Acid-Base Disorders

Kevin H. Zhao

Kathryn L. Butler

Acid-base disorders arise in a wide variety of postoperative scenarios and have severe consequences on organ function and perfusion. An abnormal pH can alter enzyme function, electron transport, membrane stability, and endanger patients to arrhythmias, hemodynamic instability, and organ ischemia.

Clinicians caring for postoperative patients with acid-base disorders must diagnose the underlying cause to provide effective treatment. Classification schemes to aid understanding of acid-base disorders include:

1. acidosis versus alkalosis

2. metabolic versus respiratory

3. anion-gap versus nonanion-gap acidosis

4. acute versus chronic

5. iatrogenic versus secondary to a disease process

Understanding the appropriate categorization of acid-base disorders guides not only the therapeutic options, but also the urgency of treatment (Fig. 24.1).

I. PATHOPHYSIOLOGY

A. Various acid-base paradigms help to quantify acid-base relationships. Traditional acid-base teaching focuses on the generation of protons (H⁺) and their neutralization through bicarbonate (HCO₃^–) buffers.

H⁺ + HCO₃^– ↔ H₂CO₃ ↔ H₂O + CO₂

The body regulates this equilibrium through the enzyme carbonic anhydrase. With regard to by-products, the kidneys eliminate bicarbonate, whereas lung ventilation removes carbon dioxide. The Henderson-Hasselbalch equation quantifies this equilibrium through the interaction of weak acids and their conjugate bases:

pH = pK_a + log₁₀ ([A^–]/[HA])

Making the appropriate substitutions from the bicarbonate-carbon dioxide equilibrium yields:

pH = pK_{a H2 CO3} + log {[HCO₃^–]/[H₂CO₃]}

Substituting and converting numerical variables yields:

pH = 6.1 + log {[HCO₃^–]/(PaCO₂^*0.03)}

Understanding the role of bicarbonate as a buffer and the Henderson-Hasselbalch equation provides clinically useful values such as base excess and base deficit. A base excess reflects an alkalotic condition, whereas a base deficit indicates an acidotic condition. Base excess and base deficit are the amount of strong acid or strong base, respectively, that must be added to each liter of blood to return the pH to 7.40 at
37°C. These values can be used to trend the severity and resolution of acid-base disorders.

FIGURE 24.1 Algorithm for categorizing metabolic acid-base disorders based on etiology and mechanism.

B. Acidosis and alkalosis have unique and varied clinical effects (Table 24.1). The severity of these effects depends on the magnitude of the acid-base disturbance and each patient’s preexisting medical
conditions. Acid-base abnormalities can be iatrogenic or due to underlying disease. Although an alkalosis caused by aggressive diuresis or an acidosis caused by permissive hypercapnia will self-resolve with discontinuation of therapy, acid-base disturbances due to lactic acidosis or hypoventilation may be life-threatening and warrant immediate intervention. Understanding the laboratory values associated with acid-base disorders provides useful diagnostic information (Fig. 24.2). Under typical circumstances, the body will attempt to compensate for the underlying disorder and minimize clinical consequences. In rare cases, the effects of an altered pH may be therapeutic and desired. For example, mild hyperventilation-induced cerebral vasoconstriction offers short-term intracranial pressure relief until a more definitive treatment can occur. Management of acid-base disorders mandates consideration of each patient’s unique clinical context.

TABLE 24.1 Clinical Effects of Acidemia and Alkalemia

	Acidemia	Alkalemia
Cardiovascular	Decreased cardiac contractility Blunted catecholamine response Hypotension Increased arrhythmias	Reduced coronary blood flow Increased cardiac contractility Increased arrhythmias
Pulmonary	Increased pulmonary vascular resistance Hyperventilation	Hypoventilation
Cerebral	Cerebral vasodilation Increased cerebral blood flow Increased intracranial pressure	Cerebral vasoconstriction Decreased cerebral blood flow Decreased intracranial pressure
Metabolic	Hyperkalemia Increased protein catabolism	Hypokalemia Hypomagnesemia Hypophosphatemia

FIGURE 24.2 Algorithm for differentiating and classifying acid-base disorders based on laboratory results. AG, anion-gap; UAG, urine anion-gap; DR, δ ratio.

II. METABOLIC DISORDERS

A. Metabolic acidosis can be caused by increased acid production, increased bicarbonate elimination, or exogenous acid administration. These categories can then be sorted into anion-gap and nonanion-gap disorders (Table 24.2).

1. The anion-gap represents unmeasured anions in the plasma, which is primarily composed of negatively charged proteins.

Anion-gap = [Na⁺] – [Cl^–] – [HCO₃^–]

In pathologic states, an increase in unmeasured anions (e.g., lactate) will cause an increased anion-gap. Because albumin is a negatively charged protein, hypoalbuminemia will result in a falsely low anion-gap and will need to be accounted for in the final calculation. The anion-gap will decrease by approximately 2.5 mEq/L for every 1 g/dL less of albumin below 4 mEq/L. A normal anion-gap is between 7 and 14 mEq/L, although it will be 11 to 18 mEq/L if the anion-gap equation includes [K⁺].

2. The etiology of the anion-gap acidosis influences time until resolution. In lactic acidosis, appropriate resuscitation causes lactate conversion to bicarbonate and resolution within hours. In the case
of excessive bicarbonate loss, such as diarrhea or renal tubular acidosis, resolution will require endogenous bicarbonate production that may take days.

TABLE 24.2 Metabolic Acidosis Causes

Anion-gap acidosis

Increased acid production

Lactic acidosis
Ketoacidosis
Uremia
Rhabdomyolysis

Intoxication

Aspirin
Ethanol
Methanol
Ethylene glycol
Paraldehyde

Nonanion-gap acidosis

Increased base loss

Diarrhea
Renal tubular acidosis
Ureterosigmoidostomy
Pancreatic fistula
Acetazolamide use
Topiramate use

Exogenous acid administration

Normal saline

3. Alkali therapy is a temporizing measure to correct a metabolic acidosis. Commonly given in the form of intravenous bicarbonate, alkali therapy can raise the pH and limit the consequences of severe acidemia (Table 24.1). The evidence supporting alkali therapy is limited, and the underlying cause must still be corrected to prevent further acid production. Sodium bicarbonate therapy is also not without risks. Bicarbonate is converted to carbon dioxide and elevates PaCO₂, which may increase a patient’s respiratory acidosis if ventilation is impaired. In shock states, correction of acidosis can worsen oxygen delivery to peripheral tissues. A sodium bicarbonate preparation can also worsen hypernatremia. Tromethamine (THAM) is an alternative to sodium bicarbonate that does not increase PaCO₂, but it has serious electrolyte side effects, and evidence does not show improvement in clinical outcomes.

B. Metabolic alkalosis can be caused by chloride losses, increased bicarbonate absorption, or bicarbonate administration. A metabolic alkalosis can be sorted into chloride-responsive or chloride-unresponsive disorders. Most chloride-responsive disorders are caused by chloride loss through the gastrointestinal tract or kidneys. Chloride-unresponsive alkalosis is less common and caused by increased mineralocorticoid activity.

C. Compensation, or the secondary response, refers to the body using the metabolic or respiratory system to shift the pH toward 7.40 during an acid-base disorder. Although metabolic changes to an underlying respiratory disorder may take days to adequately compensate, a respiratory response to a metabolic disorder can occur within hours. The degree of expected compensation is often predictable and can be calculated (see Table 24.3). It is important to remember that some
patients may mask or exacerbate an acute acid-base disorder by living in a chronic acidemic or alkalemic state because of their preexisting medical conditions.

TABLE 24.3 Predicted pH, PaCO₂, and HCO₃– Interaction and Compensation

Respiratory acidosis	Change in pH (PaCO₂ → pH)	Acute: PaCO₂ increases 1 mm Hg → pH decreases 0.008 Chronic: PaCO₂ increases 1 mm Hg → pH decreases 0.003
	Metabolic compensation	Acute: PaCO₂ increases 10 mm Hg → HCO₃^– increases 1 mEq/L Chronic: PaCO₂ increases 10 mm Hg → HCO₃^– increases 5 mEq/L
Respiratory alkalosis	PaCO₂ → pH	Acute: PaCO₂ decreases 1 mm Hg → pH increases 0.008 Chronic: PaCO₂ decreases 1 mm Hg → pH increase 0.003
	Metabolic compensation	Acute: PaCO₂ decreases 10 mm Hg → HCO₃^– decreases 2 mEq/L Chronic: PaCO₂ decreases 10 mm Hg → HCO₃^– increases 5 mEq/L
Metabolic acidosis	HCO₃^– → pH	HCO₃^– decreases 1 mEq/L → pH 0.015 decrease
	Respiratory compensation	PaCO₂ (mm Hg) = 1.5 ^* HCO₃^– (mEq/L) + 8
Metabolic alkalosis	HCO₃^– → pH	HCO₃^– increases 1 mEq/L → pH 0.015 increase
	Respiratory compensation	PaCO₂ (mm Hg) = 0.7 ^* HCO₃^– (mEq/L) + 20