Hyponatraemia Detlef Bockenhauer
Key message Plasma sodium can be low due to either excess water or deficiency of salt In clinical practice, dysnatraemias almost always reflect an abnormality of water
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Collecting duct cell: action of AVP Blood Lumen
The role of the kidneys Appropriate water excretion Under control of ADH Dependent on osmotic load (consists of salt and protein intake) Usually 15-20 mosm/kg => a 10-kg child with osmotic load of 200 mosm can adjust water excretion between 0.2 litres (Uosm 1000) and 4 litres (Uosm 50 mosm/kg)
Back to the hyponatraemic patient
Why is the sodium low? Too little salt Weight should be decreased Signs of dehydration/volume depletion Too much water Weight should be stable or increased Oedema forming states
Too much water Identify defect in water excretion Low GFR--neonates, renal insufficiency Enhanced proximal reabsorption--chf, Low albumin [Cirrhosis, Nephrosis, Enteropathy ] Defect in ascending limb function--diuretics, intrinsic lesions Inability to turn off ADH SIADH Insufficient osmotic load ( tea and toast )
Clinical euvolemic or edematous Increased body weight Too much water Serum Na U na high U osm < P osm U Na Low U osm > P osm U Na High U osm = P osm U Na High U osm > P osm Excessi water intake Heart failure Nephrosis Cirrhosis Enteropathy Low albumin Diuretics Intrinsic renal disease PKD SIADH
case 1 6-months old boy with astrocytoma Receives vincristine and carboplatin 10 days later presents for routine follow-up Examination: well perfused, wt: 4.7 kg (+0.2 kg), BP: 82 mmhg date Day 1 serum sodium 125 serum osmolality 255 urine sodium 32 urine osmolality 677
Diagnosis? Too much water? Too little salt? Too little salt? Too much water?
Clinical euvolemic or edematous Increased body weight Too much water Serum Na U na high U osm < P osm U Na Low U osm > P osm U Na High U osm = P osm U Na High U osm > P osm Excess water intake Heart failure Nephrosis Cirrhosis Enteropathy Low albumin Diuretics Intrinsic renal disease PKD SIADH
Further course date Day 4 Day 8 Day 11 Day14 weight 4.44 4.87 4.9 4.86 BP 90 120 120 145 in 462 836 917 707 out 395 593 700 486 serum sodium 126 133 135 139 serum osmolality 256 257 275 284 urine sodium 152 158 268 313 urine osmolality 657 569 610 744 sodium in (mmol/kg) 10 15 19 14
Key message Sodium is reabsorbed to preserve intravascular volume and in response to renal perfusion Kidney does not sense or detect serum sodium
Treatment Fluid restriction vaptans
Hyponatraemia-case 2 11-months old girl referred for assessment of hyponatraemia, first noted incidentally during investigations for viral illness and confirmed several times subsequently Examination: well perfused, BP: 90 mmhg biochemistries plasma urine unit Sodium 121 45 mmol/l osmolality 249 252 mosmol/kg Creatinine 0.017 <1.0 mmol/l
Diagnosis? Too much water? Too little salt? Too little salt? Too much water?
Clinical euvolemic or edematous Increased body weight Too much water Serum Na U na high U osm < P osm U Na Low U osm > P osm U Na High U osm = P osm U Na High U osm > P osm Water overload Heart failure Nephrosis Cirrhosis Enteropathy Low albumin Diuretics Intrinsic renal disease PKD SIADH
Family History Mother and maternal grandmother were known to have had hyponatraemia. Maternal uncle has developmental delay and recurrent hyponatraemia (often with seizures) Mum and grandmother don t drink
Diagnosis? Nephrogenic Syndrome of inappropriate antidiuresis X-linked inherited Gain-of-function in AVPR2: R137C/L Females usually less affected
AJKD, 2012 Apr;59(4):566-8
Treatment Intuitive by patients!?increased osmotic load during infancy (urea)
Case 3 14-week old girl, presents with 5-week history of vomiting and unusual weight gain (1.1 kg over past 2 weeks) Examination: generalised pitting oedema, BP: 120 mmhg, weight 6 kg (75 th %ile) biochemistries plasma urine unit Sodium 99 <5 mmol/l osmolality 214 450 mosmol/kg Creatinine 0.021 1.0 mmol/l Albumin 8 8.6 g/l
Diagnosis? Too much water? Too little salt? Too little salt? Too much water?
Clinical euvolemic or edematous Increased body weight Too much water Serum Na U na high U osm < P osm U Na Low U osm > P osm U Na High U osm = P osm U Na High U osm > P osm Water overload Heart failure Nephrosis Cirrhosis Enteropathy Low albumin Diuretics Intrinsic renal disease PKD SIADH
Treatment Underlying condition Diuretics NOT salt!!!
Case 4 5-months old baby presents with irritability. On examination, well perfused, systolic BP of 124 mmhg biochemistries plasma urine unit Sodium 117 91 mmol/l osmolality 243 195 mosmol/kg Creatinine 0.021 0.2 mmol/l
Diagnosis? Too much water? Too little salt? Too little salt? Too much water?
Clinical euvolemic or edematous Increased body weight Too much water Serum Na U Na high U osm < P osm U Na Low U osm > P osm U Na High U osm = P osm U Na High U osm > P osm Water overload Heart failure Nephrosis Cirrhosis Enteropathy Low albumin Diuretics Intrinsic renal disease PKD SIADH
Collecting duct cell: action of AVP Blood Lumen vaptans
Further course date Day 1 Day 3 Day 5 Day 12 Tolvaptan [mg] 2 4 7.5 vitapro serum sodium 120 124 126 143 serum osmolality 251 256 272 298 urine sodium 31 28 56 60 urine osmolality 214 228 209 288
Excess water: Conclusions SIADH and cerebral salt wasting are biochemically indistinguishable Kidneys do not sense sodium concentration, just perfusion A Uosm=Posm in the face of hyponatraemia and water overload is inappropriate Treatment aimed at underlying defect and depends on chronicity Diluting capacity can be assessed with AVPR-blockers (vaptans)
Questions?