elevated anion gap

**Definition/Calculation:** AG = Na⁺ − (Cl⁻ + HCO₃⁻). Normal ≈ 8–12 mEq/L (K⁺ not included). Represents unmeasured anions (albumin, phosphate, sulfate, organic anions) minus unmeasured cations (Ca²⁺, Mg²⁺, K⁺). Because electroneutrality must hold, a gain of an unmeasured acid anion (with H⁺ consuming HCO₃⁻) raises the gap while Cl⁻ stays normal → "normochloremic" acidosis.

**Causes of high AG metabolic acidosis (MUDPILES):** - **M**ethanol (formic acid; optic neuritis/blindness, treat w/ fomepizole) - **U**remia (retained sulfates/phosphates/organic anions in advanced CKD/AKI) - **D**KA (β-hydroxybutyrate, acetoacetate) and other ketoacidosis (alcoholic, starvation) - **P**ropylene glycol (lorazepam infusions), **P**aracetamol/acetaminophen (pyroglutamic acid), Phenformin/metformin (lactic) - **I**soniazid, **I**ron - **L**actic acidosis (shock, ischemia, sepsis, metformin; type A = hypoxic, type B = non-hypoxic) - **E**thylene glycol (oxalate crystals in urine, calcium oxalate, AKI; treat w/ fomepizole, dialysis) - **S**alicylates (mixed respiratory alkalosis + AG metabolic acidosis; tinnitus; treat w/ bicarbonate, dialysis) Newer mnemonic GOLDMARK: Glycols, Oxoproline, L-lactate, D-lactate, Methanol, Aspirin, Renal failure, Ketoacids.

**Workup/Clinical pearls:** - Check **osmolal gap** (measured − calculated osmolality) if toxic alcohol suspected: elevated in methanol, ethylene glycol (early), also isopropyl alcohol (but no acidosis; ketosis w/o acidosis). - **Delta-delta (Δ/Δ) ratio** = ΔAG / ΔHCO₃⁻ = (AG − 12)/(24 − HCO₃⁻): - 1–2: pure AG acidosis - <1: concurrent non-gap (normal AG) metabolic acidosis - >2: concurrent metabolic alkalosis (or pre-existing high HCO₃⁻/chronic respiratory acidosis) - **Winter's formula**: expected PCO₂ = 1.5(HCO₃⁻) + 8 ± 2, to assess respiratory compensation. - **Albumin correction:** corrected AG = AG + 2.5 × (4.0 − albumin g/dL). Hypoalbuminemia lowers AG and can mask a true elevation. - Low AG: hypoalbuminemia, multiple myeloma (cationic paraproteins), lithium/bromide intoxication (bromide falsely raises Cl⁻ on some assays), hypercalcemia/hypermagnesemia. - **Normal AG (hyperchloremic) acidosis** for contrast (HARDASS): Hyperalimentation, Addison's disease, RTA, Diarrhea, Acetazolamide, Spironolactone, Saline infusion. Urine AG helps differentiate GI vs renal loss.

**Management:** Treat the underlying cause (insulin/fluids for DKA, fluids/source control for lactic acidosis, fomepizole ± dialysis for toxic alcohols, dialysis for uremia/salicylate toxicity). Bicarbonate generally reserved for severe acidosis (e.g., pH <7.0–7.1), salicylate toxicity, or specific toxicologic indications.

**Board relevance:** Frequently tested with ABG interpretation (low pH, low HCO₃⁻, compensatory low PCO₂), toxicology vignettes (ethylene glycol – oxalate crystals; methanol – visual changes; salicylates – tinnitus, mixed acid-base), and DKA.