High Chloride with Low Anion Gap: Clinical Interpretation
A serum chloride of 110 mmol/L with an anion gap of 8 mEq/L represents a non-anion gap (hyperchloremic) metabolic acidosis, where the elevated chloride is compensating for low bicarbonate, keeping the anion gap in the normal-to-low range.
Understanding the Laboratory Pattern
The anion gap is calculated as: Na+ + K+ - Cl- - HCO3- 1
- Your anion gap of 8 mEq/L falls within the modern reference range of 3-11 mmol/L (or 5-12 mmol/L depending on the analyzer) 2, 3
- The traditional reference range of 8-16 mmol/L is outdated due to changes in ion-selective electrode technology 2, 3
- A chloride of 110 mmol/L is elevated (normal ~98-106 mmol/L), indicating hyperchloremic acidosis 4
What This Pattern Indicates
This combination suggests non-anion gap metabolic acidosis, where bicarbonate loss is replaced by chloride retention to maintain electroneutrality 4:
Most Common Causes to Consider:
Gastrointestinal bicarbonate loss:
- Diarrhea (most common cause)
- Small bowel fistulas
- Ureterosigmoidostomy
- The urinary anion gap would be negative (-20 ± 5.7 mmol/L) in diarrhea, indicating appropriate renal compensation 5
Renal tubular acidosis (RTA):
- Classic distal RTA (Type 1): urinary anion gap positive (23 ± 4.1 mmol/L) 5
- Hyperkalemic distal RTA (Type 4): urinary anion gap positive (30 ± 4.2 mmol/L) 5
- Proximal RTA (Type 2)
- The urinary anion gap helps distinguish renal from GI causes: positive suggests RTA, negative suggests GI losses 5
Iatrogenic causes:
- Excessive normal saline administration
- Acetazolamide use
- Topiramate therapy
Critical Distinction from High Anion Gap Acidosis
This is NOT consistent with toxic ingestions or severe metabolic derangements:
- Ethylene glycol poisoning produces anion gaps >27 mmol/L (requiring immediate hemodialysis) or 23-27 mmol/L (consider hemodialysis) 1, 6
- Diabetic ketoacidosis typically presents with anion gaps >20 mmol/L 6
- Lactic acidosis produces elevated anion gaps 6, 4
- Your anion gap of 8 mEq/L effectively rules out these life-threatening conditions 6, 4
Diagnostic Next Steps
Calculate the urinary anion gap (urine Na+ + K+ - Cl-) to differentiate causes 5:
- Negative urinary anion gap (-20 to -27 mmol/L): suggests GI bicarbonate loss with appropriate renal ammonium excretion 5
- Positive urinary anion gap (>20 mmol/L): suggests impaired renal acidification (RTA) 5
Check additional labs:
- Serum bicarbonate (will be low in metabolic acidosis)
- Arterial blood gas to confirm acidemia
- Serum potassium (high in Type 4 RTA, low in Types 1 and 2)
- Urine pH (>5.3 in distal RTA despite acidemia; <5.3 with appropriate renal response) 5
Common Pitfalls to Avoid
- Don't use the outdated anion gap reference range of 8-16 mmol/L—modern analyzers have shifted this to 3-11 mmol/L, and using old values leads to misinterpretation 2, 3
- Don't assume all metabolic acidosis has an elevated anion gap—hyperchloremic acidosis is common and has different causes requiring different management 4
- Don't overlook medication history—diuretics, NSAIDs, and ACE inhibitors can cause Type 4 RTA 5
- An anion gap <2 mmol/L is extremely rare and should prompt investigation for laboratory error or hyperglobulinemia (e.g., multiple myeloma) 3, 7
Clinical Significance
Decreased anion gaps (<3 mmol/L) occur in only 2.9% of hospitalized patients and are associated with hypoalbuminemia (nephrotic syndrome, liver cirrhosis) or hyperglobulinemia 3, 7. Your value of 8 mEq/L is normal, not decreased, so the primary abnormality is the elevated chloride indicating hyperchloremic metabolic acidosis 4, 2.