What causes decreased bicarbonate levels?

Causes of Decreased Bicarbonate

Decreased bicarbonate levels (<22 mmol/L) almost always indicate metabolic acidosis, which results from either increased acid production, decreased acid excretion by the kidneys, or gastrointestinal bicarbonate losses. 1, 2

Primary Mechanisms of Low Bicarbonate

Renal Causes

• Chronic kidney disease is the most common cause when GFR decreases below 20-25% of normal, as the kidneys lose their ability to excrete hydrogen ions and synthesize ammonia, leading to acid accumulation 2, 3
• The severity of acidosis typically correlates with the degree of renal impairment, with bicarbonate levels ranging from 12-22 mmol/L in most CKD patients 3
• Approximately 30% of hemodialysis patients have metabolic acidosis despite dialysis treatment 4

Increased Acid Production

• High protein intake increases endogenous acid production through metabolism of sulfur-containing amino acids, which is a key determinant of metabolic acidosis in dialysis patients 1, 4
• Western dietary patterns high in animal protein, cereals, and grains but low in fruits and vegetables create chronic low-grade metabolic acidosis that worsens with age 1, 2
• Increased protein breakdown (measured by protein nitrogen appearance) is independently associated with lower bicarbonate levels 4

Gastrointestinal Losses

• Diarrhea causes direct bicarbonate loss in stool, contributing to metabolic acidosis 4
• Lower gastrointestinal losses result in normal anion gap metabolic acidosis 5

Dilutional Effects

• Interdialytic fluid gain in hemodialysis patients dilutes serum bicarbonate concentration, contributing to lower measured levels 4

Important Clinical Distinctions

Metabolic Acidosis vs. Chronic Respiratory Alkalosis

A critical pitfall is misdiagnosing chronic respiratory alkalosis as metabolic acidosis, as both present with low bicarbonate 5. The key differences:

• Metabolic acidosis: pH <7.35, bicarbonate <22 mmol/L, with compensatory respiratory alkalosis 2
• Chronic respiratory alkalosis: Low bicarbonate represents renal compensation for chronically low CO2, not a primary metabolic problem 5
• Use arterial blood gas analysis to measure pH and PaCO2 when the diagnosis is unclear 1, 2
• The urine anion gap helps differentiate: negative in metabolic acidosis with appropriate renal response, positive when kidneys cannot excrete acid appropriately 5

Anion Gap Considerations

The type of metabolic acidosis provides diagnostic clues 3, 6:

• High anion gap acidosis is most common in advanced CKD, indicating accumulation of unmeasured anions 3, 6
• Normal anion gap (hyperchloremic) acidosis can occur even with stage 4-5 CKD, or may indicate gastrointestinal bicarbonate losses 3, 5
• Mixed patterns (both high anion gap and hyperchloremia) are frequently observed 6

Factors Affecting Severity

Protective Factors

• Diabetes with diabetic nephropathy is associated with less severe metabolic acidosis compared to non-diabetic kidney disease, possibly due to more efficient extrarenal bicarbonate generation 6
• Higher dialysis dose (Kt/V) reduces acidosis severity in hemodialysis patients 4
• Calcium carbonate use as a phosphate binder provides alkali supplementation and reduces acidosis 4

Aggravating Factors

• Inadequate dialysis or missed treatments worsen metabolic acidosis 4
• Low dialysate bicarbonate concentration fails to adequately replenish bicarbonate stores 1
• Chronic inflammatory states and hypercatabolic conditions accelerate acid production 1

Clinical Monitoring

Serum bicarbonate should be monitored monthly in all CKD patients stages 3-5 to detect and manage metabolic acidosis early. 1, 2, 7 The target is to maintain bicarbonate ≥22 mmol/L to prevent complications including protein catabolism, bone disease, and faster kidney disease progression 1, 2, 7