ChemPath: Potassium

Question 1

What is the normal range for serum potassium?

Answer 1

3.5-5.0 mmol/L

K+ = most abundant intracelllular
Na+ = most abundant extracellular

Question 2

What are the two main hormones involved in the regulation of potassium?

Answer 2

• Angiotensin II
• Aldosterone

Question 3

Outline how the renin-angiotensin-aldosterone system works.

Answer 3

• 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

Question 4

Outline the mechanisms of action of aldosterone.

Answer 4

• Aldosterone binds to MR on principal cells in cortical collecting duct
• Insertion of epithelial Na+ channels –> increases Na+ reabsorption
• As you reabsorb more sodium, the lumen becomes more negative
• K+ will move down (secreted) the electrochemical gradient into the lumen via K+ channels

Aldosterone –> Na+ in, K+ out

Question 5

What are the main stimuli for aldosterone release?

Answer 5

• Angiotensin II
• High potassium

Question 6

List some causes of hyperkalaemia.

Answer 6

• Reduced GFR (renal failure)
• Reduced renin activity (renal tubular acidosis type 4 - diabetic nephropathy, NSAIDs)
• Drugs - ACE inhibitors/ARBs, aldosterone antagonists (spironolcatone)
• Addison’s disease
• Potassium release from cells (rhabdomyolysis, acidosis)

Question 7

ECG change for hyperkalaemia

Answer 7

peaked T waves

Question 8

Explain how acidosis leads to hyperkalaemia.

Answer 8

• 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

Question 9

Outline the management of hyperkalaemia.

Answer 9

• **30 ml 10% calcium gluconate **- stabilizes myocardium
• 50 ml 50% dextrose + 10 Units insulin - insulin drives K+ into cells, glucose to prevent hypoglycaemia
• Nebulised salbutamol - drives K+ into cells
• Treat the cause

NOTE - salbutamol can cause hypokalemia

Question 10

List some causes of hypokalaemia.

Answer 10

• GI loss
• Renal loss
  
  • Hyperaldosteronism, Cushing’s syndrome (excess cortisol binds to MR)
  • Increased Na+ delivery to distal nephron
  • Osmotic diuresis
• Redistribution into cells
  
  • Insulin
  • Beta-agonists (e.g. Salbutamol)
  • Alkalosis
• Rare causes
  
  • Renal tubular acidosis (type 1 and 2)
  • Hypomagnesaemia

Question 11

Name two conditions that can block the triple transporter.

Answer 11

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

In loop of henle

more Na+ delivered distally

Question 12

Name two conditions that can block the Na+/Cl- cotransporter.

Answer 12

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

In collecting duct

More Na+ delivery distally

Question 13

Explain how increased delivery of sodium to the distal nephron can cause hypokalaemia.

Answer 13

• Increased delivery of Na+ to the distal nephron (e.g. because of blocking/ineffective triple transporter or Na+/Cl- cotransporter) leadas 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 into the lumen

Question 14

What are the clinical features of hypokalaemia?

Answer 14

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

Question 15

What screening test should be done in a patient with hypokalaemia and hypertension?

Answer 15

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

Question 16

Outline the management of hypokalaemia:

1. 3-3.5 mmol/L
2. <3 mmol/L

Answer 16

1. 3-3.5 mmol/L
   
   • Oral potassium chloride (2x SandoK TDS for 48 hours)
   • Re-check serum K+ concentration
2. < 3 mmol/L
   
   • IV potassium chloride infusion
   • Maximum rate: 10 mmol/hr
   • NOTE: rates > 20 mmol/hr irritating to peripheral veins (so would need be given centrally)
   TREAT THE CAUSE