II. Physiology

  1. See Acid-Base Homeostasis
  2. Respiratory compensation is immediate, so there is typically no distinction between acute and chronic Metabolic Acidosis
    1. Contrast with Respiratory Acidosis in which metabolic compensation is delayed
  3. Anion Gap
    1. Anion Gap is maintained by near balance of key cations (sNa+) and key anions (sCl-, sHCO3-)
    2. In Non-Anion Gap Metabolic Acidosis, only measured cations and anions are affected
      1. In Diarrhea, bicarbonate is lost and compensated by chloride increase
    3. In Anion Gap Metabolic Acidosis, unmeasured anions are increased
      1. Increased Lactic Acid or Ketoacids, for example, result in a significant Anion Gap

III. Types

  1. Elevated Anion Gap Metabolic Acidosis
  2. Hyperchloremic Metabolic Acidosis (normal Anion Gap)
    1. See Hyperchloremia

IV. Causes: Common

  1. Most common causes of Anion Gap Metabolic Acidosis in seriously ill patients
    1. Lactic Acidosis
    2. Acute Renal Failure
    3. Diabetic Ketoacidosis
    4. Exogenous acid toxins (e.g. Salicylate Poisoning, Ethylene Glycol Poisoning)
  2. Most common causes of Non-Anion Gap Metabolic Acidosis
    1. Bicarbonate Loss from Gastrointestinal Tract (Diarrhea) or Kidney (e.g. Renal Tubular Acidosis)
    2. Volume Resuscitation with Normal Saline

V. Causes: Metabolic Acidosis and Elevated Anion Gap (Mnemonic: "MUD PILERS")

  1. Methanol, Metformin
  2. Uremia
  3. Diabetic Ketoacidosis (DKA), Alcoholic Ketoacidosis or Starvation Ketosis
    1. Anion Gap is calculated based on the actual Sodium (NOT corrected for Hyperglycemia)
  4. Propylene Glycol
    1. Propylene Glycol is an inactive solvent in Parenteral infusions (e.g. Nitroglycerin, Phenobarbital)
      1. Prolonged exposure may result in toxicity
      2. Also causes Osmolar Gap and Lactic Acidosis (in addition to Anion Gap Metabolic Acidosis)
    2. Other Anion Gap Metabolic Acidosis causes include Propofol Infusion Syndrome
      1. Also caused by Paraldehyde, Phenformin (neither used in U.S. now)
  5. Iron, Isoniazid (due to Seizures)
    1. Isopropyl Alcohol does NOT cause a Metabolic Acidosis with Anion Gap (except Alcoholic Ketoacidosis)
  6. Lactic Acidosis
  7. Ethylene Glycol, Ethyl Alcohol
  8. Rhabdomyolysis
  9. Salicylates (do not miss Chronic Salicylate Poisoning)
  10. Other Causes
    1. Hyperalbuminemia
    2. Administered anions

VI. Causes: Metabolic Acidosis and Normal Anion Gap (Hyperchloremic Metabolic Acidosis)

  1. See Hyperchloremia
  2. Hypokalemia with Metabolic Acidosis
    1. Diarrhea
    2. Ureteral diversion
      1. Uretero-sigmoidostomy
      2. Ileal Bladder
      3. Ileal ureter
    3. Renal Tubular Acidosis (proximal or distal)
    4. Mineralocorticoid Deficiency
      1. Angiotensin Deficiency: Liver Failure
      2. ACE Inhibitor
      3. Renin Deficiency
        1. Aging
        2. Extracellular fluid volume expansion
        3. Lead
        4. Beta Blockers
        5. Prostaglandin Inhibitor
        6. Methyldopa
    5. Carbonic anhydrase inhibitor
      1. Acetazolamide
      2. Mefenamic acid
    6. Post-hypocapnia
    7. Excessive Normal Saline infused (liters)
  3. Hyperkalemia (or normal Potassium) Metabolic Acidosis
    1. Renal Failure (Early)
    2. Renal Disease
      1. SLE Interstitial Nephritis
      2. Amyloidosis
      3. Hydronephrosis
      4. Sickle Cell Nephropathy
    3. Acidifying agents
      1. Ammonium Chloride
      2. Calcium Chloride
      3. Arginine
    4. Sulfur toxicity
  4. Mnemonic: USED CARP (incomplete)
    1. Ureteral diversion
    2. Small Bowel Fistula
    3. Extra Chloride (ammonium chloride, Calcium Chloride)
    4. Diarrhea
    5. Carbonic anhydrase inhibitors (Acetazolamide, Mefenamic acid)
    6. Adrenal Insufficiency
    7. Renal Tubular Acidosis
    8. Pancreatic Fistula
    9. (2016) CALS Manual, 14th ed, 1: 44

VII. Causes: Metabolic Acidosis and Elevated Osmolal Gap

VIII. Labs: General

  1. Arterial Blood Gas
    1. Arterial pH decreased
    2. Serum bicarbonate decreased
    3. PaCO2 decreased
      1. PaCO2 drops 1.2 mmHg per 1 meq/L bicarbonate fall
      2. PaCO2 is typically the same as the last 2 digits of pH (given appropriate respiratory compensation)
        1. Example: For pH or 7.24 due to Metabolic Acidosis, expect an ABG PCO2 of 24 mmHg
        2. Significantly higher PCO2 than predicted by pH suggests hypercapnic Respiratory Failure
      3. Calculated PaCO2 = 1.5 x HCO3 + 8 (+/- 2)
        1. Useful in High Anion Gap Metabolic Acidosis
        2. Measured PaCO2 discrepancy: respiratory disorder
  2. Serum Chemistry panel
    1. Anion Gap
      1. Increased in high Anion Gap Metabolic Acidosis
      2. See labs below to further differentiate cause of Metabolic Acidosis with Anion Gap
    2. Excess Anion Gap <23 mEq/L
      1. Suggests Non-Anion Gap Metabolic Acidosis
    3. Serum Potassium
      1. Investigate normal Anion Gap Metabolic Acidosis
      2. See above
    4. Serum Chloride
      1. Elevated in normal Anion Gap Metabolic Acidosis
      2. Standard normal Na - Cl = 140 mEq/L - 102 mEq/L = 38 mEq/L
        1. Na-Cl <38 mEq/L: Hyperchloremic Metabolic Acidosis
        2. Na-Cl >38 mEq/L: Hypochloremic Metabolic Alkalosis
    5. Serum bicarbonate
      1. Decreased in increased Anion Gap Metabolic Acidosis
      2. Bicarbonate decrease matches Anion Gap increase
  3. Urinalysis with Urine pH
    1. Urine pH >6: Suggests Renal cause
    2. Urine pH <6: Suggests Gastrointestinal cause
  4. Urine Anion Gap (obtain urine Electrolytes)
    1. Decreased Urine Anion Gap <-10
      1. Extrarenal Non-Anion Gap Metabolic Acidosis
    2. Increased Urine Anion Gap >+10
      1. Renal Non-Anion Gap Metabolic Acidosis

IX. Labs: Consider in Metabolic Acidosis with Increased Anion Gap

  1. Basic chemistry panel as above (Serum Glucose, Blood Urea Nitrogen)
  2. Serum Lactate
  3. Serum Ketones (or Beta hydroxybutyrate)
  4. Salicylate Level
  5. Blood Alcohol Level
  6. Ethylene Glycol level
  7. Osmolal Gap
    1. Elevated in Toxic Alcohol ingestion (Alcohol, Ethylene Glycol, Methanol, isopropanol)
    2. Note that Isopropanol (Isopropyl Alcohol) does not increase Anion Gap, but does increase Osmolal Gap
      1. Isopropanol is the most common ingested Toxic Alcohol
      2. It also causes a Ketosis without acidosis (due to acetone which has no charge)
  8. Creatinine Phosphokinase (CPK)
  9. Iron level
  10. Serum Albumin

X. References

  1. Arieff (1993) J Crit Illn 8(2): 224-46 [PubMed]
  2. Narins (1982) Am J Med 72:496 [PubMed]
  3. Narins (1980) Medicine 59:161-95 [PubMed]
  4. Ghosh (2000) Fed Pract p. 23-33
  5. Rutecki (Dec 1997) Consultant, p. 3067-74
  6. Rutecki (Jan 1998) Consultant, p. 131-42

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