Simple and mixed acid-base disorders

Author
Burton D Rose, MD
Section Editor
Richard H Sterns, MD
Deputy Editor
Theodore W Post, MD
Last literature review version 18.2: May 2010 | This topic last updated: May 10, 2010
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INTRODUCTION Each day approximately 15,000 mmol of carbon dioxide (which
can generate carbonic acid as it combines with water) and 50 to 100 meq of nonvolatile
acid (mostly sulfuric acid derived from the metabolism of sulfur-containing amino acids)
are produced. Acid-base balance is maintained by normal pulmonary and renal excretion
of carbon dioxide and acid, respectively.
Renal excretion of acid involves the combination of hydrogen ions with urinary titratable
acids, particularly phosphate (HPO42- + H+ > H2PO4-) or with ammonia to form
ammonium [1]. (See "Chapter 11A: Renal hydrogen excretion".) The latter is the primary
adaptive response, since ammonia production from the metabolism of glutamine can be
appropriately increased in the presence of an acid load.
Acid-base balance is usually assessed in terms of the bicarbonate-carbon dioxide buffer
system:
Dissolved CO2 + H2O <> H2CO3 <> HCO3- + H+
The concentration of H2CO3 (carbonic acid) is normally so low that its role can be
ignored and the ratio between the reactants can be expressed by the HendersonHasselbalch equation:
pH = 6.10 + log ([HCO3-] [0.03 x PCO2])
where the pH is equal to (-log [H+]), 6.10 is the pKa (equal to -log Ka), Ka is the
dissociation constant for the reaction, 0.03 is equal to the solubility constant for CO2 in
the extracellular fluid, and PCO2 is equal to the partial pressure of carbon dioxide in the
extracellular fluid [2]. (See "Chapter 10B: Buffers".)
DEFINITIONS With these principles in mind, the following definitions can be made:

Acidosis A process that tends to lower the extracellular fluid pH (which is

equivalent to raising the hydrogen concentration). From the HendersonHasselbalch equation, this can be induced by a fall in the extracellular (or plasma
) bicarbonate concentration or by an elevation in the PCO2.
Alkalosis A process that tends to raise the extracellular fluid pH (which is
equivalent to lowering the hydrogen concentration). From the Henderson-

Hasselbalch equation, this can be induced by an elevation in the extracellular (or

plasma ) bicarbonate concentration or by a fall in the PCO2.
Metabolic acidosis A disorder associated with a low pH and low bicarbonate
concentration. (See "Approach to the adult with metabolic acidosis".)
Metabolic alkalosis A disorder associated with a high pH and high bicarbonate
concentration. (See "Pathogenesis of metabolic alkalosis".)
Respiratory acidosis A disorder associated with a low pH and high PCO2.
Respiratory alkalosis A disorder associated with a high pH and low PCO2.

Compensatory responses Each of the simple acid-base disorders is also associated

with a compensatory response. The Henderson-Hasselbalch equation shows that the pH is
determined by the ratio between the HCO3 concentration and PCO2, not by the value of
either one alone.
The body responds to an acid-base disorder by making compensatory respiratory or renal
responses in an attempt to normalize the pH. These responses are probably mediated at
least in part by parallel alterations in regulatory cell (renal tubular or respiratory center)
pH [3]. In metabolic acidosis, for example, ventilation is increased, resulting in a fall in
PCO2, which tends to raise the pH toward normal. Note that protection of the
HCO3/PCO2 ratio and therefore the pH requires a compensatory response that varies in
the same direction as the primary disorder (low bicarbonate leads to low PCO2).
MIXED ACID-BASE DISORDERS Some patients have two or more acid-base
disorders. An understanding of the approach to this problem requires knowledge of the
renal and respiratory compensations that have been empirically observed in patients with
simple acid-base disorders. Values substantially different from those that are expected
indicates the presence of a mixed disturbance [3].
Metabolic acidosis The respiratory compensation results in an approximately 1.2
mmHg fall in PCO2 for every 1 meq/L reduction in the plasma bicarbonate concentration
[4]. This response begins within 30 minutes [5], and is complete by 12 to 24 hours [6].
The respiratory compensation with acute metabolic acidosis is discussed separately. (See
"Approach to the adult with metabolic acidosis".)
Metabolic alkalosis The respiratory compensation tends to raise the PCO2 by 0.7
mmHg for every 1 meq/L elevation in the plasma bicarbonate concentration [7,8]. This
response may not be seen in all patients because of concurrent problems. As an example,
diuretics tend to induce metabolic alkalosis in heart failure or cirrhosis. However, both of
these disorders, are associated with hyperventilation and a low PCO2. Thus, the expected
rise in PCO2 with metabolic alkalosis may not be seen due to the underlying respiratory
alkalosis.
Respiratory acidosis The compensatory response to respiratory acid-base disorders
occurs in two stages: cell buffering that acts within minutes to hours and the renal
compensation that is not complete for 3 to 5 days. As a result, different responses are

seen with acute and chronic disorders. In acute respiratory acidosis, the plasma
bicarbonate concentration rises 1 meq/L for every 10 mmHg elevation in the PCO2
(figure 1); this ratio increases to 3.5 meq/L per 10 mmHg in chronic respiratory acidosis
(with better protection of the pH) due to increased renal acid excretion as ammonium
(figure 2) [9,10]. The renal response is carefully regulated, so that administering extra
bicarbonate results in the urinary excretion of the excess alkali without elevation in the
plasma bicarbonate concentration [9].
Respiratory alkalosis In acute respiratory alkalosis, the plasma bicarbonate
concentration falls by 2 meq/L for every 10 mmHg decline in the PCO2 (figure 1). This
ratio increases to 4 meq/L per 10 mmHg in chronic respiratory alkalosis, resulting in
almost complete normalization of the pH (figure 3) [11,12]. Reductions in both
bicarbonate reabsorption and in ammonium excretion contribute to the compensatory
reduction in the plasma bicarbonate concentration [13].
Diagnosis Evaluation of an acid-base disorder begins with measurement of the
extracellular pH, not merely the plasma bicarbonate concentration. As an example, a low
plasma bicarbonate concentration can be seen as the primary change in metabolic
acidosis and as the compensatory response in respiratory alkalosis. Once the primary
change is determined, the degree of compensation should then be assessed.
Clinical examples The following examples show how these relationships can be used
to diagnose simple or mixed metabolic and respiratory acid-base disorders [3,14]. Some
patients also have both a metabolic acidosis and metabolic alkalosis (as with vomiting in
diabetic ketoacidosis). Establishing this diagnosis requires a careful history and
comparison of the fall in plasma bicarbonate concentration to the rise in the anion gap
(the delta/delta). (See "The anion gap/HCO3 ratio in patients with metabolic
acidosis".)
Case 1 A patient with diarrhea has an arterial pH of 7.23, bicarbonate concentration of
10 meq/L, and PCO2 of 23 mmHg. The low pH indicates acidemia, and the low plasma
bicarbonate concentration indicates metabolic acidosis. The plasma bicarbonate
concentration is 14 meq/L below normal, which should lead to a 17 mmHg fall in the
PCO2 (14 x 1.2 = 17) from 40 to 23 mmHg. Thus, this patient has a simple metabolic
acidosis. A PCO2 significantly higher than this level would indicate a concurrent
respiratory acidosis. If, on the other hand, the PCO2 were lower than 20 mmHg, then a
concurrent respiratory alkalosis would be present, as might be seen with salicylate
intoxication.
Case 2 Establishing the correct diagnosis is more difficult with respiratory acid-base
disorders, because of the difference between the acute and chronic responses. Consider
the following arterial blood values: pH equals 7.27; PCO2 equals 70 mmHg; and
bicarbonate concentration equals 31 meq/L. The low pH and hypercapnia indicate that
the patient has some form of respiratory acidosis. In view of the 30 mmHg rise in the
PCO2, the plasma bicarbonate concentration should be elevated by 3 meq/L (to 27
meq/L) with acute hypercapnia, and by 11 meq/L (to 35 meq/L) with chronic

hypercapnia. The observed value of 31 meq/L is between these expected levels and could
be explained by one of three disorders:

Chronic respiratory acidosis with superimposed metabolic acidosis to lower the

plasma bicarbonate concentration, as might occur in a patient with chronic
obstructive pulmonary disease who develops diarrhea due to viral gastroenteritis.
Acute respiratory acidosis with superimposed metabolic alkalosis to elevate the
plasma bicarbonate concentration, as might occur in a patient with vomiting due
to theophylline toxicity who then develops an acute asthmatic attack.
Acute, superimposed on mild chronic respiratory acidosis, as can be induced by
pneumonia in a patient with chronic hypercapnia.

Thus, the correct diagnosis in a primary respiratory acid-base disorder can be established
only when correlated with the clinical history. This is true even when the arterial blood
values appear to represent a simple disorder. If, for example, the plasma bicarbonate
concentration had been 35 meq/L in Case 2, then the results would have been compatible
with an uncomplicated chronic respiratory acidosis. However, similar findings could have
been induced by the combination of acute hypercapnia and metabolic alkalosis. The
history should allow these possibilities to be distinguished.
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