What is the basic mechanism of acidosis in acute kidney injury?

Basic Mechanism of Acidosis in Acute Kidney Injury

Acidosis in AKI develops primarily through impaired renal hydrogen ion excretion and reduced ammonia synthesis, leading to accumulation of nonvolatile acids in the body. 1

Primary Pathophysiologic Mechanisms

Impaired Acid Excretion

• The kidneys normally excrete 50-100 mEq of hydrogen ions daily through tubular secretion and ammonia generation; AKI disrupts both processes, causing acid retention. 1
• Damaged tubular epithelium loses the ability to secrete hydrogen ions into the tubular lumen, preventing normal acid elimination. 1
• Reduced ammonia (NH₃) synthesis in the proximal tubule eliminates a critical buffer system—normally, ammonia combines with hydrogen ions to form ammonium (NH₄⁺), which is then excreted in urine. 1

Accumulation of Organic Acids

• Decreased glomerular filtration prevents clearance of organic acids including sulfates, phosphates, and other uremic toxins, which accumulate and consume bicarbonate buffer. 2, 3
• The anion gap typically increases as unmeasured anions (uremic acids) accumulate, though hyperchloremic (normal anion gap) acidosis can also occur depending on the clinical context. 3

Bicarbonate Loss and Regeneration Failure

• The kidneys normally regenerate bicarbonate through proximal tubular reabsorption and distal tubular hydrogen ion secretion; AKI impairs both mechanisms. 1
• Serum bicarbonate falls below 22 mmol/L as acid accumulates faster than the damaged kidneys can compensate, with severe AKI often producing bicarbonate levels below 18 mmol/L. 1, 4

Contributing Factors in Critical Illness

Tissue Hypoperfusion and Lactic Acidosis

• Many AKI patients have concurrent shock states that generate lactic acidosis from inadequate oxygen delivery to tissues, compounding the uremic acidosis. 5
• Septic shock produces a complex metabolic acidosis with contributions from lactate, hyperchloremia, and increased strong ion gap. 5

Impaired Respiratory Compensation

• Severe illness may limit the respiratory system's ability to compensate by hyperventilating to eliminate CO₂, allowing pH to fall further. 5
• Respiratory compensation (lowering PaCO₂) can partially offset metabolic acidosis, but this mechanism may be inadequate in critically ill patients with respiratory compromise. 5

Clinical Manifestations

Metabolic Derangements

• Metabolic acidosis in AKI is characterized by pH <7.35, serum bicarbonate <22 mmol/L, and often an elevated anion gap (>12 mEq/L) from accumulated uremic toxins. 1, 5
• Electrolyte disturbances including hyperkalemia, hypocalcemia, and hyperphosphatemia frequently accompany the acidosis. 2

Progression Pattern

• The severity of acidosis correlates with AKI stage—stage 1 AKI may show mild bicarbonate reduction (18-22 mmol/L), while stage 3 AKI often produces severe acidosis with bicarbonate <15 mmol/L. 1, 4

Common Pitfalls

• Do not assume all acidosis in AKI is purely uremic—always calculate the anion gap and measure lactate to identify concurrent lactic acidosis from hypoperfusion, which requires different management (fluid resuscitation and vasopressors rather than bicarbonate). 5, 3
• Failing to recognize that bicarbonate therapy does not address the underlying renal dysfunction and should not delay renal replacement therapy when indicated. 2
• Overlooking that rapid correction of severe acidosis with bicarbonate can precipitate life-threatening hypokalemia as alkalinization drives potassium intracellularly—monitor potassium every 2-4 hours during treatment. 4