Ketoacidosis diagnosis, Diabetic Ketoacidosis
- Blood is needed to prepare the serum.
- The urine sample may also be used.
Indications for Ketoacidosis diagnosis
- Ketone bodies are advised in patients with diabetes mellitus.
- The advice in case of uncontrolled diabetes mellitus.
- Ketoacidosis is associated with alcoholism, starvation, and a high protein diet.
Definition of Ketoacidosis
- There is inhibition of glycolysis in ketoacidosis while glycogenolysis and gluconeogenesis are stimulated.
- There is hyperglycemia and deranged acid balance, and electrolyte imbalance.
- It is acute life-threatening metabolic acidosis due to uncontrolled diabetes mellitus ( usually type 1 and infrequently type 2).
- This condition occurs when decompensation by other diseases, insulin deficiency, and excess hormone-producing glucose.
- Another definition:
- There is a lake of insulin, which leads to the metabolism of protein and fat to provide energy. Normally energy is supplied by carbohydrates.
- Ketone bodies and other metabolic acids accumulate in the blood.
- Accumulation of ketone bodies (acetone, acetoacetate, and β-hydroxybutyrate) is the principal feature of diabetic ketoacidosis.
- There is hyperglycemia. Ketones and glucose appear in the urine.
- There is hyperosmolarity.
- Low pH.
- Patients have lethargy and may go into a coma.
Pathophysiology of Ketoacidosis
- Acetyl coenzyme A (acetyl CoA) from the TCA (Tricarboxylic acid cycle) is at the junction of glucose, protein, and fat metabolism.
- Free fatty acids enter the TCA cycle at Acetyl CoA. It changes to acetoacetyl CoA.
- It then forms HMG CoA (3-hydroxy-3-methylglutaryl CoA).
- This HMG CoA can be metabolized to cholesterol or converted to acetoacetate.
- Acetoacetate can change into:
- Spontaneous decarboxylation to acetone in the lungs.
- Or Enzymatic reduction to β-hydroxybutyrate.
- Acetoacetate and β-hydroxybutyrate are called keto acids or ketone bodies.
- Ket acids are the energy source for the brain, kidneys, and cardiac muscles.
- Kidneys excrete an excess of Acetoacetate and β-hydroxybutyrate with a loss of Na+ and K+.
- Loss of Na+ and K+ from kidneys leads to retention of the H+ ions.
- In diabetes mellitus, low insulin level leads to mobilize the fatty acids from triglycerides.
- Fatty acid degradation increases as it becomes the major source of energy for the cells.
- Increased fatty acid metabolism gives rise to increased molecules of acetyl CoA.
- This excess Acetyl CoA enters the TCA cycle to produce energy.
- Still, some of it forms ketone bodies and ketosis (keto acids).
- Increased production of keto acids utilizes HCO3– and lowers the blood pH (acidosis).
- This mechanism occurs in starvation, except there is hypoglycemia instead of hyperglycemia.
- The liver takes up long-chain fatty acids.
- In the liver are reesterified to triglycerides and stored.
- Or these are converted to very-low-density lipoprotein and return to the blood.
- Infants have earlier ketonuria than adults after decreased food intake.
In uncontrolled diabetes mellitus:
- low insulin level leads to:
- increased lipolysis.
- Decreased reesterification.
- There are increased plasma-free fatty acids.
- Insulin and glucagon ratio changes.
- This ratio is changed and enhances fatty acid oxidation.
- It leads to increased ketone body formation in the liver, and decreased peripheral tissue metabolism gives rise to accumulation in the blood.
- There is an accumulation of acetoacetate ketone bodies in the blood.
Signs and Symptoms of diabetic ketoacidosis:
There may be :
- A cough.
- Chest pain.
Causes of ketone bodies formation:
- Frequent vomiting.
- Diabetes mellitus.
- Glycogen storage disease (von Gierke disease).
- During pregnancy.
Lab findings of diabetic ketoacidosis:
- The glucose level may range from 300 to 500 mg/dL.
- Ketones bodies are beta-hydroxybutyric acid, acetoacetic acid, and acetone is positive.
- These are produced during gluconeogenesis, mainly due to increased fatty acid oxidation to acetyl CoA.
- Excessive concentration of ketone bodies in the blood is called ketonemia.
- When there is increased excretion in the urine, called ketonuria.
- Electrolytes show :
- Decreased Sodium.
- Increased Potassium.
- The anion gap is increased.
- Total CO 2 decreased.
- Blood gases show:
- pH decreased.
- Metabolic acidosis.
- Bicarbonates are decreased.
Ketoacidosis (Diabetic ketosis):
|Glucose||Blood glucose level = 300 to 500 mg/dL (250 to 600 mg/dL)|
|Plasma insulin||Low or 0|
|Ketones||Positive (Acetone, Beta-hydroxybutyric acid, and acetoacetic acid)|
|Plasma acetone||Positive in diluted plasma|
Method to detect ketone bodies in the urine (Ketonuria):
Sodium nitroprusside reaction gives lavender color.
- This is very sensitive 10 times for acetoacetate than with acetone. It detects acetoacetate and acetone.
- It does not react with β-hydroxybutyrate.
- Take 0.5 to 1.0 gram (pea-size) of well-mixed nitroprusside reagent in a test tube or on the tile.
- Add a drop of a fresh urine sample to the reagent (Nitroprusside).
- After one minute, check the color.
- Results reported as:
- No color change = Ketones negative.
- Slight purple color = Ketone positive (+).
- Moderate purple color = Ketone positive (++).
- Dark purple color = Ketone positive (+++).
- A false-positive test is seen in:
- In the presence of L-dopa.
- In the presence of the increased amount of phenyl-pyruvic acid.
Gerhardt’s ferric chloride test mainly measures the acetoacetate ketone body.
- This reaction only detects acetoacetate ketones in the urine.
- Ferric chloride reacts with acetoacetate ketone body and gives red color.
- On boiling, acetoacetate loses CO2 and forms acetone. Ferric chlorides do not react with acetone, and the color disappears.
- If the red color persists, then it indicates salicylates.
Treatment of Diabetic ketoacidosis
- 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.
- Try to find the causative agent.
Question 1: What is the level of insulin in diabetic ketoacidosis.
It is low or zero.
Question 2: Does sodium nitroprusside reaction detect beta-hydroxybutyrate ketone body.
It only detects acetoacetate and acetone ketone bodies.