Diabetes Mellitus:- Part 7 – Diabetic Ketoacidosis and Ketone Bodies
- The ketones can be detected in blood and urine.
- The false-positive test may be seen in some medications.
- Prolonged exposure of the strips to air gives the false-negative result.
Definition of diabetic ketoacidosis
- Normally no ketones are present in the urine.
- Diabetic ketoacidosis is due to Ketone bodies in the blood and the urine.
- There is a presence of ketones in the blood, which are toxic acids.
- This is a complication in diabetic patients with hyperglycemia and massive fatty catabolism.
- The primary substrate for ketone body formation is free fatty acids from adipose tissue.
- This is due to the lack of insulin in uncontrolled diabetes mellitus.
- These free fatty acids are substrates for the formation of ketone bodies.
- When reesterified in the liver, these free fatty acids give rise to triglycerides and low-density lipoproteins.
- When the body can not utilize carbohydrates or glucose can not enter the cells.
Pathogenesis of ketone bodies production:
- Glucose provides energy to the body. During starvation or uncontrolled diabetes mellitus, the energy is supplied by the breakdown of fats.
- In the blood samples, mainly 78% is beta-hydroxybutyric acid, and acetone is hardly 2%.
- Ketones are formed when fats provide energy to the body. The enzymes responsible for forming ketone bodies are present in the mitochondrial.
- Acetyl-CoA from acetoacetyl-CoA by the β-oxidation.
- Acetoacetyl- CoA is the starting point of ketogenesis.
- Acetoacetate is formed from the acetoacetyl-CoA in the liver.
- In the extrahepatic tissue, acetoacetate is activated by acetoacetyl-CoA.
- Now acetoacetyl- CoA is split into acetyl-CoA by thiolase, is oxidized in the citric acid cycle, and produces CO2.
- In most cases of ketonemia, increased ketone bodies are formed in the liver and not dependant upon the utilization of ketone bodies in the extrahepatic tissue.
- Ketone bodies are:
- ketone bodies are the end product of fatty acid breakdown.
- The presence of ketones bodies in the urine indicates poorly controlled diabetes mellitus.
Definition of diabetic ketoacidosis:
- When the body can not utilize the ketone bodies produced in excess, it is called ketosis.
- These are excreted in the urine and are called ketonuria. There is the excretion of ketones more than traces.
- The elevated level of ketones in the blood is called ketonemia.
- This overproduction of the keto acids leads to acidosis or lowers blood pH.
- Ketone bodies are toxic to the brain; if present in abundance in the blood, these will leave to coma.
- Diabetic ketoacidosis is life-threatening metabolic acidosis due to uncontrolled diabetes mellitus, it is seen usually in type 1 and less common in type 2.
Procedure for ketone bodies
- Gerhardt’s ferric chloride reacts with acetoacetate only.
- Principle of Gerhardt’s test:
- The reagent is 10% ferric chloride.
- It is based on the reaction of ferric chloride (FeCl3) with acetoacetic acid only, and it will form red color.
- Principle of Gerhardt’s test:
- The procedure of Gerhardt’ test:
- Take 3 to 5 mL of urine.
- Add 5 mL of Ferric chloride solution.
- Note the color, if it is red, indicates ketone body, acetoacetic acid.
- Now boil the above solution for 5 minutes.
- Color disappear indicates acetoacetic acid. By boiling acetoacetic acid changes to acetone by losing CO2.
- The color remains red, indicating the presence of salicylates.
- Nitroprusside Method:
- It is 10 times more sensitive to acetoacetate than acetone.
- Strip method:
- Take urine (freshly voided sample) + add sodium nitroprusside (strips) = Deep violet color in positive cases.
- It has no reaction to β-hydroxybutyrate.
- Rothera’s test is the modification of the Nitroprusside method.
- Nitroprusside tube method:
- Add 0.5 to 1.0 grams of nitroprusside to the bottom of the test tube, or can put it on porcelain tile.
- Add one drop of freshly voided urine. Sufficient to moisten the powder.
- Observe for one minute for the development of mauve-purple color.
- It is easy to assess the color when testing in a test tube. Can see better against the white background.
- Results are reported as:
Color change of the reagent Test result for ketones No color change Ketones Negative Slight purple color Ketones are + Moderate purple color Ketones are ++ Dark purple color Ketones are +++
- For β-hydroxybutyrate, urine is heated to convert β-hydroxybutyrate to acetone and acetoacetate by oxidation.
- Commercial kits are available to estimate the β-hydroxybutyrate.
- Ketone bodies in the urine:
- Urine ketone bodies test detects acetoacetate and acetone.
Signs and Symptoms of diabetic ketoacidosis
- This condition is seen in carbohydrates deficiency or starvation, or frequent vomiting.
- The patient will have a thirst and a dry mouth.
- Increased frequency of urine.
- There is easy fatigue.
- There may be nausea, vomiting, and abdominal pain.
- There is a fruity odor breath.
- Difficult in concentration and confusion.
- This condition may become very serious if not treated in time.
- Ultimately patient may go into a coma.
Typical findings in diabetic ketoacidosis :
|Blood glucose||300 to 500 mg/dL|
|Blood gases||Total CO2 = decreased|
|Insulin (plasma)||0 to low|
|Serum lactate||2 to 3 mmol/L|
The complication of diabetic ketoacidosis:
- There is brain edema due to fluid accumulation.
- The patient may have a cardiac arrest.
- The patient may go into kidney failure.
- Start with saline for volume replacement.
- Insulin infusion (but delay if serum potassium level is low <_3.3 meq/L.
- Potassium replacement when the serum level is <5.5 meq/L.
- Glucose drip (5% dextrose with 0.45% saline when the plasma glucose level is <250 mg/dL).
- Continue glucose and insulin until the anion gap is <12 meq/L.