ChemPath 13: 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

Angiotensin II stimulates aldosterone production from the adrenals

Aldosterone stimulates sodium reabsorption and potassium excretion in the principal cells of the cortical collecting tubule (CCT)

NOTE: water will also be drawn in with the sodium so aldosterone should not greatly affect sodium concentration

Question 4

Outline the mechanism of action of aldosterone

Answer 4

• Aldosterone binds to MR (mineralocorticoid receptor) and stimulates the transcription of ENaC channels + 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 (renal outer medullary potassium) channels

Question 5

What are the main stimuli for aldosterone release?

Answer 5

Angiotensin II

Low potassium

Question 6

List some causes of hyperkalaemia.

Answer 6

Drugs:

• NSAIDs - Reduced renin activity
• ACEi - Blocks conversion of angiotensin 1-> 2
• ARB - Block ang 2 recptors
• Aldosterone antagonists (Spironalactone)

Conditions:

• Type 4 Renal Tubular Acidosis (Reduced renin activity)
• Addisons (adrenal insufficiency)
• Renal failure (Reduced GFR)

Intracellular spillage:

• Rhabdomyolysis - Potassium release from cells
• Acidosis - Potassium release from cells

Question 7

Explain how acidosis leads to hyperkalaemia

Answer 7

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 8

Outline the management of hyperkalaemia

Answer 8

10 mL 10% calcium gluconate - protect cardiomyocytes

1st line = 50 mL 50% dextrose + 10 U insulin - drive K+ back into cells
2nd line = Nebulised salbutamol

Treat the cause - if started new meds stop it, if condition present treat it

Question 9

List some causes of hypokalaemia

Answer 9

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

Question 10

Name two conditions that can block the triple transporter (Na / K / Cl)

Answer 10

Loop diuretics

Bartter syndrome (mutation in triple transporter)

These both increase Na+ in the lumen of CCT hence more K+ gets excreted there leading to hypokalaemia

Question 11

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

Answer 11

Thiazide diuretics

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

These both increase Na+ in the lumen of CCT hence more K+ gets excreted there leading to hypokalaemia

Question 12

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

Answer 12

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

Question 13

What are the clinical features of hypokalaemia?

Answer 13

Muscle weakness

Arrhythmia

Polyuria and polydipsia (due to DI)

Question 14

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

Answer 14

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

Question 15

Outline the management of hypokalaemia:

Answer 15

3-3.5 mmol/L

• Oral potassium chloride (2 x SandoK TDS for 48 hours)
• Re-check serum K+ concentration

< 3 mmol/L

• IV potassium chloride infusion
• Maximum rate: 10 mmol/hr
• NOTE: rates > 20 mmol/hr irritate the superficial veins

TREAT THE CAUSE

Question 16

ECG finding w/ hyperkalaemia? inital mx?

Answer 16

Peaked T waves (GLOBAL CHANGE IN ALL LEADS)

10 ml 10% calcium gluconate

Question 17

You are bleeped to review Jane Doe. A 56-year-old lady on the Endocrinology ward admitted with severe hypothyroidism. Her Past Medical History includes Hypertension and Type 2 Diabetes Mellitus. She is currently taking Levothyroxine, Ramipril, Metformin and Gliclazide.

Has hyperlkalaemia and nothing else

Which of the following is the most likely to be causing Jane’s electrolye abnormality?
Levothyroxine
Ramipril
Metformin
Gliclazide
None of the above.

Answer 17

Ramipril - blocks conversion of Ang I to Ang II -> less aldosterone -> hyperkalaemia (reduced reabsorption of Na)

Question 18

You are bleeped to review John Doe. A 45-year-old male following an Asthma attack, after a long history of poorly controlled asthma.

Hypokalaemia, rest is normal

Which of the following is the most appropriate to correct John’s electrolye abnormality?

Oral Potassium Chloride i.e. SandoK
Ramipril
IV Potassium Chloride
10ml 10% Calcium Gluconate
Nebulised Salbutamol

Answer 18

IV Potassium Chloride - hypokalaemia likely percipitated by salbutamol use

Question 19

You attend to a patient in Resus. The initial ECG shows the following;

Given the likely electrolye abnormality, what is the most appropriate initial management?

Answer 19

Peaked T Waves = Hypokalaemai mx => 10ml 10% Calcium Gluconate