Metabolic Acidosis

Clinical Background

Metabolic acidosis is heralded by a decreased concentration of plasma bicarbonate.

Etiology

Production of organic acid exceeds rates of elimination
- Beta-hydroxybutyrate and acetoacetic acid production during diabetic acidosis
- Lactic acid production during lactic acidosis
Reduced excretion of acids due to:
- Renal failure
- Renal tubular acidosis
Excessive loss of bicarbonate due to:
- Renal losses or gastrointestinal losses (eg, diarrhea)

Classification

Type is based on anion gap calculation
Anion gap = [Na] - [Cl ]+ [HCO3(neg)]
- Na = sodium, Cl = chloride, HCO3 = bicarbonate
- Normal = 7-16 mmol
High anion gap acidosis (organic acidosis)
- Methanol poisoning
  - Osmolar gap - high
  - Retained acid - formate
  - No crystals in urine
- Ethylene glycol poisoning
  - Osmolar gap - high
  - Retained acids - hippurate, glycolate, oxalate
  - Oxalate crystals in urine
- Diabetes mellitus - ketoacidosis
  - Osmolar gap - normal
  - Retained acids - acetoacetate, beta-hydroxybutyrate
- Ethanol poisoning
  - Osmolar gap - high
  - Renal failure
  - Retained acids - sulfuric, phosphoric, organic
- Starvation
  - Retained acid - beta-hydroxybutyrate
- Salicylate toxicity
  - Retained acids - salicylate, organic
- Lactic acidosis
  - Retained acid - lactate
- Paraldehyde toxicity
  - Pyruvate may be helpful in differentiating inborn errors and cardiac ischemia
Normal anion gap acidosis (inorganic acidosis)
- Gastrointestinal fluid loss
  - Severe diarrhea - results from loss of Na, K (potassium), HCO3(neg)
  - Pancreatitis - loss of HCO3(neg) production
  - Intestinal fistula - loss of Na, K, HCO3(neg)
- Renal tubular acidosis (RTA)
  - Proximal (type II) RTA - loss of HCO3(neg) due to decreased tubular secretion of H+
  - Distal (type I) RTA - decreased reabsorption of HCO3(neg)
  - Type IV RTA - inhibited Na reabsorption with abnormal K+ and H+ retention; decreased renal ammonia formation with reduced elimination of H+
- Drug-induced hyperkalemia
  - Potassium sparing diuretics
  - Angiotensin-converting enzymes (ACE) inhibitors
  - Cyclosporine
  - Trimethoprim

See Also

Diabetes Mellitus Diagnosis

Electrolyte Abnormalities, Life Threatening

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Electrolyte Panel

ARUP #: 0020410

Methodology: Ion-Selective Electrode/Enzymatic

Use:

Aid in the diagnosis of metabolic acidosis

Component tests (serum and plasma) include measurements for anion gap, carbon dioxide, chloride, potassium and sodium

Test name: Electrolytes, Urine

ARUP #: 0020498

Methodology: Ion-Selective Electrode

Use:

Aid in differentiating renal from non-renal causes of non-anion gap metabolic acidosis

A positive urine anion gap (UAG) suggests renal tubular acidosis types 1 or 4 or renal failure

UAG = [Na+]+[K+]-[Cl(neg)]

Test includes measurements for sodium, potassium, chloride, creatinine

Test name: Lactic Acid, Plasma

ARUP #: 0020045

Methodology: Enzymatic

Use:

Rule out lactic acidosis

Limitations:

Follow-up:

Test name: Pyruvic Acid

ARUP #: 0080310

Methodology: Enzymatic

Use:

Differential diagnosis of lactic acidosis

Limitations:

Follow-up:

Test name: Beta-Hydroxybutyric Acid

ARUP #: 0080045

Methodology: Enzymatic

Use:

Determine concentration of beta-hydroxybutyrate

Test name: Osmolality, Serum or Plasma

ARUP #: 0020046

Methodology: Freezing Point

Use:

Aid in differential diagnosis of metabolic acidosis due to poisoning

Limitations:

Follow-up:

Test name: Alcohols

ARUP #: 0090131

Methodology: Gas Chromatography

Use:

Diagnose isopropanol, ethanol, acetone or methanol poisoning

Limitations:

Follow-up:

Test name: Ethylene Glycol

ARUP #: 0090110

Methodology: Gas Chromatography

Use:

Diagnose ethylene glycol poisoning

Test name: Salicylate Assay

ARUP #: 0090251

Methodology: Spectrophotometry

Use:

Diagnose salicylate poisoning

Additional Tests Available

Test name: Calcium, Serum or Plasma

ARUP #: 0020027

Methodology: Spectrophotometry

Comments:

Test name: Carbon Dioxide, Serum or Plasma

ARUP #: 0020004

Methodology: Enzymatic

Comments:

Test name: Chloride, Serum or Plasma

ARUP #: 0020003

Methodology: Ion-Selective Electrode

Comments:

Test name: Creatinine, Serum or Plasma

ARUP #: 0020025

Methodology: Spectrophotometry

Comments:

Test name: Glucose Tolerance Test

ARUP #: 0020542

Methodology: Enzymatic

Comments:

Test name: Methanol

ARUP #: 0090165

Methodology: Gas Chromatography

Comments:

Test name: Potassium, Plasma or Serum

ARUP #: 0020002

Methodology: Ion-Selective Electrode

Comments:

Test name: Sodium, Plasma or Serum

ARUP #: 0020001

Methodology: Ion-Selective Electrode

Comments:

Test name: Urea Nitrogen, Serum or Plasma

ARUP #: 0020023

Methodology: Spectrophotometry

Comments:

Test name: Ethanol, Serum or Plasma - Medical

ARUP #: 0090120

Methodology: Gas Chromatography or Enzymatic

Comments:

Test name: Basic Metabolic Panel

ARUP #: 0020399

Methodology: Refer to individual components

Comments: Aid in the diagnosis of metabolic acidosisComponent tests (serum and plasma) include calcium, carbon dioxide, chloride, creatinine, glucose, potassium, sodium and urea nitrogen

References

General References

Adrogue HJ. Metabolic acidosis: pathophysiology, diagnosis and management. J Nephrol. 2006;19 Suppl 9:S62-S69.

Andrade OV, Ihara FO, Troster EJ. Metabolic acidosis in childhood: why, when and how to treat. J Pediatr (Rio J ). 2007;83(2 Suppl):S11-S21.

Casaletto JJ. Differential diagnosis of metabolic acidosis. Emerg Med Clin North Am. 2005;23(3):771-87, ix.

Eledrisi MS, Alshanti MS, Shah MF, Brolosy B, Jaha N. Overview of the diagnosis and management of diabetic ketoacidosis. Am J Med Sci. 2006;331(5):243-251.

Englehart MS, Schreiber MA. Measurement of acid-base resuscitation endpoints: lactate, base deficit, bicarbonate or what?. Curr Opin Crit Care. 2006;12(6):569-574.

Forni LG, McKinnon W, Hilton PJ. Unmeasured anions in metabolic acidosis: unravelling the mystery. Crit Care. 2006;10(4):220-.

Judge BS. Metabolic acidosis: differentiating the causes in the poisoned patient. Med Clin North Am. 2005;89(6):1107-1124.

Kamel KS, Halperin ML. An improved approach to the patient with metabolic acidosis: a need for four amendments. J Nephrol. 2006;19 Suppl 9:S76-S85.

Kellum JA. Acid-base disorders and strong ion gap. Contrib Nephrol. 2007;156:158-166.

Kitabchi AE, Nyenwe EA. Hyperglycemic crises in diabetes mellitus: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol Metab Clin North Am. 2006;35(4):725-51, viii.

Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol. 2007;2(1):162-174.

Kwon KT, Tsai VW. Metabolic emergencies. Emerg Med Clin North Am. 2007;25(4):1041-60, vi.

Laing CM, Unwin RJ. Renal tubular acidosis. J Nephrol. 2006;19 Suppl 9:S46-S52.

Lim S. Metabolic acidosis. Acta Med Indones. 2007;39(3):145-150.

Mitch WE. Metabolic and clinical consequences of metabolic acidosis. J Nephrol. 2006;19 Suppl 9:S70-S75.

Medical Reviewers

Lehman, Christopher M., M.D. Co-Medical Director, University Hospital Clinical Laboratory; Associate Professor, Clinical Pathology, University of Utah

McMillin, Gwen, Ph.D. Medical Director of Clinical Drug Abuse Testing, Clinical Toxicology and Trace Elements, Co-Medical Director for Pharmacogenomics at ARUP Laboratories; Assistant Professor, Pathology, University of Utah

Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah

Comprehensive Review: May 2008
Last Update: May 2008