Ketoacidosis diagnosis

Sample for Ketoacidosis diagnosis

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

Indications for Ketoacidosis

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.

Another definition of Ketoacidosis:

1. A lake of insulin 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.

4. In diabetes mellitus, low insulin levels mobilize fatty acids from triglycerides.
5. Fatty acid degradation increases as it becomes the cell’s major energy source.
6. 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).
7. This mechanism occurs in starvation, except there is hypoglycemia instead of hyperglycemia.
8. 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.
9. Infants have earlier ketonuria than adults after decreased food intake.

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.

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 and acetoacetic acid, and acetone is positive.
   • These are produced during gluconeogenesis due to increased fatty acid oxidation to acetyl CoA.
   • An 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/Clinical presentation
Glucose	Blood glucose level = 300 to 500 mg/dL (250 to 600 mg/dL)
Plasma insulin	Low to zero
Ketones	Positive (Acetone, Beta-hydroxybutyric acid, and acetoacetic acid)
Plasma acetone	Positive in diluted plasma
Serum BUN	Mild increase
Serum lactate	2 to 3 mmol/L
Electrolytes	Sodium Decreased K+ increased (normal, increased, or low) HCO3+ decreased (<15 meq/L) Anion gap = increased (>12 meq/L) Serum magnesium = Normal or increased Serum osmolality = <320 mOsm/L
Blood gases	pH decreased (<7.30) Total CO2 decreased
Clinical signs and symptoms	Age = It is seen in the Younger age group Fever = Normal or low Type of diabetes = Usually type 1 Onset = It is acute/subacute H/O diabetes = Usually present Acetone breath = It is Present H/O prodrome = Usually <1 day Precipitating factor = Infection seen in 30% of the cases Unknown in 20% of the cases Acetone breath smell = It is usually present Kussmaul respiration = It is present Dehydration = Less frequent Abdominal pain = It is usually present Changes in mental status = It is moderate Neurological presentation = It is rare Renal diseases = It is seen in 15% of the cases Cardiovascular diseases = It is seen in 15% of the cases H/O thrombosis = It is rarely seen Mortality =  It is <10%

 

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

Sodium nitroprusside reaction:

1. This reaction gives lavender color.
2. This is very sensitive, ten times more for acetoacetate than with acetone. It detects acetoacetate and acetone.
3. It does not react with β-hydroxybutyrate.

The procedure of Sodium nitroprusside reaction for ketone bodies:

1. Take 0.5 to 1.0 grams (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 (+++).