What are the implications of hyper and hypokalaemia?
Hyperkalaemia – Potassium is exported out of a muscle cell in order to restore resting membrane potential. If there is high amounts of potassium in the ECF, then the gradient is lowered and therefore the resting membrane potential is either slower to reach or cant be reached.
Hypokalaemia – Results in hyperpolarisation of the resting membrane potential, meaning a greater than normal stimulus is required to generate the next AP.
What 2 processes regulate potassium within the body?
Internal and external balance
Explain how internal balance regulates potassium
o Movement of K+ between ECF and ICF, occurs within minutes and responsible for moment to moment control.
o From ECF into cells – via NaKATPase
o From cells into ECF via K+ channels.
What 3 factors promote K+ uptake into the cells?
1. Hormones – insulin, aldosterone, catecholamines (adrenaline, noradreline etc.). Act via the Na-K-ATPase
2. Increased K+ in ECF
3. Alkalosis – low ECF [H+]. H+ move out of cells to correct alkalosis, resulting in K+ shift into cells to neutralise gradient.
How does insulin stimulate K+ uptake into cells? How can this be used clinically?
• K+ in splanchnic blood (circulation of the GI tract) stimulates insulin secretion
• Insulin stimulates K+ uptake by muscle cells and liver via an increase in Na-K-ATPase
• IV insulin therefore used to bring down high K+ levels.
What are catecholamines?
Adrenaline, noradrenaline etc
What 5 factors promote K+ shift out of the cells?
1. Low ECF [K+]
3. Cell lysis
4. Increase in ECF osmolarity
5. Acidosis – results in shift of H+ into cells and K+ out of cells to maintain electroneutrality.
How does exercise promote K+ shift out of the cells?
• Skeletal muscle contraction and muscle damage releases K+ into ECF
• Uptake of K+ by non-contracting tissues prevents dangerously high hyperkalaemia
• Catecholamines offset the increase in ECF [K+] by increasing K+ uptake by other cells.
How does an increase in ECF osmolarity promote K+ shift out of the cells?
• Water moves from cells into ECF
• This increases [K+] in ICF as it becomes more concentrated
• K+ then leaves down its concentration gradient.
How can hypo and hyerkalaemia affect serum pH?
• Acidosis of the ECF results in shift of H+ into cells and K+ out of cells, and vice versa with alkalosis
• Similarly, changes in ECF [K+] cause the opposite shift in H+ between ICF and ECF.
What parts of the nephron secrete K+? How is this achieved?
• Cortical collecting duct Na-K-ATPase on the apical side takes in K+. Secreted via K+ channel
What tubular factors affect K+ secretion?
• ECF [K+] – Stimulates Na-K-ATPase and increases permeability of apical K+ channels, and stimulates aldosterone secretion
• Aldosterone – Increases transcription of Na-K-ATPase, K+ channels and ENaC
• Acid base status:
o Acidosis – Decreases K+ secretion by inhibiting Na-K-ATPase and decreases K+ channel permeability
o Alkalosis – Increases K+ secretion by stimulating Na-K-ATPase and increases K+ channel permeability
What luminal factors affect K+ secretion?
Factors affecting K+ secretion by principal cells –
• Increased distal tubular flow rate washes away luminal K+, increasing K+ loss
• Increased Na delivery to distal tubule, results in more Na reabsorbed and more K+ loss
What clinical features are associated with hyperkalaemia?
• Arrhythmias of the heart, heart block
• Neuromuscular dysfunction of GI
How would you treat hyperkalaemia acutely and chronically?
• Emergency treatment – Insulin IV, Dialysis to remove excess K+, IV calcium gluconate to stabilise the membrane and reducing the excitability of the cardiac myocytes.
• Long term treatment – Treat cause, reduce intake, oral K+ binding resins to bind K+ in the gut.
How would you treat hypokalaemia?
• Treat cause
• Potassium replacement – IV or oral
• If due to increased mineralocorticoid - Potassium sparing diuretics which block action of aldosterone on principle cells