Metabolic alkalosis is primary increase in bicarbonate (HCO3−) with or without compensatory increase in partial pressure of carbon dioxide (Pco2); pH may be high or nearly normal. Common causes include prolonged vomiting, hypovolemia, diuretic use, and hypokalemia. Renal impairment of HCO3− excretion must be present to sustain alkalosis. Symptoms and signs in severe cases include headache, lethargy, and tetany. Diagnosis is clinical and with arterial blood gas and serum electrolyte measurement. The underlying condition is treated; oral or IV acetazolamide or hydrochloric acid is sometimes indicated.excretion must be present to sustain alkalosis. Symptoms and signs in severe cases include headache, lethargy, and tetany. Diagnosis is clinical and with arterial blood gas and serum electrolyte measurement. The underlying condition is treated; oral or IV acetazolamide or hydrochloric acid is sometimes indicated.
(See also Acid-Base Regulation and Acid-Base Disorders.)
Etiology of Metabolic Alkalosis
Metabolic alkalosis is bicarbonate (HCO3−) accumulation due to
Acid loss
Alkali administration
Intracellular shift of hydrogen ion ([H+] as occurs in hypokalemia)
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
Diuretic use
Volume depletion (particularly when involving loss of gastric acid and chloride [Cl] due to recurrent vomiting or nasogastric suction)
Among other causes of metabolic alkalosis are disorders that cause
Bicarbonate excess
Renal acid loss
Causes of Metabolic Alkalosis
Cause | Comments |
|---|---|
Bicarbonate (HCO3) excess | |
Chronic ingestion of calcium carbonate antacids provides Ca and HCO3- load; hypercalcemia lowers PTH, increasing HCO3 reabsorption | |
NaHCO3 loading | Occurs with overzealous loading or with loading in patients who have hypokalemia; serum becomes more alkalotic as H shifts back into cells |
Posthypercapnic* | Persistent elevation of compensatory HCO3 levels, often with volume, K, and Cl depletion |
Postorganic acidosis | Conversion of lactic acid or ketoacid to HCO3 worsened by HCO3 therapy for acidosis |
Contraction alkalosis* | |
Diuretics (all types) | NaCl loss concentrates a fixed amount of HCO3 in a smaller total body volume |
Sweat loss in cystic fibrosis | NaCl loss concentrates a fixed amount of HCO3 in a smaller total body volume |
Gastrointestinal acid loss* | |
Congenital chloridorrhea | Fecal Cl loss and HCO3 retention |
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 |
Villous adenoma | Probably secondary to K depletion |
Renal acid loss | |
Rare congenital disease causing hyperaldosteronism and hypokalemic metabolic alkalosis that manifests in early childhood with renal salt wasting and volume depletion | |
Diuretics (thiazide and loop)‡ | Multiple mechanisms: Secondary hyperaldosteronism due to volume depletion, Cl depletion, or contraction alkalosis due to relative increase in bicarbonate concentration in a smaller volume of extracellular fluid; may be Cl-unresponsive because of concomitant K depletion |
Similar to Bartter syndrome Characterized in addition by hypomagnesemia and hypocalciuria Manifests in young adults | |
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 | |
Includes congenital adrenal hyperplasia in which increased sodium absorption in distal nephron leads to K and H ion loss | |
Occurs with volume depletion, heart failure, cirrhosis with ascites, nephrotic syndrome, Cushing syndrome or disease, renal artery stenosis, or renin-secreting tumor | |
Use of glycyrrhizin-containing compounds† (eg, licorice, chewing tobacco, carbenoxolone) | Glycyrrhizin inhibition of enzymatic conversion of cortisol to less active metabolites |
Other | |
Carbohydrate refeeding after starvation | Resolution of starvation ketosis or acidosis with improved cellular function |
Laxative abuse* | Unclear mechanism but likely due to volume contraction and loss of K and Cl in stool |
Some antibiotics (eg, carbenicillin, penicillin, ticarcillin) | Contain nonreabsorbable anion, which increases K and H excretion |
* Chloride-responsive. | |
† Chloride-unresponsive. | |
‡ May be either chloride-responsive or chloride-unresponsive. | |
Ca = calcium; Cl = chloride; H = hydrogen; HCl = hydrochloric acid; HCO3 = bicarbonate; K = potassium; Mg = magnesium; NaCl = sodium chloride; NaHCO= bicarbonate; K = potassium; Mg = magnesium; NaCl = sodium chloride; NaHCO3 = sodium bicarbonate; PTH = = sodium bicarbonate; PTH =parathyroid hormone. | |
Metabolic alkalosis can be
Chloride (Cl)-responsive: Involves loss or excess secretion of Cl resulting in decreased renal exchange of chloride for bicarbonate and subsequent bicarbonate retention; it typically corrects with IV administration of NaCl-containing fluid.
Chloride-unresponsive: Due to hyperaldosteronism with resultant volume expansion and subsequent increased distal sodium delivery. Distal nephron reabsorption of sodium results in increased K and H ion secretion. This type of alkalosis typically does not correct with NaCl-containing fluids, and typically involves severe magnesium (Mg) and/or potassium (K) deficiency.
The 2 forms can coexist, eg, in patients with volume overload made hypokalemic by high-dose diuretics.
Symptoms and Signs of Metabolic Alkalosis
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. Concomitant hypokalemia may cause weakness. These electrolyte abnormalities can also lower the threshold for anginal symptoms and arrhythmias.
Diagnosis of Metabolic Alkalosis
Arterial blood gas (ABG) and serum electrolyte measurements
Diagnosis of cause (usually clinical)
Sometimes measurement of urinary Cl− and K+
Recognition of metabolic alkalosis and appropriate respiratory compensation is discussed in Diagnosis of Acid-Base Disorders and requires measurement of ABGs 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 stage 4 or 5 chronic kidney disease).
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)
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.
Urinary K < 30 mEq/day (< 30 mmol/day) signifies hypokalemia or laxative misuse.
Urinary K > 30 mEq/day (> 30 mmol/day) in a patient without hypertension suggests diuretic abuse, Bartter syndrome, or Gitelman syndrome.
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 of Metabolic Alkalosis
Cause treated
IV 0.9% saline solution for chloride-responsive metabolic alkalosis
Potassium supplementation and/or potassium-sparing diuretics for chloride-unresponsive metabolic alkalosis
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 and requires treating the specific cause. Potassium and magnesium supplementation and/or potassium-sparing diuretics are usually needed.
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 HCOis 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
Metabolic alkalosis is bicarbonate (HCO3−) accumulation due to acid loss, alkali administration, intracellular shift of hydrogen ion, or renal HCO3− retention.
Metabolic alkalosis involving loss or excess secretion of Cl is termed chloride-responsive.
The most common causes of chloride-responsive metabolic alkalosis are volume depletion (particularly when involving loss of gastric acid and chloride (Cl) due to recurrent vomiting or nasogastric suction) and diuretic use.
Investigate and treat the cause and give patients with chloride-responsive metabolic alkalosis 0.9% saline IV.
Chloride-unresponsive metabolic alkalosis is often due to increased aldosterone effect.
Investigate and treat the cause and give patients supplementary potassium and/or potassium-sparing diuretics as needed
