Serum Ketone


Serum Ketone, Serum Acetone, Acetoacetate, Beta-Hydroxybutyrate, Serum Beta Hydroxybutyrate, B-Hydroxybutyrate, 3 Hydroxybutyric Acid, Ketoacidosis, Ketosis, Acetonemia, Ketone Body, Ketone Bodies, Ketone

  • Pathophysiology
  1. Ketone Bodies
    1. Ketones are water-soluble molecules used by cells (esp. brain, heart) when Glucose is not available
      1. Most commonly form in Diabetic Ketoacidosis when Insulin is insufficient
      2. Also forms in Starvation Ketosis or Alcoholic Ketoacidosis when Glucose is insufficient
    2. Ketone use as a fuel blunts Hypoglycemia effects (esp. neurologic) despite Serum Glucose <60 mg/dl
      1. Ketones yield 4 kcal/g when metabolized via oxidative pathway
    3. Liver forms Ketone Bodies in response to low Insulin and high Glucagon
      1. Low Insulin and high Glucagon stimulates Lipase release
      2. Lipase stimulates metabolism of Triglycerides into glycerol and long chain Fatty Acids
      3. Hepatocyte mitochondria use long chain Fatty Acids to generate acetyl-CoA
      4. Acetyl-CoA is shunted to the ketogenic pathway when the oxidative pathway (Krebs Cycle) is overwhelmed
      5. Ketogenic pathway generates the Ketone Body, Acetoacetate, from acetyl-CoA
        1. Acetoacetate is in turn metabolized into Acetone and Beta-Hydroxybutyrate (see below)
  2. Acetoacetate metabolism
    1. Acetoacetate (20% remains unchanged)
    2. Acetone (2%)
      1. Forms spontaneously from Acetoacetate (also releasing carbon dioxide)
      2. Responsible of fruity breath with ketaocidosis
      3. Identified on Urine Ketones, but not on Serum Ketone assays (typically for Beta-Hydroxybutyrate)
    3. Beta-Hydroxybutyrate (78%)
      1. Hydroxyacid formed via Beta-Hydroxybutyrate dehydrogenase (and NADH)
      2. Concurrent Lactic Acidosis increases the ratio of Beta-Hydroxybutyrate to Acetoacetate
      3. Not identified on Urinalysis (Nitroprusside reaction)
      4. Ratio of Beta-Hydroxybutyrate to Acetoacetate varies based on condition
        1. Diabetic Ketoacidosis 3:1 ratio
        2. Alcoholic Ketoacidosis 8:1 ratio
          1. Urine Ketones may be negative despite significant Alcoholic Ketoacidosis
  3. Precautions
    1. Beta-Hydroxybutyrate accumulation results in Metabolic Acidosis with Anion Gap
    2. Acetone is charge neutral and does not cause a Metabolic Acidosis
      1. Isopropranol Ingestion results in acetone formation without other Ketone Bodies
      2. Isopropranol therefore causes a Ketosis without Metabolic Acidosis
      3. Ketosis without Metabolic Acidosis may also be caused by more mild cases of other Ketoacidosis
  • Technique
  1. Sample
    1. Blood sent on Ice to be run by lab immediately
  2. Testing modalities
    1. Beta-Hydroxybutyrate (preferred)
      1. Typically used in U.S. when Serum Ketones are ordered
    2. Serum Acetone
      1. Acetoacetate and Acetone measured via Nitroprusside reaction
      2. Does NOT measure Beta-Hydroxybutyrate levels (primary Ketone Body)
      3. Historically, this was the methodology used when Serum Ketones were ordered
  • Causes
  • Increased Ketones (Ketoacidosis or Acetonemia)
  1. Diabetic Ketoacidosis
  2. Acute illness, especially in children (febrile illness, Gastroenteritis, dehydration)
  3. Alcoholic Ketoacidosis (similar to Starvation Ketosis)
  4. Starvation Ketosis
    1. Ketoacids increase 10 fold to >1 mmol/L after 3 days of Fasting
  5. Type I Glycogen Storage Disease (Von Gierke's Disease)
  6. Isopropanol Ingestion (Isopropyl Alcohol or Rubbing Alcohol)
    1. Only found on acetone testing
    2. Does NOT raise serum Beta-Hydroxybutyrate levels (most common modern day testing modality)
    3. Does not result in a Metabolic Acidosis with Anion Gap
  • References
  1. Bakerman (1984) ABCs of Interpretive Lab Data, 2nd ed
  2. Bradley (1990) University of Minnesota Laboratory Handbook: Comprehensive Edition
  3. Marino (2013) ICU Book, p. 609-10
  4. Mehta and Emmett in Sterns and Traub (2019) UpToDate, Fasting Ketosis and Alcoholic Ketoacidosis, accessed 7/19/2019