Metabolic Acid-Base Disturbances

Metabolic acid-base abnormalities are caused by alterations in the SID or A_TOT , or both. An increase in the SID causes alkalemia; a decrease in the SID causes acidemia. The alternation may be caused by a change in the total or relative concentration of strong ions. For example, a decrease in the SID (i.e., more anions relative to cations) causes acidosis; this may occur because of a net increase in anions (e.g., hyperchloremia, lacticemia) or an increase in the volume of distribution of the same quantity of ions (e.g., dilutional acidosis) (see Table 41-1 ).

Metabolic acidosis is of clinical significance for two reasons: pathologies arising from the acidosis itself and pathologies arising from the cause of the acidosis. Acidosis is associated with alterations in transcellular ion pumps and increased ionized calcium. The result is vasodilation,

TABLE 41-1 -- Changes in PaCO₂ and [HCO₃ ^- ] in response to acute and chronic acid-base disturbances

Disturbances	[HCO3 - ] vs. PaCO2
Acute respiratory acidosis	ΔHCO3 - = 0.2 ΔPaCO2
Acute respiratory alkalosis	ΔHCO3 - = 0.2 ΔPaCO2
Chronic respiratory acidosis	ΔHCO3 - = 0.5 ΔPaCO2
Metabolic acidosis	ΔPaCO2 = 1.3 ΔHCO3 -
Metabolic alkalosis	ΔPaCO2 = 0.75 ΔHCO3 -
Δ, change in value; [HCO3 - ], concentration of bicarbonate ion; PaCO2 , partial pressure of arterial carbon dioxide.
Modified from Narins RB, Emmett M: Simple and mixed acid-base disorders: A practical approach. Medicine (Baltimore) 59:161–187, 1980.

diminished muscular performance (particularly myocardial), and arrhythmias. The oxyhemoglobin dissociation curve shifts rightward to increase oxygen offload into the tissues. Rapid-onset metabolic acidosis may be associated with profound hypotension, cardiac arrhythmias, and death. The malignancy of the acidosis is strongly related to the underlying disease process; lactic acidosis caused by circulatory shock is more malevolent than hyperchloremic acidosis due to excessive administration of normal saline.^[13] The body is hyperresponsive to acidosis. Increasing the hydrogen ion content in cerebrospinal fluid activates the respiratory center to stimulate respiration. Alveolar ventilation increases, reducing arterial CO₂ content and reducing the total body [H⁺ ]. Bicarbonate concentration simultaneously decreases because of buffering activity and the reduction in total CO₂ . This prevents abrupt reductions in plasma pH in acute metabolic acidosis.

Metabolic alkalosis rarely occurs as a result of acute illness. Symptoms and signs of metabolic alkalosis include widespread vasoconstriction, lightheadedness, tetany, and paresthesia. The main compensatory mechanism is hypoventilation, which may delay weaning from mechanical ventilation in critically ill patients (see Chapter 74 and Chapter 75 ).

An understanding of the mechanisms by which alterations in the SID affect acid-base balance clarifies many of the abnormalities that have remained unexplained by traditional teaching. Of key importance is the ability to differentiate the change in the SID that results from altered free water balance from that arising from altered concentrations of measured and unmeasured electrolytes.

An average man of 70 kg has a total-body water content of approximately 45 L, two thirds of which are in the intracellular space. Approximately 15 L are extracellular. The [Na⁺ ] in this compartment is 140 mEq/L, [Cl^- ] is 100 mEq/L, and [K⁺ ] is 4 mEq/L. For simplicity, we ignore magnesium, calcium, other strong ions, and CO₂ . In this system, the SID is 44 mEq/L, with this positive charge being balanced principally by weak acids. Anything that increases the SID increases the relative concentration of strong cations to strong anions and alkalinizes the solution. Anything that decreases the SID decreases the relative concentration of cations to anions and acidifies the solution.

When the volume of this compartment is expanded by 2 L, as occurs with rapid infusion of 5% dextrose, the [Na⁺ ] falls to 123 mEq/L, the [K⁺ ] falls to 3.5 mEq/L, and the [Cl^- ] falls to 88 mEq/L. The relative ratio of cations to anions also falls, and the SID decreases to 38.5 mEq/L. The system becomes more acidic. This is the basis of dilutional acidosis.

Conversely, if 2 L of free water are removed from the system and the total concentration of ions remains unchanged (as would occur with profuse sweating or dehydration), the opposite would occur. [Na⁺ ] rises to 161 mEq/L, [K⁺ ] increases to 4.6 mEq/L, and [Cl^- ] increases to 115 mEq/L. The relative ratio of cations to anions actually rises, and SID increases to 50.6 mEq/L. The system becomes more alkaline. This is the basis of contraction alkalosis.

In perioperative medicine, normal saline (0.9% NaCl), containing 154 mEq/L of sodium and 154 mEq/L of

1604

Any process that leads to dilution of the total number of ions (i.e., charged particles) in the solution can be expected to cause acidosis. As examples, consider the use of mannitol therapeutically (before the diuresis) or hyperglycemia or ethylene glycol or the pathology of methanol poisoning. This process increases the volume of water without changing the net charge and results in a dilutional acidosis. Any process that removes chloride without sodium, such as aggressive nasogastric suctioning that removes HCl, causes metabolic alkalosis (i.e., hypochloremic alkalosis) because of an increase in the SID. The alkalosis is caused by chloride loss, which obeys the law of conservation of mass (i.e., there is a finite quantity available in the ECF), not hydrogen ions, whose source, water, is unlimited. Severe diarrhea, which is associated with loss of potassium and sodium, reduces the SID, and is associated with metabolic acidosis. Aggressive use of diuretics causes a net loss of free water over sodium and chloride and causes contraction alkalosis.

The most malignant form of metabolic acidosis is associated with a net gain of unmeasured anions (i.e., electrolytes not conventionally measured on serum chemistry analysis) and, consequently, a decreased SID.

1. In dysoxia, lactate is produced, reducing the SID and causing acidosis.
2. In out-of-control diabetes (i.e., ketoacidosis), β-hydroxybutyrate and acetoacetate are produced, reducing the SID and causing acidosis.
3. In severe renal failure, SO₄ ^2- and PO₄ ^3- (i.e., fixed renal acids) are not excreted, causing acidosis.

The mechanism of acidosis is similar to previous examples. If, in our patient with [Na⁺ ] = 140 mEq/L, [Cl^- ] = 100 mEq/L, and [K⁺ ] = 4 mEq/L, an additional anion (i.e., lactate) is added at a concentration of 10 mEq/L, the SID decreases to 34 mEq/L, and the system becomes more acidemic.

The total weak acid pool, principally serum albumin and phosphate, is also an important determinant of acid-base status. Hyperphosphatemia has long been associated with the acidosis of renal failure, and hypoalbuminemia is common in clinical practice. There is a strong association between hypoalbuminemia and the severity of critical illness. This occurs because of hepatic reprioritization of visceral protein production toward acute-phase reactants, capillary leak, breakdown of preexisting albumin (so that its constituent amino acids can be used for protein synthesis), and hemodilution with isotonic fluids. Hypoalbuminemia decreases A_TOT and is associated with metabolic alkalosis.^[15]

The impact of hypoalbuminemia on acid-base balance has been grossly underestimated. Stewart's original theory was modified by Fencl and Figge.^[16] The serum albumin concentration is the core negative charge offsetting the net positive charge of the SID.^[17] Consequently, the presence of hypoalbuminemia may mask the detection of acidosis,^[18] such as by unmeasured anions (UMAs), when using the conventional tools of acid-base chemistry, pH, base deficit, and the anion gap.^[19] The presence of hypoalbuminemia has significant implications, not least for its association with adverse outcomes,^{[18] [20]} unlike abnormalities of the SID, which have not been shown to have prognostic significance. Hyperalbuminemia is very unusual; nonetheless, in cholera, when associated with hemoconcentration, it is associated with acidosis.^[21]

Fencl neatly categorized acid-base disturbances along respiratory and metabolic lines ( Table 41-2 ). This elegantly explains all known acid-base disturbances.

1605

There are significant differences between the mechanisms causing acid-base imbalances. It would be reasonable to predict significantly different outcomes for patients developing acidosis from dilution, poisoning, hyperchloremia, excessive use of normal saline infusions, or dysoxia due to increased production of lactate. The acid-base abnormalities, in themselves, may be of less clinical significance than previously thought.^[9]