Electrolyte Disorders: Hyponatraemia, Hypernatraemia, Hypokalaemia, Hyperkalaemia and Their Correction

Definition / Overview

Electrolyte disorders are among the most common and clinically consequential abnormalities encountered in internal medicine. They represent not simply abnormal numbers but reflections of underlying pathophysiology - disordered volume regulation, hormonal dysregulation, drug toxicity, or end-organ failure. The FRACP candidate must be fluent in the bedside synthesis of history, examination, and investigation to reach a diagnosis, stratify urgency, and institute evidence-based treatment while avoiding iatrogenic harm (particularly from over-rapid correction).

Hyponatraemia

Definition and Classification

• Hyponatraemia is defined as a serum $\text{Na}^+$ below $135\,\text{mmol/L}$; clinically significant is typically $<130\,\text{mmol/L}$.
• Classified by:
• Onset: Acute ($<48$ hours) vs. chronic ($\geq 48$ hours or unknown) - determines correction safety
• Severity: Mild $130-135$, Moderate $125-129$, Profound $<125\,\text{mmol/L}$
• Volume status: Hypovolaemic, euvolaemic, or hypervolaemic

Pathophysiology

Hyponatraemia almost universally reflects excess free water relative to sodium, not absolute sodium depletion. The key hormone is ADH (vasopressin), whose appropriate or inappropriate secretion drives water retention in the collecting duct. Exceptions include pseudohyponatraemia (hypertriglyceridaemia, hyperproteinaemia) and translocational hyponatraemia (hyperglycaemia, mannitol).

$$\text{Corrected Na}^+ = \text{Measured Na}^+ + 0.3 \times (\text{glucose} - 5.5)\,\text{mmol/L}$$

Aetiology by Volume Status

SIADH diagnostic criteria: Plasma $\text{Na}^+ < 135\,\text{mmol/L}$ with low plasma osmolality ($<275\,\text{mOsmol/kg}$), urine osmolality $>100\,\text{mOsmol/kg}$, urine $\text{Na}^+ > 20\,\text{mmol/L}$, clinically euvolaemic, absence of diuretics, hypothyroidism, or adrenal insufficiency.

Common SIADH causes: pulmonary disease (pneumonia, TB, malignancy), CNS disorders (stroke, meningitis, subdural haematoma), malignancy (small-cell lung cancer), drugs (opioids, SSRIs, carbamazepine, cyclophosphamide).

Clinical Features

• Mild-moderate: nausea, headache, cognitive slowing, gait disturbance
• Severe/acute: seizures, obtundation, herniation, respiratory arrest
• Chronic hyponatraemia often surprisingly asymptomatic - yet associated with falls, osteoporosis, and cognitive decline

Management

Assess urgency first - symptoms trump the number.

1. Severely symptomatic (seizures, coma): Hypertonic saline $3\%\,\text{NaCl}$ - give $150\,\text{mL}$ IV over $20$ minutes, repeat if necessary, targeting symptom resolution and a rise in $\text{Na}^+$ of $5\,\text{mmol/L}$ acutely. Seek ICU input.
2. Acute hyponatraemia ($<48$ h) - even if asymptomatic: Correct more liberally; risk of cerebral oedema outweighs osmotic demyelination risk.
3. Chronic or unknown duration:
4. Target correction rate: $\leq 8-10\,\text{mmol/L}$ per $24$ hours, maximum $18\,\text{mmol/L}$ per $48$ hours
5. Exceeding this risks osmotic demyelination syndrome (ODS) - previously called central pontine myelinolysis - a devastating, often irreversible demyelination
6. Higher-risk patients for ODS: $\text{Na}^+ < 105$, malnutrition, alcoholism, liver disease, hypokalaemia

Specific treatment by cause: - Hypovolaemic: Cautious isotonic saline ($0.9\%\,\text{NaCl}$) - beware that as ADH suppresses after volume repletion, free water excretion accelerates and $\text{Na}^+$ may rise faster than anticipated (risk of ODS) - SIADH: Fluid restriction ($500-1000\,\text{mL/day}$) first-line; if refractory, consider demeclocycline, urea, or vaptans (tolvaptan) - tolvaptan is effective but avoid in liver disease (risk of hepatotoxicity); avoid in hypovolaemia - Hypervolaemic: Treat underlying cause; fluid restriction; loop diuretics in cardiac failure

Overcorrection protocol: If $\text{Na}^+$ rises too fast, administer $\text{DDAVP}$ (desmopressin) $2\,\text{mcg}$ IV/SC + free water PO or 5% dextrose IV to halt further rise (the "clamp" technique).

Hypernatraemia

Definition and Pathophysiology

• Defined as serum $\text{Na}^+ > 145\,\text{mmol/L}$
• Always represents free water deficit relative to sodium - either water loss, inadequate intake, or (rarely) excessive sodium administration
• Intact thirst mechanism is normally highly protective; hypernatraemia implies impaired access to water or abnormal thirst (elderly, neurologically impaired, critically ill patients are most vulnerable)

Aetiology

Differentiating DI: Urine osmolality inappropriately low ($<300\,\text{mOsmol/kg}$) despite hypernatraemia. Urine osmolality $>800$ suggests extra-renal loss. Water deprivation test + DDAVP challenge distinguishes cranial from nephrogenic DI.

Clinical Features

• Thirst, irritability, confusion, weakness
• Severe: lethargy, seizures, coma; intracranial haemorrhage from cerebral dehydration (brain shrinkage tears bridging veins)
• Chronic hypernatraemia: brain accumulates idiogenic osmoles - correction must be gradual to avoid cerebral oedema

Management

1. Calculate free water deficit: $$\text{Free water deficit (L)} = 0.6 \times \text{body weight (kg)} \times \left(\frac{\text{Na}^+_{\text{measured}}}{140} - 1\right)$$

2. Acute hypernatraemia ($<48$ h): May correct more rapidly.

3. Chronic/unknown: Correct at $\leq 10-12\,\text{mmol/L}$ per $24$ hours to avoid cerebral oedema.
4. If $\text{Na}^+ \geq 170\,\text{mmol/L}$: Begin with $0.9\%\,\text{NaCl}$ to avoid too rapid a drop; transition to $0.45\%\,\text{NaCl}$ or 5% dextrose as level falls.
5. Oral/enteral water preferred if gut accessible.
6. Monitor $\text{Na}^+$ every $4-6$ hours initially; adjust infusion rate based on trajectory.
7. Cranial DI: Desmopressin (intranasal, oral, or $2\,\text{mcg}$ IM/SC) - fluid replacement still essential alongside.
8. Nephrogenic DI: Treat underlying cause (lithium toxicity, hypercalcaemia); thiazide diuretics paradoxically reduce polyuria by inducing mild hypovolaemia, enhancing proximal tubular reabsorption; low-sodium, low-protein diet.

Hypokalaemia

Definition and Pathophysiology

• Serum $\text{K}^+ < 3.5\,\text{mmol/L}$; severe $< 2.5\,\text{mmol/L}$
• Most body potassium is intracellular (98%); serum levels reflect a small pool and can be misleading in acid-base disturbances
• Alkalosis and insulin drive $\text{K}^+$ intracellularly, masking total body depletion; acidosis shifts $\text{K}^+$ extracellularly

Aetiology

Hypomagnesaemia refractory to potassium replacement - check and replace $\text{Mg}^{2+}$ concurrently; $\text{Mg}^{2+}$ is required for renal $\text{K}^+$ conservation.

Clinical Features and ECG

• Muscle weakness, cramps, fatigue; severe: flaccid paralysis, respiratory failure
• Palpitations, ventricular ectopics, tachyarrhythmias
• ECG changes: flattened T waves, prominent U waves (particularly in lateral leads), prolonged QU interval, ST depression; severe hypokalaemia predisposes to ventricular tachycardia (including torsades de pointes) and potentiates digoxin toxicity

Management

• Oral replacement preferred when $\text{K}^+ > 2.5\,\text{mmol/L}$ and haemodynamically stable: potassium chloride (KCl) $40-80\,\text{mmol/day}$ in divided doses
• IV replacement: KCl via central line at $\leq 20\,\text{mmol/hour}$ (peripheral vein max $10\,\text{mmol/hour}$ with dilution); maximum $40\,\text{mmol/hour}$ via central line in life-threatening arrhythmia with continuous cardiac monitoring
• Treat hypomagnesaemia concurrently: $\text{MgSO}_4$ $10\,\text{mmol}$ IV over $30-60$ minutes
• Address underlying cause (stop offending diuretic, treat hyperaldosteronism)
• Cardiac patients and digoxin users: Maintain $\text{K}^+ \geq 4.0\,\text{mmol/L}$

Hyperkalaemia

Definition and Risk Stratification

• Serum $\text{K}^+ > 5.5\,\text{mmol/L}$; emergency level $\geq 6.5\,\text{mmol/L}$ or any level with ECG changes
• First exclude artefact: haemolysis (red cells release $\text{K}^+$), thrombocytosis, prolonged sample transport - if clinical picture doesn't fit, repeat promptly

Aetiology

Clinical Features and ECG

Symptoms are often absent until severe; the ECG is the essential monitoring tool.

Non-cardiac: muscle weakness, paraesthesiae, ascending paralysis, nausea

Stepwise Acute Management

1. Attach cardiac monitor; obtain 12-lead ECG immediately
2. IV access and bloods: Repeat $\text{K}^+$, renal function, bicarbonate, glucose, calcium
3. Membrane stabilisation (if ECG changes or $\text{K}^+ > 6.5\,\text{mmol/L}$):
4. $\text{CaCl}_2$ 10% solution $10\,\text{mL}$ IV over $5-10$ minutes (or calcium gluconate $10\%\,$ $30\,\text{mL}$ via peripheral vein)
5. Onset within $1-3$ minutes; duration $30-60$ minutes; does not lower $\text{K}^+$

6. Repeat if ECG does not normalise in $5$ minutes

7. Transcellular shift (buy time while elimination is arranged):

8. Insulin-dextrose: actrapid $10\,\text{units}$ IV + $50\,\text{mL}$ of 50% glucose (or $125\,\text{mL}$ of 20% glucose) - lowers $\text{K}^+$ by $0.5-1.5\,\text{mmol/L}$ within $15-30$ minutes; monitor BSL
9. Nebulised salbutamol $10-20\,\text{mg}$ - additive effect, onset $30$ minutes; note: unreliable in cardiac patients and not effective in all individuals

10. Sodium bicarbonate $8.4\%\,$ $50\,\text{mmol}$ IV - primarily useful in concurrent severe metabolic acidosis; modest $\text{K}^+$-lowering effect in isolation

11. Elimination (remove $\text{K}^+$ from the body):

12. Furosemide $40-80\,\text{mg}$ IV if urine output adequate and volume status allows
13. Resonium (sodium polystyrene sulfonate) or patiromer orally/PR - onset hours; limited evidence for acute use; resonium can cause GI necrosis, use with caution

14. Dialysis - most effective; indicated for anuric AKI, refractory hyperkalaemia, or $\text{K}^+ > 7.0\,\text{mmol/L}$ with haemodynamic instability

15. Address precipitating cause: Stop causative drugs (ACEi, ARB, spironolactone, NSAIDs), treat acidosis, manage AKI

Complications & Special Considerations

Osmotic Demyelination Syndrome

• Risk with too-rapid correction of chronic hyponatraemia
• Particularly in: serum $\text{Na}^+ < 105\,\text{mmol/L}$, alcoholism, malnutrition, liver disease, concurrent hypokalaemia
• Presents subacutely $2-6$ days after correction: dysarthria, dysphagia, pseudobulbar palsy, quadriparesis, "locked-in" syndrome
• MRI T2/FLAIR: pontine and extrapontine signal
• No proven treatment; prevention is paramount

Hyperkalaemia in CKD and RAAS Therapy

• Balancing act: ACE inhibitors/ARBs are renoprotective and cardioprotective (heart failure, diabetic nephropathy) but drive hyperkalaemia
• New potassium binders (patiromer, sodium zirconium cyclosilicate) allow continuation of RAAS therapy in CKD patients who would otherwise have needed dose reduction
• Discuss with nephrology before withdrawing RAAS therapy solely for hyperkalaemia in high-benefit patients

Perioperative and ICU Contexts

• Correct $\text{K}^+ < 3.0\,\text{mmol/L}$ before elective surgery (arrhythmia risk)
• Suxamethonium (succinylcholine) is contraindicated when $\text{K}^+$ is already elevated (can acutely raise $\text{K}^+$ by $0.5-1\,\text{mmol/L}$; catastrophic in burns, rhabdomyolysis, denervation injury)
• In DKA, total body $\text{K}^+$ is depleted despite apparent normo/hyperkalaemia; as insulin is given, $\text{K}^+$ falls precipitously - commence $\text{KCl}$ replacement early once $\text{K}^+ < 5.5\,\text{mmol/L}$

Long-Case Integration and Exam Approach

Viva Framing for Electrolyte Cases

• Always interpret an electrolyte result in clinical context: what is the volume status? what is the urine telling you?
• Avoid reflexive treatment - determine acuity and chronicity before acting
• Pair every electrolyte disorder with a medication reconciliation: diuretics, ACE inhibitors, ARBs, NSAIDs, laxatives, supplements, and corticosteroids are implicated across the spectrum

Key Formulae Summary

Safety Limits for Correction