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Ketoacidosis diagnosis, Diabetic Ketoacidosis

Ketoacidosis diagnosis, Diabetic Ketoacidosis
May 20, 2022Chemical pathologyLab Tests

Ketoacidosis diagnosis

Sample

  1. Blood is needed to prepare the serum.
  2. The urine sample may also be used.

Indications for Ketoacidosis diagnosis

  1. Ketone bodies are advised in patients with diabetes mellitus.
    1. The advice in case of uncontrolled diabetes mellitus.
    2. Ketoacidosis is associated with alcoholism, starvation,  and a high protein diet.

Definition of Ketoacidosis

  1. There is inhibition of glycolysis in ketoacidosis while glycogenolysis and gluconeogenesis are stimulated.
  2. There is hyperglycemia and deranged acid balance, and electrolyte imbalance.
  3. It is acute life-threatening metabolic acidosis due to uncontrolled diabetes mellitus ( usually type 1 and infrequently type 2).
  4. This condition occurs when decompensation by other diseases, insulin deficiency, and excess hormone-producing glucose.
  5. Another definition:
    1. There is a lake of insulin, which leads to the metabolism of protein and fat to provide energy. Normally energy is supplied by carbohydrates.
    2. Ketone bodies and other metabolic acids accumulate in the blood.
    3. Accumulation of ketone bodies (acetone, acetoacetate, and β-hydroxybutyrate) is the principal feature of diabetic ketoacidosis.
    4. There is hyperglycemia. Ketones and glucose appear in the urine.
    5. There is hyperosmolarity.
    6. Low pH.
    7. Patients have lethargy and may go into a coma.

Pathophysiology of Ketoacidosis

  1. Acetyl coenzyme A (acetyl CoA) from the  TCA (Tricarboxylic acid cycle) is at the junction of glucose, protein, and fat metabolism.
  2. Free fatty acids enter the TCA cycle at Acetyl CoA. It changes to acetoacetyl CoA.
  3. It then forms HMG CoA (3-hydroxy-3-methylglutaryl CoA).
    1. This HMG CoA can be metabolized to cholesterol or converted to acetoacetate.
    2. Acetoacetate can change into:
      1. Spontaneous decarboxylation to acetone in the lungs.
      2. Or Enzymatic reduction to β-hydroxybutyrate.
      3. Acetoacetate and β-hydroxybutyrate are called keto acids or ketone bodies.
      4. Ket acids are the energy source for the brain, kidneys, and cardiac muscles.
      5. Kidneys excrete an excess of  Acetoacetate and β-hydroxybutyrate with a loss of Na+ and K+.
      6. Loss of Na+ and K+ from kidneys leads to retention of the H+ ions.
Ketones bodies and Diabetes Mellitus

Ketones bodies formation and Diabetes Mellitus

  1. In diabetes mellitus, low insulin level leads to mobilize the fatty acids from triglycerides.
  2. Fatty acid degradation increases as it becomes the major source of energy for the cells.
  3. Increased fatty acid metabolism gives rise to increased molecules of acetyl CoA.
    1. This excess Acetyl CoA enters the TCA cycle to produce energy.
    2. Still, some of it forms ketone bodies and ketosis (keto acids).
    3. Increased production of keto acids utilizes HCO3– and lowers the blood pH (acidosis).
  4. This mechanism occurs in starvation, except there is hypoglycemia instead of hyperglycemia.
  5. The liver takes up long-chain fatty acids.
    1. In the liver are reesterified to triglycerides and stored.
    2. Or these are converted to very-low-density lipoprotein and return to the blood.
  6. Infants have earlier ketonuria than adults after decreased food intake.
ketone bodies formation in diabetic and complications

ketone bodies formation in diabetes and complications

In uncontrolled diabetes mellitus:

  1. low insulin level leads to:
    1. increased lipolysis.
    2. Decreased reesterification.
    3. There are increased plasma-free fatty acids.
  2. Insulin and glucagon ratio changes.
    1. This ratio is changed and enhances fatty acid oxidation.
    2. It leads to increased ketone body formation in the liver, and decreased peripheral tissue metabolism gives rise to accumulation in the blood.
    3. There is an accumulation of acetoacetate ketone bodies in the blood.
ketone bodies ratio in diabetes mellitus

ketone bodies ratio in diabetes mellitus

Ketone bodies in diabetic patient

Ketone bodies in a diabetic patient

Signs and Symptoms of diabetic ketoacidosis:

There may be :

  1. A cough.
  2. Fever.
  3. Chills.
  4. Chest pain.
  5. Arthralgia.
  6. Dyspnoea.
  7. Tachycardia.
  8. Hypotension.
  9. Hypothermia.

Causes of ketone bodies formation:

  1. Starvation.
  2. Frequent vomiting.
  3. Diabetes mellitus.
  4. Glycogen storage disease (von Gierke disease).
  5. During pregnancy.

Lab findings of diabetic ketoacidosis:

  1. The glucose level may range from 300 to 500 mg/dL.
  2. 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.
  3. Electrolytes show :
    1. Decreased Sodium.
    2. Increased Potassium.
    3. The anion gap is increased.
    4. Total CO 2 decreased.
  4. Blood gases show:
    1. pH decreased.
    2. Metabolic acidosis.
    3. Bicarbonates are decreased.

Ketoacidosis (Diabetic ketosis):

Test Lab findings
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
Electrolytes
  1. Sodium Decreased
  2. K+ increased (normal, increased, or low)
  3. HCO3+ decreased (<5 meq/L)
  4. Anion gap = increased (>12 meq/L)
Blood gases
  1. pH decreased (<7.30)
  2. Total CO2 decreased

 

Diabetic ketoacidosis

Diabetic ketoacidosis

Method to detect ketone bodies in the urine (Ketonuria):

Sodium nitroprusside reaction gives lavender color.

    1. This is very sensitive 10 times for acetoacetate than with acetone. It detects acetoacetate and acetone.
    2. It does not react with β-hydroxybutyrate.
Sodium nitroprusside reaction for ketone bodies

Sodium nitroprusside reaction for ketone bodies

  1. Procedure:
    1. Take 0.5 to 1.0 gram (pea-size) of well-mixed nitroprusside reagent in a test tube or on the tile.
    2. Add a drop of a fresh urine sample to the reagent (Nitroprusside).
    3. After one minute, check the color.
    4. Results reported as:
      1. No color change = Ketones negative.
      2. Slight purple color = Ketone positive (+).
      3. Moderate purple color = Ketone positive (++).
      4. Dark purple color = Ketone positive (+++).
Ketones nitroprusside test in urine

Ketones nitroprusside test in urine

  1. A false-positive test is seen in:
    1. In the presence of L-dopa.
    2. In the presence of the increased amount of phenyl-pyruvic acid.

Gerhardt’s ferric chloride test mainly measures the acetoacetate ketone body.

  1. This reaction only detects acetoacetate ketones in the urine.
  2. Ferric chloride reacts with acetoacetate ketone body and gives red color.
  3. On boiling, acetoacetate loses CO2 and forms acetone. Ferric chlorides do not react with acetone, and the color disappears.
  4. If the red color persists, then it indicates salicylates.
 Ferric chloride test for acetoacetate ketone in the urine

Ferric chloride test for acetoacetate ketone in the urine

Treatment of Diabetic ketoacidosis

  1. Start with saline for volume replacement.
  2. Insulin infusion (but delay if serum potassium level is low <3.3 meq/L).
  3. Potassium replacement when the serum level is <5.5 meq/L.
  4. Glucose drip (5% dextrose with 0.45% saline when the plasma glucose level is <250 mg/dL.
  5. Continue glucose and insulin until the anion gap is <12 meq/L.
  6. Try to find the causative agent.
Question 1: What is the level of insulin in diabetic ketoacidosis.
Show answer
It is low or zero.
Question 2: Does sodium nitroprusside reaction detect beta-hydroxybutyrate ketone body.
Show answer
It only detects acetoacetate and acetone ketone bodies.

Possible References Used
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