Acid-base is another topic where tradition trumps science. We have long known that the traditional method of assessing acid base using compensation formulas and Henderson-Hasselbach equations is an inadequate explanation. Yet, this is still the pervasive teaching in medical school and residency and thereby leads to incomplete understanding of how we generate acid base disorders and how to correct for them.
A Brief History
The traditional view of acid/base is termed the Boston Approach. It subscribes to the Bronsted-Lowry theory that acids are proton donors with pCO2 being the major donor and HCO3 being the major acceptor. Hence, it utilizes the Henderson-Hasselbach approach where pH is the dependent variable and pCO2 and HCO3 are the independent variables. They derived linear equations and maps from a large number of patients with known primary compensated acid-base disturbance. For any given acid/base anomaly, compensation formulas and expected pH, pCO2, or HCO3 were determined. The true strength of the Boston Approach is the ability to classify patients with a single primary acid/base disorder into compensated vs decompensated disorders. However, this does not apply well to mixed disorders and cannot explain of a large number of acid/base derangements that are independent of pCO2 and HCO3.
Respiratory compensation of:
PaCO2 = 1.5 x HCO3 + 8 or ↓PaCO2 = 1.25 x ↓HCO3
PaCO2 = 0.9 x HCO3 + 16 or ↑PaCO2 = 0.75 x ↑HCO3
H+ = 24 x (pCO2/HCO3)
The Copenhagen approach was developed to better separate respiratory etiologies from metabolic. It introduced the concept of base excess: amount of strong acid (negative number) or base (positive number) to return the pH of 1L of serum with pCO2 of 40mmHg and temp 38C to 7.40. Here the PaCO2 is held constant so acute respiratory alkalosis or acidosis have no effect. The base deficit reflects purely metabolic component.
It is still possible to calculate compensation through this approach. In fact, it is easier.
Respiratory Compensation of Metabolic Acidosis
↓PaCO2 = ↓BE (last 2 digits of pH should equal pCO2)
Respiratory Compensation of Metabolic Alkalosis
↑PaCO2 = 0.6 x ↑BE (very variable coefficient from 0.25-1)
Metabolic Compensation of Chronic Respiratory Acidosis
↑BE = 0.4 x ↑PaCO2 (same ratios as in Boston Approach)
Metabolic Compensation of Chronic Respiratory Alkalosis
↓BE = 0.5 x ↓PaCO2 (same ratios as in Boston Approach)
While base deficit is superior for isolating metabolic disorders from respiratory, it cannot further differentiate between the different types of metabolic acidosis. Emmit and Narins introduced the Anion Gap with elevated AG implying unmeasured anions like ketones, lactate, toxins, organic acids and preserved AG implying gut or renal losses of HCO3. The AG is not robust in critically ill patients because it does not account for low albumin.
Fencl and Figge introduced the corrected anion gap to account for Alb : AG + 2.5 (4 – alb).
Despite these many modifications, they fail to explain and account for a myriad of clinically observed phenomenon: contraction alkalosis, dilutional acidosis, hyperchloremic acidosis, hypochloremic (chloride sensitive) alkalosis, hypoalbuminemic alkalosis, hyperalbuminnemic acidosis, among many things. This is because the fundamental tenets of Boston and Copenhagen approaches are wrong.
The Stewart-Fencl approach was the first to recognize that the Bronsted-Lowry theory of acid and base does not apply well in vivo. If it did, then lactate should be a base and lactic acid should be the corresponding acid. However, lactate production is acidotic in vivo and lactate consumption is alkalotic. The Stewart approach subscribes to the Arrhenius theory of acid/base which defines acid as substances that generate H+ from water and bases as substances that generate OH- from water. When viewed in this way, HCO3- is not an independent variable. Rather, it is in rapid flux to obey the fundamental physical chemistry laws of electrical neutrality, mass conservation, and dissociation constants. Back to the example of lactate, lactate production demands a decrease in anions (HCO3-) or increase in cations (H+) making this process acidotic. Lactate consumption demands a increase in anions (HCO3) or decrease in cations (H+) so this process is basic. So while pH depends on HCO3, HCO3 is actually dictated by the following, true independent variables:
- electrical neutrality (specifically, the relative concentrations of Na and Cl)
- weak acid dissociation equilibrium and conservation of mass for weak acids (specifically, albumin and phosphorous concentrations)
- bicarbonate ion formation equilibrium (which depends on PaCO2)
- water dissociation equilibrium, carbonate ion formation equilibrium (which is unchanged in physiologic parameters)
The Stewart-Fencl approach completely accounts for every variable but it is too cumbersome to apply to routine clinical use. Gilfix and Storey introduced the Base Excess Gap, a simplified hybridized version of base excess and the Stewart Approach. It basically ignores point iv because this is constant through physiologic parameters. It utilizes Copenhagen’s base deficit to completely isolate respiratory from metabolic disorders. To differentiate the multiple etiologies of metabolic acid-base derrangements, one calculates:
- Base Excess of Na : Na – 140
- Base Excess of Cl: 102 – Cl
- Base Excess of Alb: 2.5(4 – Alb)
- Base Excess Total: summation of the above
- Base Excess Gap: Base Excess from ABG – BEtotal
- This reflects the amount of strong base/acid required to titrate 1L of serum to a pH of 7.40 if there were no unmeasured anions
- This reflects the amount of unmeasured anions (lactate, ketones, organic acids, and toxins) and should be equivalent to corrected AG.
There are no new formulas! The most important lesson from Stewart’s approach is the strength of contribution that Na, Cl, and Alb toward acid-base status.
146 | 113 | 19 pH 7.45 | pCO2 39 | BE -3.3
4.6 | 25 | 1.1 Alb 0.6
- pH 7.45 // BE +3.3 – metabolic alkalosis
- pCO2 39 – inadequate respiratory compensation (she should have pCO2 of 40+3.3 = 43)
- Na 146 – contraction alkalosis, BE + 6
- Cl 113 – hyperchloremic acidosis, BE – 11
- Alb 0.6 – low albumin alkalosis, BE = 2.5 x (4.2- Alb) = + 9
- BEtot = 6-11+9 = +4 calculated base excess
- BEG = +3.3 – 4 = 0 no unmeasured anions
- Contraction alkalosis
- Hypoalbuminemic alkalosis
- Hyperchloremic acidosis
- No unmeasured anions
- Inadequate respiratory compensation or mild respiratory acidosis
140 | 103 | 19 pH 7.38 | pCO2 39 | BE -0.3
4.6 | 24 | 2.1 Alb 0.6
- pH 7.38 // BE -0.3 – metabolic acidosis
- pCO2 39 – adequate respiratory compensation 40-0.3 = 40
- Na 140 – no contribution, BDE 0
- Cl 103 – hyperchloremic acidosis, BDE +1
- Alb 0.6 – low albumin alkalosis, BDE = 2.5 x (4.2- Alb) = + 9
- BEtot = 0-0+9 = +8
- BEG = -0.3 – 8 = -8.3 there are unmeasured anions
- Hypoalbuminemic alkalosis.
- Trace hyperchloremic acidosis.
- Metabolic acidosis from unmeasured anions.
- Adequate respiratory compensation.
My Complete Approach
- Full Analysis of Metabolic Acidosis/Alkalosis
- Full Analysis of Respiratory Acidosis/Alkalosis