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
  4. Paraldehyde, Phenformin (neither used in U.S. now)
    1. Propofol Infusion Syndrome has been proposed as a replacement in mnemonic
  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

  1. Toxic Alcohol ingestion
    1. Eythylene glycol
    2. Methanol
  2. Serum Ketones are increased (Ketosis)
    1. Alcoholic Ketoacidosis
    2. Diabetic Ketoacidosis

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 a PCO2 of 24 mmHg
      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
    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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Related Studies

Ontology: Metabolic acidosis (C0220981)

Definition (NCI_NCI-GLOSS) A condition in which the blood is too acidic. It may be caused by severe illness or sepsis (bacteria in the bloodstream).
Definition (NCI) Increased acidity in the blood secondary to acid base imbalance. Causes include diabetes, kidney failure and shock.
Concepts Pathologic Function (T046)
MSH D000138
ICD10 E87.2
SnomedCT 59455009
English ACIDOSIS METABOLIC, metabolic acidosis, metabolic acidosis (diagnosis), Acidosis metabolic, Metabolic acidosis NOS, Metabolic Acidoses, Acidosis, Metabolic, Acidoses, Metabolic, Metabolic Acidosis, acidosis metabolic, metabolic acidosis disorder, Acidosis, Metabolic acidosis (disorder), acidosis; metabolic, metabolic; acidosis, Metabolic acidosis, NOS, Metabolic acidosis
Italian Acidosi metabolica, Acidosi metabolica NAS
Dutch metabole acidose NAO, acidose; metabool, metabool; acidose, metabole acidose
French Acidose métabolique SAI, ACIDOSE METABOLIQUE, Acidose métabolique
German metabolische Azidose NNB, AZIDOSE METABOLISCH, metabolische Azidose
Portuguese Acidose metabólica NE, ACIDOSE METABOLICA, Acidose metabólica
Spanish Acidosis metabólica NEOM, ACIDOSIS METABOLICA, acidosis metabólica (trastorno), acidosis metabólica, Acidosis metabólica
Japanese 代謝性アシドーシス, 代謝性アシドーシスNOS, タイシャセイアシドーシスNOS, タイシャセイアシドーシス
Czech Metabolická acidóza, Metabolická acidóza NOS, metabolická acidóza
Hungarian Metabolicus acidosis, Metabolikus acidosis, Metabolikus acidosis k.m.n.
Norwegian Metabolsk acidose

Ontology: Metabolic acidosis, normal anion gap (NAG) (C0268033)

Concepts Disease or Syndrome (T047)
SnomedCT 111377009
Spanish acidosis metabólica, hiato aniónico normal, acidosis metabólica, brecha aniónica normal (trastorno), acidosis metabólica, brecha aniónica normal, acidosis metabólica, hiato aniónico normal (trastorno), acidosis metabólica, anión gap normal, acidosis metabólica, desequilibrio aniónico normal
English Metabolic acidosis, normal anion gap (disorder), Metabolic acidosis, normal anion gap, Metabolic acidosis, normal anion gap (NAG) (disorder), Metabolic acidosis, normal anion gap (NAG), Metabolic acidosis, normal anion gap (NAG), NOS

Ontology: Metabolic acidosis, increased anion gap (IAG) (C0268036)

Concepts Disease or Syndrome (T047)
SnomedCT 25998009
Spanish acidosis metabólica, hiato aniónico aumentado (trastorno), acidosis metabólica, hiato aniónico aumentado, acidosis metabólica con anión gap aumentado, acidosis metabólica, brecha aniónica aumentada, acidosis metabólica, brecha aniónica aumentada (trastorno), acidosis metabólica, desequilibrio aniónico aumentado
English Metabolic acidosis, increased anion gap, Metabolic acidosis, increased anion gap (disorder), Metabolic acidosis, increased anion gap (IAG) (disorder), Metabolic acidosis, increased anion gap (IAG), Metabolic acidosis, increased anion gap (IAG), NOS

Ontology: Hyperchloremic metabolic acidosis (C1969073)

Concepts Finding (T033)
English Hyperchloremic metabolic acidosis