Medservatory
USMLE Step 1Renal & acid–baseEP 12 of 21

Bartter vs Gitelman: NKCC2, NCC and urine calcium

Bartter syndrome behaves like an inherited loop diuretic and Gitelman syndrome like an inherited thiazide. Both cause metabolic alkalosis, but they split on urine calcium.

  • 5:21 video
  • 3 min read
  • 6 sources
  • Published 28 Oct 2026
Video lesson · 5:21 · Watch on YouTubeSeries: Acid–Base Disorders & ABG Interpretation · @medservatory
Chapters (6)
By the end of this lesson

Match loop diuretics/Bartter syndrome and thiazides/Gitelman syndrome to their transporter defects (NKCC2 / NCC), and explain the resulting metabolic alkalosis and urinary calcium pattern.

The short version

  1. Loop diuretics and Bartter syndrome block NKCC2; thiazides and Gitelman syndrome block NCC.
  2. Both lose salt, raise renin and aldosterone, waste potassium and hydrogen, and cause a chloride-unresponsive alkalosis with normal or low blood pressure.
  3. Loop-type defects lose calcium in the urine; thiazide-type defects keep it, so urine calcium is low in Gitelman syndrome.
  4. Gitelman syndrome also wastes magnesium, so a low serum magnesium makes it more likely.

The puzzle: low potassium, alkalosis and very low urine calcium

A young woman has a potassium of 2.8 mEq/L and a bicarbonate of 33 mEq/L. Her blood pressure is normal, she takes no diuretics, and yet her urine calcium is very low. What is broken in her tubules?

This lesson is Bartter vs Gitelman: loop diuretics and Bartter syndrome on one side, thiazides and Gitelman syndrome on the other, the transporter each one blocks, and why both cause alkalosis.[1][2][5]

Bartter vs Gitelman: NKCC2 (loop) vs NCC (thiazide)

In the thick ascending limb of the loop of Henle, the link is NKCC2, which carries sodium, potassium and two chlorides into the cell. Loop diuretics block it.[1][4]

Further along, in the distal convoluted tubule, the link is NCC, the sodium chloride cotransporter. Thiazides block it.[1][5]

Bartter syndrome behaves like an inherited loop diuretic: type I is a defect in NKCC2 itself, and type II is a defect in ROMK, the potassium channel that feeds it. Gitelman syndrome behaves like an inherited thiazide, with a defect in NCC.[1]

Drug and inherited counterpart
TransporterSiteInherited counterpart
Loop diureticsNKCC2Thick ascending limbBartter syndrome (type I NKCC2, type II ROMK)
ThiazidesNCCDistal convoluted tubuleGitelman syndrome

The shared result: salt loss, aldosterone and metabolic alkalosis

Block either transporter and the body loses salt and volume. Falling volume switches on renin and aldosterone. Aldosterone makes the collecting duct keep sodium, at the price of losing potassium and hydrogen ions.[1][2]

Each hydrogen ion lost into the urine leaves a new bicarbonate behind in the blood, so alkalosis is generated. Potassium is lost in the same exchange. Volume depletion and low potassium then maintain the alkalosis, by keeping bicarbonate reabsorption high.[2]

  1. Salt and volume are lostEither transporter block causes salt wasting.
  2. Renin and aldosterone riseFalling volume switches them on.
  3. Potassium and hydrogen are lostThe collecting duct keeps sodium at their expense.
  4. Alkalosis is generated, then maintainedNew bicarbonate is made; volume depletion and low potassium keep bicarbonate reabsorption high.

Renin and aldosterone are high, yet blood pressure is normal or low, because the root problem is salt loss.[1][3] The urine keeps wasting chloride, so urine chloride is above 20 mEq/L: a chloride-unresponsive pattern.[2]

The part exams love: urine calcium and magnesium

In the thick ascending limb, potassium leaks back into the lumen through ROMK, and that makes the lumen positive. That charge pushes calcium and magnesium between cells, back into the blood. Block NKCC2 and the charge fades, so calcium pours into the urine.[4]

So with loop diuretics, urine calcium is raised; in Bartter syndrome it is normal or raised, and nephrocalcinosis can follow.[1][4]

Thiazides and Gitelman syndrome are the opposite: the kidney holds on to calcium, so urine calcium is low. Gitelman syndrome also wastes magnesium, so a low serum magnesium makes it more likely.[1][4][5]

Bartter vs Gitelman at a glance
FeatureBartter syndromeGitelman syndrome
Behaves likeLoop diureticThiazide
DefectNKCC2 (type I) or ROMK (type II)NCC
Urine calciumNormal or raised; nephrocalcinosis can followLow
MagnesiumNormal or decreasedDecreased, sometimes greatly
Blood pressureNormal or lowNormal or low
Urine chlorideAbove 20 mEq/LAbove 20 mEq/L

Working through the case: Gitelman syndrome

The practice question gives a 24-year-old woman with fatigue, cramps and salt craving, potassium 2.8 mEq/L, bicarbonate 33 mEq/L, magnesium 1.2 mg/dL, pH 7.48, PaCO₂ 46 mm Hg, high plasma renin, urine chloride 48 mEq/L and a 24-hour urine calcium of 40 mg. Start with the gas.[6]

Expected PaCO₂ for HCO₃⁻ 33
  1. 33 − 24 = a rise of 9
  2. 9 × 0.7 = 6.3
  3. 40 + 6.3 = 46.3, about 46
  4. Measured PaCO₂ is 46: appropriate compensation, one disorder only

That is a single metabolic alkalosis with no second disorder. Normal blood pressure with high renin, urine chloride above 20 and a negative diuretic screen point to renal potassium and hydrogen loss from salt wasting. Low urine calcium and low magnesium then favour the thiazide-like defect, Gitelman syndrome, over a loop-like one.[1][2][5]

Practice question

Original · USMLE style
Your turnQB-MS-S1-REN-012-01

A 24-year-old woman comes to the clinic because of months of fatigue and muscle cramps. She craves salty food. She denies vomiting, laxative use and diuretic use, and a urine diuretic screen is negative. Temperature is 36.7 C (98.1 F), pulse is 78/min, respirations are 14/min, and blood pressure is 100/62 mm Hg. Physical examination shows no abnormalities. Laboratory studies show:

Results
Serum Na⁺136 mEq/L (reference 136–145)
Serum K⁺2.8 mEq/L (reference 3.5–5.0)
Serum Cl⁻94 mEq/L (reference 98–106)
Serum HCO₃⁻33 mEq/L (reference 22–28)
Serum Mg²⁺1.2 mg/dL (reference 1.5–2.0)
Plasma renin activityelevated
Arterial pH (room air)7.48 (reference 7.35–7.45)
Arterial PCO₂ (room air)46 mm Hg (reference 35–45)
Urine Cl⁻48 mEq/L
Urine calcium, 24-hour40 mg (reference 100–300)
Which of the following is the most likely cause of this patient's findings?
Pick one option. Your answers stay on this device.

Common questions

What is the difference between Bartter and Gitelman syndrome?

Bartter syndrome behaves like an inherited loop diuretic (type I NKCC2, type II ROMK); Gitelman syndrome behaves like an inherited thiazide (NCC). Urine calcium is normal or raised in Bartter and low in Gitelman, and Gitelman also wastes magnesium.

Why do Bartter and Gitelman syndromes cause metabolic alkalosis?

Both lose salt and volume, which raises renin and aldosterone. Aldosterone makes the collecting duct keep sodium at the price of potassium and hydrogen, so new bicarbonate is generated; volume depletion and low potassium then maintain the alkalosis.

Why is urine calcium low in Gitelman syndrome and high with loop diuretics?

In the thick ascending limb, a lumen-positive charge pushes calcium back into the blood; blocking NKCC2 removes it and calcium is lost. With a thiazide-type defect the kidney holds on to calcium, so urine calcium is low.

Is blood pressure high or low in Bartter and Gitelman syndromes?

Normal or low. Renin and aldosterone are high, yet blood pressure is not raised, because the root problem is salt loss.

Transcript

Read the full narration, by chapter629 words

0:00A young woman with K+ 2.8, HCO3- 33 and very low urine calcium

A young woman has a potassium of 2.8, and a bicarbonate of 33. Her blood pressure is normal, and she takes no diuretics. Yet her urine calcium is very low. What is broken in her tubules? Today: loop diuretics and Bartter, thiazides and Gitelman, the transporter each one blocks, and why both cause alkalosis.

0:24The mental model: NKCC2 (loop) vs NCC (thiazide), Bartter and Gitelman

First, the mental model. In the thick ascending limb of the loop of Henle, the link is NKCC two, which carries sodium, potassium and two chlorides into the cell. Further along, in the distal convoluted tubule, the link is NCC, the sodium chloride cotransporter. Loop diuretics block NKCC two. Thiazides block NCC. Bartter syndrome behaves like an inherited loop diuretic: type one is a defect in NKCC two itself, and type two is a defect in ROMK, the potassium channel that feeds it. Gitelman syndrome behaves like an inherited thiazide, with a defect in NCC.

1:09The shared result: salt loss, aldosterone, K+ and H+ loss, alkalosis

Now the shared result: alkalosis. Block either, and the body loses salt and volume. Falling volume switches on renin and aldosterone. Aldosterone makes the collecting duct keep sodium, at the price of losing potassium and hydrogen ions. Hydrogen lost into the urine means new bicarbonate, so potassium falls and alkalosis is generated. Volume depletion and low potassium then maintain it, by keeping bicarbonate reabsorption high. Renin and aldosterone are high, yet blood pressure is normal or low, because the root problem is salt loss. The urine keeps wasting chloride, so urine chloride is above 20, a chloride-unresponsive pattern.

1:56The part exams love: urine calcium and magnesium

Now the part exams love: calcium. In the thick ascending limb, potassium leaks back into the lumen through ROMK, and that makes the lumen positive. That charge pushes calcium and magnesium between cells, back into the blood. Block NKCC two, the charge fades, and calcium pours into the urine. So with loop diuretics and Bartter syndrome, urine calcium is normal or raised, and nephrocalcinosis can follow. Thiazides and Gitelman syndrome are the opposite: the kidney holds on to calcium, so urine calcium is low. Gitelman syndrome also wastes magnesium, so a low serum magnesium makes it more likely. Loop: lose calcium. Thiazide: save calcium.

2:47Practice question

Your turn. A 24-year-old woman has months of fatigue and muscle cramps, and she craves salty food. Blood pressure is 100 over 62. She denies vomiting, laxatives and diuretics, and a urine diuretic screen is negative. Sodium 136, potassium 2.8, chloride 94, bicarbonate 33, magnesium 1.2 mg/dL. Arterial pH 7.48, PaCO2 46. Plasma renin is high. Urine chloride is 48 milliequivalents per litre, and 24-hour urine calcium is 40 milligrams, which is low. Which of the following is the most likely cause? A, loss of function of NKCC two. B, loss of function of NCC. C, gain of function of the collecting duct sodium channel, EN a C. D, impaired hydrogen secretion by alpha-intercalated cells. E, an aldosterone-producing adrenal adenoma. Pause here and decide. First, the gas: expected PaCO2 is about 46, so this is a single metabolic alkalosis, with no second disorder. D is out: impaired hydrogen secretion causes a metabolic acidosis, and she has an alkalosis. E is out: an adenoma gives high blood pressure and suppressed renin, and hers is normal with renin high. C is out: Liddle syndrome also gives high blood pressure. A is out: a defect in NKCC two would waste calcium, and her urine calcium is low. So the answer is B: loss of NCC, Gitelman syndrome.

4:44High-yield recap and next lesson

Three things to keep. One: loop diuretics and Bartter syndrome block NKCC two; thiazides and Gitelman syndrome block NCC. Two: both lose salt, raise aldosterone, waste potassium and hydrogen, and cause chloride-unresponsive alkalosis with normal or low blood pressure. Three: loop means calcium lost, thiazide means calcium kept, and Gitelman also lowers magnesium. Next up: respiratory acidosis, and how acute and chronic compensation differ.

Sources

Numbers in the text, e.g. [1], point here
  1. Bartter Syndrome and Gitelman Syndrome. MSD Manual Professional Version. msdmanuals.com/professional/pediatrics/congenital-renal-transport-abnormalities/bartter-syndrome-and-gitelman-syndrome
  2. Metabolic Alkalosis. MSD Manual Professional Version. msdmanuals.com/professional/endocrine-and-metabolic-disorders/acid-base-regulation-and-disorders/metabolic-alkalosis
  3. Hypokalemia. MSD Manual Professional Version. msdmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypokalemia
  4. Lee CT et al. The role of calbindin-D28k on renal calcium and magnesium handling during treatment with loop and thiazide diuretics. Am J Physiol Renal Physiol, 2015 (loop diuretics raise and thiazides lower urinary calcium). pmc.ncbi.nlm.nih.gov/articles/PMC4888563
  5. Gitelman syndrome: transport defect, hypocalciuria and hypomagnesaemia (open-access articles on PubMed Central). pmc.ncbi.nlm.nih.gov/articles/PMC8163730 · pmc.ncbi.nlm.nih.gov/articles/PMC4712579 · pmc.ncbi.nlm.nih.gov/articles/PMC12433184
  6. Nickson C. Metabolic Alkalosis. Life in the Fast Lane (LITFL), 11 Oct 2025 (expected PCO2 about 0.7 mm Hg per 1 mEq/L rise in HCO3-). litfl.com/metabolic-alkalosis/

The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.

Image credits. Illustrations: Servier Medical Art (smart.servier.com), licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/); adapted (recoloured, outlined, resized): nephron. All other diagrams are original; the patient and example values are illustrative.

Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-REN-012.

For exam study only, not medical advice. Read the medical disclaimer.

In this series

Playlist on YouTube
← Previous · EP 11Vomiting metabolic alkalosis: why the urine turns acid
  1. EP 01ABG interpretation, made simple5:35
  2. EP 02Anion gap explained: high vs normal gap metabolic acidosis5:25
  3. EP 03Winters' formula: the expected PaCO₂ in metabolic acidosis5:10
  4. EP 04Delta ratio: find the hidden second acid–base disorder5:09
  5. EP 05New bicarbonate: how the kidney excretes acid with ammonium5:23
  6. EP 06High anion gap metabolic acidosis causes, sorted by the anion5:54
  7. EP 07Osmolar gap: how toxic alcohols hide from the anion gap5:31
  8. EP 08Urine anion gap: telling diarrhea from RTA5:33
  9. EP 09Renal tubular acidosis: tell RTA types 1, 2 and 4 apart5:24
  10. EP 10Metabolic alkalosis: generation, maintenance and urine chloride5:30
  11. EP 11Vomiting metabolic alkalosis: why the urine turns acid5:36
  12. EP 12Bartter vs Gitelman: NKCC2, NCC and urine calcium5:21
  13. EP 13Respiratory acidosis compensation: acute vs chronic5:22
  14. EP 14Respiratory alkalosis compensation: acute vs chronic5:33
  15. EP 15Metabolic alkalosis compensation: the expected PaCO₂5:12
  16. EP 16Salicylate poisoning acid-base: a classic mixed disorder5:31
  17. EP 17Type A vs type B lactic acidosis: split it by mechanism5:33
  18. EP 18DKA anion gap explained: from high gap to hyperchloraemic acidosis5:42
  19. EP 19Acidosis and hyperkalemia: how pH shifts potassium5:43
  20. EP 20ABG interpretation in 6 steps: the acid-base algorithm5:32
  21. EP 21Acid-base practice cases: three ABG vignettes, one algorithm5:44