DEFINITIONS AND TERMINOLOGY I N
BLOOD ACID-BASE CHEMISTRY
Poul Astrup, Knud Engel, Kjeld Jfirgensen, Ole Siggaard-Andersen
Department of Clinical Chemistry
Rigshospitalet, Copenhagen, Denmark
The present difficulties in the understanding of medical acid-base problems
are partly due to the existing uncertainties concerning nomenclature and
definitions. Through the years this condition has led to a lively discussion. The
most important questions which are subjects of discussion and disagreement
are the following:
1. Should Brfinsted-Lowry's acid-base definitions be adopted or should the
term acid-base balance be synonymous with the term electrolyte balance?
2. Are the relevant parameters p H , Pcoz and actual bicarbonate, or is it
preferable to have a more direct measure for the accumulation of nonvolatile
acid or base than the bicarbonate value, such as, for instance, standard bicarbonate, buffer base, or base excess?
3. Is it more simple to state the acidity directly as H + concentration (or
activity) than to use pH?
4. How should the CO2-tension be symbolized and which units should be
used?
5. How is the best expression obtained for the accumulation of nonvolatile
acid or base in blood?
6. What is meant by acidosis and alkalosis, respectively? Which is the most
rational nomenclature for the various acid-base disturbances?
In an attempt to reach agreement and clarity on this subject we shall try to
summarize the views and the definitions,* which we after many years work
have reached in Copenhagen.
1. The Br@sted-Lowry acid-base definition is adopted.'.' According to the
Brfinsted-Lowry definitions an acid is defined as a molecule, which is able to
give off a hydrogen ion under the given conditions; a base is defined as a molecule which is able to accept a hydrogen ion under the given conditions.
2. The acid-base status (state) of the blood is described by the following
parameters: Hydrogen ion exponent (pH), carbon dioxide tension (Pco2)and
base excess (BE) . 2 , 4
*The terminology used in the following is, as far as possible, in accordance with the
IS0 recommendations given by the International Organization for Standardization
(ISO/R 3 l / P a r t I-XI) and by the International Union of Pure and Applied Chemistry,
IUPAC.
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Annals New York Academy of Sciences
Comments. The classical description of the acid-base status of the blood
starts with the Henderson-Hasselbalch equation:
According to this equation, p H is a function of the PCOZ
and the bicarbonate
concentration [HCOa-], and the three acid-base parameters naturally become
p H , Pcoz, and [HCOs-I. I n place of rHC03-1, total-C02 is often used. However, it is well known that as the Pco? rises the carbonic acid is buffered by
the non-bicarbonate buffers and thus the bicarbonate concentration rises
rises. In other words, from a chemical point of view the Pco2
when the PCOZ
and the bicarbonate are not mutually independent variables.
The new approach describes the blood as a buffer in equilibrium with a gas
phase. The acidity of the buffer (the pH) can be altered by two essentially independent means: either by changing the Pco2 of the gas phase or by adding
nonvolatile acid or base into the buffer. The amount of added nonvolatile acid
or base per volume is expressed as the base excess (a negative value indicating
an excess of nonvolatile acid). The actual change in pH of the buffer caused by
these means depends on the buffer capacity of the non-bicarbonate buffers.
The function between the variables may be written:
pH = F(Pcon,BE),
where F depends on the non-bicarbonate-buffer capacity.
The formula shows t h a t the two mutually independent parameters, which,
together with the buffer capacity of the nonbicarbonate buffers, determine the
pH, are the Pco2and the base excess. I t is important to realize that the bicarbonate concentration (or total-COz) actually is used in acid-base problems as
an indicator of the base excess. A series of other parameters which will be defined later, have been proposed as indicators of the base excess, for instance
standard bicarbonate, buffer base, C02-combining power, etc. For practical
purposes the choice of parameter depends on the analytico-technical facilities.
Nothing is wrong in using the plasma total-C02 for screening of the base
excess. However, it must be kept in mind that the total-COz varies not only
with the base excess but also with the Pco2. I t might as well, under certain
circumstances, be used for screening of the Pco2.
3. The Hydrogen Ion Exponent
Symbol: pH. Generally named by the symbol.
Definition: T h e negative (Briggsian) logarithm of the activity of hydrogen
ion. p H = -log a! ' . Unit: This quantity is dimensionless.
Other quantities: The activity of hydrogen ion, aHc. I t is dimensionless. The
molar concentration of hydrogen ion, CH', in nanomoles per liter, nmole/l.
Comments. The p H concept was introduced by S Q r e n ~ e nThe
. ~ p H scale
used should now be based on the standard buffers as given by T h e National
Astrup et al: Definitions and Terminology
61
Bureau of Standards, NBS.‘ The actual p H of a blood sample should refer to
the actual temperature of the patient.
The p H has proved to be a convenient means of expressing the chemical
potential of hydrogen ion, p H + , which is of primary importance for biochemical reactions.
The activity of hydrogen ion, aH’, has an order of magnitude which is inconvenient to say and write (about 10-7.4),and is no more informative than
pH. (Note: the quantity is dimensionless, and can not be given in nanomoles
per liter.)
The concentration of hydrogen ion, i.e., of free hydrogen ion, CH’, might be
mistaken for concentration of “titratable hydrogen ion” as both quantities
have been used as measures of acidity of a solution. The concentration of free
hydrogen ion can only be determined from a pH measurement, using an activity factor for correction. The activity factor for blood (or serum) is not known
with certainty, and no generally accepted value is available. If, however, an
activity factor was agreed upon, comparable values for C H + could be obtained
by all laboratories, i.e. cH+values which were determined with the same accuracy. The value of the activity factor might well be taken as 1 (exactly), to
facilitate calculations, though the systematic error introduced may be of the
magnitude 0.1-0.2, relatively.
4. The Carbon Dioxide Tension
Symbol: Pcoz. Often named by the symbol.
Definition: Equal to the partial pressure of carbon dioxide, Pcoz in a gas
phase with which the sample is in equilibrium. Unit: conventional millimeter
of mercury (mmHg).
Other quantities: The substance concentration of carbon dioxide, C C O Y , in
millimoles per liter, mmole/l.
Comments. The partial pressure of carbon dioxide is preferred to the concentration, because the latter might be mistaken for the concentration of
“total carbon dioxide,” and because the partial pressure can easily be measured accurately. The symbol Pco2 is adopted from “Standardization of Definitions and Symbols in Respiratory Physiology,” Fed. Proc. 9: 609, 1950.
The symbol Pcozis used by IS0 in relation to the gaseous phase. The unit
mmHg is still in general use. However, the unit millibar, mbar, might be more
convenient in physiology as this unit is now widely used in meteorological
barometry. The unit bar has a simple relationship to the International System
of Units, 1 bar = 10’ N / m 2 (newton per square meter). 1 mmHg = 1.33322
mbar. The unit “torr” is for all practical purposes equal to the unit “conventional millimeter of mercury.” 1 torr is defined as 1/760 atm (normal atmosphere), and 1 atm = 101,325 N/m2.
5. Base Excess’
Symbol: BE.
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Annals New York Academy of Sciences
Definition: The base concentration as measured by titration with strong
acid to p H 7.40 a t a Pco2 of 40 mmHg at 37OC (Previously 38°C). For negative values of base excess, the titration must be carried out with strong base.
Unit: milliequivalent per liter, meq/l.
Comments. A negative base excess value indicates a base deficit or an excess
of nonvolatile acid. A special way of adding nonvolatile acid or base consists
in changing the oxygen saturation of the hemoglobin. As oxyhemoglobin is a
stronger acid than reduced hemoglobin, an oxygenation of the hemoglobin
causes a decrease of the whole blood base excess. The amount of acid formed
when oxygenating human hemoglobin has, in the p H range 7.0-7.8, a constant
value of 0.3 meq per 10 g hemoglobin. T h e base excess value a t 100 per cent
oxygenation of hemoglobin (BE,,) can be found from the value a t the actual
oxygen saturation (BEact)and vice versa according to t h e formula:
BE,,
=
BE,,., - 0 . 3 H b
100
-
ox.sat.
where H b is the hemoglobin concentration in g/100 ml, and oxsat. is the
actual oxygen saturation of the whole blood, and 0.3 is a factor indicating the
amount of acid (in meq) liberated when 10 g hemoglobin is oxygenated.
The base excess may be determined by calculation from the pH, Pco2, and
the buffer capacity of non-bicarbonate buffers (see section 2, comments). The
buffer capacity of non-bicarbonate buffers is primarily dependent on the
hemoglobin concentration. This calculation gives the base excess of the whole
blood a t the actual oxygen saturation. The base excess may also be determined
more directly by titration with carbonic acid, i.e. equilibrating with different
known carbon dioxide tensions. Equilibrating with COn-02-mixturesthe
hemoglobin is 100 per cent oxygenated in uitro, and the base excess value obtained is the value for in uitro oxygenated whole blood. The base excess was
originally defined for in uitro oxygenated whole blood, b u t the concept can be
used a t other oxygen saturations as well. The differences between the base
excess values of arterial, venous, and in uitro oxygenated blood are small and
usually without clinical significances.
Other Quantities:
A. Pco2-independentquantities.
a. Standard bicarbonate' is defined as the plasma bicarbonate
concentration after equilibrium of whole blood to a P C Oof~ 40
mmHg and at 37OC (originally 38OC). Unit: meq/l. In contrast
to total-COz and actual bicarbonate, the standard bicarbonate
is independent of the P C Oof~ the sample. The deviation of a
standard bicarbonate value of a blood sample from the normal
mean value (24.0 meqil) is approximately related to the base
excess value according to the following formula:
A Standard bic. x 1.2 = base excess.
Astrup et al: Definitions and Terminology
63
The factor 1.2 is valid for blood with a normal hemoglobin concentration of 15 g/100 ml. and for a A standard bic. within ~ 1 0
meq/l.
b. “Reduced pH”’ The “reduced p H ” is defined as the p H of
blood after equilibration to a PCOZ
of 40 mmHg and a t 37°C
(originally 38OC). The quantity corresponds very closely to the
standard bicarbonate.
c. Bicarbonate of plasma under standard conditions, from oxygenated blood at pH = 7.4O1’ This quantity is defined as the bicarbonate concentration in plasma from oxygenated blood a t
COz-tensions such that p H would be 7.40 a t 37°C (originally
of
38OC). Unit: meq/l. This value is independent of the PCOZ
the sample and varies with the base excess of the oxygenated
blood and the hemoglobin concentration.
d. Buffer base” is defined as a sum of “buffer anions” of blood
(or plasma). Unit: meq/l. From a chemical point of view the
buffer base is not a well defined concept, because it depends on
the actual p H range which molecules are “buffer” anions. Thus,
in the normal physiological p H range lactate is not a buffer
anion, but as p H falls and approaches the pK of lactic acid the
lactate begins to function as a buffer anion. Using the practical
definition by Singer & Hastings, i.e. sum of bicarbonate and
proteinate, a theoretical problem arises when about 46 meq/l of
nonvolatile acid accumulates in the blood. The buffer base falls
to zero and does not register greater accumulation of acid. It is
possible, however, to define the buffer base concept in a precise
chemical way, namely as the titratable base when titrating with
strong acid or base to a pH of 7.093 a t a PCOZ
of 91.5 mmHg
adding an arbitrary constant of 41.7 meq/l. This definition resembles very much the definition of base excess, but offers no
advantage over the base excess concept. Defined in this way the
buffer base changes exactly as much as the base excess upon
addition of strong acid or base.
B. Pcoz-dependentquantities.
a. Total CO, is defined as the amount of total carbon dioxide of
blood or plasma which can be liberated by acidification with a
strong acid. Unit: millimoles per liter mmol/l. The total-COn
value of a blood sample depends on the base excess as well as the
PCOZ
value. This variation makes the total-COz value less suitable for clinical use.
b. Actual bicarbonate is defined as total-C0z minus the carbonic
acid and physically dissolved COZ ([HC03- I) = [total-COn]
-([HzC03]+ [COJ)). The amount of carbonic acid and the
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Annals New York Academy of Sciences
physically dissolved COzcan be calculated from the Pco2-value
by multiplication with the solubility coefficient. As for the totalvalue and
CO, the actual bicarbonate value varies with the PCOZ
the base excess value. The actual bicarbonate corresponds to the
alkali reserue.12
c. COz-combining-poweris defined as the total COn of the anaerobically separated plasma after equilibration to a PCOZ
of 40
mmHg13 a t room temperature. Unit: mmole/l. This value depends on the Pcoz of the blood sample during separation of cells
from plasma.
6 . Terms for Acid-Base Abnormalities
Many terms have been used through the years for characterizing abnormalities of patients and of blood samples. The clinical acid-base abnormalities
were the first to be named. So, the word acidosis was used by Naunyn
(Naunyn, B.: Gesammelte Abhandlungen, Wurzburg, 1909) for accumulation
of organic acids in patients with diabetic coma. The word has since been used
for clinical conditions with accumulation also of other acids, including carbonic acid. Correspondingly the word alkalosis has been used for clinical
conditions where bases were accumulated (or acids were lost).
When methods for measuring the acid-base values of blood became
generally available, some confusion arose about the use of the acid-base terms
when correlating the clinical conditions to the laboratory data. Since then the
development has led to two types of terms, those for the laboratory acid-base
data, and those for the clinical disturbances.
Laboratory acid-base terms. Many terms have been proposed for characterizing abnormal laboratory acid-base data, i.e. high or low values of p H , Pcoz
and base excess respectively. So, for a low p H the following terms have been
proposed: acidosis, acidaemia, hyperprotonemia, hyperhydrionemia. As the
practical use of such more or less artificial terms has been of limited value, we
propose instead to have the pH, the P C Oand
~ the base excess referred to as
“high,” “normal,” or “low.”
Clinical disturbances. Most of the clinical conditions associated with acidbase disturbances are well known and generally characterized very precisely
by different terms, for instance “diabetic acidosis,” “lactic acidosis,” “respiratory acidosis,” “respiratory alkalosis,” etc. We feel that the terms acidosis
and alkalosis should still be used, so that acidosis generally should refer to a
clinical condition, which is due to an accumulation of acid (loss of base) in the
body, while alkalosis generally should refer to a clinical condition, which is due
to an accumulation of base (loss of acid) in the body. Further, they should be
used in combination with the words respiratory and nonrespiratory (or metabolic) to characterize the etiology of the disturbance. Generally it is possible
to precisely characterize the disturbances by the blood acid-base data, but it
Astrup et al.: Definitions and Terminology
65
must be recalled, that the extracellular changes do not always reflect the intracellular changes.
Summary and Conclusions
The parameters determining the acidity of blood have been discussed from
a chemical and a theoretical point of view. It is concluded that the p H , being
the most convenient measure of the acidity, is determined by two different and
mutually independent parameters: the PCOZ
and the concentration of accumulated nonvolatile acid or base, together with the buffer capacity of the
non-bicarbonate buffers. The parameters of greatest importance for clinical
evaluation of the acid-base metabolism are the Pco2 and the concentration
of accumulated acid or base. Some of the more important of the used or proposed quantities for concentration of accumulated acid or base have been discussed, and the importance of choosing a parameter that from a chemical point
of view is an independent variable is stressed. Among these quantities the base
excess is recommended as the theoretically most satisfactory.
The terms for clinical and laboratory acid-base abnormalities have been
briefly discussed. Pathological values of pH, Pcoz and BE of the blood should
be referred to as “high” or “low,” while the special terms for the clinical abnormalities should refer to conditions which are due to accumulation of acid,
respectively base, in the body.
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