A recent AJKD Teaching Case by Adrogué & Madias contrasts the physiologic and physicochemical approaches to assessing acid-base status. Test your knowledge on this topic below.
Normal serum pH in humans is 7.40. Mathematically, pH is the negative log of [H+]. If we express the acidity of serum as a concentration of hydrogen ions, what is a normal value?
The normal values for hydrogen ion concentrations are measured in nanomol/liter, which is 10-9 mol/L. When compared to other ions such as sodium and potassium, which are measured in millimol/L (10-3), there is a 6 log difference between hydrogen ion concentration and the ions evaluated with routine chemistry panels. The body has a limited ability to survive even minor perturbations of pH, which is why buffering systems are so important. The extremes of pH that are compatible with life, 7.0 and 7.6, equate to hydrogen ion concentrations of 100 nanomol/L and 25 nanomol/L, respectively.
Using the physiologic approach to acid-base analysis, the serum albumin needs to be accounted for when considering the anion gap (AG). Assume the following lab values in the setting of metabolic acidosis: Na+ 140 mEq/l; K+ 4.0 mEq/L; Cl− 110 mEq/L; HCO3− 13 mEq/L; Albumin 2.0 g/dL.
What is the corrected AG if the low albumin is considered?
Albumin is an anion, and the anion gap must be adjusted upward for a low serum albumin concentration by adding 2.5 mEq/L for each 1 g/dL of serum albumin below the normal value (4 g/dL). In this case, the uncorrected anion gap is 140 – 110 – 13 = 17. However, the serum albumin of 2.0 g/dL is 2 below the normal value of 4. Therefore, 2 × 2.5 = 5 mEq/L, which must be added to 17, bringing the corrected anion gap to 22.
The physiochemical approach to acid-base analysis uses the concept of apparent strong ion difference (SIDa) to approximate the quantity of plasma buffer. The equation used to calculate the SIDa is:
+ [K+]) – [Cl−]
([Na+] + [K+] + [Ca++] + [Mg++]) – ([Cl−] + lactate−)
([Na+] + [K+]) – ([Cl−] + [lactate−] + [other strong anions])
All of the above are currently in use.
One of the criticisms of the physiochemical approach is that measurements of multiple ions and several equations (or a computer) are necessary to calculate values such as the apparent or effective strong ion difference. Not only can these calculations be cumbersome to interpret, but each equation also has different normal values.
The physiochemical approach considers which of the following measurements to be an “acid” anion?
In vitro observations have shown that the albumin concentration can affect acidity, although changes to serum albumin in vivo do not correlate with changes in pH or Paco2. The physiochemical approach to acid-base analysis does identify two categories not described in the physiologic approach, namely hypoalbuminemic alkalosis and hyperalbuminemic acidosis.
A homeless man is brought to the emergency room after being found unconscious and covered in vomitus. He is hypotensive and febrile on arrival. His initial labs reveal: Na+ 130 mEq/L; K+ 2.8 mEq/L; Cl– 72 mEq/L; HCO3– 21 mEq/L; Glucose 305 mg/dL; pH 7.55; Paco2 28; Pao2 60.
Using the physiologic approach, interpret these laboratory values and identify the acid-base disorder(s) in this clinical scenario.
Metabolic acidosis and metabolic alkalosis
Metabolic acidosis, metabolic alkalosis, and respiratory alkalosis
Applying the physiologic approach to this complicated acid-base disturbance reveals alkalemia with a pH of 7.55. As the Paco2 is depressed, there is a respiratory alkalosis. The bicarbonate may simply appear appropriately low due to metabolic compensation, but a closer look at the patient’s electrolytes also reveals a significant anion gap of 37. With this degree of an anion gap, there must be a concomitant anion gap metabolic acidosis. However, if a gap acidosis were the only metabolic disturbance present here, then the bicarbonate would be expected to be very low (<5 mEq/L). The bicarbonate level of 21 mEq/L is inappropriately elevated, suggesting that a metabolic alkalosis is present as well. This problem emphasizes the importance of evaluating the anion gap when using the physiologic approach.
Post Prepared by Dr. Timothy Yau, AJKD Blog Contributor. For a PDF version of the questions & answers, please click here.