Hyponatraemia

Everyone's least favourite topic has mercifully yet to appear as a Final FRCA exam SAQ/CRQ.

The resource of choice is Deranged Physiology's electrolyte section, with a full eight pages on the topic.

There is a separate page on sodium disorders in the brain injured patient, which covers some of the causes of hyponatraemia.

It appeared as a CRQ in February 2024, including classification, causes of pseudohyponatraemia and acceptable rate of sodium correction.

Resources

Sodium is the most abundant extracellular cation, accounting for 86% of plasma osmolality
Hyponatraemia describes a plasma Na⁺ <135mmol/L
Disorders of sodium balance are typically mild, but are present in ∽30% of ICU inpatients
It is associated with an increased length of stay and mortality on ICU

Normal range: 135 - 145mmol/L
Daily requirement: 2mmol/Kg

Neuroendocrine mechanisms compensate for alterations in sodium intake by increasing/decreasing sodium reabsorption in the kidney
This control is closely linked to control of ECF osmolality, volaemic state and water homeostasis

A 1-2% increase in plasma osmolality causes stimulation of hypothalamic osmoreceptors

Triggers thirst and water consumption
Triggers ADH release from the posterior pituitary

ADH acts on V₂ receptors in the collecting duct
Increases concentrations of aquaporin 2 (and 3) channels in collecting duct cell membranes
There is increased water reabsorption and a return to normal osmolality

However the baroreceptor reflex is a stronger stimulus for ADH release than the osmoreceptor reflex
Hence in hypotonic, hypovolaemic states fluid replacement is the treatment

Hypovolaemia stimulates juxtaglomerular cells, triggering renin release and activation of the RAAS
Low ECF [Na⁺] also causes aldosterone release

Aldosterone secretion occurs from the zona glomerulosa of the adrenal cortex
Acts on DCT Na⁺/Cl^- and Na⁺/K⁺ transporters, and ENaC channels in the collecting duct, to increase sodium reabsorption
Aldosterone also causes sodium reabsorption from sweat, saliva and in the colon

By severity

Mild: 129 - 135mmol/L
Moderate: 125 - 129mmol/L
Severe: <125mmol/L

By chronology

Acute <48hrs
Chronic >48hrs

By tonicity and volume status

This is where the classic breakdown of hyponatraemia into various subgroups occurs:

Hypertonic
Isotonic
Hypotonic

These are further discussed below

Less common until [Na⁺] <125mmol/L
Symptoms are largely non-specific:

Confusion, headache, imbalance
Nausea, vomiting, muscle cramps
Seizures and coma

History & examination

Full history to elicit onset of symptoms and biochemical abnormalities
Include detailed medication history
Include social history to determine alcohol consumption

Assessment of volume status
Assessment for presence of other diseases causing hyponatraemia

Investigations

Blood

FBC
LFTs
Investigate hormonal causes: TFT's, cortisol, ACTH levels, short synacthen test
Blood glucose
Consider BNP

Tests of osmolarity and sodium

Plasma osmolality
Serum sodium (comes with U&Es)
Urine osmolality
Urine sodium

Other

Urine dip inc. proteins and ketones
ECG - dysrhythmia can occur with severely low levels
CXR e.g. atypical pneumonia, heart failure, lung cancer
TTE - evidence of heart failure
Abdominal ultrasound

Tonicity-based classification and management of hyponatraemia

The patient with acute hyponatraemia and clinical features such as seizures or coma needs rapid sodium correction
One should aim to raise serum Na⁺ by 2-4% over 30mins
E.g. by giving 150ml of 2.7% NaCl over 20 minutes

Rapid correction beyond that needed to stop the patient fitting, especially of chronic hyponatraemia, is undesirable

It will lead to movement of water from neurones into the ECF, causing them to shrink
This can precipitate pontine myelinolysis (typically a concern if the presenting sodium is <120mmol/L)
One should instead change tack and aim to increase sodium by at most 0.5mmol/L/hr

Serum osmolality is 295mosm/kg i.e. hypertonic
This is essentially dilutional hyponatraemia, with the presence of extra osmotically active molecules drawing water into the extracellular space, thus diluting sodium

Aetiology

Hyperglycaemia e.g. HHS
Mannitol
Glycine e.g. following TURP
Maltose
Radiocontrast dye

Management

Calculate corrected sodium to avoid over-correction
Treat underlying cause e.g. insulin for HHS
Correct sodium according to usual guidelines

Serum osmolality is 280-295mosm/kg i.e. isotonic
This is a pseudohyponatraemia, owing to the presence of extra, non-osmotically active molecules in the plasma
They reduce the proportion of plasma composed of water, interfering with sodium measuring techniques

Typically the reductions in sodium are only minimal, as ludicrously high levels of extraneous molecules are required to cause significant drops

Aetiology

Hyperlipidaemia
Hyperproteinaemia e.g. multiple myeloma, IVIg infusion
In theory any large molecule; described with heparin

Management

Treat the underlying cause

This category contains the bulk of medical causes for hypontraemia
One can further sub-classify them according to volume status (hyper-, eu- and hypo-volaemic), but assessment of volume status is universally poorly done
It may therefore be easier to sub-classify according to objective, measurable features i.e. urine osmolality and urine sodium
This essentially leads to four groups:

Group	Urine osmolality	Urine sodium
1	High (>100mosm/kg)	Low (<40mmol/L)
2	High (>100mosm/kg)	High (>40mmol/L)
3	Low (<100mosm/kg)	Low (<40mmol/L)
4	Low (<100mosm/kg)	High (>40mmol/L)

Group 1

Due to retention of both sodium and water following RAAS activation, but with the water retained to a greater extent
Patients tend to be hypervolaemic, except in cases of true hypovolaemia e.g. GI losses, ascites, third-spacing, major haemorrhage

Aetiologies:

Cardiac failure
Nephrotic syndrome
Cirrhotic liver failure
TURP syndrome
Pregnancy

Management

Treat underlying cause
In hypovolaemia, replace appropriate fluid
Otherwise consider fluid restriction
ACE-inhibitors
Loop diuretics
Wait up to 9 months

Group 2

Due to inappropriate sodium losses but normal water retention mechanisms

Aetiologies:

Renal sodium loss e.g. thiazides, ATN, CKD, post-obstructive diuresis
Mineralocorticoid deficiency
Hypothyroidism
SIADH inc. drug causes such as excessive ADH analogues, PPI, SSRI, anticonvulsants
CSW

Management:

Treat underlying cause:

Cease offending drugs
Corticosteroids for deficiency
Levothyroxine for hypothyroidism
Fludrocortisone in CSW

Replacement of sodium e.g. with isotonic or hypertonic saline solutions
Consider drugs such as demecleocyline or tolvaptan in SIADH

Group 3

Due to excessive free water intake
Often a chronic state

Aetiologies:

Polydipsia
Inappropriate iatrogenic fluid e.g. NG water, dextrose
Beer potomania
Reset osmostat

Management:

Gradual reduction in water intake to avoid excessive over-correction of sodium
Fluid restriction
Resstoration of normal nutrition in beer potomania

Group 4

Due to both sodium and water losses, with sodium in excess of water

Aetiologies:

Post-obstructive diuresis
Polyuric phase ATN
AKI

Management

Treat underlying cause e.g. of AKI
Ride out the storm, replacing sodium as necessary