Urine for ketones, and Ketone Bodies (Ketonuria)
Urine for ketones
Sample Urine for ketones
- This is done in the urine.
- This test can also be done on blood (serum or plasma).
Precautions Urine for ketones
- Keep the urine refrigerated and in closed containers.
- Avoid loss due to evaporation and bacterial action.
- Keep the blood also refrigerated.
- Some of the drugs give false-positive results e.g.
- Ether and chloroform.
- Isopropyl alcohol.
- Valproic acid.
- Aminosalicylic acid.
- The false-negative result is seen in the following:
- When urine is kept at room temperature for a long time due to the loss of ketones in the air.
Indications Urine for ketones
- It is advised in diabetic patients for the early diagnosis of ketoacidosis.
- Ketones are done to judge the severity of the acidosis and monitor the response to the treatment.
- Testing of ketonuria in diabetetics:
- To evaluate the diabetic patient in a coma.
- To monitor people with diabetes who are on oral hypoglycemic drugs.
- Check when the patient is switched from the insulin to oral hypoglycemics; ketonuria’s appearance within 24 hours of the insulin withdrawal indicates a poor response to oral hypoglycemic drugs.
- Testing of the ketonuria is important In patients who have urine sugar positive and raised blood glucose.
- Ketonuria is done to differentiate between diabetic coma with positive ketones and insulin-shock negative ketonuria.
- This is done by screening ketonuria, which is usually seen in hospitalized patients, children, pregnant ladies, and patients with diabetes.
- During pregnancy, early detection of ketonuria is essential because ketoacidosis may lead to the fetus’s death.
- It is done to judge the severity of the acidosis and the treatment response.
- Ketonuria may provide a more accurate indicator of acidosis than blood testing.
- This is helpful in the emergency wards.
Definition of Ketone bodies
- Increased ketone bodies in the blood are called Ketonemia.
- Increased excretion in the urine is called Ketonuria.
Pathophysiology of ketone bodies
- Fat metabolism, when completely metabolized, leads to CO2 and H2O formation. So ketone bodies are not seen in the urine.
- While intermediate products are ketone bodies.
Ketone bodies are seen in:
- In the case of decreased availability of carbohydrates, like starvation or frequent vomiting.
- Another possibility is decreased utilization of carbohydrates like diabetes mellitus and glycogen storage disease.
- High fat and low carbohydrates diet are ketogenic and increase ketone bodies in the blood.
- Ketones are the end product of fatty acid metabolism.
Ketone bodies in diabetic patients:
- Ketones are formed when glucose as a source of energy is not present.
- This situation happens when there is no insulin, so glucose cannot enter the cells.
- In that case, ketone bodies are the energy source for the body, particularly the brain.
- In fasting for 3 to 4 days, then 30% to 40% of body energy is provided by the ketone bodies.
- Ketones bodies are the end product of fatty acid breakdown and consist of :
- Beta-hydroxybutyric acid.
- Acetoacetic acid.
- The β- hydroxybutyric acid + acetoacetic acid readily converts to acetone.
- It shows that the main ketone is acetone to be tested.
- Some of the kits only measure acetoacetic acid.
ketone bodies are:
- Acetone is a minor amount.
- Acetoacetate and β- hydroxybutyrate is equal in amount and is the main ketone bodies.
- In a healthy person, ketones are formed in the liver and completely metabolized, but there is a negligible amount in urine.
The outcome of Increased Ketones in the blood leads to the following:
- Electrolyte imbalance.
- If not corrected, then it leads to acidosis, coma, and ultimately death.
- Ketones are present in the urine when a threshold level of ketones exceeds the blood’s normal level.
Clinical significance of ketone bodies:
- Insulin dosage for monitoring and managing insulin-dependent diabetes mellitus, type 1 diabetes.
- Ketonuria shows insulin deficiency and needs to adjust the dose of insulin.
- This is an early sign of an insufficient dose of insulin.
- Diabetic acidosis (Inability to metabolize carbohydrates).
- Vomiting (increased loss of carbohydrates).
- Starvation (inadequate carbohydrate intake).
- Malabsorption (inadequate carbohydrate intake).
- Pancreatic diseases.
- Inborn error of amino acid metabolism.
- Ketonuria shows a deficiency of insulin and indicates the regulation of insulin dose.
- Strenuous exercise leads to ketonuria due to the overuse of carbohydrates.
Normal ketone bodies in urine
- In Urine
- Ketone bodies are negative.
- Small amount = < 20 mg/dL.
- Moderate amount = 30 to 40 mg/dL.
- Large amount = > 80 mg /dL.
- In blood or plasma.
- Acetone = < 2.0 mg/dL (<0.34 mmol/L).
- Acetoacetate = < 1 mg/dL (<0.1 mmol/L).
- β-hydroxybutyric acid = 0.21 to 2.81 mg/dL (20 to 270 µmol/L).
- Acetoacetate = Negative.
- Acetone = 0.3 mg/dL (0.05 mmol/L).
- β-hydroxybutyric acid = Negative
Serum or plasma ketone bodies
- Ketoacidosis = 10 to 70 mg/dL (1.72 to 12.04 mmol/L)
- Occupational exposure = <10 mg/dL (<1.72 mmol/L)
- Toxic concentration = >20 mg/dL (>3.44 mmol/L)
- Acetoacetate = Negative <1 mg/dL (<0.1 mmol/L)
- β-hydroxybutyric acid = 0.21 to 2.81 mg/dL (20 to 270 µmol/L)
Diagnostic test for ketone bodies
- Various types of strips are available to detect the ketone bodies.
Gerhardt’s Ferric chloride:
- It reacts only with Acetoacetate. This is an indirect method to detect the β- hydroxybutyrate in the urine.
- Nitroprusside has 10 times more sensitivity to acetoacetate than acetone.
- Acetoacetate (acetone) + sodium nitroprusside + glycine →→ purple color
- There is no reaction with β- hydroxybutyrate.
- It is reported as follows:
- Large amount OR as
- 1+, 2+, 3+.
- There are strips to detect β- hydroxybutyrate in the serum and urine are available.
- Quantitative estimation of β- hydroxybutyrate in serum or blood kits is commercially available.
Comparison of the various test strips for the detection of ketone bodies:
|Type of the test strip||Specificity||Sensitivity|
5 to 10 mg/dL
20 to 25 mg/dL
||Acetoacetic acid||5 to 10 mg/dL|
||Acetoacetic acid||5 to 10 mg/dL|
Ketone bodies are seen in:
- Diabetic patients.
- High protein diet.
- Salicylates poisoning.
- Isopropanol intake.
- Acute febrile illness (especially in infants and children).
- Renal Glycosuria.
- Glycogen storage disease (Von Gierke’s disease).
- Low carbohydrate diet.
- Pregnancy or lactation.
- Prolonged vomiting and diarrhea.
- Patients in the hospital may have ketonuria—roughly 15% show ketonuria in hospitalized patients without diabetes.
- Ketonuria may develop after anesthesia with ether and chloroform.
- Children are more prone to develop ketonuria and ketosis.
The critical value of the ketonuria:
- When ketonuria is positive, clinical action should be taken, and don’t take it lightly.
- Ketonuria positive in infants <2 years of age is a serious and critical alert.
- In diabetic patients, ketonuria positive means that diabetes is uncontrolled.
- In non-diabetics, it suggests increased Fat intake and fewer carbohydrates.