Short revision bullets only, not a replacement for the full lesson sections below.
Toggle for a short revision list before a mock or question block.
Pathophysiology
Clinical meaning
Bartter syndrome is a group of rare inherited renal tubular disorders characterized by impaired sodium chloride reabsorption in the thick ascending limb (TAL) of the loop of Henle, resulting in salt wasting, hypokalemic metabolic alkalosis, hyperreninemia, hyperaldosteronism, and normal to low blood pressure despite markedly elevated renin and aldosterone levels. The syndrome mimics the effects of chronic loop diuretic (furosemide) administration, earning it the description of a genetic furosemide-like condition.
To understand Bartter syndrome, the nurse must appreciate normal ion transport in the TAL. The TAL is responsible for reabsorbing approximately 25 to 30% of filtered sodium chloride. The primary transporter is the sodium-potassium-chloride cotransporter type 2 (NKCC2, also called BSC1) located on the luminal (apical) membrane. NKCC2 transports one sodium, one potassium, and two chloride ions from the tubular lumen into the TAL cell. This process is driven by the low intracellular sodium concentration maintained by the basolateral Na+/K+-ATPase, which pumps sodium out of the cell into the peritubular capillary. Potassium that enters the cell via NKCC2 recycles back into the lumen through the renal outer medullary potassium channel (ROMK), maintaining the lumen-positive transepithelial voltage that drives paracellular reabsorption of calcium and magnesium. Chloride exits the cell basolaterally through chloride channels (ClC-Kb, requiring its subunit barttin).
Bartter syndrome is classified into five types based on the specific gene mutation. Type I (neonatal, severe) involves loss-of-function mutations in SLC12A1 encoding NKCC2 itself. Type II (neonatal) involves mutations in KCNJ1 encoding the ROMK potassium channel. Type III (classic Bartter) involves mutations in CLCNKB encoding the basolateral chloride channel ClC-Kb. Type IV (neonatal with sensorineural deafness) involves mutations in BSND encoding barttin, the beta-subunit of ClC-Ka and ClC-Kb chloride channels expressed in both the kidney and inner ear. Type V involves gain-of-function mutations in CASR encoding the calcium-sensing receptor, which inhibits ROMK and NKCC2 activity.
The pathophysiology cascades from impaired NaCl reabsorption in the TAL. The defective transporter causes sodium chloride wasting into the urine. The resulting volume contraction activates the renin-angiotensin-aldosterone system (RAAS): juxtaglomerular cells sense reduced renal perfusion and release renin, which converts angiotensinogen to angiotensin I, then angiotensin-converting enzyme (ACE) produces angiotensin II, which stimulates aldosterone release from the adrenal zona glomerulosa. Aldosterone acts on the collecting duct principal cells to increase sodium reabsorption through epithelial sodium channels (ENaC) in exchange for potassium and hydrogen ion secretion. This aldosterone-driven exchange produces the hallmark hypokalemia and metabolic alkalosis.
Despite markedly elevated angiotensin II levels, patients with Bartter syndrome maintain normal or low blood pressure. This paradox is explained by increased production of vasodilatory prostaglandins (primarily prostaglandin E2, PGE2) by the macula densa and interstitial cells in response to the TAL dysfunction. PGE2 production is stimulated by reduced NaCl delivery to the macula densa and by the volume depletion itself, creating a compensatory vasodilatory state that counteracts the vasoconstrictive effects of angiotensin II. This prostaglandin overproduction also contributes to the polyuria, fever, and failure to thrive seen in neonatal Bartter syndrome.
The loss of the lumen-positive transepithelial voltage in the TAL (normally generated by ROMK-mediated potassium recycling) impairs paracellular reabsorption of calcium and magnesium, causing hypercalciuria and hypomagnesemia. Chronic hypercalciuria leads to nephrocalcinosis (calcium deposition in the renal medulla), which can further impair renal concentrating ability and contribute to progressive chronic kidney disease.
Clinically, neonatal Bartter syndrome (types I, II, IV) presents in the first weeks of life with severe polyuria, polydipsia, dehydration, failure to thrive, fever, and electrolyte derangements. Pregnancy may be complicated by polyhydramnios (excessive amniotic fluid) due to fetal polyuria. Classic Bartter syndrome (type III) presents later in childhood or adolescence with milder symptoms: muscle weakness, cramps, fatigue, growth retardation, salt craving, constipation, and polyuria. Laboratory findings consistently show hypokalemia (often 2.0 to 3.0 mEq/L), metabolic alkalosis (serum bicarbonate greater than 28 mEq/L), elevated renin and aldosterone, normal to low blood pressure, and elevated urinary chloride (differentiating from vomiting-induced alkalosis where urinary chloride is less than 10 mEq/L).
Treatment targets the prostaglandin-mediated and aldosterone-mediated pathophysiology. Indomethacin (a non-selective cyclooxygenase inhibitor) reduces PGE2 production, decreasing salt and water wasting and improving growth. Potassium supplementation (potassium chloride, 3 to 10 mEq/kg/day) is essential to correct and maintain normokalemia. Potassium-sparing diuretics (spironolactone, amiloride) reduce aldosterone-driven potassium wasting. Magnesium supplementation is required for concomitant hypomagnesemia. ACE inhibitors or ARBs may be used to reduce aldosterone production. Sodium chloride supplementation is needed in neonatal forms with severe salt wasting.
Exam Focus
Exam relevance
Risk factors:
- Autosomal recessive inheritance (both parents must carry the mutation; 25% recurrence risk per pregnancy)
- Consanguineous parents (increased probability of homozygous mutations for rare recessive disorders)
- Family history of Bartter syndrome or unexplained neonatal salt wasting
- Neonatal presentation: polyhydramnios during pregnancy, preterm birth, failure to thrive in first weeks of life
- Genetic mutations in SLC12A1 (NKCC2), KCNJ1 (ROMK), CLCNKB (ClC-Kb), BSND (barttin), or CASR (calcium-sensing receptor)
- Populations with high rates of consanguinity (higher carrier frequency of recessive alleles)
- Sensorineural hearing loss in infancy (suggestive of Type IV Bartter with barttin mutation)
Diagnostics:
- Serum electrolytes: hypokalemia (typically 2.0 to 3.0 mEq/L, may be severe), metabolic alkalosis (bicarbonate greater than 28 mEq/L), hypomagnesemia (less than 1.5 mg/dL in many subtypes), hyponatremia in severe cases
- Serum renin and aldosterone: both markedly elevated (hyperreninemic hyperaldosteronism) with normal or low blood pressure (distinguishing from Conn syndrome where blood pressure is elevated)
- Urine electrolytes: elevated urinary chloride (greater than 20 mEq/L, distinguishing from vomiting-induced hypokalemic alkalosis where urinary chloride is less than 10 mEq/L), elevated urinary sodium, elevated urinary calcium (hypercalciuria in types I and II)
- Renal ultrasound: nephrocalcinosis (medullary calcium deposits) especially in types I and II with chronic hypercalciuria; assess kidney size and cortical echogenicity
- Genetic testing: mutation analysis of SLC12A1, KCNJ1, CLCNKB, BSND, CASR genes for definitive diagnosis and subtype classification
- Audiometry: sensorineural hearing loss assessment for suspected Type IV (barttin mutation affecting inner ear chloride channels)
Core concept
Additional clinical detail, exam hooks, and takeaways continue in the full lesson.
Clinical scenario
Additional clinical detail, exam hooks, and takeaways continue in the full lesson.
Takeaways
Additional clinical detail, exam hooks, and takeaways continue in the full lesson.
Unlock full lesson + practice questions
3 more sections with scenarios, priorities, and review drills.
We didn’t match sample stems to this lesson in the bank yet. You can still run a topic-scoped drill with the same pathway filters—items load from your live NCLEX-RN pool.
