In this installment, we look at underlying causes of metabolic acidosis, approaches for evaluating patients with suspected metabolic acidosis, and why measurement of the anion gap is of great usefulness in these cases.
Normal acid-base balance in human beings is generally achieved by the pulmonary excretion of CO2 and the renal excretion of inorganic acids related to protein metabolism. This balance may be roughly summarized with the Henderson-Hasselbalch equation:
pH=pKa + log10 (A/HA) or:
pH=6.10 + log((HCO3-) / (0.03 X pCO2)) with a normal pH of 7.35-7.45
Acidemia refers to a metabolic condition in which, simply, the pH is low; this may be due to metabolic acidosis, respiratory acidosis, or a combination of both. Metabolic Acidosis refers to a pathologic condition in which a low pH is accompanied by a significant diminution of the serum HCO3- (versus what is normal for the patient)
Metabolic acidosis is caused by or associated with the following (these may occur in combination):
How should a patient with suspected metabolic acidosis be evaluated?
The patient’s blood electrolytes, pH and pCO2 should be measured. A venous blood gas (rather than arterial) is generally adequate for determination of the pCO2 and pH.
Most patients with a metabolic acidosis will attempt to neutralize their pH by hyperventilation, that is, by reducing their pCO2. This adaptation may occur within a few minutes and be essentially complete within hours. A variety of charts and normograms are used to evaluate the adequacy of this compensation, but the experienced clinician can generally identify the degree of compensation by sight or with a few mnemonics (eg, generally, pCO2 = 1.5 (Actual [HCO3] ) + 8 mmHg).
As an example, a patient with venous blood gas measurements of pH 7.32, HCO3-15, and pCO2 30 would demonstrate appropriate respiratory compensation for a metabolic acidosis, whereas a set of blood gases measuring pH 7.21, HCO3 15, and pCO2 39 would demonstrate both metabolic and respiratory acidosis.
When the patient is diagnosed with a metabolic acidosis, the measurement of the anion gap is of great usefulness. Recall, that the anion gap may be generally defined as: AG=unmeasured anions minus unmeasured cations. Because the unmeasured cations are usually stable in health and disease, attention may be primarily paid toward the nature and amount of the unmeasured anions.
An elevated anion gap implies the presence of an additional acid, generally dropping the serum HCO3 in a 1:1 fashion. Occasionally, this 1:1 ratio does not hold; this is called the delta gap. As remembered from Part I, the unmeasured anions are: serum proteins (albumin), organic acids, and inorganic acids. Examples of elevated anion gap metabolic acidosis include lactic acidosis, ketoacidosis, renal failure, and toxic alcohol and salicylate poisonings. Since normal anion gap metabolic acidosis implies loss of bicarbonate in most cases, examples of a normal anion gap metabolic acidosis include diarrhea, urinary diversion, proximal renal tubular acidosis, and use of carbonic anhydrase inhibitors.
In addition, most patients recovering from diabetic ketoacidosis with an elevated anion gap will in fact develop a normal anion (hyperchloremic) acidosis upon recovery.
It is critically important in defining normal versus high anion gap acidosis to be aware that:
To summarize, the evaluation of a patient with suspected metabolic acidosis should generally follow the following algorithm:
Examples demonstrating the utility of these approaches will be provided with the next entry in this series.