Acid base disorders and Osmolar Gaps

This is quick reference page to acid base disorders in toxicology and osmolar gaps. Dr Zeff Koutsogiannis a toxicologist from Melbourne talks through his approach and the errors that can occur with osmolar and anion gaps.

Zeff – Gas analysis and osmolar gaps

Zeff’s Quick gas analysis steps:

Step 1: Determine pH

  • Acidaemia pH <7.4 vs Alkalaemia pH>7.4

Step 2: Determine whether the primary process is respiratory, metabolic or both.

A respiratory disturbance alters PaCO2 and metabolic disturbance alters the serum HCO3:

  • Respiratory acidosis exists if PaCO2 >40
  • Respiratory alkalosis exists if PaCO2<40
  • Metabolic acidosis exists if HCO3 <24
  • Metabolic alkalosis exists if HCO3 >24

Step 3: Acute or chronic respiratory disturbance?

In acute disturbances the pH changes 0.08 for every 10 mmHg PaCO2 varies from 40.
1-2-HCO3-4-5 rule for change in HCO3 for every 10 mmPaCO2 varies from 40:

  • Acute respiratory acidosis HCO3 increases by 1
  • Acute respiratory alkalosis HCO3 decreases by 2
  • Chronic respiratory acidosis HCO3 increases by 4
  • Chronic respiratory alkalosis HCO3 decreases by 5

Step 4: Determine if anion gap present for metabolic acidosis.

  • Anion gap = Na – (Cl + HCO3) = 12

Step 5: Expected respiratory compensation.

In Metabolic acidosis the change in PaCO2 is in linear correlation with the change in HCO3 (the drop in HCO3 should be matched by the same change in increased PaCO2).

  • Expected PaCO2 = (1.5 x HCO3) + (8+/-2)
  • If expected PaCO2 falls outside range, then there’s an additional respiratory disturbance.

In metabolic alkalosis the response is hypoventilation, therefore the change is not linear. It will not increase greater than 50-55 to compensate for a metabolic alkalosis. Also a patient will be alkalaemic if PaCO2 is elevated to compensate for a metabolic alkalosis. If academic, then an additional respiratory acidosis is present.

  • Expected pCO2 = 0.7[HCO3] + 20 (range +/- 5)
  • Expected pCO2 = 0.9[HCO3] + 9

Step 6: Determine whether other metabolic disturbances co-exist with anion gap acidosis.

A non-anion gap acidosis or a metabolic alkalosis may co-exist.

Corrected HCO3 = measured HCO3 + (anion gap – 12)

  • If corrected HCO3 >24, metabolic alkalosis co-exists
  • If corrected HCO3 <24, non-anion gap, metabolic acidosis exists.

Correct for hypoalbuminaemia (albumin is an anion). For every 10 g/L below normal, add 2.5 to the anion gap.

The osmolar gap is useful to risk asses the potential presence of methanol or ethylene glycol when these are not readily available. Osmolar gap is the difference between the osmolality (as measured in the laboratory) and the osmolarity as calculated from measured solute concentrations. A normal osmolar gap is <10. The small gap is present due to the calculation not taking into account chloride, potassium, sulphate, phosphate, calcium, magnesium, lactate, ammonia, serum proteins and lipids.

In toxicology ethanol is fairly common to our presentations so the osmolarity formula routinely used is:

Calculated Osmolality (mOsmol/kg) = 2 x [Sodium mmol/L] + [urea mmol/L] + [glucose mmol/L] + [ethanol mmol/L]

Osmolar Gap = Measured Osmolality – Calculated Osmolality

(Ethanol conversion: To convert mg/dL to mmol/L multiply 0.22, to convert g/dL to mmol/L multiply 220)

In suspected toxic alcohol ingestions an anion gap metabolic acidosis with an elevated osmolar gap supports the diagnosis, however, a normal osmolar gap does not exclude a potentially life-threatening toxic alcohol ingestion (see Zeff’s talk for a further explanation).


Exogenous agents associated with an elevated osmolar gap:

  • Acetone
  • Ethanol
  • Ethylene glycol
  • Glycerol
  • Glycine
  • Isopropyl alcohol
  • Mannitol
  • Methanol
  • Propylene glycol

Non-toxicological causes of an elevated osmolar gap:

  • Alcoholic Ketoacidosis
  • Chronic renal failure
  • Diabetic Ketoacidosis
  • Hyperlipidaemia
  • Hyperproteinaemia
  • Massive Hypermagnesaemia
  • Severe lactic acidosis
  • Shock
  • Trauma and burns

Causes of a high anion gap acidosis (CAT MUDPILES):

  • Carbon monoxide, Cyanide
  • Alcohol, alcoholic ketoacidosis
  • Toluene
  • Metformin, Methanol
  • Uraemia
  • Diabetic Ketoacidosis
  • Paracetamol, Propylene glycol, Paraldehyde
  • Iron, Isoniazid
  • Lactic acidosis
  • Ethylene glycol
  • Salicylates, Starvation ketoacidosis

Causes of a low anion gap (<6):

  • Increased Unmeasured cations
    • Hypercalcaemia
    • Hypermagnesaemia
    • Lithium intoxication
    • Multiple myeloma
  • Decreased unmeasured anions
    • Dilution
    • Hypoalbuminaemia
  • Artefactual Hyperchloraemia
    • Bromism
    • Iodism
    • Hypertriglyceridaemia

Causes of a non-anion gap metabolic acidosis (abnormal bicarbonate loss or chloride retention):

  • Drugs
    • Acetazolamide
    • Acidifying agents
    • Cholestyramine
  • Gastroinestinal bicarbonate loss
    • Diarrhoea
    • Pancreatic fistula
  • Rapid hydration with normal saline
  • Renal bicarbonate loss
    • Renal tubular acidosis
    • Uretoenterostomy

Causes of metabolic alkalosis:

  • Administration of bases
    • Antacids
    • Dialysis
    • Milk-alkali syndrome
  • Gastrointestinal acid loss
    • Protracted vomiting or nasogastric suction
  • Renal bicarbonate retention
    • Chronic hypercapnia
    • Hypochloraemia
    • Hypokalaemia
  • Urinary acid loss
    • Adrenogenital syndrome
    • Bartter’s syndrome
    • Cushing’s syndrome
    • Diuretics
    • Licorice
    • Primary Hyperaldosteronism
  • Volume contraction

Causes of respiratory acidosis:

  • Airway obstruction
  • aspiration
  • Bronchospasm
  • Drug-induced CNS depression
  • Hypoventialtion of CNS or muscular origin
  • Pulmonary disease
  • Kyphoscoliosis
  • Lung disease
  • Neuromuscular disorders
  • Obesity

Causes of respiratory alkalosis:

  • CNS mediated hyperventilation
    • Increased intracranial pressure
    • Cerebrovascular accidents
    • Psychogenic
  • Hypoxia-mediated hyperventilation
    • Altitude
    • Anaemia
    • V/Q mismatch
  • Pulmonary
    • Congestive cardiac failure
    • Mechanical hyperventilation
    • Pneumonia
    • Pulmonary emboli
  • Sepsis
  • Toxin-induced hyperventilation
    • Nicotine
    • Salicylate
    • Xanthines

References and Resources

  • ABG Analysis
  • Joshua Steinberg’s Gas worksheet
  • EMNerd — You don’t understand the Osm gap (2015)\
  • Gabow PA et al. Diagnostic importance of an increased serum anion gap. New England Journal of Medicine 1980; 303(15):854-858
  • Koga Y et al. The irrationality of the present use of the osmole gap: applicable physical chemistry principles and recommendations to improve the validity of current practices. Toxicological Reviews 2004;23(3):203-211
  • Krasowski MD. A retrospective analysis of glycol and toxic alcohol ingestion: utility of anion and osmolal gaps. BMC Clinical Pathology 2012; 12:1
  • Purssell RA et al. The use of the osmole gap as a screening test for the presence of exogenous substances. Toxicological Reviews 2004;23(3):189-202
  • Whittier WL et al. Primer on clinical acid-base problem solving. Disease Monitoring 2004; 50:117-162

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Dr Neil Long BMBS FACEM FRCEM FRCPC. Emergency Physician at Burnaby Hospital in Vancouver. Loves the misery of alpine climbing and working in austere environments. Supporter of FOAMed, toxicology, tropical medicine, sim and ultrasound

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