Acid-Base Abnormalities and Their Causes

High anion gap  [Na⁺ − Cl^– – HCO₃⁻] metabolic acidosis with increased osmolal gap

• Ethanol (check levels)
• Methanol (suspect in a patient with severe, particularly unexplained, high-anion gap metabolic acidosis associated with altered mental status, vision problems or severe gastrointestinal distress; check vision, funduscopy for optic disc hyperemia, and serum methanol levels)
• Ethylene glycol (check serum ethylene glycol levels, serum calcium levels, urine for fluorescence, and sediment for calcium oxalate crystals)
• Propylene glycol (discontinue IV lorazepam, IV diazepam!!)
• A key point here is that “high osmolal gap is also seen in diabetic or alcoholic ketoacidosis, lactic acidosis, and in chronic, but not acute, renal failure…. [Thus] …an elevated osmolal gap alone is not diagnostic of a particular disorder in the patient with a high anion gap metabolic acidosis. If, however, the history is not suggestive of either lactic acidosis or ketoacidosis, then a high osmolal gap (particularly if greater than or equal to 25) strongly points toward methanol or ethylene glycol intoxication.” Osmolal Gap by Burton D Rose MD.
• Perhaps even more importantly, “A normal osmolar gap does not rule out the ingestion of methanol or ethylene glycol. The osmolar gap may be low or undetectable early in the course despite a significant ingestion…. Given their toxicity, as soon as methanol or ethylene glycol ingestion is strongly suggested, ethanol administration and dialysis should be arranged.” Acid Base Case Studies. 2004. Ira Kurtz MD (p. 67). Also, if methanol or ethylene glycol ingestion is suspected, the patient should be, at minimum, monitored very closely both clinically and with appropriate laboratory investigations.
• In both methanol and ethylene glycol poisoning, the anion that is causing the gap is not lactate. Rather, it is formate and oxalate, among others. Therefore, your patient might be in very big trouble if he or she has a very high anion gap, and lactate and glucose are normal!

High anion gap metabolic acidosis with normal osmolal gap

• Lactic acidosis (most common cause of high anion gap in hospitalized patients)
• Renal failure (late)
• Ketoacidosis (diabetic, alcoholic, starvation; confirm by checking serum for ketones, unless diagnosis is clear; also check serum glucose to distinguish diabetic ketoacidosis from starvation, and alcoholic ketoacidosis)
• Salicylate poisoning: check serum salicylate level and look for concomitant respiratory alkalosis (drop in pCo2 is more than ten times the drop in bicarbonate), which in the setting of toxic ingestions, tinnitus and altered mental status, is fairly specific for salicylate poisoning
• Metformin

Normal anion gap metabolic acidosis with increased osmolal gap

• Isopropyl alcohol. (Suspect in an intoxicated patient with normal acid-base status and “fruity” breath: acetone gets blown off in the course of the metabolism of isopropyl alcohol. There is no anion gap because the metabolite of isopropyl alcohol is volatile doesn’t stick around to cause an anion gap. This also explains why all the smart chemists put isopropyl alcohol in their rubbing alcohol formulations, instead of, say, methanol or ethylene glycol.
• Ethanol
• Mannitol
• Glycine

Normal anion gap metabolic acidosis with normal osmolal gap

• Negative urine anion gap (suspectextrarenal causes)
  • Diarrhea (most common cause of normal anion gap metabolic acidosis)
  • intestinal or pancreatic fistulas or drainage
  • dilutional
  • post-hypocapnic metabolic acidosis
  • acetazolamide
  • Decreased serum anions such as albumen can falsely lower the anion gap and make an anion gap metabolic acidosis look like a normal anion gap metabolic acidosis. “Always remember to correct the expected anion gap for a decreased serum albumen concentration. (id at 101).
• Positive urine anion gap [Na⁺ + K⁺ − Cl^–] (suspect renal causes such as early renal failure or renaltubularacidoses)
  • Hypokalemia
    • Urine pH > 5.5: distal Renal Tubular Acidosis (Type I)
    • Urine pH < 5.5: proximal Renal Tubular Acidosis (Type II; consider Fanconi syndrome if you see glucosuria, aminoaciduria, etc.)
  • Hyperkalemia and urine pH < 5.5
    • Renal Tubular Acidosis Type IV, hypoaldosteronism

Metabolic alkalosis

• Chloride responsive (urine chloride < 20)
  • Vomiting (hypokalemic, hypochloremic metabolic alkalosis is fairly specific for gastric outlet obstruction, e.g., pyloric stenosis)
  • Diuretic use (remote)
• Chloride resistant (urine chloride > 20)
  • Hypertensive
    • Hypermineralocorticoidism
    • Check serum aldosterone level and plasma aldosterone:renin ratio
  • Hypo-ornormotensive
    • Diuretic use (current)
    • Milk-alkali syndrome, which is hypercalcemia, metabolic alkalosis, and renal insufficiency in the setting of ingestion of large amounts of calcium and bicarbonate, or “betel nuts” with calcium hydroxide paste. The concept here is that acute renal failure usually causes acidosis; if you see alkalosis in the setting of acute renal failure, be suspicious of milk-alkali syndrome; in addition, other symptoms of hypercalcemia may be present as well such as confusion, abdominal pain; the mnemonic for hypercalcemia is “abdominal groans, pain in bones, kidney stones, and psychiatric overtones“; electrocardiogram may show short QT segment.

References

• Pocket Medicine (2010) by Marc S. Sabatine MD, MPH
• Acid Base Case Studies (2004) by Ira Kurtz MD (reviewed here)
• Clinician’s Guide to Laboratory Medicine: Pocket (2009) by Samir P. Desai MD (reviewed here)