Acid–Base and Electrolyte Disturbances

Acid–Base Balance

Normal acid–base balance is maintained by the lungs and kidneys. Carbon dioxide, a by-product of normal metabolism, is a weak acid. The lungs are able to prevent an increase in the partial pressure of carbon dioxide (P co ₂ ) in the blood by excreting the carbon dioxide (CO ₂ ) produced by the body. The pulmonary response to changes in the CO ₂ concentration is fast, as it occurs via central sensing of the P co ₂ , and there is a subsequent increase or decrease in ventilation to maintain a normal P co ₂ (35–45 mm Hg). There is an inverse relationship between P co ₂ and ventilation because an increase in ventilation decreases the P co ₂ , and a decrease in ventilation increases the P co ₂ .

The kidneys are responsible for excreting acid produced by the body. Sources of hydrogen ions include protein metabolism and incomplete metabolism of carbohydrates and fat; urine or stool losses of bicarbonate may contribute to acidemia. The hydrogen ions formed from endogenous acid production are neutralized by bicarbonate from the bicarbonate buffer system. The bicarbonate buffer system, based on the relationship between carbon dioxide and bicarbonate ( ${\text{HCO}}_3^{-}$ ), is displayed by the following equation:

This equation can help us understand how changes in CO ₂ or ${\text{HCO}}_3^{-}$ affect the acid–base balance.

Acid–Base Disorders

A pH <7.35 is defined as acidosis, and a pH >7.45 is defined as alkalosis. An acid–base disorder is respiratory in etiology when it is caused by a primary abnormality in respiratory function (a change in Pa co ₂ ) and is metabolic when the primary change is due to a variation in bicarbonate concentration. Acid–base disorders may also be mixed, which occurs when two or even three primary events act to alter the acid–base state at the same time.

In metabolic disorders, extracellular buffers (bicarbonate) rapidly titrate the presence of strong acids or bases. Intracellular buffers chiefly accomplish the buffering of respiratory disorders. Secondary respiratory compensation for metabolic acid–base disorders begins within minutes by changes in ventilation and is usually complete in 12–24 hours. In contrast, secondary metabolic compensation for respiratory disorders occurs more slowly, beginning within hours but requiring 2–5 days for completion. The kidneys increase net acid excretion in response to a primary respiratory acidosis; renal net acid excretion also increases during a metabolic acidosis if the kidneys themselves are not the cause of the metabolic acidosis. The expected compensation for primary acid–base disorders is shown in Table 59.1 . These compensatory mechanisms never return the pH back to normal until the underlying disease process has subsided or has been effectively treated.

When only one primary acid–base abnormality occurs and its compensatory mechanisms are activated, the disorder is classified as a simple acid–base disorder. When a combination of acid–base disturbances occurs, the disorder is classified as a mixed acid–base disorder. The latter should be suspected if the compensation in a given patient differs from the predicted values (see Table 59.1 ). Interpretation of data in infants and young children requires caution. Crying results in hyperventilation and can quickly change P co ₂ and consequently the pH.

Symptoms of Acid–Base Disorders

History and clinical evaluation are the first steps in assessing a patient with an acid–base disorder. Although the signs and symptoms associated with an acid–base abnormality can be nonspecific, there are certain clues that one can obtain from manifestations that can assist in the diagnosis of the acid–base disorder. Metabolic acidosis results in increased minute ventilation (manifesting as increased respiratory rate and/or effort) because of respiratory compensation. A patient may have tachypnea with a metabolic acidosis from a diarrheal illness, dehydration, poisoning, diabetic ketoacidosis, inborn errors of metabolism, or infection. In more severe acidosis (pH <7.20), the respiratory pattern is characterized by deep and rapid breaths (Kussmaul respiration). Severe acidosis may also lead to hypotension, pulmonary edema, and asystole; its harmful effects are accentuated in the presence of hypoxia. Chronic metabolic acidosis leads to poor growth and hypercalciuria with subsequent bone disease because bone buffering of acid produces marked mineral losses.

A child with metabolic alkalosis may be asymptomatic. In some cases, careful examination of the child may detect hypoventilation. One should consider metabolic alkalosis in a child who has been vomiting or in a child who has had chronic diuretic use. Severe alkalosis (pH >7.55) can lead to tissue hypoxia, mental confusion, obtundation, muscular irritability, tetany, and an increased risk of seizures and cardiac arrhythmias. Some of these signs and symptoms are related to decreased concentration of serum ionized calcium as a result of its increased binding to protein in the presence of alkalosis. Acid–base disturbances can be assessed through laboratory analysis by obtaining a basic chemistry panel and/or a blood gas analysis.

Renal Regulation of Acid–Base Balance

The kidneys are the principal regulator of bicarbonate homeostasis. The renal regulation of ${\text{HCO}}_3^{-}$ can be divided into two processes: reabsorption of ${\text{HCO}}_3^{-}$ and excretion of H ⁺ . The first role of the kidneys is to reabsorb the filtered ${\text{HCO}}_3^{-}$ so that this important extracellular buffer is not excreted in the urine. The second role of the kidneys is to excrete H ⁺ that is produced from protein and phospholipid catabolism.

Most (80–90%) of the filtered ${\text{HCO}}_3^{-}$ is reabsorbed in the proximal tubule. Bicarbonate reabsorption at this site is increased by the contraction of the extracellular fluid (ECF) volume, activation of the renin-angiotensin system (mainly through the effect of angiotensin II), elevated P co ₂ , and hypokalemia. Conversely, ${\text{HCO}}_3^{-}$ reabsorption is decreased when there is expansion of the ECF volume, inhibition of angiotensin II, a fall in P co ₂ , and an elevation of the parathyroid hormone level.

The distal tubule and collecting duct regenerate bicarbonate via H ⁺ ion secretion into the tubular lumen by an H ⁺ -adenosine triphosphatase (H ⁺ -ATPase) pump in the luminal membrane. This active secretion can generate an H ⁺ ion gradient of 1,000:1 between tubular fluid and cells, permitting the urine pH to fall to as low as 4.5. The active H ⁺ secretion is significantly influenced by the luminal electronegativity caused by active Na ⁺ reabsorption in the cortical collecting duct. Thus, in the cortical collecting duct, H ⁺ excretion is influenced by distal Na ⁺ delivery and reabsorption. In contrast, in the outer medullary portion of the collecting duct, aldosterone stimulates the H ⁺ excretion independently of Na ⁺ delivery or reabsorption. Some of the H ⁺ secreted is consumed in reclaiming the small amount of ${\text{HCO}}_3^{-}$ that escaped reabsorption at proximal sites; the rest of the H ⁺ is excreted in the urine. The ability to excrete a large amount of H ⁺ ions is dependent on the presence of buffers. The H ⁺ ions are buffered by phosphates and, to a lesser extent, by other non-reabsorbable anions. The other very important urinary buffer is ammonia (NH ₃ ), which combines with a secreted H ⁺ to generate an ammonium ion (NH ₄ ⁺ ). The proximal tubular cells generate ammonia through the metabolism of the amino acid glutamine. For every H ⁺ that is finally excreted, an ${\text{HCO}}_3^{-}$ is added to the ECF compartment. Metabolic acidosis by itself enhances NH ₄ ⁺ production and excretion. Ammonia genesis by proximal tubular cells is also stimulated by hypokalemia, whereas hyperkalemia inhibits ammonia genesis. The ability of the kidney to produce ammonia is markedly decreased in conditions such as chronic renal failure as a result of reduced renal mass and in some types of renal tubular acidosis (RTA). The ability to lower urine pH and increase net acid excretion may not be achieved until 4–6 weeks of age.

Metabolic Acidosis

A metabolic acidosis can result from addition of H ⁺ to the body, failure to excrete H ⁺ , or loss of ${\text{HCO}}_3^{-}$ . The differential diagnosis of metabolic acidosis is simplified by classifying the causes into those associated with a normal anion gap (also known as a hyperchloremic metabolic acidosis) and those associated with an increased anion gap ( Table 59.2 ).

The anion gap is easily calculated: ${\text{Na}}^{+}-\left({\text{Cl}}^{-}+{\text{HCO}}_3^{-}\right)$ . The anion gap is normally 8–16 mEq/L. When a strong acid (e.g., lactic acid) is added to or produced in the body, hydrogen ions are neutralized by bicarbonate, ${\text{HCO}}_3^{-}$ is consumed by the H ⁺ , and the bicarbonate concentration falls. The accompanying anion, such as lactate, is a new unmeasured anion, which increases the anion gap. The increase in the anion gap is usually proportional to the fall in serum ( ${\text{HCO}}_3^{-}$ ). In contrast, when ${\text{HCO}}_3^{-}$ is lost from the body, no new anion is generated. In this situation, there is a reciprocal increase in the serum Cl ⁻ to maintain electroneutrality. The anion gap does not change; the rise in (Cl ⁻ ) is proportional to the fall in ( ${\text{HCO}}_3^{-}$ ).

Metabolic Alkalosis

Metabolic alkalosis (pH >7.45) occurs as a result of a primary increase in the serum ${\text{HCO}}_3^{-}$ , which may occur as a result of (1) net loss of H ⁺ , (2) net gain of ${\text{HCO}}_3^{-}$ (or its precursors), or (3) loss of fluid with more Cl ⁻ than ${\text{HCO}}_3^{-}$ . Normally functioning kidneys can excrete large amounts of ${\text{HCO}}_3^{-}$ and should offset any increase in serum ${\text{HCO}}_3^{-}$ resulting from these causes. Therefore, factors that prevent the kidneys from excreting ${\text{HCO}}_3^{-}$ also must be present to maintain the metabolic alkalosis.