5th April 2024

Disorders of Potassium

Potassium is a predominantly (98%) intracellular cation in the body where the concentration is relatively higher (100-120 mmol/L) than blood concentration of 3.5-5.2 mmol/L. The serum potassium concentration relates to both the internal balance between intra and extracellular fluids and that determining total body potassium. This is maintained by the kidney under the control of aldosterone secreted by the zona glomerulosa of the adrenal glands. 

The Na/K ATPase enzyme helps to regulate intracellular potassium using adenosine triphosphate (ATP) as energy. For every molecule of ATP the pump uses, three sodium ions are exported and two potassium ions are imported into the cell. 

The majority of potassium (90%) is excreted in urine via the kidneys, while less than 10% is excreted through sweat and faeces.  

Hypokalaemia 

This is defined as serum potassium levels of less than 3.5 mmol/L and can be divided into:

• Mild 3.1 – 3.5 mmol/L
• Moderate 2.5 – 3.0 mmol/L
• Severe < 2.5 mmol/L

The various mechanisms causing hypokalemia include: 

• Spurious hyperkalemia, where potassium is taken up by cells outside the body, e.g., white blood cells in leukaemia. This is likely to occur if there are delays in analysing the sample.
• Transcellular redistribution due to metabolic/respiratory alkalosis and in the presence of excess insulin levels
• Potassium depletion due to diuretic use, diarrhoea, laxative use/abuse and profuse sweating 
• Medications including beta adrenoreceptor agonists such as salbutamol and in theophylline overdose. 
• Hypomagnesaemia results in hypokalemia as reduced intracellular magnesium increases potassium secretion.
• Mineralocorticoid excess in primary hyperaldosteronism (Conn’s syndrome) and secondary hyperaldosteronism (renal artery stenosis).
• Bartter syndrome, where abnormal chloride ion transport in the loop of Henle results in sodium wasting, metabolic alkalosis and potassium depletion 
• Gitelman’s syndrome is the most common cause of congenital hypokalemia characterised by a defect in the distal tubule Na+/Cl– co-transporter gene. The result is hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. Both Bartter and Gitelman’s syndrome activate the renin-angiotensin aldosterone system. 
• Vomiting causes loss of chloride ions, leading to high levels of aldosterone, which inhibits potassium reabsorption from the kidney tubules.

Clinical manifestations 

Mild hypokalemia is usually asymptomatic, but where potassium levels reach below 3.0 mmol/L, symptoms include generalised weakness, fatigue, myalgia and constipation. Potassium levels <2.5 mmol/L result in more serious problems including:

• Muscle weakness and paralysis ascending from the lower limbs
• Respiratory failure where respiratory muscles are involved
• Ileus due to involvement of the gastrointestinal muscles 
• Paraesthesia 
• Tetany
• Polyuria and polydipsia

Investigations 

Blood tests, including urea and electrolytes, serum bicarbonate, glucose and magnesium, provide useful information in hypokalemia investigations. If the patient is on digoxin, then levels should be taken at the appropriate time and a review of medications for other causative agents, such as loop/thiazide diuretics. Concurrent hyponatremia with hypokalemia is suggestive of thiazide diuretic use or marked volume depletion. Low magnesium should be corrected to allow recovery of serum potassium. 

Patients with moderate to severe hypokalemia should have an ECG performed to determine whether cardiac function is affected and to detect digoxin toxicity. Ventricular arrhythmias, including torsades de pointes, ventricular tachycardia and ventricular fibrillation, can occur. ECG findings with potassium levels < 3.0mmol/L include:

• Flat T waves
• ST segment depression
• Presence of U waves 
• Pseudo prolongation of QT interval due to flattened T waves merging into the u waves.  

Other investigations include urine potassium, sodium and urine osmolality, which is necessary to interpret urinary potassium levels. Low urine potassium is suggestive of poor intake, gastrointestinal loss or a shift into the intracellular space. High urinary sodium indicates renal loss.

A low urinary sodium in combination with high urinary potassium indicates secondary hypoaldosteronism. 

Additional tests may be indicated and directed toward finding the underlying cause of hypokalemia:

• Bone profile (calcium and phosphate)
• Arterial blood gas (to establish metabolic acidosis/alkalosis)
• Urinary calcium (in suspected Bartter’s syndrome)
• Serum renin, aldosterone and cortisol
• Low dose dexamethasone suppression test in suspected Cushing’s syndrome
• Pituitary MRI to further evaluate Cushing’s syndrome 
• CT imaging of the adrenal glands
• Renal angiogram id renal artery stenosis is suspected
• Sweat chloride test in suspected cystic fibrosis

Management 

This is almost always done by potassium replacement and the mode of administration and amount of supplementation depends on the severity of hypokalaemia. Any result should be compared with previous results and repeated urgently if inconsistent. 

Oral replacement is appropriate for mild hypokalemia and consists of potassium replacement between 20-40 mmol 2-4 times a day for three days. Potassium rich foods include bananas, tomatoes, avocados, potatoes and apricots. One medium banana contains 12 mmol potassium, the equivalent of one effervescent tablet of sando-K®).

Where oral replacement is not possible, intravenous potassium is used and can be given via a peripheral cannula not exceeding a rate of 10 mmol/hour to avoid phlebitis and discomfort. Monitoring of serum potassium is essential and once ECG abnormalities have resolved the rate of replacement can be further slowed or switched to oral formulations. 

In emergencies, higher replacement rates can be used but must be administered through a central line with continuous cardiac monitoring. The maximum replacement rate should be 0.5 mmol/kg/hour with the weight capped at 80 kg. For example, in an 80 kg adult, the maximum rate of replacement in an emergency via a central line would be 40 mmol/hour. Potassium chloride should never be bolused as it can result in fatal arrhythmias.

Hyperkalaemia 

This is defined as serum potassium levels of greater than or equal to 5.5 mmol/L and can be divided into:

• Mild 5.5 – 5.9 mmol/L
• Moderate 6 – 6.4 mmol/L
• Severe > 6.5 mmol/L

There are various mechanisms leading to hyperkalemia, including haemolysis and release of intracellular potassium from red blood cells during difficult venepuncture, delay between venepuncture and long transit time to the laboratory and taking a blood sample from the limb receiving intravenous fluids with added potassium. Other causes of hyperkalemia include:

• Transcellular redistribution which occurs in acidosis, low insulin states, hypertonicity, rhabdomyolysis and in extreme, prolonged exercise.
• Potassium retention can occur with acute kidney injury or in advanced chronic kidney injury 
• Medications including potassium sparing diuretics (spironolactone), ACE inhibitors, beta blockers, trimethoprim, heparin and digoxin at toxic levels
• Diabetic ketoacidosis: potassium shifts from the intracellular to the extracellular space due to a lack of insulin
• Addison’s disease results in decreased aldosterone levels. Normally, aldosterone promotes the excretion of potassium via the kidneys. Decreased aldosterone levels results in reduced renal excretion of potassium thus hyperkalaemia. 

Clinical manifestations 

Symptoms of hyperkalemia may be non-specific, including fatigue and weakness, but occasionally, a patient may complain of shortness of breath, palpitations, chest pain or present with muscular paralysis. Reflexes may be depressed or absent on physical examination.

Investigations 

Any spurious results should be repeated, particularly if there has been a delay between venepuncture and transport to the laboratory. 24-hour urine volume and electrolytes can be a reliable check of kidney function. Capillary blood and plasma glucose can reveal hyperglycaemia. 

If patients are on digoxin, blood digoxin levels should be taken alongside an arterial blood gas, looking for metabolic acidosis. Patients’ medications should be reviewed and those contributing to hyperkalaemia temporarily held. 

The ECG in hyperkalaemia may show:

• Peaked T waves
• Prolongation of PR interval 
• Widening of QRS
• Reduced amplitude or loss of P wave
• AV dissociation 
• Sine wave pattern 
• Asystole

In patients with heart disease who have an abnormal baseline ECG, bradycardia may be the only new abnormality on ECG.

Management 

Initial management of a patient with hyperkalaemia requires an ABCDE approach. A 12 lead ECG should be performed looking for changes of hyperkalaemia and where serum potassium is > 6.0 mmol/L continuous monitoring of cardiac rhythm is required. 

Empirical treatment is advised where hyperkalaemia is suspected. This includes intravenous calcium to reduce the risk of arrhythmias and to stabilise cardiac myocytes. Initially, 30ml of 10% calcium gluconate may be given or 10 ml of 10% calcium chloride given over 10 minutes. 

Insulin with dextrose is administered to shift potassium into the intracellular space. Typically, 10 units of soluble insulin in 50ml of 50% dextrose is used. Alternatively, 125ml of 20% dextrose can be administered over 15 minutes. Nebulised salbutamol, a beta 2 receptor agonist, is also administered to shift potassium into the intracellular space. 

To facilitate renal excretion of potassium, any reversible renal disease should be treated, for example, stopping nephrotoxic drugs that cause intrinsic renal failure. This includes aminoglycoside antibiotics and amphotericin B, drugs which cause dose-related acute tubular necrosis. Fludrocortisone may be effective for managing chronic hyperkalaemia due to hypoaldosteronism. 

Gastrointestinal excretion is achieved by using potassium binders including calcium resonium, patiromer or sodium zirconium cyclosilicate. 

Refractory hyperkalaemia requires extracorporeal removal either by dialysis or hemofiltration.

Once hyperkalemia is treated, prevention of recurrence is achieved by:

• Dietary potassium restriction
• Medication review of causative agents, i.e., changing spironolactone for a loop diuretic furosemide. 
• Correcting acidosis with sodium bicarbonate supplements 
• Potassium binding resins 
• Dialysis

References

• Potassium management. BMJ Learning. Available at: https://new-learning.bmj.com/course/10047565
• Hypokalaemia. Patient information professional article. Available at: https://patient.info/doctor/hypokalaemia