Hyponatraemia

Pathophysiology

most types due to defective urinary diulution, ie failure of water diuresis

normal water diuresis requires 3 factors: - suppression of ADH secretion - sufficient sodium and water must reach diluting sites of nephron in ascending limb of loop of Henle and distal convoluted tubule. Inadequate delivery of Na and water to distal sites may be due to ¯ GFR and/or ­ proximal tubular reabsorption. The distal tubules are not absolutely impermeable to water even in the absence of ADH, as the delivery of dilute urine falls the proportion of water that leaks from the hypotonic tubular fluid into the isotonic cortical and slightly hypertonic medullary fluid increases and the urine osmolality rises. This may even lead to excretion of urine that is hypertonic to plasma, despite the absence of ADH - ascending loop of Henle and distal tubule must function normally, reabsorbing Na while remaining impermeable to water

(History of fluid loss? Hypotension or ¯ skin turgor? ­ ­ urea?)

• extrarenal salt and water loss. Urinary Na < 10 mmol/l
  - GI (eg vomiting, diarrhoea, GI suction, fistulae)
  - abdominal sequestration (eg peritonitis, rapid reaccumulation of ascites)
  - skin (sweating, burns)
• renal (urinary Na > 20)
  - renal disease (diuretic phase ARF, postobstructive diuresis, chronic renal failure)
  - salt-wasting (cerebral/renal)
  - diuretic excess
  - mineralocorticoid deficiency (1°/2°)

Urinary Na >20 mmol/l

• acute and chronic renal failure
• temporary impairment of water diuresis (pain, drugs, emotion)
• SIADH
• endocrine (glucocorticoid deficiency, hypothyroidism)
• essential ("sick-cell syndrome")

Urinary Na <20 mmol/l

severe polydipsia

Without serum hyposmolality

	osmotic (hyperglycaemia, mannitol). Results in shift of water from cells into extracellular fluid
	artifactual: hyperlipidaemia, hyperproteinaemia and laboratory error

Types of hyponatraemia

Hyponatraemia due to volume depletion

	impaired delivery of Na and water to ascending loop and distal tubule plus high ADH due to volume depletion
	hyponatraemia per se is usually of little clinical significance. Major features are of extracellular volume contraction
	reduction of Na by more than 10-15 mmol/l is rare in absence of obvious decreases in skin turgor, postural or recumbent ¯ BP and some degree of uraemia
	in occasional patient with Na < 125 mmol/l may be desirable to administer to give some of the replacement as hypertonic saline

Hyponatraemia due to diuretics

	multiple factors contribute to hyponatraemia - salt loss may cause volume depletion - thiazides and loop diuretics inhibit salt reabsorption in the diluting segments of nephron and thereby directly limit water diuresis - thiazides most commonly associated with ¯ Na because they interfere with Na reabsorption in distal tubulre but, unlike loop diuretics, do not limit urine concentration and water retention by interfering with Na transport in the loop of Henle - K depletion contributes to ¯ Na through uncertain mechanisms
	¯ Na due to diuretic therapy for ­ BP usually mild but may be moderate or severe in patients who drink large volumes of hypotonic fluids
	elderly women especially prone to develop severe ¯ Na
	treatment is water restriction and K replacement
	Hyponatraemia associated with oedematous states
	usually associated with intravascular fluid depletion or decreased cardiac output. This leads to decreased delivery of Na and water to ascending loop and distal tubule
	decreased intravascular volume also triggers ADH secretion
	in some oedematous patients essential hyponatraemia may be an additional contributing factor
	severity and frequency of ¯ Na correlates to some extent with magnitude of oedema and seriousness of underlying condition
	¯ Na often of little clinical significance and principal features usually those of underlying disease
	symptomatic ¯ Na may occur, most often following aggressive diuretic therapy or excessive oral or parenteral intake of dilute fluids
	responds to effective therapy of underlying disease. Moderate non-progressive ¯ Na does not usually cause symptoms. Attempts to correct it by fluid restriction induce thirst and discomfort without improving clinical picture or longevity
	fluid restriction to 1-1.5 l/day may be necessary in patients with severe or progressive ¯ Na
	hypertonic saline should not be given (total body Na is high) except for clinical manifestations of extreme ¯ Na (eg coma, convulsions). Give frusemide concurrently to avoid expansion of ECF volume
	dialysis can be used to correct severe ¯ Na without ­ ECF volume

SIADH

	mainly due to water retention but urinary losses of Na may also contribute to a mild negative Na balance
	characterized by: - urine not maximally dilute even when marked hyponatraemia is induced by water loading. In most cases urine osmolality exceeds that of plasma - plasma creatinine and urea normal or low indicating that GFR is normal or high - during fluid loading (even if fluid is saline) hyponatraemia increases due to water retention and urinary Na wasting - hyponatraemia corrected by fluid restriction
	uric acid normal (as uric acid excretion tends to vary with "effective" extracellular volume hyperuricaemia is common in volume depletion)

Aetiology

	Neoplasia: especially oat cell CA lung.
	CNS disorders including: - meningitis - encephalitis - tumours - trauma - stroke
	Pulmonary disease: - tumours - infections - asthma - COPD
	Drugs: - oral hypoglycaemics: chlorpropamide, tolbutamide - antineoplastic and immunosuppressive agents: vincristine, vinblastine, cyclophosphamide - psychoactive drugs: haloperidol, thioridazine, carbamazepine, amitriptyline

Management

	treat cause
	limit fluid intake. Usually 1-1.2 l/day is sufficient restriction
	occasionally patients who are symptomatic despite water restriction may be treated by enhancing water excretion either by increasing solute excretion (by taking high salt high protein diet) or by antagonizing ADH with demeclocyline or lithium
	initial therapy with hypertonic saline may be appropriate in a few symptomatic patients with marked hyponatraemia. Concurrent administration of frusemide (which limits urinary concentration) may facilitate correction of hyponatraemia in those patients who do not respond promptly to hypertonic saline alone

Essential hyponatraemia

	thought that osmoreceptors in hypothalamus are reset to maintain a decreased level of osmolality as though it were normal
	may occur in a variety of chronic illnesses (eg pulmonary TB, CCF, hepatic cirrhosis)
	asymptomatic. Skin turgor, BP and renal function are normal unless altered by the primary disease
	definitive diagnosis requires the demonstration of normal urinary dilution in response to water loading, normal concentration during dehydration and normal renal sodium excretory responses to sodium loading and restriction
	does not require treatment

Clinical features

	neurological dysfunction is principal clinical manifestation
	due to intracellular movement of water leading to brain cell swelling
	severity of symptoms related to degree of hyponatraemia and speed of development
	? women develop more severe manifestations than men
	in chronic cases degree of swelling is reduced by cellular volume regulatory mechanisms: inorganic ions (eg K and Cl) and organic osmolytes (eg amino acids) are transported out of cells
	lethargy, confusion, stupor, coma
	if hyponatraemia develops rapidly signs of hyperexcitability (eg muscle twitching, irritability and convulsions may occur)
	¯ Na rarely causes symptoms when Na > 125 mmol/l except when decrease in concentration has been rapid

Treatment (euvolaemic hyponatraemia)

	only patients with severe symptomatic hyponatraemia should be treated with hypertonic saline
	if hyponatraemia has developed over 24 h or less hypertonic saline should be administered in an amount calculated to increase plasma Na by no more than 1-2 mmol/l/h. If chronic increase Na by no more than 0.5-1 mmol/l/h. In either case, do not raise Na by more than 12 mmol/l over first 24 h
	symptoms and clinical status, especially volume status, should be continually reassessed

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© Charles Gomersall December 1999