- What is the normal range for serum potassium?
3.5-5.0 mmol/L
- What are the two main hormones involved in the regulation of potassium?
Angiotensin II
Aldosterone
- Outline how the renin-angiotensin-aldosterone system works.
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
Angiotensin II stimulates aldosterone production 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
- Outline the mechanism of action of aldosterone.
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
- What are the main stimuli for aldosterone release?
Angiotensin II
HIGH potassium
- List some causes of hyperkalaemia.
Reduced GFR (renal failure)
Reduced renin activity (renal tubular acidosis type 4, NSAIDs)
ACE inhibitors/ARBs
Addison’s disease
Aldosterone antagonists
Potassium release from cells (rhabdomyolysis, acidosis)
- Explain how acidosis leads to hyperkalaemia.
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
- Outline the management of hyperkalaemia.
10 mL 10% calcium gluconate
50 mL 50% dextrose + 10 U insulin
Nebulised salbutamol
Treat the cause
- List some causes of hypokalaemia.
GI loss Renal loss • Hyperaldosteronism, Cushing’s syndrome • Increased sodium delivery to distal nephron • Osmotic diuresis Redistribution into cells • Insulin • Beta-agonists • Alkalosis Rare causes • Renal tubular acidosis (type 1 and 2) • Hypomagnesaemia
- Name two conditions that can block the triple transporter.
Loop diuretics Bartter syndrome (mutation in triple transporter)
- Name two conditions that can block the Na+/Cl- cotransporter.
Thiazide diuretics Gitelman syndrome (mutation in Na+/Cl- cotransporter)
- Explain how increased delivery of sodium to the distal nephron can cause hypokalaemia.
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
- What are the clinical features of hypokalaemia?
Muscle weakness
Arrhythmia
Polyuria and polydipsia (due to DI)
- What screening test should be done in a patient with hypokalaemia and hypertension?
Aldosterone: renin ratio (primary hyperaldosteronism will show high aldosterone and low renin)
- Outline the management of hypokalaemia:
a. 3-3.5 mmol/L
b. < 3 mmol/L
a. 3-3.5 mmol/L Oral potassium chloride (2 x SandoK TDS for 48 hours) Re-check serum K+ concentration b. < 3 mmol/L IV potassium chloride infusion Maximum rate: 10 mmol/hr NOTE: rates > 20 mmol/hr irritate the superficial veins TREAT THE CAUSE
