Metabolic acidosis is primary reduction in bicarbonate (HCO), typically with compensatory reduction in carbon dioxide partial pressure (P); 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 HCO 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.
(See also Acid-Base Regulation and Acid-Base Disorders.)
Etiology of Metabolic Acidosis
Metabolic acidosis is acid accumulation due to
Increased acid production or acid ingestion
Decreased acid excretion
Gastrointestinal 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 table Causes of Metabolic Acidosis).
Причини метаболічного ацидозу
Cause | Examples |
|---|---|
High anion gap | |
Ketoacidosis | Alcohol (chronic abuse) Fasting |
Lactic acidosis (due to physiologic processes) | Alcohol (chronic abuse) Primary hypoxia due to lung disorders |
Lactic acidosis (due to exogenous toxins) | Biguanides (rare except with acute kidney injury) Carbon monoxide Cyanide HIV nucleoside reverse transcriptase inhibitors Iron Isoniazid Metformin Propofol Toluene (initially high gap; subsequent excretion of metabolites normalizes gap) |
D-Lactate generation | |
— | |
— | |
Toxins metabolized to acids | Ethylene glycol (oxalate) Methanol (formate) Paraldehyde (acetate, chloracetate) Salicylates |
Normal anion gap (hyperchloremic acidosis) | |
Gastrointestinal bicarbonate (HCO3−) loss | Calcium chloride (CaCl2) Colostomy Diarrhea Enteric fistulas Ileostomy Magnesium sulfate (MgSO4) Use of ion-exchange resins |
Parenteral infusion | Arginine Ammonium chloride (NH4Cl) Lysine Rapid sodium chloride (NaCl) infusion |
Renal HCO3− loss | Acetazolamide Hyperparathyroidism Renal tubular acidosis, types 1, 2, and 4 Tubulointerstitial renal disease |
Urologic procedures | Ureteroileal conduit Ureterosigmoidostomy |
Other | Hypoaldosteronism Toluene (late) |
Ацидоз із високим аніонним розривом
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), but it also occurs with chronic alcohol use disorder (see alcoholic ketoacidosis), undernutrition, 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 or congenital methylmalonic acidemia, which are rare disorders that involve the abnormal metabolism of amino acids.
Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Lactate accumulation results from a combination of excess formation and decreased metabolism of lactate. Excess lactate production occurs during states of anaerobic metabolism. The most serious form occurs during the various types of shock. Decreased metabolism generally occurs with hepatocellular dysfunction resulting from decreased liver perfusion or as a part of generalized shock. Diseases and medications that impair mitochondrial function can cause lactic acidosis.
Renal failure causes high 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.
Ацидоз із нормальним аніонним розривом
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 a section of 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−.
The renal tubular acidoses impair either 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 of Metabolic Acidosis
Symptoms and signs (see table 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 occur 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.
Цінні поради та підводні камені
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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).
Diagnosis of Metabolic Acidosis
Arterial blood gas (ABG) and serum electrolyte measurement
Anion gap and delta gap calculated
Winters formula for calculating compensatory changes
Evaluation for cause
Recognition of metabolic acidosis and appropriate respiratory compensation are discussed in Diagnosis of Acid-Base Disorders. 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
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.
If the serum anion gap is normal, urinary electrolytes are measured and the urinary anion gap is calculated as [sodium] + [potassium] – [chloride]. A normal urinary anion gap in a person without acidosis has a value near zero. If the urinary anion gap becomes negative, there are excess unmeasured positively charged ions in the urine, typically ammonium (NH4+), which is normally secreted by the kidneys in response to volume depletion. If the urinary anion gap in a patient with non-anion gap metabolic acidosis is -30 to -50 mEq/L (-30 to -50 mmol/L), the kidneys are responding to extra-renal volume losses typically from the GI tract. An elevation in urinary anion gap in such patients (a positive calculated result) is due to the loss of unmeasured negatively charged ions in the urine and suggests renal HCO3− loss, which most commonly occurs in renal tubular acidosis (evaluation of renal tubular acidosis is discussed elsewhere).
In addition, when metabolic acidosis is present, a delta gap is calculated to identify concomitant metabolic alkalosis, and Winters formula is applied to determine whether respiratory compensation is appropriate or reflects a second acid-base disorder.
Treatment of Metabolic Acidosis
Cause treated
Sodium bicarbonate (NaHCO3) primarily for severe acidemia—give with caution
Treatment is directed at the cause. Hemodialysis is required for renal failure and sometimes for ethylene glycol, methanol, or salicylate poisoning.
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−. Clearance of additional CO2 also requires adequate minute ventilation. Patients with compromised respiratory status due to underlying pulmonary disease may not be able meet the increased minute ventilation. Patients requiring mechanical ventilatory support will need appropriate ventilator settings to account for increased minute ventilation.
Despite these and other controversies, most experts recommend giving bicarbonate IV for severe metabolic acidosis (pH < 7.0) primarily because of concerns about worsening cardiovascular instability at lower pH values.
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 of 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−. There is no consensus regarding the concentration of bicarbonate solution to use, but it is important to realize that the typical 50-mL ampule of NaHCO3 contain 50 mEq of sodium bicarbonate and can worsen volume overload and also cause hyperosmolality especially if multiple ampules are given over a short period time. Iso-osmotic formulations such as 75 mEq NaHCO3 mixed with 1 L of 0.45% saline and 150 mEq NaHCO3 mixed with 1 L of sterile water are also used.
Alternatives to sodium bicarbonate include
Lactate, either in the form of lactated Ringer's solution or sodium lactate (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.
Ключові моменти
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).
