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Difficulty: MediumInterpreting Laboratory Results

A 42-year-old woman comes to the physician due to a 3-week history of generalized weakness, fatigue, and episodic loose stools. She reports having 3 to 4 watery bowel movements daily but denies fever, abdominal pain, or blood in her stool. She has no significant past medical history and takes no medications. Her blood pressure is 110/70 mm Hg, and pulse is 88/min. Physical examination is unremarkable, with normal skin turgor and moist mucous membranes.

Laboratory studies show the following:

Serum chemistry:
TestResultReference Range
Sodium138 mEq/L138 \text{ mEq/L}136−145 mEq/L136-145 \text{ mEq/L}
Potassium2.8 mEq/L2.8 \text{ mEq/L}3.5−5.0 mEq/L3.5-5.0 \text{ mEq/L}
Chloride112 mEq/L112 \text{ mEq/L}95−105 mEq/L95-105 \text{ mEq/L}
Bicarbonate16 mEq/L16 \text{ mEq/L}22−28 mEq/L22-28 \text{ mEq/L}
Blood urea nitrogen14 mg/dL14 \text{ mg/dL}7−18 mg/dL7-18 \text{ mg/dL}
Creatinine0.8 mg/dL0.8 \text{ mg/dL}0.6−1.2 mg/dL0.6-1.2 \text{ mg/dL}
Arterial blood gas (room air):
TestResultReference Range
pH7.307.307.35−7.457.35-7.45
pCO232 mm Hg32 \text{ mm Hg}35−45 mm Hg35-45 \text{ mm Hg}
pO295 mm Hg95 \text{ mm Hg}80−100 mm Hg80-100 \text{ mm Hg}
Urine electrolytes:
TestResult
Sodium35 mEq/L35 \text{ mEq/L}
Potassium25 mEq/L25 \text{ mEq/L}
Chloride80 mEq/L80 \text{ mEq/L}

Which of the following is the most likely underlying mechanism for this patient's laboratory findings?

  1. Gastrointestinal bicarbonate lossAnswer
  2. B
    Impaired distal renal acidification
  3. C
    Defective proximal bicarbonate reabsorption
  4. D
    Renal chloride wasting and volume depletion
  5. E
    Autonomous aldosterone production

Answer

Gastrointestinal bicarbonate loss
The correct answer is gastrointestinal bicarbonate loss. The patient's laboratory results show a non-anion gap (hyperchloremic) metabolic acidosis (pH 7.307.30, HCO3−\text{HCO}_3^- 16 mEq/L16 \text{ mEq/L}, Anion Gap 10 mEq/L10 \text{ mEq/L}). In a patient with a non-anion gap metabolic acidosis, the urine anion gap (UAG) is calculated to differentiate between renal and extrarenal causes of the acidosis. The formula is UAG=(Urine Na++Urine K+)−Urine Cl−\text{UAG} = (\text{Urine Na}^+ + \text{Urine K}^+) - \text{Urine Cl}^-. In this patient, the UAG=35+25−80=−20 mEq/L\text{UAG} = 35 + 25 - 80 = -20 \text{ mEq/L}. The UAG is an indirect measure of urinary unmeasured cations, predominantly ammonium (NH4+\text{NH}_4^+). Because ammonium is excreted with chloride to maintain electroneutrality, high ammonium excretion leads to high urinary chloride and a definitively negative UAG. A negative UAG indicates an intact renal acidification response, confirming that the bicarbonate loss is extrarenal. This correlates with her recent history of chronic diarrhea.

Step-by-Step Solution

1
Analyze the basic acid-base status from the arterial blood gas and serum chemistry.
The pH of 7.307.30 and low bicarbonate (16 mEq/L16 \text{ mEq/L}) indicate a primary metabolic acidosis. The serum anion gap is calculated as Na+−(Cl−+HCO3−)=138−(112+16)=10 mEq/L\text{Na}^+ - (\text{Cl}^- + \text{HCO}_3^-) = 138 - (112 + 16) = 10 \text{ mEq/L}, which is normal (8−12 mEq/L8-12 \text{ mEq/L}). Thus, the patient has a non-anion gap metabolic acidosis (NAGMA).
Establishing the primary acid-base disorder is required before determining its specific etiology.
2
Assess the respiratory compensation using Winter's formula.
Expected pCO2=1.5×[HCO3−]+8±2=1.5×16+8±2=32±2 mm Hg\text{pCO}_2 = 1.5 \times [\text{HCO}_3^-] + 8 \pm 2 = 1.5 \times 16 + 8 \pm 2 = 32 \pm 2 \text{ mm Hg}. The measured pCO2\text{pCO}_2 is 32 mm Hg32 \text{ mm Hg}, indicating appropriate respiratory compensation without a superimposed respiratory disorder.
To ensure there is no mixed acid-base disorder complicating the presentation.
3
Calculate the urine anion gap (UAG) to determine the mechanism of the NAGMA.
UAG=Urine Na++Urine K+−Urine Cl−=35+25−80=−20 mEq/L\text{UAG} = \text{Urine Na}^+ + \text{Urine K}^+ - \text{Urine Cl}^- = 35 + 25 - 80 = -20 \text{ mEq/L}.
The UAG acts as a surrogate marker for urinary ammonium (NH4+\text{NH}_4^+) excretion, which helps distinguish between renal and extrarenal (gastrointestinal) causes of a NAGMA.
4
Interpret the meaning of the calculated urine anion gap.
A negative UAG (−20 mEq/L-20 \text{ mEq/L}) indicates that the kidneys are appropriately excreting large amounts of acid (in the form of NH4+\text{NH}_4^+, accompanied by Cl−\text{Cl}^-) in response to systemic acidosis. This confirms an extrarenal source of bicarbonate loss.
Understanding the physiological meaning of the UAG allows the definitive identification of gastrointestinal bicarbonate loss (diarrhea) over a renal defect in acidification (renal tubular acidosis).

Key Concept

The urine anion gap (UAG=Na++K+−Cl−\text{UAG} = \text{Na}^+ + \text{K}^+ - \text{Cl}^-) is utilized to differentiate the etiologies of a non-anion gap metabolic acidosis. A negative UAG indicates appropriate renal ammonium excretion (e.g., gastrointestinal bicarbonate loss from diarrhea), whereas a positive UAG suggests impaired renal acidification (e.g., renal tubular acidosis).
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Interpreting Laboratory Results

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