Serum Ketone

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

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II. 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

III. 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

IV. 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

V. 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

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Related Studies

Ontology: Acetoacetates (C0000988)

Definition (MSH) Salts and derivatives of acetoacetic acid.
Definition (CSP) salts and derivatives of acetoacetic acid.
Concepts Organic Chemical (T109)
MSH D000090
LNC LP15312-9, LP70346-9, MTHU007082
English Acetoacetates, Acetoacetates [Chemical/Ingredient], acetoacetate, Acetoacetate
Swedish Acetoacetater
Czech acetoacetáty
Finnish Asetoasetaatit
Russian ATSETOATSETATY, АЦЕТОАЦЕТАТЫ
Polish Acetylooctany
Japanese アセト酢酸類, アセトアセテート, アセト酢酸塩
French Acétoacétates, Acétylacétates
German Acetoacetate, Azetoazetate
Italian Acetoacetati
Portuguese Acetoacetatos
Spanish Acetoacetatos
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Ketone Bodies (C0022631)

Definition (MSH) The metabolic substances ACETONE; 3-HYDROXYBUTYRIC ACID; and acetoacetic acid (ACETOACETATES). They are produced in the liver and kidney during FATTY ACIDS oxidation and used as a source of energy by the heart, muscle and brain.
Definition (CSP) acetone, acetoacetic acid, and beta-hydroxybutyric acid in the context of lipid and pyruvate metabolism; may appear in urine marking metabolic abnormalities, as in diabetes mellitus.
Concepts Biologically Active Substance (T123) , Organic Chemical (T109)
MSH D007657
SnomedCT 76781009
English Bodies, Ketone, Ketone Bodies, ketone body, Ketone bodies (substance), Ketone bodies, Ketone body, Ketone body (substance), Ketone Bodies [Chemical/Ingredient], body ketone, bodies ketones, ketone bodies, body ketones, Ketone body analyte
Swedish Ketonkroppar
Czech ketolátky
Finnish Ketoaineet
Russian ATSETONOVYE TELA, KETONOVYE TELA, АЦЕТОНОВЫЕ ТЕЛА, КЕТОНОВЫЕ ТЕЛА
Spanish cuerpos de acetona, cuerpo cetónico (sustancia), cuerpos cetónicos (sustancia), cuerpo cetónico, cuerpos cetónicos, Acetonemia, Cetonemia, Acetonuria, Cetonuria, Cuerpos Cetónicos
Croatian KETONSKA TIJELA
Polish Ciała ketonowe
Portuguese Acetonemia, Cetonúria, Acetonúria, Cetonemia, Corpos Cetônicos
French Corps cétoniques
German Ketonkörper
Italian Corpi chetonici
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Ketones (C0022634)

Definition (NCI_NCI-GLOSS) A type of chemical substance used in perfumes, paints, solvents, and found in essential oils (scented liquid taken from plants). Ketones are also made by the body when there is not enough insulin.
Definition (NCI) Organic compounds with a carbonyl group (C=O) bonded to two other carbon atoms as the skeleton structure. Acetone is the simplest ketone compound.
Definition (CSP) functional group of an organic compound in which a carbon atom is double-bonded to an oxygen; neither of the other substituents attached to the carbon can be a hydrogen.
Concepts Organic Chemical (T109)
MSH D007659
SnomedCT 259390003, 59431004
LNC LP15683-3, MTHU003407
English Ketones, Ketones [Chemical/Ingredient], ketone, ketones, Ketone, Ketone (substance), Ketone, NOS
Swedish Ketoner
Czech ketony
Finnish Ketonit
Russian KETONY, КЕТОНЫ
Croatian KETONI
Polish Ketony
Norwegian Not Translated[Ketones]
Spanish cetona (sustancia), cetona, Cetonas
French Cétones
German Ketone
Italian Chetoni
Portuguese Cetonas
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Ketosis (C0022638)

Definition (MSH) A condition characterized by an abnormally elevated concentration of KETONE BODIES in the blood (acetonemia) or urine (acetonuria). It is a sign of DIABETES COMPLICATION, starvation, alcoholism or a mitochondrial metabolic disturbance (e.g., MAPLE SYRUP URINE DISEASE).
Concepts Disease or Syndrome (T047)
MSH D007662
SnomedCT 2538008
English KETOSIS, Ketosis [Disease/Finding], Ketoacidosis, Ketoacidoses, ketosis, Ketosis (disorder), Ketosis, NOS, Ketosis
Portuguese CETOSE, Cetoacidose, Cetose
Spanish CETOSIS, Cetoacidosis, cetosis (trastorno), cetosis, Cetosis
Swedish Ketos
Japanese ｹﾄｰｼｽ, ケトン血症, ケトン体血症, ケトーシス, ケトン症, ケトン体血
Czech ketóza, Ketóza, ketoacidóza
Finnish Ketoosi
Russian KETOATSIDOZ, КЕТОАЦИДОЗ
French CETOSE, Acidocétose, Cétoacidose, Cétose
German KETOSE, Ketose, Ketoazidose
Polish Ketoza
Croatian Not Translated[Ketosis]
Hungarian Ketosis
Dutch ketose, Ketose, Ketosis
Norwegian Ketoacidose, Ketose
Italian Chetosi
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: 3-Hydroxybutyric Acid (C0047456)

Definition (MSH) BUTYRIC ACID substituted in the beta or 3 position. It is one of the ketone bodies produced in the liver.
Concepts Organic Chemical (T109)
MSH D020155
Spanish Ácido 3-Hidroxibutírico
Swedish 3-hydroxubutursyra
English HYDROXYBUTYRIC ACID A 003, Butanoic acid, 3-hydroxy-, 3 Hydroxybutyric Acid, 3-Hydroxybutyric Acid, beta Hydroxybutyric Acid, beta-Hydroxybutyric Acid, 3-Hydroxybutyric Acid [Chemical/Ingredient], beta-hydroxybutyric acid, beta hydroxybutyric acid, (+/-)-3-Hydroxybutyric Acid
Czech kyselina 3-hydroxymáselná
Finnish 3-hydroksivoihappo
Russian BETA-OKSIBUTIRAT, 3-GIDROKSIBUTIRAT, 3-OKSIMASLIANAIA KISLOTA, 3-OKSIBUTIRAT, 3-GIDROKSIMASLIANAIA KISLOTA, BETA-GIDROKSIBUTIRAT, 3-ГИДРОКСИБУТИРАТ, 3-ГИДРОКСИМАСЛЯНАЯ КИСЛОТА, 3-ОКСИБУТИРАТ, 3-ОКСИМАСЛЯНАЯ КИСЛОТА, БЕТА-ГИДРОКСИБУТИРАТ, БЕТА-ОКСИБУТИРАТ
Japanese 3-ヒドロキシブタン酸, ベータ-ヒドロキシ酪酸, β-ヒドロキシブタン酸, β-ヒドロキシ酪酸, 3-ヒドロキシ酪酸塩, β-ヒドロキシ酪酸塩, β-オキシ酪酸, 3-ヒドロキシ酪酸
Italian Acido beta idrossibutirrico, Acido 3-idrossibutirrico
German HYDROXYBUTYRATSÄURE A 003, 3-Hydroxybutyratsäure
Polish Kwas 3-hydroksymasłowy, Beta-hydroksymaślan
French Acide bêta-hydroxy-butyrique, Acide bêta-hydroxybutyrique, Acide 3-hydroxy-butyrique, Acide 3-hydroxybutyrique
Portuguese Ácido 3-Hidroxibutírico
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Ketoacidosis (C0220982)

Concepts Pathologic Function (T046)
SnomedCT 56051008
English KETOACIDOSIS, ketoacidosis, keto acidosis, Ketoacidosis (disorder), Ketoacidosis, NOS, Ketoacidosis
German KETOAZIDOSE, Ketoazidose
Italian Chetoacidosi
Japanese ケトアシドーシス, ｹﾄｱｼﾄﾞｰｼｽ
French ACIDOCETOSE, Acidocétose
Portuguese CETOACIDOSE, Cetoacidose
Spanish CETOACIDOSIS, cetoacidosis (trastorno), cetoacidosis, Cetoacidosis
Czech Ketoacidóza
Hungarian Ketoacidosis
Dutch ketoacidose
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Plasma Beta Hydroxybutyrate Test (C0236311)

Concepts Laboratory Procedure (T059)
English Plasma Beta Hydroxybutyrate Test
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Serum Acetone Test (C0236485)

Concepts Laboratory Procedure (T059)
English Serum Acetone Test
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Serum Ketones Test (C1254687)

Concepts Laboratory Procedure (T059)
English Serum Ketones Test
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Acetonemia (C1260871)

Concepts Disease or Syndrome (T047)
SnomedCT 214290000, 45317003
English ACETONAEMIA, acetonemia, acetonemia (diagnosis), Acetonaemia, Acetonemia (disorder), Acetonemia
Italian Acetonemia
German Acetonaemie, AZETONAEMIE, Azetonaemie
Portuguese Acetonemia, CETONEMIA, Cetonemia
Japanese アセトン血症, ｱｾﾄﾝｹﾂｼｮｳ, ｱｾﾄﾝｹｯｼｮｳ
Spanish ACETONEMIA, acetonaemia, acetonemia (trastorno), acetonemia, Acetonemia
French ACETONEMIE, Acétonémie
Czech Acetonemie
Hungarian Acetonaemia
Dutch acetonemie
Derived from the NIH UMLS (Unified Medical Language System)

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