Metabolic Acidosis

Normal pH of arterial blood = 7.35-7.45

Alkalemia = pH >7.45

Acidemia = pH <7.35

• High-Anion Gap Metabolic Acidosis (HAGMA): Anion gap > 12
• Normal-Anion Gap Metabolic Acidosis (NAGMA): Anion gap ≤ 12

Origin of the “Anion Gap”

• Na⁺ + unknown⁺ = HCO₃^– + Cl^– + unknown^–

• Na⁺ – (HCO₃^– + Cl^–) = unknown^– – unknown⁺

• Na⁺ – HCO₃^– – Cl^– = unknown^– – unknown⁺ = ANION GAP = ~10-12

High-Anion Gap Metabolic Acidosis (HAGMA) Differential Diagnosis

• Mnemonic: KU LOST
  • Ketones (starvation, alcoholism, DKA)
    • Starvation and DKA: Decreased ability to use glucose as an energy source creates an increase in fatty acid metabolism, leading to ketone production
    • Alcohol: Ketone production is similar in etiology to starvation and DKA, however, alcohol metabolism leads to an increased conversion of NAD⁺ to NADH, which reduces acetoacetate to β-hydroxybutyrate, which is undetectable by most nitroprusside-based ketone labs
  • Uremia (renal failure)
  • Lactic Acidosis (Type A, B, or D – see Lactic Acidosis)
  • Osmolar Gap elevation
    • Lab serum osmolality – calculated serum osmolality (2xNa + glucose/18 + BUN/2.8) >10
      • Ethylene Glycol ingestion (metabolized into oxalate, which precipitates with calcium to form kidney stones)
      • Methanol ingestion (metabolized into formic acid, “fixes” optic nerve -> look for visual disturbances)
      • Propylene Glycol (think lorazepam, phenobarbitol, dilantin…medicines that may come mixed with propylene glycol)
      • Treat with fomepizole (competitive inhibitor of alcohol dehydrogenase)
    • IF OSMOLAR GAP IS ELEVATED BUT THERE IS NO ACIDOSIS
      • Think isopropyl alcohol, mannitol, hyperproteinemia, severe hyperlipidemia
  • Salicylate (Aspirin) ingestion: HAGMA as a late presentation; initial presentation will be a respiratory alkalosis as salicylates stimulate the respiratory drive center of the brain
  • Tylenol/Toluene

Normal Anion Gap Metabolic Acidosis (NAGMA) Differential Diagnosis

• Think renal tubular acidosis or diarrhea (although other more diagnoses do exist, like toluene inhalation)
  • Check urine pH: will generally be elevated in patients with distal RTA
  • Check urine ammonium
    • Urine Anion Gap can be used as a surrogate measure ₍₁₎
      • Na⁺_U + K⁺_U – Cl^–_U: Elevated if >10. This elevated finding indicates a decreased chloride excretion, which by proxy indicates a low ammonium secretion, as the two are secreted together
    • Type I (Distal) RTA: pH > 5.5, urine anion gap elevated
      • Management: Bicarbonate therapy
    • Type II (Proximal) RTA: pH < 5.5, urine anion gap frequently normal, can be diagnosed by an elevation in the serum and urine osmolality with administration of IV bicarbonate
      • Management: Treat underlying condition if possible (removing offending agents (i.e. topiramate, acetazolamide, multiple myeloma) but if unable to correct underlying condition (i.e. Fanconi Syndrome), bicarbonate therapy is recommended

Respiratory Compensation

• Winter’s Formula: Expected P_aCO₂ = (1.5 x HCO₃^–) + 8 +/- 2
  • If patient’s measured P_aCO₂ > expected P_aCO₂, there is a secondary respiratory acidosis
  • If patient’s measured P_aCO₂ < expected P_aCO₂, there is a secondary respiratory alkalosis

Secondary Metabolic Disturbance

• Delta Gap = Calculated Anion Gap – Normal Anion Gap (~10)

• Corrected HCO₃^– = Normal HCO₃^– (~24) – Delta Gap

• If measured HCO₃^– is significantly higher than the calculated corrected HCO₃^–: secondary metabolic alkalosis
• If measured HCO₃^– is significantly lower than the calculated corrected HCO₃^–: secondary metabolic acidosis

References

1. Alexander, Robert Todd, and Martin Bitzan. “Renal Tubular Acidosis.” Pediatric Clinics of North America, Elsevier, 17 Nov. 2018, http://www.sciencedirect.com/science/article/abs/pii/S0031395518301354?via=ihub.