(See also Acid-Base Regulation and Acid-Base Disorders.)
Etiology
Metabolic alkalosis is bicarbonate (HCO3−) accumulation due to
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Acid loss
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Alkali administration
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Intracellular shift of hydrogen ion (H+—as occurs in hypokalemia)
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Renal HCO3− retention
Regardless of initial cause, persistence of metabolic alkalosis indicates that the kidneys have increased their HCO3− reabsorption, because HCO3− is normally freely filtered by the kidneys and hence excreted. Volume depletion and hypokalemia are the most common stimuli for increased HCO3− reabsorption, but any condition that elevates aldosterone or mineralocorticoids (which enhance sodium [Na] reabsorption and potassium [K] and hydrogen ion [H+] excretion) can elevate HCO3−. Thus, hypokalemia is both a cause and a frequent consequence of metabolic alkalosis.
The most common causes of metabolic alkalosis are
Among other causes of metabolic alkalosis are disorders that cause
Causes of Metabolic Alkalosis
Cause |
Comments |
Gastrointestinal acid loss* |
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Congenital chloridorrhea |
Fecal Cl loss and HCO3 retention |
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Gastric acid loss due to vomiting or nasogastric suction |
Loss of HCl and acid coupled with contraction alkalosis due to release of aldosterone and subsequent resorption of HCO3 |
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Villous adenoma |
Probably secondary to K depletion |
Renal acid loss |
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Includes congenital adrenal hyperplasia |
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Occurs with volume depletion, heart failure, cirrhosis with ascites, nephrotic syndrome, Cushing syndrome or disease, renal artery stenosis, or renin-secreting tumor |
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Use of glycyrrhizin-containing compounds† (eg, licorice, chewing tobacco, carbenoxolone, Lydia Pinkham’s vegetable compound) |
Glycyrrhizin inhibition of enzymatic conversion of cortisol to less active metabolites |
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Rare congenital disease causing hyperaldosteronism and hypokalemic metabolic alkalosis that manifests in early childhood with renal salt wasting and volume depletion |
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Similar to Bartter syndrome Characterized in addition by hypomagnesemia and hypocalciuria Manifests in young adults |
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Diuretics (thiazide and loop)‡ |
Multiple mechanisms: Secondary hyperaldosteronism due to volume depletion, Cl depletion, or contraction alkalosis; may be Cl-unresponsive because of concomitant K depletion |
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Stimulate K and Mg reabsorption and H excretion; alkalosis unresponsive to NaCl and volume replacement until deficiencies corrected; low K causing H to shift into cells, raising extracellular pH |
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HCO3 excess |
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Posthypercapnic* |
Persistent elevation of compensatory HCO3 levels, often with volume, K, and Cl depletion |
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Postorganic acidosis |
Conversion of lactic acid or ketoacid to HCO3 worsened by HCO3 therapy for acidosis |
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NaHCO3 loading |
Occurs with overzealous loading or with loading in patients who have hypokalemia; serum becomes more alkalotic as H shifts back into cells |
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Chronic ingestion of calcium carbonate antacids provides Ca and HCO3 load; hypercalcemia lowers PTH, increasing HCO3 reabsorption |
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Contraction alkalosis* |
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Diuretics (all types) Sweat loss in cystic fibrosis |
NaCl loss concentrates a fixed amount of HCO3 in a smaller total body volume |
Other |
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Carbohydrate refeeding after starvation |
Resolution of starvation ketosis or acidosis with improved cellular function |
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Laxative abuse* |
Unclear mechanism |
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Some antibiotics (eg, carbenicillin, penicillin, ticarcillin) |
Contain nonreabsorbable anion, which increases K and H excretion |
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* Chloride-responsive. |
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† Chloride-unresponsive. |
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‡ May be either chloride-responsive or chloride-unresponsive. |
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Ca = calcium; Cl = chloride; H = hydrogen; HCl = hydrochloric acid; HCO3 = bicarbonate; K = potassium; Mg = magnesium; NaCl = sodium chloride; NaHCO3 = sodium bicarbonate; PTH = parathyroid hormone. |
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Metabolic alkalosis can be
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Chloride (Cl)-responsive: Involves loss or excess secretion of Cl; it typically corrects with IV administration of NaCl-containing fluid.
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Chloride-unresponsive: Does not correct with NaCl-containing fluids, and typically involves severe magnesium (Mg) and/or potassium deficiency or mineralocorticoid excess.
The 2 forms can coexist, eg, in patients with volume overload made hypokalemic by high-dose diuretics.
Symptoms and Signs
Symptoms and signs of mild alkalemia are usually related to the underlying disorder. More severe alkalemia increases protein binding of ionized calcium (Ca++), leading to hypocalcemia and subsequent headache, lethargy, and neuromuscular excitability, sometimes with delirium, tetany, and seizures. Alkalemia also lowers threshold for anginal symptoms and arrhythmias. Concomitant hypokalemia may cause weakness.
Diagnosis
Recognition of metabolic alkalosis and appropriate respiratory compensation is discussed in Diagnosis of Acid-Base Disorders and requires measurement of ABG and serum electrolytes (including Ca and Mg).
Common causes can often be determined by history and physical examination. If history is unrevealing and renal function is normal, urinary Cl− and K+ concentrations are measured (values are not diagnostic in renal insufficiency).
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Urinary Cl < 20 mEq/L (< 20 mmol/L) indicates significant renal Cl− reabsorption and hence a Cl-responsive cause (see table Causes of Metabolic Alkalosis)
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Urinary Cl > 20 mEq/L (> 20 mmol/L) suggests a chloride-unresponsive form.
Urinary K and the presence or absence of hypertension help differentiate the chloride-unresponsive alkaloses.
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Urinary K < 30 mEq/day (< 30 mmol/day) signifies hypokalemia or laxative misuse.
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Urinary K > 30 mEq/day (> 30 mmol/day) in a patient without hypertension suggests diuretic abuse or Bartter syndrome or Gitelman syndrome.
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Urinary K > 30 mEq/day (> 30 mmol/day) in a patient with hypertension requires evaluation for hyperaldosteronism, mineralocorticoid excess, and renovascular disease.
Tests in patients with hypertension typically include plasma renin activity and aldosterone and cortisol levels (see Diagnosis of Cushing Syndrome and Diagnosis of Primary Aldosteronism).
Treatment
Underlying conditions are treated, with particular attention paid to correction of hypovolemia and hypokalemia.
Patients with chloride-responsive metabolic alkalosis are given 0.9% saline solution IV; infusion rate is typically 50 to 100 mL/hour greater than urinary and other sensible and insensible fluid losses until urinary Cl rises to > 25 mEq/L (> 25 mmol/L) and urinary pH normalizes after an initial rise from bicarbonaturia.
Patients with chloride-unresponsive metabolic alkalosis rarely benefit from rehydration alone.
Patients with severe metabolic alkalosis (eg, pH > 7.6) sometimes require more urgent correction of blood pH. Hemofiltration or hemodialysis is an option, particularly if volume overload and renal dysfunction are present. Acetazolamide 250 to 375 mg orally or IV once or twice a day increases HCO3− excretion but may also accelerate urinary losses of K+ and phosphate (PO4−); volume-overloaded patients with diuretic-induced metabolic alkalosis and those with posthypercapnic metabolic alkalosis may especially benefit.
In patients with severe metabolic alkalosis (pH > 7.6) and kidney failure who otherwise cannot or should not undergo dialysis, hydrochloric acid in a 0.1 to 0.2 normal solution IV is safe and effective but must be given through a central catheter because it is hyperosmotic and scleroses peripheral veins. Dosage is 0.1 to 0.2 mmol/kg/hour. Frequent monitoring of ABGs and electrolytes is needed.
Key Points
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Metabolic alkalosis is bicarbonate (HCO3−) accumulation due to acid loss, alkali administration, intracellular shift of hydrogen ion, or renal HCO3− retention.
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The most common causes are volume depletion (particularly when involving loss of gastric acid and chloride (Cl) due to recurrent vomiting or nasogastric suction) and diuretic use.
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Metabolic alkalosis involving loss or excess secretion of Cl is termed chloride-responsive.
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Treat the cause and give patients with chloride-responsive metabolic alkalosis 0.9% saline IV.
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Chloride-resistant metabolic alkalosis is due to increased aldosterone effect.
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Treatment of chloride-resistant metabolic alkalosis involves correction of hyperaldosteronism.
