ChemPath: Potassium Flashcards
What is the normal range for serum potassium?
3.5-5.0 mmol/L
(most abundant intracellular cation)
Outline the physiological regulation of potassium:
- Loss through the GI tract
- Renal regulation and secretion (2 hormones)
- Movement from intracellular to extracellular
What are the two main hormones involved in the regulation of potassium?
- Angiotensin II
- Aldosterone
Outline how the renin-angiotensin-aldosterone system works.
- Reduced perfusion/low BP in renal artery 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
Outline the mechanisms of action of aldosterone.
- Aldosterone binds to MR steroid receptor and stimulates the transcription of ENaC channels (epithelial sodium 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
What are the main stimuli for aldosterone release?
- Angiotensin II
- High potassium
List causes of hyperkalaemia.
- Renal impairment = reduced GFR
- Drugs ACE inhibitors/ARBs/Spironolactone
- Addison’s disease (low aldosterone release)
- Potassium release from cells (rhabdomyolysis, acidosis, tumour lysis syndrome)
- Reduced renin activity (renal tubular acidosis type 4, NSAIDs)
in bold = main causes
Explain how acidosis leads to hyperkalaemia.
- 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
ECG changes associated with hyperkalaemia
- Peaked T wave (early)
- Broad QRS
- Flat P wave
- Prolonged PR
Outline the effect of hyperkalaemia on muscle contraction
Increased levels of extracellular K+ ions increase the resting membrane potential to become more positive. This increases muscle excitability as resting membrane potential is closer to activation threshold potential.
As there is further increase in potassium, the threshold potential also shifts to become more positive to parralel the also positive shift of resting membrane potential. However, a more positive membrane potential is associated with a lower Vmax (maximum contractive response) when muscle is depolarised as it triggers less Na+ voltage gated channels to open.
TLDR Therefore in summary, the early effect of mild hyperkalemia on myocyte function is to increase myocyte excitability by shifting the resting membrane potential to a less negative value and thus closer to threshold potential; but as potassium levels continue to rise, myocyte depression occurs and Vmax continues to decrease.
Outline the management of hyperkalaemia.
- 10 ml 10% calcium gluconate (cardioprotective does nothing to reduce K+)
- 50 ml 50% dextrose (prevent hypoglycaemia) + 10 U insulin (drive K+ into cells)
- Nebulised salbutamol
- Treat the cause
List some causes of hypokalaemia.
(GRRR)
Either depletion or intracellular shift.
- GI loss (diarrhoea)
- Renal loss
- Hyperaldosteronism, iatrogenic excess cortisol
- Increased sodium delivery to distal nephron
- Osmotic diuresis
- Redistribution into cells
- Insulins
- Beta-agonists
- Alkalosis (shift of K+ into cells in exchange for H+ to balance pH change)
- Rare causes
- Renal tubular acidosis (type 1 and 2)
- Hypomagnesaemia (low Mg means you can’t correct low K+ - first must correct low Mg)
Name a condition and a drug that can block the triple transporter (Na+ K+ Cl-).
Triple transporter is located in thick ascending loop (TAL) of henlee. Reabsorbs Na+, 2Cl-, K+ molecules.
- Loop diuretics
- Bartter syndrome (mutation in triple transporter)
Name two conditions that can block the Na+/Cl- cotransporter.
- Thiazide diuretics
- Gitelman syndrome (mutation in Na+/Cl- cotransporter)
Explain how increased delivery of sodium to the distal nephron can cause hypokalaemia.
- 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
