5. Potassium and electrolytes / potassium handling

Question 1

What is the most abundant intracellular cation?

Answer 1

Potassium

Question 2

What is the (normal) serum concentration of potassium?

Answer 2

3.0-5.0 mmol/L

Question 3

What is the main source of potassium?

Answer 3

Dietary

Question 4

What is the average intake of potassium?

Answer 4

80-100 mmol/day

Question 5

What hormones are involved in the regulation of potassium?

Answer 5

Angiotensin II and aldosterone

Question 6

How does the renin-angiotensin-aldosterone system work?

Answer 6

1. Reduced perfusion or low sodium will stimulate the production of renin from J-G cells.
2. Renin cleaves angiotensinogen (From liver) -> angiotensin I
3. Angiotensin I is converted to angiotensin II by ACE in the lungs
4. Angiotensin II stimulates the adrenal glands to produce aldosterone
5. Aldosterone will stimulate sodium reabsorption and potassium excretion

Question 7

How is aldosterone involved in potassium secretion?

Answer 7

1. Aldosterone acts on principal cells (cortical collecting tubule) in the collecting ducts.
2. It acts on K+ channels to allow its movement into the lumen in exchange for sodium entry to maintain electrochemical potential.
3. Water will also be drawn in with the sodium so this response should not greatly affect sodium concentration

Question 8

What is the mechanism of action of aldosterone in potassium secretion?

Answer 8

1. Aldosterone binds to mineralocorticoid receptors and stimulates the transcription of ENaC channels
2. As you resorb more sodium the lumen becomes more electro negative
3. Thus, potassium moves down electrochemical gradient through the ROMK channels (renal outer medullary potassium channel) into the lumen
4. Aldosterone binding to MR leads to increased Sgk1 (serum GC kinase 1) which normally inhibits Nedd4
5. The role of Nedd4 is to ubiquinate sodium channels and degrade them
6. By inhibiting Nedd4 aldosterone will reduce the degradation of sodium channels so you get more sodium channels on the membrane
   - I.e. the mechanism by which aldosterone increases sodium reabsorption is by reduced degradation of sodium channels

Question 9

Briefly, what are the two ways aldosterone causes increased potassium secretion?

Answer 9

1. Stimulates transcripton of ENaC channels to increase sodim resorption (thus lumen becomes electronegative and K+ moves down gradient into lumen)
2. binds to MR, leads to increased Sgk1 which inhibits Nedd4 - role is to breakdown sodium channels

Question 10

What are causes of hyperkalaemia?

Answer 10

1. Reduced GFR
2. Reduced renin activity (K+ not being secreted) e.g. diabetic nephropathy or NSAIDs
3. ACE inhibitors
4. Angiotensin II receptor blockers
5. Addison’s disease
6. Aldosterone antagonists
7. Potassium release from cells e.g. rhabdomyolysis or acidosis

Question 11

How does reduced renin activity cause hyperkalaemia?

Answer 11

Renin starts of the renin-angiotensin-aldosterone system.

Type 4 renal tubular acidosis (diabetic nephropathy) can lead to hyporeninaemic hypoaldosteronism.

NSAIDs lead to reduced aldosterone and renin in chronic use.

Question 12

How do ACE inhibitors cause hyperkalaemia?

Answer 12

ACE inhibitors 🡪 angiotensin II acts on renal tubules to increase K+ excretion, blocking ACE 🡪 less angiotensin II 🡪 K+ increases

Question 13

How do angiotensin II receptor blockers cause hyperkalaemia?

Answer 13

Angiotensin II receptor blockers 🡪 blocks function of angiotensin II

Question 14

How does Addison’s disease cause hyperkalaemia?

Answer 14

Adrenocortico insufficiency, less mineralocorticoid driven K+ excretion

Question 15

What are examples of aldosterone antagonists which may cause hyperkalaemia?

Answer 15

Spironolactone, eplerone

Question 16

How does rhabdomyolysis cause hyperkalaemia?

Answer 16

Cell death causes a large release of potassium. Also seen in a large blood transfusion where intravascular haemolysis causes potassium release.

Question 17

How does acidosis cause hyperkalaemia?

Answer 17

When there is high plasma H+ the cells try to take in more H+ ions to normalise serum pH. However, to maintain electroneutrality as H+ enters the cells, K+ exits casing hyperkalaemia

Question 18

What are ECG findings in hyperkalaemia?

Answer 18

1. Peaked T waves
2. Broad QRS
3. Prolonged PR interval
4. Bradycardia
5. Sine waves and asystole (late stage)

Question 19

How is hyperkalaemia managed?

Answer 19

1. 10ml of 10% calcium gluconate IV 🡪 stabilises cardiomyocytes against risk of arrhythmia. Doesn’t change plasma potassium
2. 50ml 50% dextrose + 10U insulin
3. Nebulised salbutamol
4. Treat underlying cause

Question 20

What are causes of hypokalaemia?

Answer 20

1. GI loss (D>V)
2. Renal loss e.g. hyperaldosteronisms, Cushing’s syndrome,
   increased sodium delivery into distal nephron, osmotic diuresis
3. Redistribution into cells e.g. insulin, beta agonists, alkalosis
4. Rare causes e.g.
   renal tubular acidosis, type 1 and 2
   hypomagnesaemia

Question 21

What may cause the triple transporter in the ascending loop of Henle to not work?

Answer 21

Furosemide (loop diuretic) inhibits the triple transporter. Prevents sodium being absorbed in ascending loop.

Bartter syndromer - mutation in triple transporter

Question 22

Why does blocking the triple transporter lead to renal potassium loss?

Answer 22

1. Triple transporters in the ascending loop of Henle reabsorb Na+, K+ and Cl-
2. If these channels are blocked sodium is not absorbed in the ascending loop of Henle and so more sodium will be delivered to the distal nephron
3. As there is more sodium reaching the distal nephron, more sodium will be reabsorbed in the distal nephron which makes the nephron more negative
4. This results in the loss of potassium down the electrochemical gradient through ROMK channels (see diagram in notes)

Question 23

Clinical features of hypokalaemia?

Answer 23

Muscle weakness, cardiac arrhythmia (U waves on ECG), polyuria and polydipsia (nephrogenic DI)

Question 24

In a patient with hypokalaemia and hypertension, why should you check the aldosterone:renin ratio?

Answer 24

To rule out Conn’s syndrome or adrenal hyperplasia. In a patient with primary hyperaldosteronism there would be high aldosterone:renin ratio because the high aldosterone will suppress renin

Question 25

How is hypokalaemia managed if serum potassium is 3.0-3.5 mmol/L?

Answer 25

Give oral KCl e.g. SandoK tablets tds for 48 hrs. Re-check serum potassium. Treat underlying cause e.g. spironolactone

Question 26

How is hypokalaemia managed if serum potassium is <3.0 mmol/L?

Answer 26

IV potassium chloride, maximum rate 10mmol/hr. Rates >20mmol/hr are highly irritating to peripheral veins. Treat the underlying cause e.g. spironolactone

Question 27

How much potassium is lost in diarrhoea and vomiting?

Answer 27

Diarrhoea has 30mmol/L more loss of potassium than vomiting (5mmol/L) leading to hypokalaemia.

Question 28

How may thiazide diuretics or Gitelman syndrome cause hypokalaemia?

Answer 28

Gitelman syndrome - mutation in Na+/Cl- channel.

More sodium is delivered to distal nephron and reabsorbed there, causing a change in the electrocheical gradient and the loss of potassium through ROMK channels.