Acidosis Metabolica

Approach to the adult with metabolic acidosis

INTRODUCTION — Each day approximately 15,000 mmol of carbon dioxide (which can generate carbonic acid as it combines with water) and 50 to 100 meq of nonvolatile acid (mostly sulfuric acid derived from the metabolism of sulfur-containing amino acids) are produced. Acid-base balance is maintained by pulmonary and renal excretion of carbon dioxideand nonvolatile acid, respectively.

Renal excretion of acid involves the combination of hydrogen ions with urinary titratable acids, particularly phosphate (HPO42- + H+ —> H2PO4-) or with ammonia to form ammonium [1]. (See "Chapter 11B: Renal hydrogen excretion"). The latter is the primary adaptive response, since ammonia production from the metabolism of glutamine can be appropriately increasedin the presence of an acid load [2].

Acid-base balance is usually assessed in terms of the bicarbonate-carbon dioxide buffer system:

  Dissolved CO2  +  H2O    H2CO3      HCO3-  +  H+

The concentration of H2CO3 (carbonic acid) is normally so low that its role can be ignored and the ratio between the reactants can be expressed by the Henderson-Hasselbalch equation:

  pH   =   6.10   +  log  ([HCO3-]  ÷  [0.03  x  PCO2])

where the pH is equal to (-log [H+]), 6.10 is the pKa (equal to -log Ka), Ka is the dissociation constant for the reaction, 0.03 is equal to the solubility constant for CO2 in the extracellular fluid, and PCO2 is equal to the partial pressure of carbon dioxide in the extracellular fluid [3]. (See "Chapter 10B: Buffers").

The approach to the adult withmetabolic acidosis will be reviewed here. The approach in children is discussed separately. (See "Approach to the child with metabolic acidosis").

METABOLIC ACIDOSIS — With these principles in mind, metabolic acidosis can be defined as a disorder associated with a low pH and a low bicarbonate concentration. It can be produced by three major mechanisms (show table 1): Increased acid generation (eg,ketoacidosis and lactic acidosis) (See "Causes of lactic acidosis") Loss of bicarbonate (eg, diarrhea or type 2 [proximal renal tubular acidosis]) or a bicarbonate precursor (eg, ketoacid anion loss in ketoacidosis) (see "The anion gap/HCO3 in metabolic acidosis") Diminished renal acid excretion (eg, renal failure or type 1 [distal] renal tubular acidosis)

Compensatory response — The initiationof metabolic acidosis is associated with a compensatory respiratory response. The Henderson-Hasselbalch equation shows that the pH is determined by the ratio between the HCO3 concentration and PCO2, not by the value of either one alone. Thus, the body responds to any acid-base disorder by making compensatory respiratory or renal responses in an attempt to normalize the pH. These responses areprobably mediated at least in part by parallel alterations in regulatory cell (renal tubular or respiratory center) pH [4]. (See "Simple and mixed acid-base disorders").



Protection of the HCO3/PCO2 ratio and therefore the pH requires a compensatory response that varies in the same direction as the primary disorder. Thus, in metabolic acidosis, ventilation is increased, resulting in a fall inPCO2, which tends to raise the pH toward normal.

The respiratory compensation results in a 1.1 to 1.2 mmHg fall in the PCO2 for every 1 meq/L reduction in the plasma bicarbonate concentration [3,5]. This response begins in the first hour and is complete by 12 to 24 hours [6]. Respiratory failure is suggested by the inability to generate such a response [7].

By comparison, the magnitude of therespiratory response is unknown with the abrupt onset of metabolic acidosis. In a well-designed study with six healthy subjects in whom a steady-state was established, a 30 minute duodenal infusion of ammonium chloride was associated with an acute fall of 0.85 mmHg in the PCO2 for every 1 meq/L reduction in the plasma bicarbonate concentration [8]. The degree of acidosis attained was relatively...