A 14 year Old Boy with an Episode Of DKA - Case Study

A 14-year-old boy with an 8-year history of  type I diabetes mellitus has been sick since yesterday when he began vomiting. His diabetes has been reasonably well controlled with a dosage of 20 units of glargine insulin taken daily. He uses a carbohydrate ratio of 1:20 and correction factor of 1:50 for mealtime bolus insulin. He has had several episodes of DKA in the past, but not for approximately 4 years. Yesterday, when he began vomiting, glucose concentration was 400 and his urine acetone was negative, so he took his usual dose of insulin. He has had intense polyuria and polydipsia for the last
24 hours. This morning, approximately 6 hours ago, his mother decided to withhold his insulin because of continued nausea and vomiting.

Physical examination reveals a drowsy young boy who can respond to questioning. His BP is 90/70 mm Hg; pulse, 124 per minute; respirations, 30 per minute; and temperature, 38.3°C (100.9°F). His mucous membranes are dry and the ocular globes are soft and sunken, but the funduscopic findings
are normal. Bowel sounds are absent and he has generalized abdominal tenderness without rebound. The deep tendon reflexes are hypoactive, but there are no localizing neurologic signs. The rest of the examination findings are normal.

Laboratory data consist of the following:

• Hgb, 16.4 g/dL; hematocrit (Hct), 53%; 
• WBC, 16,942/ mm3 (93% polymorphonuclear leukocytes); 
• BUN, 40bmg/dL; creatinine, 1.8 mg/dL; 
• glucose, 847 mg/dL; serum ketones, strongly positive at 1:4 dilution; 
• sodium, 126 mEq/L potassium, 4.3 mEq/L; chloride, 100 mEq/L; and bicarbonate, 6 mEq/L.
• Urinalysis reveals a specific gravity of 1.030; glucose of 4+; acetone, strongly positive; and trace amounts of protein. 
• Arterial blood gas analysis reveals a pH of 7.08, partial pressure of carbon dioxide (PCO2) of 12 mm Hg, and partial pressure of oxygen (PO2) of 80 mm Hg. 
• An ECG shows sinus tachycardia with flat T waves. 
• Chest radiographic study is normal. 
• Abdominal radiographs show gastric distention, but otherwise the findings are normal.

1. What is the diagnosis and pathophysiologic process of this patient's disease?
2. How is the liver involved in the genesis of DKA?
3. What is the status of the patient's fluid and electrolyte levels?
4. What are the major goals of therapy?
5. What precipitated this episode of DKA?

Answers and Discussion

1. What is the diagnosis and pathophysiologic process of this patient's disease?
This patient has type I diabetes mellitus and is presenting with an episode of  diabetic ketoacidosis (DKA).
DKA is initiated by an absolute or relative insulin deficiency and an increase in the level of counterregulatory catabolic hormones, leading to the hepatic overproduction of glucose and ketone bodies. Consistent with this, the patient's laboratory data show the presence of marked hyperglycemia, ketonemia, ketonuria, and severe metabolic acidosis. The patient's tachypnea is also consistent with his acidotic state.
The destruction of pancreatic β cells leading to type I diabetes mellitus is thought to be mediated by the activation of autoimmune processes in genetically predisposed people. The presence of antiislet and antiinsulin antibodies, the existence of inflammatory cells around the islet cells, and the temporary amelioration of new -onset type I diabetes mellitus by immunosuppressive therapy all provide strong evidence for an autoimmune basis of pancreatic β-cell destruction.

2. How is the liver involved in the genesis of DKA?
Hepatic ketogenesis and the development of DKA depend on both the rate of substrate (FFA) supply to the liver and the activation of the hepatic ketogenic process, the latter being modulated by the relative increase in the glucagon-to-insulin ratio that prevails during DKA. The insulin deficiency
leads to the activation of lipolysis and an increased supply of circulating FFA. In the liver these molecules undergo successive β-oxidation to acetyl coenzyme A (CoA). During DKA the unrestrained FFA mobilization and oxidation trigger the production of excess amounts of acetyl CoA, which undergo condensation to acetoacetyl CoA, a precursor of the ketone bodies acetoacetate, acetone, and β-hydroxybutyrate.

3. What is the status of the patient's fluid and electrolyte levels?
The patient's physical examination reveals signs of severe dehydration and intravascular hypovolemia (note his hypotension, tachycardia, and the dry mucous membranes). DKA, if not treated early, results in a severe total-body depletion of fluid (usually several liters) and electrolytes due to the following factors:

• The hyperglycemia and hyperketonemia lead to osmotic diuresis and the urinary loss of fluid and electrolytes.
• Because of acidosis, potassium is also shifted from the intracellular to extracellular fluid space and then lost during osmotic diuresis. Therefore, the serum potassium levels may not accurately reflect the total-body deficiency.
• Vomiting, as in this patient, causes the further loss of fluid and electrolytes.
• Muscle catabolism (proteolysis), which results from the insulin deficiency, leads to the loss of potassium, phosphate, magnesium, and nitrogen.

4. What are the major goals of therapy?

The immediate therapeutic goals are 

(a) to replenish the fluid (starting with isotonic saline) and electrolytes; and 

(b) to provide adequate insulin to inhibit lipolysis and ketogenesis and normalize carbohydrate metabolism, both in the liver (by inhibiting glucose production) and in the peripheral tissues (by enhancing disposal of glucose and ketone bodies). 

Insulin therapy is best administered in the form of a continuous IV infusion. During the fluid, electrolyte, and insulin therapy, the patient's blood glucose and electrolyte levels (especially potassium) should be monitored frequently and appropriate adjustments made. Additional therapeutic objectives include the identification and management of possible precipitating factors (e.g., infection, stress, and medication errors) and the implementation of measures to prevent the recurrence of DKA.

5. What precipitated this episode of DKA?

The immediate precipitating event of this patient's DKA is the withholding of insulin. An underlying stress or infection (e.g., gastroenteritis), which may also be present in this patient, should be evaluated and managed.