Step 1: Classify pH

The normal limits for arterial pH in humans are 7.35 to 7.45. This range is not affected by age or gender. An arterial pH greater than 7.45 is called alkalemia, and a pH less than 7.35 is called acidemia. If the pH is classified as abnormal, one determines whether the abnormality is of respiratory or nonrespiratory (metabolic) origin.

Step 2: Analyze Respiratory Involvement (PaCO₂)

The PaCO₂ is controlled by alveolar ventilation and is thus the indicator of respiratory involvement. The normal range for PaCO₂ in humans is 35 to 45 mm Hg and is not affected by age or gender; high and low PaCO₂ values are called hypercapnia and hypocapnia. The PaCO₂ is analyzed, keeping the pH (step 1) in mind. A PaCO₂ greater than 45 mm Hg means blood H⁺ levels (from dissociated carbonic acid) are abnormally high; this is compatible with acidemia and hypoventilation. A PaCO₂ less than 35 mm Hg has the opposite meaning; it is compatible with alkalemia and hyperventilation. If the pH is abnormal, the following question should be asked: Could the observed PaCO₂ help explain the pH abnormality? For example, if the pH is 7.50 (alkalemia) and the PaCO₂ is 30 mm Hg (hyperventilation), the respiratory system must be at least partly, if not entirely, responsible for the alkalemia.

Step 3: Analyze Nonrespiratory (Metabolic) Involvement ([HCO₃⁻])

Because it is primarily determined by nonrespiratory, or so-called metabolic factors, plasma bicarbonate concentration is the logical indicator of nonrespiratory involvement in acid-base disturbances. The normal range for arterial plasma [HCO₃⁻] in humans is 22 to 26 mEq/L and is unaffected by age or gender. Bicarbonate is a chemical base; high plasma bicarbonate (>26 mEq/L) is compatible with alkalemia, and low plasma bicarbonate (<22 mEq/L) is compatible with acidemia.

Plasma [HCO₃⁻] is not as specific and accurate in indicating metabolic acid-base disturbances as PaCO₂ is in indicating respiratory disturbances. The reason is that plasma bicarbonate responds slightly to pure respiratory (i.e., PCO₂) changes. The carbon dioxide hydration reaction explains this phenomenon. As explained in Chapter 10, an acute increase in PaCO₂ of 10 mm Hg increases [HCO₃⁻] by about 1 mEq/L. Thus, the plasma [HCO₃⁻] must be evaluated with caution; if it falls outside of the normal range but the abnormality can be explained by the effect of the carbon dioxide hydration reaction, the [HCO₃⁻] level is not responsible for any existing acid-base disorder.

Keeping the foregoing limitation in mind, the [HCO₃⁻] is inspected and compared with the pH. If the pH is abnormal, one must ask: Can the observed [HCO₃⁻] explain the pH abnormality? For example, if the arterial pH is 7.25 (acidemia) and [HCO₃⁻] is low (18 mEq/L), this is compatible with acidemia. Therefore, metabolic (nonrespiratory) factors are at least partly, if not entirely, responsible for the acidosis.

Step 4: Assess for Compensation

When the acid-base abnormality has been identified as either respiratory or metabolic, the degree of compensation present, if any, must be determined. In other words, if a respiratory acidosis exists (increased PaCO₂), have the kidneys compensated by elevating the plasma [HCO₃⁻]? Conversely, if a metabolic acidosis exists (decreased HCO₃⁻), have the lungs compensated by hyperventilating and lowering the PaCO₂?

If the pH has been restored to the normal range (7.35 to 7.45), full compensation has occurred even though pH remains on the acid or alkaline side of the range. Compensation is partial if the pH is still outside of the normal range but the noncausative component (either PaCO₂ or HCO₃⁻) is also abnormal in a way that brings the pH back toward the normal range. A compensated acid-base disturbance is sometimes referred to as a chronic acidemia or chronic alkalemia because a certain amount of time is required to bring about compensation. Partial compensation means compensatory activity has begun but has not had enough time to restore the pH to normal. The term uncompensated means the acid-base disturbance is of such recent origin that compensatory activity has not yet started. Therefore, an uncompensated condition is sometimes called an acute acidemia or acute alkalemia.

It is assumed that compensation for a primary acid-base disorder is never truly complete in the sense of restoring arterial pH all the way to 7.40.³ In a compensated disorder, the pH is on the acid or alkaline side of the normal range, depending on whether the primary causative disorder created an acidosis or an alkalosis. That is, if the pH is on the acid side of normal (<7.40 but at least ≥7.35), the main cause of the original acid-base imbalance is the component (PaCO₂ or HCO₃⁻) that, by itself, would cause an acidosis. For example, if the pH is 7.36, PaCO₂ is 80 mm Hg, and HCO₃⁻ is 44 mEq/L, compensation is present because the pH is in the normal range, although it is on the acid side of normal. The primary cause of the original acid-base disturbance (before compensatory activity started) must be the factor that would produce acidemia (i.e., the increased PaCO₂ of 80 mm Hg). Thus, this set of blood gases would be classified as compensated (chronic) respiratory acidosis. The primary disturbance is of respiratory origin, and the increased [HCO₃⁻] is a secondary metabolic compensatory response. The reason the pH is on the acid side of the normal range is that the body generally does not overcompensate; it does not increase the [HCO₃⁻] so much that it converts the previously acidotic environment to one with a pH on the alkaline side of normal. Conversely, if the pH is 7.15, PaCO₂ is 80 mm Hg, and HCO₃⁻ is 26 mEq/L, no compensation has occurred; that is, HCO₃⁻ is still normal, not elevated as would be expected if compensatory action were underway.

Compensatory activity does not correct the primary acid-base disturbance; the primary defect is still present. Compensatory activity merely works to restore the pH to the normal range. Table 13-1 summarizes acid-base and ventilatory classification. Table 13-2 classifies the degree of compensation for acid-base disturbances.

Causes

Hypoventilation causes hypercapnia, which implies inadequate ventilation. Any process that hinders alveolar ventilation can

cause respiratory acidosis. Chronic obstructive pulmonary disease (COPD) is the most frequent cause of respiratory acidosis, mostly because the airways resistance of a patient with severe COPD is so high that the patient cannot sustain the ventilatory work required to maintain a normal PaCO₂.³ Central nervous system depression (drug-induced), extreme obesity (impaired diaphragmatic movement), and neuromuscular disorders (spinal cord lesions, paralytic neuromuscular diseases) are other causes of hypoventilation and respiratory acidosis. Hypercapnia may occur in different ways. A person may have an absolute decrease in ventilation because of drug-induced central nervous system depression, or a patient with COPD and a limited ventilatory reserve may sustain a normal PaCO₂ at rest but may not accommodate the increased carbon dioxide production associated with increased physical activity.

Uncompensated hypercapnia implies the presence of acute ventilatory failure; the resulting respiratory acidosis is manifested by a low arterial pH, increased PaCO₂, and normal or slightly high [HCO₃⁻]. In this situation, a slightly increased [HCO₃⁻] is not a sign that the kidneys have started compensatory activity; it merely reflects the effect of the carbon dioxide hydration reaction on [HCO₃⁻] (see Chapter 10).

Compensation

Renal (kidney) compensation for respiratory acidosis begins as soon as PaCO₂ increases. The kidney reclaims HCO₃⁻ from the renal tubular filtrate, returning it to the blood. The arterial pH is brought into the normal range because the [HCO₃⁻]-dissolved carbon dioxide ratio is restored near its normal 20:1 range (see Chapter 10). However, this process cannot keep pace with an acutely increasing PaCO₂. Full compensation may take several days.

Over the course of developing COPD, a person’s PaCO₂ increases gradually, allowing the compensatory process enough time to keep pace with the rising PaCO₂. The arterial pH is thus maintained in the normal range. Partly compensated respiratory acidosis is characterized by increased PaCO₂, increased [HCO₃⁻], and an acid pH still not quite in the normal range. A compensated respiratory acidosis is characterized by a pH on the acid side of the normal range (<7.40 but at least ≥7.35), increased PaCO₂, and increased [HCO₃⁻]. The high [HCO₃⁻] in the presence of a high PaCO₂ is a sign that the PaCO₂ has been elevated for a considerable time (i.e., the kidneys have had sufficient time to compensate). Thus, compensated respiratory acidosis is synonymous with chronic ventilatory inadequacy. Although the pH is in the normal range, the underlying pathological process that produces hypercapnia is still present; the kidneys simply mask the problem by maintaining a normal pH range. Because hypercapnia persists, the term acidosis is retained in classifying this condition (compensated respiratory acidosis). This term emphasizes that lung function is still abnormal and has the potential to produce an acidosis.

Clinical Manifestations

Patients with neuromuscular weakness or mechanical breathing difficulties usually breathe shallowly and rapidly and are short of breath; they are often anxious and in obvious distress. Drug-induced central nervous system depression produces slow, shallow breathing and possibly apnea. Acute respiratory acidosis produces more serious physiological consequences than chronic respiratory acidosis. Rapidly increasing PaCO₂ causes cerebral vasodilation and increased intracranial pressure (ICP), possibly leading to retinal venous distention and retinal hemorrhages; in addition, the patient may develop myoclonus (spasmodic muscle jerks), asterixis (a hand-flapping tremor in which the patient cannot keep the wrists flexed with the arms extended), and mental confusion.³ An abrupt onset of hypercapnia in which PaCO₂ rises beyond 70 mm Hg can lead to coma, although patients with chronic hypercapnia can tolerate much higher PaCO₂ values.³ Hypercapnia increases the cardiac output and dilates peripheral vessels, often resulting in a bounding pulse and warm, flushed skin.

Correction

The corrective action in acute respiratory acidosis is to restore alveolar ventilation. Various respiratory therapy modalities ranging from secretion mobilization and bronchodilator drugs to endotracheal intubation and mechanical ventilation may be

needed to restore ventilation. However, if hypoventilation is chronic and compensation has restored arterial pH to the normal range, corrective action aimed at reducing the PaCO₂ is inappropriate and possibly harmful. In this situation, a rapidly decreasing PaCO₂ induces a sudden alkalosis because of renal compensation and elevated blood HCO₃⁻ levels.

Causes

Hyperventilation causes hypocapnia. Any process in which ventilatory elimination of carbon dioxide exceeds its production causes respiratory alkalosis. Causes can be divided into three categories: (1) hypoxia, (2) pulmonary diseases, and (3) central nervous system diseases. Probably the most common cause of hyperventilation in patients with pulmonary disease is arterial hypoxemia, mediated through the peripheral chemoreceptors.³ Hypoxia-induced respiratory alkalosis can be caused by high altitude or pulmonary diseases characterized by intrapulmonary shunting (e.g., pneumonia, pulmonary edema). Other pulmonary diseases associated with hyperventilation and respiratory alkalosis include interstitial fibrosis, pulmonary embolism, and acute asthma. J-receptor stimulation in the lung parenchyma may be involved in interstitial diseases, pneumonia, and pulmonary edema. The feeling of dyspnea from high airways resistance and resulting anxiety is a probable mechanism for respiratory alkalosis in acute asthma. General anxiety, fever, stimulating drugs, pain, and injuries of the central nervous system are other possible causes of hyperventilation.

Hyperventilation and respiratory alkalosis also may be iatrogenically induced (i.e., induced by health care personnel). Iatrogenic hyperventilation is most commonly associated with overly aggressive mechanical ventilation; it may also be associated with aggressive deep breathing and lung-expanding respiratory therapy procedures. Acute respiratory alkalosis is characterized by decreased PaCO₂, a high pH, and normal-range [HCO₃⁻]. An extremely slight decrease in [HCO₃⁻] is expected to be present as a result of the hydration reaction’s effect.

Clinical Manifestations

An early sign of acute respiratory alkalosis (hypocapnia) is paresthesia, a numb or tingling sensation in the extremities; light-headedness may also occur. Severe hyperventilation and alkalosis is associated with hyperactive reflexes, muscle

cramping of the hands or feet (carpopedal spasm), and possibly tetanic convulsions (a fusion of many muscle spasms producing a sustained contraction without relaxation). The low PaCO₂ level may constrict cerebral vessels enough to impair cerebral circulation, causing light-headedness, dizziness, and syncope (fainting). If respiratory alkalosis is anxiety-induced, the patient may show signs of panic and express feelings of impending doom. Vision may become impaired (tunnel vision), and speaking may become difficult.³

Compensation

The kidneys compensate for respiratory alkalosis by excreting HCO₃⁻ in the urine (bicarbonate diuresis). This activity brings the arterial pH down toward the normal range because the [HCO₃⁻]-dissolved carbon dioxide ratio is restored near its normal 20:1 range. However, renal compensation rarely causes [HCO₃⁻] to fall below 18 mEq/L.³ Renal compensation is a relatively slow process; it may take days until the compensation process is finally completed.

Partially compensated respiratory alkalosis is characterized by decreased PaCO₂, decreased [HCO₃⁻], and an alkaline pH that is still not quite down in the normal range. Compensated respiratory alkalosis is characterized by decreased PaCO₂, decreased [HCO₃⁻], and pH on the alkaline side of normal (pH >7.40 but ≤7.45). Compensated respiratory alkalosis is sometimes called chronic respiratory alkalosis or chronic alveolar hyperventilation. The underlying hyperventilation and hypocapnia are still present. Thus, the term alkalosis is used in classifying this condition, although the pH is in the normal range.

Correction

Respiratory alkalosis is corrected by removing the stimulus causing the hyperventilation. If hypoxemia is the stimulus, oxygen therapy is administered. If the cause is iatrogenic, the therapy causing the hyperventilation is reduced or eliminated. In patients with severe anxiety, reassurance and rebreathing exhaled air (breathing into a paper bag) to increase PaCO₂ may be effective.

Alveolar Hyperventilation Superimposed on Compensated Respiratory Acidosis

A patient with advanced but stable COPD and compensated respiratory acidosis may exhibit the following arterial blood gas values:

The HCO₃⁻ level is high because of renal compensatory activity. If the person now experiences an acute exacerbation of disease and becomes severely hypoxic, this may stimulate the peripheral chemoreceptors enough to increase alveolar ventilation and acutely decrease PaCO₂ despite the patient’s deranged lung mechanics.

In this case, let us assume that the patient was incapable of hyperventilating enough to decrease PaCO₂ all the way down into the normal range. Although PaCO₂ is still above normal, the acute lowering of the PaCO₂ coupled with the preexisting high compensatory level of HCO₃⁻ causes the pH to swing from the acidic to the alkalotic side of normal, as the following values illustrate:

If one pays attention to only the blood gas data and applies the strict criteria for interpretation as outlined earlier in this chapter, one would arrive at the completely incorrect interpretation of compensated metabolic alkalosis. This interpretation would lead the novice to conclude that the patient is hypoventilating to compensate for a preexisting primary metabolic alkalosis; in light of this patient’s medical history, this would be an absurd conclusion. This example illustrates the fact that blood gas data alone are an insufficient basis for rational acid-base assessment. The patient’s medical history, the physical examination, and the nature of the current problem are vital in accurately evaluating blood gas abnormalities. The above-listed blood gases are correctly described as acute

hyperventilation superimposed on compensated respiratory acidosis.

Causes

Metabolic acidosis can occur in two general ways: (1) the accumulation of fixed (nonvolatile) acid in the blood or (2) an excessive loss of HCO₃⁻ from the body. For example, a lack of blood flow leads to tissue hypoxia, anaerobic metabolism, and production of lactic acid (a fixed acid). The resulting accumulation of hydrogen ions reacts with bicarbonate ions, lowering the blood [HCO₃⁻], producing nonrespiratory or metabolic acidosis. Another example is severe diarrhea, in which large stores of HCO₃⁻ are lost from the bowel, again producing nonrespiratory acidosis.

Because of their different causative mechanisms, these two types of metabolic acidosis are treated differently; the identification of the underlying mechanism is necessary to treat metabolic acidosis effectively. The analysis of plasma electrolytes—specifically, the so-called anion gap—is helpful in determining whether metabolic acidosis was caused by a gain of fixed acids or by a loss of base.

Anion Gap

The law of electroneutrality states that the total number of positive charges in the body fluids must equal the total number of negative charges. Plasma cations (positively charged ions) are exactly balanced by anions (negatively charged ions); that is, the plasma has no net electrical charge. The routinely measured plasma electrolytes (cations and anions) in clinical medicine include only Na⁺, K⁺, Cl⁻, and HCO₃⁻, although body fluids contain many other cations and anions. The normal plasma concentrations of these routinely measured electrolytes are such that the cations (Na⁺ and K⁺) outnumber the anions (Cl⁻ and HCO₃⁻), causing what seems to be an anion gap. Generally, K⁺ is ignored in calculating the anion gap because of its very low concentration:

Aniongap(mEq/L)=[Na+]−([Cl−]+[HCO3−])

The “anion gap” can be thought of as a measure of the concentrations of other anions in the plasma besides Cl⁻ and HCO₃⁻. Figure 13-2, A