Two Little Water Cravers

Baby Mo (5mths/M)

• Chief complaint

• Repeated vomiting since 2 months old with poor weight gain

• PMH

• Gestation 40+6wks, BW 3.375kg

• Hx of fracture Rt clavicle at birth

• HbH disease – on folic supplement

• Vaccine up to date

• NKDA

• No developmental concern

HPI

• Repeated vomiting since birth ~2-3x/day • Moderate amount of undigested milk soon after feeding

• Non projectile, no bile stained

• On AF 5oz/feed, 5x/day

• Irritable, crying for milk

• Large amount of urine output ~ 7-8x/day

• BO 1x/day, YSS

• Failure to thrive • BW 50% at 1mth

• BW 25% at 2mths

• BW 0.6kg below 3% at 5mths

HPI

• No recurrent febrile episodes

• No coryzal symptoms

• No urinary symptoms

• TOCC: lives in Mainland China

• Attended Hospital in China

• USG brain unremarkable

• Abnormal thyroid function test

Physical Exam

• Afebrile

• P 158/min; SpO2 100% in RA

• AFNT

• No dysmorphism

• CR<2s, warm peripheries but dry oral mucosa

• Chest no distress, clear, AE adequate

• HS normal, no murmur

• Abd not distended, no hepatosplenomegaly, BS +ve

• Generalized hypotonia with head lag

• Spont movement of 4 limbs, reflexes normal and symmetrical

Investigations on Admission

• Hb 8.7g/dL (hypochromic microcytic)

• WBC, Plt normal

• Glucose normal

• VBG no aciodsis

• LFT normal

• RFT

• Na 167 mmol/L

• K 4.4 mmol/L

• Urea 7.8mmol/L

• Cr 32 umol/L

Hypernatremia in Children

• Na >145mmol/L

Dehydration

FENa <1%

Uosm > Posm

Extrarenal losses

Diarrhea

Skin loss

Excessive sweat

Fasting / thirst

FENa >1%

Uosm>= Posm

Osmotic Diuresis

Diuretics

Glycosuria

Post-obstructive diuresis

Non-oliguric ATN

FENa <1%

Uosm < Posm

Urine Concentrating Defect

Central DI

Nephrogenic DI

Hypernatremia in Children

Not dehydrated

FENa>1%

Uosm > Posm

Excess sodium

Increase renal solute load

Salt poisoning

FENa variable

Uosm < Posm

Central hypodipsia

Management of Baby Mo • Treat as hypernatremic dehydration

• NS bolus 10ml/kg

• ½ NS D5 solution (as maintenance + deficit replacement)

• However

• Na 171 mmol/L 174 mmol/L 177mmol/L

• K normal

• Urea 7.3mmol/L 6.4mmol/L 4.7mmol/L

• Cr 31umol/L 25umol/L 19 umol/L

• Urine ~10ml/kg/hr

• Switched IVF

• Maintenance: D5 :1/4 NS

• Urine ml to ml replacement with D5

• Gradual normalization of Na level to 155mmol/L

Polyuria

Back to Baby Mo

Further Investigations

• FENa 0.33% (hypovolemia)

• Plasma osmolality – 336mOsm/kg (H)

• Urine osmolality – 171mOsm/kg (L)

• Plasma ADH level: 30.7pg/mL (N: 1.0-13.3pg/mL)

• Water deprivation test given DDAVP (0.4mcg then 0.6mcg)

• Persistent high volume PU

• Urine osmol ~120mOsm/kg

Further Investigations

• Morning cortisol 307 (N)

• ACTH 4.4 (N)

• Low dose synacthen test: adequate cortisol response

• Growth hormone 1.9 (N)

• subclinical primary hypothyroidism:

• TSH 13.7 (H) fT4 18.1 (normal)

• Anti –TG <20 (N); anti TPO 98 (mildly raised)

• Thyroid scan: bilateral thyroid lobes uptakes present

• Urgent CT brain: NAD

Nephrogenic Diabetes Insipidus

Genetic Study

• Heterozygous AQP2 NM_000486. 5:c. 3G>T p. (Met1?)

• Heterozygous AQP2 NM_000486. 5:c 140C>T p. (Arg47Val)

• Both pathogenic

• AVPR 2 normal

• Conclusion: AQP2 related nephrogenic diabetes insipidus

Management

• Allow adequate fluid intake both day and night

• Nocturnal milk drip

• Fluid offered at 2 hourly intervals

• Management of GERD

• Nexium

• Gastrostomy feeding

• Low threshold for admission and intravenous hydration

• IV fluid hypotonic to urine

• 5% dextrose or 1/5 NS solution

• Close monitoring of body weight / fluid balance / biochemistries

Management of Hypernatremic Dehydration • Maintenance + Replacement of Loss

• Water + Sodium

• Replace over 48hrs

• Rate of correction of hypernatremia not to exceed 0.5mmol/L per hour

• Free water deficit

• (Measured Na x total body water) / (Desired Na) – (Total body water)

•

Example of Calculation

Maintenance Replacement of Loss Total Requirement

Water 100ml x 5.5 x 2 = 1100ml

Water 5.5 x 10% x 1000= 550ml (free water deficit = 455ml) (95ml loss as isotonic solution)

Water = 1100ml + 550ml = 1650ml

Sodium 3mmol/L x 5.5 x 2 = 33mmol/L

Sodium loss 154 /1000x ( 550-455) = 14mmol/L

Sodium = 33+ 14mmol/L = 47mmol/L

Body weight: 5 kg Estimated Dehydration: 10% Premorbid body weight: 5.5kg Plasma Na: 165mmol/L To correct over 48hrs

47mmol of Na in 1650ml to be given over 48hrs ie. 1/5 NS solution at 34ml/hr

Management

• Osmotic load reduction

• Consult dietician x renal solute load ~15mOsm/kg per day

• Diuretics

• Hydrochlorothiazide + amiloride (potassium sparing)

• Prostaglandin synthesis inhibitors

• Indomethacin

• Developmental Training

Renal Solute Load

• Osmotically active substances in diet

• Protein (1 gram protein yields 4 mmol Urea)

• Sodium

• Potassium

• Anions accompanying Na and K

• Renal solute load of diet = 2x (Na + K) + Protein(g) x 4

• Optimal: <15mOsm/kg/day

• Fluid (ml) required to excrete the load: 15mOsm x kg / urine osmol x 1000

• (i.e. a child with urine osmolality of 100mOsm need fluid intake of 150ml/kg/day to excrete that load)

• Carbohydrate and lipid will NOT increase osmotic load

• Metabolized without byproducts requiring renal excretion

Diuretics • Thiazides

• Inhibit reabsorption of sodium and chloride in distal convoluted tubule

• Induce mild volume depletion and thus up regulation of proximal tubular reabsorption of salt and water

• Less volume delivered to colkecting duct and lost in urine

• Hydrochlorothiazide 1mg/kg/dose BD dose

• Amiloride

• Potassium sparing effect (K supplement increase osmotic load)

• 0.1-0.3mg/kg/day

Prostaglandin Synthesis Inhibitor

• Indomethacin

• Partial chemical nephrectomy to reduce GFR

• 1-3mg/kg/day in 3-4 divided doses

• S/E: deterioration of renal function / hematological / GI upset

Progress • Catch up growth and development