Renal electrolyte handling

Sodium and ECF volume

Total body sodium sets ECF volume; plasma sodium concentration reflects water balance. The kidney matches sodium excretion to intake through:

• Renin–angiotensin–aldosterone: renin is released from juxtaglomerular cells by low renal perfusion pressure, low NaCl delivery to the macula densa and beta-1 sympathetic stimulation. Aldosterone increases ENaC and Na⁺/K⁺-ATPase in principal cells: Na⁺ in, K⁺ and H⁺ out.
• Natriuretic peptides (ANP, BNP): increase sodium excretion and inhibit renin.
• Pressure natriuresis and sympathetic activity.

Aldosterone escape: in primary hyperaldosteronism (Conn syndrome), sodium retention expands volume for a few days, then pressure natriuresis and ANP raise sodium excretion back to intake. So patients have hypertension, hypokalaemia and metabolic alkalosis but rarely oedema. Potassium wasting does not escape.

Heart failure oedema: raised venous pressure increases capillary hydrostatic pressure, and low effective arterial filling activates RAAS, sympathetic tone and ADH, so salt and water are retained continuously; there is no escape because the stimulus persists. A heart failure patient with oedema and low potassium on loop diuretics benefits from spironolactone.

Mineralocorticoid excess with low aldosterone

Hyponatraemia by volume status

• Hypovolaemic: diuretics, vomiting, diarrhoea, Addison disease (urine Na⁺ high if renal loss).
• Euvolaemic: SIADH, hypothyroidism, glucocorticoid deficiency. In secondary (pituitary) adrenal insufficiency, aldosterone is preserved so potassium is normal; hyponatraemia arises because cortisol normally restrains ADH release (and is needed for free water excretion). Hydrocortisone can raise sodium fast.
• Hypervolaemic: heart failure, cirrhosis, nephrotic syndrome.
• Pseudohyponatraemia: very high lipids or protein. Translocational: high glucose draws water out of cells.

Correcting sodium: the brain adapts

Over 1–2 days the brain adjusts its cell volume by gaining or losing organic osmolytes (inositol, glutamine, taurine). In chronic hypernatraemia (165 mmol/L for days) brain cells have gained osmolytes; rapid lowering with 5% dextrose (to 148 in 12 hours) lets water rush in, causing cerebral oedema and seizures. In chronic hyponatraemia, brain cells have lost osmolytes; rapid correction shrinks them, causing osmotic demyelination. Correct both slowly.

Infusing a very hypertonic solution (for example 140 mmol Na⁺ in 100 mL) raises ECF osmolality, expands ECF and shrinks ICF.

Potassium: distribution

98% of body K⁺ is inside cells, so small shifts change plasma levels greatly.

Correcting acidosis with bicarbonate lowers potassium; recheck it.

Potassium: renal handling

• Most filtered K⁺ is reabsorbed proximally; urinary K⁺ is set by secretion in principal cells of the late DCT and collecting duct, which rises with aldosterone, high distal Na⁺ delivery and flow (diuretics), alkalosis and high plasma K⁺.
• Raised plasma K⁺ stimulates aldosterone directly at the zona glomerulosa, independent of renin; this is the main renal compensation for hyperkalaemia.
• Heparin (including enoxaparin) suppresses aldosterone synthesis in the zona glomerulosa, causing hyperkalaemia with stable renal function.
• ACE inhibitors, ARBs, spironolactone, NSAIDs, trimethoprim and renal failure all raise K⁺; sudden collapse in a patient on antihypertensives with K⁺ 6.7 points to one of these drugs.

Hyper- and hypokalaemia on the membrane

Resting potential depends on the K⁺ gradient.

Treating hyperkalaemia (K⁺ 7.2 with ECG changes): first IV calcium gluconate 10%, which acts in minutes by raising the threshold potential, restoring the gap between resting and threshold potential and stabilising the myocardium. It does not lower K⁺. Then insulin with glucose and nebulised salbutamol shift K⁺ into cells; finally remove K⁺ (binders, dialysis).

Magnesium

Magnesium is mostly reabsorbed in the thick ascending limb (paracellular). Low Mg²⁺ (diarrhoea, high-output stoma, PPIs such as omeprazole, diuretics, alcohol) causes:

• Refractory hypokalaemia: low intracellular Mg²⁺ releases its block on ROMK channels, so K⁺ keeps leaking into urine.
• Refractory hypocalcaemia: low Mg²⁺ impairs PTH release and PTH action, so PTH is inappropriately low and IV calcium will not hold.
• Arrhythmias (torsades), worse digoxin toxicity.

Calcium

• Plasma calcium 2.2–2.6 mmol/L (8.8–10.4 mg/dL): about 45% ionised (active), 40% bound to albumin, 15% complexed. Corrected calcium adds about 0.02 mmol/L per g/L albumin below 40.
• Alkalosis increases albumin binding and lowers ionised calcium: hyperventilation causes tingling and carpopedal spasm with normal total calcium.
• Kidney: about 65% reabsorbed in the PCT (most), 25% in the thick ascending limb, and the regulated 5–10% in the DCT under PTH. Thiazides lower urinary calcium; loop diuretics raise it.
• PTH raises calcium by bone resorption, distal reabsorption and 1α-hydroxylase activation; it lowers phosphate by blocking proximal reabsorption.
• Calcitriol raises gut absorption of both calcium and phosphate.

Phosphate

• Reabsorbed mainly in the PCT (Na⁺–phosphate cotransporter), inhibited by PTH and FGF23 (from osteocytes).
• X-linked hypophosphataemic rickets (PHEX mutation, dominant, so the mother may be short with bowed legs): excess FGF23 causes urinary phosphate wasting and low calcitriol; calcium is normal and standard vitamin D does not help.
• Chronic kidney disease: phosphate retention, low calcitriol (lost 1α-hydroxylase) and low calcium drive secondary hyperparathyroidism (low Ca²⁺, high phosphate, high PTH). Treat with alfacalcidol or calcitriol (already 1α-hydroxylated) and phosphate binders such as sevelamer, which binds dietary phosphate in the gut lumen and must be taken with meals.

Gut losses and acid–base

• Diarrhoea loses HCO₃⁻ and K⁺ from the colon: hypokalaemia with normal anion gap (hyperchloraemic) metabolic acidosis; for example Cl⁻ 112, Na⁺ 131, K⁺ 2.5, anion gap 10.
• Vomiting loses HCl: hypokalaemic hypochloraemic metabolic alkalosis.

Remember Aldosterone swaps Na⁺ for K⁺; insulin and beta-2 agonists hide K⁺ in cells; calcium protects the heart; fix magnesium first.

Exam trap Calcium gluconate does not lower potassium; it raises the threshold potential.

Exam trap Refractory low K⁺ or low Ca²⁺: check magnesium.

How FCPS asks about this

• First treatment for K⁺ 7.2 with wide QRS: IV calcium gluconate 10%; then insulin–glucose and salbutamol.
• Hypertension, hypokalaemia, low renin and low aldosterone after liquorice: 11β-HSD2 inhibition.
• No oedema in Conn syndrome: aldosterone escape (pressure natriuresis, ANP).
• Hyperkalaemia on enoxaparin with stable creatinine: heparin suppresses aldosterone.
• K⁺ rise after reperfusion or during exercise: K⁺ released from muscle cells.
• Most filtered calcium reabsorbed: PCT; PTH acts on the DCT and lowers phosphate.
• CKD with low Ca²⁺, high phosphate, high PTH: secondary hyperparathyroidism; give alfacalcidol and a binder.