Metabolic acidosis is primary reduction in HCO3−, typically with compensatory reduction in Pco2; pH may be markedly low or slightly subnormal. Metabolic acidoses are categorized as high or normal anion gap based on the presence or absence of unmeasured anions in serum. Causes include accumulation of ketones and lactic acid, renal failure, and drug or toxin ingestion (high anion gap) and GI or renal HCO3− loss (normal anion gap). Symptoms and signs in severe cases include nausea and vomiting, lethargy, and hyperpnea. Diagnosis is clinical and with ABG and serum electrolyte measurement. The cause is treated; IV NaHCO3 may be indicated when pH is very low.
Metabolic acidosis is acid accumulation due to increased acid production or acid ingestion; decreased acid excretion; or GI or renal HCO3− loss. Acidemia (arterial pH < 7.35) results when acid load overwhelms respiratory compensation. Causes are classified by their effect on the anion gap (see Sidebar 1: The Anion Gap and Table 3: Causes of Metabolic Acidosis).
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High anion gap acidosis:
The most common causes of a high anion gap metabolic acidosis are
Ketoacidosis is a common complication of type 1 diabetes mellitus, but it also occurs with chronic alcoholism, undernutrition, and, to a lesser degree, fasting. In these conditions, the body converts from glucose to free fatty acid (FFA) metabolism; FFAs are converted by the liver into ketoacids, acetoacetic acid, and β-hydroxybutyrate (all unmeasured anions). Ketoacidosis is also a rare manifestation of congenital isovaleric and methylmalonic acidemia.
Lactic acidosis (see Lactic Acidosis) is the most common cause of metabolic acidosis in hospitalized patients. Lactate accumulation results from a combination of excess formation and decreased utilization of lactate. Excess lactate production occurs during states of anaerobic metabolism. The most serious form occurs during the various types of shock. Decreased utilization generally occurs with hepatocellular dysfunction from decreased liver perfusion or as a part of generalized shock.
Renal failure causes anion gap acidosis by decreased acid excretion and decreased HCO3− reabsorption. Accumulation of sulfates, phosphates, urate, and hippurate accounts for the high anion gap.
Toxins may have acidic metabolites or trigger lactic acidosis. Rhabdomyolysis is a rare cause of metabolic acidosis thought to be due to release of protons and anions directly from muscle.
Normal anion gap acidosis:
The most common causes of normal anion gap acidosis are
Normal anion gap metabolic acidosis is also called hyperchloremic acidosis because the kidneys reabsorb Cl− instead of reabsorbing HCO3−.
Many GI secretions are rich in HCO3− (eg, biliary, pancreatic, and intestinal fluids); loss due to diarrhea, tube drainage, or fistulas can cause acidosis. In ureterosigmoidostomy (insertion of ureters into the sigmoid colon after obstruction or cystectomy), the colon secretes and loses HCO3− in exchange for urinary Cl− and absorbs urinary ammonium, which dissociates into ammonia (NH3+) and hydrogen ion (H+). Ion-exchange resin uncommonly causes HCO3− loss by binding HCO3−.
The renal tubular acidoses (see Renal Tubular Acidosis (RTA)) either impair H+ secretion (types 1 and 4) or HCO3− absorption (type 2). Impaired acid excretion and a normal anion gap also occur in early renal failure, tubulointerstitial renal disease, and when carbonic anhydrase inhibitors (eg, acetazolamide) are taken.
Symptoms and Signs
Symptoms and signs (see Table 2: Clinical Consequences of Acid-Base Disorders) are primarily those of the cause. Mild acidemia is itself asymptomatic. More severe acidemia (pH < 7.10) may cause nausea, vomiting, and malaise. Symptoms may appear at higher pH if acidosis develops rapidly. The most characteristic sign is hyperpnea (long, deep breaths at a normal rate), reflecting a compensatory increase in alveolar ventilation; this hyperpnea is not accompanied by a feeling of dyspnea.
Severe, acute acidemia predisposes to cardiac dysfunction with hypotension and shock, ventricular arrhythmias, and coma. Chronic acidemia causes bone demineralization disorders (eg, rickets, osteomalacia, osteopenia).
Recognition of metabolic acidosis and appropriate respiratory compensation are discussed in Diagnosis. Determining the cause of metabolic acidosis begins with the anion gap.
The cause of an elevated anion gap may be clinically obvious (eg, hypovolemic shock, missed hemodialysis), but if not, blood testing should include glucose, BUN, creatinine, lactate, and tests for possible toxins. Salicylate levels can be measured in most laboratories, but methanol and ethylene glycol frequently cannot; their presence may be suggested by presence of an osmolar gap. Calculated serum osmolarity (2 [Na] + [glucose]/18 + BUN/2.8 + blood alcohol/5) is subtracted from measured osmolarity. A difference > 10 implies the presence of an osmotically active substance, which in the case of a high anion gap acidosis is methanol or ethylene glycol. Although ingestion of ethanol may cause an osmolar gap and a mild acidosis, it should never be considered the cause of a significant metabolic acidosis.
If the anion gap is normal and no cause is obvious (eg, marked diarrhea), urinary electrolytes are measured and the urinary anion gap is calculated as [Na] + [K] – [Cl]. A normal urinary anion gap (including in patients with GI losses) is 30 to 50 mEq/L; an elevation suggests renal HCO3− loss (for evaluation of renal tubular acidosis, see Diagnosis). In addition, when metabolic acidosis is present, a delta gap is calculated (see Sidebar 1: The Anion Gap) to identify concomitant metabolic alkalosis, and Winter's formula (see Diagnosis) is applied to see whether respiratory compensation is appropriate or reflects a 2nd acid-base disorder.
Treatment is directed at the underlying cause. Hemodialysis is required for renal failure and sometimes for ethylene glycol, methanol, and salicylate poisoning.
Treatment of acidemia with NaHCO3 is clearly indicated only in certain circumstances and is probably deleterious in others. When metabolic acidosis results from loss of HCO3− or accumulation of inorganic acids (ie, normal anion gap acidosis), HCO3− therapy is generally safe and appropriate. However, when acidosis results from organic acid accumulation (ie, high anion gap acidosis), HCO3− therapy is controversial; it does not clearly decrease mortality in these conditions, and there are several possible risks. With treatment of the underlying condition, lactate and ketoacids are metabolized back to HCO3−; exogenous HCO3− loading may therefore cause an “overshoot” metabolic alkalosis. In any condition, HCO3− may also cause Na and volume overload, hypokalemia, and, by inhibiting respiratory drive, hypercapnia. Furthermore, because HCO3− does not diffuse across cell membranes, intracellular acidosis is not corrected and may paradoxically worsen because some of the added HCO3− is converted to CO2, which does cross into the cell and is hydrolyzed to H+ and HCO3−.
Despite these and other controversies, most experts still recommend HCO3− IV for severe metabolic acidosis (pH < 7.00), with a target pH of 7.10.
Treatment requires 2 calculations. The first is the level to which HCO3− must be raised, calculated by the Kassirer-Bleich equation, using a value for [H+] of 63 nmol/L at a pH of 7.20:
63 = 24 × Pco2/HCO3−
desired HCO3− = 0.38 × Pco2
The amount of HCO3− needed to achieve that level is
NaHCO3 required (mEq) = (desired [HCO3−] − observed [HCO3−]) × 0.4 × body weight (kg)
This amount of NaHCO3 is given over several hours. Serum pH and HCO3− levels can be checked 30 min to 1 h after administration, which allows for equilibration with extravascular HCO3−.
Alternatives to NaHCO3 include
These alternatives are all of unproven benefit over NaHCO3 alone and cause complications of their own.
K+ depletion, common in metabolic acidosis, should be identified through frequent serum K+ monitoring and treated as needed with oral or parenteral KCl.
Lactic acidosis results from overproduction of lactate, decreased metabolism of lactate, or both.
Lactate is a normal byproduct of glucose and amino acid metabolism. There are 2 main types of lactic acidosis, A and B, and an unusual form, d-lactic acidosis.
Type A lactic acidosis, the most serious form, occurs when lactic acid is overproduced in ischemic tissue to generate ATP during O2 deficit. Overproduction typically occurs during tissue hypoperfusion in hypovolemic, cardiac, or septic shock and is worsened by decreased lactate metabolism in the poorly perfused liver. It may also occur with primary hypoxia due to lung disease and with various hemoglobinopathies.
Type B lactic acidosis occurs in states of normal global tissue perfusion (and hence ATP production) and is less ominous. Lactate production may be increased from local relative hypoxia as with vigorous muscle use (eg, exertion, seizures, hypothermic shivering) and with cancer and ingestion of certain drugs or toxins (see Table 3: Causes of Metabolic Acidosis). Drugs include the nucleoside reverse transcriptase inhibitors and the biguanides phenformin and, less so, metformin; although phenformin has been removed from the market in most of the world, it is still available from China (including as a component of some Chinese proprietary medicines). Metabolism may be decreased due to hepatic insufficiency or thiamin deficiency.
d-Lactic acidosis is an unusual form of lactic acidosis in which d-lactic acid, the product of bacterial carbohydrate metabolism in the colon of patients with jejunoileal bypass or intestinal resection, is systemically absorbed. It persists in circulation because human lactate dehydrogenase can metabolize only l-lactate.
Findings in and treatment of types A and B lactic acidosis are as for other metabolic acidoses. In d-lactic acidosis, the anion gap is lower than expected for the decrease in HCO3−, and there may be a urinary osmolar gap (difference between calculated and measured urine osmolarity). Treatment is IV fluids, restriction of carbohydrates, and sometimes antibiotics (eg, metronidazole).
Last full review/revision February 2013 by James L. Lewis, III, MD
Content last modified October 2013