Metabolic Acidosis

Metabolic acidosis, a condition in which there is excess buildup of acid in body fluids, is heralded by a decreased concentration of plasma bicarbonate.

Diagnosis

Indications for Testing

  • Patient with altered mental status
  • Patient with initial laboratory results that indicate the presence of acidosis

Laboratory Testing

  • Metabolic panel (Na, K, Cl, HCO3-) and arterial blood gases
    • Expect decreased bicarbonate level on both tests, along with acidosis on arterial blood gases
    • Calculate anion and osmolar gaps to further aid in differential
      • Anion gap = [Na] - ([Cl] + [HCO3-])
        • Normal = 7-16 mmol/L
      • Osmolar gap = calculated plasma osmolality - measured plasma osmolality (2[Na+] + [glucose]/18 + [blood urea nitrogen (BUN)]/2.8)
        • Normal = -10 to +10 mOsm/kg
  • Based on clinical scenario and anion gap calculation, further testing may be appropriate
    • Glucose – evaluate for diabetes mellitus (DM)
    • BUN/creatinine – evaluate for renal failure
    • Lactate/pyruvate levels – evaluate for lactic acidosis
    • Beta-hydroxybutyrate acid – evaluate for DM, starvation
    • Ethanol levels – evaluate alcohol poisoning
    • Microscopic examination of urine for crystals to differentiate methanol from ethylene glycol
      • Methanol and ethylene glycol serum levels may also be necessary
    • Salicylate levels – evaluate for salicylate poisoning
    • Anion gap may also be elevated by toxicants such as acetaminophen, iron, toluene, phenformin, paraldehyde, arsenic
    • Other testing (serum drug levels) based on results of above testing

Differential Diagnosis

Refer to the different types of metabolic acidosis in Background

Background

Classification

  • Type of metabolic acidosis is based on anion/osmolar gap calculation
    • Anion gap = [Na] - ([Cl ] + [HCO3-])
    • Osmolar gap = calculated plasma osmolality - measured plasma osmolality (2[Na+] + [glucose]/18 + [BUN]/2.8)
    • Osmolar gap may be used to differentiate between different types within high anion gap acidosis
High Anion Gap Acidosis
  Osmolar Gap Retained Acids Comments

Diabetes mellitus – ketoacidosis

Normal

Acetoacetic acid, beta-hydroxybutyric acid

 

Ethanol poisoning

High

Sulfuric, phosphoric, organic

Renal failure

Ethylene glycol poisoning

High

Oxalic acid, glycine, oxalomalic acid, formic acid

Calcium oxalate crystals in urine

Lactic acidosis

Normal

Lactic acid

 

Methanol poisoning

High

Formic acid

No crystals in urine

Paraldehyde toxicity

High

Acetic acid

 

Salicylate toxicity

High

Salicylate, organic

 

Starvation

Normal

Beta-hydroxybutyric acid

 

Diethylene glycol

High

2-hydroxethoxyacetic acid

 

Normal anion gap acidosis (inorganic acidosis)

  • Gastrointestinal fluid loss
    • Severe diarrhea – results from loss of Na, K, HCO3-
    • Pancreatitis – loss of HCO3- production
    • Intestinal fistula – loss of Na, K, HCO3-
  • Drug-induced hyperkalemia
  • Renal tubular acidosis (RTA)
    • Proximal (type II) RTA – loss of HCO3- due to decreased tubular secretion of H+
    • Distal (type I) RTA – decreased reabsorption of HCO3-
    • Type IV RTA – inhibited Na reabsorption with abnormal K+ and H+ retention; decreased renal ammonia formation with reduced elimination of H+

Low or negative anion gap (hyperchloremia)

  • Lithium toxicity
  • Monoclonal IgG gammopathy
  • Iodide or bromide intoxication – causes pseudohyperchloremia
  • Disorders of high calcium or magnesium levels

Pathophysiology

  • Excess production of organic acids exceeds rates of elimination
    • Beta-hydroxybutyrate and acetoacetic acid production during diabetic acidosis
    • Lactic acid production during lactic acidosis
  • Reduced excretion of acids
    • Renal failure
    • Renal tubular acidosis
  • Excessive loss of bicarbonate
    • Renal losses
    • Gastrointestinal losses (eg, diarrhea)

ARUP Laboratory Tests

Aid in diagnosis of metabolic acidosis, and calculation of anion gap and osmolar gap

Panel includes calcium, carbon dioxide, chloride, creatinine, glucose, potassium, sodium, and urea nitrogen

Aid in differential diagnosis of high anion gap metabolic acidosis; use in calculation of osmolar gap

Aid in assessment of etiology of anion gap acidosis

Use to identify ethanol, methanol, isopropanol, or acetone ingestion

Aid in assessment of etiology of anion gap acidosis

Determine whether ethylene glycol poisoning exists

Related Tests

Aid in diagnosis of metabolic acidosis

Aid in differentiating renal from nonrenal causes of nonanion gap metabolic acidosis

Test includes sodium, potassium, chloride, creatinine

An isolated pyruvic acid concentration has little clinical value

Preferred test is lactate to pyruvate ratio, whole blood, which reports concentrations for lactate, pyruvate, and L:P ratio on the same specimen

Screening test to evaluate kidney function

Screening test to evaluate kidney function

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite) but only when concentrations are at or above those expected during acetaminophen overdose

Monitor exposure to methanol

Screening test to evaluate kidney function

Serum test to identify acute alcohol ingestion

Preferred test for assessment of acute or chronic arsenic exposure

Differentiate between toxic inorganic and methylated species as well as benign organic forms

Results are reported as total inorganic, total methylated, and organic arsenic

Reflex pattern: if total arsenic concentration is between 35-2000 ug/L, then arsenic, fractionated, will be added to determine proportion of organic, inorganic, and methylated forms

Preferred test for assessment of acute or chronic arsenic exposure

Able to differentiate between toxic inorganic and methylated species as well as benign organic forms

Results are reported as total inorganic, total methylated, and organic arsenic

Reflex pattern: if total arsenic concentration is between 35-2000 ug/L, then arsenic, fractionated, will be added to determine proportion of organic, inorganic, and methylated forms

Medical Experts

Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer, Medical Director of Automated Core Laboratory, ARUP Laboratories
Contributor
Contributor

Lehman

Christopher M. Lehman, MD
Associate Professor of Clinical Pathology, University of Utah
Medical Director, University of Utah Health Hospital Clinical Laboratory, ARUP Laboratories

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®