Metabolic acidosis is primary reduction in bicarbonate (HCO3−), typically with compensatory reduction in carbon dioxide partial pressure (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 gastrointestinal 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 arterial blood gas (ABG) and serum electrolyte measurement. The cause is treated; IV sodium bicarbonate may be indicated when pH is very low.
Metabolic acidosis is acid accumulation due to
Increased acid production or acid ingestion
Decreased acid excretion
Gastrointestinal or renal HCO3− loss
The most common causes of a high anion gap metabolic acidosis are
Ketoacidosis
Lactic acidosis
Renal failure
Toxic ingestions
Ketoacidosis is a common complication of type 1 diabetes mellitus (see diabetic ketoacidosis Diabetic Ketoacidosis (DKA) Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia causes an osmotic diuresis with... read more ), but it also occurs with chronic alcohol use disorder (see alcoholic ketoacidosis Alcoholic Ketoacidosis Alcoholic ketoacidosis is a metabolic complication of alcohol use and starvation characterized by hyperketonemia and anion gap metabolic acidosis without significant hyperglycemia. Alcoholic... read more ), undernutrition Overview of Undernutrition Undernutrition is a form of malnutrition. (Malnutrition also includes overnutrition.) Undernutrition can result from inadequate ingestion of nutrients, malabsorption, impaired metabolism, loss... read more , and, to a lesser degree, fasting. In these conditions, the body converts from glucose metabolism to free fatty acid (FFA) metabolism; FFAs are converted by the liver into ketoacids, acetoacetic acid, and beta-hydroxybutyrate (all unmeasured anions). Ketoacidosis is also a rare manifestation of congenital isovaleric acidemia Isovaleric acidemia Valine, leucine, and isoleucine are branched-chain amino acids; deficiency of enzymes involved in their metabolism leads to accumulation of organic acids with severe metabolic acidosis. There... read more or congenital methylmalonic acidemia Methylmalonic acidemia Valine, leucine, and isoleucine are branched-chain amino acids; deficiency of enzymes involved in their metabolism leads to accumulation of organic acids with severe metabolic acidosis. There... read more .
The most common causes of normal anion gap acidosis are
Gastrointestinal (GI) or renal HCO3− loss
Impaired renal acid excretion
Normal anion gap metabolic acidosis is also called hyperchloremic acidosis because the kidneys reabsorb chloride (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 chloride (Cl−) and absorbs urinary ammonium, which dissociates into ammonia (NH3+) and hydrogen ion (H+). Ion-exchange resin uncommonly causes HCO3− loss by binding HCO3−.
Symptoms and Signs
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 Shock Shock is a state of
organ hypoperfusion with resultant cellular dysfunction and death. Mechanisms may involve decreased circulating volume, decreased cardiac output, and vasodilation, sometimes... read more ,
ventricular arrhythmias
Overview of Arrhythmias The normal heart beats in a regular, coordinated way because electrical impulses generated and spread by myocytes with unique electrical properties trigger a sequence of organized myocardial... read more
Arterial blood gas (ABG) and serum electrolyte measurement
Anion gap and delta gap calculated
Winters formula for calculating compensatory changes
Testing for cause
The cause of an elevated anion gap may be clinically obvious (eg, hypovolemic shock, missed hemodialysis), but if not, blood testing should include
BUN (blood urea nitrogen)
Creatinine
Glucose
Lactate
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 [sodium] + [glucose]/18 + BUN/2.8 + blood alcohol/5, based on conventional units) 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 sole cause of a significant metabolic acidosis.
Cause treated
Sodium bicarbonate (NaHCO3) primarily for severe acidemia—give with caution
Treatment of acidemia with sodium bicarbonate (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), bicarbonate therapy is generally safe and appropriate. However, when acidosis results from organic acid accumulation (ie, high anion gap acidosis), bicarbonate 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, sodium bicarbonate may also cause sodium 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 carbon dioxide (CO2), which does cross into the cell and is hydrolyzed to H+ and HCO3−.
Despite these and other controversies, most experts still recommend giving bicarbonate IV for severe metabolic acidosis (pH < 7.0).
Treatment requires 2 calculations (same for both conventional and SI units). The first is the level to which HCO3− must be raised, calculated by the Kassirer-Bleich equation, using a target value for [H+] of 79 nEq/L (79 nmol/L), which corresponds to a pH of 7.10:
79 = 24 × Pco2/HCO3−
or
Desired HCO3−= 0.30 × Pco2
The amount of sodium bicarbonate needed to achieve that level is
NaHCO3 required (mEq/mmol) = (desired [HCO3−] − observed [HCO3−]) × 0.4 × body weight (kg)
For example, a 70-kg man has severe metabolic acidosis with a pH of 6.92, PCO2 40 mmHg and HCO3− of 8 mEq/L (8 mmol/L). The target bicarbonate level needed to achieve a pH of 7.10 is 0.30 × 40 = 12 mEq/L (12 mmol/L). This level is 4 mEq/L (4 mmol/L) more than his current bicarbonate level of 8. To increase bicarbonate by 4, multiply 4 by 0.4 times 70 (the body weight), giving a result of 112 mEq (112 mmol) of HCO3−. This amount of sodium bicarbonate is given over several hours. Blood pH and HCO3−levels can be checked 30 minutes to 1 hour after administration, which allows for equilibration with extravascular HCO3−.
Alternatives to sodium bicarbonate include
Lactate, either in the form of lactated Ringer's solution or sodium lactate (is metabolized mEq for mEq to bicarbonate when liver function is normal)
Sodium acetate (metabolized mEq for mEq to bicarbonate when liver function is normal)
Tromethamine, an amino alcohol that buffers both metabolic (H+) and respiratory (carbonic acid [H2CO3]) acid
Carbicarb, an equimolar mixture of sodium bicarbonate and carbonate (the latter consumes CO2 and generates HCO3−)
Dichloroacetate, which enhances oxidation of lactate
These alternatives do not offer a proven benefit over sodium bicarbonate alone and can cause complications of their own.
Potassium (K+) depletion, common in metabolic acidosis, should be identified through frequent serum K+ monitoring and treated as needed with oral or parenteral potassium chloride.
Metabolic acidosis can be caused by acid accumulation due to increased acid production or acid ingestion; decreased acid excretion; or gastrointestinal or renal bicarbonate (HCO3−) loss.
Metabolic acidoses are categorized based on whether the anion gap is high or normal.
High anion gap acidoses are most often due to ketoacidosis, lactic acidosis, chronic kidney disease, or certain toxic ingestions.
Normal anion gap acidoses are most often due to gastrointestinal or renal HCO3− loss.
Calculate delta gap to identify concomitant metabolic alkalosis, and apply Winters formula to see whether respiratory compensation is appropriate or reflects a 2nd acid-base disorder.
Treat the cause.
Intravenous sodium bicarbonate (NaHCO3) is indicated when acidosis is due to a change in HCO3− level (normal anion gap acidosis).
Intravenous sodium bicarbonate is controversial in high anion gap acidosis (but may be considered when pH < 7.00, with a target pH of ≥ 7.10).
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