Hypochloremic Alkalosis Workup

The following studies may be indicated in patients with hypochloremic alkalosis:

• Amniocentesis

  • Amniotic fluid sodium and chloride concentrations may reflect fetal values; these are high in fetuses with chloride-losing diarrhea (CLD). Levels may also be elevated in patients with Bartter syndrome.
  • Although this study is not routine, α ₁ -fetoprotein levels may be elevated.
• Blood workup

  • Serum electrolyte levels may be within the reference range, especially in neonates and treated patients.
  • Typical findings include low concentrations of serum chloride, sodium, and potassium.
  • Serum pH and bicarbonate, calcium, uric acid, hemoglobin (if patient is not anemic), renin, and aldosterone levels may be elevated.
  • The serum rennin level is exponentially high in line with secondary hyperaldosteronism due to chronic volume depletion, and this finding is supported by low or normal blood pressure measurements.
  • Attention must be paid in interpreting the serum potassium level in relation to the state of metabolic alkalosis. For example, the potassium shift from serum into the intracellular compartment increases as the serum pH is high; in other words, the potassium level is less than normal by 0.6 mmol/L when measured at a serum pH of 7.5.
• Urine and stool electrolytes

  • In patients with Bartter syndrome, urine chloride, sodium, and potassium concentrations are usually measured. Urine calcium-to-creatinine and uric acid–to–creatinine ratios are usually high. Stool electrolytes cannot be measured because of well-formed or hard stool. Fractional excretion (F_ex) studies are more reliable than absolute values. Usually, results are higher than reference range values, as follows:
    • F_ex sodium concentration greater than 1%
    • F_ex potassium concentration greater than 35%
    • F_ex chloride concentration greater than 2.5% (2.7% +/- 1.1%)
  • In patients with CLD, urine chloride concentration is very low or undetectable (< 10 mmol/L). Stool is usually watery, and electrolyte studies are very helpful and diagnostic, as follows:
    • Stool chloride concentration is greater than 100 mmol/L.
    • Stool sodium and potassium concentrations are elevated.
    • Stool chloride concentration is greater than stool sodium plus potassium concentrations, which is normally less than either. Chloride concentrations are lowest in colonic secretions and are usually less than 35 mmol/L.
    • Ratio of stool chloride to combined sodium and potassium concentrations is greater than 0.6.
  • Patients with cystic fibrosis typically demonstrate high sweat chloride and sodium concentrations. Urine chloride concentration is usually very low, and stools are usually not watery as they are in patients with CLD.
• Renal function: Renal function is usually normal. Glomerular filtration rate (GFR) may be low in patients with severe disease.
• Liver function tests: Liver function test results are usually within the reference range in patients with CLD and Bartter syndrome but may be deranged in patients with cystic fibrosis.

• Ultrasonography

  • Prenatal ultrasonography may be useful in the detection of minimal polyhydramnios and assessment of intestinal fluid content, which is increased in patients with CLD.
  • Postnatal ultrasonography may be useful in the evaluation of a fluid-filled bowel, which is characteristically increased in patients with CLD. Ultrasonography may also assist in the evaluation of renal echogenicity, nephrocalcinosis, medullary or diffuse calcinosis, and renal growth. See the image below. Severe nephrocalcinosis in a 2-year-old child with Bartter syndrome.
• Wrist radiography: This may be performed to assess bone age in infants with growth failure. Wrist radiography may also help assess bone density and the presence of rickets.
• Brain CT scanning: Brain CT scans are useful for evaluation of brain growth and calcifications.
• Upper GI series: An upper GI series assists in detecting gastroesophageal reflux and pyloric stenosis, which are case-dependent conditions.^[6]
• Renal nuclear scanning: This may help assess renal function but is not useful in all patients.
• Brain MRI: This is helpful in patients who present with seizures.

• Electroencephalography: This is helpful in patients who present with seizures.
• Genetic studies

  • DNA diagnosis is available for most congenital disorders that cause hypochloremic metabolic alkalosis.
  • For CLD, the CLD (SLC26A3) locus is on band 7q22-q31.1.^{[7, 8]}
  • Bartter syndrome is identified by NKCC2, ROMK, and CLCNKB;^[9] Bartter syndrome with deafness is identified by BSND; and Bartter syndrome with autosomal dominant hypocalcemia is identified by CASR.
  • For cystic fibrosis, the CFTR locus is on band 7q31.2.
  • For Gitelman syndrome, the NCCT locus is on 16q.

Physiologic studies of renal tubules by performing maximal free water clearance during hypotonic saline diuresis is indicated.

• Oral water at 20 mL/kg is administered over 30 minutes, followed by one-half isotonic sodium chloride solution 600 mL/m²/h for 2-3 hours. During this time, urine is collected in aliquots over 30-minute periods for 4-6 aliquots. These samples are sent for evaluation of creatinine, sodium, potassium, and chloride levels, and for osmolality, pH, and volume.
• Usually, urine is diluted by administration of oral water.
• Halfway through each collection, a blood sample is obtained for evaluation of creatinine, sodium, potassium, and chloride levels, and for pH and osmolality.
• Calculate the clearance of each substance, then determine the ratio by dividing water clearance by the sum of chloride clearance and water clearance: (water clearance)/(chloride clearance + water clearance).
• Usually, the results of the above equation reflect the percentage of distal tubule sodium and chloride reabsorption. Normal values are up to 85-90%, which means that the percentage of chloride and sodium excreted should be 10-15% (this is corrected to 100 mL GFR). In patients with Bartter syndrome, the percentage of chloride and sodium excreted can reach 35% or more.

• Renal biopsy is not usually indicated, but, if performed, it may reveal interstitial fibrosis and calcium/urate crystal deposition.