Paper III — Kidney, fluids and electrolytes

Numerical Thresholds Parameter Value Normal serum osmolality 285 ± 2 mOsm/kg ADH release threshold 280 mOsm/kg Thirst threshold 5–10 mOsm/kg above the ADH threshold Hyponatremia <135 mEq/L; clinically significant <130; severe <120 True hypo-osmolality <275 mOsm/kg Hypernatremia >145 mEq/L Inappropriately concentrated urine Urine osmolality >100 mOsm/kg Urine sodium in SIADH >40 mEq/L (may approach 100)

Correction Rates — Learn These Verbatim Situation Target Complication if exceeded Hyponatremia Raise Na by 6–8 mEq/L / 24 h (4–8 in the Osmotic demyelination syndrome — acute phase) pontine and extrapontine, delayed onset Hypernatremia Lower Na by <10 mEq/L / 24 h Cerebral oedema Monitoring — hyponatremia Serum Na 2-hourly; stop if rise >0.5 — mEq/L/h Monitoring — hypernatremia Serum Na 4-hourly —

Formulae Serum osmolality = 2[Na] + glucose/18 + BUN/2.8 (mg/dL) Effective serum osmolality = 2[Na] + glucose/18 (urea excluded — freely permeable) Water replacement / 24 h (hypernatremia) = TBW × [(Nagoal/Nacurrent) − 1] + ongoing losses TBW = 0.6 × wt if <75 y; 0.5 × wt if >75 y; Nagoal = Nacurrent − 10 Calculated osmolarity (ESPEN, dehydration screening) = 1.86 × (Na + K) + 1.15 × glucose + urea + 14 (mmol/L)

Fluid Selection Fluid Sodium Use 3% saline 513 mEq/L Severe symptomatic hyponatremia. Bolus 100–150 mL (2–4 mL/kg) over 20–40 min, or infusion 0.5–1.0 mL/kg/h 0.9% saline 154 mEq/L Hypovolemic hyponatremia (1–2 L trial). Worsens SIADH. Does not lower osmolality in hypernatremia 0.45% saline 77 mEq/L Hypernatremia with combined water and solute loss (50% free water) 5% dextrose 0 Hypernatremia from pure water loss; also used to re-lower after overcorrection Oral salt — 4–12 g/day in divided doses, hypovolemic hyponatremia

Named Trials and Landmark Studies Name Message SALT-1 / SALT-2 Tolvaptan in 448 subjects — raised sodium; only a small SF-12 quality-of-life gain, significant in the US cohort only INSIGHT Tolvaptan in 107 SIADH patients — sodium 129 → 136 mEq/L but no improvement in the primary cognitive endpoint Renneboog et al. Mild chronic hyponatremia causes falls, unsteadiness and attention deficits; gait and reaction time improve on correction Verbalis (rat model) Chronic hyponatremia causes osteoporosis via osteoclastic bone resorption SALSA (JAMA Intern Med Bolus vs continuous 3% saline — both safe and effective; bolus needed less relowering therapy 2021) MacMillan (NEJM Evid 2023) 22,858 admissions — ODS only 0.05%; 7 of 12 cases had no rapid correction Seethapathy (NEJM Evid 3,274 patients — slower correction linked to higher mortality and longer stay 2023) Ayus meta-analysis (JAMA 11,811 patients — correction 8–10 mEq/L/24 h: lower in-hospital (OR 0.67) and 30-day (RR 0.55)

One-Line Volume-Status Discriminator Type Clue Urine Na Treatment Hypovolemic Orthostatic hypotension, <20 mEq/L 0.9% saline 1–2 L; oral salt. Never diuretics, GI losses fluid restrict Euvolemic (SIADH) No oedema, no postural drop; >40 mEq/L Fluid restriction 500–1500 mL/day; drugs, pneumonia, CNS or lung urea, vaptan, empagliflozin lesion Hypervolemic Oedema — heart failure, Usually low Fluid restriction + treat underlying cirrhosis, nephrotic syndrome disease; loop diuretic Final Three-Sentence Summary Physiology: ageing brings reduced thirst, reduced urinary concentrating ability, reduced free water excretion and a fall in total body water from 60% to 50% after age 75 — a narrow margin in both directions. Diagnosis: confirm true hypo-osmolality, classify by volume status using urine sodium, then review every drug and exclude hypothyroidism and adrenal insufficiency before diagnosing SIADH. Treatment: correct according to neurocognitive symptoms, not the number — up by 6–8 mEq/L per 24 hours in hyponatremia, down by less than 10 mEq/L per 24 hours in hypernatremia.