What are the primary biochemical arrangements in Diabetic Ketoacidosis (DKA)?

Primary Biochemical Derangements in Diabetic Ketoacidosis (DKA)

Diabetic ketoacidosis is characterized by the triad of hyperglycemia, ketosis, and metabolic acidosis resulting from insulin deficiency and increased counterregulatory hormones. 1

Core Biochemical Abnormalities

Metabolic Derangements

• Hyperglycemia: Blood glucose typically >250 mg/dL 1
• Metabolic acidosis:
  • Arterial pH <7.3
  • Serum bicarbonate <18 mEq/L
  • Elevated anion gap (>10-12 mEq/L) 1
• Ketosis/Ketoacidosis:
  • Elevated serum ketones (β-hydroxybutyrate and acetoacetate)
  • Positive urine ketones 1

Electrolyte Abnormalities

• Total body deficits 1:
  • Water: ~6 liters (100 mL/kg)
  • Sodium: 7-10 mEq/kg
  • Potassium: 3-5 mEq/kg
  • Phosphate: 5-7 mEq/kg
  • Magnesium: 1-2 mEq/kg
  • Calcium: 1-2 mEq/kg

Pathophysiological Mechanisms

Hormonal Alterations

1. Insulin deficiency (absolute or relative)
2. Increased counterregulatory hormones:
   • Glucagon
   • Catecholamines
   • Cortisol
   • Growth hormone 1

Metabolic Consequences

1. Glucose metabolism disruption:

   • Increased hepatic and renal glucose production
   • Impaired peripheral glucose utilization
   • Resulting in hyperglycemia 1

2. Lipid metabolism disruption:

   • Enhanced lipolysis from adipose tissue
   • Increased free fatty acid release into circulation
   • Unrestrained hepatic fatty acid oxidation to ketone bodies 1

3. Osmotic effects:

   • Glycosuria leading to osmotic diuresis
   • Dehydration
   • Electrolyte losses 1

Diagnostic Criteria by Severity

Parameter	Mild DKA	Moderate DKA	Severe DKA
Plasma glucose	>250 mg/dL	>250 mg/dL	>250 mg/dL
Arterial pH	7.25-7.30	7.00-7.24	<7.00
Serum bicarbonate	15-18 mEq/L	10 to <15 mEq/L	<10 mEq/L
Urine/serum ketones	Positive	Positive	Positive
Anion gap	>10 mEq/L	>12 mEq/L	>12 mEq/L
Mental status	Alert	Alert/drowsy	Stupor/coma

1

Clinical Manifestations Related to Biochemical Changes

• Kussmaul respirations: Deep, rapid breathing resulting from metabolic acidosis 1
• Dehydration signs: Poor skin turgor, tachycardia, hypotension 1
• Neurological changes: Ranging from alertness to profound lethargy or coma 1
• Gastrointestinal symptoms: Nausea, vomiting, abdominal pain due to acidosis and ketosis 2

Important Distinctions and Pitfalls

1. Distinguish from other ketotic states:

   • Starvation ketosis: Bicarbonate usually not lower than 18 mEq/L
   • Alcoholic ketoacidosis: Glucose rarely >250 mg/dL, often hypoglycemic 1

2. Distinguish from other causes of high anion gap metabolic acidosis:

   • Lactic acidosis
   • Salicylate, methanol, ethylene glycol ingestion
   • Chronic renal failure 1

3. Euglycemic DKA:

   • Can occur with sodium-glucose cotransporter-2 inhibitor use
   • Hyperglycemia may be absent or mild despite significant ketoacidosis 3

4. Cerebral edema risk:

   • Most common in children
   • Can develop during treatment
   • Associated with rapid correction of metabolic abnormalities 4

Understanding these biochemical derangements is crucial for proper diagnosis and management of DKA, a condition with significant morbidity and mortality if not properly treated.