Carbon dioxide is produced by each cell as a product of metabolism. ^1,23 As carbon dioxide is produced, it dissolves in intracellular fluid and can be measured as the partial pressure (P) of the dissolved gas (CO ₂). As the pressure of the dissolved gas increases inside the cell, carbon dioxide moves out of the cell into the blood. Blood transports dissolved carbon dioxide (some combined with hemoglobin as carboxyhemoglobin, most as bicarbonate) to the lung, where the partial pressure in the pulmonary capillary is greater than in the alveoli, ²¹ causing carbon dioxide to move into the alveoli. Ventilation is the only method of removing carbon dioxide. The amount of carbon dioxide in the blood is the net result of the body’s metabolism (production) and alveolar ventilation (clearance). Because metabolism does not change greatly and CO ₂ diffuses easily across membranes, the only clinically important limitation to CO ₂ removal is at the lungs. Thus Pa co₂ reflects alveolar ventilation.^3,8,11,17

In the red blood cell, the enzyme carbonic anhydrase promotes combination of a fraction of dissolved CO ₂ with water to form carbonic acid (H ₂CO ₃), which then dissociates into a hydrogen ion [H ⁺] and a bicarbonate ion [ ] ^1,23:

Therefore an increase in Pa co₂ causes pH to fall. Hypoventilation causes an increase in carbon dioxide. This is called respiratory acidosis because the respiratory system is responsible for regulating Pa co₂ as the lung regulates the amount of carbon dioxide in the body.⁸ A decrease in Pa co₂ results in less acid in the blood and causes pH to rise. A pathophysiologic process that causes hyperventilation and reduces dissolved carbon dioxide is known as respiratory alkalosis.

Nonrespiratory (metabolic) derangements can also disturb acid-base homeostasis. Normal metabolism produces hydrogen ions. Blood pH is maintained within normal limits by renal mechanisms for excreting hydrogen ions. Increased production of [H ⁺] may occur in conditions such as shock with poor perfusion of the gastrointestinal system or genetically determined aberrations of metabolism.²⁷ The hydrogen ions produced must be eliminated to avoid a fall in blood pH. Derangements also occur when hydrogen ions are lost (e.g., in gastric juice) or when bicarbonate is lost (e.g., in diarrheal fluid or ileostomy drainage). ²⁸

Authorities differ as to the best way to describe nonrespiratory derangements in acid-base status. The traditional approach relies on measurement of pH, P co₂ and [ ]. The alternative is description of acid-base status in terms of (1) strong ions (Na ⁺, K ⁺, Ca ²⁺, Mg ²⁺, Cl ⁻), strong because they remain dissociated at body pH, and (2) weak acids (hemoglobin, albumin, inorganic phosphate), weak because they are partially dissociated at body pH. Blood pH in this conceptualization is a function of the difference between strong cations and strong anions, the strong ion difference (SID). As an example, the alkalosis associated with loss of gastric fluid would be described exclusively in terms of loss of [Cl ⁻] with loss of [H ⁺] making no independent contribution to the resulting alkalemia. Advocates maintain that measurement of SID leads to greater understanding of the causes of nonrespiratory and mixed acid-base derangements. ^7,12,14,23 Others favor staying with the traditional bicarbonate-center model. ^6,18 The present discussion focuses on the traditional bicarbonate-centered approach. Readers are referred to recent reviews for comparisons of the two methods. ^14,18

A fall in blood [ ] might indicate that bicarbonate, a base and therefore a hydrogen ion acceptor, has been used up by the addition of [H ⁺]. As shown inEquation 3, a change in [ ] might also reflect a change in Pco₂. This difficulty is overcome in blood gas analyzers by correcting the P co₂ (graphically) to 40 mm Hg, yielding a “standard bicarbonate” concentration.²³The standard bicarbonate concentration and the buffering properties of hemoglobin are combined in the concept of base excess (BE). A positive value suggests a deficit of fixed (i.e., not volatile as with H ₂CO ₃) acid or an excess of base; a negative value indicates an excess of fixed acid or a deficit of base.²³An abnormality of the standard bicarbonate concentration or base excess indicates a process of nonrespiratory (metabolic) alkalosis¹⁵or nonrespiratory (metabolic) acidosis.²⁶

In the Henderson-Hasselbalch equation (Equation 2), the pH is equal to a constant, pK, plus the logarithm of the base/acid ratio. ^1,17,23 If we substitute [ ] for the base and dissolved CO ₂ for the acid, ^8,23 multiplying CO ₂ by its solubility coefficient (0.03 mEq/L/mm Hg), the equation becomes the following:

The value of pK is 6.1; normal [ ] is 24 mEq/L, and normal Pa co₂ is 40 mm Hg.

Substituting, we obtain the following:

Changes in the 20:1.2 ratio have profound effects on the pH. ^1,17 The following are two examples:

Thus far, these derangements (Figure 8-1) have been discussed as if they happened in isolation, but combined respiratory and nonrespiratory problems often occur, depending on pathologic processes in the body. Besides the four single acid-base derangements, there are combined acid-base derangements: (1) respiratory acidosis and metabolic acidosis, (2) respiratory acidosis and metabolic alkalosis, (3) respiratory alkalosis and metabolic acidosis, and (4) respiratory alkalosis and metabolic alkalosis. The combined acidoses or combined alkaloses have a cumulative effect on the pH, whereas an acidosis and alkalosis combination tends to negate the effects of each on the pH value. ^16,17,21,31

Acid-base homeostasis maintains pH near the normal range. Thus if either the respiratory or nonrespiratory acid-base system is “deranged,” the other system will become “unbalanced” in the opposite direction to counterbalance the primary process. The body attempts to maintain equilibrium by balancing a pathologic process with a physiologic process or predictable buffering response. ^3,17,28 For example, any respiratory process that leads to retention of carbon dioxide (respiratory acidosis) stimulates a nonrespiratory system, in this case the renal system, to return pH toward normal. This occurs by renal retention of bicarbonate and corresponding excretion of hydrogen ions. Given sufficient time, this may increase blood bicarbonate by as much as 3 to 4 mEq/L for each 10 mm Hg increase in carbon dioxide. Thus a neonate with a chronically increased Pa co₂ and a compensatory rise in bicarbonate may attain a near-normal pH. ¹⁷

Metabolic compensations to respiratory processes can go to remarkable extremes, but respiratory compensations to metabolic processes are limited. Hyperventilation cannot lower the Pa co₂ much below 10 mm Hg in compensation for a metabolic acidosis. Similarly, hypoventilation is limited in compensation for a metabolic alkalosis by the onset of hypoxemia. ²⁸ Hypoxemia stimulates respiratory drive, overriding compensatory hypoventilation, limiting correction of alkalemia. ¹⁷

Correction of an acid-base disturbance occurs when the health care provider detects the pathophysiologic process and directs therapy at the primary pathologic process, rather than counterbalancing it with a second pathologic process.

For example, if a respiratory acidosis is present, the clinician assesses the patient to discover the cause of the carbon dioxide retention and directs therapy at improving the ventilatory capacity of the lung, rather than attempting to increase the retention of bicarbonate.