Sunday, February 02, 2014

Euvolemic Hypotonic Hyponatremia - Causes

a.    Euvolemic hypotonic hyponatremia

Euvolemic hyponatremia has the broadest differential diagnosis. Most processes are mediated directly or indirectly through ADH, including
·       Hypothyroidism
·       Adrenal insufficiency
·       Medications

·       Syndrome of inappropriate ADH (SIADH).

The exceptions are
·       Primary polydipsia
·       Beer potomania
·       Reset osmostat.

A.   Hormonal abnormalities

·       Hypothyroidism and adrenal insufficiency can cause hyponatremia.

·       Exactly how hypothyroidism induces hyponatremia is unclear but may be related to ADH. Adrenal insufficiency may be associated with the hyperkalemia and metabolic acidosis of hypo aldosteronism.

·       Cortisol provides feedback inhibition for ADH release.

B.    Thiazide diuretics and other medications

·       Thiazides induce hyponatremia typically in older female patients within days of initiating therapy.

·       The mechanism appears to be a combination of mild diuretic-induced volume contraction, ADH effect, and intact urinary concentrating ability resulting in water retention and hyponatremia.

·       Loop diuretics do not cause hyponatremia as frequently because of disrupted medullary concentrating gradient and impaired urine concentration.

·       Nonsteroidal anti-inflammatory drugs (NSAIDs) increase ADH by inhibiting prostaglandin formation.

·       Prostaglandins and selective serotonin reuptake inhibitors (eg, fluoxetine, paroxetine, and citalopram) can cause hyponatremia, especially in geriatric patients. Enhanced secretion or action of ADH may result from increased serotonergic tone.

·       Angiotensin-converting enzyme (ACE) inhibitors do not block the conversion of angiotensin I to angiotensin II in the brain. Angiotensin II stimulates thirst and ADH secretion.

·       Hyponatremia during amiodarone-loading has been reported; it usually improves with dose reduction.

·       Abuse of 3,4-methylenedioxymethamphetamine (MDMA, also known as Ecstasy) can lead to hyponatremia and severe neurologic symptoms, including seizures, cerebral edema, and brainstem herniation. MDMA and its metabolites increase ADH release from the hypothalamus.

·       Primary polydipsia may contribute to hyponatremia since MDMA users typically increase fluid intake to prevent hyperthermia.

Hyponateremia Flowsheet

C.    Nausea, pain, surgery, and medical procedures

·       Nausea and pain are potent stimulators of ADH release.

·       Severe hyponatremia can develop after elective surgery in healthy patients, especially premenopausal women.

·       Hypotonic fluids in the setting of elevated ADH levels can produce severe, life-threatening hyponatremia.

·       Medical procedures such as colonoscopy have also been associated with hyponatremia.

D.   HIV infection

·       Hyponatremia is seen in up to 50% of hospitalized HIV patients and 20% of ambulatory HIV patients.

·       The differential diagnosis is broad:

o   Medication effect
o   Adrenal insufficiency
o   Hypoaldosteronism
o   Central nervous system or pulmonary disease
o   Malignancy
o   Volume depletion

E.     Endurance exercise hyponatremia

·       Hyponatremia after endurance exercise (eg, triathlon events and marathons) may be caused by a combination of excessive hypotonic fluid intake and continued ADH secretion.

·       Reperfusion of the exercise-induced ischemic splanchnic bed causes delayed absorption of excessive quantities of hypotonic fluid ingested during exercise. Sustained elevation of ADH prevents water excretion in this setting.

·       Current guidelines suggest that endurance athletes drink water according to thirst rather than according to specified hourly rates of fluid intake.

F.     Syndrome of inappropriate antidiuretic hormone secretion

·       Under normal circumstances, hypovolemia and hyperosmolality stimulate ADH secretion.
·       ADH release is inappropriate without these physiological cues.
·       Normal regulation of ADH release occurs from both the central nervous system and the chest via baroreceptors and neural input.
·       The major causes of SIADH are disorders affecting the central nervous system (structural, metabolic, psychiatric, or pharmacologic processes) or the lungs (infectious, mechanical, oncologic).
·       Medications commonly cause SIADH by increasing ADH or its action.
·       Some carcinomas, especially small cell lung carcinoma, can autonomously secrete ADH.

G.    Psychogenic polydipsia and beer potomania

·       Marked free water intake (generally > 10 L/d) may produce hyponatremia.
·       Euvolemia is maintained through renal excretion of sodium.
·       Urine sodium is therefore generally elevated (> 20 mEq/L), and ADH levels are appropriately suppressed.
·       As the increased free water is excreted, the urine osmolality approaches the minimum of 50 mosm/kg.

·       Polydipsia occurs in psychiatric patients. Psychiatric medications may interfere with water excretion or increase thirst through anticholinergic side effects, further increasing water intake.

·       The hyponatremia of beer potomania occurs in patients who consume large amounts of beer. Free water excretion is decreased because of decreased solute consumption and production; muscle wasting and malnutrition are contributing factors.
·       Without enough solute, these patients have decreased free water excretory capacity even if they maximally dilute the urine.

H.    Reset osmostat

·       Reset osmostat is a rare cause of hyponatremia characterized by appropriate ADH regulation in response to water deprivation and fluid challenges.
·       Patients with reset osmostat regulate serum sodium and serum osmolality around a lower set point, concentrating or diluting urine in response to hyperosmolality and hypoosmolality.

·       The mild hypo-osmolality of pregnancy is a form of reset osmostat.

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