What are the physiologic effects of metabolic acidosis?

Physiologic Effects of Metabolic Acidosis

Metabolic acidosis causes significant adverse effects on multiple organ systems, including increased protein degradation, decreased albumin synthesis, impaired muscle function, bone disease, and cardiovascular dysfunction. 1, 2

Definition and Classification

Metabolic acidosis is characterized by:

• Primary reduction in serum bicarbonate (HCO₃⁻) concentration
• Secondary decrease in arterial PCO₂ (approximately 1 mmHg for every 1 mmol/L fall in HCO₃⁻)
• Reduction in blood pH 2

Classification based on anion gap:

• Normal anion gap (hyperchloremic) acidosis
• Elevated anion gap acidosis 2

Cardiovascular Effects

Metabolic acidosis affects the cardiovascular system through several mechanisms:

• Decreased cardiac contractility and cardiac output
• Arterial vasodilation leading to hypotension
• Increased risk of arrhythmias
• Reduced responsiveness to catecholamines
• Pulmonary vasoconstriction 2, 3

Musculoskeletal Effects

Significant impact on muscle and bone metabolism:

• Increased protein degradation and muscle wasting
• Decreased albumin synthesis
• Negative nitrogen balance
• Bone demineralization and increased risk of osteomalacia
• Impaired growth in children 1, 4

Metabolic Effects

Metabolic acidosis disrupts normal cellular function:

• Increased oxidation of branched-chain amino acids (valine, leucine, isoleucine)
• Decreased plasma concentrations of branched-chain amino acids
• Impaired insulin sensitivity
• Altered thyroid hormone secretion
• Abnormal growth hormone function 1, 4

Inflammatory and Immune Effects

Acidosis affects immune function through:

• Stimulation of inflammatory pathways
• Suppression of immune response
• Increased susceptibility to infections 3

Renal Effects

Chronic metabolic acidosis impacts kidney function:

• Potential acceleration of kidney disease progression
• Increased ammonia production leading to tubular injury
• Increased renal endothelin production
• Activation of complement cascade 4

Cellular and Molecular Effects

At the cellular level, acidosis causes:

• Decreased ATP production
• Altered enzyme function
• Impaired cellular metabolism
• Disruption of protein structure and function
• Altered ion channel activity 2, 3

Severity Classification

The National Kidney Foundation classifies metabolic acidosis severity based on total CO₂ level:

Total CO₂ Level	Severity
≥19 mmol/L	Mild
<19 mmol/L	Moderate to Severe [5]

Treatment Considerations

Treatment should target a serum bicarbonate level of at least 22 mmol/L to mitigate adverse physiologic effects 1, 5:

• For acute severe acidosis (pH < 7.2):

  • IV sodium bicarbonate may be indicated, especially in cardiac arrest, circulatory insufficiency, severe shock, or severe primary lactic acidosis 6
  • Initial dose: 1-2 vials (44.6-100 mEq) IV, followed by 44.6-50 mEq every 5-10 minutes as needed 6

• For chronic metabolic acidosis:

  • Oral sodium bicarbonate: 2-4 g/day (25-50 mEq/day) 1
  • Target serum bicarbonate ≥22 mmol/L 1, 5

Cautions in Treatment

Important considerations when treating metabolic acidosis:

• Rapid correction may cause paradoxical CNS acidosis
• Risk of volume overload, hypertension, and hypocalcemia
• Potential exacerbation of vascular calcifications in chronic kidney disease
• Hypokalemia may develop during treatment 5, 6

Monitoring Parameters

Regular monitoring should include:

• Monthly serum bicarbonate measurements in maintenance dialysis patients 1
• Arterial blood gases to assess pH and response to treatment
• Electrolytes, particularly potassium, calcium, and phosphate
• Nutritional parameters (albumin, total protein) 5