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Ketones Information and Courses from MediaLab, Inc.

These are the MediaLab courses that cover Ketones and links to relevant pages within the course.

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Chemical Screening of Urine by Reagent Strip
Chemical Urinalysis Reagent Strips

A chemical urinaylsis reagent strip, also called a dipstick, for screening urine is a narrow band of paper which has been saturated with chemical indicators for specific substances or properties. Depending on the product being used, chemical urinalysis reagent strips may include test indicators for glucose, bilirubin, ketones, specific gravity, blood, pH, protein, urobilinogen, nitrite, and leukocyte esterase. The results obtained from urine screening using chemical urinalysis strips can indicate the patient's carbohydrate metabolism status, kidney and liver function, urinary tract infection, and acid-base balance. Most chemical urinalysis reagent strips can be read visually and do not require instrumentation for automatic reading, though many laboratories utilize instruments for this purpose. When performing chemical urinalysis reagent strip analysis, the directions must be performed exactly. Accurate timing is paramount in order to achieve appropriate and optimal results. In addition, the reagent strips must be stored properly in their containers with the lid tightly closed to maintain reagent reactivity. It is always essential to utilize well-mixed urine which has been collected within 2 hours of analysis.Always read the package insert for your particular brand of chemical urinalysis reagent strip, as each manufacturer may have slightly different instructions and interpretations.

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A copper reduction method (e.g. Clinitest® or Benedict's) is performed on pediatric specimens in order to check for the presence of:View Page
Ketones Overview

When the body breaks down fat for energy, three intermediate products are formed. These products, collectively referred to as ketones, include acetone, acetoacetic acid, and beta-hydroxybutyric acid. Normally, the body gets the energy it needs from carbohydrates in the diet. However, stored fat is broken down and ketones are produced and appear in the urine if the diet does not contain enough carbohydrate to supply the body with glucose for energy or if the body cannot use glucose properly.

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Testing for Ketones in the Urine

Testing for ketone bodies is based on a nitroprusside reaction. Acetoacetic acid reacts with sodium nitroferricyanide and glycine in an alkaline medium to produce a violet-to-purple colored complex. The urine chemical reagent strip method can detect as little as 5 mg/dL acetoacetic acid in urine. It does not react with acetone unless glycine is present or B-hydroxybutyric acid. Since these two compounds are derived from acetoacetic acid, their presence can be assumed if the test for ketones is positive. Ketones are reported either as negative, small, moderate or large amounts; or negative, 1+, 2+, 3+, or 4+. In some severe cases of ketosis, it may be necessary to perform tests on serial dilutions to provide more information on the quantity of ketones present.

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Ketone Bodies

Ketone bodies are usually absent in urine, but low levels may be detected during conditions of physiological stress such as fasting, rapid weight loss, frequent strenuous exercise or prolonged vomiting. The presence of ketones in these situations is due to either inadequate intake or increased loss of carbohydrates. High levels of ketones are present in the urine of individuals with uncontrolled diabetes. In diabetes the ketones are present because the body's ability to metabolize carbohydrates is defective.

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False Positive and Negative Ketone Results

False Positive KetonesFalse positive ketone results may be seen in patients after BSP or PSP dye injection due to the phthaleins. The presence of L-DOPA metabolites, some urine preservatives (e.g. 8-hydroxyquinaline), or high levels of phenylketones will also cause false positive results. Antihypertensive drugs such as methyldopa and captopril also may produce false positive results.False Negative KetonesThe presence of excess moisture/humidity can cause the ketone reagent to become nonreactive, resulting in a false negative test for ketones. Urine specimens should not remain at room temperature if testing is delayed because ketones are unstable at room temperature.

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Clinical Significance of Positive Urine Ketones

Ketone bodies are usually absent in urine. The presence of ketones in the urine most likely indicates that the body is using fats rather than carbohydrates for energy. For example, high levels of ketones may be present in the urine of individuals with uncontrolled diabetes because the body's ability to metabolize carbohydrates is defective. Detecting the presence of ketones in the urine is a valuable aid to managing and monitoring individuals with diabetes mellitus. Ketonuria is an indication that the insulin dose needs to be increased. Electrolyte imbalance and dehydration may occur when ketones accumulate in the blood. If these conditions are not corrected by adjusting the dose of insulin, the patient may develop ketoacidosis and ultimately diabetic coma. Low levels of ketones may also be detected in the urine during conditions of physiological stress such as fasting, rapid weight loss, frequent strenuous exercise or prolonged vomiting. The presence of ketones in these situations is due to either inadequate intake of carbohydrates or increased loss of carbohydrates.

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The ketone component that is measured by the nitroprusside reaction is:View Page
Which of the following can cause a false positive result for ketones? (Choose ALL correct answers)View Page
Significantly increased levels of ketones are detected in the urine with which of the following conditions? (Choose ALL correct answers)View Page

Chemical Screening of Urine by Reagent Strip (retired March 2012)
Excessive carbohydrate loss that may occur due to vomiting, or rapid weight loss may result in the presence of which of following substances not normally contained in the urine?View Page
Match the following reagent strip tests to the disease or disorder that would most likely cause a positive test result.View Page
False Negative Results

False negative results occur when elements present in the urine interfere with either the enzymatic reaction or prevent the oxidation of potassium iodide. Examples of such substances include: large quantities of ketones aspirin ascorbic acid > 50 mg/dL with some reagent strips levadopa 5-hydroxyindoleacetic acid homogentisic acid sodium fluoride ( a preservative)A specific gravity higher than 1.020 may lower glucose reagent sensitivity, especially in the presence of a high urine pH. Exposing reagent strips to excess humidity may also reduce glucose reagent reactivity.Check the package insert of the reagent strips used in your laboratory for interfering substances that may affect glucose results.

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A copper reduction method (e.g. Clinitest® or Benedict's) is performed on pediatric specimens in order to check for the presence of:View Page
Three Kinds of Ketones

When the body breaks down fat for energy, three intermediate products are formed. These products, collectively referred to as ketones, are acetone, acetoacetic acid, and beta-hydroxybutyric acid. Normally, the body gets the energy it needs from carbohydrates in the diet. However, stored fat is broken down and ketones are produced and appear in the urine if the diet does not contain enough carbohydrate to supply the body with glucose for energy or if the body cannot use glucose properly.

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Testing for Ketone Bodies

Testing for ketone bodies is based on a nitroprusside reaction. Acetoacetic acid reacts with sodium nitroferricyanide and glycine in an alkaline medium to produce a violet-to-purple colored complex. The reagent strip method can detect as little as 5 mg/dL acetoacetic acid in urine. It does not react with acetone unless glycine is present or B-hydroxybutyric acid. Since these two compounds are derived from acetoacetic acid, their presence can be assumed if the test for ketones is positive. Ketones are reported either as negative, small, moderate or large amounts; or negative, 1+, 2+, 3+, or 4+. In some severe cases of ketosis, it may be necessary to perform tests on serial dilutions to provide more information on the quantity of ketones present.

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Ketone Bodies

Ketone bodies are usually absent in urine, but low levels may be detected during conditions of physiological stress such as fasting, rapid weight loss, frequent strenuous exercise or prolonged vomiting. The presence of ketones in these situations is due to either inadequate intake or increased loss of carbohydrates. High levels of ketones are present in the urine of individuals with uncontrolled diabetes. In diabetes the ketones are present because the body's ability to metabolize carbohydrates is defective.

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False Negative Results

The presence of excess moisture/humidity can cause the ketone reagent to become nonreactive, resulting in a false negative test for ketones. Urine specimens should not remain at room temperature if testing is delayed because ketones are unstable at room temperature.

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Clinical Significance of Positive Urine Ketone Result

Ketone bodies are usually absent in urine. The presence of ketones in the urine probably indicates that the body is using fats rather than carbohydrates for energy. High levels of ketones may be present in the urine of individuals with uncontrolled diabetes because the body's ability to metabolize carbohydrates is defective. Detecting the presence of ketones in the urine is a valuable aid to managing and monitoring individuals with diabetes mellitus. Ketonuria is an indication that the insulin dose needs to be increased. Electrolyte imbalance and dehydration occur when ketones accumulate in the blood. If these conditions are not corrected by adjusting the dose of insulin, the patient may develop ketoacidosis and ultimately diabetic coma. Low levels of ketones may be detected during conditions of physiological stress such as fasting, rapid weight loss, frequent strenuous exercise or prolonged vomiting. The presence of ketones in these situations is due to either inadequate intake of carbohydrates or increased loss of carbohydrates.

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Which of the following substances can cause a false positive result for ketones? (Choose ALL of the correct answers)View Page
Significantly increased levels of ketones are detected in the urine with which of the following conditions? (Choose ALL of the correct answers)View Page

Chemistry / Urinalysis Question Bank - Review Mode (no CE)
What is the largest constituent of plasma nonprotein nitrogen:View Page

Confirmatory and Secondary Urinalysis Screening Tests
Causes of Ketonuria

Ketonuria occurs when fatty acids are moved from triglyceride stores in the body in response to inadequate intake or availability of carbohydrates. Under conditions of abnormal carbohydrate metabolism, such as occurs in diabetes mellitus, ketones accumulate in the blood (ketonemia) and are excreted in the urine (ketonuria). The accumulation of ketones is often the cause of acidosis and coma in diabetics. Ketonuria is also associated with:StarvationDigestive disturbancesDietary imbalance (high fat/low carbohydrate diet)EclampsiaProlonged vomiting and diarrheaGlycogen storage diseasesSevere, sustained exerciseFeverProlonged exposure to cold temperaturesKetones are mildly toxic to the body, tending to interfere with the excretion of uric acid, produce mild depression of the central nervous system, and cause acidosis.

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Correlation of Urine Glucose and Ketones

Screening for ketonuria is useful in following the effects of treatment for diabetes and in judging the severity of acidosis. Large amounts of ketones will appear in the urine before serum ketone levels are elevated.

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Urinary Ketones

Ketone bodies are formed in the liver as intermediates in the catabolism of fatty acids. In healthy individuals, ketone bodies are almost completely metabolized so that only negligible amounts appear in the urine.

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Acetest®

Acetest® tablets can be used for the semiquantitation of ketones in urine, serum, or whole blood. However, an assay for serum/plasma beta-hydroxybutyrate (BHB) is very important in the assessment of diabetic ketoacidosis as BHB is the predominant ketone body and the most sensitive marker for detection of acidosis. Because the nitroprusside method (reagent strips and Acetest) do not measure BHB, a specific test for this ketone body is needed.Urine to be screened for ketone bodies using the Acetest method should be tested immediately or refrigerated in a closed container since acetone is lost to the air if the sample is held at room temperature for a prolonged period.

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Diabetes and the Current American Diabetes Association Guidelines
Case B

A 14-year-old male sees his pediatrician because of fatigue, weight loss, increased appetite, thirst, and frequent urination. There is a family history of diabetes. The physician orders the following laboratory assays:Laboratory Results:Fasting plasma glucose (FPG) = 250 mg/dL (Reference interval 75 - 100 mg/dL)Serum Ketones= Positive, 1+ (Reference = Negative)FPG repeated one week later= 170 mg/dL (Reference interval 75 - 100 mg/dL)

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Case B and Case C have been diagnosed with diabetes. Select the correct statements regarding the classification of these diabetic patients.View Page
Other Complications

Ketoacidosis is always a serious complication for type 1 diabetics. Due to lack of uptake of glucose into cells by insulin, proteins and fats are utilized as energy sources. This results in excess acetyl CoA which is converted to ketone bodies. A serious acidosis results and if untreated or not resolved by the body, coma and death can occur.Most often the acetyl CoA in a type 2 patient is converted to cholesterol and results in hyperlipidemia and heart disease in these patients.The elderly type 2 diabetic is at risk for a hyperosmolar nonketotic coma. The patient becomes dehydrated due to increased urine excretion to lower the blood glucose. If reduced renal or cardiac function is also present, glucose excretion is impaired and blood glucose concentrations can become extremely high. Ketones are not produced in excess, thus the patient remains nonketotic. Insufficient hydration, elevated blood glucose, and decreased renal excretion of waste products result in an increased osmolality and total concentration of all plasma components.

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Which of the following patients is most at risk for hyperosmolar nonketotic coma?View Page
Clinical Testing

A large number of assays related to carbohydrate management and diabetes monitoring are performed in clinical laboratories, hospital nursing units, nursing homes, physician offices, clinics, and by patients at home, school, or work.Assays that will be discussed are: Blood Glucose Urine Glucose Ketones Microalbuminuria Insulin and C-Peptide Insulin Antibodies Glycosylated Proteins

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Ketones

Acetyl CoA is converted to acetone, acetoacetate, and beta-hydroxybutyrate. These are acids and when dissolved in body fluids in excess lower the blood pH. Increased ketones can result in a metabolic acidosis referred to as ketosis, ketoacidosis or diabetic acidosis. Type 1 diabetic patients are especially at risk for ketoacidosis. Urine and serum ketones are measured semiquantitatively and a diabetic in ketosis is monitored for ketones and blood pH.

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