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Dr. Fillev is Chief of Pulmonary Physiology, The Webb-Waring Institute for Medical Research, and Associate Professor of Medicine at the University of Colorado School of Medicine.

ADDRESS: University of Colorado Medical Center, 4200 East Ninth Avenue, Denver, Colorado 80220.


5. Nelson, N. M., and Riegel, K. P. : A schematic

approach to acid-base therapy in the

new-born. PEDIATRICS, 821, 1969.

6. Cllu, J., Clements, J. A., Cotton, E., Klaus,

M. I-I., Sweet, A. Y., Thomas, M. A., and

Tooley, %V. H.: The pulmonary hypoperfusion

syndrome. PEDIATRICS, 35:733, 1965.

7. Rudolph, A. M., and Yuan, S.: Response of the

pulmonary vascuiature to hypoxia and H

ion concentration changes. J. Chin. Invest.,

45:399, 1966.

8. Sinclair, J. C., Engel, K., and Silverman,

W. A.: Early correction of hvpoxemia and

acidemia in infants of low birth weight: A

controlled trial of oxygen breathing, rapid

alkali infusion, and assisted ventilation. PEDIATRICS, 42:565, 1968.

9. Dell, R. B., Engel, K., and Winters, R. W. : A

computer model for the in vivo CO2

titra-tion curve and its relevance to the acid-base

changes in respiratory distress syndrome

(RDS). American Pediatric Society, Atlantic

City, May 1966, program p. 13.

10. Winters, R. W.: Studies of acid-base

distur-bances. E. Mead Johnson Award Address,

October 1966. PEDIATRICS, 39:700, 1967.

11. Dell, R. B., Lee, C. E., and Winters, R. W.:

Effects of expansion of the volume of ECF

on the in vivo CO2 “titration” curve. Fed.

Proc., 27:509, 1968.







on the




Giles F. Filley, M.D.

Time \Vehh-’sVaring last itute for Medical Research, University of Colorado Medical Center, Denver


HE PAPERS of Kildeberg and Engel

and of Nelson and Riegel continue

what has been called, inaccurately, “The

Great Transatlantic Acid-Base Debate”1

be-tsveen two schools of acid-base physiology.

Historically at least, these can be called the

Continental and Anglo-American Schools

and their current dispute a war of words.

We will sketch their beginnings, describe

some of their differences, and indicate the

importance of the distinction between

fun-damental and derived measurement.

The Continental School was probably

founded by Hasselbalch, who in 1916

began the apparently never-ending search

for a chemical index of a “metabolic

com-ponent,” i.e., a number indicating the

quan-tity of non-volatile acid added to or lost

from the body-”corrected” for respiratory

effects. Hasselbalch’s index was typical of

the genre because it required exposing a

blood specimen in vitro to known CO2 gas

mixtures and was called a “reduced

hydro-gen ion concentration.” His successors have

tended to work meticulously in chemical

laboratories, to give special names to

de-fined magnitudes,#{176} and to incorporate these

into logical formulations. One example was

that of Singer and Hastings,4 which was



a physicochemical system at various states

of equilibrium outside the body. Another

recent and carefully developed one is that

of Siggaard-Andersen. Despite this and

other authors’ warnings, this school’s

formu-lations are subject to abuse perhaps

espe-cially by those who assume that an “Astrup

determination” is a substitute for clinical


The other school is less systematic, its

members being more often physiologists or

physicians than physical chemists. Barcroft

originally represented this school because

of his wide-ranging approach:6 though he

worked in laboratories, he also grasped the

significance of physiological adjustments on

mountain tops, and though he invented

words for measurements he was acutely

aware of the “bewitchment of our

intelli-gence by language.”7 This is clearly

cvi-denced by his being one of the first,

perhaps the first, to appreciate the danger

in using “acidosis” ambiguously


as most of

us still do today), i.e., to make it stand for

both the quantity of acid accumulation and

the intensity of acidity in the blood.t For

acid intensity, Barcroft used8 the word

acid-aemia to stand for low pH in the blood, a

0 A fundamental measurement is one which does

not depend on other fundamental measurements, e.g., pH; a measurement which depends on a fixed

relation between fundamental measurements is

called derived, e.g. the [HCOd as calculated from pH, Pco,, and the pK of plasma; more indirectly

derived measurements which do not depend on

constants or fixed relations between other

measure-ments may be called defined magnitudes, e.g.,

buffer base and base excess. These definitions are those of Campbell.’

f Hasselbalch’ himself sensed the danger of

ill-defined words when he quoted Barcroft’ on the

ambiguity of “acidosis” and added that

overcom-pensated diabetic acidosis might have to be called,

if terminology were not changed, not only “die ‘Acidose’ keine ‘Acidose’ . . . sondern das

Gegen-teil.” Neither warning was heeded and for the next

very useful word, though not officially

rec-ognized till 1966. He also emphasized the

differences between changes in circulating

blood and changes brought about by in

vitro manipulation and clearly recognized

the importance of bicarbonate transfer

be-tween blood and the body tissues.1 His

din-ical descendants are perhaps represented by \V. B. Schwartz and A. S. Relman.”

The disagreements between these schools

are exaggerated by mere verbal dispute. It

is especially unfortunate that the words

de-bated are not the ones which stand for

really important variables-namely, the

fun-damental measurements made by modern

instruments: pH, Pco2 and Po2. The time is

ripe for a synthesis of clinical acid-base





stated in ordinary language,

e.g., plain English;




based on modern

measurements; and




which synthesizes

the valuable concepts of both

schools-namely, those on which they only appear to

disagree because these concepts are

ob-scured by acid-base jargon.

One prerequisite for such a synthesis is

to recognize that a derived measurement,

despite its convenience, may be harder to

understand than a fundamental one. For

example, the derived measurement, plasma

[HCO], has always been somewhat hazy

conceptually because it is calculated from

tvo of the following fundamental

measure-ments: pH, Pco2 and total plasma CO2

con-centration. The more indirectly derived

C02-combining power



disap-pearing from use


has always been

confus-ing. Even more indirect than either of these

is the defined magnitude “base excess”

be-cause it depends on more measurements

even though expressed on a single simple

scale. All three of these closely related

quantities are convenient under certain

cir-cumstances as estimates of what Van Slyke



buffer base indices based on the properties

of blood in vitro when such indices are

misunderstood. Neglect of the bicarbonate

gradient set up between blood and

extra-vascular fluid by acute CO2 retention12 has

led to the widespread notion that “a

‘meta-bolic’ component appears to be intrinsic to

acute carbon dioxide accumulation,” that

“the whole body buffers carbonic acid very

poorly as compared with blood in vitro,”4

and to similar confusion about

life-threat-ening circumstances.’ 6 The confusion is

gradually being dissipated by the

recogni-tion that plasma {HCO] is lower than

cx-pected in acute CO2 retention because it

moves from blood to extravascular fluid

and by clear statements like the following:

“What is actually measured . . . is a

bicar-honate deficit; it seems to me that this term

has more meaning than the term metabolic


Since the fundamental measurements pH,

Pco, and Po2 are now available for guiding

therapy, perhaps the numerical results of

these measurements made in patients rather

than the ambiguous words of acid-base

tradition will be used to reconcile the

schools. The usefulness of derived

measure-ments will be in direct proportion to the

de-gree to which their derivation is

under-stood by the user.


1. Bunker, J. P.: Editorial. Anesthesiology, 26:591, 1965.

2. Hasselbalch, K. A.: Die “reduzierte” und die

“regulierte” Wasserstoffzahl des Blutes.

Biochem. Zeit., 74:56, 1916.

3. Campbell, N. R.: An account of the principles

of measurement and calculation. London:

Longmans, Green and Co., Ltd., pp. 13, 14,

94, and 95, 1928.

4. Singer, R. B., and Hastings A. B. : An

im-proved clinical method for the estimation of

disturbances of acid-base balance of human

blood. Medicine, 27:223, 1948.

5. Siggaard-Andersen, 0. : The acid-base status of

the blood. Copenhagen: Munksgaard, 1964.

6. Barcroft, J.: The Respiratory Function of the

Blood. Cambridge Universit Press, 1914.

7. Wittgenstein, L., quoted b McGraw, R. M.:

The language of medical care. New Eng. J.

Med., 279:383, 1968.

8. Barcroft, J.: The Respiratory Function of the

Blood. Part I. Lessons from High Altitudes.

Cambridge University Press, pp. 93 and 99,


9. Report of Ad Hoc Committee on Acid-Base

Terminology. Ann. N.Y. Acad. Sci., 133:251, 1966.

10. Barcroft, J.: Features in the Architecture of

Physiological Function. Cambridge

Univer-sity Press, pp. 9 and 10, 1938.

1 1. Schwartz, W. B., and Relman, A. S. : A

cri-tique of the parameters used in the

evalua-tion of acid-base disorders. New Eng. J.

Med., 268:1382, 1963.

12. Cohen, J. J., Brackett, N. C., Jr., and

Schwartz, W. B. : The nature of the carbon

dioxide titration curve in the normal dog. J.

Chin. Invest., 43:777, 1964.

13. Morris, M. E., and Millar, R. A. : Blood

pH/plasma catecholamine relationships :

res-piratory acidosis. Brit. J. Anaesth., 34:672,


14. Holaday, D. : Acute CO, retention in vivo.

Ann. N.Y. Acad. Sci., 133: 172, 1966.

15. Joels, N., and Samueloff, M. : Metabolic

aci-dosis in diffusion respiration. J. Physiol., 133:347, 1956.

16. Frumin, M. J., Epstein, R. E., and Cohen, C.:

Apneic oxygenation in man. Anesthesiology,

20:789, 1959.

17. Brown, E. B.: Plasma electrolyte composition

in dogs breathing high CO2 mixtures: source

of bicarbonate deficit in severe respiratory




Giles F. Filley

the Two Preceding Papers



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