Practice Essentials
Metabolic acidosis occurs when an increased hydrogen ion level results in decreased bicarbonate (HCO3-) in the systemic circulation. Acidemia refers to a pH below the normal range of 7.35-7.45 and indicates that a precipitating disease process or ingestion has occurred. While the state of low pH is defined by the term acidemia, the process leading to this state is called acidosis. Acidosis only becomes acidemia when the body can no longer compensate for low serum bicarbonate, although the terms are often used in the literature interchangeably.
The pH is low with a pure metabolic acidosis but may be normal or high with mixed acid-base disturbances. A serum bicarbonate below 24 mEq/L is suggestive of metabolic acidosis but can be higher in someone with concomitant metabolic alkalosis or chronic respiratory acidosis, where there is metabolic compensation via bicarbonate retention in the kidney. Identification of the underlying condition that precipitates metabolic acidosis is essential to initiating appropriate therapy. [1]
The initial therapeutic goal for patients with severe acidemia is to raise the systemic pH above 7.1-7.2, a level at which dysrhythmias become less likely and cardiac contractility and responsiveness to catecholamines are restored. [2, 3] While the administration of bicarbonate may be indicated for severe acidosis, correction of acidosis should be achieved by identifying and treating the underlying disease process rather than by targeting pH correction directly.
This article discusses the differential diagnosis of metabolic acidosis and presents a scheme for identifying the underlying cause of acidosis by doing a complete history and physical exam as well as using laboratory tests that are available in the emergency department. Clinical strategies for treating metabolic acidosis are also reviewed.
Signs and symptoms of metabolic acidosis
Metabolic acidosis can result in a variety of nonspecific changes in several organ systems, producing, among others, neurologic, cardiovascular, pulmonary, gastrointestinal (GI), and musculoskeletal dysfunction. Symptoms are often a result of and specific to the underlying etiology of the metabolic acidosis.
Workup in metabolic acidosis
Lab studies in the workup of metabolic acidosis may include the following:
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Arterial blood gas (ABG) - A low HCO3- level found on an automated sequential multiple analyzer (SMA) is often the first clue to the presence of metabolic acidosis
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Serum chemistry
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Urinalysis - If the urine pH is above 5.5 in the face of acidemia, this finding is consistent with a type I renal tubular acidosis (RTA)
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Anion gap (AG)
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Ketone levels
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Serum lactate levels
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Salicylate levels
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Iron levels
Once a metabolic acidosis has been identified, the type of metabolic acidosis present (elevated AG vs non-AG), as well as whether the patient has a mixed acid-base disorder, must be determined using a step-by-step approach (described in the Workup section).
Management of metabolic acidosis
Treating the underlying conditions in high AG states usually is sufficient to reverse the acidosis. Treatment with bicarbonate is unnecessary except in extreme cases of acidosis when the pH is less than 7.1-7.2. In such extreme cases, bicarbonate may be considered as a temporizing measure while the underlying cause is simultaneously addressed. However, the use of and indications for bicarbonate therapy are controversial.
Considerations
The primary goal of the emergency physician or practitioner in the treatment of metabolic acidosis is to identify and correct the underlying disease process. While metabolic acidosis has a broad differential, the underlying cause is often evident based on the patient’s presentation and on basic laboratory studies. Pursuit of subtle history and exam findings may elucidate the less common causes of metabolic acidosis and prompt investigation with additional laboratory testing. Mixed acid-base disorders are found using a stepwise approach to the arterial blood gases (ABGs).
Pathophysiology
Metabolic acidosis can arise in the following instances:
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When there is a rise in H+, with the ion being generated from endogenous (eg, lactate, ketones) or exogenous (salicylate, ethylene glycol, methanol) sources
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When the kidneys are unable to excrete hydrogen from dietary protein (type 1 and type IV RTA)
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When bicarbonate (HCO3-) is lost via wasting through the kidneys (type II RTA) or the GI tract (diarrhea) or through a response to respiratory alkalosis
Henderson-Hasselbalch approach to acid-base physiology
The Henderson-Hasselbalch equation describes the relationship between blood pH and the components of the H2CO3 buffering system. This qualitative description of acid-base physiology, as follows, allows the metabolic components to be separated from the respiratory components of the acid-base balance:
pH = 6.1 + log (HCO3-/H2CO3)
with 6.1 being the acid dissociation constant of H2CO3.
The metabolic components of the buffering system, specifically, bicarbonate, produced by the kidneys, and acid, from endogenous or exogenous sources, are in equilibrium.
Carbonic acid (H2CO3) is in equilibrium with the respiratory components, as shown by the following equation:
H2CO3 = pCO2 (mm Hg) X 0.03
Base excess approach to acid-base physiology
Unfortunately, the Henderson/Hasselbalch equation is not linear; the partial pressure of CO2 (pCO2) adjusts pH as part of the normal respiratory compensation for acid-base derangements. This nonlinearity of Henderson-Hasselbalch prevents the equation from quantifying the exact amount of bicarbonate deficit in a metabolic acidosis. This observation led to the development of a semiquantitative approach, base excess (BE):
BE = (HCO3- - 24.4 + [2.3 X Hgb + 7.7] X [pH - 7.4]) X (1 - 0.023 X Hgb)
Base excess attempts to give the quantitative amount of bicarbonate (mmol) that must be added or subtracted to restore 1 liter of whole blood to a pH of 7.4 at a pCO2 of 40 mmHg. To standardize BE for hemoglobin, the following formula for standardized based excess (SBE) was developed; it showed improved in vivo accuracy:
SBE = 0.9287 X (HCO3- - 24.4 + 14.83 X [pH – 7.4])
Strong ion gap approach to acid-base physiology
With regard to the evaluation of metabolic acidosis in the emergency department, the strong ion gap (SIG) theory has never really taken off; however, it may potentially have more use in the intensive care unit (ICU) setting. The SIG is similar to the AG in that accounts for the difference between unmeasured cations and anions, but the SIG approach also considers the presence of ions like lactate, beta hydroxybutyrate, acetate, and sulfates, as well as the presence of abnormal proteins, albumin, and phosphate. The AG ignores the effects that changes in strong ions may have on plasma pH. [4, 5, 6]
Approach for evaluating metabolic acidosis.
Prognosis
Because metabolic acidosis is a condition that occurs in response to a variety of disease states, the prognosis is directly related to the underlying etiology and the ability to treat or correct that particular disorder. Patients presenting with diabetic ketoacidosis (DKA) may have very good outcomes despite severe ketoacidosis (pH < 6.9). [7, 8] However, as may be expected, multiorgan failure is associated with poor prognosis. [9]
A study by Raikou indicated that in patients undergoing renal replacement therapy, an association exists between severe, uncorrected metabolic acidosis (serum bicarbonate concentrations < 20 mmol/L) and a 10-year risk for coronary heart disease of over 20%, as well as a high overall mortality rate. [10] . A study by Park et al indicated that a high rate of metabolic acidosis occurs in persons who receive kidney transplants; in about 30-70% of those transplant patients with an estimated glomerular filtration rate of under 30 mL/min per 1.73 m2, a low serum total CO2 concentration (< 22 mmol/L) was found. The study also found evidence that metabolic acidosis may increase the likelihood of graft failure and mortality in kidney transplant recipients. [11]
In a study of emergency department patients with acute kidney injury, Safari et al determined, through multivariate analysis, that metabolic acidosis is independently associated with mortality, along with sex, age over 60 years, blood urea nitrogen (BUN) concentration, hyperkalemia, cause of renal failure, and type of renal failure. [12]
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Approach for evaluating metabolic acidosis.
