezing point, was identical in the two solutions. This has been confirmed by Tesch- ler (18) and by Thomas (19). The various theories concerning the origin of the cerebrospinal fluid and the reasons for accepting it as a dialysate have been given by Fremont-Smith (20). Cameron and Moorhouse (6) first emphasized the use of the cerebrospinal fluid calcium value as representing the diffusible fraction of the serum calcium.

It should be mentioned that most of the workers who have attempted to determine the amount of diffusible calcium by ultra- filtration or by dialysis have obtained figures somewhat higher than t’he normal cerebrospinal fluid content. The objections to these procedures are given by Stewart and Percival (16) and they state their reasons why accurate results cannot be expected when such methods are employed. Salvesen and Linder (21) have analyzed protein-free edema fluids in patients with Bright’s disease and found 55 to 70 per cent of the serum calcium content in the edema fluid, and they stated that this is the diffusible calcium of the serum. Such edema fluid is derived from abnormal blood plasma in which the calcium equilibrium is probably disturbed.

Updegraff et al. (3), however, modified the method of Moritz and obtained values for the diffusible calcium of serum very similar to that of the cerebrospinal fluid. This method was also used by Snell (4) and the results of his experiments in dialyzing serum


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H. H. Merritt and W. Bauer 219

against water under 150 mm. mercury pressure coincide very closely with the cerebrospinal fluid calcium. Similar results have also been obtained by Neuhausen and Pincus (5).

Our results as shown in Table I indicate that the cerebrospinal fluid calcium content varies between 45 and 53 per cent of the serum calcium content. In 92 per cent of this series it varied between 48 per cent and 52 per cent with an average of 50 per cent for the entire series. Therefore, if the cerebrospinal fluid calcium can be considered as the diffusible calcium, our results show that approximately 50 per cent of the serum calcium is in a diffusible form. This is in agreement with the figures obtained by Cantarow (9), Pincus and Kramer (8), Lennox and Allen (22), Weston and Howard (23), Hamilton (7), and Cameron and Moorhouse (6).

II. Relation of Serum and Cerebrospinal Fluid Calcium Content to Serum Protein Content

It has been conclusively demonstrated that the serum calcium varies directly with the total serum protein (12, 21, 24, 25). We thought it would be of interest to tabulate our results in the instances where the serum proteins had been determined, in order to ascertain whether the variations in the serum calcium content associated with changes in the total serum protein content were accompanied by changes in the cerebrospinal fluid calcium. For reasons given above only cases with normal cerebrospinal fluid protein were used. Most of these cases, however, had abnormali- ties of the central nervous system, and in some the serum calcium was outside the normal limits of 9 to 11 mg. per 100 cc. Neverthe- less the relation between the calcium content of the serum and spinal fluid closely parallels that found in the normal cases in Table I. The four cases with spinal fluid calcium values of less than 4.40 mg. per 100 cc. are associated with serum calcium values of less than 9 mg. per 100 cc. The summary of Table II shows (although the number of cases in some of the groups is quite small) that there is a tendency for both the serum calcium and the cerebrospinal fluid calcium to vary directly with the serum protein. The ratio of the cerebrospinal fluid calcium to the serum calcium is relatively unchanged and in these thirty-four cases hardly varies from the ratios found in the forty-nine cases in Table I.


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TABLE II

Relationship of Serum and Cerebrospinal Fluid Calcium Content to Serum Protein Content

SSIUIR protein

gm. per 100 cc.

5.06 5.08 5.41 5.74 5.87 6.07 6.16 6.16 6.13 6.20 6.27 6.29 6.34 6.37 6.41 6.44 6.47

xi :cY %I ZT 8.80 4.60 9.57 4.42 8.40 3.84 8.70 4.20 9.31 4.80 9.20 4.60 9.60 4.70 8.60 4.60 900 4.40 8.40 3.90 9.70 4.70 9.62 5.29 8.90 4.20

10.50 5.20 9.80 5.00 9.70 5.00 9.64 4.84

Serum protein No. of csse~

gm. per 100 cc.

5 -5.5 5.5-6 6 -6.5 6.5-7 7 -8 8 -9

-

L

0.52 0.46 0.46 0.49 0.51 0.50 0.50 0.53 0.49 0 46 0.48 0.55 0.47 0.50 0.51 0.51 0.50

-

3 2

12 10 5 2

Serum protein

gm. pm 100 cc.

6.56 6.60 6.60 6.62 6.69 6.69 6.82 6.94 6.97 6.98 7.32 7.40 7.60 7.80 7.90 8.20 8.43

SelllIll

mg. per 100 cc.

8.92 9.00 9.34 9.52 9.71 9.61

-.~ 220

?I% 2: %i Fir 10.00 5.38 8.90 4.60 9.60 4.87 9.87 4.66 9.00 5.10 9.46 4.66 9.30 4.80 9.80 4.90 9.70 5.30 9.65 4.62 9.35 4.40

10.14 5.30 9.51 4.66 9.48 4.60

10.06 5.01 9.68 4.84 9.55 4.85

Ca content

mg. per 100 cc.

4.25 4.50 4.70 4.88 4.79 4.84

0.54 0.52 0.50 0.47 0.56 0.49 0.51 0.50 0.54 0.48 0.47 0.52 0.49 0.49 0.50 0.50 0.50

0.48 0.50 0.50 0.51 0.49 0.50


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III. Relation of Serum and Cerebrospina.1 Fluid Calcium and Phosphorus Content in Non-Suppurative Diseases of the

Central Nervous System

Table III gives the results of serum and cerebrospinal fluid calcium and phosphorus determinations in thirty patients with various non-suppurative diseases of the central nervous system.

It will be noted that in practically all instances the serum and the cerebrospinal fluid calcium and phosphorus contents were within normal limits. The ratio of cerebrospinal fluid calcium to the serum calcium was likewise normal. The protein content of the cerebrospinal fluid of this group showed very little elevation, only four having values of over 100 mg. per 100 cc. and only one case over 200 mg. per 100 cc. This latter spinal fluid was obtained from a man suffering from myeloma of the sacrum and a toxic polyneuritis. The total serum protein (5.60 gm. per 100 cc.) and the serum calcium (8.50 mg. per 100 cc.) were low, the cerebrospinal fluid contained 480 mg. of protein and had a calcium content of 4.80 mg., thus giving an abnormally high ratio of cerebrospinal fluid calcium to serum calcium. The average of these thirty determinations was 9.58 mg. of calcium per 100 cc. for the serum and 4.76 mg. of calcium per 100 cc. for the cerebrospinal fluid with a ratio of cerebrospinal fluid calcium to serum calcium of 50 per cent.

The phosphorus content averaged 4.0 mg. per 100 cc. for the serum and 1.53 mg. per 100 cc. for the cerebrospinal fluid. The ratio of the serum phosphorus to the cerebrospinal fluid thus being 38 per cent with a range of 31 to 45 per cent. Hamilton (7) obtained a ratio of 50 per cent in the twenty-six cases he reported. Such results suggest that the protein of the serum influences the diffusion of some of the phosphorus as well as some of the calcium, thus allowing only about half to pass through the human membrane (choroid plexus).

IV. Relation of Serum Calcium and Phosphorus in Suppurative Diseases of the Central Nervous System (Meningitis)

Table IV shows the results of twenty-one determinations in patients with meningitis arranged in order of amount of protein in the cerebrospinal fluid. It will be noted that the serum calcium was low in a number of these patients and some of these had a


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TABLE III

Serum and Cerebrospinal Fluid Calcium and Phosphorus Content in Non-Suppurative Diseases of the Central A’ervous System

Disease

Central nervous system syphilis.. . . . . . . . . . . . . . . . . .

“ ‘I “ “ I‘ ‘< “ “

hlultiple sclerosis. . . . . . . . . . ‘I “ . . . . . . . . . I‘ ‘I . . . . . ‘I “ . . . . . . . , . . . “ “ . . . . . . . . . . . “ ‘I . . . . . . “ ‘I . . . . . “ L‘ . . . . . . . . . . . ‘I “ . . . . . . . . . . ‘I “ . . . . . . . “ “ . . . . . . <‘ ‘I . . . . . . . ‘I “ . . . . . .

Parkinson’s . . . . . . . . . . “ . . . . . . . . . . . . . . . . .

Subarachnoid hemorrhage.. ,‘ “ . ‘I ‘6 .

Hematomyelia. . . . . Friedreich’s ataxia.. . . . Cerebral arteriosclerosis.. . Cerebral hemorrhage.. . , Polyneuritis. . . . . . . . . . . . . Diabetes insipidus. . . . . :, Epilepsy. . . . . . . . . . . .

Protein

g 8

m -

gm. Per 100 cc.

i.tx

i.0; i.8: i.lt

- 1

1 1 1

g.43 21 j.47 2: 5.34 2 j.40 13' 5.07 B’ 5.87 3,

3 2

8.44 4 6.27 5 6.41 2 5.08 2 7:32 4 8.20 14 7.60 23 7.70 8

8 7.40 E 6.56 2

6 5.60 4E

i

Average. . . . . . . . . . . . . . .

9.7, 9.0 9.2' 9.3' 9.6 9.5 9.6 8.9 9.7 9.3 9.3 9.6 9.5

10.0 9.8 9.7 9.7 9.E 9.5 9.2

10.: 9.4 9.: 9.4 9.f

1o.c 10.1 8.1

1o.t 9.t

- 9.!

Calcium

.64 0.47

.87 0.50 .60 0.50 .80 0.51

:.70 0.49 .85 0.51

:.84 0.50 ..20 0.47 ..90 0.50 :.60 0.50 :.80 0.51 :.80 0.50 :.50 0.46 :.50 0.46 I.90 0.50 i.00 0.51 L.70 0.48 j.00 0.51 L.42 0.4C 4.40 0.47 L.83 0.4i I.68 0.4: 4.60 0.4f 4.59 0.4E 4.80 0.5( 5.38 0.51: 5.40 0.5: 4.80 0.5f 5.40 0.9 1.38 0.4f --

4.76 0.5(

Phosphorus

I.43 J.38

I.31

I.43 I.32 I.42 I.37 3.45

0.37

222


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normal serum protein and a normal or low serum phosphorus, which, in accordance with previous observations (12, 21, 24, 25) would indicate a primary disturbance in the calcium metabolism

TABLE IV

Serum and Cerebrospinal Fluid Calcium and Phosphorus Content in Meningitis

T T Protein Calcium Phosphorus

a e d

-7 --

1:

--

-

0.51 0.56 0.52 0.56 0.55 0.50 0.49 0.60 0.55 0.55 0.51 0.54 0.60 0.58 0.60 0.49 0.60 0.66 0.56 0.68 0.66

0.56

a e $

gm. per 100 cc. % :c?

1 21 2 6.06 32 3 6.47 70 4 6.02 72 5 6.61 108 6 5.92 114 7 6.76 142 8 6.23 156 9 6.58 162

10 6.50 190 11 7.04 190 12 7.10 198 13 6.17 222 14 6.27 318 15 6.24 320 16 6.30 432 17 5.90 800 18 5.91 924 19 4.71 1140 20 5.83 1330 21 6.18 1998

- - Average............,

;“o”;, ::.! 11.00 9.70 9.05 8.95 9.20

10.20 9.50 8.80 9.39 9.05 9.45 9.36 8.77 9.17 8.95 8.94 8.40 9.40 9.40 7.80 8.40

n!J. P 100 cc.

5.60 5.40 4.68 5.00 5.08 5.10 4.67 5.10 5.14 4.98 4.83 5.06 5.26 5.35 5.15 4.44 5.04 6.20 5.30 5.30 5.52

3.80 4.32 3.58 3.70

4.08 3.90 3.94 4.49

2.50 3.55 4.50 2.73 3.46 1.40 3.70

1.9 1.6 1.75 1.5 2.24 1.73

1.9 1.6 1.3 1.6 1.2

1.73 6

F.9 1.8

0.40 0.40

0.51

0.43 0.38 0.56 0.38

0.64 0.65 0.35 0.44

1.23 0.43

0.68

- 9.18 5.15 3.52 1.72

- 0.49

-

in meningitis. The cerebrospinal fluid calcium was relatively high in most of the fluids with the majority of specimens showing a cerebrospinal fluid to serum calcium ratio of over 55 per cent. The


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average calcium content for this group was 9.18 mg. per 100 cc. for the serum and 5.15 mg. per 100 cc. for the cerebrospinal fluid and a ratio of 56.1 per cent. Most of the cerebrospinal fluids had a high protein content, and in several the increase in the cerebrospinal fluid calcium can be accounted for by assuming that some of the calcium is associated wit,h the protein of the cerebrospinal fluid. Case 21, for example, had a serum calcium of 8.4 mg. per 100 cc. which under normal conditions should be accompanied by a cerebrospinal fluid calcium of approximately 4.2 mg. The cerebrospinal fluid had 1998 mg. of protein per 100 cc. which is approximately one third of the serum protein. As the non-diffusible calcium (protein-bound calcium) is calculated as 4.2 mg., one-third of this figure would be 1.4. Therefore 4.2 mg., the calculated content of the cerebrospinal fluid, plus 1.4 mg., the calcium bound by the protein, gives 5.6 mg., which is very close to the figure determined-5.52 mg. This relation does not work out as well in all of the cases but the increase in the calcium content of the cerebrospinal fluid in meningitis can probably be accounted for by the abnormal protein present in the fluid and the increased permeability of the meninges and choroid plexus.

The phosphorus content of the serum averaged 3.52 mg. per 100 cc., slightly below the normal average, and the phosphorus content of the cerebrospinal fluid averaged 1.72 mg. per 100 cc. slightly above the normal average. The ratio of cerebrospinal fluid phosphorus to serum phosphorus was 49 per cent in these cases as contrasted with 38 per cent in the cases shown in Table III. The increase in this ratio was probably due, as in the case of the calcium, to the increased protein in the cerebrospinal fluid and the increased permeability of the choroid plexus. This hypothesis is supported by t,he work of Cohen (26). The increase in the phosphorus ratio in these cases averaged nearly twice as much as the increase in the calcium ratio.

V. Serum: Cerebrospinal Fluid Calcium in Pulmonary Tuberculosis

The serum calcium is thought to be low in acute cases of pulmonary tuberculosis especially those having hemoptysis. Brockbank (27) found the calcium of the serum decreased in the acute cases and increased in the healed cases, but stated that it is not a trust- worthy guide of the activity of the pulmonary process because of


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the individual variations. Cantoni (28) and Greisheimer and Van Winkle (29) have also studied the calcium content of the serum in pulmonary tuberculosis.

Table V shows our results in nine active cases of pulmonary tuberculosis. Five of these cases had a serum calcium content within normal limits, and four were below normal. Two of the latter cases, however, had a slightly lowered serum protein. There was no appreciable change in the ratio of the cerebrospinal fluid

TABLE V

Serum and Cerebrospinal Fluid Calcium Content in Pulmonary Tuberculosis

Case No.

Protein

SWUUl

% zr 7% :cT ‘;b” :LY % :c?

5.72 105 6.75 3.38 5.41 33 8.40 3.84 9.10 35 9.50 5.20 6.37 16 10.50 5.20 6.97 26 9.70 5.30 6.29 24 9.62 5.29 7.04 190 9.45 4.83 6.60 12 8.90 4.60 6.16 23 8.60 4.60

- Average. . . . . . . . . . . . 9.05

I

-

T

,

_-

Calcium

4.69

0.49 0.46 0.55 0.50 0.54 0.55 0.51 0.52 0.53

0.51

Phosphorus

Eki-UIll

T

Cerebro- spinal fluid

to serum calcium content. It varied from 46 to 55 per cent with an average of 51.7 which was only slightly higher than the normal average.

VI. Effects of Forced Drainage on the Relation of Serum and Cerebrospinal Fluid Calcium Content

Kubie (30) in 1928 found that the perivascular spaces of the central nervous system could be drained by draining the cerebrospinal fluid during the intravenous injection of hypotonic solutions. He suggested the use of this method in treating certain diseases


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of the central nervous system. His method was modified slightly and used by Fremont-Smith, Putnam, and Cobb (31). They performed a lumbar puncture and drained the cerebrospinal fluid for several hours. While the needle was in the spinal canal the patient was given water by mouth at frequent intervals and 0.25 to 1.0 cc. of vasopressin was injected subcutaneously to prevent diuresis. A specimen of the blood and cerebrospinal fluid were taken for analysis at the beginning and at the end of this procedure.

Table VI shows the figures for the calcium and phosphorus content of the serum and the cerebrospinal fluid in nine of these cases. In eight of the nine cases there was a drop in the calcium content of the serum and of the cerebrospinal fluid, and all but one showed a drop in the serum protein. Most of the changes in the serum and cerebrospinal fluid can be explained on the basis of dilution of the body fluids by the retained water (31).

VII. Serum and Amniotic Fluid Calcium Content

Pregnancy is the one physiological condition in which there is a recognized alteration of serum calcium, and it is presumably due to the drain on the maternal tissues in supplying the demands of the fetus. Various authors have reported a fall in the serum calcium during the latter months of pregnancy. Mazzocco and Bustos Moron (32) found a low serum calcium during pregnancy as did also Bogert and Plass (33), Widdows (34), and Bauer, Albright, and Aub (35). Larson and Fisher (36), working with parathyroidectomized dogs, found that there was a fall in serum calcium during pregnancy although a normal level had been main- tained in the animals before t,hey became pregnant.

Very little work has been done on the calcium content of the amniotic fluid and it was thought advisable to report the results obtained in our few cases.

Table VII shows the calcium content of the serum and the amniotic fluid in seven pregnant women at time of delivery. It will be noted that in six of the seven cases the serum calcium was definitely below the limits of normal, with an average of 8.59 mg. per 100 cc. A comparison of the figures with Table II indicates that this change is not due to a loss of serum proteins as they are at the lower level of normal in four of the cases and only slightly below the normal level in the remaining three cases.


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TABL

E VI

Influ

ence

of

Wat

er

Drin

king

durin

g th

e An

tidiu

retic

Ef

fect

of

Vaso

pres

sin

on t

he S

erum

an

d Ce

rebr

ospi

nal

Flui

d Ca

lcium

an

d Ph

osph

orus

Co

nten

t

Phos

phoru

s Pr

otein

Calciu

m -

-

Befor

e Af

ter

0.50

0.

45

0.47

0.

46

0.55

0.

49

0.51

0.

49

0.50

0.

49

0.51

0.

48

0.49

0.

52

0.51

0.

52

0.50

0.

48

0.49

Cereb

r;rGna

l Ca

se

No.

SWUI

II SQ

XUUl

SerllU

l

Befor

e %I :c

: 1.

20

1.50

-

_ 1

1.30

1.30

1.

25

1.60

1.

30

1.35

1.

16

Befor

e Af

ter

Befor

e Af

ter

% 2:

4.1 3.9

4.7

4.66

4.

4 4.

2 4.

6 4.

6 4.4

4.40

% ET

%

zr

3.90

4.

60

3.45

3.

20

4.18

3.

50

4.47

3.

67

4.00

3.

50

4.00

2.

90

4.30

4.

20

2.90

3.

20

3.77

3.

59 -

-

--

1

_- -

_- - .- -

-- -- , -_ I -

-

1

.- -

.- 1

.- 1:

_- -

-

1 _

-

!& zr

6.

94

6.34

6.

69

8.43

6.

47

6.40

6.

07

5.87

- Af

ter

.-

0 rm. p

er

too c

c.

7.03

6.

20

6.27

6.

69

6.13

5.

74

5.06

4.

07

_-

6.65

5.

9a

II

_-

-

-

After

%i :L

T 33

22

32

24

28

13

2 69

34

38

I % :::

27

11

56

21

23

19

44

27

16

.-

57

27

After

Be

fore

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The calcium content of the amniotic fluid was found to be between 5.4 and 8.8 mg. per 100 cc. with an average of 6.59 mg. It will be noted that the amniotic fluid had a low protein content,

TABLE VII

Serum and Amniotic Fluid Calcium Content in Pregnancy

T T Protein Calcium Phosphorus

Case No. T -

- _

-- AyuFdtic SWUlll Amniotic

fluid

“*G ET 7% :c % :cY ‘;“o”i, ::.r

6.36 219 8.76 5.40 6.30 219 8.07 7.44 6.68 120 8.53 7.40 6.20 177 9.58 8.80 5.43 250 8.30 5.75 5.74 1140 8.60 5.64 5.53 150 8.30 5.70

.- Average.. . . . . . . . . . . . . . . .I 8.59 6.59 4.5

0.94 1.20

1.07

TABLE VIII

Efect of Diet on the Serum Calcium Content in Cats

I; T Controls 3igh Ca diet for 270 days Low Ca diet -

Animrtl No. Serum Ca 1 himal No. Serum ca

401 402 403 404

--

% ::.r

11.60 10.06 9.76

11.06

337 341 357 360 362 364 356

xi ::r 10.62 10.02 12.10 11.20 11.75

9.90 10.62

A%?1 No. of days

338 160 346 160 339 160 345 160 342 269 343 267

Serum Ca

‘;“o”i, it?

11.42 10.85 9.23 9.48

10.50 10.25

Average. 10.62 10.91 10.28 -

approximately 200 to 300 mg. per 100 cc., and therefore practically none of the calcium present in the amniotic fluid was associated with the presence of protein. A complete report of other determinations on these fluids will be made later by Dr. A. Makepeace.


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‘VIII. E$ect of Diet on Calcium Content of Serum in Cats

In an endeavor to determine whether the calcium content of the diet could influence the serum calcium level, cats were fed a diet containing a known quantity of calcium.

Table VIII shows that the calcium content of the serum of four normal cats averages 10.62 mg. per 100 cc. Seven cats were fed a diet high in calcium for 270 days and the average serum calcium

TABLE IX

Calcium Content of the Serum, Cerebrospinal Fluid, and Aqueous Humor in Cats

Cerebrospinal fluid

“(7. per 100 cc.

6.10 5.62 6.25 6.04 5.47 5.41 5.78

Animal No. SWUUI

mg. per 100 cc.

337 10.62 341 10.00 357 12.10 360 11.20 362 11.75 364 9.90 356 10.62 401 11.60 402 10.06 403 9.76 404 11.06 342 10.50 343 10.25 351 9.56 297 10.31 353 10.02 314 11.63

Average.. . . . .I 10.64 I 5.79

5.72

T

Aqueous humor

mg. per 100 cc.

5.63 6.47 7.40 6.10 6.23 6.30 6.28 6.20 5.83 6.71 6.45

6.70 6.51 6.49 6.90 7.00

6.44

content was 10.91 mg. per 100 cc., while the average serum calcium content for six cats fed a diet low in calcium for a period varying from 160 to 269 days was 10.28 mg. per 100 cc.

IX. Calcium Content of Serum, Cerebrospinai Fluid, and Aqueous Humor in Cats

Table IX shows the results of our determinations in seventeen cats.2 The average calcium content of the fluids was as follows:

2 All specimens were obtained under ether anesthesia, following which the animals were sacrificed.


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serum 10.64 mg. per 100 cc., cerebrospinal fluid 5.79 mg. per 100 cc., aqueous humor 6.44 mg. per 100 cc. From these results it would appear that the serum and cerebrospinal fluid calcium content of cats is slightly higher than in humans, and that the cerebrospinal fluid calcium averages 54 per cent of the serum calcium. The aqueous humor calcium averages 60 per cent of the serum calcium.

SUMMARY

1. The normal serum calcium content was found to vary between 9.35 and 10.6 mg. per 100 cc. with an average of 10.0 mg. per 100 cc. The cerebrospinal fluid calcium ranged from 4.5 to 5.23 mg. per 100 cc. with an average of 5 mg. The ratio of the cerebrospinal fluid calcium to the serum calcium varies from 45 to 53 per cent, with an average of 50 per cent.

2. The serum and cerebrospinal fluid calcium content was found to vary directly with the serum protein in such a way that there was no significant change in the ratio of cerebrospinal fluid calcium to serum calcium with changes in the serum protein.

3. The serum and cerebrospinal fluid calcium content was

normal in various non-suppurative diseases of the central nervous system.

4. In meningitis there was a slight diminution of serum calcium content with an increase in the cerebrospinal fluid calcium content. This increase in the cerebrospinal fluid calcium content can probably be accounted for by increased permeability of the meninges and the choroid plexus and the resulting increased protein in the cerebrospinal fluid.

5. There was a slight decrease in the serum and the cerebrospinal fluid calcium content in pulmonary tuberculosis.

6. Water drinking during the antidiuretic action of vasopressin caused a decrease in the serum and cerebrospinal fluid calcium.

7. There was a definite decrease in serum calcium content at the end of pregnancy. The amniotic fluid calcium content was found to vary between 5.4 and 8.8 mg. per 100 cc. with an average of 6.59 mg. per 100 cc.

8. The calcium content of the diet had a slight influence on the level of the serum calcium of cats.

9. In cats the cerebrospinal fluid calcium content averaged 54 per cent of the serum calcium, and the aqueous humor calcium content averaged 60 per cent of the serum calcium.


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H. H. Merritt and W. Bauer

10. In non-suppurative diseases of the central nervous system, the cerebrospinal fluid phosphorus content was found to vary between 31 and 45 per cent of the serum phosphorus with an average of 38 per cent. In suppurative diseases of the nervous system, the ratio of cerebrospinal fluid phosphorus to serum phosphorus varied between 35 and 123 per cent with an average of 40 per cent.

One of us (H. H. M.) takes this opportunity to thank Dr. Frank Fremont-Smith for his aid and guidance in this work, and for the data on serum and cerebrospinal fluid protein.

BIBLIOGRAPHY

1. Rona, P., and Takahashi, D., Biochem. Z., 49,370 (1913). 2. Cushny, A. R.,J. Physiol., 63,391(1919-20). 3. Updegraff, H., Greenberg, D. M., and Clark, G. W., J. BioZ. Chem., ‘71,

87 (1926-27). 4. Snell, A. M., Proc. staff Meetings Mayo Clinic, 6,17 (1930). 5. Neuhausen, B. S., andpincus, J. B., J. Biol. Chem., 67, 99 (1923). 6. Cameron, A. T., and Moorhouse, V. H. K., J. Biol. Chem., 63, 687

(1925). 7. Hamilton, B., J. Biol. Chem., 66,101 (1925). 8. Pincus, J. B., andKramer, B., J. Biol. Chem., 6’7,463 (1923). 9. Cantarow, A., Arch. Znt. Med., 44,670 (1929).

10. Fiske, C. H., and Logan, M. A., unpublished data. 11. Clark, E. P., and Collip, J. B., J. Biol. Chem., 63,461 (1925). 12. Blackfan, K. D., and Hamilton, B., Bull. Johns Hopkins Hosp., 41, 322

(1927). 13. Fiske, C. H., and Subbarow, Y., J. Biol. Chem., 66,375 (1925). 14. Dyer, B., J. Chem. Sot., 47,811 (1895). 15. Denis, W., and Ayer, J. B., Arch. Znt. Med., 26,436 (1920). 16. Stewart, C. P., and Percival, G. H., Physiol. Rev., 8,283 (1928). 17. Mestrezat, W., Le liquide cephalo-rachidien normal et pathologique,

valeur clinique de l’examen chimique, Paris, 170 (1912). 18. Teschler, L., Deutsch. Z. Nervenheilk., 103,87 (1928). 19. Thomas, G. W., unpublished data. 20. Fremont-Smith, F., Arch. Neural. and Psychiat., 17,317 (1927). 21. Salvesen, H. A., andLinder, G. C., J. BioZ. Chem., 68,617 (1923-24). 22. Lennox, W. G., and Allen, M., Arch. Neural. and Psychiat., in press. 23. Weston, P. G., and Howard, M. Q., Arch. Neurol. and Psychiat., 8,179

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28. Cantoni, O., Riv. pat. din. tuberc., 3,265 (1929). 29. Greisheimer, E. M., and Van Winkle, C. C., Am. Rev. Tuberc., 16, 270

(1927). 30. Kubie, L. S., Arch. New-ok and Psychiat., 19,997 (1928). 31. Fremont-Smith, F., Putnam, T. J., and Cobb, S., Arch. Neural. and

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(1921). 33. Bogert, L. J., and Plass, E. D., Am. J. Obst. and Gynec., 6,427 (1923). 34. Widdows, S. T., Biochem. J., 17, 34 (1923). 35. Bauer, W., Albright, F., andAub, J. C., J. Clin. Inv., 7,75 (1929). 36. Larson, E., and Fisher, N. F., Endocrinology, 11,233 (1927).


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H. Houston Merritt and Walter BauerAND BLOOD SERUM

BETWEEN CEREBROSPINAL FLUIDCALCIUM AND PHOSPHORUS

PLASMA: III. THE DISTRIBUTION OFCEREBROSPINAL FLUID AND BLOOD

THE EQUILIBRIUM BETWEEN

1931, 90:215-232.J. Biol. Chem.

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