Bartter Syndrome

• Brenner and Rector's The Kidney, 2-Volume Set, p. 3151
• NKF Primer on Kidney Diseases, 8e, p. 176

Pathophysiology

Genetic Classification (Types 1-6)

Clinical Features

Antenatal / Neonatal Bartter

• Maternal polyhydramnios (fetal polyuria)
• Premature birth
• Postnatal: severe polyuria, vomiting, failure to thrive
• Hypercalciuria and nephrocalcinosis (especially types 1, 2, 4)
• Marked electrolyte wasting: hypokalemia, metabolic alkalosis
• Type 4: add sensorineural deafness
• Type 2 neonates: paradoxical hyperkalemia initially (ROMK also mediates K+ secretion in collecting duct; other channels compensate within the first week)

Classic (Postnatal) Bartter - predominantly Type 3

• Failure to thrive, polyuria, polydipsia
• Hypokalemic, hypochloremic metabolic alkalosis
• Normal to low blood pressure despite elevated renin/aldosterone
• Vascular resistance to angiotensin II
• ~20% hypomagnesemia
• Often hypercalciuria (but less than antenatal form)
• Additional findings: growth hormone deficiency, hypophosphatemia with renal phosphate wasting, hyperparathyroidism

Distinguishing Bartter from Gitelman Syndrome

Diagnosis

• Biochemistry: hypokalemia, metabolic alkalosis, elevated plasma renin and aldosterone, normal-to-low blood pressure
• Urine: elevated Cl-, often hypercalciuria
• Exclude: surreptitious vomiting (low urine Cl-), diuretic abuse (urine diuretic screen), laxative abuse
• Genetic testing: confirms subtype
• Kidney ultrasound: may show nephrocalcinosis in antenatal types

Treatment

1. Salt and potassium supplementation - mainstay; IV saline in severely affected neonates
2. Indomethacin (COX inhibitor) - reduces PGE2, improves polyuria, raises K+, decreases renin activity; especially useful in antenatal/neonatal forms. Risk of necrotizing enterocolitis and bowel perforation in neonates.
3. Selective COX-2 inhibitors (rofecoxib, celecoxib) - proposed as alternatives with lower GI risk, though cardiovascular safety concerns exist with long-term use
4. Potassium-sparing diuretics (amiloride, spironolactone, eplerenone) - help correct hypokalemia but worsen salt wasting; use with great caution, especially in infants
5. ACE inhibitors / propranolol - reduce aldosterone-driven K+ losses
6. Magnesium supplementation - when hypomagnesemia is present

Key Points

• Bartter syndrome = "loop diuretic in a gene" - loss of TAL salt reabsorption
• Always consider if a patient has persistent hypokalemic metabolic alkalosis + normal/low BP + elevated renin/aldosterone
• Type 4 = deafness (barttin mutation)
• Type 2 = paradoxical neonatal hyperkalemia
• Type 6 (MAGED2) = transient (resolves spontaneously)
• Prostaglandins amplify the phenotype - COX inhibition is a cornerstone of therapy in severe forms
• Gitelman vs. Bartter: calcium is the key discriminator (hypercalciuria vs. hypocalciuria)

Bartter Syndrome - Simple Explanation

What is it?

The Chain Reaction

Broken salt recycler in kidney
        ↓
Salt leaks into urine (salt wasting)
        ↓
Body thinks it's "low on volume/fluid"
        ↓
Hormones (renin, aldosterone) shoot up to compensate
        ↓
Aldosterone tells kidneys to dump K+ and H+ instead
        ↓
Low potassium (hypokalemia) + alkalosis

Simple Analogy

• Normally, workers (transport proteins) reclaim salt at every station
• In Bartter, the station in the middle (Loop of Henle) has a broken worker
• Salt floods downstream, overwhelms the later stations, and the body loses potassium trying to compensate
• Blood pressure stays low despite high alarm hormones, because the body never actually has enough salt

The 4 Broken Workers (Types 1-4)

Who Gets It & When?

• Severe types (1, 2, 4): Problems start in the womb - baby urinates excessively, causing the amniotic fluid to overflow (polyhydramnios). Baby is born premature and very sick.
• Milder type (3): Problems show up in childhood - kid doesn't grow well, drinks too much water, muscles are weak.

What Does the Patient Look Like?

• Always tired and weak (low potassium affects muscles)
• Drinks a lot, pees a lot (can't concentrate urine)
• Poor growth in children
• Normal or low blood pressure - even though the body is producing huge amounts of blood pressure hormones (the body just doesn't respond to them properly)
• May have kidney stones/calcium deposits in severe types
• Type 4: also deaf

How is it Different from Gitelman Syndrome?

Treatment (Simple)

1. Give extra salt and potassium - replace what's being lost
2. Indomethacin (anti-inflammatory) - the kidneys in Bartter over-produce inflammatory signals (prostaglandins) that make things worse; blocking these helps reduce polyuria and potassium loss
3. Potassium-sparing drugs (amiloride, spironolactone) - help hold on to potassium
4. ACE inhibitors - dampen the overactive hormone system

One-Line Summary

Bartter syndrome is a genetic kidney leak where the salt recycler in the Loop of Henle is broken, causing the body to waste salt and potassium, triggering sky-high hormones - but blood pressure stays low because the leak is never fixed.

Levels of Scans in Pregnancy - Simple Guide

Overview - The Timeline

Week 6-10       Week 11-14         Week 18-22         Week 28-36+
    |               |                   |                   |
Early/Dating    1st Trimester       Anomaly Scan        Growth/
  Scan          Combined Scan      (The Big Scan)      Wellbeing Scan

Level 1 - Early / Dating Scan (6-10 Weeks)

What it checks:

• Is the pregnancy inside the uterus? (rules out ectopic)
• How many babies? (twins?)
• Is there a heartbeat?
• Measures the Crown-Rump Length (CRL) to confirm exact dates

Simple example:

"Patient comes in unsure of her dates. The scan shows a single fetus with CRL of 22mm = 9 weeks and 2 days exactly."

What it can find:

• Miscarriage (no heartbeat)
• Ectopic pregnancy (sac outside uterus = emergency)
• Twin/triplet pregnancy
• Blighted ovum (empty sac)

Level 2 - First Trimester Combined Scan (11-14 Weeks)

The scan part checks:

• Nuchal Translucency (NT) - measures a fluid pad at the back of the baby's neck
• A thicker NT = higher chance of Down syndrome or heart defects
• Normal NT = less than 3.5mm

The blood test part checks:

• PAPP-A (pregnancy-associated plasma protein A) - low in Down syndrome
• Free beta-hCG - high in Down syndrome

Combined, this detects:

• ~95% of Down syndrome (Trisomy 21) at a 5% false-positive rate
• Trisomy 18 (Edwards syndrome)
• Trisomy 13 (Patau syndrome)

Simple example:

"NT measured at 4.5mm (thick). Blood tests show low PAPP-A and high hCG. Combined risk = 1 in 50 for Down syndrome. Offered further testing (NIPT or amniocentesis)."

Level 3 - Anomaly Scan / "The Big Scan" (18-22 Weeks)

What's measured (Biometry):

Organs checked one by one:

• Cerebral ventricles (fluid spaces - enlarged = hydrocephalus?)
• Cerebellum (banana-shaped = spina bifida sign)
• Cavum septi pellucidi (small space in midline brain)
• Cisterna magna

• Lips (cleft lip)
• Palate (cleft palate harder to see)
• Eyes, nose

• 4-chamber heart view (size, position, chambers equal?)
• Outflow tracts (left and right ventricular outflow)
• Lungs (any masses?)
• Diaphragm intact?

• Stomach bubble visible? (if absent = oesophageal atresia)
• Bowel loops (bright = cystic fibrosis marker?)
• Kidneys (both present, no hydronephrosis)
• Bladder visible?
• Abdominal wall - cord insertion normal? (exomphalos/gastroschisis?)

• Full spinal column intact (open spina bifida = gap visible)

• All 4 limbs present
• Bone lengths normal

• Placental position (low-lying = possible previa?)
• Cord = 3 vessels (2 arteries + 1 vein - only 2 vessels = kidney abnormality risk)
• Amniotic fluid volume

Simple examples:

"Scan at 20 weeks: stomach bubble absent. Diagnosis = likely oesophageal atresia (EA). Baby referred to tertiary centre."

"Scan at 20 weeks: posterior fossa shows 'banana sign' and 'lemon-shaped' head. Diagnosis = Arnold-Chiari malformation (associated with open spina bifida)."

"Placenta covers the cervix completely = placenta praevia. Mother warned about bleeding risk, planned C-section."

Level 4 - Growth / Wellbeing Scan (28 Weeks Onwards)

What it checks:

• Fetal growth - is the baby on its centile?
• Doppler flow studies:
  • Umbilical artery (resistance = placenta struggling?)
  • Middle cerebral artery (brain-sparing effect?)
  • Ductus venosus (late sign of compromise)
• Amniotic fluid volume (too little = oligohydramnios; too much = polyhydramnios)
• Fetal movements and breathing movements (Biophysical Profile)

Simple example:

"Mother with hypertension at 32 weeks. Growth scan shows AC on 3rd centile (small). Umbilical artery Doppler shows absent end-diastolic flow = placental insufficiency. Decision made for early delivery."

Special/Advanced Level - Detailed/Tertiary Scan (Level 3 Ultrasound)

Extra things checked (on top of standard anomaly scan):

• Full cardiac survey (fetal echo)
• Brain: third & fourth ventricles, vermis, cisterna magna with measurements
• Nuchal fold thickness (15-20 weeks - Down syndrome marker)
• Ribs, palate in detail
• Looking for ascites

Simple example:

"Routine anomaly scan shows a bright bowel. Referred for detailed scan: confirmed echogenic bowel + dilated bowel loops. Concern for cystic fibrosis or Down syndrome. Offered amniocentesis."

Screening Blood Tests That Go With the Scans

Quadruple screen pattern to remember:

Quick Summary - One Table

• Creasy & Resnik's Maternal-Fetal Medicine, Principles and Practice
• Textbook of Family Medicine, 9e, p. 482
• Tietz Textbook of Laboratory Medicine, 7th ed., p. 2897