ChemPath: Potassium

3.5-5.0 mmol/L

• Angiotensin II • Aldosterone

• Reduced perfusion or low sodium will stimulate the production of renin from the juxta-glomerular cells • This cleaves angiotensinogen to angiotensin I • This is then converted by ACE in the lungs to angiotensin II → stimulates aldosterone release from the adrenals • Aldosterone stimulates sodium reabsorption and potassium excretion in the principal cells of the cortical collecting tubule NOTE: water will also be drawn in with the sodium so aldosterone should not greatly affect sodium concentration

Principal cortical cells collecting duct

• Aldosterone binds to MR and stimulates the transcription of ENaC channels • Aldosterone binding to MR also leads to increased Sgk1 which inhibits Nedd4 • Nedd4 usually ubiquitinates sodium channels and degrades them • Inhibition of Nedd4 leads to preservation of sodium channels thereby increasing sodium reabsorption • As you reabsorb more sodium, the lumen becomes more negative and K+ will move down the electrochemical gradient into the lumen via ROMK channels

Sodium resorbed - making the lumen more negative K then excreted along the electrochemical gradient

• Angiotensin II • High serum potassium (most potent stimulator)

• Renal failure (low GFR, reduced excretion) • Drugs (ACEi / ARBs / Aldosterone antagonists) • Low Aldosterone • Addisons • Type 4 renal tubular acidosis (low renin, low aldosterone) • Release from cells (Rhabdomyolysis, acidosis)

• When plasma H+ concentration is high, the cells try to take in more H+ from the plasma • To maintain electrochemical neutrality, K+ must leave the cell when H+ enters • This leads to hyperkalaemia

• 10 ml 10% calcium gluconate • 50 ml 50% dextrose + 10 U insulin • In reality - 100ml 20% dextrose • Nebulised salbutamol - beta agonists drive K into cell • Treat the cause

• GI loss (diarrhoea) • Renal loss • Hyperaldosteronism (Conn’s), Cushing’s syndrome (binding to MR) • Increased sodium delivery to distal nephron • Osmotic diuresis • Redistribution into cells • Insulins • Beta-agonists • Alkalosis • Rare causes • Renal tubular acidosis (type 1 and 2) • Hypomagnesaemia

More Na to distal tubules causes increased exchange of K Block of Na/CL channels by Thiazides and Gitelman’s syndrome

• Loop diuretics • Bartter syndrome (mutation in triple transporter)

• Thiazide diuretics • Gitelman syndrome (mutation in Na+/Cl- cotransporter)

• Increased delivery of Na+ to the distal nephron (e.g. because of blocking/ineffective triple transporter or Na+/Cl- cotransporter) leads to increased reabsorption of Na+ in the distal nephron • This leads to the lumen of the distal nephron becoming more negative • This results in the movement of K+ down the electrochemical gradient through ROMK channels into the lumen

Increased Na resorption in distal tubule Increased Electronegative gradient Increased K loss

• Muscle weakness • Arrythmia • Polyuria and polydipsia (hypokalaemia leads to nephrogenic DI)

Aldosterone: renin ratio (primary hyperaldosteronism will show high aldosterone and low renin)

• 3-3.5 mmol/L • Oral potassium chloride (2x SandoK TDS for 48 hours) • Re-check serum K+ concentration • < 3 mmol/L • IV potassium chloride infusion • Maximum rate: 10 mmol/hr • NOTE: rates > 20 mmol/hr irritate the superficial veins, needs to be given centrally • TREAT THE CAUSE