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Acid-base disorders

Last updated: July 12, 2021

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Acid-base disorders are a group of conditions characterized by changes in the concentration of hydrogen ions (H+) or bicarbonate (HCO3-), which lead to changes in the arterial blood pH. These conditions can be categorized as acidoses or alkaloses and have a respiratory or metabolic origin, depending on the cause of the imbalance. Diagnosis is made by arterial blood gas (ABG) interpretation. In the setting of metabolic acidosis, calculation of the anion gap is an important resource to narrow down the possible causes and reach a precise diagnosis. Treatment is based on identifying the underlying cause.

Pathophysiology of acid-base disorders [1]
Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis
  • ↓ (compensation)
  • ↑ (compensation)
  • ↑ (compensation)
  • ↓ (compensation)
  • ↑ Production/ingestion of H+ or loss of HCO3-
  • Loss of H+ or ↑ production/ingestion of HCO3-
Common causes

*pH values may be within the reference range in the case of completely compensated alkalosis or acidosis.


pH and pCO2 are the most important lab values to assess the acid-base status in any patient.

  • pH scale
    • A logarithmic scale that expresses the acidity or alkalinity of a solution based on the concentration of hydrogen ions (pH = -log[H+])
    • The neutral value of pH is 7, with lower values being acidic and higher values being basic.
  • Henderson-Hasselbalch equation allows for calculation of HCO3- from pH and pCO2: pH = 6.1 + log ([HCO3-] / 0.03 x pCO2)

Assessment of acid-base status [1]

Start with an ABG and then proceed in the following order:

  1. Evaluate blood pH:
    • pH < 7.35 (acidemia): Primary disorder is an acidosis.
    • pH > 7.45 (alkalemia): Primary disorder is an alkalosis.
  2. Evaluate pCO2 (partial pressure of carbon dioxide in blood, reference range: 33–45 mm Hg) to determine whether the primary acid-base disorder is respiratory or metabolic:
  3. Evaluate HCO3- (reference range: 22–28 mEq/L):
  4. Evaluate pO2:

SMORE: change of pCO2 in the Same direction as pH Metabolic disorder; change of pCO2 in the Opposite direction of pH REspiratory disorder

Compensation (acid-base) [5][6]

  • Definition: physiological changes that occur in acid-base disorders in an attempt to maintain normal body pH
  • Compensatory changes
    • In metabolic disorders: rapid compensation within minutes by changes in minute ventilation
    • In respiratory disorders: typically slow compensation over several hours to days by changes in the urinary pH
Compensation mechanisms in acid-base disorders
Primary disorder Compensatory process Expected compensation*
Metabolic acidosis
Metabolic alkalosis
Respiratory acidosis Acute compensation
  • Buffers in blood
  • Expected HCO3- = 24 + [0.1 x (pCO2 - 40)] (+/- 3)
Chronic compensation
  • Expected HCO3- = 24 + [0.4 x (pCO2 - 40)] (+/- 3)
Respiratory alkalosis Acute compensation
  • Buffers in blood
  • Expected HCO3- = 24 - [0.2 x (40 - pCO2)] (+/- 3)
Chronic compensation
  • Expected HCO3- = 24 - [0.5 x (40 - pCO2)] (+/- 3)
*If the expected compensation does not occur, a secondary acid-base disturbance will be present in addition to the primary disorder.

An anion gap represents the difference between the concentration of unmeasured anions and the concentration of unmeasured cations.

Calculation [1]

  • Anion gap = [Unmeasured anions] - [Unmeasured cations]
    • [Unmeasured anions] = [Total anions] - [Routinely measured anions]
    • [Unmeasured cations] = [Total cations] - [Routinely measured cations]
  • Since maintenance of electrical neutrality requires that the total concentration of cations approximate that of anions, the anion gap formula can also be expressed as: anion gap = [Routinely measured cations] - [Routinely measured anions]
  • If potassium concentration is normal, anion gap ≈ [Na+] - ([Cl-] + [HCO3-]) (reference range: 6–12 mmol/L)
  • If potassium levels are also taken into consideration: anion gap = ([Na+] + [K+]) - ([Cl-] + [HCO3-]) (reference range: 10–16 mmol/L)
  • An increase of unmeasured anions can increase the anion gap (see “High anion gap metabolic acidosis” below).


Causes of high anion gap acidosis (MUDPILES): Methanol intoxication, Uremia, Diabetic ketoacidosis, Paraldehyde, Isoniazid or Iron overdose, Inborn error of metabolism, Lactic acidosis, Ethylene glycol intoxication, Salicylate intoxication

Causes of normal anion gap acidosis (FUSEDCARS): Fistula (biliary, pancreatic), Ureterogastric conduit, Saline administration, Endocrine (Addison disease, hyper-PTH), Diarrhea, Carbonic anhydrase inhibitor, Ammonium chloride, Renal tubular acidosis, Spironolactone

A neGUTive urine anion gap implies GI loss of bicarbonate.

Treatment of acid-base disorders should always address the underlying cause. Some steps in urgent management are listed below. [1]

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