Medicine – Hyperkalaemia

Hyperkalaemia is an abnormally high serum potassium concentration. It is clinically important because potassium strongly influences the resting membrane potential of cardiac and skeletal muscle cells, and severe hyperkalaemia can cause rapidly progressive conduction abnormalities, ventricular arrhythmias and cardiac arrest.

A commonly used definition is:

Serum K⁺ >5.0–5.5 mmol/L, depending on the laboratory.

The urgency of treatment depends not only on the potassium concentration but also on the ECG, symptoms, rate of rise, renal function and underlying cause.

1. Major Mechanisms of Hyperkalaemia

The causes can be divided into four useful groups:

Spurious or pseudohyperkalaemia.

Excess potassium administration.

Reduced renal potassium excretion.

Redistribution of potassium from cells into extracellular fluid.

This classification helps determine whether the patient has genuine excess total-body potassium or simply a shift of potassium from the intracellular to extracellular compartment.

2. Spurious Hyperkalaemia

Before treating an unexpected potassium result, consider:

Pseudohyperkalaemia.

This means the measured potassium is elevated in the blood sample even though the patient’s true circulating potassium is not significantly elevated.

The classic cause is:

Haemolysis of the blood sample.

3. Haemolysis

Red blood cells contain a high intracellular concentration of potassium.

If red cells rupture during or after venepuncture:

Intracellular K⁺ is released into the sample.

↓

Laboratory potassium rises.

↓

Falsely elevated potassium result.

Therefore:

UNEXPECTED HIGH K⁺ + HAEMOLYSED SAMPLE → CONSIDER PSEUDOHYPERKALAEMIA.

However, if the potassium is severely elevated or the ECG is abnormal, urgent management should not be delayed simply while waiting for a repeat result.

4. Other Causes of Pseudohyperkalaemia

Pseudohyperkalaemia can also occur with:

Difficult or traumatic venepuncture.

Prolonged tourniquet application.

Repeated fist clenching during blood collection.

Marked thrombocytosis.

Marked leukocytosis.

Therefore the blood result should always be interpreted in its clinical context.

5. Excessive Potassium Intake

The original notes place excessive intake under “spurious,” but this requires correction.

Excessive potassium intake causes genuine hyperkalaemia, not pseudohyperkalaemia.

This may occur from:

Excessive intravenous potassium administration.

Excessive oral potassium supplements.

Potassium-containing salt substitutes.

Dietary potassium alone rarely causes severe hyperkalaemia when renal function and aldosterone activity are normal because healthy kidneys can increase potassium excretion.

The risk becomes much greater in:

Kidney failure or impaired aldosterone activity.

6. Decreased Renal Potassium Excretion

The kidneys are the major route for potassium elimination.

Therefore:

Reduced renal K⁺ excretion

is one of the most important mechanisms of hyperkalaemia.

Major causes include:

Acute kidney injury.

Chronic kidney disease.

Hypoaldosteronism.

Addison disease.

Potassium-retaining medications.

7. Acute Kidney Injury

The older term:

Acute oliguric renal failure

is now generally replaced by:

Acute kidney injury – AKI.

Severe AKI, particularly when associated with:

Oliguria or anuria,

can markedly reduce urinary potassium excretion.

Therefore potassium accumulates in the extracellular fluid.

8. Why Hyperkalaemia Is Dangerous in AKI

AKI may simultaneously produce:

Reduced potassium excretion

and

Metabolic acidosis.

Acidosis may further increase extracellular potassium in some settings.

Therefore:

AKI + OLIGURIA + ACIDOSIS → HIGH RISK OF HYPERKALAEMIA.

Severe refractory hyperkalaemia is an important indication for:

Urgent dialysis.

9. Chronic Kidney Disease

The older term:

Chronic renal failure

is now generally replaced by:

Chronic kidney disease – CKD.

As functioning nephron mass falls, the kidneys become progressively less able to excrete potassium.

Adaptive mechanisms can maintain potassium balance for a considerable period, so severe hyperkalaemia is particularly likely in:

Advanced CKD

or when an additional precipitant is present.

10. Common Precipitants in CKD

A patient with CKD may develop hyperkalaemia after:

AKI.

Dehydration.

ACE inhibitor or ARB therapy.

Potassium-sparing diuretics.

NSAIDs.

Excess potassium supplementation.

Metabolic acidosis.

Therefore medication review is essential.

11. Aldosterone and Potassium

Aldosterone normally acts on the distal nephron to promote:

Sodium reabsorption

and

Potassium secretion.

Therefore:

↓ Aldosterone production or action → ↓ renal K⁺ excretion → hyperkalaemia.

12. Addison Disease

Addison disease, or primary adrenal insufficiency, causes deficiency of:

Aldosterone

and

Cortisol.

Aldosterone deficiency reduces renal potassium excretion.

Therefore:

ADDISON DISEASE → ↓ ALDOSTERONE → K⁺ RETENTION → HYPERKALAEMIA.

Hyponatraemia may occur simultaneously.

13. Hypoaldosteronism

Other forms of hypoaldosteronism can also cause hyperkalaemia.

An important example is:

Hyporeninaemic hypoaldosteronism, often associated with diabetic kidney disease and type 4 renal tubular acidosis.

The characteristic pattern may include:

Hyperkalaemia + mild normal-anion-gap metabolic acidosis.

14. Spironolactone

Spironolactone is a mineralocorticoid receptor antagonist.

It blocks the action of:

Aldosterone.

This decreases potassium secretion in the collecting duct.

Therefore:

Spironolactone → K⁺ retention → hyperkalaemia.

The risk is greater in CKD or when combined with other drugs that suppress the renin–angiotensin–aldosterone system.

15. Amiloride

Amiloride blocks epithelial sodium channels:

ENaC

in the collecting duct.

This decreases the electrochemical gradient that normally promotes potassium secretion.

Therefore:

Amiloride → ↓ renal K⁺ secretion → hyperkalaemia.

16. ACE Inhibitors

ACE inhibitors reduce:

Angiotensin II

and consequently reduce:

Aldosterone secretion.

Therefore:

ACE inhibitor → ↓ aldosterone → ↓ K⁺ excretion → hyperkalaemia.

Examples include:

Ramipril.

Lisinopril.

Enalapril.

The risk increases in patients with:

CKD, diabetes, AKI or concurrent potassium-retaining medications.

17. Angiotensin Receptor Blockers

An important addition is:

ARBs, such as losartan.

Like ACE inhibitors, they reduce aldosterone activity and can therefore cause:

Hyperkalaemia.

18. NSAIDs

NSAIDs inhibit renal prostaglandin synthesis.

This can reduce renal perfusion and suppress:

Renin release.

Reduced renin leads to reduced aldosterone activity.

Therefore:

NSAIDs → ↓ renin/aldosterone + possible AKI → hyperkalaemia.

The risk is especially important in patients with pre-existing:

CKD or volume depletion.

19. Other Drugs Causing Hyperkalaemia

Important additional medications include:

Trimethoprim, which has an amiloride-like effect on ENaC.

Heparin, which can reduce aldosterone synthesis.

Tacrolimus and ciclosporin.

ARBs.

Potassium supplements.

Therefore unexplained hyperkalaemia should always trigger a:

Medication review.

20. Redistribution of Potassium

Most body potassium is normally located:

Inside cells.

Certain conditions cause potassium to move from the intracellular compartment into extracellular fluid.

This produces:

Redistribution hyperkalaemia.

Important examples include:

Acidosis.

Rhabdomyolysis.

Tumour lysis syndrome.

Digoxin toxicity.

Insulin deficiency and hyperglycaemic hyperosmolality can also contribute.

21. Acidosis

The original notes correctly include:

Acidosis.

In some forms of metabolic acidosis, particularly mineral/inorganic acid acidosis, extracellular H⁺ promotes movement of potassium out of cells.

Therefore:

H⁺ moves into cells

while:

K⁺ moves out

to help maintain electroneutrality.

This contributes to:

Hyperkalaemia.

22. Important Acidosis Clarification

The relationship between acidosis and potassium is not identical in every type of acidosis.

Hyperkalaemia is particularly associated with:

Mineral acidosis

and with conditions involving:

Insulin deficiency, hyperosmolality or impaired renal function.

Organic acidoses do not necessarily cause the same degree of direct H⁺/K⁺ exchange.

23. Rhabdomyolysis

Skeletal muscle cells contain large amounts of intracellular potassium.

In rhabdomyolysis:

Muscle cells break down.

↓

Intracellular K⁺ is released.

↓

Hyperkalaemia develops.

Other substances released include:

Myoglobin.

Phosphate.

Creatine kinase.

Hyperkalaemia may become especially severe if rhabdomyolysis also causes:

AKI.

24. Tumour Lysis Syndrome

Tumour lysis syndrome occurs when large numbers of malignant cells rapidly break down.

Cellular contents enter the circulation, producing:

Hyperkalaemia.

Hyperphosphataemia.

Hyperuricaemia.

Secondary:

Hypocalcaemia.

Therefore:

TUMOUR LYSIS → ↑ K⁺ + ↑ PHOSPHATE + ↑ URIC ACID + ↓ Ca²⁺.

25. Digoxin Toxicity

The original notes correctly include:

Digoxin poisoning.

Digoxin inhibits:

Na⁺/K⁺-ATPase.

In acute severe toxicity, potassium movement into cells is reduced.

Therefore extracellular potassium rises:

Acute digoxin toxicity → hyperkalaemia.

The degree of hyperkalaemia can be an important marker of severe acute toxicity.

26. ECG Changes in Hyperkalaemia

Hyperkalaemia alters myocardial depolarisation and repolarisation.

The traditional sequence is:

Peaked T waves

↓

PR prolongation

↓

P-wave flattening

↓

P-wave disappearance

↓

QRS widening

↓

Sine-wave pattern

↓

Ventricular fibrillation or asystole.

However, the ECG does not always progress predictably, and dangerous hyperkalaemia can occasionally exist without classic ECG changes.

27. Peaked T Waves

An early classic ECG manifestation is:

Tall, narrow, peaked or “tented” T waves.

These reflect altered ventricular:

Repolarisation.

They may be particularly prominent in the:

Precordial leads.

28. P-Wave Changes

As hyperkalaemia becomes more severe:

P-wave amplitude decreases.

This reflects impaired atrial conduction.

Eventually:

P waves may disappear completely.

29. PR Prolongation

The:

PR interval increases

as atrioventricular conduction slows.

Therefore:

Hyperkalaemia → conduction slowing → PR prolongation.

30. QRS Widening

Further elevation of potassium causes slowing of ventricular depolarisation.

Therefore:

QRS complexes become progressively wider.

Marked QRS widening is a dangerous sign of severe cardiac toxicity.

31. Sine-Wave Pattern

In extreme hyperkalaemia:

Widened QRS complexes merge with T waves.

This produces a:

Sine-wave or sinusoidal appearance.

This represents:

Pre-terminal cardiac toxicity

and may rapidly progress to:

Ventricular fibrillation or asystole.

32. ECG Changes – Note Form

T waves:

Tall + peaked + tented.

↓

P waves:

Become smaller.

↓

PR interval:

Prolongs.

↓

P waves:

May disappear.

↓

QRS:

Widens.

↓

QRS + T merge:

Sine-wave pattern.

↓

VF / asystole / cardiac arrest.

33. Treatment Principles

Treatment of severe hyperkalaemia can be understood as four separate objectives:

1. Protect the heart.

2. Shift potassium into cells.

3. Remove potassium from the body.

4. Identify and treat the underlying cause.

This framework is more useful than simply memorising a drug list.

34. Intravenous Calcium – Protect the Heart

The original notes correctly include:

Intravenous calcium gluconate.

Calcium antagonises the adverse electrophysiological effects of hyperkalaemia on cardiac tissue.

Therefore:

IV CALCIUM → STABILISES THE CARDIAC MEMBRANE.

35. Calcium Does Not Lower Potassium

This is extremely important:

CALCIUM DOES NOT REDUCE THE SERUM POTASSIUM CONCENTRATION.

Its purpose is to:

Protect the myocardium while other treatments lower potassium.

Its effect begins rapidly but is temporary.

36. Insulin and Dextrose – Shift Potassium Into Cells

The original notes correctly include:

Intravenous insulin + dextrose/glucose.

Insulin stimulates:

Na⁺/K⁺-ATPase

and drives potassium:

From extracellular fluid → into cells.

Therefore:

INSULIN → RAPID TEMPORARY FALL IN SERUM K⁺.

Glucose is usually administered to reduce the risk of:

Hypoglycaemia.

Blood glucose requires monitoring after treatment.

37. Nebulised Salbutamol

The original notes correctly include:

Salbutamol nebulisers.

Salbutamol is a:

β₂-adrenergic agonist.

β₂ stimulation increases Na⁺/K⁺-ATPase activity and shifts potassium:

Into cells.

Therefore nebulised salbutamol can provide an additional temporary reduction in:

Serum K⁺.

It should not be relied upon as the sole treatment for severe hyperkalaemia.

38. Sodium Bicarbonate

Sodium bicarbonate is not routinely effective for every case of hyperkalaemia.

However, it may be considered in selected patients with significant:

Metabolic acidosis.

Its potassium-lowering effect is less predictable than insulin.

39. Removing Potassium From the Body

Treatments such as:

Insulin

and

Salbutamol

mainly redistribute potassium into cells.

They do not remove substantial potassium from the body.

Definitive potassium removal may require:

Renal excretion.

Gastrointestinal potassium binders.

or

Dialysis.

40. Furosemide

The original notes include:

Furosemide.

This loop diuretic can increase urinary potassium excretion if the patient has:

Adequate renal function and urine production.

Therefore it may be useful in selected patients, particularly when volume overload is also present.

It will be much less useful in:

Severe oliguric or anuric kidney failure.

41. Calcium Resonium

The original notes include:

Calcium resonium, or calcium polystyrene sulfonate.

This is a gastrointestinal:

Cation-exchange resin.

It binds potassium in the gastrointestinal tract and promotes its removal in stool.

However, it has a relatively slow and variable effect and is:

Not appropriate as the sole emergency treatment of life-threatening hyperkalaemia.

42. Newer Potassium Binders

Modern potassium-lowering options also include agents such as:

Sodium zirconium cyclosilicate

and

Patiromer.

Their role depends on the urgency and clinical context. They do not replace immediate cardiac protection and intracellular shifting therapy when severe ECG-toxic hyperkalaemia is present.

43. Dialysis

Dialysis directly removes potassium from the bloodstream.

It is particularly important when hyperkalaemia is:

Severe.

Refractory to medical treatment.

Recurrent after temporary intracellular shifting.

or associated with:

Severe kidney failure.

Therefore:

REFRACTORY SEVERE HYPERKALAEMIA = IMPORTANT INDICATION FOR URGENT DIALYSIS.

44. Emergency Treatment – Note Form

STEP 1 – Protect the heart

ECG changes / severe hyperkalaemia

↓

IV calcium gluconate

↓

Cardiac membrane stabilisation.

↓

Does NOT lower K⁺.

STEP 2 – Shift K⁺ into cells

IV insulin + glucose

and/or

Nebulised salbutamol.

↓

Serum K⁺ falls temporarily.

STEP 3 – Remove K⁺ from body

Depending on circumstances:

Loop diuretic if kidneys can excrete K⁺.

Potassium-binding therapy.

Dialysis when severe/refractory or renal failure prevents adequate excretion.

STEP 4 – Treat the cause

Stop or review potassium-raising drugs.

Treat AKI.

Correct appropriate acid–base disturbance.

Treat rhabdomyolysis/tumour lysis.

Treat adrenal insufficiency when present.

45. Causes – Note Form

SPURIOUS:

Haemolysed blood sample.

Traumatic venepuncture.

Marked thrombocytosis/leukocytosis.

EXCESS POTASSIUM:

IV potassium.

Oral potassium supplements.

Potassium-rich salt substitutes.

Especially dangerous with impaired renal function.

DECREASED EXCRETION:

AKI, especially oliguria/anuria.

Advanced CKD.

Addison disease.

Hypoaldosteronism.

DRUGS:

Spironolactone.

Amiloride.

ACE inhibitors.

ARBs.

NSAIDs.

Trimethoprim.

Heparin.

Tacrolimus/ciclosporin.

Potassium supplements.

REDISTRIBUTION / CELL RELEASE:

Acidosis.

Insulin deficiency/hyperosmolality.

Rhabdomyolysis.

Tumour lysis syndrome.

Acute digoxin toxicity.

46. Important Corrections to the Original Notes

The original classification of:

“Excessive intake” under “spurious”

should be corrected.

Haemolysis → pseudohyperkalaemia.

Excessive potassium administration → true hyperkalaemia.

The older terms:

“Acute renal failure”

and

“Chronic renal failure”

are better replaced with:

Acute kidney injury – AKI

and

Chronic kidney disease – CKD.

The ECG sequence in the original notes is useful, but remember:

ECG changes do not correlate perfectly with the serum potassium concentration.

A normal-looking ECG does not reliably exclude dangerous hyperkalaemia.

The original treatment list is broadly correct, but it is much easier to remember according to purpose:

CALCIUM → PROTECTS HEART.

INSULIN/GLUCOSE → SHIFTS K⁺ INTO CELLS.

SALBUTAMOL → SHIFTS K⁺ INTO CELLS.

FUROSEMIDE → INCREASES RENAL K⁺ EXCRETION IF KIDNEYS FUNCTION.

POTASSIUM BINDERS → REMOVE K⁺ THROUGH GI TRACT.

DIALYSIS → DIRECTLY REMOVES K⁺.

Key Clinical Pattern

For rapid recall:

HYPERKALAEMIA = THINK KIDNEYS + DRUGS + ALDOSTERONE + CELL BREAKDOWN/SHIFT.

AKI / CKD → ↓ K⁺ EXCRETION.

SPIRONOLACTONE / AMILORIDE / ACEi / ARB / NSAID → K⁺ RETENTION.

ADDISON / HYPOALDOSTERONISM → ↓ ALDOSTERONE → K⁺ RETENTION.

RHABDOMYOLYSIS / TUMOUR LYSIS → CELL BREAKDOWN → K⁺ RELEASE.

ACIDOSIS → K⁺ SHIFT OUT OF CELLS.

For the ECG:

PEAKED T → PR PROLONGATION → P WAVES FLATTEN/DISAPPEAR → QRS WIDENS → SINE WAVE → ARREST.

For emergency treatment, remember:

CALCIUM = PROTECT THE HEART.

INSULIN + GLUCOSE = SHIFT K⁺ INTO CELLS.

SALBUTAMOL = SHIFT K⁺ INTO CELLS.

DIURETIC/BINDER = REMOVE K⁺ WHEN APPROPRIATE.

DIALYSIS = DEFINITIVE RAPID REMOVAL WHEN SEVERE OR REFRACTORY.