Chem path 4: Potassium balance & cases

Question 1

What is the most abundant intracellular cation?

Answer 1

Potassium (sodium is the most abundant extracellular cation)

Question 2

What are the two main hormones involved in potassium regulation?

Answer 2

Ang II and aldosterone

Question 3

What are the two main triggers for aldosterone release?

Answer 3

AngII and high potassium

Question 4

Outline the RAAS

Answer 4

angiotensinogen from the liver is converted to AngI by renin released from JGA. Ang I –> Ang II by ACE in lungs. Ang II acts on the adrenals to release aldosterone. Aldosterone –> K+ excretion and Na+ retentino

Question 5

Which zone of the kidney releases aldosterone

Answer 5

Zona glomerulosa

Question 6

What are some triggers for renin release?

Answer 6

Low BP in renal artery, Low Na+ in macula densa, SNS Beta-1-receptor activation

Question 7

OUtline the MOA of aldosterone

Answer 7

Aldosterone binds to MR steroid receptors and stimulates the transcription of epithelial Na channels (EnaC). Sodium reabsorption then occurs through the ENaC channels leading to an electronegative lumen. This drives potassium secretion through ROMK (renal outer medullary potassium) channels in to the lumen. Aldosterone binding to MR receptors leads to increased Sgk1 which inhibits Nedd4. The role of Nedd4 is to ubiquinate and degrade sodium channels. Therefore, by increasing Sgk1 levels you get less degradation of sodium channels.

Question 8

What are the main causes of hyperkalaemia?

Answer 8

Reduced GFR
Reduced renin (T4 RTA, NSAIDs)
ACEi
Aldosterone antagonists i.e. spironalactone
Addison’s
ARBs
Potassium release from cells: rhabdomyolysis, acidosis

Question 9

How does acidosis lead to hyperkalaemia?

Answer 9

Causes K+ to leak out of cells as H+/K+ transporter is disrupted with H+ taken in to cells to stabilise the disturbance and K+ excreted in response (to maintain membrane electronegativity)

Question 10

In type 4 RTA what happens to renin and aldosterone?

Answer 10

They are both low

Question 11

What are the ECG changes associated with hyperkalaemia?

Answer 11

Peaked T waves (main ECG change)
Broad QRS
Flattened P waves
Prolonged PR and bradycardia
sine wave (latest sign)

Question 12

When would you treat hyperkalaemia?

Answer 12

K+ >6.5 or if there are ECG changes

Question 13

What is the acute treatment for hyperkalaemia?

Answer 13

10ml 10% calcium gluconate (stabilise the membrane to prevent VF)
200/100ml 10%/20% dextrose +10U insulin (drive K+ into cells)
Nebulised salbutamol
Tx underlying cause

Question 14

What are the causes of hypoklalaemia? (GRRR)

Answer 14

GI losses (Diarrhoea, vomiting, fistulas)
Renal (alkalosis, MR excess i.e. cushing’s, Conn’s/hyperaldosteronism, Increased Na+ delivery to DCT, osmotic diuresis)
Redistribution (insulin/insulinomas, beta agonists, alkalosis)
Rare (RTA 1+2), hypomagnasaemia

Question 15

What could cause an increased delivery of Na+ to the DCT?

Answer 15

Blockage of triple (loop diuretics) or co-transporter (Thiazides)
Bartter syndrome: impairment of triple transporter
Gitelman syndrome: impairment of co-transporter

Question 16

What are the clinical features of hypokalaemia?

Answer 16

Muscle weakness, cardiac arrhythmias, polyuria and polydipsia (nephrogenic DI)

Question 17

What are the ECG changes seen in hypokalaemia?

Answer 17

ST depression, flat T waves, U waVES

Question 18

What screening test would you order in a patient with hypertension and hypokalaemia?

Answer 18

You would be suspecting Conn’s syndrome so would do an aldosterone:renin ratio. In conn’s you suspect a high ratio as the high aldosterone should suppress the renin

Question 19

What is the management of hypokalaemia?

Answer 19

If [K+] = 3.0-3.5 then 2x oral SandoK tablets TDS for 48hrs +re-check serum K+

If [K+] <3.0 then IV potassium chloride, maximum rate 10mmol/hr (Rates >20mmol/hr –> irritable peripheral veins and possible arrhythmias

Treat underlying cause

Question 20

Hyperkalaemia is a side-effect of which of the following drugs:

Furosemide
Bendroflumethathiazide
Salbutamol
Ramipril

Answer 20

Ramipril (ACEi) –> blocks eventual aldosterone production

Question 21

Outline the differences between RTA types 1,2 and 4

Answer 21

Type 1 = classic distal RTA, hypokalaemia as less H+excretion
Type 2 = proximal distal RTA, less HCO3- resorption
Type 4 = hyperkalaemia + hypoaldosteronism