Some Observations on the Clinical Approach to Metabolic Acidosis

Abstract

The first step in the clinical approach to patients with metabolic acidosis is to deal with emergencies and to anticipate and prevent dangers associated with therapy. The traditional clinical analysis for the presence of metabolic acidosis suffers from a number of limitations that at times hinders one's ability to reach a proper diagnosis. Our aim here is to raise awareness of some of the nuanced difficulties and illustrate why other considerations add value.In patients with metabolic acidosis, analyses based on the anion gap in plasma (P anion gap ) 1 or the strong ion difference 2 have major deficiencies. For example, the diagnosis of metabolic acidosis may be missed if one relies solely on pH and the concentration of bicarbonate (HCO 3 Ϫ ) in plasma (P HCO3 ) without considering changes in the content of HCO 3 Ϫ in the extracellular fluid (ECF) compartment. In addition, the rules of respiratory compensation, which are based solely on the arterial PCO 2 rather than the more valuable PCO 2 in capillary blood-draining skeletal muscle (as reflected by the venous PCO 2 ), fail to assess the effectiveness of the bulk of the bicarbonate buffer system to remove H ϩ and, hence, whether more H ϩ will bind to intracellular proteins in vital organs, such as the brain or the heart. 3 DIAGNOSIS OF METABOLIC ACIDOSISThe traditional definition of metabolic acidosis is based on a low pH in plasma, a low P HCO3 , and a high value for the P anion gap if its basis is added acids. A major decrease in ECF volume (ECFV), however, will raise the P HCO3 because this parameter is the ratio of the content of HCO 3 Ϫ in the ECF compartment to the ECFV. This explains why the diagnosis of metabolic acidosis was missed in a patient with diabetic ketoacidosis and a very low ECFV, for whom the provisional diagnosis was hyperglycemic hyperosmolar nonketotic coma. 4 In fact, a severe degree of metabolic acidosis was clearly evident after calculation of the content of HCO 3 Ϫ in the ECF compartment. Similarly, the presence of a severe degree of metabolic acidosis was missed in patients with massive diarrhea as a result of cholera, because the P HCO3 was in the near-normal range. 5 Again, this error was revealed by calculation of the content of HCO 3 Ϫ in the ECF compartment. 6 Failure to recognize the presence of metabolic acidosis led to a severe degree of acidemia when the ECFV was re-expanded with a solution that did not contain HCO 3 Ϫ 7 or one of its precursors, organic anions that undergo metabolism to neutral end products. Moreover, pulmonary edema developed in this patient before his intravascular volume was reexpanded completely. Perhaps the development of acidemia led to constriction of the venous capacitance vessels and hence a significant increase in central blood volume. 8 We suggest that one must calculate the content of HCO 3 Ϫ in the ECF compartment to deduce whether metabolic acidosis is present when there is a significantly contracted ECFV. A quantitative assessment of the ECFV is required for this purpose. Because the physica...

Differential Diagnosis of Nongap Metabolic Acidosis

“…Individuals with distal and proximal RTA with normal renal function or those given hydrochloric acid precursors have a pure nongap acidosis. By contrast, those with CKD (with or without hyporeninemic hypoaldosteronism), certain organic acidoses such as ketoacidosis, toluene intoxication, and D-lactic acidosis, or profuse diarrhea (sufficient to produce hyperproteinemia and hypotension-induced lactic acidosis) can have a nongap acidosis, a high anion gap acidosis, or both (12,(25)(26)(27). Therefore, a combined nongap and high anion gap metabolic acidosis would be evidence against distal or proximal RTA with normal renal function, or less than extreme gastrointestinal bicarbonate loss.…”

“…If the history and physical examination along with simple laboratory studies do not enable the clinician to determine the cause of the metabolic acidosis, assessment of renal acidification is indicated (25,26,33).…”

“…+ Excretion Because direct measurements of urinary NH 4 + excretion are not available in most clinical laboratories, investigators have made use of the effect of changes in urinary NH 4 + and its accompanying anions on urinary charge (urine anion gap) or osmolality (urine osmolal gap) to indirectly estimate urinary NH 4 + concentration (25,(36)(37)(38)(39).…”

“…When anions other than Cl 2 , such as b-hydroxybutyrate or acetoacetate in ketoacidosis or hippurate in toluene intoxication, are excreted in the company of NH 4 + (13,25,26), the value for NH 4 + derived using the urine anion gap will significantly underestimate the actual urinary NH 4 + excretion (25). An additional situation in which the urinary anion gap (or other measures of renal acidification) might not reflect a Maximal renal NH 4 + excretion will be reached by 3-5 days and could be less than this if values are obtained after ,3-5 days.…”

“…To overcome some of the limitations of the urine anion gap, the urine osmolal gap was developed (25,41,42). The osmolality of the urine is the result of the presence of the charged cations and their accompanying anions, as well as that of the neutral substances, including creatinine, urea, and glucose.…”