7. Disorders of potassium balance
Potassium
Potassium is an abundant electrolyte in the body, and potassium ion (K+) is the dominant cation in the intracellularcellular space. 98% of all potassium in the body is intracellular. In the intracellular space the concentration is approx 150 mM, while in the extracellular space it is just 3.5 – 5.5 mM.
The serum potassium level depends in two things:
- The internal potassium balance, the balance between the intracellular and extracellular compartments
- The external potassium balance, the balance between potassium intake and potassium loss
Abnormally low or high potassium (hypokalaemia and hyperkalaemia, respectively), are common but potentially lethal disorders in the worst case.
Reference range
| Parameter | Sample | Reference range |
|---|---|---|
| Potassium | Serum | 3.5 - 5.5 mmol/L |
Function of potassium
The main function of potassium is to maintain fluid and electrolyte balance. Potassium is involved in nerve impulse transmission and muscle contraction by maintaining the resting membrane potantial.
Because there is much more potassium in the intracellular space than the extracellular, there is a large concentration gradient from the intracellular space to the extracellular. To maintain this gradient, potassium is constantly pumped into cells by the Na+/K+-ATPase.
Regulation of potassium level
The potassium level is mainly regulated by the renin-angiotensin-aldosterone system in the kidneys. Increasing levels of potassium stimulates RAAS and therefore aldosterone production, which in turn stimulates the Na+/K+-ATPase in the distal tubules and collecting duct. This causes K+ and H+ loss. This system is very effective and therefore prevents hyperkalaemia from developing, as long as the kidneys are functioning.
The daily intake of potassium in the diet is approximately 40 – 120 mmol K+. This extra potassium reaches the extracellular space and not the cells in normal cases. 90% of excreted potassium is excreted by the kidneys, the remaining through the GI tract.
Hypokalaemia
| Hypokalaemia | |
|---|---|
| Definition | Serum potassium level < 3.5 |
| Symptoms | Muscle weakness, constipation/ileus |
| Complications | Ventricular arrhythmia, rhabdomyolysis |
| Causes | Loop diuretics, gastrointestinal loss, hyperaldosteronism |
| Treatment | P.o. or i.v. supplementation |
Hypokalaemia is a disorder of potassium homeostasis characterised by low levels of potassium (<3.5 mmol/L). It's a relatively uncommon electrolyte abnormality. It's most frequently caused by loop diuretics, gastrointestinal loss, or hyperaldosteronism. Most common symptoms include muscle weakness and constipation, as well as ECG changes. Management involves treating the underlying cause and p.i. or i.v. supplementation. Hypokalaemia can be lethal due to rhabdomyolysis or ventricular arrhythmia. Hypokalaemia is less common than hyperkalaemia.
Grading of severity
| Potassium level | Severity |
|---|---|
| 3.5 - 3.0 | Mild |
| 2.9 - 2.5 | Moderate |
| < 2.5 | Severe |
Etiology
Hypokalaemia can occur due to increased potassium loss, redistribution of potassium into cells, or (rarely) insufficient potassium intake. Because the kidneys can reduce potassium excretion to a minimum, and the daily potassium requirement is really low, insufficient intake of potassium rarely causes hypokalaemia by itself, but it may contribute to hypokalaemia due to other causes
| Increased potassium loss | Redistribution of potassium into cells |
|---|---|
| Loop diuretics | Excessive insulin (treatment of diabetic ketoacidosis or hyperglycaemic hypoerosmolar syndrom, refeeding syndrome) |
| Vomiting or other gastrointestinal loss | Excessive beta-adrenergic activity (severe stress (like myocardial infarction, traumatic head injury, alcohol withdrawal), administration of beta-adrenergic agonists) |
| Hyperaldosteronism, e.g. due to hormone-producing adrenal adenoma | Alkalosis |
Upper gastrointestinal fluids don't contain much potassium, so loss of the fluid itself does not cause severe hypokalaemia. However, the resulting hypovolaemia can cause hyperaldosteronism, which can cause hypokalaemia. Lower gastrointestinal fluids, however, contain much potassium, and so loss of these fluids (usually due to diarrhoea) can cause hypokalaemia.
Clinical features
Symptoms are more severe if the drop in serum potassium is rapid than if it is chronic. Mild hypokalaemia is usually asymptomatic. Moderate hypokalaemia can cause muscle weakness, constipation, ileus, and restless legs. Severe hypokalaemia can cause arrhythmia, rhabdomyolysis, and paresis. Hyporeflexia is a possible sign.
Severe hypokalaemia can cause ECG changes:
- Low or inverted T-waves
- Presence of U-waves
- ST depression
- Supraventricular or ventricular tachyarrhythmia
- Prolonged QT interval
Diagnosis and evaluation
The serum potassium level may be up to 0,5 units higher than the true level of potassium in the blood, due to release of potassium from thrombocytes. To get the most accurate potassium value, an arterial blood gas should be taken.
The cause of hypokalaemia is usually evident from the list of medications, the anamnesis, or from clinical features of the underlying cause.
A urine potassium of > 20 mmol/L in the setting of hypokalaemia is indicative of renal loss of potassium.
Hyperkalaemia
| Hyperkalaemia | |
|---|---|
| Definition | Serum potassium > 5.0 |
| Symptoms | Muscle weakness |
| Complications | Fatal arrhythmia |
| Causes | Chronic kidney disease, RAAS inhibitors |
| Treatment | Calcium gluconate i.v., insulin + glucose |
Hyperkalaemia is a disorder of potassium homeostasis characterised by high levels of potassium (>4.5 mmol/L). It's a relatively common electrolyte abnormality, and more common than hypokalaemia. Hyperkalaemia almost always occurs in the context of reduced potassium excretion by the kidneys, either due to kidney disease or due to medications which reduce the excretion. The most common symptom is muscle weakness, and the most dangerous complication is fatal arrhythmia. Treatment involves stabilising the cardiac membrane by using calcium, moving potassium into cells by using insulin and glucose, and by increased potassium removal from the body by dialysis, potassium-losing diuretics, or a gastrointestinal cation exchanger.
Grading of severity
| Potassium level | Severity |
|---|---|
| 5.1 - 5.9 | Mild |
| 6.0 - 6.9 | Moderate |
| > 7.0 | Severe |
Etiology
| Increased potassium release from cells | Decreased renal potassium excretion |
|---|---|
| Metabolic acidosis | Chronic kidney disease, especially end-stage |
| Massive cell death (rhabdomyolysis, haemolysis, tumor lysis syndrome, burn injury) | Acute kidney injury |
| Non-selective beta blockers | Potassium-sparing diuretics (mineralocorticoid receptor antagonists, amiloride) |
| ACE inhibitors, angiotensin II blocker | |
| Addison disease | |
| Trimethoprim, NSAIDs |
The most common cause of hyperkalaemia is chronic kidney disease and acute kidney injury. In healthy people, the kidney can excrete usually excrete any potassium which is superfluous, but in case of kidney disease, this mechanism doesn't work, and so people with kidney disease are at risk for hyperkalaemia if ingesting potassium-rich foods.
Metabolic acidosis causes hyperkalaemia as the cells tries to buffer the acidosis by movement of H+ ions from the extracellular to the intracellular space. In exchange, cells move K+ ions out, to maintain electrical neutrality.
Non-selective beta blockers inhibit beta-2-adrenergic stimulation of potassium movement into cells. Selective beta blockers don't inhibit the beta-2 receptor and therefore don't cause this effect.
Trimethoprim blocks sodium channels in the collecting tubule, which indirectly impairing potassium secretion. NSAIDs somewhat impair renin secretion and aldosterone release, potentially causing mild hyperkalaemia, but only rarely causes more severe potassium elevation.
Haemolysis of the blood sample causes release of potassium from RBCs, which causes the laboratory to falsely report hyperkalaemia. This is known as pseudohyperkalaemia. Most labs should be able to detect when haemolysis occurs, so this shouldn't be a big problem. Clenching the hand of the arm the blood sample is taken from also causes falsely elevated potassium, as the "exercise" causes potassium release from skeletal muscle.
Clinical features
Symptoms are more severe if the increase in serum potassium is rapid than if it is chronic. Mild hyperkalaemia is asymptomatic. Moderate or severe hyperkalaemia can cause ascending muscle weakness.
Hyperkalaemia can cause ECG changes. These changes are not necessarily proportional to potassium level:
- Early changes
- Tall peaked T-waves
- Shortened QT interval
- Later changes
- Prolonged PQ interval
- Wide QRS, eventually
- Supraventricular or ventricular tachyarrhythmia
- Shrinkage, later absence of P wave
- Bundle branch block (left or right)
- AV block
Diagnosis and evaluation
The serum potassium level may be up to 0,5 units higher than the true level of potassium in the blood, due to release of potassium from thrombocytes. To get the most accurate potassium value, an arterial blood gas should be taken.
The cause of hyperkalaemia is usually trivial to determine from anamnesis, clinical features, or regular blood test. It's simple to determine whether there is kidney injury, based on creatinine and urea levels. If no cause is immediately obvious, aldosterone levels should be measured.