Chapter 196Serum Total Carbon Dioxide

Centor RM.


We measure serum total CO2 content in lieu of measuring serum bicarbonate. The total CO2 content includes the serum bicarbonate as well as available forms of carbon dioxide (i.e., dissolved CO2 and carbonic acid). Generally, the serum bicarbonate comprises about 95% of the total CO2 content; thus we can use this measurement as an excellent estimator of serum bicarbonate. The total CO2 content normally equals 23 to 30 mEq/L of serum.


Most laboratories use an autoanalyzer for measuring total CO2 content. This method measures the amount of CO2 liberated from the sample after adding a strong acid. The CO2 diffuses across a dialysis membrane. A bicarbonate-carbonate buffer solution containing an indicator dye absorbs the CO2. A colorimeter then evaluates the new color, which it converts to a total CO2 measurement.

Two potential problems exist with this method: (1) the color reagent may change with time, thus the laboratory must frequently check standardization curves; (2) exposure of the sample to air will allow loss of CO2, as much as 6 mEq/L in an hour.

Arterial blood gas reports generally include a bicarbonate value. The blood gas machine measures pH and pCO2 and then calculates a bicarbonate value using the Henderson–Hasselbalch equation. Generally, a concurrent venous total CO2 content will exceed this value by less than 2 to 4 mEq/L, of which 1 to 2 mEq/L represents the difference between venous and arterial blood; the remaining difference comes from dissolved CO2.

Basic Science

The kidneys and lungs maintain daily acid–base balance. Understanding this normal physiology allows us to appreciate abnormalities. This discussion refers to bicarbonate rather than total CO2 content, as we measure total CO2 content as a surrogate for bicarbonate.

Bicarbonate and carbonic acid constitute the major buffer pair in body fluids. Carbonic acid dissociates into hydrogen ion and bicarbonate with a dissociation constant of 7.95 × 10−7. Carbonic acid also maintains an equilibrium with H2O and CO2.

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We usually describe dissociation constants and hydrogen ion concentrations as negative logarithms. Thus, the negative logarithm of the dissociation constant equals 6.1. This value is called the pKa. Normal hydrogen ion concentration equals 40 nanoequivalents/liter, corresponding to a pH of 7.4.

The familiar Henderson-Hasselbalch equation derives from these facts:

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Carbonic acid concentration is proportional to the partial pressure of carbon dioxide (pCO2) in the blood. Multiplying the pCO2 by a constant (0.03) estimates the carbonic acid concentration, giving the useful form of the above equation:

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Changes in hydrogen ion concentration (pH) result from changes in either bicarbonate or carbon dioxide. Measurement of total CO2 content can help us explain acid–base disorders (when the pH and pCO2 are known). Furthermore, since we often measure total CO2 content as part of automated chemistry determinations, this measurement can provide the first clue to acid–base disturbances.

We produce approximately 1 mEq/kg daily of hydrogen ions (derived from metabolism of proteins primarily). The kidney normally excretes this daily acid load. Failure of excretion forces the reaction of H+ and HCO3, resulting in a decrease of bicarbonate concentration.

Bicarbonate reabsorption occurs primarily in the proximal tubule. Carbonic anhydrase controls this absorption. The patient's volume status has a major influence on absorption, since sodium is reabsorbed along with this bicarbonate. Thus, volume contraction stimulates both sodium and bicarbonate reabsorption. This results in an increased total CO2 content. Likewise, volume expansion can lead to a mild decrease in total CO2 content.

Hydrogen ion concentration (pH) is another major determinant of bicarbonate reabsorption. Thus, the kidney will respond to changes in ventilation (pCO2) with compensatory changes in bicarbonate reabsorption. For example, chronic hypoventilation (↑ pCO2) causes a decreased pH. This decreased pH stimulates bicarbonate reabsorption, thus the patient will have an increased total CO2 content.

Clinical Significance

The major caveat concerning total CO2 content involves the interpretation of an isolated measurement. One cannot diagnose acid–base disturbances from an isolated total CO2 measurement. In order to characterize an acid–base disturbance, one needs pH, pCO2, total CO2, as well as a measurement of the anion gap. Given that caveat, one can use the following guidelines.

Low levels of total CO2 result from either metabolic acidosis or as a compensation to respiratory alkalosis. Bicarbonate levels below 10 mEq/L virtually identify metabolic acidosis as the cause, as compensation for respiratory alkalosis will not drive the bicarbonate that low.

If metabolic acidosis is present, one should distinguish between increased anion gap and nonanion gap acidosis. The simplest formula for the anion gap is:

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Table 196.1 lists the differential of an anion gap acidosis. Generally, one does not consider this differential until the gap exceeds 20 mEq/L. Table 196.2 gives the differential for nonanion gap acidosis.

Table 196.1. Causes of Increased Anion Gap Metabolic Acidosis.

Table 196.1

Causes of Increased Anion Gap Metabolic Acidosis.

Table 196.2. Causes of Normal Anion Gap (Hyperchloremic) Metabolic Acidosis.

Table 196.2

Causes of Normal Anion Gap (Hyperchloremic) Metabolic Acidosis.

Similar to the interpretation of a decreased bicarbonate level, an increased bicarbonate level may result from either a metabolic alkalosis or as compensation to respiratory acidosis. Table 196.3 lists the causes of metabolic alkalosis.

Table 196.3. Causes of Metabolic Alkalosis.

Table 196.3

Causes of Metabolic Alkalosis.

In summary, the serum total CO2 content can give clues to acid–base abnormalities. When used in conjunction with the pH and pCO2, this measurement helps us define possible causes of metabolic imbalance, especially in acutely ill patients.


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