Chem path 4: Potassium balance & cases Flashcards
What is the most abundant intracellular cation?
Potassium (sodium is the most abundant extracellular cation)
What are the two main hormones involved in potassium regulation?
Ang II and aldosterone
What are the two main triggers for aldosterone release?
AngII and high potassium
Outline the RAAS
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
Which zone of the kidney releases aldosterone
Zona glomerulosa
What are some triggers for renin release?
Low BP in renal artery, Low Na+ in macula densa, SNS Beta-1-receptor activation
OUtline the MOA of aldosterone
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.
What are the main causes of hyperkalaemia?
Reduced GFR
Reduced renin (T4 RTA, NSAIDs)
ACEi
Aldosterone antagonists i.e. spironalactone
Addison’s
ARBs
Potassium release from cells: rhabdomyolysis, acidosis
How does acidosis lead to hyperkalaemia?
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)
In type 4 RTA what happens to renin and aldosterone?
They are both low
What are the ECG changes associated with hyperkalaemia?
Peaked T waves (main ECG change) Broad QRS Flattened P waves Prolonged PR and bradycardia sine wave (latest sign)
When would you treat hyperkalaemia?
K+ >6.5 or if there are ECG changes
What is the acute treatment for hyperkalaemia?
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
What are the causes of hypoklalaemia? (GRRR)
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
What could cause an increased delivery of Na+ to the DCT?
Blockage of triple (loop diuretics) or co-transporter (Thiazides)
Bartter syndrome: impairment of triple transporter
Gitelman syndrome: impairment of co-transporter
What are the clinical features of hypokalaemia?
Muscle weakness, cardiac arrhythmias, polyuria and polydipsia (nephrogenic DI)
What are the ECG changes seen in hypokalaemia?
ST depression, flat T waves, U waVES
What screening test would you order in a patient with hypertension and hypokalaemia?
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
What is the management of hypokalaemia?
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
Hyperkalaemia is a side-effect of which of the following drugs:
Furosemide
Bendroflumethathiazide
Salbutamol
Ramipril
Ramipril (ACEi) –> blocks eventual aldosterone production
Outline the differences between RTA types 1,2 and 4
Type 1 = classic distal RTA, hypokalaemia as less H+excretion
Type 2 = proximal distal RTA, less HCO3- resorption
Type 4 = hyperkalaemia + hypoaldosteronism
