Causes of metabolic acidosis

In practically every CICM exam paper, the candidates are presented with an ABG (sometimes several) which expect the diagnosis of a metabolic acidosis of some sort. It is therefore essential to develop some sort of mnemonic aid to recall the differential diagnosis of metabolic acidosis. In spite of its many obvious disadvantages, the anion gap classification of metabolic acid-base disorders is useful tool.

Causes of Metabolic Acidosis

The MUDPILES mnemonic is showing its age. Nowhere is there space for citrate, for instance. This is a problem, as several SAQs (eg. Question 3.3 from the second paper of 2013) present the candidate with a citrate-based acidosis. The "P" in PILES used to be "Paraldehyde", but paraldehyde has fallen out of favour since the 1980s, and so "Pyroglutamic acidosis" is probably a better substitute. Iron is not a cause of a high anion gap on its own (in fact, ionised iron is cationic) but it can cause the anion gap to increase when it is removed from solution by its conversion to ferric hydroxide.   Also, methanol and ethylene glycol are insufficiently distinct to merit their own individual places in the mnemonic (both are toxic alcohols). In spite of these concerns, the MUDPILES meme is still propagated throughout the medical school curricula, as the educators cynically expect their graduates to never have to seriously think about acidosis. It's simply irrelevant in the skin lesion clinic, cath lab or endoscopy suite. After all, you can always call the ICU if you can't make sense of the blood gas; they will sort it out.

A diagnostic approach to metabolic acidosis

Though a metabolic acidosis of one sort or another appears in virtually every written paper, the actual approach to metabolic acidosis has only been asked about once, in the dark past of the CICM fellowship papers - namely, Question 11(16) from the second paper of 2003.

1) Calculate the anion gap

  • (Na+ + K+) - (Cl- + HCO3-)
  • The anion gap achieves a diagnostic classification of metabolic acidosis
  • A raised anion gap identifies unmeasured anions (eg. lactate, ketones, metabolic byproducts of toxic alcohols) as potential causes of the acidosis
  • A normal anion gap identifies changes in chloride and bicarbonate as causes of the metabolic acidosis

2) Calculate the delta ratio

  • Delta ratio = (change in anion gap) / (change in bicarbonate)
  • The delta ratio quantifies the contribution to the acidosis of unmeasured anions and the chloride-bicarbonate balance
  • This way, mixed acid-base disorders may be revealed.

3) Measure urinary electrolytes and calculate the urinary anion gap (for normal anion gap metabolic acidosis)

  • Urinary anion gap can be used to differentiate between gastrointestinal and renal causes for the normal anion gap metabolic acidosis.
  • A high urinary anion gap suggests that there is a renal cause for the acidosis (i.e. that chloride and ammonium excretion is inappropriately low)
  • A low or negative urinary anion gap suggests that there is an appropriate attempt to excrete chloride and ammonium, and that the cause of acidosis is extrarenal.

4) Measure the serum osmolality and calculate the osmolar gap 

  • The osmolar gap will reveal whether there are osmotically active substances in the bloodstream which are not measured as a part of the normal bicohemistry. These may be responsible for the raised anion gap metabolic acidosis.
  • The osmolar gap may narrow the list of differentials
  • The osmolar gap may be elevated even where there is no acidosis (eg. after mannitol). 


Kraut, Jeffrey A., and Nicolaos E. Madias. "Metabolic acidosis: pathophysiology, diagnosis and management." Nature Reviews Nephrology 6.5 (2010): 274-285.


Fencl, Vladimir, et al. "Diagnosis of metabolic acid–base disturbances in critically ill patients." American journal of respiratory and critical care medicine162.6 (2000): 2246-2251.


Moviat, M. A. M., F. M. P. Van Haren, and J. G. Van Der Hoeven. "Conventional or physicochemical approach in intensive care unit patients with metabolic acidosis." Critical Care 7.3 (2003): R41.


Park, M., et al. "Clinical utility of standard base excess in the diagnosis and interpretation of metabolic acidosis in critically ill patients." Brazilian Journal of Medical and Biological Research 41.3 (2008): 241-249.