Acid-base disorders

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.

Overview

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)
  • 0.03 = solubility constant of pCO2
  • 6.1 = pKa of carbonic acid

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:
   • pH and pCO₂ change in the opposite direction: respiratory disorder
     • ↓ pH and ↑ pCO₂: respiratory acidosis
     • ↑ pH and ↓ pCO₂: respiratory alkalosis
   • pCO₂ and pH change in the same direction: metabolic disorder
     • ↓ pH and ↓ pCO₂: metabolic acidosis (calculate anion gap to identify the possible causes)
     • ↑ pH and ↑ pCO₂: metabolic alkalosis
   • Suspect a mixed acid-base disorder if:
     • pCO₂ or HCO₃^- is abnormal and pH is normal or did not change as expected (e.g., a very high pCO₂ and a mild acidosis).
     • pCO₂ and HCO₃^- shift towards acidosis (↑ pCO₂ and ↓ HCO₃^-) or alkalosis (↓ pCO₂ and ↑ HCO₃^‑).
     • Lesser- or greater-than-expected compensatory response (see “Compensation” below)
3. Evaluate HCO₃^- (reference range: 22–28 mEq/L):
   • High: metabolic alkalosis or compensated respiratory acidosis
   • Normal: non-compensated respiratory disorders
   • Low: metabolic acidosis or compensated respiratory alkalosis
4. Evaluate pO₂:
   • High: hyperoxemia
   • Low: hypoxemia

• Example
  • pH = 7.5, pCO₂ = 20 mmHg, HCO₃ = 22 mEq/L, pO₂ = 70 mmHg
  • Alkalosis (↑ pH), respiratory disorder (↓ pCO₂), non-compensated (normal HCO₃), hypoxemia (↓ pO₂): non-compensated respiratory alkalosis with hypoxemia

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

Compensation ^[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

[

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).

Interpretation

• Normal anion gap metabolic acidosis (also known as hyperchloremic acidosis)
  • Primary loss of HCO₃^- compensated with ↑ Cl^- → normal anion gap
  • Etiology
    • Endogenous: diarrhea; , biliary or pancreatic fistula; , renal tubular acidosis; , Addison disease
    • Exogenous: drugs (e.g., carbonic anhydrase inhibitors), uptake of acids containing chloride ions (e.g., HCl)
  • Further evaluation: urine anion gap = [urine Na⁺] + [urine K⁺] - [urine Cl^-]
    • Positive urine anion gap: renal acidification (e.g., due to renal tubular acidosis)
    • Negative urine anion gap: GI loss of bicarbonate (e.g., due to diarrhea)
• High anion gap metabolic acidosis
  • Increased concentration of organic acids such as lactate, ketoacids (beta-hydroxybutyrate, acetoacetate), oxalic acid, formic acid, or glycolic acid; → no compensatory increase of Cl^- → ↑ anion gap
  • Etiology
    • Endogenous: lactic acidosis, diabetic ketoacidosis, renal insufficiency/uremia
    • Exogenous: salicylate intoxication, ethanol intoxication, methanol intoxication, ethylene glycol intoxication (a component of antifreeze products)
  • Further evaluation: delta ratio = (anion gap - 12) / (24 - [HCO₃^-]) ^[7]
    • Delta ratio < 1 : A hyperchloremic or normal anion gap metabolic acidosis is present in addition to a high anion gap metabolic acidosis.
    • Delta ratio 1–2 : Only a high anion gap metabolic acidosis is present.
    • Delta ratio > 2 : A chronic respiratory acidosis or a metabolic alkalosis is present in addition to a high anion gap metabolic acidosis.
• Abnormal anion gap without metabolic acidosis ^[8]
  • Hypoalbuminemia → ↓ [Unmeasured anions] → ↓ anion gap
  • Paraproteinemia (e.g., multiple myeloma), severe hypercalcemia, severe hypermagnesemia, and/or lithium intoxication → ↑ [Unmeasured cations] → ↓ anion gap
  • Severe hyperphosphatemia → ↑ [Unmeasured anions] → ↑ anion gap ^[9]
  • Severe hypocalcemia and/or hypomagnesemia → ↓ [Unmeasured cations] → ↑ anion gap

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]

• Respiratory acidosis: Treat underlying cause; (see “Treatment” in “COPD”, “Opioid intoxication”, and “Benzodiazepine overdose” articles).
• Respiratory alkalosis
  • Treat underlying cause.
  • In the event of hyperventilation syndrome; , patients benefit from reassurance and rebreathing into a paper bag.
• Metabolic acidosis
  • Acute severe metabolic acidosis (pH < 7.1): intravenous sodium bicarbonate
  • Chronic metabolic acidosis: oral sodium bicarbonate along with treatment of the underlying cause (e.g., diarrhea, renal tubular acidosis)
  • Electrolyte disturbances: correction (e.g., see “Disorders of potassium balance”)
  • See “Diabetic ketoacidosis” and “Salicylate toxicity”.
• Metabolic alkalosis
  • Volume depletion: isotonic saline to increase urinary bicarbonate excretion and correct extracellular volume loss
  • Bicarbonate excess: acetazolamide
  • Electrolyte disturbances: correction