College Answer

A metabolic acidosis is a process which, if uncorrected, would lead to an acidaemia.  It is usually associated with a low bicarbonate concentration (or total CO2), but an acidosis may be masked by a co-existing metabolic alkalosis.  A simple classification is to categorise acidosis into accumulation of acids (measured, i.e. chloride [hyperchloraemic metabolic acidosis] or unmeasured [increased anion gap metabolic acidosis]), or renal or gastrointestinal loss of bicarbonate (with absorption of chloride, resulting in hyperchloraemic metabolic acidosis). The anion gap (Na + K – Cl – HCO3) is usually determined primarily by negatively charged plasma proteins and has a range of approximately 10 to 16 mmol/L.  This will be decreased by about 2.5 mmol/L for every decrease inalbumin by 10 g/L.  An increased anion gap (which can occur in the absence of a low bicarbonate concentration) may be due to a fall in unmeasured cations (Ca, Mg), or more commonly to the presence of unmeasured anions (e.g. lactate [d- or l-], ketoacids, formate [methanol], glycolate and oxalate [ethylene glycol].  Some of these can be specifically measured.  Calculation of an osmolar gap may also help as a screening test for methanol or ethylene glycol intoxication once alcohol has been excluded (calculated osmolality = 2*Na + Glucose + Urea + ethanol/4.6).   Urinary pH (inappropriately alkaline for an acidaemia) and electrolytes may facilitate eliciting the specific cause of the renal bicarbonate loss (e.g. renal tubular acidosis).

Discussion

The college answer - I assume - outlines in prose the features which the examiners would have been looking for. The answer, in my opinion, calls for a systematic and structural response. The candidate ought to demonstrate that their approach to the evaluation of metabolic acidosis is not a disorganised bafflement of various physiological principles and biochemical tests.

Thus:

• 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
• Calculate the delta ratio
  • (change in antion 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
• For normal anion gap metabolic acidosis, measure urinary electrolytes and calculate the urinary anion gap
  • 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.
• For high anion gap metabolic acidosis, 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

Given that one cannot predict the opinions of the examiners regarding Stewart's physicochemical approach to acid-base disorders, in an answer like this one, the candidate should probably give it a miss.