Why BHB Levels Are Not Markedly Elevated in AKA/SKA and Bicarbonate Is Low in SKA
The apparent paradox of "not very high" BHB in AKA and SKA relates to measurement methodology rather than actual ketone body concentrations—standard nitroprusside-based ketone tests fail to detect β-hydroxybutyrate (the predominant ketone in these conditions), while bicarbonate levels below 18 mEq/L in SKA reflect the severity of metabolic acidosis from ketone accumulation without the confounding factors present in AKA.
Understanding the BHB Measurement Problem
Why BHB Appears "Not Very High"
- Standard ketone testing uses the nitroprusside method, which only detects acetoacetate and acetone but does NOT measure β-hydroxybutyrate (β-OHB), the strongest and most prevalent ketone body in ketoacidosis 1
- This creates a false impression that ketones are low or absent when BHB is actually markedly elevated 2, 3
- In AKA specifically, the β-hydroxybutyrate to acetoacetate ratio is extremely elevated (7:1 in AKA versus 3:1 in DKA), meaning even less acetoacetate is available for detection by standard tests 4
- Routine urine or serum ketone testing with ketostix may be negative in AKA despite profoundly elevated β-hydroxybutyrate levels 2
The Metabolic Redox State Explanation
- AKA occurs in a high redox state with elevated NADH (nicotinamide adenine dinucleotide and hydrogen), which favors conversion of acetoacetate to β-hydroxybutyrate 5
- The lactate to pyruvate ratio in AKA (19:1) is significantly higher than in DKA (11:1), reflecting this increased reducing environment 4
- This metabolic milieu shifts the equilibrium heavily toward β-OHB production, making standard tests even less useful 4
Bicarbonate Levels in Different Ketoacidotic States
Why Bicarbonate Is Profoundly Low (<18 mEq/L) in SKA
- Starvation ketoacidosis causes serum bicarbonate to drop below 18 mEq/L due to accumulation of ketone bodies (primarily β-hydroxybutyrate) that consume bicarbonate buffer 6
- The American College of Physicians notes that AKA often presents with profoundly low bicarbonate levels (often <18 mEq/L), causing severe acidosis 6
- In contrast, simple starvation ketosis (without the "acidosis" component) typically maintains bicarbonate above 18 mEq/L 6
Comparing Bicarbonate Across Ketoacidotic Conditions
- DKA diagnostic criteria specify bicarbonate <15 mEq/L for diagnosis, with mild DKA showing bicarbonate 15-18 mEq/L, moderate DKA 10-15 mEq/L, and severe DKA <10 mEq/L 1
- AKA typically presents with bicarbonate levels similar to or lower than DKA, often <18 mEq/L 6
- The resolution criterion for DKA includes achieving serum bicarbonate ≥18 mEq/L 1
Clinical Implications and Pitfalls
Avoiding Diagnostic Errors
- Do not rely on standard urine or serum ketone measurements by nitroprusside method to assess ketosis severity or treatment response in AKA or SKA 1
- During treatment, β-OHB converts back to acetoacetate, which may falsely suggest worsening ketosis when the patient is actually improving 1
- Request specific β-hydroxybutyrate measurement if available, rather than relying on ketostix or standard serum ketone panels 2, 3
Treatment Considerations
- AKA resolves much faster than DKA (mean 6±1 hours versus 16±2 hours) with appropriate fluid and glucose administration 4
- Intravenous glucose and saline are the essentials of AKA management; insulin, bicarbonate, and phosphate are usually not needed 3
- The similar initial hormonal profiles (decreased insulin, elevated counterregulatory hormones) in both DKA and AKA explain why both produce ketoacidosis, but the metabolic differences (glucose levels, redox state) account for the clinical distinctions 4
Key Distinguishing Features
- AKA: normal to mildly elevated glucose (rarely >250 mg/dL) or hypoglycemia, profoundly elevated β-OHB/acetoacetate ratio, bicarbonate often <18 mEq/L 6, 4
- DKA: glucose >250 mg/dL, bicarbonate <18 mEq/L (mild) to <10 mEq/L (severe), lower β-OHB/acetoacetate ratio 1, 4
- Starvation ketosis (without acidosis): bicarbonate typically remains >18 mEq/L 6