eMedicine Specialties > Emergency Medicine > Endocrine & Metabolic

Metabolic Acidosis

Author: Antonia Hipp, DO, Assistant Professor, Assistant Residency Director, Department of Emergency Medicine, State University of New York Downstate Medical Center/Kings County Hospital Center; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center
Coauthor(s): Richard Sinert, DO, Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center
Contributor Information and Disclosures

Updated: Sep 11, 2008

Introduction

Background

Metabolic acidosis is a clinical disturbance characterized by an increase in plasma acidity. Metabolic acidosis should be considered a sign of an underlying disease process. Identification of this underlying condition is essential to initiate appropriate therapy.

This article discusses the differential diagnosis of metabolic acidosis and presents a scheme for identifying the underlying cause of acidosis by using laboratory tests that are available in the emergency department. Clinical strategies for treating metabolic acidosis are also reviewed.

Pathophysiology

There are 3 approaches to understanding acid/base balance: A qualitative approach using the Henderson/Hasselbalch equation, a semiqualitative approach with base excess, and the Strong Ion Theory. The 3 theories are reviewed below.

Henderson-Hasselbalch approach to acid/base physiology

The Henderson-Hasselbalch equation describes the relationship between blood pH and the components of the H₂ CO₃ buffering system. This qualitative description of acid/base physiology allows the metabolic component to be separated from the respiratory components of acid/base balance.
 
pH = 6.1 + log (HCO₃/ H₂ CO₃)

Bicarbonate (HCO₃) is in equilibrium with the metabolic components.

• Bicarbonate production in the kidney
• Acid production from endogenous or exogenous sources

Carbonic acid (H₂ CO₃) is in equilibrium with the respiratory component, as shown by the below equation:

• Increase in the generation of H⁺ from endogenous (eg, lactate, ketones) or exogenous acids (eg, salicylate, ethylene glycol, methanol)
• Inability of the kidneys to excrete the hydrogen from dietary protein intake (type I, IV renal tubular acidosis)
• The loss of bicarbonate (HCO₃) due to wasting through the kidney (type II renal tubular acidosis) or the gastrointestinal tract (diarrhea)
• The kidneys response to a respiratory alkalosis

Unfortunately, the Henderson/Hasselbalch equation is not linear; pCO₂ adjusts pH as part of the normal respiratory compensation for acid/base derangements. This nonlinearity of Henderson-Hasselbalch prevents this 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).

Base excess attempts to give a quantitative amount of bicarbonate (mmol) that is required to be added or subtracted to restore 1 L of whole blood to a pH of 7.4 at a pCO₂ of 40 mm Hg. To standardize BE for hemoglobin, the following formula was developed with improved in vivo accuracy, the standardized base excess (SBE):

These classical descriptions of acid/base physiology often failed to account for acid/base findings in critically ill patients. An alkalosis was often noted in critically ill patients as their serum albumin level decreased, which could not be quantified by Henderson Hasselbalch or BE. Also, the "dilutional" acidosis frequently encountered after a large infusion of normal saline could not be explained by either of these 2 approaches to acid/base balance.

Both Henderson Hasselbalch and BE assume that the cations (Ca²⁺, Mg²⁺) and anions (Cl^-, albumin, PO4^-) in plasma remain unchanged in a patient with metabolic acidosis. Yet, in critically ill patients, these ions are known to be in dynamic flux. During the 1980s, Dr. Peter Stewart developed an acid/base theory (Strong Ion) using quantitative chemistry, which accounted for fluctuations of all the ions dissolved in plasma. Based on the requirements for electrical neutrality in any solution as any one of the concentrations of these ions changes, water must dissociate into H⁺ or OH^- to balance the charge. The pH in this scheme is not a consequence of the ratio of acid to base in solution but determined by 3 independent variables:

• Strong ion difference (SID) – Ions almost completely dissociated at physiologic pH.

SID = [Na⁺ + K⁺ + Ca²⁺ + Mg²⁺] – [Cl^- + Lactate^-]

(Ca^{2 +} and Mg^{2 +} are the concentrations of their ionized forms, Mg²⁺ X 0.7 = ionized Mg^{2 +} concentration)

• Total weak acid concentration (Atot) – Ions that can exist dissociated (A-) or associated (AH) at physiologic pH (buffers)

Atot = 0.325275 X [albumin] + 2 X [phosphate]

• pCO ₂ (mm Hg)

The Henderson Hasselbalch equation can be reformulated with variables from the Strong Ion Theory to give a more generalizeable solution to pH.

Once a metabolic acidosis is suspected by low bicarbonate concentration, an arterial blood gas analysis should be obtained. The low HCO₃ level can be caused either by a primary metabolic acidosis or as the metabolic compensation for a respiratory alkalosis. The direction of the pH will separate metabolic acidosis (pH <7.35) from a respiratory alkalosis (pH > 7.45). 

The normal respiratory response (Kussmaul breathing) to a metabolic acidosis is a decrease in pCO₂. This is given by the Winter’s equation:

Failure to have an appropriate respiratory response to metabolic acidosis represents a failure of airway and/or breathing, which must be addressed before any other workup commences.

Once an appropriate respiratory response for a metabolic acidosis has been established, the workup for the presence of unmeasured anions can progress by using the traditional anion gap, the delta-delta approach, or the strong ion gap. This allows the differential of metabolic acidosis to be narrowed and the appropriate therapy applied. 

To differentiate between the causes of metabolic acidosis, one traditionally calculates the anion gap (AG), corresponding the presence of unmeasured anions.

The anion gap allows for the differentiation of 2 groups of metabolic acidosis. Metabolic acidosis with a high AG is associated with the addition of endogenously or exogenously generated acids. Metabolic acidosis with a normal AG is associated with the loss of HCO₃ from the kidney or GI tract, or the failure of the kidney to excrete H⁺.

The delta/delta concept allows for the partitioning of metabolic acidosis into an anion gap and a non-anion gap component, which can occur contemporaneously. The concept behind delta/delta is based on the assumption that for every increase in anion gap of 1 mmol/L above normal (12 mmol), serum HCO₃ ^- will drop by an equal amount.

If the delta HCO₃ ^- is greater than the delta anion gap, then a concomitant non-anion gap acidosis must exist along side the anion gap acidosis. One example would be a patient with a congenital renal tubular acidosis in diabetic ketoacidosis (DKA).

Stewart provides a replacement for the standard anion gap and delta/delta, which allows one to directly measure the amount of unmeasured anions in solution corrected for changes from normal of Ca^{2 +}, Mg^{2 +}, albumin, and phosphate.¹ This is the Strong Ion Gap (SIG).

All the strong ions are expressed in mEq/L, and only the ionized portions of Mg^{2 +} and Ca^{2 +} are considered (to convert total to ionized Mg^{2 +}, multiply by 0.7). Because of the complexity of the above equation, several Internet resources are available to calculate the SIG. For example, http://www.anaesthetist.com/icu/elec/ionz/Findex.htm#Stewart.htmis a good resource. The normal SIG is between 0 and 2. SIG has been shown to be better than blood lactate, pH, or injury severity scores in trauma patients and pediatric surgery patients as a predictor of mortality. 

Mortality/Morbidity

The mortality and morbidity of patients with metabolic acidosis is dependent upon the nature of the underlying cause and the ability to correct it.

Clinical

History

Metabolic acidosis can result in a variety of nonspecific changes in several organ systems, including, but not limited to, neurologic, cardiovascular, pulmonary, gastrointestinal, and musculoskeletal dysfunction. Symptoms are often specific to and a result of the underlying etiology of the metabolic acidosis.

• Head, eyes, ears, nose, throat (HEENT)
  • Tinnitus, blurred vision, and vertigo can occur with salicylate poisoning.
  • Visual disturbances, dimming, photophobia, scotomata, and frank blindness can be seen in methanol intoxication.
• Cardiovascular
  • Palpitations
  • Chest pain
• Neurologic
  • Headache
  • Visual changes
  • Mental confusion
• Pulmonary - Subjective dyspnea from the patient's observation of hyperventilation
• Gastrointestinal
  • Nausea and vomiting
  • Abdominal pain
  • Diarrhea
  • Polyphagia
• Musculoskeletal
  • Generalized muscle weakness
  • Bone pain

Physical

• Neurologic
  • Cranial nerve palsies may occur with ethylene glycol intoxication.
  • Retinal edema may be seen in methanol ingestions.
  • Lethargy, stupor, and coma may occur in severe metabolic acidosis, particularly when it is associated with a toxic ingestion.
• Cardiovascular: Severe acidemia (ie, pH <7.10) can predispose a patient to potentially fatal ventricular arrhythmias, and it can reduce cardiac contractility and the inotropic response to catecholamines, resulting in hypotension and congestive heart failure.
• Pulmonary
  • Patients with acute metabolic acidosis demonstrate tachypnea and hyperpnea as prominent physical signs.
  • Kussmaul respiration, an extremely intense respiratory effort, may be present.
  • Hyperventilation, in the absence of obvious lung disease, should alert the clinician to the possibility of an underlying metabolic acidosis.
• Musculoskeletal: Chronic metabolic acidosis (eg, uremia, renal tubular acidosis [RTA]) is associated with substantial bone disease from bone buffering of calcium carbonate.
  • Long bone malformations in pediatric patients (eg, vitamin D resistant, rickets)
  • Fractures in adult patients

Causes

• Inability to excrete the dietary H⁺ load
  • Renal failure - Diminished NH₄ ⁺ production
  • Hypoaldosteronism - Type 4 RTA
  • Diminished H⁺ secretion - Type 1 (distal) RTA
• Increased H⁺ load
  • Lactic acidosis - Numerous causes, including circulatory failure, drugs and toxins, and hereditary causes (see Lactic Acidosis)
  • Ketoacidosis - Diabetes, alcoholism, and starvation
  • Ingestions -Salicylates, methanol, ethylene glycol, isoniazid, iron, paraldehyde, sulfur, toluene, ammonium chloride, phenformin/metformin, and hyperalimentation fluids
• GI HCO₃ ^- loss
  • Diarrhea
  • Pancreatic, biliary, or intestinal fistulas
  • Ureterosigmoidostomy
  • Cholestyramine
• Renal HCO₃ ^- loss -  Type 2 (proximal) RTA
• Acetazolamide

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