Ideally, for evaluating acid-base status, an arterial blood-gas sample and venous biochemistry profile on blood collected and handled appropriately should be done and interpreted together as indicated under the summary of laboratory detection of acid-base disturbances. Biochemical test results associated with acid-base status on a chemistry panel are the following:
- Bicarbonate: This is a dependent variable and the main buffer for accumulated non-carbonic acids, such as lactate or ketones. Bicarbonate does not buffer carbonic acid (carbon dioxide combined with water). A change in bicarbonate can be due to a primary metabolic disorder or compensation (secondary to) a primary respiratory disturbance. Distinguishing which is primary and secondary requires a blood gas analysis and assessment of the patient for the cause of acid-base disturbances. Note that storage of blood on cells will cause in vitro lactic acid accumulation, which will decrease the bicarbonate in the tube.
To interpret the bicarbonate concentration and determine why it is low or high, one can look at the anion gap and corrected chloride. Look at the anion gap first if bicarbonate is low and the corrected chloride if the bicarbonate is high. Look at both anion gap and corrected chloride if bicarbonate is normal (if they are all normal, there is likely not an acid-base disturbance).- Low bicarbonate, high anion gap: Supports a high anion gap or titration acidosis due to accumulation of a noncarbonic (non-volatile) acid that does not contain chloride, e.g. ketoacidosis, ethylene glycol toxicosis. This type of metabolic acidosis is always primary.
- Low bicarbonate, normal anion gap, high corrected chloride: Supports a bicarbonate loss acidosis, with retention of chloride, e.g. secretory diarrhea in calves. This type of acidosis can be primary (e.g. diarrhea in calves) or secondary to a primary respiratory alkalosis (where the kidney excretes bicarbonate and retains chloride, via reducing ammoniagenesis in the proximal tubules [NH4Cl is retained] and decreasing H+-ATPase activity in the distal tubules [with secondary retention of chloride]).
- High bicarbonate, low corrected chloride, anion gap usually normal: Supports a metabolic alkalosis with loss of a chloride-containing non-carbonic acid. This can be primary (e.g. loss of HCl with vomiting gastric contents) or secondary to a primary respiratory acidosis (where the kidney excretes hydrogen with chloride by increasing ammoniagenesis in the proximal tubules and increasing H+-ATPase activity in the distal tubules).
- High bicarbonate, normal corrected chloride, anion gap usually normal: This is uncommon and could be due to administration of bicarbonate-rich fluids (primary metabolic alkalosis), a mixed primary hyperchloremic metabolic acidosis and primary metabolic alkalosis with alkalosis dominating, or an error in measurement of bicarbonate (e.g. severe muscle injury).
- Anion gap: This should be assessed in conjunction with the bicarbonate and is data that is not provided by standard blood-gas analysis. The anion gap principally helps with distinguishing between a primary titration or high anion gap metabolic acidosis and a loss of bicarbonate or normal anion gap metabolic acidosis (can be primary or secondary) as indicated above. Mild changes in the anion gap should not be over-interpreted. The anion gap is a calculation but it means unmeasured anions (which are far more abundant) minus unmeasured cations (which are far less abundant).
- Strong ions: Of the “measured” strong ions (chloride and sodium), chloride is the most important, because changes in chloride that are disproportionate to changes in free water or sodium (as calculated by the corrected chloride or “eye-balled”) indicate a metabolic acid-base disturbance.
- High corrected chloride or a chloride concentration that is disproportionately high compared to the sodium concentration: Usually associated with a metabolic acidosis, i.e. low bicarbonate concentration and a normal anion gap. As indicated above, this can be primary or secondary to a primary respiratory alkalosis.
- Low corrected chloride or a chloride concentration that is disproportionately low compared to the sodium concentration: Usually associated with a metabolic alkalosis, i.e. high bicarbonate concentration and a normal anion gap. As indicated above, this can be primary or secondary to a primary respiratory acidosis.
- Renal tests: Because the kidney may be the cause of an acid-base disturbance and is the main organ compensating for a primary respiratory disturbance or correcting for a primary metabolic disturbance, renal test results (urea nitrogen and creatinine) should always be evaluated along with acid-base results (along with urinalysis results, if available).
- “Unmeasured” ions:
- Phosphate: Although results are provided on the chemistry panel, phosphate is an “unmeasured” anion. Increases in phosphate, e.g. moderate to severe azotemia (usually of renal origin) is associated with a hyperphosphatemic acidosis per strong ion principles. Phosphate, along with hippurate, sulfates and citrates, are normally produced from amino acid metabolism and normally excreted by the kidney (“titratable acidity”). Decreased renal function with inability to excrete the acid load may result in a primary high anion gap or titration metabolic acidosis due to accumulation of these acids, however a mild hyperphosphatemia from a mild azotemia is unlikely to induce major acid-base abnormalities. Thus phosphate is usually considered along with renal test results when evaluating the renal response or contribution to an acid-base disturbance.
- Albumin: This is negatively charged at physiologic pH and acts as a weak acid (H+ only weakly dissociates from the protein). Low albumin (more common than high albumin) may mildly affect the anion gap (decrease with low albumin, increase with high albumin) because it is an “unmeasured” anion (but a weak one!). A decrease in albumin is considered a hypoproteinemic alkalosis by strong ion principles.
- Magnesium and calcium: Free ionized versions of these minerals (in g/dL quantities in serum, calcium is far more abundant than magnesium) may alter the anion gap (decrease).
- γ-globulins: Immunoglobulins are cationic at physiologic pH. Marked increases in immunoglobulins (e.g. multiple myeloma) may affect the anion gap (decrease).
