Acid-base disturbances are first characterized by the initial change in pH. There are four major classes of acid-base disturbances: respiratory acidosis, respiratory alkalosis, metabolic acidosis, and metabolic alkalosis. The acid-base disturbances are further categorized as compensated or uncompensated. Compensation attenuates the acid-base disturbance and returns the pH toward normal. There can be a respiratory compensation for an initial metabolic disorder, and there can be a renal (metabolic) compensation for an initial respiratory disorder.
Respiratory acidosis results from inadequate ventilation (hypoventilation). Pco2 rises, leading to a drop in pH (acidosis). If the acidosis persists for more than 12 hours, the acidosis may be partially compensated by increased renal H+ loss. During respiratory acidosis, HCO3– may rise slightly due to equilibration with excess CO2.There is a 1 mEq/L increase in HCO3– per 10 mm Hg increase Pco2 that represents chemical equilibrium and is not part of a renal compensation.
Respiratory acidosis is often accompanied by hypoxia. Common causes include ventilation/perfusion mismatch or a central respiratory depression from a barbiturate overdose.
Respiratory alkalosis results from excessive ventilation (hyperventilation). In respiratory alkalosis, Pco2 falls, leading to an increase in pH (alkalosis). If the alkalosis persists for more than 12 hours, the alkalosis may be partially compensated by decreased renal H+ excretion. During respiratory alkalosis, HCO3– may fall acutely owing to equilibration with depleted CO2. There is a 2 mEq/L decrease in HCO3– per 10 mm Hg decrease Pco2 that is chemical and not part of the renal compensation. Common causes of respiratory alkalosis include hyperventilation from voluntary effort (anxiety) or stimulation of central respiratory centers secondary to meningitis or a fever.
Metabolic acidosis results from a loss of HCO3– or a gain of non-CO2 acid. The acidosis may be acutely attenuated by increased respiratory loss of CO2 because of the much more rapid response time of the respiratory system. If the kidneys are also functioning, the renal compensation for acidosis is to excrete acidic urine. Chronically, the renal excretion of H+ is enhanced as the renal ability to produce ammonium from glutamine is induced. Common causes of metabolic acidosis include renal failure, uncontrolled diabetes (ketoacidosis), and diarrhea.
Metabolic alkalosis results from a gain of HCO3– or loss of a non-CO2 acid. In metabolic acidosis, HCO3– accumulates, binding H+ and causing pH to rise (alkalosis). The alkalosis may be acutely attenuated by decreasing respiratory loss of CO2. If the kidneys are working properly, renal compensation for alkalosis is to excrete HCO3–, making the urine alkaline. Common causes of metabolic acidosis include ingestion of antacids, loss of gastric acid (vomiting), and enhanced renal H+ loss in hyperaldosteronism.
Determination of Acid-Base Disturbances
An acid-base algorithm allows the determination of the acid- base disturbance. The first step is to assess the pH. A pH of less than 7.35 is acidotic. A pH of greater than 7.45 is alkalotic. If either pH disturbance exists, the next step is to examine the CO2 and HCO3– levels to identify the cause.
In acidosis, determine if the cause is excess CO2. If so, it is at least a respiratory acidosis. Then assess the HCO3–. If the HCO3– is normal (after accounting for the 1 mEq HCO3– increase per 10 mm Hg Pco2 increase), then it is a simple respiratory acidosis. If the HCO3– is higher than expected, there has been some renal compensation for the respiratory acidosis. If the HCO3– is lower than expected, the acidosis has two causes: a combined respiratory and metabolic acidosis.
If the acidosis is not associated with an increase in CO2, it is not a respiratory acidosis. The next step is to assess the HCO3–. If the HCO3– is lower than expected, it is a metabolic acidosis. Then assess the CO2 (again, adjusting expectations for the 1 mEq HCO3– increase per 10 mm Hg Pco2). If the CO2 is normal, it is a simple metabolic acidosis. If the CO2 is lower than expected, there has been a respiratory compensation for the metabolic acidosis. If the CO2 is elevated, it is a combined metabolic and respiratory acidosis.
The “error” box is reached when an acidosis is not associated with either an increase in CO2 or a decrease in HCO3–. In this case, an error in reporting of the values is a likely possibility. The equivalent steps can be used to identify the cause of alkalosis.
The anion gap is clinically useful in the differential diagnosis of acid-base disorders. The anion gap is due to the presence of anions that are not measured in a standard plasma analysis, such as the negative charges associated with proteins. It is calculated as
Plasma [Na+] – ([Cl–] + [HCO3–])
and a normal anion gap is approximately 10-16 mEq/L. An anion gap of 17 or higher represents an increased anion gap, and an anion gap of 9 or lower represents a decreased anion gap.
Acid-base disturbances that are characterized by an increased, normal, or decreased anion gap have little mechanistically in common. However, the anion gap is useful in the differential diagnosis, since it eliminates some possible causes of the acid-base disturbance.
An increased anion gap can come from an increase in the unmeasured anions (hyperalbuminemia, lactic acidosis, ketoacidosis) or a decrease in the unmeasured cations (hypocalcemia, hypokalemia, hypomagnesemia). If the decrease in HCO3– is offset by an increase in Cl–, there is a hyperchloremic acidosis but a normal anion gap.