The
Pathology Service of St Vincent's Hospital, Sydney
Under the Care of the Sisters of Charity
| SydPath Information Sheet | Dr Graham Jones |
| Ketones | |
| Physiology
The ketones
which may be found in the circulation are acetoacetate, beta-hydroxybutrate and acetone.
They are produced in the liver in an environment of low insulin and low intracellular
carbohydrate as an adaptive mechanism to provide non-carbohydrate fuel for the brain and
other tissues in times of starvation. Acetoacetate is produced from acetyl CoA and may
then either be converted enzymatically to beta-hydroxybutyrate or non-enzymatically to to
acetone. The interconversion of acetoacetate and beta-hydroxybutyrate requries the enzyme
beta-hydroxybutyrate dehydrogenase and the ratio of the two metabolites depends on the
prevailing concentrations of NAD and NAHD.
Pathology
As stated above, ketone production is a protective mechanism during starvation to provide energy to the brain and other tissues. After consumption of available glycogen the body switches largely to fatty acids as a source of energy. In contrast to fatty acids, ketones can pass the blood-brain barrier to deliver energy to this organ. In early starvation ketones are also used for energy by muscle cells but later these convert to fatty acids to conserve ketones for the brain. These mechanisms assist in preserving carbohydrate supplies for cells dependent on sugars for energy supply such as red cells and the renal medulla. In other clinical settings the presence of ketones, and the acompanying acidosis, can be markedly deleterious to the body. The most common of these are diabetic ketoacidosis and alcoholic ketoacidosis. In these settings the decrease in NAD relative to NADH leads to a relatively greater increase in beta-hydroxybutyrate than acetoacetate. Thus acetoacetate may be low in untreated cases of diabetic ketoacidosis, but then paradoxically increase in response to therapy. Additionally the molar increase in betahydroxybutyrate constitutes the major contributor to the increased anion gap seen in these patients. These factors make beta-hydroxybutyrate a preferable marker for ketoacidosis compared to acetoacetate. Causes of Elevated Ketones
The sample requirement for measurement of beta-hydroxybutyrate is either a blood gas syringe (arterial or venous) or a Full Blood Count tube (EDTA, purple top). The assay is available 7 days / 24 hours and samples should be delivered to the laboratory within 2 hours of collection. The assay is quantitative up to 6 mmol/L. Acetoacetate can be measured on a spot urine sample using the ketone pad on standard uninalysis dipsticks. Reference Interval Expected results for whole blood beta-hydroxybutyrate in patients without ketoacidosis is less than 0.6 mmol/L. Concentrations greater than 3 mmol/L haev been proposed as an indication of significant keto-acidosis.
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| Further information available for SydPath clients from Dr Graham Jones: 8382-9160 | |
The
Pathology Service of St Vincent's Hospital, Sydney |
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| Last updated 05/01/04 | |