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Hypochloremic Alkalosis Workup

  • Author: Abbas AlAbbad, MD; Chief Editor: Luis O Rohena, MD  more...
 
Updated: Mar 13, 2014
 

Laboratory Studies

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 testing for alpha1 -fetoprotein is not routine, levels may be elevated.

Blood workup

Serum electrolyte levels may be within the reference range, especially in neonates and treated patients. However, typical findings include low concentrations of serum chloride, sodium, and potassium. 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 rises; thus, the potassium level is less than normal by 0.6 mmol/L when measured at a serum pH of 7.5.

Serum pH and bicarbonate, calcium, uric acid, hemoglobin (if patient is not anemic), renin, and aldosterone levels may be elevated. The serum renin 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.

Urine and stool studies

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 (Fex) studies are more reliable than absolute values. Usually, results are higher than reference range values, as follows:

  • F ex sodium concentration >1%
  • F ex potassium concentration >35%
  • F ex chloride concentration >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 >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 (usually < 35 mmol/L)
  • The 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.

Kidney and liver function tests

Renal function is usually normal. The glomerular filtration rate (GFR) may be low in patients with severe disease.

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.

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.[6, 7] Bartter syndrome is identified by NKCC2, ROMK, and CLCNKB[8] ; 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.

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 (see the images below) 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.

Severe nephrocalcinosis in a 2-year-old child with Severe nephrocalcinosis in a 2-year-old child with Bartter syndrome.
Renal ultrasonograph of an infant with congenital Renal ultrasonograph of an infant with congenital chloride-losing diarrhea showing diffuse sclerosis.
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Physiologic Study of Tubule

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

Oral administration of water 20 mL/kg over 30 minutes is followed by administration of a one-half isotonic sodium chloride solution at a rate of 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, as well as for osmolality, pH, and volume. Usually, urine is diluted by oral administration of water. Halfway through each collection, a blood sample is obtained for evaluation of creatinine, sodium, potassium, and chloride levels, and for pH and osmolality. The clearance of each substance is calculated, and a ratio is derived by means of the following formula:

  • Water clearance/(chloride clearance + water clearance)

Usually, the result of this formula reflects 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% (corrected to a GFR of 100 mL/min/1.73 m2). In patients with Bartter syndrome, the percentage of chloride and sodium excreted can reach 35% or more.

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Other Studies

Additional studies that may be considered include the following:

  • Wrist radiography - This may be performed to determine bone age in infants with growth failure; it may also help assess bone density and the presence of rickets
  • Upper gastrointestinal (GI) series - This helps detect gastroesophageal reflux and pyloric stenosis, which are case-dependent conditions [9]
  • Computed tomography (CT) of the brain - This is useful for evaluation of brain growth and calcifications
  • Magnetic resonance imaging (MRI) of the brain - This is helpful in patients who present with seizures
  • Electroencephalography (EEG) - This is also helpful in patients who present with seizures
  • Renal nuclear scanning - This may facilitate assessment of renal function but is not useful in all patients
  • Renal biopsy - This is not usually indicated, but if it is performed, it may reveal interstitial fibrosis and calcium/urate crystal deposition
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Contributor Information and Disclosures
Author

Abbas AlAbbad, MD Associate Professor, Alfaisal University College of Medicine; Acting Head and Consultant Pediatric Transplant Nephrologist, Section of Pediatric Transplant Nephrology, Department of Kidney and Pancreas Transplantation, Organ Transplant Center, King Faisal Specialist Hospital and Research Center, Saudi Arabia

Abbas AlAbbad, MD is a member of the following medical societies: American Academy of Pediatrics, International Pediatric Transplant Association, International Society for Peritoneal Dialysis

Disclosure: Nothing to disclose.

Coauthor(s)

Sunil Sinha, MD Assistant Professor, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Sunil Sinha, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Acknowledgements

Sadek Al-Omran, MD Consultant Of Pediatrics and Pediatric Nephrologist, Departments of Pediatrics and Pediatric Nephrology, Maternity and Children's Hospital-Al-Ahsa, Saudi Arabia

Disclosure: Nothing to disclose.

Robert J Ferry Jr, MD Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Eli Lilly & Co Grant/research funds Investigator; MacroGenics, Inc Grant/research funds Investigator; Ipsen, SA (formerly Tercica, Inc) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Grant/research funds Investigator; Bristol-Myers-Squibb Grant/research funds Other; Amylin Other; Pfizer Grant/research funds Other; Takeda Grant/research funds Other

Pinar Ozand, MD, PhD Head, Section of Inborn Errors of Metabolism, Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Saudia Arabia

Disclosure: Nothing to disclose.

Christian J Renner, MD Consulting Staff, Department of Pediatrics, University Hospital for Children and Adolescents, Erlangen, Germany

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
  1. Akil I, Ozen S, Kandiloglu AR, Ersoy B. A patient with Bartter syndrome accompanying severe growth hormone deficiency and focal segmental glomerulosclerosis. Clin Exp Nephrol. 2010 Jun. 14(3):278-82. [Medline].

  2. Naesens M, Steels P, Verberckmoes R. Bartter's and Gitelman's syndromes: from gene to clinic. Nephron Physiol. 2004. 96(3):p65-78. [Medline].

  3. Al-Abbad A, Nazer H, Sanjad SA, Al-Sabban E. Congenital chloride diarrhea: A single center experience with ten patients. Ann Saudi Med. 1995 Sep. 15(5):466-9. [Medline].

  4. [Guideline] Grosse SD, Boyle CA, Botkin JR, et al. Newborn screening for cystic fibrosis: evaluation of benefits and risks and recommendations for state newborn screening programs. MMWR Recomm Rep. 2004 Oct 15. 53:1-36. [Medline].

  5. Aranzamendi RJ, Breitman F, Asciutto C, Delgado N, Castanos C. [Dehydration and metabolic alkalosis: an unusual presentation of cystic fibrosis in an infant]. Arch Argent Pediatr. 2008 Oct. 106(5):443-6. [Medline].

  6. Hoglund P, Haila S, Socha J, et al. Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea. Nat Genet. 1996 Nov. 14(3):316-9. [Medline].

  7. Makela S, Kere J, Holmberg C. SLC26A3 mutations in congenital chloride diarrhea. Hum Mutat. 2002 Dec. 20(6):425-38. [Medline].

  8. Simon DB, Bindra RS, Mansfield TA, et al. Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. Nat Genet. 1997 Oct. 17(2):171-8. [Medline].

  9. Hulka F, Campbell TJ, Campbell JR, Harrison MW. Evolution in the recognition of infantile hypertrophic pyloric stenosis. Pediatrics. 1997 Aug. 100(2):E9. [Medline].

 
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Infant with severe metabolic alkalosis resulting from congenital chloride-losing diarrhea.
Watery stool from an infant with congenital chloride-losing diarrhea. Chloride level was 205 mmol/L.
Renal ultrasonograph of an infant with congenital chloride-losing diarrhea showing diffuse sclerosis.
Severe nephrocalcinosis in a 2-year-old child with Bartter syndrome.
Visible bowel loops in an infant with congenital chloride-losing diarrhea.
 
 
 
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