Laboratory of James L. Gamble
I T IS NOT from a desire to be tantalizing that only three pages of this classic of pediatric investigation are shown here (Figs. 1-3). The title page reveals it was so lengthy a paper (actually 62 pages) that a “¿Contents―was believed to be necessary. Although the article is based on observa tions from only four subjects, the studies are known to have extended over 2 years.
The investigations were so thoughtfully planned that they have served as models to subsequent generations of workers in the field. The data are presented within the framework of a clear exposition of concept and subjected to a searching analysis and logical interpretation. It would be a reck
0Reproduced by permission from the Journal of
Biological Chemistry, 57:633, 1923.
less editor who would seek to improve on the characteristic style or dare to strike out a single paragraph.
The first public appearance of one of Gamble's famous diagrams is shown on the page 633 of his paper; that it is the product of his own draftsmanship is easily recog nized by those who ever watched him pre pare charts for lectures or papers in his laboratory study.
Dr. Gamble was 40 years old when this paper appeared, but it was his first im portant contribution. There was still time for a long series of equally fundamental papers. Take heart you despondent quarto generians and stir among the scoffing youngsters!
C.D.M.
904 A PEDIATRIC CLASSIC
THE METABOLISM OF FIXED BASE DURING FASTING. B@ J. L. GAMBLE, G. S. ROSS,t ANDF. F. TISDALL..
(From the Laboratory of the Department of Pediatrics, the Johns Hopkins
University, Baltimore.)
(Received for publication, June 30, 1923.)
CONTENTS.
I. Introduction . 633
H. Significance of total base concentrations in the body fluids 635
III. Source of fixed base available for use in the process of acid excre
tion during fasting 640
IV. Factors determining the amounts of acid substances claiming
excretion in the urine during fasting 657
V. The regulation of fixed base excretion 660
VI. Data illustrating the separate control of acid and of base con
centrations in the body fluids 680
VII. Acid-base values in the plasma during fasting 683
VIII. Summary 692
I.
INTRODUCTION.
The data presented in this paper were obtained from four epileptic children who were being fasted as a therapeutic measure. It has recently been quite thoroughly shown that epileptic seizures either disappear entirely or else are much reduced as to frequency and severity during the course of a period of fasting, and also that occasionally following a fast there is for a long inter val (months) no recurrence of convulsions. The presence of a metabolic factor in the causation of epilepsy is thus definitely indicated. We have at present no knowledge as to whether this factor occupies an•initial or a supplementary position in the pathogenesis of the disease. The fact of its presence, however, provides basis for the hope that further study will reveal its
* The expense of this study was in a large part defrayed by a grant from the Epilepsy Medical Research Fund of the Johns Hopkins University.
f Cooper Travelling Fellow of McGill University. 633
TU JOURNAL 0? BIOLOGICAL CRENW?RT, VOL. LVII, NO. 3
636
Metabolism of Fixed Base
within the body at constant values. We have chosen to stu(ly particularly the manner of maintenance of t.otal base because of its prominence among the values which together sustain the structural integrity of the body fluids. It should be said here, however, that regardless of its relative importance no single structural, factor can correctly be expected to be sustained with an absolute rigidity in the presence of alteration of other factors. rfhe interdepend ence of the values for the struc tural factors in blood for example, regarding blood as a physicochem ical mechanism, has recently been
demonstrated and emphasized by
L. J. Henderson (3).
With the purpose of illustrating the importance of the total base value we wish to describe here, with the help of the diagram in Fig. 1, the structural significance of the base concentration in blood plasma. In this diagram the average usual total base concen tration, i.e. the sum of the sepa rate concentrations of Na@, K@, (‘a―,and Mg―,is represented by the height of the left hand col umn. Expressed as 0.1 N base this amounts to 156 cc. per 100 cc. of blood plasma. In the right hand column are indicated separately the usual amounts of the acid substances which bind the
base of the plasma. Beginning at the top the concentration of HCO3' is seen to bind about one-fifth of the plasma base. Below this value the huge concentration of Cl' covers nearly three-fifths of the base column. The next block in the acid column represents the combined concentrations of HPO4―,SO4―,and organic acids. It will be seen that after laying off these values a considerable
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C.-,@Or9@Acid'
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Fia. 1. The normal acid-base composition of blood plasma.
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906 A PEDIATRIC CLASSIC
Gamble, Ross, and Tisdall
637
portion of the base column remains uncovered. It is a reasonable
surmise that this remainder of the total base represents the base binding value of the serum proteins which may, at the reaction of blood plasma, be correctly regarded as acid substances.' Four of the acid substances which are carried bound in the plasma are being conveyed for excretion in the urine. These are HCI, H3P04, H2S04, and the organic acids. Remembering that a 24 hour urine specimen will usually contain roughly the same amount of each of these four acids, the “¿threshold―character of the concentration of bound HC1 is strikingly apparent in the diagram. The other two values, bound carbonic acid and protein, do not under usual cir cumstances enter the urine. Remaining in the plasma they have to do with stabilizing the reaction of the blood.
The character of the base in the plasma, i.e. the fact that it is practically entirely fixed base, is of cardinal importance from the point of view of the adjustments necessary in the metabolism of acids and base. The minute concentration of the base ammonia in the plasma would be approximately measured by the thickness of the line at the top of the base column. In contrast with this
The values for Na, K@,Ca, and Mg, used in eonstructing this dia
gram are given as mg. per 100 cc. of serum in Table I. Bicarbonate is taken as 60 volumes per cent of 002 bound, and chloride as 6.0 gm. of NaC1 per liter. The average phosphate content of the serum is assumed to he repre sented by 5 mg. of P per 106 cc. On the basis of Sorensen's data HPO4―at pH 7.4 is assigned 1.8 times its molecular equivalence of univalent base. According to Denis' measurements (4) the plasma contains about 1 mg. of inorganic S per 100 cc. The size of the normal organic acid concentration is not known. It is here given a value of about the magnitude of (HPO4―) and (SO411). The base assumed to be bound by protein is simply the remainder of base after addition of the concentrations taken as normal for the other acid radicles.
The acid-base composition of the plasma in terms of cc. of 0.1 normal per
100 cc., according to these data and as represented in the diagram is as
follows:
Base Acid.
Na@ 143.4 1100,' 27.0
K .5.1 (‘1' 103.0
Ca 5.0 11P04― 3.0
Mg― 2.@ SOS― 1.0
Organic acid 2.0
Total LiG.() Protein 20.0 Total 1.56.0
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1960;26;903
Pediatrics
C. D. M.
Laboratory of James L. Gamble
A PEDIATRIC CLASSIC: Facsimile Excerpts from the First Major Paper from the
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