Hyperkalemia is an elevated serum potassium concentration (>5.0 mEq/L) that can impair cardiac conduction and lead to life-threatening arrhythmias.

Hyperkalaemia

Hyperkalaemia (hyper- = excessive, -kal- from Latin kalium = potassium, -aemia = in the blood) is defined as a serum potassium concentration > 5.0 mmol/L ^[1]^[2].

It is one of the most dangerous electrolyte disturbances because potassium is the principal determinant of the resting membrane potential of excitable cells (cardiac myocytes, skeletal muscle, neurons). Even modest elevations can alter cardiac conduction and cause lethal arrhythmias.

Clinically, it is stratified as:

Severity	Serum K⁺ (mmol/L)	Clinical Significance
Mild	5.0–5.9	Usually asymptomatic; monitor
Moderate	6.0–6.4	ECG changes may appear; start worrying ^[1]
Severe	≥ 6.5	Medical emergency; risk of fatal arrhythmia

"Higher than 6, start worrying" ^[1]

Key Concept — Why Is Hyperkalaemia So Dangerous?

Potassium sets the resting membrane potential (RMP) of all excitable cells via the Nernst equation. Normally the RMP of a cardiac myocyte is about −90 mV. As extracellular K⁺ rises, the RMP becomes less negative (depolarised). This initially makes cells more excitable (peaked T waves) but then inactivates sodium channels, slowing conduction (widened QRS) and eventually causing asystole or ventricular fibrillation.

Prevalence: Hyperkalaemia is found in 1–10% of hospitalised patients, and is much more common in patients with chronic kidney disease (CKD), heart failure, and diabetes mellitus — all highly prevalent in Hong Kong ^[2]^[3].
Hong Kong context:
- Ageing population → high prevalence of CKD, heart failure, and type 2 diabetes mellitus (T2DM).
- Diabetic nephropathy is the most common cause of renal impairment (~51%) in Hong Kong ^[4] — these patients are especially vulnerable because of hyporeninemic hypoaldosteronism (Type 4 RTA) and frequent use of RAAS blockers.
- Widespread use of RAAS blockade (ACEi, ARB, MRA) in cardio-renal protection → iatrogenic hyperkalaemia is a major clinical concern.
Mortality: Severe hyperkalaemia (K⁺ ≥ 6.5 mmol/L) is associated with a 30-day mortality of 20–30% in hospitalised patients. Cardiac arrest from hyperkalaemia has an extremely poor resuscitation rate.
Sex: Slightly more common in males, partly because of higher muscle mass (larger K⁺ reservoir) and higher rates of CKD/cardiovascular disease.

Category	Risk Factors
Renal	CKD (especially stages 4–5), AKI, renal transplant rejection, obstructive uropathy
Endocrine	Diabetic nephropathy → hyporeninemic hypoaldosteronism ^[4], Addison's disease, hypoaldosteronism
Drugs	ACEi, ARB, aldosterone antagonist/MRA (spironolactone, eplerenone), renin inhibitor (aliskiren), RNA interference targeting hepatic angiotensinogen ^[5], K⁺-sparing diuretics (amiloride, triamterene), CNI (cyclosporin, tacrolimus) ^[1], NSAIDs, trimethoprim, heparin, digoxin overdose, succinylcholine, beta-blockers
Dietary	Excessive K⁺ intake (bananas, oranges, potatoes, salt substitutes containing KCl) — usually only significant if renal excretion is impaired
Tissue destruction	Rhabdomyolysis, burns, trauma, tumour lysis syndrome, massive haemolysis
Metabolic	Metabolic acidosis (especially non-anion-gap / mineral acidosis), DKA
Other	Elderly age, dehydration/hypovolaemia, constipation (loss of colonic K⁺ secretion pathway)

"Name 4 classes of drugs that can cause RAAS blockade: ACEi, ARB, Aldosterone antagonist/MRA, Renin inhibitor (aliskiren), RNA interference targeting hepatic angiotensinogen" ^[5]

4. Anatomy & Physiology of Potassium Homeostasis

Total body K⁺ ≈ 3500 mmol (50–55 mmol/kg body weight).
98% of K⁺ is intracellular (ICF); only 2% is extracellular (ECF). ^[2]
The normal serum K⁺ is 3.5–5.0 mmol/L; intracellular K⁺ is ~140 mmol/L.
This massive 40:1 intracellular-to-extracellular gradient is maintained by the Na⁺/K⁺-ATPase pump (3 Na⁺ out, 2 K⁺ in per cycle), which is the single most important determinant of K⁺ distribution.

Because only 2% of total body K⁺ is in the ECF, even tiny shifts from ICF to ECF can dramatically raise serum K⁺.

4.2 Potassium Regulation — Two Systems

Potassium homeostasis involves two regulatory arms:

90% of daily K⁺ excretion is renal; 10% is via the GI tract (colon).
In the kidney:
- K⁺ is freely filtered at the glomerulus.
- ~65% is reabsorbed in the proximal convoluted tubule (PCT) (passive, paracellular, follows Na⁺/water reabsorption).
- ~25% is reabsorbed in the thick ascending limb of the loop of Henle via the NKCC2 transporter (Na⁺-K⁺-2Cl⁻ cotransporter — the target of loop diuretics).
- The principal cells of the cortical collecting duct (CCD) are the main site of regulated K⁺ secretion:
  - Aldosterone stimulates ENaC (epithelial Na⁺ channels) → Na⁺ reabsorption → creates a lumen-negative electrical gradient → K⁺ secretion via ROMK channels.
  - High tubular flow rate (e.g., from loop diuretics or volume expansion) washes away luminal K⁺, maintaining the concentration gradient for continued secretion.
  - Distal Na⁺ delivery: More Na⁺ in the CCD lumen → more Na⁺ reabsorbed via ENaC → more K⁺ secreted.

Therefore, aldosterone is the single most important hormonal regulator of K⁺ excretion. Any process that reduces aldosterone action (hypoaldosteronism, ACEi, ARB, MRA, Type 4 RTA) will impair K⁺ excretion and predispose to hyperkalaemia ^[1]^[5].

Factors that shift K⁺ INTO cells (↓ serum K⁺):

Factor	Mechanism
Insulin	Stimulates Na⁺/K⁺-ATPase → K⁺ uptake into cells
β₂-adrenergic agonists (e.g., salbutamol)	Stimulate Na⁺/K⁺-ATPase via cAMP
Alkalosis	H⁺ leaves cells in exchange for K⁺ entering cells
Aldosterone	Also has a minor transcellular shifting effect

Factors that shift K⁺ OUT OF cells (↑ serum K⁺):

Factor	Mechanism
Acidosis	Transcellular shift of H⁺ into cells → K⁺ moves out to maintain electroneutrality ^[2]
Insulin deficiency	Loss of Na⁺/K⁺-ATPase stimulation
β-blockers	Block β₂-mediated K⁺ uptake
Hyperosmolality (e.g., hyperglycaemia)	Solvent drag — water moves out of cells, K⁺ follows
Cell lysis / tissue destruction	Rhabdomyolysis, haemolysis, tumour lysis → release of intracellular K⁺
Digitalis overdose	Inhibits Na⁺/K⁺-ATPase directly → K⁺ cannot enter cells ^[2]
Succinylcholine	Depolarising agent opens ACh receptor channels → K⁺ efflux

Important — DKA and K⁺: A Classic Exam Trap

In DKA, there is apparent hyperkalaemia due to transcellular shift (insulin deficiency + acidosis + hyperosmolality), but total body K⁺ is actually DEPLETED due to osmotic diuresis. Once you give insulin and correct the acidosis, K⁺ rapidly shifts back into cells → dangerous hypokalaemia can result. Always monitor K⁺ closely and supplement as needed before serum K⁺ drops below 5.5. ^[2]

TTKG = (Urine K⁺ / Plasma K⁺) × (Plasma Osm / Urine Osm) ^[1]
It estimates the K⁺ gradient across the CCD, reflecting aldosterone bioactivity.
In hyperkalaemia:
- TTKG < 6 → inappropriate renal response to hyperkalaemia (i.e., the kidney is NOT excreting enough K⁺; suggests hypoaldosteronism or CCD dysfunction) ^[1]
- TTKG > 10 → appropriate renal response (kidneys are working hard to excrete K⁺; problem is likely extra-renal — excessive intake, transcellular shift, or tissue breakdown) ^[1]

"TTKG for an adequate response would be very large, as it would mean the kidneys are working hard to excrete more potassium — so if this is low, concerning as it means the kidneys are not excreting potassium" ^[1]

Note on TTKG

Recent evidence questions the accuracy of TTKG in some settings (e.g., urea recycling in CCD). Some guidelines no longer routinely recommend it. However, it remains in the HKUMed curriculum and is frequently tested. Know the concept and the thresholds.

5. Aetiology & Pathophysiology

Hyperkalaemia fundamentally arises from one or more of three mechanisms:

Increased K⁺ input into the ECF (excessive intake, transcellular shift out of cells, tissue destruction)
Decreased K⁺ output from the ECF (impaired renal excretion)
Pseudohyperkalaemia (artefactual elevation)

Renal failure and hypoaldosteronism are the important causes. ^[1]

"Repeating [K⁺] if no apparent cause of the hyperkalemia is found, e.g. pseudohyperkalemia, haemolysis with forceful blood taking" ^[1]

Cause	Mechanism
Haemolysis during venepuncture	Forceful aspiration, prolonged tourniquet time, small-bore needle → red cell lysis → K⁺ leaks out in vitro
Thrombocytosis (platelets > 500 × 10⁹/L)	K⁺ released from platelets during clotting in the blood tube
Leukocytosis (WBC > 70 × 10⁹/L)	K⁺ released from fragile white cells
Delayed sample processing	K⁺ leaks from cells over time
Fist clenching during blood draw	Local K⁺ release from forearm muscles

In the lab, haemolysis is detected by the haemolytic index (HI); if elevated, the sample is flagged and K⁺ may be unreliable. ^[2]

Clinical pearl: If K⁺ is unexpectedly high and there are no ECG changes, repeat the sample with a free-flowing draw (no tourniquet, no fist clenching, large-bore needle). If the patient has thrombocytosis/leukocytosis, send a plasma (heparinised) sample instead of a serum (clotted) sample.

5.2 Increased K⁺ Input into ECF

Cause	Pathophysiology
Metabolic acidosis	H⁺ enters cells → K⁺ exits to maintain electroneutrality (transcellular exchange). Mineral (non-anion-gap) acidosis causes more shift than organic acidosis ^[2]
DKA	Insulin deficiency + acidosis + hyperosmolality → K⁺ shift out of cells. BUT total body K⁺ is depleted from osmotic diuresis ^[2]
Hyperosmolality	Hyperglycaemia, mannitol → water drag pulls K⁺ out of cells
Digitalis overdose	Inhibits Na⁺/K⁺-ATPase → K⁺ cannot re-enter cells. Risk factors: elderly, hypothyroidism, hypokalaemia ^[2]
β-blockers	Block β₂-mediated Na⁺/K⁺-ATPase stimulation
Succinylcholine	Depolarising muscle relaxant → ACh receptor activation → K⁺ efflux (especially dangerous in burns, denervation injuries, immobility — upregulated extra-junctional receptors)
Hyperkalemic periodic paralysis	Rare, AD inheritance (SCN4A mutation), infantile/childhood onset, triggers: exercise, fasting, cold, anaesthesia, K⁺ ingestion ^[6]

Cause	Pathophysiology
Rhabdomyolysis	Skeletal muscle necrosis → massive release of intracellular contents (K⁺, CK, myoglobin, PO₄³⁻, uric acid)
Burns / trauma / crush injury	Same mechanism — cell membrane disruption
Tumour lysis syndrome	Rapid tumour cell turnover after chemotherapy → release of K⁺, PO₄³⁻, uric acid, LDH. Accompanied by: high phosphate, AST, LDH, uric acid; low calcium (due to ↑PO₄³⁻) ^[2]
Haemolysis (in vivo)	↑PO₄, K, CK, AST, LDH, uric acid, Mg; ↓ALP, amylase, GGT ^[2]

Oral K⁺ supplements (KCl, Slow-K), IV K⁺ infusion (especially if given too fast)
K⁺-containing salt substitutes
Massive blood transfusion (stored RBCs leak K⁺; older units have higher K⁺)

Excessive intake alone rarely causes sustained hyperkalaemia in a patient with normal renal function — the kidneys can excrete up to 200 mmol K⁺/day. It becomes significant only when combined with impaired excretion.

5.3 Decreased K⁺ Output from ECF (Impaired Renal Excretion)

This is the most common mechanism for clinically significant, sustained hyperkalaemia.

Condition	Pathophysiology
CKD (stages 4–5)	Reduced nephron mass → fewer functioning collecting ducts to secrete K⁺. Hyperkalaemia usually becomes significant when GFR < 15–20 mL/min (or earlier if combined with drugs/acidosis)
AKI	Sudden fall in GFR → acute inability to excrete K⁺. Especially in oliguric AKI
Obstructive uropathy	Post-renal → reduced urine flow → impaired K⁺ washout

Condition	Pathophysiology
Hyporeninemic hypoaldosteronism (Type 4 RTA)	Most common cause in adults is diabetic nephropathy — destruction of JG apparatus due to vascular hyalinosis → ↓ renin → ↓ aldosterone → impaired K⁺ secretion and impaired H⁺ secretion (hence hyperchloraemic metabolic acidosis) ^[4]
Addison's disease (primary adrenal insufficiency)	Destruction of adrenal cortex → ↓ aldosterone + ↓ cortisol
Congenital adrenal hyperplasia	21-hydroxylase deficiency → ↓ aldosterone synthesis
Heparin / LMWH	Directly inhibit aldosterone synthase in the zona glomerulosa
ACEi / ARB	Block AngII production/action → ↓ aldosterone release → K⁺ retention. "Blocking aldosterone, more potassium retention" ^[5]
MRA (spironolactone, eplerenone)	Block aldosterone receptor in CCD → impaired ENaC activation → impaired K⁺ secretion
Calcineurin inhibitors (cyclosporin, tacrolimus)	Inhibit ROMK channels in CCD + ↓ aldosterone sensitivity → impaired K⁺ secretion
Trimethoprim / Pentamidine	Block ENaC directly (amiloride-like effect) → impaired K⁺ secretion
NSAIDs	Inhibit prostaglandin-mediated renin release → ↓ renin → ↓ AngII → ↓ aldosterone

High Yield — Drugs Causing Hyperkalaemia

The most commonly tested drugs causing hyperkalaemia are ACEi, ARB, K⁺-sparing diuretics (spironolactone, eplerenone, amiloride, triamterene), CNI (cyclosporin, tacrolimus), NSAIDs, trimethoprim, heparin, and digoxin. ^[1]^[2]^[5]

Severe heart failure or cirrhosis → reduced effective circulating volume → avid proximal Na⁺ reabsorption → less Na⁺ reaches the CCD → less Na⁺ to reabsorb via ENaC → less K⁺ secretion.
Severe volume depletion → same mechanism.

Pseudohypoaldosteronism (types 1 & 2) — genetic resistance to aldosterone action
Gordon syndrome (pseudohypoaldosteronism type 2 / familial hyperkalaemia with hypertension) — gain-of-function WNK kinase mutation → increased NCC activity in DCT → excessive Na⁺ reabsorption proximally → less Na⁺ delivery to CCD → impaired K⁺ secretion. Treated with thiazides.
Obstructive uropathy — structural damage to CCD

6. Classification

Hyperkalaemia can be classified in several ways:

Grade	Serum K⁺	Clinical Action
Mild	5.0–5.9 mmol/L	Identify cause, dietary advice, medication review
Moderate	6.0–6.4 mmol/L	ECG, consider treatment
Severe	≥ 6.5 mmol/L	Medical emergency — immediate treatment

Pseudohyperkalaemia — artefactual (no true elevation in vivo)
Redistribution (transcellular shift) — total body K⁺ may be normal or even low
Excessive intake — usually in the context of impaired excretion
Impaired excretion — renal failure, hypoaldosteronism, drugs

Acute — hours to days (e.g., AKI, tumour lysis, rhabdomyolysis, DKA)
Chronic — weeks to months (e.g., CKD, chronic RAAS blockade, Type 4 RTA)

"Rate of rise of [K⁺] is important — more tolerable with chronic hyperK⁺" ^[1]. This is because chronic elevation allows the cardiac cells to partially adapt by altering ion channel expression. Conversely, a rapid rise from 4.0 to 6.5 is far more dangerous than a chronic K⁺ of 6.5 in a CKD patient.

7. Clinical Features

Hyperkalaemia is frequently asymptomatic until it causes cardiac arrest — this is why it is called a "silent killer." When symptoms do occur:

Symptom	Pathophysiological Basis
Muscle weakness / fatigue	Depolarisation of the resting membrane potential → Na⁺ channel inactivation → impaired action potential generation in skeletal muscle. Usually occurs when [K⁺] > 8 mmol/L ^[1]
Paraesthesias (tingling, numbness)	Same mechanism affecting sensory nerve fibres
Flaccid paralysis	Extreme depolarisation → complete Na⁺ channel inactivation → no action potential possible → flaccid (not spastic) paralysis. Typically ascending (legs before arms), proximal > distal
Nausea, vomiting	Smooth muscle dysfunction in the GI tract
Palpitations	Cardiac arrhythmia — the patient may sense irregular or rapid heartbeats
Chest pain / dyspnoea	If cardiac ischaemia or arrhythmia results in reduced cardiac output
Sudden cardiac death	VF or asystole — may be the first and only "symptom"

Important

Many patients with significant hyperkalaemia are completely asymptomatic. Never rely on symptoms to decide whether hyperkalaemia is dangerous — always check the ECG and treat based on the K⁺ level and ECG changes.

7.2 Signs

ECG changes follow a classic progressive sequence as K⁺ rises ^[1]^[2]^[7]:

Serum K⁺ (approximate)	ECG Change	Pathophysiological Explanation
5.5–6.0	Peaked (tall, narrow, tented) T waves	Accelerated repolarisation of ventricular myocytes due to ↑K⁺ conductance through K⁺ channels
6.0–7.0	Prolonged PR interval, flattened P waves	Slowed atrial conduction due to depolarised RMP → Na⁺ channel inactivation in atrial tissue
7.0–7.5	Widened QRS complex	Same Na⁺ channel inactivation in ventricular myocardium → slowed ventricular conduction
> 7.5	Loss of P wave	Complete atrial standstill — atrial conduction has ceased entirely
> 8.0	Sine wave pattern	QRS merges with T wave into a smooth sinusoidal curve — pre-terminal rhythm
> 9.0–10.0	VF → Asystole	Complete loss of organised electrical activity → cardiac arrest

"ECG: peaked T, widening of QRS, loss of P, sine wave, asystole" ^[1]

High Yield — ECG Progression

The classic ECG progression of hyperkalaemia is: Peaked T waves → PR prolongation / flattened P → Widened QRS → Loss of P wave → Sine wave → VF/Asystole. This is an extremely high-yield exam topic. However, remember that this progression is not always orderly — patients can jump from peaked T waves directly to VF. Treat any ECG changes urgently.

Important caveats:

The rate of rise matters more than the absolute value — a patient with CKD and chronic K⁺ of 6.5 may have minimal ECG changes, while a patient who acutely rises from 4.0 to 6.5 may have dramatic changes ^[1].
Hypocalcaemia potentiates the cardiac toxicity of hyperkalaemia (because calcium normally stabilises the myocardial membrane). Conversely, hypercalcaemia is somewhat protective.
Hyponatraemia also worsens hyperkalaemic cardiotoxicity (reduced Na⁺ gradient → further impairs conduction).
ECG changes may be absent even with dangerous levels of K⁺ — never use ECG alone to rule out dangerous hyperkalaemia.

Sign	Pathophysiological Basis
Hypotonia / areflexia	Depolarisation block of LMN and muscle — similar mechanism to depolarising neuromuscular block
Ascending weakness	Lower limbs first (proximal > distal), may progress to respiratory muscles in extreme cases
No sensory involvement (typically)	Motor fibres are more susceptible because they depend on repetitive high-frequency firing

Sign	Basis
Hypotension	If cardiac output is compromised by arrhythmia
Signs of the underlying cause	e.g., Kussmaul breathing (DKA), uraemic fetor (renal failure), Addisonian hyperpigmentation, signs of volume depletion

When confronted with hyperkalaemia, think systematically:

Is it real? → Exclude pseudohyperkalaemia (repeat sample, check for haemolysis, check platelet/WBC counts)
Is it dangerous RIGHT NOW? → Get an ECG immediately. If ECG changes are present → emergency treatment regardless of the absolute value.
Why is K⁺ high? → History (diet, drugs, symptoms of renal failure/adrenal insufficiency/tissue damage), physical examination (volume status, signs of uraemia), basic labs (RFT, VBG/ABG, glucose, CK)
Is it a shift or a true excess? → Acidosis, DKA, and tissue destruction cause redistributive hyperkalaemia; renal failure and hypoaldosteronism cause true retention.

"History, diet, drug history (ACEi, ARB, K⁺ sparing diuretics, CNI); repeating [K⁺] if no apparent cause; physical examination (volume depletion); renal function test; TTKG" ^[1]

Exam Approach — Structured History for Hyperkalaemia

Drug history — the most important part. Go through every medication.
Diet — K⁺-rich foods, salt substitutes
Renal history — known CKD? Dialysis? Recent AKI?
Endocrine history — diabetes (Type 4 RTA), Addison's (fatigue, weight loss, hyperpigmentation, salt craving)
Tissue damage — recent trauma, surgery, crush injury, new chemotherapy (tumour lysis), dark urine (rhabdomyolysis/haemolysis)
Acidosis clues — DKA (polyuria, polydipsia, vomiting), diarrhoea (non-anion-gap metabolic acidosis)
Family history — periodic paralysis

High Yield Summary

Hyperkalaemia = serum K⁺ > 5.0 mmol/L. Severe (≥ 6.5 mmol/L) is a medical emergency.
98% of K⁺ is intracellular. The Na⁺/K⁺-ATPase pump maintains this gradient. Even small transcellular shifts can dangerously raise serum K⁺.
The two most important causes are renal failure and hypoaldosteronism (especially Type 4 RTA in diabetic nephropathy).
Drugs are the most common iatrogenic cause — ACEi, ARB, MRA, K⁺-sparing diuretics, CNI, NSAIDs, trimethoprim, heparin, digoxin.
DKA trap: apparent hyperkalaemia from transcellular shift, but total body K⁺ is depleted. Treating DKA can unmask severe hypokalaemia.
Always exclude pseudohyperkalaemia (haemolysed sample, thrombocytosis, leukocytosis) before treating.
ECG progression: Peaked T → PR prolongation / flat P → Wide QRS → Loss of P → Sine wave → VF/Asystole. But this progression is not always orderly.
Rate of rise matters: acute rise is more dangerous than chronic elevation at the same K⁺ level.
Symptoms are unreliable — many patients are asymptomatic until cardiac arrest. Muscle weakness typically occurs only when K⁺ > 8 mmol/L.
TTKG < 6 in hyperkalaemia = inappropriate renal response → think hypoaldosteronism or CCD dysfunction.

Active Recall - Hyperkalaemia (Definition to Clinical Features)

^[1] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf (Hyperkalemia section, pp. 29–30) ^[2] Senior notes: Ryan Ho Chemical Path.pdf (pp. 16, Potassium section) ^[3] Lecture slides: GC 034. Chronic Kidney Disease and its Complications.pdf ^[4] Senior notes: Block A - Nephrology Interactive Tutorial.pdf (p. 4, Case P2 — diabetic nephropathy and Type 4 RTA) ^[5] Senior notes: Block A - Drugs and the Kidney.pdf (p. 6, RAAS blockade and hyperkalaemia) ^[6] Senior notes: Ryan Ho Neurology.pdf (p. 194, Hyperkalemic periodic paralysis) ^[7] Lecture slides: GC 044. Electrolyte and Acid-Base Disorders.pdf ^[8] Lecture slides: Chemical Pathology Seminar_Potassium.pdf ^[9] Lecture slides: MBBS IV Electrolytes_2024.pdf ^[10] Senior notes: Ryan Ho Critical Care.pdf (p. 25, AKI section) ^[11] Senior notes: Ryan Ho Cardiology.pdf (p. 83, Causes of arrhythmia) ^[12] Senior notes: Ryan Ho Endocrine.pdf (p. 29, TPP and rebound hyperkalaemia)

Differential Diagnosis of Hyperkalaemia

When you encounter a raised serum K⁺, the clinical task is not simply to treat it but to work out why it is elevated — because the underlying cause determines definitive management and recurrence prevention. The differential diagnosis is approached in a structured, mechanism-based fashion.

Before diving into specific diagnoses, always ask three sequential questions:

Is it real? → Exclude pseudohyperkalaemia first.
Where is the K⁺ coming from? → Increased input (shift vs. tissue destruction vs. dietary) or decreased output (renal failure vs. hypoaldosteronism vs. drugs)?
Is there a treatable/reversible cause? → Drugs, volume depletion, acidosis, obstruction?

"History, diet, drug history (ACEi, ARB, K⁺ sparing diuretics, CNI); repeating [K⁺] if no apparent cause; physical examination (volume depletion); renal function test; TTKG" ^[1]

2. Structured Differential Diagnosis

The differentials are best organised by mechanism, because this is how you think through the problem at the bedside. Each category is explained from first principles.

This is listed first because you must always exclude it before initiating treatment. The K⁺ is genuinely normal inside the patient; it only appears high in the blood tube.

Cause	Mechanism / Why It Happens
Haemolysed specimen	Forceful blood taking (small needle, prolonged tourniquet, vigorous aspiration) → RBCs rupture in vitro → intracellular K⁺ leaks into the sample ^[1]^[2]
Thrombocytosis (platelet count > 500 × 10⁹/L)	Platelets release K⁺ during the clotting process inside a serum (clotted) tube. The more platelets, the more K⁺ released. Send a plasma (heparinised) tube instead to avoid this. ^[2]^[3]
Leukocytosis (WBC > 70 × 10⁹/L, e.g. leukaemia)	Fragile leukaemic white cells lyse easily in the sample tube → K⁺ release ^[2]^[3]
EDTA contamination	EDTA anticoagulant tubes contain K-EDTA salt. If blood from an EDTA tube contaminates the biochemistry sample, the K⁺ is falsely elevated (also causes falsely low Ca²⁺, Mg²⁺, Zn²⁺) ^[3]
Delayed sample processing / aged sample	K⁺ slowly leaks from cells over time at room temperature ^[3]
Prolonged fist clenching	Local K⁺ release from forearm muscles during venepuncture

High Yield — Pseudohyperkalaemia

"Repeating [K⁺] if no apparent cause of the hyperkalemia is found — e.g. pseudohyperkalemia, hemolysis with forceful blood taking" ^[1]. If K⁺ is unexpectedly elevated with no ECG changes and no clinical explanation, repeat the sample with a free-flowing draw. For patients with markedly elevated platelets or WBC, always request a plasma (heparin tube) K⁺ level.

Chemical pathology lecture: "Hyperkalemia → diagnostic pathway → have to first confirm genuine hyperkalemia" ^[4]

2.2 Increased K⁺ Input into the ECF

In these conditions, total body K⁺ may be normal or even depleted — the K⁺ is merely shifting compartments. This distinction is critical because treatment must address the shift (not simply remove K⁺ from the body).

Differential	Mechanism (First Principles)	Key Clinical Clues
DKA / Insulin deficiency	Insulin normally drives Na⁺/K⁺-ATPase → K⁺ into cells. In insulin deficiency, this pump is understimulated → K⁺ stays in ECF. Additionally, hyperosmolality from hyperglycaemia causes osmotic water (and K⁺) movement out of cells. DKA leads to hyperkalemia primarily due to insulin deficiency and hyperosmolality rather than acidaemia alone ^[3]	Polyuria, polydipsia, Kussmaul breathing, fruity breath, high glucose, anion-gap metabolic acidosis
Metabolic acidosis (mineral/non-AG)	H⁺ enters cells to be buffered → K⁺ exits to maintain electroneutrality (H⁺/K⁺ exchange). Mineral (non-anion-gap) acidosis causes more K⁺ shift than organic acidosis ^[2]	Raised Cl⁻, low HCO₃⁻, normal anion gap
Digitalis (digoxin) overdose	Directly inhibits Na⁺/K⁺-ATPase → K⁺ cannot re-enter cells → accumulates in ECF. Risk factors: elderly, hypothyroidism, hypokalaemia (paradoxically increases digoxin toxicity binding) ^[2]^[3]	Nausea, visual disturbances (yellow halos), bradycardia or arrhythmia, characteristic "reverse tick" ST depression on ECG
β-blockers	Block β₂-adrenergic stimulation of Na⁺/K⁺-ATPase → reduced cellular K⁺ uptake. Beta-blockers reduce cellular uptake of potassium and can directly block renin release → resultant hyperK ^[5]	Usually mild (0.5 mmol/L rise); medication history
Succinylcholine	Depolarising neuromuscular blocker → opens ACh receptor channels → massive K⁺ efflux from muscle. Especially dangerous in burns, denervation, prolonged immobility (upregulated extrajunctional receptors)	Recent anaesthetic / ICU setting
Hyperkalemic periodic paralysis	Rare, AD inheritance (SCN4A mutation) → defective Na⁺ channel inactivation → sustained depolarisation → K⁺ efflux. Triggers: exercise, fasting, cold, anaesthesia, K⁺ ingestion ^[6]^[3]	Childhood onset, episodic weakness with myotonia between attacks, mild hyperK during episodes, family history
Hyperosmolality (e.g., hyperglycaemia, mannitol)	Water drags K⁺ out of cells (solvent drag) as it follows the osmotic gradient from ICF to ECF	High serum osmolality, high glucose

Classic Exam Trap — DKA

"DKA results in osmotic diuresis → depletion of body's K reserve. Apparent hyperK only a result of mobilization of intracellular K. Normalization of ketone levels may result in hypokalaemia → must monitor K level" ^[2]. Never be falsely reassured by a "normal" or elevated K⁺ on admission in DKA — total body K⁺ is depleted, and correction will unmask severe hypokalaemia.

These conditions involve actual cellular death with release of the vast intracellular K⁺ pool (remember, intracellular [K⁺] ≈ 140 mmol/L, so even modest cell destruction releases a lot of K⁺).

Differential	Mechanism	Key Clinical Clues / Accompanying Lab Features
Rhabdomyolysis	Skeletal muscle necrosis → release of K⁺, CK, myoglobin, PO₄³⁻, uric acid, LDH ^[2]	Dark ("Coca-Cola") urine, muscle pain, massively elevated CK (often > 10,000 U/L), AKI from myoglobin cast nephropathy
Tumour lysis syndrome (TLS)	Rapid tumour cell turnover after chemotherapy → release of intracellular contents. Accompanied by: high phosphate, AST, LDH, uric acid; low calcium (due to ↑PO₄³⁻ binding Ca²⁺) ^[2]	Recent chemotherapy for high-tumour-burden malignancy (e.g., Burkitt lymphoma, ALL, high-grade NHL), hyperuricaemia, hyperphosphataemia, hypocalcaemia
Haemolysis (in vivo)	RBC destruction → release of intracellular contents. ↑PO₄, K, CK, AST, LDH, uric acid, Mg; ↓ALP, amylase, GGT ^[2]	Jaundice, dark urine, anaemia, elevated LDH, low haptoglobin, raised unconjugated bilirubin
Burns / trauma / crush injury	Direct cell membrane disruption → K⁺ release	Clinical history, elevated CK
Massive blood transfusion	Stored RBCs progressively leak K⁺ (older units have higher K⁺ content in the storage medium)	Transfusion setting; usually requires large volume (> 6–10 units)

Differential	Mechanism	Notes
Oral K⁺ supplements (Slow-K, KCl)	Direct exogenous K⁺ load	Usually only significant if renal excretion is simultaneously impaired
IV K⁺ infusion (too fast or too concentrated)	Direct parenteral K⁺ load	Iatrogenic — check infusion rate (should not exceed 20 mmol/h peripherally or 40 mmol/h centrally with monitoring)
K⁺-containing salt substitutes	These use KCl instead of NaCl	Common in Hong Kong among hypertensive patients advised to reduce salt — ask specifically!
Diet (bananas, oranges, potatoes, dried fruits, coconut water)	High K⁺ content	Only clinically relevant in CKD or concurrent drug-impaired excretion

2.3 Decreased K⁺ Output from the ECF (Impaired Renal Excretion)

This is the most important and most common category of sustained, clinically significant hyperkalaemia. The kidney normally excretes 90% of the daily K⁺ load, so any impairment in renal K⁺ handling is devastating.

Differential	Mechanism	Notes
CKD (especially stages 4–5, GFR < 15–20 mL/min)	Fewer functioning nephrons → reduced CCD K⁺ secretory capacity. Also often compounded by metabolic acidosis and concurrent use of RAAS blockade	Diabetic nephropathy is the most common cause of renal impairment (~51% in HK) ^[7]; these patients are especially vulnerable
AKI (any cause — pre-renal, renal, post-renal)	Sudden reduction in GFR → acute inability to excrete K⁺. Especially dangerous in oliguric/anuric AKI	"If patient is anuric, potential for hyperkalemia" ^[8]; common in hospital — check RFT
Obstructive uropathy (bilateral or in a solitary kidney)	Post-renal obstruction → reduced urine flow → impaired K⁺ washout from CCD	BPH, bladder tumour, bilateral ureteric stones, retroperitoneal fibrosis ^[9]

Aldosterone is the master regulator of renal K⁺ secretion. Any disruption in the renin → angiotensin II → aldosterone → ENaC/ROMK axis will impair K⁺ excretion.

Differential	Mechanism (From First Principles)	Key Clues
Type 4 RTA (hyporeninemic hypoaldosteronism)	Most common cause in adults is diabetic nephropathy → vascular hyalinosis destroys JG apparatus → ↓ renin → ↓ AngII → ↓ aldosterone → impaired K⁺ and H⁺ secretion in CCD ^[7]^[10]	Long-standing diabetes, CKD, hyperchloraemic (non-AG) metabolic acidosis, mild-moderate hyperkalaemia
Addison's disease (primary adrenal insufficiency)	Autoimmune or infectious destruction of the entire adrenal cortex → ↓ aldosterone + ↓ cortisol	Fatigue, weight loss, hyperpigmentation (↑ACTH → ↑MSH), salt craving, postural hypotension, hyponatraemia + hyperkalaemia
Congenital adrenal hyperplasia (21-hydroxylase deficiency — salt-wasting form)	↓ aldosterone synthesis (enzymatic block)	Neonatal salt-wasting crisis, ambiguous genitalia (female), hyperkalaemia
Heparin / LMWH	Directly inhibits aldosterone synthase (CYP11B2) in zona glomerulosa	Post-operative / hospitalised patients on heparin prophylaxis
ACEi / ARB	ACEi blocks ACE → ↓AngII → ↓ aldosterone. ARB blocks AT1 receptor → same downstream effect. "Blocking aldosterone, more potassium retention" ^[10]	Very common in HK (used for HT, HF, DKD); usually mild hyperkalaemia
Aldosterone antagonist / MRA (spironolactone, eplerenone)	Directly block mineralocorticoid receptor in CCD → ENaC not activated → Na⁺ not reabsorbed → K⁺ not secreted ^[10]	Used in HF, resistant HT, Conn's syndrome
Renin inhibitor (aliskiren)	Blocks renin directly → ↓AngII → ↓ aldosterone ^[10]	Less commonly used
Calcineurin inhibitors (cyclosporin, tacrolimus)	Inhibit ROMK channels in CCD + reduce aldosterone sensitivity → impaired K⁺ secretion ^[1]	Post-transplant patients
NSAIDs	Inhibit COX → ↓ prostaglandin-mediated renin release → ↓ renin → ↓ AngII → ↓ aldosterone. Also reduce GFR by blocking afferent arteriolar vasodilation	Very common OTC use; especially dangerous in CKD patients already on ACEi/ARB
Trimethoprim / Pentamidine	Block ENaC directly (amiloride-like effect) → impaired Na⁺ reabsorption → impaired K⁺ secretion	Trimethoprim used commonly for UTI (Bactrim); dose-related effect
Finerenone (non-steroidal MRA)	Blocks MR but molecular structure permits much more targeted action → hyperkalemia side effect much lower than conventional MRAs (can combine with ACEi/ARB) ^[7]	Newer agent for diabetic kidney disease; lower risk than spironolactone but still present

High Yield — The 'Triple Whammy'

The combination of ACEi/ARB + NSAID + diuretic (or ACEi/ARB + MRA + any volume depletion) is sometimes called the "triple whammy" — it dramatically increases the risk of both AKI and hyperkalaemia. In Hong Kong, where RAAS blockade is widely used and NSAIDs are readily available OTC, this combination is a frequent cause of hospital admissions with dangerous hyperkalaemia.

"Remember that these drugs (RAAS blockers) are beneficial, so do not stop them when there is just mild hyperkalemia → stopping them would remove all renoprotective and cardioprotective effects, so decide on a case-by-case basis. E.g. prescribe loop diuretics, low K diet" ^[10]

Differential	Mechanism	Notes
Severe heart failure	↓ effective circulating volume → neurohormonal activation → avid proximal Na⁺ reabsorption → less Na⁺ reaches CCD → less to exchange for K⁺	Often compounded by ACEi/ARB + MRA use
Cirrhosis	Same mechanism (↓ effective circulating volume)	Usually combined with diuretic-induced electrolyte disturbance
Severe volume depletion	↓ renal perfusion + avid proximal reabsorption → reduced distal flow	Dehydration, haemorrhage

Differential	Mechanism	Notes
Pseudohypoaldosteronism type 1	Genetic loss-of-function of ENaC or MR → aldosterone resistance	Neonatal salt wasting, high aldosterone levels
Gordon syndrome (pseudohypoaldosteronism type 2 / FHHt)	Gain-of-function WNK kinase mutation → ↑ NCC activity in DCT → excessive Na⁺ reabsorbed in DCT → less Na⁺ delivered to CCD → less K⁺ secreted. Also causes Cl⁻-dependent hypertension	Hyperkalaemia + hypertension + metabolic acidosis; responds to thiazides
Obstructive uropathy (chronic)	Structural damage to CCD epithelium → impaired K⁺ secretion	Bilateral obstruction
Sickle cell nephropathy	Medullary ischaemia → CCD damage	Known sickle cell disease
SLE nephritis / Amyloidosis	CCD infiltration and dysfunction	Features of underlying disease

The following flowchart represents the systematic approach to narrowing down the cause of hyperkalaemia:

4. Key Differentiating Features — High-Yield Comparison Tables

Feature	Renal Failure	Hypoaldosteronism
GFR	Reduced (Cr elevated)	May be normal or mildly reduced
TTKG	May be low (fewer nephrons)	< 6 (inappropriate renal response) ^[1]
Acid-base	AG metabolic acidosis (uraemic acids) in advanced CKD; may be non-AG in early CKD	Non-AG (hyperchloraemic) metabolic acidosis
Other electrolytes	↑ PO₄, ↑ urea, ↓ Ca²⁺	Usually isolated K⁺ + HCO₃⁻ disturbance
Common cause in HK	Diabetic nephropathy, IgA nephropathy	Type 4 RTA from diabetic nephropathy ^[7]

Feature	DKA	True K⁺ Excess (e.g., CKD)
Total body K⁺	Depleted (osmotic diuresis) ^[2]	Normal or elevated
Mechanism	Transcellular shift (insulin deficiency + acidosis + hyperosmolality)	Impaired excretion
Response to insulin	K⁺ drops (may cause dangerous hypokalaemia)	K⁺ drops transiently (shift effect only)
Risk	Hypokalaemia during treatment	Persistent hyperkalaemia

Feature	Addison's Disease	Type 4 RTA
Renin	High (↓ aldosterone → no negative feedback)	Low (JG apparatus destroyed) ^[7]
Aldosterone	Low	Low
Cortisol	Low	Normal
Clinical features	Hyperpigmentation, fatigue, weight loss, postural hypotension	Usually diabetic patient, mild CKD
Na⁺	Low (no aldosterone → Na⁺ wasting)	Usually normal

Lab marker	Rhabdomyolysis	Tumour Lysis Syndrome	In-Vivo Haemolysis
CK	Massively elevated ( > 10,000 U/L)	May be mildly elevated	Mildly elevated
LDH	Elevated	Markedly elevated	Elevated
Uric acid	Elevated	Markedly elevated ^[2]	Elevated
Phosphate	Elevated	Markedly elevated (causes ↓Ca²⁺) ^[2]	Elevated
Calcium	Low (PO₄ binding)	Low ^[2]	Usually normal
Haptoglobin	Normal	Normal	Low (consumed by binding free Hb)
Myoglobin	Elevated (dark urine)	Normal	Free Hb in plasma
Blood film	Normal	Blast cells	Spherocytes, schistocytes, reticulocytosis

This deserves special emphasis because it is the most common modifiable cause of hyperkalaemia in clinical practice, and a frequent exam question.

Drug Class	Mechanism	Lecture Reference
ACEi (e.g., ramipril, perindopril)	Blocks ACE → ↓AngII → ↓ aldosterone → K⁺ retention	^[10]
ARB (e.g., losartan, valsartan)	Blocks AT1 receptor → ↓ aldosterone effect	^[10]
MRA (spironolactone, eplerenone)	Blocks MR in CCD → ENaC not activated → K⁺ not secreted	^[10]
Renin inhibitor (aliskiren)	Blocks renin → ↓ AngII → ↓ aldosterone	^[10]
K⁺-sparing diuretics (amiloride, triamterene)	Block ENaC directly → impaired Na⁺/K⁺ exchange	^[1]
CNI (cyclosporin, tacrolimus)	Inhibit ROMK + reduce aldosterone sensitivity	^[1]
NSAIDs	↓ PG-mediated renin release + ↓ afferent arteriolar vasodilation → ↓ GFR + ↓ aldosterone	^[10]
Trimethoprim	ENaC blocker (amiloride-like)	^[1]
Heparin / LMWH	Inhibit aldosterone synthase	—
Digoxin (in overdose)	Inhibits Na⁺/K⁺-ATPase → K⁺ stays extracellular	^[2]^[3]
β-blockers	↓ β₂-mediated cellular K⁺ uptake + ↓ renin release	^[5]

Exam Approach — Systematic Drug Review for Hyperkalaemia

When facing a hyperkalaemia question in an exam, go through each drug class systematically using the renin → AngII → aldosterone → ENaC/ROMK axis and the Na⁺/K⁺-ATPase pump. Every drug that disrupts any part of either system can cause hyperkalaemia. This two-axis mental model covers virtually every drug-induced cause.

Population	Most Likely Differentials	Why?
Elderly diabetic on ACEi + spironolactone	Type 4 RTA + drug-induced (RAAS blockade) ^[7]^[10]	High prevalence of diabetic nephropathy in HK; standard HF/DKD therapy includes dual RAAS blockade
Post-operative patient	AKI (pre-renal from hypovolaemia), succinylcholine (if used during anaesthesia), heparin, massive blood transfusion, rhabdomyolysis (prolonged surgery)	Multiple simultaneous insults
Oncology patient post-chemotherapy	Tumour lysis syndrome ^[2]	Especially high-grade lymphomas, leukaemias
Young patient with episodic weakness	Hyperkalemic periodic paralysis (SCN4A) ^[6] or secondary causes (renal, adrenal)	Family history, myotonia between attacks
Patient with hyperpigmentation and hypotension	Addison's disease	Autoimmune adrenalitis → ↓ cortisol + ↓ aldosterone
CKD patient started on Bactrim for UTI	Trimethoprim-induced (ENaC blockade)	Common clinical scenario; dose-dependent
Transplant patient	CNI-induced (cyclosporin/tacrolimus) ^[1]	Standard immunosuppression post-transplant

Clinical Clue	Points Toward
Medication list (most important!)	Drug-induced (RAAS blockade, NSAIDs, CNI, trimethoprim, digoxin, β-blockers, heparin)
Elevated creatinine	Renal failure (AKI or CKD)
Acidosis (low HCO₃⁻)	DKA, Type 4 RTA, uraemic acidosis, lactic acidosis
High CK	Rhabdomyolysis
High LDH + uric acid + PO₄ + low Ca²⁺	Tumour lysis syndrome
Low LDH/haptoglobin + raised bilirubin	Haemolysis
Hyperpigmentation, postural hypotension, hyponatraemia	Addison's disease
Long-standing diabetes with CKD	Type 4 RTA (hyporeninemic hypoaldosteronism) ^[7]
TTKG < 6	Inappropriate renal K⁺ handling → hypoaldosteronism or CCD dysfunction ^[1]
Episodic weakness + myotonia + family history	Hyperkalemic periodic paralysis
No clinical explanation + no ECG changes	Pseudohyperkalaemia → repeat sample

High Yield Summary — Differential Diagnosis of Hyperkalaemia

Always exclude pseudohyperkalaemia first — haemolysed sample, thrombocytosis, leukocytosis, EDTA contamination. Repeat sample if in doubt.
Three mechanistic categories: Increased input (shift, tissue destruction, dietary), decreased output (renal failure, hypoaldosteronism, drugs), and pseudohyperkalaemia.
Renal failure and hypoaldosteronism are the two most important causes of sustained hyperkalaemia.
Drug-induced hyperkalaemia is the most common modifiable cause — think ACEi/ARB/MRA/NSAIDs/CNI/trimethoprim/heparin/digoxin/β-blockers.
DKA = apparent hyperkalaemia with total body K⁺ depletion — treating DKA unmasks dangerous hypokalaemia.
Tissue destruction triad to recognise: Rhabdomyolysis (↑↑CK), TLS (↑LDH + ↑uric acid + ↑PO₄ + ↓Ca²⁺), Haemolysis (↓haptoglobin + ↑LDH + ↑unconjugated bilirubin).
Type 4 RTA (diabetic nephropathy → JG destruction → ↓renin → ↓aldosterone) is the most common cause of hyporeninemic hypoaldosteronism in adults — extremely important in HK.
TTKG < 6 in hyperkalaemia = inappropriate renal response → hypoaldosteronism or CCD dysfunction.
Triple whammy (ACEi/ARB + NSAID + diuretic/volume depletion) is a common and dangerous combination.
Use the two-axis model: renin-AngII-aldosterone-ENaC/ROMK axis (external balance) + Na⁺/K⁺-ATPase axis (internal balance) to systematically identify the cause.

Active Recall - Differential Diagnosis of Hyperkalaemia

References

^[1] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf (Hyperkalemia section, pp. 29–30) ^[2] Senior notes: Ryan Ho Chemical Path.pdf (p. 16, Potassium section) ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (pp. 50–52, Hyperkalemia section) ^[4] Senior notes: Chemical Pathology Data interpretation.pdf (Case 2 — Hyperkalemia diagnostic pathway) ^[5] Senior notes: Block A - I have fluctuating BP_ cushing syndrome; adrenal diseases and tumours; other endocrine tumours.pdf (p. 8, beta-blockers and K⁺) ^[6] Senior notes: Ryan Ho Neurology.pdf (p. 194, Hyperkalemic periodic paralysis) ^[7] Senior notes: Block A - Nephrology Interactive Tutorial.pdf (p. 4, diabetic nephropathy and Type 4 RTA) ^[8] Senior notes: Block A - Polyuria and polydipsia_ glucose metabolism; diabetes mellitus; diabetic ketoacidosis.pdf (p. 13, DKA treatment) ^[9] Senior notes: Ryan Ho Critical Care.pdf (p. 25, AKI and post-renal causes) ^[10] Senior notes: Block A - Drugs and the Kidney.pdf (p. 6, RAAS blockade and hyperkalaemia)

Diagnostic Criteria, Algorithm & Investigations for Hyperkalaemia

Unlike many conditions, hyperkalaemia does not have a formal multi-criterion "diagnostic checklist" (like the Jones criteria for rheumatic fever or the KDIGO criteria for AKI). The diagnosis is fundamentally biochemical — it is made by a serum or plasma potassium concentration above the reference range.

Parameter	Threshold	Why the Difference?
Plasma K⁺ > 5.0 mmol/L	Measured in a heparinised (plasma) tube where blood does not clot	Plasma includes clotting proteins and is obtained by addition of anticoagulants followed by centrifugation ^[14]
Serum K⁺ > 5.5 mmol/L	Measured in a clotted (serum) tube	Serum is prepared by allowing blood to clot before removing blood cells and therefore contains ↑[K⁺] due to ↑release from platelets during clotting ^[14]

The 0.5 mmol/L difference between plasma and serum thresholds exists because platelets release K⁺ during the in-vitro clotting process. This is why serum K⁺ is always slightly higher than plasma K⁺ from the same patient. In patients with thrombocytosis, this difference can be dramatic — and this is the basis of pseudohyperkalaemia.

High Yield — Plasma vs. Serum K⁺

Plasma K⁺ > 5.0 mmol/L = hyperkalaemia. Serum K⁺ > 5.5 mmol/L = hyperkalaemia. The higher serum threshold accounts for K⁺ released from platelets during clotting. If a patient has thrombocytosis or leukocytosis, always use a plasma (heparin tube) sample to get the true K⁺ ^[14]^[3].

Severity Grading (Determines Urgency of Response)

Severity	Serum K⁺	Clinical Implication
Mild	< 5.5 mmol/L	Moderate — investigate and monitor ^[14]
Moderate	5.5–6.4 mmol/L	ECG changes may begin; requires treatment
Severe	> 6.5 mmol/L	Severe — perform ECG urgently; treat immediately ^[14]

"Cardiac arrhythmia may occur with [K⁺] > 6.0. ECG: peaked T, widening of QRS, loss of P, sine wave, asystole. Higher than 6, start worrying" ^[1]

The critical additional criterion for emergency treatment is not just the K⁺ level but the presence of ECG changes, because:

A patient with K⁺ of 6.8 mmol/L and a normal ECG may be safely treated with non-emergency measures.
A patient with K⁺ of 6.2 mmol/L and a widened QRS is a medical emergency requiring immediate IV calcium.

The rate of rise matters — chronic hyperkalaemia is more tolerable than acute rises ^[1]. A CKD patient chronically at 6.0 may have no ECG changes, whereas a patient who rises acutely from 4.0 to 6.0 may have dangerous peaked T waves.

The approach to diagnosing hyperkalaemia follows a logical stepwise pathway. Think of it as answering five questions in sequence:

Step 1: Is it real? → Exclude pseudohyperkalaemia Step 2: Is it dangerous right now? → ECG Step 3: What is the renal function? → RFT (creatinine, urea, eGFR) Step 4: Is it a shift problem or an excretion problem? → ABG/VBG, glucose, CK, drug history Step 5: If excretion problem — where in the aldosterone axis? → TTKG, renin, aldosterone

Approach: (1) Rule out factitious ↑[K⁺] — most common cause — repeat sample if query. (2) Decide on severity. (3) Further investigations — perform ECG if > 6.5 mmol/L, review test profile for RF and DKA, review drug Hx especially K-sparing diuretics and oral intake. Note that samples (urine K ± other blood) should be saved before Tx ^[14]

"Name 5 methods of obtaining a diagnosis of hyperkalemia: (1) History, diet, drug history — ACEi, ARB, K⁺ sparing diuretics, CNI. (2) Repeating [K⁺] if no apparent cause — e.g. pseudohyperkalemia, hemolysis with forceful blood taking. (3) Physical examination — volume depletion. (4) Renal function test. (5) TTKG < 6 → indicates an inappropriate renal response to hyperkalemia" ^[1]

Detailed Diagnostic Approach — Expanded from Senior Notes [15]

Step-by-step approach (from Ryan Ho Urogenital):

Obtain ECG: urgent Tx if risk of fatal arrhythmia ^[15]
Exclude pseudohyperK: commonest cause of hyperK ^[15]
- Double check: especially if normal RFT (renal failure is the commonest cause of true hyperK) ^[15]
- Whole blood sample? (released from RBCs)
- Serum sample? (released from PLT during clotting)
- EDTA plasma sample? (contains K)
- Haemolyzed sample? (released from blood cells)
- Drip arm contamination?
- Recheck serum [K] if in doubt ^[15]
Review drug Hx: K supplement, NSAID, ACEi/ARB, K-sparing diuretics ^[15]
Ix: repeat RFT, ABG, ECG ^[15]
Consider increased intake: rarely the cause unless acute consumption of very large K⁺ load ^[15]
Consider redistribution: usually presents with acute transient hyperK ^[15]
- Acute severe acidosis: DKA, renal failure, other acidosis
- Tissue trauma: trauma, burns, rhabdomyolysis, tumour-lysis syndrome — often a/w ↑PO₄, AST, LDH, urate with ↓Ca
- Haemolysis, digitalis, β-blockers ^[15]
Consider impaired excretion: MAJOR cause of persistent hyperK ^[15]
- Renal failure: most important cause, easily identified by serum creatinine
- Hypoaldosteronism is usually suspected if serum creatinine is normal ^[15]
  - ↓renin ↓Ald → hyporeninemic hypoaldosteronism (DM-related, NSAID-related)
  - ↑renin ↓Ald → hyperreninemic hypoaldosteronism (ACEi-related, adrenal insufficiency, 21-hydroxylase deficiency)
  - ↑renin ↑Ald → aldosterone resistance (K⁺-sparing diuretics, trimethoprim-related, tubulointerstitial disorder, pseudohypoaldosteronism) ^[15]

High Yield — Renin/Aldosterone Pattern for Localisation

This renin-aldosterone pattern is extremely high-yield for exams because it localises the lesion along the RAAS axis:

↓ Renin, ↓ Aldosterone → Problem is at the JG apparatus (destroyed → can't make renin). Classic: Type 4 RTA in diabetic nephropathy, NSAIDs.
↑ Renin, ↓ Aldosterone → Renin is high (trying to stimulate aldosterone) but adrenal gland can't respond. Classic: Addison's disease, ACEi/ARB (blocks AngII → adrenal gets no signal), 21-hydroxylase deficiency.
↑ Renin, ↑ Aldosterone → Both are high but the CCD is resistant. Classic: K⁺-sparing diuretics, trimethoprim, pseudohypoaldosteronism.

4. Investigation Modalities — Detailed with Key Findings & Interpretation

4.1 Bedside Investigations

Why? The ECG tells you whether the heart is in immediate danger. It is the single investigation that determines whether you are in "emergency" or "non-emergency" management mode. You do not need to wait for confirmation of the K⁺ level to act on ECG findings.

ECG Finding	Approximate K⁺ Level	Interpretation / Mechanism
Peaked (tall, narrow, tented) T waves	5.5–6.5 mmol/L	Accelerated repolarisation — increased K⁺ conductance through IKr channels during phase 3 of the cardiac action potential ^[1]^[14]
Prolonged PR interval	6.0–7.0 mmol/L	Slowed atrial conduction — depolarised RMP → Na⁺ channel inactivation → slower phase 0 upstroke in atrial myocytes
Flattened / absent P waves	7.0–8.0 mmol/L	Atrial standstill — complete failure of atrial conduction
Widened QRS	7.0–8.0 mmol/L	Slowed ventricular conduction — same Na⁺ channel inactivation mechanism in ventricular myocardium
Sine wave pattern	> 8.0 mmol/L	QRS merges with T wave — pre-terminal; impending VF or asystole
VF / Asystole	> 9–10 mmol/L	Complete loss of organised electrical activity

"ECG changes of hyperK: 6–7 mmol/L (tall, peaked T waves), 8–10 mmol/L (aberrant QRS complexes), 11 mmol/L (fusion of QRS and T waves), 10–12 mmol/L (ventricular fibrillation)" ^[14]

Critical Clinical Point

The ECG progression is not always orderly. Some patients skip from peaked T waves directly to VF. Never use the ECG alone to "rule out" dangerous hyperkalaemia — treat based on the K⁺ level AND ECG together. Conversely, if ECG changes are present but you haven't received the lab result yet, treat empirically as hyperkalaemia while awaiting confirmation.

Additional ECG findings to look for simultaneously:

ST depression / T-wave inversion in leads other than the classical hyperkalaemia pattern → consider concurrent ischaemia
Bradycardia → may occur with severe hyperkalaemia (sinus bradycardia or high-degree AV block)
"Pseudo-STEMI" pattern → severe hyperkalaemia can mimic ST elevation, especially in V1-V3. Don't rush to the cath lab without checking K⁺!

Assessment	What to Look For	Why
Blood pressure	Hypotension (Addison's, severe arrhythmia, shock) or hypertension (CKD, Gordon syndrome)	Volume status and haemodynamic stability
Heart rate	Bradycardia (severe hyperK), tachycardia (compensatory, DKA)	Arrhythmia assessment
Respiratory rate	Kussmaul breathing (deep, rapid)	Suggests metabolic acidosis (DKA, uraemic acidosis)
JVP, peripheral oedema	Elevated JVP + oedema → fluid overload (CKD, AKI, HF)	Volume status
Skin turgor, mucous membranes	Dehydration → pre-renal AKI, DKA	Volume depletion
Urine output	Oliguria/anuria → AKI, obstructive uropathy	Renal function

Finding	Significance
Blood	Rhabdomyolysis (myoglobin gives false positive for blood on dipstick), haemolysis, glomerulonephritis
Protein	CKD (diabetic nephropathy), glomerulonephritis
Glucose	DKA (glycosuria from hyperglycaemia), Fanconi syndrome (renal glycosuria)
Leucocytes / nitrites	UTI → possible obstructive uropathy

4.2 Blood Investigations

"Renal failure is the most important cause, easily identified by serum creatinine" ^[15]

Component	Normal Range (HK)	Interpretation in Hyperkalaemia
Serum Creatinine	66–106 μmol/L (male)	Elevated → renal failure (AKI or CKD). Note: GFR already reduced by ≥ 50% by the time Cr rises ^[13]
Serum Urea	3.2–7.5 mmol/L	Elevated → renal failure, dehydration (pre-renal), GI bleeding, high-protein diet
eGFR (CKD-EPI equation)	> 90 mL/min/1.73m²	Hyperkalaemia usually becomes significant when GFR < 15–20 mL/min
Na⁺	136–148 mmol/L	Low → Addison's (combined hypoNa + hyperK is classic), SIADH, CKD
Cl⁻	100–110 mmol/L	High Cl⁻ with low HCO₃⁻ → non-anion-gap metabolic acidosis (Type 4 RTA)
HCO₃⁻	22–26 mmol/L	Low → metabolic acidosis. "Relates with hyperkalemia — correct metabolic acidosis may improve the hyperkalemia" ^[10]

Key pattern recognition from Nephrology Data Interpretation ^[11]:

High urea + high creatinine + high ALP (renal osteodystrophy) + hypoalbuminaemia + hyperphosphataemia + low HCO₃⁻ (metabolic acidosis) + hypocalcaemia → CKD ^[11]
Hyperkalaemia in this context may be from renal failure itself, or from Type 4 RTA (if the patient is diabetic), or from ACEi/ARB use ^[11]

Ratio	Suggests
> 100:1	Pre-renal failure — avid urea reabsorption in dehydration (urea is passively reabsorbed, creatinine is not) ^[13]
< 40:1	ATN (intrinsic renal failure) — tubules cannot reabsorb urea ^[13]

Why? Acid-base status is tightly linked to K⁺ homeostasis. This is the investigation that reveals whether acidosis is contributing to the hyperkalaemia.

Parameter	Interpretation
pH	Low → acidosis (drives K⁺ out of cells). High → alkalosis (would be unusual with hyperK)
pCO₂	Low pCO₂ + low HCO₃⁻ → metabolic acidosis with respiratory compensation
HCO₃⁻	Low → metabolic acidosis. Check anion gap to classify
Anion gap	= [Na⁺] − [Cl⁻] − [HCO₃⁻]. Normal ≤ 14 mmol/L
Lactate	Elevated → tissue hypoperfusion (shock), lactic acidosis

Key anion gap interpretation:

High AG metabolic acidosis: DKA (ketoacids), uraemic acidosis (retained acids), lactic acidosis, toxic ingestion
Normal AG (hyperchloraemic) metabolic acidosis: Type 4 RTA (most relevant to hyperkalaemia), diarrhoea, Type 1 RTA, Type 2 RTA

"Diabetes is associated with Type IV RTA — cannot excrete potassium. RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys" ^[11]

Test	Interpretation
Serum glucose	High → DKA/HHS (hyperglycaemia causes osmotic K⁺ shift), pre-existing diabetes
Serum/urine ketones	Positive → DKA (transcellular shift mechanism; total body K⁺ depleted)

Test	Interpretation
CK	Massively elevated (> 10,000 U/L) → rhabdomyolysis (skeletal muscle necrosis releasing K⁺, myoglobin, PO₄³⁻)
Urine myoglobin	Positive → rhabdomyolysis (dark urine, dipstick positive for "blood" without RBCs on microscopy)

"Tissue trauma: often a/w ↑PO₄, AST, LDH, urate with ↓Ca" ^[15]

Test	Tumour Lysis	Rhabdomyolysis	Haemolysis
LDH	↑↑↑	↑	↑↑
Uric acid	↑↑↑	↑	↑
PO₄³⁻	↑↑↑ (binds Ca²⁺ → hypocalcaemia) ^[2]	↑	↑
Ca²⁺	↓↓ (PO₄ precipitation) ^[2]	↓	Normal
AST	↑	↑↑	↑
Haptoglobin	Normal	Normal	↓↓ (consumed binding free Hb)

Test	When to Order
Serum digoxin level	Suspected digoxin toxicity (nausea, visual changes, bradycardia, bidirectional VT)
Serum tacrolimus / cyclosporin level	Transplant patients on CNI

Finding	Significance
Thrombocytosis (platelets > 500 × 10⁹/L)	Pseudohyperkalaemia if serum sample used ^[3]^[14]
Leukocytosis (WBC > 70 × 10⁹/L)	Pseudohyperkalaemia + possible TLS if leukaemia ^[3]^[14]
Normocytic anaemia	CKD (↓ EPO production), haemolysis

4.3 Urine Investigations

TTKG = (Urine K⁺ / Plasma K⁺) × (Plasma Osm / Urine Osm) ^[1]

TTKG Value	Interpretation
> 10	Appropriate renal response — kidneys are excreting K⁺ maximally. Problem is extra-renal (intake, shift, tissue destruction)
< 6	Inappropriate renal response — kidneys are NOT excreting enough K⁺ despite hyperkalaemia. This indicates hypoaldosteronism or CCD dysfunction ^[1]

"TTKG for an adequate response would be very large, as it would mean the kidneys are working hard to excrete more potassium — so if this is low, concerning as it means the kidneys are not excreting potassium" ^[1]

Prerequisites for valid TTKG: Urine osmolality must be > plasma osmolality (i.e., urine is concentrated, confirming ADH activity and intact medullary concentrating ability). If urine is dilute, TTKG is unreliable.

Value	Interpretation
< 20 mmol/L	Pre-renal failure (avid Na⁺ reabsorption due to hypovolaemia) → reduced distal Na⁺ delivery → impaired K⁺ secretion
> 40 mmol/L	Intrinsic renal failure (ATN — tubules cannot reabsorb Na⁺) or adequate Na⁺ delivery (not pre-renal)

FENa = (Urine Na × Plasma Cr) / (Plasma Na × Urine Cr) × 100 ^[13]

FENa	Interpretation
< 1%	Pre-renal failure (intact tubular reabsorption) ^[13]
> 2%	ATN (failed tubular reabsorption) ^[13]

This helps differentiate whether the renal failure contributing to hyperkalaemia is pre-renal (reversible with fluids) or intrinsic (needs renal support).

4.4 Endocrine Investigations (When Hypoaldosteronism Suspected)

Order these when: RFT is relatively normal (or only mildly impaired), TTKG is low, and drug causes have been excluded.

Pattern	Diagnosis	Mechanism
↓ Renin, ↓ Aldosterone	Hyporeninemic hypoaldosteronism (Type 4 RTA)	JG apparatus destroyed (DM) or renin suppressed (NSAIDs) → no renin → no AngII → no aldosterone ^[15]^[7]
↑ Renin, ↓ Aldosterone	Hyperreninemic hypoaldosteronism	Adrenal gland cannot make aldosterone despite high renin/AngII drive. Causes: Addison's, ACEi/ARB, 21-hydroxylase deficiency ^[15]
↑ Renin, ↑ Aldosterone	Aldosterone resistance	CCD is resistant to aldosterone. Causes: K⁺-sparing diuretics (block ENaC/MR), trimethoprim, pseudohypoaldosteronism ^[15]

Step	Detail
Baseline	Measure serum cortisol at 0 min (typically 9 AM)
Stimulation	Give 250 μg IV synthetic ACTH (synacthen/cosyntropin)
Repeat	Measure cortisol at 30 and 60 min
Normal response	Cortisol > 500 nmol/L (or > 18 μg/dL) at 30 or 60 min
Addison's	Cortisol fails to rise adequately → confirms primary adrenal insufficiency

Pattern	Interpretation
Low cortisol + high ACTH	Primary adrenal insufficiency (Addison's)
Low cortisol + low/normal ACTH	Secondary adrenal insufficiency (pituitary)

4.5 Imaging

Finding	Interpretation
Small kidneys bilaterally	CKD (chronic scarring and nephron loss)
Normal-sized kidneys with raised Cr	AKI (or early CKD, diabetic nephropathy, polycystic kidneys, amyloidosis, HIV nephropathy)
Hydronephrosis (dilated pelvicalyceal system)	Obstructive uropathy → post-renal AKI
Increased echogenicity	Chronic parenchymal disease
Medullary nephrocalcinosis	Type 1 RTA, hyperparathyroidism

USG kidneys is essential in any AKI workup to exclude obstruction (which is potentially rapidly reversible).

Used when USG is equivocal or for better delineation of obstruction, stones, or masses.
In the presence of renal impairment, try avoiding a contrast CT to prevent nephrotoxicity ^[16].

Indicated when primary aldosteronism or Addison's disease is suspected.
Look for adrenal atrophy (Addison's), adrenal adenoma (Conn's), bilateral hyperplasia, calcified adrenals (TB, haemorrhage).

Test	When to Order	Interpretation
24-hour urine K⁺	To quantify total daily K⁺ excretion	> 30 mmol/day with hyperK → renal K⁺ wasting is unlikely; < 30 mmol/day → impaired renal excretion
Urine anion gap = [urine Na⁺ + K⁺] − [urine Cl⁻]	Differentiating cause of non-AG metabolic acidosis	Positive UAG → impaired NH₄⁺ excretion (RTA). Negative UAG → appropriate NH₄⁺ excretion (diarrhoea) ^[12]
Aldosterone:Renin Ratio (ARR)	Screening for primary aldosteronism (if hypokalaemia is the presentation, not hyperkalaemia — but important differential context)	ARR > 30 with Ald ≥ 10 → suggestive of primary aldosteronism (90% sens, 90% spec) ^[17]
Genetic testing	Suspected hyperkalemic periodic paralysis	SCN4A mutation
Serum digoxin level	Suspected toxicity	Therapeutic range 0.5–2.0 ng/mL; toxicity > 2.0 ng/mL

Priority	Investigation	Purpose
IMMEDIATE	12-lead ECG	Assess cardiac toxicity — determines emergency vs. non-emergency pathway
IMMEDIATE	Repeat K⁺ (plasma heparin tube if pseudohyperK suspected)	Confirm true hyperkalaemia
URGENT	RFT (Na, K, Cl, urea, Cr, HCO₃⁻, eGFR)	Identify renal failure; check bicarbonate for acidosis
URGENT	VBG/ABG	Acid-base status (metabolic acidosis ↔ hyperkalaemia link)
URGENT	Glucose ± ketones	DKA screen
URGENT	CBC	Exclude thrombocytosis/leukocytosis (pseudohyperK); anaemia (CKD)
DIRECTED	CK, LDH, uric acid, PO₄, Ca²⁺	Tissue destruction panel (rhabdo, TLS, haemolysis)
DIRECTED	Spot urine K⁺, Na⁺, Osm + TTKG	Assess renal K⁺ handling — appropriate vs inappropriate response
DIRECTED	FENa	Pre-renal vs intrinsic AKI
DIRECTED	Plasma renin + aldosterone	Localise defect in RAAS axis
DIRECTED	Drug levels (digoxin, CNI)	Toxicity screen
DIRECTED	USG kidneys	CKD vs AKI, exclude obstruction
SPECIALISED	Short synacthen test	Addison's disease
SPECIALISED	CT/MRI adrenals	Adrenal pathology
SPECIALISED	Genetic testing (SCN4A)	Hyperkalemic periodic paralysis

High Yield Summary — Diagnosis of Hyperkalaemia

Diagnosis is biochemical: Plasma K⁺ > 5.0 or Serum K⁺ > 5.5 mmol/L. The serum threshold is higher because platelets release K⁺ during clotting.
First step: Always exclude pseudohyperkalaemia — repeat sample, use plasma tube if thrombocytosis/leukocytosis.
Most urgent investigation: 12-lead ECG. ECG changes determine emergency vs. non-emergency management.
The five-step approach: (1) Real? (2) Dangerous? (ECG) (3) Renal function? (RFT) (4) Shift or excretion? (ABG, glucose, CK, drugs) (5) Where in the aldosterone axis? (TTKG, renin, aldo)
TTKG < 6 in hyperkalaemia = inappropriate renal response → hypoaldosteronism or CCD dysfunction.
Renin/Aldo patterns: ↓R ↓A = hyporeninemic hypoaldo (Type 4 RTA, NSAIDs); ↑R ↓A = hyperreninemic hypoaldo (Addison's, ACEi); ↑R ↑A = aldo resistance (K-sparing diuretics, trimethoprim).
Tissue destruction triad: ↑PO₄ + ↑LDH + ↑uric acid + ↓Ca²⁺ = tumour lysis; ↑↑CK = rhabdomyolysis; ↓haptoglobin = haemolysis.
Save samples before treatment — urine K⁺ and other bloods should be collected before giving IV insulin/dextrose or other treatments that will alter the K⁺ level.
USG kidneys is essential in any AKI to exclude obstructive uropathy (reversible cause).
FENa < 1% → pre-renal; FENa > 2% → ATN.

Active Recall - Diagnosis & Investigations of Hyperkalaemia

References

^[1] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf (Hyperkalemia section, pp. 29–30) ^[2] Senior notes: Ryan Ho Chemical Path.pdf (p. 16, Potassium section) ^[3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (pp. 50–52, Hyperkalemia section) ^[7] Senior notes: Block A - Nephrology Interactive Tutorial.pdf (p. 4, diabetic nephropathy and Type 4 RTA) ^[10] Senior notes: Block A - Drugs and the Kidney.pdf (p. 6, RAAS blockade and hyperkalaemia) ^[11] Senior notes: Block A – Nephrology Data Interpretation.pdf (pp. 9–10, CKD interpretation and Type 4 RTA) ^[12] Senior notes: Block A - Nephrotology Teaching Clinic RTD.pdf (p. 23–27, urine anion gap and RTA) ^[13] Senior notes: Maksim Medicine Notes.pdf (p. 216, AKI criteria and pre-renal vs ATN table) ^[14] Senior notes: Ryan Ho Chemical Path.pdf (pp. 14, Hyperkalaemia approach and plasma vs serum) ^[15] Senior notes: Ryan Ho Urogenital.pdf (p. 29, Diagnostic approach to hyperkalaemia) ^[16] Senior notes: Block A - Two cases of polyuria and polydipsia.pdf (p. 4, avoiding contrast in renal impairment) ^[17] Senior notes: Ryan Ho Endocrine.pdf (p. 58, ARR screening for primary aldosteronism)

Management of Hyperkalaemia

The management of hyperkalaemia rests on four pillars, applied in a logical sequence. Thinking from first principles, every intervention targets one of three physiological goals:

Protect the heart — Stabilise the cardiac membrane so that the elevated K⁺ does not cause a lethal arrhythmia (buys time, does NOT lower K⁺)
Shift K⁺ into cells — Temporarily redistribute K⁺ from ECF to ICF to rapidly lower serum K⁺ (buys time; total body K⁺ unchanged)
Remove K⁺ from the body — The only definitive way to reduce total body K⁺ (takes longer but is the real fix)
Treat the underlying cause — Prevent recurrence

The urgency with which you apply these pillars depends on whether the situation is an emergency or non-emergency.

High Yield — Management Sequence

Think of the mnemonic C-BIG-K-D for emergency hyperkalaemia management:

C = Calcium (IV) — cardioprotection
B = Bicarbonate (NaHCO₃) — shift
I = Insulin + dextrose — shift
G = Give salbutamol (nebulised β₂-agonist) — shift
K = Kayexalate / K binders — remove
D = Dialysis — remove

Feature	Emergency	Non-Emergency
K⁺ level	K⁺ ≥ 6.5 mmol/L, or rapidly rising ^[9]	K⁺ 5.0–6.4 without ECG changes
ECG changes	Any hyperkalaemic ECG change (peaked T, wide QRS, sine wave)	Normal ECG
Symptoms	Muscle weakness, haemodynamic instability, cardiac arrest	Asymptomatic
Management	IV calcium → shift agents → removal → dialysis if refractory ^[1]	Dietary modification, drug review, oral K⁺ binders, loop diuretics, correct underlying cause

Hyperkalaemia: symptoms (arrhythmia, weakness) usually only when K > 6. Mx: IV Ca, NaHCO₃⁻ infusion, dextrose/insulin drip, PO polysulphonate, dialysis ^[9]

4. Detailed Treatment Modalities

4.1 EMERGENCY MEASURES

"IV calcium → effect seen within minutes. Cardioprotective effects, increase threshold potential. No reduction of serum potassium, buys time. May repeat injection 5 minutes later if effect not seen" ^[1]

Parameter	Detail
Drug	10% Calcium Gluconate (preferred) or 10% Calcium Chloride
Dose	10–30 mL of 10% calcium gluconate IV over 2–5 minutes ^[18]
Onset	Within 1–3 minutes ^[1]
Duration	30–60 minutes
Repeat	May repeat after 5 minutes if ECG changes persist ^[1]
Mechanism	Ca²⁺ raises the cardiac myocyte threshold potential (from approximately −70 mV towards −55 mV), moving it further from the depolarised resting membrane potential. This restores the voltage gap between resting potential and threshold, reducing the risk of spontaneous depolarisation and arrhythmia. Think of it as widening the "safety margin" of excitability.

Why does calcium NOT lower serum K⁺? Because it does not affect K⁺ distribution or excretion at all — it purely modifies the electrical properties of the cardiac membrane. It is purely a temporising measure.

Indication	Contraindication
Any hyperkalaemia with ECG changes	Digoxin toxicity — IV calcium can precipitate fatal arrhythmias in digitalis-intoxicated hearts (calcium potentiates digoxin's effect on Na⁺/K⁺-ATPase). In digoxin toxicity, use digoxin-specific antibody fragments (Digibind/DigiFab) instead
K⁺ ≥ 6.5 even without ECG changes	Hypercalcaemia (relative — if life-threatening hyperK, still give it)
Cardiac arrest from hyperK

Calcium Gluconate vs. Calcium Chloride:

Calcium gluconate is preferred for peripheral IV access because it is less caustic to veins. It contains ~2.2 mmol Ca²⁺ per 10 mL.
Calcium chloride delivers 3× more ionised Ca²⁺ per volume but is extremely irritant — can cause tissue necrosis if extravasated. Reserved for central line administration or cardiac arrest.

High Yield — Digoxin Toxicity Exception

If the patient is on digoxin and has hyperkalaemia from digoxin toxicity, do NOT give IV calcium — it can cause "stone heart" (intractable VF). Instead, use digoxin-specific antibody fragments as the antidote, which will bind free digoxin, restore Na⁺/K⁺-ATPase function, and lower K⁺.

"IV insulin/dextrose → shifting K⁺ into cells. Effect onset within 1 hour, with effect lasting 5–6 hours. 10 units to 3 g glucose (60 mL D50)" ^[1]

Parameter	Detail
Drug	Actrapid (soluble/regular insulin) 10 units IV + 50 mL of 50% dextrose (D50) given simultaneously
Onset	15–30 minutes (some sources say up to 1 hour) ^[1]
Peak effect	30–60 minutes
Duration	5–6 hours ^[1]
Expected K⁺ drop	0.5–1.2 mmol/L
Mechanism	Insulin stimulates the Na⁺/K⁺-ATPase pump on skeletal muscle and hepatocyte membranes → drives K⁺ from ECF into ICF. The dextrose is given to prevent hypoglycaemia (insulin's glucose-lowering effect).

Indication	Contraindication / Caution
Emergency hyperkalaemia (after or concurrent with IV calcium)	Hypoglycaemia — monitor capillary blood glucose (CBG) hourly for 6 hours after administration. If patient is already hypoglycaemic, give more dextrose
Any K⁺ > 6.0 requiring rapid reduction	Avoid dextrose if patient is already severely hyperglycaemic (e.g., DKA with glucose > 14 mmol/L) — give insulin alone and monitor glucose closely

Paediatric protocol: "10% Ca gluconate, DI drip, NaHCO₃, Ventolin in nebulizer, oral resonium C" ^[18]

Important — Insulin-Dextrose in DKA

In DKA, the patient already has insulin deficiency and is being given an insulin infusion as part of DKA management. This insulin itself will shift K⁺ into cells. "If patient is anuric, potential for hyperkalemia → so in these special situations hold off on the potassium for a while, then replenish accordingly with patients on ECG monitoring" ^[8]. Conversely, as insulin works and acidosis corrects, K⁺ may plummet dangerously — monitor K⁺ every 1–2 hours and supplement early.

"NaHCO₃ infusion → shifting K⁺ into cells. Effect seen within 30 minutes, can last for several hours" ^[1]

Parameter	Detail
Drug	8.4% NaHCO₃ (1 mmol/mL) — typically 50–100 mL IV over 15–30 minutes, or as an infusion
Onset	30 minutes ^[1]
Duration	Several hours
Expected K⁺ drop	Variable (0.5–1.0 mmol/L); most effective when concurrent metabolic acidosis exists
Mechanism	Correcting acidosis → H⁺ leaves cells down its concentration gradient → K⁺ enters cells to maintain electroneutrality → serum K⁺ falls. Additionally, bicarbonate itself may have a direct (though debated) stimulatory effect on Na⁺/K⁺-ATPase.

Indication	Contraindication / Caution
Hyperkalaemia with concurrent metabolic acidosis (most effective in this setting)	Hypernatraemia — 1 mmol HCO₃⁻ carries 1 mmol Na⁺, so 200 mmol NaHCO₃ = more than 1 litre of normal saline in Na⁺ load ^[19]
	Fluid overload — significant volume expansion from Na⁺ load ^[19]
	Hypocalcaemia (especially in CKD) — alkalosis decreases ionised Ca²⁺, can precipitate tetany ^[19]
	Paradoxical cerebral acidosis if corrected too rapidly — CO₂ crosses BBB faster than HCO₃⁻ ^[19]
	Pulmonary oedema (volume load)

"Risks of NaHCO₃ therapy: hypernatraemia, induce hypokalaemia (by shifting K into cells, particularly in patients with existing hypokalaemia), decrease ionic calcium, volume expansion, paradoxical cerebral acidosis" ^[19]

NaHCO₃ — Less Effective Without Acidosis

If the patient is NOT acidotic, NaHCO₃ is much less effective at lowering K⁺. In non-acidotic hyperkalaemia, insulin-dextrose and salbutamol are the preferred shift agents. NaHCO₃ should be reserved primarily for patients with concurrent metabolic acidosis.

Parameter	Detail
Drug	Salbutamol 10–20 mg via nebuliser (note: this is 4–8× the standard bronchodilator dose of 2.5–5 mg)
Onset	15–30 minutes
Duration	2–4 hours
Expected K⁺ drop	0.5–1.0 mmol/L (additive with insulin-dextrose)
Mechanism	β₂-adrenergic receptor activation → stimulates Na⁺/K⁺-ATPase via the cAMP/PKA pathway → drives K⁺ into cells. Also stimulates pancreatic insulin secretion (minor contribution).

Indication	Contraindication / Caution
Adjunct to insulin-dextrose in emergency hyperkalaemia	Tachyarrhythmia (β₂-agonists increase heart rate) — use with caution if patient already has significant tachycardia or known arrhythmia
Can be used alone if IV access is delayed	Ischaemic heart disease — increased myocardial O₂ demand
	~40% of patients are "non-responders" to salbutamol — do not rely on it as the sole agent

The high dose (10–20 mg) is necessary because the K⁺-shifting effect requires much higher receptor occupancy than the bronchodilator effect.

"Urgent hemodialysis — most effective in removing K⁺, but takes time to set up" ^[1]

Parameter	Detail
Mechanism	K⁺ is removed from the blood by diffusion down its concentration gradient into a low-K⁺ dialysate across a semipermeable membrane
Onset	Once running, K⁺ drops rapidly (can remove 25–50 mmol/h)
Limitation	Requires vascular access (temporary dialysis catheter), machine setup, staffing — typically takes 30–60 minutes to initiate
Expected K⁺ drop	1.0–1.5 mmol/L per hour of dialysis

Indication	Contraindication / Caution
K⁺ > 6.5 or rapidly rising, refractory to medical therapy ^[9]	Haemodynamic instability — intermittent HD can cause hypotension due to fluid shifts. Consider CRRT (continuous renal replacement therapy) instead for unstable patients ^[18]
Oliguric/anuric AKI (medical measures alone cannot sustain K⁺ removal if the kidneys aren't working)	Difficult vascular access
CKD Stage 5 on dialysis (already has dialysis access)
Concurrent refractory acidosis, fluid overload, uraemia

Dialysis indications for AKI (mnemonic: AEIOU): ^[9]

A = Acidosis (pH < 7.1 refractory to bicarbonate)
E = Electrolyte imbalance (hyperK > 6.5 refractory to medical Rx)
I = Intoxication (drug removal in overdose, e.g., lithium, methanol)
O = Overload (fluid overload refractory to diuretics)
U = Uraemia (features: pericarditis, neuropathy, encephalopathy)

Intermittent HD vs. CRRT:

	Intermittent HD	CRRT
Speed	Rapid removal of toxins — esp useful for emergency situation (severe hyperK, intoxication, TLS) ^[18]	Slower, continuous
Haemodynamic effect	Considerable haemodynamic instability and fluid shifts with hypotension, cerebral oedema ^[18]	Better tolerated haemodynamically
Setting	Can be done in dialysis unit	ICU
Cost	Less expensive	More expensive
Best for	Stable patients needing rapid K⁺/toxin removal	Haemodynamically unstable patients (e.g., septic shock + AKI)

4.2 NON-EMERGENCY MEASURES

These are used for mild-to-moderate hyperkalaemia (K⁺ 5.0–6.4 without ECG changes) and as ongoing management after the emergency phase is stabilised.

"Low K diet" ^[20]

Parameter	Detail
Target	Restrict dietary K⁺ to < 40–60 mmol/day (normal intake ~70–100 mmol/day)
Foods to limit	Bananas, oranges, tomatoes, potatoes, spinach, avocado, dried fruits, coconut water, chocolate, nuts, legumes, salt substitutes (KCl)
Mechanism	Reduces the exogenous K⁺ load that the impaired kidneys must excrete

Particularly important in CKD patients. In Hong Kong, herbal teas and soups (e.g., "老火湯") may contain significant K⁺ from long-cooked vegetables — counsel patients specifically about these.

"Remove underlying cause — remove drugs, volume expansion for depletion" ^[1]

Action	Drugs to Review	Nuance
Stop or reduce	K⁺ supplements, K⁺-sparing diuretics (amiloride, triamterene), trimethoprim	Usually straightforward to stop
Careful risk-benefit analysis	ACEi, ARB, MRA	"Remember that these drugs are beneficial, so do not stop them when there is just mild hyperkalemia → stopping them would remove all renoprotective and cardioprotective effects, so decide on a case-by-case basis. E.g. prescribe loop diuretics, low K diet" ^[10]
Stop if contributing	NSAIDs, CNI (adjust dose/level), heparin
Medication adjustments	"Adjust medication — ACEi/ARB → less aldosterone effect, more sodium dumping and potassium reabsorption" ^[20]	Consider dose reduction rather than cessation if cardio-renal benefit is high

Clinical Pearl — ACEi/ARB and Hyperkalaemia

Mild hyperkalaemia (K⁺ 5.0–5.5) in a patient on ACEi/ARB for diabetic nephropathy or heart failure is extremely common and does NOT automatically mandate stopping the drug. The cardio-renal benefits are enormous. Instead: (1) low K⁺ diet, (2) add a loop diuretic, (3) correct any acidosis with oral NaHCO₃, (4) consider adding a K⁺ binder (Patiromer or Lokelma). Only stop ACEi/ARB if K⁺ is persistently > 6.0 despite optimisation or if there is severe renal deterioration ^[10]^[20].

"Correct metabolic acidosis" ^[1]

Parameter	Detail
Drug	Oral sodium bicarbonate (500 mg – 1 g TDS) for chronic acidosis in CKD
Mechanism	Correcting acidosis reverses the H⁺/K⁺ transcellular shift → K⁺ re-enters cells → serum K⁺ falls
Target	Serum HCO₃⁻ > 22 mmol/L
Caution	Na⁺ load → watch for fluid overload and hypertension

"Relates with hyperkalemia — so if you correct metabolic acidosis may improve the hyperkalemia" ^[10]

"Loop diuretic if not oliguric" ^[1]

Parameter	Detail
Drug	Furosemide 20–80 mg PO or IV (dose depends on renal function — higher doses needed in CKD)
Mechanism	Blocks NKCC2 in the thick ascending limb → increases Na⁺ and fluid delivery to the CCD → more Na⁺ available for reabsorption via ENaC → creates a more negative lumen → drives K⁺ secretion via ROMK. Also increases tubular flow rate → washes away secreted K⁺, maintaining the concentration gradient for continued secretion.
Onset	IV: 5 minutes; PO: 30–60 minutes
Indication	Non-oliguric patients with residual renal function
Contraindication	Oliguric/anuric patients (diuretics cannot work if there is no urine flow) — in these patients, dialysis is needed
Caution	Volume depletion, ototoxicity with high doses, hyponatraemia

"Cation-exchange resin — Na/Ca resin. Oral or enema. E.g. Lokelma, Patiromer" ^[1]

These agents work in the GI tract (primarily the colon) by exchanging K⁺ for another cation (Na⁺ or Ca²⁺), thereby removing K⁺ from the body via faecal excretion.

Drug	Trade Name / Type	Mechanism	Onset	Key Points
Sodium Zirconium Cyclosilicate (SZC)	Lokelma	Inorganic crystal that selectively traps K⁺ in exchange for Na⁺ and H⁺ in the GI tract	~2 hours ^[20]	Faster onset than Patiromer; well tolerated; can cause oedema (Na⁺ load)
Patiromer	Veltassa	Organic polymer that binds K⁺ in exchange for Ca²⁺ in the colon	~4–7 hours ^[20]	No Na⁺ load (exchanges Ca²⁺ instead); may cause hypomagnesaemia; separate from other oral meds by 3 hours (can bind other drugs)
Calcium Resonium (Calcium Polystyrene Sulfonate)	Resonium Calcium	Cation-exchange resin that binds K⁺ in exchange for Ca²⁺ in the colon	4–6 hours (oral); 1–2 hours (rectal/enema)	Older agent; available as oral or enema ^[1]
Sodium Polystyrene Sulfonate (SPS)	Kayexalate / Resonium A	Cation-exchange resin that binds K⁺ in exchange for Na⁺	4–6 hours	Rare but serious side effect: colonic necrosis — especially when given with sorbitol or in post-operative patients ^[20]

"Name 4 potassium lowering drugs: (1) Non-potassium-sparing diuretics, (2) Oral potassium binders — Patiromer onset 4–7 hours, Sodium zirconium cyclosilicate onset 2 hours, Sodium polystyrene sulfonate — colonic necrosis" ^[20]

High Yield — K⁺ Binders Are NOT Emergency Treatment

"Oral potassium binders have onset time in the hours — for long-term control. Acute phase of hyperkalemia just use normal treatment, using intravenous calcium to stabilize the rhythm first. IV calcium gluconate, insulin-dextrose, inhaled beta-2 agonist if patient is still conscious" ^[20]. Do NOT rely on K⁺ binders for emergency management — they are too slow. Use them for chronic management and as maintenance after the acute phase is controlled.

Drug	Advantages	Disadvantages
Lokelma	Fast onset (2h), selective for K⁺, well tolerated	Na⁺ load → may worsen oedema/HT in HF patients
Patiromer	No Na⁺ load (Ca²⁺ exchange), good for HF patients	Slower onset (4–7h), may bind other oral medications, hypoMg
Calcium Resonium	Widely available, cheap, can be given rectally	Less selective, constipation, slower onset
Kayexalate (SPS)	Widely available	Colonic necrosis risk ^[20], Na⁺ load, unpalatable

"Volume expansion for depletion" ^[1]

Parameter	Detail
Fluid	Normal saline (0.9% NaCl)
Mechanism	Restoring intravascular volume → improves renal perfusion → restores GFR → increases tubular flow and distal Na⁺ delivery → enhances K⁺ secretion
Indication	Pre-renal AKI contributing to hyperkalaemia
Caution	Fluid overload in CKD/HF patients — use with monitoring (JVP, lung auscultation, fluid balance chart)

The emergency and non-emergency measures above are all temporising. Definitive management requires identifying and treating the root cause to prevent recurrence.

Underlying Cause	Specific Treatment
DKA	Insulin infusion + IV fluids + K⁺ monitoring (replace K⁺ when < 5.5) ^[8]
Rhabdomyolysis	Aggressive IV normal saline (target UO 200–300 mL/h), alkalinisation of urine (NaHCO₃), treat compartment syndrome if present
Tumour lysis syndrome	Aggressive hydration 3 L/m²/day, rasburicase (recombinant urate oxidase), K⁺ correction + ECG monitoring, RRT if necessary ^[21]
Addison's disease	IV hydrocortisone 100 mg stat + NS resuscitation (acute crisis); long-term: oral hydrocortisone + fludrocortisone
AKI (pre-renal)	Volume resuscitation, stop nephrotoxic drugs
AKI (post-renal / obstruction)	Urological intervention — urinary catheter, nephrostomy, ureteric stent
Type 4 RTA	Oral NaHCO₃ (correct acidosis → improves K⁺), low-K diet, fludrocortisone (synthetic mineralocorticoid, 0.1 mg/day — replaces missing aldosterone effect), loop diuretics
Drug-induced	"Adjust medication" — dose reduction or cessation of offending agent, with risk-benefit assessment ^[20]
CKD-related	"Low K diet, control acidosis with oral bicarbonate, other oral potassium lowering drugs, adjust medication" ^[20]

5. Special Scenarios

If a patient arrests and hyperkalaemia is suspected (e.g., known CKD patient, dialysis patient):
- IV calcium chloride 10 mL of 10% via central line (faster Ca²⁺ delivery than gluconate) — can give via peripheral if no central access
- IV NaHCO₃ 50 mmol (50 mL of 8.4%)
- IV insulin 10 units + D50 50 mL
- Standard ACLS (CPR, adrenaline, defibrillation if shockable rhythm)
- Urgent dialysis as soon as return of spontaneous circulation (ROSC)

"If patient is anuric, potential for hyperkalemia → so in these special situations hold off on the potassium for a while, then replenish accordingly with patients on ECG monitoring" ^[8]

DKA protocol already includes insulin infusion → this will shift K⁺ into cells
Do NOT give K⁺ supplements until K⁺ < 5.5 mmol/L (even though total body K⁺ is depleted)
If K⁺ < 3.3 mmol/L → hold insulin and replace K⁺ first (hypokalaemia is more immediately life-threatening than hyperglycaemia)
Monitor K⁺ every 1–2 hours

"Hyperkalemic acidosis is a common complication in late-stage CKD patients" ^[20]

Long-term strategy:

Low K⁺ diet (dietitian referral)
Oral NaHCO₃ (correct chronic acidosis)
Loop diuretics (if residual urine output)
Oral K⁺ binders (Patiromer, Lokelma, Calcium Resonium) ^[20]
Careful RAAS blockade dose adjustment (not necessarily stopping — benefits often outweigh risks)
Dialysis when approaching ESKD

Finerenone (non-steroidal MRA) has a much lower hyperkalemia side effect than conventional MRAs and can be combined with ACEi/ARB ^[7] — this is a newer option for diabetic kidney disease that allows continued RAAS blockade with lower K⁺ risk.

Treatment	Category	Mechanism	Onset	Duration	K⁺ Reduction?	Key Caution
IV Calcium	Cardioprotection	↑ Threshold potential	Minutes	30–60 min	No	C/I in digoxin toxicity
IV Insulin + Dextrose	Shift	Na⁺/K⁺-ATPase activation	15–30 min	5–6 hours	Yes (0.5–1.2)	Hypoglycaemia — check CBG hourly
IV NaHCO₃	Shift	H⁺/K⁺ exchange	30 min	Hours	Yes (0.5–1.0)	Na⁺ load, fluid overload, ↓iCa²⁺
Nebulised Salbutamol	Shift	Na⁺/K⁺-ATPase via cAMP	15–30 min	2–4 hours	Yes (0.5–1.0)	Tachycardia; 40% non-responders
Haemodialysis	Removal	Diffusion into dialysate	During session	Until K⁺ re-equilibrates	Yes (most effective)	Haemodynamic instability, access
Loop diuretics	Removal	↑ Distal Na⁺ delivery + flow	5 min IV	Hours	Yes (moderate)	Not useful if oliguric
Oral K⁺ binders	Removal	GI K⁺ exchange	2–7 hours	Hours–days	Yes (slow)	SPS: colonic necrosis; not for acute Mx
Low K⁺ diet	Prevention	↓ Exogenous K⁺ intake	N/A	Ongoing	Preventive	Patient education needed
Oral NaHCO₃	Correction	Correct chronic acidosis	Hours	Ongoing	Yes (indirect)	Na⁺ load
Fludrocortisone	Replacement	Mineralocorticoid replacement	Days	Ongoing	Yes (chronic)	HTN, fluid retention, hypoK if over-replaced

High Yield Summary — Management of Hyperkalaemia

Emergency management follows a strict order: (1) IV Calcium for cardioprotection (fastest, does NOT lower K⁺), (2) Shift agents (insulin-dextrose, NaHCO₃, salbutamol) to temporarily lower serum K⁺, (3) Remove K⁺ from the body (dialysis, loop diuretics, K⁺ binders), (4) Treat the underlying cause.
IV Calcium Gluconate is the FIRST drug in emergency hyperkalaemia — onset within minutes, raises threshold potential, buys time. Contraindicated in digoxin toxicity.
IV Insulin 10 units + 50 mL D50 is the most reliable shift agent — onset 15–30 min, lasts 5–6 hours, drops K⁺ by 0.5–1.2 mmol/L. Monitor glucose hourly for 6 hours.
NaHCO₃ is most effective when metabolic acidosis is present. Risks include hypernatraemia, volume overload, decreased ionic calcium, and paradoxical cerebral acidosis.
Haemodialysis is the most effective method of K⁺ removal but takes time to set up. Indicated when K⁺ is refractory to medical therapy, oliguric AKI, or concurrent indications (AEIOU).
K⁺ binders (Lokelma, Patiromer, Calcium Resonium) are NOT emergency treatment — onset is hours. They are for chronic management and maintenance.
SPS (Kayexalate) can cause colonic necrosis — a rare but serious complication.
Do not reflexively stop ACEi/ARB for mild hyperkalaemia — the cardio-renal benefits are too important. Instead, add loop diuretics, correct acidosis, restrict dietary K⁺, and consider K⁺ binders.
In DKA: apparent hyperkalaemia masks total body K⁺ depletion. Do not supplement K⁺ until K⁺ < 5.5. Monitor very closely — hypokalaemia will emerge as insulin is given.
Dialysis indications (AEIOU): Acidosis, Electrolytes (hyperK), Intoxication, Overload, Uraemia.

Active Recall - Management of Hyperkalaemia

References

^[1] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf (pp. 30, Management of hyperkalemia) ^[7] Senior notes: Block A - Nephrology Interactive Tutorial.pdf (p. 4, finerenone and diabetic nephropathy management) ^[8] Senior notes: Block A - Polyuria and polydipsia_ glucose metabolism; diabetes mellitus; diabetic ketoacidosis.pdf (p. 13, DKA treatment and K⁺ monitoring) ^[9] Senior notes: Ryan Ho Critical Care.pdf (p. 26, AKI management and dialysis indications) ^[10] Senior notes: Block A - Drugs and the Kidney.pdf (p. 6, RAAS blockade and hyperK management) ^[18] Senior notes: Adrian Lui Pediatrics Notes.pdf (p. 332, AKI management including hyperK treatment) ^[19] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf (p. 8, Risks of NaHCO₃ therapy) ^[20] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf (p. 28, Hyperkalemia and acidosis management in CKD) ^[21] Senior notes: Ryan Ho Haematology.pdf (p. 72, TLS management)

Complications of Hyperkalaemia

Hyperkalaemia is itself a complication of other conditions (CKD, AKI, drugs, DKA, etc.), but it also causes its own set of dangerous complications. Additionally, the treatment of hyperkalaemia carries iatrogenic risks that must be anticipated and monitored. Both sets of complications are covered here.

1. Complications of Hyperkalaemia Itself

The complications of hyperkalaemia all stem from the same fundamental mechanism: elevated extracellular K⁺ depolarises the resting membrane potential (RMP) of excitable cells, which initially makes them hyper-excitable but then progressively inactivates voltage-gated Na⁺ channels, slowing or abolishing conduction.

The heart is the organ most vulnerable to hyperkalaemia because orderly cardiac conduction depends on rapid, sequential Na⁺ channel activation across atrial and then ventricular myocardium. When extracellular K⁺ is elevated:

The RMP becomes less negative (moves from −90 mV towards −70 mV or less)
Voltage-gated Na⁺ channels partially inactivate (they require a sufficiently negative RMP to "reset" from the inactivated to the resting state)
Phase 0 upstroke velocity slows → slower conduction → widened QRS
Phase 3 repolarisation accelerates (more K⁺ channels open due to higher extracellular K⁺) → peaked T waves
Eventually, conduction ceases entirely → asystole or the disordered depolarisation degenerates into VF

Complication	Mechanism	Clinical Significance
Cardiac arrhythmias	Depolarised RMP → Na⁺ channel inactivation → heterogeneous conduction slowing → re-entry circuits → arrhythmia. May occur with [K⁺] > 6.0 ^[1]	The leading cause of death from hyperkalaemia. Includes sinus bradycardia, junctional rhythms, idioventricular rhythm, VT, VF, and asystole
Cardiac arrest (VF or asystole)	Complete conduction failure or degeneration into fibrillation	"ECG: peaked T, widening of QRS, loss of P, sine wave, asystole" ^[1]. May be the first and only manifestation — "silent killer"
Sinus bradycardia / SA block	SA node depolarisation failure	Profound bradycardia may cause syncope or haemodynamic collapse
AV block (any degree)	Slow conduction through AV node and His-Purkinje system	1st degree → 2nd degree → complete heart block progression
Pseudo-STEMI pattern	Severe hyperkalaemia can cause ST elevation (especially V1-V3) mimicking acute MI	Must check K⁺ before rushing to the cath lab — misdiagnosis can delay appropriate treatment

"Cardiac arrhythmia: may occur with [K⁺] > 6.0. Rate of rise of [K⁺] important — more tolerable with chronic hyperK⁺" ^[1]

High Yield — Cardiac Arrest from Hyperkalaemia

Cardiac arrest from hyperkalaemia has a very poor prognosis unless the K⁺ is rapidly corrected. Standard ACLS (Advanced Cardiac Life Support) algorithms may be ineffective if the underlying cause is hyperkalaemia — the heart will not respond to defibrillation or adrenaline until the membrane is stabilised with IV calcium and the K⁺ is lowered. Always consider hyperkalaemia in any peri-arrest or arrest situation, especially in CKD, dialysis, or AKI patients.

Factors that worsen cardiac toxicity at any given K⁺ level:

Factor	Why It Worsens Toxicity
Rapid rate of rise	Cardiac cells have no time to adapt (upregulate compensatory K⁺ excretion channels)
Hypocalcaemia	Ca²⁺ normally stabilises the cardiac membrane by raising the threshold potential. Low Ca²⁺ → threshold closer to the depolarised RMP → easier to trigger arrhythmia. This is why CKD patients (who often have concurrent hypocalcaemia from ↑PO₄³⁻) are especially at risk ^[11]
Hyponatraemia	Reduced Na⁺ gradient → further slows phase 0 upstroke → compounds conduction delay
Acidosis	Shifts more K⁺ out of cells (worsens the hyperkalaemia) AND directly impairs cardiac contractility
Hypothermia	Slows all ion channel kinetics → exacerbates conduction delay
Digoxin	Already inhibits Na⁺/K⁺-ATPase → synergistic toxicity with hyperkalaemia

The same depolarisation-block mechanism that affects the heart also affects skeletal muscle and peripheral nerves, but typically at higher K⁺ levels because the heart is more sensitive.

Complication	K⁺ Level (Approx.)	Mechanism	Clinical Features
Muscle weakness	Usually > 8 mmol/L ^[1]	Na⁺ channel inactivation in skeletal muscle → impaired action potential propagation → reduced force generation	Proximal > distal, lower limbs > upper limbs
Flaccid paralysis	Very high K⁺ (> 8–9)	Complete depolarisation block → no action potentials at all in skeletal muscle	Ascending weakness, areflexia, hypotonia — resembles Guillain-Barré clinically but with hyperK on bloods
Respiratory failure	Extreme K⁺	Diaphragm and intercostal muscles affected by the same depolarisation block	Life-threatening; may require intubation and mechanical ventilation
Paraesthesias	Variable	Sensory nerve fibre depolarisation block	Tingling, numbness — often early and non-specific

"Consequences: vague muscle weakness (first sign, no correlation with K level), flaccid paralysis, paraesthesia, cardiac arrhythmia" ^[14]

Important — Weakness vs. Cardiac Risk

Muscle weakness is often considered the "first sign" of hyperkalaemia, but in practice, fatal cardiac arrhythmia can occur BEFORE muscle weakness becomes clinically apparent — weakness typically requires K⁺ > 8, while arrhythmias can start at K⁺ > 6. Never wait for neuromuscular symptoms to decide whether to treat urgently.

Complication	Mechanism	Clinical Significance
Worsening metabolic acidosis	Hyperkalaemia itself can worsen acidosis via two mechanisms: (1) K⁺ enters cells, displacing H⁺ out → intracellular alkalosis suppresses ammoniagenesis in the PCT → ↓ NH₄⁺ excretion → ↓ acid excretion. (2) Elevated K⁺ in the CCD inhibits the apical H⁺/K⁺-ATPase, reducing H⁺ secretion.	Creates a vicious cycle: hyperkalaemia → acidosis → more K⁺ shifted out of cells → worse hyperkalaemia → worse acidosis. This is particularly important in Type 4 RTA where both hyperkalaemia and hyperchloraemic metabolic acidosis coexist ^[11]

"Hyperkalemic acidosis is a common complication seen in late-stage CKD patients" ^[20]

Hyperkalaemia rarely occurs in isolation — it is almost always a manifestation of an underlying condition that carries its own complications.

Underlying Cause	Additional Complications (Beyond HyperK)
AKI	Fluid overload (peripheral oedema, pulmonary oedema, hypertension), metabolic acidosis (Kussmaul breathing), uraemia (pericarditis, neuropathy, encephalopathy) ^[9]
CKD	Normochromic normocytic anaemia (↓ EPO), renal osteodystrophy (secondary hyperparathyroidism, ↑ALP), hyperphosphataemia, hypocalcaemia, fluid retention, hypertension ^[11]^[22]
DKA	Cerebral oedema (especially in paediatrics with over-aggressive fluid resuscitation), ARDS, thrombosis
Tumour lysis syndrome	AKI from uric acid nephropathy and acute nephrocalcinosis, hypocalcaemia (→ tetany, arrhythmia), hyperphosphataemia ^[23]
Rhabdomyolysis	AKI from myoglobin cast nephropathy, compartment syndrome, DIC
Addison's disease	Adrenal crisis (hypotension, shock, hypoglycaemia, hyponatraemia)

2. Complications of Hyperkalaemia Treatment (Iatrogenic)

Every treatment for hyperkalaemia carries its own risk profile. These are commonly tested in exams because they represent the clinical balance between treating a dangerous condition and avoiding treatment-related harm.

Complication	Mechanism	Prevention
Tissue necrosis from extravasation	Calcium chloride (especially) is extremely caustic. Calcium gluconate is safer peripherally but can still cause damage	Use calcium gluconate for peripheral IV. Reserve calcium chloride for central lines or cardiac arrest. Ensure good IV access before infusion
Fatal arrhythmia in digoxin toxicity	Ca²⁺ potentiates digoxin's inhibition of Na⁺/K⁺-ATPase → "stone heart" (intractable VF)	Contraindicated in digoxin toxicity — use digoxin-specific antibodies instead
Hypercalcaemia (with repeated doses)	Excessive Ca²⁺ administration	Monitor iCa²⁺ if giving multiple doses

Complication	Mechanism	Prevention
Hypoglycaemia	Insulin's glucose-lowering effect persists beyond the K⁺-shifting effect. The dextrose may be metabolised faster than expected	Monitor capillary blood glucose (CBG) hourly for at least 6 hours post-administration. Have D50 ready for rescue
Rebound hyperkalaemia	Insulin effect wears off after 5–6 hours → K⁺ shifts back out of cells if the underlying cause is not addressed	Ensure definitive K⁺ removal (dialysis, diuretics, K⁺ binders) is initiated concurrently
Fluid overload (from dextrose volume)	Volume load, especially in oliguric AKI or HF patients	Use concentrated D50 rather than large-volume D10 in fluid-restricted patients

Hypoglycaemia is the most common complication of insulin-dextrose treatment for hyperkalaemia — reported in up to 20% of patients. It is entirely preventable with glucose monitoring.

"Risks of NaHCO₃ therapy: hypernatraemia, induce hypokalaemia, decrease ionic calcium, volume expansion, paradoxical cerebral acidosis" ^[19]

Complication	Mechanism	Prevention
Hypernatraemia	1 mmol HCO₃⁻ carries 1 mmol Na⁺ — 200 mmol NaHCO₃ delivers more Na⁺ than 1 litre of normal saline ^[19]	Monitor serum Na⁺; limit total dose; use carefully in patients prone to Na⁺ retention
Volume overload	Significant Na⁺ load → water retention → pulmonary oedema ^[19]	Avoid in patients with heart failure or oliguric CKD unless dialysis is available
Hypokalaemia (overshoot)	Alkalosis from NaHCO₃ shifts K⁺ into cells; particularly dangerous in patients who already have depleted total body K⁺ (e.g., DKA) ^[19]	Monitor K⁺ closely after NaHCO₃; have K⁺ replacement ready
Decreased ionised calcium	Alkalosis increases protein binding of Ca²⁺ → ↓ ionised Ca²⁺ → tetany, arrhythmia. Especially problematic in CKD patients with pre-existing hypocalcaemia ^[19]	Monitor iCa²⁺; give IV calcium gluconate if tetany develops
Paradoxical cerebral acidosis	CO₂ produced from HCO₃⁻ breakdown crosses the BBB faster than HCO₃⁻ itself → converted to H⁺ + HCO₃⁻ by carbonic anhydrase in the CSF → paradoxical CNS acidosis ^[19]	Avoid over-rapid correction; give infusion rather than bolus

Complication	Mechanism	Prevention
Tachycardia / palpitations	β₂ (and some β₁) adrenergic stimulation → ↑ heart rate and contractility	Use with caution in patients with ischaemic heart disease or pre-existing tachyarrhythmia
Tremor	β₂-mediated skeletal muscle activation	Usually mild and self-limiting
Hypokalaemia (overshoot)	Excessive K⁺ shift into cells if used in combination with insulin-dextrose and NaHCO₃	Monitor K⁺; be aware that ~40% of patients are non-responders (unpredictable effect)
Lactic acidosis	β₂-mediated glycogenolysis and lipolysis → lactate production	Usually transient

Drug	Complication	Mechanism
Sodium polystyrene sulfonate (SPS / Kayexalate)	Colonic necrosis — rare but potentially fatal	SPS (especially with sorbitol) causes direct mucosal injury and ischaemic necrosis of the colonic wall. Risk factors: post-operative state, uraemia, bowel hypomotility ^[20]
SPS	Constipation / faecal impaction	Resin swells in the colon; especially in patients with reduced GI motility
Lokelma (SZC)	Oedema / fluid overload	Na⁺ load from exchange mechanism
Patiromer	Hypomagnesaemia	Binds Mg²⁺ in addition to K⁺ ^[20]
Patiromer	Drug interactions (binds other oral medications)	Non-selective binding in the GI tract — separate from other medications by ≥ 3 hours
All K⁺ binders	Hypokalaemia (overshoot)	Over-correction if used aggressively or combined with other K⁺-lowering measures ^[20]

High Yield — Colonic Necrosis from SPS

"Which renal drug has the complication of colonic necrosis? → Sodium polystyrene sulfonate, SPS" ^[20]. This is a rare but devastating complication that is frequently tested. It occurs more often when SPS is given with sorbitol (an osmotic cathartic), in post-operative patients, or in patients with bowel hypomotility. Newer agents (Patiromer, Lokelma) have a better safety profile and are increasingly preferred.

Complication	Mechanism	Prevention
Hypotension	Rapid fluid removal → ↓ intravascular volume → haemodynamic instability	Use CRRT instead of intermittent HD in haemodynamically unstable patients ^[18]
Dialysis disequilibrium syndrome	Rapid urea removal from plasma → osmotic gradient → water shifts into brain cells → cerebral oedema	More common in first dialysis sessions with very high urea; use slower dialysis with smaller urea clearance
Hypokalaemia (overshoot)	Dialysis can drop K⁺ too rapidly, especially with low-K⁺ dialysate	Use K⁺-containing dialysate (2.0 mmol/L) for patients not in severe hyperK; monitor K⁺ during and after dialysis
Arrhythmia	Rapid electrolyte shifts (K⁺, Ca²⁺, Mg²⁺) during dialysis → electrical instability	Continuous cardiac monitoring during dialysis
Bleeding	Heparin anticoagulation for the dialysis circuit	Use regional citrate anticoagulation if high bleeding risk
Vascular access complications	Central venous catheter insertion → pneumothorax, infection, thrombosis	Aseptic technique, USG-guided insertion, regular line care

"Intermittent HD: considerable haemodynamic instability and fluid shifts with hypotension, cerebral oedema" ^[18]

This deserves special emphasis because it is a common clinical trap: treating hyperkalaemia too aggressively (or treating the underlying cause, e.g., DKA) can swing the patient into dangerous hypokalaemia.

Hypokalaemia complications ^[1]:

Muscle weakness, paralysis (proximal muscle myopathy)
Cardiac arrhythmia, particularly when [K⁺] < 2.0
ECG changes: large U wave, loss of T wave, prolonged QT interval
Ileus, constipation
Rhabdomyolysis
Polyuria

Scenario	Why Overcorrection Occurs	Prevention
DKA treatment	Insulin shifts K⁺ into cells; correction of acidosis shifts more K⁺ in; total body K⁺ was depleted by osmotic diuresis. K⁺ can plummet from "normal" to < 3.0 within hours	Monitor K⁺ every 1–2 hours; supplement K⁺ when serum K⁺ < 5.5; hold insulin if K⁺ < 3.3
Multiple shift agents simultaneously	Insulin-dextrose + NaHCO₃ + salbutamol → additive K⁺ shift into cells	Monitor K⁺ 1–2 hours after interventions
Aggressive dialysis	Low-K⁺ dialysate removes K⁺ too quickly	Use K⁺-containing dialysate for moderate hyperkalaemia
Thyrotoxic periodic paralysis treatment	Rebound hyperkalaemia (40–59%) when transcellular shift reverses ^[24] — the reverse problem, but important to know	IV K⁺ replacement should not exceed 10–20 mmol/h; do not over-replace ^[24]

Category	Complication	Key Mechanism
Cardiac	VF, asystole, bradycardia, AV block, pseudo-STEMI	Depolarisation → Na⁺ channel inactivation → conduction failure
Neuromuscular	Weakness, flaccid paralysis, respiratory failure	Same depolarisation block in skeletal muscle
Metabolic	Worsening acidosis (vicious cycle)	↓ Ammoniagenesis, ↓ H⁺ secretion
Tx: IV Calcium	Extravasation necrosis, stone heart (digoxin)	Caustic agent; Ca²⁺ potentiates digoxin toxicity
Tx: Insulin-Dextrose	Hypoglycaemia (most common), rebound hyperK	Insulin effect outlasts glucose; K⁺ shift reverses
Tx: NaHCO₃	Hypernatraemia, volume overload, ↓iCa²⁺, cerebral acidosis	Na⁺ load; alkalosis ↓ ionised Ca²⁺; CO₂ crosses BBB
Tx: Salbutamol	Tachycardia, non-responders (40%)	β-adrenergic stimulation
Tx: SPS (Kayexalate)	Colonic necrosis	Direct mucosal injury
Tx: Patiromer	HypoMg, drug interactions	Binds Mg²⁺ and other drugs in gut
Tx: Dialysis	Hypotension, disequilibrium, overshoot hypoK	Rapid solute/fluid removal
Overcorrection	Hypokalaemia → arrhythmia, paralysis, ileus	Excessive shift agents or dialysis

High Yield Summary — Complications of Hyperkalaemia

Cardiac arrhythmia and cardiac arrest are the most feared and most lethal complications — they can occur before any neuromuscular symptoms appear. Always treat based on K⁺ level and ECG, not symptoms.
Concurrent hypocalcaemia, hyponatraemia, acidosis, and rapid rate of rise all worsen cardiac toxicity at any given K⁺ level — CKD patients with all of these derangements are at highest risk.
The hyperkalaemia–acidosis vicious cycle is clinically important: hyperkalaemia impairs renal NH₄⁺ and H⁺ excretion → worsens acidosis → shifts more K⁺ out of cells → worsens hyperkalaemia. Breaking this cycle with NaHCO₃ addresses both problems simultaneously.
Treatment complications are commonly tested: hypoglycaemia from insulin-dextrose (most common), colonic necrosis from SPS (rare but serious), volume overload and hypernatraemia from NaHCO₃, and haemodynamic instability from dialysis.
Overcorrection to hypokalaemia is a real danger — especially in DKA (total body K⁺ depleted), with multiple simultaneous shift agents, or aggressive dialysis. Monitor K⁺ frequently and have K⁺ replacement ready.
IV calcium is contraindicated in digoxin toxicity — this is a must-know exam point.
Muscle weakness typically requires K⁺ > 8 mmol/L but fatal arrhythmia can begin at K⁺ > 6.0 — do not use neuromuscular symptoms as a gauge for urgency.

Active Recall - Complications of Hyperkalaemia

References

^[1] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf (pp. 27, 29–30, Hyperkalemia symptoms and complications) ^[9] Senior notes: Ryan Ho Critical Care.pdf (p. 26, AKI complications including hyperK management) ^[11] Senior notes: Block A – Nephrology Data Interpretation.pdf (pp. 9–10, CKD lab findings and hyperkalaemia interpretation) ^[14] Senior notes: Ryan Ho Chemical Path.pdf (p. 14, Consequences of hyperkalaemia) ^[18] Senior notes: Adrian Lui Pediatrics Notes.pdf (p. 332, HyperK initial Tx and IHD vs CRRT comparison) ^[19] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf (p. 8, Risks of NaHCO₃ therapy) ^[20] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf (p. 28, Hyperkalemic acidosis management and SPS colonic necrosis) ^[22] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf (p. 23, Complications of CKD) ^[23] Senior notes: Block A - High white cell count_ acute and chronic leukaemia; bone marrow transplantation; immunogenetics.pdf (p. 15, Tumour lysis syndrome) ^[24] Senior notes: Ryan Ho Endocrine.pdf (p. 29, TPP rebound hyperkalaemia)

High Yield Summary

Hyperkalaemia = serum K⁺ > 5.0 mmol/L. Severe (≥ 6.5 mmol/L) is a medical emergency.
98% of K⁺ is intracellular. The Na⁺/K⁺-ATPase pump maintains this gradient. Even small transcellular shifts can dangerously raise serum K⁺.
The two most important causes are renal failure and hypoaldosteronism (especially Type 4 RTA in diabetic nephropathy).
Drugs are the most common iatrogenic cause — ACEi, ARB, MRA, K⁺-sparing diuretics, CNI, NSAIDs, trimethoprim, heparin, digoxin.
DKA trap: apparent hyperkalaemia from transcellular shift, but total body K⁺ is depleted. Treating DKA can unmask severe hypokalaemia.
Always exclude pseudohyperkalaemia (haemolysed sample, thrombocytosis, leukocytosis) before treating.
ECG progression: Peaked T → PR prolongation / flat P → Wide QRS → Loss of P → Sine wave → VF/Asystole. But this progression is not always orderly.
Rate of rise matters: acute rise is more dangerous than chronic elevation at the same K⁺ level.
Symptoms are unreliable — many patients are asymptomatic until cardiac arrest. Muscle weakness typically occurs only when K⁺ > 8 mmol/L.
TTKG < 6 in hyperkalaemia = inappropriate renal response → think hypoaldosteronism or CCD dysfunction.

High Yield Summary — Differential Diagnosis of Hyperkalaemia

Always exclude pseudohyperkalaemia first — haemolysed sample, thrombocytosis, leukocytosis, EDTA contamination. Repeat sample if in doubt.
Three mechanistic categories: Increased input (shift, tissue destruction, dietary), decreased output (renal failure, hypoaldosteronism, drugs), and pseudohyperkalaemia.
Renal failure and hypoaldosteronism are the two most important causes of sustained hyperkalaemia.
Drug-induced hyperkalaemia is the most common modifiable cause — think ACEi/ARB/MRA/NSAIDs/CNI/trimethoprim/heparin/digoxin/β-blockers.
DKA = apparent hyperkalaemia with total body K⁺ depletion — treating DKA unmasks dangerous hypokalaemia.
Tissue destruction triad to recognise: Rhabdomyolysis (↑↑CK), TLS (↑LDH + ↑uric acid + ↑PO₄ + ↓Ca²⁺), Haemolysis (↓haptoglobin + ↑LDH + ↑unconjugated bilirubin).
Type 4 RTA (diabetic nephropathy → JG destruction → ↓renin → ↓aldosterone) is the most common cause of hyporeninemic hypoaldosteronism in adults — extremely important in HK.
TTKG < 6 in hyperkalaemia = inappropriate renal response → hypoaldosteronism or CCD dysfunction.
Triple whammy (ACEi/ARB + NSAID + diuretic/volume depletion) is a common and dangerous combination.
Use the two-axis model: renin-AngII-aldosterone-ENaC/ROMK axis (external balance) + Na⁺/K⁺-ATPase axis (internal balance) to systematically identify the cause.

High Yield Summary — Diagnosis of Hyperkalaemia

Diagnosis is biochemical: Plasma K⁺ > 5.0 or Serum K⁺ > 5.5 mmol/L. The serum threshold is higher because platelets release K⁺ during clotting.
First step: Always exclude pseudohyperkalaemia — repeat sample, use plasma tube if thrombocytosis/leukocytosis.
Most urgent investigation: 12-lead ECG. ECG changes determine emergency vs. non-emergency management.
The five-step approach: (1) Real? (2) Dangerous? (ECG) (3) Renal function? (RFT) (4) Shift or excretion? (ABG, glucose, CK, drugs) (5) Where in the aldosterone axis? (TTKG, renin, aldo)
TTKG < 6 in hyperkalaemia = inappropriate renal response → hypoaldosteronism or CCD dysfunction.
Renin/Aldo patterns: ↓R ↓A = hyporeninemic hypoaldo (Type 4 RTA, NSAIDs); ↑R ↓A = hyperreninemic hypoaldo (Addison's, ACEi); ↑R ↑A = aldo resistance (K-sparing diuretics, trimethoprim).
Tissue destruction triad: ↑PO₄ + ↑LDH + ↑uric acid + ↓Ca²⁺ = tumour lysis; ↑↑CK = rhabdomyolysis; ↓haptoglobin = haemolysis.
Save samples before treatment — urine K⁺ and other bloods should be collected before giving IV insulin/dextrose or other treatments that will alter the K⁺ level.
USG kidneys is essential in any AKI to exclude obstructive uropathy (reversible cause).
FENa < 1% → pre-renal; FENa > 2% → ATN.

High Yield Summary — Management of Hyperkalaemia

Emergency management follows a strict order: (1) IV Calcium for cardioprotection (fastest, does NOT lower K⁺), (2) Shift agents (insulin-dextrose, NaHCO₃, salbutamol) to temporarily lower serum K⁺, (3) Remove K⁺ from the body (dialysis, loop diuretics, K⁺ binders), (4) Treat the underlying cause.
IV Calcium Gluconate is the FIRST drug in emergency hyperkalaemia — onset within minutes, raises threshold potential, buys time. Contraindicated in digoxin toxicity.
IV Insulin 10 units + 50 mL D50 is the most reliable shift agent — onset 15–30 min, lasts 5–6 hours, drops K⁺ by 0.5–1.2 mmol/L. Monitor glucose hourly for 6 hours.
NaHCO₃ is most effective when metabolic acidosis is present. Risks include hypernatraemia, volume overload, decreased ionic calcium, and paradoxical cerebral acidosis.
Haemodialysis is the most effective method of K⁺ removal but takes time to set up. Indicated when K⁺ is refractory to medical therapy, oliguric AKI, or concurrent indications (AEIOU).
K⁺ binders (Lokelma, Patiromer, Calcium Resonium) are NOT emergency treatment — onset is hours. They are for chronic management and maintenance.
SPS (Kayexalate) can cause colonic necrosis — a rare but serious complication.
Do not reflexively stop ACEi/ARB for mild hyperkalaemia — the cardio-renal benefits are too important. Instead, add loop diuretics, correct acidosis, restrict dietary K⁺, and consider K⁺ binders.
In DKA: apparent hyperkalaemia masks total body K⁺ depletion. Do not supplement K⁺ until K⁺ < 5.5. Monitor very closely — hypokalaemia will emerge as insulin is given.
Dialysis indications (AEIOU): Acidosis, Electrolytes (hyperK), Intoxication, Overload, Uraemia.

High Yield Summary — Complications of Hyperkalaemia

Cardiac arrhythmia and cardiac arrest are the most feared and most lethal complications — they can occur before any neuromuscular symptoms appear. Always treat based on K⁺ level and ECG, not symptoms.
Concurrent hypocalcaemia, hyponatraemia, acidosis, and rapid rate of rise all worsen cardiac toxicity at any given K⁺ level — CKD patients with all of these derangements are at highest risk.
The hyperkalaemia–acidosis vicious cycle is clinically important: hyperkalaemia impairs renal NH₄⁺ and H⁺ excretion → worsens acidosis → shifts more K⁺ out of cells → worsens hyperkalaemia. Breaking this cycle with NaHCO₃ addresses both problems simultaneously.
Treatment complications are commonly tested: hypoglycaemia from insulin-dextrose (most common), colonic necrosis from SPS (rare but serious), volume overload and hypernatraemia from NaHCO₃, and haemodynamic instability from dialysis.
Overcorrection to hypokalaemia is a real danger — especially in DKA (total body K⁺ depleted), with multiple simultaneous shift agents, or aggressive dialysis. Monitor K⁺ frequently and have K⁺ replacement ready.
IV calcium is contraindicated in digoxin toxicity — this is a must-know exam point.
Muscle weakness typically requires K⁺ > 8 mmol/L but fatal arrhythmia can begin at K⁺ > 6.0 — do not use neuromuscular symptoms as a gauge for urgency.

Hyperkalaemia

1. Definition

2. Epidemiology

3. Risk Factors

4. Anatomy & Physiology of Potassium Homeostasis

4.1 Potassium Distribution

4.2 Potassium Regulation — Two Systems

A. External Balance (Renal Excretion) — Long-term regulation (hours to days)

B. Internal Balance (Transcellular Shift) — Rapid regulation (minutes to hours)

4.3 The TTKG (Trans-Tubular Potassium Gradient)

5. Aetiology & Pathophysiology

5.1 Pseudohyperkalaemia (Always Exclude First!)

5.2 Increased K⁺ Input into ECF

A. Transcellular Shift (K⁺ moves from ICF → ECF)

B. Tissue Destruction / Cell Lysis (K⁺ released from damaged cells)

C. Excessive Intake

5.3 Decreased K⁺ Output from ECF (Impaired Renal Excretion)

A. Reduced GFR (Renal Failure)

B. Reduced Aldosterone Production or Action

C. Reduced Distal Na⁺ Delivery or Tubular Flow

D. CCD Defects (Rare)

5.4 Summary Aetiological Framework

6. Classification

6.1 By Severity

6.2 By Mechanism

6.3 By Chronicity

7. Clinical Features

7.1 Symptoms

7.2 Signs

A. Cardiovascular — The Most Dangerous Manifestation

B. Neuromuscular Signs

C. Other Signs

8. Approach to Hyperkalaemia — Thinking Framework (Pre-Diagnosis)

Active Recall - Hyperkalaemia (Definition to Clinical Features)

References

1. The Overarching Framework — Three Questions

2. Structured Differential Diagnosis

2.1 Pseudohyperkalaemia (Artefactual — No True In-Vivo Elevation)

2.2 Increased K⁺ Input into the ECF

A. Transcellular Shift (K⁺ Redistributes from ICF → ECF)

B. Tissue Destruction / Cell Lysis (Release of Intracellular K⁺ Stores)

C. Excessive Dietary / Iatrogenic Intake

2.3 Decreased K⁺ Output from the ECF (Impaired Renal Excretion)

A. Reduced GFR (Renal Failure)

B. Reduced Aldosterone Production or Action (Hypoaldosteronism)

C. Reduced Distal Na⁺ Delivery or Tubular Flow

D. Intrinsic CCD / Tubular Defects (Rare)

3. Differential Diagnosis Decision Algorithm

4. Key Differentiating Features — High-Yield Comparison Tables

4.1 Renal Failure vs. Hypoaldosteronism

4.2 DKA-Related Hyperkalaemia vs. True K⁺ Excess

4.3 Addison's Disease vs. Type 4 RTA

4.4 Tissue Destruction — Differentiating Rhabdomyolysis vs. TLS vs. Haemolysis

5. Drug-Induced Hyperkalaemia — A Detailed Differential (Extremely Common in Clinical Practice)

6. Differential Diagnosis of Hyperkalaemia in Special Populations (Hong Kong Focus)

7. Approach to Narrowing the Differential — Clinical Clues

Active Recall - Differential Diagnosis of Hyperkalaemia

1. Diagnostic Criteria

2. Diagnostic Algorithm — Systematic Approach

3. Diagnostic Algorithm — Mermaid Diagram

4. Investigation Modalities — Detailed with Key Findings & Interpretation

4.1 Bedside Investigations

A. ECG (12-lead) — THE Most Urgent Investigation

B. Vital Signs & Volume Assessment

C. Urine Dipstick

4.2 Blood Investigations

A. Renal Function Test (RFT) — The Most Important Blood Test

B. Urea:Creatinine Ratio

C. Venous / Arterial Blood Gas (VBG/ABG)

D. Glucose & Ketones

E. Creatine Kinase (CK) & Myoglobin

F. Tissue Destruction Panel (LDH, Uric Acid, PO₄, Ca²⁺)

G. Full Drug Level Assays (When Indicated)

H. Complete Blood Count (CBC)

4.3 Urine Investigations

A. Spot Urine K⁺ & Urine Osmolality → TTKG Calculation

B. Spot Urine Na⁺

C. Fractional Excretion of Sodium (FENa)

4.4 Endocrine Investigations (When Hypoaldosteronism Suspected)

A. Plasma Renin Activity (PRA) / Direct Renin Concentration + Serum Aldosterone