Acid Base Balance

From this equation, respiratory disorders are defined by changes in CO₂ and metabolic disorders result from changes in the HCO₃ ⁻. Increases in CO₂ cause a respiratory acidosis while decreases in CO₂ cause a respiratory alkalosis. Similarly, an increase in HCO₃ ⁻ causes a metabolic alkalosis and a decrease causes a metabolic acidosis. From this it would appear that by this equation, [H⁺] is determined by two variables, CO₂ and HCO₃ ⁻.

By reviewing the derivation of the Henderson–Hasselbalch equation we discover that these two variables are interdependent and not independent as these definitions would suggest. The Henderson–Hasselbalch equation is derived from the carbonic acid equilibrium and its associated equilibrium equation.

$\begin{array}{l}{\mathrm{CO}}_2+{\mathrm{H}}_2\mathrm{O}={\mathrm{H}}_2{\mathrm{CO}}_3={{\mathrm{H}\mathrm{CO}}_3}^{-}+{\mathrm{H}}^{+}\\ {}\kern0.72em \left(\mathrm{carbonic}\kern0.24em \mathrm{acid}\kern0.24em \mathrm{equilibrium}\right)\end{array}$

$\begin{array}{l} {\mathrm{K \, (equilibrium \, constant)}} = {[\mathrm {CO_2}][\mathrm {H_{2}O}]/[\mathrm {H^+}][\mathrm {HCO_3^-}]}\\ \qquad \qquad \kern0.72em \left(\mathrm{(equilibrium)}\kern0.24em \mathrm{equation}\right)\end{array}$

From this equilibrium, it is seen that an increase in CO₂ results in hydration of the CO₂ and an increase in H₂CO₃. The H₂CO₃ will partially dissociate yielding equimolar quantities of H⁺ and HCO₃ ⁻. Both changes will be dictated by the equilibrium equation and its associated constant. As a result a change in CO₂ must be matched by a change in HCO₃ ⁻. Thus, CO₂ and HCO₃ ⁻ are dependent on each other and not truly independent determinants of pH as is commonly implied.

Metabolic Indices

The CO₂–HCO₃ ⁻ relationship has resulted in the proposal of multiple metabolic indices. These indices are intended to circumvent the CO₂–HCO₃ ⁻ relationship. One of these indices is the standard bicarbonate concentration (SBC). The SBC attempts to correct for the interrelationship by standardization of the CO₂. By exposing a blood sample to CO₂ at a partial pressure of 40 mmHg, the sample will equilibrate to this standard CO₂ partial pressure. From this standardization, any deviation of the HCO₃ ⁻ from normal will be an indicator of a nonrespiratory problem. In 1960, Siggaard-Andersen proposed that the BE be the standard metabolic index.

Anion Gap

When using the SBC or the BE, the origin of a metabolic deviation is left unexplained. For instance, an abnormal BE would not tell a clinician whether a metabolic acidosis is a result of ketoacidosis, lactic acidosis, or hyperchloremia. For further understanding of a metabolic acidosis, the anion gap is utilized.

The anion gap is based on the concept of electroneutrality. The sum of the positive ions and the negative ions in a solution must be zero, (Σcations = Σanions). In other words, any body fluid will have no net charge. This charge balance means that the charge of Na⁺, K⁺, Mg²⁺, Ca²⁺, and H⁺ must be balanced by an equal and opposite charge of Cl⁻, SO₄ ²⁻, PO₄ ³⁻, CO₃ ²⁻, HCO₃ ⁻, OH⁻, lactate, and the charges on the proteins. The anion gap can be defined as

$\begin{array}{l}\mathrm{Anion}\kern0.24em \mathrm{gap}=\left[{\mathrm{Na}}^{+}\right]-\left(\left[{\mathrm{Cl}}^{-}\right]+\left[{{\mathrm{HCO}}_3}^{-}\right]\right)\\ {}=\mathrm{Unmeasured}\kern0.24em \mathrm{anions}-\mathrm{Unmeasured}\kern0.24em \mathrm{cations}\end{array}$

By this definition K⁺, Ca²⁺, and Mg²⁺ have been relegated into a grouping of unmeasured cations. Likewise, SO₄ ²⁻, PO₄ ³⁻, lactate, and the proteins have been grouped into unmeasured anions. An increase in anion gap represents an increase in unmeasured anions or a decrease in unmeasured cations, and a decrease in anion gap can be caused by a decrease in unmeasured anions or an increase in unmeasured cations.

Traditional Approach of Arterial Blood gas Analysis

Arterial blood gases are routinely used to assess acid-base disturbances, which can be analyzed as follows (Fig. 45.1, Table 45.1):

Fig. 45.1

Approach to determine acid-base disorder

Table 45.1

Simplified approach to blood gas analysis (approximate equality)

pH, normal 7.4	Is there an acidosis or alkalosis
PaCO₂	Is the change in PaCO₂ consistent with respiratory component; if not, does the change in HCO₃ indicate a metabolic component
Acute respiratory acidosis	10 units increase in PaCO₂ = 1 unit increase in HCO₃
Chronic respiratory acidosis	10 units increase in PaCO₂ = 4 units increase in HCO₃
Acute respiratory alkalosis	10 units decrease in PaCO₂ = 2 units decrease in HCO₃
Chronic respiratory alkalosis	10 units decrease in PaCO₂ = 5 units decrease in HCO₃
Metabolic acidosis	1 unit decrease in HCO₃ = 1 unit decrease in PaCO₂
Metabolic alkalosis	10 units increase in HCO₃ = 7 units increase in PaCO₂

For example, a patient with a pH of 7.27, PaCO₂ 60, HCO₃ 25, has respiratory acidosis. If the HCO₃ would have been 29, the patient would have chronic (compensated) respiratory acidosis

pH—The normal pH is 7.35–7.45. A blood pH less than 7.35 is termed as acidosis, while a pH higher than 7.45 is termed as alkalosis.

PaCO₂—The normal PaCO₂ is 35–45 mmHg. A PaCO₂ less than 35 mmHg is termed as respiratory alkalosis, while a PaCO₂ more than 45 mmHg is termed as respiratory acidosis. Adequacy of ventilation can be assessed by calculation of the dead space (V _D) to tidal volume (V _T) ratio, using the Bohr dead space equation:

$\begin{array}{c}{V}_{\mathrm{D}}/{V}_{\mathrm{T}}=\left({\mathrm{P}}_{\mathrm{A}}{\mathrm{CO}}_2-{\mathrm{ETCO}}_2\right)/{\mathrm{P}\mathrm{ACO}}_2,\\ {}\mathrm{the}\kern0.24em \mathrm{normal}\kern0.24em \mathrm{ratio}\kern0.24em \mathrm{should}\kern0.24em \mathrm{be}\kern0.24em \mathrm{less}\kern0.24em \mathrm{than}\kern0.24em 0.3\end{array}$

PaO₂—Hypoxia is defined as a PaO₂ < 60 mmHg. Adequacy of ventilation can be assessed by measuring the

(a)

Alveolar-arterial gradient of oxygen: PAO₂ − PaO₂

$\begin{array}{c}{\mathrm{PAO}}_2=\left(\begin{array}{l}\mathrm{atmospheric}\kern0.24em \mathrm{pressure}-\\ {}\mathrm{water}\kern0.24em \mathrm{vapor}\kern0.24em \mathrm{pressure}\end{array}\right)\\ {}\times {\mathrm{FiO}}_2-{\mathrm{PaCO}}_2/0.8\end{array}$

where 0.8 is the respiratory quotient and is the ratio of CO₂ produced to O₂ consumed. Normally, about 80 % of CO₂ is produced for 100 % O₂ consumed (200 ml CO₂:250 ml of O₂)

(b)

Ratio of PaO₂:FiO₂, the P/F ratio. The lower the ratio, the worse the oxygenation. A P/F ratio less than 300 denotes acute lung injury, whereas a P/F ratio less than 200 denotes ARDS.

HCO₃—The normal HCO₃ is 22–26 mmol/L. A HCO₃ less than 22 is termed as metabolic acidosis, while a HCO₃ more than 26 is termed as metabolic alkalosis.

Assess compensatory changes.

Regulation of pH in the Body

Regulation of pH or the hydrogen ion concentration in the human body occurs mainly via three processes: the buffer systems, central and peripheral chemoreceptors, and the renal system. Causes and compensatory mechanisms for acid base disturbances are summarized in Tables 45.2 and 45.3. Adverse effects of acid-base disturbances are summarized in Table 45.4.

Table 45.2

Causes and compensation of respiratory acidosis and alkalosis

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