There are many ways to interpret acid-base disorders. The deeper you dive, the more complex the world of acid-base becomes. The added complexity can improve our understanding and identification of specific disease processes, which can help guide treatment. However, complexity removes the user-friendly nature of traditional acid-base analysis and limits its use bedside. Moreover, the more complex things become, the more likely it is that an error in calculations or interpretations will occur.

The learning objectives for this lecture are:

1.  To review the basic principles of acid-base chemistry.

2.  To briefly describe the three major approaches to acid-base.

3.  To introduce an integrated approach to acid-base

a.  Understand how to use the bicarbonate-centered approach, including the anion gap.

b.  Explore the use of base excess and strong ion to assess complex cases.

Principles of Acid-Base

pH represents the activity of hydrogen within a solution. pH is a measure of hydrogen proton concentration: pH = -log₁₀[H⁺]

As there is a negative (-) in the equation, the lower the pH the higher the concentration of protons in that solution:

Figure 1

When an acid is added to a solution, it dissociates into its conjugate base + protons. A strong acid will dissociate more, such that the number of protons released will be higher, thus the pH will be lower: Acid ⇌ Conjugate base- + H+

The pH of an acid in solution can be obtained using the following equation:

Figure 2

where pKa is the acid dissociation constant. This is the Henderson-Hasselbalch equation. Carbonic acid is the major buffer in the body. It has two equilibria, as it can dissociate into carbon dioxide and water, or bicarbonate and protons. We can apply the above equation for pH to carbonic acid:

Carbonic acid equilibria: CO₂ + H₂O ⇌ H₂CO₃ ⇌ HCO₃^- + H⁺

Figure 3

The acid in this equation is represented by PCO₂, which is measurable. Using this equation, the pH of a blood sample can be calculated. It is important to realize that clinical acid-base is not perfect. There are inherent errors associated with sampling and machine errors. The formulae used by machines can differ and are typically designed for humans. There is still much that we do not know and many variables that we do not measure.

Approaches to Acid-Base

The three typical approaches to acid-base disorders are the bicarbonate-centered approach (also called the traditional or Boston approach), the base excess approach, and the strong ion approach (also known as the Stewart approach).

The bicarbonate-centered approach uses the carbonic acid equilibria and the associated Henderson-Hasselbalch equations (see above). Carbon dioxide describes the respiratory component and bicarbonate describes the metabolic component. Four processes can be described: respiratory acidosis, respiratory alkalosis, metabolic acidosis, and metabolic alkalosis.

The base excess approach is similar; however, it recognizes that bicarbonate is not the only descriptor of the metabolic component. Bicarbonate is also influenced by carbon dioxide (see the carbonic acid equilibria), so does not truly describe the metabolic component separately from the respiratory component.

The Standard Base Excess (SBE) is defined as:

• The amount of acid/alkali needed to return extracellular fluid to pH 7.4 (i.e., normal).
• Under standard conditions (37°C, PCO₂ 40 mm Hg, haemoglobin [Hb] 50 g/L).

This allows a more comprehensive description of the metabolic component, having controlled for temperature, carbon dioxide, and haemoglobin (another buffer system). The normal base excess is between -2 to +2; a positive base excess describes a metabolic alkalosis, whereas a negative base excess describes a metabolic acidosis.

The strong ion approach uses a different definition of an acid. An acid is commonly defined as a proton donor (Brønstead-Lowry), i.e., add protons to a solution. With more protons, the pH decreases, thus a proton donor is acidifying. Strong ion defines an acid as something that, when added to a solution, causes an increase in protons (Arrhenius).

Strong ion theory respects the law of electroneutrality, where positive and negative charges must be equal within a solution. The addition of an anion, e.g., chloride or lactate, will cause positively charged protons to be released from the solution (from water). Thus, anions are acidifying and the magnitude of acidification depends on how dissociated (hence ‘strong’) that anion is when added to a specific solution.

The strong ion approach defines three independent variables that determine acid-base status: the strong ions (Na⁺, Cl^-, lactate, etc., the total non-volatile weak acids and carbon dioxide. The first two represent the metabolic component, the latter represents the respiratory component.

Each approach has pros and cons. For example, strong ion provides a more detailed analysis of the processes that are occurring; however, it is complex and cumbersome to use bedside. When analysing acid-base bedside, the two most important things are:

1.  The pH (the overall balance of effects), as this has direct clinical consequences.

2.  The process(es) that are occurring: what makes protons [H⁺] change in one direction or the other.

An Integrated Approach

Various simplified forms to the strong ion approach have been proposed. These approaches are easier to use bedside and allow swifter analysis of complex acid-base disorders. These simplifications typically only consider the strong ion approach; we can combine the bicarbonate-centered, base excess and strong ion approaches bedside, swiftly and easily.

An integrated approach…

1.  Starts with the bicarbonate-centered approach.

a.  Initial steps:

i.  Compensations.

ii.  Anion gap.

2. Then uses a base-excess approach to strong ion to further evaluate complex cases and search for hidden processes.

A. Initial Steps

1.  What is the pH? - this defines the overall process as normal/acidaemia/alkalaemia.

2.  What is the respiratory component? - acidosis/alkalosis.

3.  What is the metabolic component? - acidosis/alkalosis.

4.  Which changes the most? - this identifies the primary disorder.

Figure 4

• Compensation occurs in the same direction (i.e., if PCO₂ increases, HCO₃- increases to compensate).
• If Δ PCO₂ > Δ HCO₃- → respiratory acidosis/alkalosis with metabolic compensation.
• If Δ HCO3- > Δ PCO₂ → metabolic acidosis/alkalosis with respiratory compensation.
• If HCO₃- and PCO₂ change in different directions → mixed disorder.

B. Compensation

5. Evaluate compensation

(Adapted from Silverstein and Hopper 2015)

If the change in the secondary process is explained by compensation, there is a simple disorder with compensation. If not, there is a mixed disorder (i.e., two processes occurring concurrently).

C. Anion Gap

1.  The anion gap further describes a metabolic acidosis using “unmeasured anions.” There are two forms of metabolic acidosis, either bicarbonate is lost from the system (through the kidneys or the intestines), or an acid is added to the system. If an acid is added, the associated conjugate base accumulates, leading to an increase in the anion gap: Anion Gap = [Na⁺ + K⁺] - [Cl^- + HCO₃^-] (range 15–20 mmol/L, various with machines).

2.  There are three modifiers of the anion gap:

a.  Albumin is a weak acid. Loss of albumin causes alkalaemia. This will decrease the anion gap.

b.  Phosphates are acids. Hyperphosphataemia causes acidaemia. This will increase the anion gap.

c.  Bromide is falsely measured as chloride. Patients receiving potassium bromide for seizures can have a very low or negative anion gap.

Base Excess Approach to Strong Ion

3.  The base excess represents the sum of everything metabolic. The Standard Base Excess (SBE, see above) is provided by the blood gas analyzer. The effects of lactate, NaCl and albumin on SBE can be evaluated.

4.  Lactate is an anion and, therefore, it is acidifying. The lactate effect can be simplified as BE_Lactate = [lactate] mmol/L x -1. Lactate will decrease base excess.

5.  The sodium (i.e., free water effect) and chloride effects can be evaluated separately. It is simpler to evaluate them together. The normal difference between sodium and chloride is 30 to 35 mmol/L, though this depends on each laboratory’s reference range. BE_NaCl = (Na⁺ - Cl^-) - (normal difference).

a.  The normal BE_NaCl should equal 0.

b.  If BE_NaCl is positive, there is an alkalosis.

c.  If BE_NaCl is negative, there is an (hyperchloraemic) acidosis.

d.  As both sodium and chloride are univalent, the result for BE_NaCl can be directly added to the SBE to accommodate for the NaCl effect.

6.  Albumin is negatively charged. For every 10 g/L decrease in albumin, base excess increases by 2.5 mmol/L. Thus, BE_Albumin can be calculated.

7.  The base excess gap (BE_Gap) is the resultant SBE after BE_Lactate, BE_NaCl and BE_Albumin have been accounted for:

a.  BE_Gap = SBE - (BE_Lactate + BE_NaCl + BE_Albumin).

b.  BE_Gap = normal base excess = -2 to +2.

c.  A high BE_Gap indicates a hidden alkalosis.

d.  A low BE_Gap indicates a hidden acidosis.

Conclusion

Each approach to acid-base has its pros and cons. Determining the pH (the overall balance) and the individual processes that are occurring may be more useful than specific numbers and measurements. An integrated approach combines the bicarbonate-centered, base excess and strong ion approaches to better understand the processes that are occurring. With practice, this approach can be used efficiently bedside.

References

1.  Story DA. Stewart acid-base: A simplified bedside approach. Anesth Analg. 2016;123(2):511–515.

2.  Magder S, Emami A. Practical approach to physical-chemical acid-base management. Stewart at the bedside. Ann Am Thorac Soc. 2015;12(1):111–117.

3.  Kishen R, Honoré PM, Jacobs R, et al. Facing acid-base disorders in the third millennium - the Stewart approach revisited. Int J Nephrol Renovasc Dis. 2014;7:209–217.

4.  Hopper K. Traditional acid-base analysis. In: Silverstein DC, Hopper K, ed. Small Animal Critical Care Medicine, 2nd ed. Elsevier Saunders: Saint Louis, MO; 2015:289–295.

5.  Kurtz I, Kraut J, Ornekian V, Nguyen MK. Acid-base analysis: a critique of the Stewart and bicarbonate-centered approaches. Am J Physiol Renal Physiol. 2008;294(5):F1009–1031.

6.  Hopper K, Epstein SE, Kass PH, Mellema MS. Evaluation of acid-base disorders in dogs and cats presenting to an emergency room. Part 1: comparison of three methods of acid-base analysis. J Vet Emerg Crit Care (San Antonio). 2014;24(5):493–501.

7.  Hopper K, Epstein SE, Kass PH, Mellema MS. Evaluation of acid-base disorders in dogs and cats presenting to an emergency room. Part 2: comparison of anion gap, strong ion gap, and semiquantitative analysis. J Vet Emerg Crit Care (San Antonio). 2014;24(5):502–508.