Pediatric Metabolic Alkalosis 

Metabolic alkalosis is an acid-base disturbance caused by an elevation in the plasma bicarbonate (HCO₃) concentration. This condition is not a disease; it is a sign or state encountered in certain disease processes. Although metabolic alkalosis may not be referred to as often as metabolic acidosis, it is the most common acid-base abnormality in hospitalized adults. Alkalosis refers to a loss of acid or gain of base in the extracellular fluid (ECF); alkalemia refers to a change in blood pH. Alkalosis is not necessarily accompanied by alkalemia.

The 2 types of metabolic alkalosis (ie, chloride-responsive, chloride-resistant) are classified based on the amount of chloride in the urine.

Chloride-responsive metabolic alkalosis involves urine chloride levels of less than 10 mEq/L and is characterized by decreased ECF volume and low serum chloride levels, such as occurs with vomiting. This type responds to administration of chloride salt.

Chloride-resistant metabolic alkalosis involves urine chloride levels of more than 20 mEq/L and is characterized by increased ECF volume. As the name implies, this type resists administration of chloride salt. Primary aldosteronism is an example of chloride-resistant metabolic alkalosis.

For a review of metabolic alkalosis in patients of all ages, see Metabolic Alkalosis.

Causes of metabolic alkalosis include (1) loss of hydrogen ions (eg, due to vomiting or renal acid losses that exceed acid production from cellular metabolism), (2) disproportionate chloride loss compared with HCO₃ loss (ie, the plasma concentration of HCO₃ increases upon restriction to a smaller space of distribution), and (3) HCO₃ administration (unusual because additional HCO₃ is very quickly eliminated by the kidneys). Loss of hydrochloric acid due to vomiting is an especially common cause.

The consequences of metabolic alkalosis on organ systems depend on the severity of the alkalemia and the degree of respiratory compensation. Mild-to-moderate metabolic alkalosis is rarely clinically significant in isolation. If the elevated plasma HCO₃ concentration is not accompanied by a rise in PCO₂, the elevation of pH is much more severe.

Effects of severe alkalemia

The respiratory effects of metabolic alkalosis are twofold. An increase in blood pH shifts the oxygen-hemoglobin dissociation curve to the left. This creates a tighter bond between hemoglobin and oxygen, causing decreased oxygen delivery to tissues. Hypoxemia may be worsened by a compensatory hypoventilation to elevate PCO₂. Hypoventilation may be severe enough to cause apnea and respiratory arrest.

Cardiovascular effects often result from the association of hypokalemia with metabolic alkalosis. Life-threatening arrhythmias are the most significant adverse effect of metabolic alkalosis. Direct arteriolar constriction is further worsened by electrolyte disturbances. Ventricular and supraventricular arrhythmias that are often unresponsive to antiarrhythmic agents can occur.

Neuromuscular effects of severe metabolic alkalosis may include headache, seizures, and obtundation and marked muscle weakness. These resolve only with correction of the pH.

Electrolyte imbalances in metabolic alkalosis include a decrease in ionized calcium levels due to increased binding of calcium to plasma proteins; consequences include tetany and seizures. Total-body potassium loss may contribute to alkalemia, and serum potassium is intracellularly shifted in alkalemia. Weakness and cardiac arrhythmias may result from severe hypokalemia.

Compensation mechanisms

The body compensates for metabolic alkalosis through buffering of excess HCO₃ and hypoventilation. Intracellular buffering occurs through sodium/hydrogen and potassium/hydrogen ion exchange, with eventual formation of CO₂ and water from HCO₃.

Within several hours, elevated levels of HCO₃ and metabolic alkalosis stimulate a chemoreceptor inhibition of the respiratory center, resulting in hypoventilation and increased PCO₂ levels. This mechanism produces a rise in PCO₂ of as much as 0.7 mm Hg for each 1-mEq/L increase in HCO₃. Hypoventilation may cause hypoxemia.

Etiologically, metabolic alkalosis can be divided into chloride-responsive alkalosis (urine chloride < 20 mEq/L), chloride-resistant alkalosis (urine chloride >20 mEq/L). Causes of chloride-responsive metabolic alkalosis include the following:

• Gastric fluid loss (eg, vomiting, nasogastric [NG] drainage)
• Volume contraction (eg, secondary to loop or thiazide diuretics)
• Congenital chloride diarrhea
• Posthypercapnia syndrome (especially in mechanically ventilated patients with chronic lung disease)
• Cystic fibrosis (in toddlers)

Causes of chloride-resistant metabolic alkalosis include the following:

• Primary aldosteronism
• Bartter syndrome (renal sodium, potassium, and chloride wasting; often presents as failure to thrive)^[1]
• Deoxycorticosterone (DOC) excess syndrome (congenital adrenal hyperplasia variant)
• Liddle syndrome (autosomal dominant; unregulated sodium resorption in renal collecting duct)
• Excessive ingestion of licorice
• Chronic potassium depletion (eg, anorexia nervosa)
• Primary reninism
• Hyperglucocorticoidism
• Milk-alkali syndrome (excess calcium plus bicarbonate intake and vomiting)

Regarding gastric losses (eg, vomiting, NG drainage), HCO₃ produced by the pancreas normally neutralizes HCl produced by the gastric mucosa, so that no net gain or loss of hydrogen ions or bicarbonate occurs. When gastric acid is lost through vomiting or removed by suction, plasma HCO₃ levels increase. In addition, the loss of potassium and volume contraction due to vomiting potentiate metabolic alkalosis.

Diuretics produce increased renal losses of sodium, which is followed by excretion of chlorides. To maintain electrical neutrality in the ECF, HCO₃ reabsorption in renal tubules increases. Additionally, increased sodium in the distal tubules increases sodium-potassium exchange. The loss of potassium, in turn, leads to intracellular accumulation of hydrogen ions and its secretion in the distal tubules. Diuretics also promote the loss of magnesium in the urine, which further lowers potassium levels through an unknown mechanism.

Volume contraction concentrates the existing levels of HCO₃ in the ECF. In addition, it stimulates release of renin-angiotensin, which causes increased potassium and hydrogen ion losses in the kidney.

Regarding posthypercapnia syndrome, chronic CO₂ retention causes a compensatory increase in HCO₃ levels. When a patient with chronic CO₂ retention receives treatment that abruptly drops the CO₂ level, metabolic alkalosis becomes evident.

Because metabolic alkalosis is a manifestation of a disease process rather than a disease itself, the incidence is unknown. In a review of 2000 hospitalized adults, Hodgkin et al noted that metabolic alkalosis was the most common acid-base disorder.^[2] No racial or sexual differences in incidence are noted.

Metabolic alkalosis can occur in people of any age. A higher incidence of metabolic alkalosis after cardiac surgery in younger children has been reported, however.^[3]

The overall prognosis in patients with metabolic alkalosis depends on the underlying etiology. Chloride-responsive metabolic alkalosis responds to volume resuscitation and chloride repletion. Chloride-resistant metabolic alkalosis may be more difficult to control. Prognosis is good with prompt treatment and avoidance of hypoxemia.

Severe metabolic alkalosis is associated with increased morbidity and mortality, probably because of its profound influences on multiple organ systems and, more importantly, because of tissue anoxia caused by hypoventilation and shift of the oxygen-dissociation curve to the left.^[4]

Educate patients placed on long-term diuretic therapy and those with diseases that can lead to metabolic alkalosis to recognize the symptoms of moderate-to-severe alkalosis. This knowledge allows them to promptly seek medical care.