Acid-base balance revisited: Stewart and strong ions

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Understanding acid-base physiology is a core requirement for anesthesiologists and intensivists and other physicians responsible for the care of critically ill and injured. Despite a long history, clinical acid-base physiology remains a confusing area for many clinicians and numerous misconceptions exist. The application of principles of physical chemistry to clinical acid-base physiology allows for a valuable new perspective on an old problem and may provide important insights.

Section snippets

Acid-base: A brief history

During the 1950s there was a paradigm shift in the approach acid-base physiology and pathology.3 Bicarbonate was promoted from being an important factor in acid-base balance4 to being the central factor for control of the non-respiratory (metabolic) component of acid-base balance.5, 6, 7 One reason for this shift was a desire among clinical chemists to define acids along the lines of the Bronsted-Lowry definition that had become popular with physical chemists: an acid is a hydrogen donor.5, 8, 9

Water: A unique substance

While water is the solvent for physiological solutions, water also dissociates to produce hydrogen (H+) ions and hydroxyl (OH) ions.19 Under the Stewart approach, water is the principal source of hydrogen ions in physiological solutions.16

As temperature increases, the dissociation of water increases, which in turn increases the H+ concentration. The dissociation of water can be expressed in terms of the law of mass action: Kw=[H+]×[OH][H2O] Where Kw is the dissociation constant of water, [H+]

Strong and weak acids

One question is how to determine when an acid is weak or strong. Stewart16 noted that in general, lactic acid is regarded as a weak acid by chemists, compared to the many strong acids available in the laboratory. Stewart also noted that whether an acid is weak or strong is relative to the surrounding acid-base environment. At pH 7.40 lactic acid is more than 99.9% dissociated and can be thought of as a strong acid; that is, all the lactic acid is assumed to be in the lactate anion form. The

Albumin and phosphate

Stewart did not go far in delineating which were the important weak acids in plasma but as early as 1908 Henderson25 recognized a role for phosphate and speculated on the role of plasma proteins. By the 1930s Van Slyke4 had confirmed the role of plasma proteins. Over the last 15 years researchers have tried to identify which plasma proteins are important and to quantify the anionic role of the proteins and phosphate. The major group in this area since Van Slyke has been Figge’s group.26, 27

New views on stewart

Several papers have used complex mathematical analyses to examine detailed physiology.35, 36 In plasma, albumin is the principal weak-acid with a smaller effect from phosphate.38 Staempfli and Constable35 studied the acid-base effects of albumin using the assumption that albumin has both a weak-acid component and a strong anion component. While using different methodology, the authors derived similar results to Figge.27 This study complements Constable’s remodeling of Stewart’s mathematics that

Clinical application

Stewart’s approach to acid-base disorders has growing popularity among clinicians, particularly in anesthesia and critical care.12, 23, 24, 30 Recently, using Stewart’s work, there have been advances in quantifying non-respiratory acid-base changes, particularly in quantifying the role of unmeasured ions. Until recently the anion-gap has been the principal approach to determining the presence of unmeasured ions, including lactate.12, 39 The Stewart approach highlights the effect of albumin on

Intravenous fluids

Crystalloid solutions are a mainstay of perioperative and critical care medicine. Discussion of fluids for intravenous use illuminates a number of the issues in the methodology of the Stewart approach16 to acid-base physiology and pathophysiology. Water can be used clinically in the treatment of hypernatremia in critically ill patients. What is not obvious is that the administration of water may aggravate metabolic acidosis. Post infusion acidosis is usually associated with administration of

Intravenous fluids with anions other than chloride

Several randomized clinical studies47, 49, 53 have shown that perioperative use of solutions containing anions other than chloride results in less acidosis than 0.9% saline. Commercially available fluids include: Hartmann’s, Ringer’s Lactate, and Plasmalyte (Table 1). Scheingraber’s group49 examined acid-base changes in patients undergoing gynecologic surgery. Patients received 30ml/kg/hr of 0.9% saline or Ringers Lactate. After 120 minutes of infusion the Ringer’s Lactate group had a mean pH

Renal failure in the ICU

Two recent papers, from the same research group, have examined the clinical chemistry of patients with acute renal failure of critical illness requiring renal-replacement therapy in the ICU.59, 60 The first study compared the patients with acute renal failure to control groups of critically patients without acute renal failure.59 Patients with renal failure had a mean base-excess of −7.5 mmol/l largely due to increased concentrations of unmeasured anions and phosphate. This pattern was

Predicting outcome

In critically ill children, Balsubramanyan and colleagues61 estimated the SIG from the standard base-excess and found that standard base-excess <−5 mmol/l, when due to unmeasured anions was an important predictor of mortality. This finding was not supported by a recent study of critically ill adults that found that the neither SIG nor the base-excess effect from unmeasured ions were strong predictors of mortality but were good predictors of a blood lactate >5 mmol/l.59 This study59 also found

Measurement error

One challenge to all clinical chemistry is the reliability of the results obtained from the laboratory, whether a central laboratory or point-of-care. Morimatsu and colleagues66 examined the agreement in measuring biochemical variables at two sites in one hospital. One site was the central hospital laboratory the other was an adult intensive care unit point-of-care machine. The measured biochemical variables included sodium and chloride, important for calculating both the strong-ion-difference

Conclusions

Stewart’s work continues to grow in popularity. The physiological underpinning of the approach is becoming increasingly sophisticated35 while the clinical application is becoming more straightforward and the clinical utility more obvious.24, 30 Clinical application of approaches such as the modified anion-gap40 and the SIG69 are being assisted by the availability of lab coat sized personal computers. Challenges include relating the acid-base variables to outcome and optimizing the reliability

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