ChemPath: Potassium

Question 1

What is the normal range for serum potassium?

Answer 1

3.5-5.0 mmol/L

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

Where aldosterone acts

Answer 4

Principal cortical cells

collecting duct

Question 5

Outline the mechanisms of action of aldosterone.

Answer 5

• 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

Question 6

How Na affects K excretion

Answer 6

Sodium resorbed - making the lumen more negative

K then excreted along the electrochemical gradient

Question 7

What are the main stimuli for aldosterone release?

Answer 7

• Angiotensin II
• High potassium

Question 8

List some causes of hyperkalaemia.

Answer 8

• Reduced GFR (renal failure)
• Reduced renin activity (renal tubular acidosis type 4, NSAIDs)
• ACE inhibitors/ ARBs (losartan)
• Addison’s disease
• Aldosterone antagonists (spirinolactone / epleronone)
• Potassium release from cells (rhabdomyolysis, acidosis)

Question 9

Causes of hyperkalaemia if someone asks

Answer 9

1. Renal failure (reduced Excretion)
2. Drugs (ACEi / Angiotensin / Aldosterone antagonists)
3. Low Aldosterone
   
   1. Addisons
   2. Type 4 renal tubular acidosis (low renin, low aldosterone)
4. Release from cells (Rhabdomyolysis, acidosis)

Question 10

Explain how acidosis leads to hyperkalaemia.

Answer 10

• 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 11

Outline the management of hyperkalaemia.

Answer 11

• 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

Question 12

List some causes of hypokalaemia.

Answer 12

• GI loss (diarrhoea)
• Renal loss
  
  • Hyperaldosteronism, 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

Question 13

Describe Renal K handling

Answer 13

More Na to distal tubules causes increased exchange of K

Block of Na/CL channels by Thiazides and Gitelman’s syndrome

Question 14

Name two conditions that can block the triple transporter.

Answer 14

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

Question 15

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

Answer 15

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

Question 16

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

Answer 16

• 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 ROMK channels into the lumen

Question 17

Why Distal Na resorption causes reduced K

Answer 17

Increased Na resorption in distal tubule
Increased Electronegative gradient

Increased K loss

Question 18

What are the clinical features of hypokalaemia?

Answer 18

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

Question 19

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

Answer 19

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

Question 20

Outline the management of hypokalaemia:

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

Answer 20

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 irritate the superficial veins, needs to be given centrally
   • TREAT THE CAUSE