II. Pathophysiology
- Images
- Ketone Bodies
- Ketones are water-soluble molecules used by cells as fuel (esp. brain, heart) when Glucose is not available
- Most commonly form in Diabetic Ketoacidosis when Insulin is insufficient
- Also forms in Starvation Ketosis or Alcoholic Ketoacidosis when Glucose is insufficient
- Ketone use as a fuel blunts Hypoglycemia effects (esp. neurologic) despite Serum Glucose <60 mg/dl
- Ketones yield 4 kcal/g when metabolized via oxidative pathway
- Liver forms Ketone Bodies in response to low Insulin and high Glucagon
- Low Insulin and high Glucagon stimulates Lipase release
- Lipase stimulates metabolism of Triglycerides into Glycerol and long chain Fatty Acids
- Hepatocyte mitochondria use long chain Fatty Acids to generate acetyl-CoA
- Acetyl-CoA is shunted to the ketogenic pathway when the oxidative pathway (Krebs Cycle) is overwhelmed
- Ketogenic pathway generates the Ketone Body, Acetoacetate, from acetyl-CoA
- Acetoacetate is in turn metabolized into Acetone and Beta-Hydroxybutyrate (see below)
- Ketones are water-soluble molecules used by cells as fuel (esp. brain, heart) when Glucose is not available
- Acetoacetate metabolism
- Acetoacetate (20% remains unchanged)
- Acetone (2%)
- Forms spontaneously from Acetoacetate (also releasing carbon dioxide)
- Responsible of fruity breath with ketaocidosis
- Identified on Urine Ketones, but not on Serum Ketone assays (typically for Beta-Hydroxybutyrate)
- Beta-Hydroxybutyrate (78%)
- Hydroxyacid formed via Beta-Hydroxybutyrate dehydrogenase (and NADH)
- Concurrent Lactic Acidosis increases the ratio of Beta-Hydroxybutyrate to Acetoacetate
- Not identified on Urinalysis (Nitroprusside reaction)
- Ratio of Beta-Hydroxybutyrate to Acetoacetate varies based on condition
- Diabetic Ketoacidosis 3:1 ratio
- Alcoholic Ketoacidosis 8:1 ratio
- Urine Ketones may be negative despite significant Alcoholic Ketoacidosis
- Precautions
- Beta-Hydroxybutyrate accumulation results in Metabolic Acidosis with Anion Gap
- Acetone is charge neutral and does not cause a Metabolic Acidosis
- Isopropranol Ingestion results in acetone formation without other Ketone Bodies
- Isopropranol therefore causes a Ketosis without Metabolic Acidosis
- Ketosis without Metabolic Acidosis may also be caused by more mild cases of other Ketoacidosis
III. Technique
- Sample
- Blood sent on Ice to be run by lab immediately
- Testing modalities
- Beta-Hydroxybutyrate (preferred)
- Typically used in U.S. when Serum Ketones are ordered
- Serum Acetone
- Acetoacetate and Acetone measured via Nitroprusside reaction
- Does NOT measure Beta-Hydroxybutyrate levels (primary Ketone Body)
- Historically, this was the methodology used when Serum Ketones were ordered
- Beta-Hydroxybutyrate (preferred)
IV. Causes: Increased Ketones (Ketoacidosis or Acetonemia)
- Diabetic Ketoacidosis
- Acute illness, especially in children (febrile illness, Gastroenteritis, Dehydration)
- Alcoholic Ketoacidosis (similar to Starvation Ketosis)
-
Starvation Ketosis
- Ketoacids increase 10 fold to >1 mmol/L after 3 days of Fasting
- Type I Glycogen Storage Disease (Von Gierke's Disease)
-
Isopropanol Ingestion (Isopropyl Alcohol or Rubbing Alcohol)
- Only found on acetone testing
- Does NOT raise serum Beta-Hydroxybutyrate levels (most common modern day testing modality)
- Does not result in a Metabolic Acidosis with Anion Gap
V. References
- Bakerman (1984) ABCs of Interpretive Lab Data, 2nd ed
- Bradley (1990) University of Minnesota Laboratory Handbook: Comprehensive Edition
- Marino (2013) ICU Book, p. 609-10
- Mehta and Emmett in Sterns and Traub (2019) UpToDate, Fasting Ketosis and Alcoholic Ketoacidosis, accessed 7/19/2019
Images: Related links to external sites (from Bing)
Related Studies
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 |
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 |
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 |
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 |
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 |
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, ケトアシドーシス |
French | ACIDOCETOSE, Acidocétose |
Portuguese | CETOACIDOSE, Cetoacidose |
Spanish | CETOACIDOSIS, cetoacidosis (trastorno), cetoacidosis, Cetoacidosis |
Czech | Ketoacidóza |
Hungarian | Ketoacidosis |
Dutch | ketoacidose |
Ontology: Plasma Beta Hydroxybutyrate Test (C0236311)
Concepts | Laboratory Procedure (T059) |
English | Plasma Beta Hydroxybutyrate Test |
Ontology: Serum Acetone Test (C0236485)
Concepts | Laboratory Procedure (T059) |
English | Serum Acetone Test |
Ontology: ketogenesis (C0599816)
Concepts | Molecular Function (T044) |
English | ketogenesis |
Ontology: Serum Ketones Test (C1254687)
Concepts | Laboratory Procedure (T059) |
English | Serum Ketones Test |
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 |