Metabolic acidosis

Definition

Metabolic acidosis is a primary decrease in blood bicarbonate (HCO₃⁻), usually with a compensatory fall in the partial pressure of carbon dioxide (Pco₂) through increased breathing. The pH may be markedly low or only slightly below normal. Acidemia refers to an arterial pH below 7.35. It develops when the acid load exceeds respiratory compensation.

Classification

Classification is based on the anion gap: sodium minus (chloride plus bicarbonate). It reflects unmeasured anions (phosphate, sulfate, negatively charged proteins, organic acids) and is typically about 12 mmol/L. With low albumin, the normal range shifts downwards by about 2.5 mmol/L for every 10 g/L fall in albumin.

• High anion gap acidosis: accumulation of unmeasured acid anions, such as ketones, lactate, sulfates or metabolites of methanol, ethylene glycol and salicylates.
• Normal anion gap (hyperchloraemic) acidosis: loss of bicarbonate via the gut or kidney or impaired renal acid excretion; the kidney reabsorbs chloride instead of bicarbonate.
• Mixed disorders: the delta gap (difference between measured and normal anion gap) detects an additional metabolic alkalosis, and Winters' formula an additional respiratory disorder.

Aetiopathogenesis

The basic mechanisms are increased acid production or intake, reduced acid excretion and loss of bicarbonate via the gastrointestinal tract or the kidneys.

With a high anion gap

• Ketoacidosis: a common complication of type 1 diabetes, and also in alcohol use disorder, undernutrition and, to a lesser extent, fasting; the liver converts free fatty acids into acetoacetic acid and beta-hydroxybutyrate.
• Lactic acidosis: the most common cause of metabolic acidosis in hospital patients; increased production in anaerobic metabolism (above all shock, hypoxia, seizures) and reduced clearance in hepatic dysfunction; also caused by toxins such as carbon monoxide or cyanide. D-lactate arises in short bowel syndrome and bacterial overgrowth.
• Renal failure: reduced acid excretion; sulfate, phosphate, urate and hippurate widen the anion gap.
• Toxins with acidic metabolites: methanol (formate), ethylene glycol (oxalate), salicylates and paraldehyde.
• Rhabdomyolysis: a rare cause, due to release of protons and anions from muscle.

With a normal anion gap

• Gastrointestinal bicarbonate loss: diarrhea, fistulas, ileostomy, ureterosigmoidostomy (the colon exchanges bicarbonate for chloride and absorbs ammonium) and ion-exchange resins.
• Renal causes: renal tubular acidosis types 1 and 4 (impaired H⁺ secretion) and type 2 (impaired bicarbonate reabsorption), early renal failure, tubulointerstitial kidney disease and carbonic anhydrase-blocking agents.
• Other causes: hypoaldosteronism, hyperkalemia, hyperparathyroidism and rapid intake of large amounts of sodium chloride.

Clinical features

• Mild acidemia: itself causes no symptoms; symptoms of the underlying cause predominate.
• Marked acidemia (pH below 7.10): nausea, vomiting and malaise; with rapid development even at a higher pH.
• Kussmaul breathing: a characteristic sign; deep breaths at a normal rate reflecting respiratory compensation, without a sensation of breathlessness.
• Severe acute acidemia: cardiac dysfunction with hypotension and shock, ventricular arrhythmias and coma.
• Chronic acidemia: disorders of bone mineralisation (rickets, osteomalacia, osteopenia).
• Electrolytes: metabolic acidosis can contribute to hyperkalemia through a shift of potassium out of cells.

Diagnosis

Blood gas analysis and electrolytes

• pH and bicarbonate: pH below 7.35 with low bicarbonate; Pco₂ falls in compensation by about 1.2 mmHg for every 1 mmol/L fall in bicarbonate.
• Winters' formula: expected Pco₂ = 1.5 × HCO₃⁻ + 8 (± 2). If measured Pco₂ is higher, there is an additional respiratory acidosis; if lower, a respiratory alkalosis.
• Anion gap: always calculated; an increase almost always indicates metabolic acidosis. A normal anion gap with bicarbonate below 24 mmol/L and high chloride indicates hyperchloraemic acidosis.
• Delta gap: the difference between measured and normal anion gap is added to the measured bicarbonate; if the result is above the normal range, an additional metabolic alkalosis is present.

Search for the cause

• With a high anion gap: urea, creatinine, glucose, lactate and possible toxins; salicylate levels are available in most laboratories.
• Osmolar gap: measured minus calculated serum osmolarity. A value above 10 in high anion gap acidosis points to methanol or ethylene glycol; calcium oxalate crystals in the urine suggest ethylene glycol.
• With a normal anion gap: urine anion gap = urinary sodium + potassium − chloride. A negative value (about −30 to −50 mmol/L) indicates preserved ammonium excretion and thus extrarenal, usually gastrointestinal, losses; a positive value suggests renal bicarbonate loss, most commonly renal tubular acidosis.

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Further reading (open access)

1. MSD Manual Professional: Metabolic Acidosis
2. MSD Manual Professional: Acid-Base Disorders
3. MSD Manual Professional: Hyperkalemia
4. StatPearls: Anion Gap and Non-Anion Gap Metabolic Acidosis

Cross-references